FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Roe, B Whittington, LA Fein, SB Teisl, MF AF Roe, B Whittington, LA Fein, SB Teisl, MF TI Is there competition between breast-feeding and maternal employment? SO DEMOGRAPHY LA English DT Article ID UNITED-STATES; 1ST BIRTH; WOMEN; WORK; DURATION; MOTHERS; VARIABLES; CHILDREN AB Theory suggests that the decision to return to employment after childbirth and the decision to breast-feed may be jointly determined. We estimate models of simultaneous equations for two different aspects of the relationship between maternal employment and breastfeeding using 1993-1994 data from the U.S. Food and Drug Administration's Infant Feeding Practices Study. We first explore the simultaneous duration of breast-feeding and work leave following childbirth. We find that the duration of leave from work significantly affects the duration of breast-feeding, but the effect of breast-feeding on work leave is insignificant. We also estimate models of the daily hours of work and breast-feedings at infant ages 3 months and 6 months postpartum. At both times, the intensity of work effort significantly affects the intensify of breast-feeding, but the reverse is generally not found. Competition clearly exists between work and breast-feeding for many women in our sample. C1 Ohio State Univ, Dept Agr Econ, Columbus, OH 43210 USA. Georgetown Univ, Georgetown Publ Policy Inst, Washington, DC 20057 USA. Univ Maine, Dept Resource Econ & Policy, Orono, ME USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Fein, SB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-727,200 C St SW, Washington, DC 20204 USA. RI Roe, Brian/A-7386-2009; OI Roe, Brian/0000-0003-4228-2889; teisl, mario/0000-0002-2021-9208 NR 35 TC 116 Z9 117 U1 0 U2 5 PU POPULATION ASSN AMER PI WASHINGTON PA 1722 N ST NW, WASHINGTON, DC 20036 USA SN 0070-3370 J9 DEMOGRAPHY JI Demography PD MAY PY 1999 VL 36 IS 2 BP 157 EP 171 DI 10.2307/2648105 PG 15 WC Demography SC Demography GA 193RA UT WOS:000080149200002 PM 10332608 ER PT J AU Hempel, R Schupke, H McNeilly, PJ Heinecke, K Kronbach, C Grunwald, C Zimmermann, G Griesinger, C Engel, J Kronbach, T AF Hempel, R Schupke, H McNeilly, PJ Heinecke, K Kronbach, C Grunwald, C Zimmermann, G Griesinger, C Engel, J Kronbach, T TI Metabolism of retigabine (D-23129), a novel anticonvulsant SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID SEIZURES AB Retigabine (D-23129, N-(2-amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester) is a potent anticonvulsant ina variety of animal models. Rats metabolized [C-14]retigabine mainly through glucuronidation and acetylation reactions. Glucuronides were detected in incubates with liver microsomes or slices, in plasma, and in bile and feces but were absent in urine (0-24 h) that contained about 2% of the dose as retigabine and approximately 29% of the dose in > 20 metabolites, which are derived mainly from acetylation reactions. About 67% of the radioactivity was excreted into feces, approximately 10% of the dose as glucuronide, The metabolite pattern in the urine (0-24 h) of dogs was comparatively simple in that retigabine (13%), retigabine-N-glucuronide (5%), and retigabine-N-glucoside (1%) were present. In the same 24-h interval, about 39% of unchanged retigabine was excreted into feces. Plasma profiling and spectroscopic analysis (liquid chromatography with tandem mass spectrometry NMR) of two isolated urinary metabolites obtained after single oral dosing of 600 mg retigabine in healthy volunteers indicated that both acetylation and glucuronidation are major metabolic pathways of retigabine in humans, We found that in vitro assays with liver slices from rat and humans reveal the major circulating metabolites in vivo. C1 Arzneimittelwerk Dresden GmbH, Biochem Dresden, ASTA Med Grp, Corp Res & Dev, D-01445 Radebeul, Germany. US FDA, Lab Clin Pharmacol, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Laurel, MD USA. Univ Frankfurt, Inst Organ Chem, D-6000 Frankfurt, Germany. RP Hempel, R (reprint author), Arzneimittelwerk Dresden GmbH, Biochem Dresden, ASTA Med Grp, Corp Res & Dev, Meissner Str 191, D-01445 Radebeul, Germany. NR 10 TC 60 Z9 61 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAY PY 1999 VL 27 IS 5 BP 613 EP 622 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 192WT UT WOS:000080103200011 PM 10220491 ER PT J AU Jayadev, S Smith, RD Jagadeesh, G Baukal, AJ Hunyady, L Catt, KJ AF Jayadev, S Smith, RD Jagadeesh, G Baukal, AJ Hunyady, L Catt, KJ TI N-linked glycosylation is required for optimal AT(1a) angotensin receptor expression in COS-7 cells SO ENDOCRINOLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; AGONIST-INDUCED PHOSPHORYLATION; ADRENAL GLOMERULOSA CELLS; ANGIOTENSIN-II RECEPTOR; LIGAND-BINDING; HORMONE RECEPTOR; OLIGOSACCHARIDES; IDENTIFICATION; MEMBRANE; RESIDUES AB The nature and role of glycosylation in AT, angiotensin receptor (AT(1)-R) function were investigated by expressing glycosylation-deficient influenza hemagglutinin (HA) epitope-tagged rat AT(1a)-Rs (HA-AT(1a)-Rs) in COS-7 cells. All three asparagine residues (Asn(4), Asn(176) Asn(188)) contained within consensus sites for N-linked glycosylation could be glycosylated in Cos-7 cells and appeared to be glycosylated on the endogenous AT(1)-R in bovine adrenal glomerulosa cells. Heterogeneity of glycosylation at each site accounted for the broad migration pattern of the AT(1)-R in SDS-PAGE. Mutation at each glycosylation site, either alone or in combination, had little effect on Ligand binding parameters (although the N4K mutant had higher affinity) or signaling activity. However, an increasing number of mutated glycosylation sites was associated with decreasing cell surface receptor expression, which was minimal for the unglycosylated N4K/N176Q/N188Q receptor. Decreased surface expression of mutant HA-AT(1a)-Rs was correlated with decreased total cell receptor content as revealed by immunoblotting with an anti-HA antibody. These findings suggest that glycosylation enhances receptor stability, possibly by protecting nascent receptors from proteolytic degradation. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. US FDA, CDER, Div Cardiorenal Prod, Rockville, MD 20857 USA. Semmelweis Univ, Dept Physiol, H-1088 Budapest, Hungary. RP Catt, KJ (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM catt@helix.nih.gov RI Jagadeesh, Gowraganahalli/G-6408-2010 NR 28 TC 37 Z9 37 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1999 VL 140 IS 5 BP 2010 EP 2017 DI 10.1210/en.140.5.2010 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 187RP UT WOS:000079801200008 PM 10218949 ER PT J AU DeVito, M Biegel, L Brouwer, A Brown, S Brucker-Davis, F Cheek, AO Christensen, R Colborn, T Cooke, P Crissman, J Crofton, K Doerge, D Gray, E Hauser, P Hurley, P Kohn, M Lazar, J McMaster, S McClain, M McConnell, E Meier, C Miller, R Tietge, J Tyl, R AF DeVito, M Biegel, L Brouwer, A Brown, S Brucker-Davis, F Cheek, AO Christensen, R Colborn, T Cooke, P Crissman, J Crofton, K Doerge, D Gray, E Hauser, P Hurley, P Kohn, M Lazar, J McMaster, S McClain, M McConnell, E Meier, C Miller, R Tietge, J Tyl, R TI Screening methods for thyroid hormone disruptors SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE developmental toxicity; endocrine disruptors; neurobehavioral toxicity; screens; thyroid hormone; thyroid hormone receptors ID RETINOID-X-RECEPTOR; SPERM PRODUCTION; POLYCHLORINATED-BIPHENYLS; NEONATAL-HYPOTHYROIDISM; BRAIN-DEVELOPMENT; RISK ASSESSMENT; HEPATIC NUCLEI; RAT FETUS; THYROXINE; BINDING AB The U.S. Congress has passed legislation requiring the EPA to implement screening tests for identifying endocrine-disrupting chemicals. A series of workshops was sponsored by the EPA, the Chemical Manufacturers Association, and the World Wildlife Fund; one workshop focused on screens for chemicals that alter thyroid hormone function and homeostasis. participants at this meeting identified and examined methods to detect alterations in thyroid hormone synthesis, transport, and catabolism. In addition, some methods to detect chemicals that bind to the thyroid hormone receptors acting as either agonists or antagonists were also identified. Screening methods used in mammals as well as other vertebrate classes were examined. There was a general consensus that all known chemicals which interfere with thyroid hormone function and homeostasis act by either inhibiting synthesis, altering serum transport proteins, or by increasing catabolism of thyroid hormones. There are no direct data to support the assertion that certain environmental chemicals bind and activate the thyroid hormone receptors; further research is indicated. In light of this, screening methods should reflect known mechanisms of action. Most methods examined, albeit useful for mechanistic studies, were thought to be too specific and therefore would not be applicable for broad-based screening. Determination of serum thyroid hormone concentrations following chemical exposure in rodents was thought to be a reasonable initial screen. Concurrent histologic evaluation of the thyroid would strengthen this screen. Similar methods in teleosts may be useful as screens, but would require indicators of tissue production of thyroid hormones. The use of tadpole metamorphosis as a screen may also be useful; however, this method requires validation and standardization prior to use as a broad-based screen. C1 US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Haskell Lab Ind Med, Newark, DE 19714 USA. Wageningen Univ Agr, Dept Toxicol, Wageningen, Netherlands. Natl Water Res Inst, Burlington, ON, Canada. World Wildlife Fund, Washington, DC 20037 USA. Tulane Univ, Med Ctr, Ctr Bioenvironm Res, New Orleans, LA 70112 USA. Bayer Corp, Agr Div Toxicol, Stillwell, KS 66085 USA. Univ Illinois, Coll Vet Med, Urbana, IL 61801 USA. Dow Chem Co, Midland, MI 48674 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Vet Adm Med Ctr, Psychiat Serv, Baltimore, MD 21218 USA. US EPA, Off Pesticide Prevent & Tox Res, Washington, DC 20460 USA. Hoffmann La Roche Inc, Preclin Dev Adm, Nutley, NJ 07110 USA. Hoffmann La Roche Inc, Preclin Dev Adm, Raleigh, NC 27613 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP DeVito, M (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, MD-74, Res Triangle Pk, NC 27711 USA. RI Crofton, Kevin/J-4798-2015; OI Crofton, Kevin/0000-0003-1749-9971; gray jr, leon earl/0000-0002-1111-4754 NR 107 TC 125 Z9 131 U1 0 U2 11 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 1999 VL 107 IS 5 BP 407 EP 415 DI 10.2307/3434545 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 195BF UT WOS:000080228700025 PM 10210697 ER PT J AU Klontz, KC AF Klontz, KC TI Does imbibing alcohol protect against enteric pathogens? SO EPIDEMIOLOGY LA English DT Editorial Material ID HELICOBACTER-PYLORI INFECTION; SALMONELLA-ENTERITIDIS; CIGARETTE-SMOKING; HEPATITIS-A; EPIDEMIOLOGY; CONSUMPTION; ADULTS; WINE; RISK; MEN C1 US FDA, Ctr Food Safety & Appl Nutr, Epidemiol Branch, Washington, DC 20204 USA. RP Klontz, KC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Epidemiol Branch, 200 C St SW, Washington, DC 20204 USA. NR 25 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 1999 VL 10 IS 3 BP 207 EP 209 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 189EM UT WOS:000079891400001 PM 10230824 ER PT J AU Vionnet, J Concepcion, N Warner, T Zapata, G Hanover, J Vann, WF AF Vionnet, J Concepcion, N Warner, T Zapata, G Hanover, J Vann, WF TI Purification of CMP-N-acetylneuraminic acid synthetase from bovine anterior pituitary glands SO GLYCOBIOLOGY LA English DT Article DE CMP-sialic acid synthetase; enzyme purification; pituitary glands; sialic acid metabolism ID CYTIDINE-5'-MONOPHOSPHOSIALATE SYNTHASE; GROUP-B; NUCLEAR; PROTEINS; LIVER; ACETYLGLUCOSAMINE; LOCALIZATION; PEPTIDE; CLONING AB CMP-beta-N-acetylneuraminic acid (CMP-neuNAc) is the substrate for the sialylation of glycoconjugates by sialyltransferases in microbes and higher eukaryotes. CMP-neuNAc synthetase catalyzes the formation of this substrate, CMP-neuNAc, from CTP and neuNAc. In this report we describe the purification of CMP-neuNAc synthetase from bovine anterior pituitary glands. The enzyme was purified by ion exchange, gel filtration, and affinity chromatography, The protein was homogeneous on SDS-PAGE with a molecular weight of 52 kDa, a subunit size similar to that of the E.coli K1 (48.6 kDa), The identity of the 52 kDa protein band was confirmed by native gel electrophoresis in that the position of the enzyme activity in gel slices coincided with the position of major bands in the stained gel. Photoaffinity labeling with I-125-ASA-CDP ethanolamine resulted in the modification of a 52 kDa polypeptide that was partially protected against modification by the substrate CTP, Enzyme activity in crude fractions could be adsorbed onto an immunoadsorbent prepared from antibody against the purified 52 kDa protein. Taken together these data suggest that the 52 kDa polypeptide purified by this procedure described in this report is indeed CMP-neuNAc synthetase. The active enzyme chromatographed on a gel filtration column at 158 kDa suggesting it exists in its native form as an oligomer. C1 US FDA, CBER, OVRR, Div Bacterial Prod,Lab Bacterial Toxins, Bethesda, MD 20892 USA. US FDA, CBER, OVRR, Div Bacterial Prod,Lab Bacterial Polysaccharides, Bethesda, MD 20892 USA. Genentech Inc, S San Francisco, CA 94080 USA. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Vann, WF (reprint author), US FDA, CBER, OVRR, Div Bacterial Prod,Lab Bacterial Toxins, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 26 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD MAY PY 1999 VL 9 IS 5 BP 481 EP 487 DI 10.1093/glycob/9.5.481 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 191YL UT WOS:000080049700006 PM 10207180 ER PT J AU Poley, GE Slater, JE AF Poley, GE Slater, JE TI Drug and vaccine allergy SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article ID HIV-INFECTED PATIENTS; IMMUNODEFICIENCY-VIRUS INFECTION; RAPID ORAL DESENSITIZATION; GUILLAIN-BARRE-SYNDROME; TRIMETHOPRIM-SULFAMETHOXAZOLE; ADVERSE REACTIONS; INTRAVENOUS IMMUNOGLOBULIN; HYPERSENSITIVITY REACTIONS; CLINICAL-EXPERIENCE; IMMUNE GLOBULIN AB Treatment of allergic reactions to drugs is an important part of pediatric practice. This articles focuses on five specific areas of interest: active vaccines, immune globulins, beta-lactam antibiotics, sulfonamide use in patients with HIV, and children with multiple drug allergies. Severe react-ions to active and passive immunization are uncommon, whereas reactions to beta-lactam and sulfonamide antimicrobials are more common. In all cases, a stepwise approach to the evaluation of patients who may five a drug allergy can lead to the effective diagnosis. prevention, and treatment of such reactions. C1 US FDA, Lab Immunobiochem, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Childrens Natl Med Ctr, Dept Allergy Immunol & Pulm Med, Washington, DC 20010 USA. RP Slater, JE (reprint author), US FDA, Lab Immunobiochem, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-422, Rockville, MD 20852 USA. NR 67 TC 7 Z9 7 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 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 1999 VL 19 IS 2 BP 409 EP + DI 10.1016/S0889-8561(05)70096-5 PG 15 WC Allergy; Immunology SC Allergy; Immunology GA 188WB UT WOS:000079871300012 ER PT J AU Craig, WA AF Craig, WA TI The mathematics of antimicrobials SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Editorial Material ID THIGH-INFECTION; ANTIBIOTICS; MODEL C1 Univ Wisconsin, Sch Med, Madison, WI 53706 USA. Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. US FDA, Antiinfect Drugs Advisory Comm, Rockville, MD 20857 USA. RP Craig, WA (reprint author), William S Middleton Mem Vet Hosp, 2500 Overlook Terrace, Madison, WI 53706 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD MAY PY 1999 VL 8 IS 4 BP 191 EP 194 DI 10.1097/00019048-199905000-00007 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 191HK UT WOS:000080016900007 ER PT J AU Lake, DF Salgaller, ML van der Bruggen, P Bernstein, RM Marchalonis, JJ AF Lake, DF Salgaller, ML van der Bruggen, P Bernstein, RM Marchalonis, JJ TI Construction and binding analysis of recombinant single-chain TCR derived from tumor-infiltrating lymphocytes and a cytotoxic T lymphocyte clone directed against MAGE-1 SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE single chain TCR ID HUMAN GENE MAGE-1; CELL RECEPTOR; ESCHERICHIA-COLI; ANTIGEN; PEPTIDE; MELANOMA; LIGANDS; SPECIFICITIES; GENERATION; REPERTOIRE AB The TCR is responsible for the specificity of cytotoxic T lymphocytes (CTL) by recognizing peptides presented in the context of MHC. By producing recombinant soluble TCR, it is possible to study this interaction at the molecular level. We generated single-chain TCR (scTCR) from tumor infiltrating lymphocytes (TIL) and one CTL clone directed against melanoma-associated antigen (MAGE)-1, Sixty-eight day anti-MAGE-1 TIL and one cloned anti-MAGE-1 CTL were analyzed by PCR for their V-alpha, and Vp gene usage. The TIL population showed a restriction in V, and Vp usage with only V(alpha)4 and V(alpha)9 and V(beta)2 and V(beta)7 expressed. The anti-MAGE-1 CTL clone demonstrated absolute restriction with only V(alpha)12 and V(beta)1 expressed. DNA sequence analysis was performed on all V regions. For the TIL, each possible V-alpha-V-beta combination (i.e. V(alpha)4-V(beta)2, V(alpha)9-V(beta)2, V(alpha)4-V(beta)7 and V(alpha)9-V(beta)7) was constructed as a distinct scTCR and the recombinant proteins expressed in bacteria. From the anti-MAGE-1 TIL, V(alpha)4-V(beta)2 scTCR demonstrated binding activity to HLA-A1(+) cells pulsed with MAGE-1 peptide. Results obtained from screening a panel of our scTCR constructs on HLA-A1(+) cells pulsed with MAGE-1 peptide or irrelevant peptide demonstrated that V(beta)2 plays a significant role in binding to the MAGE-1 peptide. Amino acid alignment analysis showed that each Vp sequence is distinctly different from the others. These findings demonstrate that soluble TCR in single-chain format have binding activity. Furthermore, the results indicate that in TCR, like antibodies, one chain may contribute a dominant portion of the binding activity. C1 Univ Arizona, Dept Microbiol & Immunol, Tucson, AZ 85724 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. NW Biotherapeut LLC, Seattle, WA USA. Ludwig Inst Canc Res, Brussels, Belgium. US FDA, Rockville, MD 20857 USA. RP Lake, DF (reprint author), Univ Arizona, Dept Microbiol & Immunol, Tucson, AZ 85724 USA. NR 37 TC 8 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 1999 VL 11 IS 5 BP 745 EP 751 DI 10.1093/intimm/11.5.745 PG 7 WC Immunology SC Immunology GA 201ZV UT WOS:000080628400013 PM 10330280 ER PT J AU McDaniel, JP Syin, C Lin, DT Joshi, MB Li, SP Goldman, ND AF McDaniel, JP Syin, C Lin, DT Joshi, MB Li, SP Goldman, ND TI Expression and characterisation of a Plasmodium falciparum protein containing domains homologous to sarcalumenin and a tyrosine kinase substrate, eps15 SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Article DE sarcoplasmic reticulum; sarcalumenin; tyrosine kinase substrate; Plasmodium falciparum ID SARCOPLASMIC-RETICULUM; CALCIUM; IDENTIFICATION; GLYCOPROTEIN; CULTURE AB We have identified in Plasmodium falciparum a novel gene encoding a putative bi-functional protein, termed PfPast-1, from genomic and cDNA libraries. Analysis indicated that the sequence encodes a 62 kDa protein of 529 amino acid residues with two distinctive domains: a sarcalumenin-like domain of approximately 320 amino acids at the amino half of the molecule, which shares homology to a major sarcoplasmic reticulum lumenal protein, sarcalumenin, and an eps15 homology domain of about 90 amino acids located at the carbonyl terminus. The eps15 homology domain, first identified in a tyrosine kinase substrate, eps15, and found in increasing numbers of mammalian proteins, has recently been suggested as a protein-protein interaction domain involved in intracellular sorting. Genomic sequences encoding similar proteins containing both the sarcalumenin-like and eps15 homology domains have been identified in humans and Drosophila. RNA blot analysis revealed the presence of a single messenger RNA transcript approximately 3.7 kb in size, which is expressed in all the developmental stages examined with the highest level in extracellular gametes followed by erythrocytic asexual stages, and the lowest in the gametocytes. In the attempt to define its biological function, we have expressed a full-length recombinant PfPast-1 protein in Escherichia coli. Specific immune serum directed against the recombinant protein recognised a similar to 55 kDa protein in the parasite lysate. Further characterisation of PfPast-1 may help in elucidation of its functions in P. falciparum. (C) 1999 Australian Society for Parasitology. Published by Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP McDaniel, JP (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 20 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD MAY PY 1999 VL 29 IS 5 BP 723 EP 730 DI 10.1016/S0020-7519(99)00024-7 PG 8 WC Parasitology SC Parasitology GA 208LQ UT WOS:000080993000009 PM 10404267 ER PT J AU Witter, FR Barditch-Crovo, P Rocco, L Trapnell, CB AF Witter, FR Barditch-Crovo, P Rocco, L Trapnell, CB TI Duration of vaginal retention and potential duration of antiviral activity for five nonoxynol-9 containing intravaginal contraceptives SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE nonoxynol-9; contraception; vagina; HIV; AIDS ID HIV-INFECTION; WOMEN; QUANTITATION; TRANSMISSION AB Objective: The purpose of this study was to determine the vaginal retention of five nonoxynol-9 intravaginal contraceptives. Method: An open-label crossover study in 10 premenopausal volunteers was performed at an outpatient clinical research center. The outcomes are described utilizing the median and range. Result: At 8 h post-instillation, the median amounts of nonoxynol-9 present in the vagina were: Delfon(R) 7.68 mg, Conceptrol(R) 5.18 mg,Advantage 24(R) 1.95 mg, VCF(R) 1.74 mg, and Semicid(R) 1.51 mg respectively. Our calculated theoretical minimal amount needed to protect against HIV infection is 2.00 mg. Conclusion: The best vehicle for retaining nonoxynol-9 in the vagina appears to be foam. Further research in the effectiveness of nonoxynol-9 in prevention of the spread of HIV infection should be directed toward the use of foam vehicles to deliver nonoxynol-9 to the vagina. (C) 1999 International Federation of Gynecology and Obstetrics. C1 Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Clin Pharmacol, Baltimore, MD 21205 USA. US FDA, Rockville, MD 20857 USA. RP Witter, FR (reprint author), Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. FU OCPHP CDC HHS [PR-00052]; PHS HHS [223943002] NR 14 TC 18 Z9 19 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD MAY PY 1999 VL 65 IS 2 BP 165 EP 170 DI 10.1016/S0020-7292(99)00018-1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 202JD UT WOS:000080647800008 PM 10405061 ER PT J AU Tolleson, WH Couch, LH Melchior, WB Jenkins, GR Muskhelishvili, M Muskhelishvili, L McGarrity, LJ Domon, O Morris, SM Howard, PC AF Tolleson, WH Couch, LH Melchior, WB Jenkins, GR Muskhelishvili, M Muskhelishvili, L McGarrity, LJ Domon, O Morris, SM Howard, PC TI Fumonisin B-1 induces apoptosis in cultured human keratinocytes through sphinganine accumulation and ceramide depletion SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE fumonisin B-1; ceramide; sphinganine; sphingolipids; apoptosis ID TUMOR-NECROSIS-FACTOR; PROTEIN-KINASE-C; PAPILLOMAVIRUS TYPE-16 DNA; PROGRAMMED CELL-DEATH; HAMSTER OVARY CELLS; FUSARIUM-MONILIFORME; SPHINGOID BASES; SIGNAL-TRANSDUCTION; IONIZING-RADIATION; FACTOR-ALPHA AB Fumonisin B-1 stimulates apoptosis in a variety of cell types and tissues. We examined the role of sphingolipid changes in fumonisin B-1-stimulated apoptosis. Sphinganine accumulated rapidly, sphingosine levels remained unchanged, and ceramides decreased during fumonisin B-1 exposure. Increased DNA fragmentation, decreased viability, and apoptotic morphology were observed in cells exposed to fumonisin B-1, sphinganine, or N-acetylsphingosine. Coexposure to N-acetylsphingosine or beta-chloroalanine, which blocks sphinganine accumulation, partially protected cells from fumonisin B-1-induced apoptosis. These results illustrate three sphingolipid-dependent mechanisms for inducing apoptosis: accumulation of excess ceramide, accumulation of excess sphinganine, and depletion of ceramide or complex sphingolipids derived from ceramide. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Genet Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. RP Tolleson, WH (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU NIA NIH HHS [IAG 224-93-0001] NR 65 TC 55 Z9 55 U1 1 U2 2 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 MAY PY 1999 VL 14 IS 5 BP 833 EP 843 PG 11 WC Oncology SC Oncology GA 187GQ UT WOS:000079779100002 PM 10200332 ER PT J AU Yaes, RJ AF Yaes, RJ TI The slope of the sigmoid dose response curve for tumor control SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter ID STEEPNESS C1 US FDA, Ctr Drug Evaluat & Res, Div Med Imaging & Radiopharmaceut Drug Prod, Rockville, MD 20857 USA. RP Yaes, RJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Med Imaging & Radiopharmaceut Drug Prod, Rockville, MD 20857 USA. NR 11 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 1999 VL 44 IS 2 BP 470 EP 471 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 189NA UT WOS:000079910400035 PM 10928846 ER PT J AU Jacobs, A Avalos, J Brown, P Wilkin, J AF Jacobs, A Avalos, J Brown, P Wilkin, J TI Does photosensitivity predict photococarcinogenicity? SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Review DE drug safety; photosensitivity; photogenotoxicity; photococarcinogenicity ID INDUCED SKIN CARCINOGENESIS; ORNITHINE DECARBOXYLASE INDUCTION; TRANS-RETINOIC ACID; HAIRLESS MOUSE SKIN; PHOTOMUTAGENESIS TEST DEVELOPMENT; SOLAR-SIMULATED RADIATION; PARA-AMINOBENZOIC ACID; PANOXYL GEL 5-PERCENT; HRA SKH MOUSE; ULTRAVIOLET-RADIATION AB Assessment of short-term and long-term effects of light (phototesting) is part of the safety evaluation of drugs. Results are incorporated into drug package inserts to advise patients and health care providers about the use of drug products on sun-exposed skin. We undertook an exhaustive literature search and a search of archived studies at the Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA), in order to evaluate the potential of short-term photoassays to predict long-term effects of drugs used in sunlight (280-700 nm). The correlation between the findings from the photococarcinogenicity assays in mice that used exposure to simulated sunlight and those from photogenotoxicity and photosensitivity studies was examined. Results indicated that photosensitivity and photogenotoxicity assays did not necessarily predict effects in photococarcinogenicity studies in mice. Effects of drugs on skin that are not due to photoactivation of drug can be important factors in enhancement of UV-induced skin carcinogenesis. C1 US FDA, Div Dermatol & Dent Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Jacobs, A (reprint author), US FDA, Div Dermatol & Dent Drug Prod, Ctr Drug Evaluat & Res, HFD-540,5600 Fishers Lane, Rockville, MD 20857 USA. NR 144 TC 13 Z9 13 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 MAY-JUN PY 1999 VL 18 IS 3 BP 191 EP 198 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 192EY UT WOS:000080066500005 ER PT J AU Biles, JE White, KD McNeal, TP AF Biles, JE White, KD McNeal, TP TI Determination of the diglycidyl ether of bisphenol A and its derivatives in canned foods SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE diglycidyl ether of bisphenol A; epoxy; vinyl plastisol; can coating; migration ID LIQUID; MIGRATION; SIMULANTS AB Migration of the diglycidyl ether of bisphenol A (DGEBA) to food from can enamels and can pull-top seals is reported. Derivatives of DGEBA are also determined in some foods. Levels of DGEBA in the foods surveyed in this study range from nondetected (<0.3 ppb) to 50 mg/kg as determined by liquid-liquid extraction or solid-phase extraction coupled with high-pressure liquid chromatography using fluorescence detection. Confirmation of the analytes is by gas and/or liquid chromatography with mass spectral analysis, Fourier transform infrared spectroscopy with 30 degrees specular reflectance/transmittance is used to characterize the coated food contact surfaces. Stability studies with DGEBA in water, acid, and saline solutions show conversion to the hydrolysis products and chloro adducts occurs readily. The presence of DGEBA derivatives in food demonstrates that analysis for DGEBA migration alone is not a good indicator of total migration from can coatings to foods. C1 US FDA, Off Premarket Approval, Washington, DC 20204 USA. US FDA, Off Sci Anal & Support, Washington, DC 20204 USA. RP Biles, JE (reprint author), US FDA, Off Premarket Approval, HFS-245,, Washington, DC 20204 USA. NR 15 TC 46 Z9 46 U1 2 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY PY 1999 VL 47 IS 5 BP 1965 EP 1969 DI 10.1021/jf9810867 PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 198MD UT WOS:000080427200028 PM 10552479 ER PT J AU Plakas, SM El Said, KR Bencsath, FA Musser, SM Walker, CC AF Plakas, SM El Said, KR Bencsath, FA Musser, SM Walker, CC TI Determination of flumequine in channel catfish by liquid chromatography with fluorescence detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ANGUILLA-ANGUILLA L; OXOLINIC ACID; FISH-TISSUES; QUINOLONE ANTIBACTERIALS; PIROMIDIC ACIDS; SALMON; PLASMA; HPLC; CONFIRMATION; EXTRACTION AB Rapid methods are described for determination of flumequine (FLU) residues in muscle and plasma of farm-raised channel catfish (Ictalurus punctatus). FLU residues were extracted from tissues with an acidified methanol solution, and extracts were cleaned up on C-18 solid-phase extraction cartridges. FLU concentrations were determined by liquid chromatography (LC) using a C18 analytical column and fluorescence detection (excitation, 325 nm; emission, 360 nm). Mean recoveries of FLU from fortified muscle were 87-94% at 5 levels ranging from 10 to 160 ppb (5 replicates per level). FLU recoveries from fortified plasma were 92-97% at 5 levels ranging from 20 to 320 ppb. Limits of detection (signal-to-noise ratio, 3:1) for the method as described were 3 and 6 ppb for muscle and plasma, respectively. Relative standard deviations (RSDs) for recoveries were less than or equal to 12%. Live catfish were dosed with C-14-labeled or unlabeled FLU to generate incurred residues. Recoveries of C-14 residues throughout extraction and cleanup were 90 and 94% for muscle and plasma, respectively. RSDs for incurred FLU at 2 levels in muscle and plasma ranged from 2 to 6%. The identity of FLU in incurred tissues was confirmed by LC/mass spectrometry. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. US FDA, Instrumentat & Biophys Branch, Washington, DC 20204 USA. US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. RP Plakas, SM (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Island, AL 36528 USA. NR 19 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 MAY-JUN PY 1999 VL 82 IS 3 BP 614 EP 619 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 201NJ UT WOS:000080601400007 PM 10367379 ER PT J AU Placencia, AM Peeler, JT AF Placencia, AM Peeler, JT TI Microbial ranking of porous packaging materials (exposure chamber method), ASTM method: Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A collaborative study involving 11 laboratories was conducted to measure the microbial barrier effectiveness of porous medical packaging. Two randomly cut samples from each of 6 commercially available porous materials and one positive and one negative control were tested by one operator in each of 11 laboratories. Microbial barrier effectiveness was measured in terms of logarithm reduction value (LRV), which reflects the log(10) microbial penetration of the material being tested. The logarithm of the final concentration is subtracted from that of the initial concentration to obtain the LRV. Thus the higher the LRV, the better the barrier. Repeatability standard deviations ranged from 6.42 to 16.40; reproducibility standard deviations ranged from 15.50 to 22.70. Materials B(53), C(50), D(CT), and E(45MF) differ significantly from the positive control. The microbial ranking of porous packaging materials (exposure chamber method), ASTM method, has been adopted First Action by AOAC INTERNATIONAL. C1 US FDA, Minneapolis, MN 55401 USA. RP Placencia, AM (reprint author), US FDA, 240 Hennepin Ave, Minneapolis, MN 55401 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1999 VL 82 IS 3 BP 648 EP 655 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 201NJ UT WOS:000080601400011 PM 10367383 ER PT J AU Chase, GW Eitenmiller, RR Long, AR AF Chase, GW Eitenmiller, RR Long, AR TI Analysis of beta-carotene in medical food by liquid chromatography with matrix solid-phase dispersion SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ALPHA-TOCOPHERYL ACETATE; RETINYL PALMITATE; MILK AB A liquid chromatographic method is described for analysis of beta-carotene in medical food. The nutrient is extracted from medical food without saponification by matrix solid-phase dispersion and quantitated by isocratic normal-phase chromatography with a Si 60 column and a mobile phase of hexane containing 0.125% (v/v) isopropyl alcohol. The limit of quantitation is 0.02 mu g/mL at 436 nm, Standard response was linear over the concentration range of 0.02-1.0 mu g/mL (r(2) = 0.99998). Recoveries were determined on a zero control reference material containing added p-carotene at various levels. Recoveries averaged 91.2% (n = 25) with coefficients of variation from 0.50 to 3.10%. The method provides a rapid, specific, sensitive, and easily controlled assay for analysis of beta-carotene in fortified medical food. In addition, retinyl palmitate can be assayed simultaneously with an in-line fluorescence detector. 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 11 TC 4 Z9 4 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1999 VL 82 IS 3 BP 663 EP 665 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 201NJ UT WOS:000080601400013 PM 10367385 ER PT J AU Casterline, JL Oles, CJ Ku, YO AF Casterline, JL Oles, CJ Ku, YO TI Measurement of sugars and starches in foods by a modification of the AOAC total dietary fiber method SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A separation scheme for the determination of sugars and starch in processed food was developed. It is based on AOAC Method 985.29 for total dietary fiber with these modifications: carbohydrate starches are separated into soluble and insoluble fractions before they are hydrolyzed; acetonitrile is used instead of ethanol to separate sugars from enzyme-resistant carbohydrates, proteins, and other macromolecules; and a solid-phase extraction filter is included to remove substances that interfere with high-performance liquid chromatography (HPLC). Recovery studies indicate a >97% sugar recovery. Twenty foods were analyzed. After enzymatic hydrolysis, fructose, glucose, sucrose, maltose, and lactose were extracted and determined by HPLC using a refractive index detector. Starch content was calculated from the increase in the amount of glucose. The results were compared with values listed on the "Nutrition Facts" panel for that food. The analyzed amounts of sugars and starches were 73-96% of declared values. C1 US FDA, Ctr Drug Evaluat & Res, Div Sci & Appl Technol, Off Food Labeling, Washington, DC 20204 USA. RP Ku, YO (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Sci & Appl Technol, Off Food Labeling, 200 C St SW, Washington, DC 20204 USA. NR 6 TC 18 Z9 20 U1 1 U2 13 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 1999 VL 82 IS 3 BP 759 EP 765 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 201NJ UT WOS:000080601400025 PM 10367393 ER PT J AU Betz, JM AF Betz, JM TI Plant toxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LOCOWEED OXYTROPIS-SERICEA; SOUTHERN BRAZIL; PYRROLIZIDINE ALKALOIDS; CARDIAC GLYCOSIDE; CALCIUM-OXALATE; CATTLE; SHEEP; INTOXICATION; OLEANDER; TOXICITY C1 US FDA, Div Nat Prod, Washington, DC 20204 USA. RP Betz, JM (reprint author), US FDA, Div Nat Prod, Washington, DC 20204 USA. NR 61 TC 2 Z9 2 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1999 VL 82 IS 3 BP 781 EP 784 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 201NJ UT WOS:000080601400029 PM 10367396 ER PT J AU Shelly, LL Fuchs, C Miele, L AF Shelly, LL Fuchs, C Miele, L TI Notch-1 inhibits apoptosis in murine erythroleukemia cells and is necessary for differentiation induced by hybrid polar compounds SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE differentiation-inducing drugs; apoptosis; cancer; notch-1 ID HEXAMETHYLENE BISACETAMIDE; INTRACELLULAR DOMAIN; NEOPLASTIC LESIONS; TRANSFORMED-CELLS; DROSOPHILA NOTCH; HUMAN HOMOLOG; GENE; EXPRESSION; LEUKEMIA; PROTEINS AB Strikingly increased expression of notch-1 has been demonstrated in several human malignancies and pre-neoplastic lesions. However, the functional consequences of notch-1 overexpression in transformed cells remain unclear. We investigated whether endogenously expressed notch-1 controls cell Fate determination in mouse erythroleukemia (MEL) cells during pharmacologically induced differentiation. We found that notch-1 expression is modulated during MEL cell differentiation. Premature downregulatian of notch-1 during differentiation, by antisense S-oligonucleotides or by enforced expression of antisense notch-1 mRNA, causes MEL cells to abort the differentiation program and undergo apoptosis. Downregulation of notch-1 expression in the absence of differentiation inducer increases the likelihood of spontaneous apoptosis. We conclude that in MEL cells, endogenous notch-1 expression controls the apoptotic threshold during differentiation and growth. In these cells, notch-1 allows differentiation by preventing apoptosis of pre-committed cells. This novel function of notch-1 may play a role in regulating apoptosis susceptibility in notch-1 expressing tumor cells. (C) 1999 Wiley-Liss, Inc. C1 Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. NIH, Cell Biol Lab, Ctr Biol Evaluat & Res, Food & Drug Adm, Bethesda, MD 20892 USA. RP Miele, L (reprint author), Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Room 204,2160 S 1st Ave, Maywood, IL 60153 USA. EM lmiele@luc.edu NR 40 TC 92 Z9 95 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAY 1 PY 1999 VL 73 IS 2 BP 164 EP 175 DI 10.1002/(SICI)1097-4644(19990501)73:2<164::AID-JCB3>3.0.CO;2-0 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 183JV UT WOS:000079551200003 PM 10227380 ER PT J AU Romanova, LY Alexandrov, IA Blagosklonny, MV Nordan, RP Garfield, S Acs, P Nguyen, P Trepel, J Blumberg, PM Mushinski, JF AF Romanova, LY Alexandrov, IA Blagosklonny, MV Nordan, RP Garfield, S Acs, P Nguyen, P Trepel, J Blumberg, PM Mushinski, JF TI Regulation of actin cytoskeleton in lymphocytes: PKC-delta disrupts IL-3-induced membrane ruffles downstream of Rac1 SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PROTEIN-KINASE-C; FOCAL ADHESION KINASE; CELL-CYCLE PROGRESSION; TYROSINE PHOSPHORYLATION; PHORBOL ESTER; GROWTH-FACTOR; LEUKEMIA-CELLS; CDC42 GTPASES; MAP KINASE; CROSS-TALK AB In the murine pre-B lymphoid cell line Baf3, the presence of IL-3 is required for the formation of membrane ruffles that intensely stain for actin and are responsible for the elongated cell phenotype. Withdrawal of IL-3 dissolves ruffled protrusions and converts the cell phenotype to round. Flow cytometric analysis of the cell shape showed that an inactive analog of Rad but not inactive RhoA or inactive cdc42 rounds the cells in the presence of IL-3. Constitutively activated Rad restores the elongated cell phenotype to IL-3-starved cells. We conclude that the activity of Rad is necessary and sufficient for the IL-3-induced assembly of membrane ruffles. Similar to the IL-3 withdrawal, phorbol 12-myristate 13-acetate (PMA) dissolves actin-formed membrane ruffles and rounds the cells in the presence of IL-3. Flow cytometric analysis of the cell shape demonstrated that in the presence of IL-3 the PMA-induced cell rounding cannot be abolished by constitutively active Rad but can be imitated by inactive Rad. These data indicate that PMA disrupts the IL-3 pathway downstream of Rad. Cells rounded by PMA return to the elongated phenotype concomitantly with PKC depletion. PMA-induced cell rounding can be reversed by the PKC-specific inhibitor GF109203X. Experiments with overexpression in Baf3 of individual PKC isoforms and a dominant negative PKC-delta indicate that activation of PKC-delta but not other PKC isoforms is responsible for disruption of membrane ruffles. Published 1999 Wiley-Liss, Inc.(dagger) C1 NIH, NCI, Genet Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Romanova, LY (reprint author), NIH, NCI, Genet Lab, Bldg 37,Rm 2B23,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM romanovl@dc37a.nci.nih.gov NR 45 TC 16 Z9 20 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1999 VL 179 IS 2 BP 157 EP 169 DI 10.1002/(SICI)1097-4652(199905)179:2<157::AID-JCP6>3.0.CO;2-4 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 183KU UT WOS:000079553400006 PM 10199555 ER PT J AU Jerian, S Keegan, P AF Jerian, S Keegan, P TI Cardiotoxicity associated with paclitaxel trastuzumab combination therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Jerian, S (reprint author), US FDA, Rockville, MD 20857 USA. NR 2 TC 9 Z9 9 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1999 VL 17 IS 5 BP 1647 EP 1648 PG 2 WC Oncology SC Oncology GA 195TH UT WOS:000080267900050 PM 10334560 ER PT J AU Waynant, RW Chakrabarti, K Kaczmarek, RA Dagenais, I AF Waynant, RW Chakrabarti, K Kaczmarek, RA Dagenais, I TI Testing optimum viewing conditions for mammographic image displays SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT 16th Symposium for Computer Applications in Radiology on PACS - Performance Improvement in Radiology (SCAR 99), at the Annual Meeting of SCAR CY MAY 06-09, 1999 CL HOUSTON, TEXAS SP Soc Comp Applicat Radiol ID LUMINANCE AB The viewbox luminance and viewing room light level are important parameters in a medical film display, but these parameters have not had much attention. Spatial variations and too much room illumination can mask real signal or create the false perception of a signal. This presentation looks at how scotopic light sources and dark-adapted radiologists may identify more real diseases. Copyright (C) 1999 by W.B. Saunders Company. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. Off Hlth & Ind Programs, Rockville, MD USA. RP Waynant, RW (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, HFZ-134,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 4 TC 4 Z9 4 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 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD MAY PY 1999 VL 12 IS 2 SU 1 BP 209 EP 210 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 197GB UT WOS:000080356100066 PM 10342217 ER PT J AU Weagant, SD Jagow, JA Jinneman, KC Omiecinski, CJ Kaysner, CA Hill, WE AF Weagant, SD Jagow, JA Jinneman, KC Omiecinski, CJ Kaysner, CA Hill, WE TI Development of digoxigenin-labeled PCR amplicon probes for use in the detection and identification of enteropathogenic Yersinia and Shiga toxin-producing Escherichia coli from foods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POLYMERASE CHAIN-REACTION; DNA COLONY HYBRIDIZATION; ENTEROCOLITICA; AMPLIFICATION AB By including digoxigenin-11-dUTP in a polymerase chain reaction (PCR), amplification products were produced that contained nonisotopic markers for use as DNA hybridization probes. Because these labeled amplicons encode pathogenic traits for specific foodborne bacteria, they can be used to detect the presence of potentially virulent organisms that may be present in foods. This technology allows the synthesis of a variety of shelf-stable probe reagents for detecting a number of foodborne microbes of public health concern. We used this technology to detect four genes in two potential pathogens: virF and yadA in enteropathogenic Yersinia and stx(1) and stx(2) in Shiga-like toxin-producing Escherichia coli. Results of DNA hybridizations of dot blots of 68 Yersinia strains and 24 of 25 E. coli strains were consistent with results of equivalent PCR analyses. DNA colony hybridization with nonisotopic virF probes of colonies arising on spread plates from artificially contaminated food homogenates was able to detect potentially pathogenic Y. enterocolitica. When compared with oligonucleotide probes, amplicon probes are much less sensitive to changes in hybridization and wash temperatures, allowing greater reproducibility. Labeled probe preparations were reused more than five times and have been stored at -20 degrees C for more than 8 months. This method conveniently generates probes that are safe, stable, inexpensive, reusable, and reliable. C1 US FDA, Seattle Dist Lab, Bothell, WA 98041 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98041 USA. Univ Washington, Dept Environm Hlth, Seattle, WA 98105 USA. RP Weagant, SD (reprint author), US FDA, Seattle Dist Lab, 22201 23rd Dr SE,POB 3012, Bothell, WA 98041 USA. FU NIEHS NIH HHS [P42 ES004696] NR 19 TC 14 Z9 14 U1 0 U2 1 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 1999 VL 62 IS 5 BP 438 EP 443 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 194PV UT WOS:000080203500002 PM 10340661 ER PT J AU Podhorniak, LV Leake, S Schenck, FJ AF Podhorniak, LV Leake, S Schenck, FJ TI Stability of tetracycline antibiotics in raw milk under laboratory storage conditions SO JOURNAL OF FOOD PROTECTION LA English DT Article AB Raw milk samples collected from bulk milk tankers may be screened for the presence of tetracycline antibiotics using rapid screening tests. If tetracycline residues are detected, the milk may be shipped to a laboratory for high-pressure liquid chromatography (HPLC) analysis. Because the milk may be shipped on ice blocks, it is important to know whether tetracycline residues are stable at that temperature and for how long. Control raw milk samples fortified with 50 ppb each chlortetracycline, demeclocycline, methacycline hydrochloride, minocycline, oxytetracycline, and tetracycline were incubated at 4 degrees C or 25 degrees C, then analyzed using a metal chelate affinity chromatography extraction and HPLC. No loss of tetracycline was observed after 48 h of storage at 4 degrees C or 24 h at 25 degrees C. Losses ranging from 4 to 13% and 0 to 18% were noted after 72 h at 4 degrees C and 48 h at 25 degrees C, respectively. C1 US FDA, Baltimore Dist Lab, Baltimore, MD 21201 USA. RP Schenck, FJ (reprint author), US FDA, Baltimore Dist Lab, 900 Madison Ave, Baltimore, MD 21201 USA. NR 2 TC 16 Z9 16 U1 0 U2 9 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 1999 VL 62 IS 5 BP 547 EP 548 PG 2 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 194PV UT WOS:000080203500021 PM 10340680 ER PT J AU Gans, HA Maldonado, Y Yasukawa, LL Beeler, J Audet, S Rinki, MM DeHovitz, R Arvin, AM AF Gans, HA Maldonado, Y Yasukawa, LL Beeler, J Audet, S Rinki, MM DeHovitz, R Arvin, AM TI IL-12, IFN-gamma, and T cell proliferation to measles in immunized infants SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIMPLEX VIRUS-INFECTION; INTERFERON-GAMMA; EARLY-LIFE; NEUTRALIZATION TEST; CYTOKINE PRODUCTION; MEDIATED-IMMUNITY; VACCINE ANTIGENS; UNITED-STATES; HELPER TYPE-1; DNA VACCINES AB Measles infection in infants is associated with severe complications, and secondary infections are attributed to generalized immunosuppression, Measles binding to its monocyte receptor down-regulates IL-12 which is expected to diminish Th1-like cytokine responses, including IFN-gamma, Whether young infants can be immunized effectively against measles is an important public health issue. We evaluated Ag-specific IL-12, IFN-gamma, and T cell responses of infants at 6 (n = 60), 9 (n = 36), or 12 mo (n = 56) of age and 29 vaccinated adults, IL-12 and IFN-gamma release by PBMC stimulated with measles Ag increased significantly after measles immunization in infants. IL-12 and IFN-gamma concentrations were equivalent in younger and older infants, but IL-12 concentrations were significantly lower in infants than in adults (p = 0.04). IL-12 production by monocytes was down-regulated by measles; the addition of recombinant human IL-12 enhanced IFN-gamma production by PBMC stimulated with measles Ag, but infant T cells released significantly less IFN-gamma than adult T cells under this condition, Of particular interest, the presence of passive Abs to measles had no effect on the specific T cell proliferation or IFN-gamma production after measles stimulation. Cellular immunity to measles infection and vaccination may be limited in infants compared with adults as a result of less effective IFN-gamma and IL-12 production in response to measles Ags. These effects were not exaggerated in younger infants compared with effects in infants who were immunized at 12 mo. In summary, infant T cells were primed with measles Ag despite the presence of passive Abs, but their adaptive immune responses were limited compared with those of adults. C1 Stanford Univ, Med Ctr, Sch Med, Dept Pediat,Infect Dis Div, Stanford, CA 94305 USA. US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Viral Prod,Dept Hlth & Human Serv, Rockville, MD 20867 USA. Palo Alto Med Fdn, Dept Pediat, Palo Alto, CA 94301 USA. RP Gans, HA (reprint author), Stanford Univ, Med Ctr, Sch Med, Dept Pediat,Infect Dis Div, Stanford, CA 94305 USA. FU NIAID NIH HHS [AI37127] NR 68 TC 107 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 MAY 1 PY 1999 VL 162 IS 9 BP 5569 EP 5575 PG 7 WC Immunology SC Immunology GA 189EZ UT WOS:000079892600073 PM 10228039 ER PT J AU Suffredini, AF Hochstein, HD McMahon, FG AF Suffredini, AF Hochstein, HD McMahon, FG TI Dose-related inflammatory effects of intravenous endotoxin in humans: Evaluation of a new clinical lot of Escherichia coli O : 113 endotoxin SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TUMOR-NECROSIS-FACTOR AB The administration of reference endotoxin (Escherichia coli O:113, Lot EC-5) to humans has been an important means to study inflammation in vivo; however, the supply of Lot EC-5 is depleted. A new lot of reference endotoxin (Clinical Center reference endotoxin [CCRE]), derived from the original bulk material extracted from E. coli O:113, was processed. The effects of 0-, 1-, 2-, and 4-ng/kg doses of intravenous CCRE and EC-5 were studied in 20 male subjects. CCRE resulted in dose-related increases in symptoms, temperature (P = .016), total leukocyte count (P = .014), tumor necrosis factor-alpha (P = .004), interleukin (IL)-1 receptor antagonist (P = .004),IL-6 (P = .005), IL-8 (P = .011), cortisol (P < .05), and C-reactive protein (P = .04), These responses were attenuated (all P < .012) in subjects given Lot EC-5 (4 ng/kg) in comparison with those in subjects given CCRE, showing that, over several years, EC-5 had lost potency. Thus, in healthy subjects, the magnitude of exposure to CCRE results in a graded dose response of major components of innate immunity. C1 NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. US FDA, Div Prod Qual Control, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Clin Res Ctr, New Orleans, LA USA. RP Suffredini, AF (reprint author), NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 7D-43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 14 TC 112 Z9 116 U1 2 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1999 VL 179 IS 5 BP 1278 EP 1282 DI 10.1086/314717 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 189TQ UT WOS:000079922600034 PM 10191237 ER PT J AU Lytle, CD Baker, KH AF Lytle, CD Baker, KH TI Ability of a viral penetration test (ASTM F1671-95) to detect small holes SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE viral penetration; barrier test; protective clothing; biological hazard ID BARRIERS AB A modified version of ASTM Test Method F1671-95, Test Method for Resistance of Materials Used in Protective Clothing to Penetration by Blood-Borne Pathogens Using Phi-X174 Bacteriophage Penetration as a Test System, was characterized using as test material pieces of condom latex with laser-drilled holes of known size. The modified test included the initial 5-min, no-pressure period together with the I-min, 2-psi period, but eliminated the final 54-min, no-pressure period. Virus penetration was detected for all holes with diameters above 1.0 mu m. The quantitative results were in good agreement with calculated fluid flow through a cylinder (Poiseuille equation) for holes above 2 mu m. A brief argument is presented suggesting that the final 54-min period at no pressure be eliminated from the test protocol. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Lytle, CD (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 8 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0090-3973 J9 J TEST EVAL JI J. Test. Eval. PD MAY PY 1999 VL 27 IS 3 BP 231 EP 233 PG 3 WC Materials Science, Characterization & Testing SC Materials Science GA 287YP UT WOS:000085535300009 ER PT J AU Jensen, PS Bhatara, VS Vitiello, B Hoagwood, K Feil, M Burke, LB AF Jensen, PS Bhatara, VS Vitiello, B Hoagwood, K Feil, M Burke, LB TI Psychoactive medication prescribing practices for US children: Gaps between research and clinical practice SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE pharmacoepidemiology; psychopharmacology; medication safety and efficacy; childhood mental disorders; prescribing practices ID CARBAMAZEPINE-INDUCED MANIA; PSYCHOPHARMACOLOGY; PSYCHIATRISTS; PRESCRIPTION; ADHD AB Objective: To determine national pediatric prescribing practices for psychotropic agents and to examine these practices in view of the available evidence concerning their safety and efficacy in this age group. Method: Prescribing data from 2 national databases based on surveys of office-based medical practices were determined and reviewed vis-g-vis available safety and efficacy evidence. Results: Data indicate that levels of psychotropic prescribing in children and adolescents are greatest for stimulants, resulting in nearly 2 million office visits and 6 million drug "mentions" in 1995. Selective serotonin reuptake inhibitors were the second most prescribed psychotropic agents, while anticonvulsant mood stabilizers (prescribed for a psychiatric reason), tricyclic antidepressants, central adrenergic agonists, antipsychotics, benzodiazepines, and lithium were also prescribed for a substantial number of office visits. Comparison of prescribing frequencies with available safety and efficacy data indicates significant gaps in knowledge for commonly used agents. Conclusions: Most psychotropic agents require further sustained study to ensure appropriate health care expenditures and vouchsafe children's safety. Recommendations for researchers, parents, federal agencies, and industry are offered as a means to accelerate the pace of research progress. C1 NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. Univ S Dakota, Sch Med, Sioux Falls, SD USA. NIMH, Child Serv Program, Serv Res Branch, Bethesda, MD 20892 USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. RP Jensen, PS (reprint author), NIMH, Child & Adolescent Treatment & Prevent Intervent, 6001 Execut Blvd,Room 8223,MSC 9669, Bethesda, MD 20892 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 46 TC 166 Z9 168 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1999 VL 38 IS 5 BP 557 EP 565 DI 10.1097/00004583-199905000-00017 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 190HE UT WOS:000079956100017 PM 10230187 ER PT J AU Pareo-Tubbeh, SL Romero, LJ Baumgartner, RN Garry, PJ Lindeman, RD Koehler, KM AF Pareo-Tubbeh, SL Romero, LJ Baumgartner, RN Garry, PJ Lindeman, RD Koehler, KM TI Comparison of energy and nutrient sources of elderly Hispanics and non-Hispanic whites in New Mexico SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID RURAL BIETHNIC POPULATION; UNITED-STATES POPULATION; NHANES-II SURVEY; QUANTITATIVE DATA; AMERICAN DIET; HISTORY QUESTIONNAIRE; ANGLO-AMERICANS; PUERTO-RICANS; CONSUMPTION; FOLATE AB Objective Identification and comparison of frequently consumed foods and important food sources of energy, protein, total fat, vitamin A, vitamin C, vitamin E, vitamin B-6, folate, and calcium of elderly Hispanics and non-Hispanic whites. Design Dietary intake data were collected using a modified Health Habits and History Questionnaire (a food frequency questionnaire) for 735 subjects who participated in the New Mexico Elder Health Survey. Subjects The sample consisted of 330 Hispanics (176 men and 154 women)and 405 non-Hispanic whites (214 men and 191 women) between the ages of 65 and 96 years. Subjects mere those with food frequency data among 883 participants who completed the clinical visit of the New Mexico Elder Health Survey. Results Results show the top-ranked frequently consumed foods by gender and ethnicity and top-ranked food sources of energy and 8 nutrients. Regional foods were important sources of nutrients in the diets of both Hispanics and non-Hispanic-whites, however, more so for the Hispanics. Chile sauces were notable sources of vitamin A, vitamin C, and folate among both groups. Both ethnic groups demonstrated selection of low-fat and skim milk and moderation in consumption of red meat. Applications These data will be useful for designing nutrition education programs, for studying the relationship between diet and disease among elderly Hispanics and non-Hispanic whites, and for designing assessment instruments for the elderly and other ethnic populations. C1 Univ New Mexico, Sch Med, Clin Nutr Program, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Dept Family Community & Emergency Med, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Dept Internal Med, Albuquerque, NM 87131 USA. US FDA, CFSAN, Washington, DC 20204 USA. RP Koehler, KM (reprint author), US FDA, CFSAN, HFS-728,200 C St SW, Washington, DC 20204 USA. FU NCRR NIH HHS [RROO997]; NIA NIH HHS [AG10491, AG02049] NR 54 TC 17 Z9 18 U1 2 U2 4 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAY PY 1999 VL 99 IS 5 BP 572 EP 582 DI 10.1016/S0002-8223(99)00141-8 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 194EZ UT WOS:000080180300016 PM 10333779 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 infects dendritic cells and suppresses human immunodeficiency virus type 1 replication in coinfected cultures SO JOURNAL OF VIROLOGY LA English DT Article ID CD4+ T-CELLS; HIV-1 INFECTION; MASSIVE LYMPHADENOPATHY; PRODUCTIVE INFECTION; SINUS HISTIOCYTOSIS; LANGERHANS CELLS; HHV-6 INFECTION; LYMPHOCYTES-T; BLOOD; AIDS AB Human herpesvirus 6 (HHV-6) has been implicated as a cofactor in the progressive loss of CD4(+) T cells observed in AIDS patients. Because dendritic cells (DC) play an important role in the immunopathogenesis of human immunodeficiency virus (HIV) disease, we studied the infection of DC by HHV-6 and coinfection of DC by HHV-6 and HIV. Purified immature DC (derived from adherent peripheral blood mononuclear cells in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4) could be infected with HHV-6, as determined by PCR analyses, intracellular monoclonal antibody staining, and presence of virus in culture supernatants. However, HHV-6-infected DC demonstrated neither cytopathic changes nor functional defects. Interestingly, HHV-6 markedly suppressed HIV replication and syncytium formation in coinfected DC cultures. This HHV-6-mediated anti-HIV effect was DC specific, occurred when HHV-6 was added either before or after HIV, and was not due to decreased surface expression or function of CD4, CXCR4, or CCR5. Conversely, HIV had no demonstrable effect on HHV-6 replication, These findings suggest that HHV-6 may protect DC from HIV-induced cytopathicity in AIDS patients. We also demonstrate that interactions between HIV and herpesviruses are complex and that the observable outcome of dual infection is dependent on the target cell type. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Blauvelt, A (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. EM Andrew_Blauvelt@nih.gov NR 68 TC 38 Z9 40 U1 0 U2 1 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 1999 VL 73 IS 5 BP 4019 EP 4028 PG 10 WC Virology SC Virology GA 185ZG UT WOS:000079701100060 PM 10196298 ER PT J AU Muller, L Kikuchi, Y Probst, G Schechtman, L Shimada, H Sofuni, T Tweats, D AF Muller, L Kikuchi, Y Probst, G Schechtman, L Shimada, H Sofuni, T Tweats, D TI ICH-harmonised guidances on genotoxicity testing of pharmaceuticals: evolution, reasoning and impact SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Review DE genotoxicity; mutagenicity; test guidance; harmonisation; mouse lymphoma assay; chromosomal damage ID MOUSE LYMPHOMA-CELLS; MICRONUCLEUS ASSAY; IN-VITRO; CHEMICAL-STRUCTURE; MUTATION ASSAYS; BONE-MARROW; CARCINOGENS; MUTAGENS; VIVO; RECOMMENDATIONS AB The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has convened an expert working group which consisted of the authors of this paper and their respective committees, consulting soups and task forces. Two ICH guidances regarding genotoxicity testing have been issued: S2A, 'Guidance on Specific Aspects of Regulatory Genotoxicity Tests' and S2B, 'Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals.' Together, these guidance documents now form the regulatory backbone for genotoxicity resting and assessment of pharmaceuticals in the European Union, Japan, and the USA. These guidances do not constitute a revolutionary new approach to genotoxicity testing and assessment, instead they are an evolution from preexisting regional guidelines, guidances and technical approaches. Both guidances describe a number of specific criteria as well as a general test philosophy in genotoxicity testing, Although these guidances were previously released within the participating regions in their respective regulatory communiques, to ensure their wider distribution and better understanding, the texts of the guidances are reproduced here in their entirety (see Appendix A) and the background for the recommendations are described. The establishment of a standard battery for genotoxicity testing of pharmaceuticals was one of the most important issues of the harmonisation effort. This battery currently consists of: (i) a test for gene mutation in bacteria, (ii) an in vitro test with cytogenetic evaluation of chromosomal damage with mammalian cells or an in vitro mouse lymphoma ik assay, (iii) an in vivo test for chromosomal damage using rodent hematopoietic cells. A major change in testing philosophy is the acceptance of the interchangeability of testing for chromosomal aberrations in mammalian cells and the mouse lymphoma rk assay. This agreement was reached on the basis of the extensive review of databases and newly generated experimental data which are in part described in this publication. The authors are fully aware of the fact that some of the recommendations given in these ICH guidances are transient in nature and that the dynamic qualities and ongoing evolution of genetic toxicology makes necessary a continuous maintenance process that would serve to update the guidance as necessary. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Fed Inst Drugs & Med Devices, D-13353 Berlin, Germany. Rabiton Inst, Toyonaka, Osaka 5650082, Japan. Eli Lilly & Co, Greenfield, IN 46140 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Daiichi Pharmaceut Co Ltd, Edogawa Ku, Tokyo 134, Japan. Natl Inst Hlth Sci, Setagaya Ku, Tokyo 158, Japan. Glaxo Wellcome Inc, Ware SG12 0DP, Herts, England. RP Muller, L (reprint author), Fed Inst Drugs & Med Devices, Seestr 10, D-13353 Berlin, Germany. NR 32 TC 103 Z9 112 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD MAY PY 1999 VL 436 IS 3 BP 195 EP 225 DI 10.1016/S1383-5742(99)00004-6 PG 31 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 204LV UT WOS:000080766500001 PM 10354523 ER PT J AU Paule, MG Chelonis, JJ Buffalo, EA Blake, DJ Casey, PH AF Paule, MG Chelonis, JJ Buffalo, EA Blake, DJ Casey, PH TI Operant test battery performance in children: Correlation with IQ SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE intelligence quotients; operant behavior; learning; motivation; color and position discrimination; short-term memory; memory; operant test battery; timing behavior ID BEHAVIORAL-TEST BATTERY; RHESUS-MONKEYS; RESPONSE SEQUENCES; NONHUMAN-PRIMATES; MARIJUANA SMOKE; INFANT MONKEYS; ALZHEIMER-TYPE; MEMORY; ACQUISITION; DIAZEPAM AB The relationship between intelligence and money-(nickel-)reinforced operant behaviors were compared in 115 six year old children. The Operant Test Battery (OTB) consists of tasks thought to engender responses dependent upon specific brain functions that include motivation, color and position discrimination, learning, short-term memory, and time estimation. OTB endpoints were compared with Full Scale, Verbal and Performance IQ scores. Highly significant correlations were noted between several OTB measures (e.g., color and position discrimination accuracy) and IQ scores, but not in others (e.g., motivation task response rate). The results demonstrate the relevance of these measures as metrics of important brain functions. Additionally, since laboratory animals can readily perform these same tasks, these kinds of behaviors in laboratory animals should be useful in studying the effects of neuroactive/neurotoxic compounds on aspects of cognitive function in animals and in predicting adverse effects of such agents on related brain functions in humans. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Serv, Dept Pediat, Little Rock, AR USA. Univ Arkansas Med Serv, Dept Pharmacol & Toxicol, Little Rock, AR USA. Univ Calif San Diego, Program Neurosci, La Jolla, CA 92093 USA. RP Paule, MG (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 64 TC 63 Z9 64 U1 4 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 MAY-JUN PY 1999 VL 21 IS 3 BP 223 EP 230 DI 10.1016/S0892-0362(98)00045-2 PG 8 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 202XP UT WOS:000080677700002 PM 10386825 ER PT J AU Denny, VF Kopis, EM Marsik, FJ AF Denny, VF Kopis, EM Marsik, FJ TI Elements for a successful disinfection program in the pharmaceutical environment SO PDA JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY LA English DT Article C1 Peak Peak Pharmaceut Associates, Boulder, CO USA. Steris Corp, St Louis, MO USA. US FDA, OGD, Div Antiinfect Drug Prod, Rockville, MD 20857 USA. RP Denny, VF (reprint author), 2706 Winding Trail Pl, Boulder, CO 80304 USA. NR 17 TC 1 Z9 1 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 MAY-JUN PY 1999 VL 53 IS 3 BP 115 EP 124 PG 10 WC Engineering, Biomedical; Pharmacology & Pharmacy SC Engineering; Pharmacology & Pharmacy GA 221MR UT WOS:000081731300004 PM 10754700 ER PT J AU Swann, JP AF Swann, JP TI The 1941 sulfathiazole disaster and the birth of good manufacturing practices SO PDA JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY LA English DT Article AB The beginning of modem standards for good manufacturing practices can be traced to an incident that began in December 1940, when the Winthrop Chemical Company of New York put on the market sulfathiazole tablets contaminated with phenobarbital. Hundreds of deaths and injuries resulted FDA's investigation into Winthrop's sulfathiazole production and the agency's efforts to retrieve the Winthrop drug remaining on the market revealed numerous control deficiencies in the plant and serious irregularities in the firm's attempt To recall the tainted tablets. The incident prompted FDA to require detailed controls in sulfathiazole production at Winthrop and throughout the industry, an approach that became the basis for production control standards for all pharmaceuticals. C1 US FDA, Hist Off, Rockville, MD 20857 USA. RP Swann, JP (reprint author), US FDA, Hist Off, Room 13-51,5600 Fishers Lane, Rockville, MD 20857 USA. NR 105 TC 3 Z9 3 U1 1 U2 2 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 MAY-JUN PY 1999 VL 53 IS 3 BP 148 EP 153 PG 6 WC Engineering, Biomedical; Pharmacology & Pharmacy SC Engineering; Pharmacology & Pharmacy GA 221MR UT WOS:000081731300009 PM 10754705 ER PT J AU Itzhak, Y Martin, JL Black, MD Ali, SF AF Itzhak, Y Martin, JL Black, MD Ali, SF TI Effect of the dopaminergic neurotoxin MPTP on cocaine-induced locomotor sensitization SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE cocaine; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); sensitization; locomotoractivity; dopamine transporter; nucleus accumbens; striatum ID NITRIC-OXIDE SYNTHASE; INDUCED BEHAVIORAL SENSITIZATION; NUCLEUS-ACCUMBENS DOPAMINE; MESOLIMBIC DOPAMINE; 6-HYDROXYDOPAMINE LESIONS; EXPERIMENTAL PARKINSONISM; BINDING-SITES; RAT STRIATUM; MICE; METHAMPHETAMINE AB The blockade of dopamine (DA) uptake via the dopamine transporter (DAT) in the nucleus accumbens (NAC) and striatum by cocaine has a major role in the reinforcing and psychomotor stimulating effects of the drug. Here we investigated the effect of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the expression and induction of sensitization to the locomotor stimulating effect of cocaine. MPTP (20 mg/kg x 4) caused 72 and 76% depletion of DAT sites in the NAC and striatum, respectively, in C57BL/6 mice. The magnitude of this depletion 3 and 19 days after MPTP administration was the same. To determine the effect of MPTP on the expression of the sensitized response to cocaine, cocaine-experienced mice (20 mg/kg for 5 days) received MPTP 3 days before a challenge cocaine injection was given on day 15. Cocaine/MPTP mice were significantly more sensitive to the challenge cocaine injection than the cocaine/saline-pretreated mice. To determine whether depletion of NAC and striatal DAT affects the induction of sensitization to cocaine, mice were pretreated with MPTP 3 days before the administration of cocaine (20 mg/kg for 5 days). The magnitude of the sensitized response of MPTP/cocaine-pretreated mice to cocaine challenge was the same as the sensitized response of mice treated with saline/cocaine, while the number of DAT binding sites in the MPTP/cocaine group was significantly lower than the saline/cocaine group. The present study indicates that MPTP exacerbates the expression of locomotor sensitization to cocaine, but it had no effect on the induction of sensitization. We conclude that the expression, but not the induction, of locomotor sensitization to cocaine may be dependent on the level of DAT binding sites. (C) 1999 Elsevier Science Inc. 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, Miami, FL 33101 USA. FU NIDA NIH HHS [R01DA08584] NR 42 TC 14 Z9 14 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 1999 VL 63 IS 1 BP 101 EP 107 DI 10.1016/S0091-3057(98)00246-9 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 193ZX UT WOS:000080168600013 PM 10340529 ER PT J AU Ilev, IK Waynant, RW AF Ilev, IK Waynant, RW TI All-fiber-optic sensor for liquid level measurement SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article AB An experimental realization of a simple all-fiber-optic sensor for liquid level measurement is demonstrated. It is an intensity-modulated on-off switching sensor whose operating principle is based on the frustrated-total-internal-reflection effect caused by the refractive-index change of the surrounding medium. The basic optical element in the scheme is a sensing single fiber which serves simultaneously to transmit both the forward laser emission to the investigated medium and the useful signal backreflected from the fiber tip that is the sensing element. In order to achieve a maximum sensor sensitivity, we use a specially shaped fiber tip in two profile variants: angled and retroreflecting. The experimental investigations of the sensor properties and the results obtained at the pure-water level measurement confirm the sensor potential in liquid level determination with a high accuracy, exceeding 10 mu m. [S0034-6748(99)01305-2]. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Tech Univ Sofia, Inst Appl Phys, BG-1156 Sofia, Bulgaria. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-134, Rockville, MD 20857 USA. NR 10 TC 47 Z9 47 U1 0 U2 12 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD MAY PY 1999 VL 70 IS 5 BP 2551 EP 2554 DI 10.1063/1.1149792 PG 4 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 193AU UT WOS:000080113600056 ER PT J AU Schwetz, B AF Schwetz, B TI Commentary - Rodent carcinogenicity studies on magnetic fields SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Schwetz, B (reprint author), US FDA, HF-32,Room 17-35,Parklawn Bldg,5600 Fishers Lane, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 1999 VL 27 IS 3 BP 286 EP 286 DI 10.1177/019262339902700303 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 199KB UT WOS:000080479100003 PM 10356704 ER PT J AU Goering, PL Aposhian, HV Mass, MJ Cebrian, M Beck, BD Waalkes, MP AF Goering, PL Aposhian, HV Mass, MJ Cebrian, M Beck, BD Waalkes, MP TI The enigma of arsenic carcinogenesis: Role of metabolism SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Society-of-Toxicology CY MAR 01-05, 1998 CL SEATTLE, WASHINGTON SP Soc Toxicol ID TUMOR-SUPPRESSOR GENE; ENZYMATIC METHYLATION; IN-VITRO; MONOMETHYLARSONIC ACID; DRINKING-WATER; URINARY CONCENTRATIONS; MARMOSET MONKEYS; DNA METHYLATION; RABBIT LIVER; RAT-LIVER AB Inorganic arsenic is considered a high-priority hazard, particularly because of its potential to be a human carcinogen. In exposed human populations, arsenic is associated with tumors of the lung, skin, bladder, and liver. While it is known to be a human carcinogen, carcinogenesis in laboratory animals by this metalloid has never been convincingly demonstrated. Therefore, no animal models exist for studying molecular mechanisms of arsenic carcinogenesis, The apparent human sensitivity, combined with our incomplete understanding about mechanisms of carcinogenic action, create important public health concerns and challenges in risk assessment, which could be met by understanding the role of metabolism in arsenic toxicity and carcinogenesis. This symposium summary covers three critical major areas involving arsenic metabolism: its biodiversity, the role of arsenic metabolism in molecular mechanisms of carcinogenesis, and the impact of arsenic metabolism on human risk assessment. In mammals, arsenic is metabolized to mono- and dimethylated species by methyltransferase enzymes in reactions that require S-adenosyl-methionine (SAM) as the methyl donating cofactor. A remarkable species diversity in arsenic methyltransferase activity may account for the wide variability in sensitivity of humans and animals to arsenic toxicity. Arsenic interferes with DNA methyltransferases, resulting in inactivation of tumor suppressor genes through DNA hypermethylation, Other studies suggest that arsenic-induced malignant transformation is linked to DNA hypomethylation subsequent to depletion of SAM, which results in aberrant gene activation, including oncogenes, Urinary profiles of arsenic metabolites may be a valuable tool for assessing human susceptibility to arsenic carcinogenesis. While controversial, the idea that unique arsenic metabolic properties may explain the apparent non-linear threshold response for arsenic carcinogenesis in humans. In order to address these outstanding issues, further efforts are required to identify an appropriate animal model to elucidate carcinogenic mechanisms of action, and to define dose-response relationships. C1 US FDA, Div Life Sci, Ctr Devices & Radiol Hlth, HFZ 112, Rockville, MD 20852 USA. Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA. Univ Arizona, Ctr Toxicol, Tucson, AZ 85721 USA. US EPA, Biochem & Pathobiol Branch, Div Environm Carcinogenesis, Natl Hlth & Environm Effects Lab, Res Triangle Pk, NC 27711 USA. CINVESTAV, Secc Toxicol Ambiental, Mexico City 14000, DF, Mexico. Gradient Corp, Cambridge, MA 02138 USA. NIEHS, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC USA. RP Goering, PL (reprint author), US FDA, Div Life Sci, Ctr Devices & Radiol Hlth, HFZ 112, 12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 58 TC 186 Z9 198 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 1999 VL 49 IS 1 BP 5 EP 14 DI 10.1093/toxsci/49.1.5 PG 10 WC Toxicology SC Toxicology GA 251PX UT WOS:000083455000002 PM 10367337 ER PT J AU Gray, G AF Gray, G TI Covariances in multiplicative estimates SO TRANSACTIONS OF THE AMERICAN FISHERIES SOCIETY LA English DT Article ID CATCH AB Multiplicative estimators, in which a quantity is calculated as the product of two or more estimated factors, are relatively common in fisheries work. Creel surveys and stock assessment data are two obvious examples. If the same multiplicative factor is used in several estimates, or if there is covariance between multiplicative factors, then covariances will be induced in the estimates produced. These covariances can be large in some instances. This paper reviews general results for the variance and covariance of products, provides estimators for the induced covariances in some common fisheries applications, and demonstrates the use of the estimators in some simplified examples. C1 Natl Marine Fisheries Serv, Fisheries Stat & Econ Div, Silver Spring, MD 20910 USA. RP Gray, G (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Biostat, HFZ-542,1350 Piccard Dr, Rockville, MD 20850 USA. NR 11 TC 1 Z9 1 U1 2 U2 4 PU AMER FISHERIES SOC PI BETHESDA PA 5410 GROSVENOR LANE SUITE 110, BETHESDA, MD 20814-2199 USA SN 0002-8487 J9 T AM FISH SOC JI Trans. Am. Fish. Soc. PD MAY PY 1999 VL 128 IS 3 BP 475 EP 482 DI 10.1577/1548-8659(1999)128<0475:CIME>2.0.CO;2 PG 8 WC Fisheries SC Fisheries GA 351WZ UT WOS:000089183600007 ER PT J AU Honig, PK AF Honig, PK TI Self-management education for adults with asthma improves health outcomes - Comment SO WESTERN JOURNAL OF MEDICINE LA English DT Editorial Material C1 Off Drug Evaluat Food & Drug Adm, CDER Pulm Grp, Rockville, MD 20857 USA. RP Honig, PK (reprint author), Off Drug Evaluat Food & Drug Adm, CDER Pulm Grp, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD MAY PY 1999 VL 170 IS 5 BP 266 EP 266 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 203DV UT WOS:000080693100016 ER PT J AU Bai, RL Ewell, JB Nguyen, NY Hamel, E AF Bai, RL Ewell, JB Nguyen, NY Hamel, E TI Direct photoaffinity labeling of cysteine 211 or a nearby amino acid residue of beta-tubulin by guanosine 5 '-diphosphate bound in the exchangeable site SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP; BINDING; BRAIN AB Tubulin with [8-C-14]GDP bound in the exchangeable site was exposed to ultraviolet light, and radiolabel was cross-linked to two peptide regions of the beta-subunit. Following enrichment for peptides cross-linked to guanosine by boronate chromatography, we confirmed that the cysteine 12 residue was the major site of crosslinking. However, significant radiolabel was also incorporated into a peptide containing amino acid residues 206 through 224. Although every amino acid in this peptide except cysteine 211 was identified by sequential Edman degradation, implying that this was the amino acid residue cross-linked to guanosine, radiolabel at C-8 was usually lost during peptide processing (probably during chromatography at pH 10). Consequently, the radiolabeled amino acid could not be unambiguously identified. C1 NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, NIH, Frederick, MD 21702 USA. US FDA, Ctr Biol Evaluat & Res, Facil Biotechnol Resources, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev,NIH, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Hamel, E (reprint author), NIH, Lab Drug Discovery Res & Dev, Bldg 37,Rm 5D02,37 Convent Dr, Bethesda, MD 20892 USA. NR 17 TC 10 Z9 10 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 30 PY 1999 VL 274 IS 18 BP 12710 EP 12714 DI 10.1074/jbc.274.18.12710 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 192BC UT WOS:000080056800073 PM 10212253 ER PT J AU Joseph, LP AF Joseph, LP TI Breast cancer detection SO SCIENCE LA English DT Letter C1 US FDA, Ctr Devices & Radiol Hlth, Off Hlth & Ind Programs, Rockville, MD 20850 USA. RP Joseph, LP (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Hlth & Ind Programs, Rockville, MD 20850 USA. NR 1 TC 0 Z9 1 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 30 PY 1999 VL 284 IS 5415 BP 743 EP 743 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 192AW UT WOS:000080056200020 PM 10336395 ER PT J AU Pogribna, M Pogribny, IP James, SJ AF Pogribna, M Pogribny, IP James, SJ TI DNA lesions induced by folate/methyl deficiency in vitro precede DNA hypomethylation in human lymphocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 3 Z9 3 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 23 PY 1999 VL 13 IS 7 SU S BP A1452 EP A1452 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400751 ER PT J AU Pogribny, IP Yi, P James, SJ AF Pogribny, IP Yi, P James, SJ TI A new method to rapidly assess differences in genome-wide and CpG island methylation in normal and neoplastic DNA. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 23 PY 1999 VL 13 IS 7 SU S BP A1550 EP A1550 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401313 ER PT J AU Hopper, ML AF Hopper, ML TI Automated one-step supercritical fluid extraction and clean-up system for the analysis of pesticide residues in fatty matrices SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE automation; sample handling; food analysis; fats; pesticides; organochlorine compounds; organophosphate compounds ID MICROWAVE-ASSISTED EXTRACTION; TOTAL DIET; FOOD; ORGANOCHLORINE AB An automated supercritical fluid extraction and in-line clean-up system has been developed for organochlorine and organophosphate pesticide residues contained in fats. This procedure utilizes supercritical carbon dioxide modified with 3% acetonitrile at 27.58 MPa and 60 degrees C to extract and separate the pesticide residues from the fat on a C-1 bonded phase preparative column at 95 degrees C. The automated C-1 system recovers 86 of 117 nonpolar to moderately polar organochlorine and organophosphate pesticides from fats. Ten of the 31 pesticides not recovered through the system are not recovered through the conventional clean-up sorbent, Florisil. Pesticide residues can be separated from 0.68 g of butter fat and 0.67 g corn oil, resulting in 2.9 mg of butterfat and 2.1 mg corn oil residue co-eluting into the pesticide fraction. Also, this integrated method can extract and clean-up a 5 g sample of fatty foods containing <18% fat and 70% moisture. The automated C-1 system is reproducible and the amount of co-extracted sample residue in the pesticide fraction yields results comparable to the current methodology, which uses organic solvent extraction and gel permeation chromatography, along with a final Florisil column clean-up step. This automated C-1 system simplifies the extraction and clean-up step while reducing solvent usage and hazardous waste. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US FDA, Total Diet & Pesticide Res Ctr, Lenexa, KS 66285 USA. RP Hopper, ML (reprint author), US FDA, Total Diet & Pesticide Res Ctr, POB 15905, Lenexa, KS 66285 USA. NR 13 TC 41 Z9 45 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 23 PY 1999 VL 840 IS 1 BP 93 EP 105 DI 10.1016/S0021-9673(99)00228-9 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 190RV UT WOS:000079979200010 PM 10335613 ER PT J AU Schwartz, PJ Turner, EH Garcia-Borreguero, D Sedway, J Vetticad, RG Wehr, TA Murphy, DL Rosenthal, NE AF Schwartz, PJ Turner, EH Garcia-Borreguero, D Sedway, J Vetticad, RG Wehr, TA Murphy, DL Rosenthal, NE TI Serotonin hypothesis of winter depression: behavioral and neuroendocrine effects of the 5-HT1A receptor partial agonist ipsapirone in patients with seasonal affective disorder and healthy control subjects SO PSYCHIATRY RESEARCH LA English DT Review DE 5-HT1A receptors; seasonal affective disorder; ipsapirone; cortisol; prolactin; adrenocorticotropic hormone; ACTH ID CORTICOTROPIN-RELEASING HORMONE; OBSESSIVE-COMPULSIVE DISORDER; LIGHT THERAPY; META-CHLOROPHENYLPIPERAZINE; TRYPTOPHAN DEPLETION; CORTISOL SECRETION; NEURO-ENDOCRINE; M-CPP; BUSPIRONE CHALLENGE; RETINAL PROJECTION AB Winter depressions in seasonal affective disorder (SAD) are associated with central serotonergic (5-HT) dysfunction. SAD patients demonstrate rather specific, state-dependent, abnormal increases in 'activation-euphoria' ratings following intravenous infusion of the 5-HT receptor agonist meta-chlorophenylpiperazine (m-CPP). Several studies are also consistent with abnormal serotonergic regulation of the hypothalamic-pituitary-adrenal (HPA) axis in SAD. Here, we investigated the effects of the 5-HT1A receptor partial agonist ipsapirone, which produces behavioral effects and HPA-axis activation, to further characterize the 5-HT receptor subtype-specificity of these disturbances in SAD. Eighteen SAD patients and 18 control subjects completed two drug challenges (ipsapirone 0.3 mg/kg and placebo) separated by 3-5 days in randomized order. We measured behavioral responses with the NIMH self-rating scale, and plasma ACTH, cortisol, and prolactin concentrations. Compared with placebo, ipsapirone was associated with significant increases in self-rated 'functional deficit' and 'altered self-reality', and in each of the hormones. There were no differences between groups on any measures. The level of depression in SAD patients was inversely correlated with their ipsapirone-induced cortisol responses. There were significant drug x order effects on baseline 'anxiety' scores, ACTH and cortisol concentrations, such that subjects were significantly more stressed (higher 'anxiety', ACTH and cortisol) prior to their first challenge compared with their second. In conclusion, post-synaptic 5-HT1A receptors appear to function normally in SAD. The previously observed m-CPP-induced behavioral abnormality may be mediated by either 5-HT2C or 5-HT7 receptors. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. VAMC, Cincinnati, OH USA. Food & Drug Adm, Rockville, MD USA. NIMH, Sect Biol Rhythms, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Schwartz, PJ (reprint author), 787 Ludlow Ave 2, Cincinnati, OH 45220 USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 109 TC 22 Z9 24 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD APR 19 PY 1999 VL 86 IS 1 BP 9 EP 28 DI 10.1016/S0165-1781(99)00017-7 PG 20 WC Psychiatry SC Psychiatry GA 198PT UT WOS:000080433700002 PM 10359479 ER PT J AU Wang, XM Sakuma, T Asafu-Adjaye, E Shiu, GK AF Wang, XM Sakuma, T Asafu-Adjaye, E Shiu, GK TI Determination of ginsenosides in plant extracts from Panax ginseng and Panax quinquefolius L. by LC/MS/MS SO ANALYTICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DESORPTION MASS-SPECTROMETRY; SAPONIN AB An HPLC/MS/MS method has been developed for the characterization and quantification of ginsenosides contained in extracts of the root of Panax ginseng (Korean ginsengs) and Panax quinquefolius L. (American ginsengs). The [M + H](+) and [M + Na](+) ions were observed for ginsenoside standards (Rb1, Rb2, Re, Rd, Re, Rf, Rg1) and four different ginseng extracts. The glycosidic linkages, the core, and the attached sugar(s) of the ginsenosides can be determined from the collision-induced dissociation spectra from the protonated molecules. The relative distribution of these ginsenosides in each extract of American or Korean ginseng was established. C1 Perkin Elmer Sciex Instruments, Concord, ON L4K 4V8, Canada. US FDA, Prod Qual Res Lab, Rockville, MD 20850 USA. RP Wang, XM (reprint author), Perkin Elmer Sciex Instruments, 71 4 Valley Dr, Concord, ON L4K 4V8, Canada. NR 13 TC 176 Z9 199 U1 2 U2 47 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD APR 15 PY 1999 VL 71 IS 8 BP 1579 EP 1584 DI 10.1021/ac980890p PG 6 WC Chemistry, Analytical SC Chemistry GA 186XU UT WOS:000079756900017 PM 10221076 ER PT J AU Teruya-Feldstein, J Jaffe, ES Burd, PR Kingma, DW Setsuda, JE Tosato, G AF Teruya-Feldstein, J Jaffe, ES Burd, PR Kingma, DW Setsuda, JE Tosato, G TI Differential chemokine expression in tissues involved by Hodgkin's disease: Direct correlation of eotaxin expression and tissue eosinophilia SO BLOOD LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Hematology CY DEC 05-09, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol ID NF-KAPPA-B; INTERFERON-INDUCIBLE PROTEIN-10; TUMOR-NECROSIS-FACTOR; IN-VIVO; FUNCTIONAL-CHARACTERIZATION; RECEPTOR CCR3; T-LYMPHOCYTES; MESSENGER-RNA; CELLS; CHEMOATTRACTANT AB Hodgkin's disease (HD) is a lymphoid malignancy characterized by infrequent malignant cells surrounded by abundant inflammatory cells. In this study, we examined the potential contribution of chemokines to inflammatory cell recruitment in different subtypes of HD. Chemokines are small proteins that are active as chemoattractants and regulators of cell activation. We found that HD tissues generally express higher levels of interferon-gamma-inducible protein-10 (IP-10), Mig. RANTES, macrophage inflammatory protein-1 alpha (MIP-1 alpha). and eotaxin, but not macrophage-derived chemotactic factor (MDC), than tissues from lymphoid hyperplasia (LH). Within HD subtypes, expression of IP-10 and Mig was highest in the mixed cellularity (MC) subtype, whereas expression of eotaxin and MDC was highest in the nodular sclerosis (NS) subtype. A significant direct correlation was detected between evidence of Epstein-Barr virus (EBV) infection in the neoplastic cells and levels of expression of IP-10, RANTES, and MIP-1 alpha. Levels of eotaxin expression correlated directly with the extent of tissue eosinophilia. By immunohistochemistry, IP-10, Mig, and eotaxin proteins localized in the malignant Reed-Sternberg (RS) cells and their variants, and to some surrounding inflammatory cells. Eotaxin was also detected in fibroblasts and smooth muscle cells of vessels. These results provide evidence of high level chemokine expression in HD tissues and suggest that chemokines may play an important role in the recruitment of inflammatory cell infiltrates into tissues involved by HD. (C) 1999 by The American Society of Hematology. C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Teruya-Feldstein, J (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 47 TC 96 Z9 99 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1999 VL 93 IS 8 BP 2463 EP 2470 PG 8 WC Hematology SC Hematology GA 184YY UT WOS:000079642400004 PM 10194423 ER PT J AU Rafii, F Lunsford, P Hehman, G Cerniglia, CE AF Rafii, F Lunsford, P Hehman, G Cerniglia, CE TI Detection and purification of a catalase-peroxidase from Mycobacterium sp. Pyr-1 SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE Mycobacterium; catalase; peroxidase; isoniazid ID ISONIAZID RESISTANCE; TUBERCULOSIS; GENE; SMEGMATIS; KATG AB A catalase-peroxidase from Mycobacterium sp. Pyr-1, a strain capable of growth on pyrene, was purified to homogeneity by anion exchange and hydroxyapatite column chromatography. The enzyme, like the M. tuberculosis T-catalase, reduced nitroblue tetrazolium in the presence of isoniazid (INH) and H2O2 It also oxidized 3,3',5,5'-tetramethylbenzidine and other substrates of the catalase-peroxidase of M. tuberculosis in the presence of either tert-butyl hydroperoxide or H2O2. It had a UV/visible absorption spectrum (Soret peak at 406 nm) similar to that of the catalase-peroxidase of M. tuberculosis (Soret peak at 408 nm) and identical to that of the catalase-peroxidase of M. smegmatis. After electrophoresis on non-denaturing gels the enzyme showed one single protein band with both catalase and peroxidase activity, which were lost after electrophoresis on SDS-PAGE. The enzyme was inhibited by sodium azide, glutathione, 2-mercaptoethanol, and isoniazid, but not by isonicotinic acid. The optimum enzyme activity was obtained at pH 4.5 and at 25 degrees C. (C) 1999 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Rafii, F (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 15 TC 6 Z9 6 U1 1 U2 6 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 APR 15 PY 1999 VL 173 IS 2 BP 285 EP 290 DI 10.1111/j.1574-6968.1999.tb13515.x PG 6 WC Microbiology SC Microbiology GA 184YF UT WOS:000079640800002 PM 10227157 ER PT J AU Lee, JC Chen, DT Hung, HN Chen, JJ AF Lee, JC Chen, DT Hung, HN Chen, JJ TI Analysis of drug dissolution data SO STATISTICS IN MEDICINE LA English DT Article ID SELECTION AB Drug absorption in the human body depends on the dissolution rate of the drug. Suitable dissolution characteristics are important to ensure that the drug will achieve the desired therapeutic effects. To assess the similarity of dissolution rates of several drug lots, we apply a general growth curve model with different covariance structures. The Box-Cox power transformation and the naive log transformation are applied to a function of the dissolution rate. The predictive sample-reuse, or cross-validation, method is employed in selecting an appropriate model with best predictive accuracy. A testing procedure for examining the similarity among the drug lots is also conducted. A partially Bayesian approach is used for the assessment of dissolution equivalence. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Natl Chiao Tung Univ, Inst Stat, Hsinchu, Taiwan. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Lee, JC (reprint author), Natl Chiao Tung Univ, Inst Stat, Hsinchu, Taiwan. NR 11 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 0277-6715 J9 STAT MED JI Stat. Med. PD APR 15 PY 1999 VL 18 IS 7 BP 799 EP 814 DI 10.1002/(SICI)1097-0258(19990415)18:7<799::AID-SIM81>3.0.CO;2-Y PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 183XT UT WOS:000079580200004 PM 10327528 ER PT J AU Holcomb, C Lacey, PL McCoy, TW Stancil, MA Benson, JA Cobb, LL Ray, ML Park, MM Franko, EA Scarborough, MF Blake, PA Simons, MM Dauphinais, L Vukelic, PJ Kruger, KJ Shireley, LA Gregos, E Friedman, M Richey, N Hammond, R Monroe, T Cheek, J AF Holcomb, C Lacey, PL McCoy, TW Stancil, MA Benson, JA Cobb, LL Ray, ML Park, MM Franko, EA Scarborough, MF Blake, PA Simons, MM Dauphinais, L Vukelic, PJ Kruger, KJ Shireley, LA Gregos, E Friedman, M Richey, N Hammond, R Monroe, T Cheek, J TI Outbreaks of gastrointestinal illness of unknown etiology associated with eating burritos - United States, October 1997 October 1998 (Reprinted from MMWR, vol 48, pg 210-213, 1999) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Hall Cty Hlth Dept, Hall Cty Environm Hlth, Gainesville, GA 30503 USA. Geprgia Dept Human Resources, Div Publ Hlth, Atlanta, GA 30334 USA. Aberdeen Area Indian Hlth Serv, Rapid City, SD USA. N Dakota Dept Hlth, Bismarck, ND USA. Hillsborough Cty Dept Hlth, Tampa, FL USA. Florida Dept Hlth, Bur Environm Epidemiol, Tallahassee, FL USA. Kansas Dept Hlth & Environm, Topeka, KS USA. Indian Hlth Serv Headquarters, Albuquerque, NM USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. US FDA, Off Reg Operat, Rockville, MD 20857 USA. Food Safety & Inspect Serv, Off Publ Hlth & Sci, USDA, Washington, DC USA. CDC, Natl Ctr Environm Hlth, Hlth Studies Branch, Div Environm Hazards & Hlth Effects, Atlanta, GA 30333 USA. CDC, Natl Ctr Infect Dis, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. RP Holcomb, C (reprint author), Hall Cty Hlth Dept, Hall Cty Environm Hlth, Gainesville, GA 30503 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 14 PY 1999 VL 281 IS 14 BP 1263 EP 1264 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 184TC UT WOS:000079628700012 ER PT J AU Goering, PL Thomas, D Rojko, JL Lucas, AD AF Goering, PL Thomas, D Rojko, JL Lucas, AD TI Mercuric chloride-induced apoptosis is dependent on protein synthesis SO TOXICOLOGY LETTERS LA English DT Article DE mercury; apoptosis; flow cytometry; cycloheximide ID PROGRAMMED CELL-DEATH; UV-INDUCED IMMEDIATE; HUMAN T-CELLS; DELAYED APOPTOSIS; DNA FRAGMENTATION; FLOW-CYTOMETRY; TRANSFERASE; MECHANISMS; NECROSIS; NUCLEUS AB Apoptosis is a mode of cell death with morphologic and biochemical features that distinguish it from necrosis. Recent studies demonstrating that mercury compounds initiate apoptosis in cultured cells did not elucidate if the biochemical mechanism of apoptosis involved a dependence on macromolecular synthesis post-insult, i.e. programmed cell death. The objectives of this in vitro study were (1) to determine if HgCl2 cytotoxicity includes an apoptotic component, and (2) to determine if apoptosis is dependent on protein synthesis, i.e. proceeds by an inducible mechanism. Suspensions of mouse lymphoma (L5178Y-R) cells were exposed to 0, 1, 5, or 10 mu M HgCl2 and apoptosis was evaluated utilizing qualitative and quantitative methods. At 24 h after exposure, transmission electron microscopy revealed a concentration-related increase in morphologic changes typical of apoptosis: margination of condensed chromatin to the nuclear membrane, dilation of the rough endoplasmic reticulum, cytoplasmic condensation and vacuolation, nuclear dissolution, and plasma membrane blebbing. An increase in Hg-induced DNA fragmentation (DNA 'ladder') was observed using agarose gel electrophoresis. Time- and concentration-dependent increases in the percent of apoptotic cells were observed at 1, 6, 12, and 24 h after HgCl2 exposure using a flow cytometric method that discriminates between cells according to size and granularity. Pretreatment of cells with cycloheximide (CHX), an inhibitor of translation, prior to HgCl2 exposure resulted in a 25-50% reduction in apoptotic cells 24 h after exposure to 10 and 20 mu M HgCl2. and concomitantly reduced the overall cytotoxicity compared to HgCl2 alone. These results, although limited to a single cell line, support the hypothesis that HgCl2 induces apoptosis that is dependent, at least in part, upon protein synthesis. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Ctr Devices & Radiol Hlth, Div Life Sci, Rockville, MD 20852 USA. Pathol Associates Int, Frederick, MD USA. RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Life Sci, 12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 31 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD APR 12 PY 1999 VL 105 IS 3 BP 183 EP 195 DI 10.1016/S0378-4274(99)00002-8 PG 13 WC Toxicology SC Toxicology GA 195KZ UT WOS:000080251000002 PM 10355539 ER PT J AU Nightingale, SL AF Nightingale, SL TI New easy-to-understand labels for OTC drugs SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item 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 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 7 PY 1999 VL 281 IS 13 BP 1164 EP 1164 DI 10.1001/jama.281.13.1164 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 181VW UT WOS:000079464400010 PM 10199413 ER PT J AU Nightingale, SL AF Nightingale, SL TI Workshop on Medical Device Clinical Trial Development and Design SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item 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 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 7 PY 1999 VL 281 IS 13 BP 1164 EP 1164 DI 10.1001/jama.281.13.1164 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 181VW UT WOS:000079464400009 PM 10199413 ER PT J AU Nightingale, SL AF Nightingale, SL TI New information for physicians regarding mammography results SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item 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 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 7 PY 1999 VL 281 IS 13 BP 1164 EP 1164 DI 10.1001/jama.281.13.1164 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 181VW UT WOS:000079464400008 PM 10199413 ER PT J AU Hinkley, SF Jiang, J Mazzola, EP Jarvis, BB AF Hinkley, SF Jiang, J Mazzola, EP Jarvis, BB TI Atranones: Novel diterpenoids from the toxigenic mold Stachybotrys atra SO TETRAHEDRON LETTERS LA English DT Article ID TRICHOTHECENES; BIOSYNTHESIS AB The toxigenic mold Stachybotrys atra produces a new class of elaborated diterpenoid dolabellanes, the C-24 atranones, which have several unusual structural features, including an enol-lactone ring system. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Jarvis, BB (reprint author), Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. OI Hinkley, Simon F.R./0000-0002-1831-8389 NR 18 TC 21 Z9 21 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD APR 2 PY 1999 VL 40 IS 14 BP 2725 EP 2728 DI 10.1016/S0040-4039(99)00350-0 PG 4 WC Chemistry, Organic SC Chemistry GA 180UM UT WOS:000079403600019 ER PT J AU Asthana, S Raffaele, KC Greig, NH Schapiro, MB Blackman, MR Soncrant, TT AF Asthana, S Raffaele, KC Greig, NH Schapiro, MB Blackman, MR Soncrant, TT TI Neuroendocrine responses to intravenous infusion of physostigmine in patients with Alzheimer disease SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE physostigmine; HPA-axis; Alzheimer disease; memory; cortisol ID CORTICOTROPIN-RELEASING HORMONE; CEREBROSPINAL-FLUID; MEMORY; ARECOLINE; PITUITARY; ACETYLCHOLINE; CORTISOL; DEMENTIA; TACRINE; SYSTEM AB We have reported that physostigmine, a reversible cholinesterase inhibitor, enhances verbal memory in patients with Alzheimer disease (AD). To elucidate the mechanism of cognition enhancement, plasma hormones were measured during high-dose acute and low-dose chronic steady-state intravenous infusions of physostigmine in nine subjects with AD. High-dose hormone responses were measured during and for 24 h after the infusion of physostigmine 1-1.5 mg over 45-60 min. Chronic responses were measured during continuous intravenous infusions of physostigmine at doses (0.5-25 mg/day) that escalated over 2 weeks, and then during 1 week infusion of the dose that optimized cognition (2-12 mg/day) or placebo administered in a randomized double-blind, crossover design. A replicable improvement in verbal memory was found in five subjects. High-dose physostigmine infusion that produced noxious side effects resulted in significant elevation above baseline in plasma levels of adrenocorticotrophic hormone (ACTH) (p = 0.0001), cortisol (p = 0.0001), and beta-endorphin (p = 0.0001). Chronic physostigmine administration, in the absence of adverse effects, produced no significant elevation in ACTH (p = 0.08), cortisol (p = 0.70), or beta-endorphin (p = 0.82). These results indicate that high-dose physostigmine activates the hypothalamic-pituitary-adrenal (HPA) axis, likely representing a "stress response." In contrast, cognition-enhancing doses do not produce a peripheral corticosteroid response. Thus, physostigmine-induced memory improvement is independent of the activation of the HPA axis. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. US FDA, Washington, DC 20204 USA. Johns Hopkins Univ, Sch Med, Hopkins Bayview Med Ctr, Baltimore, MD USA. RP Asthana, S (reprint author), VA Puget Sound Hlth Care Syst, Amer Lake Div, GRECC 182 B, Tacoma, WA 98493 USA. NR 40 TC 5 Z9 5 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD APR-JUN PY 1999 VL 13 IS 2 BP 102 EP 108 DI 10.1097/00002093-199904000-00008 PG 7 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 268NQ UT WOS:000084422800008 PM 10372954 ER PT J AU Lipicky, RJ Stockbridge, N AF Lipicky, RJ Stockbridge, N CA ABPM Steering Comm TI Role of ABPM in clinical development or antihypertensive drugs SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract DE ABPM; placebo; drug development C1 US FDA, Div Cardiorenal Drug Prod, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 1999 VL 12 IS 4 SU S BP 152A EP 152A PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 188FR UT WOS:000079836600539 ER PT J AU Altekruse, SF Yang, S Timbo, BB Angulo, FJ AF Altekruse, SF Yang, S Timbo, BB Angulo, FJ TI A multi-state survey of consumer food-handling and food-consumption practices SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE food poisoning; behavior; demography ID HEMOLYTIC-UREMIC-SYNDROME; SALMONELLA-ENTERITIDIS; RAW-MILK; INFECTIONS; CALIFORNIA; KNOWLEDGE; DISEASE; SAFETY AB Introduction: In the United States, foodborne infections cause an estimated 6.5-33 million illnesses a year. Also included in the burden of foodborne illnesses are sequelae such as hemolytic uremic syndrome, Guillain-Barre syndrome, and reactive arthritis. Surveillance for risky food-handling and food-consumption practices can be used to identify high-risk populations, develop educational efforts, and evaluate progress toward risk reduction. Design: In 1995 and 1996, Behavioral Risk Factor Surveillance System interviews of 19,356 adults ill eight states (1995: Colorado, Florida, Missouri, New York, and Tennessee; 1996: Indiana, New Jersey, and South Dakota) included questions related to food-handling and/or food-consumption practices. Risky food-handling and food-consumption practices were not uncommon. Overall, 19% of respondents did not adequately wash hands or cutting boards after contact with raw meat or chicken. During the previous year, 20% ate pink hamburgers, 50% ate undercooked eggs, 8% ate raw oysters, and 1% drank I alv milli. Men were more likely to report risky practices than women. The prevalence of most risky behaviors increased with increasing socioeconomic status. Conclusion: Targeted education efforts may reduce the frequency of these behaviors. Periodic surveillance call be used to assess effectiveness. In addition to consumer education, prevention efforts are needed throughout the food chain including on the farm, in processing, distribution, and at retail. (C) 1999 American Journal of Preventive Medicine. C1 Ctr Dis Control & Prevent, NCID, FDDB A38, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Assessment & Support, Div Market Studies,Epidemiol Branch HFS728, Washington, DC 20204 USA. RP Yang, S (reprint author), Ctr Dis Control & Prevent, NCID, FDDB A38, Div Bacterial & Mycot Dis, 1600 Clifton Rd, Atlanta, GA 30333 USA. NR 32 TC 116 Z9 119 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 1999 VL 16 IS 3 BP 216 EP 221 DI 10.1016/S0749-3797(98)00099-3 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 177UL UT WOS:000079229400009 PM 10198661 ER PT J AU Pletnikov, MV Rubin, SA Vasudevan, K Moran, TH Carbone, KM AF Pletnikov, MV Rubin, SA Vasudevan, K Moran, TH Carbone, KM TI Developmental brain injury associated with abnormal play behavior in neonatally Borna disease virus-infected Lewis rats: a model of autism SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Borna disease virus; Lewis rat; social interaction; play; brain; development ID SOCIAL-INTERACTION; JUVENILE RATS; FEMALE RATS; CEREBELLAR; NEUROBIOLOGY; MICE AB Play behavior, nonsocial exploratory activity, and nonplay social interaction were observed in male juvenile Lewis rats with brain developmental injury following neonatal infection with Borna disease virus (BDV). These behaviors were tested using the 'intruder-resident' paradigm, with social isolation of residents for six days prior to testing. Four experimental pairings of infected (BDV) and uninfected (NL) rats were studied as follows: NL-NL; NL-BDV; BDV-NL; and BDV-BDV (the first member is the resident, the second member is the intruder). Observation of social activities was carried out for 10 min on two consecutive days, Nonsocial exploratory activity (e.g, ambulation and rearing) was similar in BDV and NL residents. Duration of nonplay social investigation (e.g. sniffing, approach, and follow) was higher in BDV residents as compared to NL residents when tested on the first test day. On the second day, all rats showed similar level of nonplay social interaction. When confronted with NL intruders, NL residents exhibited significantly more play behavior compared to the NL-BDV, BDV-NL and BDV-BDV pairs, when play behavior was measured by the number of 'pins'. Moreover, irrespective of a type of intruder, NL residents demonstrated higher play soliciting behavior than BDV residents, indicating attenuated readiness to play in BDV-infected rats. The number of pins and play solicitations in BDV-NL pairs significantly increased over the two days of testing, while play activity in NL-BDV pairs declined on the second test day. This pattern suggests that the degree of social reinforcement on the first day of testing affected the level of play on the second day. These data demonstrate deficits in play behavior and other social interactions following BDV-associated developmental brain injury, thus supporting the value of the neonatally BDV-infected rat as an animal model of autism. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US FDA, Lab Pediat & Resp Viral Dis, OVRR, CBER, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Pletnikov, MV (reprint author), US FDA, Lab Pediat & Resp Viral Dis, OVRR, CBER, Bldg 29A,Room 1A-21,HFM-460,8800 Rockville Pike, Bethesda, MD 20892 USA. FU NIMH NIH HHS [MH 48948] NR 28 TC 69 Z9 73 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD APR PY 1999 VL 100 IS 1-2 BP 43 EP 50 DI 10.1016/S0166-4328(98)00111-9 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 176EG UT WOS:000079137600005 PM 10212052 ER PT J AU Mahmood, I Yuan, R AF Mahmood, I Yuan, R TI A comparative study of allometric scaling with plasma concentrations predicted by species-invariant time methods SO BIOPHARMACEUTICS & DRUG DISPOSITION LA English DT Article DE allometry; equivalent time; kallynochron; apolysichron; dienetichrons ID PHARMACOKINETICS; CIPROFLOXACIN; HUMANS; METABOLISM; CLEARANCE; ANIMALS; DRUGS; RABBITS; RATS; DOG AB The objective of this study is to compare the empirical allometric approaches with species invariant time methods using equivalent time, kallynochron, apolysichron, and dienetichrons. Pharmacokinetic parameters (clearance, volume of distribution, and elimination half-life) of ethosuximide, cyclosporine and ciprofloxacin were scaled-up from animal data obtained from the literature. Two methods were utilized to generate plots for the prediction of clearance in humans: (i) clearance versus body weight (simple allometric equation); and (ii) the product of clearance and maximum life-span potential (MLP) versus body weight. Plasma concentrations of each of the drugs were predicted using elementary and complex Dedrick plots, equivalent time with an exponent of 0.25 and equivalent time with the exponent obtained from the plot of body weight and half-life. Plasma concentrations of cyclosporine and ciprofloxacin were also predicted by MLP normalization (dienetichrons). Almost similar results in the pharmacokinetic parameters of the tested drugs were obtained by the allometric approach and by the species invariant time methods. Copyright (C) 1999 John Wiley & Sons, Ltd. 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-360,1451 Rockville Pike, Rockville, MD 20852 USA. NR 24 TC 23 Z9 23 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0142-2782 J9 BIOPHARM DRUG DISPOS JI Biopharm. Drug Dispos. PD APR PY 1999 VL 20 IS 3 BP 137 EP 144 DI 10.1002/(SICI)1099-081X(199904)20:3<137::AID-BDD165>3.0.CO;2-I PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 182LV UT WOS:000079501200004 PM 10211866 ER PT J AU Von Tungeln, LS Xia, QS Bucci, T Heflich, RH Fu, PP AF Von Tungeln, LS Xia, QS Bucci, T Heflich, RH Fu, PP TI Tumorigenicity and liver tumor ras-protooncogene mutations in CD-1 mice treated neonatally with 1-and 3-nitrobenzo[a]pyrene and their trans-7,8-dihydrodiol and aminobenzo[a]pyrene metabolites SO CANCER LETTERS LA English DT Article DE neonatal CD-1 mouse; liver tumors; Ki-ras oncogene; 1-nitrobenzo[a]pyrene; 3-nitrobenzo[a]pyrene ID HAMSTER OVARY CELLS; DNA ADDUCT FORMATION; MOUSE ASSAY; 6-NITROCHRYSENE; MUTAGENICITY; B6C3F(1) AB The environmental pollutants 1- and 3-nitrobenzo[a]pyrene (1- and 3-NBaP) are metabolized by mammalian microsomes through ring oxidation to 1-NBaP trans-7,8-dihydrodiol and 3-NBaP trans-7,8-dihydrodiol, and by nitroreduction to 1- and 3-aminobenzo[a]pyrene. To determine if these compounds are tumorigenic, 1- and 3-NBaP, along with several of their metabolites and the parent benzo[a]pyrene (BaP) and its trans-7,8-dihydrodiol metabolite, were tested in the neonatal CD-I mouse bioassay. Male mice were administered i.p, injections at a total dose of 100 or 400 nmol per mouse on 1, 8 and 15 days after birth. While the liver tumor incidences for BaP, BaP trans-7,8-dihydrodiol, and the positive control 6-nitrochrysene (6-NC) were significantly higher than in the solvent control animals, all the other tested compounds exhibited no tumorigenicity. The frequency of Ha- and Ki-ras mutations in liver tumors of mice treated with BaP, BaP trans-7,8-dihydrodiol, and 6-NC were higher than in the few liver tumors isolated from control mice or mice treated with the NBaPs or their metabolites. Since 1- and 3-NBaP and their metabolites are potent mutagens in the Salmonella assay and moderate mutagens in the Chinese hamster ovary (CHO) mammalian mutagenicity assay, our results indicate that the in vitro mutagenicity of these compounds does not correlate with their tumorigenicity. (C) 1999 Published by Elsevier Science Ltd. AU rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. 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 20 TC 3 Z9 4 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 APR 1 PY 1999 VL 137 IS 2 BP 137 EP 143 DI 10.1016/S0304-3835(98)00341-3 PG 7 WC Oncology SC Oncology GA 194TT UT WOS:000080210200003 PM 10374834 ER PT J AU Chae, YH Thomas, T Guengerich, FP Fu, PP El-Bayoumy, K AF Chae, YH Thomas, T Guengerich, FP Fu, PP El-Bayoumy, K TI Comparative metabolism of 1-, 2-, and 4-nitropyrene by human hepatic and pulmonary microsomes SO CANCER RESEARCH LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; RAT-LIVER MICROSOMES; CELL LINE HEPG2; SPRAGUE-DAWLEY RATS; DNA-BINDING; HUMAN CYTOCHROME-P450; CHEMICAL CARCINOGENESIS; ENVIRONMENTAL MUTAGEN; ESCHERICHIA-COLI; A/J MICE AB Determining the capability of humans to metabolize the mononitropyrene (mono-NP) isomcrs 1-, 2-, and 4-NP and understanding which human cytochrome P450 (P450) enzymes are involved in their activation and/or detoxification is important in the assessment of individual susceptibility to these environmental carcinogens. We compared the ability of 15 human hepatic and 8 pulmonary microsomal samples to metabolize each of the three isomers, Human hepatic microsomes were competent in metabolizing all three isomers, Qualitatively similar metabolic patterns were observed, although at much lower levels, upon incubating mono-NP with pulmonary microsomes. Ring-oxidized metabolites (phenols and transdihydrodiols) were produced from all three isomers. However, the nitroreductive metabolism leading to the formation of aminopyrene was evident only with 4-NP. The role of specific P450 enzymes in the human hepatic microsomal metabolism of mono-NP was investigated by correlating the P450-dependent catalytic activities in each microsomal sample with the levels of individual metabolites formed by the same microsomes and by examining the effects of agents that can either inhibit or stimulate specific P450 enzymes in mono-NP metabolism On the basis of these studies, we attribute most of the hepatic microsomal metabolism of 1- and 4-NP to P450 3A4, although a minor role for P450 1A2 cannot be ruled out. Specifically, P450 3A4 was responsible for the formation of 3-hydroxy-1-nitropyrene from 1-NP and the formation of trans-9,10-dihydro-9,10-dihydroxy-4-nitropyrene, 9(10)-hydroxy-4-nitropyrene, and 4-aminopyrene from 4-NP, None of the p450 enzymes examined (P450s 3A4, 1A2, 2E1, 2A6, 2D6, and 2C9) appeared to be involved in catalyzing the formation of trans-4,5-dihydro-4,5-dihydroxy-2-nitropyrene and 6-hydroxy-2-nitropyrene from 2-NP in human hepatic microsomes. These results, the first report on the comparative metabolism of mono-NP in humans, clearly demonstrate that the role of specific human P450 enzymes in catalyzing oxidative and reductive pathways of mono-NP is dependent upon the position of the nitro group. C1 Amer Hlth Fdn, Div Canc Etiol & Prevent, Valhalla, NY 10595 USA. Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA. Vanderbilt Univ, Ctr Mol Toxicol, Sch Med, Nashville, TN 37232 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP El-Bayoumy, K (reprint author), Amer Hlth Fdn, Div Canc Etiol & Prevent, 1 Dana Rd, Valhalla, NY 10595 USA. FU NCI NIH HHS [CA 35519, CA 44353]; NIEHS NIH HHS [ES 00267] NR 55 TC 41 Z9 41 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1999 VL 59 IS 7 BP 1473 EP 1480 PG 8 WC Oncology SC Oncology GA 182ZJ UT WOS:000079527800018 PM 10197616 ER PT J AU Chew, GL Higgins, KM Milton, DK Burge, HA AF Chew, GL Higgins, KM Milton, DK Burge, HA TI The effects of carpet fresheners and other additives on the behaviour of indoor allergen assays SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE ELISA; Der f 1; Der p 1; Fel d 1; Bla g 1; carpet freshener; allergens ID IN-HOUSE DUST; P-I; MITE; EXPOSURE; ASTHMA; CHILDHOOD AB Background Chemical agents such as tannic acid and detergents have been shown to introduce non-random bias in allergen measurement. Objective We investigated how several substances that are commonly found in floor dust (carpet fresheners, powdered pesticides, and table salt) affected immunoassays of purified standard allergens. Methods Three sets of experiments were conducted to: (1) screen for interference with allergen enzyme-linked immunosorbent assay (ELISA); (2) test for concentration-response; and (3) assess the site-of-action of a given dust additive (i.e. the effect on allergen binding to primary or secondary antibody), The ELISAs are commercially available two-site monoclonal antibody assays for Der p 1, Der f 1, and Fel d 1, and a monoclonal/polyclonal assay for Bla g 1. Outcomes are reported in terms of reaction rate (colour change per unit time), which is directly proportional to the amount of bound allergen. Results in. the initial screening experiments, carpet fresheners tended to decrease Der p 1 assay reaction rates, increase Der f 1 assay rates, and produce little change in Fel d 1 assay rates. Three carpet fresheners decreased Der p 1 assay rate responses in a concentration-dependent manner. Two carpet fresheners noticeably increased Der f 1 assay reaction rates in both the screening and the concentration-response tests. Powdered pesticides increased reaction rates in the Bla g 1 assays and increased the slope of the dilution curve compared with that of the purified allergen. Salt decreased the reaction rates of Bla g 1 assays at allergen concentrations greater than 0.01 U/mL. For each of the four allergens, the largest effects of dust additives occurred when secondary antibody binding was altered. Conclusions Some common household dust components can introduce systematic error into immunoassays for arthropod allergens. C1 Columbia Univ, Sch Publ Hlth, Div Environm Hlth Sci, New York, NY 10032 USA. US FDA, Rockville, MD 20857 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 USA. RP Chew, GL (reprint author), Columbia Univ, Sch Publ Hlth, Div Environm Hlth Sci, 60 Haven Ave B-1, New York, NY 10032 USA. RI Milton, Donald/G-3286-2010 OI Milton, Donald/0000-0002-0550-7834 NR 15 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD APR PY 1999 VL 29 IS 4 BP 470 EP 477 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 189HQ UT WOS:000079899400008 PM 10202361 ER PT J AU Kanegane, H Wakiguchi, H Kanegane, C Kurashige, T Miyawaki, T Tosato, G AF Kanegane, H Wakiguchi, H Kanegane, C Kurashige, T Miyawaki, T Tosato, G TI Increased cell-free viral DNA in fatal cases of chronic active Epstein-Barr virus infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MONONUCLEOSIS; INTERLEUKIN-10 AB We have studied the nature of Epstein-Barr virus (EBV) infection in 33 patients with chronic active EBV infection. The study population included 14 patients with fatal chronic EBV infection and 19 patients with nonfatal chronic EBV infection, as well as 18 patients with acute EBV-induced infectious mononucleosis and 10 healthy controls. EBV DNA was measured in serum or plasma samples from the patients by semiquantitative polymerase chain reaction-based assay. EBV DNA was detected in serum or plasma samples from 62% (9/14) of patients with fatal chronic active EBV infection. In contrast, only 11% (2/19) of patients with nonfatal chronic active EBV infection and 11% (2/18) of patients with infectious mononucleosis displayed EBV DNA. None of the healthy controls tested positive. Cell-free circulating EBV DNA may represent an important feature of chronic active EBV infection and may provide a useful tool to monitor the severity of this illness. C1 Toyama Med & Pharmaceut Univ, Fac Med, Dept Pediat, Toyama 9300194, Japan. Kochi Med Sch, Dept Pediat, Nankoku, Kochi, Japan. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD USA. RP Kanegane, H (reprint author), Toyama Med & Pharmaceut Univ, Fac Med, Dept Pediat, 2630 Sugitani, Toyama 9300194, Japan. NR 14 TC 20 Z9 22 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 1999 VL 28 IS 4 BP 906 EP 909 DI 10.1086/515224 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 184KP UT WOS:000079611600039 PM 10825059 ER PT J AU Mahmood, I Sahajwalla, C AF Mahmood, I Sahajwalla, C TI Clinical pharmacokinetics and pharmacodynamics of buspirone, an anxiolytic drug SO CLINICAL PHARMACOKINETICS LA English DT Review ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CALCIUM-CHANNEL ANTAGONISTS; MASS-SPECTROMETRY; HUMAN-PLASMA; SIMULTANEOUS QUANTITATION; HEALTHY-SUBJECTS; DIAZEPAM; 1-(2-PYRIMIDINYL)PIPERAZINE; DISPOSITION; METABOLITE AB Buspirone is an anxiolytic drug given at a dosage of 15 mg/day, The mechanism of action of the drug is not well characterised, but it may exert its effect by acting on the dopaminergic system in the central nervous system or by binding to serotonin (5-hydroxytryptamine) receptors. Following a oral dose of buspirone 20mg, the drug is rapidly absorbed. The mean peak plasma concentration (C-max) is approximately 2.5 mu g/L, and the time to reach the peak is under 1 hour. The absolute bioavailability of buspirone is approximately 4%. Buspirone is extensively metabolised. One of the major metabolites of buspirone is 1-pyrimidinylpiperazine (1-PP), which may contribute to the pharmacological activity of buspirone. Buspirone has a volume of distribution of 5.3 L/kg, a systemic clearance of about 1.7 L/h/kg. an elimination half-life of about 2.5 hours and the pharmacokinetics are linear over the dose range 10 to 40mg. After multiple-dose administration of buspirone 10 mg/day for 9 days, there was no accumulation of either parent compound or metabolite (1-PP). Administration with food increased the Cma,and area under the plasma concentration-time curve (AUC) of buspirone 2-fold. After a single 20mg dose, the C-max and AUC increased 2-fold in patients with renal impairment as compared with healthy volunteers. The C-max and AUC were 15-fold higher for the same dose in patients with hepatic impairment compared with healthy individuals. The half-lift: of buspirone in patients with hepatic impairment was twice that in healthy individuals, The pharmacokinetics of buspirone were not affected by age or gender. Coadministration of buspirone with verapamil, diltiazem, erythromycin and Itraconazole substantially increased the plasma concentration of buspirone, whereas cimetidine and alprazolam had negligible effects. Rifampicin (rifampin) decreased the plasma concentrations of buspirone almost 10-fold. C1 US FDA, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut HFD860, Woodchester Off Ctr 2, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut HFD860, Woodchester Off Ctr 2, 1451 Rockville Pike,Room 4079, Rockville, MD 20852 USA. NR 48 TC 66 Z9 67 U1 0 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PD APR PY 1999 VL 36 IS 4 BP 277 EP 287 DI 10.2165/00003088-199936040-00003 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 192HD UT WOS:000080071700003 PM 10320950 ER PT J AU Barditch-Crovo, P Trapnell, CB Ette, E Zacur, HA Coresh, J Rocco, LE Hendrix, CW Flexner, C AF Barditch-Crovo, P Trapnell, CB Ette, E Zacur, HA Coresh, J Rocco, LE Hendrix, CW Flexner, C TI The effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DRUG-INTERACTIONS; SEVERE NEUTROPENIA; METABOLISM; WOMEN; LIVER; ETHINYLESTRADIOL; ETHYNYLESTRADIOL; CYTOCHROME-P-450; MICROSOMES; ESTRADIOL AB Background: Rifampin (INN, rifampicin), a CYP34A inducer, results in significant interactions when coadministered with combination oral contraceptives that contain norethindrone (INN, norethisterone) and ethinyl estradiol (INN, ethinylestradiol), Little is known about the effects of rifabutin, a related rifamycin. Objectives and Methods: The relative effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethindrone were evaluated in a prospective, randomized, double-blinded crossover study in 12 premenopausal women who were on a stable oral contraceptive regimen that contained 35 mu g ethinyl estradiol/l mg norethindrone, Subjects were randomized to receive 14 days of rifampin or rifabutin from days 7 through 21 of their menstrual cycle. After a 1-month washout period (only the oral contraceptives were taken), subjects were crossed over to the other rifamycin, Results: Rifampin significantly decreased the mean area under the plasma concentration-time curve from time 0 to 24 hours [AUC(0-24)] of ethinyl estradiol and the mean AUC(0-24) of norethindrone, Rifabutin significantly decreased the mean AUC(0-24) of ethinyl estradiol and the mean AUC(0-24) of norethindrone. The effect of rifampin was significantly greater than rifabutin on each AUC(0-24), Despite these changes, subjects did not ovulate (as determined by progesterone concentrations) during the cycle in which either rifamycin was administered, Levels of mean follicle-stimulating hormone increased 69% after rifampin. Conclusion: In this study, rifampin (600 mg daily) was a more significant inducer of ethinyl estradiol and norethindrone clearance than rifabutin (300 mg daily), but neither agent reversed the suppression of ovulation caused by oral contraceptives. The carefully monitored oral contraceptive administration and the limited exposure to rifamycins may restrict the application of this study to clinical situations. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. US FDA, Rockville, MD 20857 USA. RP Barditch-Crovo, P (reprint author), Johns Hopkins Hosp, Div Clin Pharmacol, Harvey 502,600 N Wolfe St, Baltimore, MD 21287 USA. RI Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 FU NCRR NIH HHS [RR-00052, RR-00722]; PHS HHS [223943002] NR 41 TC 63 Z9 65 U1 0 U2 4 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 APR PY 1999 VL 65 IS 4 BP 428 EP 438 DI 10.1016/S0009-9236(99)70138-4 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 190AZ UT WOS:000079940500012 PM 10223781 ER PT J AU Behrman, RE AF Behrman, RE TI FDA approval of antiretroviral agents: An evolving paradigm. SO DRUG INFORMATION JOURNAL LA English DT Article DE antiretroviral agents; FDA regulatory requirements; traditional approval; viral load reduction AB The approach to traditional approval of antiretroviral agents in the United States has recently evolved. As in the past, companies can provide confirmatory clinical endpoint data following accelerated approval; alternatively, they can base their claim of efficacy primarily on data demonstrating a sustained reduction in plasma HIV-1 RNA. This change was fueled by issues associated with conducting long-term clinical endpoint trials given the rapidly changing treatment strategies for HIV and the availability of potent combination regimens. The Food and Drug Administration (FDA) hopes that this new approach will help direct more resources to ambitious, collaborative clinical trials. The rapid evolution of traditional approval also illustrates the importance of close collaboration between industry, academia, and the FDA. This field would not have moved forward so rapidly without consensus initiatives such as the Surrogate Marker Collaborative Group, which provided evidence suggesting that a virologic response, in terms of changes in HIV-1 RNA, is a strong predictor of clinical benefit. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 1, Rockville, MD 20857 USA. RP Behrman, RE (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 1, 1451 Rockville Pike, Rockville, MD 20857 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD APR-JUN PY 1999 VL 33 IS 2 BP 337 EP 341 PG 5 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 204GP UT WOS:000080756000002 ER PT J AU Haffner, ME AF Haffner, ME TI Orphan drugs: The United States experience SO DRUG INFORMATION JOURNAL LA English DT Article DE orphan drugs; rare diseases; Orphan Drug Act; Food and Drug Administration AB This paper provides an overview of orphan drug legislation in the United States. Since passage of the Orphan Drug Act in 1983, 182 designated orphan products have received Food and Drug Administration approval for rare disease treatment or diagnosis. Incentives provided in the act-seven years of marketing exclusivity, protocol assistance, true credits, the orphan products grant program which authorizes grant moneys to support pivotal clinical trials, and user fee waiver-are discussed. Issues, challenges, and successes are outlined. important international initiatives in orphan drug legislation triggered by the United States Orphan Drug Act are highlighted. C1 US FDA, Off Ophan Prod Dev, Rockville, MD 20857 USA. RP Haffner, ME (reprint author), US FDA, Off Ophan Prod Dev, 5600 Fishers Lane,Room 8-73, Rockville, MD 20857 USA. NR 0 TC 2 Z9 3 U1 0 U2 1 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD APR-JUN PY 1999 VL 33 IS 2 BP 565 EP 568 PG 4 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 204GP UT WOS:000080756000026 ER PT J AU McNeil, MM Sweat, LB Carter, SL Watson, CB Holloway, JT Manning, R Altekruse, SF Blake, PA AF McNeil, MM Sweat, LB Carter, SL Watson, CB Holloway, JT Manning, R Altekruse, SF Blake, PA TI A Mexican restaurant-associated outbreak of Salmonella Enteritidis type 34 infections traced to a contaminated egg farm SO EPIDEMIOLOGY AND INFECTION LA English DT Article; Proceedings Paper CT 37th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 28-OCT 03, 1997 CL TORONTO, CANADA ID UNITED-STATES; PHAGE TYPE-4 AB In May 1996, the Georgia Division of Public Health was notified about a cluster of persons with Salmonella Enteritidis (SE) infections in Waycross, Georgia. A matched pair case-control study to determine risk factors for illness found a statistically significant association of SE infection with a history of having eaten at Restaurant A during the 5 days before onset of illness (relative risk = 13 [95% confidence interval (CI) = 3-62, P < 0.01]). In a second case-control study, to determine specific food exposures, consumption of a deep-fried Mexican dish (chile relleno) (4 of 21 cases vs. 0 of 26 controls, odds ratio undefined, 95% CI > 1.46, P = 0.034) was found to be significantly associated with SE infection. An environmental investigation found evidence of suboptimal food storage and cooking temperatures at Restaurant A; cross contamination of foods may have contributed to the low attributable risk identified for chile rellenos. Five of 37 Restaurant A food and environment specimens yielded SE strains. All five positive specimens were from chiles rellenos. Of the seven outbreak-associated strains (six patient isolates and one food isolate from Restaurant A) for which phage typing was conducted, all were phage type 34. A FDA traceback investigation through Restaurant A's single-egg supplier identified the potential source as three interrelated farms in South Carolina. Environmental culture from one of these farms yielded SE phage type 34. As a result of this outbreak, FDA helped institute a statewide egg quality-assurance programme in South Carolina to minimize SE contamination of eggs. C1 Georgia Dept Human Resources, Epidemiol & Prevent Branch, Atlanta, GA 30303 USA. Georgia Dept Human Resources, State Publ Hlth Lab, Div Publ Hlth, Atlanta, GA 30303 USA. SE Hlth Unit, Waycross, GA 31501 USA. Ware Cty Hlth Dept, Waycross, GA 31501 USA. Food & Drug Adm, Atlanta, GA 30333 USA. RP McNeil, MM (reprint author), Ctr Dis Control & Prevent, Div Bacterial & Mycot Dis, Mycot Dis Branch, Mailstop C-23, Atlanta, GA 30333 USA. NR 23 TC 5 Z9 5 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD APR PY 1999 VL 122 IS 2 BP 209 EP 215 DI 10.1017/S0950268899002216 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 201KV UT WOS:000080594700004 PM 10355784 ER PT J AU Uhl, K Grace, JM Kocisko, DA Jennings, BT Mitchell, AL Brewer, TG AF Uhl, K Grace, JM Kocisko, DA Jennings, BT Mitchell, AL Brewer, TG TI Effects of Plasmodium berghei infection on cytochromes P-450 2E1 and 3A2 SO EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS LA English DT Article DE cytochrome P-450; liver microsomes; Sprague-Dawley rats; malaria; Western blotting; isozymes ID ENDOTOXIN-INDUCED FEVER; PERFUSED-RAT-LIVER; MALARIA INFECTION; MICROSOMAL CYTOCHROME-P-450; PHARMACOKINETICS; THEOPHYLLINE; METABOLISM; HYDROXYLATION; PURIFICATION; ELIMINATION AB Metabolism and disposition of most drugs used to treat malaria are substantially altered in malaria infection. Few data are available that specify effects of malaria infection on drug metabolism pathways in humans or animal model systems. In this report, studies were undertaken to determine the effect of Plasmodium berghei infection on cytochrome P-450 (CYP450) 2E1 and 3A2-mediated metabolism and enzyme expression in rat liver microsomes. Malaria infection (MAL) resulted in significant decreases in total cytochrome P-450 content (56%, P <0.05) and NADPH cytochrome P-450 reductase activity (32%, P <0.05) as compared to control (CON) rats. Chlorzoxazone 4-hydroxylase activity (CYP2E1-mediated) showed no significant difference between CON and MAL microsomes while testosterone 6-beta-hydroxylase activity (CYP3A2-mediated) was reduced by 41% (P <0.05) in MAL. Enzyme kinetic studies and immunoblot analysis indicate that the loss of activity for CYP3A2 in malaria infection is due to significantly decreased CYP3A2 protein expression. The altered expression of CYP450s in malaria infection should be taken into account when treating patients with malaria in order to minimize drug-drug interactions or toxicity. C1 Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA. Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. RP Uhl, K (reprint author), US FDA, Off Clin Pharmacol Biopharmaceut, 9201 Corp Blvd,HFD-880, Rockville, MD 20850 USA. NR 40 TC 4 Z9 4 U1 0 U2 2 PU MEDECINE ET HYGIENE PI GENEVA 4 PA 78 AVE ROSERALE, 1211 GENEVA 4, SWITZERLAND SN 0378-7966 J9 EUR J DRUG METAB PH JI Eur. J. Drug Metabol. Pharmacokinet. PD APR-JUN PY 1999 VL 24 IS 2 BP 169 EP 176 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 236RG UT WOS:000082611900010 PM 10510746 ER PT J AU Chu, Y Hu, HM Winter, H Wood, WJ Doran, T Lashley, D Bashey, J Schuster, J Wood, J Lowe, BA Vetto, JT Weinberg, AD Puri, R Smith, JW Urba, WJ Fox, BA AF Chu, Y Hu, HM Winter, H Wood, WJ Doran, T Lashley, D Bashey, J Schuster, J Wood, J Lowe, BA Vetto, JT Weinberg, AD Puri, R Smith, JW Urba, WJ Fox, BA TI Examining the immune response in sentinel lymph nodes of mice and men SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Article; Proceedings Paper CT 1st International Congress on the Sentinel Node in Diagnosis and Treatment of Cancer CY APR 07-10, 1999 CL AMSTERDAM, NETHERLANDS DE tumor vaccine-draining lymph nodes; immune deviation; sentinel lymph nodes; immunological monitoring; tumor vaccines ID T-CELLS; ANTIGEN; TYPE-1; INTERLEUKIN-2; EXPRESSION; VACCINE; IL-12 AB Recently, it was recognized that an immune response develops along one of two major pathways. One leads to a destructive immune response (type I), while the alternative leads to a nondestructive immune response (type 2). Our studies in animal models suggest that therapeutic vaccines induce a tumor-specific type immune response while ineffective vaccines induce a type 2 response. These results have led us to examine the immune response in sentinel lymph nodes draining tumor vaccines of patients entered onto clinical trials for melanoma, breast and renal cell cancer. C1 Providence Portland Med Ctr, Robert W Franz Canc Res Ctr, Earle A Chiles Res Inst, Lab Mol & Tumor Immunol, Portland, OR 97213 USA. Oregon Grad Inst, Dept Biochem & Mol Biol, Portland, OR 97291 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Oregon Canc Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapy, Bethesda, MD 20892 USA. RP Fox, BA (reprint author), Providence Portland Med Ctr, Robert W Franz Canc Res Ctr, Earle A Chiles Res Inst, Lab Mol & Tumor Immunol, 4805 NE Glisan, Portland, OR 97213 USA. EM foxb@ohsu.edu RI Winter, Hauke/I-1394-2013 OI Winter, Hauke/0000-0001-8911-6218 FU NCI NIH HHS [1R21CA76078-01, R03-CA70299-02] NR 13 TC 6 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD APR PY 1999 VL 26 IS 4 SU S BP S50 EP S53 DI 10.1007/s002590050578 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 185XJ UT WOS:000079696000009 PM 10199933 ER PT J AU Cheeseman, MA Machuga, EJ Bailey, AB AF Cheeseman, MA Machuga, EJ Bailey, AB TI A tiered approach to threshold of regulation SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE threshold of regulation; structure-activity relationships; structural alerts; food additives; mutagenicity; food packaging ID NATIONAL-TOXICOLOGY-PROGRAM; CARCINOGENIC POTENCY DATABASE; CHEMICAL-STRUCTURE; ANIMAL BIOASSAYS; RODENT CARCINOGENS; CHRONOLOGICAL SUPPLEMENT; 44 CHEMICALS; MUTAGENICITY; SALMONELLA; CLASSIFICATION AB This paper presents methods for extending the principle of a single "threshold of regulation" to a range of dietary concentrations between 0.5 and 15 parts per billion by using structure-activity relationships, genotoxicity. and short-term toxicity data. Thc database used to develop the FDA's threshold of regulation was examined to determine whether structural parameters or the result of certain short-term toxicity tests could be used to define a subset of less potent substances that supports higher threshold levels, In addition, results of reproductive toxicity rests for 3306 compounds and other multidose toxicity tests for 2542 compounds were compared with the database of carcinogenic potencies to establish that carcinogenic endpoints are the must conservative toxicity endpoint for establishing thresholds of regulation. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Cheeseman, MA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-200,200 C St SW, Washington, DC 20204 USA. NR 44 TC 108 Z9 111 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD APR PY 1999 VL 37 IS 4 BP 387 EP 412 DI 10.1016/S0278-6915(99)00024-1 PG 26 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 210UD UT WOS:000081122300012 PM 10418955 ER PT J AU Bush, LM Williams, RA AF Bush, LM Williams, RA TI Diet and health: new problems new solutions SO FOOD POLICY LA English DT Article AB Our premise is that the US government has an established role in both tracking diet related diseases and in prevention of these diseases. As such, we note that the four major causes of morbidity and mortality associated with diet are heart disease, cancer, cerebrovascular disease and diabetes, The trends for these are generally toward decreasing incidence with the exception of diabetes, undoubtedly due in some part to US policies on nutrition. However, the trend for overweight, which is closely related with those illnesses: and for diabetes is increasing. We also note that there are socioeconomic concerns with overweight and the other illnesses that are negatively correlated with income and positively correlated with minority status. Also, children are increasingly becoming a concern due to the increasing incidence of overweight among children. The US government's role has been primarily in regulations addressing labeling and food fortification and developing dietary guidance. In terms of getting people to eat a healthier diet there are three avenues: (1) relying on individual choice between groups of foods; (2) relying on individual choice within groups of foods, or (3) presenting consumers with better food choices by encouraging manufacturers to reformulate foods. We argue that the latter has been neglected as a policy tool in the US arena and that we should be both tracking these foods and formulating policy to encourage positive development of these foods. We raise some possibilities for further study as to how and whether US policy can or should encourage such markets. (C) 1999 Published by Elsevier Science Ltd, All rights reserved. C1 US Dept HHS, Off Assistant Secretary Planning & Evaluat, Off Hlth Policy, Washington, DC 20201 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Market Studies, Washington, DC 20204 USA. RP Bush, LM (reprint author), US Dept HHS, Off Assistant Secretary Planning & Evaluat, Off Hlth Policy, Room 432E,200 Independence Ave SW, Washington, DC 20201 USA. NR 4 TC 8 Z9 9 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0306-9192 J9 FOOD POLICY JI Food Policy PD APR-JUN PY 1999 VL 24 IS 2-3 BP 135 EP 144 DI 10.1016/S0306-9192(99)00018-4 PG 10 WC Agricultural Economics & Policy; Economics; Food Science & Technology; Nutrition & Dietetics SC Agriculture; Business & Economics; Food Science & Technology; Nutrition & Dietetics GA 209YT UT WOS:000081078300003 ER PT J AU Kodell, RL Chen, JJ Jackson, CD Gaylor, DW AF Kodell, RL Chen, JJ Jackson, CD Gaylor, DW TI Using short-term tests to predict carcinogenic activity in the long-term bioassay SO HUMAN AND ECOLOGICAL RISK ASSESSMENT LA English DT Article DE Ames test; logistic regression; classification; positive predictivity; negative predictivity ID NATIONAL TOXICOLOGY PROGRAM; CHEMICAL-STRUCTURE; SALMONELLA ASSAY; LIVER; PROLIFERATION; MUTAGENICITY; RODENTS; ABILITY; MODEL AB A method for classifying chemicals with respect to carcinogenic potential based on short-term test results is presented. The method utilizes the logistic regression model to translate results from short-term toxicity assays into predictions of the likelihood that a chemical will be carcinogenic if tested in a long-term bioassay. The proposed method differs from previous approaches in two ways. First, statistical confidence limits on probabilities of cancer rather than central estimates of those probabilities are used for classification. Second, the method does not classify all chemicals in a data base with respect to carcinogenic potential. Instead, it identifies chemicals with highest and lowest likelihood of testing positive for carcinogenicity in the bioassay. A subset of chemicals with intermediate likelihood of being positive remains unclassified, and will require further testing, perhaps in a long-term bioassay. Two data bases of binary short-term and long-term test results from the literature are used to illustrate and evaluate the proposed procedure. A cross-validation analysis of one of the data sets suggests that, for a sufficiently rich data base of chemicals, the development of a robust predictive system to replace the bioassay for some unknown chemicals is a realistic goal. C1 US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Off Risk Assessment Policy & Res, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kodell, RL (reprint author), US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 26 TC 1 Z9 1 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 1999 VL 5 IS 2 BP 427 EP 443 PG 17 WC Biodiversity Conservation; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 194WE UT WOS:000080217100017 ER PT J AU Ruiz-Hidalgo, MJ Garces, C Laborda, J AF Ruiz-Hidalgo, MJ Garces, C Laborda, J TI Notch-1 expression levels in 3T3-L1 cells influence ras signaling and transformation by oncogenic ras SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE adipogenesis; differentiation; Notch; ras oncogene; 3T3 cells ID PROTEIN-KINASE ACTIVATION; ADIPOCYTIC DIFFERENTIATION; PREADIPOCYTES; ADIPOGENESIS; FIBROBLASTS; RECEPTOR; GENES AB Notch proteins participate in interactions between several cell types involved on the specification of numerous cell fates during development. We previously showed that enforced downregulation of Notch-1 expression prevented adipogenesis of 3T3-L1 cells. Since adipogenesis of 3T3-L1 cells can be induced by oncogenic ras, we studied whether this was also the case in 3T3-L1 cells with decreased levels of Notch-1 expression. We found that oncogenic ras induces transformation and not differentiation of 3T3-L1 cells with diminished levels of Notch-1. This result suggests that Notch-1 is implicated in the interpretation of signals leading to activation of p21 Ras. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Immunobiol Lab, Rockville, MD 20852 USA. RP Laborda, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Immunobiol Lab, Bldg 29B,Room 3NN04,HFM 564,1401 Rockville Pike, Rockville, MD 20852 USA. RI Laborda, Jorge/L-5726-2014; Ruiz-Hidalgo, Maria/L-1956-2014 OI Laborda, Jorge/0000-0002-9210-838X; NR 32 TC 10 Z9 10 U1 0 U2 4 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 APR PY 1999 VL 14 IS 4 BP 777 EP 783 PG 7 WC Oncology SC Oncology GA 178QW UT WOS:000079278300022 PM 10087329 ER PT J AU Maxwell, RJ Cohen, E Donoghue, DJ AF Maxwell, RJ Cohen, E Donoghue, DJ TI Determination of sarafloxacin residues in fortified and incurred eggs using on-line microdialysis and HPLC programmable fluorescence detection SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE ASTED; on-line microdialysis; fluorescence; HPLC; sarafloxacin; chicken; eggs ID PERFORMANCE LIQUID-CHROMATOGRAPHY; OXOLINIC ACID; ONLINE DIALYSIS; LAYING HENS; FLUMEQUINE; PLASMA; FISH; ENROFLOXACIN; RESISTANCE; LIVER AB Isolation of sarafloxacin (SAR) from fortified and incurred chicken eggs was done by a combination of liquid-liquid extraction and aqueous on-line microdialysis performed on an automated trace enrichment of dialysates (ASTED) system. The ASTED system coupled a sample cleanup procedure with HPLC and programmable fluorescence detection. Overall recoveries of 87-102% for SAR were obtained from samples fortified over a range of 1-100 ng/g. The relative standard deviation values ranged from 22 to 26% for samples fortified between 1 and 5 ng/g and from 2 to 12% for samples fortified between 10 and 100 ng/g. The limits of detection and quantitation were 0.2 and 1 ng/g, respectively. Eggs containing incurred SAR, which were collected over a 3-day dosing period and for 5 consecutive days thereafter, also were analyzed by using this technique. Because the method is automated, 35 samples can be processed within a 24-h period, which enables large data sets to be acquired over a short time period. C1 ARS, Eastern Reg Res Ctr, USDA, Wyndmor, PA 19038 USA. US FDA, Ctr Vet Med, Div Anim Res, Laurel, MD 20708 USA. RP Maxwell, RJ (reprint author), ARS, Eastern Reg Res Ctr, USDA, 600 E Mermaid Lane, Wyndmor, PA 19038 USA. NR 22 TC 28 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 1999 VL 47 IS 4 BP 1563 EP 1567 DI 10.1021/jf980986k PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 189HL UT WOS:000079899000045 PM 10564017 ER PT J AU Fleischman, GJ AF Fleischman, GJ TI Predicting temperature range in food slabs undergoing short-term/high-power microwave heating SO JOURNAL OF FOOD ENGINEERING LA English DT Article AB A closed-form solution to the heat equation, derived for one-dimensional microwave-heated slabs, is presented. The microwave energy distribution used in the heat equation is obtained from Maxwell's equations. Therefore, the potential exists of standing waves of microwave energy within the food. This phenomenon contributes to the nonuniform temperature pattern characteristic of microwave heating but is often neglected in theoretical predictions of temperatures. The solution allows temperature to be calculated as a function of thermal, geometric and dielectric properties of the food being heated and is valid for all microwave power levels and durations of heating. Previous work allowed such a solution only if very long durations and very low power levels of microwave heating were used. That the solution is closed-form allows its implementation in spreadsheet format. Simplifications to the closed-form solution that retain the standing wave phenomenon are shown. Their accuracy, however, is limited to approximately 40 s of heating. Results from the full dosed-form solution, using parameters measured in beef, show that the range of temperatures experienced by a microwave-heated beef slab is a sensitive function of slab width and time, with ranges as great as 50 degrees C, It is shown that thermal insulation at the slab faces slightly increases the temperature range. Another feature of the theoretical solution is the extreme sensitivity of temperature range to slab width in the 1-3 cm width interval, with decreasing sensitivity as slab widths increase beyond 4 cm. Sensitivity increases, however, as time increases, regardless of slab width. Lastly, a time-invariant temperature range minimum is seen in the 3-4 cm slab width interval. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Fleischman, GJ (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 8 TC 16 Z9 16 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0260-8774 J9 J FOOD ENG JI J. Food Eng. PD APR-MAY PY 1999 VL 40 IS 1-2 BP 81 EP 88 DI 10.1016/S0260-8774(99)00040-0 PG 8 WC Engineering, Chemical; Food Science & Technology SC Engineering; Food Science & Technology GA 196BT UT WOS:000080289700010 ER PT J AU Adams, AM Miller, KS Wekell, MM Dong, FM AF Adams, AM Miller, KS Wekell, MM Dong, FM TI Survival of Anisakis simplex in microwave-processed arrowtooth flounder (Atheresthes stomias) SO JOURNAL OF FOOD PROTECTION LA English DT Article ID STERILIZATION; DESTRUCTION; COOKING; FOOD AB The purpose of this study was to define the relationship between survival and temperature of nematodes of the species Anisakis simplex in microwave-processed arrowtooth flounder (Atheresthes stomias). Ten fillets (each 126 to 467 g, 0.5 to 1.75 cm thick), with an average of five larvae of Anisakis simplex per fillet, were processed to target temperatures on high (100%) power using a commercial 700-W microwave oven. Fillets were neither covered nor rotated and had a temperature probe inserted to two-thirds depth into the thickest portion. After the fillet was digested using a 1% pepsin solution, the viability of nematodes was determined by viewing them under a dissecting microscope. Survival rates were 31% at 140 degrees F (60 degrees C), 11% at 150 degrees F (65 degrees C), 2% at 160 degrees F (71 degrees C), 3% at 165 degrees F (74 degrees C), and 0% at 170 degrees F (77 degrees C). Microwave processing of standardized fillet "sandwiches," 14 cm long, 4.5 cm wide, and approximately 1.75 cm high, each of which was preinoculated with 10 live nematodes, resulted in no survival at either 160 degrees F or 170 degrees F. Using ultraviolet light to detect both viable and nonviable nematodes in fillet sandwiches as an alternative method to pepsin digestion resulted in survival rates of 1% at 140 degrees F (60 degrees C), 3% at 145 degrees F (63 degrees C), and 0% at 150 degrees F (65 degrees C). Smaller fillet sandwiches, which most likely had fewer cold spots during microwave processing, required 150 degrees F (65 degrees C), whereas larger whole fillets required 170 degrees F (77 degrees C) to kill larvae of Anisakis simplex. The parasites were most likely inactivated by a thermal mechanism of microwave treatment. Damage to the nematodes was often evident from ruptured cuticles that were no longer resistant to digestive enzymes. The high hydrostatic pressure and low chloride content of the pseudocoelomic fluid probably contributed greatly to the damage incurred by the larvae. C1 US FDA, Seafood Prod Res Ctr, Bothell, WA 98041 USA. Univ Washington, Sch Fisheries, Inst Food Sci & Technol, Seattle, WA 98105 USA. RP Adams, AM (reprint author), US FDA, Seafood Prod Res Ctr, POB 3012,22201 23rd Dr SE, Bothell, WA 98041 USA. EM aadams@ora.fda.gov NR 24 TC 27 Z9 31 U1 0 U2 4 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 1999 VL 62 IS 4 BP 403 EP 409 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 185DU UT WOS:000079653500017 PM 10419216 ER PT J AU Shapiro, SZ Maudru, T Peden, KWC AF Shapiro, SZ Maudru, T Peden, KWC TI Detection of human immunodeficiency virus type 1 after infection of unstimulated peripheral blood mononuclear cells SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID NUCLEAR-LOCALIZATION SIGNAL; REVERSE-TRANSCRIPTASE ASSAY; NONDIVIDING CELLS; MOLECULAR CLONE; HIV-1 INFECTION; MATRIX PROTEIN; TROPIC HIV-1; LYMPHOCYTES; REPLICATION; RETROVIRUS AB Application of a highly sensitive PCR-based reverse transcriptase (RT) assay to the analysis of the infection of CD4(+) cell lines with human immunodeficiency virus type 1 (HIV-1) demonstrated that virus production can be detected as early as 24 h after infection. Most of the signal at 24 h was due to virus production, as it could be substantially reduced by prior treatment with the RT inhibitor zidovudine. Virus production at 24 and 48 h was unaffected by the protease inhibitor indinavir. Infection of unstimulated peripheral blood mononuclear cells (PBMC) with a macrophage-tropic HIV-1 isolate yielded increasing virus production for 2-3 weeks, while infection with a T-cell line-tropic isolate yielded only low and sporadic virus production. Productive infection of unstimulated PBMC by the macrophage-tropic virus required functional Gag matrix and Vpr proteins; therefore, the monocyte-derived macrophage is probably the virus-producing cell in these cultures. C1 US FDA, Ctr Biol Evaluat & Res, Lab Retrovirus Res, Bethesda, MD 20892 USA. RP Peden, KWC (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Retrovirus Res, Bldg 29A,Room 3D08,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 22 TC 4 Z9 4 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD APR PY 1999 VL 80 BP 857 EP 861 PN 4 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 182WN UT WOS:000079521300005 PM 10211953 ER PT J AU Ichino, M Mor, G Conover, J Weiss, WR Takeno, M Ishii, KJ Klinman, DM AF Ichino, M Mor, G Conover, J Weiss, WR Takeno, M Ishii, KJ Klinman, DM TI Factors associated with the development of neonatal tolerance after the administration of a plasmid DNA vaccine SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEPATITIS-B VIRUS; CIRCUMSPOROZOITE PROTEIN; T-CELLS; IMMUNE-RESPONSES; NEWBORN MICE; IMMUNIZATION; INJECTION; INDUCTION; MALARIA; ACQUISITION AB A plasmid DNA vaccine encoding the circumsporozoite protein of malaria (pCSP) induces tolerance rather than immunity when administered to newborn mice. We find that this tolerance persists for >1 yr after neonatal pCSP administration and interferes with the induction of protective immunity in animals challenged with live sporozoites. Susceptibility to tolerance induction wanes rapidly with age, disappearing within 1 wk of birth. Higher doses of plasmid are more tolerogenic, and susceptibility to tolerance is not MHC-restricted. CD8(+) T cells from tolerant mice suppress the in vitro Ag-specific immune response of cells from adult mice immunized with pCSP, Similarly, CD8(+) T cells from tolerant mice transfer nonresponsiveness to naive syngeneic recipients, These findings clarify the cellular basis and factors contributing to the development of DNA vaccine-induced neonatal tolerance. C1 US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. USN, Med Res Inst, Malaria Program, Bethesda, MD 20889 USA. RP Klinman, DM (reprint author), US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bldg 29A,Room 3D10, Bethesda, MD 20892 USA. EM klinman@al.cber.fda.gov RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 34 TC 36 Z9 38 U1 1 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 1999 VL 162 IS 7 BP 3814 EP 3818 PG 5 WC Immunology SC Immunology GA 178QT UT WOS:000079278000012 PM 10201898 ER PT J AU Olds, GR King, C Hewlett, J Olveda, R Wu, G Ouma, J Peters, P McGarvey, S Odhiambo, O Koech, D Liu, CY Aligui, G Gachihi, G Kombe, Y Parraga, I Ramirez, B Whalen, C Horton, RJ Reeve, P AF Olds, GR King, C Hewlett, J Olveda, R Wu, G Ouma, J Peters, P McGarvey, S Odhiambo, O Koech, D Liu, CY Aligui, G Gachihi, G Kombe, Y Parraga, I Ramirez, B Whalen, C Horton, RJ Reeve, P TI Double-blind placebo-controlled study of concurrent administration of albendazole and praziquantel in schoolchildren with schistosomiasis and geohelminths SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID KENYAN SCHOOL-CHILDREN; URINARY SCHISTOSOMIASIS; TARGETED CHEMOTHERAPY; HAEMATOBIUM INFECTION; TRICHURIS-TRICHIURA; COGNITIVE FUNCTION; MANSONI INFECTION; COMMUNITY; EFFICACY; TRIAL AB A double-blind placebo-controlled study of the concurrent administration of albendazole and praziquantel was conducted in >1500 children with high-prevalences of geohelminths and schistosomiasis. The study sites were in China and the Philippines, including 2 strains Of Schistosoma japonicum,: and 2 different regions of Kenya, 1 each with endemic Schistosoma mansoni or Schistosoma haematobium. Neither medication affected the cure rate of the other. There was no difference between the side effect rate from albendazole or the double placebo. Praziquantel-treated children had more nausea, abdominal pain, and headache but these side effects were statistically more common in children with schistosomiasis, suggesting a strong influence of dying parasites. The subjects were followed for 6 months for changes in infection status, growth parameters, hemoglobin, and schistosomiasis morbidity, In all 4 sites, a significant 6-month increase in serum hemoglobin was observed in children who received praziquantel, strongly supporting population-based mass treatment. C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. Res Inst Trop Med, Manila, Philippines. US FDA, Off Vaccines Res & Review, Div Viral Prod, Washington, DC 20204 USA. Nanjing Univ, Nanjing 210008, Peoples R China. Sichuan Inst Parasit Dis, Sichuan, Peoples R China. Kenya Med Res Inst, Nairobi, Kenya. Minist Hlth, Div Vector Borne Dis, Nairobi, Kenya. Brown Univ, Sch Med, Miriam Hosp, Providence, RI 02912 USA. SmithKline Beecham, Brentfore, England. RP Olds, GR (reprint author), Metrohlth Med Ctr, Dept Med, 2500 MetroHlth Dr, Cleveland, OH 44109 USA. RI McGarvey, Stephen/I-1788-2014 NR 42 TC 92 Z9 92 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1999 VL 179 IS 4 BP 996 EP 1003 DI 10.1086/314686 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 182MY UT WOS:000079503800029 PM 10068597 ER PT J AU Canas, BJ Yurawecz, MP AF Canas, BJ Yurawecz, MP TI Ethyl carbamate formation during urea complexation for fractionation of fatty acids SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Letter C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Canas, BJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW,HFS-347, Washington, DC 20204 USA. NR 9 TC 21 Z9 21 U1 1 U2 5 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD APR PY 1999 VL 76 IS 4 BP 537 EP 537 DI 10.1007/s11746-999-0038-y PG 1 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 190JH UT WOS:000079959000021 ER PT J AU Haverkos, HW AF Haverkos, HW TI Relative rates of AIDS among racial/ethnic groups by exposure categories (vol 91, pg 17, 1999) SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Correction C1 US FDA, Rockville, MD 20857 USA. RP Haverkos, HW (reprint author), US FDA, HFD-530,5600 Fishers Ln, Rockville, MD 20857 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD APR PY 1999 VL 91 IS 4 BP 192 EP 192 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 194XX UT WOS:000080221000002 ER PT J AU Lewis, AM Alling, DW Banks, SM Soddu, S Cook, JL AF Lewis, AM Alling, DW Banks, SM Soddu, S Cook, JL TI Evaluating virus-transformed cell tumorigenicity SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE tumorigenicity; tumorigenicity assays; transformed phenotype; animal models; DNA tumor viruses; adenovirus type 12; simian virus 40 ID SYRIAN-HAMSTER CELLS; HETEROGENEITY; INHIBITION; GROWTH AB The tumorigenicity of adenovirus (Ad) 12-transformed mouse cells was evaluated by analyzing the relationship of tumor cell dose to tumor incidence and tumor latency. The tumor producing dose 50% endpoint values used to define these relationships remained stable during 52 weeks of serial passage in tissue culture and were not determined by low frequency events within the cell population. The data from these analyses suggest that the phenotype of Ad12-transformed mouse cells is influenced by two set of traits-those traits that determine the threshold number of cells required for tumor formation and those that extend the cell dose-dependent tumor latency period. Both traits are established independently of cell immortalization, and both can be influenced by the immunological status of tumor-challenged animals. These observations were verified by using mouse cells transformed by Ad5 and SV40. The biological and molecular processes that contribute to these traits remain to be determined. The approach developed by this analysis provides a reliable, quantitative means of evaluating endogenous traits that determine transformed cell tumorigenicity. This method can also be used to test the effects of tumor cell manipulations or changes in host response that could alter expression or detection of these neoplastic cell traits. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIH, Viral Pathogenesis Sect, Immunopathol Lab, Bethesda, MD 20892 USA. NIAID, Off Intramural Director, NIH, Bethesda, MD 20892 USA. Natl Jewish Med & Res Ctr, Dept Med, Robert W Lisle Res Lab Immunol & Tumor Cell Biol, Denver, CO 80206 USA. RP Lewis, AM (reprint author), US FDA, OVRR, CBER, HFM 400,1401 Rockville Pike, Rockville, MD 20852 USA. NR 17 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD APR PY 1999 VL 79 IS 1 BP 41 EP 50 DI 10.1016/S0166-0934(98)00182-7 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 191PQ UT WOS:000080031100005 PM 10328534 ER PT J AU Ray, SC Wang, YM Laeyendecker, O Ticehurst, JR Villano, SA Thomas, DL AF Ray, SC Wang, YM Laeyendecker, O Ticehurst, JR Villano, SA Thomas, DL TI Acute hepatitis C virus structural gene sequences as predictors of persistent viremia: Hypervariable region 1 as a decoy SO JOURNAL OF VIROLOGY LA English DT Article ID NON-B-HEPATITIS; NON-A; ENVELOPE GLYCOPROTEIN; ANTIBODY-RESPONSE; MUTATION-RATE; DRUG-USERS; RNA LEVELS; INFECTION; DIVERSITY; EVOLUTION AB We hypothesized that hepatitis C virus (HCV) persistence is related to the sequence variability of putative envelope genes. This hypothesis was tested by characterizing quasispecies in specimens collected every six months from a cohort of acutely HCV-infected subjects (mean duration of specimen collection, 72 months after seroconversion). We evaluated 5 individuals who spontaneously cleared viremia and 10 individuals with persistent viremia by cloning 33 1-kb amplicons that spanned E1 and the 5' half of E2, including hypervariable region 1 (HVR1), To assess the quasispecies complexity and to detect variants For sequencing, the first PCR-positive sample was examined by using a previously described method that combines heteroduplex analysis and analysis of single-stranded conformational polymorphisms. The ratio of nonsynonymous to synonymous substitutions (d(N)/d(S)) within each sample was evaluated as an indicator of relative selective pressure. Amino acid sequences were analyzed for signature patterns, glycosylation signals, and charger Quasispecies complexity was higher and E1 d(N)/d(S) ratios (selective pressure) were lower in those with persistent viremia; the association with persistence was strengthened by the presence of a combination of both characteristics, In contrast, a trend toward higher HVR1 d(N)/d(S), ratios was detected among those with persistent viremia. We did not detect any such association for factors that may affect complexity such as serum HCV RNA concentration, HVR1 had a lower positive charge in subjects with persistent viremia, although no consistent motifs were detected. Our data suggest that HCV persistence is associated with a complex quasispecies and immune response to HVR1. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Third Mil Med Univ, SW Hosp, Dept Infect Dis, Chongqing, Peoples R China. RP Thomas, DL (reprint author), Div Infect Dis, 720 Rutland Ave,Ross 1159, Baltimore, MD 21205 USA. RI Laeyendecker, Oliver/B-9331-2009; Ray, Stuart/B-7527-2008; Ticehurst, John/I-7532-2012; OI Ray, Stuart/0000-0002-1051-7260; Laeyendecker, Oliver/0000-0002-6429-4760 FU Intramural NIH HHS [Z99 AI999999]; NIAID NIH HHS [IU19 AI-40035, N01AI40035, U19 AI040035] NR 59 TC 148 Z9 161 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 APR PY 1999 VL 73 IS 4 BP 2938 EP 2946 PG 9 WC Virology SC Virology GA 175XY UT WOS:000079122400043 PM 10074143 ER PT J AU Sakurai, H Williamson, RA Crowe, JE Beeler, JA Poignard, P Bastidas, RB Chanock, RM Burton, DR AF Sakurai, H Williamson, RA Crowe, JE Beeler, JA Poignard, P Bastidas, RB Chanock, RM Burton, DR TI Human antibody responses to mature and immature forms of viral envelope in respiratory syncytial virus infection: Significance for subunit vaccines SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; COMBINATORIAL LIBRARIES; FUSION GLYCOPROTEIN; SYNTHETIC PEPTIDES; F-GLYCOPROTEIN; FAB FRAGMENTS; RSV; MICE; PROTECTION; CHILDREN AB A number of antibodies generated during human respiratory syncytial virus (RSV) infection have been cloned by the phage library approach. Antibodies reactive with an immunodominant epitope on the F glycoprotein of this virus have a high affinity for affinity-purified F antigen. These antibodies, however, have a much lower affinity for mature F glycoprotein on the surface of infected cells and are nonneutralizing. In contrast, a patent neutralizing antibody has a high affinity for mature F protein but a much lower affinity for purified F protein or F protein in viral lysates. The data indicate that at least two F protein immunogens are produced during natural RSV infection: immature F, found in viral lysates, and mature F, found on infected cells or virions. Binding studies with polyclonal human immunoglobulin G suggest that the antibody responses to the two immunogens are of similar magnitudes. Competitive binding studies suggest that overlap between the responses is relatively limited. A mature envelope with an antigenic configuration different from that of the immature envelope has an evolutionary advantage in that the infecting virus is less subject to neutralization by the humoral response to the immature envelope that inevitably arises following lysis of infected cells. Subunit vaccines may be at a disadvantage because they most often resemble immature envelope molecules and ignore this aspect of viral evasion. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Kaneka Corp, Takasago Inst, Takasago, Hyogo 676, Japan. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. US FDA, Rockville, MD 20857 USA. NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Williamson, RA (reprint author), Scripps Res Inst, Dept Immunol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM anthony@scripps.edu; burton@scripps.edu RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 FU NIAID NIH HHS [AI 39162] NR 41 TC 42 Z9 43 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1999 VL 73 IS 4 BP 2956 EP 2962 PG 7 WC Virology SC Virology GA 175XY UT WOS:000079122400045 PM 10074145 ER PT J AU Major, ME Mihalik, K Fernandez, J Seidman, J Kleiner, D Kolykhalov, AA Rice, CM Feinstone, SM AF Major, ME Mihalik, K Fernandez, J Seidman, J Kleiner, D Kolykhalov, AA Rice, CM Feinstone, SM TI Long-term follow-up of chimpanzees inoculated with the first infectious clone for hepatitis C virus SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; HUMORAL IMMUNE-RESPONSE; NON-B HEPATITIS; HYPERVARIABLE REGION-1; NON-A; NONSTRUCTURAL PROTEIN-3; ANTIBODY-RESPONSE; HYPERIMMUNE SERUM; ENVELOPE PROTEINS; CELL EPITOPE AB Two chimpanzees (Ch1535 and Ch1536) became infected with hepatitis C virus (HCV) following intrahepatic inoculation with RNA transcribed from a full-length cDNA clone of the virus. Both animals were persistently infected and have been followed for 60 weeks. They showed similar responses to infection, with transient liver enzyme elevations and liver inflammatory responses, which peaked at weeks 17 (Ch1535) and 12 (Ch1536) postinoculation (p.i.). Antibody responses to structural and nonstructural proteins were first detected at weeks 13 (Ch1535) and 10 (Ch1536) p.i. Serum RNA titers increased steadily during the first 10 to 13 weeks but decreased sharply in both animals following antibody and inflammatory responses. Despite direct evidence of humoral immune responses to multiple viral antigens, including hypervariable region 1 (HVR1), both animals remained chronically infected. Detailed sequence analysis of serum HCV RNA revealed no change in the majority HVR1 sequence in Ch1535 and a single-amino-acid mutation in Ch1536, with very little clonal variation in either animal. Full-length genome analysis at week 60 revealed several amino acid substitutions localized to antigens E1, E2, p7, NS3, and NS5. Of these, 55.6 and 40% were present as the majority sequence in serum RNA isolated at week 26 p.i. (Ch1535) and week 22 p.i. (Ch1536), respectively, and could represent immune escape mutations. Mutations accumulated at a rate of 1.57 x 10(-3) and 1.48 x 10(-3) nucleotide substitutions/site/year for Ch1535 and Ch1536, respectively. Taken together, these data indicate that establishment of a persistent HCV infection in these chimpanzees is not due to changes in HVR1; however, the possibility remains that mutations arising in other parts of the genome contributed to this persistence. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Hepatatis Res Lab, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. RP Feinstone, SM (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Hepatatis Res Lab, Bldg 29A,Rm 1D14,HFM 448,8800 Rockville Pike, Bethesda, MD 20892 USA. EM feinstone@cber.fda.gov OI Kleiner, David/0000-0003-3442-4453 FU NCI NIH HHS [CA57973, R01 CA057973]; NIAID NIH HHS [N01AI40034] NR 71 TC 105 Z9 111 U1 0 U2 0 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 1999 VL 73 IS 4 BP 3317 EP 3325 PG 9 WC Virology SC Virology GA 175XY UT WOS:000079122400086 PM 10074186 ER PT J AU Baker, EH Chaput, MP Clavet, CR Varney, GW To, TM Lytle, CD AF Baker, EH Chaput, MP Clavet, CR Varney, GW To, TM Lytle, CD TI Evaluation of endoscope sheaths as viral barriers SO LARYNGOSCOPE LA English DT Article DE endoscope sheath; viral barrier; quality assurance ID VIRUS; CONDOMS AB Objectives: Evaluate ENT endoscope sheaths as barriers to virus passage. Study Design "Defective" sheaths covering an endoscope were, challenged with virus to determine how many virus particles could be recovered from the endoscope, Methods: Sheaths with small laser-drilled holes (2 to 30 mu m) were challenged with high-titer virus suspensions (10(8) viruses/mL). The inside of the sheath and the endoscope were separately rinsed to recover any virus that penetrated through the hole in the sheath. In an attempt to assess the possible importance of holes in the sheaths, a sequential test was conducted with an initial virus challenge outside a defective sheath (30-micron hole in the sheath), after which the possibly contaminated endoscope was removed and inserted into a second defective sheath (with a 20-micron hole at the same location) to determine whether the contaminating virus would pass outward through the second sheath. Results: Small volumes of virus-containing fluid penetrated through the hole, e.g;, 500 virus particles passed through one of three 30-mu m holes. A significant fraction of those virus particles was occasionally found on the endoscope after removal from the sheath, Similar results were obtained with sheaths that had small tears (34-84 mu m in length, from punctures with fine wires), Although some virus penetration could occur during the initial challenge contaminating the endoscope, no virus was detected passing outward through the second sheath. Conclusions: Use of a sheath combined with intermediate level disinfection should provide a safe instrument for ENT endoscopy. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. US FDA, Winchester Engn & Analyt Ctr, Winchester, MA USA. RP Baker, EH (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-470,9200 Corp Blvd, Rockville, MD 20852 USA. EM khb@cdrh.fda.gov NR 15 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 1999 VL 109 IS 4 BP 636 EP 639 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 183EM UT WOS:000079541100022 ER PT J AU Sehat, N Rickert, R Mossoba, MM Kramer, JKG Yurawecz, MP Roach, JAG Adlof, RO Morehouse, KM Fritsche, J Eulitz, KD Steinhart, H Ku, Y AF Sehat, N Rickert, R Mossoba, MM Kramer, JKG Yurawecz, MP Roach, JAG Adlof, RO Morehouse, KM Fritsche, J Eulitz, KD Steinhart, H Ku, Y TI Improved separation of conjugated fatty acid methyl esters by silver ion-high-performance liquid chromatography SO LIPIDS LA English DT Article ID LINOLEIC-ACID; GAS-CHROMATOGRAPHY; ISOMERS; IDENTIFICATION; MILK; TISSUE; CHEESE; CLA AB Operating from one to six silver ion-high-performance liquid chromatography (Ag+-HPLC) columns in series progressively improved the resolution of the methyl esters of conjugated linoleic acid (CLA) isomeric mixtures from natural and commercial products. in natural products, the 8 trans, 10 cis-octadecadienoic (18:2) acid was resolved from the more abundant 7 trans, 9 cis-18:2, and the 10 trans, 12 cis-18:2 was separated from the major 9 cis, 11 trans-18:2 peak. In addition, both ii trans, 13 cis-18:2 and ii cis, 13 trans-18:2 isomers were found in natural products and were separated; the presence of the latter, 11 cis, 13 trans-18:2, was established in commercial CLA preparations. Three Ag+-HPLC columns in series appeared to be the best compromise to obtain satisfactory resolution of most CLA isomers found in natural products. A single Ag+-HPLC column in series with one of several normal-phase columns did not improve the resolution of CLA isomers as compared to that of the former alone. The 20:2 conjugated fatty acid isomers ii cis, 13 trans-20:2 and 12 trans, 14 cis-20:2, which were synthesized by alkali isomerization from ii cis, 14 cis-20:2, eluted in the same region of the Ag+-HPLC chromatogram just before the corresponding geometric CLA isomers. Therefore, CLA isomers will require isolation based on chain length prior to Ag+-H PLC separation. The positions of conjugated double bonds in 20:2 and 18:2 isomers were established by gas chromatography-electron ionization mass spectrometry as their 4,4-dimethyloxazoline derivatives. The double-bond geometry was determined by gas chromatography-direct deposition-Fourier transform infrared spectroscopy and by the Ag+-HPLC relative elution order. C1 US FDA, Off Food Labeling, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Univ Hamburg, Inst Food Chem, Hamburg, Germany. Agr & Agri Food Canada, Food Res Ctr, So Crop Protect, Guelph, ON N1G 2W1, Canada. ARS, USDA, NCAUR, Peoria, IL 61604 USA. RP Ku, Y (reprint author), US FDA, Off Food Labeling, Ctr Food Safety & Appl Nutr, HFS-175,200 C St SW, Washington, DC 20204 USA. NR 18 TC 123 Z9 129 U1 2 U2 21 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD APR PY 1999 VL 34 IS 4 BP 407 EP 413 DI 10.1007/s11745-999-0379-3 PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 194ZU UT WOS:000080225300011 PM 10443974 ER PT J AU Arani, RB Rao, MB AF Arani, RB Rao, MB TI A result on a 2x2 survival experiment (vol 146, pg 63, 1997) SO MATHEMATICAL BIOSCIENCES LA English DT Correction C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. N Dakota State Univ, Dept Stat, Fargo, ND 58105 USA. RP Arani, RB (reprint author), Univ Alabama, Ctr Comprehens Canc, Biostat Unit, 1824 6th Ave S-WTI 153, Birmingham, AL 35294 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD APR PY 1999 VL 158 IS 1 BP 93 EP 93 PG 1 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 185BJ UT WOS:000079648000004 ER PT J AU Pande, M Cameron, JA Vig, PJS Ali, SF Desaiah, D AF Pande, M Cameron, JA Vig, PJS Ali, SF Desaiah, D TI Inhibition of calcium ATPase by phencyclidine in rat brain SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE calcium; ATPase; central nervous system; phencyclidine; inhibition; in vitro; in vivo ID NICOTINIC ACETYLCHOLINE-RECEPTOR; CHANNEL; BINDING; NMDA; MODULATION; DOPAMINE; NEURONS; OPIATE; SYSTEM AB Phencyclidine (PCP) is a potent psychotomimetic drug of abuse and has profound effect on the functioning of the central nervous system (CNS). Many of the CNS functions are known to be mediated by calcium (Ca2+). In the present study we have investigated the effects of PCP on Ca2+ ATPase activity in rat brain both in vitro and in vivo. For in vitro studies, synaptic membrane fractions prepared from normal rat brain were incubated with PCP at different concentrations (25-100 mu M) before the addition of substrate. For n vivo studies, rats were treated with a single moderate dose of PCP (10 mg/kg, IP) and animals were sacrificed at 1,2, 6 and 12 h after treatment. Ca2+ ATPase activity in synaptic membrane fractions was assayed by estimation of inorganic phosphate. PCP inhibited the Ca2+ ATPase in vitro in a concentration dependent manner with significant effect at 50 and 100 mu M. A significant time-dependent reduction of the Ca2+ ATPase activity was evident in vivo. As early as 2 h after the treatment of rats with PCP the ATPase activity was significantly reduced. The reduction of Ca2+ ATPase observed even at 12 h after treatment suggesting a prolonged presence of the drug in the brain tissue. Further, kinetic studies in vitro indicated PCP to be a competitive inhibitor of Ca2+ ATPase with respect to the substrate, ATP. The present findings indicate that PCP inhibits synaptic membrane Ca2+ ATPase thus altering cellular Ca2+ homeostasis in CNS which may partially explain the pharmacological effects of the drug and/or its neurotoxicity. C1 Univ Mississippi, Med Ctr, Dept Neurol, Jackson, MS 39216 USA. Jackson State Univ, Dept Biol, Jackson, MS USA. NCTR, Div Neurotoxicol, Sect Neurochem, Jefferson, AR USA. RP Desaiah, D (reprint author), Univ Mississippi, Med Ctr, Dept Neurol, Jackson, MS 39216 USA. FU NHLBI NIH HHS [T32HL07635] NR 33 TC 3 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD APR PY 1999 VL 194 IS 1-2 BP 173 EP 177 DI 10.1023/A:1006911420745 PG 5 WC Cell Biology SC Cell Biology GA 202GP UT WOS:000080644200020 PM 10391137 ER PT J AU Khan, AA Nawaz, MS Khan, SA Cerniglia, CE AF Khan, AA Nawaz, MS Khan, SA Cerniglia, CE TI Identification of Aeromonas trota (hybridization group 13) by amplification of the aerolysin gene using polymerase chain reaction SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE PCR; Aeromonas trota; aerolysin gene; hybridization group 13; detection ID CLINICAL SPECIMENS; SEQUENCE; VERONII; GROWTH AB Aeromonas trota is recognized as an important enteropathogen, and its haemolysin (aerolysin) is purported to be one of the virulence factors. Rapid detection and identification of A. trota is important for early and specific diagnosis of the infectious diseases that it causes. Synthetic oligonucleotide primers were used in a polymerase chain reaction (PCR) technique to amplify a species-specific sequence of the aerA gene, which encodes the aerolysin of A. trota. A DNA fragment of 622 bp was amplified from both lysed cells and isolated DNA from A. trota. The identity of the amplified 622 bp fragment was confirmed by digestion with BamHI restriction endonuclease, which produced the predicted 557 and 65 bp fragments. The lower limit for detection of the aerA gene by PCR amplification was 10 pg of total DNA or 10-15 cells ml(-1). Primer specificity for A. trota was determined by the PCR assay with eel Is of 55 strains of Aeromonas spp., including all of the 14 currently recognized DNA hybridization groups. A strain of Aeromonas enteropelogenes that had been reclassified as A. trota was also PCR positive. The method described here can be used to detect aerolysin-producing A. trota (hybridization group 13) strains from environmental and clinical samples without the use of selective media or additional biochemical tests. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Khan, AA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 18 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD APR PY 1999 VL 13 IS 2 BP 93 EP 98 DI 10.1006/mcpr.1999.0222 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 190CL UT WOS:000079943900003 PM 10208799 ER PT J AU Brenneman, KA Cattley, RC Ali, SF Dorman, DC AF Brenneman, KA Cattley, RC Ali, SF Dorman, DC TI Manganese-induced developmental neurotoxicity in the CD rat: Is oxidative damage a mechanism of action? SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 15th International Neurotoxicology Conference CY OCT 26-29, 1997 CL LITTLE ROCK, ARKANSAS SP Agcy Tox Substances & Dis Registry, US EPA, Natl Human & Environm Effects Res Lab, Natl Ctr Environm Assessment, Ferroalloys Assoc, Int Manganese Inst, Natl Inst Environm Hlth Sci, Ethyl Corp, NINDS, Ctr Dis Control & Prevent DE manganese; developmental neurotoxicity; oxidative damage; ROS; 8-OHdG; CD rat ID DEGENERATIVE DISEASES; MITOCHONDRIAL-DNA; ELEVATED 8-HYDROXYDEOXYGUANOSINE; PEROXISOME PROLIFERATORS; PARKINSONS-DISEASE; MAGNETIC-RESONANCE; CHEMICAL FORM; HEPATIC DNA; BRAIN; CHLORIDE AB Inhalation of high concentrations of manganese (Mn) is associated with an extrapyramidal motor disorder in humans. Oxidative damage, mediated by increased levels of Mn in dopaminergic brain regions and mitochondria, is a hypothesized mechanism of action for Mn-induced neuronal degeneration and loss. To test this proposed mechanism, developing CD rats, which may be at an increased risk for Mn-induced neurotoxicity, were exposed orally to 0, 25, or 50 mg/kg/day of MnCl2 from postnatal day (PND) I to 49 Brain regional and mitochondrial Mn levels, brain regional reactive oxygen species (ROS) levels, and whole-brain nuclear and mitochondrial 8-OHdG levels were used to evaluate Mn-mediated oxidative damage. High-dose Mn exposure was associated with increased spontaneous motor activity on PND 21 and decreased body weights on PND 49. On PND 21, Mn concentrations were increased in brain regions and mitochondrial fractions in both low- and high-dose groups. ROS levels were elevated in cerebellum but not striatum. On PND 49, Mn concentrations in brain regions and mitochondrial fractions were increased only in the high-dose group. Mn exposure did not significantly alter 8-OHdG levels in either mitochondrial or nuclear DNA. Selective uptake of Mn by the striatum or mitochondrial fraction was not demonstrated at either time point. These data allow us to conclude that oral exposure to high levels of Mn in developing CD rats resulted in increased brain regional and mitochondrial Mn levels, increased motor activity, and decreased body weights but not in selective accumulation of Mn in the striatum or mitochondr ial fraction of any brain region or elevations in striatal ROS or whole-brain 8-OHdG levels. These findings do not support the hypothesis that oxidative damage, as assessed by ROS and 8-OHdG levels, is a mechanism of action in Mn-induced developmental neurotoxicity in the CD rat. (C) 1999 Inter Press, Inc. C1 Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Brenneman, KA (reprint author), Chem Ind Inst Toxicol, 6 Davis Dr,POB 12137, Res Triangle Pk, NC 27709 USA. NR 59 TC 51 Z9 53 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD APR-JUN PY 1999 VL 20 IS 2-3 BP 477 EP 487 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 205ZE UT WOS:000080850400030 PM 10385906 ER PT J AU Koller, E Gibert, G Green, L Mann, M Bernstein, B AF Koller, E Gibert, G Green, L Mann, M Bernstein, B TI Thrombotic events associated with megestrol acetate in patients with AIDS cachexia SO NUTRITION LA English DT Article ID ACTIVATED PROTEIN-C; 3RD-GENERATION ORAL-CONTRACEPTIVES; VENOUS THROMBOSIS; ANOREXIA; CANCER; RESISTANCE; MUTATION; WOMEN; RISK C1 US FDA, Ctr Drug Evaluat, Rockville, MD 20857 USA. Vet Affairs Ctr, Washington, DC USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Koller, E (reprint author), US FDA, Ctr Drug Evaluat, Parklawn Bldg,Room 14 B04-HFD 510,5600 Fishers La, Rockville, MD 20857 USA. NR 16 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD APR PY 1999 VL 15 IS 4 BP 294 EP 298 DI 10.1016/S0899-9007(99)00007-6 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 188GH UT WOS:000079838100007 PM 10319362 ER PT J AU Gans, HA Lew-Yasukawa, L Beeler, J DeHovitz, R Maldonado, Y Arvin, AM AF Gans, HA Lew-Yasukawa, L Beeler, J DeHovitz, R Maldonado, Y Arvin, AM TI Immune responses of 6, 9 and 12 month old infants immunized with measles or mumps vaccine and the effects of passive antibodies on these responses SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Stanford Univ, Med Ctr, Stanford, CA 94305 USA. US FDA, Hlth & Human Serv, Rockville, MD 20857 USA. Palo Alto Med Fdn, Palo Alto, CA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 939 BP 161A EP 161A DI 10.1203/00006450-199904020-00956 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476700940 ER PT J AU Viraraghavan, R Pikis, A Rakusan, TA Patel, KM Rodriguez, WJ AF Viraraghavan, R Pikis, A Rakusan, TA Patel, KM Rodriguez, WJ TI Nasopharyngeal carriage of Streptococcus pneumoniae: Is there a difference between HIV-infected patients and non-HIV well children? A 3 year outpatient experience SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. US FDA, CDER, Div Special Pathogens & Immunol Drug Prod, Rockville, MD 20857 USA. NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 1035 BP 177A EP 177A DI 10.1203/00006450-199904020-01052 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476701036 ER PT J AU Salive, ME Stein, DH AF Salive, ME Stein, DH TI Predictors and correlates of prevention research careers: A national study of residency graduates SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT 124th Annual Meeting of the American-Public-Health-Association CY NOV 17-21, 1996 CL NEW YORK, NEW YORK SP Amer Public Hlth Assoc DE physician professional practice; preventive medicine; education, medical; residency training; clinical research ID PUBLIC-HEALTH; MEDICINE; REFORM AB Background Factors associated with research productivity among residency graduates are not well understood, The objectives of this study are to describe research productivity among preventive medicine residency (PMR) graduates and to identify factors that are correlated with high levels of productivity. Methods. A detailed survey was mailed to all (n = 1,070) graduates from U.S. PMRs between 1979 and 1989, Main outcome measures for this analysis were (1) 25% of the workweek or more research time and (2) 20 or more publications since training completion. Results. A total of 797 completed surveys were received for a response rate of 75%. Among respondents, 33% devoted at least 25% of their time to research and 13% had 20 or more publications. Independent positive predictors (P < 0.05) based on education and training of high research productivity as measured by both outcomes included research self-motivation, training at the Centers for Disease Control and Prevention, and clinical board certification. Concurrent correlates of current high research productivity by both outcomes included employment by the federal government or academia and academic appointment. Conclusions, Factors associated with high research productivity could be utilized to improve the resident selection process and promote research careers. This could enhance research programs and education and promote the overall prevention research agenda. (C) 1999 American Health Foundation and Academic Press. C1 NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Dermatol, Baltimore, MD 21205 USA. RP Salive, ME (reprint author), US FDA, Epidemiol Branch, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-220, Rockville, MD 20852 USA. NR 23 TC 4 Z9 4 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD APR PY 1999 VL 28 IS 4 BP 430 EP 436 DI 10.1006/pmed.1998.0449 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 183MF UT WOS:000079556800013 PM 10090873 ER PT J AU Gaylor, DW Kodell, RL Chen, JJ Krewski, D AF Gaylor, DW Kodell, RL Chen, JJ Krewski, D TI A unified approach to risk assessment for cancer and noncancer endpoints based on benchmark doses and uncertainty safety factors SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID DEVELOPMENTAL TOXICITY; CHEMICAL CARCINOGENESIS; RESPONSE MODELS; EXPOSURE; VARIABILITY; TOXICOLOGY; BIOASSAYS; POTENCY; ISSUES; RATES AB A fundamental goal of toxicology is to determine safe levels of human exposure to toxic substances. In the absence of information to establish dose-response relationships at low exposure levels generally experienced by humans, high-dose to low-dose linear extrapolation is generally used for estimating carcinogenic risks and the no-observed-adverse-effect-level divided by uncertainty (safety) factors is widely used for establishing human exposure guidelines for noncancer effects. The basis and impact of this dichotomy is examined and questioned. It is proposed that a unified approach be adopted for establishing human exposure guidelines for both cancer and noncancer endpoints. It is suggested that a lower confidence limit on the dose estimated to produce an excess incidence of adverse health effects in 10% of the individuals in a human study or 10% of the animals in laboratory experiments be used as a point-of-departure. This dose would be divided by appropriate uncertainty factors to establish human exposure guidelines. For severe irreversible adverse health effects we suggest a total default uncertainty factor (divisor) for animal data on the order of 10,000, which is comparable to current guidelines. For reversible biological effects a smaller default uncertainty factor on the order of 1000 may be employed. This is comparable to the divisor often used currently when the point-of-departure is the lowest-observed-adverse-effect-level. It is asserted that the toxicological information generally available does not warrant numerical estimates of risk at low levels of human exposure. Rather, we support a unified approach for all adverse health effects of dividing a benchmark dose by appropriate uncertainty factors to establish guidelines for human exposures to toxic substances. (C) 1999 Academic Press. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Ottawa, Fac Med, Ottawa, ON, Canada. RP Gaylor, DW (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 75 TC 21 Z9 23 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 1999 VL 29 IS 2 BP 151 EP 157 DI 10.1006/rtph.1998.1279 PN 1 PG 7 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 203FC UT WOS:000080696400005 PM 10341145 ER PT J AU Carey, RF Lytle, CD Cyr, WH AF Carey, RF Lytle, CD Cyr, WH TI Implications of laboratory tests of condom integrity SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; SEXUAL TRANSMISSION; LATEX CONDOMS; BARRIERS; SENSITIVITY; EFFICACY AB Background: There is sufficient evidence from Food and Drug Administration laboratory experiments and clinical studies to draw conclusions about the relative importance of holes and breakage to condoms. The laboratory test methods determined penetration of viruses or virus-size microspheres through holes in condoms under conditions that simulated or exaggerated those expected in actual use, and determined the frequency with which condoms might pass virus or microspheres and the amounts of passage in each case. Goals: To summarize and comment on the significance of test results on latex, polyurethane, and natural membrane condoms as barriers to virus passage. Study Design: Published and unpublished data addressing three distinct concerns were analyzed: (1) passage of virus or microspheres through small holes or pores inherent in the material of "intact" condoms which are undetectable by the standard water leak quality assurance test, (2) passage of virus or microspheres through larger holes in "leaker" condoms detectable by the water leak test but marketed because of the finite acceptable quality level (AQL) of the test, and (3) passage of virus through condoms that break during use. Results: Extrapolating to the passage of semen expected during actual use allowed an analysis of the relative importance of breakage and water-leak-detectable or water-leak-undetectable holes. Conclusions: The relative importance of breaks and holes is related to the volume of semen that contains an "infectious dose" of a sexually transmitted disease (STD). When 0.1 mL to 1.0 mL exposures to semen are necessary for disease transmission, the risk during latex condom use primarily results not from holes, but from breakage of condoms. For smaller volumes of semen exposure (0.00001 mt and less), the presence of holes can be as important as breaks. The same qualitative argument pertains to a comparison of "leaker" condoms to the large majority of "intact" condoms. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20852 USA. RP Lytle, CD (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, HFZ-112,9200 Corp Blvd, Rockville, MD 20852 USA. EM cdl@cdrh.fda.gov NR 32 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD APR PY 1999 VL 26 IS 4 BP 216 EP 220 DI 10.1097/00007435-199904000-00006 PG 5 WC Infectious Diseases SC Infectious Diseases GA 184YJ UT WOS:000079641100006 PM 10225589 ER PT J AU Hansen, DK LaBorde, JB Wall, KS Holson, RR Young, JF AF Hansen, DK LaBorde, JB Wall, KS Holson, RR Young, JF TI Pharmacokinetic considerations of dexamethasone-induced developmental toxicity in rats SO TOXICOLOGICAL SCIENCES LA English DT Article ID CEREBROSPINAL-FLUID; PRENATAL EXPOSURE; RETINOIC ACID; CLEFT-PALATE; CD-1 MICE; MOUSE; TERATOGENICITY; CORTICOSTEROIDS; 2-METHOXYETHANOL; EMBRYOTOXICITY AB Dexamethasone (DEX) has been shown to elicit growth stunting and cleft palate in rat fetuses. This investigation characterized DEX dosimetry as various pharmacokinetic parameters and evaluated their impact on developmental toxicity endpoints. DEX pharmacokinetics was evaluated as a single dose on either gestation day (GD) 9 or 14, as well as on GD 14 after multiple daily dosing from GD 9 to GD 14. An additional set of pregnant rats was dosed with DEX on GD 9 through GD 14, pharmacokinetic evaluation was conducted on GD 14 through GD 14, and teratological evaluation was conducted following sacrifice on GD 20. For all pharmacokinetic evaluations, a subcutaneous (sc) injection of 0.8 mg DEX/kg body weight together with 50 mu Ci H-3-DEX was administered to Sprague-Dawley rats. Blood, urine, and feces were collected for 24 or 48 h. At GD 20 sacrifice, maternal tissues as well as fetal brain and liver samples were collected as part of the laparotomy. All samples were assayed using scintillation spectrometry. DEX pharmacokinetic parameters remained similar whether dosing occurred early (GD 9) or late (GD 14) in organogenesis, or dosing occurred on multiple sequential days (GD 9-14). DEX produced maternal and fetal weight loss, fetal lethality, and cleft palate. DEX alpha-half-life was positively correlated with the percentage of implants affected [(number of non-live + number with cleft palate)/number of implants]/litter. Neither the area under the concentration-time curve (AUC), the maximum maternal plasma concentration (C-max), nor the terminal phase beta-half-life correlated with any fetal outcome parameters. The correlation between the percentage of the litter that was affected and half-life was improved if AUC was added in a stepwise multiple regression. These data suggest that the length of time that DEX is present in the maternal plasma at a sufficiently high concentration (i.e., slower tissue distribution of DEX) appears to be important in determining the risk of an adverse outcome in the offspring. C1 US FDA, Div Genet & Reprod Toxicol, Dept Hlth & Human Serv, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biometry & Risk Assessment, Dept Hlth & Human Serv, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Pathol Associates Int, Jefferson, AR 72079 USA. RP Hansen, DK (reprint author), US FDA, Div Genet & Reprod Toxicol, Dept Hlth & Human Serv, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT-130, Jefferson, AR 72079 USA. NR 51 TC 23 Z9 25 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 1999 VL 48 IS 2 BP 230 EP 239 DI 10.1093/toxsci/48.2.230 PG 10 WC Toxicology SC Toxicology GA 251PW UT WOS:000083454900009 PM 10353314 ER PT J AU Barroso, D AF Barroso, D TI Neisseria meningitidis nasopharynx colonization of diseased patients on presentation and on discharge SO TROPICAL DOCTOR LA English DT Article ID MENINGOCOCCAL DISEASE; CARRIAGE AB Fifty-one meningococcal disease patients were randomly selected and a paired throat swab was taken before and after specific therapy. Neisseria meningitidis nasopharyngeal carriage after intravenous antibiotic therapy were found in only two cases (4%; 95% confidence interval (CI) 0.5-13). All close contacts of the cases received chemoprophylaxis and throat swabs taken 10 days later were negative. C1 Sao Sebastiao State Inst Infect Dis, Rio De Janeiro, Brazil. RP Barroso, D (reprint author), US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 0049-4755 J9 TROP DOCT JI Trop. Dr. PD APR PY 1999 VL 29 IS 2 BP 108 EP 109 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 196NW UT WOS:000080315300016 PM 10418306 ER PT J AU Talaat, AM Trucksis, M Kane, AS Reimschuessel, R AF Talaat, AM Trucksis, M Kane, AS Reimschuessel, R TI Pathogenicity of Mycobacterium fortuitum and Mycobacterium smegmatis to goldfish, Carassius auratus SO VETERINARY MICROBIOLOGY LA English DT Article DE fish; virulence; mycobacteria; Mycobacterium fortuitum; Mycobacterium smegmatis; pathogenesis ID RAPIDLY GROWING MYCOBACTERIA; INFECTION; TUBERCULOSIS; DOG; IDENTIFICATION; PATHOGENESIS; MONOCYTES; DISEASE; FISH AB Despite the ubiquitous presence of atypical mycobacteria in the environment and the potential risk of infection in humans and animals, the pathogenesis of diseases caused by infection with atypical mycobacteria has been poorly characterised. In this study, goldfish, Carassius auratus were infected either with the rapidly growing fish pathogen, Mycobacterium fortuitum or with another rapidly growing mycobacteria, Mycobacterium smegmatis. Bacterial persistence and pathological host response to mycobacterial infection in the goldfish are described. Mycobacteria were recovered from a high percentage of inoculated fish that developed a characteristic chronic granulomatous response similar to that associated with natural mycobacterial infection. Both M. fortuitum and M. smegmatis were pathogenic to fish. Fish infected with M. smegmatis ATCC 19420 showed the highest level of giant cell recruitment compared to fish inoculated with M. smegmatis mc(2)155 and M. fortuitum. Of the three strains of mycobacteria examined, M. smegmatis ATCC 19420 was the most virulent strain to goldfish followed by M. fortuitum and M, smegmatis mc(2)155, respectively. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Maryland, Sch Med, Dept Med, Div Geog Med,Ctr Vaccine Dev, Baltimore, MD 21201 USA. Vet Affairs Med Ctr, Med Serv, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. RP US FDA, Ctr Vet Med, Res Off, 4801 Muirkirk Rd, Laurel, MD 20708 USA. EM rreimsch@bangate.fda.gov NR 41 TC 33 Z9 35 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 EI 1873-2542 J9 VET MICROBIOL JI Vet. Microbiol. PD APR 1 PY 1999 VL 66 IS 2 BP 151 EP 164 DI 10.1016/S0378-1135(99)00002-4 PG 14 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 182XA UT WOS:000079522400006 PM 10227476 ER PT J AU Tan, W Lin, DX Xiao, Y Kadlubar, FF Chen, JS AF Tan, W Lin, DX Xiao, Y Kadlubar, FF Chen, JS TI Chemoprevention of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced carcinogen-DNA adducts by Chinese cabbage in rats SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GLUTATHIONE S-TRANSFERASES; FOOD-BORNE CARCINOGEN; BRASSICA VEGETABLES; TISSUES; HUMANS; PHIP AB AIM The food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo [4, 5-b]pyridine (PhIP) induces colon and mammary gland tumors in rats and has been implicated in the etiology of human colorectal cancer. This study was conducted to examine the potentially preventive effect of Chinese cabbage (Brassica chinensis), a brassica vegetable most commonly consumed in China, against this carcinogen-induced DNA adduct formation in rats and its possible mechanisms. METHODS Sprague-Dawley rats were maintained for 10 days on basal diet or diet containing 20 % (w/w) freeze-dried cabbage powder prior to administration of a single dose of PhIP (10 mg/ kg) by oral gavage. Rats were sacrificed at 20 h after PhIP treatment and PhIP-DNA adducts in the colon, heart, lung and liver were analyzed using P-32-postlabeling technique. Levels of hepatic cytochrome P450 (CYP) 1A1 and 1A2, as indicated by 7-ethoxyresorufin O-deethylase and 7-methlxyresorufin O-demethylase activity, and cytosolic glutathione S-transferases (GSTs) towards 1-chloro-2, 4-dinitrobenzene (CDNB) in the liver, lung and colon were measured. RESULTS Rats pre-treated with Chinese cabbage and given a single dose of PhIP had reduced levels of PhIP-DNA adducts in the colon, heart, lung and liver, with inhibition rates of 82.3%, 60.6%, 48.4% and 48.9%, respectively (P < 0.01). The enzyme assays revealed that Chinese cabbage induced both CYP1A1 and 1A2 activity, but the induction was preferential for CYP1A1 over 1A2 (81% vs 51%). GST activity towards CBNB in the liver and lung, but not colon, was also significantly increased by cabbage treatment. CONCLUSION The results indicate that Chinese cabbage has a preventive effect on PhIP-initiated carcinogenesis in rats and the mechanism is likely to involve the induction of detoxification enzymes. C1 Chinese Acad Med Sci, Inst Canc, Dept Chem Etiol & Carcinogenesis, Beijing 100021, Peoples R China. Beijing Union Med Coll, Beijing 100021, Peoples R China. Beijing Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Beijing 100083, Peoples R China. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Chinese Acad Prevent Med, Inst Nutr & Food Hyg, Beijing 100050, Peoples R China. RP Lin, DX (reprint author), Chinese Acad Med Sci, Inst Canc, Dept Chem Etiol & Carcinogenesis, POB 2258, Beijing 100021, Peoples R China. NR 14 TC 6 Z9 6 U1 0 U2 0 PU W J G PRESS PI BEIJING PA PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD APR PY 1999 VL 5 IS 2 BP 138 EP 142 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188KE UT WOS:000079844700014 ER PT J AU Yu, XW Imam, SZ Newport, GD Slikker, W Ali, SF AF Yu, XW Imam, SZ Newport, GD Slikker, W Ali, SF TI Ibogaine blocked methamphetamine-induced hyperthermia and induction of heat shock protein in mice SO BRAIN RESEARCH LA English DT Article DE ibogaine; methamphetamine; hyperthermia; heat-shock-protein; caudate nucleus; striatum; neurotoxicity ID NITRIC-OXIDE SYNTHASE; INDUCED NEUROTOXICITY; MORPHINE; TEMPERATURE; MOUSE; RATS; 7-NITROINDAZOLE; METABOLISM; INHIBITOR; BRAIN AB Body temperature changes and heat shock protein (HSP-72) induction in the caudate nucleus were studied in female C57BL/6N mice pretreated with ibogaine (50 mg/kg) and sacrificed 48 h. after a single dose of methamphetamine (20 mg/kg). Methamphetamine injection resulted in hyperthermia and induced HSP-72 expression, whereas treatment with ibogaine alone produced hypothermia. The ibogaine followed by methamphetamine injection showed no hyperthermia and decreased HSP-72 expression. These data indicate that pretreatment with ibogaine can completely block methamphetamine-induced hyperthermia and HSP-72 expression in the striatum. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. NR 22 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 27 PY 1999 VL 823 IS 1-2 BP 213 EP 216 DI 10.1016/S0006-8993(99)01154-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 179QP UT WOS:000079340400025 PM 10095030 ER PT J AU Wong, L Deb, TB Thompson, SA Wells, A Johnson, GR AF Wong, L Deb, TB Thompson, SA Wells, A Johnson, GR TI A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN PANCREATIC-CANCER; TYROSINE PHOSPHORYLATION; EPITHELIAL-CELLS; KINASE-ACTIVITY; AUTOPHOSPHORYLATION SITES; HEPARAN-SULFATE; HUMAN-PLACENTA; ERBB-2 KINASE; FACTOR FAMILY; FACTOR-ALPHA AB The epidermal growth factor receptor (EGFR) mediates the actions of a family of bioactive peptides that include epidermal growth factor (EGF) and amphiregulin (AR). Here we have studied AR and EGF mitogenic signaling in EGFR devoid NR6 fibroblasts that ectopically express either wild type EGFR (WT) or a truncated EGFR that lacks the three major sites of autophosphorylation (c'1000). COOH-terminal truncation of the EGFR significantly impairs the ability of AR to (i) stimulate DNA synthesis, (ii) elicit Elk-1 transactivation, and (iii) generate sustained enzymatic activation of mitogen-activated protein kinase. EGFR truncation had no significant effect on AR binding to receptor but did result in defective GRB2 adaptor function. In contrast, EGFR truncation did not impair EGF mitogenic signaling, and in c'1000 cells EGF was able to stimulate the association of ErbB2 with GRB2 and SHC. Elk-1 transactivation was monitored when either ErbB2 or a truncated dominant-negative ErbB2 mutant (ErbB2-(1-813)) was overexpressed in cells. Overexpression of full-length ErbB2 resulted in a strong constitutive transactivation of Elk-1 in c'1000 but only slightly stimulated Elk-1 in WT or parental NR6 cells. Conversely, overexpression of ErbB2-(1-813) inhibited EGF-stimulated Elk-1 transactivation in c'1000 but not in WT cells. Thus, the cytoplasmic tail of the EGFR plays a critical role in AR mitogenic signaling but is dispensable for EGF, since EGF-activated truncated EGFRs can signal through ErbB2. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. Berlex Biosci, Dept Prot Chem & Biophys, Richmond, CA 94804 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Vet Adm Med Ctr, Birmingham, AL 35294 USA. RP Johnson, GR (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bldg 29A,Rm 3B-16,8800 Rockville Pike, Bethesda, MD 20892 USA. OI Wells, Alan/0000-0002-1637-8150 FU PHS HHS [R01-54739] NR 69 TC 16 Z9 21 U1 1 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 MAR 26 PY 1999 VL 274 IS 13 BP 8900 EP 8909 DI 10.1074/jbc.274.13.8900 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181PV UT WOS:000079451600076 PM 10085134 ER PT J AU Pierce, LR Finlayson, J Epstein, JS Gaines, A Varricchio, F AF Pierce, LR Finlayson, J Epstein, JS Gaines, A Varricchio, F TI Hemolysis associated with 25% human albumin diluted with sterile water - United States, 1994-1998 (Reprinted from MMWR, vol 48, pg 157, 1999) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 US FDA, Div Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. CDC, Hosp Infect Program, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. NR 11 TC 5 Z9 5 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 24 PY 1999 VL 281 IS 12 BP 1076 EP 1077 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 177EP UT WOS:000079197100012 ER PT J AU Ang, CYW Liu, FF Johnson, FJ Rafii, F AF Ang, CYW Liu, FF Johnson, FJ Rafii, F TI Antimicrobial activities of St John's Wort extracts SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR USA. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 1999 VL 217 MA 017-AGFD BP U29 EP U29 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 176JN UT WOS:000079148100018 ER PT J AU Chang, HC Holland, RD Churchwell, MI Bumpus, JA Doerge, DR AF Chang, HC Holland, RD Churchwell, MI Bumpus, JA Doerge, DR TI Inactivation of peroxidase from Coprinus cinereus by 4-chloroaniline derivatives on protein residues. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ No Iowa, Cedar Falls, IA 50614 USA. 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 MAR 21 PY 1999 VL 217 MA 051-AGRO BP U73 EP U73 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 176JN UT WOS:000079148100152 ER PT J AU Cramer, GM Bangerter, K Fernando, R Meaburn, GM Pellizzari, ED AF Cramer, GM Bangerter, K Fernando, R Meaburn, GM Pellizzari, ED TI Hair mercury analysis and its application to exposure studies in NHEXAS and NHANES IV. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 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 MAR 21 PY 1999 VL 217 MA 030-ENVR BP U724 EP U724 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 176JN UT WOS:000079148102241 ER PT J AU Gehring, TA Ang, C AF Gehring, TA Ang, C TI Determination of sulfonamides in channel catfish and black tiger shrimp by liquid chromatography with postcolumn derivatization and fluorescence 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 MAR 21 PY 1999 VL 217 MA 069-AGRO BP U79 EP U79 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 176JN UT WOS:000079148100170 ER PT J AU Liu, FF Ang, CYW Springer, D AF Liu, FF Ang, CYW Springer, D TI High-performance liquid chromatographic determination of biologically active components in extracts of St. John's wort leaves and dietary supplements SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 1999 VL 217 MA 102-AGFD BP U54 EP U54 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 176JN UT WOS:000079148100102 ER PT J AU Perkins, R Anson, J Tong, W Branham, W Blair, R Hass, B Fang, H Shi, L Chen, Y Meehan, J Nossaman, R Welsh, W Sheehan, D AF Perkins, R Anson, J Tong, W Branham, W Blair, R Hass, B Fang, H Shi, L Chen, Y Meehan, J Nossaman, R Welsh, W Sheehan, D TI A knowledge base for mining of endocrine disruptor data. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Missouri, St Louis, MO 63121 USA. ROW Sci, Jefferson, AR USA. 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 MAR 21 PY 1999 VL 217 MA 005-CINF BP U550 EP U550 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 176JN UT WOS:000079148101700 ER PT J AU Snyder, JM Hopper, ML King, JW AF Snyder, JM Hopper, ML King, JW TI Extraction and enrichment of pesticides for analysis by using binary supercritical fluid mixtures. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 USDA ARS, Natl Ctr Agr Utilizat Res, Peoria, IL 61604 USA. US FDA, Total Diet Res Ctr, Lenexa, KS 66214 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 MAR 21 PY 1999 VL 217 MA 086-AGRO BP U84 EP U84 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 176JN UT WOS:000079148100187 ER PT J AU Welsh, WJ Yu, SJ Chen, Y Tong, W Perkins, R Sheehan, D AF Welsh, WJ Yu, SJ Chen, Y Tong, W Perkins, R Sheehan, D TI Quantitative structure-activity relationship (QSAR) models useful for risk assessment in predicting suspected endocrine disrupting compounds (EDCs). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. ROW Sci Inc, Jefferson, AR 72079 USA. Univ Missouri, Dept Chem, St Louis, MO 63121 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 MAR 21 PY 1999 VL 217 MA 052-COMP BP U656 EP U656 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 176JN UT WOS:000079148102027 ER PT J AU Yu, SJ Welsh, WJ Chen, Y Tong, W Perkins, R Sheehan, D AF Yu, SJ Welsh, WJ Chen, Y Tong, W Perkins, R Sheehan, D TI Quantitative structure-activity relationship (QSAR) models for predicting the estrogenic activity of xenoestrogens. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. ROW Sci Inc, Jefferson, AR 72079 USA. Univ Missouri, Dept Chem, St Louis, MO 63121 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 MAR 21 PY 1999 VL 217 MA 117-COMP BP U675 EP U676 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 176JN UT WOS:000079148102092 ER PT J AU Prasad, GL Masuelli, L Raj, MHG Harindranath, N AF Prasad, GL Masuelli, L Raj, MHG Harindranath, N TI Suppression of src-induced transformed phenotype by expression of tropomyosin-1 SO ONCOGENE LA English DT Article DE tropomyosin; src; oncogenes; transformation; tumor suppression; cytoskeleton ID MAMMARY EPITHELIAL-CELLS; PROTEIN-TYROSINE KINASES; EPIDERMAL GROWTH-FACTOR; RAT FIBROBLASTS; C-SRC; CDNA; ACTIN; ORGANIZATION; CYTOSKELETON; ONCOGENE AB Suppression of high M-r tropomyosins (TMs) is a common feature of transformed cells. Previous work from this laboratory has demonstrated that the isoform 1 of TM, TM1, acts as an anti-oncogene in ras-transformed murine fibroblasts. In this study, we have investigated whether TM1 is a ras-specific suppressor, or a general suppressor protein of the cellular transformation. V-src transformed fibroblasts, which express decreased TM1, were transduced with a full-length cDNA to overexpress TM1. Both the control and the transduced cells expressed v-src kinase at comparable levels. TM1 expressing (src-T1) cells grew at a lower rate in monolayer, exhibited well spread, flat morphology than the control cells. Enhanced expression of TM1 resulted in improved microfilamental architecture. More significantly, src-T1 cells completely failed to grow under anchorage independent conditions. These data demonstrate that TM1 is as an anti-oncogene of functionally diverse oncogenes, and it is a class II tumor suppressor protein. C1 Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19104 USA. Univ La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy. Louisiana State Univ, Med Ctr, Dept Obgyn & Biochem, New Orleans, LA 70112 USA. US FDA, CBER, Div Hematol Prod, Bethesda, MD 20892 USA. RP Prasad, GL (reprint author), Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19104 USA. NR 45 TC 48 Z9 53 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 18 PY 1999 VL 18 IS 11 BP 2027 EP 2031 DI 10.1038/sj.onc.1202264 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 177DC UT WOS:000079191300013 PM 10208425 ER PT J AU Smith, SW Topliff, AR Danigelis, M Zvosec, DL Schrag, LL Freiwald, SA Gunn, SR Setzer, SC Rock, M Osterholm, MT Benson, BE Padilla, J Voorhees, R Sewell, CM Williams, L Shepherd, G Coody, G Simpson, DM AF Smith, SW Topliff, AR Danigelis, M Zvosec, DL Schrag, LL Freiwald, SA Gunn, SR Setzer, SC Rock, M Osterholm, MT Benson, BE Padilla, J Voorhees, R Sewell, CM Williams, L Shepherd, G Coody, G Simpson, DM CA CDC TI Adverse events associated with ingestion of gamma-butyrolactone - Minnesota, New Mexico, and Texas, 1998-1999 (Reprinted from MMWR, vol 48, pg 137-140, 1999) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Hennepin Cty Med Ctr, Dept Emergency Med, Minneapolis, MN 55415 USA. Hennepin Reg Poison Ctr, Minneapolis, MN USA. Methodist Hosp, St Louis Pk, MN USA. Minnesota Dept Hlth, Minneapolis, MN 55414 USA. New Mexico Poison Ctr, Albuquerque, NM USA. New Mexico Dept Hlth, Santa Fe, NM USA. N Texas Poison Ctr, Dallas, TX USA. Texas Dept Hlth, Austin, TX 78756 USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. CDC, Environm Hazards & Epidemiol Sect, Hlth Studies Branch, Div Environm Hazards & Hlth Effects,Natl Ctr Envi, Atlanta, GA 30333 USA. CDC, Div Appl Publ Hlth Training, Epidemiol Program Off, Atlanta, GA 30333 USA. RP Smith, SW (reprint author), Hennepin Cty Med Ctr, Dept Emergency Med, Minneapolis, MN 55415 USA. NR 11 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 MAR 17 PY 1999 VL 281 IS 11 BP 979 EP 980 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 175EE UT WOS:000079079400010 ER PT J AU Lester, DS Lyon, RC McGregor, GN Engelhardt, RT Schmued, LC Johnson, GA Johannessen, JJ AF Lester, DS Lyon, RC McGregor, GN Engelhardt, RT Schmued, LC Johnson, GA Johannessen, JJ TI 3-Dimensional visualization of lesions in rat brain using magnetic resonance imaging microscopy SO NEUROREPORT LA English DT Article DE 3-D; brain lesions; imaging; microscopy; MRI; neurotoxicity ID DOMOIC ACID; NEURONAL DEGENERATION; NEUROTOXIC LESION; RESOLUTION; HISTOLOGY; POISON AB HIGH-RESOLUTION (< 50 mu m) magnetic resonance imaging microscopy (MRM) has been used to identify brain regions and localization of excitotoxin-induced lesions in fixed rat brains, subsequently confirmed using standard histology. The anatomical extent of lesions identified by MRM Nas identical to that seen in histological sections and various histopathological changes could be visualized. In contrast to the time involved in preparing and examining histological sections, lesions in intact brains could be rapidly identified and visualized in three dimensions by examining digitally generated sections in any plane. This study shows that MRM has tremendous potential as a prescreening tool for neurotoxicity and neuropathology. These observations suggest that MRM has the potential to affect pathology much as conventional MRI has influenced clinical imaging. NeuroReport 10:737-741 (C) 1999 Lippincott Williams & Wilkins. C1 US FDA, Div Appl Pharmacol Res, Laurel, MD 20708 USA. US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. NCI, Frederick Biomed Supercomp Ctr, SAIC Frederick, FCRDC, Frederick, MD USA. Duke Univ, Med Ctr, Ctr In Vivo Microscopy, Durham, NC USA. US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Lester, DS (reprint author), US FDA, Div Appl Pharmacol Res, 8301 Muirkirk Rd,Rm 2009, Laurel, MD 20708 USA. OI Johnson, G.Allan/0000-0002-7606-5447 FU PHS HHS [P41 05959] NR 14 TC 18 Z9 20 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 17 PY 1999 VL 10 IS 4 BP 737 EP 741 DI 10.1097/00001756-199903170-00014 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 180PA UT WOS:000079393300016 PM 10208540 ER PT J AU Gursel, M Tunca, S Ozkan, M Ozcengiz, G Alaeddinoglu, G AF Gursel, M Tunca, S Ozkan, M Ozcengiz, G Alaeddinoglu, G TI Immunoadjuvant action of plasmid DNA in liposomes SO VACCINE LA English DT Article DE immunological adjuvants; DNA vaccine; liposomes ID TUMOR-NECROSIS-FACTOR; B SURFACE-ANTIGEN; T-CELL RESPONSES; BACTERIAL-DNA; SYNTHETIC OLIGONUCLEOTIDES; SEQUENCE SPECIFICITY; FACTOR-ALPHA; CPG MOTIFS; ADJUVANTS; VACCINATION AB Bacterial DNA and oligodeoxynucleotides containing immunostimulatory sequences with a CpG motif stimulated a Th1 type response in vivo. The adjuvant action of a non-coding plasmid DNA derived from pRc/CMV HBS (encoding the S region of hepatitis B surface antigen, HBsAg) in mice was investigated. The role of methylation on the adjuvanticity of the plasmid as well as the effect of vaccine formulation employed on the outcome of antigen-specific humoral and cellular responses were also studied. The results demonstrated that plasmid DNA acted as a Th1 promoting adjuvant when mixed as such or co-entrapped in liposomes with a very low dose of antigen. However. the adjuvant activity was lost when separate liposome entrapped formulations of both the antigen and the plasmid DNA were mixed, indicating a necessity for the antigen and the plasmid DNA to contact the same APC for optimal immune activation. A decreased adjuvanticity of plasmid DNA upon methylation with HpaII methyltransferase was also demonstrated. A mechanism that may help partially explain the reduction in adjuvanticity after modification of C residues is also discussed. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Middle E Tech Univ, Dept Biol Sci, Biotechnol Res Unit, TR-06531 Ankara, Turkey. RP Gursel, M (reprint author), US FDA, Div Viral Prod, Room 3D22,Bldg 29A, Bethesda, MD 20892 USA. RI Gursel, Mayda /H-1812-2012 NR 36 TC 44 Z9 48 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 17 PY 1999 VL 17 IS 11-12 BP 1376 EP 1383 DI 10.1016/S0264-410X(98)00383-1 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 175YG UT WOS:000079123200013 PM 10195773 ER PT J AU Hori, K Burd, PR Furuke, K Kutza, J Weih, KA Clouse, KA AF Hori, K Burd, PR Furuke, K Kutza, J Weih, KA Clouse, KA TI Human immunodeficiency virus-1-infected macrophages induce inducible nitric oxide synthase and nitric oxide (NO) production in astrocytes: Astrocytic NO as a possible mediator of neural damage in acquired immunodeficiency syndrome SO BLOOD LA English DT Article ID NF-KAPPA-B; MONOCYTE-DERIVED MACROPHAGES; VIRUS TYPE-1 REPLICATION; BLOOD MONONUCLEAR-CELLS; NECROSIS-FACTOR-ALPHA; IN-VITRO; HIV-1 INFECTION; VIRAL REPLICATION; AIDS DEMENTIA; HUMAN BRAIN AB Nitric oxide (NO) plays an important role in normal neural cell function. Dysregulated or overexpression of NO contributes to neurologic damage associated with various pathologies, including human immunodeficiency virus (HIV)-associated neurological disease. Previous studies suggest that HIV-infected monocyte-derived macrophages (MDM) produce low levels of MO in vitro and that inducible nitric oxide synthase (iNOS) is expressed in the brain of patients with neurologic disease. However, the levels of NO could not account for the degree of neural toxicity observed. In this study, we found that induction of iNOS with concomitant production of NO occurred in primary human astrocytes, but not in MDM, when astrocytes were cocultured with HIV-1-infected MDM. This coincided with decreased HIV replication in infected MDM. Supernatants from cocultures of infected MDM and astrocytes also stimulated iNOS/NO expression in astrocytes, but cytokines known to induce iNOS expression (interferon-gamma. interleukin-1 beta. and tumor necrosis factor-alpha) were not detected. In addition, the recombinant HIV-1 envelope protein gp41, but not rgp120. induced iNOS in cocultures of uninfected MDM and astrocytes. This suggests that astrocytes may be an important source of NO production due to dysregulated iNOS expression and may constitute one arm of the host response resulting in suppression of HIV-1 replication in the brain. It also leads us to speculate that neurologic damage observed in HIV disease may ensue from prolonged, high level production of NO. This is a US government work. There are no restrictions on its use. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Rockville, MD 20852 USA. RP Clouse, KA (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, HFM-508,1401 Rockville Pike, Rockville, MD 20852 USA. EM clouse@cber.fda.gov NR 66 TC 82 Z9 84 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 1999 VL 93 IS 6 BP 1843 EP 1850 PG 8 WC Hematology SC Hematology GA 176RT UT WOS:000079166100009 PM 10068656 ER PT J AU Bichsel, VE Winestock, KD Finbloom, DS AF Bichsel, VE Winestock, KD Finbloom, DS TI An 83 kDa monocyte-specific isoform of STAT5A is generated by N-terminal proteolytic cleavage. SO FASEB JOURNAL 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A1145 EP A1145 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132902870 ER PT J AU Buffington, CK Cowan, GSM Li, J Feuers, RH Hart, RW AF Buffington, CK Cowan, GSM Li, J Feuers, RH Hart, RW TI A lack of association between portal free fatty acids, fat distribution, and metabolic aberrations in the morbidly obese. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Tennessee, Memphis, TN 38163 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A926 EP A926 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901613 ER PT J AU Chowdhury, P Soulsby, ME Ali, SF Pasley, JN Rayford, PL AF Chowdhury, P Soulsby, ME Ali, SF Pasley, JN Rayford, PL TI Simulated microgravity induced peroxidative injury in rat brain. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A1039 EP A1039 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132902264 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 FASEB JOURNAL 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A1149 EP A1149 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132902897 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 FASEB JOURNAL 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A1152 EP A1152 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132902912 ER PT J AU Furuke, K Bloom, ET AF Furuke, K Bloom, ET TI Redox regulation of Fas-induced apoptosis and Fas ligand expression in human natural killer cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A963 EP A963 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901828 ER PT J AU Guthrie, JF Morton, JF AF Guthrie, JF Morton, JF TI Sources of added sugars in the diets of Americans SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, 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 15 PY 1999 VL 13 IS 5 SU S BP A695 EP A695 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132900283 ER PT J AU Guthrie, JF Derby, BM Chanmugam, P AF Guthrie, JF Derby, BM Chanmugam, P TI Black-white differences in knowledge, attitudes and practices related to cholesterol control SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 USA. Louisiana State Univ, Baton Rouge, LA 70803 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 15 PY 1999 VL 13 IS 5 SU S BP A868 EP A868 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901276 ER PT J AU Horvath-Arcidiacono, JA Bloom, ET AF Horvath-Arcidiacono, JA Bloom, ET TI NK cells in the human anti-pig response: Response to cytokines 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 15 PY 1999 VL 13 IS 5 SU S BP A963 EP A963 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901826 ER PT J AU James, SJ Melnyk, S Pogribna, M Miller, BJ Pogribny, IP AF James, SJ Melnyk, S Pogribna, M Miller, BJ Pogribny, IP TI Genomic instability and tumorigenic transformation in folate deficient chinese hamster ovary cells. 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 15 PY 1999 VL 13 IS 5 SU S BP A916 EP A916 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901555 ER PT J AU Lipicky, RJ Vargas, F Knudsen, K Grassi, D Gill-Kumar, P AF Lipicky, RJ Vargas, F Knudsen, K Grassi, D Gill-Kumar, P TI Flecainide, encainide and moricizine: Effects on voltage dependent sodium and potassium conductance. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 1, Div Cardiorenal Drug Prod, 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 15 PY 1999 VL 13 IS 5 SU S BP A1098 EP A1098 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132902603 ER PT J AU O'Hanlon, TP Lawless, O Miller, FW AF O'Hanlon, TP Lawless, O Miller, FW TI Histopathology and T cell receptor (TRC) gene expression in silicone breast implant (SBI) capsules and other inflammatory tissues. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Ctr Arthrit Immunol & Environm Disorders, Olney, MD 20832 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 15 PY 1999 VL 13 IS 5 SU S BP A1130 EP A1130 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132902787 ER PT J AU Oravecz, T Guan, E Boykins, R Gorrell, MD Norcross, MA AF Oravecz, T Guan, E Boykins, R Gorrell, MD Norcross, MA TI Inhibition of Th2-type chemokine signaling by CD26-mediated enzymatic cleavage SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Centenary Inst Canc Med, Newtown, NSW, Australia. 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 15 PY 1999 VL 13 IS 5 SU S BP A941 EP A941 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901694 ER PT J AU Rosenberg, AS Hansal, SA Morris, D Love, P Sechler, JMG AF Rosenberg, AS Hansal, SA Morris, D Love, P Sechler, JMG TI Rescue of T memory responses in vivo following delivery of an apoptotic signal SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A1140 EP A1140 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132902846 ER PT J AU Scott, D Agranovich, I Golding, B AF Scott, D Agranovich, I Golding, B TI Conversion of an allergic responses from Th2 to Th1 by neonatal administration of the antigen together with a strong Th1 stimulus. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, CDER, Rockville, MD 20857 USA. US FDA, DH, 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 15 PY 1999 VL 13 IS 5 SU S BP A650 EP A650 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132900020 ER PT J AU Vazquez, N Dickensheets, HL Donnelly, RP AF Vazquez, N Dickensheets, HL Donnelly, RP TI Il-4 suppresses IFN-gamma-induced Fc gamma-RI (CD64) gene expression in human monocytes by inhibiting Stat1-alpha activation. SO FASEB JOURNAL 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A1152 EP A1152 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132902911 ER PT J AU Williams, JA Pontzer, CH Shacter, E AF Williams, JA Pontzer, CH Shacter, E TI Differential effects of p38 kinase inhibition on expression of macrophage IL-10 and IL-6: The role of PGE(2). SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, CBER, Div Hematol Prod, Bethesda, MD 20892 USA. Univ Maryland, College Pk, MD 20742 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 15 PY 1999 VL 13 IS 5 SU S BP A1148 EP A1148 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132902888 ER PT J AU Joshi, MB Lin, DT Chiang, PH Goldman, ND Fujioka, H Aikawa, M Syin, C AF Joshi, MB Lin, DT Chiang, PH Goldman, ND Fujioka, H Aikawa, M Syin, C TI Molecular cloning and nuclear localization of a histone deacetylase homologue in Plasmodium falciparum SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; histone deacetylase; nuclear protein; transcription regulation ID PROTEINS; IDENTIFICATION AB Reversible acetylation of core histones plays an important role in transcriptional regulation, cell cycle progression and developmental events. The acetylation state of histones is controlled by a dynamic equilibrium between activities of histone acetylase and deacetylase enzymes. Histone deacetylase (HDAC) was recently suggested to be the target of a fungus-derived antiprotozoal agent exhibiting structural similarity to known HDAC inhibitors. We have initiated a study of HDAC of human malaria parasite, Plasmodium falciparum, to evaluate its potential as the target for novel antimalarials and its role in parasite development. We have isolated HDAC1 gene from the P. falciparum genomic and cDNA libraries. The nucleotide sequence contains no intervening sequence and its open reading frame (ORF) codes for a protein of 449 amino acid residues. We have named the protein, PfHDAC1, as the sequence shows significant homology to yeast, human and other eukaryotic HDACs. Northern blot analysis of the total RNA from different asexual and sexual stages of the parasite reveals the presence of single mRNA transcript, which is predominantly expressed in mature asexual blood stages and in gametocytes. Antiserum raised against a carboxyl terminal peptide immunoprecipitated an in vitro translated P. falciparum HDAC gene product and recognized a approximate to 50 kDa protein in the Triton X-100 insoluble fraction of parasites. Immunoelectron microscopy analysis showed majority of the protein localized in the nucleus of P. falciparum. To our knowledge, this is the first HDAC gene isolated from the malaria parasite. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. Tokai Univ, Inst Med Sci, Kanagawa 2591193, Japan. RP Syin, C (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM syin@cber.fda.gov FU NIAID NIH HHS [AI-35827] NR 22 TC 55 Z9 57 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD MAR 15 PY 1999 VL 99 IS 1 BP 11 EP 19 DI 10.1016/S0166-6851(98)00177-7 PG 9 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 182QU UT WOS:000079510300002 PM 10215020 ER PT J AU Delongchamp, RR Malling, HV Chen, JB Heflich, RH AF Delongchamp, RR Malling, HV Chen, JB Heflich, RH TI An estimator of the mutant frequency in assays using transgenic animals SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Poisson distribution; maximum likelihood estimation; confidence interval; transgenic mutation assay ID MOUSE MUTATION ASSAY; STATISTICAL-ANALYSIS; SELECTION; MICE; LYMPHOCYTES; VARIABILITY; DESIGN AB The Poisson distribution is a fundamental probability model for count data, and is a natural model for the observed plaque counts in mutation assays using animals with lambda or Phi X174 transgenes. The Poisson likelihood for observed counts is a function of the mutant fraction, and it is straightforward to derive the associated maximum likelihood estimate of the mutant fraction and its variance. The estimate is easy to calculate, and if not the same, very similar to ad hoc estimates in current use. The model indicates the proper way to combine data from a number of plates, possibly prepared with different sample dilutions. The estimator of the mutant fraction is biased as a consequence of dividing by a random variable, the plaque count used to calculate the total recovered plaque-forming units. Fortunately, the bias becomes negligible as this count becomes large. On the other hand, increasing this count can increase the variance by decreasing the amount of sample assayed for mutant phages. Concurrent heed to the bias and the variance provides some guidance as to the optimum allocation of a sample into portions assayed for mutant phages and total recovered phages. The distribution of the estimate of the mutant fraction is related to the binomial distribution. This relationship implies a binomial distribution for the mutant count conditional on an overall count (either the sum of mutant and counted total plaques or the sum of counted mutant and non-mutant plaques). A special but important case occurs when each plate can be evaluated for mutant plaques and non-mutant plaques. Then, the observed proportion of mutants estimates the mutant fraction. More generally, the relationship to a binomial distribution provides a procedure for calculating a confidence interval. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NIEHS, Mammalian Genet Grp, Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Delongchamp, RR (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT-20,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD MAR 15 PY 1999 VL 440 IS 1 BP 101 EP 108 DI 10.1016/S1383-5718(99)00007-8 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 178ER UT WOS:000079253800010 PM 10095133 ER PT J AU Deatly, AM Coleman, JW McMullen, G McAuliffe, JM Jayarama, V Cupo, A Crowley, JC McWilliams, T Taffs, RE AF Deatly, AM Coleman, JW McMullen, G McAuliffe, JM Jayarama, V Cupo, A Crowley, JC McWilliams, T Taffs, RE TI Poliomyelitis in intraspinally inoculated poliovirus receptor transgenic mice SO VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NUCLEOTIDE-SEQUENCE; REPLICATION; EXPRESSION; VACCINE; MODEL; GENE AB Mice transgenic with the human poliovirus receptor gene develop clinical signs and neuropathology similar to those of human poliomyelitis when neurovirulent polioviruses are inoculated into the central nervous system (CNS). Factors contributing to disease severity and the frequencies of paralysis and mortality include the poliovirus strain, dose, and gender of the mouse inoculated. The more neurovirulent the virus, as defined by monkey challenge results, the higher the rate of paralysis, mortality, and severity of disease. Also, the time to disease onset is shorter for more neurovirulent viruses. Male mice are more susceptible to polioviruses than females. TGM-PRG-3 mice have a 10-fold higher transgene copy number and produce 3-fold more receptor RNA and protein levels in the CNS than TGM-PRG-1 mice. CNS inoculations with type III polioviruses differing in relative neurovirulence show that these mouse lines are similar in disease frequency and severity, demonstrating that differences in receptor gene dosage and concomitant receptor abundance do not affect susceptibility to infection. However, there is a difference in the rate of accumulation of clinical signs. The time to onset of disease is shorter for TGM-PRG-3 than TGM-PRG-1 mice. Thus, receptor dosage affects the rate of appearance of poliomyelitis in these mice. (C) 1999 Academic Press. C1 Wyeth Lederle Vaccines & Pediat, Viral Vaccine Res, Pearl River, NY 10965 USA. Wyeth Lederle Vaccines & Pediat, Qual Control, Pearl River, NY 10965 USA. Dutchess Community Coll, Poughkeepsie, NY 12601 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Deatly, AM (reprint author), Wyeth Lederle Vaccines & Pediat, Viral Vaccine Res, 401 N Middletown Rd, Pearl River, NY 10965 USA. NR 31 TC 6 Z9 8 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 MAR 15 PY 1999 VL 255 IS 2 BP 221 EP 227 DI 10.1006/viro.1998.9574 PG 7 WC Virology SC Virology GA 178JQ UT WOS:000079262900003 PM 10069947 ER PT J AU Arichi, T Saito, T Major, ME Shirai, M Feinstone, SM Berzofsky, JA AF Arichi, T Saito, T Major, ME Shirai, M Feinstone, SM Berzofsky, JA TI Dna vaccine for prophylaxis of hepatitis C virus (HCV) infection: Induction of HCV specific CTLs and protection from HCV-recombinant vaccinia infection in HLA-A2.1 transgenic mouse model. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A634 EP A634 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033303656 ER PT J AU Brorson, K Wei, D Krasnokutsky, M Stein, KE AF Brorson, K Wei, D Krasnokutsky, M Stein, KE TI Anti-polysaccharide antibody affinity SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, CBER, Rockville, MD 20857 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 12 PY 1999 VL 13 IS 4 SU S BP A333 EP A333 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301925 ER PT J AU Fritsche, J Cook, KK Satchithanandam, S Mossoba, MM Rader, JI AF Fritsche, J Cook, KK Satchithanandam, S Mossoba, MM Rader, JI TI Correlation between dihydro-vitamin K and trans-fatty acid contents in margarines and margarines-like products. 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 12 PY 1999 VL 13 IS 4 SU S BP A238 EP A238 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301372 ER PT J AU Huang, LY Sousa, CRE Golding, B Scott, DE AF Huang, LY Sousa, CRE Golding, B Scott, DE TI In situ splenic IL-12 production and dendritic cell migration stimulated by a potent Th1-inducing adjuvant. 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 12 PY 1999 VL 13 IS 4 SU S BP A632 EP A632 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033303649 ER PT J AU James, SJ Pogribna, M Pogribny, IP Yi, P Gaylor, DW AF James, SJ Pogribna, M Pogribny, IP Yi, P Gaylor, DW TI 677C -> T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene may be a maternal risk factor for Down Syndrome. 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 12 PY 1999 VL 13 IS 4 SU S BP A223 EP A223 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301288 ER PT J AU Lee, H Gerrior, S AF Lee, H Gerrior, S TI Micronutrient and dietary fiber intakes by consumers who drink whole or reduced-fat milks. 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 12 PY 1999 VL 13 IS 4 SU S BP A264 EP A264 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301522 ER PT J AU Li, J Feuers, RJ Desai, VG Hart, RW Cowan, GSM Buffington, CK AF Li, J Feuers, RJ Desai, VG Hart, RW Cowan, GSM Buffington, CK TI Dysfunction of mitochondrial electron transport in the morbidly obese SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Tennessee, Memphis, TN 38163 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A563 EP A563 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033303248 ER PT J AU Li, SY Duffy, P Lu, MH Hart, RW AF Li, SY Duffy, P Lu, MH Hart, RW TI Effect of different levels of caloric restriction on DNA damage in rat brain cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S 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 226QW UT WOS:000082033303467 ER PT J AU Melnyk, S Hine, J James, SJ AF Melnyk, S Hine, J James, SJ TI Intracellular and plasma thiol profiles using a new HPLC method with electrochemical (EC) detection. 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 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 12 PY 1999 VL 13 IS 4 SU S BP A222 EP A222 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301281 ER PT J AU Mitchell, GV Jenkins, MY Grundel, E AF Mitchell, GV Jenkins, MY Grundel, E TI Natural tocopherols present in dietary supplements of carotenoids may confound their biological effects. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Off Food Labeling, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A240 EP A240 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301386 ER PT J AU Muthukkumar, S Jennings, H Stein, K AF Muthukkumar, S Jennings, H Stein, K TI Response to meningococcal group C polysaccharide (MCPS)-tetanus toxoid (TT) conjugate vaccine is regulated during development SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. Natl Res Council Canada, Ottawa, ON K1J 66, Canada. 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 12 PY 1999 VL 13 IS 4 SU S BP A280 EP A280 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301615 ER PT J AU Oravecz, T Pall, M Wang, J Norcross, MA AF Oravecz, T Pall, M Wang, J Norcross, MA TI Autocrine chemokine production is a key regulator of CCR5 expression in T cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 12 PY 1999 VL 13 IS 4 SU S BP A294 EP A294 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301699 ER PT J AU Principato, M Grenade, C Weaver, J Osborne, R Robl, M AF Principato, M Grenade, C Weaver, J Osborne, R Robl, M TI Tissue-specific immune responsesivness to staphylococcal enterotoxin in the aged gut-associated lymphatics. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Laurel, MD 20708 USA. Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A291 EP A291 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301682 ER PT J AU Rader, JI Weaver, CM Angyal, G AF Rader, JI Weaver, CM Angyal, G TI Fortification of enriched cereal-grain products in the US with folic acid: The first year. 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 12 PY 1999 VL 13 IS 4 SU S BP A267 EP A267 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301542 ER PT J AU Stewart, CW Mock, NI Mock, DM Hansen, D AF Stewart, CW Mock, NI Mock, DM Hansen, D TI Maternal biotin deficiency (BD) causes fetal malformations (FM) by inducing fetal BD. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A229 EP A229 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301324 ER PT J AU Whittaker, P San, RHC Seifried, HE Dunkel, VC AF Whittaker, P San, RHC Seifried, HE Dunkel, VC TI Genotoxicity of iron compounds. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. BioReliance, Rockville, MD 20850 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 12 PY 1999 VL 13 IS 4 SU S BP A574 EP A574 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033303311 ER PT J AU Yi, P Pogribny, IP Melnyk, S Pogribna, M James, SJ AF Yi, P Pogribny, IP Melnyk, S Pogribna, M James, SJ TI DNA hypomethylation in individuals with elevated homocysteine levels and 677C-T mutation in the methylenetetrahydrofolate reductase gene. 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 12 PY 1999 VL 13 IS 4 SU S BP A223 EP A223 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301285 ER PT J AU Jobbagy, Z Olah, Z Petrovics, G Eiden, MV Leverett, BD Dean, NM Anderson, WB AF Jobbagy, Z Olah, Z Petrovics, G Eiden, MV Leverett, BD Dean, NM Anderson, WB TI Up-regulation of the Pit-2 phosphate transporter retrovirus receptor by protein kinase C epsilon SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID APE LEUKEMIA-VIRUS; OSTEOBLAST-LIKE CELLS; NIH 3T3 CELLS; ECOTROPIC MURINE RETROVIRUSES; AMINO-ACID TRANSPORTER; PARATHYROID-HORMONE; SURFACE RECEPTOR; GROWTH; INVOLVEMENT; STIMULATION AB The membrane receptors for the gibbon ape leukemia retrovirus and the amphotropic murine retrovirus serve normal cellular functions as sodium-dependent phosphate transporters (Pit-1 and Pit-2, respectively). Our earlier studies established that activation of protein kinase C (PKC) by treatment of cells with phorbol 12-myristate 13-acetate (PMA) enhanced sodium-dependent phosphate (Na/P-i) uptake, Studies now have been carried out to determine which type of Na/P-i transporter (Pit-1 or Pit-2) is regulated by PKC and which PKC isotypes are involved in the up-regulation of Na/P-i uptake by the Na/P-i transporter/viral receptor. It was found that the activation of short term (2-min) Na/P-i uptake by PMA is abolished when cells are infected with amphotropic murine retrovirus (binds Pit-2 receptor) but not with gibbon ape leukemia retrovirus (binds Pit-1 receptor), indicating that Pit-2 is the form of Na/P-i, transporter/viral receptor regulated by PKC, The PKC-mediated activation of Pit-2 was blocked by pretreating cells with the pan-PKC inhibitor bisindolylmaleimide but not with the conventional PKC isotype inhibitor Go 6976, suggesting that a novel PKC isotype is required to regulate Pit-2. Overexpression of PKC epsilon, but not of PKC alpha, -delta, or -zeta was found to mimic the activation of Na/P-i uptake. To further establish that PKC epsilon is involved in the regulation of Pit-2, cells were treated with PKC epsilon-selective antisense oligonucleotides, Treatment with PKC epsilon antisense oligonucleotides decreased the PMA-induced activation of Na/P-i uptake. These results indicate that PMA-induced stimulation of Na/P-i uptake by Pit-2 is specifically mediated through activation of PKC epsilon. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. ISIS Pharmaceut, Carlsbad Res Ctr, Dept Pharmacol, Carlsbad, CA 92008 USA. RP Anderson, WB (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 37,Rm 1E-14,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 34 TC 22 Z9 22 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 MAR 12 PY 1999 VL 274 IS 11 BP 7067 EP 7071 DI 10.1074/jbc.274.11.7067 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175DV UT WOS:000079078400035 PM 10066763 ER PT J AU Vallejo, A Mas, A Heredia, A Altisent, C Lorenzo, I Soriano, V Hewlett, IK AF Vallejo, A Mas, A Heredia, A Altisent, C Lorenzo, I Soriano, V Hewlett, IK TI V3-loop and nef gene sequences of HIV-1 isolates from a hemophiliac cohort with long-term non-progressive infection SO AIDS LA English DT Letter ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTORS; NONPROGRESSORS; INDIVIDUALS; CORECEPTORS; SURVIVORS; CCR5 C1 US FDA, CBER, Mol Virol Lab, Rockville, MD 20852 USA. Inst Salud Carlos III, Infect Dis Serv, Madrid, Spain. Hosp Gen Valle Hebron, Haemophilia Sect, Barcelona, Spain. Hosp La Fe, Sect Congenital Coagulopathies, E-46009 Valencia, Spain. RP Vallejo, A (reprint author), US FDA, CBER, Mol Virol Lab, HFM-315,1401 Rockville Pike, Rockville, MD 20852 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 14 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 11 PY 1999 VL 13 IS 4 BP 532 EP 534 DI 10.1097/00002030-199903110-00019 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 177EN UT WOS:000079196100019 PM 10197389 ER PT J AU Thompson, PA Seyedi, F Lang, NP MacLeod, SL Wogan, GN Anderson, KE Tang, YM Coles, B Kadlubar, FF AF Thompson, PA Seyedi, F Lang, NP MacLeod, SL Wogan, GN Anderson, KE Tang, YM Coles, B Kadlubar, FF TI Comparison of DNA adduct levels associated with exogenous and endogenous exposures in human pancreas in relation to metabolic genotype SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE aromatic amine; DNA adduct; pancreas; oxidative damage; lipid peroxidation ID WHITE BLOOD-CELLS; LIPID-PEROXIDATION; MASS-SPECTROMETRY; ESCHERICHIA-COLI; AROMATIC-AMINES; CIGARETTE-SMOKE; TOBACCO-SMOKE; FATTY-ACIDS; LIVER DNA; CANCER AB Recently, we examined normal human pancreas tissue for DNA adducts derived from either exogenous chemical exposure and/or endogenous agents. In an effort to explain the different types and levels of DNA adducts formed in the context of individual susceptibility to cancer, we have focused on gene-environment interactions. Here, we report on the levels of hydrophobic aromatic amines (AAs), specifically those derived from 4-aminobiphenyl (ABP), and DNA adducts associated with oxidative stress in human pancreas. Although these adducts have been reported in several human tissues by different laboratories, a comparison of the levels of these adducts in the same tissue samples has not been performed. Using the same DNA, the genotypes were determined for N-acetyltransferase 1 (NAT1), the glutathione S-transferase (GST) M1, GSTP1, GSTT1, and NAD(P)H quinone reductase-1 (NQO(1)) as possible modulators of adduct levels because their gene products are involved in the detoxification of AAs, lipid peroxidation products and in redox cycling. These results indicate that ABP-DNA adducts, malondialdehyde-DNA adducts, and 8-oxo-2'-deoxyguanosine (8-oxo-dG) adducts are present at similar levels. Of the metabolic genotypes examined, the presence of ABP-DNA adducts was strongly associated with the putative slow NAT1*4/*4 genotype, suggesting a role for this pathway in ABP detoxification. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. MIT, Cambridge, MA 02139 USA. John L McClellan Mem Vet Adm Med Ctr, Little Rock, AR 72205 USA. Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Univ Minnesota, Minneapolis, MN 55454 USA. RP Thompson, PA (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, HFT-100,3900 NCTR Rd, Jefferson, AR 72079 USA. EM pthompson@nctr.fda.gov NR 65 TC 33 Z9 33 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAR 8 PY 1999 VL 424 IS 1-2 BP 263 EP 274 DI 10.1016/S0027-5107(99)00024-X PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 175VU UT WOS:000079117000022 PM 10064866 ER PT J AU Merritt, K Hitchins, VM Neale, AR AF Merritt, K Hitchins, VM Neale, AR TI Tissue colonization from implantable biomaterials with low numbers of bacteria SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE infection; Staphylococcus aureus; Staphylococcus epidermidis; multifilament; monofilament ID INFECTION AB This study was undertaken to evaluate the risk of infection (defined as the recovery of the relevant organism from the implant site) in a mouse model when low numbers of bacteria were present on an implanted biomaterial. Segments of different types of suture with adherent bacteria were implanted subcutaneously into mice. The infection risk with Staphylococcus aureus was greater than with Staphylococcus epidermidis RP62A or Candida albicans. The infection risk with the implantation of multifilament sutures was significantly greater than with monofilament sutures. When <10 colony forming units (cfu) of S. aureus were present on monofilament suture material, the infection rate was 3%. When <10 cfu of S. aureus were present on multifilament suture material, the infection rate was 7%. An infection rate of 15% occurred with <10 cfu of S. aureus on multifilament nylon sutures. When >10 but <20 cfu of S. aureus were present, the infection rates were 4 and 51%, respectively. These data confirm that the infection rate with multifilament sutures (or porous materials) is greater than with monofilament sutures (or solid materials) when the organisms are encountered at implantation (acute model) and indicate that a significant risk of infection may occur when only a few organisms are on a device at implantation. (C) 1999 John Wiley & Sons, Inc. C1 US FDA, CDRH, OST, Div Life Sci, Rockville, MD 20852 USA. RP Merritt, K (reprint author), 17704 Stoneridge Dr, Gaithersburg, MD 20878 USA. NR 13 TC 43 Z9 43 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD MAR 5 PY 1999 VL 44 IS 3 BP 261 EP 265 DI 10.1002/(SICI)1097-4636(19990305)44:3<261::AID-JBM4>3.0.CO;2-M PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 154LK UT WOS:000077890500004 PM 10397928 ER PT J AU Cohen, E Maxwell, RJ Donoghue, DJ AF Cohen, E Maxwell, RJ Donoghue, DJ TI Automated multi-residue isolation of fluoroquinolone antimicrobials from fortified and incurred chicken liver using on-line microdialysis and high-performance liquid chromatography with programmable fluorescence detection SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE fluoroquinolones; sarafloxacin; oxolinic acid; flumequine ID ONLINE DIALYSIS; OXOLINIC ACID; SAMPLE PREPARATION; BIOLOGICAL SAMPLES; FISH-TISSUES; UV DETECTION; FLUMEQUINE; PLASMA; ENROFLOXACIN; METABOLITE AB Isolation of the quinolones, sarafloxacin (SAR), oxolinic acid (OXA), and flumequine (FMQ), from fortified chicken liver tissues, and SAR incurred chicken Liver tissues was achieved by combined liquid-liquid extraction and aqueous on-line microdialysis using the automated trace enrichment of dialysates (ASTED) system. Analysis of tissue isolates after ASTED clean-up was performed using reversed-phase HPLC and programmable fluorescence detection. Overall recoveries of SAR, OXA and FMQ from samples fortified over a concentrations range of 1-100 ppb were 94, 97 and 87% with overall inter-assay variability of 4.2, 4.1 and 3.6%, respectively. Chicken liver samples incurred with SAR at three concentration levels also were tested by the ASTED method. The method exhibited high peak resolution (3.4-4.2 on average), a high signal-to-noise ratio, and demonstrated good precision. The ASTED-HPLC method overall had a lower limit of detection (LOD) of 0.2 ppb, and a Limit of quantitation (LOQ) of 1 ppb. (C) 1999 Elsevier Science B.V. All rights reserved. C1 ARS, Eastern Reg Res Ctr, USDA, Wyndmoor, PA 19038 USA. US FDA, Ctr Vet Med, Div Anim Res, Laurel, MD 20708 USA. RP Maxwell, RJ (reprint author), ARS, Eastern Reg Res Ctr, USDA, 600 E Mermaid Lane, Wyndmoor, PA 19038 USA. EM rmaxwell@arserrc.gov NR 29 TC 34 Z9 35 U1 0 U2 4 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 MAR 5 PY 1999 VL 724 IS 1 BP 137 EP 145 DI 10.1016/S0378-4347(98)00591-X PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 175PN UT WOS:000079103700015 PM 10202966 ER PT J AU Nightingale, SL AF Nightingale, SL TI Warning on abbokinase SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item 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 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 3 PY 1999 VL 281 IS 9 BP 786 EP 786 DI 10.1001/jama.281.9.786 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 170KF UT WOS:000078804300005 PM 10070983 ER PT J AU Nightingale, SL AF Nightingale, SL TI Cerebyx labels changed SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item 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 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 3 PY 1999 VL 281 IS 9 BP 786 EP 786 DI 10.1001/jama.281.9.786 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 170KF UT WOS:000078804300007 PM 10070983 ER PT J AU Nightingale, SL AF Nightingale, SL TI Celecoxib for arthritis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item 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 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 3 PY 1999 VL 281 IS 9 BP 786 EP 786 DI 10.1001/jama.281.9.786 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 170KF UT WOS:000078804300006 PM 10070983 ER PT J AU Temple, R AF Temple, R TI Meta-analysis and epidemiologic studies in drug development and postmarketing surveillance SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID RANDOMIZED TRIALS; CLINICAL-TRIALS; METAANALYSIS; NEED C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Temple, R (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Ln,HFD-101, Rockville, MD 20857 USA. NR 32 TC 56 Z9 56 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 3 PY 1999 VL 281 IS 9 BP 841 EP 844 DI 10.1001/jama.281.9.841 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 170KF UT WOS:000078804300036 PM 10071007 ER PT J AU Suzuki, K Mori, A Ishii, KJ Saito, J Singer, DS Klinman, DM Krause, PR Kohn, LD AF Suzuki, K Mori, A Ishii, KJ Saito, J Singer, DS Klinman, DM Krause, PR Kohn, LD TI Activation of target-tissue immune-recognition molecules by double-stranded polynucleotides SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; PROTEIN-KINASE PKR; I GENE-EXPRESSION; ANTIGEN PRESENTATION; EPITHELIAL-CELLS; CPG MOTIFS; DISEASE; INTERFERON; AUTOIMMUNITY; INDUCTION AB Abnormal expression of major histocompatibility complex (MHC) class I and class II in various tissues is associated with autoimmune disease. Autoimmune responses can be triggered by viral infections or tissue injuries. We show that the ability of a virus or a tissue injury to increase MHC gene expression is duplicated by any fragment of double-stranded (ds) DNA or dsRNA introduced into the cytoplasm of nonimmune cells. Activation is sequence-independent, is induced by ds polynucleotides as small as 25 bp in length, and is not duplicated by single-stranded polynucleotides. In addition to causing abnormal MHC expression, the ds nucleic acids increase the expression of genes necessary for antigen processing and presentation: proteasome proteins (e.g., LMP2), transporters of antigen peptides; invariant chain, HLA-DM, and the costimulatory molecule B7.1. The mechanism is different from and additive to that of gamma-interferon (gamma IFN), i.e., ds polynucleotides increase class I much more than class II, whereas gamma IFN increases class II more than class I. The ds nucleic acids also induce or activate Stat1, Stat3, mitogen-activated protein kinase, NF-kappa B, the class II transactivator, RPX5, and the IFN regulatory factor 1 differently from gamma IFN. CpG residues are not responsible for this effect, and the action of the ds polynucleotides could be shown in a variety of cell types in addition to thyrocytes. We suggest that this phenomenon is a plausible mechanism that might explain how viral infection of tissues or tissue injury triggers autoimmune disease; it is potentially relevant to host immune responses induced during gene therapy. C1 NIDDKD, Metab Dis Branch, Cell Regulat Sect, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Lab Retroviral Res, Ctr Biol & Evaluat Res, Bethesda, MD 20892 USA. US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol & Evaluat Res, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), NIDDKD, Metab Dis Branch, Cell Regulat Sect, NIH, Bethesda, MD 20892 USA. EM lenk@bdg10.niddk.nih.gov RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 39 TC 140 Z9 147 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 1999 VL 96 IS 5 BP 2285 EP 2290 DI 10.1073/pnas.96.5.2285 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600086 PM 10051633 ER PT J AU Moysich, KB Mendola, P Schisterman, EF Freudenheim, JL Ambrosone, CB Vena, JE Shields, PG Kostyniak, P Greizerstein, H Graham, S Marshall, JR AF Moysich, KB Mendola, P Schisterman, EF Freudenheim, JL Ambrosone, CB Vena, JE Shields, PG Kostyniak, P Greizerstein, H Graham, S Marshall, JR TI An evaluation of proposed frameworks for grouping polychlorinated biphenyl (PCB) congener data into meaningful analytic units SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE polychlorinated biphenyls; epidemiologic studies; data reduction; methodological issues ID RISK ASSESSMENT; DIOXINS; TOXICITY; CHILDREN; HEALTH AB Background Polychlorinated biphenyls (PCBs) have been associated with a variety of health outcomes. Enhanced laboratory techniques can provide a relatively large number of individual PCB congeners for investigation. However to dare there are no established frameworks for grouping a large number of PCB congeners into meaningful analytic units. Methods In a case-control study of serum PCB levels on breast cancer risk, measured levels of 56 PCB congener peaks were available for analysis. We considered several approaches for grouping these compounds based on 1) chlorination, 2) factor analysis, 3) enzyme induction, 4) enzyme induction and occurrence, and 5) enzyme induction, occurrence, and other toxicological aspects. The utility of a framework was based on the mechanism of biologic actions within each framework, lack of collinearity among congener groups, and frequency of detection of PCB congener groups in measured serum levels of 192 healthy postmenopausal women. Results Most participants had detectable levels for the proposed PCB congeners groups, using degree of chlorination as a grouping framework. In addition, the previously proposed grouping approach based on enzyme induction, occurrence, and other toxicological aspects was an applicable alternative to the crude approach of grouping by degree of chlorination. Grouping these congeners with respect to P450 enzyme induction activity, and the previously proposed framework based on enzyme induction and occurrence, did not fit these data as well, because only a small proportion of participants had detectable levels for the congener groups with the greatest toxicological potential. Statistical grouping did not result in an interpretable and meaningful clustering of these exposures. Conclusions In these data, grouping with respect to degree of chlorination and the previously proposed framework based on enzyme induction, occurrence, and other toxicological aspects were the most useful approaches to reducing a large number of PCB congeners into meaningful analytic units. Factors affecting the utility of the proposed grouping frameworks are discussed. (C) 1999 Wiley-Liss, Inc. C1 Roswell Pk Canc Inst, Dept Canc Prevent Epidemiol & Biostat, Buffalo, NY 14263 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. SUNY Buffalo, Toxicol Res Ctr, Buffalo, NY 14260 USA. Arizona Canc Ctr, Tucson, AZ 85724 USA. RP Moysich, KB (reprint author), Roswell Pk Canc Inst, Dept Canc Prevent Epidemiol & Biostat, Elm & Carlton St, Buffalo, NY 14263 USA. RI Shields, Peter/I-1644-2012; OI Mendola, Pauline/0000-0001-5330-2844; Schisterman, Enrique/0000-0003-3757-641X FU NCI NIH HHS [CA 11535, CA/ES 62995] NR 25 TC 35 Z9 36 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAR PY 1999 VL 35 IS 3 BP 223 EP 231 DI 10.1002/(SICI)1097-0274(199903)35:3<223::AID-AJIM2>3.0.CO;2-L PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 163KW UT WOS:000078405500002 PM 9987555 ER PT J AU Cross, CE Lee, YJ Wong, PS Shacter, E Shigenaga, M Eiserich, JP van der Vliet, A Tarkington, BK Syvanen, M AF Cross, CE Lee, YJ Wong, PS Shacter, E Shigenaga, M Eiserich, JP van der Vliet, A Tarkington, BK Syvanen, M TI Houseflies: A novel biomonitor of oxidative atmospheric pollutants SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Univ Calif Davis, Ctr Comparat Resp Biol & Med, Davis, CA 95616 USA. US FDA, Bethesda, MD 20014 USA. Univ Calif Berkeley, Dept Biochem, Berkeley, CA 94720 USA. Univ Alabama, Ctr Free Rad Biol, Birmingham, AL 35233 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A891 EP A891 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237104987 ER PT J AU Aszalos, A Thompson, K Yin, JJ Ross, DD AF Aszalos, A Thompson, K Yin, JJ Ross, DD TI Combinations of P-glycoprotein blockers, verapamil, PSC833, and cremophor act differently on the multidrug resistance associated protein (MRP) and on P-glycoprotein (Pgp) SO ANTICANCER RESEARCH LA English DT Article DE P-glycoprotein; multidrug resistance associated protein; blockers ID HUMAN TUMOR-CELLS; EXPRESSION; GENE; TRANSPORTER; RHODAMINE-123; LINES AB Clinical studies are currently in progress to evaluate functional modifiers of P-glycoprotein (Pgp), an efflux pump associated with resistance to cancer chemotherapy. However, the effects of these modifiers on a more recently discovered efflux pump, the multidrug resistance associated protein (MRP), have not yet been fully characterized. MRP is expressed in: most human tissues and is overexpressed in several tumor types. For these reasons, we have investigated the effects of three prototype Pgp modifiers, which act by different modes on the function of Pgp, on the function of MRP in two MRP-overexpressing cell lines: UMCC/VP lung and MCF-7/VP breast cancer cells. Clinically optimal plasma levels of verapamil, cremophor; and PSC833 have been shown to completely block the function of Pgp in Pgp-over expressing cells. However, in the two MRP-over expressing cell lines, these modifiers only partially blocked the function of MRP and combinations of these optimal concentrations acted antagonistically. Similar antagonistic effects were seen with combinations of suboptimal concentration levels of these blockers, while these combinations resulted in synergistic effects in Pgp overexpressing cells. For two biophysical parameters measured at the plasma membrane, membrane fluidity and membrane potential, the effects of these modifiers were essentially similar in Pgp and MRP expressing cells. We suggest that the 170 kD Pgp and the 190 kD MRP glycoproteins, imbedded in the plasma membranes, respond differently to simultaneous effects of the investigated prototype resistance modifiers. These results also suggest that the identification of the specific mechanism of drug resistance is important for the selection of chemotherapeutic strategies to block the efflux pump on the cancer cell. C1 US FDA, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. US FDA, Ctr Food Safety & Nutr, Washington, DC 20204 USA. Univ Maryland, Greenbaum Canc Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Div Hematol Oncol, Baltimore, MD 21201 USA. Baltimore Vet Adm Med Ctr, Baltimore, MD USA. RP Aszalos, A (reprint author), US FDA, Ctr Drug Evaluat & Res, HFD-910,8301 Muirkik Rd, Laurel, MD 20708 USA. RI Yin, Jun Jie /E-5619-2014 NR 27 TC 42 Z9 42 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 1999 VL 19 IS 2A BP 1053 EP 1064 PG 12 WC Oncology SC Oncology GA 202JQ UT WOS:000080649100024 PM 10368654 ER PT J AU Ito, S Ansari, P Sakatsume, M Dickensheets, H Vazquez, N Donnelly, RP Larner, AC Finbloom, DS AF Ito, S Ansari, P Sakatsume, M Dickensheets, H Vazquez, N Donnelly, RP Larner, AC Finbloom, DS TI Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma-induced genes by suppressing tyrosine phosphorylation of STAT1 SO BLOOD LA English DT Article ID DNA-BINDING PROTEINS; HUMAN MONOCYTES; T-CELLS; PROMOTER; ACTIVATION; INDUCTION; RECEPTOR; FAMILY; TRANSCRIPTION; RESPONSES AB Interleukin-10 (IL-10) helps maintain polarized T-helper cells in a T-helper lymphocyte 2 (Th2) phenotype. Part of this process involves the prevention of the development of Th1 cells, which are a primary source of interferon gamma (IFN gamma), a potent activator of monocytes and an inhibitor of Th2 proliferation. Because monocytes and macrophages are important mediators of Th1-type responses, such as delayed-type hypersensitivity. we sought to determine if IL-10 could directly mediate inhibition of IFN gamma- and IFN alpha-induced gene expression in these cells. Highly purified monocytes were incubated with IL-10 for 60 to 90 minutes before the addition of IFN gamma or IFN alpha. IL-10 preincubation resulted in the inhibition of gene expression for several IFN-induced genes, such as IP-10, ISG54, and intercellular adhesion molecule-1. The reduction in gene expression resulted from the ability of IL-10 to suppress IFN-induced assembly of signal transducer and activator of transcription (STAT) factors to specific promoter motifs on IFN alpha- and IFN gamma-inducible genes. This was accomplished by preventing the IFN-induced tyrosine phosphorylation of STAT1, a component of both IFN alpha- and IFN gamma-induced DNA binding complexes. Therefore, IL-10 can directly inhibit STAT-dependent early response gene expression induced by both IFN alpha and IFN gamma in monocytes by suppressing the tyrosine phosphorylation of STAT1. This may occur through the ability of IL-10 to induce expression of the gene, suppressor of cytokine signaling 3 (SOCS3). This is a US government work. There are no restrictions on its use. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. RP Finbloom, DS (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, 29 Lincoln Dr Bldg 29A,Room 2D20, Bethesda, MD 20892 USA. NR 48 TC 268 Z9 282 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1999 VL 93 IS 5 BP 1456 EP 1463 PG 8 WC Hematology SC Hematology GA 168TM UT WOS:000078708800003 PM 10029571 ER PT J AU Yao, L Sgadari, C Furuke, K Bloom, ET Teruya-Feldstein, J Tosato, G AF Yao, L Sgadari, C Furuke, K Bloom, ET Teruya-Feldstein, J Tosato, G TI Contribution of natural killer cells to inhibition of angiogenesis by interleukin-12 SO BLOOD LA English DT Article ID INTERFERON-INDUCIBLE PROTEIN-10; STIMULATORY FACTOR INTERLEUKIN-12; ENDOTHELIAL GROWTH-FACTOR; NECROSIS IN-VIVO; NK CELLS; RECOMBINANT IL-12; HUMAN-LYMPHOCYTES; TUMOR-REGRESSION; GAMMA PRODUCTION; T-LYMPHOCYTES AB Interleukin-12 (IL-12) inhibits angiogenesis in vivo by inducing interferon-gamma (IFN-gamma) and other downstream mediators. Here, we report that neutralization of natural killer (NK) cell function with antibodies to either asialo GM1 or NK 1.1 reversed IL-12 inhibition of basic fibroblast growth factor (bFGF)-induced angiogenesis in athymic mice. By immunohistochemistry, those sites where bFGF-induced neovascularization was inhibited by IL-12 displayed accumulation of NK cells and the presence of IP-10-positive cells. Based on expression of the cytolytic mediators perforin and granzyme B, the NK cells were locally activated. Experimental Burkitt lymphomas treated locally with IL-12 displayed tumor tissue necrosis, vascular damage, and NK-cell infiltration surrounding small vessels. After activation in vitro with IL-12 NK cells from nude mice became strongly cytotoxic for primary cultures of syngeneic aortic endothelial cells. Cytotoxicity was neutralized by antibodies to IFN-gamma. These results document that NK cells are required mediators of angiogenesis inhibition by IL-12 and provide evidence that NK-cell cytotoxicity of endothelial cells is a potential mechanism by which IL-12 can suppress neovascularization. C1 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. NCI, Pathol Lab, Hematopathol Sect, Bethesda, MD 20892 USA. RP Yao, L (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bldg 29A,Room 2D06,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 52 TC 153 Z9 158 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1999 VL 93 IS 5 BP 1612 EP 1621 PG 10 WC Hematology SC Hematology GA 168TM UT WOS:000078708800022 PM 10029590 ER PT J AU Beland, FA McDaniel, LP Marques, MM AF Beland, FA McDaniel, LP Marques, MM TI Comparison of the DNA adducts formed by tamoxifen and 4-hydroxytamoxifen in vivo SO CARCINOGENESIS LA English DT Article ID BREAST-CANCER PATIENTS; DERIVATIVE METABOLITE-E; HUMAN LIVER; ALPHA-ACETOXYTAMOXIFEN; ENDOMETRIAL CARCINOMA; UTERINE PEROXIDASE; ESTROGEN-RECEPTOR; N-DEMETHYLATION; RATS; IDENTIFICATION AB Tamoxifen is a liver carcinogen in rats and has been associated with an increased risk of endometrial cancer in women, Recent reports of DNA adducts in leukocyte and endometrial samples from women treated with tamoxifen suggest that it may be genotoxic to humans. One of the proposed pathways for the metabolic activation of tamoxifen involves oxidation to 4-hydroxytamoxifen, which may be further oxidized to an electrophilic quinone methide, In the present study, we compared the extent of DNA adduct formation in female Sprague-Dawley rats treated by gavage with seven daily doses of 54 mu mol/kg tamoxifen or 4-hydroxytamoxifen and killed 24 h after the last dose. Liver weights and microsomal rates of ethoxyresorufin O-deethylation, 4-dimethylaminopyrine N-demethylation and p-nitrophenol oxidation were not altered by tamoxifen or 4-hydroxytamoxifen treatment. Uterine weights were decreased significantly and uterine peroxidase activity was decreased marginally in treated as compared with control rats. DNA adducts were assayed by P-32-post-labeling in combination with HPLC. Two major DNA adducts were detected in liver DNA from rats administered tamoxifen, These adducts had retention times comparable with those obtained from in vitro reactions of alpha-acetoxytamoxifen and 4-hydroxytamoxifen quinone methide with DNA, Hepatic DNA adduct levels in rats administered 4-hydroxytamoxifen did not differ from those observed in control rats. Likewise, adduct levels in uterus DNA from rats treated with tamoxifen or 4-hydroxytamoxifen were not different from those detected in control rats. These data suggest that a metabolic pathway involving 4-hydroxytamoxifen is not a major pathway in the activation of tamoxifen to a DNA-binding derivative in Sprague-Dawley rats. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Tecn Lisboa, Ctr Quim Estrutural, Complexo 1, Inst Super Tecn, P-1049001 Lisbon, Portugal. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM fbeland@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 69 TC 47 Z9 47 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 1999 VL 20 IS 3 BP 471 EP 477 DI 10.1093/carcin/20.3.471 PG 7 WC Oncology SC Oncology GA 174ZL UT WOS:000079066400018 PM 10190564 ER PT J AU Bryan, PJ Steffan, RJ DePaola, A Foster, JW Bej, AK AF Bryan, PJ Steffan, RJ DePaola, A Foster, JW Bej, AK TI Adaptive response to cold temperatures in Vibrio vulnificus SO CURRENT MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; ACCLIMATION PROTEINS; BACILLUS-SUBTILIS; SHOCK PROTEINS; OYSTERS; SHELLSTOCK; INFECTIONS; VIRULENCE; INDUCTION; HEAT AB The effectiveness of rapid chilling or freezing of oysters to reduce Vibrio vulnificus levels in shellfish may be compromised by product handling procedures that permit cold adaptation. When a V. vulnificus culture was shifted from 35 degrees C to 6 degrees C conditions, it underwent transition to a non-culturable state. Cells adapted to 15 degrees C prior to change to 6 degrees C condition, however, remain viable and culturable. In addition, cultures adapted to 15 degrees C were able to survive better upon freezing at -78 degrees C compared with cultures frozen directly from 35 degrees C. Inhibition of protein synthesis by addition of chloramphenicol in a V. vulnificus culture immediately prior to the exposure to the adaptive temperature eliminated inducible cold tolerance. These results suggest that cold-adaptive "protective" proteins may enhance survival and tolerance at cold temperatures. In addition, removal of iron from the growth medium by adding 2,2'-Dipyridyl prior to cold adaptation decreased the viability by approximately 2 logarithm levels. This suggests that iron plays an important role in adaptation at cold temperatures. Analysis of total cellular proteins on an SDS polyacrylamide gel electrophoresis, labeled with S-35-methionine during exposure at 15 degrees C, showed elevated expressions of a 6-kDa and a 40-kDa protein and decreased expression of an 80-kDa protein. These results suggest that, for V. vulnificus, survival and tolerance at cold temperatures could be due to the expression of cold-adaptive proteins other than previously documented major cold shock proteins such as CS7.4 and CsdA. In this study, for the first time we have shown that exposure to an intermediate cold temperature (15 degrees C) causes a cold adaptive response, helping this pathogen remain in culturable state when exposed to a much colder temperature (6 degrees C). This adaptive nature to cold temperatures could be important for shellfish industry efforts to reduce the risk of V. vulnificus infection from consuming raw oysters. C1 Univ Alabama, Dept Biol, Birmingham, AL 35294 USA. Envirogen Inc, Lawrenceville, NJ 08648 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. Univ S Alabama, Dept Microbiol & Immunol, Mobile, AL 36688 USA. RP Bej, AK (reprint author), Univ Alabama, Dept Biol, 1300 Univ Blvd, Birmingham, AL 35294 USA. NR 39 TC 46 Z9 49 U1 2 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD MAR PY 1999 VL 38 IS 3 BP 168 EP 175 DI 10.1007/PL00006782 PG 8 WC Microbiology SC Microbiology GA 166ZP UT WOS:000078608300006 PM 9922468 ER PT J AU Rafii, F Ruseler-Van Embden, JGH Van Lieshout, LMC AF Rafii, F Ruseler-Van Embden, JGH Van Lieshout, LMC TI Changes in bacterial enzymes and PCR profiles of fecal bacteria from a patient with ulcerative colitis before and after antimicrobial treatments SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE ulcerative colitis; antimicrobial agents; PCR; enzymes ID INFLAMMATORY BOWEL-DISEASE; CROHNS-DISEASE; MUCIN; PATHOGENESIS; GLYCOSIDASES; MICROFLORA; FLORA; FECES; MUCUS AB A 26-year-old female patient, suffering from recurrent attacks of ulcerative colitis accompanied by extraintestinal symptoms (erythema nodosum and pyoderma gangrenosum), was evaluated for the effect of antibacterial agents on the intestinal bacteria and their enzymatic activities. The enzymes were assayed both at the onset of disease symptoms and after treatment with each of five drug regimens (fluconazole and cefadroxil, cefuroxime axetil and cestriaxone sodium, ciprofloxacin and cestriaxone sodium, ciprofloxacin alone, and ciprofloxacin, metronidazole, and cephalexin). The activities of azoreductase, nitroreductase, oxidoreductase, glucuronidase, and sulfatase were generally lower following all of the treatments, especially when ciprofloxacin was included. The DNA from each sample was amplified by PCR, using random primers. Profiles of amplified DNA on agarose gels showed different patterns, indicating differences in the microflora before and after the antimicrobial treatments. The clinical response to antibacterial therapy was consistent with the decreased bacterial enzymatic activities and changes in the microbial population. Ciprofloxacin, which was associated with the most dramatic falls in enzymatic activity, also had the best clinical results. We conclude that intestinal bacteria and their enzymes play important roles in ulcerative colitis and that population changes can be monitored using PCR profiles. C1 Natl Ctr Toxicol Res, Food & Drug Adm, Div Microbiol, Jefferson, AR 72079 USA. Erasmus Univ, Dept Immunol, NL-3000 DR Rotterdam, Netherlands. RP Rafii, F (reprint author), Natl Ctr Toxicol Res, Food & Drug Adm, Div Microbiol, Jefferson, AR 72079 USA. NR 28 TC 15 Z9 16 U1 0 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAR PY 1999 VL 44 IS 3 BP 637 EP 642 DI 10.1023/A:1026634229934 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 175GP UT WOS:000079085300030 PM 10080162 ER PT J AU Gensheimer, KF Fukuda, K Brammer, L Cox, N Patriarca, PA Strikas, RA AF Gensheimer, KF Fukuda, K Brammer, L Cox, N Patriarca, PA Strikas, RA TI Preparing for pandemic influenza: The need for enhanced surveillance SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material C1 Maine Bureau Hlth, Augusta, ME 04330 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. US FDA, Rockville, MD 20857 USA. RP Gensheimer, KF (reprint author), Maine Bureau Hlth, Augusta, ME 04330 USA. NR 2 TC 20 Z9 20 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAR-APR PY 1999 VL 5 IS 2 BP 297 EP 299 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 186NH UT WOS:000079735500019 PM 10221887 ER PT J AU Chen, T Goldstein, JS O'Boyle, K Whitman, MC Brunswick, M Kozlowski, S AF Chen, T Goldstein, JS O'Boyle, K Whitman, MC Brunswick, M Kozlowski, S TI ICAM-1 co-stimulation has differential effects on the activation of CD4(+) and CD8(+) T cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T lymphocyte subset; adhesion molecule; cytokine ID MONOCLONAL-ANTIBODY; ADHESION MOLECULE-1; LYMPHOCYTES-T; COSTIMULATION; INTERLEUKIN-2; LEISHMANIASIS; REQUIREMENTS; LIGAND; VCAM-1; GAMMA 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/co-stimulatory molecule signals. To isolate the effects of the adhesion/ co-stimulatory molecule ICAM-1,we have stimulated purified murine CD4(+) and CD8(+) T cells with plate-bound anti-CD3 in the presence or absence of plate-bound soluble ICAM-1. In this report, we demonstrate that the co-immobilization of soluble ICAM-1 and anti-CD3 leads to a much greater increase in IL-2 production by CD8(+) T cells than CD4(+) T cells. The ICAM-1-induced enhancement we observed has differential sensitivity to LFA-1 blockade, depending on the T cell subsets and cytokine evaluated. These effects may play an important role in the generation and modulation of immune responses. C1 US FDA, Ctr Biol Evaluat & Res, DMA, Bethesda, MD 20892 USA. RP Kozlowski, S (reprint author), US FDA, Ctr Biol Evaluat & Res, DMA, 8800 Rockville Pike,Bldg 29B-3NN22, Bethesda, MD 20892 USA. NR 24 TC 22 Z9 22 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 1999 VL 29 IS 3 BP 809 EP 814 DI 10.1002/(SICI)1521-4141(199903)29:03<809::AID-IMMU809>3.3.CO;2-O PG 6 WC Immunology SC Immunology GA 176KE UT WOS:000079149600010 PM 10092083 ER PT J AU Luecke, RH Wosilait, WD Young, JF AF Luecke, RH Wosilait, WD Young, JF TI Mathematical modeling of human embryonic and fetal growth rates SO GROWTH DEVELOPMENT AND AGING LA English DT Article DE growth; human; embryonic; fetal; Gompertz ID COMPUTER-MODEL; PREGNANCY AB A mathematical model for human embryonic/fetal growth data from implantation to birth is developed. In previous work, it was shown that an unbiased estimate for human fetal growth data from about day 50 post-conception until term could be calculated from the Gompertz equation. This period represents a range of embryonic/fetal weights from one to 3500 g. When the Gompertz equation is extended, with no change of parameters, to the prenatal period before 50 days, the predicted weights have a consistent bias which might have a biological basis. Early embryonic growth immediately following fertilization is exponential; i.e., one cell goes to 2, then 4, then 8... etc., with essentially no decrease in relative growth rate. Except for possible small changes in cell size and cell mitosis cycle time, such exponential growth can be considered as a special case of the Gompertz equation with alpha, the relative rate of decrease of the relative growth rate, equal to zero. The relative growth rate begins to decrease about 20 days post-conception, at the time of cell differentiation into organ precursors. Although the "Hayflick Limit" of the maximum of 50 to 60 cell divisions for human cells would tend to cause a decrease in growth rate, it can be shown that the effect is insignificant during embryonic/fetal growth. The observed decrease in the growth rate might be a result of a decreasing fraction of cells in the pool of dividing cells. For the Gompertz equation model, alpha at this time changes from zero to alpha positive number. Analysis of fetal growth data shows that a rapidly becomes large and then decreases over a period of several days to become a constant positive value for the remainder of the prenatal term. Good fits of empirical embryonic/fetal growth data were obtained by nonlinear regression with calculation of the embryonic/fetal weights through numerical integration of the differential Gompertz equations and the functionality of alpha. C1 Univ Missouri, Dept Chem Engn, Columbia, MO 65211 USA. Univ Missouri, Sch Med, Dept Pharmacol, Columbia, MO 65211 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Luecke, RH (reprint author), Univ Missouri, Dept Chem Engn, Columbia, MO 65211 USA. NR 23 TC 11 Z9 11 U1 1 U2 4 PU GROWTH PUBLISHING CO INC PI HULLS COVE PA PO BOX 205, HULLS COVE, ME 04644-0205 USA SN 1041-1232 J9 GROWTH DEVELOP AGING JI Growth Dev. Aging PD SPR-SUM PY 1999 VL 63 IS 1-2 BP 49 EP 59 PG 11 WC Developmental Biology; Geriatrics & Gerontology SC Developmental Biology; Geriatrics & Gerontology GA 244KW UT WOS:000083051100004 PM 10885857 ER PT J AU Rickert, R Steinhart, H Fritsche, J Sehat, N Yurawecz, MP Mossoba, MM Roach, JAG Eulitz, K Ku, Y Kramer, JKG AF Rickert, R Steinhart, H Fritsche, J Sehat, N Yurawecz, MP Mossoba, MM Roach, JAG Eulitz, K Ku, Y Kramer, JKG TI Enhanced resolution of conjugated linoleic acid isomers by tandem-column silver-ion high performance liquid chromatography SO HRC-JOURNAL OF HIGH RESOLUTION CHROMATOGRAPHY LA English DT Article DE conjugated linoleic acid (CLA); silver-ion high performance liquid chromatography (Ag+-HPLC); cheese; analysis; silver-ion chromatography; tandem-column Ag+-HPLC ID TRANS-FATTY-ACIDS; IDENTIFICATION AB A commercial mixture of conjugated linoleic acid (CLA) isomers, reportedly consisting of six components, was recently resolved into 12 peaks attributed to CLA isomers using silver-ion high performance liquid chromatography (Ag+-HPLC). In this study, the coupling of two analytical silver-ion high performance liquid chromatography columns (tandem-column Ag+-HPLC) in series led to the enhanced resolution of CLA isomers, Many CLA isomers mere baseline resolved and the pair 18:2 8,10 c/t and 18:2 7,9 c/t found in cheese products, was resolved for the first time, In this work, a similar commercial CLA mixture was separated into 16 peaks, while CLA isomers from cheese also gave rise to 16 peaks, As expected, the CLA isomers were separated into three geometric groups in the order trans,trans, cis/trans, and cis,cis. Semi-preparative Ag+-HPLC, followed by gas chromatography-mass spectroscopy of the dimethyloxazoline derivatives, was used to confirm the identity of the newly resolved positional CLA isomers. The double bond configuration of CLA isomers was established by gas chromatography-Fourier transform infrared spectroscopy, Tw minor t,t CLA isomers found in cheese, presumably 18:2 t6t8 and 18:2 t13t15, mere also separated. The CLA isomeric composition of 16 commercial cheese products was determined. C1 Univ Hamburg, Dept Food Chem, Inst Biochem & Food Chem, D-20146 Hamburg, Germany. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Food Res Ctr, So Crop Protect, Guelph, ON N1G 2W1, Canada. RP Rickert, R (reprint author), Univ Hamburg, Dept Food Chem, Inst Biochem & Food Chem, Grindelallee 117, D-20146 Hamburg, Germany. NR 24 TC 27 Z9 28 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0935-6304 J9 HRC-J HIGH RES CHROM JI HRC-J. High Resolut. Chromatogr. PD MAR PY 1999 VL 22 IS 3 BP 144 EP 148 PG 5 WC Chemistry, Analytical SC Chemistry GA 172LF UT WOS:000078925100002 ER PT J AU Klinman, DM Conover, J Leiden, JM Rosenberg, AS Sechler, JMG AF Klinman, DM Conover, J Leiden, JM Rosenberg, AS Sechler, JMG TI Safe and effective regulation of hematocrit by gene gun administration of an erythropoietin-encoding DNA plasmid SO HUMAN GENE THERAPY LA English DT Article ID SKELETAL-MUSCLE; CIRCUMSPOROZOITE PROTEIN; INTRAMUSCULAR INJECTION; SYSTEMIC DELIVERY; EXPRESSION VECTOR; MICE; VACCINES; IMMUNIZATION; CYTOKINE; ADENOVIRUS AB This work examines the effect of delivering a DNA plasmid encoding murine erythropoietin (pVRmEpo) to BALB/c mice by gene gun, Whereas intramuscular injection elicits a rise in hematocrit persisting >8 months, intradermal delivery triggers the dose-dependent secretion of biologically active erythropoietin (Epo) for similar to 1 month. Repeated administration of pVRmEpo by gene gun elicits a stable increase in hematocrit. The source of the Epo produced following gene gun delivery was analyzed by periodically grafting the site of injection onto naive recipients. Results indicate that both stationary cells (presumably keratinocytes) and migratory (presumably dendritic) cells were transfected and secreted biologically active Epo in vivo. Gene gun administration of plasmid DNA appears to be safe, and provides an additional strategy for achieving the regulated secretion of an exogenous gene product. C1 US FDA, Retroviral Immunol Sect, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. US FDA, Immunol Lab, Div Hematol Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Retroviral Immunol Sect, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg 29A,Rm 3D10, Bethesda, MD 20892 USA. EM klinman@A1.cber.fda.gov NR 37 TC 26 Z9 27 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR 1 PY 1999 VL 10 IS 4 BP 659 EP 665 DI 10.1089/10430349950018733 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 175RG UT WOS:000079108300013 PM 10094209 ER PT J AU Hood, HL Bronaugh, RL AF Hood, HL Bronaugh, RL TI A comparison of skin viability assays for in vitro skin absorption/metabolism studies SO IN VITRO & MOLECULAR TOXICOLOGY-A JOURNAL OF BASIC AND APPLIED RESEARCH LA English DT Article ID INVITRO PERCUTANEOUS-ABSORPTION; METABOLISM AB Often the receptor fluid used. in an in vitro percutaneous absorption or metabolism study should preserve skin viability. Verification of skin viability is often required. N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid (HEPES)-buffered Hanks' balanced salt solution (HHBSS) has been shown to maintain skin viability for at least 24 h in a flow-through diffusion cell. Sometimes HHBSS is supplemented with 4% bovine serum albumin (BSA) to facilitate partitioning of Lipophilic compounds into this receptor fluid. The rate of lactate appearance in the receptor fluid (after formation in skin) is normally a good indicator of skin viability. However, BSA has been found to interfere with the measurement of lactate formation. The micromoles of lactate formed per hour by hairless guinea pig (HGP) skin was reduced approximately 40% at the end of a 24-h study by inclusion of BSA in the receptor fluid. Therefore, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetra-zolium bromide (MTT) assay was adapted to determine skin viability. Some loss of MTT reduction to formazan was observed after 24-h perfusion of HGP and fuzzy rat skin in diffusion cells. However, no loss of this activity occurred in studies with human skin. Importantly, viability determinations with the MTT assay were unaffected by the addition of BSA to the receptor fluid. C1 US FDA, Off Cosmet & Colors, Laurel, MD 20708 USA. RP Bronaugh, RL (reprint author), US FDA, Off Cosmet & Colors, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 13 TC 2 Z9 2 U1 1 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1097-9336 J9 IN VITRO MOL TOXICOL JI In Vitro Mol. Toxicol.-J. Basic Appl. Res. PD SPR PY 1999 VL 12 IS 1 BP 3 EP 9 PG 7 WC Toxicology SC Toxicology GA 321JY UT WOS:000087453400002 ER PT J AU Zhang, GH Mann, DM Tsai, CM AF Zhang, GH Mann, DM Tsai, CM TI Neutralization of endotoxin in vitro and in vivo by a human lactoferrin-derived peptide SO INFECTION AND IMMUNITY LA English DT Article ID PERMEABILITY-INCREASING PROTEIN; TUMOR-NECROSIS-FACTOR; BACTERIAL-ENDOTOXIN; MONOCLONAL-ANTIBODIES; ESCHERICHIA-COLI; ANTIBIOTIC CLASS; BINDING PROTEIN; LIPOPOLYSACCHARIDE; RECEPTOR; LIMULUS AB Endotoxin (lipopolysaccharide [LPS]) is the major pathogenic factor of gram-negative septic shock, and endotoxin-induced death is associated with the host overproduction of tumor necrosis factor alpha (TNF-alpha). In the search for new antiendotoxin molecules, we studied the endotoxin-neutralizing capacity of a human lactoferrin-derived 33-mer synthetic peptide (GRRRRSVQWCAVSQPEATKCFQWQRNMRKVRGP; designated LF-33) representing the minimal sequence for lactoferrin binding to glycosaminoglycans. LF-33 inhibited the coagulation of the Limulus amebocyte lysate and the secretion of TNF-alpha by RAW 264.7 cells induced by lipid A and four different endotoxins with a potency comparable to that of polymyxin B. The first six residues at the N terminus of LF-33 were critical for its antiendotoxin activity. The endotoxin-neutralizing capacity of LF-33 and polymyxin B was attenuated by human serum. Coinjection of Escherichia coli LPS (125 ng) with LF-33 (2.5 mu g) dramatically reduced the lethality of LPS in the galactosamine-sensitized mouse model. Significant protection of the mice against the lethal LPS challenge was also observed when LF-33 (100 mu g) was given intravenously after intraperitoneal injection of LPS. protection was correlated with a reduction in TNF-alpha levels in the mouse serum. These results demonstrate the endotoxin-neutralizing capability of LF-33 in vitro and in vivo and its potential use for the treatment of endotoxin-induced septic shock. C1 Amer Red Cross, Jerome H Holland Lab, Plasma Derivat Dept, Rockville, MD 20855 USA. US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Inst Biochem Sci, Washington, DC 20037 USA. RP Zhang, GH (reprint author), Amer Red Cross, Jerome H Holland Lab, Plasma Derivat Dept, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. EM zhanggu@usa.redcross.org FU NIAID NIH HHS [AI39691] NR 44 TC 108 Z9 111 U1 0 U2 3 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 1999 VL 67 IS 3 BP 1353 EP 1358 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 169FF UT WOS:000078736300046 PM 10024582 ER PT J AU Krause, PR Straus, SE AF Krause, PR Straus, SE TI Herpesvirus vaccines - Development, controversies, and applications SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID SIMPLEX VIRUS TYPE-2; VARICELLA-ZOSTER VIRUS; CONGENITAL CYTOMEGALOVIRUS-INFECTION; RENAL-TRANSPLANT RECIPIENTS; PLACEBO-CONTROLLED TRIAL; GENITAL HERPES; GLYCOPROTEIN-D; UNITED-STATES; PROTECTIVE IMMUNITY; HEALTHY-CHILDREN AB Herpesviruses present difficult challenges in vaccine development because of their ability to evade immune clearance. Data and recommendations regarding the live-attenuated varicella vaccine are discussed. Approaches to developing vaccines to prevent herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV)-associated illnesses also are considered. C1 US FDA, Ctr Biol Evaluat & Res, OVRR, Lab DNA Viruses, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, Ctr Biol Evaluat & Res, OVRR, Lab DNA Viruses, 29A-1C16,HFM-457,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 88 TC 20 Z9 20 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 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 1999 VL 13 IS 1 BP 61 EP + DI 10.1016/S0891-5520(05)70043-X PG 22 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 185DA UT WOS:000079651800007 PM 10198792 ER PT J AU De Angelis, E Grassi, M Gullick, WJ Johnson, GR Rossi, GB Tempesta, A De Angelis, F De Luca, A Salomon, DS Normanno, N AF De Angelis, E Grassi, M Gullick, WJ Johnson, GR Rossi, GB Tempesta, A De Angelis, F De Luca, A Salomon, DS Normanno, N TI Expression of cripto and amphiregulin in colon mucosa from high risk colon cancer families SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE cripto; amphiregulin; colon carcinoma ID FACTOR-RELATED PEPTIDES; IMMUNOHISTOCHEMICAL DETECTION; COLORECTAL TUMORS; GROWTH; PROLIFERATION; CELLS; OLIGODEOXYNUCLEOTIDES; INHIBITION; CARCINOMAS; PROGNOSIS AB We assessed the expression of the epidermal growth factor (EGF)-related peptides, cripto-I (CR-I) and amphi-regulin (AR), in a small panel of human colon adenomas and carcinomas. CR-I immunoreactivity was found in 17/31 (55%) of colon adenomas, and in 33/39 (84%) colon carcinomas. AR immunostaining was observed in 16/26 adenomas (61%) and in 20/26 carcinomas (77%). CR-I and AR staining were also assessed in 29 specimens from 24 individuals that belong to families with high incidence of colorectal carcinoma, and in 5 non-high risk individuals. Expression of CR-I was detected in 18/29 (62%) of high risk colon mucosa specimens, but only in 1/5 (20%) specimens from non-high risk individuals, while AR staining was found in 20/29 (69%) and in 4/5 (80%) of colon mucosa samples from high and low risk individuals, respectively. A majority (21/29; 72%) of the specimens from the high risk individuals had a high proliferative rate, as measured by Ki-67 staining. A statistically significant correlation was found between high proliferative rate, increased expression of CR-I and reduced expression of AR in the mucosa specimens from high risk individuals, suggesting that these might represent early events in colon tumorigenesis. C1 Fdn Pascale, ITN, Serv Oncol Sperimentale D, I-80131 Naples, Italy. Fdn Pascale, Serv Endoscopia, ITN, I-80131 Naples, Italy. Hammersmith Hosp, Imperial Canc Res Fund, Mol Oncol Unit, London W12 0HS, England. NCI, Tumor Growth Factor Sect, LTIB, NIH, Bethesda, MD 20892 USA. US FDA, DCB, Bethesda, MD 20892 USA. RP Normanno, N (reprint author), Fdn Pascale, ITN, Serv Oncol Sperimentale D, I-80131 Naples, Italy. RI De Luca, Antonella/J-8737-2016; OI De Luca, Antonella/0000-0001-5762-447X; Normanno, Nicola/0000-0002-7158-2605 NR 16 TC 19 Z9 20 U1 1 U2 1 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 MAR PY 1999 VL 14 IS 3 BP 437 EP 440 PG 4 WC Oncology SC Oncology GA 169VQ UT WOS:000078770100005 PM 10024674 ER PT J AU Junod, SW AF Junod, SW TI Our children's toxic legacy: How science and law fail to protect us from pesticides. SO ISIS LA English DT Book Review C1 US FDA, Rockville, MD 20857 USA. RP Junod, SW (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0021-1753 J9 ISIS JI Isis PD MAR PY 1999 VL 90 IS 1 BP 154 EP 155 DI 10.1086/384305 PG 2 WC History & Philosophy Of Science SC History & Philosophy of Science GA 199BU UT WOS:000080460100069 ER PT J AU Nesheim, S Trucksess, MW Page, SW AF Nesheim, S Trucksess, MW Page, SW TI Molar absorptivities of aflatoxins B-1, B-2, G(1), and G(2) in acetonitrile, methanol, and toluene-acetonitrile (9+1) (modification of AOAC official method 971.22): Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Four laboratories participated in a mini-collaborative study of AOAC Official Method 971.22, Standards for Aflatoxins, Thin-Layer Chromatographic Method, to extend the method to 3 replacement solvents for benzene for calibration of standard aflatoxin solutions. Triplicate test sample vials, each containing 25 mu g of the respective aflatoxin for each of the 4 aflatoxins and for each of the solvents, were prepared and sent to each collaborator. The collaborators dissolved the aflatoxin in each vial in 2 mt solvent, measured the UV spectrum, and reported the absorptivity maxima near 350 nm, The concentrations of the aflatoxins in the test samples were determined by dissolving identical test samples in benzene-acetonitrile (98 + 2) and following the procedure described in AOAC Official Method 971.22, These concentrations were, in turn, used to determine the molar absorptivities in the other 3 solvents (see Table 1), AOAC Official Method 971.22 has been modified to extend its applicability to 3 replacement solvents for benzene for calibration of standard aflatoxin solutions. C1 US FDA, Div Nat Prod, Washington, DC 20204 USA. RP Nesheim, S (reprint author), US FDA, Div Nat Prod, 200 C St SW, Washington, DC 20204 USA. NR 2 TC 14 Z9 14 U1 2 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1999 VL 82 IS 2 BP 251 EP 258 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 179PT UT WOS:000079338400007 PM 10191531 ER PT J AU Vongbuddhapitak, A Trucksess, MW Atisook, K Suprasert, D Horwitz, W AF Vongbuddhapitak, A Trucksess, MW Atisook, K Suprasert, D Horwitz, W TI Laboratory proficiency testing of aflatoxins in corn and peanuts - A cooperative project between Thailand and the United States SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID QUALITY ASSURANCE AB The objective of this project was to conduct an aflatoxin proficiency test program in government, academia, and industry laboratories in Thailand. Aflatoxin-free corn and peanuts and corn and peanuts naturally contaminated with aflatoxins diluted to approximately 25 mu g/kg were analyzed. Homogeneity of prepared, naturally contaminated test samples was checked on multiple replicates. The test was conducted according to the ISO/IUPAC/AOAC INTERNATIONAL Harmonized Protocol with z scores indicating laboratory performance. The participants used 3 methods: enzyme-linked immunosorbent assay, thin-layer chromatography, and the minicolumn, Of 19 laboratories that reported results for aflatoxins in naturally contaminated corn, 13(68%) performed satisfactorily, on the basis of the mean obtained by an expert laboratory, a calculated target value for standard deviation, and the z score, Of 21 laboratories that reported results for aflatoxins in naturally contaminated peanuts, 10(48%) performed satisfactorily For aflatoxin-free corn, 6 laboratories reported finding aflatoxins at greater than or equal to 10 ng/g, chiefly by the minicolumn method; for aflatoxin-free peanuts, 1 laboratory reported finding aflatoxins at >10 ng/g, Subsequently, a workshop of lectures and laboratory sessions was conducted to improve performance. A new and simple successive outlier removal procedure applied to the same data removed the same laboratories as did the use of z scores. C1 Minist Publ Hlth, Dept Med Sci, Nonthaburi 11000, Thailand. US FDA, Joint Inst Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Minist Publ Hlth, Dept Med Sci, Tiwanond Rd, Nonthaburi 11000, Thailand. NR 7 TC 5 Z9 5 U1 1 U2 1 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1999 VL 82 IS 2 BP 259 EP 263 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 179PT UT WOS:000079338400008 PM 10191532 ER PT J AU Chase, GW Eitenmiller, RR Long, AR AF Chase, GW Eitenmiller, RR Long, AR TI Analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in medical foods 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 and retinyl palmitate in medical food. 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 chromatographed isocratically with a mobile phase of 0.5% (v/v) and 0.125% (v/v) isopropyl alcohol in hexane, respectively. Recovery studies performed on a medical food zero control reference material (ZRM) fortified with the analytes averaged 99.7% (n = 25) for retinyl palmitate and 101% (n = 25) for all-rac-a-tocopheryl acetate. Coefficients of variation were 0.87-2.63% for retinyl palmitate and 1.42-3.20% 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 medical foods. Use of chlorinated solvents is avoided. 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 6 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 MAR-APR PY 1999 VL 82 IS 2 BP 271 EP 275 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 179PT UT WOS:000079338400010 PM 10232898 ER PT J AU Hepp, NM AF Hepp, NM TI Arsenic determination in certifiable color additives by dry ashing followed by hydride generation atomic absorption spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SELENIUM; INTERFERENCES; SPECTROPHOTOMETRY; SPECTROSCOPY AB The preparations of digested samples of certifiable color additives by dry ashing and wet digestion for arsenic analysis by hydride generation atomic ab sorption spectrometry (AAS) were compared. The dry ashing technique was based on the preparation used in ASTM D4606-86 for determination of As and Se in coal. The acid digestion method used nitric and sulfuric acids heated by microwaves in sealed vessels. The digested color additives were analyzed for As by using hydride generated from sodium borohydride mixed with the acidified solution on a flow injection system leading to an atomic absorption spectrometer. Dry ashing was preferable to wet digestion because wet digestion yielded poor recoveries of added As. Dry ashing followed by hydride generation AAS gave determination limits of 0.5 ppm As in the color additives. At a specification level of 3 ppm As, the precision of the method using dry ashing was +/- 0.4 ppm (95% confidence interval). C1 US FDA, Washington, DC 20204 USA. RP Hepp, NM (reprint author), US FDA, HFS-126,200 C St SW, Washington, DC 20204 USA. NR 22 TC 4 Z9 4 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 1999 VL 82 IS 2 BP 327 EP 330 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 179PT UT WOS:000079338400016 PM 10191538 ER PT J AU McClure, FD AF McClure, FD TI A statistical evaluation of the Youden Matched-Pairs Procedure SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB AOAC INTERNATIONAL currently permits investigators to use the Youden Matched-Pairs Procedure to obtain estimates of the method performance indicators repeatability and reproducibility (s(r) and s(R), respectively). This report explains the statistical model assumptions upon which the procedure is based, provides validity tests for several of these assumptions, explains conditions under which Youdens' "precision error" is not consistent with precision estimate Sr Or SR as defined by AQAC INTERNATIONAL, and indicates when precision estimates based on the procedure should be interpreted with caution or should not be used. C1 US FDA, Ctr Food Safety & Appl Nutr, Dept Hlth & Human Serv, Off Sci Anal & Support,Div Math, Washington, DC 20204 USA. RP McClure, FD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Dept Hlth & Human Serv, Off Sci Anal & Support,Div Math, 200 C St SW, Washington, DC 20204 USA. NR 6 TC 3 Z9 3 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 1999 VL 82 IS 2 BP 375 EP 383 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 179PT UT WOS:000079338400022 PM 10191544 ER PT J AU Nelson, K Jones, J Jacobson, S Reimschuessel, R AF Nelson, K Jones, J Jacobson, S Reimschuessel, R TI Elevated blood urea nitrogen (BUN) levels in goldfish as an indicator of gill dysfunction SO JOURNAL OF AQUATIC ANIMAL HEALTH LA English DT Article ID GENTAMICIN-INDUCED NEPHROTOXICITY; ACUTE EXPOSURE; RAINBOW-TROUT; COPPER; CHEMISTRY; FISH; RAT AB We examined the effects of copper-induced gill proliferation and gentamicin-induced renal tubular injury on serum creatinine and blood urea nitrogen (BUN) in goldfish Carassius auratus. Fish were given intraperitoneal injections of gentamicin or phospate-buffered saline and kept in either freshwater or copper-treated (100 mu g/L) water. Those fish injected with gentamicin showed histologic signs of tubular necrosis. The copper-treated fish had extensive gill epithelial cell hypertrophy and hyperplasia. Serum BUN levels were significantly higher in copper-exposed fish than in freshwater fish, regardless of gentamicin treatment. Serum creatinine levels were unchanged by any of the treatments. This indicates that excretion of nitrogenous wastes across gill membranes is an important part of endogenous toxin removal. However, creatinine serum levels are apparently unaffected by either gill damage or kidney failure. Elevated BUN levels in teleosts may serve as a clinical indication of respiratory and excretory compromise due to respiratory epithelial cell hypertrophy and hyperplasia. C1 Michigan State Univ, Coll Vet Med, E Lansing, MI 48823 USA. Univ Maryland, Sch Med, Dept Pathol, Aquat Pathobiol Ctr, Baltimore, MD 21201 USA. RP Reimschuessel, R (reprint author), US FDA, Ctr Vet Med, OR, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 32 TC 6 Z9 6 U1 1 U2 5 PU AMER FISHERIES SOC PI BETHESDA PA 5410 GROSVENOR LANE SUITE 110, BETHESDA, MD 20814-2199 USA SN 0899-7659 J9 J AQUAT ANIM HEALTH JI J. Aquat. Anim. Health PD MAR PY 1999 VL 11 IS 1 BP 52 EP 60 DI 10.1577/1548-8667(1999)011<0052:EBUNBL>2.0.CO;2 PG 9 WC Fisheries; Veterinary Sciences SC Fisheries; Veterinary Sciences GA 212JV UT WOS:000081214300007 ER PT J AU Chiu, LT Zhan, DJ Hart, RW Own, ZY Fu, PP AF Chiu, LT Zhan, DJ Hart, RW Own, ZY Fu, PP TI Effect of caloric restriction on in vitro metabolism and DNA binding of the environmental potent tumorigen 7-chlorobenz[a]anthracene SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Article DE caloric restriction; 7-chlorobenz[a]anthracene; mouse liver microsomal metabolism; DNA binding ID MOUSE-LIVER MICROSOMES; POLYCYCLIC AROMATIC-HYDROCARBONS; STEREOSELECTIVE METABOLISM; RAT-LIVER; PANCREATIC CARCINOGENESIS; MAMMARY TUMORIGENESIS; CHEMICAL CARCINOGENS; MALE B6C3F(1); 7-BROMOBENZANTHRACENE; CANCER AB The effect of caloric restriction (CR) on the metabolism and DNA binding of 7-chlorobenz[a]anthracene (7-Cl-BA), a tumorigenic environmental contaminant, by liver microsomes of 9-month-old male B6C3F(1) mice and 9- and 12-month-old female B6C3F1 mice was studied. Mice mere fed ad libitum (AL), or starting at 14 weeks of age, received 60% of the calories consumed by control mice and were sacrified at 9 or 12 months of age. After microsomal incubations, metabolites were extracted, purified by reversed-phase HPLC, and identified by comparison of their UV-visible and mass spectral data with those of standards. In each case, ten metabolites were identified: 7-Cl-BA trans-3,4-dihydrodiol, 7-Cl-BA trans-5,6-dihydrodiol, 7-Cl-BA trans-8,9-dihydrodiol, 7-Cl-BA trans-10,11-dihydrodiol, 7-Cl-BA 5,6-epoxide, and 4-, 5-, 6-, 8-, and 9-OH-7-Cl-BA. The quantity of 7-Cl-BA trans-3,4-dihydrodiol was formed in a higher yield from the AL microsomes than from the CR microsomes. Metabolism was also performed in the presence of calf thymus DNA, and the resulting modified DNA was isolated and analyzed by both P-32-postlabeling/TLC and P-32-postlabeling/HPLC. Only one DNA adduct, which was derived from 7-Cl-BA trans-3,4-dihydrodiol, was detected in all cases. The levels of adduct formation from CR microsomes were lower than those from the AL microsomes of the same sex and same age. Thus, our results indicate that CR inhibits the formation of the proximate metabolite, 7-Cl-BA trans-3,4-dihydrodiol, and significantly reduces the DNA adduct formation. C1 Providence Univ, Inst Appl Chem, Shalu, Taiwan. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 36 TC 0 Z9 0 U1 0 U2 0 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 1999 VL 7 IS 1 BP 23 EP 36 PG 14 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 182KN UT WOS:000079498300003 ER PT J AU Buchanan, RL Edelson, SG AF Buchanan, RL Edelson, SG TI pH-dependent stationary-phase acid resistance response of enterohemorrhagic Escherichia coli in the presence of various acidulants SO JOURNAL OF FOOD PROTECTION LA English DT Article ID LISTERIA-MONOCYTOGENES INACTIVATION; SALMONELLA-TYPHIMURIUM; TOLERANCE RESPONSE; ORGANIC-ACIDS; NONTHERMAL INACTIVATION; ENVIRONMENTAL STRESSES; STAPHYLOCOCCUS-AUREUS; SURVIVAL; ADAPTATION; O157-H7 AB The effect of acidulant identity on the pH-dependent stationary-phase acid resistance response of enterohemorrhagic Escherichia coli was studied. Nine strains of E. coli (seven O157:H7, one O111:H-, and one biotype 1 reference strain) were cultured individually for 18 h at 37 degrees C in tryptic soy broth (TSB) plus 1% dextrose and in TSB without dextrose to yield acid resistance induced and noninduced stationary-phase cells, respectively. These cultures were then inoculated into brain heart infusion broth (BHI) supplemented with 0.5% citric, malic, lactic, or acetic acid and adjusted to pH 3.0 with HCl. The BHI tubes were incubated at 37 degrees C for up to 7 h and samples were removed after 0, 2, 5, and 7 h and plated for counting CFU on BHI agar and MacConkey agar (MA). The results were compared to data previously obtained with HCl only. Acid resistance varied substantially among the isolates, being dependent on the strain, the acidulant, and the induction of pH-dependent acid resistance. Hydrochloric acid was consistently the least damaging to cells; lactic acid was the most detrimental. The relative activity of the other acids was strain dependent. Inducing pH-dependent acid resistance increased the already substantial acid tolerance of stationary-phase E. coli. The extent of injury also varied with acid and strain, with as much as a 5-log-cycle differential between BHI agar and MA CFU counts. The accurate determination of the survival of enterohemorrhagic E. coli in acidic foods must take into account the biological variability of the microorganism with respect to its acid resistance and its ability to enhance survival through the induction of physiological stress responses. C1 ARS, Food Safety Res Unit, USDA, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. RP Buchanan, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. EM rbuchana@bangate.fda.gov NR 39 TC 85 Z9 87 U1 1 U2 5 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 1999 VL 62 IS 3 BP 211 EP 218 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 173NB UT WOS:000078985700001 PM 10090238 ER PT J AU Buchanan, RL Edelson, SG Boyd, G AF Buchanan, RL Edelson, SG Boyd, G TI Effects of pH and acid resistance on the radiation resistance of enterohemorrhagic Escherichia coli SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ELECTRON-BEAM IRRADIATION; HEMOLYTIC-UREMIC SYNDROME; LISTERIA-MONOCYTOGENES; SALMONELLA-TYPHIMURIUM; GAMMA-IRRADIATION; NONTHERMAL INACTIVATION; ENVIRONMENTAL STRESSES; TOLERANCE RESPONSE; APPLE CIDER; COMMERCIAL MAYONNAISE AB The effects of pH and the induction of pH-dependent stationary-phase acid resistance on the radiation resistance of Escherichia coli were determined for seven enterohemorrhagic strains and one nonenterohemorrhagic strain. The isolates were grown in acidogenic or nonacidogenic media to pH levels of approximately 4.7 and 7.2, respectively. The cells were then transferred to brain heart infusion (BHI) broth adjusted to pH 4.0, 4.5, 5.0, and 5.5 (with HCl) that was preequilibrated to 2 degrees C, and cultures were then irradiated using a Cs-137 source. Surviving cells and the extent of injury were determined by plating on BHI and MacConkey agars both immediately after irradiation and after subsequent storage at 2 degrees C for 7 days. Decreasing the pH of the BHI in which E. coli was irradiated had relatively little effect on the microorganism's radiation resistance. Substantial differences in radiation resistance were noted among strains, and induction of acid resistance consistently increased radiation resistance. Comparison of E. coli levels immediately after irradiation and after 7 days of refrigerated storage suggested that irradiation enhanced pH-mediated inactivation of the pathogen. These results demonstrate that prior growth under conditions that induce a pH-dependent stationary phase cross-protects E. coli against radiation inactivation and must be taken into account when determining the microorganism's irradiation D value. C1 ARS, Food Safety Res Unit, USDA, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. RP Buchanan, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. EM rbuchana@bangate.fda.gov NR 48 TC 33 Z9 33 U1 0 U2 3 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD MAR PY 1999 VL 62 IS 3 BP 219 EP 228 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 173NB UT WOS:000078985700002 PM 10090239 ER PT J AU Blakistone, B Chuyate, R Kautter, D Charbonneau, J Suit, K AF Blakistone, B Chuyate, R Kautter, D Charbonneau, J Suit, K TI Efficacy of oxonia active against selected spore formers SO JOURNAL OF FOOD PROTECTION LA English DT Article; Proceedings Paper CT Annual Meeting of the Institute-of-Food-Technologists CY JUN 14-17, 1997 CL ORLANDO, FLORIDA SP Inst Food Technologists ID HYDROGEN-PEROXIDE; BACILLUS SPORES; RESISTANCE AB Alternatives to hydrogen peroxide are being sought for use in aseptic packaging systems because this sterilant is efficacious at temperatures higher than some of the newer packaging materials can tolerate. Earlier in this century, peracetic acid was known to be bactericidal, sporicidal, and virucidal but was not widely used because of handling, toxicity, and stability problems. Sanitizer suppliers have capitalized on the efficacy of hydrogen peroxide, acetic acid, and peracetic acid stabilized with a sequestering agent. Formulations have been improved and marketed as Oxonia Active, and its use as an alternative sterilant to hydrogen peroxide merits evaluation. Oxonia was assessed: at a concentration of 2% and a temperature of 40 degrees C against a number of spore-forming organisms, including foodborne pathogens. Spores tested in aqueous suspension showed an order of sensitivity (least to greatest) to Oxonia as follows: Bacillus cereus > B. subtilis A > B. stearothermophilus > B. subtilis var. globigii > B. coagulans > Clostridium sporogenes (PA3679) > C. botyricum > C. botulinum type B (nonproteolytic) > C. botulinum type B (proteolytic) = C. botulinum type A = C. botulinum type E. B. subtilis A and B. stearothermophilus spores tested in the dry state were less sensitive to Oxonia than when tested in aqueous suspension. B, cereus, a foodborne pathogen, proved to be markedly less sensitive to Oxonia under the: described test conditions. The decreased sensitivity to Oxonia by the foodborne pathogen B. cereus raises concern about the efficacy of the sterilant for aseptic packaging of low-acid foods. Further work will be needed to determine if this decreased sensitivity is an inherent property of the organism that affords unusual protection against Oxonia or if the challenge parameters selected were at the minimum conditions for efficacy. C1 Natl Food Processors Assoc, Washington, DC 20005 USA. US FDA, Washington, DC 20204 USA. RP Blakistone, B (reprint author), Natl Food Processors Assoc, 1350 Eye St NW, Washington, DC 20005 USA. NR 17 TC 13 Z9 13 U1 0 U2 3 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAR PY 1999 VL 62 IS 3 BP 262 EP 267 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 173NB UT WOS:000078985700009 PM 10090246 ER PT J AU Kaine, LA Jackson, DS Heitkemper, DT AF Kaine, LA Jackson, DS Heitkemper, DT TI Ion chromatographic analysis of corrosive materials in product tampering investigations SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; ion chromatography; product tamperings; corrosives AB Investigations of product tampering cases involving corrosives focus on the cause of extreme pH, and then attempt to determine the source of the contaminant. The application of ion chromatography to several product tampering cases is discussed. Examples include lye in cold medicine, ammonia in milk, and strong acids in eye drops and a food supplement. C1 US FDA, Forens Chem Ctr, Inorgan Branch, Cincinnati, OH 45237 USA. RP Kaine, LA (reprint author), US FDA, Forens Chem Ctr, Inorgan Branch, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD MAR PY 1999 VL 44 IS 2 BP 413 EP 416 PG 4 WC Medicine, Legal SC Legal Medicine GA 293AW UT WOS:000085830200029 ER PT J AU Markovic, O Markovic, N Belledonne, M AF Markovic, O Markovic, N Belledonne, M TI Cervical acid phosphatase-papanicolaou (CAP-PAP) test SO JOURNAL OF HISTOTECHNOLOGY LA English DT Article DE cervical cancer screening; false negatives ID QUALITY-CONTROL; CATHEPSIN-D; SMEARS; CANCER; CELLS; ERRORS AB The high proportion of false negative results in cervical cancer screening and the lack of an inexpensive and rapid method for rescreening cervical smears led us to search for a way to maximize the detection of false negative cases. We describe a simple, rapid, and inexpensive procedure, the cervical acid phosphatase-Papanicolaou test (CAP-PAP test), that can alleviate the problem of false negatives. For research purposes, CAP-PAP test is immediately applicable in all laboratories currently doing the standard PAP test. It does not require special training for screeners or purchasing of additional expensive instruments. Additional cost per test is less than $1.00. The CAP-PAP test is compatible with automation. C1 BioSciCon Inc, Rockville, MD 20852 USA. US FDA, CDER, Rockville, MD 20857 USA. BioLab Med, Rockville, MD USA. RP Markovic, O (reprint author), BioSciCon Inc, 259 Congressional Lane 602, Rockville, MD 20852 USA. NR 35 TC 2 Z9 2 U1 0 U2 0 PU NATL SOC HISTOTECHNOLOGY PI BOWIE PA 4201 NORTHVIEW DR, STE 502, BOWIE, MD 20716-1073 USA SN 0147-8885 J9 J HISTOTECHNOL JI J. Histotechnol. PD MAR PY 1999 VL 22 IS 1 BP 43 EP 47 PG 5 WC Cell Biology SC Cell Biology GA 176HB UT WOS:000079144700006 ER PT J AU Dickensheets, HL Donnelly, RP AF Dickensheets, HL Donnelly, RP TI Inhibition of IL-4-inducible gene expression in human monocytes by type I and type II interferons SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-for-Leukocyte-Biology on Molecular Mechanisms of Leukocyte Signal Transduction CY AUG 22-25, 1998 CL UNIV CA SAN DIEGO, LA JOLLA, CALIFORNIA SP Soc Leukocyte Biol HO UNIV CA SAN DIEGO DE IL-4 receptor; tyrosine kinases; STAT6; STAT-binding elements; SOCS genes ID RECEPTOR-GAMMA-CHAIN; INTERLEUKIN-4-INDUCED TRANSCRIPTION FACTOR; HUMAN PERIPHERAL-BLOOD; NECROSIS-FACTOR-ALPHA; IFN-GAMMA; MEMBRANE EXPRESSION; ENDOTHELIAL-CELLS; IL-4; STAT6; CYTOKINES AB The Th2-type cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), induce expression of a distinct subset of genes in human monocytes, including Fc epsilon RIIb (CD23), 15-lipoxygenase, IL-1 receptor antagonist (IL-1ra), and type I and type II IL-1 receptors (IL-1R), Type I interferons (IFN-alpha and IFN-beta) and type II interferon (IFN-gamma) inhibit induction of these genes by IL-4 and IL-13, However, the mechanism by which IFNs mediate this inhibition has not been defined. In this overview, we discuss the role of the transcription factor, STAT6 (signal transducer and activator of transcription-6) in mediating IL-4- and IL-13-induced gene expression in monocytes. We also discuss our recent findings that type I and type II IFNs suppress IL-4/IL-13-inducible gene expression by inhibiting tyrosine phosphorylation and nuclear translocation of STAT6, The ability of type I and type II IFNs to inhibit IL-4/IL-13-induced STAT6 activity is dose- and time-dependent, and is not unique to monocytes because IFNs induce the same effects in fibroblasts, Inhibition of STAT6 activity is not evident unless cells are preincubated with IFN for at least 1 h before IL-4 stimulation. Furthermore, inhibition can he blocked by actinomycin D, indicating a requirement for de novo transcription. We propose a model in which stimulation of monocytes by IFN activates de novo synthesis of an inhibitory factor, possibly one or more members of the SOCS/ SSI/CIS gene family, capable of suppressing activation of STAT6 by IL-4 and IL-13, Because STAT6 activation plays an essential role in IL-4/IL-13-induced gene expression, the ability of IFN-beta and IFN-gamma to inhibit STAT6 activity provides an explanation for how IFNs can suppress IL-4/IL-13-inducible gene expression. C1 US FDA, Div Cytokine Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Dickensheets, HL (reprint author), US FDA, CBER, Div Cytokine Biol, HFM-505,1401 Rockville Pike, Rockville, MD 20852 USA. NR 45 TC 47 Z9 54 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 1999 VL 65 IS 3 BP 307 EP 312 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 172BM UT WOS:000078902300005 PM 10080532 ER PT J AU Zhang, J Andrade, ZA Yu, ZX Andrade, SG Takeda, K Sadirgursky, M Ferrans, VJ AF Zhang, J Andrade, ZA Yu, ZX Andrade, SG Takeda, K Sadirgursky, M Ferrans, VJ TI Apoptosis in a canine model of acute Chagasic myocarditis SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Trypanosoma cruzi; apoptosis; acute myocarditis; dog; nick end labeling; electron microscopy ID PROGRAMMED CELL-DEATH; NITRIC-OXIDE SYNTHASE; TRYPANOSOMA-CRUZI; DNA FRAGMENTATION; HEART-FAILURE; MITOCHONDRIAL-DNA; PRESSURE-OVERLOAD; TARGET-CELLS; INFARCTION; MYOCYTES AB Histologic, ultrastructural and nick end labeling studies were made to evalute the occurrence of apoptosis in the hearts of dogs with acute myocarditis due to experimental infection with T. cruzi. The best results for the detection of apoptosis by nick end labeling were obtained by a method combining the use of terminal deoxynucleotidyl transferase, CoCl2 and fluorescein-conjugated deoxyuridine triphosphate. followed by counterstaining of DNA with 4'6-diamidino-2-phenylindole (DAPI) and examination by laser scanning confocal fluorescence microscopy. Apoptosis was found in: (1) cardiac myocytes: (2) endothelial cells of capillaries and venules: (3) immune effector cells, including macrophages, interstitial dendritic cells (antigen-presenting cells) and granular and agranular lymphocytes, and (4) intra- and extracellular forms of T, cruzi. The apoptosis in myocytes and endothelial cells affected cells that were not infected by T, cruzi and was probably caused by the release of toxic mediators of inflammation. The apoptosis of immune effector cells could be related either to the subsidence of inflammation or to modulation (and even failure) of the immune response. The finding of apoptosis in T, cruzi confirms the results of other studies showing that this phenomenon occurs during the differentiation of trypomastigotes in vitro. Thus. apoptosis constitutes an important and multifactorial event in the pathogenesis of acute Chagasic myocarditis. (C) 1999 Academic Press. C1 NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. US FDA, Div Appl Pharmacol Res, Laurel, MD 20708 USA. Ministerio Saude, Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Muniz, BR-41945 Salvador, BA, Brazil. RP Ferrans, VJ (reprint author), NHLBI, Pathol Sect, NIH, Bld 10 2N240,10 Ctr Dr MSC-1518, Bethesda, MD 20892 USA. NR 49 TC 42 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAR PY 1999 VL 31 IS 3 BP 581 EP 596 DI 10.1006/jmcc.1998.0893 PG 16 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 174EQ UT WOS:000079021500010 PM 10198189 ER PT J AU Lehr, GJ Barry, TL Petzinger, G Hanna, GM Zito, SW AF Lehr, GJ Barry, TL Petzinger, G Hanna, GM Zito, SW TI Isolation and identification of process impurities in trimethoprim drug substance by high-performance liquid chromatography, atmospheric pressure chemical ionization liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE trimethoprim; impurities; liquid chromatography; atmospheric pressure chemical ionization liquid chromatography mass spectroscopy; proton nuclear magnetic resonance spectroscopy AB Twenty-two lots of recently synthesized trimethoprim drug substance, from five different manufacturers, in three different countries of origin, China, Israel and the United States, were investigated for the presence of impurities. A liquid chromatographic system, using gradient elution, and a mobile phase consisting of 0.25% TEA/0.1% formic acid (pH 5.8)-acetonitrile, was used to separate and detect two significant, recurring impurities in trimethoprim drug substance. The two impurities were isolated by preparative liquid chromatography and identified, using a combination of liquid chromatography/mass spectroscopy and nuclear magnetic resonance, as 2,4-diamino-5-(4-ethoxy-3,5-dimethoxybenzyl) pyrimidine and 2,4-diamino-5-(3-bromo-4,5-dimethoxybenzyl) pyrimidine. These impurities were not detected by the compendial method and were present at significant levels in 17 of the lots tested. Total impurity concentrations were in the range of 0.1-2.1%. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US FDA, Dept Hlth & Human Serv, NE Reg Lab, Brooklyn, NY 11232 USA. St Johns Univ, Coll Pharm & Allied Hlth Profess, Jamaica, NY 11439 USA. RP Lehr, GJ (reprint author), US FDA, Dept Hlth & Human Serv, NE Reg Lab, 850 3rd Ave, Brooklyn, NY 11232 USA. NR 9 TC 21 Z9 22 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD MAR PY 1999 VL 19 IS 3-4 BP 373 EP 389 DI 10.1016/S0731-7085(98)00138-1 PG 17 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 165YH UT WOS:000078549100013 PM 10704103 ER PT J AU Roe, B Levy, AS Derby, BM AF Roe, B Levy, AS Derby, BM TI The impact of health claims on consumer search and product evaluation outcomes: Results from FDA experimental data SO JOURNAL OF PUBLIC POLICY & MARKETING LA English DT Article ID NUTRITION LABEL FORMATS; CEREAL MARKET; EDUCATION ACT; INFORMATION; BEHAVIOR; CHOICE; PERFORMANCE; EXPERIENCE AB The authors report results of a mall-intercept study regarding the effects of health claims on consumer information search and processing behavior. Results suggest that the presence of health and nutrient-content claims on food packages induces respondents to truncate information search to the front panel of packages. Respondents who either truncate information search or view claims provide more positive summary judgments of products and give greater weight to the information mentioned in claims than to the information available in the Nutrition Facts panel. The presence of a claim also is associated with a halo effect (rating the product higher on other health attributes not mentioned in the claim) and, for one of the three products tested, a magic-bullet effect (attributing inappropriate health benefits to the product). The authors discuss the policy implications of these results for Food and Drug Administration health claim regulations. C1 Ohio State Univ, Dept Agr Environm & Dev Econ, Columbus, OH 43210 USA. US FDA, Consumer Studies Branch, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. RP Roe, B (reprint author), Ohio State Univ, Dept Agr Environm & Dev Econ, Columbus, OH 43210 USA. RI Roe, Brian/A-7386-2009 OI Roe, Brian/0000-0003-4228-2889 NR 45 TC 180 Z9 181 U1 3 U2 45 PU AMER MARKETING ASSOC PI CHICAGO PA 311S WACKER DR, STE S800, CHICAGO, IL 60606-6629 USA SN 0743-9156 J9 J PUBLIC POLICY MARK JI J. Public Policy Mark. PD SPR PY 1999 VL 18 IS 1 BP 89 EP 105 PG 17 WC Business SC Business & Economics GA 202QQ UT WOS:000080664000009 ER PT J AU Adam, M Mossoba, MM Dawson, T Chew, M Wasserman, S AF Adam, M Mossoba, MM Dawson, T Chew, M Wasserman, S TI Comparison of attenuated total reflection infrared spectroscopy to capillary gas chromatography for trans fatty acid determination SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE attenuated total reflection; gas chromatography; infrared; peer-verified study; trans fatty acids AB Gas chromatography (GC) has been a standard analytical tool in lipid chemistry. The rapid attenuated total reflection (ATR) infrared (IR) American Oil Chemists' Society (AOCS) Recommended Practice (Cd 14d-97) was compared to the capillary GC AOCS Recommended Practice (Ce 1f-97) that was optimized to accurately determine total trans fatty acids on highly polar stationary phases. This comparative evaluation was validated in an independent laboratory. These procedures were used to quantitate the total trans fatty acid levels in partially hydrogenated vegetable oils, measured as neat(without solvent) triacylglycerols (TAG) by ATR and as fatty acid methyl ester (FAME) derivatives by capillary GC. Unlike FAME, TAG determination by ATR required no derivatization, but samples had to be melted prior to measurement. Five blind replicates for each of three accuracy standards and three test samples were analyzed by each technique. The GC and ATR determinations were in good agreement. Accuracy was generally high. The ratios of ATR mean trans values (reported as percentage of total TAG) to the true values (based on the amount of trielaidin added gravimetrically) were 0.89, 0.98, and 1.02 for accuracy standards having about 1, 10, and 40% trans levels. The corresponding GC values, determined as percentage of total FAME, were 0.98, 0.99 and 1.04. The ratios of mean trans values determined by these techniques were ATR/GC 0.85, 1.04, and 1.01 for test samples having trans levels of about 0.7, 8, and 38%, respectively. The optimized GC procedure also minimized the expected low bias in trans values due to GC peak overlap found with the GC Official Method Ce 1c-89. Satisfactory repeatability and reproducibility were obtained by both ATR and GC. C1 Lipton, Baltimore, MD 21229 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Perdue Farms Inc, Salisbury, MD 21802 USA. RP Adam, M (reprint author), Lipton, 3701 Southwestern Blvd, Baltimore, MD 21229 USA. NR 14 TC 11 Z9 11 U1 1 U2 3 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD MAR PY 1999 VL 76 IS 3 BP 375 EP 378 DI 10.1007/s11746-999-0244-7 PG 4 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 181HQ UT WOS:000079436300013 ER PT J AU Hilbert, SL Luna, RE Zhang, J Wang, Y Hopkins, RA Yu, ZX Ferrans, VJ AF Hilbert, SL Luna, RE Zhang, J Wang, Y Hopkins, RA Yu, ZX Ferrans, VJ TI Allograft heart valves: The role of apoptosis-mediated cell loss SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID SULFOXIDE-INDUCED APOPTOSIS; DIFFERENTIATION; DEATH AB Objective: The purpose of this study was to determine whether apoptosis of endothelial and connective tissue cells is responsible for the loss of cellularity observed in implanted aortic allograft valves. Methods: Fresh (n = 6) and cryopreserved (n = 4) aortic allograft valves were retrieved at 2 days to 20 weeks after implantation in an ovine model. Sections of these valves were studied with the use of histologic and electron microscopic methods, nick end-labeling and dual immunostaining for factor VIII-related antigen and proliferating cell nuclear antigen, followed by counterstaining for DNA and laser scanning confocal fluorescence microscopic observation. Results: The endothelial cells and cusp connective tissue cells of implanted valvular allografts showed loss of proliferating cell nuclear antigen (indicative of cessation of mitotic activity) and evidence of apoptosis (nick end labeling). The latter was manifested by nuclear condensation and pyknosis, positive nick end labeling, and formation of intra- and extracellular apoptotic bodies derived from the fragmentation of apoptotic cells, These changes began to develop at 2 days after implantation, peaking at 10 to 14 days, and became complete by 20 weeks, at which time the valves had the typical acellular morphologic features of allografts implanted for long periods of time. Conclusions: Apoptosis occurs in endothelial cells and cuspal connective tissue cells of implanted allografts and appears to be a cause of their loss of cellularity. This apoptosis may be related to various factors, including immunologic and chemical injury, and hypoxia during valve processing and reperfusion injury at the time of implantation. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Surg, Washington, DC 20007 USA. Brown Univ, Sch Med, Dept Surg, Providence, RI 02912 USA. RP Hilbert, SL (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-150,9200 Corp Blvd, Rockville, MD 20850 USA. NR 24 TC 34 Z9 38 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAR PY 1999 VL 117 IS 3 BP 454 EP 462 DI 10.1016/S0022-5223(99)70324-7 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 172KB UT WOS:000078921100005 PM 10047647 ER PT J AU Pritchard, WF Abel, DB Karanian, JW AF Pritchard, WF Abel, DB Karanian, JW TI The US Food and Drug Administration investigational device exemptions (IDE) and clinical investigation of cardiovascular devices: Information for the investigator SO JOURNAL OF VASCULAR SURGERY LA English DT Review ID MEDICAL DEVICES AB The conduct of a clinical investigation of a medical device to determine the safety and effectiveness of the device is covered by rile investigational device exemptions (IDE) regulation. The purpose of IDE regulation is "to encourage, to the extent consistent with the protection of public health and safety and with ethical standards, the discovery and development of useful devices intended for human use, and to that end to maintain optimum freedom for scientific investigators in their pursuit of this purpose" (Federal Food, Drug, and Cosmetic Act). Conducting a clinical investigation may require an approved IDE application. The US Food and Drug Administration encourages early interaction with the agency through the pre-IDE process during the development of a device or technology and during the preparation of an IDE application. This facilitates approval of the IDE application and progression into the clinical investigation. This paper reviews the terminology and applicability of the IDE regulation and the type of study that requires an IDE application to the Food and Drug Administration. The pre-IDE process and the development of an IDE, application for a significant risk study of a cardiovascular device are discussed. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Off Sci & Technol, Div Phys Sci, Hydrodynam & Acoust Branch, Rockville, MD USA. Off Device Evaluat, Div Cardiovasc Resp & Neurol Devices, Circulatory Support & Prothet Grp, Rockville, MD USA. RP Pritchard, WF (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-132,9200 Corp Blvd, Rockville, MD 20850 USA. NR 5 TC 4 Z9 4 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAR PY 1999 VL 29 IS 3 BP 566 EP 574 DI 10.1016/S0741-5214(99)70288-0 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 175PP UT WOS:000079103800024 PM 10069924 ER PT J AU Lapham, CK Zaitseva, MB Lee, S Romanstseva, T Golding, H AF Lapham, CK Zaitseva, MB Lee, S Romanstseva, T Golding, H TI Fusion of monocytes and macrophages with HIV-1 correlates with biochemical properties of CXCR4 and CCR5 SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTOR; CELL-LINES; T-CELL; INFECTION; TROPISM; ENTRY; 7-TRANSMEMBRANE; GLYCOPROTEINS; CORECEPTOR AB Human macrophages can be infected more efficiently by M-tropic than by T-tropic HIV-1 strains, despite surface expression of both CXCR4 and CCR5 co-receptors. Western blot analyses of total cell extracts and surface proteins from multiple sets of monocytes and macrophages demonstrated substantial differences between CXCR4 molecules. CXCR4 was mainly a monomer in monocytes, but was mainly a species of higher molecular weight (90 kDa) on the surface of macrophages. CCR5 was monomeric in both cell types. A constitutive association between CD4 and the co-receptors was seen in monocytes and macrophages. However, CD4 co-precipitated with CCR5 and CXCR4 monomers, but not with the high-molecular-weight forms of CXCR4, indicating that the high-molecular-weight CXCR4 species in macrophages are not available for association with CD4, which may contribute to the inefficient entry of T-tropic strains into mature macrophages. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Lapham, CK (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, HFM-454,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Lapham@CBER.FDA.GOV NR 33 TC 99 Z9 101 U1 0 U2 1 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 MAR PY 1999 VL 5 IS 3 BP 303 EP 308 DI 10.1038/6523 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 171FH UT WOS:000078851600035 PM 10086386 ER PT J AU Bright, RA Torrence, ME Daley, WR McClellan, WM AF Bright, RA Torrence, ME Daley, WR McClellan, WM TI Preliminary survey of the occurrence of anaphylactoid reactions during haemodialysis SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Letter ID ACE-INHIBITORS; HEMODIALYSIS; BRADYKININ C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Bright, RA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RI Bright, Roselie/D-2240-2016 NR 10 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAR PY 1999 VL 14 IS 3 BP 799 EP 800 DI 10.1093/ndt/14.3.799 PG 2 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 177DP UT WOS:000079192400065 PM 10193851 ER PT J AU Donoghue, DJ Hairston, M AF Donoghue, DJ Hairston, M TI Oxytetracycline transfer into chicken egg yolk or albumen SO POULTRY SCIENCE LA English DT Article DE drug residues; oxytetracycline; eggs; yolk; albumen ID LAYING HENS; RESIDUES; CHROMATOGRAPHY; AMPICILLIN; MEDICATION AB This study was conducted to determine whether the approved doses of oxytetracycline (OTC) for breeder hens and meat-type poultry would produce drug residue transfer into egg components when fed to laying hens. Twenty hens were assigned to equal groups (n = 10) and fed either 50 or 200 g/ton OTC for 5 d. Oxytetracycline concentrations in egg components were determined daily during a 2-d pretreatment control period, the 5-d dosing period, and following drug withdrawal. The stability and drug content of the medicated feed were determined the day dosing was started and the day of withdrawal. Residues of OTC were not detectable during the predosing, dosing, or withdrawal period in egg yolks. Oxytetracycline residues were detectable, however, in egg albumen during the 5th d of treatment and the Ist d of medicated feed withdrawal. These concentrations were close to the limit of the assay's sensitivity (117 ppb). These data indicate that illegal or unintentional dosing of laying hens with feed medicated at the doses allowed for breeder hens or meat-type poultry should not produce consistently detectable levels of residues of OTC in eggs. C1 US FDA, Div Anim Res, Ctr Vet Med, Laurel, MD 20708 USA. RP Donoghue, DJ (reprint author), US FDA, Div Anim Res, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 15 TC 12 Z9 16 U1 0 U2 1 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD MAR PY 1999 VL 78 IS 3 BP 343 EP 345 PG 3 WC Agriculture, Dairy & Animal Science SC Agriculture GA 171VV UT WOS:000078885500006 PM 10090259 ER PT J AU Schmued, L Slikker, W Clausing, P Bowyer, J AF Schmued, L Slikker, W Clausing, P Bowyer, J TI d-fenfluramine produces neuronal degeneration in localized regions of the cortex, thalamus, and cerebellum of the rat SO TOXICOLOGICAL SCIENCES LA English DT Article DE dexfenfluramine; anterior cingulate cortex; intralaminar thalamus; Purkinje cells; neuronal degeneration; neurotoxicity; anoretic; Fluoro-Jade ID SEROTONIN SYNDROME; 5-HT3 RECEPTOR; BRAIN; HYPOTHERMIA; INNERVATION; DRUGS; 5-HYDROXYTRYPTAMINE; MECHANISMS; NORFENFLURAMINE; PATHOPHYSIOLOGY AB d-Fenfluramine is a potent serotonin (5-HT) reuptake inhibitor/releaser and, until its recent recall, was prescribed as an anoretic agent. This study demonstrates that 10 mg/kg d-fenfluramine ip, when administered to rats in a warm (27 degrees C) environment, produces neuronal degeneration within select brain regions. Degeneration was detected and localized using a recently developed fluorescent marker of neuronal degeneration, Fluoro-Jade. The most extensive cortical damage was in the anterior cingulate region. In the medial thalamus, degeneration was frequently seen within the intralaminar nuclei, and somewhat less frequently observed within the paraventricular nucleus, the mediodorsal nucleus, and the gelatinosis nucleus. Cerebellar damage occurred primarily in medial Purkinje cells and occasionally in granule cells or basket cells. Degeneration was not observed in either saline-injected control animals or in rats given even higher doses of 25 mg/kg d-fenfluramine but kept in a cooler environment (23 degrees C). The degeneration was clearly most prominent in animals with body temperatures of 41 degrees to 42 degrees C, but this degeneration was not seen in animals given saline that became extremely hyperthermic in a 37 degrees C environment. Behavioral signs such as tremors, myoclonus, rigidity, and splayed legs were seen in all animals with extensive neurodegeneration. The areas damaged by d-fenfluramine, when hyperthermia occurs, could play a role in the expression of the serotonin syndrome. Elevated extracellular 5-HT levels alone are probably not sufficient for neurotoxicity, and additional factors such as hyperthermia, regional specificity of 5-HT receptor subtypes, blood flow, and/or neuronal networks may be involved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Scantox Biol Labs, DK-4623 Lille, Skensved, Denmark. RP Bowyer, J (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. NR 48 TC 26 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 1999 VL 48 IS 1 BP 100 EP 106 DI 10.1093/toxsci/48.1.100 PG 7 WC Toxicology SC Toxicology GA 251PV UT WOS:000083454800013 PM 10330689 ER PT J AU Friedlander, LG Brynes, SD Fernandez, AH AF Friedlander, LG Brynes, SD Fernandez, AH TI The human food safety evaluation of new animal drugs SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article AB The pre-approval risk assessment process for new animal drugs is described in this article. The toxicological and residue chemistry data needed by the FDA for the human food safety evaluation of a new animal drug is also discussed. C1 US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Div Human Food Safety,Residue Chem Team, Rockville, MD 20855 USA. RP Friedlander, LG (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Div Human Food Safety,Residue Chem Team, HFV-151,7500 Standish Pl, Rockville, MD 20855 USA. NR 3 TC 12 Z9 12 U1 1 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 1999 VL 15 IS 1 BP 1 EP + PG 12 WC Veterinary Sciences SC Veterinary Sciences GA 178JK UT WOS:000079262400002 PM 10088208 ER PT J AU Bataller, N Keller, WC AF Bataller, N Keller, WC TI Monitoring adverse reactions to veterinary drugs - Pharmacovigilance SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article AB The Food and Drug Administration Center for Veterinary Medicine (CVM) monitors reports of adverse drug experiences (ADE) for animal drug products, medicated feeds, and veterinary devices. The term most frequently applied to this monitoring activity is pharmacovigilance. An ADE is either an undesired effect or the lack of a desired effect. During 1997, the CVM received over 4,000 reports. Every report is evaluated by a veterinarian using an algorithm and entered into a computer database. In instances where public or animal health is judged to be at risk, the initial review leads to follow-up activity. The final result can be a product safety communication, change in labeling, or in rare circumstances, removal of the product from the market or even withdrawal of FDA approval to market the product. The purpose of this article is to provide a brief description of the pharmacovigilance program for animal drugs in food-producing animals, and answer some of the more commonly received questions about adverse experience reporting. C1 US FDA, Ctr Vet Med, Div Epidemiol & Surveillance, Rockville, MD 20855 USA. US FDA, Ctr Vet Med, Marketed Prod Sci & Regulatory Review Team 1, Rockville, MD 20855 USA. US FDA, Ctr Vet Med, Off Surveillance & Compliance, Rockville, MD 20855 USA. RP Bataller, N (reprint author), US FDA, Ctr Vet Med, Div Epidemiol & Surveillance, 7500 Standish Pl,HFV-214, Rockville, MD 20855 USA. NR 1 TC 5 Z9 5 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 1999 VL 15 IS 1 BP 13 EP + PG 20 WC Veterinary Sciences SC Veterinary Sciences GA 178JK UT WOS:000079262400003 PM 10088209 ER PT J AU Paige, JC Tollefson, L Miller, MA AF Paige, JC Tollefson, L Miller, MA TI Health implications of residues of veterinary drugs and chemicals in animal tissues SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID VEAL; RISK AB The animal drug approval process in the United States is based upon the premise that the presence of drug residues in meat and poultry above tolerance is a public health hazard. Tolerances represent the maximum level of concentration of antimicrobials permitted in animal tissues at the time of slaughter The tolerances are intended to ensure that residual drugs will have no harmful effects if ingested. The purpose of this article is to present existing evidence of the acute and chronic health consequences that may occur because of food of animal origin contaminated with illegal residues above the tolerance. The impact of food-borne drug residues on the gut microflora, residue detection limitations, and the responsibility of the veterinary practitioner in ensuring food safety is discussed. C1 US FDA, Ctr Vet Med, Off Surveillance & Compliance, Div Epidemiol & Surveillance, Rockville, MD 20855 USA. US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Div Human Food & Consultat Serv, Rockville, MD 20855 USA. RP Paige, JC (reprint author), US FDA, Ctr Vet Med, Off Surveillance & Compliance, Div Epidemiol & Surveillance, 7500 Standish Pl,HFV-218, Rockville, MD 20855 USA. NR 33 TC 24 Z9 24 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 1999 VL 15 IS 1 BP 31 EP + PG 14 WC Veterinary Sciences SC Veterinary Sciences GA 178JK UT WOS:000079262400004 PM 10088210 ER PT J AU Paige, JC Chaudry, MH Pell, FM AF Paige, JC Chaudry, MH Pell, FM TI Federal surveillance of veterinary drugs and chemical residues (with recent data) SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article AB The National Residue Program is a dynamic risk-based program involving many Federal agencies, with the objective of preventing illegal drug residues and chemicals in the food supply. Surveillance is the systematic collection, analysis, and interpretation of residue data for public health action. This consists of assessing the cause(s) of the problem, recommending educational incentives, and intervention of prevention and control measures. The role of residue databases in formulating policy decisions and identifying risk factors for drug residues is discussed. A descriptive analysis, of 5 years (1992-1996) field investigative reports of drug residue occurrence in food animals is presented. The results showed that violative residues occurred predominately in culled dairy cows and bob veal calves. C1 US FDA, Epidemiol Team, Ctr Vet Med,Div Epidemiol & Surveillance, Off Surveillance & Compliance, Rockville, MD 20855 USA. US FDA, Ctr Vet Med,Compliance Informat Management Team, Div Compliance, Off Surveillance & Compliance, Rockville, MD 20855 USA. Food Safety & Inspect Serv, USDA, Omaha, NE USA. RP Paige, JC (reprint author), US FDA, Epidemiol Team, Ctr Vet Med,Div Epidemiol & Surveillance, Off Surveillance & Compliance, 7500 Standish Pl,HFV-218, Rockville, MD 20855 USA. NR 6 TC 14 Z9 14 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 1999 VL 15 IS 1 BP 45 EP + PG 18 WC Veterinary Sciences SC Veterinary Sciences GA 178JK UT WOS:000079262400005 PM 10088211 ER PT J AU Talley, MR AF Talley, MR TI The National Milk Safety Program and drug residues in milk SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article AB Control of animal drug residues in milk and milk products presents special challenges to both the industry that produces it and the government agencies charged with protecting the public health. Animal drug residues in milk are the result of the treatment of animals in the milking herd. The only method of prevention is proper management of animal drug use at the farm level. This involves dairy producers and their veterinarians. After milk leaves the farm, the involvement of the FDA, states, and processors focuses on monitoring milk and milk products to determine compliance. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. US FDA, Off Surveillance & Compliance, Rockville, MD 20855 USA. RP Talley, MR (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl,HFV-216, Rockville, MD 20855 USA. NR 4 TC 6 Z9 6 U1 1 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 1999 VL 15 IS 1 BP 63 EP + PG 13 WC Veterinary Sciences SC Veterinary Sciences GA 178JK UT WOS:000079262400006 PM 10088212 ER PT J AU Payne, MA Craigmill, AL Riviere, JE Baynes, RE Webb, AI Sundlof, SF AF Payne, MA Craigmill, AL Riviere, JE Baynes, RE Webb, AI Sundlof, SF TI The Food Animal Residue Avoidance Databank (FARAD) - Past, present and future SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID EXTRALABEL USE; DATA-BANK; DRUGS; VETERINARY AB The Food Animal Residue Avoidance Databank (FARAD) was created in 1982 as a cooperative state and federal educational outreach program. FARAD's mission has remained unchanged in the last fifteen years: to assist producers, veterinarians, and allied professionals in the production of animal foods free of illegal chemical contaminants. At its core, FARAD is a collection of databases that users can efficiently access with the assistance of program experts. In order to meet emerging challenges related to technical and trade issues in food safety, current FARAD projects include inter-species data extrapolation, novel kinetic modeling, and international information exchange. C1 Univ Calif Davis, Coll Vet Med, FARAD, Environm Toxicol Extens, Davis, CA 95616 USA. N Carolina State Univ, Coll Vet Med, Ctr Cutaneous Toxicol & Residue Pharmacol, Raleigh, NC USA. Univ Florida, Coll Vet Med, Gainesville, FL USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Payne, MA (reprint author), Univ Calif Davis, Coll Vet Med, FARAD, Environm Toxicol Extens, 1 Shields Ave, Davis, CA 95616 USA. RI Riviere, Jim/A-9210-2008 OI Riviere, Jim/0000-0001-8412-9650 NR 23 TC 5 Z9 5 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1999 VL 15 IS 1 BP 75 EP + PG 15 WC Veterinary Sciences SC Veterinary Sciences GA 178JK UT WOS:000079262400007 PM 10088213 ER PT J AU Landy, RB Kim, IS Lee, Y Hoffman, MK AF Landy, RB Kim, IS Lee, Y Hoffman, MK TI Regulatory approaches for controlling pesticide residues in food animals SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID TOTAL DIET; POULTRY; PROGRAM; MEAT AB This article discusses the various approaches utilized in con trolling pesticide residues in food animals. EPA, FDA, and USDA programs are examined, as are state regulatory agencies. Based on monitoring results, it appears that most pesticides are being used in the appropriate manner and that thresholds for pesticides, deemed to be adequate to protect human health, are seldom exceeded. C1 US EPA, Off Res & Dev, Annapolis, MD 21401 USA. Food Safety & Inspect Serv, Off Publ Hlth & Sci, Washington, DC USA. US FDA, Ctr Food Safety & Appl Nutr, Contaminants Stand Monitoring & Programs Branch, Washington, DC 20204 USA. RP Landy, RB (reprint author), US EPA, Off Res & Dev, Power Technol Bldg,Suite 200,201 Defense Highway,, Annapolis, MD 21401 USA. NR 28 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 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1999 VL 15 IS 1 BP 89 EP + PG 20 WC Veterinary Sciences SC Veterinary Sciences GA 178JK UT WOS:000079262400008 PM 10088214 ER PT J AU Headrick, ML Hollinger, K Lovell, RA Matheson, JC AF Headrick, ML Hollinger, K Lovell, RA Matheson, JC TI PBBs, PCBs, and dioxins in food animals, their public health implications SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID POLYCHLORINATED-BIPHENYLS PCBS; MILK; DDE; CHILDREN; WORKSHOP; EXPOSURE AB Polybrominated biphenyls (PBBs), polychlorinated biphenyls (PCBs), and dioxins are shown to have toxic potential in food animals and humans through laboratory research and investigation of accidental exposures. This article discusses the ball clay incident, as well as other examples of known accidental exposures to PBBs and PCBs. Background information regarding the mechanism of toxicity and effects in animals and humans is also included. C1 US FDA, Ctr Vet Med, Epidemiol Team, Div Epidemiol & Surveillance, Rockville, MD 20855 USA. US FDA, Ctr Vet Med, Feed Safety Team, Div Anim Feeds, Rockville, MD 20857 USA. US FDA, Ctr Vet Med, Off Surveillance & Compliance, Rockville, MD 20857 USA. RP Headrick, ML (reprint author), US FDA, Ctr Vet Med, Epidemiol Team, Div Epidemiol & Surveillance, 7500 Standish Pl,HFV-218, Rockville, MD 20855 USA. NR 41 TC 20 Z9 20 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 1999 VL 15 IS 1 BP 109 EP + PG 25 WC Veterinary Sciences SC Veterinary Sciences GA 178JK UT WOS:000079262400009 PM 10088215 ER PT J AU Hollinger, K Ekperigin, HE AF Hollinger, K Ekperigin, HE TI Mycotoxicosis in food producing animals SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID OCHRATOXIN-A; RISK ASSESSMENT; CYCLOPIAZONIC ACID; CULTURE MATERIAL; FUMONISINS; ZEARALENONE; AFLATOXIN; CORN; MILK; CHICKENS AB Mycotoxins are toxic secondary metabolites of fungi. Diseases caused by mycotoxins are collectively referred to as mycotoxicosis. Disease is usually initiated after ingestion of feeds containing toxic doses of mycotoxins. Signs and symptoms vary and depend on the animal, the organ system involved, and on the dose and type of mycotoxins ingested. The symptoms can range from acute death, immunosuppression to skin lesions or to signs of hepatotoxicity, nephrotoxicity, neurotoxicity, or genotoxicity. Ln addition to concerns over adverse effects of mycotoxins on food animals consuming mycotoxin-contaminated feeds, there is also a public health concern over the potential for human beings to consume animal-derived food products such as meat, milk, or eggs, containing residues of those mycotoxins or their metabolites. C1 US FDA, Ctr Vet Med, Epidemiol Team, Div Epidemiol & Surveillance, Rockville, MD 20855 USA. US FDA, Ctr Vet Med, Feed Safety Team, Div Anim Feeds, Rockville, MD 20855 USA. US FDA, Ctr Vet Med, Off Surveillance & Compliance, Rockville, MD 20855 USA. RP Hollinger, K (reprint author), US FDA, Ctr Vet Med, Epidemiol Team, Div Epidemiol & Surveillance, HFV-218,7500 Standish Pl, Rockville, MD 20855 USA. NR 73 TC 35 Z9 39 U1 3 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1999 VL 15 IS 1 BP 133 EP + PG 34 WC Veterinary Sciences SC Veterinary Sciences GA 178JK UT WOS:000079262400010 PM 10088216 ER PT J AU Leighton, JK AF Leighton, JK TI Center for veterinary medicine's perspective on the beef hormone case SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article AB Steroidal sex hormones and synthetic derivatives are used in the US to enhance growth in food-producing animals. The European Economic Community has banned use of these same substances, reportedly on the grounds of food safety. The US maintains that this ban was and is a disguised restriction on trade. The technical grounds for bringing this case and the impact of the findings of the World Trade Organization on the regulation of animal drugs in the US is discussed. C1 US FDA, Div Human Food Safety, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20857 USA. RP Leighton, JK (reprint author), Ctr Drug Evaluat & Res, Div Oncol Drug Prod, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 9 TC 2 Z9 2 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 1999 VL 15 IS 1 BP 167 EP + PG 15 WC Veterinary Sciences SC Veterinary Sciences GA 178JK UT WOS:000079262400011 PM 10088217 ER PT J AU Thompson, SR AF Thompson, SR TI International harmonization issues SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article AB With the globalization of trade in many product sectors occurring at a rapid pace, interest in international harmonization issues relating to veterinary products continues to grow. Because of the potential impact on trade, there has been a focus for several years on harmonization of maximum residue limits (MRLs) or tolerances on a global basis. There has also been interest, especially on the part of pharmaceutical companies, to facilitate the approval of a veterinary product in multiple countries. This article discusses two major international initiatives that have been formed to address these harmonization areas of concern for veterinary products. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Thompson, SR (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl,MPN2,HFV-3, Rockville, MD 20855 USA. NR 6 TC 4 Z9 4 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 1999 VL 15 IS 1 BP 181 EP + PG 16 WC Veterinary Sciences SC Veterinary Sciences GA 178JK UT WOS:000079262400012 PM 10088218 ER PT J AU Kla, J Tollefson, L AF Kla, J Tollefson, L TI Producer quality assurance programs SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article AB Animal commodity organizations have developed voluntary quality assurance educational programs to guide their members in producing the highest quality, safest product possible. This chapter describes programs implemented by the National Pork Producers Council, the National Cattlemen's Beef Association, the National Milk Producers Federation, the American Veal Association, and the National Broiler Council. Veterinarians should strongly encourage their clients' participation in these programs to help ensure a safe food supply. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Kla, J (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1999 VL 15 IS 1 BP 197 EP + PG 13 WC Veterinary Sciences SC Veterinary Sciences GA 178JK UT WOS:000079262400013 PM 10088219 ER PT J AU Duncan, R Muller, J Lee, N Esmaili, A Nakhasi, HL AF Duncan, R Muller, J Lee, N Esmaili, A Nakhasi, HL TI Rubella virus-induced apoptosis varies among cell lines and is modulated by Bcl-X-L and caspase inhibitors SO VIROLOGY LA English DT Article ID MOLECULAR-BIOLOGY; CONGENITAL-RUBELLA; MEDIATED APOPTOSIS; CYTOCHROME-C; DEATH; PROTEASES; FAMILY; PROTEINS; IMPROVEMENT; EXPRESSION AB Rubella virus (RV) causes multisystem birth defects in the fetuses of infected women. To investigate the cellular basis of this pathology, we examined the cytopathic effect of RV in three permissive cell lines: Vero 76, RK13, and BHK21. Electron microscopy and the TUNEL assay showed that the cytopathic effect resulted from RV-induced programmed cell death (apoptosis) in all three cell lines, but the extent of apoptosis varied among these cells. At 48 h postinfection, the RK13 cell line showed the greatest number of apoptotic cells, the Vero 76 cell line was similar to 3-fold less, and BHK21 had very few. An increased multiplicity of infection and longer time postinfection were required for the BHK21 cell line to reach the level of apoptotic cells in Vero 76 at 48 h. Purified RV induced apoptosis in a dose-dependent fashion, but not UV-inactivated RV or virus-depleted culture supernatant Specific inhibitors of the apoptosis-specific proteases caspases reduced RV-induced apoptosis and led to higher levels of RV components in infected cells. To address the role of regulatory proteins in RV-induced apoptosis, the antiapoptotic gene Bcl-2 or Bcl-X-L was transfected into RK13 cells. Although a high level of Bcl-2 family proteins was expressed, no protection was observed from apoptosis induced by RV, Sindbis virus, or staurosporine in RK13 cells. In BHK21 cells, however, increased expression of Bcl-X-L protected cells from apoptosis. The observed variability in apoptotic response to RV of these cell lines demonstrates that programmed cell death is dependent on the unique properties of each cell and may be indicative of how selective organ damage occurs in a congenital rubella syndrome fetus. C1 US FDA, Ctr Biol Evaluat & Res, Lab Parasit Biol & Biochem, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Viral Dis, Bethesda, MD 20892 USA. RP Nakhasi, HL (reprint author), Bldg 29,Room 425,1401 Rockville Pike,HFM 416, Rockville, MD 20852 USA. RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 57 TC 31 Z9 35 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 MAR 1 PY 1999 VL 255 IS 1 BP 117 EP 128 DI 10.1006/viro.1998.9562 PG 12 WC Virology SC Virology GA 174DB UT WOS:000079017900014 PM 10049827 ER PT J AU Zhu, M Aviles, FJ Conte, ED Miller, DW Perschbacher, PW AF Zhu, M Aviles, FJ Conte, ED Miller, DW Perschbacher, PW TI Microwave mediated distillation with solid-phase microextraction: determination of off-flavors, geosmin and methylisoborneol, in catfish tissue SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE off-flavour compounds; catfish; distillation device; geosmin; methylisoborneol ID EXTRACTION AB Presented is a rapid distillation device for use with solid-phase microextraction (SPME). We apply this device specifically for determining two semivolatile off-flavor compounds, methylisoborneol and geosmin, in channel catfish. The presence of these two compounds in channel catfish filets results in unwelcome tastes. In the presented procedure, a catfish tissue sample is placed within a sample container located inside the microwave device. Microwave radiation is applied and distillates formed migrate through a condenser via a purge gas and are collected in a sample vial. A SPME fiber is placed within the stirred collected distillate and methylisoborneol and geosmin are extracted. Qualitative and quantitative results of these extractions are obtained using a gas chromatograph-ion trap mass spectrometer. This solventless technique results in detection limits far below the human threshold for these off-flavor compounds in channel catfish. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Western Kentucky Univ, Dept Chem, Bowling Green, KY 42101 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Univ Arkansas, Aquaculture Expt Stn, Pine Bluff, AR 71601 USA. RP Conte, ED (reprint author), Western Kentucky Univ, Dept Chem, Bowling Green, KY 42101 USA. NR 12 TC 32 Z9 36 U1 1 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD FEB 19 PY 1999 VL 833 IS 2 BP 223 EP 230 DI 10.1016/S0021-9673(98)01010-3 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 170KV UT WOS:000078805600009 ER PT J AU Reeves, VB AF Reeves, VB TI Confirmation of multiple sulfonamide residues in bovine milk by gas chromatography-positive chemical ionization mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE sulfonamides; drug residues; sulfamethazine ID LIQUID-CHROMATOGRAPHY; SWINE TISSUES; SULFAMETHAZINE; ASSAY AB Gas chromatography-mass spectrometry (GC-MS) using positive chemical ionization was utilized to confirm the presence of 10 ng ml(-1) of nine sulfonamides (SFAs) in bovine milk (50 ml). After the addition of a surrogate and hydroxylamine hydrochloride, the SFAs are extracted with ethyl acetate followed by cyclohexyl solid-phase extraction clean-up. The methylamidotrifluoroacetyl derivatives are prepared and analyzed in selected ion monitoring mode. For regulatory confirmation, the required specificity was achieved by monitoring the molecular ion plus three to five fragment ions for each SFA. Retention times for all SFAs were within 0.1 min of their respective standard. The relative ion abundances were within 10% of those obtained with standards diluted to the same concentration, analyzed on the same day. Concentration was critical, especially for the early eluting SFAs, as the enhancement of the relative abundance of the parent was more pronounced in extracted samples then in the standards. The sensitivity of the mass spectrometer for the different SFAs varied greatly. The amount of SFA necessary to obtain spectra that would meet the confirmation criteria varied from 25 ng on column for the least sensitive to less than 3 ng for the more robust. (C) 1999 Published by Elsevier Science B.V. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Reeves, VB (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 20 TC 87 Z9 99 U1 0 U2 10 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 19 PY 1999 VL 723 IS 1-2 BP 127 EP 137 DI 10.1016/S0378-4347(98)00548-9 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 168PE UT WOS:000078700800014 PM 10080640 ER PT J AU Thompson, HC Rushing, LG Gehring, T Lochmann, R AF Thompson, HC Rushing, LG Gehring, T Lochmann, R TI Persistence of gentian violet and leucogentian violet in channel catfish (ictalurus punctatus) muscle after water-borne exposure SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE gentian violet; leucogentian violet ID MALACHITE GREEN; RAINBOW-TROUT; LIQUID-CHROMATOGRAPHY; ONCORHYNCHUS-MYKISS; VISIBLE DETECTION; TISSUE AB Gentian violet is a triphenylmethane dye that is an antifungal/antiparastic agent. GV is similar to malachite green that has been used in the aquaculture industry for treatment or prevention of external fungal and parasitic infections in fish and fish eggs although it (MG) is not approved for this use. For these reasons, GV's potential for misuse by the aquaculture industry is high. The uptake and depletion of gentian violet (GV) were determined in channel catfish (Ictalurus punctatus) after water-borne exposure (100 ng ml(-1), 1 h) under simulated aquaculture farming conditions. Leucogentian violet (LGV) was rapidly formed, concentrated in the muscle tissue, and very slowly eliminated from muscle tissue. An isocratic (60% acetonitrile-40% water; 0.05 M ammonium acetate buffer, pH 4.5) HPLC system consisting of a 5 mu m LC-CN 250x4.6 mm I.D. column, a 20x2.0 mm I.D. PbO2 oxidative post-column, and a UV-VIS detector set at 588 nm were used to determine uptake and depletion of tissue residues of GV and LGV with time. GV was rapidly depleted and converted to its major metabolite, LGV, which was detected out to 79 days. Therefore, LGV is the appropriate target analyte for monitoring exposure of channel catfish to GV. (C) 1999 Published by Elsevier Science B.V. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, DHHS, Jefferson, AR 72079 USA. Univ Arkansas, Dept Fisheries & Aquaculture, Pine Bluff, AR 71611 USA. RP Rushing, LG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, DHHS, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 22 TC 20 Z9 21 U1 2 U2 6 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 19 PY 1999 VL 723 IS 1-2 BP 287 EP 291 DI 10.1016/S0378-4347(98)00536-2 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 168PE UT WOS:000078700800031 PM 10080657 ER PT J AU Wechsler, E D'Aleo, C Hill, VA Hopper, J Myers-Wiley, D O'Keefe, E Jacobs, J Guido, F Huang, A Dodt, SN Rowan, B Sherman, M Greenberg, A Schneider, D Noone, B Fanella, L Williamson, BR Dinda, E Mayer, M Backer, M Agasan, A Kornstein, L Stavinsky, F Neal, B Edwards, D Haroon, M Hurley, D Colbert, L Miller, J Mojica, B Carloni, E Devine, B Cambridge, M Root, T Schoonmaker, D Shayegani, M Hastback, W Wallace, B Kondracki, S Smith, P Matiuck, S Pilot, K Acharya, M Wolf, G Manley, W Genese, C Brooks, J Dembek, Z Hadler, J AF Wechsler, E D'Aleo, C Hill, VA Hopper, J Myers-Wiley, D O'Keefe, E Jacobs, J Guido, F Huang, A Dodt, SN Rowan, B Sherman, M Greenberg, A Schneider, D Noone, B Fanella, L Williamson, BR Dinda, E Mayer, M Backer, M Agasan, A Kornstein, L Stavinsky, F Neal, B Edwards, D Haroon, M Hurley, D Colbert, L Miller, J Mojica, B Carloni, E Devine, B Cambridge, M Root, T Schoonmaker, D Shayegani, M Hastback, W Wallace, B Kondracki, S Smith, P Matiuck, S Pilot, K Acharya, M Wolf, G Manley, W Genese, C Brooks, J Dembek, Z Hadler, J TI Outbreak of Vibrio parahaemolyticus infection associated with eating raw oysters and clams harvested from Long Island Sound - Connecticut, New Jersey, and New York, 1998 (Reprinted from MMWR, vol 48, pg 48, 1999) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Westchester Cty Hlth Dept, New Rochelle, NY USA. Nassau Cty Dept Hlth, Div Dis Control, Mineola, NY USA. Suffolk Cty Dept Hlth Serv, Hauppauge, NY USA. New York City Bur Labs, Enter Pathogens Lab, New York, NY USA. New York City Bur Labs, Environm Microbiol Lab, New York, NY USA. New York City Dept Hlth, New York, NY USA. Bur Community Sanitat & Food Protect, New York, NY USA. Wadsworth Ctr Labs & Res, Albany, NY USA. New York State Dept Hlth, Albany, NY 12237 USA. New York State Dept Environm Conservat, New York, NY USA. Bur Communicable Dis Control, New York, NY USA. Bur Labs, New York, NY USA. New Jersey State Dept Hlth, Trenton, NJ 08625 USA. Connecticut Dept Publ Hlth, US FDA, Hartford, CT USA. US Fish & Wildlife Serv, USDA, Washington, DC USA. CDC, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Foodborne & Diarrheal Dis Branch, Atlanta, GA 30333 USA. CDC, Epidemiol Program Off, Div Appl Publ Hlth Training, State Branch, Atlanta, GA 30333 USA. RP Wechsler, E (reprint author), Westchester Cty Hlth Dept, New Rochelle, NY USA. NR 1 TC 12 Z9 13 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 17 PY 1999 VL 281 IS 7 BP 603 EP 604 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 165YA UT WOS:000078548400010 ER PT J AU Misbin, RI AF Misbin, RI TI Troglitazone-associated hepatic failure SO ANNALS OF INTERNAL 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 29 Z9 29 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 FEB 16 PY 1999 VL 130 IS 4 BP 330 EP 330 PN 1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 166PY UT WOS:000078587200019 PM 10068399 ER PT J AU Furuke, K Shiraishi, M Mostowski, HS Bloom, ET AF Furuke, K Shiraishi, M Mostowski, HS Bloom, ET TI Fas ligand induction in human NK cells is regulated by redox through a calcineurin-nuclear factors of activated T cell-dependent pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; CYCLOSPORINE-A; KAPPA-B; TRANSCRIPTION FACTOR; UP-REGULATION; EXPRESSION; APOPTOSIS; BINDING; DEATH; CD95 AB Fas ligand (FasL) on cytotoxic lymphocytes is important for mediating apoptosis of activated lymphocytes and other target cells. We have reported that NK cell functions, such as proliferation, cell death, and killing activity, are subject to regulation by cellular redox status. Here, we report that expression of Fast protein and mRNA in activated NK cells is also regulated by redox, Ligation of CD16 on IL-2-preactivated NK cells resulted in reduction of intracellular peroxide level as well as induction of Fast expression. This CD16-induced Fast expression was suppressed by oxidative stress, including thiol deprivation or treatment with hydrogen peroxide (H2O2), Addition of thiol-reducing compounds, such as L-cystine, 2-ME, or N-acetyl cysteine, restored FasL expression. These data suggest that CD16 stimulation requires cellular reducing status for Fast induction in NK cells. Because Fast gene activation following CD16 cross-linking is regulated by the NF of activated T cells (NFAT), we examined the effect of oxidative stresses on NFAT activation, Electrophoretic mobility shift assays revealed that both thiol insufficiency and H2O2 treatment suppressed DNA-binding activity of NFAT and that addition of thiol-reducing compounds reversed or even enhanced it. Furthermore, these oxidative stresses inhibited activity of calcineurin, a serine/threonine phosphatase that regulates NFAT activation. These results suggest that suppression of calcineurin and NFAT activation is a mechanism by which oxidative stress inhibits Fast induction in activated NK cells and further support the hypothesis that thiol-reducing compounds might be required for maintenance of optimal NK functions under physiologic oxidative conditions. C1 US FDA, Ctr Biol Evaluat Res, Div Cellular & Gene Therapies, Lab Cellular Immunol HFM 518, Bethesda, MD 20892 USA. RP Bloom, ET (reprint author), US FDA, Ctr Biol Evaluat Res, Div Cellular & Gene Therapies, Lab Cellular Immunol HFM 518, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 44 TC 77 Z9 77 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 15 PY 1999 VL 162 IS 4 BP 1988 EP 1993 PG 6 WC Immunology SC Immunology GA 165FV UT WOS:000078510800017 PM 9973469 ER PT J AU Elkins, KL Rhinehart-Jones, TR Stibitz, S Conover, JS Klinman, DM AF Elkins, KL Rhinehart-Jones, TR Stibitz, S Conover, JS Klinman, DM TI Bacterial DNA containing CpG motifs stimulates lymphocyte-dependent protection of mice against lethal infection with intracellular bacteria SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; TULARENSIS STRAIN LVS; FRANCISELLA-TULARENSIS; INTERFERON-GAMMA; NUCLEOTIDE-SEQUENCE; CELL ACTIVATION; IMMUNE-RESPONSE; T-CELLS; RESISTANCE; OLIGODEOXYNUCLEOTIDES AB Bacterial DNA containing unmethylated CpG motifs activates mammalian lymphocytes and macrophages to produce cytokines and polyclonal Ig. These include IFN-gamma, IL-12, TNF-alpha, and IL-6, which are important in the control of intracellular bacterial infection. Here, we show that bacterial DNA, as well as synthetic oligonucleotides containing CpG motifs, induce protection against large lethal doses of Francisella tularensis live vaccine strain (LVS) and Listeria monocytogenes, Methylation of DNA at CpG dinudeotides or inversion of the motif abolished this protection, Surprisingly, DNA-mediated protection was highly dependent on lymphocytes, particularly B cells, as well as the production of IFN-gamma. Optimal protection was elicited 2-3 days after inoculation with DNA and persisted for up to 2 wk, Further, animals surviving lethal challenge developed pathogen-specific secondary immunity. These findings indicate that host innate immune responses to bacterial DNA may contribute to the induction of protective immunity to bacteria and the subsequent development of memory. C1 Ctr Biol Evaluat & Res, Div Bacterial Prod, Lab Mycobacteria, Rockville, MD 20852 USA. Ctr Biol Evaluat & Res, Div Bacterial Prod, Lab Enter & Sexually Transmitted Dis, Rockville, MD 20852 USA. Ctr Biol Evaluat & Res, Div Viral Prod, Lab Retrovirol, Retroviral Immunol Sect, Rockville, MD 20852 USA. RP Elkins, KL (reprint author), Ctr Biol Evaluat & Res, Div Bacterial Prod, Lab Mycobacteria, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. NR 39 TC 235 Z9 248 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 1999 VL 162 IS 4 BP 2291 EP 2298 PG 8 WC Immunology SC Immunology GA 165FV UT WOS:000078510800054 PM 9973506 ER PT J AU Imam, SZ Newport, GD Islam, F Slikker, W Ali, SF AF Imam, SZ Newport, GD Islam, F Slikker, W Ali, SF TI Selenium, an antioxidant, protects against methamphetamine-induced dopaminergic neurotoxicity SO BRAIN RESEARCH LA English DT Article DE methamphetamine; neurotoxicity; selenium; dopamine; caudate nucleus; oxidative stress ID DISMUTASE TRANSGENIC MICE; NITRIC-OXIDE SYNTHASE; GLUTATHIONE-PEROXIDASE; PARKINSONS-DISEASE; 7-NITROINDAZOLE; INHIBITOR; STRIATUM AB Dopaminergic changes were studied in the caudate nucleus of adult female mice after pre- and post-treatment with an antioxidant, selenium, 72 h after the multiple injections of methamphetamine (METH, 4 x 10 mg/kg, i.p. at 2-h interval) or an equivalent volume of saline. Selenium treatment prevented the depletion of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in caudate nucleus resulting from the METH treatment. These data suggest that METH-induced neurotoxicity is mediated by free radical and selenium plays a protective role against METH-induced dopaminergic neurotoxicity. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Hamdard Univ, Dept Med Elementol & Toxicol, Neurotoxicol Lab, New Delhi, India. Univ Arkansas Med Sci, Dept Neurol & Biochem & Mol Biol, 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 NR 31 TC 51 Z9 52 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 13 PY 1999 VL 818 IS 2 BP 575 EP 578 DI 10.1016/S0006-8993(98)01311-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 166DD UT WOS:000078560200049 PM 10082851 ER PT J AU Hussain, S Ali, SF AF Hussain, S Ali, SF TI Manganese scavenges superoxide and hydroxyl radicals: an in vitro study in rats SO NEUROSCIENCE LETTERS LA English DT Article DE manganese; superoxide ions; hydroxyl ions; Mn-superoxide dismutase; antioxidant ID NITRITE FORMATION; DISMUTASE; BRAIN; NEUROTOXICITY; INHIBITION; CHLORIDE; ASSAY AB The present study was designed to investigate the role of manganese (Mn) as an antioxidant element. In vitro experiments have been conducted to evaluate the ability of Mn in scavenging oxygen free radicals. Superoxide (O.-) and hydroxyl (OH.-) radicals were generated in vitro by using xanthine and xanthine oxidase system and fenton reactions respectively. Different concentrations of Mn (II) and Mn (III) were used in the reaction mixture to evaluate free radical scavenging ability of Mn. The results indicated that Mn scavenged superoxide radicals at nanomolar concentrations whereas hydroxyl radicals were scavenged at micromolar concentrations. In addition, Mn-superoxide dismutase (SOD) activity was measured in different regions of brain in adult male rats treated with MnCl2. The results showed that Mn-SOD activity increased in Mn treated animals. Therefore, the data support the hypothesis that Mn is one of the essential elements which can protect against oxidative damage, however, at higher concentrations Mn can be neurotoxic by generating the free radicals. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 20 TC 44 Z9 46 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD FEB 12 PY 1999 VL 261 IS 1-2 BP 21 EP 24 DI 10.1016/S0304-3940(98)01005-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 170MR UT WOS:000078809900006 PM 10081917 ER PT J AU Lacroix, L Lacoste, J Reddoch, JF Mergny, JL Levy, DD Seidman, MM Matteucci, MD Glazer, PM AF Lacroix, L Lacoste, J Reddoch, JF Mergny, JL Levy, DD Seidman, MM Matteucci, MD Glazer, PM TI Triplex formation by oligonucleotides containing 5-(1-propynyl)-2 '-deoxyuridine: Decreased magnesium dependence and improved intracellular gene targeting SO BIOCHEMISTRY LA English DT Article ID HELIX-FORMING OLIGONUCLEOTIDE; MESSENGER-RNA LEVELS; MAMMALIAN-CELLS; COOPERATIVE BINDING; SHUTTLE VECTOR; STRANDED DNA; OLIGODEOXYNUCLEOTIDES; ANTISENSE; MUTAGENESIS; INHIBITION AB Oligonucleotides capable of sequence-specific triple helix formation have been proposed as DNA binding ligands useful for modulation of gene expression and for directed genome modification. However, the effectiveness of such tripler-forming oligonucleotides (TFOs) depends on their ability to bind to their target sites within cells, and this can be limited under physiologic conditions. In particular, tripler formation in the pyrimidine motif is favored by unphysiologically low pH and high magnesium concentrations. To address these limitations, a series of pyrimidine TFOs were tested for third-strand binding under a variety of conditions. Those containing 5-(1-propynyl)-2'-deoxyuridine (pdU) and 5-methyl-2'-deoxycytidine (5meC) showed superior binding characteristics at neutral pH and at low magnesium concentrations, as determined by gel mobility shift assays and thermal dissociation profiles. Over a range of Mg2+ concentrations, pdU-modified TFOs formed more stable triplexes than did TFOs containing 2'-deoxythymidine. At 1 mM Mg2+, a Delta Tm of 30 degrees C was observed for pdU- versus T-containing 15-mers (of generic sequence 5' TTTTCTTTTTTCTTTTCT 3') binding to the cognate A:T bp rich site, indicating that pdU-containing TFOs are capable of substantial binding even at physiologically low Mg2+ concentrations. In addition, the pdU-containing TFOs were superior in gene targeting experiments in mammalian cells, yielding 4-fold higher mutation frequencies in a shuttle vector-based mutagenesis assay designed to detect mutations induced by third-strand-directed psoralen adducts. These results suggest the utility of the pdU substitution in the pyrimidine motif for tripler-based gene targeting experiments. C1 Yale Univ, Boyer Ctr 354, Dept Therapeut Radiol, New Haven, CT 06536 USA. Yale Univ, Boyer Ctr 354, Dept Genet, New Haven, CT 06536 USA. Museum Natl Hist Nat, Biophys Lab, CNRS,UA481, INSERM,U201, F-75005 Paris, France. US FDA, Washington, DC 20204 USA. NIA, NIH, Baltimore, MD 21224 USA. Gilead Sci Inc, Foster City, CA 94404 USA. RP Glazer, PM (reprint author), Yale Univ, Boyer Ctr 354, Dept Therapeut Radiol, 295 Congress Ave, New Haven, CT 06536 USA. RI Lacroix, Laurent/C-7024-2009; Mergny, Jean-Louis/E-2860-2013 OI Lacroix, Laurent/0000-0002-6382-9057; Mergny, Jean-Louis/0000-0003-3043-8401 FU NCI NIH HHS [CA64186] NR 41 TC 53 Z9 54 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 9 PY 1999 VL 38 IS 6 BP 1893 EP 1901 DI 10.1021/bi982290q PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 170ZK UT WOS:000078837200027 PM 10026270 ER PT J AU De Luca, A Casamassimi, A Selvam, MP Losito, S Ciardiello, F Agrawal, S Salomon, DS Normanno, N AF De Luca, A Casamassimi, A Selvam, MP Losito, S Ciardiello, F Agrawal, S Salomon, DS Normanno, N TI EGF-related peptides are involved in the proliferation and survival of MDA-MB-468 human breast carcinoma cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID EPIDERMAL GROWTH-FACTOR; MAMMARY EPITHELIAL-CELLS; ANTISENSE OLIGONUCLEOTIDES; CANCER CELLS; APOPTOSIS; AMPHIREGULIN; EXPRESSION; CRIPTO; ALPHA; DEATH AB A majority of human breast carcinomas co-express the epidermal growth factor (EGF)-like peptides CRIPTO (CR), amphiregulin (AR) and transforming growth factor alpha (TGF-alpha). MDA-MB-468 breast carcinoma cells express CR, AR and TGF alpha, while SK-BR-3 cells express CR and TGF-alpha. Anti-sense phosphorothioate oligodeoxynucleotides (AS S-oligos) directed against either CR or TGF-alpha inhibit the proliferation of both cell lines. A 40-50% growth inhibition was observed at a 2-mu M concentration of each AS S-oligo. Treatment with the AR AS S-oligo also resulted in a significant inhibition of MDA-MB-468 anchorage dependent growth (ADG), No significant growth inhibition was observed when MDA-MB-468 or SK-BR-3 cells were treated with a mis-sense S-oligo, The AS S-oligos inhibited the expression of AR, CR or TGF-alpha proteins and mRNAs, as assessed by immuno-cytochemistry and semi-quantitative RT-PCR. An additive growth-inhibitory effect was observed when MDA-MB-468 cells were treated with a combination of EGF-related AS S-oligos, Indeed, treatment of MDA-MB-468 cells with a combination of AR, CR and TGF-alpha AS S-oligos resulted in about 70% growth inhibition at a concentration of 0.7 mu M each. Finally, treatment of MDA-MB-468 cells with a combination either of the 3 AS S-oligos or of an EGF receptor-blocking antibody (MAb 225) and either CR, AR or TGF alpha AS S-oligos resulted in a significant increase in DNA fragmentation. Our data suggest that the EGF-related peptides are involved in the proliferation and survival of breast carcinoma cells. (C) 1999 Wiley-Liss, Inc. C1 ITN, Fdn Pascale, I-80131 Naples, Italy. DBA, CBER, Food & Drug Adm, Rockville, MD USA. Univ Naples Federico II, Fac Med & Chirurg, Dipartimento Endocrinol & Oncol Mol & Clin, Cattedra Oncol Med, Naples, Italy. Hybridon Inc, Cambridge, MA USA. NCI, LTIB, Tumor Growth Factor Sect, NIH, Bethesda, MD 20892 USA. RP Normanno, N (reprint author), ITN, Fdn Pascale, I-80131 Naples, Italy. RI De Luca, Antonella/J-8737-2016; OI De Luca, Antonella/0000-0001-5762-447X; Ciardiello, Fortunato/0000-0002-3369-4841; Normanno, Nicola/0000-0002-7158-2605 NR 20 TC 36 Z9 37 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 9 PY 1999 VL 80 IS 4 BP 589 EP 594 DI 10.1002/(SICI)1097-0215(19990209)80:4<589::AID-IJC17>3.0.CO;2-D PG 6 WC Oncology SC Oncology GA 159AH UT WOS:000078149300017 PM 9935161 ER PT J AU Rubin, SA Bautista, JR Moran, TH Schwartz, GJ Carbone, KM AF Rubin, SA Bautista, JR Moran, TH Schwartz, GJ Carbone, KM TI Viral teratogenesis: brain developmental damage associated with maturation state at time of infection SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE brain; damage; development; virus; Borna disease ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; BORNA-DISEASE; CYCLOSPORINE-A; MOUSE-BRAIN; RATS; ABNORMALITIES; PATHOGENESIS; NEURONS; CELLS AB The rat brain continues to mature after birth and is particularly vulnerable to developmental damage following perinatal insult. Borna disease virus (BDV) infection of postnatal day one (PND-1) rat brain causes a non-encephalitic, persistent infection associated with developmental neuroanatomical and behavioral abnormalities. To test the hypothesis that BDV infection during different brain developmental stages yields variable pathological and clinical disease sequelae, rats were examined for BDV-induced neuroanatomical and behavioral abnormalities following inoculation with BDV on PND-15, and the findings were compared to those resulting from inoculation on PND-1. Similar to rats inoculated with BDV on PND-1, PND-15 inoculated rats developed a persistent infection associated with body weight stunting, abnormal salt taste preference and hippocampal neuron degeneration. However, unlike rats infected with BDV on PND-1, PND-15 inoculated rats did not show signs of cerebellar hypoplasia or hyperactivity. Thus, the risk of BDV-induced damage to specific brain regions, and their associated behaviors, appears, in part, dependent upon the brain's developmental stage at time of BDV-infection. These studies provide evidence of the selective vulnerability of specific neuroanatomic regions and behaviors in developing nervous system to virus-induced damage. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US FDA, Lab Pediat & Resp Viral Dis, DVP, CBER, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Carbone, KM (reprint author), US FDA, Lab Pediat & Resp Viral Dis, DVP, CBER, Bldg 29A,Room 1A21,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 44 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD FEB 5 PY 1999 VL 112 IS 2 BP 237 EP 244 DI 10.1016/S0165-3806(98)00180-1 PG 8 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 167BQ UT WOS:000078613100008 ER PT J AU Nightingale, SL AF Nightingale, SL TI FDA conference on human subject protection SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item 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 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 FEB 3 PY 1999 VL 281 IS 5 BP 408 EP 408 DI 10.1001/jama.281.5.408 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 161YT UT WOS:000078318500008 PM 9952188 ER PT J AU Nightingale, SL AF Nightingale, SL TI Reporting adverse events and product problems electronically SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item 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 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 FEB 3 PY 1999 VL 281 IS 5 BP 408 EP 408 DI 10.1001/jama.281.5.408 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 161YT UT WOS:000078318500010 PM 9952188 ER PT J AU Nightingale, SL AF Nightingale, SL TI Lyme disease vaccine approved SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item 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 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 FEB 3 PY 1999 VL 281 IS 5 BP 408 EP 408 DI 10.1001/jama.281.5.408 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 161YT UT WOS:000078318500007 PM 9952188 ER PT J AU Nightingale, SL AF Nightingale, SL TI Journal editors act to enhance reporting of public health hazards SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item 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 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 FEB 3 PY 1999 VL 281 IS 5 BP 408 EP 408 DI 10.1001/jama.281.5.408 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 161YT UT WOS:000078318500009 PM 9952188 ER PT J AU Friedman, MA AF Friedman, MA TI Opportunities and challenges: The FDA's future SO ACADEMIC MEDICINE LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Friedman, MA (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD FEB PY 1999 VL 74 IS 2 BP 176 EP 177 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 168RF UT WOS:000078705800024 ER PT J AU Lee, CH Tsai, CM AF Lee, CH Tsai, CM TI Quantification of bacterial lipopolysaccharides by the purpald assay: Measuring formaldehyde generated from 2-keto-3-deoxyoctonate and heptose at the inner core by periodate oxidation SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID ACID; ENDOTOXINS; REGION; PROTEIN AB We have adapted the purpald assay (M, S. Quesenberry and Y. C. Lee, Anal. Biochem. 234, 50-55, 1996) to quantify lipopolysaccharide (LPS) content in solution in 96-well microtiter plates at room temperature. This method employs the oxidation of unsubstituted terminal vicinal glycol groups in 2-keto-3-deoxyoctonate (Kdo) and L-(or D-)glycero-D-manno-heptose of LPS molecules by periodate to release formaldehyde. The formaldehyde is quantified at 550 nm (or 530-570 nm) by reacting with purpald reagent followed by oxidation with NaIO4. The sensitivity of the purpald assay is comparable to that of the Kdo assay for LPS determination. However, the purpald assay is superior to the Kdo assay because: (i) No acid hydrolysis of the samples and no boiling in the assay process are required; thus, it can be directly carried out with microtiter plates for a large number of samples at room temperature, (ii) The purpald assay can detect many types of LPS from various bacteria since LPS contains Kdo and heptose which possess unsubstituted terminal vicinal glycol in its structure, while the Kdo assay cannot detect LPS from certain bacteria (e.g., Haemophilus influenzae, Bordetella pertussis, and Vibrio cholerae) due to substitution at the C-4 and C-5 positions of Kdo. C1 US FDA, Lab Bacterial Polysaccharides, Div Bacterial Prod, OVRR,CBER, Bethesda, MD 20892 USA. RP Lee, CH (reprint author), US FDA, Lab Bacterial Polysaccharides, Div Bacterial Prod, OVRR,CBER, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 28 TC 83 Z9 88 U1 2 U2 12 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD FEB 1 PY 1999 VL 267 IS 1 BP 161 EP 168 DI 10.1006/abio.1998.2961 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 162RG UT WOS:000078360100020 PM 9918668 ER PT J AU Manch-Citron, JN Dey, A Ewell, JB Nguyen, NY AF Manch-Citron, JN Dey, A Ewell, JB Nguyen, NY TI Mutant analysis of Prevotella sp plaA-lacZ fusion protein expression in Escherichia coli: support for an essential role of the stem-loop SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE site-directed mutagenesis; stem-loop formation; fusion protein; translational initiation; translational enhancer ID RIBOSOME-BINDING-SITE; TRANSLATION INITIATION SIGNAL; MESSENGER-RNA ACTS; SECONDARY STRUCTURE; GENE-EXPRESSION; GAMMA-SUBUNIT; PSEUDOKNOT; EFFICIENT; SEQUENCES; ELEMENTS AB This study investigated the involvement of RNA folding in the synthesis of a fusion protein with beta-galactosidase activity. The coding gap region of the Prevotella loescheii adhesin gene plaA was fused in-frame with the Escherichia coli lacZ gene on plasmid pSK105. N-Terminal sequencing of the expressed plaA-lacZ protein indicated that it resulted from translational initiation at a fortuitous ribosomal-binding site within the plaA sequence at nt 570. Specific mutations were introduced in the stem-loop region that precedes the gap sequence. Analysis of stem-loop mutants, together with the introduction of compensatory mutations that restored activity, supports a requirement for stem-loop formation within the plaA sequence preceding the translational initiation site. A mutation reducing the predicted size of the loop, but preserving the stem structure, inactivated fusion protein synthesis. A suppressor mutation predicted to restore the size of the loop restored efficient fusion protein synthesis. In addition, the sequence preceding the translational start site of the plaA-lacZ fusion has several similarities to sequences that function as translational enhancers in prokaryotes. These include a stem-loop structure, an A-U rich region preceding the initiation codon, and a region of homology to 16S rRNA. C1 Univ Missouri, Sch Dent, Dept Oral Biol, Kansas City, MO 64108 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Manch-Citron, JN (reprint author), Univ Missouri, Sch Dent, Dept Oral Biol, 650 E 25th St, Kansas City, MO 64108 USA. EM jcitron@umkc.edu NR 39 TC 0 Z9 0 U1 0 U2 0 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA SN 0008-4166 EI 1480-3275 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD FEB PY 1999 VL 45 IS 2 BP 153 EP 161 DI 10.1139/cjm-45-2-153 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA 204JK UT WOS:000080760800008 ER PT J AU Ambrosone, CB Freudenheim, JL Thompson, PA Bowman, E Vena, JE Marshall, JR Graham, S Laughlin, R Nemoto, T Shields, PG AF Ambrosone, CB Freudenheim, JL Thompson, PA Bowman, E Vena, JE Marshall, JR Graham, S Laughlin, R Nemoto, T Shields, PG TI Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants, and risk of breast cancer SO CANCER RESEARCH LA English DT Article ID LIPID-PEROXIDATION; ALCOHOL-CONSUMPTION; UNITED-STATES; DNA-ADDUCTS; NEW-YORK; CELLS; OVEREXPRESSION; PHENOTYPE; DISEASES; SEQUENCE AB Oxidative stress, resulting from the imbalance between prooxidant and antioxidant states, damages DNA, proteins, cell membranes, and mitochondria and seems to play a role in human breast carcinogenesis. Dietary sources of antioxidants (chemical) and endogenous antioxidants (enzymatic), including the polymorphic manganese superoxide dismutase (MnSOD), can act to reduce the load of oxidative stress. We hypothesized that the valine-to-alanine substitution that seems to alter transport of the enzyme into the mitochondrion. changing its efficacy in fighting oxidative stress, was associated with breast cancer risk and that a diet rich in sources of antioxidants could ameliorate the effects on risk. Data were collected in a case-control study of diet and breast cancer in western New York from 1986 to 1991. Caucasian women with incident, primary, histologically confirmed breast cancer were frequency-matched on age and county of residence to community controls. Blood specimens were collected and processed from a subset of participants in the study (266 cases and 295 controls). Using a RFLP that distinguishes a valine (V) to alanine (A) change in the -9 position in the signal sequence of the protein for MnSOD, we characterized MnSOD genotypes in relation to breast cancer risk, We also evaluated the effect of the polymorphism on risk among low and high consumers of Fruits and vegetables. Premenopausal women who were homozygous for the A allele had a 4-fold increase in breast cancer risk in comparison to those with 1 or 2 V alleles (odds ratio, 4.3; 95% confidence interval, 1.7-10.8). Risk was most pronounced among women below the median consumption of fruits and vegetables and of dietary ascorbic acid and cu-tocopherol, with little increased risk for those with diets rich in these foods, Relationships were weaker among postmenopausal women, although the MnSOD AA genotype was associated with an almost 2-fold increase in risk (odds ratio, 1.8; confidence interval, 0.9-3.6), No appreciable modification of risk by diet was detected for these older women. These data support the hypothesis that MnSOD and oxidative stress play a significant role in breast cancer risk, particularly in premenopausal women, The finding that risk was greatest among women who consumed lo rc er amounts of dietary antioxidants and was minimal among high consumers indicates that a diet rich in sources of antioxidants may minimize the deleterious effects of the MnSOD polymorphism, thereby supporting public health recommendations for the consumption of diets rich in fruits and vegetables as a preventive measure against cancer. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. RP Ambrosone, CB (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. RI Shields, Peter/I-1644-2012 FU NCI NIH HHS [CA/ES62995, CA01633, CA11535] NR 45 TC 287 Z9 299 U1 2 U2 8 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 FEB 1 PY 1999 VL 59 IS 3 BP 602 EP 606 PG 5 WC Oncology SC Oncology GA 163EU UT WOS:000078390900020 PM 9973207 ER PT J AU Gutierrez, MI Cherney, B Hussain, A Mostowski, H Tosato, G Magrath, I Bhatia, K AF Gutierrez, MI Cherney, B Hussain, A Mostowski, H Tosato, G Magrath, I Bhatia, K TI Bax is frequently compromised in Burkitt's lymphomas with irreversible resistance to Fas-induced apoptosis SO CANCER RESEARCH LA English DT Article ID PROGRAMMED CELL-DEATH; B-CELLS; CD95 FAS/APO-1; C-MYC; DIFFERENTIAL EXPRESSION; MEDIATED APOPTOSIS; BCL-X; LYMPHOCYTES; LIGAND; LINES AB We have analyzed the Pas-mediated death pathway in a panel of ii Epstein-Barr virus (EBV)-negative and 10 EBV-positive Burkitt's lymphoma (BL) cell lines. We show that the increased expression of Fas in EBV-positive cell lines is mediated via LMP-1. Four of the 21 BL cell lines are readily responsive to Pas-mediated cell death signals. Of the remaining 17 cell lines, 10 can be sensitized by up-regulating Pas either via exogenous expression of LMP-I or via treatment with CD40L. These same cell lines can also be sensitized by treatment with cycloheximide (CHX), which, however, does not result in up-regulation of Pas. Neither up-regulation of Pas, nor treatment with CHX, restore Fas sensitivity in seven BL cell lines. Further analyses indicated that 5 of the 7 cell lines land none of the 14 responsive cell lines) were also compromised in the integrity/expression of the proapoptotic gene Bax. Thus, in most BL cell lines, the Fas pathway seems to be inhibited, although the mechanism of inhibition varies. The correlation between Bax mutation and irreversible (by CD40L or CHX) Pas resistance raises the possibility, for the first time, that Bas may play a critical function in Pas-mediated cell death in BL. C1 NCI, Pediat Oncol Branch, Lymphoma Biol Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. RP Bhatia, K (reprint author), NCI, Pediat Oncol Branch, Lymphoma Biol Sect, NIH, Bldg 10,Room 13N240,10 Ctr Dr,MSC 1928, Bethesda, MD 20892 USA. NR 48 TC 51 Z9 52 U1 0 U2 1 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 FEB 1 PY 1999 VL 59 IS 3 BP 696 EP 703 PG 8 WC Oncology SC Oncology GA 163EU UT WOS:000078390900033 PM 9973220 ER PT J AU Chen, T Aidoo, A Mittelstaedt, RA Casciano, DA Heflich, RH AF Chen, T Aidoo, A Mittelstaedt, RA Casciano, DA Heflich, RH TI Hprt mutant frequency and molecular analysis of Hprt mutations in Fischer 344 rats treated with thiotepa SO CARCINOGENESIS LA English DT Article ID ETHYL-N-NITROSOUREA; ACUTE NONLYMPHOCYTIC LEUKEMIA; CANCER CHEMOTHERAPEUTIC-AGENTS; BONE-MARROW TRANSPLANTATION; SISTER-CHROMATID EXCHANGES; CHINESE-HAMSTER CELLS; IN-VIVO MUTATION; N,N',N''-TRIETHYLENETHIOPHOSPHORAMIDE THIOTEPA; CHROMOSOMAL-ABERRATIONS; MASS-SPECTROMETRY AB Thiotepa is a bifunctional alkylating anticancer drug that is a rodent carcinogen and a suspected human carcinogen. In order to determine the sensitivity of mutant induction in the Hprt lymphocyte assay for detecting tumorigenic doses of thiotepa, Fischer 344 rats were treated for 4 weeks with thiotepa using a procedure adapted from a carcinogenesis protocol, At various times after beginning the treatment regimen, rats were killed and the lymphocyte Hprt assay was performed on splenic lymphocytes isolated from the animals. The 6-thioguanine-resistant T lymphocyte mutant frequency increased with time during the period of thiotepa exposure and declined slightly thereafter. Significant dose-dependent increases in mutant frequency were found using concentrations of thiotepa that eventually result in lymphoproliferative tumors. Hprt mRNA from mutant lymphocytes was reverse transcribed to cDNA, amplified by PCR and examined for mutations by DNA sequencing. This analysis indicated that the major type of point mutation was G:C-->T:A transversion and that 33% of the mutants contained simple or complex frameshifts, Also, a multiplex PCR performed on DNA from mutant clones that were expanded in vitro indicated that 34% of the clones had deletions in the Hprt gene. These results indicate that the induction of lymphocyte Hprt mutants is a sensitive biomarker for the carcinogenicity of thiotepa and that the types of mutations found in the lymphocyte Hprt gene reflect the kinds of DNA damage produced by thiotepa. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Heflich, RH (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM rheflich@nctr.fda.gov NR 74 TC 18 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1999 VL 20 IS 2 BP 269 EP 277 DI 10.1093/carcin/20.2.269 PG 9 WC Oncology SC Oncology GA 164DW UT WOS:000078448100013 PM 10069464 ER PT J AU Rodriguez, S Schmidl, M Luallen, T Welch, R Manley, C Miyamoto, Y Gordon, D Jones, J Salovaara, H McLaughlin, M AF Rodriguez, S Schmidl, M Luallen, T Welch, R Manley, C Miyamoto, Y Gordon, D Jones, J Salovaara, H McLaughlin, M TI A discussion with the panelists SO CEREAL FOODS WORLD LA English DT Editorial Material C1 Univ Ulster, No Ireland Ctr Diet & Hlth, Coleraine BT52 1SA, Londonderry, North Ireland. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CEREAL CHEMISTS PI ST PAUL PA 3340 PILOT KNOB RD, ST PAUL, MN 55121-2097 USA SN 0146-6283 J9 CEREAL FOOD WORLD JI Cereal Foods World PD FEB PY 1999 VL 44 IS 2 BP 103 EP 105 PG 3 WC Food Science & Technology SC Food Science & Technology GA 169KY UT WOS:000078748300010 ER PT J AU Chae, YH Ji, BY Lin, JM Fu, PP Cho, BP El-Bayoumy, K AF Chae, YH Ji, BY Lin, JM Fu, PP Cho, BP El-Bayoumy, K TI Nitroreduction of 4-nitropyrene is primarily responsible for DNA adduct formation in the mammary gland of female CD rats SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID SPRAGUE-DAWLEY RATS; ENVIRONMENTAL MUTAGEN 1-NITROPYRENE; CHEMICAL CARCINOGENESIS; CARBON-BLACK; A/J MICE; METABOLISM; 2-NITROPYRENE; IDENTIFICATION; INVITRO; TUMORIGENICITY AB We determined whether DNA adducts derived from 4-nitropyrene (4-NP) are formed via nitroreduction or ring oxidation. DNA adduct markers derived from both pathways were prepared and, consequently, were compared with those obtained in vivo in rats treated with 4-NP. Following in vitro reaction of 9,10-epoxy-9,10-dihydro-4-nitropyrene (4-NP-9,10-epoxide), an intermediate metabolite derived from ring oxidation of 4-NP, with calf thymus DNA (average level of binding in two determinations was 8.5 nmol/mg of DNA), DNA was enzymatically hydrolyzed to deoxyribonucleosides and the DNA hydrolysates were analyzed by HPLC. Electrospray mass and (1)H NMR spectra of the major products indicated that these adducts are deoxyguanosine (dG) derivatives that resulted from N(2)-dG substitution at the 9- or 10-position of the pyrene nucleus. However, these adducts were not detected in vivo in the rat mammary gland and liver following the administration of 4-NP. Nitroreduction of 4-NP catalyzed by xanthine oxidase in the presence of DNA resulted in three major putative DNA adducts (level of binding of 12.0 +/- 1.1 nmol/mg of DNA, n = 4) designated as peak 1 (46%), peak 2 (25%), and peak 3 (17%). Although peak 1 was further resolved into peaks la and Ib, both were unstable and gradually decomposed to peak 2, and the latter was unequivocally identified as pyrene-4,5-dione. On the basis of electrospray mass spectral analysis, peak 3 was tentatively identified as a deoxyinosine-derived 4-aminopyrene adduct. None of the adducts derived from nitroreduction of 4-NP catalyzed by xanthine oxidase coeluted with the synthetic standard N-(deoxyguanosin-8-yl)-4-aminopyrene prepared by reacting dG with N-acctoxy-4-aminopyrene. Nevertheless, HPLC analysis of the hydrolysates of liver and mammary DNA obtained from rats treated with [(3)H]-4-NP yielded four radioactive peaks, all of which coeluted with the markers derived from the nitroreduction pathway. These results indicate that nitroreduction is primarily responsible for DNA adduct formation in the liver and, especially, in the mammary gland which is the organ susceptible to carcinogenesis by this environmental agent. C1 Amer Hlth Fdn, Div Canc Etiol & Prevent, Valhalla, NY 10595 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Rhode Isl, Coll Pharm, Dept Biomed Sci, Kingston, RI 02881 USA. RP El-Bayoumy, K (reprint author), Amer Hlth Fdn, Div Canc Etiol & Prevent, 1 Dana Rd, Valhalla, NY 10595 USA. FU NCI NIH HHS [CA 35519] NR 45 TC 13 Z9 14 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD FEB PY 1999 VL 12 IS 2 BP 180 EP 186 DI 10.1021/tx9802318 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 168GW UT WOS:000078684300010 PM 10027796 ER PT J AU Averbuch, M Katzper, M Fang, C AF Averbuch, M Katzper, M Fang, C TI Baseline pain and response to medications in post surgery dental pain model. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, CDER, Div Analges Drugs, 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 1999 VL 65 IS 2 MA PI3 BP 118 EP 118 DI 10.1016/S0009-9236(99)80003-4 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169KR UT WOS:000078747600004 ER PT J AU Mehta, M Parmelee, T Balian, JD Lesko, L AF Mehta, M Parmelee, T Balian, JD Lesko, L TI Hepatic impairment (HI) studies submitted in new drug applications (NDAs). SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, CDER, Off Clin Pharm & 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 1999 VL 65 IS 2 MA PI47 BP 129 EP 129 DI 10.1016/S0009-9236(99)80047-2 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169KR UT WOS:000078747600048 ER PT J AU Sun, H Pelsor, F Lazor, J AF Sun, H Pelsor, F Lazor, J TI Limited sampling design in clinical pediatric population pharmacokinetic (PPK) studies. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, OCPB, Rockville, MD 20850 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 1999 VL 65 IS 2 MA PI94 BP 140 EP 140 DI 10.1016/S0009-9236(99)80094-0 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169KR UT WOS:000078747600095 ER PT J AU Spyker, DA Kroen, ML Gray, G Wang, Y Flynn, B AF Spyker, DA Kroen, ML Gray, G Wang, Y Flynn, B TI Confidence interval (CI) calculations for within-patient correlations - ECG p-wave detection. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, CDRH, Rockville, MD 20857 USA. CRMD, Sylmar, CA 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 1999 VL 65 IS 2 MA PII4 BP 148 EP 148 DI 10.1016/S0009-9236(99)80122-2 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169KR UT WOS:000078747600123 ER PT J AU Davit, B Cherstniakova, S Mojsiak, J Cantilena, L AF Davit, B Cherstniakova, S Mojsiak, J Cantilena, L TI In vitro inhibition of LAAM metabolism by HIV protease inhibitors. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, CDER, Rockville, MD 20857 USA. USUHS, Div Clin Pharmacol, Bethesda, MD USA. NIDA, NIH, Rockville, 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 1999 VL 65 IS 2 MA PII31 BP 154 EP 154 DI 10.1016/S0009-9236(99)80149-0 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169KR UT WOS:000078747600150 ER PT J AU LeCluyse, EL Sahi, J Sinz, M Woolf, T Hawke, R Hamilton, G Lesko, LJ Huang, SM AF LeCluyse, EL Sahi, J Sinz, M Woolf, T Hawke, R Hamilton, G Lesko, LJ Huang, SM TI Troglitazone induces CYP3A4 in cultured human hepatocytes. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. Warner Lambert Parke Davis, Parke Davis Pharmaceut Res, Ann Arbor, MI 48105 USA. US FDA, CDER, Off Clin Pharmacol & Biopharmaceut, 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 1999 VL 65 IS 2 MA PII40 BP 157 EP 157 DI 10.1016/S0009-9236(99)80158-1 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169KR UT WOS:000078747600159 ER PT J AU Al-Habet, S Baweja, R Mishina, E AF Al-Habet, S Baweja, R Mishina, E TI Utility of cholinesterase inhibition in the PK, PD, and BA studies of anti-cholinesterases (anti-AChE). SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Off Clin Pharmacol & Biopharmaceut, DPEI, 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 1999 VL 65 IS 2 MA PII89 BP 169 EP 169 DI 10.1016/S0009-9236(99)80207-0 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169KR UT WOS:000078747600208 ER PT J AU Parekh, A Barsamian, A Balian, JD Lesko, L AF Parekh, A Barsamian, A Balian, JD Lesko, L TI Clinical relevance and labeling of food-effect bioavailability (FEB) studies. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, CDER, Off Clin Pharm & Biopharm, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 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 1999 VL 65 IS 2 MA PII109 BP 174 EP 174 DI 10.1016/S0009-9236(99)80227-6 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169KR UT WOS:000078747600228 ER PT J AU Zhao, H Sun, H Chow, MSS AF Zhao, H Sun, H Chow, MSS TI Prediction of the effect of systemic acidosis (SA) on lidocaine (L) disposition kinetics in pigs using a physiologically based pharmacokinetic (PBPK) model. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Univ Connecticut, Storrs, CT USA. Hartford Hosp, Hartford, CT 06115 USA. US FDA, Rockville, MD 20857 USA. Chinese Univ, Hong Kong, Hong Kong. NR 0 TC 1 Z9 1 U1 2 U2 4 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 1999 VL 65 IS 2 MA PIII19 BP 181 EP 181 DI 10.1016/S0009-9236(99)80256-2 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169KR UT WOS:000078747600257 ER PT J AU Ibrahim, S Knapton, A Licht, T Aszalos, A AF Ibrahim, S Knapton, A Licht, T Aszalos, A TI Influence of antipsychotic, antiemetic, and antifungal drugs on the function of P-glycoprotein in Caco-2 cells. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, CDER, Rockville, MD 20857 USA. NCI, NIH, Bethesda, MD 20814 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 1999 VL 65 IS 2 MA PIII90 BP 199 EP 199 DI 10.1016/S0009-9236(99)80324-5 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169KR UT WOS:000078747600325 ER PT J AU Mazzotta, P Magee, LA AF Mazzotta, P Magee, LA TI Pharmacologic and non-pharmacologic management of nausea and vomiting of pregnancy; A systematic critical review of the safety and effectiveness of treatment. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, CDER, Rockville, MD 20857 USA. NCI, NIH, Bethesda, MD 20892 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 1999 VL 65 IS 2 MA PIII93 BP 199 EP 199 DI 10.1016/S0009-9236(99)80327-0 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169KR UT WOS:000078747600328 ER PT J AU Ibrahim, S Huang, S Gillespie, W Honig, P Malinowski, H Williams, R Lesko, L AF Ibrahim, S Huang, S Gillespie, W Honig, P Malinowski, H Williams, R Lesko, L TI Clinical pharmacology studies in patients with renal impairment (RI): Past experience and regulatory perspectives. 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 1999 VL 65 IS 2 MA PIII99 BP 201 EP 201 DI 10.1016/S0009-9236(99)80333-6 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169KR UT WOS:000078747600334 ER PT J AU Burns, DL AF Burns, DL TI Biochemistry of type IV secretion SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID COMPLEX TRANSPORT APPARATUS; PERTUSSIS TOXIN SECRETION; AGROBACTERIUM-TUMEFACIENS VIRB7; T-DNA TRANSFER; ESSENTIAL VIRULENCE PROTEIN; NUCLEOTIDE-BINDING SITE; BORDETELLA-PERTUSSIS; CONJUGAL TRANSFER; TRANSFER GENES; PLANT-CELLS AB In the past year, our knowledge of type IV transporters of Gram-negative bacteria has further expanded. Advances include the discovery of additional members of this family of proteins, increased knowledge of the morphologies of type IV transporters, and a better understanding of the mechanisms by which macromolecules are exported by these systems. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Burns, DL (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-434,Bldg 29,Room 418,8800 Rockville Pike, Bethesda, MD 20892 USA. EM burns@cber.fda.gov NR 53 TC 89 Z9 90 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD FEB PY 1999 VL 2 IS 1 BP 25 EP 29 DI 10.1016/S1369-5274(99)80004-6 PG 5 WC Microbiology SC Microbiology GA 166AC UT WOS:000078553200003 PM 10047550 ER PT J AU Tang, YM Chen, GF Thompson, PA Lin, DX Lang, NP Kadlubar, FK AF Tang, YM Chen, GF Thompson, PA Lin, DX Lang, NP Kadlubar, FK TI Development of an antipeptide antibody that binds to the C-terminal region of human CYP1B1 SO DRUG METABOLISM AND DISPOSITION LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the American-Association-for-Cancer-Research CY APR 12-16, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Canc Res ID CYTOCHROME-P450 CYP1B1; CULTURED-CELLS; MCF-7 CELLS; EXPRESSION; SEQUENCE; TUMORS; CDNA; 1B1; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; 4-HYDROXYLATION AB An antipeptide antibody was raised against a 14-mer synthetic peptide (CDFRANPNEPA KMN) corresponding to the amino acid sequence from 491 to 504 of human cytochrome P-450 (CYP)1B1. Rabbit-derived antisera demonstrated the ability to induce moderately high antibody titers (>1:10(5)) as judged by enzyme-linked immunosorbent assay. In Western blot analysis, the purified antibody recognized a single protein band (estimated as 56 kDa) in microsomes prepared from human and rodent tissues. No significant cross-reactivity to either human CYP1A1 or human CYP1A2 protein was detected. Titration studies using recombinant human CYP1B1 and an enhanced chemiluminescence-based detection method demonstrated a minimal detection sensitivity for this antiserum at about 0.34 ng/band in 8 x 7-cm minigels. The immunoprecipitation and immunoinhibition results indicate that this antisera recognizes the nondenatured human CYP1B1 protein but does not inhibit its enzyme activity. Using this antibody, CYP1B1 protein was detected in nine different human tissues and in cultured cells induced by various chemicals. This highly specific, highly sensitive antibody provides an important tool to study tissue distribution and cellular expression levels of CYP1B1, with negligible cross-reactivity from the other members of the CYP1 family. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Beijing Union Med Coll, Chinese Acad Med Sci, Inst Canc, Beijing, Peoples R China. RP Tang, YM (reprint author), Natl Ctr Toxicol Res, HFT-100,3900 NCTR Rd, Jefferson, AR 72079 USA. EM ytang@nctr.fda.gov NR 40 TC 40 Z9 40 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD FEB PY 1999 VL 27 IS 2 BP 274 EP 280 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 164TX UT WOS:000078480600019 PM 9929516 ER PT J AU Sheehan, DM Willingham, E Gaylor, D Bergeron, JM Crews, D AF Sheehan, DM Willingham, E Gaylor, D Bergeron, JM Crews, D TI No threshold dose for estradiol-induced sex reversal of turtle embryos: How little is too much? SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE biologically based dose-response model; development; endocrine disruptors; estrogens; risk assessment; safety testing; sex determination; sex reversal; threshold; turtle ID RISK ASSESSMENT; TEMPERATURE; EXPOSURE; MODELS; MICE AB Risk assessments for nongenotoxic chemicals assume a threshold below which no adverse outcomes are seen. However, when an endogenous chemical, such as 17 beta-estradiol (E-2), occurs at a concentration sufficient to cause an effect, the threshold is already exceeded. Under these circumstances, exogenous estradiol is not expected to provide a threshold dose. This principle is demonstrated for E-2 in the red-eared slider, a turtle with temperature-dependent sex determination. In this species, gonadal sex is determined by egg incubation temperature; female development requires endogenous estrogen produced by elevated temperature. While normal production of females by endogenous estrogens is not an adverse effect, exogenous estrogens can sex reverse presumptive males, which can be an adverse effect. A large dose-response study was conducted using seven doses and a vehicle control (starting n = 300/group); a single E-2 dose was applied to the eggshell of recently laid eggs. Animals were sexed after hatching. The incubation temperature chosen, 28.6 degrees C, generates a minority of females. Thus, the criteria for testing the threshold hypothesis were met, i.e., there is evidence that there is endogenous estrogen and that it generates an irreversible response. The lowest E-2 dose tested, 400 pg/egg (40 ng/kg), sex reversed 14.4% of the animals, demonstrating very low dose sensitivity. The data were fit with a modified Michaelis-Menten equation, which provided an estimate of 1.7 ng/egg for endogenous estradiol, The median effective dose (ED50) was 5.0 +/- 2.0 ng/egg (35% confidence limits), of which 1.7 ng/egg was endogenous estradiol and 3.3 ng/egg came from the applied estradiol. There was no apparent threshold dose for E-2. A smaller replication confirmed these results. These results provide a simple biologically based dose-response model and suggest that chemicals which act mechanistically like E-2 may also show no threshold dose. If so, even low environmental concentrations of such chemicals may carry risk for sex reversal. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Dev Toxicol, Jefferson, AR 72079 USA. Univ Texas, Dept Zool, Austin, TX 78712 USA. RP Sheehan, DM (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU NIMH NIH HHS [NIMH 00135] NR 31 TC 63 Z9 64 U1 1 U2 7 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 1999 VL 107 IS 2 BP 155 EP 159 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 170QA UT WOS:000078816500026 PM 9924012 ER PT J AU Ishii, KJ Weiss, WR Ichino, M Verthelyi, D Klinman, DM AF Ishii, KJ Weiss, WR Ichino, M Verthelyi, D Klinman, DM TI Activity and safety of DNA plasmids encoding IL-4 and IFN gamma SO GENE THERAPY LA English DT Article DE plasmid DNA; DNA vaccine; cytokines; gene therapy ID IMMUNE-RESPONSES; COSTIMULATORY MOLECULES; PLASMODIUM-YOELII; INTERFERON-GAMMA; IMMUNIZATION; VACCINES; PROTECTION; CYTOKINES; COINOCULATION; TUBERCULOSIS AB Cytokine-encoding DNA plasmids can act as 'genetic adjuvants: improving the immune response stimulated by co-administered DNA vaccines. We examined whether plasmids encoding the Th1 cytokine IFN gamma (pIFN gamma) or the Th2 cytokine IL-4 (pIL-4) have long-term effects on immune homeostasis when administered to adult mice, or alter immune maturation in neonates. Both plasmids boosted immunity against a co-administered vaccine, with pIFN gamma promoting the development of a Th1 response (characterized by the production of IgG2a antibodies), and pIL-4 preferentially stimulating a Th2 response (characterized by increased IgG1 antibody production). Both pIFN gamma and pIL-4 influenced the ratio of cells actively secreting Th1 versus Th2 cytokines, consistent with an effect on Th cell maturation. Interestingly, this effect persisted for only a few weeks and was not magnified by repeated plasmid administration. Cytokine-encoding plasmids had no long-term effect on the immune response of newborn or adult mice to subsequent antigenic stimulation, nor did they selectively induce the production of pathogenic anti-DNA autoantibodies. These results suggest cytokine-encoding plasmids may be safe as immune adjuvants. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Retroviral Immunol Sect, Bethesda, MD 20892 USA. USN, Med Res Inst, Malaria Program, Bethesda, MD 20889 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Retroviral Immunol Sect, Bethesda, MD 20892 USA. RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 33 TC 29 Z9 35 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD FEB PY 1999 VL 6 IS 2 BP 237 EP 244 DI 10.1038/sj.gt.3300799 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 167QQ UT WOS:000078645100012 PM 10435108 ER PT J AU Shayiq, RM Roberts, DW Rothstein, K Snawder, JE Benson, W Ma, X Black, M AF Shayiq, RM Roberts, DW Rothstein, K Snawder, JE Benson, W Ma, X Black, M TI Repeat exposure to incremental doses of acetaminophen provides protection against acetaminophen-induced lethality in mice: An explanation for high acetaminophen dosage in humans without hepatic injury SO HEPATOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; RAT-LIVER; 3-(CYSTEIN-S-YL)ACETAMINOPHEN ADDUCTS; TREATED MICE; HEPATOTOXICITY; PARACETAMOL; METABOLISM; HEPATOCYTES; PROTEIN; GLUTATHIONE AB In studies designed to simulate a clinical observation in which an individual became tolerant to normally lethal doses of acetaminophen (APAP), mice were pretreated with increasing doses of APAP for 8 days and challenged on day 9 with normally supralethal doses of APAP. These animals developed minimal hepatotoxicity after a challenge dose with a fourfold increase in LD50 to 1,350 mg/kg, The pretreatment regimen resulted in hepatic changes including: centrilobular localization of 3-(cysteine-S-yl)APAP protein adducts, selective down-regulation of cytochrome P4502E1 (CYP2E1) and CYP1A2 that produced the toxic metabolite, N-acetyl-p-benzoquinone imine, higher levels of reduced glutathione (GSH), centrilobular inflammation, and a fourfold increase in hepatocellular proliferation. The protection against the lethal APAP doses afforded by pretreatment is secondary to these changes and to the associated regional shift in the bioactivation of the APAP challenge dose from centrilobular to periportal regions where CYP2E1 is not found, protective GSH is more abundant, and where cell-proliferative responses are better able to sustain repair. This shift in APAP bioactivation results in less-intense covalent binding that is more diffuse and spread uniformly throughout the hepatic lobe, most likely contributing to protection by delaying the early onset of liver injury that has been generally associated with centrilobular localization of the adducts, Intervention of APAP pretreatment-induced cell division in mice with colchicine left them resistant to a 500-mg/kg (normally lethal) dose of APAP, but unable to survive a 1,000-mg/kg APAP challenge dose. The data demonstrate multiple mechanistic components to the protection afforded by APAP pretreatment, Whereas metabolic and physiological changes not dependent on cell proliferation are adequate to protect against 500 mg/kg APAP, these changes plus a potentiated cell-proliferative response are necessary for protection against the supralethal 1,000-mg/kg APAP dose. Furthermore, the data document an uncoupling of the traditional association between covalent binding and toxicity, and suggest that the assessment of toxicity following repeated or chronic APAP exposure must consider altered drug interactions and parameters besides those historically used to assess acute overdose. C1 Thomas Jefferson Univ, Div Clin Pharmacol, Philadelphia, PA 19107 USA. Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19122 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Shayiq, RM (reprint author), Thomas Jefferson Univ, Div Clin Pharmacol, Mail Code MOB-811,1100 Walnut St, Philadelphia, PA 19107 USA. NR 67 TC 70 Z9 72 U1 0 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 1999 VL 29 IS 2 BP 451 EP 463 DI 10.1002/hep.510290241 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 162FB UT WOS:000078333900019 PM 9918922 ER PT J AU Vazquez-Torres, A Jones-Carson, J Wagner, RD Warner, T Balish, E AF Vazquez-Torres, A Jones-Carson, J Wagner, RD Warner, T Balish, E TI Early resistance of interleukin-10 knockout mice to acute systemic candidiasis SO INFECTION AND IMMUNITY LA English DT Article ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; EXPERIMENTAL VAGINAL CANDIDIASIS; MURINE CANDIDIASIS; HOST-DEFENSE; SCID MICE; T-CELLS; ALBICANS; NEUTROPHILS; RESPONSES; MUCOSAL AB In contrast to immunocompetent controls, interleukin-10 (IL-10) knockout (KO) mice eliminated an experimental intravenous inoculation with Candida albicans from their kidneys. Improved clearance of C. albicans from the kidneys of IL-10 KO mice was evident at 24 h after intravenous challenge with the fungus. Conversely, mice with a deletion of the IL-4 cytokine gene were more susceptible to systemic candidiasis than were immunocompetent controls. The hyperresistance of IL-10 KO mice to acute systemic candidiasis did not seem to correlate with nitric oxide-mediated immunity, but rather, it appeared to be associated with more efficient effector function of innate cells, possibly neutrophils. In support of the latter hypothesis, we observed that neutrophils from IL-10 KO mice were more efficient at killing C. albicans blastoconidia and hyphae than were neutrophils from immunocompetent control mice. Neither IL-10 KO nor IL-4 KO mice that were monoassociated,vith C. albicans for 4 weeks showed any histologic evidence of systemic candidiasis of endogenous origin. In contrast to systemic candidiasis, we observed no significant (P < 0.05) differences in susceptibility among IL-10 KO, IL-4 KO, and wild-type (immunocompetent) mice to orogastric candidiasis. Our results suggest that IL-10 exerts a negative effect on the early, innate response to acute systemic candidiasis; however, in comparison to immunocompetent control (wild-type) mice, neither IL-10 nor IL-4 deficiency enhanced susceptibility to orogastric candidiasis. C1 Univ Wisconsin, Sch Med, Dept Surg, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Surg Pathol, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. Univ Colorado, Hlth Sci Ctr, Dept Infect Dis, Denver, CO 80262 USA. Natl Jewish Med & Res Ctr, Dept Med, Denver, CO 80220 USA. Natl Ctr Toxicol Res, Dept Microbiol, Jefferson, AR 72079 USA. RP Balish, E (reprint author), Univ Wisconsin, Sch Med, Dept Surg, 1300 Univ Ave,4638 MSC, Madison, WI 53706 USA. EM balish@surgery.wisc.edu NR 29 TC 60 Z9 66 U1 0 U2 2 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 FEB PY 1999 VL 67 IS 2 BP 670 EP 674 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 160VE UT WOS:000078251400029 PM 9916075 ER PT J AU Cook, DM Farizo, KM Burns, DL AF Cook, DM Farizo, KM Burns, DL TI Identification and characterization of PtlC, an essential component of the pertussis toxin secretion system SO INFECTION AND IMMUNITY LA English DT Article ID ISLET-ACTIVATING PROTEIN; ESSENTIAL VIRULENCE PROTEIN; BORDETELLA-PERTUSSIS; AGROBACTERIUM-TUMEFACIENS; SUBCELLULAR-LOCALIZATION; ADENYLATE-CYCLASE; ADP-RIBOSYLATION; MEMBRANE-PROTEIN; BINDING DOMAIN; DNA TRANSFER AB PtlC is a member of a set of proteins necessary for the secretion of pertussis toxin (PT) from Bordetella pertussis. Using polyclonal antibodies specific for PtlC, we identified PtlC as a protein with an apparent molecular weight of 85,000 that localizes to the membrane fraction of bacterial cell extracts. We found that a mutant strain of B. pa-tussis that contains an in-frame deletion in ptlC is unable to secrete PT and that PT secretion is fully restored by expressing ptlC in trans, indicating that PtlC is essential for transport of PT across the bacterial membrane(s). PT secretion was inhibited in wild-type B. pertussis after introduction of a plasmid expressing a mutant ptlC altered in the putative nucleotide-binding region, suggesting that this region of PtlC is essential for proper function. Moreover, the observed dominant negative phenotype suggests that PBC either functions as a multimer or interacts with some other component(s) necessary for secretion of PT. C1 US FDA, Ctr Biol Evaluat & Res, Lab Pertussis, Bethesda, MD 20892 USA. RP US FDA, Ctr Biol Evaluat & Res, Lab Pertussis, HFM-434,Bldg 39,Room 418,8800 Rockville Pike, Bethesda, MD 20892 USA. EM burns@cber.fda.gov NR 37 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 1999 VL 67 IS 2 BP 754 EP 759 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 160VE UT WOS:000078251400041 PM 9916087 ER PT J AU Khachik, F Steck, A Pfander, H AF Khachik, F Steck, A Pfander, H TI Isolation and structural elucidation of(13Z,13 ' Z,3R,3 ' R,6 ' R)-lutein from marigold flowers, kale, and human plasma SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Brassica oleracea (Acephala); carotenoid metabolites in plants; carotenoid oxidation products; HPLC mass spectrometry; Z/E Z(cis/trans)-isomers; marigold flowers; new serum/plasma carotenoids; NMR; Tagetes erecta (orangeade); UV-visible ID LIQUID-CHROMATOGRAPHY; DIETARY CAROTENOIDS; OXIDATION-PRODUCTS; GREEN VEGETABLES; IDENTIFICATION; LUTEIN; EXTRACTS; QUANTIFICATION; SEPARATION; CONSTITUENTS AB (13Z,13'Z,3R,3'R,6'R)-Lutein has been isolated and purified from extracts of marigold flowers, fresh raw kale (Brassica oleracea var. Acephala), and human plasma and fully characterized by H-1 and C-13 NMR, UV/vis, and MS. While the concentration of (13Z,13'Z)-lutein in kale and human plasma compared to (all-E,3R,3'R,6'R)-lutein was found to be quite low, this compound was readily isolated by fractional crystallization of lutein from marigold extracts. Thus, the mother liquors from two consecutive crystallizations of lutein from a saponified extract of marigold flowers were enriched in (13Z,13'Z)-lutein (8.7% of total carotenoids) and employed for the isolation of this compound by HPLC. The identity of the di-Z-lutein in kale and human plasma has been established by comparison of the HPLC-UV/vis-MS profiles of the purified compounds with those of a fully characterized sample, isolated from marigolds. 3-Hydroxy-beta,epsilon-caroten-3'-one and 3'-epilutein have also been identified in extracts from marigolds. C1 Univ Maryland, Joint Inst Food Safety & Appl Nutr, Dept Chem & Biochem, College Pk, MD 20742 USA. Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland. RP Khachik, F (reprint author), Univ Maryland, Joint Inst Food Safety & Appl Nutr, Dept Chem & Biochem, College Pk, MD 20742 USA. RI Khachik, Frederick/C-5055-2009 NR 23 TC 36 Z9 39 U1 2 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD FEB PY 1999 VL 47 IS 2 BP 455 EP 461 DI 10.1021/jf980823w PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 168NE UT WOS:000078698500017 PM 10563916 ER PT J AU Rosa, F AF Rosa, F TI Databases in the assessment of the effects of drugs during pregnancy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID GASTROSCHISIS AB There is limited information on the effects of marketed drugs in pregnant women, largely because premarketing studies are not conducted in this population unless the agent is intended for specific use during pregnancy. Current information on the use of available medications during pregnancy includes 3 types of data: (1) case reports, (2) case-control studies, and (3) cohort studies. Assessments of pregnancy risk related to medication use most commonly involve ease reports, and each year the Food and Drug Administration catalogs approximately 1000 suspected adverse drug experiences during pregnancy. The Food and Drug Administration, working with Michigan Medicaid, has developed a database of several hundred thousand pregnancy outcomes. Results of this study for asthma medications used between 1980 and 1992 are presented. However, interpretation of the results is complicated, and substantially more data are required, particularly as new medications become available. C1 US FDA, Div Drug Epidemiol & Surveillance, Rockville, MD 20857 USA. RP Rosa, F (reprint author), US FDA, Div Drug Epidemiol & Surveillance, Rockville, MD 20857 USA. NR 13 TC 9 Z9 10 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 FEB PY 1999 VL 103 IS 2 SU S BP S360 EP S361 DI 10.1016/S0091-6749(99)70264-2 PN 2 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 171KA UT WOS:000078861500008 PM 9949339 ER PT J AU Caron, A Menu, P Faivre-Fiorina, B Labrude, P Alayash, AI Vigneron, C AF Caron, A Menu, P Faivre-Fiorina, B Labrude, P Alayash, AI Vigneron, C TI Cardiovascular and hemorheological effects of three modified human hemoglobin solutions in hemodiluted rabbits SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE oxygen carriers; blood flow; hemodilution; viscosity ID CROSS-LINKED HEMOGLOBIN; ENDOTHELIUM-DEPENDENT RELAXATION; STRIATED SKIN MUSCLE; NITRIC-OXIDE; DCLHB(TM); RATS; PRESSURE; HAMSTER; RINGS AB The cardiovascular effects of human albumin (Alb) and three human hemoglobin (Hb) solutions, dextran-benzene-tetracarboxylate Hb, alpha alpha-crosslinked Hb, and o-raffinose-polymerized Hb were compared in anesthetized rabbits undergoing acute isovolemic hemodilution with Hct reduction from 41.4 +/- 2.7 to 28.8 +/- 1.6%. The impact of the vasoconstricting properties of Hb was examined by measuring heart rate (HR), mean arterial pressure (MAP), abdominal aortic, and femoral arterial blood flow, vascular resistance (VR), and aortic distension during the first 3 h after hemodilution. The impact of the hemorheological parameters was assessed by measurements of hemodiluted blood viscosity. In contrast to Alb, the Hb solutions elicited an immediate increase in MAP (20-38%). The effects of Alb and Hb solutions on HR, as well as on aortic and femoral arterial blood flow, were similar. VR decreased with Alb (20-28%) and increased with all three Hb solutions (30-90%), but the MAP and VR rising trends were different with each Hb solution. Aortic distension decreased in Hb groups compared with the Alb group for the first 60 min. The viscosity of hemodiluted blood was similar for all groups at high shear rates but was dependent on the viscosity of the solutions at low shear rates. We conclude that the vasoconstriction elicited by the Hb solutions overrides the vasodilation associated with viscosity changes due to hemodilution and would be the major factor responsible to the cardiovascular changes. C1 Univ Nancy 1, Sch Pharm, Dept Hematol & Physiol, F-54001 Nancy, France. US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Bethesda, MD 20892 USA. RP Caron, A (reprint author), Fac Pharm, Lab Hematol & Physiol, 5 Rue Albert Lebrun, F-54001 Nancy, France. RI FAIVRE , Beatrice/B-7535-2012 NR 28 TC 28 Z9 28 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD FEB PY 1999 VL 86 IS 2 BP 541 EP 548 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 191EQ UT WOS:000080009800017 PM 9931189 ER PT J AU Misbin, RI AF Misbin, RI TI Comment on the ethics of placebo-controlled trials in patients with type 2 diabetes mellitus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter C1 US FDA, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. RP Misbin, RI (reprint author), 5727 Crawford Dr, Rockville, MD 20851 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1999 VL 84 IS 2 BP 823 EP 823 DI 10.1210/jc.84.2.823 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 164KW UT WOS:000078464000080 PM 10022465 ER PT J AU Anderson, JM Langone, JJ AF Anderson, JM Langone, JJ TI Issues and perspectives on the biocompatibility and immunotoxicity evaluation of implanted controlled release systems SO JOURNAL OF CONTROLLED RELEASE LA English DT Article; Proceedings Paper CT 25th International Symposium on Controlled Release of Bioactive Materials CY JUN 22, 1998 CL LAS VAGAS, NEVADA DE controlled release; biocompatibility; immunotoxicity ID MICROSPHERES AB Over the past decade, significant advances and discoveries in cell and molecular biology and biomaterials have provided a foundation for the research and development of new, complex controlled release systems. Many of these new controlled release systems utilize active biological components, i.e., proteins and cells, to achieve their intended therapeutic goal. Utilization of bioactive biological materials in implantable controlled release systems has prompted a broad as well as an in-depth interest in the safety and efficacy of these systems. This short review is intended to provide individuals with a perspective on standards and guidance documents which specifically address biological and immunotoxicity response evaluation for safety of controlled release systems from a regulatory point of view. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Anderson, JM (reprint author), Case Western Reserve Univ, Inst Pathol, 2085 Adelbert Rd, Cleveland, OH 44106 USA. NR 20 TC 91 Z9 95 U1 1 U2 12 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 FEB 1 PY 1999 VL 57 IS 2 BP 107 EP 113 DI 10.1016/S0168-3659(98)00178-3 PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 164GY UT WOS:000078456000001 PM 9971889 ER PT J AU Forng, RY Atreya, CD AF Forng, RY Atreya, CD TI Mutations in the retinoblastoma protein-binding LXCXE motif of rubella virus putative replicase affect virus replication SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID NONSTRUCTURAL PROTEINS; GENE-PRODUCT; IDENTIFICATION; INFECTION; CYCLINS; CELLS; DIFFERENTIATION; PHOSPHORYLATION; GROWTH AB The rubella virus (RV)-encoded protein NSP90, which contains the retinoblastoma protein (Rb)binding motif LXCXE, interacts with Rb and RV replication is reduced in cells lacking Rb. Whether the LXCXE motif of RV NSP90 itself is essential for Rb binding and virus replication is not known. Therefore, in the present study, the functional role of this motif was investigated by site-directed mutagenesis in a plasmid from which infectious RV RNA can be produced, Three critical mutations in the motif, two substitutions at the conserved cysteine residue (C --> G and C --> R) and a deletion of the entire motif, were created. A cell-free translated NSP90 C terminus polypeptide containing the deletion did not bind to Rb and a polypeptide carrying the C --> R substitution had barely detectable binding affinity for Rb, Rb binding by the C --> G mutant was reduced significantly compared to that of wild-type protein, Correlating with the binding results, mutant viruses containing the LXRXE and LXGXE motifs had a reduction in replication to < 0.5% and 47% of the wild-type, respectively, while deletion of the motif was found to be lethal. By the first serial passage, replication of the LXRXE-carrying virus had increased from < 0.5% to 2% of the wildtype, Sequencing of the genome of this virus revealed a nucleotide change that altered the motif from LXRXE to LXSXE, which is a known Rb-binding motif in two protein phosphatase subunits, Thus, our results clearly demonstrate that the LXCXE motif is required for efficient RV replication. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, HFM-460,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Atreya@CBER.FDA.GOV NR 24 TC 19 Z9 20 U1 1 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD FEB PY 1999 VL 80 BP 327 EP 332 PN 2 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 168MM UT WOS:000078696800007 PM 10073691 ER PT J AU Ambrosone, CB Coles, BF Freudenheim, JL Shields, PG AF Ambrosone, CB Coles, BF Freudenheim, JL Shields, PG TI Glutathione-S-transferase (GSTM1) genetic polymorphisms do not affect human breast cancer risk, regardless of dietary antioxidants SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Assembly and Physiology of Apolipoprotein B-Containing Lipoproteins - Its Not Just for Heart Disease Anymore, as part of Experimental Biology 98 CY APR 18-22, 1998 CL SAN FRNACISCO, CALIFORNIA SP Amer Soc Nutr Sci, Energy & Macronutrient Res Interest Sect, Egg Nutr Ctr, Amer Heart Assoc, W States Affiliate, Merck Res Labs, Bristol Meyers Squibb Pharmaceut Res Inst, Parke Davis Pharmaceut Res DE breast neoplasms; epidemiology/molecular; glutathione-S-transferase; oxidative stress; antioxidants ID NEW-YORK; SUSCEPTIBILITY; EPIDEMIOLOGY; FAMILY AB Glutathione-S-transferases catalyze the detoxication of carcinogen metabolites and reactive oxygen species (ROS) produced through a number of mechanisms. Glutathione-S-transferase (GST) M1 is polymorphic, and the null allele results in a lack of enzyme activity. Because there are indications that ROS may be involved in breast carcinogenesis, we sought to determine whether the GSTM1 null allele was associated with increased breast cancer, particularly among women with tower consumption of dietary sources of alpha-tocopherol, carotenoids and ascorbic acid. in a study of diet and cancer in western New York, women with primary, incident, histologically confirmed breast cancer (n = 740) and community controls (n = 810) were interviewed and an extensive food-frequency questionnaire administered. A subset of these women provided a blood specimen. DNA was extracted and genotyping performed for GSTM1. Data were available for 279 cases and 340 controls. The null allele did not increase breast cancer risk, regardless of menopausal status. There were also no differences in associations between the polymorphism and risk among lower and higher consumers of dietary sources of antioxidants or smokers and nonsmokers. These results indicate that GSTM1 genetic polymorphisms are not associated with breast cancer risk, even in an environment low in antioxidant defenses. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Ambrosone, CB (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. FU NCI NIH HHS [CA/ES62995, CA11535, CA01633] NR 23 TC 29 Z9 31 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 1999 VL 129 IS 2 SU S BP 565S EP 568S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 167YP UT WOS:000078662900028 PM 10064333 ER PT J AU Gilkeson, G Cannon, C Oates, J Reilly, C Goldman, D Petri, M AF Gilkeson, G Cannon, C Oates, J Reilly, C Goldman, D Petri, M TI Correlation of serum measures of nitric oxide production with lupus disease activity SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE lupus; nitric oxide; disease activity; glomerulonephritis ID SYNTHASE; CELLS; EXPRESSION; MICE; GLOMERULONEPHRITIS; INFLAMMATION; MODULATION; ARTHRITIS; TYPE-2 AB Objective, To determine whether serum measures of nitric oxide production correlate with disease activity in patients with systemic lupus erythematosus (SLE). Methods. We assayed the levels of serum nitrate/nitrite from 26 patients with SLE followed for 1-3 years and nitrotyrosine levels in sera from 28 additional patients with SLE; sera from 19 controls were tested in both assays. Lupus disease activity was determined via the physician's global assessment, the Lupus activity Index, and the SLE Disease Activity Index (SLEDAI) at the time of serum collection for the initial set of 26 patients, Statistical correlations were determined using the Wilcoxon rank sum method and one-way ANOVA testing. Results. Serum levels of nitrate/nitrite were significantly higher in 26 patients with SLE compared to 19 controls (SLE, mean 29.5 mu M/ml. range 1-438; controls, mean 9.6 mu M/ml. range 0-51; p = 0.0004). Overall, there was a significant correlation between serum nitrate/nitrite: levels and SLEDAI scores (p = 0.0065). Renal variables within the SLEDAI had the highest correlation with serum nitrate/nitrite (p = 0.0028). Serum nitrotyrosine levels were also significantly higher in patients with SLE versus controls (p = 0.007) and in active SLE versus those with inactive SLE (p = 0.008). Conclusion. Serum nitrate/nitrite levels correlated with SLE disease activity, especially nephritis, in the majority of patients studied. Serum nitrotyrosine levels also differentiated controls from patients with lupus and patients with active from those with inactive disease. Due to the ease and low cost of these assays, serum measures of nitric oxide production appear a potentially useful adjunctive laboratory measure of disease activity in SLE and further implicate nitric oxide as an important mediator of disease in SLE. C1 Ralph H Johnson VAMC, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. US FDA, Bethesda, MD 20014 USA. Johns Hopkins Sch Med, Baltimore, MD USA. RP Gilkeson, G (reprint author), 912 CSB,MUSC,171 Ashley Ave, Charleston, SC 29425 USA. EM gilkeson@musc.edu NR 20 TC 64 Z9 69 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD FEB PY 1999 VL 26 IS 2 BP 318 EP 324 PG 7 WC Rheumatology SC Rheumatology GA 162CJ UT WOS:000078327600015 PM 9972965 ER PT J AU Harris, GR Gammell, PM AF Harris, GR Gammell, PM TI Sensitivity measurements of piezoelectric polymer hydrophones from 0.2-2 MHz using a broadband-pulse technique SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID FREQUENCY-RESPONSE; FIELD; DISK AB It is widely recognized that the sensitivity of hydrophones used to measure medical diagnostic ultrasound fields should be uniform over several octaves above the center frequency (i.e., above the mean of the upper and lower -3 dB frequencies in the transmitted acoustic-pressure spectrum). However. a bandwidth extending to at least ten times below the diagnostic pulse-center frequency is needed for accurate (error approximate to 5%) measurement of the peak rarefactional pressure. Since at present it is not common for manufacturers of medical-use hydrophones to provide sensitivity information below 1-2 MHz, a study was undertaken to determine these low-frequency sensitivities. The technique uses broadband, plane-wave pressure pulses generated by electrical short-pulse excitation of a thick piezoelectric ceramic disk. The hydrophone response is calculated from measurements of the source transducer and hydrophone-voltage waveforms. The frequency responses of both needle-type and spot-poled membrane polymer hydrophones were measured using this technique. The spot-poled membrane hydrophones had -3-dB bandwidths extending below 0.2 MHz, the lower limit for the calibration technique. The needle-type hydrophones studied, however, all exhibited a response roll-off of greater than 3 dB in the frequency range studied. Therefore, given the above bandwidth criterion as a function of diagnostic pulse-center frequency, the sensitivity to at least 0.2 MHz should be established for diagnostic-use hydrophones, because a uniform response below I MHz cannot be assumed. [S0001-4966(99)01002-4]. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Harris, GR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 14 TC 25 Z9 25 U1 0 U2 3 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD FEB PY 1999 VL 105 IS 2 BP 725 EP 731 DI 10.1121/1.426263 PN 1 PG 7 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 161KL UT WOS:000078287800015 ER PT J AU Pritchard, WF Abel, DB Karanian, JW AF Pritchard, WF Abel, DB Karanian, JW TI The US Food and Drug Administration investigational device exemptions and clinical investigation of cardiovascular devices: Information for the investigator SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE Food and Drug Administration; investigational device exemption ID MEDICAL DEVICES AB The conduct of a clinical investigation of a medical device to determine the safety and effectiveness of the device is covered by the investigational device exemptions (IDE) regulation. The purpose of IDE regulation is "to encourage, to the extent consistent with the protection of public health and safety and with ethical standards, the discovery and development of useful devices intended for human use, and to that end to maintain optimum freedom for scientific investigators in their pursuit of this purpose." Conducting a clinical investigation may require an approved IDE application. The US Food and Drug Administration encourages early interaction with the agency through the pre-IDE approval process during the development of a device or technology and during the preparation of an IDE application. This facilitates approval of the IDE application and progression into the clinical investigation. This paper reviews the terminology and applicability of the IDE regulation and the type of study that requires an IDE application to the Food and Drug Administration. The pre-IDE approval process and the development of an IDE application for a significant risk study of a cardiovascular device are discussed. C1 US FDA, Ctr Devices & Radiol Hlth, Hydrodynam & Acoust Branch, Div Phys Sci,Off Sci & Technol, Rockville, MD 20850 USA. US FDA, Ctr Devices & Radiol Hlth, Circulatory Support & Prosthet Grp, Div Cardiovasc Resp & Neurol Devices,Off Dev Eval, Rockville, MD 20850 USA. RP Pritchard, WF (reprint author), US FDA, Ctr Devices & Radiol Hlth, Hydrodynam & Acoust Branch, Div Phys Sci,Off Sci & Technol, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 5 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 1999 VL 10 IS 2 BP 115 EP 122 DI 10.1016/S1051-0443(99)70452-5 PN 1 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 177XC UT WOS:000079235500001 PM 10082096 ER PT J AU Nakashima, Y Nakashima, O Hsia, CC Kojiro, M Tabor, E AF Nakashima, Y Nakashima, O Hsia, CC Kojiro, M Tabor, E TI Vascularization of small hepatocellular carcinomas: correlation with differentiation SO LIVER LA English DT Article DE angiogenesis; arteriole; hepatocellular carcinoma; portal tract; vascularization ID ADENOMATOUS HYPERPLASIA; ANGIOGRAPHY; PROGRESSION; MICROBUBBLES; PATHOLOGY; FEATURES; LIVER; CT AB Background: Hepatocellular carcinoma (HCC) is generally considered a hypervascular tumor when visualized by angiography. However, small HCCs are not always found to be hypervascular. Methods: To evaluate this, 50 HCCs less than or equal to 3 cm in diameter were studied. The 50 tumors consisted of 16 well-differentiated HCCs, 25 moderately differentiated HCCs, and 9 that were each a mixture of well- and moderately differentiated HCC. Results: The mean number of portal tracts in the well-differentiated HCCs was 34% of the number in the surrounding nontumorous liver, and few intratumoral arterioles were seen. In contrast, the mean number of portal tracts in the moderately differentiated HCCs was 0.6% of the number in the surrounding nontumorous liver, and abundant intratumoral arterioles were seen. For HCCs that contained both well-differentiated and moderately differentiated tumor, the distribution of portal tracts and intratumoral arterioles in each portion was similar to that seen in well-differentiated or moderately differentiated HCC alone, respectively. HCCs that were larger than 1.5 cm in diameter had fewer portal tracts and more intratumoral arterioles than HCCs whose diameters were less than or equal to 1.5 cm. Conclusions: As small HCCs increase in size and become increasingly dedifferentiated, the number of portal tracts apparently decreases and intratumoral arterioles develop. These findings may reflect changes in the hemodynamics as the HCC develops. C1 US FDA, CBER HFM 310, 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, CBER HFM 310, Div Transfus Transmitted Dis, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 27 TC 91 Z9 98 U1 0 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0106-9543 J9 LIVER JI Liver PD FEB PY 1999 VL 19 IS 1 BP 12 EP 18 DI 10.1111/j.1478-3231.1999.tb00003.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 158FC UT WOS:000078104500003 PM 9928760 ER PT J AU McBean, AM Turner, CF Fitterman, LK Pate, K Reilly, T Smith, TK Trontell, A Witt, MB Penberthy, L Lessler, JT Forsyth, BH Wheeless, S Mierzwa, F Miller, HG AF McBean, AM Turner, CF Fitterman, LK Pate, K Reilly, T Smith, TK Trontell, A Witt, MB Penberthy, L Lessler, JT Forsyth, BH Wheeless, S Mierzwa, F Miller, HG TI Monitoring the health status and impact of treatment on Americans - The medicare beneficiary health status registry SO MEDICAL CARE LA English DT Article DE survey measurement; elderly population; Medicare; monitoring systems; health status ID INSTRUMENTAL ACTIVITIES; CAGE QUESTIONNAIRE; ALCOHOLISM; VALIDATION AB OBJECTIVE. A major new survey program, the Medicare Beneficiary Health Status Registry (MBHSR), has been proposed to improve the monitoring of the health status of Medicare beneficiaries. The MBHSR would collect data by mail with telephone follow up of nonrespondents to permit economical assessment of a total Registry of approximately 200,000 Medicare beneficiaries, approximately 54,000 of whom would be surveyed in any given year. (Surveys would be conducted of samples of new enrollees who would be reinterviewed every five years.) METHOD. TO assess the feasibility of that approach, a field test was conducted with a probability sample (n = 1,922) that comprised approximately equal numbers of new Medicare enrollees (aged, 65) and current beneficiaries (age range, 76-80). The field test was designed to assess the quality of the data that this design would produce. FINDINGS. Results indicate that the proposed design of the MBHSR could achieve response rates of approximately 80% among both age cohorts using a survey instrument that took 30 minutes to complete. Internal reliability of Activities of Daily Living, Instrumental Activities of Daily Living, Mobility, Mental Health Index, General Health, and Prostate Symptomatology scales ranged from 0.77 to 0.93. When measurements were repeated approximately 30 days after the initial survey, moderate to high levels of cross temporal correlation (range, 0.64-0.96) were found for most indexes, with the exception of prostate symptomatology. In addition, an earlier comparison of survey responses in the MBHSR field test to Medicare payment records indicated that the MBHSR field test obtained highly accurate reports of most of the major surgeries that were recorded in Medicare claims files. CONCLUSION. The design proposed for the MBHSR is feasible. If implemented, it should produce acceptably high rates of response and data quality. C1 Res Triangle Inst, Program Hlth & Behav Measurement, Washington, DC 20036 USA. Univ Minnesota, Sch Publ Hlth, Dept Hlth Management & Policy, Minneapolis, MN USA. Hlth Care Financing Adm, Baltimore, MD USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Westat, Rockville, MD USA. US FDA, Rockville, MD 20857 USA. Merck & Co Inc, Outcomes Res & Management, W Point, PA USA. RP Turner, CF (reprint author), Res Triangle Inst, Program Hlth & Behav Measurement, 1615 M St NW, Washington, DC 20036 USA. EM cft@rti.org FU PHS HHS [500-90-0053] NR 26 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 1999 VL 37 IS 2 BP 189 EP 203 DI 10.1097/00005650-199902000-00009 PG 15 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 165JK UT WOS:000078517500009 PM 10024123 ER PT J AU Wang, RF Campbell, WL Cao, WW Colvert, RM Holland, MA Cerniglia, CE AF Wang, RF Campbell, WL Cao, WW Colvert, RM Holland, MA Cerniglia, CE TI Diagnosis of mouse hepatitis virus contamination in mouse population by using nude mice and RT-PCR SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE mouse hepatitis virus; RT-PCR; diagnosis ID POLYMERASE CHAIN-REACTION; INFECTION AB Mouse hepatitis virus (MHV) infection in laboratory mouse populations is a serious problem, because the MHV infections are known to interfere with research results. Confirmation of indirect serological detection methods by viral isolation is difficult. Reverse transcription plus polymerase chain reaction (RT-PCR) was used to test 94 mouse tissue samples from suspected naturally MHV infected mice. Positive results were only obtained from two Colon samples and one mixed sample with colon and liver. The low positive rate is probably due to the virus being rapidly cleared by the MHV antibodies produced in the mouse. However, RT-PCR detection of MHV in nude mice placed in the same cages with other non-nude mice or placed in cages with used dirty bedding, showed a very high positive rate: 10 out of 12 colon samples were positive (83%), and 5 out of 10 faecal samples were positive (50%). A single-tube, single step RT-PCR method and two procedures for isolation of the viral RNA for the RT-PCR assay were also included in this article. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wang, RF (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 11 TC 8 Z9 9 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD FEB PY 1999 VL 13 IS 1 BP 29 EP 33 DI 10.1006/mcpr.1998.0211 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 168UU UT WOS:000078712200004 PM 10024430 ER PT J AU Slater, JE Paupore, EJ O'Hehir, RE AF Slater, JE Paupore, EJ O'Hehir, RE TI Murine B-cell and T-cell epitopes of the allergen Hev b 5 from natural rubber latex SO MOLECULAR IMMUNOLOGY LA English DT Article DE latex; Hev b 5; epitope; mouse; T-cell; B-cell; immunotherapy ID IN-VIVO; DENDRITIC CELLS; IMMUNIZATION; HEV-B-5; INHIBITION; INDUCTION; CLONING AB Hev b 5, a proline-rich acidic protein with a predominantly random secondary structure, is a major allergen in natural rubber latex and a candidate for specific immunotherapy of latex allergy. As a first step in the identification of candidate peptides for immunotherapy, we have begun to identify the B-cell and T-cell epitopes of Hrv b 5 in BALB/c mice. The mice were immunized with a Hev b 5 fusion protein. The B-cell epitopes were determined by the SPOTS method using overlapping octamers or by ELISA inhibition using a series of overlapping 20-mers. The T-cell epitopes were determined by the proliferation and cytokine release of splenocytes cultured in the presence of the 20-mers. Potential antibody binding regions included residues in regions 1-38, 55-74, 109-128 and 132-151. Examination of the binding sequences for common motifs suggested enhanced antibody binding to the KXEE or KEXE sequences, where X is empty, threonine or alanine. Splenocyte stimulation and cytokine release suggest T-cell epitopes with the regions 1-20, 37-56, 73-101 and 109-146, Since they may contain major T-cell epitopes but do not exhibit significant antibody binding, peptide regions 38-48 and 75-101 are candidates for specific immunotherapy to Hev b 5 in the BALB/c mouse model. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC 20010 USA. Alfred Hosp, Dept Allergy Asthma & Clin Immunol, Prahran, Vic 3181, Australia. Monash Univ, Prahran, Vic 3181, Australia. RP Slater, JE (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Immunobiochem, HFM-422,1401 Rockville Pike, Rockville, MD 20852 USA. RI O'Hehir, Robyn/H-3627-2011 OI O'Hehir, Robyn/0000-0002-3489-7595 NR 18 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD FEB PY 1999 VL 36 IS 2 BP 135 EP 143 DI 10.1016/S0161-5890(99)00021-8 PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 201BX UT WOS:000080575700006 PM 10378685 ER PT J AU Jacobson, ED Shein, MJ AF Jacobson, ED Shein, MJ TI Untitled SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Letter C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Jacobson, ED (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD FEB PY 1999 VL 22 IS 2 BP 400 EP 401 DI 10.1111/j.1540-8159.1999.tb00462.x PG 2 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 171WM UT WOS:000078887200029 PM 10087563 ER PT J AU Kaus, LC Gillespie, WR Hussain, AS Amidon, GL AF Kaus, LC Gillespie, WR Hussain, AS Amidon, GL TI The effect of in vivo dissolution, gastric emptying rate, and intestinal transit time on the peak concentration and area-under-the-curve of drugs with different gastrointestinal permeabilities SO PHARMACEUTICAL RESEARCH LA English DT Article DE biopharmaceutic classification system; peak concentration; permeability ID IN-VITRO; ABSORPTION; BIOAVAILABILITY; HUMANS; MODEL AB Purpose. To theoretically investigate the impact of gastric emptying half-time, intestinal transit time and the time for 85% in vivo dissolution on the peak concentration and area-under-the curve of model drugs. Methods. Simulations were performed using mathematical models of gastrointestinal physiology and pharmacokinetics of model drugs with different,gastrointestinal permeability. They were used to investigate the effect of different permutations of gastric emptying times, intestinal transit times, dissolution rates and effective permeabilities on the maximum plasma drug concentration and the area-under-the-curve of immediate release tablets relative to an oral solution (i.e,, Cmax(tablet)/ Cmax(solution) and AUC(tablet)/AUC(solution)). Results. The higher the permeability of the drug, the more sensitive the Cmax ratio is to dissolution rate and gastric emptying rate. As the intestinal transit time becomes more rapid, the sensitivity to T85% dissolution time and gastric emptying half-time increases. There is less dependence for the AUC ratio on the gastric emptying time and dissolution rate. Conclusions. Under the assumptions of the models, the criterion of 85% dissolution in 15 minutes (T85%) for classifying a rapidly dissolving drug product is relatively conservative since the Cmax ratio exceeded 0.8 for a T85% dissolution time of one hour and a gastric emptying half-time faster than 0.2 hour over a wide range of permeabilities. C1 GloboMax LLC, Hanover, MD 21076 USA. US FDA, CDER, OTR, Rockville, MD 20857 USA. Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. RP Gillespie, WR (reprint author), GloboMax LLC, 7250 Pkwy Dr,Suite 430, Hanover, MD 21076 USA. NR 13 TC 31 Z9 33 U1 0 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD FEB PY 1999 VL 16 IS 2 BP 272 EP 280 DI 10.1023/A:1018836727001 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 176HL UT WOS:000079145600016 PM 10100314 ER PT J AU Merrill, RM Kessler, LG Udler, JM Rasband, GC Feuer, EJ AF Merrill, RM Kessler, LG Udler, JM Rasband, GC Feuer, EJ TI Comparison of risk estimates for selected diseases and causes of death SO PREVENTIVE MEDICINE LA English DT Article DE disease incidence; disease mortality; lifetime risk; age-conditional risk; life table ID ACUTE MYOCARDIAL-INFARCTION; PROSTATE-CANCER INCIDENCE; DEVELOPING BREAST-CANCER; CORONARY HEART-DISEASE; DIABETES-MELLITUS; UNITED-STATES; ALZHEIMERS-DISEASE; PHYSICAL-ACTIVITY; STROKE INCIDENCE; MORTALITY-RATES AB Background. Lifetime risk estimates of disease are limited by long-term data extrapolations and are less relevant to individuals who have already lived a period of time without the disease, but are approaching the age at which the disease risk becomes common. In contrast, short-term age-conditional risk estimates, such as the risk of developing a disease in the next 10 years among those alive and free of the disease at a given age, are less restricted by long-term extrapolation of current rates and can present patients with risk information tailored to their age. This study focuses on short-term age-conditional risk estimates for a broad set of important chronic diseases and nondisease causes of death among white and black men and women. Methods. The Feuer et al. (1993, Journal of the National Cancer Institute) [15] method was applied to data from a variety of sources to obtain risk estimates for select cancers, myocardial infarction, diabetes mellitus, multiple sclerosis, Alzheimer's, and death from motor vehicle accidents, homicide or legal intervention, and suicide. Results. Acute deaths from suicide, homicide or legal intervention, and fatal motor vehicle accidents dominate the risk picture for persons in their 20s, with only diabetes mellitus and end-stage renal disease therapy (for blacks only) having similar levels of risk in this age range. Late in life, cancer, acute myocardial infarction, Alzheimer's, and stroke become most common. The chronic diseases affecting the population later in life present the most likely diseases someone will face. Several interesting differences in disease and death risks were derived and reported among age specific race and gender subgroups of the population. Conclusion, Presentation of risk estimates for a broad set of chronic diseases and nondisease causes of death within short-term age ranges among population subgroups provides tailored information that may lead to better educated prevention, screening, and control behaviors and more efficient allocation of health resources. (C) 1999 American Health Foundation and Academic Press. C1 NCI, Div Canc Control & Populat Sci, Can Control Res Program, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20850 USA. RP Merrill, RM (reprint author), Brigham Young Univ, Dept Hlth Sci, 229-L RB, Provo, UT 84602 USA. NR 93 TC 25 Z9 27 U1 3 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD FEB PY 1999 VL 28 IS 2 BP 179 EP 193 DI 10.1006/pmed.1998.0399 PG 15 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 165EC UT WOS:000078506100010 PM 10048110 ER PT J AU Bandyopadhyay, PK Russell, GW Chakrabarti, K AF Bandyopadhyay, PK Russell, GW Chakrabarti, K TI Optically stimulated luminescence in KCl : Cu x-irradiated at room temperature SO RADIATION MEASUREMENTS LA English DT Article ID SINGLE-CRYSTALS; NACL-CU; F-CENTERS; MECHANISM; IONS; LICL AB Optically stimulated luminescence (OSL) has been observed in single crystals of KCI:Cu x-irradiated at room temperature. It is shown that electrons are liberated from anion sites during the OSL process. The OSL predominantly involves emission due to radiative transition (d<->s) of monovalent copper ions present in the lattice. The OSL emission shows a strong temperature dependence indicating a thermally assisted process. Electron-hole recombination followed by energy transfer to the Cu activator is suggested as a possible OSL mechanism in KCI:Cu. Preliminary results of OSL in KBr:Cu are also presented. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Hendrix Coll, Dept Phys, Minneapolis, AR 72032 USA. US FDA, Div Mammog Qual & Radiat Programs, Rockville, MD 20850 USA. RP Bandyopadhyay, PK (reprint author), Hendrix Coll, Dept Phys, 1600 Washington Ave, Minneapolis, AR 72032 USA. NR 28 TC 16 Z9 16 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-4487 J9 RADIAT MEAS JI Radiat. Meas. PD FEB PY 1999 VL 30 IS 1 BP 51 EP 57 DI 10.1016/S1350-4487(98)00091-2 PG 7 WC Nuclear Science & Technology SC Nuclear Science & Technology GA 180RN UT WOS:000079399100007 ER PT J AU Suleiman, OH Spelic, DC McCrohan, JL Symonds, GR Houn, F AF Suleiman, OH Spelic, DC McCrohan, JL Symonds, GR Houn, F TI Mammography in the 1990s: The United States and Canada SO RADIOLOGY LA English DT Article DE breast, radiography, quality assurance; quality assurance ID FILM DENSITY; CANCERS AB PURPOSE: To evaluate trends in mammography quality before and after the implementation of the Mammography Quality Standards Act (MQSA) of 1992 and to compare technical data collected in the United States with corresponding data obtained from the first survey of mammography facilities conducted in 1994-1995 in Canada. MATERIALS AND METHODS: Data from MQSA inspections conducted in 1997 were analyzed and compared with survey data on U.S. mammography facilities acquired before the MQSA. Technical indicators of mammography quality such as radiation dose, phantom image score, film processing, and darkroom fog were Ed. RESULTS: In the United States phantom image scores, along with other technical measures of performance such as film processing, darkroom fog, and x-ray beam quality, have improved continuously since 1985. The U.S. mean glandular dose has increased to 1.6 mGy compared with the Canadian dose of 1.1 mGy. The mean total phantom image score with artifact substraction was 11.1 in Canada in 1994-1995 and 11.8 in the U.S. in 1997. CONCLUSION: Mammography quality is better today than it has been at any other time in the United States. With the exception of radiation dose, Canadian technical measures of performance are comparable to measures before MQSA in the United States. C1 US FDA, Ctr Devices & Radiol Hlth, Div Mammog Qual & Radiat Programs, Rockville, MD 20850 USA. Hlth Canada, Radiat Protect Bur, Consumer & Clin Radiat Hazards Div, Ottawa, ON K1A 0L2, Canada. RP Suleiman, OH (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Mammog Qual & Radiat Programs, HFZ-240,1350 Piccard Dr, Rockville, MD 20850 USA. NR 16 TC 42 Z9 43 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1999 VL 210 IS 2 BP 345 EP 351 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 161FE UT WOS:000078277900008 PM 10207413 ER PT J AU Valodia, P Seymour, MA Miller, R McFadyen, ML Folb, PI AF Valodia, P Seymour, MA Miller, R McFadyen, ML Folb, PI TI Factors influencing the population pharmacokinetic parameters of phenytoin in adult epileptic patients in South Africa SO THERAPEUTIC DRUG MONITORING LA English DT Article DE patient factors; phenytoin; population pharmacokinetic parameters AB The influence of various covariates (including weight, race, smoking, gender, age, mild-to-moderate alcohol intake, and body surface area) on the population pharmacokinetic parameters of phenytoin in adult epileptic patients in South Africa was investigated. The parameters were the maximum metabolic rate (Vm) and the Michaelis-Menten (MM) constant (Km) of phenytoin. The study population comprised 332 black and colored epileptic patients (note: ''black'' refers to indigenous people of South Africa, who speak one of the Bantu languages as their native language; "colored" refers to people considered to be of mixed race, classified as such by the apartheid former government of South Africa). The influence of covariates on Vm and Km estimates was determined using nonlinear mixed-effects modeling (NONMEM). Parameter models describing the factors that could potentially influence Vm and Km were tested using the Michaelis-Menten parallel MM and first-order elimination models, to which 853 steady state dose-to-serum concentration pairs were fitted. The results indicated that body weight, smoking, race, and age (65 years or older), in descending order of importance, significantly influenced Vm (p < 0.05). Although a significant difference (p = 0.03) in Km was found between black and colored patients, incorporating the influence of race in Km in the final regression model did not improve the fit of the model to the data, which indicated that the variability in Km was accounted for by Vm. The scaling factors for smoking, colored patients and age (65 years or older) in Vm were 1.16, 1.10, and 0.88, respectively. These factors should be taken into account when adjusting phenytoin dose. C1 Univ Western Cape, Dept Pharmacol, ZA-7535 Bellville, South Africa. Warner Lambert Pty Ltd, Cape Town, South Africa. Univ Durban Westville, Dept Pharmacol, Durban, South Africa. Univ Cape Town, Dept Pharmacol, ZA-7925 Cape Town, South Africa. US FDA, Rockville, MD 20857 USA. RP Valodia, P (reprint author), Univ Western Cape, Dept Pharmacol, Private Bag X17, ZA-7535 Bellville, South Africa. NR 21 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD FEB PY 1999 VL 21 IS 1 BP 57 EP 62 DI 10.1097/00007691-199902000-00009 PG 6 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 164WM UT WOS:000078486600008 PM 10051055 ER PT J AU Sprando, RL Collins, TFX Black, TN Olejnik, N Rorie, JI West, LJ Bowers, JD Sass, N Robl, M AF Sprando, RL Collins, TFX Black, TN Olejnik, N Rorie, JI West, LJ Bowers, JD Sass, N Robl, M TI Light microscopic observations on the reproductive tract of the male sand rat, Psammomys obesus SO TISSUE & CELL LA English DT Article DE Psammomys obesus; sand rats; reproductive tract; testis ID EPIDIDYMIS; SPERMATOGENESIS; DEFERENS; CELL AB The anatomy of the reproductive tract of the male sand rat, Psammomys obesus, was examined by light microscopy. Histologically, the reproductive tract is similar to other rodent species. Seminiferous tubules in the 1-month-old sand rat do not contain a tubular lumen but Sertoli cells, spermatogonia and spermatocytes are present. A full complement of germ cells is present in the seminiferous tubules by 2.5 months and spermatogenesis is well established. The interstitial space is not well defined until 2.5 months when cell types typical of most rodent species are observed. The epididymis is not noticeably segmented into lobules. An epididymal lumen is not observed until 2.5 months. Cauda epididymal sperm are not observed in the 1 or 2.5-month-old animals and cauda epididymal sperm counts from the 7.5 and 12.5-month-old animals are highly variable. The epididymis, proximal and middle regions of the vas deferens, seminal vesicles and prostate display morphological and histological characteristics similar to other rodent species. The distal end of the vas deferens is not expanded to form an ampulla. C1 US FDA, Ctr Food Safety Appl Nutr, Div Toxicol Res, Laurel, MD 20708 USA. RP Sprando, RL (reprint author), US FDA, Ctr Food Safety Appl Nutr, Div Toxicol Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 46 TC 9 Z9 9 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0040-8166 J9 TISSUE CELL JI Tissue Cell PD FEB PY 1999 VL 31 IS 1 BP 99 EP 115 DI 10.1054/tice.1999.0003 PG 17 WC Anatomy & Morphology; Cell Biology SC Anatomy & Morphology; Cell Biology GA 190MD UT WOS:000079966100013 PM 10368991 ER PT J AU Castlebury, LA Sutherland, JB Tanner, LA Henderson, AL Cerniglia, CE AF Castlebury, LA Sutherland, JB Tanner, LA Henderson, AL Cerniglia, CE TI Short Communication: Use of a bioassay to evaluate the toxicity of beauvericin to bacteria SO WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE anaerobes; bacteria; beauvericin; bioassay; mycotoxins ID LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; CORN AB An agar diffusion bioassay was used to compare the sensitivities of bacteria to the mycotoxin beauvericin. Bacillus pumilus LACB101 was inhibited by filter-paper disks containing 0.1 mu g of beauvericin; B. cereus, B. mycoides, B. sphaericus, Paenibacillus alvei, P. azotofixans, P. macquariensis, and P. pulvifaciens by 1 mu g; and P. validus by 25 mu g. The anaerobes Eubacterium biforme, Peptostreptococcus anaerobius, P. productus, Bifidobacterium adolescentis, and Clostridium perfringens were also inhibited by beauvericin. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), ARS, Systemat Bot & Mycol Lab, USDA, Beltsville, MD 20705 USA. NR 12 TC 19 Z9 19 U1 1 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0959-3993 J9 WORLD J MICROB BIOT JI World J. Microbiol. Biotechnol. PD FEB PY 1999 VL 15 IS 1 BP 131 EP 133 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 200PK UT WOS:000080548800022 ER PT J AU Gu, ML Leppla, SH Klinman, DM AF Gu, ML Leppla, SH Klinman, DM TI Protection against anthrax toxin by vaccination with a DNA plasmid encoding anthrax protective antigen SO VACCINE LA English DT Article DE DNA vaccine; anthrax; toxin ID BACILLUS-ANTHRACIS; EUKARYOTIC CELLS; SPORE CHALLENGE; LETHAL FACTOR; MICE; ACTIVATION; ADJUVANTS; INJECTION; VACCINES; SEQUENCE AB A DNA vaccine encoding the immunogenic and biologically active portion of anthrax protective antigen (PA) was constructed. Spleen cells from BALB/c mice immunized intramuscularly with this vaccine were stimulated to secrete IFN gamma and IL-4 when exposed to PA in vitro. Immunized mice also mounted a humoral immune response dominated by IgG1 anti-PA antibody production, the subclass previously shown to confer protection against anthrax toxin. A 1:100 dilution of serum from these animals protected cells in vitro against cytotoxic concentrations of PA. Moreover, 7/8 mice immunized three times with the PA DNA vaccine were protected against lethal challenge with a combination of anthrax protective antigen plus lethal factor. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Sect Retroviral Immunol, Bethesda, MD 20014 USA. NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Sect Retroviral Immunol, Bldg 29A,Room 3 D 10, Bethesda, MD 20014 USA. EM klinman@a1.cber.fda.gov NR 27 TC 66 Z9 67 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 28 PY 1999 VL 17 IS 4 BP 340 EP 344 DI 10.1016/S0264-410X(98)00210-2 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 146EB UT WOS:000077414100006 PM 9987172 ER PT J AU Matrician, L Ange, G Burns, S Fanning, L Kioski, C Cage, G Harter, G Reese, D McFall, D Komatsu, K Englund, R AF Matrician, L Ange, G Burns, S Fanning, L Kioski, C Cage, G Harter, G Reese, D McFall, D Komatsu, K Englund, R TI Nosocomial Burkholderia cepacia infection and colonization associated with intrinsically contaminated mouthwash - Arizona, 1998 (Reprinted from MMWR, pg 47, 926, 1998) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Arizona Dept Hlth Serv, Phoenix, AZ 85007 USA. Natl Ctr Infect Dis, Hosp Infect Program, Atlanta, GA USA. US FDA, Invest Br, Phoenix Resident Post, Rockville, MD 20857 USA. CDC, Atlanta, GA 30333 USA. RP Matrician, L (reprint author), Arizona Dept Hlth Serv, Phoenix, AZ 85007 USA. NR 1 TC 2 Z9 2 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 27 PY 1999 VL 281 IS 4 BP 318 EP 318 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 158JB UT WOS:000078111300013 ER PT J AU Burkhart, GA AF Burkhart, GA TI Time for action on drug safety SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Burkhart, GA (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 27 PY 1999 VL 281 IS 4 BP 319 EP 319 DI 10.1001/jama.281.4.319 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 158JB UT WOS:000078111300014 PM 9929075 ER PT J AU Morris, SM Aidoo, A Chen, JJ Chou, MW Casciano, DA AF Morris, SM Aidoo, A Chen, JJ Chou, MW Casciano, DA TI Aflatoxin B-1-induced Hprt mutations in splenic lymphocytes of Fischer 344 rats. Results of an intermittent feeding trial SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE aflatoxin B-1; continuous dosing; intermittent dosing; rat spleen lymphocyte; Hprt mutation ID HEPATOCELLULAR CARCINOMAS; P53 GENE; RESTRICTION; RISK; B-1 AB In a previous study, we found an increase in the mutant frequency at the Hypoxanthine phosphoribosyl transferase (Hprt) locus in the splenic lymphocytes of Fischer 344 rats acutely exposed to aflatoxin B-1 (AFB(1)). Because an acute exposure may not reflect the exposure pattern of individuals whose diet may contain AFB(1)-contaminated foodstuffs, we sought to determine if the feeding regimen affected the induction of Hprt mutations in the rat splenic lymphocyte. Thus, Fischer 344 rats were fed either (A) a control diet, (B) various doses of AFB(1) for three four-week periods interspersed with two four-week periods of the control diet, or (C) continuously fed 1.6 ppm of AFB(1). Not only was a significant increase in the mutant frequency detected in the lymphocytes of rats fed a dose as low as 0.01 ppm of AFB(1), but the increase in the mutant frequency at the end of the 20-week experimental period was consistent with an accumulation of damage induced by AFB(1). These results indicate that the rat lymphocyte/Hprt assay is useful for detecting chronic low level exposures. Further, these data suggest that an intermittent, low-level exposure to AFB(1) may present a human health risk. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, US Dept HHS, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, US Dept HHS, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, US Dept HHS, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Morris, SM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, US Dept HHS, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM smorris@nctr.fda.gov NR 18 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JAN 25 PY 1999 VL 423 IS 1-2 BP 33 EP 38 DI 10.1016/S0027-5107(98)00222-X PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 166HC UT WOS:000078569300006 PM 10029671 ER PT J AU Dobrovolsky, VN Casciano, DA Heflich, RH AF Dobrovolsky, VN Casciano, DA Heflich, RH TI Tk(+/-) mouse model for detecting in vivo mutation in an endogenous, autosomal gene SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE thymidine kinase; knockout; N-ethyl-N-nitrosourea; mutation; 5-bromo-2 '-deoxyuridine ID ETHYL-N-NITROSOUREA; THYMIDINE KINASE LOCUS; LACI TRANSGENIC MICE; LYMPHOMA-CELLS; ADENINE PHOSPHORIBOSYLTRANSFERASE; MAMMALIAN-CELLS; SHUTTLE VECTORS; L5178Y/TK+/ MOUSE; ESCHERICHIA-COLI; INVIVO EXPOSURE AB Tk(+/-) transgenic mice were created using an embryonic stem cell line in which one allele of the endogenous thymidine kinase (Tk) gene was inactivated by;targeted homologous recombination. Breeding Tk(+/-) parents produced viable Tk(-/-) knockout (KO) mice. Splenic lymphocytes from KO mice were used in reconstruction experiments for determining the conditions necessary for recovering Tk somatic cell mutants from Tk(+/-) mice. The cloning efficiency of KO lymphocytes was not affected by the toxic thymidine analogues 5-bromo-2'-deoxyuridine (BrdUrd) or trifluorothymidine (TFT), or by BrdUrd in the presence of lymphocytes from Tk(+/-) animals; however, it was easier to identify clones resistant to BrdUrd than to TFT when Tk(+/-) cells were present. Tk(+/-) mice were treated with vehicle or 100 mg/kg of N-ethyl-N-nitrosourea (ENU), and after 4 months, the frequency of Tk mutant lymphocytes was measured by resistance to BrdUrd. The frequency of Tk mutants was 22 +/- 5.9 X 10(-6) in control animals and 80 +/- 31 X 10(-6) in treated mice. In comparison, the frequency of Hprt mutant lymphocytes, as measured by resistance to 6-thioguanine, was 2.0 +/- 1.2 X 10(-6) in control animals and 84 +/- 28 X 10(-6) in the ENU-treated mice. Analysis of BrdUrd-resistant lymphocyte clones derived from the ENU-treated animals revealed point mutations in the non-targeted Tk allele. These results indicate that the selection of BrdUrd-resistant lymphocytes from Tk(+/-) mice may be used for assessing in vivo mutation in an endogenous, autosomal gene. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Dobrovolsky, VN (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 54 TC 33 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JAN 25 PY 1999 VL 423 IS 1-2 BP 125 EP 136 DI 10.1016/S0027-5107(98)00234-6 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 166HC UT WOS:000078569300016 PM 10029690 ER PT J AU Alayash, AI Ryan, BAB Eich, RF Olson, JS Cashon, RE AF Alayash, AI Ryan, BAB Eich, RF Olson, JS Cashon, RE TI Reactions of sperm whale myoglobin with hydrogen peroxide - Effects of distal pocket mutations on the formation and stability of the ferryl intermediate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CROSS-LINKED HEMOGLOBIN; VASCULAR ENDOTHELIAL-CELLS; SITE-DIRECTED MUTAGENESIS; NITRIC-OXIDE; HISTIDINE RESIDUE; LIGAND-BINDING; OXIDATION; OXYGEN; MECHANISM; BLOOD AB Distal pocket mutants of sperm whale oxymyoglobin (oxy-Mb) were reacted with a 2.5-fold excess of hydrogen peroxide (HOOH) in phosphate buffer at pH 7.0, 37 degrees C. We describe a mechanism composed of three instinct steps: 1) initial oxidation of oxy- to ferryl-Mb, 2) autoreduction of the ferryl intermediate to ferric metmyoglobin (metMb), and 3) reaction of metMb with an additional HOOH molecule to regenerate the ferryl intermediate creating a pseudoperoxidase catalytic cycle. Mutation of Leu-29(B10) to Phe slows the initial oxidation reaction 3-fold but has little effect on the rate of ferryl. reduction to ferric met-aquo-myoglobin. In contrast, the Val-68(E11) to Phe mutation causes a small, 60% increase in the initial oxidation reaction and a much larger 2.5-fold increase in the rate of autoreduction. Double insertion of Phe at both the B10- and E11-positions (L29F/V68F) produces a mutant with oxidation characteristics of both single mutants, slow initial oxidation, and rapid autoreduction, but an extraordinarily high affinity for O-2. Replacing His-64(E7) with Gln produces 3-4-fold increases in both processes. Combining the mutation H64Q with L29F results in a myoglobin with enhanced resistance to metMb formation in the absence of antioxidant enzymes (i.e. catalase and superoxide dismutase) due to its own high pseudoperoxidase activity, which rapidly removes any DOOR produced in the initial stages of autoxidation. This double substitution occurs naturally in the myoglobin of Asian elephants, and similar multiple replacements have been used to reduce selectively the rate of nitric oxide (NO)-induced oxidation of both recombinant MbO(2) and HbO(2) blood substitute prototypes without altering O-2 affinity. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77005 USA. Univ Maine, Dept Biochem Microbiol & Mol Biol, Orono, ME 04469 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM Alayash@A1.cber.fda.gov OI Olson, John/0000-0002-0760-5403 FU NHLBI NIH HHS [HL47020]; NIGMS NIH HHS [GM35649, GM08280] NR 59 TC 79 Z9 79 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 22 PY 1999 VL 274 IS 4 BP 2029 EP 2037 DI 10.1074/jbc.274.4.2029 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 159QL UT WOS:000078185200028 PM 9890961 ER PT J AU Golding, H Ouyang, J Zaitseva, M Broder, CC Dimitrov, DS Lapham, C AF Golding, H Ouyang, J Zaitseva, M Broder, CC Dimitrov, DS Lapham, C TI Increased association of glycoprotein 120-CD4 with HIV type 1 coreceptors in the presence of complex-enhanced anti-CD4 monoclonal antibodies SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE-MEDIATED FUSION; SYNCYTIA FORMATION; CD4-GP120 COMPLEX; DOWN-MODULATION; CD4; BINDING; RECEPTOR; GP120; INFECTION AB CD4-specific monoclonal antibodies (CG1, CG7, and CG8), which bind,vith a 5- to 10-fold higher avidity to preformed CD4-gp120 complexes than to CD4, were previously shown to recognize newly identified conformational epitopes in the D1-CDR3 region of CD4, In the current study, these and other complex-enhanced MAbs were tested in three separate assays of HIV-1 coreceptor (CXCR4/CCR5) recruitment. In these assays, the CD4-specific MAbs CG1, -7, and -8 stabilized the association of coreceptor, gp120, and CD4 in trimolecular complexes. In contrast, the gp120-specific, complex-enhanced MAbs 48d and 17b were inhibitory. These data suggest that conformational changes in the CDR3 region of CD4-D1, induced by gp120 binding, may be involved in coreceptor association and thus play a positive role in the HIV-1 cell fusion process. C1 US FDA, Div Viral Prod, CBER, Bethesda, MD 20892 USA. NCI, Sect Membrane Struct & Funct, FCRDC, NIH, Frederick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. RP Golding, H (reprint author), US FDA, Div Viral Prod, CBER, Bldg 29B,Room 4NN04,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 6 Z9 6 U1 0 U2 1 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 20 PY 1999 VL 15 IS 2 BP 149 EP 159 DI 10.1089/088922299311574 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160JB UT WOS:000078225900006 PM 10029247 ER PT J AU Li, MF Xu, F Muller, J Huang, XJ Hearing, VJ Gorelik, E AF Li, MF Xu, F Muller, J Huang, XJ Hearing, VJ Gorelik, E TI Loss of retrovirus production in JB/RH melanoma cells transfected with H-2K(b) and TAP-1 genes SO VIROLOGY LA English DT Article ID INCREASED SENSITIVITY; EXPRESSION; ANTIGEN; MOUSE; INHIBITION; ANTIBODIES; DNA AB JB/RH1 melanoma cells, as well as other melanomas of C57BL/6 mice (B16 and JB/MS), express a common melanoma-associated antigen (MAA) encoded by an ecotropic melanoma-associated retrovirus (MelARV). JB/RH1 cells do not express the H-2K(b) molecules due to down-regulation of the H-2Kb and TAP-1 genes. When JB/RH1 cells were transfected with the H-2K(b) and cotranfected with the TAP-1 gene, it resulted in the appearance of H-2K(b) molecules and an increase in their immunogenicity, albeit they lost expression of retrovirus-encoded MAA recognized by MM2-9B6 mAb. Loss of MAA was found to result from a complete and stable elimination of ecotropic MelARV production in the H-2K(b)/TAP-1-transfected JB/RH1 cells. Northern blot analysis showed no differences in ecotropic retroviral messages in MelARV-producing and -nonproducing melanoma cells, suggesting that loss of MelARV production was not due to down-regulation of MelARV transcription. Southern blot analysis revealed several rearrangements in the proviral DNA of H-2K(b)-positive JB/RH1 melanoma cells. Sequence analysis of the ecotropic proviral DNA from these cells showed numerous nucleotide substitutions, some of which resulted in the appearance of a novel intraviral PstI restriction site and the loss of a HindIII restriction site in the pol region. PCR amplification of the proviral DNAs indicates that an ecotropic provirus found in the H-2K(b)-positive cells is novel and does not preexist in the parental H-2K(b)-negative melanoma cells. Conversely, the ecotropic provirus of the parental JB/RH1 cells was not amplifable from the H-2K(b)-positive cells. Our data indicate that stable loss of retroviral production in the H-2K(b)/TAP-1-transfected melanoma cells is probably due to the induction of recombination between a productive ecotropic MelARV and a defective nonecotropic provirus leading to the generation of a defective ecotropic provirus and the loss of MelARV production and expression of the retrovirus-encoded MAA. (C) 1999 Academic Press. C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. US FDA, Div Viral Prod, Bethesda, MD 20014 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gorelik, E (reprint author), Univ Pittsburgh, Inst Canc, Biomed Sci Tower,Room W954, Pittsburgh, PA 15213 USA. FU NCI NIH HHS [CA59903] NR 26 TC 0 Z9 0 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 20 PY 1999 VL 253 IS 2 BP 230 EP 240 DI 10.1006/viro.1998.9472 PG 11 WC Virology SC Virology GA 162MW UT WOS:000078351600010 PM 9918881 ER PT J AU Chen, ZG Smithberger, J Sun, B Eggerman, TL AF Chen, ZG Smithberger, J Sun, B Eggerman, TL TI Prevention of heteroduplex formation in mRNA quantitation by reverse transcription polymerase chain reaction SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID MESSENGER-RNA; RT-PCR; GENE-EXPRESSION; COMPETITIVE PCR C1 US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NEI, Sect Immunoregulat, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Eggerman, TL (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 8 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 15 PY 1999 VL 266 IS 2 BP 230 EP 232 DI 10.1006/abio.1998.2938 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 162LY UT WOS:000078349400009 PM 9888980 ER PT J AU Sullivan, PS Schable, C Koch, W Do, AN Spira, T Lansky, A Ellenberger, D Lal, RB Hyer, C Davis, R Marx, M Paul, S Kent, J Armor, R McFarland, J Lafontaine, J Mottice, S Cassol, SA Michael, N AF Sullivan, PS Schable, C Koch, W Do, AN Spira, T Lansky, A Ellenberger, D Lal, RB Hyer, C Davis, R Marx, M Paul, S Kent, J Armor, R McFarland, J Lafontaine, J Mottice, S Cassol, SA Michael, N CA Seronegative AIDS Clinical Study Grp TI Persistently negative HIV-1 antibody enzyme immunoassay screening results for patients with HIV-1 infection and AIDS: serologic, clinical, and virologic results SO AIDS LA English DT Article DE HIV infection; seronegativity; antibody response ID HUMAN-IMMUNODEFICIENCY-VIRUS; GROUP-O INFECTIONS; UNITED-STATES; RISK; INDIVIDUALS; ABSENCE; SEROCONVERSION; COHORT; BLOOD; TIME AB Objective: To describe persons with HIV infection and AIDS but with persistently negative HIV antibody enzyme immunoassay (EIA) results. Design: Surveillance for persons meeting a case definition for HIV-1-seronegative AIDS. Setting: United States and Canada. Patients: A total of eight patients with seronegative AIDS identified from July 1995 through September 1997. Main outcome measures: Clinical history of HIV disease, history of HIV test results, and CD4 cell counts from medical record review; results of testing with a panel of EIA for antibodies to HIV-1, and HIV-1 p24 antigen; and viral subtype. Results: Negative HIV EIA results occurred at CD4 cell counts of 0-230 x 10(6)/l, and at HIV RNA concentrations of 105 000-7 943 000 copies/ml. Using a panel of HIV EIA on sera from three patients, none of the HIV EIA detected infection with HIV-1, and signal-to-cut-off ratios were less than or equal to 0.8 for all test kits evaluated. Sera from five patients showed weak reactivity in some HIV EIA, but were non-reactive in other HIV EIA. All patients were infected with HIV-1 subtype B. Conclusions: Rarely, results of EIA tests for antibodies to HIV-1 may be persistently negative in some HIV-1 subtype B-infected persons with AIDS. Physicians treating patients with illnesses or CD4 cell counts suggestive of HIV infection, but for whom results of HIV EIA are negative, should consider p25 antigen, nucleic acid amplification, or viral culture testing to document the presence of HIV. (C) 1999 Lippincott Williams & Wilkins. C1 Ctr Dis Control & Prevent, Surveillance Branch, Div HIV AIDS Prevent Surveillance & Epidemiol, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Div HIV STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. US FDA, Rockville, MD 20857 USA. Multnomah Cty Hlth Dept, Portland, OR USA. Georgia Dept Human Resources, Div Publ Hlth, Atlanta, GA USA. Colorado Dept Publ Hlth & Environm, Denver, CO USA. New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. Michigan Dept Community Hlth, Lansing, MI USA. Texas Dept Hlth, Austin, TX 78756 USA. New York City Dept Hlth, New York, NY 10013 USA. S Carolina Dept Publ Hlth, Columbia, SC USA. Utah Dept Publ Hlth, Salt Lake City, UT USA. Ottawa Gen Hosp, Res Inst, Ottawa, ON K1H 8L6, Canada. Walter Reed Army Inst Res, Rockville, MD USA. RP Sullivan, PS (reprint author), Ctr Dis Control & Prevent, Surveillance Branch, Div HIV AIDS Prevent Surveillance & Epidemiol, Natl Ctr HIV STD & TB Prevent, 1600 Clifton Rd,MS E-47, Atlanta, GA 30333 USA. RI Sullivan, Patrick/A-9436-2009; OI Sullivan, Patrick/0000-0002-7728-0587 NR 26 TC 32 Z9 34 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 14 PY 1999 VL 13 IS 1 BP 89 EP 96 DI 10.1097/00002030-199901140-00012 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 178BT UT WOS:000079246400012 PM 10207549 ER PT J AU Hussain, S Hass, BS Slikker, W Ali, SF AF Hussain, S Hass, BS Slikker, W Ali, SF TI Reduced levels of catalase activity potentiate MPP+-induced toxicity: comparison between MN9D cells and CHO cells SO TOXICOLOGY LETTERS LA English DT Article DE antioxidant; catalase; CHO cells; MN9D cells; MPTP; MPP+; neurotoxicity ID NIGRAL IRON CONTENT; PARKINSONS-DISEASE; ANTIOXIDANT ENZYMES; TRANSGENIC MICE; MOUSE-BRAIN; MPTP; NEUROTOXICITY; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; GLUTATHIONE; RESISTANT AB 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to be toxic by inducing oxygen free radicals in the mammalian nervous system, especially in the nigrostriatal dopaminergic system. The present study was designed to compare the toxic effects of MPP+, the active metabolite of MPTP, in MN9D neuronal cells that exhibit relatively low levels of catalase activity, as compared to CHO cells, which exhibit high levels of catalase activity. The survival of the MN9D cells in the presence of 250 mu M MPP+ was less than 10%, whereas CHO cells exhibited 70% survival at the same concentration of MPP+. The ED50 values of MPP+ in MN9D and CHO cell lines were 60-600 mu M, respectively. MN9D cells contain less catalase, an enzyme believed to be involved in the detoxification of free radicals compared to CHO cells. The catalase activity was 2 Units/mg protein in MN9D cells and 30 U/mg protein in CHO cells. The catalase activity in CHO cells increased with increasing MPP+ concentrations from 100-500 mu M, however, it decreased at 1 mM MPP+. In contrast, catalase activity in MN9D remained the same at all MPP+ concentrations. When the CHO cells were pre-treated with 10-25 mM 3-aminotriazole (3-AT), which inhibits catalase activity, and exposed to MPP+ at various concentrations, they became susceptible to MPP+. It is evident from these data that the differential susceptibility to MPP+ in these two cell lines are due to differences in catalase activity. In addition, the inhibition of constituentive catalase activity in CHO cells by 3-AT treatment enhances their susceptibility. In conclusion, the study demonstrates that catalase activity represents an important defence mechanism in MPTP-induced toxicity. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol & Neurol, Little Rock, AR 72205 USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. EM Sali@nctr.fda.gov NR 36 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD JAN 11 PY 1999 VL 104 IS 1-2 BP 49 EP 56 DI 10.1016/S0378-4274(98)00231-8 PG 8 WC Toxicology SC Toxicology GA 166DK UT WOS:000078560800007 PM 10048749 ER PT J AU De Veau, EJI AF De Veau, EJI TI Determination of non-protein bound phenylbutazone in bovine plasma using ultrafiltration and liquid chromatography with ultraviolet detection SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE protein binding; phenylbutazone ID PHARMACOKINETICS; EXCRETION AB A liquid chromatographic procedure using UV detection was coupled with ultrafiltration for the quantitation of free phenylbutazone in bovine plasma, in the range of 20 ng/ml to 2.0 mu g/ml. Whole plasma samples (0.5 to 1 ml) were placed in a 2-ml centrifugal concentrator with a molecular-mass cut-off membrane of 10 000 and centrifuged at 4500 g for 2 h at 4 degrees C using a fixed angle rotor. The ultrafiltrate was transferred to an LC vial with a 200-mu l insert and 100 mu l was injected into an LC system. The chromatographic system used a C-18 reversed-phase column connected to a UV detector set gt 264 nm. The mobile phase was 0.2 M sodium phosphate buffer (pH 7)-methanol (I:1). Recoveries of phenylbutazone from protein-free plasma water fortified at levels of 20 ng/ml to 2 mu g/ml ranged from 91 to 93%, with relative standard deviations (R.S.D.s) ranging from 1 to 4%. The concentration of incurred non-protein bound phenylbutazone obtained from a cow intravenously dosed twice with 2 g phenylbutazone, 8 h apart, was 111, 26 and 11 ng/ml for 2, 72 and 104 h post first phenylbutazone dose, respectively. (C) 1999 Published by Elsevier Science BN. All rights reserved. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP De Veau, EJI (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 15 TC 16 Z9 16 U1 1 U2 6 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 JAN 8 PY 1999 VL 721 IS 1 BP 141 EP 145 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 159RA UT WOS:000078186600015 PM 10027645 ER PT S AU Wear, KA AF Wear, KA BE Schneider, SC Levy, M McAvoy, BR TI A model for ultrasonic backscatter from trabecular bone SO 1999 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 SE Ultrasonics Symposium LA English DT Proceedings Paper CT 1999 IEEE Ultrasonics International Symposium CY OCT 17-20, 1999 CL TAHOE, NV SP IEEE Ultrason Ferroelect & Frequency Control Soc ID HIP FRACTURE; CANCELLOUS BONE; HUMAN CALCANEUS; OS CALCIS; ATTENUATION; VELOCITY; DENSITY; WOMEN; COEFFICIENTS; PREDICTION AB A model describing the frequency dependence of backscatter from trabecular bone is presented. Scattering is assumed to originate from the surfaces of trabeculae, which are modeled as long thin cylinders. Measurements from human calcaneus in vitro are in good agreement with theory. For mediolateral insonification at diagnostic frequencies, backscatter coefficient is approximately proportional to frequency cubed. At higher frequencies, the frequency response flattens out. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NR 31 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 0-7803-5722-1; 0-7803-5723-X J9 ULTRASON PY 1999 BP 1307 EP 1310 PG 4 WC Acoustics; Instruments & Instrumentation; Physics, Applied SC Acoustics; Instruments & Instrumentation; Physics GA BQ43A UT WOS:000088356000282 ER PT S AU Harris, GR AF Harris, GR BE Schneider, SC Levy, M McAvoy, BR TI Medical ultrasound exposure measurements: Update on devices, methods, and problems SO 1999 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 SE Ultrasonics Symposium LA English DT Proceedings Paper CT 1999 IEEE Ultrasonics International Symposium CY OCT 17-20, 1999 CL TAHOE, NV SP IEEE Ultrason Ferroelect & Frequency Control Soc ID INTENSITY FOCUSED ULTRASOUND; ACOUSTIC OUTPUT; PRESSURE DETERMINATION; FIBEROPTIC HYDROPHONE; MEMBRANE HYDROPHONE; FREQUENCY-RESPONSE; INSITU EXPOSURE; SHOCK-WAVES; SENSITIVITY; POWER AB Medical ultrasound fields span a wide range of exposure conditions, from the continuous, low-frequency vibrations of surgical fragmentation needles, to the intense, broadband pressure pulses produced by extracorporeal shock wave lithotripters. Each of these diverse conditions of use presents its own exposure measurement challenges. Furthermore, the sensors and techniques used to evaluate ultrasound exposures have had to evolve as new or expanded clinical applications have emerged. In this paper some of the more notable of these developments are presented and discussed. Topics covered include recent work on devices and techniques, methods of calibration, progress in standardization, and current problem areas, including the effects of nonlinear propagation. Emphasis is given to miniature hydrophones because of the prominent role they continue to play in ultrasound exposure measurements. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 109 TC 8 Z9 8 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 0-7803-5722-1; 0-7803-5723-X J9 ULTRASON PY 1999 BP 1341 EP 1352 PG 12 WC Acoustics; Instruments & Instrumentation; Physics, Applied SC Acoustics; Instruments & Instrumentation; Physics GA BQ43A UT WOS:000088356000290 ER PT S AU Gray-Rowlands, S AF Gray-Rowlands, S BE Wirtanen, G Salo, S Mikkola, A TI New FDA guidelines SO 30TH R3-NORDIC CONTAMINATION CONTROL SYMPOSIUM SE VTT SYMPOSIA LA English DT Meeting Abstract CT 30th R3-Nordic Contamination Control Symposium CY MAY 30-JUN 02, 1999 CL HELSINKI, FINLAND SP R3 Nordic C1 US FDA, CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TECHNICAL RESEARCH CENTRE FINLAND PI ESPOO PA INFORMATION SERVICE, PO BOX 2000, FIN-02044 VT ESPOO, FINLAND SN 0357-9387 BN 951-38-5268-7 J9 VTT SYMP PY 1999 VL 193 BP 385 EP 385 PG 1 WC Engineering, Electrical & Electronic; Food Science & Technology; Pharmacology & Pharmacy SC Engineering; Food Science & Technology; Pharmacology & Pharmacy GA BN92U UT WOS:000083509200039 ER PT J AU Tollefson, L Fedorka-Cray, PJ Angulo, FJ AF Tollefson, L Fedorka-Cray, PJ Angulo, FJ TI Public health aspects of antibiotic resistance monitoring in the USA SO ACTA VETERINARIA SCANDINAVICA LA English DT Article; Proceedings Paper CT 11th Internordic Symposium of the Nordic-Committee-for-Veterinary-Scientific-Cooperation (NKVet) CY NOV 07-08, 1997 CL SUNDVOLDEN, NORWAY SP Nord Comm Vet Sci Cooperat ID SALMONELLA-TYPHIMURIUM; ANIMALS; CATTLE C1 US FDA, Ctr Vet Med, MPH, DVM, Rockville, MD 20857 USA. USDA ARS, Richard B Russell Agr Res Ctr, Athens, GA 30613 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Tollefson, L (reprint author), US FDA, Ctr Vet Med, MPH, DVM, Rockville, MD 20857 USA. NR 15 TC 0 Z9 0 U1 1 U2 1 PU DANSKE DYRLAEGEFORENING PI VANLOSE PA ROSENLUNDS ALLE 8, DK-2720 VANLOSE, DENMARK SN 0044-605X J9 ACTA VET SCAND JI Acta Vet. Scand. PY 1999 SU 92 BP 67 EP 75 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 272MZ UT WOS:000084655600009 ER PT J AU Aziz, KJ AF Aziz, KJ TI Tumor markers: Reclassification and new approaches to evaluation SO ADVANCES IN CLINICAL CHEMISTRY, VOL 33 SE ADVANCES IN CLINICAL CHEMISTRY LA English DT Review ID PROSTATE-SPECIFIC ANTIGEN; CARCINOEMBRYONIC ANTIGEN; COLORECTAL-CANCER; BREAST-CANCER; FREE PSA; ASSAYS; SERUM; PURIFICATION; IMMUNOASSAYS; SENSITIVITY C1 US FDA, Div Clin Lab Devices, Rockville, MD 20850 USA. RP Aziz, KJ (reprint author), US FDA, Div Clin Lab Devices, Rockville, MD 20850 USA. NR 39 TC 2 Z9 2 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2423 J9 ADV CLIN CHEM PY 1999 VL 33 BP 169 EP 199 PG 31 WC Medical Laboratory Technology SC Medical Laboratory Technology GA BM55S UT WOS:000079094400004 ER PT J AU Wilcox, NL AF Wilcox, NL TI Validation and regulatory acceptance of alternative test methods and international co-operation SO ALTEX-ALTERNATIVEN ZU TIEREXPERIMENTEN LA English DT Article DE 3R; international harmonization; validation; regulatory acceptance AB The U.S. Food and Drug Administration (FDA) is committed to facilitating the development, validation, and regulatory acceptance of new toxicological testing methods. FDAs mission emphasizes protecting public health by using the best science through the most efficient means available. New technologies currently under development have the potential to better predict human and animal endpoints in safety assessment, and to reduce, refine, and replace animal use in product testing. Tremendous progress in the alternatives arena has been made and includes: (1) international harmonization on validation criteria for new test methods, (2) development of a process for the review and validation of new test methods by the European Centre for the Validation of Alternative Methods (ECVAM) and the Interagency Coordinating Committee on the Validation of alternative Methods (ICCVAM), and (3) successful regulatory acceptance and implementation of new validated methods in toxicity testing. There are many participants to be commended for their accomplishments on these complex issues. However there is much to be done, and continued cooperation between stakeholders internationally is essential. Moreover mutual agreement must be reached regarding the validation status of those methods subjected to rigorous, expert peer review by organizations such as ECVAM and ICCVAM. International harmonization, based upon sound scientific principles, will prevent duplication of scarce resources, minimize unnecessary use of animals, facilitate safety assessment and regulatory acceptance, and ultimately reduce research-to-market time for regulated products. C1 US FDA, DVM, MPH, Rockville, MD 20857 USA. RP Wilcox, NL (reprint author), US FDA, DVM, MPH, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 1999 VL 16 IS 3 BP 163 EP 166 PG 4 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 251VQ UT WOS:000083467400015 ER PT J AU Teisl, MF Roe, B Levy, AS AF Teisl, MF Roe, B Levy, AS TI Ecocertification: Why it may not be a "field of dreams" SO AMERICAN JOURNAL OF AGRICULTURAL ECONOMICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Agricultural-Economics-Association CY AUG 08-11, 1999 CL NASHVILLE, TENNESSEE SP Amer Agr Econ Assoc ID FOREST C1 Univ Maine, Dept Resource Econ & Policy, Orono, ME 04469 USA. Ohio State Univ, Dept Agr Environm & Dev Econ, Columbus, OH 43210 USA. US FDA, Consumer Studies Branch, Rockville, MD 20857 USA. RP Teisl, MF (reprint author), Univ Maine, Dept Resource Econ & Policy, Orono, ME 04469 USA. RI Roe, Brian/A-7386-2009; OI Roe, Brian/0000-0003-4228-2889; teisl, mario/0000-0002-2021-9208 NR 7 TC 33 Z9 33 U1 0 U2 3 PU AMER AGRICULTURAL ECONOMICS ASSOC PI AMES PA 415 SOUTH DUFF AVE, STE C, AMES, IA 50010-6600 USA SN 0002-9092 J9 AM J AGR ECON JI Am. J. Agr. Econ. PY 1999 VL 81 IS 5 BP 1066 EP 1071 DI 10.2307/1244085 PG 6 WC Agricultural Economics & Policy; Economics SC Agriculture; Business & Economics GA 285VM UT WOS:000085409000010 ER PT J AU Flynn, KM Ferguson, SA Newbold, RR AF Flynn, KM Ferguson, SA Newbold, RR TI Estrogen mimics cause minimal behavioral alterations in rats. SO AMERICAN ZOOLOGIST LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC INTEGRATIVE COMPARATIVE BIOLOGY PI MCLEAN PA 1313 DOLLEY MADISON BLVD, NO 402, MCLEAN, VA 22101 USA SN 0003-1569 J9 AM ZOOL JI Am. Zool. PY 1999 VL 39 IS 5 SI SI MA 145 BP 25A EP 26A PG 2 WC Zoology SC Zoology GA 292NE UT WOS:000085800400146 ER PT J AU Eppler, B Patterson, TA Zhou, W Millard, WJ Dawson, R AF Eppler, B Patterson, TA Zhou, W Millard, WJ Dawson, R TI Kainic acid (KA)-induced seizures in Sprague-Dawley rats and the effect of dietary taurine (TAU) supplementation or deficiency SO AMINO ACIDS LA English DT Article DE amino acids; taurine; kainic acid; epilepsy; anticonvulsants; neuroprotection; excitatory amino acids ID TEMPORAL-LOBE EPILEPSY; AMINO-ACIDS; BRAIN; NEUROTRANSMITTER; MANIPULATION; RELEVANCE; GLUTAMATE; INJECTION; AGONISTS AB Male Sprague-Dawley rats received TAU supplementation (1.5% in drinking water) or TAU deficient diets for 4 weeks to test for a possible neuroprotective role of TAU in KA-induced (10 mg/kg s.c.) seizures. TAU supplementation significantly increased serum and hippocampal TAU levels, but not TAU content in temporal cortex or striatum. TAU deficient diets did not attenuate serum or tissue TAU levels. Dietary TAU supplementation failed to decrease the number or latency of partial or clonic-tonic seizures or wet dog shakes, whereas a TAU deficient diet decreased the number of clonic-tonic and partial seizures. This study does not support previous observations of an anticonvulsant effect of TAU against KA-induced seizures. KA-treatment decreased alpha(2)-adrenergic receptor binding sites and TAU content in the temporal cortex across all dietary treatment groups, supporting previous evidence of severe KA-induced damage and neuronal loss in this brain region. C1 Univ Florida, Coll Pharm, Dept Pharmacodynam, JHMHC, Gainesville, FL 32610 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Eppler, B (reprint author), Univ Florida, Coll Pharm, Dept Pharmacodynam, JHMHC, Box 100487, Gainesville, FL 32610 USA. NR 53 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PY 1999 VL 16 IS 2 BP 133 EP 147 DI 10.1007/BF01321532 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186KU UT WOS:000079729100003 PM 10319185 ER PT J AU Hayward, DG Hooper, K Andrzejewski, D AF Hayward, DG Hooper, K Andrzejewski, D TI Tandem-in-time mass spectrometry method for the sub-parts-per-trillion determination of 2,3,7,8-chlorine-substituted dibenro-p-dioxins and -furans in high-fat foods SO ANALYTICAL CHEMISTRY LA English DT Article ID POLYCHLORINATED DIBENZOFURANS; ENVIRONMENTAL-SAMPLES; UNITED-STATES; MS-MS; PCDDS; PCDFS; MILK; FISH; IDENTIFICATION; EXPOSURE AB Limits of quantitation (LOQs) for a quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) method were evaluated through replicate analysis of unfortified peanut oil, shortening, lamb at, and butter for all 2,3,7,8-chlorine-substituted polychlorodibenzo-p-dioxins (PCDDs) and polychlorodibenzofurans (PCDFs), Ten congeners were measurable in butter (0.27-2.5 pg/g) and nine congeners were measurable in lamb fat (0.09-2.6 pg/g) with good precision. LOQs for high-fat foods were estimated by triplicate analysis of peanut oil fortified at two levels. Accurate! and reproducible results were achieved at 0.5 pg/g for most PGDD/Fs (1.0 pg/g for heptachlorodibenzo-p-dioxin and heptachlorodibenzofuran and 2.0 pg/g for octachlorodibenzofuran) and at 0.2 pg/g for 2,3,7,8-tetrachlorodibenzofuran (TCDF) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), QISTMS distinguished between catfish and chicken eggs with elevated TCDD levels from background samples collected from the most regions of the continental United States. QISTMS determined the extent of TCDD contamination in butter, lamb fat, and cottonseed oil collected from rural villages in Kazakhstan. Replicate analysis of catfish and chicken eggs by the QISTMS method produced comparable results to high-resolution mass spectrometry (HRMS). Lower limits of detection will be needed if QISTMS is to fully complement HRMS in the measurement of TCDD levels in food. C1 US FDA, Washington, DC 20204 USA. Calif Environm Protect Agcy, Hazardous Mat Lab, Berkeley, CA 94704 USA. RP Hayward, DG (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. NR 38 TC 31 Z9 37 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JAN 1 PY 1999 VL 71 IS 1 BP 212 EP 220 DI 10.1021/ac980282+ PG 9 WC Chemistry, Analytical SC Chemistry GA 155BF UT WOS:000077925500040 PM 9921129 ER PT J AU Lawless, LS AF Lawless, LS TI Morphological comparisons between two species of Blattella (Dictyoptera : Blattellidae) SO ANNALS OF THE ENTOMOLOGICAL SOCIETY OF AMERICA LA English DT Article DE Blattella; morphology; cockroach ID COCKROACHES; ASAHINAI; GERMANICA; CARRIERS AB Asian, Blattella asahinai Mizukubo, and. German cockroaches, Blattella germanica (L.), exhibit behavioral differences but are morphologically similar. Recently, the Asian cockroach has been introduced into Florida: it lives indoors and outdoors, is moving northward, and is a potential vector of disease. The German cockroach is cosmopolitan, lives indoors, has been found in food processing firms and warehouses, and is a known vector of disease. It has become a necessity in the food and pest control industry to differentiate between Asian and German cockroaches. A proper method of extermination may be developed by determining the species. The morphological differences in 4 body structures (left mandible, light tegmen, hind-wings, and cerci) that may be used to differentiate the 2 species are presented. C1 US FDA, Baltimore, MD 21201 USA. RP Lawless, LS (reprint author), US FDA, 900 Madison Ave, Baltimore, MD 21201 USA. NR 18 TC 6 Z9 6 U1 0 U2 3 PU ENTOMOL SOC AMER PI LANHAM PA 9301 ANNAPOLIS RD, LANHAM, MD 20706 USA SN 0013-8746 J9 ANN ENTOMOL SOC AM JI Ann. Entomol. Soc. Am. PD JAN PY 1999 VL 92 IS 1 BP 139 EP 143 PG 5 WC Entomology SC Entomology GA 162MJ UT WOS:000078350400019 ER PT J AU Chapman, LE Mertz, GJ Peters, CJ Jolson, HM Khan, AS Ksiazek, TG Koster, FT Baum, KF Rollin, PE Pavia, AT Holman, RC Christenson, JC Rubin, PJ Behrman, RE Bell, LJW Simpson, GL Sadek, RF AF Chapman, LE Mertz, GJ Peters, CJ Jolson, HM Khan, AS Ksiazek, TG Koster, FT Baum, KF Rollin, PE Pavia, AT Holman, RC Christenson, JC Rubin, PJ Behrman, RE Bell, LJW Simpson, GL Sadek, RF CA Ribavirin Study Grp TI Intravenous ribavirin for hantavirus pulmonary syndrome: safety and tolerance during 1 year of open-label experience SO ANTIVIRAL THERAPY LA English DT Article ID SOUTHWESTERN UNITED-STATES; GENETIC IDENTIFICATION; THERAPY; OUTBREAK; DISEASE; FEVER AB Intravenous ribavirin was provided non-selectively for investigational open-label use among persons with suspected hantavirus pulmonary syndrome (HPS) in the United States between 4 June 1993 and 1 September 1994, Therapy was initiated prior to laboratory confirmation of hantavirus infection because most deaths from HPS occur within 48 h of hospitalization. Thirty patients with confirmed HPS, 105 patients without HPS and 5 patients without adequate diagnostic testing for HPS were enrolled. This observational study arguably provides the most complete information available on ribavirin-associated adverse effects. Although ribavirin was generally well tolerated, 71% of recipients became anaemic and 19% underwent transfusion, An apparent excess of hyperamylasaemia/pancreatitis was either therapy-associated or due to enrolment bias. The 30 enrolled HPS patients had a case-fatality rate of 47% (14/30), It is not possible to assess efficacy with this study design. However, comparison of survival curves for the 30 enrolled HPS patients and 34 patients who developed HPS during the same time period but were not enrolled did not suggest an appreciable drug effect. A randomized, placebo-controlled trial that enrols patients during the prodrome phase would be necessary to assess the efficacy and further define the safety of intravenous ribavirin for HPS. C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Hantavirus Task Force, Atlanta, GA 30333 USA. Univ New Mexico, Sch Med, Dept Internal Med, Albuquerque, NM 87131 USA. US FDA, Rockville, MD 20857 USA. Univ Colorado, Sch Med, Denver, CO USA. Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. Infect Dis Consultants Ltd, Phoenix, AZ USA. New Mexico Dept Hlth, Santa Fe, NM USA. RP Chapman, LE (reprint author), Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Hantavirus Task Force, Atlanta, GA 30333 USA. NR 34 TC 87 Z9 93 U1 0 U2 0 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON WC1V 6QA, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 1999 VL 4 IS 4 BP 211 EP 219 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 276XJ UT WOS:000084903400003 PM 10723500 ER PT J AU Suleiman, OH Stern, SH Spelic, DC AF Suleiman, OH Stern, SH Spelic, DC TI Patient dosimetry activities in the United States: the nationwide evaluation of X-ray trends (NEXT) and tissue dose handbooks SO APPLIED RADIATION AND ISOTOPES LA English DT Article ID ATTENUATION PHANTOM; EXPOSURE; FLUOROSCOPY; EQUIVALENT; QUALITY AB In the United States the Food and Drug Administration (FDA) in collaboration with the Conference of Radiation Control Program Directors (CRCPD) and state and local government agencies surveys clinical facilities about X-ray system air kerma and ancillary data related to patient dosimetry for a variety of diagnostic X-ray examinations. The survey program is known as the Nationwide Evaluation of X-ray TI-ends (NEXT). The survey utilizes reference patient-equivalent phantoms in the collection of comprehensive technical information. With knowledge of the skin-entrance air kerma, specific tissue doses can be calculated. An overview of NEXT and previously published FDA tissue dose handbooks for diagnostic X-ray examinations is presented. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Suleiman, OH (reprint author), US FDA, Ctr Devices & Radiol Hlth, 1350 Piccard Dr,HFZ-240, Rockville, MD 20850 USA. NR 64 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD JAN PY 1999 VL 50 IS 1 BP 247 EP 259 DI 10.1016/S0969-8043(98)00073-6 PG 13 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 160KA UT WOS:000078228300018 PM 10028641 ER PT J AU Wilkin, JK AF Wilkin, JK TI Use of topical products for maintaining remission in rosacea SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material C1 US FDA, Div Dermatol & Dental Drug Prod, Rockville, MD 20857 USA. RP Wilkin, JK (reprint author), US FDA, Div Dermatol & Dental Drug Prod, 9201 Corp Blvd, Rockville, MD 20857 USA. NR 6 TC 11 Z9 13 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 1999 VL 135 IS 1 BP 79 EP 80 DI 10.1001/archderm.135.1.79 PG 2 WC Dermatology SC Dermatology GA 158JL UT WOS:000078112200014 PM 9923787 ER PT J AU Yang, M Koga, M Katoh, T Kawamoto, T AF Yang, M Koga, M Katoh, T Kawamoto, T TI A study for the proper application of urinary naphthols, new biomarkers for airborne polycyclic aromatic hydrocarbons SO ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID N-ACETYLATION POLYMORPHISM; GENETIC POLYMORPHISMS; 5'-FLANKING REGION; CYP1A1 GENOTYPES; CANCER; NAPHTHALENE; EXPOSURE; JAPANESE; 1-HYDROXYPYRENE; METABOLISM AB Urinary naphthols, 1- and 2-naphthol, recently have been suggested as route-specific biomarkers for exposure to airborne polycyclic aromatic hydrocarbons. For the proper application of urinary naphthols as biomarkers, we studied effects of lifestyle on urinary naphthols levels in 119 Japanese male workers. After improving the detection limit of urinary naphthols up to 0.27 mu g/L by high-resolution capillary gas chromatography/mass spectrometry/selected ion monitoring, urinary naphthols were detectable in approximately 90% of the subjects. Among detectable samples, the geometrical mean (GM) of urinary 1-naphthol concentration was 5.13 mu g/L (geometrical standard deviation, GSD, 4.90), while the GM of urinary 2-naphthol concentration was 3.16 mu g/L (GSD, 5.61). We observed that urinary 1- and 2-naphthol level were three- and sevenfold higher, respectively, among smokers than among nonsmokers (p < 0.01). The ratios of urinary 2-naphthol to 1-naphthol were significantly higher among smokers than nonsmokers (p < 0.05). The number of cigarettes smoked and urinary cotinine levels were also positively related to the concentration of urinary naphthols (p < 0.01), while other lifestyle factors, i.e., age and consumption of alcohol, greasy or salty food, sweets, fruits, vegetables, meat, or fish, were not. We also studied whether genetic polymorphisms of enzymes, which were involved in naphthalene metabolism, affected urinary naphthols levels. The cytochrome P450 (CYP) 1A1 exon 7 genetic polymorphism was not related to urinary naphthol levels. Among smokers, the subjects with c1/c2 or c2/c2 type of CYP2E1, which was determined by CYP2E1 RsaI polymorphism in 5'-flaking region, showed higher concentrations of urinary 2-naphthol than the subjects with c1/c1 type regardless of creatinine-correction (p < 0.05) and the subjects with glutathione S-transferase (GST) M1 deficient type showed higher concentrations of both urinary 1- and 2-naphthol than those with GSTM1 normal type but only without creatinine-correction (p < 0.05). Thus, when urinary naphthols are used as biomarkers, smoking and the genetic polymorphisms of CYP2E1 and GSTM1 should be considered. C1 Univ Occupat & Environm Hlth, Dept Environm Hlth, Yahatanishi Ku, Kitakyushu, Fukuoka 8078555, Japan. Prefectural Univ Kumamoto, Fac Human Life Sci, Analyt Environm Chem Lab, Kumamoto 8620920, Japan. Univ Occupat & Environm Hlth, Sch Hlth Sci, Yahatanishi Ku, Kitakyushu, Fukuoka 8078555, Japan. RP Yang, M (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 32 TC 87 Z9 90 U1 0 U2 5 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 JAN PY 1999 VL 36 IS 1 BP 99 EP 108 PG 10 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 146RE UT WOS:000077443500013 PM 9828267 ER PT B AU Blum, D AF Blum, D BE Scerbo, MW Mouloua, M TI Problem identification in complex automated medical systems SO AUTOMATION TECHNOLOGY AND HUMAN PERFORMANCE: CURRENT RESEARCH AND TRENDS LA English DT Meeting Abstract CT 3rd Conference on Automation Technology and Human Performance CY MAR 25-28, 1998 CL NORFOLK, VA SP Dept Psychol, Old Dominion Univ, Coll Sci, Old Dominion Univ, NASA Langley Res Ctr, Off Naval Res, Human Factors & Ergonom Soc, Tidewater Chapter C1 US FDA, CDRH, Off Surveillance & Biometr, Div Postmarket Surveillance, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 USA BN 0-8058-3135-5 PY 1999 BP 324 EP 325 PG 2 WC Computer Science, Cybernetics; Engineering, Industrial; Ergonomics; Psychology SC Computer Science; Engineering; Psychology GA BL92Z UT WOS:000077172900068 ER PT B AU Swayze, SC AF Swayze, SC BE Scerbo, MW Mouloua, M TI Technology and nursing: Electronic fetal monitors SO AUTOMATION TECHNOLOGY AND HUMAN PERFORMANCE: CURRENT RESEARCH AND TRENDS LA English DT Meeting Abstract CT 3rd Conference on Automation Technology and Human Performance CY MAR 25-28, 1998 CL NORFOLK, VA SP Dept Psychol, Old Dominion Univ, Coll Sci, Old Dominion Univ, NASA Langley Res Ctr, Off Naval Res, Human Factors & Ergonom Soc, Tidewater Chapter C1 US FDA, CDRH, Off Surveillance & Biometr, Div Postmarket Surveillance, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 USA BN 0-8058-3135-5 PY 1999 BP 324 EP 324 PG 1 WC Computer Science, Cybernetics; Engineering, Industrial; Ergonomics; Psychology SC Computer Science; Engineering; Psychology GA BL92Z UT WOS:000077172900067 ER PT B AU Parmentier, CM AF Parmentier, CM BE Scerbo, MW Mouloua, M TI Use error with infusion pumps: Misloading SO AUTOMATION TECHNOLOGY AND HUMAN PERFORMANCE: CURRENT RESEARCH AND TRENDS LA English DT Meeting Abstract CT 3rd Conference on Automation Technology and Human Performance CY MAR 25-28, 1998 CL NORFOLK, VA SP Dept Psychol, Old Dominion Univ, Coll Sci, Old Dominion Univ, NASA Langley Res Ctr, Off Naval Res, Human Factors & Ergonom Soc, Tidewater Chapter C1 US FDA, CDRH, Off Surveillance & Biometr, Div Postmarket Surveillance, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 USA BN 0-8058-3135-5 PY 1999 BP 326 EP 326 PG 1 WC Computer Science, Cybernetics; Engineering, Industrial; Ergonomics; Psychology SC Computer Science; Engineering; Psychology GA BL92Z UT WOS:000077172900069 ER PT J AU Davis, CC Barber, I Swicord, ML AF Davis, CC Barber, I Swicord, ML TI Food and Drug Administration low-level extremely-low-frequency magnetic field exposure facility SO BIOELECTROMAGNETICS LA English DT Article DE ELF; exposure system; Helmholtz coils; mu-metal screening; in vitro effects ID ELECTROMAGNETIC-FIELDS; HUMAN-CELLS; CONSTRAINTS; EXPRESSION; MYC AB We describe the design, construction details, and performance characteristics of an exposure system designed to provide very well controlled extremely-low-frequency magnetic field exposures of in vitro samples. This system uses Helmholtz coils placed inside temperature-controlled mu-metal chambers to provide simultaneous ac and de field exposures at any relative angle with minimal residual background field. The system has both exposed and sham-exposed chambers and is operated under computer control in such a way as to ensure blind exposure of samples. (C) 1999 Wiley-Liss, Inc. C1 Univ Maryland, Dept Elect Engn, College Pk, MD 20742 USA. Ctr Devices & Radiol Hlth, Rockville, MD USA. RP Davis, CC (reprint author), Univ Maryland, Dept Elect Engn, College Pk, MD 20742 USA. FU PHS HHS [223 92 6075] NR 17 TC 8 Z9 8 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0197-8462 J9 BIOELECTROMAGNETICS JI Bioelectromagnetics PY 1999 VL 20 IS 4 BP 203 EP 215 DI 10.1002/(SICI)1521-186X(1999)20:4<203::AID-BEM1>3.0.CO;2-L PG 13 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 187FC UT WOS:000079775400001 PM 10230934 ER PT J AU Blair, RM Fang, H Gaylor, D Sheehan, DM AF Blair, RM Fang, H Gaylor, D Sheehan, DM TI Analysis of dose-response data with the Michaelis-Menton equation, a fundamental equation of biologically based systems, and the no-threshold hypothesis. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 1999 VL 60 SU 1 MA 148 BP 139 EP 139 PG 1 WC Reproductive Biology SC Reproductive Biology GA 211CA UT WOS:000081141300213 ER PT J AU Branham, WS Blair, RM Dial, S Moland, C Hass, B Fang, H Tong, W Shi, L Perkins, R Sheehan, DM AF Branham, WS Blair, RM Dial, S Moland, C Hass, B Fang, H Tong, W Shi, L Perkins, R Sheehan, DM TI Use of quantitative structure-activity relationships (QSAR) to predict relative binding affinities (RBAs) of phytoestrogens for rat uterine estrogen receptor (ER) and estrogen binding proteins in rat amniotic fluid and human pregnancy plasma. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Div Genet & Reprod Technol, Jefferson, AR USA. ROW Sci Inc, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1999 VL 60 SU 1 MA 341 BP 199 EP 199 PG 1 WC Reproductive Biology SC Reproductive Biology GA 211CA UT WOS:000081141300404 ER PT J AU Chen, JJ Kodell, RL AF Chen, JJ Kodell, RL TI A decision-tree strategy for combining diagnostic tests for prediction SO BIOMETRICAL JOURNAL LA English DT Article DE classification; decision-tree; negative predictivity; positive predictivity ID CARCINOGENICITY; TOXICITY; ACCURACY AB In the context of medical screening, various diagnostic tests have been developed for determining whether a disease is present in an individual. Similarly, in the context of toxicological screening, a variety of short-term assays have been developed to predict whether a chemical would be carcinogenic if tested in a long-term bioassay. In both contexts, it is a challenge to combine the results of several predictive tests in a way that improves on the predictivity of the individual tests. Increases in positive predictivity can be accompanied by decreases in negative predictivity, and vice versa. This article presents a decision-tree classification model for combining results from several independent short-term or diagnostic tests to quantify the likelihood of a true positive result (patient has disease, or chemical is carcinogenic). The decision-tree strategy determines the most advantageous sequence for conducting the predictive tests. The classification model is based on statistical confidence limits on the predictive probability of disease (carcinogenicity) rather than on the central estimate of the predictive probability. This model is applied to the assessment of the abilities of four short-term tests in the prediction of chemical carcinogenicity under the assumption of independence among the four tests, and is used to demonstrate a testing strategy for the application of three pancreatic cancer diagnostic tests. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 16 TC 1 Z9 1 U1 0 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1999 VL 41 IS 2 BP 235 EP 250 DI 10.1002/(SICI)1521-4036(199905)41:2<235::AID-BIMJ235>3.0.CO;2-U PG 16 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 192BA UT WOS:000080056600007 ER PT J AU Rubin, SA Sylves, P Vogel, M Pletnikov, M Moran, TH Schwartz, GJ Carbone, KM AF Rubin, SA Sylves, P Vogel, M Pletnikov, M Moran, TH Schwartz, GJ Carbone, KM TI Borna disease virus-induced hippocampal dentate gyrus damage is associated with spatial learning and memory deficits SO BRAIN RESEARCH BULLETIN LA English DT Article DE virus; rat; behavior; brain; Morris water maze ID WATER-MAZE; AGED RATS; HIPPOCAMPECTOMIZED RATS; SYNAPTIC PLASTICITY; AFFECTIVE-DISORDERS; BIPOLAR DISORDER; WORKING MEMORY; INFECTION; SCHIZOPHRENIA; ENCEPHALITIS AB In neonatally inoculated rats, Borna disease virus (BDV) leads to a persistent infection of the brain in the absence of an inflammatory response and is associated with neuroanatomic, developmental, physiologic, and behavioral abnormalities. One of the most dramatic sites of BDV-associated damage in the neonatal rat brain is the dentate gyrus, a neuroanatomic region believed to play a major role in spatial learning and memory. The absence of a generalized inflammatory response to neonatal BDV infection permits direct effects of viral damage to the dentate gyrus to be examined. in this report, neonatally BDV-infected rats at various stages of dentate gyrus degeneration were evaluated in the Morris water maze, a swimming test that assesses the rats' capacity to navigate by visual cues. Our data demonstrate progressive spatial learning and memory deficits in BDV-infected rats that coincided with a gradual decline in the estimated hippocampal dentate gyrus neuron density. (C) 1999 Elsevier Science Inc. C1 US FDA, Ctr Biol Evaluat & Res, OVRR, DVP, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Maryland Psychiat Res Inst, Catonsville, MD USA. RP Carbone, KM (reprint author), US FDA, Ctr Biol Evaluat & Res, OVRR, DVP, Bldg 29A,Room 1A21,8800 Rockville Pike, Bethesda, MD 20892 USA. EM carbonek@a1.cber.fda.gov OI Vogel, Michael/0000-0002-8402-1495 FU NIMH NIH HHS [MH48948] NR 65 TC 57 Z9 59 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD JAN 1 PY 1999 VL 48 IS 1 BP 23 EP 30 DI 10.1016/S0361-9230(98)00133-6 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 182LX UT WOS:000079501400003 PM 10210164 ER PT J AU Myers, MR Lytle, CD Routson, LB AF Myers, MR Lytle, CD Routson, LB TI A mathematical model for simulating virus transport through synthetic barriers SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article ID PARTICLE DEPOSITION; LAMINAR-FLOW; CYLINDRICAL CHANNELS; PARALLEL-PLATE; ADSORPTION; CONDOMS AB Synthetic barriers such as gloves, condoms and masks are widely used in efforts to prevent disease transmission. Due to manufacturing defects tears arising during use, or material porosity, there is inevitably a risk associated with use of these barriers. An understanding of virus transport through the relevant passageways would be valuable in quantifying the risk. However, experimental investigations involving such passageways are difficult to perform, owing to the small dimensions involved. This paper presents a mathematical model for analyzing and predicting virus transport through barriers. The model incorporates a mathematical description of the mechanisms of virus transport, which include carrier-fluid flow, Brownian motion, and attraction or repulsion via virus-barrier interaction forces. The critical element of the model is the empirically determined rate constant characterizing the interaction force between the virus and the barrier. Once the model has been calibrated through specification of the rate constant, it can predict virus concentration under a wide variety of conditions. The experiments used to calibrate the model are described, and the rate constants are given for four bacterial viruses interacting with a latex membrane in saline. Rate constants were also determined for different carrier-fluid salinities, and the salt concentration was found to have a pronounced effect. Validation experiments employing laser-drilled pores in condoms were also performed to test the calibrated model. Model predictions of amount of transmitted virus through the drilled holes agreed well with measured values. Calculations using determined rate constants show that the model can help identify situations where barrier-integrity tests could significantly underestimate the risk associated with barrier use. (C) 1999 Society for Mathematical Biology. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy,HFZ-132, Rockville, MD 20852 USA. EM mrm@cdrh.fda.gov NR 25 TC 6 Z9 7 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 1999 VL 61 IS 1 BP 113 EP 140 DI 10.1006/bulm.1998.0080 PG 28 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 168ED UT WOS:000078677600005 PM 10071512 ER PT J AU Kaferstein, F Abdussalam, M AF Kaferstein, F Abdussalam, M TI Food safety in the 21st century SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article AB The global importance of food safety is not fully appreciated by many public health authorities despite a constant increase in the prevalence of foodborne illness. Numerous devastating outbreaks of salmonellosis, cholera, enterohaemorrhagic Escherichia coli infections, hepatitis A and other diseases have occurred in both industrialized and developing countries. In addition, many of the re-emerging or newly recognized pathogens are foodborne or have the potential of being transmitted by food and/or drinking water. More foodborne pathogens can be expected because of changing production methods, processes, practices and habits. During the early 21st century, foodborne diseases can be expected to increase, especially in developing countries, in part because of environmental and demographic changes. These vary from climatic changes, changes in microbial and other ecological systems, to decreasing freshwater supplies. However, an even greater challenge to food safety will come from changes resulting directly in degradation of sanitation and the immediate human environment. These include the increased age of human populations, unplanned urbanization and migration and mass production of food due to population growth and changed food habits. Mass tourism and the huge international trade in food and feed is causing food and feedborne pathogens to spread transnationally. As new toxic agents are identified and new toxic effects recognized, the health and trade consequences of toxic chemicals in food will also have global implications. Meeting the huge challenge of food safety in the 21st century will require the application of new methods to identify, monitor and assess foodborne hazards. Both traditional and new technologies for assuring food safety should be improved and fully exploited. This needs to be done through legislative measures where suitable, but with much greater reliance on voluntary compliance and education of consumers and professional food handlers. This will be an important task for the primary health care system aiming at "health for all". C1 US FDA, Food Safety & Inspect Serv, Joint Inst Food Safety & Appl Nutr, Washington, DC 20204 USA. WHO, Programme Food Safety & Food Aid, CH-1211 Geneva 27, Switzerland. RP Kaferstein, F (reprint author), US FDA, Food Safety & Inspect Serv, Joint Inst Food Safety & Appl Nutr, 200 C St SW,HFS-6, Washington, DC 20204 USA. NR 15 TC 55 Z9 60 U1 1 U2 9 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA DISTRIBUTION AND SALES, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 1999 VL 77 IS 4 BP 347 EP 351 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 194KG UT WOS:000080191000009 PM 10327714 ER PT J AU Taffs, RE Enterline, JC Rusmil, K Muhilal Suwardi, SS Rustama, D Djatnika Cobra, C Semba, RD Cohen, N Asher, DM AF Taffs, RE Enterline, JC Rusmil, K Muhilal Suwardi, SS Rustama, D Djatnika Cobra, C Semba, RD Cohen, N Asher, DM TI Oral iodine supplementation does not reduce neutralizing antibody responses to oral poliovirus vaccine SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article ID IMMUNE-RESPONSE; INFANTS; IMMUNOGENICITY; IMMUNIZATION; DEFICIENCY AB Iodine deficiency is a major cause of impaired mental development, goitre, and cretinism in many parts of the world. Because existing immunization programmes can be used to deliver oral iodized oil (010) to infants at risk, it was important to know whether 010 could adversely affect the antibody response to vaccines, such as trivalent oral poliovirus vaccine (OPV). A randomized, double-blind, placebo-controlled clinical trial was conducted in Subang, West Java, Indonesia, in which 617 eight-week-old infants received either 010 or a placebo (poppy-seed oil) during a routine visit for their first dose of OPV as part of the Expanded Programme on Immunization (EPI). The infants received two boosters of OPV at 4-week intervals after the first dose, and were followed up when 6 months old. Neutralizing antibody titres to poliovirus serotypes 1, 2, and 3 were com pared in serum samples that were ta ken from 478 of these infants just before the first dose of OPV and at 6 months. It was found that oral iodized oil did not reduce the antibody responses to any of the three serotypes of OPV. These results indicate that oral iodine may safely be delivered to infants at the same time as oral poliovirus vaccine according to current EPI immunization schedules. C1 US FDA, Ctr Biol Evaluat & Res, Lab Method Dev, Rockville, MD 20857 USA. Univ Pajajaran, Hasan Sadikin Hosp, Dept Paediat, Bandung, Indonesia. Minist Hlth, Nutr Res & Dev Ctr, Bogor, Indonesia. World Bank, Int Finance Corp, Washington, DC USA. Johns Hopkins Sch Med, Dept Ophthalmol, Baltimore, MD USA. Focus Asia, Jakarta, Indonesia. RP Taffs, RE (reprint author), HFM 255,1401 Rockville Pike, Rockville, MD 20852 USA. NR 24 TC 4 Z9 4 U1 0 U2 1 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA DISTRIBUTION AND SALES, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 1999 VL 77 IS 6 BP 484 EP 491 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 212RF UT WOS:000081229500006 PM 10427933 ER PT J AU Altekruse, SF Henley, SJ Thun, MJ AF Altekruse, SF Henley, SJ Thun, MJ TI Deaths from hematopoietic and other cancers in relation to permanent hair dye use in a large prospective study (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE hair-dye; multiple myeloma; non-Hodgkin's lymphoma ID COLORING PRODUCTS; MULTIPLE-MYELOMA; RISK; MORTALITY; LYMPHOMA; WOMEN; MEN AB Objectives: To assess in a large prospective study whether women who used permanent hair dye, especially dark dye for many years, experienced increased death rates from hematopoietic and other cancers that have been associated with hair dye use in some previous reports. Methods: In 1982, 547,586 women provided information on use of permanent hair dye and other lifestyle factors when enrolled in an American Cancer Society (ACS) prospective study. We extended mortality follow-up from 7 to 12 years. Using Cox proportional hazards modeling we compared death rates from hematopoietic and other cancers among women according to their hair dye use at baseline with death rates in unexposed women. Results: The adjusted death rate from all cancers combined was marginally lower among women who ever used hair dye than nonusers (relative risk [RR] = 0.9; 95% confidence interval [CI] = 0.9-1.0). Mortality from all hematopoietic cancers was marginally higher among users than nonusers (RR = 1.1; CI = 1.0-1.2), and increased with an index that combined duration of use and darker coloration (test of trend p = 0.02). Women who used black or brown dye for 10 or more years experienced somewhat higher death rates from non-Hodgkin's lymphoma and (for black dye only) multiple myeloma. The temporal increase in death rates from non-Hodgkin's lymphoma and multiple myeloma between 1982-88 and 1989-94 was similar for women in our study who never used hair dyes to the increase among all US women. Conclusions: If prolonged use of dark permanent hair dyes contributes to death rates from non-Hodgkin's lymphoma and multiple myeloma, then the increase is small and difficult to detect reliably even in large prospective studies. The use of permanent hair dye is unlikely to be a major contributor to the temporal rise in non-Hodgkin's lymphoma and multiple myeloma in the US. C1 Amer Canc Soc, Atlanta, GA 30329 USA. US FDA, Washington, DC 20204 USA. RP Thun, MJ (reprint author), Amer Canc Soc, 1599 Clifton Rd, Atlanta, GA 30329 USA. RI Henley, Jane/A-4698-2010 NR 21 TC 52 Z9 55 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PY 1999 VL 10 IS 6 BP 617 EP 625 DI 10.1023/A:1008926027805 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 255WJ UT WOS:000083692900014 PM 10616830 ER PT J AU Moysich, KB Shields, PG Freudenheim, JL Schisterman, EF Vena, JE Kostyniak, P Greizerstein, H Marshall Jr Graham, S Ambrosone, CB AF Moysich, KB Shields, PG Freudenheim, JL Schisterman, EF Vena, JE Kostyniak, P Greizerstein, H Marshall, JR Graham, S Ambrosone, CB TI Polychlorinated biphenyls, cytochrome P4501A1 polymorphism, and postmenopausal breast cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LUNG-CANCER; CYP1A1; WOMEN; PESTICIDES; RESIDUES; SERUM; PCBS AB In experimental systems, polychlorinated biphenyls (PCBs) induce cytochrome P4501A1 (CYP1A1), which is involved in metabolism of steroid hormones and polycyclic aromatic hydrocarbons in humans. A genetic polymorphism coding for a valine to isoleucine substitution in exon 7 has been associated with lung cancer risk in Japanese populations. In a previous study, we found no association between CYP1A1 genotype and breast cancer risk. However, we were interested in determining whether genotype would relate to risk when PCB body burden was taken into account. In a subset of a ease-control study in western New York, 154 postmenopausal women with incident, primary, histologically confirmed postmenopausal breast cancer and 192 community controls were interviewed and underwent phlebotomy. Serum levels of 56 PCB peaks were determined by high resolution gas chromatography with electron capture. PCR-RFLP analyses of the CYP1A1 polymorphism were performed. Unconditional logistic regression was used to compute adjusted odds ratios and 95% confidence intervals. Among women with serum PCB levels above the median of the distribution in the control group, there was increased risk of breast cancer associated with the presence of at least one valine allele, compared with women who were homozygous for the isoleucine alleles (odds ratio, 2.93; 95% confidence interval, 1.17-7.36), Among women with low PCB body burden, no association between CYP1A1 genotype and breast cancer risk was observed, Adjustment for serum lipids and body mass index did not affect the magnitude of the observed associations. PCB body burden may modify the effect of the polymorphism on postmenopausal breast cancer risk through increased CYP1A1 enzyme induction or by activation by specific PCB congeners, These results should be considered preliminary, pending replication by other studies. C1 SUNY Buffalo, Dept Social & Prevent Med, 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), New York State Dept Hlth, Roswell Pk Canc Inst, Dept Canc Prevent Epidemiol & Biostat, Elm & Carlton St, Buffalo, NY 14263 USA. EM kmoysich@sc3103.med.buffalo.edu RI Shields, Peter/I-1644-2012; OI Schisterman, Enrique/0000-0003-3757-641X FU NCI NIH HHS [CA11535]; NIDA NIH HHS [DAMD-95-1-5022, DAMD1 7-94-J-4108] NR 29 TC 101 Z9 106 U1 2 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 1999 VL 8 IS 1 BP 41 EP 44 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 158LC UT WOS:000078116100006 PM 9950238 ER PT J AU Hammons, GJ Yan, Y Lopatina, NG Jin, B Wise, C Blann, EB Poirier, LA Kadlubar, FF Lyn-Cook, BD AF Hammons, GJ Yan, Y Lopatina, NG Jin, B Wise, C Blann, EB Poirier, LA Kadlubar, FF Lyn-Cook, BD TI Increased expression of hepatic DNA methyltransferase in smokers SO CELL BIOLOGY AND TOXICOLOGY LA English DT Article DE human DNA methyltransferase; smoking ID CYTOSINE-DNA; COLON-CANCER; SIGNALING PATHWAY; METHYLATION; CELLS; PROGRESSION; INHIBITION; NEOPLASIA; LIVER; ASSAY AB The DNA methyltransferase enzyme (DNA MTase) catalyzes DNA methylation at cytosines in CpG dinucleotides. 5-Methylcytosine modification of DNA is important in gene regulation, DNA replication, chromatin organization and disease. Increased levels of DNA MTase have been associated with the initiation and promotion of cancer. This study was conducted to assess whether cigarette smoking and other factors, such as age and gender, influence DNA MTase expression in nontumorous tissue. DNA MTase was significantly (p < 0.05) higher in samples from cigarette smokers; the mean level of DNA MTase mRNA was almost 2-fold higher in these samples than in those from nonsmokers. Levels of DNA MTase mRNA were higher in samples from females than in those from males, but the difference was not statistically significant. Age was not associated with DNA MTase levels. Increased levels of DNA MTase in individuals who smoke may indicate a greater susceptibility to the risk of cancer since increased levels of this enzyme are found in cancer cell lines and human tumors. The results of this study suggest that further investigations of increased expression of this enzyme as a predisposing factor for cancer susceptibility are needed. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Lyn-Cook, BD (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, HFT-100, Jefferson, AR 72079 USA. NR 41 TC 16 Z9 18 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0742-2091 J9 CELL BIOL TOXICOL JI Cell Biol. Toxicol. PY 1999 VL 15 IS 6 BP 389 EP 394 DI 10.1023/A:1007658000971 PG 6 WC Cell Biology; Toxicology SC Cell Biology; Toxicology GA 301PM UT WOS:000086318600007 PM 10811534 ER PT J AU Katta, SK Jackson, LS Sumner, SS Hanna, MA Bullerman, LB AF Katta, SK Jackson, LS Sumner, SS Hanna, MA Bullerman, LB TI Effect of temperature and screw speed on stability of fumonisin B(1) in extrusion-cooked corn grits SO CEREAL CHEMISTRY LA English DT Article ID HUMAN ESOPHAGEAL CANCER; FUSARIUM-MONILIFORME; MYCOTOXINS; COOKING; FOODS; EXPANSION; TOXICITY; PRODUCT; RATS; LEUKOENCEPHALOMALACIA AB Corn grits spiked with fumonisin B(1) (FB(1)) at a level of 5 mu g/g were extrusion cooked in a corotating twin-screw extruder at different temperatures (140, 160, 180, and 200 degrees C) and screw speeds (40, 80, 120, and 160 rpm). Good recoveries of FB(1) were obtained from the nonextruded as well as the extruded grits by using high-performance liquid chromatography. Both the barrel temperature and the screw speed significantly (P less than or equal to 0.05) affected the extent of fumonisin reduction in extruded grits. As expected, the FB(1) recovered decreased with an increase in temperature and a decrease in screw speed. The amount of FB(1) lost from cooking grits at the different extrusion parameters used in this study ranged from 34 to 95%. About 46-76% of the spiked FB(1) was lost when the grits were cooked at temperatures and screw speeds that resulted in acceptable product expansion and color. C1 Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. Univ Nebraska, Dept Biol Syst Engn, Lincoln, NE 68583 USA. RP Bullerman, LB (reprint author), Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. EM lbullerman@foodsci.unl.edu NR 47 TC 42 Z9 44 U1 1 U2 4 PU AACC INTERNATIONAL PI ST PAUL PA 3340 PILOT KNOB RD, ST PAUL, MN 55121-2097 USA SN 0009-0352 J9 CEREAL CHEM JI Cereal Chem. PD JAN-FEB PY 1999 VL 76 IS 1 BP 16 EP 20 DI 10.1094/CCHEM.1999.76.1.16 PG 5 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 161PD UT WOS:000078296900005 ER PT J AU Beland, FA Doerge, DR Churchwell, MI Poirier, MC Schoket, B Marques, MM AF Beland, FA Doerge, DR Churchwell, MI Poirier, MC Schoket, B Marques, MM TI Synthesis, characterization, and quantitation of a 4-aminobiphenyl-DNA adduct standard SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CARCINOGEN-DNA ADDUCTS; P-32 POSTLABELING ASSAY; P-32-POSTLABELING ANALYSIS; SENSITIVITY; RADIOIMMUNOASSAY; CHROMATOGRAPHY; ENHANCEMENT; METABOLITES; INVIVO; CELLS AB P-32-Postlabeling is a powerful technique for the detection of DNA adducts; however, quantitation of DNA adducts by this method can result in errors due to differences in hydrolysis and labeling efficiencies between adducted and normal nucleotides. We have synthesized a DNA sample modified with 4-aminobiphenyl to serve as a quantitation standard for P-32- postlabeling and other DNA adduct detection methodologies. [2,2'-H-3]-N-Hydroxy-4-aminobiphenyl was reacted with calf thymus DNA at pH 5 to give 62 +/- 0.8 adducts/10(8) nucleotides (mean +/- SD) on the basis of H-3 content. HPLC analyses following enzymatic hydrolysis to nucleosides indicated one major adduct, N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP). The adduct identity was confirmed by HPLC/electrospray ionization mass spectrometry, which indicated a modification level of 19 +/- 1.7 dG-C8-4-ABP/10(8) nucleotides. P-32-Postlabeling analysis gave a value of 0.84 dG-C8-4-ABP/10(8) nucleotides, while a dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) indicated levels of 82 +/- 26 and 63 +/- 20 dG-C8-4ABP/10(8) nucleotides after enzymatic hydrolysis to nucleotides and nucleosides, respectively. The utility of the DNA adduct standard was determined by assessing the level of dG-C8-4-ABP in liver DNA from mice treated with [2,2'-H-3]-4-aminobiphenyl. P-32-Postlabeling analyses, based upon measuring the extent of the P-32 incorporation, underestimated the levels of dG-C8-4-ABP, while DELFIA, using a G-C8-4-ABP quantitation standard, overestimated the adduct levels. The adduct levels determined by HPLC/electrospray ionization mass spectrometry best; reflected those obtained from H-3 incorporation. When the P-32-postlabeling analyses and the DELFIA were conducted using the DNA modified in vitro with dG-C8-4-ABP as a quantitation standard, accurate estimations of the extent of in vivo formation of dG-C8-4-ABP were obtained. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. Natl Inst Environm Hlth, Dept Biochem, H-1097 Budapest, Hungary. Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110, Jefferson, AR 72079 USA. EM fbeland@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 30 TC 55 Z9 55 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 1999 VL 12 IS 1 BP 68 EP 77 DI 10.1021/tx980172y PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 159FE UT WOS:000078160600008 PM 9894020 ER PT J AU Ueyama, T Gu, XX Tsai, CM Karpas, AB Lim, DJ AF Ueyama, T Gu, XX Tsai, CM Karpas, AB Lim, DJ TI Identification of common lipooligosaccharide types in isolates from patients with otitis media by monoclonal antibodies against nontypeable Haemophilus influenzae 9274 SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID NONTYPABLE HEMOPHILUS-INFLUENZAE; DETOXIFIED LIPOOLIGOSACCHARIDE; NEISSERIA-MENINGITIDIS; LIPOPOLYSACCHARIDES; PROTEINS; STRAIN; CELLS AB Twenty-one murine monoclonal antibodies (MAbs) were induced by nontypeable Haemophilus influenzae (NTHi) 9274, Nineteen MAbs were specific for the lipooligosaccharide (LOS) as determined by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. When the MAbs were assayed with five LOS prototype strains by ELISA, all bound to strain 3198 LOS (type III), while six of the MAbs were also reactive with LOSs from strain 1479 (type I), 5657 (type IV), or 7502 (type V). Ten MAbs had complement-mediated bactericidal activity, and three MAbs were opsonophagocytic against the homologous strain. Five LOS MAbs with different specificities were used to analyze 155 NTHi clinical isolates from the United States and from Japan. These isolates were classified into nine groups by ELISA. Only four isolates (2.6%) were not recognized by any of the five MAbs. Most of the isolates (91.6%) were in four groups which bound three of the live MAbs. One of three MAbs, 6347C11, had strong activity against the homologous strain and was also bactericidal to 45 clinical isolates (29%) which belonged to the four common patterns (25 belonged to pattern 1). These data indicate that these MAbs can be used for LOS typing in which almost all NTNi strains can be typed according to the LOS antigenicity. Among NTHi, at least one conserved LOS epitope which is a target of bactericidal antibodies exists. We conclude that strain 9274 LOS, which is the target for bactericidal antibodies, is a candidate for LOS-based NTHi vaccines. C1 NIDCD, Immunol Lab, NIH, Rockville, MD 20850 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NICHHD, Dev & Mol Immun Lab, Bethesda, MD 20892 USA. RP Gu, XX (reprint author), NIDCD, Immunol Lab, NIH, 5 Res Ct,2A31, Rockville, MD 20850 USA. EM guxx@nidcd.nih.gov NR 25 TC 11 Z9 11 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 JAN PY 1999 VL 6 IS 1 BP 96 EP 100 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 156BE UT WOS:000077980900017 PM 9874671 ER PT J AU Meyerhoff, A AF Meyerhoff, A TI US Food and Drug Administration approval of AmBisome (liposomal amphotericin B) for treatment of visceral leishmaniasis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; KALA-AZAR; SODIUM STIBOGLUCONATE; ANTIMONY; AMASTIGOTES; PENTOSTAM; DONOVANI; REGIMENS; INDIA AB In August 1997, AmBisome (liposomal amphotericin B, Nexstar, San Dimas, CA) was the first drug approved for the treatment of visceral leishmaniasis by the U.S. Food and Drug Administration. The growing recognition of emerging and reemerging infections warrants that safe and effective agents to treat such infections he readily available in the United States. The following discussion of the data submitted in support of the New Drug Application for AmBisome for the treatment of visceral leishmaniasis shows the breadth of data from clinical trials that can be appropriate to support approval for drugs to treat tropical diseases. C1 US FDA, Div Special Pathogens & Immunol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. RP Meyerhoff, A (reprint author), US FDA, Div Special Pathogens & Immunol Drug Prod, Ctr Drug Evaluat & Res, 9201 Corp Blvd HFD-590, Rockville, MD 20850 USA. NR 23 TC 131 Z9 132 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN PY 1999 VL 28 IS 1 BP 42 EP 48 DI 10.1086/515085 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 162RE UT WOS:000078359900009 PM 10028069 ER PT J AU Mahmood, I Balian, JD AF Mahmood, I Balian, JD TI The pharmacokinetic principles behind scaling from preclinical results to phase I protocols SO CLINICAL PHARMACOKINETICS LA English DT Review ID METABOLIC-CLEARANCE; INTERSPECIES CORRELATION; PLASMA BINDING; RHESUS-MONKEYS; VITRO DATA; HUMANS; PARAMETERS; DRUGS; RATS; DOG AB Extrapolation of animal data to assess pharmacokinetic parameters in humans is an important tool in drug development. Allometric scaling has many proponents, and many different approaches and techniques have been proposed to optimise the prediction of pharmacokinetic parameters from animals to humans. The allometric approach is based on the power function Y = aW(b), where the bodyweight of the species is plotted against the pharmacokinetic parameter of interest on a log-logs scale. Clearance, volume of distribution and elimination half-life are the 3 most frequently extrapolated pharmacokinetic parameters. Clearance is not predicted very well terror between predicted and observed clearance >30%) using the basic allometric equation in most cases. Thus, several other approaches have been proposed. An early approach was the concept of neoteny, where the clearance is predicted on the basis of species bodyweight and maximum life-span potential. A second approach uses a 2-term power equation based on brain and bodyweight to predict the intrinsic clearance of drugs that are primarily eliminated by phase I oxidative metabolism. Most recently, the use of the product of brain weight and clearance has been proposed. A literature review reveals different degrees of success of improved prediction with the different methods for various drugs. In a comparative study, the determining factor in selecting a method for prediction of clearance was found to be the value of the exponent. Integration of in vitro data into in vivo clearance to improve the predictive performance of clearance has also been suggested. Although there are proponents of using body surface area instead of bodyweight, no advantage has been noted in this approach. It has also been noted that the unbound clearance of a drug cannot be predicted any better than the total body clearance (CL). In general, there is a good correlation between bodyweight and volume of the central compartment (V-c); hence, V-c does not face the same complications as CL. The relationship between elimination half-life (t1/2 beta) and bodyweight across species results in poor correlation, most probably because of the hybrid nature of this parameter. When a reasonable prediction of CL and V-c is made, t1/2 beta may be predicted from the equation t1/2 beta = 0.693V(c)/CL. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1 HFD860, Woodmont Off Ctr 2, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1 HFD860, Woodmont Off Ctr 2, Room 4079,1451 Rockville Pike, Rockville, MD 20852 USA. EM Mahmoodi@CDER.FDA.GOV NR 58 TC 49 Z9 50 U1 0 U2 3 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PD JAN PY 1999 VL 36 IS 1 BP 1 EP 11 DI 10.2165/00003088-199936010-00001 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 162WG UT WOS:000078369600001 PM 9989339 ER PT J AU Ajayi, FO Brewer, T Greenfield, R Fleckenstein, L AF Ajayi, FO Brewer, T Greenfield, R Fleckenstein, L TI Absolute bioavailability of halofantrine-HCl: Effect of ranitidine and pentagastrin treatment SO CLINICAL RESEARCH AND REGULATORY AFFAIRS LA English DT Article ID FALCIPARUM-MALARIA; FOOD; PHARMACOKINETICS; WR-171,669 AB The first part of this study dealt with determination of the absolute oral bioavailability of halofantrine using six beagle dogs that were randomly assigned to two groups. The beagles in Group I had a single 5 mg/kg intravenous dose of halofantrine in the first period and a single 250 mg oral dose of halofantrine tablet in the second period with a washout period of six weeks. Those in Group II received the intravenous and oral doses in the opposite order. The effect of gastric pH on the absolute bioavailability was evaluated in the second part of the study. Six beagles received a single 5 mg/kg intravenous dose in the first period. They were randomly assigned to two groups six weeks after the intravenous dose. Those in Group I had 6 mu g/kg pentagastrin intravenously 30 minutes before a single 259 mg oral dose of halofantrine tablet in the second period. They received 2.5 mg/kg intramuscular doses of ranitidine 10 and 2 hours before a single 250 mg oral dose of halofantrine tablet in the third period. Those in Group II received the above treatments in opposite order. A six weeks washout period separated treatment periods two and three. Blood samples were obtained at specified times over 28 days following drug administration. Quantitation of halofantrine in plasma was by HPLC using fluorescence detection. The absolute oral bioavailability by AUC of halofantrine was low and highly variable with a mean (+/-SD) of 6.3 (4.7)% A value of 7.9 (5.2)%, not significantly different from control, was observed following inhibition of gastric acid secretion by ranitidine. However, statistically significant (p less than or equal to 0.05) increases in halofantrine bioavailability with a value of 16.1 (7.0)% was observed following stimulation of gastric acid secretion by pentagastrin. C1 Walter Reed Army Inst Res, Div Expt Therapeut, Washington, DC 20307 USA. RP Ajayi, FO (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. OI Fleckenstein, Lawrence/0000-0001-5320-4531 NR 16 TC 3 Z9 3 U1 1 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1060-1333 J9 CLIN RES REGUL AFF JI Clin. Res. Regul. Affairs PY 1999 VL 16 IS 1-2 BP 13 EP 28 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 199LU UT WOS:000080484200003 ER PT J AU Alizadeh, A Eisen, M Davis, RE Ma, C Sabet, H Tran, T Powell, JI Yang, L Marti, GE Moore, DT Hudson, JR Chan, WC Greiner, T Weisenburger, D Armitage, JO Lossos, I Levy, R Botstein, D Brown, PO Staudt, LM AF Alizadeh, A Eisen, M Davis, RE Ma, C Sabet, H Tran, T Powell, JI Yang, L Marti, GE Moore, DT Hudson, JR Chan, WC Greiner, T Weisenburger, D Armitage, JO Lossos, I Levy, R Botstein, D Brown, PO Staudt, LM TI The lymphochip: A specialized cDNA microarray for the genomic-scale analysis of gene expression in normal and malignant lymphocytes SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 64th Symposia: Signaling and Gene Expression in the Immune System CY JUN 02-07, 1999 CL NEW YORK, NEW YORK SP Alafi Capital Co, Amgen Inc, BASF Biores Corp, Bayer Corp, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med, Diagnost Prod Corp, Du Pont Pharmaceut Co, Forest Labs, Genentech Inc, Genet Inst, Glaxo Wellcome Inc, Hoechst Marion Roussel, Hoffmann La Roche Inc, Johnson & Johnson, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Parke Davis Pharmaceut Res, PE Biosyst, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genet Inc, Schering Plough Corp, SmithKline Beecham Pharmaceut, Wyeth Ayerst Res, Zeneca Grp PLC ID B-CELL LINE; OLIGONUCLEOTIDE ARRAYS; GERMINAL-CENTERS; DNA MICROARRAY; PATTERNS; MUTATION; HYPERMUTATION; HYBRIDIZATION; LYMPHOMAS; EXPANSION C1 NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94035 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94035 USA. Stanford Univ, Sch Med, Dept Med, Stanford, CA 94035 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94035 USA. NIH, Bioinformat & Mol Anal Sect, CBEL, CTT, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Res Genet Inc, Huntsville, AL 35801 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Med, Omaha, NE 68198 USA. RP Alizadeh, A (reprint author), NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. OI Eisen, Michael/0000-0002-7528-738X; Alizadeh, Arash Ash/0000-0002-5153-5625 NR 32 TC 182 Z9 187 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1999 VL 64 BP 71 EP 78 DI 10.1101/sqb.1999.64.71 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 317KW UT WOS:000087225400011 PM 11232339 ER PT J AU Zheng, Q AF Zheng, Q TI Solution to the hazard function of some two-stage carcinogenesis models when normal cell growth is piecewise linear SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE carcinogenesis model; hazard function ID SURVIVAL AB A closed form expression is obtained for the hazard function for three stochastic two-stage carcinogenesis models, when the normal cell growth is assumed to be piecewise linear. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 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 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 1999 VL 28 IS 8 BP 1921 EP 1929 DI 10.1080/03610929908832395 PG 9 WC Statistics & Probability SC Mathematics GA 215BH UT WOS:000081361700011 ER PT J AU Chen, HZ Piantadosi, S AF Chen, HZ Piantadosi, S TI Uniqueness of permuted treatment estimator distributions in the proportional hazards model SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE permutation tests; partial likelihood; proportional hazards; randomization procedure AB We discuss findings regarding the permutation distributions of treatment effect estimators in the proportional hazards model. For fixed sample size n, we will prove that all uncensored and untied event times yield the same permutation distribution of treatment effect estimators in the proportional hazards model. In other words this distribution is irrelevant with respect to the actual event times. We will show several uniqueness properties under different conditions. These properties are useful for small sample permutation tests and also helpful to large sample cases. C1 US FDA, Rockville, MD 20852 USA. Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. NR 6 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 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 1999 VL 28 IS 12 BP 2803 EP 2819 DI 10.1080/03610929908832451 PG 17 WC Statistics & Probability SC Mathematics GA 263JU UT WOS:000084122200002 ER PT S AU Wagner, RF Gagne, RM Myers, KJ Wear, KA AF Wagner, RF Gagne, RM Myers, KJ Wear, KA BE Doi, K MacMahon, H Giger, ML Hoffmann, KR TI Image quality issues for computer-aided diagnosis SO COMPUTER-AIDED DIAGNOSIS IN MEDICAL IMAGING SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 1st International Workshop on Computer-Aided Diagnosis CY SEP 20-23, 1998 CL CHICAGO, IL SP Aurora Technol, Deus Technol, LLC, Fuji Med Syst, GE Med Syst, Konica Corp, R2 Technol Inc, Siemens Med Engn Grp, Silicon Graph Inc, Toshiba Corp, Univ Chicago, Dept Radiol, Univ Chicago, Canc Res Ctr ID CLUSTERED MICROCALCIFICATIONS; OBJECTIVE ASSESSMENT; DIGITAL RADIOGRAPHY; WAVELET TRANSFORM; INFORMATION; MAMMOGRAMS; SYSTEMS; NOISE; SNR AB We present an overview of the contemporary objective approach to image quality assessment in diagnostic imaging. This approach uses the performance of algorithmic or computational model observers (M.O.) to assess image quality for specified detection and discrimination tasks. These observers are closely related to computational algorithms used in computer-aided diagnosis (CAD). To the extent that the M.O.s mimic CAD observers, they provide a basis for image quality assessment for systems used in CAD. 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 24 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50058-8 J9 INT CONGR SER PY 1999 VL 1182 BP 533 EP 542 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BP14T UT WOS:000084227800078 ER PT S AU Wagner, RF Mossoba, JT Chan, HP Sahiner, B Petrick, N AF Wagner, RF Mossoba, JT Chan, HP Sahiner, B Petrick, N BE Doi, K MacMahon, H Giger, ML Hoffmann, KR TI Finite-Sample dependence of classifier assessment in Computer-Aided Diagnosis SO COMPUTER-AIDED DIAGNOSIS IN MEDICAL IMAGING SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 1st International Workshop on Computer-Aided Diagnosis CY SEP 20-23, 1998 CL CHICAGO, IL SP Aurora Technol, Deus Technol, LLC, Fuji Med Syst, GE Med Syst, Konica Corp, R2 Technol Inc, Siemens Med Engn Grp, Silicon Graph Inc, Toshiba Corp, Univ Chicago, Dept Radiol, Univ Chicago, Canc Res Ctr ID VARIANCE; DESIGN; SIZE AB We present a brief review of a framework for understanding both the mean performance of a classifier as a function of the number of samples available for its training, as well as the expected variability of performance as a function of the number of training samples and the number of test samples. 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 9 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 SN 0531-5131 BN 0-444-50058-8 J9 INT CONGR SER PY 1999 VL 1182 BP 555 EP 560 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BP14T UT WOS:000084227800080 ER PT J AU Manch-Citron, JN Dey, A Schneider, R Nguyen, NY AF Manch-Citron, JN Dey, A Schneider, R Nguyen, NY TI The translational hop junction and the 5 ' transcriptional start site for the Prevotella loescheii adhesin encoded by plaA SO CURRENT MICROBIOLOGY LA English DT Article ID COLI TRPR GENE; SEQUENCE; EXPRESSION; MITOCHONDRIA AB The Prevotella loescheii adhesin gene, plaA, contains a coding gap between a small open reading frame (ORF-I) and a large open reading frame (ORF-2). Translation of the plaA mRNA requires bypassing this 29-nt coding gap on the plaA transcript. We have determined the N-terminal peptide sequence of the SO34 adhesin beyond the gap sequence. This sequence shows that the peptide junction between ORF-1 and ORF-2 is continuous in the adhesin and supports the conclusion that synthesis of the SO34 adhesin occurs by a ribosomal hop mechanism. To elucidate upstream signals, we used the 5' RACE (rapid amplification of cDNA ends) technique to map the start point of the plaA mRNA. DNA sequencing of plasmids with the 5' RACE products placed the 5' end of plaA mRNA 270 nt upstream from the plaA start codon. A region corresponding to a Bacteroides fragilis promoter consensus sequence precedes this start site. C1 Univ Missouri, Sch Dent, Dept Oral Biol, Kansas City, MO 64108 USA. US FDA, Ctr Biol Evaluat & Res, Food & Drug Adm, Bethesda, MD 20892 USA. RP Manch-Citron, JN (reprint author), Univ Missouri, Sch Dent, Dept Oral Biol, 650 E 25th St, Kansas City, MO 64108 USA. FU NIDCR NIH HHS [R29 DE11804] NR 32 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD JAN PY 1999 VL 38 IS 1 BP 22 EP 26 DI 10.1007/PL00006766 PG 5 WC Microbiology SC Microbiology GA 148HL UT WOS:000077499200004 PM 9841777 ER PT J AU Gubina, E Ruiz-Hidalgo, MJ Baladron, V Laborda, J AF Gubina, E Ruiz-Hidalgo, MJ Baladron, V Laborda, J TI Assignment of DLK1 to human chromosome band 14q32 by in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID REPEAT MOTIFS; PROTEIN; IDENTIFICATION; PREF-1 C1 US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Laborda, J (reprint author), US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 564,Bldg 29B-3NN04, Rockville, MD 20852 USA. RI Laborda, Jorge/L-5726-2014; Ruiz-Hidalgo, Maria/L-1956-2014; Baladron, Victoriano/L-1758-2014 OI Laborda, Jorge/0000-0002-9210-838X; Baladron, Victoriano/0000-0003-4574-8760 NR 7 TC 10 Z9 10 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1999 VL 84 IS 3-4 BP 206 EP 207 DI 10.1159/000015259 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 212AX UT WOS:000081195000018 PM 10393432 ER PT J AU Boykins, RA Oravecz, T Unsworth, E Syin, C AF Boykins, RA Oravecz, T Unsworth, E Syin, C TI Chemical synthesis and characterization of chemokine RANTES and its analogues SO CYTOKINE LA English DT Article DE analogues; chemical synthesis; chemokines; RANTES ID PROTEINS; PURIFICATION; LYMPHOCYTES; ANTAGONIST; INHIBITION; MCP-3; GENE AB RANTES, a polypeptide of 68 amino acid residues, is a member of the C-C chemokine subfamily including other monocyte chemoattractants such as MIP-1 alpha, MIP-1 beta, MCP-1, MCP-2 and MCP-3, To provide a chemically defined RANTES in quantity suitable for structure-function studies, RANTES and its analogues were synthesized, using a modified solid-phase chemistry approach. The fully protected RANTES and RANTES(3-68) were assembled by automated solid-phase methodology using Fmoc chemistry. Deprotection and cleavage of the resin bound peptides yielded crude peptides, which were then folded and further purified by reverse-phase HPLC. The chemically synthesized RANTES with its identity and purity established, was found to be immunochemically and functionally indistinguishable from the recombinant human RANTES, RANTES and its analog, RANTES(3-68), have recently been used as the substrate in the study of dipeptidyl peptidase IV (CD26)-mediated processing of RANTES and its effect on receptor specificity. (C) 1999 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Div Allergen Prod & Parasitol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Facil Biotechnol Resources, Bethesda, MD 20892 USA. RP Syin, C (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Allergen Prod & Parasitol, HFM-416,Bldg 29,Room 203,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 19 TC 3 Z9 3 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1043-4666 J9 CYTOKINE JI Cytokine PD JAN PY 1999 VL 11 IS 1 BP 8 EP 15 DI 10.1006/cyto.1998.0391 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 169ZW UT WOS:000078781300002 PM 10080874 ER PT J AU Lamb, LS Gee, AP Hazlett, LJ Musk, P Parrish, RS O'Hanlon, TP Geier, SS Folk, RS Harris, WG McPherson, K Lee, C Henslee-Downey, PJ AF Lamb, LS Gee, AP Hazlett, LJ Musk, P Parrish, RS O'Hanlon, TP Geier, SS Folk, RS Harris, WG McPherson, K Lee, C Henslee-Downey, PJ TI Influence of T cell depletion method on circulating gamma delta T cell reconstitution and potential role in the graft-versus-leukemia effect SO CYTOTHERAPY LA English DT Article DE gamma delta(+) T-cells; T-cell depletion; graft-versus-leukemia effect; flow cytometric analysis; bone marrow transplantation; disease-free survival ID BONE-MARROW TRANSPLANTATION; MISMATCHED RELATED DONORS; LYMPHOMA-CELLS; LYMPHOCYTES; ACTIVATION; CLONES; SUBSET AB Background Our laboratory previously reported that leukemia patients who developed greater than or equal to 10% gamma delta(+) T cells during the first six-months after receiving an anti-TCR alpha beta T-cell-depleted (TCD) graft from a partially mismatched related donor (PMRD) had a disease-free survival (DFS) advantage. These gamma delta(+) T cells were V delta 1(+)CD3(+)CD4(-)CD8(-)CD69(+)HLADR(+) and are cytotoxic to K562 cells. Methods In order to determine wheather the anti-alpha beta TCD regimen was associated with these findings, we recieved TCD PMRD grafts using gamma delta(+) T cells from patients who recieved TCD PMRD grafts using the anti-TCR alpha beta MAb T10B9-1A31 (previously reported) with similar patients who received grafts using the anti-CD3 MAb OKT3. Results Increased cytotoxic V delta 1(+) T cells were seen in 10 of 43 T10B9 TCD patients compared to 7 of 100 in the OKT3 TCP group (23% versus 7%, p = 0.010). T10B9 patients with incresed gamma delta(+) T cells also exhibited a higher range of increased gamma delta(+) T cells and the length of time the gamma delta(+) T cells remained high was longer when compared to OKT3 patients. Patients with increased gamma delta(+) T cells whose grafts were T-cell depleted with T-cell showed a significant decrease in relapse (p = 0.038). Similar rates and reduction in relapse were seen in OKT3 TCD patients, although significant was not reached due to the small number of patients with increased gamma delta(+) T cells. Estimated 3 year disease-free survival was significantly improved in T10B9 patients with increased gamma delta(+) T cells (0.79 versus 0.31, p = 0.009), a trend also seen in OKT3 patients (p = 0.091). Discussion These observations indicate that V delta 1(+)CD4(-)Cd8(-)cytotoxic T cells are associated with lower relapse rates and improved survival, and thus may have a role in a graft-versus-leukemia effect. C1 Univ S Carolina, Sch Med, Palmetto Richland Mem Hosp, Cell Anal & Sorting Lab,Div Transplantat Med, Columbia, SC 29203 USA. Baylor Coll Med, Ctr Gene Therapy, Houston, TX 77030 USA. S Carolina Canc Ctr, Div Biometry & Res Comp, Columbia, SC USA. US FDA, Bethesda, MD 20014 USA. RP Lamb, LS (reprint author), Univ S Carolina, Sch Med, Palmetto Richland Mem Hosp, Cell Anal & Sorting Lab,Div Transplantat Med, 7 Richland Med Pk, Columbia, SC 29203 USA. NR 30 TC 28 Z9 28 U1 0 U2 2 PU ISIS MEDICAL MEDIA LTD PI OXFORD PA 59 ST ALDATES, OXFORD OX1 1ST, ENGLAND SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 1999 VL 1 IS 1 BP 7 EP 19 DI 10.1080/0032472031000141295 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 277ZL UT WOS:000084963400004 PM 19746645 ER PT J AU Shohat, M Ben Amitai, D Shohat, B Mosberg, R Narinski, R Klein, T Okon, E Roizman, P Cowan, EP Alexander, R David, M AF Shohat, M Ben Amitai, D Shohat, B Mosberg, R Narinski, R Klein, T Okon, E Roizman, P Cowan, EP Alexander, R David, M TI Atopic dermatitis and HTLV-1-associated myelopathy: Associated or coincidental disorders? SO DERMATOLOGY LA English DT Article DE atopic dermatitis; human T lymphotropic virus; HTLV-1-associated myelopathy ID HTLV-I INFECTION; T-CELL LEUKEMIA; VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; ANTIBODY-RESPONSE; CHILDREN; RATS AB Reports from Jamaica have indicated that some patients with infective dermatitis or atopic dermatitis (AD) are seropositive for antibodies to human T-lymphotropic virus type 1 (HTLV-1). We describe a 32-year-old Israeli woman with long-term AD and paresthesia in the distal parts of the extremities. Neurological examination revealed a positive Babinski's sign. HLA typing demonstrated that this patient has the common HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis haplotype for DRB1* DQB1*. The presence of HTLV-1 was demonstrated with polymerase chain reaction; HTLV-1-antibodies were detected by the Western blot method and by inoculation of the patient's peripheral blood mononuclear cells into F344 rats. This study confirms the presence of HTLV-1 antibodies and proviral genome in a patient with AD which later evolved into HAM/TSP. We cannot yet conclude whether these two diseases are associated or coincidental disorders. Copyright (R) 2000 S. Karger AG. Basel. C1 Rabin Med Ctr, Dept Dermatol, IL-49100 Petah Tiqwa, Israel. Rabin Med Ctr, Cellular Immunol Unit, IL-49100 Petah Tiqwa, Israel. Rabin Med Ctr, Dept Neurol, IL-49100 Petah Tiqwa, Israel. Rabin Med Ctr, Tissue Typing Lab, IL-49100 Petah Tiqwa, Israel. Rabin Med Ctr, Casper Inst Pathol, IL-49100 Petah Tiqwa, Israel. Ctr Biol Evaluat & Res, Div Transfus Transmitted Dis, Rockville, MD USA. RP Shohat, M (reprint author), Rabin Med Ctr, Dept Dermatol, Beilinson Campus, IL-49100 Petah Tiqwa, Israel. NR 26 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-8665 J9 DERMATOLOGY JI Dermatology PY 1999 VL 199 IS 4 BP 356 EP 360 DI 10.1159/000018291 PG 5 WC Dermatology SC Dermatology GA 271XG UT WOS:000084619700016 PM 10640850 ER PT J AU Garces, C Ruiz-Hidalgo, MJ Bonvini, E Goldstein, J Laborda, J AF Garces, C Ruiz-Hidalgo, MJ Bonvini, E Goldstein, J Laborda, J TI Adipocyte differentiation is modulated by secreted delta-like (dlk) variants and requires the expression of membrane-associated dlk SO DIFFERENTIATION LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; FETAL ANTIGEN-1; PROTEIN-STRUCTURE; GENE-EXPRESSION; PREF-1; PG2; IDENTIFICATION; CDNA; RNA AB Previous studies demonstrate that the deltalike (dlk) sad preadipocyte factor 1 (Pref-1) genes encode similar proteins. Pref-1 is downregulated during adipocyte differentiation, and expression of ectopic Pref-1 inhibits adipogenesis. We explored whether dlk functions similarly to Pref-1 and studied the role of alternately spliced dlk variants encoding membrane-associated or secreted forms. We also studied whether enforced downregulation of dlk/Pref-1 may enhance the differentiation response of non-committed cells. Ectopic expression of a potentially secreted dlk variant, conditioned media from dlk expressing cells or several individual epidermal-growth-factor-dlk peptides inhibited 3T3-L1 differentiation. This demonstrates that dlk and Pref-1 are functionally equivalent, dlk gene mRNA encoding for secreted variants decreased much faster than total dlk gene mRNA during differentiation of 3T3-L1 cells. In fact, total dlk or membrane-associated dlk protein expression increased during the first hours of differentiation. Cells sorted for lowest levels of dlk protein diminished or lost their ability to differentiate. These data suggest that membrane and secreted dlk protein variants play opposite roles in the control of adipogenesis. In addition, enforced downregulation of dlk protein expression in the weakly adipogenic Balb/c 3T3 cell line dramatically enhanced adipogenesis in response to insulin. These results indicate that dlk protein not only participates in processes leading to inhibition of adipogenesis but that the control of its expression and different spliced variants is essential for the adipogenic response to extracellular signals. C1 US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Laborda, J (reprint author), US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Bldg 29B,Room 3NN04,HFM 564,1401 Rockville Pike, Rockville, MD 20852 USA. RI Laborda, Jorge/L-5726-2014; Ruiz-Hidalgo, Maria/L-1956-2014 OI Laborda, Jorge/0000-0002-9210-838X; NR 24 TC 92 Z9 93 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD JAN PY 1999 VL 64 IS 2 BP 103 EP 114 DI 10.1046/j.1432-0436.1999.6420103.x PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 168CD UT WOS:000078672400004 PM 10234807 ER PT J AU Buesing, MA McSweegan, E AF Buesing, MA McSweegan, E TI Submitting biologics applications to the Center for Biologics Evaluation and Research electronically SO DRUG INFORMATION JOURNAL LA English DT Article DE Investigational New Drug; biologic product license; electronic; guidance; CBER AB The Food and Drug Administration (FDA) has gained significant experience with computer-assisted licensing applications, and has concluded that continued reliance on customized formats is a burden for the FDA and industry. As a result, the FDA is working to standardize the content and format of electronically submitted applications, and to establish procedures for electronic applications that will: create minimal additional work for industry and reviewers, establish consistency across the FDA's centers, and expedite the review process. The FDA is proposing to move to a paperless regulatory process by the year 2002. Toward that goal, the FDA's Center for Biologics Evaluation and Research (CBER) has released new guidance for the electronic submission of biologic and product license applications; case report forms, tabulations, and statistical data; and lot release protocols. A pilot program for Investigational New Drug applications also has been initiated. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP McSweegan, E (reprint author), NIAID, DMID, NIH, Solar Bldg,Rm 3A34, Bethesda, MD 20892 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JAN-MAR PY 1999 VL 33 IS 1 BP 1 EP 15 PG 15 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 192WJ UT WOS:000080102400001 ER PT J AU Sankoh, AJ Huque, MF Russell, HK D'Agostino, RB AF Sankoh, AJ Huque, MF Russell, HK D'Agostino, RB TI Global two-group multiple endpoint adjustment methods applied to clinical trials SO DRUG INFORMATION JOURNAL LA English DT Article DE clinical trials; closure principle; endpoint-specific procedures; global procedures; multiple endpoint adjustments; nominal significance level; power ID END-POINTS; BONFERRONI PROCEDURE; BINARY OUTCOMES; TESTS; DESIGN; ALTERNATIVES AB Often, clinical trial results are reported and used for claiming a treatment effect without adjusting for the multiplicity arising from the presence of multiple endpoints. It is well recognized that this practice is likely to inflate the type I error rate unless the endpoints are highly correlated. To control such an inflation of the type I error rate, two approaches, both appropriate on their own grounds, are in use. One is the 'global' approach which aims at demonstrating overall treatment effect and considers all given endpoints simultaneously. The other approach, often called the 'endpoint-specific' approach, assesses significance for each endpoint separately, assuring meaningful control of the overall type I error rate. This paper addresses and discusses some of these global multiple endpoint adjustment methods in the context of clinical trial applications where two treatments are being compared (for example, active treatment with a placebo), and gives some simulation results to assess their performance regarding the alpha-level protection and power. C1 US FDA, Ctr Drug Evaluat & Res, Div Biometr, Rockville, MD 20857 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. RP Sankoh, AJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Biometr, Room 9B-07,5600 Fishers Lane, Rockville, MD 20857 USA. NR 37 TC 12 Z9 12 U1 1 U2 3 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JAN-MAR PY 1999 VL 33 IS 1 BP 119 EP 140 PG 22 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 192WJ UT WOS:000080102400015 ER PT J AU Sankoh, AJ AF Sankoh, AJ TI Interim analyses: An update of an FDA reviewer's experience and perspective SO DRUG INFORMATION JOURNAL LA English DT Article DE administrative interim analysis; interim analysis for sample size adjustment; multiple comparisons; unplanned interim analysis ID CLINICAL-TRIALS AB Food and Drug Administration (FDA) clinical and statistical guidelines request that sponsors document considerations which will govern the conduct of interim analyses in clinical trials. These considerations include clearly stating the reasons for such interim analyses, the planned number of or the (information/calendar) times when the interim analyses will be carried out, adequate stopping rules, and measures taken to minimize bias. Statistical reviewers at the FDA often encounter clinical trials whose conduct and analyses present interim analysis issues that require serious considerations. These issues include: conducting one or more unplanned (posthoc) interim analyses without any stated purpose or reason, leaving the final p-values unadjusted for interim analyses, resizing the trial without p-value adjustment after interim analyses on treatment differences, changing the design and conduct of the trial after interim looks without addressing their impact on the final results, and so forth. These questionable practices of interim analysis observed in clinical trial submissions raise concern among (statistical) reviewers at the FDA. This paper addresses some of these practices and their impact on the review and approval process of clinical trial submissions. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Sankoh, AJ (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane,9B-07, Rockville, MD 20857 USA. NR 19 TC 6 Z9 7 U1 0 U2 2 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JAN-MAR PY 1999 VL 33 IS 1 BP 165 EP 176 PG 12 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 192WJ UT WOS:000080102400020 ER PT J AU Hoff, PM Lassere, Y Pazdur, R AF Hoff, PM Lassere, Y Pazdur, R TI Tegafur/uracil plus calcium folinate in colorectal cancer - Double modulation of fluorouracil SO DRUGS LA English DT Article; Proceedings Paper CT Conference on Oral Chemotherapy - Past, Present and Future Directions CY FEB 26-28, 1998 CL CANCUN, MEXICO SP Sarah Cannon Canc Ctr ID ANTI-TUMOR ACTIVITY; LOW-DOSE LEUCOVORIN; PHASE-I; ORAL REGIMEN; URACIL UFT; BIOCHEMICAL MODULATION; INFUSION FLUOROURACIL; ADJUVANT THERAPY; CARCINOMA; FTORAFUR AB The oral chemotherapeutic agent tegafur/uracil (UFT(R)) is the first of a new class of anticancer drugs called dihydropyrimidine dehydrogenase inhibitory fluoropyrimidines. Tegafur/uracil combines uracil with the fluorouracil prodrug tegafur in a 4: 1 molar ratio;Uracil competitively inhibits the degradation of fluorouracil, which results in the concentration of fluorouracil remaining at sustained levels in both plasma and tumour. Tegafur/uracil has been commercially available in Japan since 1983 and examined extensively in various tumours. Trials conducted in the US have focused on the combination of tegafur/uracil plus calcium folinate (calcium leucovorin) [ORZEL(R)]. Several phase I and II trials have evaluated the maximum tolerated dose, pharmacokinetics, efficacy, and safety of this combination in the treatment of colorectal cancer. Results have shown that tegafur/uracil at 300 mg/m(2)/day in divided doses given every 8 hours for 28 days provides prolonged exposure to fluorouracil. Furthermore, tegafur/uracil + calcium folinate is well tolerated, with dose-limiting toxicity manifesting as diarrhoea. Compared with intravenous fluorouracil plus folinic acid (leucovorin) regimens, tegafur/uracil + calcium folinate has similar efficacy with less toxicity and is more convenient because it is an oral regimen. Early studies have also shown potential cost savings because of fewer complications. C1 US FDA, Div Oncol Drug Prod, Rockville, MD 20857 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol & Digest Dis, Houston, TX 77030 USA. RP Pazdur, R (reprint author), US FDA, Div Oncol Drug Prod, 5600 Fishers Lane,HFD-150, Rockville, MD 20857 USA. NR 43 TC 12 Z9 12 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 1999 VL 58 SU 3 BP 77 EP 83 DI 10.2165/00003495-199958003-00011 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 279XY UT WOS:000085071400012 PM 10711845 ER PT S AU Berglund, BA Boring, DL Howlett, AC AF Berglund, BA Boring, DL Howlett, AC BE Honn, KV Marnett, LJ Nigam, S Dennis, EA TI Investigation of structural analogs of prostaglandin amides for binding to and activation of CB1 and CB2 cannabinoid receptors in rat brain and human tonsils SO EICOSANOIDS AND OTHER BIOACTIVE LIPIDS IN CANCER, IMFLAMMATION AND RADIATION INJURY, 4 SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 5th International Conference on Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Related Diseases CY SEP 17-20, 1997 CL LA JOLLA, CALIFORNIA ID ANANDAMIDE; CYCLOOXYGENASE-2; POTENT C1 St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA. US FDA, Ctr Drug Evaluat & Res, Div New Drug Chem 3, Rockville, MD 20857 USA. RP Berglund, BA (reprint author), St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, 1402 South Grand, St Louis, MO 63104 USA. NR 17 TC 25 Z9 27 U1 0 U2 0 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46138-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1999 VL 469 BP 527 EP 533 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA BP58H UT WOS:000085570100077 PM 10667378 ER PT J AU Altekruse, SF Stern, NJ Fields, PI Swerdlow, DL AF Altekruse, SF Stern, NJ Fields, PI Swerdlow, DL TI Campylobacter jejuni - An emerging foodborne pathogen SO EMERGING INFECTIOUS DISEASES LA English DT Article ID RISK-FACTORS; RAW-MILK; THERMOPHILIC CAMPYLOBACTERS; INTESTINAL COLONIZATION; BROILER-CHICKENS; GUILLAIN-BARRE; POULTRY; INFECTION; PREVALENCE; SALMONELLA AB Campylobacter jejuni is the most commonly reported bacterial cause of foodborne infection in the United States. Adding to the human and economic costs are chronic sequelae associated with C. jejuni infection-Guillain-Barre syndrome and reactive arthritis. In addition, an increasing proportion of human infections caused by C. jejuni are resistant to antimicrobial therapy. Mishandling of raw poultry and consumption of undercooked poultry are the major risk factors for human campylobacteriosis. Efforts to prevent human illness are needed throughout each link in the food chain. C1 US FDA, Blacksburg, VA USA. USDA, Athens, GA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Altekruse, SF (reprint author), Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Duckpond Rd, Blacksburg, VA 24060 USA. NR 65 TC 480 Z9 496 U1 8 U2 61 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN-FEB PY 1999 VL 5 IS 1 BP 28 EP 35 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 171HN UT WOS:000078857700004 PM 10081669 ER PT J AU Dobrovolsky, VN Chen, T Heflich, RH AF Dobrovolsky, VN Chen, T Heflich, RH TI Molecular analysis of in vivo mutations induced by N-ethyl-N-nitrosourea in the autosomal Tk and the X-linked Hprt genes of mouse lymphocytes SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE mutation; Tk; Hprt; PCR; N-ethyl-N-nitrosourea; loss of heterozygosity ID HAMSTER OVARY CELLS; LYMPHOMA-CELLS; IN-VIVO; THYMIDINE KINASE; TRANSGENIC MICE; ESCHERICHIA-COLI; INVIVO EXPOSURE; SHUTTLE VECTORS; MESSENGER-RNA; HETEROZYGOSITY AB The endogenous; autosomal Tk gene is a potentially useful reporter of in vivo mutation since it may recover a wider range of mutational events than the X-linked Hprt gene or bacterial transgenes. In this study, we characterized mutations produced in the Tk gene of Tk(+/-) mice and compared them with mutations induced in the Hprt gene. Treatment of Tk(+/-) mice with N-ethyl-N-nitrosourea (ENU) resulted in dose-related increases in Tk mutants, as measured by the Frequency of 5-bromodeoxyuridine-resistant (BrdUrd(r)) spleen lymphocytes. ENU-induced mutant frequencies in the Hprt gene, determined by measuring 6-thioguanine-resistant (TG(r)) lymphocytes, were similar to the Tk mutant frequencies. Allele-specific PCR of DNA from Br-dUrd(r) lymphocyte clones suggested that 35% of clones From mice treated with ENU and 65% of clones from untreated animals hod loss of heterozygosity (LOH) of the Tk gene: due to deletion of the Functional Tk allele. Reverse transcriptase-PCR/sequencing analysis of BrdUrd(r) and TG(r) clones from ENU-treated mice indicated that point mutations in both genes predominantly occurred at A:T basepairs; however, A:T-->G:C transition was the most common mutation in the Tk gene, while A:T --> T:A transversion was the most frequent mutation in the Hprt gene. Substitution at A:T basepairs in the Hprt gene occurred disproportionately with the mutated dT on the nontranscribed DNA strand, while this strand bias for mutation was not seen in the Tk gene. The results indicate that the specificity of ENU-induced point mutation differs between the two endogenous genes and that the autosomal Tk gene Of Tk(+/-) mice is capable of recovering mutations caused by LOH. Environ. Mol. Mutagen. 34:30-38, 1999. Published 1999 Wiley-Liss, Inc.dagger C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Dobrovolsky, VN (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 48 TC 21 Z9 21 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 1999 VL 34 IS 1 BP 30 EP 38 DI 10.1002/(SICI)1098-2280(1999)34:1<30::AID-EM5>3.0.CO;2-R PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 230WX UT WOS:000082275600005 PM 10462721 ER PT J AU Bigger, CAH AF Bigger, CAH TI In memoriam: Anthony Dipple SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Biographical-Item C1 US FDA, HFD 530, Div Antiviral Drug Prod, Rockville, MD 20857 USA. RP Bigger, CAH (reprint author), US FDA, HFD 530, Div Antiviral Drug Prod, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 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 1999 VL 34 IS 4 BP 227 EP 232 DI 10.1002/(SICI)1098-2280(1999)34:4<227::AID-EM1>3.0.CO;2-8 PG 6 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 275EE UT WOS:000084805800001 PM 10618169 ER PT J AU Dunkel, VC San, RHC Seifried, HE Whittaker, P AF Dunkel, VC San, RHC Seifried, HE Whittaker, P TI Genotoxicity of iron compounds in Salmonella typhimurium and L5178Y mouse lymphoma cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE iron; mutagenicity; Salmonella; mouse lymphoma ID METAL-COMPOUNDS; MUTAGENICITY; TOXICOLOGY; TRANSPORT; RADICALS; SYSTEM; DAMAGE; CANCER; ASSAY; RISK AB The mutagenic activity of elemental and salt forms of iron (Fe), including compounds currently being used in dietary supplements and for food fortification, were evaluated for mutagenicity in Salmonella typhimurium and L5178Y mouse lymphoma cells. Except for the weak response obtained with ferrous fumarate, none of the compounds induced a mutagenic response in Salmonella. In the mouse lymphoma assay, responses were related to the Fe compound and/or reduction of ferric (Fe+3) to ferrous (Fe+2). Responses with the elemental forms of Fe were divergent. Electrolytic Fe with a relatively larger particle size and irregular shape was negative. The smaller-sized carbonyl Fe, which after 4 hr attached to and was taken up by the cells, induced mutagenic responses both with and without S9. With ferric chloride (FeCl3) and ferric phosphate (FePO4), there was an increase in mutant frequency only with S9. With the Fe+2 compounds, ferrous sulfate (FeSO4) and ferrous fumarate (FeC4H2O4), positive responses were observed without S9. The Fe chelate, sodium Fe(III)EDTA was positive in both the presence and absence of S9. The lowest effective doses (LED) for induction of mutagenicity were identified for these compounds and an LED ratio calculated. The LED ratio ranges from 1 for FeSO4 to 30 for carbonyl Fe, which are similar to oral ID50 values obtained in animal studies. (C) 1999 Wiley Liss, Inc. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Bio Reliance Corp Inc, Rockville, MD USA. NCI, NIH, Bethesda, MD 20892 USA. RP Dunkel, VC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. EM VCD@CFSAN.FDA.GOV FU NCI NIH HHS [N01-CB-40509] NR 35 TC 24 Z9 24 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 1999 VL 33 IS 1 BP 28 EP 41 DI 10.1002/(SICI)1098-2280(1999)33:1<28::AID-EM4>3.0.CO;2-S PG 14 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 163YF UT WOS:000078433900004 PM 10037321 ER PT J AU Dearfield, KL Benz, RD AF Dearfield, KL Benz, RD TI Can the new genetic toxicology tests be used for regulatory safety decisions? SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material C1 US EPA, Washington, DC 20460 USA. US FDA, Washington, DC 20204 USA. RP Dearfield, KL (reprint author), US EPA, ORD 8103R,401 M St SW, Washington, DC 20460 USA. NR 0 TC 2 Z9 3 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 1999 VL 33 IS 2 BP 91 EP 93 PG 3 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 184EZ UT WOS:000079598600001 PM 10217063 ER PT J AU Sotomayor, RE Sahu, S Washington, M Hinton, DM Chou, M AF Sotomayor, RE Sahu, S Washington, M Hinton, DM Chou, M TI Temporal patterns of DNA adduct formation and glutathione S-transferase activity in the testes of rats fed aflatoxin B-1: A comparison with patterns in the liver SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE AFB(1); testis; liver; DNA adducts; GST; rats ID DEVELOPMENTAL EXPRESSION; HAMSTER LIVERS; METABOLISM; INVITRO; CELLS; IDENTIFICATION; CONJUGATION; EPIDIDYMIS; MODULATION; SUBUNIT AB Fisher-344 male rats were fed 1.6 ppm of aflatoxin B-1 (AFB(1)) continuously and intermittently For several weeks. At various time periods, DNA was isolated from the testes and livers and analyzed for AFB(1)-DNA adducts. The ability of the testis to detoxify AFB(1) was also investigated by the gluathione S-transferase (GST) activity assay and compared with that of the liver. The levels of testicular AFB(1)-DNA adducts were 2.4 to 8.1 times lower than those of the liver after 4 to 16 weeks of continuous treatment and 2.2 to 46.2 times lower after 8 to 20 weeks of intermittent treatment. The testicular DNA adducts markedly decreased over time. By 16 weeks of continuous and 20 weeks of intermittent exposure, they had decreased 37 and 91%, respectively. In contrast, hepatic AFB(1)-DNA adducts increased four-fold from 4 to 16 weeks of continuous treatment but increased at a much slower rate after intermittent exposure. In both the liver and testis, significant levels of AFB(1)-DNA adducts persisted for at least 1 month after ending the treatment, suggesting that this type of lesion was poorly repaired. In control rots, the testis showed significantly higher GST activity than the liver. In treated rots, these differences were significant during the first 12 weeks of continuous treatment but not at later times. Tissue-specific differences such as germ-cell depletion and increased testicular detoxification may play an important role in the observed differential pattern of DNA adduct formation between the testis and liver. Environ. Mel. Mutagen. 33. 293-302, 1999 (C) 1999 Wiley-Liss, Inc. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sotomayor, RE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-509,MOD-1,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 41 TC 15 Z9 16 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 1999 VL 33 IS 4 BP 293 EP 302 DI 10.1002/(SICI)1098-2280(1999)33:4<293::AID-EM6>3.0.CO;2-E PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 212ZU UT WOS:000081248200006 PM 10398377 ER PT J AU Fu, PP Von Tungeln, LS Chiu, LH Own, ZY AF Fu, PP Von Tungeln, LS Chiu, LH Own, ZY TI Halogenated-polycyclic aromatic hydrocarbons: A class of genotoxic environmental pollutants SO ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS-PART C OF JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH LA English DT Review ID TUMOR-INITIATING ACTIVITY; RAT-LIVER MICROSOMES; TRANS-DIHYDRODIOL METABOLITES; DIFFERENT CHLORINATION REACTIONS; RECEPTOR LIGANDS PRESENT; REGION DIOL-EPOXIDES; MALE B6C3F1 MOUSE; STEREOSELECTIVE METABOLISM; RADICAL CATIONS; H-RAS C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Providence Univ, Inst Appl Chem, Taichung, Taiwan. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 130 TC 13 Z9 15 U1 2 U2 6 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1059-0501 J9 ENVIRON CARCIN ECO R JI Environ. Carcinog. Ecotoxical. Rev.-Pt. C J. Env. Sci. Health PY 1999 VL 17 IS 2 BP 71 EP 109 PG 39 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 261WD UT WOS:000084032500001 ER PT J AU Chetty, M Gouws, E Miller, R Moodley, SV AF Chetty, M Gouws, E Miller, R Moodley, SV TI The use of a side effect as a qualitative indicator of plasma chlorpromazine levels SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE chlorpromazine; metabolites; side-effects; blood levels ID METABOLITES; SCHIZOPHRENIA; DRUGS AB Chlorpromazine (CPZ) is widely used in South African hospitals. The purpose of this study was to determine whether any physiological parameter (side-effect) could be correlated with plasma concentrations of CPZ or its metabolites. In the absence of a blood level, such a correlation could serve as a qualitative indicator of the amount of chlorpromazine in the body. Such a marker can assist the psychiatrist with therapeutic decisions regarding poor compliance and the lack of response with the drug. Fifteen schizophrenic patients were included in this study and regression analysis was used to determine any correlation between CPZ, 7-hydroxychlorpromazine, Chlorpromazine-N-oxide, Nor(1) chlorpromazine, Nor(2)chlorpromazine, chlorpromazine sulfoxide, Nor(2) chlorpromazine sulfoxide and blood pressure, pulse rate, sedation and finger tremor. No correlation was seen between blood pressure or pulse rate and plasma concentrations of CPZ or the metabolites. A good correlation was seen between sedation, 7-hydroxychlorpromazine (P=0.035) and chlorpromazine sulfoxide (P=0.016). The results suggest that as the levels of chlorpromazine sulfoxide increase, the probability of sedation increases, while increasing levels of 7-hydroxychlorpromazine have the opposite effect. A good correlation was also seen between finger tremor and chlorpromazine levels (P=0.035). These results suggest that there is a 50% probability that the patient would experience finger tremor when the plasma concentration of chlorpromazine is 46 ng/ml. This study demonstrated the potential for the use of sedation and finger tremor as qualitative indicators of the plasma concentration of CPZ and two metabolites. Further studies with larger patient numbers are warranted. (C) 1999 Elsevier Science B.V./ECNP. All rights reserved. C1 Univ Witwatersrand, Dept Expt & Clin Pharmacol, ZA-2193 Johannesburg, South Africa. MRC S Africa, Durban, South Africa. US FDA, Dept Biopharmaceut, Washington, DC 20204 USA. Ft Napier Hosp, Pietermartizburg, South Africa. RP Chetty, M (reprint author), Univ Witwatersrand, Dept Expt & Clin Pharmacol, 7 York Rd, ZA-2193 Johannesburg, South Africa. NR 19 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD JAN PY 1999 VL 9 IS 1-2 BP 77 EP 82 DI 10.1016/S0924-977X(98)00005-4 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 166VG UT WOS:000078597900011 PM 10082231 ER PT S AU Baines, J Chen, JS Dagher, SM Fisher, CE Grunow, W Hattan, DG Johnson, FN Kawamura, Y Knaap, AGAC Kuznesof, P Larsen, JC Meyland, I Mutamba, J Pacin, AM Pascal, G Petersen, B Verger, PJP Vilu, R Walker, R Wallin, H Wilson, J Abbott, PJ Blumenthal, H Bosch, X Greig, J Gry, J Hecker, EFF Henry, S Herrman, JL Hotchkiss, JH Kroes, R Lupton, J Mattia, A Moy, G Munro, IC Nishikawa, A Paakkanen, J Portier, CJ Renwick, AG Riordan, M Semino, G Shubik, P Speijers, GJA Vavasour, E Whitehouse, DB AF Baines, J Chen, JS Dagher, SM Fisher, CE Grunow, W Hattan, DG Johnson, FN Kawamura, Y Knaap, AGAC Kuznesof, P Larsen, JC Meyland, I Mutamba, J Pacin, AM Pascal, G Petersen, B Verger, PJP Vilu, R Walker, R Wallin, H Wilson, J Abbott, PJ Blumenthal, H Bosch, X Greig, J Gry, J Hecker, EFF Henry, S Herrman, JL Hotchkiss, JH Kroes, R Lupton, J Mattia, A Moy, G Munro, IC Nishikawa, A Paakkanen, J Portier, CJ Renwick, AG Riordan, M Semino, G Shubik, P Speijers, GJA Vavasour, E Whitehouse, DB GP WHO WHO TI E(v)aluation of certain food additives and contaminants - Forty-ninth report of the joint FAO/WHO Expert Committee on Food Additives SO EVALUATION OF CERTAIN FOOD ADDITIVES AND CONTAMINANTS: FORTY-NINTH REPORT OF THE JOINT FAO/WHO EXPERT COMMITTEE ON FOOD ADDITIVES SE WHO Technical Report Series LA English DT Review C1 Australia New Zealand Food Author, Canberra, ACT, Australia. Chinese Acad Prevent Med, Inst Nutr & Food Hyg, Beijing, Peoples R China. Amer Univ Beirut, Dept Biol, Beirut, Lebanon. MAFF, Risk Assessment & Management Branch, London, England. Fed Inst Hlth Protect Consumers & Vet Med, Food Toxicol Div, Berlin, Germany. US FDA, Div Hlth Effects Evaluat, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Natl Acad Sci, Food Chem Codex, Washington, DC 20418 USA. Natl Inst Hlth Sci, Div Food Addit, Tokyo 158, Japan. Natl Inst Publ Hlth & Environm, Ctr Subst & Risk Assessment, NL-3720 BA Bilthoven, Netherlands. US FDA, Div Prod Manufacture & Use, Off Premarket Approval, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Minist Food Agr & Fisheries, Danish Vet & Food Adm, Inst Toxicol, Dept Biochem & Mol Toxicol, Soborg, Denmark. Minist Hlth & Child Welf, Dept Nutr, Harare, Zimbabwe. Sci Res Commiss Buenos Aires Prov, Buenos Aires, DF, Argentina. Minist Higher Educ & Res, Natl Ctr Sci Res, Paris, France. Novigen Sci Inc, Washington, DC USA. Univ Paris 05, Foch Res Ctr, Paris, France. Tallinn Univ Technol, Dept Biochem, EE-200108 Tallinn, Estonia. Univ Surrey, Sch Biol Sci, Surrey, England. VTT Biotechnol & Food Res, Espoo, Finland. Resources Future Inc, Ctr Risk Management, Washington, DC 20036 USA. RP Baines, J (reprint author), Australia New Zealand Food Author, Canberra, ACT, Australia. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 122 TC 3 Z9 3 U1 0 U2 1 PU WORLD HEALTH ORGANIZATION PI GENEVA PA DISTRIBUTION & SALES SERVICE, 1211 27 GENEVA, SWITZERLAND SN 0512-3054 BN 92-4-120884-8 J9 WHO TECH REP SER JI WHO Tech. Rep. Ser. PY 1999 VL 884 BP 1 EP + PG 97 WC Chemistry, Analytical; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA BN37H UT WOS:000081718600001 ER PT J AU Applegren, LE Arnold, D Boisseau, J Boobis, AR Ellis, RL Livingston, RC McLean, JG MacNeil, JD Miller, MA Miterna, ES Palermo-Neto Pinter, A Martinez, JLR Sinhaseni, P Soback, S Wells, R Cernigilia, CE Chamberlain, P Chernausek, SD Fuchs, R Good, EAM Hansen, MK Heitzman, RJ Herrman, JL Mitsumori, K Nord, CE Olsen, P Paakkanen, J Pronk, MEJ Ritter, L Roberts, G Roestal, B Sills, RC Sundlof, S Ungemach, FR Weber, N AF Applegren, LE Arnold, D Boisseau, J Boobis, AR Ellis, RL Livingston, RC McLean, JG MacNeil, JD Miller, MA Miterna, ES Palermo-Neto Pinter, A Martinez, JLR Sinhaseni, P Soback, S Wells, R Cernigilia, CE Chamberlain, P Chernausek, SD Fuchs, R Good, EAM Hansen, MK Heitzman, RJ Herrman, JL Mitsumori, K Nord, CE Olsen, P Paakkanen, J Pronk, MEJ Ritter, L Roberts, G Roestal, B Sills, RC Sundlof, S Ungemach, FR Weber, N CA Joint FAO WHO Expert Comm Food Additives TI Evaluation of certain veterinary drug residues in food - Fiftieth report of the Joint FAO/WHO Expert Committee on Food Additives SO EVALUATION OF CERTAIN VETERINARY DRUG RESIDUES IN FOOD SE WHO TECHNICAL REPORT SERIES LA English DT Article C1 Swedish Univ Agr Sci, Fac Vet Med, Biomed Ctr, Dept Pharmacol & Toxicol, Uppsala, Sweden. Fed Inst Hlth Protect Consumers & Vet Med, Berlin, Germany. Natl Agcy Vet Med, Nalt Ctr Vet & Food Studies, Fougeres, France. Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Med, Div Med,Sect Clin Pharmacol, London, England. Dept Agr, Off Publ Hlth & Sci, Sci Res & Oversight Staff, Washington, DC USA. US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20857 USA. Canadian Food Inspect Agcy, Hlth Anim Lab, Ctr Vet Drug Residues, Saskatoon, SK, Canada. Univ Nairobi, Coll Agr & Vet Sci, Fac Vet Med, Dept Publ Hlth Pharmacol & Toxicol, Kabete, Kenya. Univ Sao Paulo, Fac Vet Med & Anim Husb, Dept Pathol, Sao Paulo, Brazil. Natl Inst Environm Hlth, Budapest, Hungary. Minist Agr & Anim Husb, Nalt Lab Vet Sci, Toxicol & Residues Sect, San Jose, Costa Rica. Chulalongkorn Univ, Inst Hlth Res, Bangkok, Thailand. Minist Agr, Kimron Vet Inst, Natl Residue Lab, Beit Dagan, Israel. US FDA, Natl Ctr Toxicol Res, Dept Microbiol & Chem, Jefferson, AR 72079 USA. US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Div Human Food Safety, Rockville, MD 20857 USA. Childrens Hosp, Med Ctr, Div Endocrinol, Cincinnati, OH 45229 USA. Inst Med Res & Occupat Hlth, Dept Expt Toxicol & Ecotoxicol, Zagreb, Croatia. Minist Agr Fisheries & Food, Vet Med Directorate, Surrey, England. Consumers Union, Consumer Policy Inst, Yonkers, NY USA. WHO, Int Programme Chem Safety, CH-1211 Geneva, Switzerland. Natl Inst Hlth Sci, Biol Safety Res Ctr, Div Pathol, Tokyo 158, Japan. Huddinge Univ Hosp, Karolinska Inst, Dept Immunol Microbiol Pathol & Infect Dis, S-14186 Huddinge, Sweden. Danish Vet & Food Adm, Inst Food Safety & Toxicol, Pathol Sect, Soborg, Denmark. FAO, Div Food & Nutr, Food Qual & Stand Serv, Food Qual Liaison Grp, I-00100 Rome, Italy. Natl Inst Publ Hlth & Environm, Ctr Subst & Risk Assessment, Bilthoven, Netherlands. Univ Guelph, Canadian Network Toxicol Ctr, Guelph, ON, Canada. Commonwealth Dept Hlth & Family Serv, Therapeut Goods Adm, Chem Prod Assessment Sect, Woden, ACT, Australia. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Leipzig, Fac Vet Med, Inst Pharmacol Pharm & Toxicol, Leipzig, Germany. RP Applegren, LE (reprint author), Swedish Univ Agr Sci, Fac Vet Med, Biomed Ctr, Dept Pharmacol & Toxicol, Uppsala, Sweden. NR 8 TC 3 Z9 3 U1 0 U2 4 PU WORLD HEALTH ORGANIZATION PI GENEVA PA 1211 27 GENEVA, SWITZERLAND SN 0512-3054 J9 WHO TECH REP SER PY 1999 VL 888 BP 1 EP 95 PG 95 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA BN61F UT WOS:000082354800001 ER PT S AU Von Bredow, J Myers, M Wagner, D Valdes, JJ Loomis, L Zamani, K AF Von Bredow, J Myers, M Wagner, D Valdes, JJ Loomis, L Zamani, K BE Frazier, TW Richardson, DC TI Agroterrorism - Agricultural infrastructure vulnerability SO FOOD AND AGRICULTURAL SECURITY: GUARDING AGAINST NATURAL THREATS AND TERRORIST ATTACKS AFFECTING HEALTH, NATIONAL FOOD SUPPLIES, AND AGRICULTURAL ECONOMICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Conference on Food and Agricultural Security CY SEP 28-30, 1998 CL WASHINGTON, D.C. SP FEd Bur Investigat Lab, USDA ARS, Amer Vet Med Assoc, Dept Def Vet Serv Activ, Louisiana State Univ, FMI Sci Lab, Natl Consortium Genom Resources Management & Serv AB The intentional contamination of animal feed to reduce the availability of animal-derived human food or to infect human populations is seldom mentioned, but animal feed could be an easy target for bioterrorists, The period of delay between the contamination of the animal feed and adulteration of the human food product provides an additional degree of uncertainty about the source of the contamination and minimizes the possibility of apprehending the terrorist, The less obvious and more natural the source of biological contamination, the greater the likelihood that the animal feed contamination will be mistaken as a natural phenomenon. However, the problems related to managing natural food contamination and intentional food contamination remain the same. Rapid testing and separation of contaminated feed are important steps, followed by the more specific identification of the contaminant to determine the source of adulteration and/or the possibility of decontamination, At this time identification of the bioagents is dependent on the availability of antibody-specific test systems. The rapid development of specific antibodies for the development of sensitive and specific test kits is the key to identifying contamination and dealing effectively with the disposal or decontamination of the animal feed and, ultimately, preventing the contamination of animal-derived human food products. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. USA, Chem & Biol Def, Edgewood Res Dev & Engn Ctr, Aberdeen Proving Ground, MD 21100 USA. New Horizons Diagnost Corp, Dev & Engn, Columbia, MD 21045 USA. Pentagon, Off Director Def Res & Engn, Washington, DC 20301 USA. RP Von Bredow, J (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. RI Zamani, Kaveh/A-9182-2011 NR 17 TC 2 Z9 2 U1 1 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-230-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 894 BP 168 EP 180 PG 13 WC Agricultural Economics & Policy; Agronomy; Biotechnology & Applied Microbiology; Food Science & Technology SC Agriculture; Biotechnology & Applied Microbiology; Food Science & Technology GA BP47M UT WOS:000085238200026 ER PT J AU Suydam, LA Elder, DK AF Suydam, LA Elder, DK TI FDAMA update SO FOOD AND DRUG LAW JOURNAL LA English DT Article; Proceedings Paper CT FDLI 42nd Annual Educational Conference CY DEC 16-17, 1998 CL WASHINGTON, D.C. SP FDLI C1 US FDA, Rockville, MD 20857 USA. Food & Drug Adm, New England Dist Off, Boston, MA USA. RP Suydam, LA (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 1 Z9 1 U1 1 U2 1 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1999 VL 54 IS 1 BP 21 EP 33 PG 13 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 188CX UT WOS:000079828400004 PM 11758557 ER PT J AU Levitt, JA AF Levitt, JA TI An overview from the director of the center for food safety and applied nutrition SO FOOD AND DRUG LAW JOURNAL LA English DT Article; Proceedings Paper CT FDLI Food Regulatory Update 98 Meeting CY JUN 02, 1998 CL WASHINGTON, D.C. SP FDLI C1 Food & Drug Adm, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. RP Levitt, JA (reprint author), Food & Drug Adm, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1999 VL 54 IS 1 BP 43 EP 48 PG 6 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 188CX UT WOS:000079828400006 PM 11758559 ER PT J AU Dickinson, EH AF Dickinson, EH TI FDA's role in making exclusivity determinations SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Off Chief Counsel, Rockville, MD 20857 USA. RP Dickinson, EH (reprint author), US FDA, Off Chief Counsel, Rockville, MD 20857 USA. NR 4 TC 9 Z9 9 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1999 VL 54 IS 2 BP 195 EP 203 PG 9 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 214YU UT WOS:000081355800004 PM 11758573 ER PT J AU Malkin, BJ AF Malkin, BJ TI FDA's role in administering the Hatch-Waxman Act SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Hlth Assessment Policy Staff, Rockville, MD 20857 USA. RP Malkin, BJ (reprint author), US FDA, Hlth Assessment Policy Staff, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1999 VL 54 IS 2 BP 211 EP 214 PG 4 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 214YU UT WOS:000081355800006 PM 11758575 ER PT J AU Halpern, TH AF Halpern, TH TI Guidelines for the promotion of dietary supplements: Examining government regulation five years after enactment of the Dietary Supplement Health and Education Act of 1994 SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 Akin Gump Strauss Hauer & Feld LLP, Food & Drug Practice Grp, Washington, DC USA. US FDA, OTC Drug Review, Rockville, MD 20857 USA. RP Halpern, TH (reprint author), Akin Gump Strauss Hauer & Feld LLP, Food & Drug Practice Grp, Washington, DC USA. NR 26 TC 0 Z9 0 U1 0 U2 1 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1999 VL 54 IS 4 BP 567 EP 586 PG 20 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 283YN UT WOS:000085303800006 ER PT J AU Dunne, J Svistunenko, DA Alayash, AI Wilson, MT Cooper, CE AF Dunne, J Svistunenko, DA Alayash, AI Wilson, MT Cooper, CE TI Increased free radical formation by hemoglobin based oxygen carriers. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Univ Essex, Colchester CO4 3SQ, Essex, England. US FDA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 1999 VL 27 SU 1 MA 18 BP S19 EP S19 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 254EL UT WOS:000083598900044 ER PT J AU Mandavilli, BS Ali, SF Van Houten, B AF Mandavilli, BS Ali, SF Van Houten, B TI Age dependent DNA damage after MPTP treatment in mice SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Univ Texas, Sealy Ctr Mol Sci, Med Branch, Galveston, TX 77555 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72709 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 1999 VL 27 SU 1 MA 429 BP S140 EP S140 DI 10.1016/S0891-5849(99)90965-6 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 254EL UT WOS:000083598900454 ER PT J AU Shacter, E Lee, YJ AF Shacter, E Lee, YJ TI Hydrogen peroxide inhibits activation, not activity, of cellular caspase-3 SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Immunol Lab, Bethesda, MD 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 1999 VL 27 SU 1 MA 338 BP S109 EP S109 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 254EL UT WOS:000083598900363 ER PT J AU Shacter, E Lee, YJ Williams, JA AF Shacter, E Lee, YJ Williams, JA TI Inhibition of apoptosis by oxidative stress: Mechanisms and consequences SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 US FDA, CBER, Bethesda, MD 20892 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 1999 VL 27 SU 1 MA P8 BP S5 EP S5 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 254EL UT WOS:000083598900010 ER PT J AU Toyokuni, S Sagripanti, JL AF Toyokuni, S Sagripanti, JL TI Iron chelators modulate the production of DNA strand breaks and 8-hydroxy-2 '-deoxyguanosine SO FREE RADICAL RESEARCH LA English DT Article DE iron; chelate; 8-hydroxy-2 '-deoxyguanosine; DNA strand break; reactive oxygen species; carcinogenesis ID RENAL-CELL CARCINOMA; FERRIC NITRILOTRIACETATE; IDIOPATHIC HEMOCHROMATOSIS; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; SINGLE-STRAND; CARCINOGENESIS; DAMAGE; RATS; NEPHROTOXICITY AB The interaction of chelators and reducing agents is of particular importance in understanding iron-associated pathology since catalytic iron undergoes cyclic reduction and oxidation in vivo. Therefore, we treated plasmid DNA with free or chelated Fe(III) in the presence of biological reductants, and simultaneously measured the number of single strand breaks (SSBs) and oxidative base modification (8-hydroxy-2'-deoxyguanosine; 8-OHdG) by quantitative gel electrophoresis and HPLC with electrochemical detection, respectively. Production of SSBs and 8-OHdG was Linearly correlated suggesting that these two different lesions share a common chemical mechanism. The levels of both lesions were enhanced when Fe(III) was chelated to citrate or nitrilotriacetic acid. Reducing agents showed different potency in inducing DNA damage catalyzed by chelated iron (L-ascorbate > L-cysteine > H2O2) Chelation increased SSB formation by similar to 8-fold and 8-OHdG production by similar to 4-fold. The ratio of SSB/8-OHdG catalyzed by chelated iron, which is twice as high as by unchelated iron, indicates that chelation affects iron-catalyzed oxidative DNA damage in a specific way favoring strand breakage over base modification, Since iron is mostly chelated in biological systems, the production of genomic and mitochondrial DNA damage, particularly strand breaks, in diseases involving iron overload is likely to be higher than previously predicted from studies using unchelated iron. C1 Kyoto Univ, Grad Sch Med, Dept Pathol & Biol Dis, Sakyo Ku, Kyoto 6068501, Japan. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Mol Biol Branch, Rockville, MD 20852 USA. RP Toyokuni, S (reprint author), Kyoto Univ, Grad Sch Med, Dept Pathol & Biol Dis, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan. RI Toyokuni, Shinya/C-1358-2010 OI Toyokuni, Shinya/0000-0002-5757-1109 NR 29 TC 14 Z9 15 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 1999 VL 31 IS 2 BP 123 EP 128 DI 10.1080/10715769900301631 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 230NX UT WOS:000082258200005 PM 10490241 ER PT S AU Bhat, RV Gould, GW Gross, R Kesavan, PC Kristiansen, E Lustre, AO Morehourse, KM Osuide, GE Roberts, TA Sapora, O Weise, HP Brynjolfsson, A Diehl, JF Ehlermann, DAE Farkas, J Haruvy, Y Kaferstein, FK Loaharanu, P Moy, GG Raffi, J Satin, M Takeguchi, CA Taub, IA AF Bhat, RV Gould, GW Gross, R Kesavan, PC Kristiansen, E Lustre, AO Morehourse, KM Osuide, GE Roberts, TA Sapora, O Weise, HP Brynjolfsson, A Diehl, JF Ehlermann, DAE Farkas, J Haruvy, Y Kaferstein, FK Loaharanu, P Moy, GG Raffi, J Satin, M Takeguchi, CA Taub, IA GP JOINT FAO AEA/WHO JOINT FAO AEA/WHO JOINT FAO AEA/WHO TI High-dose irradiation: Wholesomeness of food irradiated with doses above 10 kGy - Introduction SO HIGH-DOSE IRRADIATION: WHOLESOMENESS OF FOOD IRRADIATED WITH DOSES ABOVE 10 KGY SE WHO Technical Report Series LA English DT Review ID ELECTRON-SPIN-RESONANCE; FREE-RADICAL REACTIONS; DEBONED CHICKEN MEAT; GAMMA-IRRADIATION; IONIZING-RADIATION; MICROBIOLOGICAL SAFETY; LISTERIA-MONOCYTOGENES; CLOSTRIDIUM-BOTULINUM; STAPHYLOCOCCUS-AUREUS; OCHRATOXIN PRODUCTION C1 Indian Council Med Res, Natl Inst Nutr, Jamai Osmania, Hyderabad, India. German Agcy Tech Cooperat, Eschborn, Germany. Bhabha Atom Res Ctr, Biosci Grp, Bombay, Maharashtra, India. Min Food Agr & Fisheries, Danish Vet & Food Adm, Dept Pathol, Inst Toxicol, Soborg, Denmark. Natl Food Author, Food Dev Ctr, Manila, Philippines. Ctr Food Safety & Appl Nutr, Food & Drug Adm, Off Premarket Approval, Washington, DC USA. Natl Agcy Food & Drug Adm & Control, Lagos, Nigeria. Ist Super Sanita, Comparat Toxicol & Ecotoxicol Lab, Rome, Italy. Fed Inst Mat Res & Testing, Berlin, Germany. Inst Proc Engn, Fed Res Ctr Nutr, Karlsruhe, Germany. Univ Horticulture & Food Ind, Dept Refrigerat & Liverstock Prod Technol, Budapest, Hungary. Adv Projects Initiat, Div Appl Radiat Therapyb, Yavne, Israel. WHO, Programme Food Safety & Food Aid, CH-1211 Geneva, Switzerland. IAEA, Joint FAO IAEA Div Nucl Techn Food & Agr, Food Preservat Sect, Int Consultat Grp Food Irradiat, Vienna, Austria. Fac Sci & Tech St Jerome, Lab Res Qual Food, F-13397 Marseille, France. FAO, Agr Support Syst Div, Agroind & Postharvest Management Serv, I-00100 Rome, Italy. Phoenix Regulatory Associates Ltd, Sterling, VA USA. USA, Natick Res, Sustainabil Directorate, Dev & Engn Ctr, Natick, MA 01760 USA. RP Bhat, RV (reprint author), Indian Council Med Res, Natl Inst Nutr, Jamai Osmania, Hyderabad, India. NR 489 TC 5 Z9 5 U1 2 U2 6 PU WORLD HEALTH ORGANIZATION PI GENEVA PA DISTRIBUTION & SALES SERVICE, 1211 27 GENEVA, SWITZERLAND SN 0512-3054 BN 92-4-120890-2 J9 WHO TECH REP SER JI WHO Tech. Rep. Ser. PY 1999 VL 890 BP 1 EP 193 PG 193 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA BP37U UT WOS:000084899400001 ER PT J AU Goldstein, DS Golczynska, A Stuhlmuller, J Holmes, C Rea, RF Grossman, E Lenders, J AF Goldstein, DS Golczynska, A Stuhlmuller, J Holmes, C Rea, RF Grossman, E Lenders, J TI A test of the "epinephrine hypothesis" in humans SO HYPERTENSION LA English DT Article DE epinephrine; norepinephrine; nervous system, sympathetic; yohimbine; nitroprusside ID SYMPATHETIC-NERVE ACTIVITY; HUMAN FOREARM; NOREPINEPHRINE; RELEASE; STIMULATION; REMOVAL; PLASMA; HYPERTENSION; ACTIVATION; INFUSION AB According to the "epinephrine hypothesis," circulating epinephrine taken up by sympathetic nerves is coreleased with norepinephrine during sympathetic stimulation and binding of coreleased epinephrine to presynaptic beta-adrenoceptors augments exocytotic release of norepinephrine, contributing to high blood pressure. This study examined whether infusion of a physiologically active amount of epinephrine affects subsequent vascular responses and the estimated rate of entry of norepinephrine into regional venous plasma (norepinephrine spillover). Each of 3 experiments included intravenous infusion of H-3-norepinephrine, measurements of forearm vascular resistance, and intra-arterial infusion of epinephrine (3 ng/min per deciliter forearm volume). In experiment I, subjects underwent lower body negative pressure (LBNP-25 mm Hg) before and after intra-arterial epinephrine; in experiment 2, LBNP and intra-arterial yohimbine before and after intra-arterial epinephrine; and in experiment 3, intravenous nitroprusside before and after intra-arterial epinephrine. In all subjects, intra-arterial epinephrine produced ipsilateral pallor and decreased forearm vascular resistance. Ipsilateral venous epinephrine increased by 10-fold. Epinephrine did not affect forearm vasoconstrictor responses to LBNP or vasodilator responses to intra-arterial yohimbine or intravenous nitroprusside; did not affect venous norepinephrine levels or norepinephrine spillover during LBNP, yohimbine, LBNP during yohimbine, or nitroprusside; and did not increase venous epinephrine levels during any of these manipulations. Loading of forearm sympathetic terminals with epinephrine therefore does not augment subsequent neurogenic vasoconstriction or norepinephrine release in the human forearm in response to sympathetic stimulation. The findings are inconsistent with the epinephrine hypothesis. C1 NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. US FDA, Dept Hlth & Human Serv, Rockville, MD USA. Mayo Clin, Rochester, MN USA. Chaim Sheba Med Ctr, Dept Internal Med D, IL-52621 Tel Hashomer, Israel. Univ Nijmegen St Radboud Hosp, Dept Internal Med, NL-6500 HB Nijmegen, Netherlands. RP Goldstein, DS (reprint author), NINDS, Clin Neurosci Branch, NIH, Bldg 10,Room 6N252,10 Ctr Dr MSC 1620, Bethesda, MD 20892 USA. NR 24 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 1999 VL 33 IS 1 BP 36 EP 43 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 161JM UT WOS:000078285500008 PM 9931079 ER PT B AU Mackison, F AF Mackison, F BE Dennis, J TI Laser pointers - A regulatory perspective SO ILSC'99: PROCEEDINGS OF THE INTERNATIONAL LASER SAFETY CONFERENCE SE LASER INSTITUTE OF AMERICA - PROCEEDINGS LA English DT Proceedings Paper CT International Laser Safety Conference (ILSC 99) CY MAR 08-11, 1999 CL ORLANDO, FL SP Laser Inst Amer AB This paper presents an overview of the Federal regulations covering laser products and the process of importation of laser pointers. It also presents the results of testing the radiation output of 212 pointers collected from 18 different shipments of laser pointers being imported for distribution in U.S. Commerce. Results of evaluation compliance of the [pointers with the labeling and user information requirements of the Federal performance standard for laser products are also given. C1 US FDA, Off Compliance, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Mackison, F (reprint author), US FDA, Off Compliance, Ctr Devices & Radiol Hlth, 2098 Gaither Rd, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LASER INST AMERICA PI ORLANDO PA 12424 RESEARCH PKWY, STE 130, ORLANDO, FL 32826 USA BN 0-912035-17-4 J9 LIA P PY 1999 VL 4 BP 136 EP 146 PG 11 WC Engineering, Biomedical; Public, Environmental & Occupational Health; Ophthalmology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Public, Environmental & Occupational Health; Ophthalmology; Radiology, Nuclear Medicine & Medical Imaging GA BN49H UT WOS:000082032700016 ER PT B AU Dennis, JE AF Dennis, JE BE Dennis, J TI What are reasonably foreseeable conditions of operation? SO ILSC'99: PROCEEDINGS OF THE INTERNATIONAL LASER SAFETY CONFERENCE SE LASER INSTITUTE OF AMERICA - PROCEEDINGS LA English DT Proceedings Paper CT International Laser Safety Conference (ILSC 99) CY MAR 08-11, 1999 CL ORLANDO, FL SP Laser Inst Amer AB Ideally, organizations that develop standards must strive to make their standards as clear and unambiguous as possible. Unclear or ambiguous requirements lead to inconsistencies in interpretation and application by manufacturers, regulatory agencies, consultants and third-party testers or certifying organizations. The results are varying degrees of compliance with standards. This condition sets the stage for unfair competition, frustrating one of the primary goals of standards. In this presentation, various situations will be considered with their impact on the compliance of products with applicable standards. The conclusion is that in the development of standards, requirements must be crafted to avoid ambiguity and to avoid the possibility of more than one interpretation. C1 US FDA, Ctr Devices & Radiol Hlth, Off Compliance, Rockville, MD 20857 USA. RP Dennis, JE (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Compliance, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LASER INST AMERICA PI ORLANDO PA 12424 RESEARCH PKWY, STE 130, ORLANDO, FL 32826 USA BN 0-912035-17-4 J9 LIA P PY 1999 VL 4 BP 180 EP 183 PG 4 WC Engineering, Biomedical; Public, Environmental & Occupational Health; Ophthalmology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Public, Environmental & Occupational Health; Ophthalmology; Radiology, Nuclear Medicine & Medical Imaging GA BN49H UT WOS:000082032700020 ER PT S AU Waynant, RW Ilev, IK Gannot, I AF Waynant, RW Ilev, IK Gannot, I BE Saad, M Harrington, JA TI Medical applications of infrared fibers and waveguides SO INFRARED OPTICAL FIBERS AND THEIR APPLICATIONS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT SPIE Conference on Infrared Optical Fibers and Their Applications CY SEP 21-22, 1999 CL BOSTON, MA SP SPIE DE fibers; infrared; waveguide; evanescent wave ID FLEXIBLE WAVE-GUIDES; LASER-RADIATION AB Recent work has been done to study the transmission properties of infrared fibers (sapphire, fluoride and chalcogenide) and hollow reflecting waveguides for a range of cw and pulsed infrared lasers. Performance of these devices for medical applications has also been studied. Work has been focused on lowering costs and improving performance as well as on fabrication of novel handpieces that increase safety and improve energy transfer for cosmetic therapy. Evanescent wave coupling to tissue for diagnostic and therapeutic applications is also being evaluated. C1 US FDA, Rockville, MD 20857 USA. RP Waynant, RW (reprint author), US FDA, Rockville, MD 20857 USA. NR 6 TC 2 Z9 2 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3442-6 J9 P SOC PHOTO-OPT INS PY 1999 VL 3849 BP 2 EP 6 DI 10.1117/12.372788 PG 5 WC Optics SC Optics GA BP35C UT WOS:000084810400001 ER PT J AU Rotheram-Borus, MJ Murphy, DA Swendeman, D Chao, B Chabon, B Zhou, S Birnbaum, J O'Hara, P AF Rotheram-Borus, MJ Murphy, DA Swendeman, D Chao, B Chabon, B Zhou, S Birnbaum, J O'Hara, P TI Substance use and its relationship to depression, anxiety, and isolation among youth living with HIV SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE adolescents; HIV; substance use ID BISEXUAL MALE-ADOLESCENTS; SOCIAL SUPPORT; AFRICAN-AMERICAN; EMOTIONAL DISTRESS; HOMOSEXUAL MEN; RISK BEHAVIOR; GAY; SYMPTOMS; DETERMINANTS; PREVALENCE AB Reductions from lifetime to recent levels of substance use, the time since HIV diagnosis, physical health symptoms, CD4 counts, emotional distress, and social supports were examined among 227 (20% female; 22% African American, 27% Angle, 35% Latino) youth living with HN (YLH) ages 13 to 24 years. Substance use pervaded the lives of these youth. Male YLH had used more drugs, more often, and for longer periods than women. However, there had been major reductions in use. Being male, having high emotional distress, and having fewer negative social supports were significantly associated with greater reductions in substance use. There was a trend for the length of time that an individual was seropositive being associated with reductions in substance use. The counterintuitive findings suggest that there must be a re-examination of the role of the social support networks of youth living with HN, as well as the ways in which emotional distress interacts with risk behaviors. C1 Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA 90406 USA. Montefiore Med Ctr, Dept Psychiat, Bronx, NY 10467 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Kings Cty Hosp Ctr, Brooklyn, NY 11203 USA. Middle Tennessee State Univ, Murfreesboro, TN 37130 USA. RP Rotheram-Borus, MJ (reprint author), Univ Calif Los Angeles, Dept Psychiat, 10920 Wilshire Blvd,Suite 350, Los Angeles, CA 90024 USA. NR 56 TC 8 Z9 8 U1 1 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PY 1999 VL 6 IS 4 BP 293 EP 311 DI 10.1207/s15327558ijbm0604_1 PG 19 WC Psychology, Clinical SC Psychology GA 303CL UT WOS:000086403200001 PM 16250672 ER PT J AU Murata, T Taguchi, J Puri, RK Mohri, H AF Murata, T Taguchi, J Puri, RK Mohri, H TI Sharing of receptor subunits and signal transduction pathway between the IL-4 and IL-13 receptor system SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Review DE interleukin-4 receptor; interleukin-13 receptor; Janus protein tyrosine kinase; signal transduction ID CELL CARCINOMA-CELLS; INTERLEUKIN (IL)-13 BINDING; COMMON GAMMA-CHAIN; HUMAN GLIOMA-CELLS; RESTING B-CELLS; PSEUDOMONAS EXOTOXIN; FUNCTIONAL COMPONENT; ALPHA CHAIN; MYELOID CELLS; GROWTH-FACTOR AB In this review, we summarize the subunit structure of the interleukin (IL)-4 and IL-13 receptor system and the molecular mechanism of signals through the cytokine receptor systems. We have demonstrated that two different forms of IL-4R exist, classical and alternative. Classical IL-4R is predominantly expressed in hematopoietic cells and consists of IL-4R p140 (beta) and IL-2R gamma(gamma(c)) chains. The alternative form of IL-4R is predominantly expressed in nonhematopoietic cells and consists of IL-4R beta and n-13R alpha' chains. Moreover, the alternative form of IL-4R is also used as a functional component in the IL-13R complex. For signal transduction through IL-4R and IL-13R, we have demonstrated that in nonhematopoietic cells, Janus protein tyrosine kinase (JAK) 2 is phosphorylated and activated instead of JAK3 tyrosine kinase. While JAK3 is required for signal transducer and activator of transcription-6 (STAT6) activation in hematopoietic cells, we recently demonstrated that in nonhematopoietic cells JAK2 is required for STAT6 activation for the alternative form of IL-4R. Thus, a major difference exists between hematopoietic and nonhematopoietic cells with regard to structure and signal transduction through the IL-4R and IL-13R systems. (C) 1999 The Japanese Society of Hematology. C1 Yokohama City Univ, Sch Med, Dept Internal Med 1, Yokohama, Kanagawa 236, Japan. US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD USA. RP Murata, T (reprint author), Yokohama City Univ, Sch Med, Dept Internal Med 1, Yokohama, Kanagawa 236, Japan. NR 56 TC 50 Z9 50 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD JAN PY 1999 VL 69 IS 1 BP 13 EP 20 PG 8 WC Hematology SC Hematology GA 284RM UT WOS:000085346300004 PM 10641437 ER PT J AU Fiddler, W Pensabene, JW Gates, RA Donoghue, DJ AF Fiddler, W Pensabene, JW Gates, RA Donoghue, DJ TI Supercritical fluid extraction of organochlorine pesticides in eggs SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE supercritical fluid extraction; SFE; organochlorine pesticides; OCPs; chicken eggs ID RESIDUES; CLEANUP AB The efficacy of supercritical fluid extraction (SFE) for the recovery of 16 common organochlorine pesticides (OCPs) from liquid whole eggs was investigated by employing supercritical carbon dioxide (SC-CO2) without the use of a solvent modifier to minimize interfering coextractives. The OCPs tested included aldrin; alpha-, beta-, delta-, and gamma-BHCs; p,p'-DDD, -DDE, and -DDT; dieldrin; endosulfans I, II, and sulfate; endrin; endrin aldehyde; heptachlor; and heptachlor epoxide. The SFE conditions were as follows: 10000 psi (680 bar),40 degrees C, SC-CO2 now rate of 3.0 L/min with an extraction time of 40 min for a total of 120 L of CO2. The OCPs were trapped off-line in an SPE cartridge containing Florisil and then eluted by an acetone/hexane mixture and analyzed by gas chromatography-electron capture detection (GC-ECD). Recovery studies were carried out on homogenized eggs fortified at the 0.05, 0.10, and 0.20 ppm levels. At the lowest level, 0.05 ppm, recoveries ranged from 81.8 to 108.3%, with CVs <9.8%. All recoveries were significantly higher than those obtained by an AOAC/ FDA solvent extraction method. Eggs containing incurred endosulfan I were also effectively extracted by SFE. This study suggests that the application of SFE for the extraction of OCPs from eggs will. result in significant savings in analysis time and lower solvent use and disposal costs compared to conventional solvent extraction procedures. C1 ARS, USDA, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. US FDA, Div Anim Res, Ctr Vet Med, Laurel, MD 20708 USA. RP Fiddler, W (reprint author), ARS, USDA, Eastern Reg Res Ctr, 600 E Mermaid Lane, Wyndmoor, PA 19038 USA. NR 25 TC 30 Z9 32 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JAN PY 1999 VL 47 IS 1 BP 206 EP 211 DI 10.1021/jf980436m PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 158UT UT WOS:000078136200035 PM 10563873 ER PT J AU Brenner, RJ Taffs, R Focks, DA Wiechmann, G Anderson, MC Horowitz, E Milne, D Westmoreland, J Hulme, C Quander, T Togias, A AF Brenner, RJ Taffs, R Focks, DA Wiechmann, G Anderson, MC Horowitz, E Milne, D Westmoreland, J Hulme, C Quander, T Togias, A TI A new approach to environmental assessment in cockroach (CR) related asthma. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. US FDA, Bethesda, MD 20014 USA. Univ Florida, USDA ARS, Gainesville, FL 32611 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 1999 VL 103 IS 1 SU S MA 907 BP S236 EP S236 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000909 ER PT J AU Choudhury, BK Klinman, D Wild, JS Sur, N Alam, R Sur, S AF Choudhury, BK Klinman, D Wild, JS Sur, N Alam, R Sur, S TI Anti-inflammatory effects of CpG ODN in a murine model of asthma: a critical role for IFN-gamma. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. US FDA, Bethesda, MD 20014 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 801 BP S208 EP S208 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000803 ER PT J AU Markovi-Housley, Z Schirmer, T Soldatova, LN Muller, UR AF Markovi-Housley, Z Schirmer, T Soldatova, LN Muller, UR TI A preliminary crystallographic structure of a recombinant bee venom hyaluronidase. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Ziegler Spital, Bern, Switzerland. Univ Basel, Bioctr, CH-4056 Basel, Switzerland. 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 650 BP S170 EP S170 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000653 ER PT J AU Soldatova, LN Burk, SH Pastor, RW AF Soldatova, LN Burk, SH Pastor, RW TI Stability of house dust mite allergens in glycerinated extracts. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 606 BP S158 EP S158 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000610 ER PT J AU Tomazic-Jezic, VJ Woolhizer, MR Beezhold, DH AF Tomazic-Jezic, VJ Woolhizer, MR Beezhold, DH TI Quantification of latex proteins by inhibition ELISA. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIOSH, HELD, Morgantown, WV USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. GRI, Sayre, PA USA. NR 0 TC 5 Z9 5 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 1999 VL 103 IS 1 SU S MA 619 BP S162 EP S162 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000622 ER PT J AU Wild, JS Klinman, DM Choudhury, BK Sur, N Alam, R Sur, S AF Wild, JS Klinman, DM Choudhury, BK Sur, N Alam, R Sur, S TI Long-term prevention of allergic lung inflammation by CpG ODN in a murine model of asthma. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 479 BP S125 EP S125 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000484 ER PT J AU Trucksess, MW Giler, J Young, K White, KD Page, SW AF Trucksess, MW Giler, J Young, K White, KD Page, SW TI Determination and survey of ochratoxin A in wheat, barley, and coffee - 1997 SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Ochratoxin A (OA) is a nephrotoxic and nephrocarcinogenic mycotoxin produced by Aspergillus and Penicillium species. it has been found mainly in cereal grains and coffee beans. The purpose of this study was to investigate the occurrence of OA in cereal grains and in coffee imported to the United States. A modified liquid chromatographic (LC) method for determining OA in green coffee was applied to wheat, barley, green coffee, and roasted coffee. The test sample was extracted with methanol-1% NaHCO3 (7 + 3), and the extract was filtered. The filtrate was diluted with phosphate-buffered saline (PBS), filtered, and passed through an immunoaffinity column. After the column was washed with PBS and then with water, OA was eluted with methanol, The eluate was evaporated to dryness, and the residue was dissolved in acetonitrile-water (1 + 1). OA was separated on a reversed-phase Cls LC column with acetonitrile-water-acetic acid (55 + 45 + 1) as eluant and quantitated with a fluorescence detector. Recoveries of OA from the 4 commodities spiked over the range 1-4 ng/g were 71-96%, The limit of detection was about 0.03 ng/g, OA contamination at >0.03 ng/g was found in 56 of 383 wheat samples, 11 of 103 barley samples, 9 of 19 green coffee samples, and 9 of 13 roasted coffee samples. None of the coffee samples contained OA at >5 ng/g; only 4 samples of wheat and 1 sample of barley were contaminated above this level. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. USDA ARS, Washington, DC 20204 USA. RP Trucksess, MW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 10 TC 126 Z9 129 U1 0 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1999 VL 82 IS 1 BP 85 EP 89 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 165KA UT WOS:000078518900013 PM 10028675 ER PT J AU Ware, GM Zhao, YH Kuan, SS Carman, AS AF Ware, GM Zhao, YH Kuan, SS Carman, AS TI Preparative method for isolating alpha-zearalenol and zearalenone using extracting disk SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SOLID-PHASE EXTRACTION; LIQUID-CHROMATOGRAPHIC DETERMINATION; GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; FLUORESCENCE DETECTION; PEANUT PRODUCTS; DRINKING-WATER; METABOLITES; CORN; IDENTIFICATION AB A liquid chromatographic method is described for the determination of zearalenol and zearalenone in corn. Zearalenol and zearalenone are extracted from corn with methanol-water (1+1) and cleaned up using a solid-phase extraction (SPE) disk, separated on a reversed-phase analytical column, and detected with a fluorescence detector. The SPE disk concentrated and cleanly separated zearalenol and zearalenone from sample interferences. Standard calibration curves for zearalenol and zearalenone for the concentration range 25-500 ng/mL were linear. The small extract disk had a column capacity equivalent to 1 g extracted corn. Zearalenol and zearalenone were added at levels ranging from 10 to 2000 ng/g to a control sample that contained no detectable levels of zearalenol and zearalenone. Both toxins were recovered from spiked samples at 106.3 and 103.8%, with coefficients of variation of 7.6 and 13.0%, respectively. The method has an estimated reliable limit of detection and limit of quantitation around 10 and 40 ng/g for each toxin, respectively. C1 US FDA, Natl Toxins Res Ctr, New Orleans, LA 70122 USA. RP Ware, GM (reprint author), US FDA, Natl Toxins Res Ctr, 4298 Elysian Fields Ave, New Orleans, LA 70122 USA. NR 22 TC 12 Z9 12 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 1999 VL 82 IS 1 BP 90 EP 94 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 165KA UT WOS:000078518900014 PM 10028676 ER PT J AU Chase, GW Eitenmiller, RR Long, AR AF Chase, GW Eitenmiller, RR Long, AR TI A liquid chromatographic method for analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in medical food using matrix solid-phase dispersion in conjunction with a zero reference material 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 and retinyl palmitate in medical food. The vitamins are extracted from medical food without saponification by matrix solid-phase dispersion and chromatographed by normal-phase chromatography with fluorescence detection. Retinyl palmitate and all-rac-alpha-tocopheryl acetate are quantitated isocratically with a mobile phase of 0.125% (v/v) and 0.5% (v/v) isopropyl alcohol in hexane, respectively. Results compared favorably with label declarations on retail medical foods. Recoveries determined on an analyte-fortified zero reference material for a milk-based medical food averaged 98.3% (n = 25) for retinyl palmitate spikes and 95.7% (n = 25) for all-rac-alpha-tocopheryl acetate spikes. Five concentrations were examined for each analyte, and results were linear (r(2) = 0.995 for retinyl palmitate and 0.9998 for all-rac-alpha-tocopheryl acetate) over the concentration range examined, with coefficients of variation in the range 0.81-4.22%. The method provides a rapid, specific, and easily controlled assay for analysis of retinyl palmitate and all-rac-alpha-tocopheryl acetate in fortified medical foods. 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 9 TC 11 Z9 11 U1 0 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1999 VL 82 IS 1 BP 107 EP 111 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 165KA UT WOS:000078518900016 PM 10028678 ER PT J AU Danielson, JW Thompson, RD Bell, E AF Danielson, JW Thompson, RD Bell, E TI Sporicidal testing of commercial germicides using a chemical standard and a calibrated bioindicator SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID BACILLUS-SUBTILIS SPORES AB The AOAC sporicidal method uses as a standard the resistance of spores on carriers to 2.5N HCl. This resistance is variable at exposure times ranging from 2 to 20 min, The method described in this paper uses a glutaraldehyde standard and distinguishes various levels of sporicidal activity in the presence of 1-5% glutaraldehyde by using appropriate spore strains, spore preparations, and spore levels. The resistances of 2 Bacillus subtilis 19659 spore preparations cultured in 10% Columbia broth plus manganese and nutrient agar plus minerals, as well as that of B. subtilis var. niger cultured on Lab-Lemco agar, were tested. T-soy broth was a better recovery medium than fluid thioglycollate or modified fluid thioglycollate for B. subtilis 19659 spores exposed to HCl. Sporicidal tests were done on B. subtilis 19659 spores with 2 types of spore preparations. A commercial glutaraldehyde germicide was used for comparison of the sporicidal activity of the glutaraldehyde standard. Two strains of B, subtilis spores and 4 levels of spores (20 000-80 000, 100 000-400 000, 500 000-800 000, and 1 000 000 and up) were removed from check penicylinders from the same batches used for sporicidal tests. B, subtilis var. niger spores were the most resistant to HCl, while B. subtilis 19659 spores were more resistant to glutaraldehyde. Sporicidal activities of a commercial germicide containing 2.5% glutaraldehyde with additives and another containing 5% glutaraldehyde in phosphate buffer were similar. Both totally destroyed high levels of B. subtilis 19659 spores cultured in 10% Columbia broth plus manganese. Results indicate that use of a glutaraldehyde standard, calibrated numbers of spores on penicylinders (bioindicators), and appropriate spore strains and preparations can reduce the variability of sporicidal testing of commercial germicides. C1 US FDA, Cent Lab Microbiol Invest, Minneapolis, MN 55401 USA. US FDA, Minneapolis Dist Lab, Minneapolis, MN 55401 USA. Gustavus Adolphus Coll, St Peter, MN 56082 USA. RP Danielson, JW (reprint author), US FDA, Cent Lab Microbiol Invest, 240 Hennepin Ave, Minneapolis, MN 55401 USA. NR 15 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 1999 VL 82 IS 1 BP 151 EP 159 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 165KA UT WOS:000078518900022 PM 10028684 ER PT J AU Rafii, F Coleman, T AF Rafii, F Coleman, T TI Cloning and expression in Escherichia coli of an azoreductase gene from Clostridium perfringens and comparison with azoreductase genes from other bacteria SO JOURNAL OF BASIC MICROBIOLOGY LA English DT Article ID HUMAN INTESTINAL MICROFLORA; AZO DYES; REDUCTION; ACTIVATION; DRUG AB A genomic library of Clostridium perfringens ATCC 3626 was constructed in phage lambda gt11 and screened with an antibody against the C. perfringens azoreductase, which catalyzes the reduction of azo dyes to aromatic amines. A positive recombinant phage, containing a 3.8 kb DNA fragment insert was selected and purified. Lytic and lysogenic Escherichia coli cultures infected with the recombinant phage had higher azoreductase activity than cultures infected only with the vector lambda gt11. The 3.8 kb DNA fragment was amplified by PCR and found to hybridize with one band from C. perfringens DNA digested with EcoR1, indicating the presence of a single copy of the azoreductase gene. The fragment also hybridized with DNA from other azoreductase-producing Clostridium species, a Eubacterium sp., Enterobacter cloacae, Citrobacter amalonaticus and E. coli, but not with DNA from some other species of anaerobic bacteria capable of reducing azo dyes. The data indicate that the sequence of the azoreductase gene of C, perfringens is conserved in some anaerobes and facultative anaerobes, but not in others, and that different types of azoreductase genes must be found in other anaerobic bacteria. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Rafii, F (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM FRafii@nctr.fda.gov NR 20 TC 29 Z9 31 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0233-111X J9 J BASIC MICROB JI J. Basic Microbiol. PY 1999 VL 39 IS 1 BP 29 EP 35 DI 10.1002/(SICI)1521-4028(199903)39:1<29::AID-JOBM29>3.3.CO;2-N PG 7 WC Microbiology SC Microbiology GA 166LL UT WOS:000078578000005 PM 10071864 ER PT J AU Kidder, LH Colarusso, P Stewart, SA Levin, IW Appel, NM Lester, DS Pentchev, PG Lewis, EN AF Kidder, LH Colarusso, P Stewart, SA Levin, IW Appel, NM Lester, DS Pentchev, PG Lewis, EN TI Infrared spectroscopic imaging of the biochemical modifications induced in the cerebellum of the Niemann-Pick type C mouse SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE infrared spectroscopic imaging; FTIR spectroscopy; Niemann-Pick type C; neuropathology; cerebellum ID DISEASE TYPE-C; MURINE MODEL; TISSUE; STORAGE; CLASSIFICATION; CARCINOMA; SECTIONS; MUTATION; SYSTEMS; SPECTRA AB We have applied Fourier transform infrared (IR) spectroscopic imaging to the investigation of the neuropathologic effects of a genetic lipid storage disease, Niemann-Pick type C (NPC). Tissue sections both from the cerebella of a strain of BALB/c mice that demonstrated morphology and pathology of the human disease and from control animals were used. These samples were analyzed by standard histopathological procedures as well as this new IR imaging approach. The IR absorbance images exhibit contrast based on biochemical variations and allow for the identification of the cellular layers within the tissue samples. Furthermore, these images provide a qualitative description of the localized biochemical differences existing between the diseased and control tissue in the absence of histological staining. Statistical analyses of the IR spectra extracted from individual cell layers of the imaging data sets provide concise quantitative descriptions of these biochemical changes. The results indicate that lipid is depleted specifically in the white matter of the NPC mouse in comparison to the control samples. Minor differences were noted for the granular layers, but no significant differences were observed in the molecular layers of the cerebellar tissue. These changes are consistent with significant demyelination within the cerebellum of the NPC mouse. (C) 1999 Society of Photo-Optical Instrumentation Engineers. [S1083-3668(99)00401-3]. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Laurel, MD 20708 USA. NINDS, NIH, Dev & Metab Neurol Branch, Mol & Cellular Pathol Sect, Bethesda, MD 20892 USA. RP Lewis, EN (reprint author), 9000 Rockville Pike,Bldg 5,Room B1-38, Bethesda, MD 20892 USA. NR 29 TC 21 Z9 22 U1 0 U2 2 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN PY 1999 VL 4 IS 1 BP 7 EP 13 DI 10.1117/1.429915 PG 7 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 229FY UT WOS:000082183900002 PM 23015163 ER PT J AU Hood, HL Bronaugh, RL AF Hood, HL Bronaugh, RL TI A comparison of skin viability assays for in vitro skin absorbtion/metabolism studies SO JOURNAL OF COSMETIC SCIENCE LA English DT Article ID INVITRO PERCUTANEOUS-ABSORPTION C1 Bristol Myers Squibb, Clairol Div, Stamford, CT USA. Off Cosmet & Colors, Food & Drug Adm, Washington, DC USA. RP Hood, HL (reprint author), Bristol Myers Squibb, Clairol Div, Stamford, CT USA. NR 6 TC 1 Z9 1 U1 1 U2 3 PU SOC COSMETIC CHEMISTS PI NEW YORK PA 120 WALL STREET, SUITE 2400, NEW YORK, NY 10005-4088 USA SN 0037-9832 J9 J COSMET SCI JI J. Cosmet. Sci. PD JAN-FEB PY 1999 VL 50 IS 1 BP 63 EP 64 PG 2 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA 175RP UT WOS:000079109000010 ER PT J AU Lipe, GW Duhart, H Newport, GD Slikker, W Ali, SF AF Lipe, GW Duhart, H Newport, GD Slikker, W Ali, SF TI Effect of manganese on the concentration of amino acids in different regions of the rat brain SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART B-PESTICIDES FOOD CONTAMINANTS AND AGRICULTURAL WASTES LA English DT Article DE manganese; amino acids; neurotransmitters; body weight; neurotoxicity AB The present study was designed to determine if chronic exposure of weanlings and adult rats to Mn produces significant alterations in amino acid concentrations in different regions of the rat brain. Weanling (30 day old) and adult (90 day old) male rats were exposed to 10 and 20 mg Mn/kg body weight per day, by gavage, for 30 days. Forty-eight hours after the last dose, animals were sacrificed by decapitation and brains were dissected into different regions to determine the concentration of amino acids by HPLC/EC. A dose dependent decrease in body weight gain was found in the adult, but not in the weanling rats. Significant increases occurred in concentrations of aspartate, glutamate, glutamine, taurine and gamma-aminobutyric acid (GABA) in the cerebellum of the adult rats dosed with 20 mg/kg per day, Mn. A significant decrease in the concentration of glutamine was observed in caudate nucleus and hippocampus of weanling rats dosed with 10 mg/kg, Mn. These data suggest that chronic Mn exposure can produce a decrease in body weight gain in adult rats and alterations in amino acids in different regions of weanling and adult rat brains. C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Lipe, GW (reprint author), US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 17 TC 37 Z9 40 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-1234 J9 J ENVIRON SCI HEAL B JI J. Environ. Sci. Health Part B-Pestic. Contam. Agric. Wastes PY 1999 VL 34 IS 1 BP 119 EP 132 DI 10.1080/03601239909373187 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 168UV UT WOS:000078712300008 PM 10048208 ER PT J AU Schenck, FJ Casanova, J AF Schenck, FJ Casanova, J TI Rapid screening for organochlorine and organophosphorus pesticides in milk using C-18 and graphitized carbon black solid phase extraction cleanup SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART B-PESTICIDES FOOD CONTAMINANTS AND AGRICULTURAL WASTES LA English DT Article DE milk; pesticides; solid phase extraction ID CAPILLARY GAS-CHROMATOGRAPHY; RESIDUES AB A rapid, multiresidue, solid phase extraction (SPE) technique for the isolation and gas chromatographic determination of organochlorine and moderately polar organophosphorus pesticide residues in milk is described. Milk is sonicated with an acetonitrile-acetone-methanol mixture and centrifuged. The supernatant is subjected to a cleanup using both C-18 and graphitized carbon black SPE columns. The pesticide residues are determined by gas chromatography with electron capture and flame photometric detection. The method required minimal volumes of solvent and resulted in the production of minimal volumes of hazardous waste. C1 US FDA, Baltimore Dist Lab, Baltimore, MD 21201 USA. US FDA, SE Reg Lab, Atlanta, GA 30309 USA. RP Schenck, FJ (reprint author), US FDA, Baltimore Dist Lab, 900 Madison Ave, Baltimore, MD 21201 USA. NR 15 TC 12 Z9 12 U1 0 U2 5 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-1234 J9 J ENVIRON SCI HEAL B JI J. Environ. Sci. Health Part B-Pestic. Contam. Agric. Wastes PY 1999 VL 34 IS 3 BP 349 EP 362 DI 10.1080/03601239909373202 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 194XV UT WOS:000080220800001 PM 10227188 ER PT J AU Fu, PP Herreno-Saenz, D AF Fu, PP Herreno-Saenz, D TI Nitro-polycyclic aromatic hydrocarbons: A class of genotoxic environmental pollutants SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review ID DNA ADDUCT FORMATION; HAMSTER OVARY CELLS; RAT-LIVER MICROSOMES; DIRECT-ACTING MUTAGENICITY; AIRBORNE PARTICULATE MATTER; DIESEL-EXHAUST PARTICLES; SALMONELLA-TYPHIMURIUM; METABOLIC-ACTIVATION; CHEMICAL CARCINOGENESIS; INTESTINAL MICROFLORA C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Puerto Rico, Dept Pharmacol, San Juan, PR 00936 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 187 TC 12 Z9 12 U1 1 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 1999 VL 17 IS 1 BP 1 EP 43 DI 10.1080/10590509909373506 PG 43 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 195HU UT WOS:000080245200001 ER PT J AU Hammack, TS Amaguana, RM June, GA Sherrod, PS Andrews, WH AF Hammack, TS Amaguana, RM June, GA Sherrod, PS Andrews, WH TI Relative effectiveness of selenite cystine broth, tetrathionate broth, and Rappaport-Vassiliadis medium for the recovery of Salmonella spp. from foods with a low microbial load SO JOURNAL OF FOOD PROTECTION LA English DT Article ID HIGHLY CONTAMINATED FOODS; SELECTIVE ENRICHMENT; MEAT-PRODUCTS; GREEN BROTH; RAW FLESH; RV AB The relative effectiveness of Rappaport-Vassiliadis (RV) medium, selenite cystine (SC) broth, and tetrathionate (TT) broth for the recovery of Salmonella spp. from foods with a low microbial load was determined. RV medium made from its individual ingredients and incubated at 42 degrees C was compared with a commercial preparation of SC broth, incubated at 35 degrees C, and TT broth incubated at 35 and 43 degrees C, for the recovery of Salmonella spp. Twenty-one artificially contaminated food types that included dairy foods, spices, and egg products, as well as other low-microbial-load foods, were analyzed. The foods were inoculated with single Salmonella serovars at target levels ranging from 0.04 to 0.4 CFU/g. No significant differences (P less than or equal to 0.05) among the selective enrichment broths for the recovery of Salmonella spp. from 18 of the foods were observed. Significantly fewer Salmonella-positive test portions of gelatin, guar gum, and nonfat dry milk were recovered with RV medium than with SC broth incubated at 35 degrees C and TT broth incubated at 35 and 43 degrees C. IT broth incubated at 35 degrees C recovered the greatest number of Salmonella-positive test portions. For the recovery of Salmonella spp. from foods with a law microbial load, it is recommended that TT broth incubated at 35 degrees C and RV medium incubated at 42 degrees C be used. C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. RP Hammack, TS (reprint author), US FDA, Div Microbiol Studies, 200 C St,SW,HSF-516, Washington, DC 20204 USA. NR 27 TC 25 Z9 27 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 JAN PY 1999 VL 62 IS 1 BP 16 EP 21 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 159YA UT WOS:000078201900003 PM 9921822 ER PT J AU LeBeau, M Andollo, W Hearn, WL Baselt, R Cone, E Finkle, B Fraser, D Jenkins, A Mayer, J Negrusz, A Poklis, A Walls, C Raymon, L Robertson, M Saady, J AF LeBeau, M Andollo, W Hearn, WL Baselt, R Cone, E Finkle, B Fraser, D Jenkins, A Mayer, J Negrusz, A Poklis, A Walls, C Raymon, L Robertson, M Saady, J TI Recommendations for toxicological investigations of drug-facilitated sexual assaults SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; drug-facilitated; sexual assault; drug rape; date rape; forensic toxicology ID GC-MS; FLUNITRAZEPAM; URINE; BENZODIAZEPINES; BLOOD; HAIR; NCI AB The recent increase in reports of drug-facilitated sexual assaults has caused alarm in the general public and prompted forensic toxicologists from across North America to address the toxicological issues surrounding this matter. The authors have developed recommendations and guidelines to inform law enforcement, medical, and scientific personnel of the requirements for per forming successful toxicological examinations in cases of drug-facilitated rape. C1 Fed Bur Invest, FBI Lab, Chem Unit, Washington, DC 20535 USA. Dade Cty Med Examiner Dept, Miami, FL 33136 USA. Inst Chem Toxicol, Foster City, CA 94404 USA. Natl Inst Drug Abuse, Baltimore, MD 21224 USA. US FDA, Cincinnati, OH 45202 USA. Cuyahoga Cty Coroners Off, Cleveland, OH 44106 USA. Univ Toronto, Toronto, ON, Canada. Ctr Forens Sci, Toronto, ON M7A 2G8, Canada. Univ Illinois, Chicago, IL 60612 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Univ Miami, Miami, FL 33177 USA. Natl Med Serv, Willow Grove, PA 19090 USA. Virginia Div Forens Sci, Richmond, VA 23219 USA. RP LeBeau, M (reprint author), Fed Bur Invest, FBI Lab, Chem Unit, Washington, DC 20535 USA. NR 22 TC 108 Z9 116 U1 0 U2 16 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 JAN PY 1999 VL 44 IS 1 BP 227 EP 230 PG 4 WC Medicine, Legal SC Legal Medicine GA 293AV UT WOS:000085830100039 PM 9987892 ER PT J AU Shirai, M Arichi, T Chen, M Nishioka, M Ikeda, K Takahashi, H Enomoto, N Saito, T Major, ME Nakazawa, T Akatsuka, T Feinstone, SM Berzofsky, JA AF Shirai, M Arichi, T Chen, M Nishioka, M Ikeda, K Takahashi, H Enomoto, N Saito, T Major, ME Nakazawa, T Akatsuka, T Feinstone, SM Berzofsky, JA TI T cell recognition of hypervariable region-1 from hepatitis C virus envelope protein with multiple class II MHC molecules in mice and humans: Preferential help for induction of antibodies to the hypervariable region SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NON-B-HEPATITIS; CHRONIC NON-A; DIFFERENT DETERMINANTS; MONOCLONAL-ANTIBODIES; NUCLEOTIDE-SEQUENCE; HYPERIMMUNE SERUM; IMMUNE-RESPONSE; LYMPHOCYTES-T; ANTIGEN; EPITOPE AB Hypervariable region-1 (HVR1) from the hepatitis C virus (HCV) envelope protein is thought to be a target for neutralizing Abs, To explore HVR1 recognition by helper T cells, and their role in Ab responses, we attempted to generate helper T cells specific for HVR1 in mice of three MHC types, and with PBMC from HCV-infected HLA-diverse humans. In both species, HVR1 was presented by >1 class II MHC molecule to CD4(+) helper T cells and showed surprising interisolate cross-reactivity, The epitope for two DR4(+) patients was mapped to a more conserved C-terminal sequence containing a DR4 binding motif, possibly accounting for cross-reactivity, Strikingly, Abs to patients' own HVR1 sequences were found only in patients with T cell responses to HVR1, even though all had Abs to envelope protein, suggesting that induction of Abs to HVR1 depends on helper T cells specific for a sequence proximal to the Ab epitope, Thus, helper T cells specific for HVR1 may be functionally important in inducing neutralizing Abs to HCV, These results may be the first example of "T-B reciprocity," in which proximity of a helper T cell epitope determines Ab epitope specificity, in a human disease setting. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. Yamaguchi Univ, Sch Med, Dept Microbiol, Yamaguchi, Japan. Kagawa Med Sch, Dept Transfus Med, Kagawa 76107, Japan. Kagawa Med Sch, Dept Internal Med 3, Kagawa 76107, Japan. Nippon Med Sch, Dept Microbiol & Immunol, Tokyo 113, Japan. Tokyo Med & Dent Univ, Dept Internal Med 2, Tokyo 113, Japan. US FDA, Lab Hepatitis Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bldg 10,Room 6B-12, Bethesda, MD 20892 USA. NR 50 TC 44 Z9 46 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 1999 VL 162 IS 1 BP 568 EP 576 PG 9 WC Immunology SC Immunology GA 151YK UT WOS:000077748100073 PM 9886434 ER PT J AU Pothuluri, JV Freeman, JP Fu, PP Cerniglia, CE AF Pothuluri, JV Freeman, JP Fu, PP Cerniglia, CE TI Biotransformation of 1-nitrobenzo[e]pyrene by the fungus Cunninghamella elegans SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE nitro-PAHs; metabolism; Cunninghamella elegans; biotransformation ID POLYCYCLIC AROMATIC-HYDROCARBONS; METABOLISM; DETOXIFICATION; TRANSFORMATION; FLUORANTHENE; SULFATE AB Biotransformation of 1-nitrobenzo[e]pyrene (l-nitro-BeP), an environmental pollutant derived from the nitration of a non-carcinogen, benzo[e]pyrene, was studied using the fungus Cunninghamella elegans ATCC 36112, After 72 h incubation, 89% of 1-nitro-[(3)H]BeP added had been metabolized to two major metabolites. These metabolites were separated by reversed-phase high performance liquid chromatography and identified by (1)H NMR, UV-visible, and mass spectral techniques as 1-nitro-6-benzo[e]pyrenylsulfate and 1-nitrobenzo[e]pyrene 6-O-beta-glucopyranoside. Comparison of the fungal metabolism patterns of 1-nitro-BeP and BeP indicates that the nitro group at the C-l position of BeP altered the regioselectivity of metabolism. 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, Jefferson, AR 72079 USA. NR 25 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1367-5435 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD JAN PY 1999 VL 22 IS 1 BP 52 EP 57 DI 10.1038/sj.jim.2900601 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 180BG UT WOS:000079364600009 ER PT J AU Godar, DE AF Godar, DE TI UVA1 radiation triggers two different final apoptotic pathways SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE apoptosis; cyclosporine A; mitochondrial transmembrane potential; reactive oxygen species ID MITOCHONDRIAL PERMEABILITY TRANSITION; PROGRAMMED CELL-DEATH; ULTRAVIOLET-RADIATION; DELAYED APOPTOSIS; INDUCED IMMEDIATE; OXIDATIVE STRESS; SUPEROXIDE ANION; DOSE UVA1; INDUCTION; BCL-2 AB Because ultraviolet-A1 (UVA1; 340-400 nm) radiation is used therapeutically, this in vitro study addressed the question "how does it work?" To begin addressing this question, UVA1 radiation was first established to reduce the survival of transformed T and B lymphocytes in a linear dose-dependent manner using clonogenic reproductive assays, and that cell death occurs by apoptosis using transmission electron microscopy, Annexin V, and flow cytometry, The primary mechanism was determined to be immediate pre-programmed cell death, an apoptotic mechanism that does not require protein synthesis post-insult, by quantifying the apoptotic cells over time in the absence or presence of a translation inhibitor. To explore how UVA1 radiation induces immediate pre-programmed cell death apoptosis, reactive oxygen species and mitochondrial activity were altered during exposure using a variety of agents, while a specific fluorescent probe, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide, was used to examine mitochondrial transmembrane depolarization. To show that UVA1 mediates singlet-oxygen damage to the mitochondrial membranes, X-rays, UVB (290-320 nm), 8-methoxypsoralen and UVA, vitamin K-3, anti-Fas antibody, and blocking antibody were the negative controls, while rose bengal or protoporphyrin IX with visible light were the positive controls. Cyclosporine A, which inhibits the mitochondrial megapore from opening, was used with singlet-oxygen and superoxide-anion generators to distinguish between the two final apoptotic pathways. The collective results show that UVA1 radiation primarily mediates singlet-oxygen damage triggering immediate pre-programmed cell death apoptosis (T < 20 min) by immediately opening the cyclosporine A-sensitive ("S" site) mitochondrial megapore, while superoxide anions initiate another cyclosporine A-insensitive ("P" site) final apoptotic pathway. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Godar, DE (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12709 Twinbrook Pkwy, Rockville, MD 20857 USA. OI GODAR, DIANNE/0000-0002-7690-5223 NR 51 TC 120 Z9 126 U1 1 U2 3 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 JAN PY 1999 VL 112 IS 1 BP 3 EP 12 DI 10.1046/j.1523-1747.1999.00474.x PG 10 WC Dermatology SC Dermatology GA 153BR UT WOS:000077813300001 PM 9886256 ER PT J AU Ma, X Sun, J Riemann, H Robertson, S Marshall, J Papasavvas, E Moore, A Donnelly, R Trinchieri, G Montaner, LJ AF Ma, X Sun, J Riemann, H Robertson, S Marshall, J Papasavvas, E Moore, A Donnelly, R Trinchieri, G Montaner, LJ TI Inhibition of Interleukin-12 production in human monocyte-derived macrophages by Tumor Necrosis Factor SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Wistar Inst, Philadelphia, PA 19104 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 1999 SU S MA 149 BP 34 EP 34 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 225QX UT WOS:000081973200147 ER PT J AU Chase, GW Eitenmiller, RR Long, AR AF Chase, GW Eitenmiller, RR Long, AR TI A liquid chromatographic method for the analysis of retinyl acetate in soy based infant formula using matrix solid phase dispersion SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article AB Retinyl acetate in soy based infant formula was extracted by matrix solid phase dispersion (MSPD) and chromatographed by isocratic normal phase chromatography on a Si 60 column with a mobile phase of 0.28% (v/v) isopropanol in hexane. Detection was by fluorescence (Ex lambda=325, Em lambda=470). Fluorescence response was linear (r(2)=0.999) from 0.10 - 2.5 mu g/mL. Recoveries determined on a soy based infant formula zero control reference material (ZRM) containing added analyte at five levels averaged 94.79% (n=25) with CV's from 0.57-3.53%. The method expands the use of MSPD extraction to the analysis of retinyl acetate in soy based infant formulas. 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 7 TC 3 Z9 3 U1 0 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 1999 VL 22 IS 8 BP 1205 EP 1212 DI 10.1081/JLC-100101727 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 194CP UT WOS:000080174800008 ER PT J AU Rasooly, A Ito, Y AF Rasooly, A Ito, Y TI Toroidal coil Countercurrent Chromatography separation and analysis of staphylococcal enterotoxin a (SEA) in milk SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID FLOW-THROUGH CENTRIFUGE; ROTATING SEALS; FOODS AB Countercurrent Chromatography (CCC) utilizes continuous partitioning of solute between two immiscible solvent phases without a solid support. The absence of solid support makes CCC a suitable method for food analysis because it permits analysis of crude and complex materials that are not amenable to conventional solid-supported chromatography. CCC was evaluated for its ability to separate Staphylococcal enterotoxin A (SEA), a common cause of food poisoning, from milk. Although many foods can be analyzed for SEA directly by Western blot analysis, milk samples generally require some purification because the high concentration of milk proteins distorts SDS-PAGE mobility. Milk samples containing SEA were separated by toroidal coil CCC and the fractions were analyzed by Western immunoblotting. Fractions containing SEA were pooled, concentrated by ultrafiltration, and rechecked by Western immunoblotting. Concentrating the fractions increased the sensitivity of Western immunoblotting by approximately an order of magnitude. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Microbial Studies, Washington, DC 20204 USA. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10,Room 7N322, Bethesda, MD 20892 USA. NR 15 TC 12 Z9 12 U1 0 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 1999 VL 22 IS 9 BP 1285 EP 1293 DI 10.1081/JLC-100101732 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 200ZB UT WOS:000080569200002 ER PT J AU Shaikh, B Rummel, N Donoghue, D AF Shaikh, B Rummel, N Donoghue, D TI Determination of sulfamethazine and its major metabolites in egg albumin and egg yolk by high performance liquid chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID SUPERCRITICAL-FLUID EXTRACTION; SULFONAMIDES; RESIDUE; TISSUE; DRUGS; MILK AB A quantitative liquid chromatographic method for the determination of sulfamethazine (SMZ), N4-acetyl sulfamethazine (N4-acetyl-SMZ), and desamino sulfamethazine (desamino-SMZ) in egg albumin and egg yolk is described. Egg albumin or yolk was homogenized in acetonitrile and centrifuged. The supernatant was evaporated to dryness and residue reconstituted in the mobile phase. Albumin extract was directly analyzed by high performance liquid chromatography (HPLC). Hexane was added to the yolk sample, vortex mixed, and centrifuged to separate the layers. The top hexane layer was removed and a small amount of salt was added to break the emulsions. The lower aqueous layer was analyzed by HPLC. The HPLC system included a reversed phase column, a gradient mobile phase of 5-15% acetonitrile and 0.01M phosphate buffer, and a UV detector set at 268 nm. The recovery of SMZ and N4-acetyl-SMZ, both fortified at 1 ppm levels, from egg albumin was 101 and 88% and from egg yolk was 79 and 91%, respectively. The recovery of desamino-SMZ at 2 ppm fortification level from egg albumin and egg yolk was 84 and 63%, respectively. The method was applied to detect the presence of SMZ and its potential metabolites in eggs collected after dosing hens with SRZ. Parent drug, SMZ, was the major compound transferred to both egg albumin and yolk. Small concentration of N4-acetyl-SMZ metabolite were also detected in some eggs; however, no desamino-SMZ or other metabolites were detected. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Shaikh, B (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 14 TC 14 Z9 14 U1 1 U2 6 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 1999 VL 22 IS 17 BP 2651 EP 2662 DI 10.1081/JLC-100102049 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 247HQ UT WOS:000083215700006 ER PT J AU Ali, SF Martin, JL Black, MD Itzhak, Y AF Ali, SF Martin, JL Black, MD Itzhak, Y TI Melatonin, an antioxidant, protects against methamphetamine but not against MPTP-induced dopaminergic neurotoxicity SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Miami, Sch Med, Dept Psychiat, Miami, FL 33152 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S190 EP S190 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500752 ER PT J AU Imam, SZ Crow, JP Newport, GD Slikker, W Islam, F Ali, SF AF Imam, SZ Crow, JP Newport, GD Slikker, W Islam, F Ali, SF TI Peroxynitrite scavenger, FeTMPyP, protects against methamphetamine-induced dopaminergic neurotoxicity in mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Hamdard Univ, Dept Toxicol, New Delhi, India. Univ Alabama, Dept Anesthesiol, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S190 EP S190 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500751 ER PT J AU Slikker, W Clausing, P Bowyer, JF Schmued, L AF Slikker, W Clausing, P Bowyer, JF Schmued, L TI D-fenfluramine and hyperthermia combined produce neuronal degeneration in localized regions of the cortex, thalamus, and cerebellum of the rat SO JOURNAL OF NEUROCHEMISTRY 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S190 EP S190 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500753 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 transporter: Effects of hypo- and hyperglycemia revisited SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE blood-brain barrier; diabetes; GLUT1; glucose transporters ID EXPERIMENTAL DIABETES-MELLITUS; RAT ADIPOSE-CELLS; MESSENGER-RNA; SKELETAL-MUSCLE; EXPRESSION; PROTEIN; INSULIN; GLUT4; METABOLISM; PERFUSION AB The transport of glucose across the blood-brain barrier (BBB) is mediated by the high molecular mass (55-kDa) isoform of the GLUT1 glucose transporter protein. In this study we have utilized the tritiated, impermeant photolabel 2-N-[4-(1-azi-2,2,2-trifluoroethyl)[2-H-3]propyl],3-bis(D-mannose-4-yloxy)-2-propylamine to develop a technique to specifically measure the concentration of GLUT1 glucose transporters on the luminal surface of the endothelial cells of the BBB, We have combined this methodology with measurements of BBB glucose transport and immunoblot analysis of isolated brain microvessels for labeled luminal GLUT1 and total GLUT1 to reevaluate the effects of chronic hypoglycemia and diabetic hyperglycemia on transendothelial glucose transport in the rat. Hypoglycemia was induced with continuous-release insulin pellets (6 U/day) for a 12- to 14-day duration; diabetes was induced by streptozotocin (65 mg/kg i.p,) for a 14- to 21-day duration. Hypoglycemia resulted in 25-45% increases in regional BBB permeability-surface area (PA) values for D-[C-14]glucose uptake, when measured at identical glucose concentration using the in situ brain perfusion technique. Similarily, there was a 23 +/- 4% increase in total GLUT1/mg of microvessel protein and a 52 +/- 13% increase in luminal GLUT1 in hypoglycemic animals, suggesting that both increased GLUT1 synthesis and a redistribution to favor luminal transporters account for the enhanced uptake. A corresponding (twofold) increase in cortical GLUT1 mRNA was observed by in situ hybridization, In contrast, no significant changes were observed in regional brain glucose uptake PA, total microvessel 55-kDa GLUT1, or luminal GLUT1 concentrations in hyperglycemic rats. There was, however, a 30-40% increase in total cortical GLUT1 mRNA expression, with a 96% increase in the microvessels. Neither condition altered the levels of GLUT3 mRNA or protein expression. These results show that hypoglycemia, but not hyperglycemia, alters glucose transport activity at the BBB and that these changes in transport activity result from both an overall increase in total BBB GLUT1 and an increased transporter concentration at the luminal surface. C1 NIDDK, Expt Diabet Metab & Nutr Sect, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. US FDA, NIH, Bethesda, MD 20014 USA. Penn State Univ, Coll Med, Hershey, PA 17033 USA. Texas Tech Univ, Hlth Sci Ctr, Amarillo, TX USA. Univ Bath, Dept Biochem, Bath BA2 7AY, Avon, England. RP Simpson, IA (reprint author), Bldg 10,Rm 5N102,10 Ctr Dr,1420, Bethesda, MD 20892 USA. NR 44 TC 172 Z9 176 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 1999 VL 72 IS 1 BP 238 EP 247 DI 10.1046/j.1471-4159.1999.0720238.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 149MQ UT WOS:000077609600028 PM 9886075 ER PT J AU Nikula, TK McDevitt, MR Finn, RD Wu, CC Kozak, RW Garmestani, K Brechbiel, MW Curcio, MJ Pippin, CG Tiffany-Jones, L Geerlings, MW Apostolidis, C Molinet, R Geerlings, MW Gansow, OA Scheinberg, DA AF Nikula, TK McDevitt, MR Finn, RD Wu, CC Kozak, RW Garmestani, K Brechbiel, MW Curcio, MJ Pippin, CG Tiffany-Jones, L Geerlings, MW Apostolidis, C Molinet, R Geerlings, MW Gansow, OA Scheinberg, DA TI Alpha-emitting bismuth cyclohexylbenzyl DTPA constructs of recombinant humanized anti-CD33 antibodies: Pharmacokinetics, bioactivity, toxicity and chemistry SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE monoclonal antibodies; alpha-particles; Bi-213; Bi-212; CHX-A-DTPA; HuM195; M195 ID ACUTE MYELOGENOUS LEUKEMIA; PARTICLE-MEDIATED RADIOIMMUNOTHERAPY; MONOCLONAL-ANTIBODY; M195 ANTI-CD33; BI-212; THERAPY; RADIONUCLIDES; GENERATOR; TRIAL; IMMUNOREACTIVITY AB The alpha-particle-emitting radionuclides have several physical characteristics that make them attractive candidates for radioimmunotherapy: (a) high linear energy transfer; (b) short path lengths (50-80 mu m); and (c) limited ability of cells to repair damage to DNA. This article describes the pharmacokinetic, bioactivity, toxicity and chemical characteristics of cr-particle-emitting, Bi-213 and Bi-212 radiometal conjugated HuM195 (anti-CD33) constructs. Conjugation of HuM195 to SCN-CHX-A-DTPA resulted in the attachment of up to 10 chelating ligand molecules per antibody. Results: Radiolabeling efficiency of the CHX-A-DTPA-HuM195 construct with 213Bi was 78% +/- 10% (n = 46) after 10 min at specific activities of up to 1110 MBq/mg. The immunoreactivity of the Bi-213-labeled CHX-A-DTPA-HuM195 construct was 84% +/- 10% (n = 28) and was independent of the specific activity, The bismuth-labeled CHX-A-DTPA-HuM195 construct was rapidly internalized into the cell in a time-dependent manner ranging from 50% at 1 h to 65% at 24 h. Bi-205/Bi-206-labeled constructs were stable for at least 2 d in vitro in the presence of human serum at 37 degrees C. After injection into mice, there was no uptake or toss of bismuth to mouse tissues, which do not express CD33, or to the kidney, which has avidity for free bismuth. Mice injected intraperitoneally with doses of (Bi-213)CHX-A-DTPA-HuM195 ranging from 18.5 to 740 MBq/kg showed no toxicity, but at 2590 MBq/kg, two of the three mice died within 2 wk and a third mouse showed significant reductions in white blood cell counts. Mice injected intraveneously with doses of (Bi-213)CHX-A-DTPA-HuM195 up to 370 MBq/kg exhibited little toxicity, but 666 MBq/kg was above the MTD for mice. Leukemia cell killing in vitro with bismuth-labeled HuM195 showed dose- and specific activity-dependent killing of CD33+ HL60 cells; approximately 50% killing was observed when two bismuth atoms (50 fM radiolabeled antibody) were initially bound onto the target cell surface. Conclusion: Alpha-emitting antibodies are among the most potent cytotoxic agents known, yet are specific and appear safe in vivo. The physical and biochemical characteristics of the Bi-213 isotope and its generation, as well as the biochemistry of the Bi-213-labeled CHX-A-DTPA-HuM195 construct, make it possible to use the constructs safely and feasibly in humans at therapeutic levels. C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. MAP Med Technol Inc, Tikkakoski, Finland. NCI, Chem Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Pharmactinium Inc, Wilmington, DE USA. Commiss European Communities, Joint Res Ctr, Inst Transuranium Elements, D-7500 Karlsruhe, Germany. RP Scheinberg, DA (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [P01 CA33049, R01 CA55349, U01 CA58260] NR 58 TC 129 Z9 129 U1 1 U2 11 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 JAN PY 1999 VL 40 IS 1 BP 166 EP 176 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 158KM UT WOS:000078114700041 PM 9935073 ER PT J AU Woodcock, J AF Woodcock, J TI Clinical Trials for the Treatment of Secondary Wasting and Cachexia - Keynote address SO JOURNAL OF NUTRITION LA English DT Editorial Material C1 US FDA, Ctr Drugs, Rockville, MD 20852 USA. RP Woodcock, J (reprint author), US FDA, Ctr Drugs, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 1999 VL 129 IS 1 SU S BP 225S EP 226S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 160PA UT WOS:000078238000003 PM 9915904 ER PT J AU Mann, M AF Mann, M TI Approved pharmacologic interventions for wasting: An overview and lessons learned SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Workshop on Clinical Trials for the Treatment of Secondary Wasting and Cachexia - Selection of Appropriate Endpoints CY MAY 22-23, 1997 CL BETHESDA, MARYLAND SP US FDA, Off AIDS Res, Natl Canc Inst, NIMH, Bristol Myers Squibb, Abbott Labs, Serono Labs Inc, Amer Inst Canc Res, Roxane Labs, NIDA, SmithKline Beecham, NIA, Eli Lilly & Co C1 US FDA, Div Reprod & Urol Drug Prod, Rockville, MD 20857 USA. RP Mann, M (reprint author), US FDA, Div Reprod & Urol Drug Prod, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 1999 VL 129 IS 1 SU S BP 303S EP 305S PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 160PA UT WOS:000078238000018 PM 9915919 ER PT J AU Hirschfeld, S AF Hirschfeld, S TI Working group session report: Cancer SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Workshop on Clinical Trials for the Treatment of Secondary Wasting and Cachexia - Selection of Appropriate Endpoints CY MAY 22-23, 1997 CL BETHESDA, MARYLAND SP US FDA, Off AIDS Res, Natl Canc Inst, NIMH, Bristol Myers Squibb, Abbott Labs, Serono Labs Inc, Amer Inst Canc Res, Roxane Labs, NIDA, SmithKline Beecham, NIA, Eli Lilly & Co ID CACHEXIA; NUTRITION C1 US FDA, Rockville, MD 20852 USA. RP Hirschfeld, S (reprint author), US FDA, Rockville, MD 20852 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 15 TC 1 Z9 1 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 1999 VL 129 IS 1 SU S BP 306S EP 307S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 160PA UT WOS:000078238000019 PM 9915920 ER PT J AU Senior, JR Maroni, BJ AF Senior, JR Maroni, BJ TI Working group session report: Chronic renal and gastrointestinal disease SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Workshop on Clinical Trials for the Treatment of Secondary Wasting and Cachexia - Selection of Appropriate Endpoints CY MAY 22-23, 1997 CL BETHESDA, MARYLAND SP US FDA, Off AIDS Res, Natl Canc Inst, NIMH, Bristol Myers Squibb, Abbott Labs, Serono Labs Inc, Amer Inst Canc Res, Roxane Labs, NIDA, SmithKline Beecham, NIA, Eli Lilly & Co C1 US FDA, Gastrointestinal Div, Rockville, MD 20857 USA. Emory Univ, Div Renal, Atlanta, GA 30322 USA. RP Senior, JR (reprint author), US FDA, Gastrointestinal Div, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 1999 VL 129 IS 1 SU S BP 313S EP 314S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 160PA UT WOS:000078238000022 PM 9915923 ER PT J AU Dowell, JA Hussain, A Devane, J Young, D AF Dowell, JA Hussain, A Devane, J Young, D TI Artificial neural networks applied to the in vitro in vivo correlation of an extended-release formulation: Initial trials and experience SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID INVITRO DISSOLUTION; BIOAVAILABILITY; TABLETS AB Artificial neural networks applied to in vitro-in vivo correlations (ANN-IVIVC) have the potential to be a reliable predictive tool that overcomes some of the difficulties associated with classical regression methods, principally, that of providing an a priori specification of the regression equation structure. A number of unique ANN configurations are presented, that have been evaluated for their ability to determine an IVIVC from different formulations of the same product. Configuration variables included a combination of architectural structures, learning algorithms, and input-output association structures. The initial training set consisted of two formulations and included the dissolution from each of the six cells in the dissolution bath as inputs, with associated outputs consisting of 1512 pharmacokinetic time points from nine patients enrolled in a crossover study. A third formulation IVIVC data set was used for predictive validation. Using these data, a total of 29 ANN configurations were evaluated. The ANN structures included the traditional feed forward, recurrent, jump connections, and general regression neural networks, with input-output association types consisting of the direct mapping of the dissolution profiles to the pharmacokinetic observations, mapping the individual dissolution points to the individual observations, and using a "memorative" input-output association. The ANNs were evaluated on the basis of their predictive performance, which was excellent for some of these ANN models. This work provides a basic foundation for ANN-IVIVC modeling and is the basis for continued modeling with other desirable inputs, such as formulation variables and subject demographics. C1 Univ Maryland, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, Invitro Invivo Relat Cooperat Working Grp, Baltimore, MD 21201 USA. US FDA, Rockville, MD 20855 USA. Elan Corp plc, Athlone, Ireland. RP Young, D (reprint author), GloboMax LLC, 7250 Pkwy Dr,Suite 430, Hanover, MD 21076 USA. NR 21 TC 30 Z9 34 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 JAN PY 1999 VL 88 IS 1 BP 154 EP 160 DI 10.1021/js970148p PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 155RL UT WOS:000077960100024 PM 9874718 ER PT J AU Kang, SH Klotz, JH AF Kang, SH Klotz, JH TI Updating exact P-values for the conditional likelihood ratio test of independence SO JOURNAL OF STATISTICAL COMPUTATION AND SIMULATION LA English DT Article DE exact test; network algorithm; multivariate hypergeometric distribution; homogeneity; two way contingency table ID RXC CONTINGENCY-TABLES; FISHERS EXACT TEST; FIXED MARGINS; ALGORITHM; FEXACT AB We consider the exact likelihood ratio test of independence conditioned on row and column margins in an r x c contingency table with multinomial sampling. We develop an update algorithm to compute the exact P-value of the test and show it is better than the network algorithm in terms of computing speed. In the algorithm the P-value is reduced to a sum of probabilities for 2 x 2 contingency tables, which we compute using the hypergeometric distribution. The same algorithm can also be used for testing homogeneity of independent multinomial populations. C1 Univ Wisconsin, Madison, WI USA. RP Kang, SH (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, US FDA, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 0094-9655 J9 J STAT COMPUT SIM JI J. Stat. Comput. Simul. PY 1999 VL 63 IS 3 BP 201 EP 215 DI 10.1080/00949659908811953 PG 15 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 208UN UT WOS:000081010400001 ER PT J AU Herman, BA Carey, RF AF Herman, BA Carey, RF TI Validation of a corona discharge technique to test male latex condoms for pinhole defects SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE latex; condoms; holes; electrical discharge ID VIRUS; BARRIERS; AIDS AB The Center for Devices and Radiological Health, Food and Drug Administration, evaluated a prototype device using novel technology to detect pinholes in male latex condoms. This device uses multiple electrodes, maintained at high positive voltage, which interrogate a latex condom placed on a conducting mandrel. An electric discharge occurs only when a small hole is present in the condom and is sensed by the device. The mandrel is rotated to map out the entire surface of the condom. Using latex condoms with laser-drilled holes ranging from approximately 1 to 30 mu m in diameter, we examined the sensitivity of this device. The smallest holes were detected, and the overall false negative rate was 2%. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Herman, BA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0090-3973 J9 J TEST EVAL JI J. Test. Eval. PD JAN PY 1999 VL 27 IS 1 BP 3 EP 6 PG 4 WC Materials Science, Characterization & Testing SC Materials Science GA 287YM UT WOS:000085535100001 ER PT J AU Haverkos, HW Turner, JF Moolchan, ET Cadet, JL AF Haverkos, HW Turner, JF Moolchan, ET Cadet, JL TI Relative rates of AIDS among racial/ethnic groups by exposure categories SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE AIDS; race/ethnicity; sexual behavior; sexually transmitted diseases ID UNITED-STATES; ADULTS; HETEROSEXUALS; PREVENTION; HISPANICS; BEHAVIORS; BLACK AB The relative rates of acquired immunodeficiency syndrome (AIDS) were calculated among racial/ethnic populations using Centers for Disease Control and Prevention HN (human immunodeficiency virus)/Surveillance reports assuming that racial/ethnic distributions reflect that of the US Census Data from 1990. For comparison, a rate of 1 was assigned to whites in each calculation. The overall relative rates were whites-1, African Americans-4.7, Hispanics-3, Asian/Pacific Islanders-0.4, and Native Americans-0.5. Acquired immunodeficiency syndrome surveillance data show higher rates of AIDS for African Americans and Hispanics compared with whites, Asians/Pacific Islanders, and Native Americans. The relative rates for African Americans and Hispanics compared with whites were highest for injecting drug users, heterosexual contact, and pediatric patients. These results led us to explore possible explanations for increased AIDS reporting in African Americans and Hispanics. We then explored available national datasets regarding those variables. The analyses indicate that variables such as access and receptivity to HIV prevention and treatment efforts, race/ethnicity, sexual behaviors, sexually transmitted diseases, socioeconomic status, and substance abuse interact in a complex fashion to influence HIV transmission and progression to AIDS in affected communities. C1 Natl Inst Drug Abuse, Natl Inst Hlth, Baltimore, MD USA. RP Haverkos, HW (reprint author), US FDA, HFD 530,5600 Fishers Ln, Rockville, MD 20837 USA. NR 34 TC 22 Z9 22 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD JAN PY 1999 VL 91 IS 1 BP 17 EP 24 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 166UN UT WOS:000078595900004 PM 10063784 ER PT J AU Love, L Couig, MP AF Love, L Couig, MP TI The MedWatch program 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 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 1999 VL 37 IS 6 BP 803 EP 807 PG 5 WC Toxicology SC Toxicology GA 262UZ UT WOS:000084086900017 PM 10584596 ER PT J AU Hutter, JC Luu, HMD Mehlhaff, PM Killam, AL Dittrich, HC AF Hutter, JC Luu, HMD Mehlhaff, PM Killam, AL Dittrich, HC TI Physiologically based pharmacokinetic model for fluorocarbon elimination after the administration of an octafluoropropane-albumin microsphere sonographic contrast agent SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE imaging; pharmacokinetics; fluorocarbon ID TWO-DIMENSIONAL ECHOCARDIOGRAPHY; MYOCARDIAL PERFUSION; RISK; DELINEATION; GASES; AREA AB A physiologically based pharmacokinetic model was developed to evaluate the kinetics of one of the newest sonographic contrast agents available, FS069 or Optison. This material consists of octafluoropropane gas encapsulated in proteinaceous microspheres, injected intravenously for use as a myocardial contrast agent in humans. This model has sis compartments: two lung compartments (alveolar and dead volume), and compartments for the heart, slowly perfused tissue, richly perfused tissue, and gastrointestinal tract. The model was developed to determine the distribution and excretion of the octafluoropropane in the body. Despite the high affinity of octafluoropropane for tissue, the model predicted that nearly 100% of the material would be exhaled from the lungs within 6 min. The model verified the results of a phase I clinical trial with 10 healthy subjects. Ventilation rate was found to play a critical role in the complete excretion of this contrast agent. The physiologically based pharmacokinetic model was a useful tool for evaluating the safety of FS069. This model can be used a basis for developing similar models for other types of contrast agents. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. Mol Biosyst, San Diego, CA USA. RP Hutter, JC (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy,HFZ-150, Rockville, MD 20852 USA. NR 24 TC 21 Z9 22 U1 0 U2 5 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 JAN PY 1999 VL 18 IS 1 BP 1 EP 11 PG 11 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 153NY UT WOS:000077840200001 PM 9952073 ER PT J AU McCarthy, SA DePaola, A Cook, DW Kaysner, CA Hill, WE AF McCarthy, SA DePaola, A Cook, DW Kaysner, CA Hill, WE TI Evaluation of alkaline phosphatase- and digoxigenin-labelled probes for detection of the thermolabile hemolysin (tlh) gene of Vibrio parahaemolyticus SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article ID THERMOSTABLE DIRECT HEMOLYSIN; OLIGONUCLEOTIDE PROBE; VULNIFICUS; SEQUENCES AB The biochemical identification and enumeration of Vibrio parahaemolyticus as described in the FDA Bacteriological Analytical Manual is expensive and labour-intensive. To reduce fort necessary to verify the identity of V. parahaemolyticus, the use of a thermolabile haemolysin (tlh) gene probe is proposed. An alkaline phosphatase (AP)-labelled probe was evaluated for specificity against 26 strains of V: parahaemolyticus, 88 strains of other Vibrio species and 10 strains of non-vibrio io species, tested, the probe hybridized only with the 26 strains of V. parahaemolyticus, indicating species specificity. Two hundred and six suspect V. parahaemolyticus isolates from oysters were tested by this probe and API-20E diagnostic strips, there there 97% agreement between results, A digoxigenin (DIG)labelled probe for detection of the tlh gene fragment was prepared by PCR and compared with the AP-labelled probe. When tested on 584 suspect V. parahaemolyticus results obtained with the AP- and DIG-labelled probes, were in 98% agreement. These results suggest that the probes are equivalent for detection of the V. parahaemolyticus tlh gene. C1 US FDA, GCSL, Dauphin Island, AL 36528 USA. US FDA, Bothell, WA USA. RP McCarthy, SA (reprint author), US FDA, GCSL, POB 158, Dauphin Island, AL 36528 USA. NR 21 TC 78 Z9 89 U1 2 U2 7 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 JAN PY 1999 VL 28 IS 1 BP 66 EP 70 DI 10.1046/j.1365-2672.1999.00467.x PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 163DP UT WOS:000078388000014 PM 10030035 ER PT J AU Taga, K Yamauchi, A Bloom, ET AF Taga, K Yamauchi, A Bloom, ET TI Target cell-induced apoptosis in IL-2-activated human natural killer cells SO LEUKEMIA & LYMPHOMA LA English DT Article DE IL-2 activated; NK cells; natural Killer cells; target cell induced apoptosis; apoptosis ID MATURE T-CELLS; FAS LIGAND; NK CELLS; TYROSINE PHOSPHORYLATION; INTERCELLULAR-ADHESION; SIGNAL-TRANSDUCTION; DNA FRAGMENTATION; INDUCED DEATH; DIFFERENTIAL EXPRESSION; MEDIATED CYTOTOXICITY AB We demonstrated that tumor cells induce cell death in lymphokine-activated NK (LAK) cells, but not in non-activated NK cells. Cell death in LAK cells involves nuclear condensation and DNA cleavage, all of which are characteristic features of apoptosis. The mechanism involves signaling through integrins and requires src family tyrosine kinases and protease activities. Engagement of an apoptotic signal molecule, Fas, may also trigger LAK cell death by apoptosis. It appears that LAK cells rapidly die by apoptosis after attacking tumor cells. This phenomenon may provide a means for potential tumor target cells to escape from natural immunosurveillance during therapeutic interventions such as those using IL-2 or LAK cells. C1 US FDA, Div Hematol Prod, Ctr Biol Evaluat Res, Bethesda, MD 20014 USA. US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat Res, Bethesda, MD 20014 USA. RP Yamauchi, A (reprint author), Kyoto Univ, Grad Sch Med, Dept Surg Gastroenterol, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 606, Japan. NR 49 TC 4 Z9 4 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 1999 VL 32 IS 5-6 BP 451 EP 458 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 166CW UT WOS:000078559500004 PM 10048417 ER PT J AU Siegel, JN AF Siegel, JN TI Development of an FDA guidance document for clinical trials in SLE SO LUPUS LA English DT Article DE clinical trials; disease activity; lupus nephritis ID LUPUS NEPHRITIS AB To make the process of developing new therapeutic agents more efficient, it is critical that investigators and industry sponsors understand in advance what information they will need to provide to the US Food and Drug Administration (FDA) in order to license and market their product. To facilitate that process, the FDA publishes guidance documents describing current thinking about various issues that arise at all stages of product development. The FDA is currently in the process of formulating a guidance document about clinical development programs for systemic lupus erythematosus (SLE). The goal of this document is to describe some of the types of clinical trials that could be used to demonstrate safety and efficacy of therapeutic agents in SLE. C1 US FDA, CBFR, OTRR, Div Clin Trials Design & Anal, Rockville, MD 20857 USA. RP Siegel, JN (reprint author), US FDA, CBFR, OTRR, Div Clin Trials Design & Anal, Rockville, MD 20857 USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 1999 VL 8 IS 8 BP 581 EP 585 DI 10.1191/096120399680411425 PG 5 WC Rheumatology SC Rheumatology GA 255HP UT WOS:000083663700003 PM 10568893 ER PT B AU Reuter, N AF Reuter, N BE Nahas, GG Sutin, KM Harvey, D Agurell, S Pace, N Cancro, R TI FDA regulation of prescription of controlled substances SO MARIHUANA AND MEDICINE LA English DT Proceedings Paper CT Conference on Marihuana and Medicine CY MAR 20-21, 1998 CL NEW YORK UNIV SCH MED, NEW YORK, NY SP Stuart Mott Fdn, Helen Clay Frick Fdn, Jeremiah Milibank Fdn, Astra Pain Control, Swedish Acad Pharm Sci HO NEW YORK UNIV SCH MED AB The Federal Food, Drug, and Cosmetic Act requires the premarket approval of new drugs prior to their marketing. FDA accomplishes this through regulations that establish Investigational New Drug Applications (INDs) and New Drug Application (NDAs). FDA IND regulations address phases of clinical investigations, from Phase I trials involving few subjects, to Phase III trials with thousands of subjects. Under these regulations FDA will not allow an investigation to proceed if human subjects would be exposed to unreasonable risks, investigators are not qualified, or if the investigation protocol is deficient. FDA also requires adequate animal toxicology studies to show it is reasonably safe to administer the drug to human subjects. FDA drug approval regulations protect the public by ensuring that adequate scientific studies have been performed to provide a rational basis on which to conclude that the benefits of a drug outweigh its risks and by assuring that the product is accompanied by sufficient information to permit its accurate prescription. FDA regulations require that the marketing application (NDA) include adequate tests to show whether or not the drug is safe for use under the conditions prescribed, recommended or suggested in the labeling. In addition, there must be substantial evidence, consisting of adequate and well-controlled clinical investigations, that the drug product will have the effect it purports or is represented to have under the conditions prescribed, recommended or suggested in the labeling. Importantly, manufacturing methods and controls must be adequate to assure the identity, strength, quality purity, stability, or bioavailability of the drug product. FDA regulations set forth the "essentials of adequate and well-controlled clinical investigation," including requirements that the study design permits a valid comparison with a control (including, placebo, dose comparison, no treatment, active, and historical) to provide a quatitative assessment of drug effect. C1 US FDA, Domest & Int Drug Control, Washington, DC 20204 USA. RP Reuter, N (reprint author), US FDA, Domest & Int Drug Control, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 0-89603-593-X PY 1999 BP 751 EP 755 PG 5 WC Substance Abuse; Medicine, Legal; Pharmacology & Pharmacy SC Substance Abuse; Legal Medicine; Pharmacology & Pharmacy GA BM81E UT WOS:000079827200076 ER PT S AU Wagner, RF Chan, HP Sahiner, B Petrick, N Mossoba, JT AF Wagner, RF Chan, HP Sahiner, B Petrick, N Mossoba, JT BE Hanson, KM TI Components of variance in ROC analysis of CADx classifier performance. II: Applications of the bootstrap SO MEDICAL IMAGING 1999: 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 1999 Conference - Image Processing CY FEB 22-25, 1999 CL SAN DIEGO, CA SP Soc Photo Opt Instrumentat Engineers, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE computer-aided diagnosis; classifier performance; ROC analysis; components of variance; bootstrap analysis ID COMPUTER-AIDED DIAGNOSIS; SAMPLE-SIZE; DESIGN; CURVES AB We review components-of-variance models for the uncertainty in estimates of the area under the ROC curve, A,, for the case of classical discriminants where we wish the uncertainty to generalize to a population of training cases as well as to a population of testing cases. A key observation from our previous work facilitates the use of resampling strategies to analyze a finite data set and classifier in terms of the components-of-variance models. In particular, we demonstrate the use of the statistical bootstrap in combination with a four-term variance model to solve for the contributions to the uncertainty in A, that result from a given finite training sample, a given finite test sample, and their interaction. At the same time one obtains an expression from which one can predict the change in uncertainty in estimates of A, that would result from a given change in the number of training samples and change in the number of test samples. This expression provides a quantitative design tool for estimating the size that would be required in a larger pivotal study from the results of a smaller pilot study for the purpose of achieving a desired precision in A, and the desired generalizability. 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 19 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 0-8194-3133-8 J9 P SOC PHOTO-OPT INS PY 1999 VL 3661 BP 523 EP 532 DI 10.1117/12.348608 PN 1&2 PG 10 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BN14N UT WOS:000080862400050 ER PT S AU Brown, DG Pastel, MS Myers, KJ AF Brown, DG Pastel, MS Myers, KJ BE Hanson, KM TI Transform neural network for Fourier detection task SO MEDICAL IMAGING 1999: 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 1999 Conference - Image Processing CY FEB 22-25, 1999 CL SAN DIEGO, CA SP Soc Photo Opt Instrumentat Engineers, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE neural network; Fourier transform; phase uncertainty; detection; ideal observer ID PERFORMANCE AB Complex-valued weights are used in the first layer of a feed forward neural network to produce a "transform" neural network. This network was applied to a phase-uncertain sine wave detection task against a Gaussian white noise background. When compared with results of a human observer study on this task by Burgess et al.,(1) performance of the transform network was found to be nearly equal to that of an ideal observer and far superior to that of the human observers. Performance was found to be dramatically affected by initial values of the weights, which is explained in terms of concepts from statistical decision theory. C1 US FDA, Ctr Devices & Radiol Hlth HFZ140, Rockville, MD 20857 USA. RP Brown, DG (reprint author), US FDA, Ctr Devices & Radiol Hlth HFZ140, Rockville, MD 20857 USA. NR 6 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 0-8194-3133-8 J9 P SOC PHOTO-OPT INS PY 1999 VL 3661 BP 674 EP 679 DI 10.1117/12.348623 PN 1&2 PG 6 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BN14N UT WOS:000080862400065 ER PT J AU Sagripanti, JL AF Sagripanti, JL TI DNA damage mediated by metal ions with special reference to copper and iron SO METAL IONS IN BIOLOGICAL SYSTEMS, VOL 36 SE METAL IONS IN BIOLOGICAL SYSTEMS LA English DT Review ID DOUBLE-STRAND BREAKS; RENAL-CELL CARCINOMA; HYDROGEN-PEROXIDE; HYDROXYL RADICALS; SINGLE-STRAND; FERRIC NITRILOTRIACETATE; MAMMALIAN CHROMATIN; CHEMICAL GERMICIDES; SERUM TRANSFERRIN; OXIDATIVE DAMAGE C1 US FDA, CDRH, Mol Biol Branch, Rockville, MD 20852 USA. RP Sagripanti, JL (reprint author), US FDA, CDRH, Mol Biol Branch, 12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 117 TC 12 Z9 12 U1 1 U2 2 PU MARCEL DEKKER PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0161-5149 J9 MET IONS BIOL SYST PY 1999 VL 36 BP 179 EP 209 PG 31 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA BM76L UT WOS:000079715100006 PM 10093925 ER PT S AU Levy, DD Cebula, TA AF Levy, DD Cebula, TA BE Caporale, LH TI Mutagenesis patterns in a tRNA mutation marker gene altered to include repetitive sequence replicated in mutS E-coli SO MOLECULAR STRATEGIES IN BIOLOGICAL EVOLUTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Molecular Strategies in Biological Evolution CY JUN 27-29, 1998 CL NEW YORK, NEW YORK SP NY Acad Sci ID ESCHERICHIA-COLI; HOTSPOTS C1 US FDA, Washington, DC 20204 USA. RP Levy, DD (reprint author), US FDA, HFS237,200 C St SW, Washington, DC 20204 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-192-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 870 BP 392 EP 395 DI 10.1111/j.1749-6632.1999.tb08911.x PG 4 WC Genetics & Heredity; Multidisciplinary Sciences SC Genetics & Heredity; Science & Technology - Other Topics GA BN31U UT WOS:000081585400052 PM 10415506 ER PT J AU Sutherland, JB Freeman, JP Williams, AJ Deck, J AF Sutherland, JB Freeman, JP Williams, AJ Deck, J TI Biotransformation of phthalazine by Fusarium moniliforme and Cunninghamella elegans SO MYCOLOGIA LA English DT Article; Proceedings Paper CT Annual Meeting of the Mycological-Society-of-America CY JUN 12, 1998 CL SAN JUAN, PUERTO RICO SP Mycol Soc Amer DE azaarenes; heterocyclic compounds; N-oxides; phthalazinone ID MOLYBDENUM-CONTAINING HYDROXYLASE; ISOQUINOLINE; MUTAGENICITY; OXIDATION; LIVER AB Fusarium moniliforme and Cunninghamella elegans were grown in fluid Sabouraud medium at 28 C. They were dosed with 6.2 mM phthalazine and then incubated for. 3 d with shaking at 125 rpm. After extraction with ethyl acetate, the metabolites were purified by HPLC and identified by the UV/visible, mass, and NMR spectra. The results show that F. moniliforme oxidized about 42% of tl le phthalazine to 1(2H)-phthalazinone (= 1-hydroxyphthalazine) and that C. elegans oxidized about 6% of the phthalazine to a novel metabolite, phthalazine N-oxide (= phthalazine 2-oxide). C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 16 TC 2 Z9 2 U1 1 U2 2 PU NEW YORK BOTANICAL GARDEN PI BRONX PA PUBLICATIONS DEPT, BRONX, NY 10458 USA SN 0027-5514 J9 MYCOLOGIA JI Mycologia PD JAN-FEB PY 1999 VL 91 IS 1 BP 114 EP 116 DI 10.2307/3761198 PG 3 WC Mycology SC Mycology GA 166ZT UT WOS:000078608600010 ER PT J AU Dickey, R Jester, E Granade, R Mowdy, D Moncreiff, C Rebarchik, D Robl, M Musser, S Poli, M AF Dickey, R Jester, E Granade, R Mowdy, D Moncreiff, C Rebarchik, D Robl, M Musser, S Poli, M TI Monitoring brevetoxins during a Gymnodinium breve red tide: Comparison of sodium channel specific cytotoxicity assay and mouse bioassay for determination of neurotoxic shellfish toxins in shellfish extracts SO NATURAL TOXINS LA English DT Article DE neurotoxic shellfish poisoning; brevetoxins; brevetoxin metabolism; cytotoxicity; mouse bioassay; liquid chromatography-mass spectrometry ID PTYCHODISCUS-BREVIS; DINOFLAGELLATE; CIGUATOXINS; SAXITOXINS AB In October of 1996, a Gymnodinium breve bloom occurred in shellfish harvesting waters of Alabama, Mississippi and Louisiana, Gulf of Mexico, USA. Bloom densities reached 5.6 x 10(5) cells liter(-1) and bloom residence at shellfish sampling stations ranged from 3 to 28 days. Brevetoxin-2 dominated G. breve toxin profiles in bloom seawater extracts. Shellfish toxicity, assessed by mouse bioassay, exceeded the guidance level for up to 75 days after the bloom had dissipated. Cytotoxicity assays and mouse bioassays showed similar temporal patterns of shellfish toxicity, but the two methods differed in estimations of brevetoxin-3 equivalent toxicity by a factor of 93 to 1. LC-ESI-MS showed the temporal patterns in shellfish toxicity reflected metabolism of G. breve toxins. The molecular ions m/z 1004, 1017 and 1033 dominated LC-ESI-MS spectra of toxic chromatographic fractions from the extracts and were identified as brevetoxin metabolites on the basis of LC-APCI-MS-MS. The discrepancy between cytotoxicity and mouse bioassay estimates of brevetoxin-3 equivalent toxicity resulted from the difference in extraction efficiency of solvents used in the respective methods and the relative sensitivity of the assays to toxin metabolite mixtures present in the extracts. The normalized cytotoxicity assay showed 75% agreement with mouse bioassay positive lest samples and 64% agreement with mouse bioassay negative test samples. Published in 1999 by John Wiley & Sons, Ltd. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Gulf Coast Res Lab, Ocean Springs, MS 39564 USA. US FDA, Ctr Food & Appl Nutr, Laurel, MD 20708 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. USA, Med Res Inst Infect Dis, Toxinol Div, Ft Detrick, MD 21702 USA. RP Dickey, R (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville St, Dauphin Isl, AL 36528 USA. EM rdickey@oc.fda.gov RI Tyurina, Natalia/F-7720-2014 OI Tyurina, Natalia/0000-0002-6188-1556 NR 21 TC 70 Z9 73 U1 2 U2 16 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1056-9014 J9 NAT TOXINS JI Nat. Toxins PY 1999 VL 7 IS 4 BP 157 EP 165 PG 9 WC Toxicology SC Toxicology GA 310YQ UT WOS:000086857500006 PM 10797644 ER PT S AU Ali, SF Martin, JL Black, MD Itzhak, Y AF Ali, SF Martin, JL Black, MD Itzhak, Y BE Trembly, B Slikker, W TI Neuroprotective role of melatonin in methamphetamine- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MARYLAND SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL 33152 USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. NR 0 TC 7 Z9 7 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 1-57331-222-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 119 EP 119 DI 10.1111/j.1749-6632.1999.tb07986.x PG 1 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700010 PM 10668418 ER PT S AU Scallet, AC AF Scallet, AC BE Trembly, B Slikker, W TI Estrogens: Neuroprotective of neurotoxic? SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MARYLAND SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr ID SEXUALLY DIMORPHIC NUCLEUS; RECEPTOR-ALPHA-IMMUNOREACTIVITY; FOREBRAIN CHOLINERGIC NEURONS; MALE RHESUS-MONKEYS; BETA-ENDORPHIN; PREOPTIC AREA; RAT-BRAIN; HYPOTHALAMIC-LESIONS; NEURAL DEVELOPMENT; ESTRADIOL AB The present paper reviews the major modes of action of estrogen on the molecular, cellular, tissue, and neurobehavioral levels of mammalian physiology, with an emphasis on the brain as an estrogen target tissue. We draw a distinction between receptor- and nonreceptor-mediated actions, as well as delineate the range of different signal transduction pathways that might be available within a given tissue to mediate estrogenic effects. We consider species differences relevant to understanding the predictability of effects in humans from data obtained in rats or monkeys. Finally, we emphasize the importance of developmental stage in determining whether estrogenic effects are beneficial dr harmful; "neuroprotective" or "neurotoxic." C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Scallet, AC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 49 TC 11 Z9 11 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 1-57331-222-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 121 EP 132 DI 10.1111/j.1749-6632.1999.tb07988.x PG 12 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700012 PM 10668420 ER PT S AU Binienda, Z Johnson, JR Tyler-Hashemi, AA Rountree, RL Sapienza, PP Ali, SF Kim, CS AF Binienda, Z Johnson, JR Tyler-Hashemi, AA Rountree, RL Sapienza, PP Ali, SF Kim, CS BE Trembly, B Slikker, W TI Protective effect of L-carnitine in the neurotoxicity induced by the mitochondrial inhibitor 3-nitropropionic acid (3-NPA) SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MARYLAND SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr ID ACETYL-L-CARNITINE; RAT-BRAIN; TOXICITY C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Res, Washington, DC 20204 USA. RP Binienda, Z (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 14 TC 15 Z9 15 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 1-57331-222-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 173 EP 178 DI 10.1111/j.1749-6632.1999.tb07992.x PG 6 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700016 PM 10668424 ER PT S AU Bowyer, JF Davies, DL AF Bowyer, JF Davies, DL BE Trembly, B Slikker, W TI Changes in mRNA levels for heat-shock/stress proteins (Hsp) and a secretory vesicle associated cysteine-string protein (Csp1) after amphetamine (AMPH) exposure SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MARYLAND SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr ID METHAMPHETAMINE-INDUCED HYPERTHERMIA; SHOCK-PROTEIN; NEURONAL DEGENERATION; DROSOPHILA; DOPAMINE; NEUROTOXICITY; BRAIN; MOUSE; RAT; TEMPERATURE AB Damage to nerve terminals, reactive gliosis and somatic degeneration can result when pronounced hyperthermia occurs during amphetamine (AMPH) exposure. The effects of AMPH-induced hyperthermia and damage on the relative mRNA levels for several heat shock/stress proteins (Hsp27, Hsp60, Hsp70 and Hsc70), as well as secretory vesicle associated cysteine-string protein (Csp1) were determined In both the striatum and substantia nigra using reverse transcriptase polymerase chain reaction (RT-PCR). These changes were compared to changes in Hsp mRNA levels seen in primary rat cerebral astrocyte cultures after heat shock/stress. Striatal Hsp70 mRNA increased about 2-fold over control levels at 16 hr after AMPH-induced hyperthermia, and was the only Hsp species to significantly increase in response to AMPH. Hsp70 mRNA levels returned to control within 14 days after AMPH. Two-fold increases in Hsp79 mRNA were also seen in primary cultures of rat cerebrum 24 hr after heat shock. In primary cultures and brain tissue, the increased Hsp70 mRNA levels were still more than 500-fold less than constitutive Hsc70 mRNA and 50-fold less than Hsp60 levels. Hsp27 mRNA was not present in the striatum, nigra and primary cell cultures. Thus, the expression of Hsp species mRNA measured was very similar in brain tissue and primary cell cultures. Because only a modest induction of Hsp 70 mRNA occurred, the Hsp species evaluated may only play a minor role in AMPH neurotoxicity, However, further studies are necessary to determine whether large increases in Hsp 70 are occurring In selected neurons or glia in the striatum, RT-PCR products for Csp1 were produced in total RNA obtained from brain but not from cultured astrocytes, suggesting that the Csp1 mRNA measured by RT-PCR is of neuronal origin. Csp1 mRNA levels were acutely downregulated in neurons in the substantia nigra, possibly in response to damage, but not the striatum after AMPH exposure. A slight long-term upregulation at 4 months of Csp1 mRNA may occur in the striatum but not in nigra. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Anat, Little Rock, AR 72205 USA. RP Bowyer, JF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 38 TC 14 Z9 14 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 1-57331-222-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 314 EP 329 DI 10.1111/j.1749-6632.1999.tb08009.x PG 16 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700029 PM 10668437 ER PT S AU Plata-Salaman, CR Ilyin, SE Gayle, D Romanovitch, A Carbone, KM AF Plata-Salaman, CR Ilyin, SE Gayle, D Romanovitch, A Carbone, KM BE Trembly, B Slikker, W TI Regional cytokine, cytokine receptor and neuropeptide mRNA changes associated with behavioral and neuroanatomical abnormalities in persistent, noninflammatory virus infection of neonatal rats SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MARYLAND SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr C1 US FDA, HFM 460, DVP,OVRR,CBER, Lab Pediat & Resp Viral Dis, Rockville, MD 20852 USA. Univ Delaware, Sch Life & Hlth Sci, Div Mol Biol, Newark, DE 19716 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Carbone, KM (reprint author), US FDA, HFM 460, DVP,OVRR,CBER, Lab Pediat & Resp Viral Dis, 14401 Rockville Pike, Rockville, MD 20852 USA. NR 0 TC 3 Z9 3 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 1-57331-222-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 469 EP 469 DI 10.1111/j.1749-6632.1999.tb08026.x PG 1 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700043 PM 10668451 ER PT S AU Paule, MG Popke, EJ Pearson, E Hammond, T AF Paule, MG Popke, EJ Pearson, E Hammond, T BE Trembly, B Slikker, W TI Development of a nonhuman primate model for studying the consequences of long-term neuroprotectant administration on complex brain functions in developing animals SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MARYLAND SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Paule, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 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 1-57331-222-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 470 EP 470 DI 10.1111/j.1749-6632.1999.tb08027.x PG 1 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700044 PM 10668452 ER PT S AU Clausing, P Bowyer, JF AF Clausing, P Bowyer, JF BE Trembly, B Slikker, W TI Time course of brain temperature and caudate/putamen microdialysate levels of amphetamine and dopamine in rats after multiple doses of d-amphetamine SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MARYLAND SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr ID BODY-TEMPERATURE; CAUDATE-PUTAMEN; METHAMPHETAMINE NEUROTOXICITY; RECEPTOR SUBTYPES; RELEASE; THERMOREGULATION; BEHAVIOR; HYPERTHERMIA; FENFLURAMINE; ENVIRONMENT AB Brain temperature monitoring and microdialysis were performed simultaneously in the caudate/putamen (CPu) of conscious, freely moving rats dosed with d-amphetamine (AMPH), The brain temperature was determined via a thermistor inserted through a microdialysis guide cannula located in the left CPu, while the microdialysis probe was positioned in the right Cpu, The peak AMPH and dopamine (DA) levels were reached 40 to 60 min after dosing, while peak brain temperature was not achieved until 20 to 40 min thereafter in rats becoming moderately hyperthermic, Those rats becoming severely hyperthermic (temperatures above 41.0 degrees C) had microdialysate concentrations of AMPH and DA almost 2-fold higher than those with moderate hyperthermia after the second dose of 5 mg/kg AMPH, However, these peaks were not reached until 60 to 80 min after dosing, This was probably due, in part, to the longer half-life of AMPH in the severely hyperthermic group, The changes in brain temperature observed after exposure to neurotoxic doses of AMPH closely paralleled core body temperature changes previously reported during AMPH exposure, Temperature plays an important role in many types of neurotoxicity, and monitoring brain temperature during microdialysis studies can be done continuously, and with less chance of damage to the microdialysis equipment than most of the traditional methods used to measure core body temperature. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Dept Gen Toxicol, DK-4623 Lille Skensved, Denmark. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 32 TC 18 Z9 18 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 1-57331-222-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 495 EP 504 DI 10.1111/j.1749-6632.1999.tb08031.x PG 10 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700047 PM 10668455 ER PT S AU Klein, M Calderon, S Hayes, B AF Klein, M Calderon, S Hayes, B BE Trembly, B Slikker, W TI Abuse liability assessment of neuroprotectants SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MARYLAND SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr ID RHESUS-MONKEYS; DEPENDENCE AB There has been considerable interest in the potential of N-methyl-D aspartate (NMDA) receptor antagonists in the treatment of a diverse group of neurological disorders including cerebral ischemia and neurodegeneration.(8,16,19) The amino acids L-glutamate and L-aspartate have been shown to possibly mediate excitatory synaptic transmission in the central nervous system (CNS) via selective excitatory amino acid receptors. Competitive and noncompetitive antagonists acting at the NMDA receptors have been shown to possess relevant activity. However, NMDA antagonists can produce a variety of adverse neurobehavioral effects in both animals and humans.(9-12,14,17,18) These adverse events are particularly pronounced with NMDA antagonists (phencyclidine (PCP), ketamine, and MK-801) that have dissociative anesthetic properties and block NMDA receptor-mediated responses by binding to the cation channel of the NMDA receptor complex, When a new pharmaceutical product demonstrates structural similarity and/or a similar pharmacological profile with a known drug of abuse, the characterization of its abuse potential is needed by the FDA for scientific review.(1,3,4,22) The abuse liability assessment is based upon an evaluation of data on the chemistry, pharmacology (preclinical and clinical), pharmacokinetics, and pharmacodynamic: profiles of the drug, and the adverse events/effects reported in clinical trials, The evaluation of the drug's abuse potential is determined relative to pharmacologically similar drugs. This includes determination of the drug's receptor binding efficacy, preclinical pharmacology, reinforcing efficacy, discriminative stimulus effects, dependence-producing potential, pharmacokinetics, and assessment of the clinical efficacy-safety database relative to abuse and clinical abuse liability studies.(2,7,9,13,20-22) It has been well established that high-affinity noncompetitive NMDA antagonists have reinforcing efficacy and can serve as discriminative stimuli in operant procedures. In a variety of species:in drug discrimination studies, each antagonist is capable of generalizing to the others, and it is believed that these effects may be mediated through the NMDA blockade, The generalization of each substance for another:suggests production of common subjective effects in humans. C1 US FDA, Ctr Drug Evaluat & Res, Div Anesthet Crit Care & Addict Drug Prod, Controlled Subst Evaluat Team, Rockville, MD 20857 USA. RP Klein, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Anesthet Crit Care & Addict Drug Prod, Controlled Subst Evaluat Team, 5600 Fisher Lane, Rockville, MD 20857 USA. NR 20 TC 17 Z9 17 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 1-57331-222-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 515 EP 525 DI 10.1111/j.1749-6632.1999.tb08033.x PG 11 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700049 PM 10668457 ER PT S AU Slikkker, W Youdim, M Palmer, GC Hall, E Williams, C Trembly, B AF Slikkker, W Youdim, M Palmer, GC Hall, E Williams, C Trembly, B BE Trembly, B Slikker, W TI The future of neuroprotection SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MARYLAND SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NIMH, Fogarty Int Ctr, NIH, Bethesda, MD USA. Astra Arcus USA, Rochester, NY USA. Parke Davis Pharmaceut Res, Neurosci Therapeut, Ann Arbor, MI USA. Univ Aukland, Dept Paediat, Aukland, New Zealand. Vet Affairs Med Ctr, Neurosurg Sect, Togus, ME USA. RP Slikkker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 0 TC 32 Z9 32 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 1-57331-222-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 529 EP 533 DI 10.1111/j.1749-6632.1999.tb08035.x PG 5 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700050 PM 10668458 ER PT J AU Ferguson, SA Holson, RR AF Ferguson, SA Holson, RR TI Neonatal dexamethasone on day 7 causes mild hyperactivity and cerebellar stunting SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE glucocorticoids; dexamethasone; hyperactivity; cerebellum; rat ID GRANULE CELL GENESIS; RAT-BRAIN; HYDROCORTISONE; GLUCOCORTICOIDS; CORTICOSTEROIDS; MATURATION; STRESS AB To investigate the effects of glucocorticoid treatment on central nervous system development, rats were injected with dexamethasone (DEX) (1-3 mg/kg) on postnatal day (PND) 3 or 7. DNA and protein content and concentration were measured in the cerebellum and hippocampus on PND 28 and 112. Whole and regional brain weights were measured at PND 28, 84, and 112. Nest odor preference (PND 10-11), open field activity (PND 18-21), running wheel activity (PND 50-56), and complex maze performance (PND 60-63) were measured in rats treated twice with 1.5 mg/kg DEX on PND 7. DEX treatment on PND 7 resulted in reductions in PND 28 whole brain and regional weights (frontal cortex, cerebellum, and brain stem) and, by PND 112, all except whole brain and cerebellar weights had recovered. A mild syndrome of hyperactivity (increased open field rearing and activity) was apparent in rats treated with DEX on PND 7. These results are discussed in terms of the developmental stage specificity in production of brain, and, specifically, cerebellar insults and their resulting effects. (C) 1999 Elsevier Science Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 32 TC 40 Z9 42 U1 0 U2 1 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 JAN-FEB PY 1999 VL 21 IS 1 BP 71 EP 76 DI 10.1016/S0892-0362(98)00029-4 PG 6 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 160QY UT WOS:000078243500008 PM 10023803 ER PT J AU Lyn-Cook, BD Rogers, T Yan, Y Blann, EB Kadlubar, FF Hammons, GJ AF Lyn-Cook, BD Rogers, T Yan, Y Blann, EB Kadlubar, FF Hammons, GJ TI Chemopreventive effects of tea extracts and various components on human pancreatic and prostate tumor cells in vitro SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID RED-BLOOD-CELLS; GREEN TEA; BLACK TEA; OXIDATIVE DAMAGE; RAS GENES; CANCER; CARCINOGENESIS; POLYPHENOLS; APOPTOSIS; MICE AB Pancreatic and prostate cancers pose serious problems to human health. To determine the potential for chemopreventive intervention against pancreatic and prostate cancers, black and green tea extracts and components of these extracts were examined in vitro for their effect on tumor cell growth. Components included a mixture of polyphenols from green tea (GTP), mixtures of polyphenols (BTP) and of theaflavins (MF) from black tea, and the purified components epicatechin-3-gallate (ECG) and epigallocatechin-3-gallate (EGCG). Two human cell lines, pancreatic adenocarcinoma (HPAC) and prostate tumor (LNCaP) were exposed to these agents for 24 hours. Results showed inhibition (approx 90%) of cell growth in pancreatic tumor cells by black and green tea extracts (0.02%). GTP (10 mu g/ml) and MF (100 mu g/ml) significantly inhibited growth (approx 90%); ECG and EGCG inhibited growth as well (approx 95%). Black and green tea extracts, GTP, and EGCG decreased the expression of the K-ras gene, as determined by reverse transcription-polymerase chain reaction. Green and black tea extracts decreased the multidrug-resistant gene (mdr-1), although GTP and EGCG increased expression. Similar data were obtained in the prostate cell line LNCaP. All agents significantly inhibited, growth. These agents increased expression of the mdr-1 gene. This study suggests that components from black and green tea extracts can modulate the expression of genes known to play a role in the carcinogenesis process and, therefore, may be potential agents for chemoprevention against pancreatic cancer. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Tuskegee Univ, Tuskegee, AL 36083 USA. RP Lyn-Cook, BD (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, HFT-100, Jefferson, AR 72079 USA. NR 43 TC 73 Z9 78 U1 0 U2 1 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 1999 VL 35 IS 1 BP 80 EP 86 DI 10.1207/S1532791480-86 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 264LH UT WOS:000084183400013 PM 10624710 ER PT J AU Nishizawa, Y Yamamoto, T Tanigaki, Y Kasugai, T Mano, M Ishiguro, S Fushiki, S Poirier, LA Nishizawa, Y AF Nishizawa, Y Yamamoto, T Tanigaki, Y Kasugai, T Mano, M Ishiguro, S Fushiki, S Poirier, LA Nishizawa, Y TI Methylcobalamin decreases mRNA levels of androgen-induced growth factor in androgen-dependent Shionogi carcinoma 115 cells SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID ESTROGEN; COBALAMIN; CULTURE; PROLIFERATION; INHIBITION; CLONING; INVIVO; MICE AB Methylcobalamin (MeCbl) is an important enzyme cofactor required for methionine synthase activity. It also inhibits, in a dose-dependent manner, the proliferation of an androgen-dependent cell line, SC-3, derived from an androgen-dependent mouse mammary tumor (Shionogi carcinoma 115). In SC-3 cells, androgen induces the production of androgen-induced growth factor (AIGF), an autocrine growth factor increasing the proliferation of SC-3 cells. MeCbl treatment suppressed the androgen-induced, AIGF-mediated growth of SC-3 cells, as well as the androgen-induced increase of AIGF mRNA. In SC-3 cells, androgen receptors linked with androgen form complexes that tightly bind DNA and act as transcription factors in the nucleus to regulate the expression of specific genes such as AIGF. The number and dissociation constants of androgen receptors in control and MeCbl-treated SC-3 cells were the same. Similarly, the extent of binding of normal androgen receptors in nuclei from control and MeCbl-treated cells was virtually identical. The androgen receptors from control and MeCbl-treated cells showed similar capacities for conversion to a form that tightly binds to DNA on heat activation. These results suggest that the reduction of AIGF mRNA, subsequent to the nuclear binding of androgen receptors, may be a partial cause of the growth-inhibitory activity of MeCbl in SC-3 cells. C1 Osaka Med Ctr Canc & Cardiovasc Dis, Dept Pathol, Higashinari Ku, Osaka 5378511, Japan. Osaka Med Ctr Canc & Cardiovasc Dis, Dept Cell Biol, Osaka 5378511, Japan. Osaka Univ, Grad Sch Pharmaceut Sci, Dept Clin & Expt Pathophysiol, Osaka, Japan. Kyoto Prefectural Univ Med, Res Inst Neurol Dis & Geriatr, Kyoto, Japan. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Nishizawa, Y (reprint author), Osaka Med Ctr Canc & Cardiovasc Dis, Dept Pathol, Higashinari Ku, Nakamichi 1-3-3, Osaka 5378511, Japan. NR 22 TC 3 Z9 3 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 1999 VL 35 IS 2 BP 195 EP 201 DI 10.1207/S15327914NC352_15 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 284RL UT WOS:000085346200015 PM 10693175 ER PT J AU Cohen, LA Zhao, ZL Pittman, B Khachik, F AF Cohen, LA Zhao, ZL Pittman, B Khachik, F TI Effect of dietary lycopene on N-methylnitrosourea-induced mammary tumorigenesis SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID GAP JUNCTIONAL COMMUNICATION; DIGESTIVE-TRACT CANCERS; BETA-CAROTENE; PROSTATE-CANCER; EPIDEMIOLOGIC EVIDENCE; SERUM MICRONUTRIENTS; SEROLOGIC PRECURSORS; LIPID-PEROXIDATION; ALPHA-TOCOPHEROL; SUBSEQUENT RISK AB Epidemiological studies suggest protective effects of lycopene-rich foods on several types of cancer, including prostate and gastrointestinal tract. Moreover, an inverse association between serum lycopene concentrations and several types of cancer has been reported. However, few studies have focused on breast cancer, and they have shown little association between lycopene consumption and cancer risk. In this report, we used the N-methylnitrosourea (NMU)-induced rat mammary tumor model to compare the effects of pure lycopene with a lycopene-rich tomato carotenoid oleoresin (TCO) on NMU-induced mammary tumorigenesis. Rats were fed diets supplemented with 250 and 500 ppm crystalline lycopene or TCO beginning seven days before initiation with NMU (55 days of age) to termination (18 wk after NMU). Neither pure lycopene nor lycopene in the form of a mixed carotenoid oleoresin exerted an inhibitory effect on tumor incidence, latency, multiplicity volume, or total tumors per group compared with unsupplemented controls. Weight gains in all groups were similar. Assay of serum lycopene concentrations in lycopene-supplemented groups indicated that median levels of 7,12,60, and 87 ng/ml were attained in blood of groups supplemented with 250 and 500 ppm lycopene and 250 and 500 ppm TCO, respectively. The results of this animal study are consistent with epidemiological reports indicating that lycopene does not protect against breast cancer. C1 Amer Hlth Fdn, Div Nutr & Endocrinol, Valhalla, NY 10595 USA. Amer Hlth Fdn, Div Epidemiol, New York, NY 10017 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Cohen, LA (reprint author), Amer Hlth Fdn, Div Nutr & Endocrinol, 1 Dana Rd, Valhalla, NY 10595 USA. RI Khachik, Frederick/C-5055-2009 FU NCI NIH HHS [CN-55163] NR 60 TC 18 Z9 18 U1 1 U2 2 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 1999 VL 34 IS 2 BP 153 EP 159 DI 10.1207/S15327914NC3402_5 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 248QQ UT WOS:000083287200005 PM 10578482 ER PT J AU Jenkins, MY Mitchell, GV Grundel, E AF Jenkins, MY Mitchell, GV Grundel, E TI Dietary vitamin E and beta-carotene sources influence vitamin A and E storage in young rats fed marginal and adequate vitamin E SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID ALPHA-TOCOPHERYL SUCCINATE; CARDIOVASCULAR-DISEASE; ORAL SUPPLEMENTATION; DUNALIELLA-BARDAWIL; LUNG-CANCER; FOLLOW-UP; PLASMA; ANTIOXIDANT; RETINOL; CELLS AB The effects of two vitamin E levels (30 and 75 IU/kg diet) and the interrelation of two vitamin E sources [dl-alpha-tocopheryl acetate (dl-alpha-TA) and d-alpha-tocopheryl acid succinate (d-alpha-TAS)] and three vitamin A sources [retinyl palmitate (RP), all-trans synthetic beta-carotene (SBC), and natural beta-carotene (NBC)] were studied. Dietary vitamin A sources provided 4,000 IU/kg. Twelve groups of Fischer 344 rats (10/group) were fed designated diets for eight weeks. For RP, SEC, and NBC, the increase in each vitamin E source from a marginal to an adequate dietary level caused a significant increase in liver and heart alpha-tocopherol. Among rats fed diets with an adequate level of vitamin E, d-alpha-TAS was nor as effective as dl-alpha-TA in increasing liver alpha-tocopherol levels. Plasma retinol was lower in rats fed d-alpha-TAS than in those fed dl-alpha-TA. Among rats fed diets with an adequate level of dl-alpha-TA, those fed SEC had significantly higher liver and heart alpha-tocopherol concentrations than did all other groups (p < 0.05). Liver retinol equivalents for rats fed NBC were approximately 66% lower than those in rats fed SEC or RP (p < 0.05). The roles of the two vitamin E sources in alpha-tocopherol metabolism are not equivalent. These data indicate that vitamin A source influences the magnitude of the tissue vitamin A and E changes in response to the two vitamin E sources. C1 US FDA, Off Food Labelling HFS175, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Jenkins, MY (reprint author), US FDA, Off Food Labelling HFS175, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 57 TC 1 Z9 1 U1 1 U2 1 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 1999 VL 34 IS 2 BP 235 EP 241 DI 10.1207/S15327914NC3402_16 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 248QQ UT WOS:000083287200016 PM 10578493 ER PT J AU Hammons, GJ Fletcher, JV Stepps, KR Smith, EA Balentine, DA Harbowy, ME Kadlubar, FF AF Hammons, GJ Fletcher, JV Stepps, KR Smith, EA Balentine, DA Harbowy, ME Kadlubar, FF TI Effects of chemoprotective agents on the metabolic activation of the carcinogenic arylamines PhIP and 4-aminobiphenyl in human and rat liver microsomes SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID HETEROCYCLIC AROMATIC-AMINES; INDUCED COLON CARCINOGENESIS; HUMAN URINARY-BLADDER; FOOD-DERIVED MUTAGEN; GREEN TEA EXTRACTS; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; CYTOCHROME P4501A2; DNA-ADDUCTS; ORGANOSULFUR COMPOUNDS; COLORECTAL-CANCER AB Carcinogenic aromatic amines, including the heterocyclic amines, may pose a significant health risk to humans. To determine the potential for chemoprotective intervention against the carcinogenicity of these arylamines and to better understand their mechanism of action, a range of agents, most of them natural dietary constituents, was examined in vitro for their ability to modulate the N-hydroxylation of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) and 4-aminobiphenyl (ABP), an initial step in their bioactivation. Experiments were conducted with rat and human liver microsomes. The agents (diallyl sulfide, indole-3-carbinol, alpha-angelicalactone, cafestol/kahweol palmitates, cafestol, kahweol, benzylisothiocyanate, genistin, formononetin, daidzin, equol, biochanin A, Oltipraz, tannic acid, quercetin, ethoxyquin, green tea, and black tea) comprised a variety of chemical classes that included sulfur-containing compounds, antioxidants, flavonoids, phytoestrogens, diterpenes, and polyphenols. Several of these agents, quercetin, ethoxyquin, and black tea, were found to strongly inhibit PhIP N-hydroxylation in rat liver microsomes, resulting in a nearly 85-90% decrease in activity at 100 mu M or 0.2%. Tannic acid and green tea, in addition to these agents, were also strong inhibitors of ABP N-hydroxylation. In human liver microsomes, each of these agents was strongly inhibitory (approx 85-95% at 100 mu M or 0.02%) of PhIP and ABP N-hydroxylation. Theaflavins and polyphenols were judged to be the primary inhibiting components in the teas, the theaflavins showing the most potent effect These results demonstrate that chemoprotective agents can inhibit the bioactivation of carcinogenic arylamines, and this is likely to be one of the mechanisms of protection. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Thomas J Lipton Co, Englewood Cliffs, NJ 07632 USA. RP Hammons, GJ (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, HFT-100,3900 NCRT Rd, Jefferson, AR 72079 USA. OI Harbowy, Matthew/0000-0003-4861-9411 NR 60 TC 36 Z9 37 U1 1 U2 4 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 1999 VL 33 IS 1 BP 46 EP 52 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 184DM UT WOS:000079594800007 PM 10227043 ER PT B AU Pirillo, P AF Pirillo, P GP MTS MTS TI A versatile, portable and low cost computerized data logging and charting system compatible with electronic nautical charts SO OCEANS '99 MTS/IEEE : RIDING THE CREST INTO THE 21ST CENTURY, VOLS 1-3 LA English DT Proceedings Paper CT MTS/IEEE Conference on Riding the Crest Into the 21st Century (OCEANS 99) CY SEP 13-16, 1999 CL SEATTLE, WA SP Marine Technol Soc, Ocean Engn Soc, Inst Elect & Electr Engn C1 US FDA, CFSAN, Div Cooperat Programs, Washington, DC 20204 USA. RP Pirillo, P (reprint author), US FDA, CFSAN, Div Cooperat Programs, HFS-628,200 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 0-933957-24-6 PY 1999 BP 1526 EP 1530 PG 3 WC Engineering, Marine; Engineering, Electrical & Electronic; Oceanography SC Engineering; Oceanography GA BP25F UT WOS:000084482300250 ER PT J AU Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Marcy, SM Murray, DL Overturf, GD Prober, CG Saari, T Weiner, LB Whitley, RJ Peter, G Pickering, LK Baker, CJ Hirsch, AT Jacobs, RF MacDonald, NE Schwartz, B Orenstein, WA 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 Saari, T Weiner, LB Whitley, RJ Peter, G Pickering, LK Baker, CJ Hirsch, AT Jacobs, RF MacDonald, NE Schwartz, B Orenstein, WA Hardegree, MC Rabinovich, NR Breiman, RF TI Poliomyelitis prevention: Revised recommendations for use of inactivated and live oral poliovirus vaccines SO PEDIATRICS LA English DT Article AB Since 1997 when the American Academy of Pediatrics (AAP) issued revised guidelines for the prevention of poliomyelitis, substantial progress in global eradication of poliomyelitis has occurred and the use of inactivated poliovirus vaccine (IPV) has increased considerably in the United States with a corresponding decrease in the use of oral poliovirus vaccine (OPV). Surveys indicate that the majority of physicians now routinely immunize chit dren with the sequential IPV-OPV or IPV-only regimens. Nevertheless, vaccine-associated paralytic poliomyelitis (VAPP) continues to occur, albeit infrequently, in children who have received the OPV-only regimen and their contacts. To reduce further the risk of VAPP, the AAP now recommends that children in the United States receive IPV for the first 2 doses of the polio vaccine series in most circrumstances. Exceptions include a parent's refusal to permit the number of injections necessary to administer the other routinely recommended vaccines at the 2- and 4-month visits. Either IPV or OPV can be administered for the third and fourth doses. Assuming continuing progress toward global eradication, a recommendation of IPV-only immunization for children in the United States is anticipated by 2001. C1 AAP Council Pediat Practice, New York, NY USA. Canadian Pediat Soc, Calgary, AB, Canada. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD USA. Natl Vaccine Program Off, Washington, DC USA. NR 5 TC 21 Z9 21 U1 1 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 1999 VL 103 IS 1 BP 171 EP 172 PG 2 WC Pediatrics SC Pediatrics GA 157KW UT WOS:000078060900043 ER PT J AU Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Marcy, SM AF Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Marcy, SM TI Recommended childhood immunization schedule - United States, January December 1999 SO PEDIATRICS LA English DT Article C1 AAP Council Pediat Practice, New York, NY USA. Canadian Pediat Soc, Calgary, AB, Canada. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD USA. Natl Vaccine Program Off, Washington, DC USA. NR 6 TC 18 Z9 18 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 1999 VL 103 IS 1 BP 182 EP 185 PG 4 WC Pediatrics SC Pediatrics GA 157KW UT WOS:000078060900045 ER PT J AU Kharidia, J Jackson, AJ Ouderkirk, LA AF Kharidia, J Jackson, AJ Ouderkirk, LA TI Use of truncated areas to measure extent of drug absorption in bioequivalence studies: Effects of drug absorption rate and elimination rate variability on this metric SO PHARMACEUTICAL RESEARCH LA English DT Article DE bioequivalence; truncated area; clearance ID PLASMA-CONCENTRATION; PERFORMANCE AB Purpose. To compare the applicability and accuracy of truncated area (AUCt; where t represents truncated time) versus area to the last quantifiable time point [AUC(0-T)] for assessing bioequivalence. Drugs with either very low or very high intra-subject variability in clearance (CL) were selected for study. Clearance variability was defined by the number of subjects with a quantifiable plasma value (Cp) at each collection time from 24 hrs to last collection time (T). Methods. Data for amiodarone and danazol, drugs with different distributions of subject CL were examined. For amiodarone, the number of subject samples observed (test + reference) at the time of the last quantifiable concentrations was 60 at 240 hrs(T), 16 at 144 hrs and 4 at 96 hrs; while danazol had 4 at 96 hr(T), 3 at 72 hrs, 16 at 60 hrs, 7 at 48 hrs, 14 at 36 hrs, 11 at 24 hrs, 13 and 2 at 16 and 12 hrs, respectively. Simulations (Scenarios A and B) were performed to obtain populations (N = 24) with CL patterns similar to those of amiodarone and danazol. For scenario A (CL pattern similar to amiodarone), lognormally distributed CL values (28.8 L/HR) with intra-subject coefficient of variation (CV) of 25%, 40% and 60% gave the desired CL pattern. Scenario B (CL pattern similar to danazol) required that a subpopulation with an increase in CL of 40% from baseline (i.e., 40.32 L/HR) in 5%, 10% and 20% of the population represent the desired distribution. Power was evaluated by the percentage of times the simulated trials were declared bioequivalent (i.e., the number of times the test vs. reference 90% CI was within 80-125%), while accuracy was determined when the true difference in fraction absorbed (i.e., 1.25) was within the CI. Each simulation was repealed 300 times. Results, The simulation results for Scenario A indicated that the statistical results using truncated area (AUCt) had power and accuracy equivalent to that obtained using the AUC(0-T) metric. However, results for Scenario B indicated that AUCt had less power and accuracy than that obtained using AUC(0-T). The confidence interval (CI) for amiodarone was the same whether AUC (0-T) or AUCt was used as the metric for extent, while for danazol, the AUC(0-T) and AUCt differed in the lower limit by 7%. Conclusions. The truncated area, AUCt- has the: greatest power and accuracy when the population clearance is such that most subjects have measurable plasma concentrations at last collection time(T), resulting in a proportional loss of data from each subject. C1 US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Compendial Operat Staff, Rockville, MD 20857 USA. RP Jackson, AJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20857 USA. EM jacksonan@cder.fda.gov NR 11 TC 8 Z9 8 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JAN PY 1999 VL 16 IS 1 BP 130 EP 134 DI 10.1023/A:1018839300168 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 158QB UT WOS:000078125700021 PM 9950291 ER PT J AU Lai, CC Chen, HJ Chun, MI Tang, YH Yang, YC Li, SY Sun, X AF Lai, CC Chen, HJ Chun, MI Tang, YH Yang, YC Li, SY Sun, X TI Synthesis and bacterial mutagenicity of oxidized derivatives of nitro-polycyclic aromatic hydrocarbons SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE synthesis; tumorigenicity; nitro-polycyclic aromatic hydrocarbons ID DIRECT-ACTING MUTAGENICITY; GROUP ORIENTATION; METABOLISM AB A series of oxidized derivatives of nitrophenanthrene and nitrobenz-[a]anthracene were synthesized and their mutagenicities in Salmonella typhimurium TA98, TA98NR, TA98/1,8-DNP6, TA100, and TA100NR were determined. These compounds exhibited markedly different mutagenicities. Orientation of the nitro group is an important structural feature for correlation with mutagenic potency. C1 Providence Univ, Inst Appl Chem, Taichung, Taiwan. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Lai, CC (reprint author), Providence Univ, Inst Appl Chem, Taichung, Taiwan. NR 14 TC 0 Z9 0 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 16 IS 1-4 BP 61 EP 69 DI 10.1080/10406639908020573 PG 9 WC Chemistry, Organic SC Chemistry GA 297HD UT WOS:000086076100008 ER PT J AU Herreno-Saenz, D Von Tungeln, LS Hart, RW Fu, PP AF Herreno-Saenz, D Von Tungeln, LS Hart, RW Fu, PP TI Effect of dietary restriction and age on the formation of DNA adducts from the mouse liver microsome-mediated metabolism of 2-nitropyrene SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE 2-nitropyrene; DNA adducts; dietary restriction; mouse liver microsomes ID CALORIC RESTRICTION; FISCHER-344 RAT; 1-NITROPYRENE; 4-NITROPYRENE; ENZYMES AB N-(Deoxyguanosin-8-yl)-2-aminopyrene and N-(deoxyadenosin-8-yl)2-aminopyrene were formed from metabolism of 2-nitropyrene (2-NP) in vitro and in vivo. The effects of dietary restriction (DR) and age on the formation of these DNA adducts were studied. In the presence of calf thymus DNA, [G-H-3]2-NP was metabolized by liver microsomes of 5-, 9-, and 12-month old male B6C3F(1) mice fed ad libitum (AL microsomes) or by liver microsomes of 5-, 9-, and 12-month old male B6C3F(1) mice fed a restricted diet (DR microsomes). In all cases, both adducts were detected. The total quantities formed from 5-, 9-, and 12-month AL microsomes, and 5-, 9-, and 12-month DR microsomes were 5.58+/-1.78, 8.79+/-2.32, 3.57+/-0.34, 1.63+/-0.40, 5.46+/-0.21, and 4.15+/-0.94 pmol 2-NP/mg DNA, respectively. These results suggest the effect of DR on DNA adduct formation may be age dependent. However, the ratio of dG/dA adduct formation was similar in all cases and was independent of age and caloric intake of the mice used for the microsomal preparations. C1 Univ Puerto Rico, San Juan, PR 00936 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Herreno-Saenz, D (reprint author), Univ Puerto Rico, Med Sci Campus, San Juan, PR 00936 USA. NR 12 TC 0 Z9 0 U1 1 U2 1 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 16 IS 1-4 BP 151 EP 159 DI 10.1080/10406639908020582 PG 9 WC Chemistry, Organic SC Chemistry GA 297HD UT WOS:000086076100017 ER PT J AU Hong, F Von Tungeln, LS Fu, PP Watson, F AF Hong, F Von Tungeln, LS Fu, PP Watson, F TI Stereoselective metabolism of anthracene, 9-methylanthracene, 9,10-dimethylanthracene 9-chloroanthracene, and 9-nitroanthracene by liver microsomes of neonatal male B6C3F(1) mice SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE stereoselective metabolism; anthracene; neonatal mouse ID MOUSE; TUMORIGENICITY; BIOASSAY AB Stereoselective metabolism of anthracene, 9-methylanthracene (9-M-A), 9,10-dimethylanthracene (9,10-DMA), 9-chloroanthracene (9-Cl-A), and 9-nitroanthracene (9-nitro-A) by liver microsomes of neonatal (15-day old) male B6C3F(1) mice in the presence of a NADPH regenerating system was conducted. After incubation, reversed-phase HPLC separation, and spectral analyses the following were identified: anthracene trans-1,2-dihydrodiol, 9-M-A trans-1,2- and -3,4-dihydrodiol, 9,10-DMA trans-1,2-dihydrodiol, 9-Cl-A trans-1,2- and -3,4-dihydrodiol, and 9-nitro-A trans-1,2- and -3,4-dihydrodiol. Circular dichroism (CD) spectral analysis indicated the major enantiomers of the anthracene, 9-M-A, 9,10-DMA, and 9-Cl-A trans-dihydrodiols all had R,R absolute configurations. These results indicate that these compounds are metabolized in a stereoselective manner by liver microsomes of neonatal male B6C3F(1) mice. C1 NE Louisiana Univ, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hong, F (reprint author), NE Louisiana Univ, Monroe, LA 71209 USA. NR 11 TC 0 Z9 0 U1 0 U2 4 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 16 IS 1-4 BP 235 EP 244 DI 10.1080/10406639908020590 PG 10 WC Chemistry, Organic SC Chemistry GA 297HD UT WOS:000086076100025 ER PT J AU Von Tungeln, LS Xia, QS Fu, PP AF Von Tungeln, LS Xia, QS Fu, PP TI Benz[a]anthracene is a potent liver tumorigen in the neonatal B6C3F(1) mouse SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE liver tumors; benz[a]anthracene; neonatal mouse; tumorigenicity bioassay; K-ras-oncogene ID H-RAS; MICE; 7-BROMOBENZANTHRACENE; DERIVATIVES; ACTIVATION; ONCOGENES; BIOASSAY; ASSAY AB Benz[a]anthracene (BA) has been reported to be a noncarcinogen or a borderline weak carcinogen in several chronic bioassay systems. For comparison, we determined its tumorigenicity in the neonatal male B6C3F(1) mouse. Mice were administered i.p. injections (1600 nmol total dose per mouse) within 24 hrs of birth and at 8 and 15 days of age. BA induced hepatocellular adenomas and carcinomas in 75 and 25% of the mice, respectively, while the solvent control (DMSO) induced 8 and 4%, respectively. Analysis by RT-PCR indicated that 86% (12/14) of BA-induced liver tumors had activated ras protooncogenes, 11 with a pattern of GGC-->CGC at K-ras codon 13. Our results clearly demonstrate that BA is a potent tumorigenicity in the neonatal B6C3F(1) mouse and induces a unique type of K-ras-oncogene activation. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Von Tungeln, LS (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 16 IS 1-4 BP 245 EP 254 DI 10.1080/10406639908020591 PG 10 WC Chemistry, Organic SC Chemistry GA 297HD UT WOS:000086076100026 ER PT J AU Krawetz, DW AF Krawetz, DW TI Photo was "right on" SO PUBLIC HEALTH REPORTS LA English DT Letter C1 US FDA, Cincinnati Dist Off, Cincinnati, OH 45267 USA. RP Krawetz, DW (reprint author), US FDA, Cincinnati Dist Off, Cincinnati, OH 45267 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 1999 VL 114 IS 1 BP 6 EP 6 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 158DB UT WOS:000078099800006 PM 9925161 ER PT B AU Suleiman, OH AF Suleiman, OH GP NCRP NCRP TI Doses in diagnostic radiology: How and why they vary SO RADIATION PROTECTION IN MEDICINE: CONTEMPORARY ISSUES SE PROCEEDINGS OF THE NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS LA English DT Proceedings Paper CT 35th Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurement CY APR 07-08, 1999 CL ARLINGTON, VA SP Natl Council Radiat Protect ID ATTENUATION PHANTOM; MAMMOGRAPHY; EXPOSURE AB In diagnostic radiology entrance air kerma and derived tissue doses vary over a wide range of values. The Nationwide Evaluation of Xray Trends (N.E.X.T.) surveys, and the Mammography Quality Standards Act of 1992 (MQSA) inspections use standard, clinically representative phantoms for the determination of air kerma. Examinations for which phantoms exist and standard surveys have been conducted include chest and abdominal radiography, fluoroscopy, computed tomography, mammography, dental radiography, and most recently pediatric radiography. Observed differences in air kerma and the mean glandular (breast) dose and how these differences relate to factors such as the type of image receptor, the use of grids, beam quality, and processing quality, and the relationship of these factors to image quality will be presented. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Suleiman, OH (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 31 TC 0 Z9 0 U1 0 U2 0 PU NATL COUNCIL RADIATION PROTECTION MEASUREMENTS PI BETHESDA PA 7910 WOODMONT AVE, SUITE 1016, BETHESDA, MD 20814 USA BN 0-929600-62-2 J9 P NAT C RAD PY 1999 IS 21 BP 167 EP 179 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BT45S UT WOS:000173048200008 ER PT J AU Qi, Z AF Qi, Z TI Comments on the hazard function of a two-stage carcinogenesis model SO RADIATION RESEARCH LA English DT Letter ID CANCER 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, HFT-20,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 1999 VL 151 IS 1 BP 120 EP 120 PG 1 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 154VQ UT WOS:000077910400037 ER PT J AU Turnipseed, SB Roybal, JE Rupp, HS Gonzales, SA Pfenning, AP Hurlbut, JA AF Turnipseed, SB Roybal, JE Rupp, HS Gonzales, SA Pfenning, AP Hurlbut, JA TI Confirmation of avermectin residues in food matrices with negative-ion atmospheric pressure chemical ionization liquid chromatography mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID IVERMECTIN; CATTLE; TISSUES; LIVER AB A multi-residue LC/MS method has been developed to confirm avermectin drug residues in several food matrices, Ivermectin (IVR), doramectin (DOR), eprinomectin (EPR) and moxidectin (MOX) are confirmed using atmospheric pressure chemical ionization (APCI) with negative ion detection and selected ion monitoring of three to four ions for each compound. The drug residues are extracted from tissue or milk using previously published procedures. IVR and DOR are confirmed at 20 ppb levels in fortified salmon muscle; IVR is also confirmed in tissue from salmon dosed with the drug. Residues of DOR IVR, and EPR are confirmed in fortified milk at the 20 ppb level and in fortified beef liver at 40 ppb, Residues of MOX can also be confirmed in these matrices, but at slightly higher levels (40-80 ppb), Copyright (C) 1999 John Wiley & Sons, Ltd. C1 US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. US FDA, NW Reg Lab, Bothell, WA 98021 USA. RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. NR 12 TC 37 Z9 42 U1 1 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 1999 VL 13 IS 6 BP 493 EP 499 DI 10.1002/(SICI)1097-0231(19990330)13:6<493::AID-RCM514>3.0.CO;2-4 PG 7 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 177JG UT WOS:000079206400006 PM 10204245 ER PT J AU Breen, JG Claggett, TW Kimmel, GL Kimmel, CA AF Breen, JG Claggett, TW Kimmel, GL Kimmel, CA TI Heat shock during rat embryo development in vitro results in decreased mitosis and abundant cell death SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE hyperthermia; apoptosis; skeletal defects; cell cycle; mitosis ID NEURAL-TUBE DEFECTS; SEGMENTAL ANOMALIES; DEVELOPMENT INVITRO; CHICK-EMBRYO; HYPERTHERMIA; CYCLE; INDUCTION; TERATOGEN; EXPOSURE; EXPRESSION AB Epidemiologic studies strongly suggest that in utero exposure to hyperthermia results in developmental defects in humans, Rats, mice, guinea pigs, and other species exposed to hyperthermia also exhibit a variety of developmental defects. Studies in our laboratory have focused on exposure to hyperthermia on Gestation Day (GD) 10 of rats in vivo or in vitro. Within 24 h after in vivo or in vitro exposure, delayed or abnormal CNS, optic cup, somite, and limb development can be observed. At birth, only rib and vertebral malformations are seen after hyperthermia on GD 10, and these have been shown to be due to alterations in somite segmentation. Unsegmented somites have been thought to result from a cell-cycle block in the presomitic mesoderm, from which somites emerge individually during normal development. In the present study, DNA fragmentation (terminal deoxynucleotidyl transferase (TdT) catalyzed fluorescein-12-dUTP DNA end-labelling), indicative of apoptotic cell death, and changes in cell proliferation were examined in vitro in 37 degrees C control and heat treated (42 degrees C for 15 min) GD 10 CD rat embryos. Embryos were returned to 37 degrees C culture following exposure and evaluated 5, 8, or 18 h later. A temperature-related increase in TdT labelled cells was observed in the CNS, optic vesicle, neural tube, and somites, Increased cell death in the presomitic mesoderm also was evident. Changes in cell proliferation were examined using the cell-specific abundance of proliferating cell nuclear antigen (PCNA) and the quantification of mitotic figures. In neuroectodermal cells in the region of the optic cup, a change in the abundance of PCNA was not apparent, but a marked decrease in mitotic figures was observed. A significant change in cell proliferation in somites was not detected by either method. These results suggest that acute hyperthermia disrupts embryonic development through a combination of inappropriate cell death and/or altered cell proliferation in discrete regions of the developing rat embryo. Furthermore, postnatal vertebral and rib defects following disrupted somite development may be due, in part, to abundant cell death occurring in the presomitic mesoderm. (C) 1999 Elsevier Science Inc. C1 US EPA, Natl Ctr Environm Assessment, NCEAW 8623D, Washington, DC 20460 USA. Pathol Associates Int, Frederick, MD USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Kimmel, CA (reprint author), US EPA, Natl Ctr Environm Assessment, NCEAW 8623D, Washington, DC 20460 USA. NR 25 TC 23 Z9 27 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN-FEB PY 1999 VL 13 IS 1 BP 31 EP 39 DI 10.1016/S0890-6238(98)00056-2 PG 9 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 169UG UT WOS:000078766700003 PM 10080297 ER PT J AU Satchithanandam, S Gallo, LL Vahouny, GV Kritchevsky, D AF Satchithanandam, S Gallo, LL Vahouny, GV Kritchevsky, D TI The lymphatic absorption of dihydrolanosterol and cholesterol in the rat SO RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY LA English DT Article ID LANOSTEROL 14-ALPHA-METHYL DEMETHYLASE; SUBSTRATE-BASED INHIBITORS; SITOSTEROL AB Dihydrolanosterol (DHL) and its analogs have been studied extensively as cholesterol biosynthesis inhibitors. They inhibit specific steps in cholesterol synthesis by inhibiting lanosterol demethylase and by suppressing HMG-CoA reductase. The present study was designed to estimate the lymphatic absorption of DHL. For comparison, a cholesterol group was included. The left thoracic duct of male Wistar rats weighing between 210 and 230 g was cannulated. A lipid emulsion containing 0.75 mu Ci of either [H-3]-DHL or [H-3]-cholesterol was given intragastrically. After the lipid meal, lymph was collected at 3 h intervals up to 9 h and then at 24 h. Radioactivity of DHL and cholesterol in the lymph was estimated. Lipid extracts of lymph specimens were also subjected to thin layer chromatography and fractions of DHL, cholesterol and their esters were isolated and the masses were estimated. There were no differences in lymph volumes between the two groups. However, absorption and esterification of DHL in lymph were significantly reduced compared with the cholesterol group. The marked decrease in the esterification of DHL is likely due to its poor absorption into the mucosal cell and subsequently into the lymphatic system. The amount of DHL available in the mucosal cell for esterification may be a limiting factor. C1 George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. Univ Penn, Sch Med, Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. RP Satchithanandam, S (reprint author), US FDA, Off Food Labeling, Room 1090,HFS-175,200 C St SW, Washington, DC 20204 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU P J D PUBLICATIONS LTD PI WESTBURY PA PO BOX 966, WESTBURY, NY 11590 USA SN 1078-0297 J9 RES COMMUN MOL PATH JI Res. Commun. Mol. Pathol. Pharmacol. PD JAN PY 1999 VL 103 IS 1 BP 91 EP 100 PG 10 WC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy GA 213YU UT WOS:000081301500009 PM 10440574 ER PT J AU Xing, L Welsh, WJ Tong, W Perkins, R Sheehan, DM AF Xing, L Welsh, WJ Tong, W Perkins, R Sheehan, DM TI Comparison of estrogen receptor alpha and beta subtypes based on comparative molecular field analysis (CoMFA) SO SAR AND QSAR IN ENVIRONMENTAL RESEARCH LA English DT Article DE CoMFA; 3D-QSAR; endocrine disrupting compounds; estrogen receptor alpha (ER-alpha); estrogen receptor beta (ER-beta) ID ER-BETA; PHYSICOCHEMICAL PARAMETERS; BINDING; IDENTIFICATION; INHIBITORS; SUPERFAMILY; ACTIVATION; BREAST; CANCER; ACID AB A substantial body of evidence indicates that both humans and wildlife suffer adverse health effects from exposure to environmental chemicals that are capable of interacting with the endocrine system. The recent cloning of the estrogen receptor beta subtype (ER-beta) suggests that the selective effects of estrogenic compounds may arise in part by the control of different subsets of estrogen-responsive promoters by the two ER subtypes, ER-alpha and ER-beta. In order to identify the structural prerequisites for ligand-ER binding and to discriminate ER-alpha and ER-beta in terms of their ligand-binding specificities, Comparative Molecular Field Analysis (CoMFA) was employed to construct a three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) model on a data set of 31 structurally-diverse compounds for which competitive binding affinities have been measured against both ER-alpha and ER-beta. Structural alignment of the molecules in CoMFA was achieved by maximizing overlap of their steric and electrostatic fields using the Steric and Electrostalic ALignment (SEAL) algorithm. The final CoMFA models, generated by correlating the calculated 3D steric and electrostatic fields with the experimentally observed binding affinities using partial least-squares (PLS) regression, exhibited excellent self-consistency (r(2) > 0.99) as well as high internal predictive ability (q(2) > 0.65) based on cross validation. CoMFA-predicted values of RBA for a test set of compounds outside of the training set were consistent with experimental observations. These CoMFA models can serve as guides for the rational design of ER ligands that possess preferential binding affinities for either ER-alpha or ER-beta. These models can also prove useful in risk assessment programs to identify real or suspected EDCs. C1 Univ Missouri, Dept Chem, St Louis, MO 63121 USA. Univ Missouri, Ctr Mol Elect, St Louis, MO 63121 USA. ROW Sci, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. RP Welsh, WJ (reprint author), Univ Missouri, Dept Chem, St Louis, MO 63121 USA. NR 44 TC 25 Z9 26 U1 0 U2 4 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1062-936X J9 SAR QSAR ENVIRON RES JI SAR QSAR Environ. Res. PY 1999 VL 10 IS 2-3 BP 215 EP + DI 10.1080/10629369908039177 PG 25 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications; Environmental Sciences; Mathematical & Computational Biology; Toxicology SC Chemistry; Computer Science; Environmental Sciences & Ecology; Mathematical & Computational Biology; Toxicology GA 234JY UT WOS:000082482000009 PM 10491851 ER PT J AU Weigmann, HJ Lademann, J Von Pelchrzim, R Sterry, W Hagemeister, T Molzahn, R Schaefer, M Lindscheid, M Schaefer, H Shah, VP AF Weigmann, HJ Lademann, J Von Pelchrzim, R Sterry, W Hagemeister, T Molzahn, R Schaefer, M Lindscheid, M Schaefer, H Shah, VP TI Bioavailability of clobetasol propionate - Quantification of drug concentrations in the stratum corneum by dermatopharmacokinetics using tape stripping SO SKIN PHARMACOLOGY AND APPLIED SKIN PHYSIOLOGY LA English DT Article DE tape stripping; high performance liquid chromatography; quantitative determination of clobetasol propionate; penetration; vehicle influence AB The concentration of clobetasol propionate in the stratum corneum after application of three different formulations was determined, quantifying the influence of the formulations on the bioavailability of the drug. The stratum corneum was sampled by tape stripping. The concentrations of clobetasol propionate were determined quantitatively by HPLC. After application of Clobetasol Propionate Cream USP, 0.05%, and Temovate Cream, 0.05%, identical amounts of the drug were found in the stratum corneum, whereas after application of Temovate epsilon Emollient 0.05%, the quantity was clearly decreased. From results obtained measuring the drug concentration in the adjacent sites of the skin where the creams had not been applied, it became clear that clobetasol propionate in Temovate epsilon Emollient, migrated to a large extent in the lateral direction. This explains the lower concentration measured for this formulation in the skin areas where the cream had been applied. In general, a lateral distribution of the applied drug must be taken into account when positioning the application areas on the forearm. C1 Klinikum Humboldt Univ Berlin, Klin Dermatol Venerol & Allergol Asthmapoliklin, D-10098 Berlin, Germany. Humboldt Univ, Math Nat Wissensch Fak, Inst Chem, Berlin, Germany. Loreal Res, Ctr Charles Zviak, Clichy, France. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Weigmann, HJ (reprint author), Klinikum Humboldt Univ Berlin, Klin Dermatol Venerol & Allergol Asthmapoliklin, Campus Charite Mitte, D-10098 Berlin, Germany. RI Linscheid, Michael/D-2125-2009 NR 7 TC 44 Z9 44 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-2868 J9 SKIN PHARMACOL APPL JI Skin Pharmacol. Appl. Skin Physiol. PD JAN-APR PY 1999 VL 12 IS 1-2 BP 46 EP 53 DI 10.1159/000029845 PG 8 WC Dermatology; Pharmacology & Pharmacy SC Dermatology; Pharmacology & Pharmacy GA 204ND UT WOS:000080769700006 PM 10325583 ER PT J AU Sotomayor, RE Ehling, UH Sega, GA AF Sotomayor, RE Ehling, UH Sega, GA TI Differential sensitivities of spermatogonial and postspermatogonial cell stages of the mouse to induction of unscheduled DNA synthesis by ethyl- and methyl-nitrosourea SO TERATOGENESIS CARCINOGENESIS AND MUTAGENESIS LA English DT Article DE UDS; spermatogonia; ENU; MNU; mice ID MALE-MICE; ALKYLATING-AGENTS; GERM-CELLS; LOCUS; ETHYLNITROSOUREA; METHANESULFONATE; SPERMATOCYTES; MUTAGENICITY; MUTATIONS; RADIATION AB An autoradiographic procedure was used to measure unscheduled DNA synthesis (UDS, DNA repair synthesis) in spermatogonial and postspermatogonial cell stages of mice after treatment with two doses of N-ethyl-N-nitrosourea (ENU) and N-methyl-N-nitrosourea (MNU). Significant levels of UDS were measured in type A spermatogonia, meiotic spermatocytes, round spermatids, and early elongating spermatids but not in mature spermatids. The extent of UDS varied according to the germ cell stage and the dose. At equimolar concentrations, MNU was more efficient than ENU in eliciting a UDS response in all germ cells. After ENU treatment, type A spermatogonia showed the highest UDS response, while round and elongating spermatids showed the lowest. After MNU treatment, pachytene spermatocytes exhibited the highest UDS response while type A spermatogonia showed the lowest. The high UDS response of type A spermatogonia to ENU parallels the well-known high mutational sensitivity of spermatogonia to this chemical. Similarly the high UDS response observed in meiotic spermatocytes and early spermatid stages after MNU treatment correlates with the high mutational sensitivity of postspermatogonial stages to MNU. Thus, the present results, like the specific locus mutation studies, indicate that ENU and MNU each has a unique effect on the spermatogenic cells. This effect is likely due to the different mechanism of action of ENU and MNU at the level of DNA and also to the physiological differences between different germ-cell stages. Teratogenesis Carcinog. Mutagen. 19:339-351, 1999. Published 1999 Wiley-Liss,Inc. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Res, Laurel, MD 20708 USA. GSF Forschungszentrum Umwelt & Gesundheit GMBH, Inst Saugetiergenet, Neuherberg, Germany. Oak Ridge Natl Lab, Div Chem & Analyt Sci, Oak Ridge, TN 37831 USA. RP Sotomayor, RE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Res, HFS-509,MOD-1,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 41 TC 8 Z9 8 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 0270-3211 J9 TERATOGEN CARCIN MUT JI Teratogenesis Carcinog. Mutagen. PY 1999 VL 19 IS 5 BP 339 EP 351 DI 10.1002/(SICI)1520-6866(1999)19:5<339::AID-TCM4>3.0.CO;2-O PG 13 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 240XC UT WOS:000082851500004 PM 10495451 ER PT J AU Pilaro, AM Serabian, MA AF Pilaro, AM Serabian, MA TI Preclinical development strategies for novel gene therapeutic products SO TOXICOLOGIC PATHOLOGY LA English DT Article DE animal studies; adenovirus; plasmid DNA; vector; genetic disease AB With over 220 investigational new drug applications currently active, gene therapy represents one of the fastest growing areas in biotherapeutic research. Initially conceived for replacing defective genes in diseases such as cystic fibrosis or inborn errors of metabolism with genes encoding the normal, or wild-type, gene product, gene therapy has expanded into other novel applications such as treatment of cancer or cardiovascular disease, where the risk:benefit profiles may be more acceptable in relation to the severity of the disease. Different types of vectors, including modified retroviruses, adenoviruses, adenovirus-associated viruses, and herpesviruses and plasmid DNA, are used to transfer foreign genetic material into patients' cells or tissues. Developing a toxicology program to determine the safety of these agents, therefore, requires a modified approach that encompasses the pharmacology and toxicity of both the gene product itself and the vector system used for delivery in the context of the application for the clinical trial. In general, the issues involved in designing and developing appropriate preclinical testing to determine the safety of these products are similar to those encountered for other recombinant molecules, including protein biotherapeutics. Limitations to some of the typical toxicology studies conducted for a traditional drug development program may exist for these agents, and nontraditional approaches may be required to demonstrate their safety. Many factors may affect the safety and clinical activity of these agents, including the route, frequency, and duration of exposure and the type of vector employed. Other safety considerations include quantitation of the duration and degree of expression of the vector in target and other tissues, the effects of gene expression on organ pathology and/or histology, evaluation of trafficking of gene-transduced cells or vector after injection, and interactions of the host immune system with the transduced cell population. Because of the unique concerns regarding each of these therapies, the Center for Biologics Evaluation and Research encourages sponsors to obtain toxicity data whenever possible while evaluating the pharmacologic activity of the vector in a species or animal model relevant to their clinical indication. Sponsors are encouraged to discuss preclinical study design and results with the Center during product development to facilitate early identification of safety concerns prior to entry of these novel agents into the clinical setting and to ensure an uninterrupted course of development while addressing issues required for licensure. C1 US FDA, Ctr Biol Evaluat & Res, OTRR, DCTDA, Rockville, MD 20852 USA. RP Pilaro, AM (reprint author), US FDA, Ctr Biol Evaluat & Res, OTRR, DCTDA, Woodmont I,HFM-579,1401 Rockville Pike, Rockville, MD 20852 USA. NR 4 TC 18 Z9 23 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN-FEB PY 1999 VL 27 IS 1 BP 4 EP 7 DI 10.1177/019262339902700102 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 165GT UT WOS:000078513200002 PM 10367665 ER PT J AU Black, LE Bendele, AM Bendele, RA Zack, PM Hamilton, M AF Black, LE Bendele, AM Bendele, RA Zack, PM Hamilton, M TI Regulatory decision strategy for entry of a novel biologic therapeutic with a clinically unmonitorable toxicity into clinical trials: Pre-IND meetings and a case example SO TOXICOLOGIC PATHOLOGY LA English DT Article DE risk-benefit; regulatory strategy; safety margins; histopathology; pre-IND; FDA interactions AB The following material was derived from a synthesis of case histories taken from investigational new drug (IND) applications and drug sponsors' experiences, utilizing fictionalized data to avoid any resemblance to any proprietary information; any such resemblance is accidental. These examples are used as an instructional scenario to illustrate appropriate handling of a difficult toxicology issue. In this scenario, a drug caused a toxicity in animals that was detected only by histopathologic analysis; if it were to develop in patients, no conventional clinical methods could be identified to monitor for it. It is not unusual for a firm to cancel clinical development plans for a lead drug candidate that causes such a toxicity, especially if such a drug is intended for use as a chronic therapeutic in a population of patients with a chronic disease. This case synthesis was inspired by a Food and Drug Administration (FDA) agreement to allow such a product to proceed into clinical trials after substantive pre-IND discussions and agreement on well-considered toxicology program designs. The scientists most closely involved in the strategy development included the sponsor's toxicologist, veterinary toxicologic pathologist, and pharmacokineticist, as well as the FDA's reviewing pharmacologist. The basis of this decision was thorough toxicity characterization (1-month studies in 2 species); correlating toxicities with a particular cumulative area under the curve (AUC) in both species; identification of the most sensitive species (the species that showed the lower AUC correlating with toxicity); allometric assessment of clearance of the drug in 3 nonhuman species; construction of a model of human kinetics (based on extrapolation from animal kinetics); and finally, estimation of clinical safety factors (ratios of the human estimated cumulative AUC at the proposed clinical doses, over the animal cumulative AUC that correlated with the no adverse effect levels). Industry and FDA scientists negotiated a joint assessment of risk and benefit in patients, resulting in the FDA permitting such a compound to enter into clinical trials for a serious autoimmune disease. Such constructive, early communication starts with the pre-IND meeting, and the conduct and planning for this meeting can be very important in establishing smooth scientific and regulatory groundwork for the future of a drug under IND investigation. C1 US FDA, CBER, OTRR, Rockville, MD 20852 USA. RP Black, LE (reprint author), US FDA, CBER, OTRR, HFM-579,1401 Rockville Pike, Rockville, MD 20852 USA. NR 6 TC 3 Z9 3 U1 0 U2 2 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN-FEB PY 1999 VL 27 IS 1 BP 22 EP 26 DI 10.1177/019262339902700105 PG 5 WC Pathology; Toxicology SC Pathology; Toxicology GA 165GT UT WOS:000078513200005 PM 10367668 ER PT J AU Serabian, MA Pilaro, AM AF Serabian, MA Pilaro, AM TI Safety assessment of biotechnology-derived pharmaceuticals: ICH and beyond SO TOXICOLOGIC PATHOLOGY LA English DT Article DE preclinical trials; toxicity testing; biotherapeutics; S6 document AB Many scientific discussions, especially in the past 8 yr, have focused on definition of criteria for the optimal assessment of the preclinical toxicity of pharmaceuticals. With the current overlap of responsibility among centers within the Food and Drug Administration (FDA), uniformity of testing standards, when appropriate, would be desirable. These discussions have extended beyond the boundaries of the FDA and have culminated in the acceptance of formalized, internationally recognized guidances. The work of the international Committee on Harmonisation (ICH) and the initiatives developed by the FDA are important because they (a) represent a consensus scientific opinion, (b) promote consistency, (c) improve the quality of the studies performed, (d) assist the public sector in determining what may be generally acceptable to prepare product development plans, and (e) provide guidance for the sponsors in the design of preclinical toxicity studies. Disadvantages associated with such initiatives include (a) the establishment of a historical database that is difficult to relinquish, (b) the promotion of a check-the-box approach, i.e., a tendancy to perform only the minimum evaluation required by the guidelines, (c) the creation of a disincentive for industry to develop and validate new models, and (d) the creation of state-of-the-art guidances that may not allow for appropriate evaluation of novel therapies. The introduction of biotechnology-derived pharmaceuticals for clinical use has often required the application of unique approaches to assessing their safety in preclinical studies. There is much diversity among these products, which include the gene and cellular therapies, monoclonal antibodies, human-derived recombinant regulatory proteins, blood products, and vaccines. For many of the biological therapies, there will be unique product issues that may require specific modifications to protocol design and may raise additional safety concerns (e.g., immunogenicity). Guidances concerning the design of preclinical studies for such therapies are generally based on the clinical indication. Risk versus benefit decisions are made with an understanding of the nature of the patient population, the severity of disease, and the availability of alternative therapies. Key components of protocol design for preclinical studies addressing the risks of these agents include (a) a safe starting dose in humans, (b) identification of potential target organs, (c) identification of clinical parameters that should be monitored in humans, and (d) identification of at-risk populations. One of the distinct aspects of the safety evaluation of biotechnology-derived pharmaceuticals is the use of relevant and often nontraditional species and the use of animal models of disease in preclinical safety evaluation. Extensive contributions were made by the Center for Biologics Evaluation and Research to the ICH document on the safety of biotherapeutics, which is intended to provide worldwide guidance for a framework approach to the design and review of preclinical programs. Rational, scientifically sound study design and early identification of the potential safety concerns that may be anticipated in the clinical trial can result in preclinical data that facilitate use of these novel therapies for use in humans without duplication of effort or the unnecessary use of animals. C1 US FDA, Ctr Biol Evaluat & Res, OTRR, DCTDA, Rockville, MD 20852 USA. RP Serabian, MA (reprint author), US FDA, Ctr Biol Evaluat & Res, OTRR, DCTDA, Woodmont I,HFM-579,1401 Rockville Pike, Rockville, MD 20852 USA. NR 5 TC 28 Z9 32 U1 2 U2 13 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN-FEB PY 1999 VL 27 IS 1 BP 27 EP 31 DI 10.1177/019262339902700106 PG 5 WC Pathology; Toxicology SC Pathology; Toxicology GA 165GT UT WOS:000078513200006 PM 10367669 ER PT J AU Puri, RK AF Puri, RK TI Development of a recombinant interleukin-4-Pseudomonas exotoxin for therapy of glioblastoma SO TOXICOLOGIC PATHOLOGY LA English DT Article DE interleukin-4 receptors; recombinant chimeric protein; interleukin-4 Pseudomonas exotoxin; glioblastoma; cytotoxicity; antitumor activity; toxicology ID RECEPTOR GAMMA-CHAIN; CELL-CARCINOMA-CELLS; CIRCULARLY PERMUTED INTERLEUKIN-4; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; FUNCTIONAL COMPONENT; IL-13 RECEPTOR; SARCOMA-CELLS; EXPRESSION; CANCER AB About 12,000 Americans are diagnosed with malignant astrocytoma each year. Despite surgery, radiotherapy, and chemotherapy, the prognosis of these patients remains poor. Targeted toxins based on the identification of novel antigens or receptors provide a promising new approach to treating cancer. We have identified one such cell surface protein in the form of interleukin (IL)-4 receptors (IL-4R) on human malignant astrocytoma. Normal brain tissues from frontal cortex and temporal lobe cortex do not express IL-4R. To target IL-4R, we generated a chimeric fusion protein composed of IL-4 and Pseudomonas exotoxin (IL4-PE). This toxin is highly cytotoxic to IL-4R-bearing human brain cancer cells. Preclinical toxicologic experiments were performed in mice, rats, and guinea pigs to determine an maximum tolerated dose. Intrathecal administration in cynomolgus monkeys produced high cerebrospinal fluid levels without any central nervous system or other abnormalities. When IL4-PE was injected into the right frontal cortex of rats, localized necrosis was observed at 1,000 but not less than or equal to 100 mu g/ml doses. Intravenous administration of this biologic to monkeys produced reversible grade 3 or grade 4 elevations of hepatic enzymes in a dose-dependent manner. These results indicate that localized administration can produce nontoxic levels of IL4-PE that may have significant activity against astrocytoma. In vivo experiments with nude mice have demonstrated that IL4-PE has significant antitumor activity against human glioblastoma tumor model. Intratumor administration of IL4-PE has been initiated for the treatment of malignant astrocytoma in a phase I clinical trial. C1 NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 28 TC 21 Z9 22 U1 0 U2 1 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN-FEB PY 1999 VL 27 IS 1 BP 53 EP 57 DI 10.1177/019262339902700111 PG 5 WC Pathology; Toxicology SC Pathology; Toxicology GA 165GT UT WOS:000078513200011 PM 10367674 ER PT J AU Pierce, LR Gaines, A Finlayson, JS Varricchio, F Epstein, JS AF Pierce, LR Gaines, A Finlayson, JS Varricchio, F Epstein, JS TI Hemolysis and acute renal failure due to the administration of albumin diluted in sterile water SO TRANSFUSION LA English DT Letter C1 US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Div Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Pierce, LR (reprint author), US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 7 TC 6 Z9 6 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 1999 VL 39 IS 1 BP 110 EP 111 PG 2 WC Hematology SC Hematology GA 157FQ UT WOS:000078050300020 PM 9920177 ER PT S AU Kodell, RL Gaylor, DW AF Kodell, RL Gaylor, DW BE Bailer, AJ Maltoni, C Bailar, JC Belpoggi, F Brazier, JV Soffritti, M TI Combining uncertainty factors in deriving human exposure levels of noncarcinogenic toxicants SO UNCERTAINTY IN THE RISK ASSESSMENT OF ENVIRONMENTAL AND OCCUPATIONAL HAZARDS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Workshop on Uncertainty in the Risk Assessment of Environmental and Occupational Hazards CY SEP 24-26, 1998 CL BOLOGNA, ITALY SP European Fdn Oncol & Environm Sci B Ramazzini, Int Stat Inst, Miami Univ, Univ Chicago, Natl Ctr Toxicol Res, NIEHS, NIOSH, Akzo Nobel NV, Reg Agcy Prevent & Envoronm, Agcy Tox Subst & Dis Registry, Collegium Ramazzini, DSM ID NONCANCER RISK ASSESSMENT; DEVELOPMENTAL TOXICITY; MODELS; RFD AB Acceptable levels of human exposure to noncarcinogenic toxicants in environmental and occupational settings generally are derived by reducing experimental no-observed-adverse-effect levels (NOAELs) or benchmark doses (BDs) by a product of uncertainty factors (Barnes and Dourson, Ref, 1). These factors are presumed to ensure safety by accounting for uncertainty in dose extrapolation, uncertainty in duration extrapolation, differential sensitivity between humans and animals, and differential sensitivity among humans. The common default value for each uncertainty factor is 10. This paper shows how estimates of means and standard deviations of the approximately lognormal distributions of individual uncertainty factors can be used to estimate percentiles of the distribution of the product of uncertainty factors, An appropriately selected upper percentile, for example, 95th or 99th, of the distribution of the product can be used as a combined uncertainty factor to replace the conventional product of default factors. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Off Risk Assessment Policy & Res, Jefferson, AR 72079 USA. RP Kodell, RL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 25 TC 9 Z9 9 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 1-57331-236-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 895 BP 188 EP 195 DI 10.1111/j.1749-6632.1999.tb08085.x PG 8 WC Public, Environmental & Occupational Health; Multidisciplinary Sciences SC Public, Environmental & Occupational Health; Science & Technology - Other Topics GA BP49Z UT WOS:000085328100013 PM 10676417 ER PT J AU Klinman, DM Barnhart, KM Conover, J AF Klinman, DM Barnhart, KM Conover, J TI CpG motifs as immune adjuvants SO VACCINE LA English DT Article DE oligodeoxynucleotides; adjuvant; DNA vaccine ID IMMUNOSTIMULATORY DNA-SEQUENCES; CIRCUMSPOROZOITE PROTEIN; INTERFERON-GAMMA; PLASMID DNA; INTERLEUKIN-12; CYTOKINE; MICE; IMMUNIZATION; LYMPHOCYTES; ACTIVATION AB Bacterial DNA contains immunostimulatory motifs that trigger an innate immune response characterized by the production of predominantly Th1-type cytokines. These motifs consist of an unmethylated CpG dinucleotide flanked by two 5' purines and two 3' pyrimidines. We examined whether synthetic oligodeoxynucleotides (oligos) expressing these motifs would act as adjuvants to boost the immune response to DNA- and protein-based immunogens. In vivo experiments demonstrate that CpG-containing oligos augment antigen-specific serum antibody levels by up to tenfold, and IFN gamma production by up to sixfold. These effects were optimized by physically linking the CpG-containing motifs to the immunogen. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. Vical Inc, San Diego, CA 92121 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. EM Klinman@A1.CBER.FDA.GOV NR 22 TC 223 Z9 240 U1 2 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN PY 1999 VL 17 IS 1 BP 19 EP 25 DI 10.1016/S0264-410X(98)00151-0 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 129RG UT WOS:000076476300003 PM 10078603 ER PT J AU Nelson, R Schaffner, AE Li, YX Walton, MK AF Nelson, R Schaffner, AE Li, YX Walton, MK TI Distribution of GABA(c)-like responses among acutely dissociated rat retinal neurons SO VISUAL NEUROSCIENCE LA English DT Article DE retina; bipolar cell; GABA; oxonol; rat ID GABA-LIKE IMMUNOREACTIVITY; BIPOLAR CELL TERMINALS; CAT RETINA; HORIZONTAL CELLS; GANGLION-CELLS; XENOPUS OOCYTES; RECEPTOR SUBUNIT; LIPID-MEMBRANES; FUNCTIONAL-ROLE; GATED CURRENTS AB GABAergic responses of acutely dissociated rat retinal neurons, including both bipolar cells (BCs) and other, morphologically round cells (RCs), were assayed with the fluorescent (FL), voltage-sensitive probe oxonol DiBaC(4)(5). Using intensified video microscopy and simultaneous recording, GABA responses were identified in one-third of cells in a typical microscope field; of these 85% hyperpolarized (0.05-0.3 log unit FL decreases) while the remainder depolarized (0.05-0.2 log unit FL increases). GABA-sensitive cells were also TACA-sensitive (trans-4-Aminocrotonic acid), and these ligands appeared interchangeable in ability to evoke responses. In RCs, an asymmetric co-responsive pattern was observed between GABA- and muscimol-evoked events. Muscimol-sensitive RCs responded well to GABA, but not all GABA-sensitive RCs responded to muscimol. In GABA-sensitive BCs, muscimol responses were typically weak or absent. Few BCs or RCs responded to CACA (cis-4-Aminocrotonic acid). Bicuculline-resistant GABA responses occurred in similar to 80% of GABA-responsive RCs and BCs. Both bicuculline-sensitive (GABA(A)-like) and bicuculline-insensitive (GABA(C)-like) responses were resistant to picrotoxin. Although a small minority of GABA-sensitive cells hyperpolarized in response to R(+)baclofen, bicuculline-insensitive responses were not antagonized by 2-hydroxysaclofen, and were abolished in low [Cl-](o). Results suggested (1) that bicuculline-insensitive, Cl--dependent, GABA(C)-like responses were broadly distributed and predominant among dissociated rat retinal neurons; (2) that muscimol was a particularly weak agonist for rat retinal BCs; and (3) that oxonol was a sensitive probe for retinal GABA responses. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Clin Trial Design & Anal, OTRR, CBER, Rockville, MD 20857 USA. RP Nelson, R (reprint author), NINDS, Neurophysiol Lab, NIH, Bldg 36,Room 2C02,36 Convent Dr,MSC 4066, Bethesda, MD 20892 USA. NR 50 TC 8 Z9 8 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD JAN-FEB PY 1999 VL 16 IS 1 BP 179 EP 190 PG 12 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 163GV UT WOS:000078397100016 PM 10022489 ER PT J AU Busch, M Chamberland, M Epstein, J Kleinman, S Khabbaz, R Nemo, G AF Busch, M Chamberland, M Epstein, J Kleinman, S Khabbaz, R Nemo, G TI Oversight and monitoring of blood safety in the United States SO VOX SANGUINIS LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSFUSION-TRANSMITTED VIRUSES; FROZEN WHOLE-BLOOD; NON-A; POSTTRANSFUSION HEPATITIS; INFECTION; RISK; DONORS; HIV-1; TRANSMISSION AB The US blood safety vigilance system is composed of a network of interwoven programs, now organized under a formal structure, with the Assistant Secretary of Health and DHHS Blood Safety Committee bearing overall responsibility. It takes advantage of the breadth of expertise and close collaborative relationship of transfusion medicine and infectious disease scientists within and outside of the government. Core elements include an array of ongoing surveillance programs for monitoring established as well as new and emerging infectious agents that may pose a risk to blood safety, and the existence of historical and contemporary repositories of donor and recipient specimens that enable rapid investigation of putative new risks. This report summarizes the historical events that shaped the US blood safety oversight system, reviews the current organization and decision-making processes related to blood safety issues, and highlights key surveillance systems and research programs which monitor the US and global blood supplies for known and potential emerging risks. C1 Blood Ctr Pacific, Res Serv, San Francisco, CA 94118 USA. Blood Ctr Pacific, Sci Serv, San Francisco, CA 94118 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, AIDS Program, Atlanta, GA USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ British Columbia, Victoria, BC, Canada. Westat Inc, Rockville, MD USA. NHLBI, US Natl Inst Hlth, Div Blood Dis & Resources, Bethesda, MD 20892 USA. RP Busch, M (reprint author), Blood Ctr Pacific, Res Serv, 270 Masonic Ave, San Francisco, CA 94118 USA. NR 62 TC 30 Z9 31 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 1999 VL 77 IS 2 BP 67 EP 76 DI 10.1159/000031079 PG 10 WC Hematology SC Hematology GA 242BV UT WOS:000082919100001 PM 10516550 ER PT J AU Case, J Ford, DS Chung, A Collins, R Kochman, S Mazda, T Overbeeke, M Perera, R Sakuldamrongpanich, T Scott, M Voak, D Zupanska, B AF Case, J Ford, DS Chung, A Collins, R Kochman, S Mazda, T Overbeeke, M Perera, R Sakuldamrongpanich, T Scott, M Voak, D Zupanska, B TI International reference reagents: Antihuman globulin - An ISBT/ICSH joint working party report SO VOX SANGUINIS LA English DT Article C1 Natl Blood Grp Reference Lab, Sydney, NSW, Australia. Canadian Blood Serv, Ottawa, ON, Canada. Amer Natl Red Cross Blood Serv, Rockville, MD USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Japanese Red Cross Tokyo Metropolitan Blood Ctr, Tokyo, Japan. Netherlands Red Cross, Blood Transfus Serv, Amsterdam, Netherlands. Natl Blood Transfus Serv, Colombo, Sri Lanka. Thai Red Cross Soc, Natl Blood Ctr, Bangkok, Thailand. Int Blood Grp Reference Lab, Bristol, Avon, England. E Anglian Blood Transfus Ctr, Cambridge, England. Natl Inst Haematol & Blood Transfus, Warsaw, Poland. Gamma Biologicals Inc, Houston, TX 77092 USA. RP Case, J (reprint author), Gamma Biologicals Inc, 3700 Magnum Rd, Houston, TX 77092 USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 1999 VL 77 IS 2 BP 121 EP 127 PG 7 WC Hematology SC Hematology GA 242BV UT WOS:000082919100028 PM 10516559 ER PT J AU Miller, D Conte, ED Shen, CY Perschbacher, PW AF Miller, D Conte, ED Shen, CY Perschbacher, PW TI Colorimetric approach to cyanobacterial off-flavor detection SO WATER SCIENCE AND TECHNOLOGY LA English DT Article; Proceedings Paper CT 5th International Symposium on Off-Flavours in the Aquatic Environment CY OCT 13-16, 1997 CL PARIS, FRANCE SP French Natl Comm IAWQ, Int Assoc Water Quality, Aguas Barcelona, CIRSEE Lyonnaise Eaux, Compagnie Gen Eaux, SAGEP Paris DE colorimetric; geosmin; MIB ID 2-METHYLISOBORNEOL; METHYLISOBORNEOL; GEOSMIN; WATER; ODOR AB A colorimetric method to quantify methylisoborneol and geosmin in water and fish flesh based on a spot test by Wood and Snoeyink was developed. To test water samples, one liter of filtered water is pumped through a solid phase extraction device and the off-flavor eluted from the device with toluene. The toluene is combined with a 1 percent vanillin in concentrated sulfuric acid and agitated for 30 min to produce the color change. The standard solution is yellow and at increasing concentrations of 2-methylisoborneol or geosmin the color changes from light orange to blood red. Extraction from 1 liter of water results in a sensitivity of 1 ppb. This is suitable for quality control of seafood. For use in measuring action levels (high and low ppt levels for aquaculture and drinking water, respectively), extraction from greater volumes will be required. (C) 1999 Published by Elsevier Science Ltd on behalf of the IAWQ. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Western Kentucky Univ, Dept Chem, Bowling Green, KY USA. Univ Arkansas, Aquaculture Fisheries Ctr, Pine Bluff, AR 71611 USA. RP Miller, D (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 12 TC 1 Z9 1 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0273-1223 J9 WATER SCI TECHNOL JI Water Sci. Technol. PY 1999 VL 40 IS 6 BP 165 EP 169 DI 10.1016/S0273-1223(99)00553-3 PG 5 WC Engineering, Environmental; Environmental Sciences; Water Resources SC Engineering; Environmental Sciences & Ecology; Water Resources GA 249GF UT WOS:000083324400023 ER PT J AU Cai, ZJ Das Gupta, P Emafo, PO Haghighi, S Rydberg, U Sellers, EM Wieniawski, W Ramstrom, L Grand, P Cone, M Cortes-Maramba, N Stead, H Sartorius, N Reinstein, JA Druce, HM Idanpaan-Heikkila, JE Yoshida, T Hutchinson, KD Klein, M Szendrei, K AF Cai, ZJ Das Gupta, P Emafo, PO Haghighi, S Rydberg, U Sellers, EM Wieniawski, W Ramstrom, L Grand, P Cone, M Cortes-Maramba, N Stead, H Sartorius, N Reinstein, JA Druce, HM Idanpaan-Heikkila, JE Yoshida, T Hutchinson, KD Klein, M Szendrei, K CA WHO TI WHO expert committee on drug dependence - Thirty-first report - Introduction SO WHO EXPERT COMMITTE ON DRUG DEPENDENCE - 31ST REPORT SE WHO TECHNICAL REPORT SERIES LA English DT Article C1 Beijing Med Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. Min Hlth Family Welfare, New Delhi, India. Food Drug & Clin Labs, Teheran, Iran. Karolinska Hosp, Magnus Huss Clin, Dept Clin Neurosci, S-10401 Stockholm, Sweden. Univ Toronto, Womens Coll Hosp, Ctr Res Womens Hlth, Toronto, ON, Canada. Polish Pharmacopoela Commiss, Warsaw, Poland. Int Council Alcohol & Addict, Lausanne, Switzerland. Int Criminal Police Org, Drugs Subdirectorate, Lyon, France. Int Federat Pharmaceut Manufacturers Assoc, Geneva, Switzerland. Int Narcot Control Board, Vienna, Austria. UN, Int Drug Control Programme, Vienna, Austria. World Psychiat Assoc, Geneva, Switzerland. World Self Modificat Ind, London, England. Whitehall Robins Healthcare, Clin Res, Madison, NJ USA. WHO, Div Drug Management & Policies, CH-1211 Geneva, Switzerland. Drug Enforcement Agcy, Off Divers Control, Washington, DC USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Albert Szent Gyorgyi Med Univ, H-6701 Szeged, Hungary. RP Cai, ZJ (reprint author), Beijing Med Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. NR 6 TC 0 Z9 0 U1 1 U2 1 PU WORLD HEALTH ORGANIZATION PI GENEVA PA 1211 27 GENEVA, SWITZERLAND SN 0512-3054 J9 WHO TECH REP SER PY 1999 VL 887 BP 1 EP 23 PG 23 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BP73C UT WOS:000086011200001 ER PT S AU Corran, P Griffiths, E Grachev, V van den Besselaar, AMHP Poller, L Tripodi, A Beeser, H Denson, KWE Heuck, C Hubbard, AR Lewis, SM Padilla, A Preston, FE Sakuragawa, N Thorpe, R Wadhwa, M AF Corran, P Griffiths, E Grachev, V van den Besselaar, AMHP Poller, L Tripodi, A Beeser, H Denson, KWE Heuck, C Hubbard, AR Lewis, SM Padilla, A Preston, FE Sakuragawa, N Thorpe, R Wadhwa, M GP WHO TI WHO Expert Committee on Biological Standardization - Introduction SO WHO EXPERT COMMITTEE ON BIOLOGICAL STANDARDIZATION - 48TH REPORT SE WHO TECHNICAL REPORT SERIES LA English DT Article; Proceedings Paper CT Meeting of the WHO Expert Committee on Biological Standardization CY OCT 27-31, 1999 CL GENEVA, SWITZERLAND SP WHO, Expert Comm Biol Standardizat ID INTERNATIONAL SENSITIVITY INDEX; ORAL ANTICOAGULANT CONTROL; TICK-BORNE ENCEPHALITIS; SYNTHETIC PEPTIDE VACCINES; LONG-TERM STABILITY; PROTHROMBIN TIME; LYOPHILIZED PLASMAS; THROMBOPLASTIN CALIBRATION; NORMALIZED RATIO; MULTICENTER CALIBRATION C1 Natl Inst Hyg, Mexico City, DF, Mexico. Louis Pasteur Sci Inst Publ Hlth, Brussels, Belgium. Minist Hlth, Tarasevich State Inst Standardizat & Control Med, Moscow, Russia. Natl Inst Biol Stand & Control, Div Virol, Potters Bar EN6 3QG, Herts, England. Razi Vaccine & Serum Res Inst, Teheran, Iran. McMaster Univ, Dept Pathol, Hamilton, ON, Canada. Minist Hlth & Family Welf, Natl Inst Biol, New Delhi, India. Natl Inst Control Pharmaceut & Biol Prod, Beijing, Peoples R China. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Corran, P (reprint author), Natl Inst Hyg, Mexico City, DF, Mexico. RI Hubbard, Anthony/E-2605-2013; Thorpe, Robin/E-6853-2013; Grachev, Viktor/E-3539-2014; Vaccine & Serum Research Institute, Razi /A-3892-2017 NR 98 TC 10 Z9 10 U1 1 U2 3 PU WORLD HEALTH ORGANIZATION PI GENEVA PA 1211 27 GENEVA, SWITZERLAND SN 0512-3054 BN 92-4-120889-9 J9 WHO TECH REP SER PY 1999 VL 889 BP 1 EP 111 PG 111 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BQ23X UT WOS:000087701900001 ER PT J AU Addae-Mensah, I Haggag, AA Majumdar, MK Paal, TL Rabouhans, ML Takeda, Y Williams, RL Yang, ZY AF Addae-Mensah, I Haggag, AA Majumdar, MK Paal, TL Rabouhans, ML Takeda, Y Williams, RL Yang, ZY TI WHO Expert Committee on specifications for pharmaceutical preparations - Introduction SO WHO EXPERT COMMITTEE ON SPECIFICATIONS FOR PHARMACEUTICAL PREPARATIONS - THIRTY-FIFTH REPORT SE WHO TECHNICAL REPORT SERIES LA English DT Article C1 Univ Ghana, Legon, Ghana. Tanta Univ, Fac Pharm, Tanta, Egypt. WHO, Collaborating Ctr Qual Assurance, Cent Drugs Lab, Calcutta, W Bengal, India. WHO, Collaborating Ctr Drug Informat & Qual Assurance, Natl Inst Pharm, Budapest, Hungary. British Pharmacopoeia Commiss, London, England. Soc Japanense Pharmacopoeia, Tokyo, Japan. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Guangzhou Municipal Inst Drug Control, Guangzhou, Peoples R China. RP Addae-Mensah, I (reprint author), Univ Ghana, Legon, Ghana. NR 18 TC 1 Z9 1 U1 1 U2 1 PU WORLD HEALTH ORGANIZATION PI GENEVA PA 1211 27 GENEVA, SWITZERLAND SN 0512-3054 J9 WHO TECH REP SER PY 1999 VL 885 BP 1 EP 19 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BN25B UT WOS:000081277000001 ER PT B AU Oriani, JA AF Oriani, JA BE Smith, DJ Gingerich, WH BeconiBarker, MG TI US Food and Drug Administration's perspective on aquaculture drug residues SO XENOBIOTICS IN FISH LA English DT Proceedings Paper CT International Symposium on Xenobiotic Pharmacokinetics and Metabolism by Fish held at the Annual Meeting of the American-Chemical-Society CY APR 01-02, 1998 CL DALLAS, TX SP Amer Chem Soc AB The U.S. Food and Drug Administration's (FDA) Center for Veterinary Medicine (CVM) evaluates the safety and efficacy of each animal drug prior to its approval. Human food safety data must be provided on the safety of the drug residues remaining in the animal's edible tissue after treatment and the time that residues take to deplete to an acceptable level. Conducting human food safety studies with aquatic species is very different from similar studies in terrestrial animals. Sponsors are permitted to generate preliminary data under compassionate investigational new animal drug applications (INAD's). CVM's recent studies to bridge microbiological and chemical methods, FDA's compliance program for seafood, and the implication of recent legislation on drugs approved for minor use is discussed. C1 US FDA, Ctr Vet Med, Div Human Food Safety, Rockville, MD 20855 USA. RP Oriani, JA (reprint author), US FDA, Ctr Vet Med, Div Human Food Safety, Rockville, MD 20855 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-46189-7 PY 1999 BP 15 EP 23 PG 9 WC Chemistry, Analytical; Environmental Sciences SC Chemistry; Environmental Sciences & Ecology GA BQ66R UT WOS:000089123700002 ER PT B AU Plakas, SM Doerge, DR Turnipseed, SB AF Plakas, SM Doerge, DR Turnipseed, SB BE Smith, DJ Gingerich, WH BeconiBarker, MG TI Disposition and metabolism of malachite green and other therapeutic dyes in fish SO XENOBIOTICS IN FISH LA English DT Proceedings Paper CT International Symposium on Xenobiotic Pharmacokinetics and Metabolism by Fish held at the Annual Meeting of the American-Chemical-Society CY APR 01-02, 1998 CL DALLAS, TX SP Amer Chem Soc ID CATFISH ICTALURUS-PUNCTATUS; PERFORMANCE LIQUID-CHROMATOGRAPHY; PROLIFERATIVE KIDNEY-DISEASE; TROUT ONCORHYNCHUS-MYKISS; RAINBOW-TROUT; LEUCOMALACHITE GREEN; CHANNEL CATFISH; TRIPHENYLMETHANE DYE; CONTACT SENSITIVITY; VISIBLE DETECTION AB The triphenylmethane dye malachite green has been used in aquaculture worldwide for treatment of parasitic and fungal infections in fish and shellfish. Other dyes (i.e., acriflavine, methylene blue) exhibit similar antimicrobial properties and are widely marketed for treatment of external infections in ornamental fish. None of these compounds are regulated for use in food fish production in the United States. Concern about the health risks associated with drug residues in aquaculture products prompted our studies of the uptake, metabolism, and elimination of selected dyes in the channel catfish. Malachite green was the primary focus because of its toxicological properties and long history of use in aquaculture. Analytical methods were developed for the determination of parent compound and metabolites in fish tissues. Distribution and persistence of residues in the tissues, including edible flesh, were characterized. This chapter summarizes current knowledge of the disposition and metabolism of malachite green and other therapeutic dyes in aquatic species. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. RP Plakas, SM (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Island, AL 36528 USA. NR 95 TC 11 Z9 11 U1 2 U2 6 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-46189-7 PY 1999 BP 149 EP 166 PG 18 WC Chemistry, Analytical; Environmental Sciences SC Chemistry; Environmental Sciences & Ecology GA BQ66R UT WOS:000089123700011 ER PT J AU Hastings, KL AF Hastings, KL TI What are the prospects for regulation in immunotoxicology? SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 8th International Congress of Toxicology CY JUL 05-09, 1998 CL PARIS, FRANCE SP Soc Francaise Toxicol DE immunotoxicology; immunosuppression; hypersensitivity; autoimmunity; regulatory guidance ID LYMPH-NODE ASSAY; RISK ASSESSMENT; IMMUNE; TESTS AB Evaluating the immunotoxic potential of investigational new drugs is a standard component of non-clinical safety assessment. Effects evaluated include the potential for drugs to induce hypersensitivity and/or autoimmune reactions or to produce unintended immunosuppression. The Center for Drug Evaluation and Research (CDER) is considering approaches for evaluating potential immunotoxicity. In particular, two methods are being examined for potential recommendation where indicated: immune cell phenotype determination and the murine local lymph node assay. Issues concerning immunotoxicology testing will be discussed. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20857 USA. RP Hastings, KL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Special Pathogen & Immunol Drug Prod, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 28 PY 1998 VL 103 BP 267 EP 270 PG 4 WC Toxicology SC Toxicology GA 164KE UT WOS:000078462400041 ER PT J AU Slikker, W Scallet, AC Gaylor, DW AF Slikker, W Scallet, AC Gaylor, DW TI Biologically-based dose-response model for neurotoxicity risk assessment SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 8th International Congress of Toxicology CY JUL 05-09, 1998 CL PARIS, FRANCE SP Soc Francaise Toxicol DE neurotoxicity risk assessment; biologically-based dose-response model; excitotoxic amino acids; domoic acid; quantitative histological techniques ID MONKEYS MACACA-FASCICULARIS; DOMOIC ACID; MICE; INTOXICATION; DEGENERATION; RATS AB Domoic acid is a tricarboxylic amino acid that is structurally-related to kainic acid and glutamic acid. It is produced by phytoplankton that may contaminate seafood. To determine domoate's toxicological effects and their pathogenesis, cynomolgus monkeys were dosed intravenously at one of a range of bolus doses from 0.25 to 4.0 mg/kg. Histochemical staining, using silver methods, revealed degenerating axons and cell bodies. Doses in the range of 0.5-1.0 mg/kg produced a small area of silver grains restricted to axons of the hippocampal CA2 stratum lucidum, the most sensitive brain area identified. Quantitation of the abundance of these silver grains yielded continuous dose-response data. A four step quantitative risk estimation approach was used: (1) determination of a dose-response model; (2) determination of the distribution of measurements (variability) about the model; (3) determination of an adverse or abnormal level with the use of the control data; and (4) estimation of the probability that a measure is beyond the abnormal level as a function of dose. The currently used safety-factor (S-F) approach, the benchmark (BM) approach and this quantitative (Q) approach was used to assess the same data set. Assuming a 5% oral absorption of domoic acid, acceptable doses would be achieved if subjects ate 200 g of seafood containing 12, 6 and 10 ppm domoic acid for the S-F, BM and Q approaches, respectively. This quantitative approach uses all the available data, takes into account the variability of the data and provides an actual risk at a given dose of domoic acid. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM wslikker@nctr.fda.gov NR 19 TC 3 Z9 4 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 EI 1879-3169 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 28 PY 1998 VL 103 BP 429 EP 433 PG 5 WC Toxicology SC Toxicology GA 164KE UT WOS:000078462400068 ER PT J AU Shirai, T Takahashi, S Cui, L Yamada, Y Tada, M Kadlubar, FF Ito, N AF Shirai, T Takahashi, S Cui, L Yamada, Y Tada, M Kadlubar, FF Ito, N TI Use of polyclonal antibodies against carcinogen-DNA adducts in analysis of carcinogenesis SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 8th International Congress of Toxicology CY JUL 05-09, 1998 CL PARIS, FRANCE SP Soc Francaise Toxicol DE carcinogen-DNA adduct antibody; DMAB; PhIP ID 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; IMMUNOHISTOCHEMICAL DEMONSTRATION; PROSTATE; TARGET; LOCALIZATION; TISSUES; ORGANS; RATS AB Polyclonal antibodies against 3,2'-dimethyl-4-aminobiphenyl (DMAB)- and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts were raised for their immunohistochemical demonstration in paraffin-embedded sections. Both carcinogens target multiorgans in rats with colon, mammary glands and prostate as common tumor sites. PhIP is particularly important because it is a cooked food-derived carcinogen to which man is exposed on a daily bases. Dose-related nuclear staining in various tissue of rats was observed 24 h after single applications of both carcinogens but no observable decrease in staining intensity was evident in most organs by 168 h. Staining specificity in terms of sites of tumor development was lacking. However, in target organs, semiquantitative data on adduct formation correlated with alteration in tumor response by modifying factor(s). Furthermore, human prostate tissue implanted into nude mice showed positive staining. Thus, the antibodies can be applied as tools to clarify tissue or cell-specific carcinogenesis, carcinogen-exposure levels and metabolic activation in various species, including man after tissue transplantation. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Nagoya City Univ, Sch Med, Dept Pathol 1, Mizuho Ku, Nagoya, Aichi 4678601, Japan. Nagoya City Univ, Sch Med, Dept Urol, Mizuho Ku, Nagoya, Aichi 4678601, Japan. Aichi Shukutoku Univ, Aichi, Japan. Natl Ctr Toxicol Res, Res Off, Jefferson, AR 72079 USA. RP Shirai, T (reprint author), Nagoya City Univ, Sch Med, Dept Pathol 1, Mizuho Ku, 1-Kawasumi, Nagoya, Aichi 4678601, Japan. NR 16 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 28 PY 1998 VL 103 BP 441 EP 446 PG 6 WC Toxicology SC Toxicology GA 164KE UT WOS:000078462400070 ER PT J AU DeGeorge, J AF DeGeorge, J TI Challenges in application of new approaches to carcinogenicity testing for pharmaceuticals SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 8th International Congress of Toxicology CY JUL 05-09, 1998 CL PARIS, FRANCE SP Soc Francaise Toxicol DE carcinogenic potential; pharmaceuticals AB Both evolutionary and revolutionary changes in testing and evaluation of the carcinogenic potential of pharmaceuticals have recently been embodied into guidances generated under the auspices of the International Conference on Harmonisation (ICH). These have formally been implemented and have changed the acceptable approaches available to industry and the evaluation necessary by regulatory authorities. The guidances increase flexibility, obligating industry and regulatory authorities to use more scientific, evidence-based decision making in their processes. The changes are anticipated to significantly improve the relevance of the assessment of carcinogenic risk for humans. The increased flexibility, the numerous decision points, the lack of comprehensive direction in the guidances, and the need for scientific justification of the testing approach, however, have led to confusion and occasional disagreement on appropriate test strategies for specific drugs. To address this problem in the United States, CDER engages in dialogue with industry to reach agreement on approach and dose selection prior to initiation of pivotal studies. Internationally, however, agreement on test approaches will only be achieved by broader communication between regulatory authorities that also involves industry. Published by Elsevier Science Ireland Ltd. C1 US FDA, Off Review Management, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP DeGeorge, J (reprint author), US FDA, Off Review Management, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 EI 1879-3169 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 28 PY 1998 VL 103 BP 565 EP 568 PG 4 WC Toxicology SC Toxicology GA 164KE UT WOS:000078462400091 ER PT J AU Bowen, DL AF Bowen, DL TI Risk of mineral oil - Comment SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Bowen, DL (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 TC 0 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 24 PY 1998 VL 339 IS 26 BP 1947 EP 1948 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 150ZN UT WOS:000077696600031 ER PT J AU Azzam, HS Grinberg, A Lui, K Shen, H Shores, EW Love, PE AF Azzam, HS Grinberg, A Lui, K Shen, H Shores, EW Love, PE TI CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE CD5; thymocyte; development; signal transduction ID ANTIGEN RECEPTOR; CD4(+)CD8(+) THYMOCYTES; POSITIVE SELECTION; TRANSGENIC MICE; DEFICIENT MICE; MONOCLONAL-ANTIBODIES; LYMPHOCYTES-T; ZETA-CHAIN; B-CELLS; IN-VIVO AB Recent data indicate that the cell surface glycoprotein CD5 functions as a negative regulator of T cell receptor (TCR)-mediated signaling. In this study, we examined the regulation of CD5 surface expression during normal thymocyte ontogeny and in mice with developmental and/or signal transduction defects. The results demonstrate that low level expression of CDS on CD4(-)CD8(-) (double negative, DN) thymocytes is independent of TCR gene rearrangement; however, induction of CD5 surface expression on DN thymocytes requires engagement of the pre-TCR and is dependent upon the activity of p56(lck). At the CD4(+)CD8(+) (double positive, DP) stage, intermediate CD5 levels are maintained by low affinity TCR-major histocompatibility complex (MHC) interactions, and. CD5 surface expression is proportional to both the surface level and signaling capacity of the TCR. High-level expression of CD5 on DP and CD4(+) or CD8(+) (single positive, SP) thymocytes is induced by engagement of the alpha/beta-TCR by (positively or negatively) selecting ligands. Significantly, CD5 surface expression on mature SP thymocytes and T cells was found to directly parallel the avidity or signaling intensity of the positively selecting TCR-MHC-ligand interaction. Taken together, these observations suggest that the developmental regulation of CD5 in response to TCR signaling and TCR avidity represents a mechanism for tine tuning of the TCR signaling response. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. RP Love, PE (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. EM pel@helix.nih.gov NR 52 TC 341 Z9 341 U1 0 U2 7 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 DEC 21 PY 1998 VL 188 IS 12 BP 2301 EP 2311 DI 10.1084/jem.188.12.2301 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 151HA UT WOS:000077713600011 PM 9858516 ER PT J AU Pike, SE Yao, L Jones, KD Cherney, B Appella, E Sakaguchi, K Nakhasi, H Teruya-Feldstein, J Wirth, P Gupta, G Tosato, G AF Pike, SE Yao, L Jones, KD Cherney, B Appella, E Sakaguchi, K Nakhasi, H Teruya-Feldstein, J Wirth, P Gupta, G Tosato, G TI Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE endothelial cells; angiogenesis; cell growth; cancer; antitumor agent ID INTERFERON-INDUCIBLE PROTEIN-10; NECROSIS IN-VIVO; HUMAN B-CELLS; NITRIC-OXIDE; INTEGRIN ALPHA(V)BETA(3); ENDOTHELIAL-CELLS; POTENT INHIBITOR; TERMINAL DOMAIN; RECEPTOR; REGRESSION AB All endothelial cell inhibitor sas purified from supernatant of an Epstein-Barr virus-immortalized cell line and identified as fragments of calreticulin. The purified recombinant NH2-terminal domain of calreticulin (amino acids 1-180) inhibited the proliferation of endothelial cells, but not calls of other lineages, and suppressed angiogenesis in vivo. We have named this NH2 terminal domain of calreticulin vasostatin. When inoculated into athymic mice, vasostatin significantly reduced growth of human Burkitt lymphoma and human colon carcinoma. Compared with other inhibitors of angiogenesis, vasostatin is a small, soluble, and stable molecule that is easy to produce and deliver. As an angiogenesis inhibitor that specifically targets proliferating endothelial cells, vasostatin has a unique potential for cancer treatment. C1 Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NCI, Cell Biol Lab, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), Ctr Biol Evaluat & Res, Bldg 29A,Room 2D16,HFM535,1401 Rockville Pike, Rockville, MD 20852 USA. NR 46 TC 204 Z9 226 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 21 PY 1998 VL 188 IS 12 BP 2349 EP 2356 DI 10.1084/jem.188.12.2349 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 151HA UT WOS:000077713600016 PM 9858521 ER PT J AU Reepmeyer, JC Revelle, LK Vidavsky, I AF Reepmeyer, JC Revelle, LK Vidavsky, I TI Detection of clobetasol propionate as an undeclared steroid in zinc pyrithione formulations by high-performance liquid chromatography with rapid-scanning ultraviolet spectroscopy and mass spectrometry SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 22nd International Symposium on High Performance Liquid Phase Separations and Related Techniques CY MAY 02-08, 1998 CL ST LOUIS, MISSOURI DE pharmaceutical analysis; cosmetics; clobetasol propionate; steroids; zinc pyrithione AB Clobetasol propionate, an anti-inflammatory glucocorticosteroid, was detected in an over-the-counter topical drug product with no indication on the label of this compound as an ingredient. The product was formulated as a topical spray, a cream, or a shampoo and labeled to contain zinc pyrithione as the active ingredient. The finding of clobetasol propionate in the pharmaceutical products was shown by comparison to an authenticated standard of clobetasol propionate by retention time on normal-phase and reversed-phase HPLC, UV spectroscopy, LC-MS and LC-MS-MS. A simple method was developed and validated for the assay of clobetasol propionate by isocratic reversed-phase HPLC. Several lots contained clobetasol propionate at therapeutic levels of 0.02-0.06%. Zinc pyrithione formulations from two other manufacturers were free of clobetasol propionate. (C) 1998 Elsevier Science B.V. All rights reserved. C1 US FDA, Div Testing & Appl Analyt Dev, St Louis, MO 63101 USA. Washington Univ, Mass Spectrometry Resource, St Louis, MO 63130 USA. RP Reepmeyer, JC (reprint author), US FDA, Div Testing & Appl Analyt Dev, St Louis, MO 63101 USA. NR 7 TC 10 Z9 10 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD DEC 18 PY 1998 VL 828 IS 1-2 BP 239 EP 246 DI 10.1016/S0021-9673(98)00786-9 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 152ZP UT WOS:000077808500025 ER PT J AU Wang, RF Khan, AA Cao, WW Cerniglia, CE AF Wang, RF Khan, AA Cao, WW Cerniglia, CE TI Identification and sequencing of a cDNA encoding 6-phosphogluconate dehydrogenase from a fungus, Cunninghamella elegans and expression of the gene in Escherichia coli SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE cloning; 6-phosphogluconate dehydrogenase; Cunninghamella elegans ID METABOLISM; BIOTRANSFORMATION; FAMILY AB The fungus, Cunninghamella elegans has been widely used in bioremediation and microbial models of mammalian studies in many laboratories. Using the polymerase chain reaction to randomly amplify the insert directly from the single non-blue plaques of a C. elegans cDNA library, then partly sequencing and comparing with GenBank sequences, we have identified a clone which contains C. elegans 6-phosphogluconate dehydrogenase gene. The polymerase chain reaction product was cloned into a plasmid, pGEM-T Easy vector for full insert DNA sequencing. The 6-phosphogluconate dehydrogenase gene (1458 bases) and the deduced protein sequence were determined from the insert DNA sequence. The gene was found by open reading frame analysis and confirmed by the alignment of the deduced protein sequence with other published 6-phosphogluconate dehydrogenase sequences. Several highly conserved regions were found for the 6-phosphogluconate dehydrogenase sequences. The 6-phosphogluconate dehydrogenase gene was subcloned and over-expressed in a plasmid-E. coli system (pQE30). The cell lysate of this clone has a very high 6-phosphogluconate dehydrogenase enzyme activity. Most of the recombinant protein in this system was formed as insoluble inclusion bodies, but soluble in high concentration of urea-buffer. Ni-NTA resin was used to purify the recombinant protein which showed 6-phosphogluconate dehydrogenase enzyme activity. The recombinant protein has a predicted molecular size correlating with that revealed by sodium dodecylsulfate-polyacrylamide gel electrophoresis analysis, The C. elegans 6-phosphogluconate dehydrogenase was in a cluster with yeast' 6-phosphogluconate dehydrogenase in the phylogenetic tree. Bacterial 6-phosphogluconate dehydrogenase and higher organisms' 6-phosphogluconate dehydrogenase were found in different clusters. (C) 1998 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wang, RF (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM rwang@nctr.fda.gov NR 17 TC 3 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0378-1097 EI 1574-6968 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD DEC 15 PY 1998 VL 169 IS 2 BP 397 EP 402 DI 10.1111/j.1574-6968.1998.tb13346.x PG 6 WC Microbiology SC Microbiology GA 146VF UT WOS:000077452300027 PM 9868787 ER PT J AU Dong, F Liu, XW de Koning, JP Touw, IP Henninghausen, L Larner, A Grimley, PM AF Dong, F Liu, XW de Koning, JP Touw, IP Henninghausen, L Larner, A Grimley, PM TI Stimulation of stat5 by granulocyte colony-stimulating factor (G-CSF) is modulated by two distinct cytoplasmic regions of the G-CSF receptor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SEVERE CONGENITAL NEUTROPENIA; PROTEIN-TYROSINE-PHOSPHATASE; DNA-BINDING ACTIVITY; GENE-EXPRESSION; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; RAPID ACTIVATION; MOTH-EATEN; INTERFERON; MUTATIONS AB In a manner similar to many other cytokines, treatment of cells with granulocyte CSP (G-CSF) has been shown to induce the tyrosine phosphorylation of the STAT proteins. Activation of Stat1 and Stat5 by G-CSF requires the membrane-proximal cytoplasmic domain of the receptor, including box1 and box2, while G-CSF-stimulated tyrosine phosphorylation of Stat3 also requires a region distal to box 2, In this study, we show that although the membrane-proximal 55 amino acids of the G-CSF receptor are sufficient for activation of Stat5, the maximal rate of Stat5 activation requires an additional 30 amino acids of the cytoplasmic domain. In contrast, the distal carboxyl-terminal region of the receptor appears to down-regulate Stat5 activation in that deletion of this carboxyl terminus results in increased amplitude and prolonged duration of Stat5 activation by G-CSF, Significantly, expression of a truncated dominant-negative Stat5 protein in hemopoietic cells not only inhibits G-CSF-dependent cell proliferation, but also suppresses cell survival upon G-CSF withdrawal. We further show that a potential protein tyrosine phosphatase may play a critical role in the down-regulation of G-CSF-stimulated Stat5 activation. These results demonstrate that two distinct cytoplasmic regions of the G-CSF receptor are involved in the regulation of the intensity and duration of Stat5 activation, and that Stat5 may be an important player in G-CSF-mediated cell proliferation and survival. C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. Erasmus Univ, Inst Hematol, Rotterdam, Netherlands. RP Larner, A (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, 9500 Euclid Ave,FFb-37, Cleveland, OH 44195 USA. NR 50 TC 64 Z9 65 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 DEC 15 PY 1998 VL 161 IS 12 BP 6503 EP 6509 PG 7 WC Immunology SC Immunology GA 146NG UT WOS:000077436400010 PM 9862674 ER PT J AU Hollinger, K Wray, C Evans, S Pascoe, S Chappell, S Jones, Y AF Hollinger, K Wray, C Evans, S Pascoe, S Chappell, S Jones, Y TI Salmonella Typhimurium DT104 in cattle in Great Britain SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT Symposium on Post-Harvest Food, at the 135th Annual Meeting of the AVMA CY JUL 25, 1998 CL BALTIMORE, MARYLAND SP AVMA ID RESISTANCE C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. VLA, Cent Vet Lab, Dept Bacteriol, Addlestone KT15 3N, Surrey, England. VLA, Cent Vet Lab, Dept Epidemiol, Addlestone KT15 3N, Surrey, England. RP Hollinger, K (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl HFV-218, Rockville, MD 20855 USA. RI Evans, Sarah/C-8174-2011; Chappell, Samantha/E-1765-2011 NR 6 TC 23 Z9 23 U1 0 U2 2 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 DEC 15 PY 1998 VL 213 IS 12 BP 1732 EP 1733 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 146ZP UT WOS:000077464000012 PM 9861960 ER PT J AU Altekruse, SF AF Altekruse, SF TI Campylobacter jejuni in foods SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT Symposium on Post-Harvest Food, at the 135th Annual Meeting of the AVMA CY JUL 25, 1998 CL BALTIMORE, MARYLAND SP AVMA ID CARCASSES C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Altekruse, SF (reprint author), Virginia Polytech Inst & State Univ, Coll Vet Med, Dept Large Anim Clin Sci, Phase 2,Duckpond Dr, Blacksburg, VA 24061 USA. NR 8 TC 11 Z9 11 U1 0 U2 2 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 DEC 15 PY 1998 VL 213 IS 12 BP 1734 EP 1735 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 146ZP UT WOS:000077464000014 PM 9861962 ER PT J AU Paige, JC AF Paige, JC TI The issues of residues and human health SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT Symposium on Post-Harvest Food, at the 135th Annual Meeting of the AVMA CY JUL 25, 1998 CL BALTIMORE, MARYLAND SP AVMA ID DRUG C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Paige, JC (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. NR 8 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 DEC 15 PY 1998 VL 213 IS 12 BP 1735 EP 1736 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 146ZP UT WOS:000077464000015 ER PT J AU Miller, MA Altekruse, SF AF Miller, MA Altekruse, SF TI The President's national Food Safety Initiative SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT Symposium on Post-Harvest Food, at the 135th Annual Meeting of the AVMA CY JUL 25, 1998 CL BALTIMORE, MARYLAND SP AVMA C1 FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Miller, MA (reprint author), Coll Vet Med, Dept Large Anim Clin Sci, Phase 2,Duckpond Dr, Blacksburg, VA 24060 USA. NR 8 TC 1 Z9 2 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD DEC 15 PY 1998 VL 213 IS 12 BP 1737 EP 1739 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA 146ZP UT WOS:000077464000016 PM 9861964 ER PT J AU Fedorka-Cray, PJ Dargatz, DA Wells, SJ Wineland, NE Miller, MA Tollefson, L Petersen, KE AF Fedorka-Cray, PJ Dargatz, DA Wells, SJ Wineland, NE Miller, MA Tollefson, L Petersen, KE TI Impact of antimicrobic use in veterinary medicine SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT Symposium on Post-Harvest Food, at the 135th Annual Meeting of the AVMA CY JUL 25, 1998 CL BALTIMORE, MARYLAND SP AVMA C1 USDA ARS, Richard B Russell Agr Res Ctr, Athens, GA 30613 USA. USDA, Anim & Plant Hlth Inspect Serv, Ctr Epidemiol & Anim Hlth, Ft Collins, CO 80521 USA. FDA, Ctr Vet Med, Rockville, MD 20855 USA. USDA, Food Safety Inspect Serv, Emerging Pathogens & Zoonot Dis Div, Washington, DC 20250 USA. RP Fedorka-Cray, PJ (reprint author), USDA ARS, Richard B Russell Agr Res Ctr, POB 5677, Athens, GA 30613 USA. NR 6 TC 5 Z9 5 U1 0 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 DEC 15 PY 1998 VL 213 IS 12 BP 1739 EP 1741 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA 146ZP UT WOS:000077464000017 PM 9861965 ER PT J AU Nowell, SA Leakey, JEA Warren, JF Lang, NP Frame, LT AF Nowell, SA Leakey, JEA Warren, JF Lang, NP Frame, LT TI Identification of enzymes responsible for the metabolism of heme in human platelets SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRAUMATIC BRAIN INJURY; HUMAN-LIVER; RAT-BRAIN; UDP-GLUCURONOSYLTRANSFERASE; BILIVERDIN REDUCTASE; GILBERTS-SYNDROME; OXYGENASE-1 HO-1; CARBON-MONOXIDE; IN-VIVO; EXPRESSION AB The major enzymes involved in the degradation of heme were identified in human platelets. It was determined that heme oxygenase activity levels in umbilical cord blood platelets were higher, whereas biliverdin reductase activity levels were comparable with that found in platelets from adults. In membranes prepared from adenosine diphosphate-activated platelets, UDP-glucuronic acid-dependent bilirubin conjugation was detected, whereas activity was negligible in unactivated platelets and undetected in serum and heat-inactivated platelets, and in platelets prepared from umbilical cord blood. Platelet fractions were analyzed by Western blot and shown to express heme oxygenase, biliverdin reductase, and UDP-glucuronosyltransferases, and there was concordance with known developmental profiles found in other tissues. Heme oxygenase expression was higher, whereas UGT expression was lower, in neonatal compared with adult platelets. These data suggest that platelets are involved in multiple steps of heme and bilirubin metabolism and that developmental regulation of these enzymes may be similar to that in other human tissues. C1 John L McClellan Mem Vet Affairs Med Ctr, Surg Serv 112LR, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Surg Oncol, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Microbiol & Chem HFT230, Jefferson, AR 72079 USA. Reece Ctr, Inst Environm & Human Hlth, Lubbock, TX 79416 USA. RP Lang, NP (reprint author), John L McClellan Mem Vet Affairs Med Ctr, Surg Serv 112LR, 4300 W 7th St, Little Rock, AR 72205 USA. FU NCI NIH HHS [CA 58697, CA 55751]; NIA NIH HHS [AG 15722] NR 44 TC 24 Z9 26 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 DEC 11 PY 1998 VL 273 IS 50 BP 33342 EP 33346 DI 10.1074/jbc.273.50.33342 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 146YY UT WOS:000077462500038 PM 9837908 ER PT J AU Kwon, OS Newport, GD Slikker, W AF Kwon, OS Newport, GD Slikker, W TI Quantitative analysis of free sphingoid bases in the brain and spinal cord tissues by high-performance liquid chromatography with a fluorescence detection SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE psychosine; sphinganine; sphingosine ID LONG-CHAIN BASES; GALACTOSYLSPHINGOSINE PSYCHOSINE; PICOMOLE RANGE AB The o-phthaldialdehyde precolumn derivatives of psychosine, sphinganine and sphingosine extracted from brain and spinal cord tissues were determined by high-performance liquid chromatography-fluorescence detection. This method was developed with the purpose of detecting an endogenous amount of psychosine, sphingosine and sphinganine using small aliquots of brain tissues and spinal cord in rats. These sphingolipid bases were extracted in various ratios of chloroform-methanol and several pH values. Recovery of the method is about 81% in 12 ng/tube (final volume, 320 mu l), 90-95% in 45 ng/tube of sphingosine and sphinganine within 2-12% relative standard deviation. Detection limits of these sphingoid bases were about 0.05 pmol/mg brain tissue. In the forebrain, brainstem and spinal cord of rats at three different ages of postnatal days (PND) 1, PND 13 and 6 months old, the endogenous concentrations of psychosine, sphingosine and sphinganine were determined. From these results, this method is suitable for the determination of sphingoid bases in small aliquot of brain and spinal cord tissues. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72211 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kwon, OS (reprint author), Korea Inst Sci & Technol, Bioanal & Biotransformat Res Ctr, Sungbuk Gu, Hawologk Dong 39-1, Seoul 136791, South Korea. NR 12 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD DEC 11 PY 1998 VL 720 IS 1-2 BP 9 EP 14 DI 10.1016/S0378-4347(98)00449-6 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 153AK UT WOS:000077810400002 PM 9892061 ER PT J AU Honig, PK Jenkins, JK AF Honig, PK Jenkins, JK TI Exercise-induced asthma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Honig, PK (reprint author), US FDA, Rockville, MD 20857 USA. NR 2 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 DEC 10 PY 1998 VL 339 IS 24 BP 1784 EP 1784 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 146XU UT WOS:000077459700014 PM 9867555 ER PT J AU DeJarnette, JB Sommers, CL Huang, K Woodside, KJ Emmons, R Katz, K Shores, EW Love, PE AF DeJarnette, JB Sommers, CL Huang, K Woodside, KJ Emmons, R Katz, K Shores, EW Love, PE TI Specific requirement for CD3 epsilon in T cell development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTIGEN RECEPTOR; ALPHA-BETA; SURFACE EXPRESSION; TCR/CD3 COMPLEX; MICE; GENE; CD3-DELTA; CHAIN; REARRANGEMENT; THYMOCYTES AB T cell antigen receptor (TCR) and pre-TCR complexes are composed of clonotypic heterodimers in association with dimers of signal transducing invariant subunits (CD3 gamma, -delta, -epsilon, and zeta). The role of individual invariant subunits in T cell development has been investigated by generating gene-specific mutations in mice. Mutation of CD3 gamma, -delta, or zeta results in an incomplete block in development, characterized by reduced numbers of mature T cells that express low levels of TCR. In contrast, mature T cells are absent from CD3 epsilon(-/-) mice, and thymocyte development is arrested at the early CD4(-)CD8(-) stage, Although these results suggest that CD3 epsilon is essential for pre-TCR and TCR expression/function, their interpretation is complicated by the fact that expression of the CD3 gamma and CD3 delta genes also is reduced in CD3 epsilon(-/-) mice. Thus, it is unclear whether the phenotype of CD3 epsilon(-/-) mice reflects the collective effects of CD3 gamma, -delta, and -epsilon deficiency. By removing the selectable marker (PGH-NEO) from the targeted CD3 epsilon gene via Cre/loxP-mediated recombination, we generated mice that lack CD3 epsilon yet retain normal expression of the closely linked CD3 gamma and CD3 delta genes. These (CD3 epsilon(Delta/Delta)) mice exhibited an early arrest in T cell development, similar to that of CD3 epsilon(-/-) mice. Moreover, the developmental defect could be rescued by expression of a CD3 epsilon transgene. These results identify an essential role for CD3E in T cell development not shared by the CD3 gamma, CD3 delta, or zeta-family proteins and provide further evidence that PGK-NEO can influence the expression of genes in its proximity. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. RP Love, PE (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bldg 6B,Room 2B-210 MSC-2780,9000 Rockville Pike, Bethesda, MD 20892 USA. EM pel@helix.nih.gov NR 28 TC 83 Z9 83 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 8 PY 1998 VL 95 IS 25 BP 14909 EP 14914 DI 10.1073/pnas.95.25.14909 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146NJ UT WOS:000077436700059 PM 9843989 ER PT J AU Imada, K Bloom, ET Nakajima, H Horvath-Arcidiacono, JA Udy, GB Davey, HW Leonard, WJ AF Imada, K Bloom, ET Nakajima, H Horvath-Arcidiacono, JA Udy, GB Davey, HW Leonard, WJ TI Stat5b is essential for natural killer cell-mediated proliferation and cytolytic activity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE natural killer cells; Stat5b; Stat5a; interleukin 2; interleukin 15 ID RECEPTOR-BETA-CHAIN; DEFECTIVE LYMPHOID DEVELOPMENT; COLONY-STIMULATING FACTOR; MICE LACKING JAK3; IL-2 RECEPTOR; TARGETED DISRUPTION; GENE-EXPRESSION; DEFICIENT MICE; GAMMA-CHAIN; SIGNAL-TRANSDUCTION AB We have analyzed the immune system in Stat5-deficient mice. Although Stat5a(-/-) splenocytes have a partial defect in anti-CD3-induced proliferation that can be overcome by high dose interleukin (IL)-2, we now demonstrate that defective proliferation in Stat5b(-/-) splenocytes cannot be corrected by this treatment. Interestingly, this finding may be at least partially explained by diminished expression of the IL-2 receptor beta chain (IL-2R beta), which is a component of the receptors for both IL-2 and IL-15, although other defects may also exist. Similar to the defect in proliferation ill activated splenocytes, freshly isolated splenocytes from Stat5b(-/-) mice exhibited greatly diminished proliferation ill response to IL-2 and IL-15. This results from both a decrease in the number and responsiveness of natural killer (NK) cells. Corresponding to the diminished proliferation, basal as well as IL-2- and IL-15-mediated boosting of NK cytolytic activity was also greatly diminished. These data indicate an essential nonredundant role for Stat5b for potent NK cell-mediated proliferation and cytolytic activity. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. US FDA, Div Cell & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Minist Agr & Forestry, Verificat Agcy, Te Kuiti, New Zealand. AgRes, Dairy Sci Grp, Hamilton, New Zealand. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Room 7N252, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov NR 49 TC 200 Z9 201 U1 0 U2 0 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 DEC 7 PY 1998 VL 188 IS 11 BP 2067 EP 2074 DI 10.1084/jem.188.11.2067 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 147JA UT WOS:000077484700010 PM 9841920 ER PT J AU Nightingale, SL AF Nightingale, SL TI New professional labeling for aspirin SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item 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 2 Z9 2 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 DEC 2 PY 1998 VL 280 IS 21 BP 1817 EP 1817 DI 10.1001/jama.280.21.1817 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 141ZZ UT WOS:000077176600006 PM 9846762 ER EF