FN Thomson Reuters Web of Science™ VR 1.0 PT J AU KAPLAN, JE MASUR, H HOLMES, KK MCNEIL, MM SCHONBERGER, LB NAVIN, TR HANSON, DL GROSS, PA JAFFE, HW LANIER, D SCHRAM, N COOPER, E FREEDBERG, KA MAYER, K BLINKHORN, R ELLNER, J ANGULO, F BERKELMAN, R BREIMAN, R BRYAN, R BUEHLER, J CLADWELL, B CASTRO, K CHILDS, JE CHU, S CIESIELSKI, C DROTMAN, DP EDLIN, B ELLERBROCK, T FLEMING, P GEITER, L HAJJEH, R HANSON, D HOLMBERG, S HUGHES, J JAFFE, H JONES, J JURANEK, D KAPLAN, JE KELLER, D MARTONE, W MILLER, B NAVIN, T NESLUND, V OSTROFF, S PELLETT, PE PINNER, R REEF, S REEVES, WC REGNERY, R RICHARDS, F ROGERS, M SIMONDS, RJ SIMONE, P SMITH, D SOLOMON, S SPIEGEL, R STEWART, J SWERDLOW, D VERNON, S WARD, J NEAL, J SCHLECH, W WILFERT, C HORSBURGH, R MCGOWAN, J RIMLAND, D GOLDBERGER, M TRAPNELL, CB BARR, D TORRES, G STETLER, H GROSS, P ELSADAR, W COTTON, D GREAVES, W BARTLETT, J CHAISSON, R FEINBERG, J QUINN, T HORMAN, J MACDONALD, K WILSON, M SPERLING, R AVANDANO, A BAKER, AC KALICA, A KOVACS, J POLIS, M SCHNITTMAN, S NELSON, C PHAIR, J BENSON, C WOOD, B HUGHES, W LUFT, B HYSLOP, N WHITLEY, R AMPEL, N DREW, WL KOEHLER, J WOFSY, C AF KAPLAN, JE MASUR, H HOLMES, KK MCNEIL, MM SCHONBERGER, LB NAVIN, TR HANSON, DL GROSS, PA JAFFE, HW LANIER, D SCHRAM, N COOPER, E FREEDBERG, KA MAYER, K BLINKHORN, R ELLNER, J ANGULO, F BERKELMAN, R BREIMAN, R BRYAN, R BUEHLER, J CLADWELL, B CASTRO, K CHILDS, JE CHU, S CIESIELSKI, C DROTMAN, DP EDLIN, B ELLERBROCK, T FLEMING, P GEITER, L HAJJEH, R HANSON, D HOLMBERG, S HUGHES, J JAFFE, H JONES, J JURANEK, D KAPLAN, JE KELLER, D MARTONE, W MILLER, B NAVIN, T NESLUND, V OSTROFF, S PELLETT, PE PINNER, R REEF, S REEVES, WC REGNERY, R RICHARDS, F ROGERS, M SIMONDS, RJ SIMONE, P SMITH, D SOLOMON, S SPIEGEL, R STEWART, J SWERDLOW, D VERNON, S WARD, J NEAL, J SCHLECH, W WILFERT, C HORSBURGH, R MCGOWAN, J RIMLAND, D GOLDBERGER, M TRAPNELL, CB BARR, D TORRES, G STETLER, H GROSS, P ELSADAR, W COTTON, D GREAVES, W BARTLETT, J CHAISSON, R FEINBERG, J QUINN, T HORMAN, J MACDONALD, K WILSON, M SPERLING, R AVANDANO, A BAKER, AC KALICA, A KOVACS, J POLIS, M SCHNITTMAN, S NELSON, C PHAIR, J BENSON, C WOOD, B HUGHES, W LUFT, B HYSLOP, N WHITLEY, R AMPEL, N DREW, WL KOEHLER, J WOFSY, C TI USPHS/IDSA GUIDELINES FOR THE PREVENTION OF OPPORTUNISTIC INFECTIONS IN PERSONS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS - INTRODUCTION SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID IMMUNE-DEFICIENCY-SYNDROME; MYCOBACTERIUM-AVIUM COMPLEX; PNEUMOCYSTIS-CARINII PNEUMONIA; HIV-SEROPOSITIVE PATIENTS; HYDROPHILA-ASSOCIATED COLITIS; CENTRAL-NERVOUS-SYSTEM; ACQUIRED-IMMUNODEFICIENCY; AIDS PATIENT; TRIMETHOPRIM-SULFAMETHOXAZOLE; PULMONARY CRYPTOCOCCOSIS C1 NIH, BETHESDA, MD 20892 USA. WASHINGTON UNIV, SEATTLE, WA USA. US DEPT HHS, AGCY HLTH CARE POLICY & RES, ROCKVILLE, MD 20852 USA. AMER ASSOC PHYSICIANS HUMAN RIGHTS, SAN FRANCISCO, CA USA. AMER FDN AIDS RES, ROCKVILLE, MD USA. BOSTON UNIV, SCH MED, BOSTON, MA 02118 USA. BROWN UNIV, PROVIDENCE, RI 02912 USA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. COUNCIL STATE & TERR EPIDEMIOLOGISTS, ATLANTA, GA USA. DALHOUSIE UNIV, HALIFAX, NS, CANADA. DUKE UNIV, DURHAM, NC USA. EMORY UNIV, ATLANTA, GA 30322 USA. US FDA, ROCKVILLE, MD 20857 USA. GAY MENS HLTH CRISIS INC, NEW YORK, NY USA. GEORGIA DEPT HUMAN RESOURCES, ATLANTA, GA USA. HACKENSACK MED CTR, HACKENSACK, NJ 07604 USA. HARLEM HOSP MED CTR, NEW YORK, NY USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. HOWARD UNIV, WASHINGTON, DC 20059 USA. JOHNS HOPKINS UNIV, BALTIMORE, MD USA. MARYLAND DEPT HLTH, BALTIMORE, MD USA. MINNESOTA DEPT PUBL HLTH, MINNEAPOLIS, MN USA. MT AUBURN HOSP, CAMBRIDGE, MA 02238 USA. MT SINAI MED CTR, NEW YORK, NY 10029 USA. NATL ASSOC PERSONS AIDS, WASHINGTON, DC USA. NHLBI, BETHESDA, MD 20892 USA. NIAID, BETHESDA, MD 20892 USA. NATL MINOR AIDS COUNCIL, WASHINGTON, DC USA. NORTHWESTERN UNIV, CHICAGO, IL 60611 USA. RUSH MED COLL, CHICAGO, IL 60612 USA. SEATTLE KING CTY DEPT HLTH, SEATTLE, WA USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. SUNY STONY BROOK, STONY BROOK, NY 11794 USA. TULANE UNIV, NEW ORLEANS, LA 70118 USA. UNIV ALABAMA, BIRMINGHAM, AL USA. UNIV ARIZONA, TUCSON, AZ USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. UNIV SO CALIF, LOS ANGELES, CA USA. UNIV WASHINGTON, ST LOUIS, MO USA. RP KAPLAN, JE (reprint author), CTR DIS CONTROL & PREVENT, NATL IMMUNIZATION PROGRAM, DIV HIV AIDS, MAILSTOP G-29, ATLANTA, GA 30333 USA. RI Childs, James/B-4002-2012 NR 172 TC 42 Z9 42 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1995 VL 21 SU 1 BP S1 EP S11 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RN616 UT WOS:A1995RN61600001 PM 8547495 ER PT J AU SANDBERG, JA BINIENDA, Z LIPE, G ROSE, LM PARKER, WB ALI, SF SLIKKER, W AF SANDBERG, JA BINIENDA, Z LIPE, G ROSE, LM PARKER, WB ALI, SF SLIKKER, W TI PLACENTAL-TRANSFER AND FETAL DISPOSITION OF 2',3'-DIDEOXYCYTIDINE AND 2',3'-DIDEOXYINOSINE IN THE RHESUS-MONKEY SO DRUG METABOLISM AND DISPOSITION LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; CEREBROSPINAL-FLUID; ZIDOVUDINE AZT; PHASE-I; ACQUIRED-IMMUNODEFICIENCY; FETOPLACENTAL PASSAGE; PHARMACOKINETICS; INFECTION; CHILDREN; INVITRO C1 US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. SO RES INST,BIRMINGHAM,AL 35255. FU NIEHS NIH HHS [Y01-ES-10187] NR 45 TC 6 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD AUG PY 1995 VL 23 IS 8 BP 881 EP 884 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RP094 UT WOS:A1995RP09400016 PM 7493557 ER PT J AU HARRIS, RZ BENET, LZ SCHWARTZ, JB AF HARRIS, RZ BENET, LZ SCHWARTZ, JB TI GENDER EFFECTS IN PHARMACOKINETICS AND PHARMACODYNAMICS SO DRUGS LA English DT Review ID ORAL-CONTRACEPTIVE STEROIDS; SEX-RELATED DIFFERENCES; MENSTRUAL-CYCLE; DRUG-METABOLISM; THEOPHYLLINE PHARMACOKINETICS; HEALTHY-VOLUNTEERS; PROTEIN-BINDING; HUMAN-LIVER; PREDNISOLONE DISPOSITION; ANTIPYRINE DISPOSITION AB There are a number of examples of sex differences in drug pharmacokinetics and pharmacodynamics. Recent advances in the characterisation of specific isozymes involved in drug metabolism now allow for the preliminary identification of enzyme systems that are affected by sex, While current data are somewhat limited and not in complete ageement, the majority of studies show that apparent cytochrome P450 (CYP) 3A4 activity is higher in women than in men, whereas the activity of many other systems involved in drug metabolism may be higher in men than in women. Women and men also show different pharmacodynamic responses to a variety of drugs, While the clinical significance of these sex differences remains to be determined, we anticipate that they will be most important in the administration of drugs that have a narrow therapeutic range, In addition, sex differences in drug metabolism may be involved in the higher incidence of adverse reactions to drugs in women compared with men. Further research is needed to determine the scope and significance of these sex differences. Female-specific issues such as pregnancy, menopause, oral contraceptive use and menstruation may also have profound effects on drug metabolism. These effects can often be clinically important. Pregnancy may increase the elimination of antiepileptic agents, reducing their efficacy. Oral contraceptive use can interfere with the metabolism of many drugs and, conversely, certain drugs can impair contraceptive efficacy. More research is needed to determine the impact of menopause, hormone replacement and menstruation on drug therapy. C1 UNIV CALIF SAN FRANCISCO,DEPT PHARM,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. RP HARRIS, RZ (reprint author), US FDA,DIV BIOPHARMACEUT,CDER ORR PKB1,5600 FISHERS LANE,RM 13B-16,HFD426,ROCKVILLE,MD 20857, USA. RI Benet, Leslie/K-8286-2016 FU NIA NIH HHS [AG 5940, AG 9550]; NIGMS NIH HHS [GM 26691] NR 169 TC 340 Z9 350 U1 0 U2 21 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 PD AUG PY 1995 VL 50 IS 2 BP 222 EP 239 DI 10.2165/00003495-199550020-00003 PG 18 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RK776 UT WOS:A1995RK77600003 PM 8521756 ER PT J AU FALK, LA DOUGHERTY, SF PLUZNIK, DH AF FALK, LA DOUGHERTY, SF PLUZNIK, DH TI COLCHICINE DOWN-REGULATES LPS-INDUCED GM-CSF PRODUCTION IN MURINE MACROPHAGES SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 8 BP 847 EP 847 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP116 UT WOS:A1995RP11600362 ER PT J AU MILLER, KG POOLE, CF CHICHILA, TMP AF MILLER, KG POOLE, CF CHICHILA, TMP TI SOLVENT-ASSISTED SUPERCRITICAL-FLUID EXTRACTION FOR THE ISOLATION OF SEMIVOLATILE FLAVOR COMPOUNDS FROM THE CINNAMONS OF COMMERCE AND THEIR SEPARATION BY SERIES-COUPLED COLUMN GAS-CHROMATOGRAPHY SO HRC-JOURNAL OF HIGH RESOLUTION CHROMATOGRAPHY LA English DT Article DE SUPERCRITICAL FLUID EXTRACTION; SERIES-COUPLED COLUMN GAS CHROMATOGRAPHY; CHEMOMETRIC CLASSIFICATION; SEMIVOLATILE FLAVOR COMPOUNDS; CINNAMON ID VOLATILE CONSTITUENTS; SFE-GC; OILS AB Solvent-assisted supercritical fluid extraction is superior to Soxhlet extraction, solvent extraction at reflux, and simultaneous steam distillation solvent extraction for the isolation of semivolatile compounds from the cinnamons of commerce, Optimized extraction conditions are described using carbon dioxide at 300 atm and 70 degrees C to extract 0.5 g of powdered cinnamon mixed with 4.5 g of anhydrous sodium sulfate to which 1.0 ml of acetonitrile was added at the start of the sequential 30 min static and 30 min dynamic extraction, The semivolatile compounds were collected by solvent trapping in ethyl acetate and analyzed directly by series coupled-column gas chromatography after filtration and partial solvent evaporation, Twenty-one compounds identified by mass spectrometry were quantified in twenty-four samples of cinnamon and cassia purchased in Sri Lanka, Korea, United Kingdom, and the United States of America, True cinnamon is easily distinguished from cassia by the presence of eugenol, absence of delta-cadinene, much lower amounts of coumarin, and larger amounts of benzyl benzoate. Principal component analysis using the relative composition of the twelve major semivolatile compounds provides a clear distinction between true cinnamon and cassia as well as useful interspecies differences which can be used for further classification. C1 UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,ZENECA SMITHKLINE BEECHAM CTR ANALYT CHEM,LONDON SW7 2AY,ENGLAND. US FDA,PESTICIDES & IND CHEM RES CTR,DETROIT,MI 48207. RP MILLER, KG (reprint author), WAYNE STATE UNIV,DEPT CHEM,DETROIT,MI 48202, USA. NR 26 TC 3 Z9 3 U1 0 U2 11 PU DR ALFRED HUTHIG VERLAG GMBH PI HEIDELBERG 1 PA POSTFACH 102869, W-69018 HEIDELBERG 1, GERMANY SN 0935-6304 J9 HRC-J HIGH RES CHROM JI HRC-J. High Resolut. Chromatogr. PD AUG PY 1995 VL 18 IS 8 BP 461 EP 471 PG 11 WC Chemistry, Analytical SC Chemistry GA RW290 UT WOS:A1995RW29000001 ER PT J AU GUPTA, RK EGAN, W BRYLA, DA ROBBINS, JB SZU, SC AF GUPTA, RK EGAN, W BRYLA, DA ROBBINS, JB SZU, SC TI COMPARATIVE IMMUNOGENICITY OF CONJUGATES COMPOSED OF ESCHERICHIA-COLI O111 O-SPECIFIC POLYSACCHARIDE, PREPARED BY TREATMENT WITH ACETIC-ACID OR HYDRAZINE, BOUND TO TETANUS TOXOID BY 2 SYNTHETIC SCHEMES SO INFECTION AND IMMUNITY LA English DT Article ID SHIGELLA-DYSENTERIAE TYPE-1; INFLUENZAE TYPE-B; LIPID-A CORE; CHAIN-LENGTH; LIPOPOLYSACCHARIDE; ANTIGEN; ANTIBODIES; OLIGOSACCHARIDE; IMMUNIZATION; VACCINES AB Escherichia coli O111, of various H types and virulence factors, causes enteritis throughout the world, especially in young children. This O type is found rarely in healthy individuals. Serum antibodies to the O-specific polysaccharide of O111 lipopolysaccharide (LPS) protect mice and dogs against infection with this E. coli serotype. The O111 O-specific polysaccharide is composed of a pentasaccharide repeat unit with two colitoses bound to the C-3 and C-6 of glucose in a trisaccharide backbone; this structure is identical to that of Salmonella adelaide (O35), another enteric pathogen. Nonpyrogenic O111 O-specific polysaccharide was prepared by treatment of its LPS with acetic acid (O-SP) or the organic base hydrazine (DeA-LPS). The O-SP had a reduced concentration of colitose. These products were derivatized with adipic acid dihydrazide (ADH) or thiolated with N-succinimidyl-3(2-pyridyldithio) propionate (SPDP). The four derivatives were covalently bound to tetanus toroid (TT) by carbodiimide-mediated condensation or with SPDP to form conjugates. Immunization of BALB/c and general-purpose mice by a clinically acceptable route showed that DeA-LPST-TTADH, of the four conjugates, elicited the highest level of LPS antibodies. Possible reasons to explain this differential immunogenicity between the four conjugates are discussed. C1 NICHHD,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 52 TC 27 Z9 29 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1995 VL 63 IS 8 BP 2805 EP 2810 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RK640 UT WOS:A1995RK64000001 PM 7542631 ER PT J AU DEVI, SJN HAYAT, U FRASCH, CE KREGER, AS MORRIS, JG AF DEVI, SJN HAYAT, U FRASCH, CE KREGER, AS MORRIS, JG TI CAPSULAR POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES OF CARBOTYPE-1 VIBRIO-VULNIFICUS - CONSTRUCTION, IMMUNOGENICITY, AND PROTECTIVE EFFICACY IN A MURINE MODEL SO INFECTION AND IMMUNITY LA English DT Article ID EXTRACELLULAR CYTOLYSIN; ELASTOLYTIC PROTEASE; LIVER-DISEASE; VIRULENCE; MICE; PURIFICATION; SEPTICEMIA; INFECTIONS; FEATURES; EPIDEMIOLOGY AB Vibrio vulnificus causes septicemia and wound infections in immunocompromised humans. The capsular polysaccharide of Vibrio vulnificus (VvPS) is critical for virulence. We synthesized conjugate vaccines of carbotype 1 VvPS under conditions and in formulations suitable for human use. Purified VvPS was conjugated to tetanus toroid (TT) or to inactivated V. vulnificus cytolysin or elastase by two different schemes. All conjugates elicited elevated anticapsular immunoglobulin G (IgG) and IgM and antiprotein IgG responses in mice compared with saline placebo. The conjugates prepared through carboxyl activation of VvPS (VvPS-TTa, VvPS-cytolysin, acid VvPS-elastase) were more immunogenic than the one prepared through hydroxyl activation (VvPS-TTb). The protective efficacy of conjugated and unconjugated formulations of VvPS and that of protein carriers were evaluated in a mouse septicemia model. Eighty percent of mice actively immunized with VvPS-TTa vaccine survived challenge with carbotype 1 V. vulnificus, while VvPS cytolysin and VvPS-elastase conjugates conferred 44 and 40% protection, respectively. Control mice immunized with VvPS, cytolysin, or elastase alone, or saline only, showed 70 to 100% mortality. VvPS-TTa vaccine is nontoxic, immunogenic, and protective in mice. C1 VET AFFAIRS MED CTR,INFECT DIS SECT,BALTIMORE,MD 21201. US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,OFF VACCINE RES & REVIEW,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. MED SCI RES INST,HERNDON,VA 22070. NR 51 TC 26 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1995 VL 63 IS 8 BP 2906 EP 2911 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RK640 UT WOS:A1995RK64000016 PM 7622211 ER PT J AU KOTOB, SI HAUSMAN, SZ BURNS, DL AF KOTOB, SI HAUSMAN, SZ BURNS, DL TI LOCALIZATION OF THE PROMOTER FOR THE PTL GENES OF BORDETELLA-PERTUSSIS, WHICH ENCODE PROTEINS ESSENTIAL FOR SECRETION OF PERTUSSIS TOXIN SO INFECTION AND IMMUNITY LA English DT Note ID ADENYLATE-CYCLASE; OPERON; MODULATION; SUBUNIT; MUTANTS; MODEL AB The ptl locus of Bordetella pertussis, which encodes proteins necessary for the secretion of pertussis toxin into the extracellular medium, is located directly downstream from the ptx locus, which encodes the structural subunits of the toxin. We have found that the ptx promoter is essential for expression of the ptl genes. A strain of B. pertussis which lacked only the ptx promoter region but which retained all other portions of the ptx-ptl region did not produce PtlF. Moreover, insertion of a functional ptx promoter from B. pertussis at the 5' end of the ptx region of Bordetella bronchiseptica resulted in the production of PtlF in B. bronchiseptica, a species which normally does not produce PtlF. These results suggest that the ptx operon is larger than originally proposed and contains both the ptx and ptl genes. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BETHESDA,MD 20892. NR 24 TC 32 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1995 VL 63 IS 8 BP 3227 EP 3230 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RK640 UT WOS:A1995RK64000064 PM 7622254 ER PT J AU KOMOLPRASERT, V LAWSON, AR HARGRAVES, WA AF KOMOLPRASERT, V LAWSON, AR HARGRAVES, WA TI ANALYTICAL METHOD FOR QUANTIFYING BUTYRIC-ACID, MALATHION, AND DIAZINON IN RECYCLED POLY(ETHYLENE-TEREPHTHALATE) SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Note DE ANALYTICAL METHOD; CONTAMINANT(S); RECYCLED POLY(ETHYLENE TEREPHTHALATE); PETE ID POLY(ETHYLENE-TEREPHTHALATE); DIFFUSION C1 NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. RP KOMOLPRASERT, V (reprint author), US FDA,DIV FOOD PROC & PACKAGING,6502 S ARCHER RD,SUMMIT ARGO,IL 60501, USA. NR 7 TC 8 Z9 8 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD AUG PY 1995 VL 43 IS 8 BP 1963 EP 1965 DI 10.1021/jf00056a001 PG 3 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA RR802 UT WOS:A1995RR80200001 ER PT J AU SHAIKH, B AF SHAIKH, B TI DEVELOPMENT AND VALIDATION OF A LIQUID-CHROMATOGRAPHIC METHOD FOR THE DETERMINATION OF FUROSEMIDE, A DIURETIC, IN BOVINE-MILK SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE FUROSEMIDE; DIURETIC; BOVINE MILK; INCURRED RESIDUE; HPLC; REVERSED PHASE; FLUORESCENCE DETECTION ID FLUORESCENCE DETECTION; PLASMA; URINE AB A rapid and sensitive reversed phase liquid chromatographic (LC) procedure was developed and validated for the quantitation of furosemide, a diuretic, in bovine milk. Whole milk was defatted by initial centrifugation at room temperature. The resulting skim milk was deproteinated with acetonitrile and centrifuged again. The acetonitrile from the supernatant was evaporated, and the remaining aqueous portion was directly analyzed by LC. The LC conditions employed include a Spherisorb 5 ODS 2 column, a phosphate/acetonitrile buffer (pH 3), and a fluorescence detector set at 272 and 410 nm excitation and emission wavelengths, respectively. The average recoveries of furosemide from milk fortified at 5, 10, and 20 ppb were 108, 91, and 85%, respectively, with corresponding CVs of 14, 8, and 6%. The method was validated by assaying milk obtained from a cow dosed intravenously with 500 mg of furosemide. The furosemide concentrations in 8 and 24 h milk samples were determined to be about 150 and 5 ppb, respectively. No furosemide was detected in 32 and 48 h samples. RP SHAIKH, B (reprint author), US FDA,CTR VET MED,BARC E,BLDG 328A,BELTSVILLE,MD 20705, USA. NR 14 TC 9 Z9 9 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD AUG PY 1995 VL 43 IS 8 BP 2117 EP 2121 DI 10.1021/jf00056a029 PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA RR802 UT WOS:A1995RR80200029 ER PT J AU SCHERMERHORN, PG CHU, PS KIJAK, PJ AF SCHERMERHORN, PG CHU, PS KIJAK, PJ TI DETERMINATION OF SPECTINOMYCIN RESIDUES IN BOVINE-MILK USING LIQUID-CHROMATOGRAPHY WITH ELECTROCHEMICAL DETECTION SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE SPECTINOMYCIN; ELECTROCHEMICAL DETECTION; MILK ID PLASMA AB A method capable of quantifying spectinomycin in raw bovine milk was developed and validated for 100-400 ng/mL. In this procedure the milk is centrifuged at -4 degrees C and the top fat layer removed. The defatted milk is deproteinated by precipitation with 30% trichloroacetic acid and centrifugation. The supernatant is washed sequentially with dichloromethane, hexane, and ethyl acetate. An aliquot of the separated aqueous layer is prepared for HPLC analysis by mixing with 1-decanesulfonic acid and filtering. The analyte is separated from the matrix components using an ion-pair mobile phase and a reversed-phase column; the analyte is quantified with an electrochemical detector. Mean recoveries are 80% for milk fortified at 100 ng/mL, 76% for milk fortified at 200 ng/mL, and 77% for milk fortified at 400 ng/mL. The intralaboratory coefficients of variations are 18%, 6%, and 9%, respectively. RP SCHERMERHORN, PG (reprint author), US FDA,CTR VET MED,BELTSVILLE,MD 20705, USA. NR 12 TC 14 Z9 15 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD AUG PY 1995 VL 43 IS 8 BP 2122 EP 2125 DI 10.1021/jf00056a030 PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA RR802 UT WOS:A1995RR80200030 ER PT J AU GUNDBERG, CM LOOKER, AC CALVO, MS AF GUNDBERG, CM LOOKER, AC CALVO, MS TI RACIAL ETHNIC-DIFFERENCES IN CIRCULATING OSTEOCALCIN SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 YALE UNIV,NEW HAVEN,CT 06520. NCHS,HYATTSVILLE,MD 20782. US FDA,WASHINGTON,DC 20204. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S300 EP S300 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400645 ER PT J AU LOOKER, AC JOHNSTON, CC WAHNER, HW DUNN, WL CALVO, MS HARRIS, TB HEYSE, SP LINDSAY, RL AF LOOKER, AC JOHNSTON, CC WAHNER, HW DUNN, WL CALVO, MS HARRIS, TB HEYSE, SP LINDSAY, RL TI DEFINING LOW FEMUR BONE-DENSITY LEVELS IN MEN SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NCHS,HYATTSVILLE,MD 20782. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. NIA,BETHESDA,MD 20892. US FDA,WASHINGTON,DC 20204. INDIANA UNIV,INDIANAPOLIS,IN 46223. HELEN HAYES HOSP,W HAVERSTRAW,NY 10993. NIAMS,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S468 EP S468 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401318 ER PT J AU PARK, YK CALVO, MS AF PARK, YK CALVO, MS TI POTENTIAL IMPACT OF CALCIUM FORTIFICATION OF CEREAL-GRAIN INGREDIENTS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S462 EP S462 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401294 ER PT J AU VIDAL, MA KAUP, SM JOHNSON, WA CRENSHAW, TD AF VIDAL, MA KAUP, SM JOHNSON, WA CRENSHAW, TD TI RELATIONSHIPS AMONG MECHANICAL-PROPERTIES AND MINERAL-COMPOSITION OF FEMURS FROM MINIATURE SWINE RANGING IN AGE FROM 0.4 TO 14 YEARS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV WISCONSIN,MADISON,WI 53706. US FDA,LAUREL,MD 20708. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S478 EP S478 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401355 ER PT J AU FALK, LA MCNALLY, R PERERA, PY KENNY, J VOGEL, SN AF FALK, LA MCNALLY, R PERERA, PY KENNY, J VOGEL, SN TI LPS-INDUCIBLE RESPONSES IN SEVERE COMBINED IMMUNODEFICIENCY (SCID) MICE SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article ID GAMMA-INTERFERON-PRODUCTION; EARLY ENDOTOXIN TOLERANCE; MACROPHAGE ACTIVATION; NECROSIS-FACTOR; IFN-GAMMA; LIPID-A; T-CELL; LIPOPOLYSACCHARIDE; PROLIFERATION; STIMULATION AB Lipopolysaccharide (LPS) is a potent bacterial product that has been shown to act on many different cell types both in vivo and in vitro, Injection of immunologically competent mice with LPS results in increased serum cytokine levels, followed by an array of pathophysiologic alterations that can ultimately lead to death, In this study, we examined the response of severe combined immunodeficient (SCID) mice to LPS, These mice lack mature T and B cells and have been shown to be an important model for analyzing the contribution of innate immune responses to infectious agents, Injection of SCID mice with LPS resulted in increases in CSF, TNF, and IFN levels in serum that were similar to the responses of immunocompetent controls, In response to LPS, both SCID and control mice exhibited similar levels of hypoglycemia, LPS-induced toxicity was assessed in D(+)-galactosamine-sensitized animals, SCID mice were comparably sensitive to the lethal effects of LPS as control BALB/c mice. To assess the role of natural killer (NK) cells in LPS-induced cytokine responses, BALB/c and SCID mice were injected with anti-asialo-GM1 antibody prior to injection of LPS, No significant effect on LPS-induced CSF or blood glucose levels were seen, although NK-depleted SCID mice produced somewhat more IFN in response to LPS than normal mice. Thus, NK cells are not a major source of these early LPS-induced cytokines, These data suggest that mature T and B cells and NK cells do not contribute to the initial wave of cytokines produced in response to LPS, but may contribute as secondary producers of cytokines involved in the cytokine cascade elicited by LPS injection. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL & IMMUNOL,BETHESDA,MD 20814. US FDA,DIV HEMATOL PROD,BETHESDA,MD 20014. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. NR 43 TC 6 Z9 6 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PD AUG PY 1995 VL 2 IS 4 BP 273 EP 280 PG 8 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA RX432 UT WOS:A1995RX43200007 ER PT J AU GRANT, MA EKLUND, CA SHIELDS, SC AF GRANT, MA EKLUND, CA SHIELDS, SC TI MONITORING DAIRY SILAGE FOR 5 BACTERIAL GROUPS WITH POTENTIAL FOR HUMAN PATHOGENESIS SO JOURNAL OF FOOD PROTECTION LA English DT Article DE LISTERIA MONOCYTOGENES; YERSINIA ENTEROCOLITICA; MOTILE AEROMONADS; CAMPYLOBACTER SP; ENTEROHEMORRHAGIC ESCHERICHIA-COLI; SILAGE; DAIRY ID LISTERIA-MONOCYTOGENES; YERSINIA-ENTEROCOLITICA; AEROMONAS-HYDROPHILA; MILK; PREVALENCE; TEMPERATURE; RECOVERY; OUTBREAK; GROWTH AB Two types of silage routinely used at a dairy research facility were monitored over a 20-month period for five bacterial groups which have been associated with human pathogenesis. Those monitored were Listeria monocytogenes, Yersinia enterocolitica (motile), motile aeromonads, Campylobacter sp., and enterohemorrhagic Escherichia coli. Of 46 total silage samples, 8.7% were positive for L. monocytogenes, 6.5% for Y. enterocolitica, and 10.9% for motile aeromonads. Campylobacter spp, and enterohemorrhagic E. coli were not isolated. The presence of pathogens was associated with elevated pH in silage samples. C1 US FDA,BOTHELL,WA 98041. NR 41 TC 7 Z9 7 U1 0 U2 0 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 1995 VL 58 IS 8 BP 879 EP 883 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA RQ829 UT WOS:A1995RQ82900010 ER PT J AU REDDY, NR VILLANUEVA, M KAUTTER, DA AF REDDY, NR VILLANUEVA, M KAUTTER, DA TI SHELF-LIFE OF MODIFIED-ATMOSPHERE-PACKAGED FRESH TILAPIA FILLETS STORED UNDER REFRIGERATION AND TEMPERATURE-ABUSE CONDITIONS SO JOURNAL OF FOOD PROTECTION LA English DT Article DE SHELF LIFE; FISH; MODIFIED ATMOSPHERE; PACKAGING ID CARBON-DIOXIDE; CLOSTRIDIUM-BOTULINUM; FISHERY PRODUCTS; TOXIN PRODUCTION; STORAGE; EXTENSION; SPOILAGE; GROWTH AB We investigated the shelf life of fresh Tilapia spp. fillets packaged in high-barrier film under both 100% air and a modified atmosphere (MA) of 75% CO2:25% N-2, and stored under refrigeration (4 degrees C) and abuse temperatures (8 and 16 degrees C). The chemical spoilage indicators trimethylamine, K-value, and surface pH, as well as microbial counts, were compared with the sensory characteristics of spoilage. For fillets packaged under 100% air, the shelf life was 9 to 13 days at a storage temperature of 4 degrees C, but decreased to 3 to 6 days at 16 degrees C. However, the shelf life of MA-packaged fillets stored at 4 degrees C increased to >25 days when the lag phase and generation time of the bacteria were extended. MA-packaged fillets stored under temperature-abuse conditions (8 and 16 degrees C) had a shorter shelf life. The trimethylamine content associated with onset of sensory spoilage for MA-packaged fillets increased as storage temperature increased and differed for each temperature. The surface pH and K-values of MA-packaged fillets were not good indicators of spoilage onset. C1 LIQUID CARBON IND CORP,CTR TECH,CHICAGO,IL 60626. US FDA,DIV HACCP PROGRAM,WASHINGTON,DC 20204. RP REDDY, NR (reprint author), US FDA,NATL CTR FOOD SAFETY & TECHNOL,DIV FOOD PROC & PACKAGING,SUMMIT ARGO,IL 60501, USA. NR 34 TC 41 Z9 41 U1 0 U2 0 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 1995 VL 58 IS 8 BP 908 EP 914 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA RQ829 UT WOS:A1995RQ82900014 ER PT J AU KLONTZ, KC TIMBO, B FEIN, S LEVY, A AF KLONTZ, KC TIMBO, B FEIN, S LEVY, A TI PREVALENCE OF SELECTED FOOD-CONSUMPTION AND PREPARATION BEHAVIORS ASSOCIATED WITH INCREASED RISKS OF FOOD-BORNE DISEASE SO JOURNAL OF FOOD PROTECTION LA English DT Article DE FOOD-BORNE DISEASE; SHELLFISH; SALMONELLA; ESCHERICHIA COLI O157-H7 ID UNITED-STATES; FACTOR SURVEILLANCE AB Although not well quantified, a portion of food-borne illnesses results from voluntary behaviors that are entirely avoidable, such as eating raw foods of animal origin or engaging in unsafe food preparation practices. A telephone survey of 1,620 respondents was conducted to assess the prevalence of selected self-reported food consumption and preparation behaviors associated with increased risks of food-borne illness and the demographic characteristics related to such behaviors. The percentages of survey respondents who reported consuming raw foods of animal origin were 53%, raw eggs; 23%, undercooked hamburgers; 17%, raw clams or oysters; and 8%, raw sushi or ceviche. A fourth of the respondents said that after cutting raw meat or chicken, they use the cutting board again without cleaning it. Safer food consumption and preparation behaviors were consistently reported by persons who were female, were at least 40 years old, and had a high-school education or less. These findings suggest that risky food consumption and preparation behaviors are common in the United States and that educational campaigns aimed at changing these behaviors may need to be targeted to specific groups of persons. RP KLONTZ, KC (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SCI ANAL & SUPPORT,200 C ST SW,WASHINGTON,DC 20204, USA. NR 18 TC 85 Z9 89 U1 2 U2 4 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 1995 VL 58 IS 8 BP 927 EP 930 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA RQ829 UT WOS:A1995RQ82900017 ER PT J AU FINBLOOM, DS WINESTOCK, KD AF FINBLOOM, DS WINESTOCK, KD TI IL-10 INDUCES THE TYROSINE PHOSPHORYLATION OF TYK2 AND JAK1 AND THE DIFFERENTIAL ASSEMBLY OF STAT1-ALPHA AND STAT3 COMPLEXES IN HUMAN T-CELLS AND MONOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GAMMA SIGNAL-TRANSDUCTION; DNA-BINDING FACTOR; INTERFERON-ALPHA; TRANSCRIPTION FACTOR; RESPONSE ELEMENTS; INTERLEUKIN-10; GENE; RECEPTOR; KINASE; PROMOTER AB IL-10 affects monocytes and T cells by driving the progression of immune responsiveness such that Th2 lymphocyte-mediated effects predominate. In this report, we show that in monocytes and T cells IL-10 stimulates tyrosine phosphorylation of the signal transducers and activators of transcription, STAT1 alpha and STAT3, in a differential manner such that the relative formation of homo- and heterodimers varies between the two cell types. Moreover, monocytes express a novel IL-10-stimulated STAT protein with an M(r) of 70 kDa that is recognized by the anti-STAT3 Ab but is not observed in T cells. IL-10 treatment of both T cells and monocytes results in the ligand-induced tyrosine phosphorylation of tyk2 and Jak1, but not Jak2 or Jak3. Selective modulation of immune responsiveness by IL-10 in cells such as monocytes and T cells may result in part from the differential activation of STAT protein pairs. RP FINBLOOM, DS (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,29 LINCOLN DR,MSC 4555,BETHESDA,MD 20892, USA. NR 60 TC 274 Z9 284 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1995 VL 155 IS 3 BP 1079 EP 1090 PG 12 WC Immunology SC Immunology GA RK898 UT WOS:A1995RK89800010 PM 7543512 ER PT J AU DONNELLY, RP FREEMAN, SL HAYES, MP AF DONNELLY, RP FREEMAN, SL HAYES, MP TI INHIBITION OF IL-10 EXPRESSION BY IFN-GAMMA UP-REGULATES TRANSCRIPTION OF TNF-ALPHA IN HUMAN MONOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CYTOKINE PRODUCTION; INTERFERON-GAMMA; INTERLEUKIN-10 IL-10; RECEPTOR ANTAGONIST; FACTOR CACHECTIN; GENE-EXPRESSION; RELEASE; CELL; LIPOPOLYSACCHARIDE AB Stimulation of human monocytes with LPS induces expression of multiple cytokines, including TNF-alpha, IL-1 beta, IL-6, and IL-10. IL-10 expression is delayed relative to that of TNF-alpha, IL-1 beta, and IL-6. Furthermore, IL-10 feedback inhibits expression of TNF-alpha, IL-1 beta, and IL-6, thus providing an efficient autocrine mechanism for controlling proinflammatory cytokine production in monocytes. The Th1-type lymphokine, IFN-gamma, markedly up-regulates TNF-alpha production in monocytes. However, the precise mechanism by which IFN-gamma mediates this effect is unknown. We examined the effects of IFN-gamma on IL-10 expression in LPS-stimulated monocytes, and the relationship between IL-10 and TNF-alpha production in these cells. LPS stimulation induced rapid, ordered expression of multiple cytokines. Steady-state mRNA levels for TNF-alpha increased rapidly, reached maximal levels by 2 to 3 h poststimulation, and then declined sharply. IL-1 beta and IL-6 mRNA levels also increased markedly following stimulation with LPS, but decreased more slowly than did TNF-alpha. Down-regulation of mRNA for TNF-alpha, IL-1 beta, and IL-6 coincided with a delayed and more gradual increase in IL-10 mRNA levels. Furthermore, neutralization of IL-10 with anti-IL-10 Abs prolonged TNF-alpha mRNA expression, and significantly increased net TNF-alpha production. IFN-gamma suppressed expression of IL-10 mRNA and protein in a dose-dependent manner. Moreover, inhibition of IL-10 production correlated with a marked increase in both the magnitude and duration of TNF-alpha expression. Thus, potentiation of TNF-alpha production by IFN-gamma in monocytes is coupled to inhibition of endogenous IL-10 expression. RP DONNELLY, RP (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,HFM-505,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 44 TC 134 Z9 136 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1995 VL 155 IS 3 BP 1420 EP 1427 PG 8 WC Immunology SC Immunology GA RK898 UT WOS:A1995RK89800044 PM 7636207 ER PT J AU GAZZINELLI, RT BALA, S STEVENS, R BASELER, M WAHL, L KOVACS, J SHER, A AF GAZZINELLI, RT BALA, S STEVENS, R BASELER, M WAHL, L KOVACS, J SHER, A TI HIV-INFECTION SUPPRESSES TYPE-1 LYMPHOKINE AND IL-12 RESPONSES TO TOXOPLASMA-GONDII BUT FAILS TO INHIBIT THE SYNTHESIS OF OTHER PARASITE-INDUCED MONOKINES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACQUIRED IMMUNODEFICIENCY SYNDROME; STIMULATORY FACTOR INTERLEUKIN-12; ACTIVATED HUMAN MACROPHAGES; IMMUNE-DEFICIENCY SYNDROME; CD8+ LYMPHOCYTES-T; GAMMA-INTERFERON; FACTOR-ALPHA; MYCOBACTERIUM-TUBERCULOSIS; CEREBRAL TOXOPLASMOSIS AB Individuals infected with Toxoplasma gondii normally develop resistance to the parasite, resulting in an asymptomatic chronic infection. In AIDS patients, this resistance is lost leading to reactivation of infection and development of encephalitis. To characterize the cytokine response of T. gondii-iniected individuals, PBMC were cultured in vitro in the presence or absence of crude tachyzoite Ags (STAg). When stimulated with STAg, PBMC from T.gondii-infected donors, but not controls, produced high levels of Type 1 lymphokines (IL-2 and IFN-gamma) as well as the monokine IL-12, in the absence of detectable Type 2 lymphokines (IL-4 and IL-5). In contrast, cells of individuals from both groups produced high levels of IL-1, IL-6, and TNF-alpha when exposed to the same Ag preparation. By using highly purified elutriated cells, we demonstrated that monocytes are a major source of these monokines. The above findings were further expanded by analyzing the cytokine responses induced by STAg in PBMC from patients co-infected with T.gondii and HIV. Our results demonstrate that parasite-specific IL-2 and IFN-gamma responses are greatly impaired even before AIDS development, as is IL-12 synthesis by PBMC from HIV-infected individuals stimulated with STAg. In contrast, the release of IL-6 and TNF-alpha triggered by STAg is either not affected or augmented during HIV infection. C1 NIAID,CCM CC,PARASIT DIS LAB,IMMUNOBIOL SECT,BETHESDA,MD 20892. NIDR,BETHESDA,MD 20892. US FDA,DAVDP,ROCKVILLE,MD 20857. PRI DYNCORP,FREDERICK,MD 21701. UNIV FED MINAS GERAIS,INST CIENCIAS BIOL,DEPT BIOCHEM & IMMUNOL,BELO HORIZONT,MG,BRAZIL. NR 56 TC 74 Z9 75 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1995 VL 155 IS 3 BP 1565 EP 1574 PG 10 WC Immunology SC Immunology GA RK898 UT WOS:A1995RK89800059 PM 7636218 ER PT J AU MALEK, A IVY, D BLANN, E MATTISON, DR AF MALEK, A IVY, D BLANN, E MATTISON, DR TI IMPACT OF COCAINE ON HUMAN PLACENTAL FUNCTION USING AN IN-VITRO PERFUSION SYSTEM SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Article DE COCAINE; TRANSPORT; HUMAN PLACENTA; IN VITRO PERFUSION ID PERINATAL MORBIDITY; PREGNANCY; EXPOSURE; CARDIOTOXICITY; PROGESTERONE; GROWTH AB The transport of cocaine from the maternal to fetal circulation and the effect of cocaine on placental function was investigated in vitro using dually perfused term human placentae with recirculation of both maternal and fetal pefusates. In the first experimental group (n = 5, 2 hr), after addition of H-3-cocaine and C-14-inulin to the maternal circulation, steady state concentrations were achieved within 20 min on the maternal side. However, in the following 100 min, uptake of H-3-cocaine remained higher than of the C-14-inulin on the maternal side. H-3-Cocaine was transported more rapidly than C-14-inulin into the fetal circulation and was detected within 10-15 min of initiation of perfusion. In the second experimental group (n = 6), the maternofetal permeability of C-14-inulin was determined in the same placental perfusion in both the absence (control period, 2 hr) and presence of cocaine (test phase, 2 hr) with its H-3-tracer. After the addition of cocaine (2-3 mg/L), the transfer of C-14-inulin was reduced from 6.59 to 3.64 mL/gm per min (p < .001), indicating that cocaine alters placental permeability. In addition to its effect on placental permeability, cocaine decreases the rate of release of hCG into the maternal circulation-reduced from 3.11 (control period) to 1.62 IU/min (test phase, p < .01). C1 UNIV ARKANSAS MED SCI HOSP,DEPT OBSTET & GYNECOL,LITTLE ROCK,AR. UNIV ARKANSAS MED SCI HOSP,DIV INTERDISCIPLINARY TOXICOL,LITTLE ROCK,AR. NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 34 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1056-8719 J9 J PHARMACOL TOXICOL JI J. Pharmacol. Toxicol. Methods PD AUG PY 1995 VL 33 IS 4 BP 213 EP 219 DI 10.1016/1056-8719(95)00018-D PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RK210 UT WOS:A1995RK21000005 PM 8527829 ER PT J AU CLAUSING, P GOUGH, B HOLSON, RR SLIKKER, W BOWYER, JF AF CLAUSING, P GOUGH, B HOLSON, RR SLIKKER, W BOWYER, JF TI AMPHETAMINE LEVELS IN BRAIN MICRODIALYSATE, CAUDATE-PUTAMEN, SUBSTANTIA-NIGRA AND PLASMA AFTER DOSAGE THAT PRODUCES EITHER BEHAVIORAL OR NEUROTOXIC EFFECTS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DOPAMINE RELEASE; RAT-BRAIN; METHAMPHETAMINE; TEMPERATURE; METABOLISM AB Extracellular levels of d-amphetamine (AMPH) in caudate/putamen were determined using microdialysis and HPLC quantitation after s.c. doses that produced increased motor activity (1 mg/kg), stereotypic behavior (2.5 mg/kg) or dopamine depletion in the caudate/putamen (4 x 5 mg/kg). In 6-mo-old rats exposed to neurotoxic doses of AMPH sulfate (4 x 5 mg/kg in a 23 degrees C environment), extracellular caudate/putamen AMPH rose to levels of 7.9 +/- 0.9 mu M after the first dose and peaked at 15.1 +/- 2.5 mu M after the third dose with no further increases after the fourth dose. After one or three doses of 5 mg/kg, peak plasma and tissue levels of AM PH were 1.7 +/- 0.2 and 2.9 +/- 0.3 mu M in plasma, 36 +/- 6 and 73 +/- 10 in substantia nigra and 25 +/- 4 and 50 +/- 8 in caudate/putamen, respectively. Caudate/putamen extracellular AMPH levels were about three times higher (in either 6- or 12-mo-old rats) after 4 x 15 mg/kg in a 10 degrees C environment and tissue levels in caudate/putamen and substantia nigra were three to five times higher after three doses of AMPH. However, these higher levels did not produce dopamine depletion in the caudate/putamen, while the lower doses (4 x 5 mg/kg) given at 23 degrees C did. Estimated caudate/putamen extracellular AMPH levels of 2.5 to 5 mu M after single doses (1 and 2.5 mg/kg) that caused hyperactivity and stereotypic behavior are compatible with the 2 to 10 mu M AMPH concentrations reported to be necessary to produce pronounced dopamine release in vitro. The results show that: 1) the blockade of AMPH neurotoxicity after 4 x 15 mg/kg produced by inhibiting hyperthermia during AMPH exposure is not the result of reduced caudate/putamen extracellular or tissue AMPH levels; 2) the increased AMPH neurotoxicity in older animals is not due to higher plasma or caudate/putamen tissue levels even though extracellular caudate/putamen levers are greater and 3) the determination of extracellular AMPH concentrations facilitates the comparison of in vivo vs. in vitro experiments. C1 NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. NR 33 TC 55 Z9 55 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1995 VL 274 IS 2 BP 614 EP 621 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RN983 UT WOS:A1995RN98300005 PM 7636721 ER PT J AU KOERNER, JE GORDON, M AF KOERNER, JE GORDON, M TI LIPOSOMAL PROSTAGLANDIN E(1) DOES NOT REDUCE MYOCARDIAL INFARCT SIZE IN ANESTHETIZED DOGS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID ISCHEMIC MYOCARDIUM RP KOERNER, JE (reprint author), US FDA,PUBL HLTH SERV,ROCKVILLE,MD 20857, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG PY 1995 VL 26 IS 2 BP 575 EP 575 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RM094 UT WOS:A1995RM09400041 PM 7608466 ER PT J AU BELAND, FA DOOLEY, KL HANSEN, EB SHELDON, WG AF BELAND, FA DOOLEY, KL HANSEN, EB SHELDON, WG TI 6-MONTH TOXICITY COMPARISON OF THE ANTITUBERCULOSIS DRUGS ACONIAZIDE AND ISONIAZID IN FISCHER-344 RATS SO JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY LA English DT Article DE TUBERCULOSIS; ACONIAZIDE; ISONIAZID; LIVER TOXICITY ID TUBERCULOSIS AB Aconiazide, a hydrazone derivative of isoniazid, has been proposed for the treatment of tuberculosis. The toxicity of aconiazide was assessed by treating male and female Fischer 344 (F344) rats daily by gavage for 6 months at doses up to 400 mg/kg body wt. For comparison, the toxicity of isoniazid was determined following treatment in an identical manner at equimolar doses. Aconiazide resulted in only one death during the 6-month experiment, whereas isoniazid caused a significant increase in morbidity and mortality. Each drug induced significant dose-related decreases in body weight in both sexes, and isoniazid caused a significant decrease in liver weight in male rats. Isoniazid also induced centrilobular hepatic necrosis in male rats, a lesion not observed upon aconiazide treatment. Plasma drug levels were >10-fold greater in rats administered isoniazid as compared to aconiazide. The higher levels of free drug observed with isoniazid may contribute to greater toxicity of isoniazid compared to aconiazide. C1 NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079. PATHOL ASSOCIATES INC,JEFFERSON,AR. RP BELAND, FA (reprint author), NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,HFT-110,JEFFERSON,AR 72079, USA. NR 30 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0730-0913 J9 J AM COLL TOXICOL JI J. Am. Coll. Toxicol. PD AUG PY 1995 VL 14 IS 4 BP 328 EP 342 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RL882 UT WOS:A1995RL88200004 ER PT J AU BURWEN, DR OLSEN, SM BLAND, LA ARDUINO, MJ REID, MH JARVIS, WR AF BURWEN, DR OLSEN, SM BLAND, LA ARDUINO, MJ REID, MH JARVIS, WR TI EPIDEMIC ALUMINUM INTOXICATION IN HEMODIALYSIS-PATIENTS TRACED TO USE OF AN ALUMINUM PUMP SO KIDNEY INTERNATIONAL LA English DT Article ID DIALYSIS ENCEPHALOPATHY; REGULAR HEMODIALYSIS; WATER; TOXICITY; SUCRALFATE; FRACTURES; DEMENTIA AB This study was designed to identify the source, risk factors, and clinical consequences of an outbreak of aluminum intoxication in hemodialysis patients using case-control and cohort studies. In 1991, a dialysis center in Pennsylvania [Dialysis Center A (DCA)] identified a number of patients with elevated serum aluminum levels. All patients receiving dialysis at DCA during January 1, 1987 to March 26, 1992 were involved in the study. A case-patient was defined as any patient with a serum aluminum level greater than or equal to 100 mu g/liter after greater than or equal to 5 dialysis sessions at DCA. Fifty-nine case-patients were identified. Risk factors for elevated serum aluminum levels were receipt of bicarbonate- (rather than acetate-) based dialysate, higher number of sessions using bicarbonate dialysis, receipt of acid concentrate (used in bicarbonate dialysis) passed through one of two electric pumps, and a greater number of sessions using this concentrate. The electric pumps had an aluminum casing, casing cover, and impeller. Elevated levels of aluminum were found in acid concentrate after passing through a pump. Seizures and mental status changes requiring hospitalization were associated with aluminum exposure. We found that epidemic aluminum intoxication was caused by the use of an electric pump with aluminum housing to deliver acid concentrate used in bicarbonate dialysis. This outbreak demonstrates why it is essential to insure that all fluid pathways, storage tanks, central delivery systems, and pumps are compatible with low pH fluids before converting from acetate to bicarbonate dialysis. C1 US PHS,CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,HOSP INFECT PROGRAM,ATLANTA,GA 30333. US PHS,US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD. RI Arduino, Matthew/C-1461-2012 OI Arduino, Matthew/0000-0001-7072-538X NR 40 TC 70 Z9 72 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD AUG PY 1995 VL 48 IS 2 BP 469 EP 474 DI 10.1038/ki.1995.315 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA RK810 UT WOS:A1995RK81000017 PM 7564114 ER PT J AU SOBRIAN, SK ALI, SF SLIKKER, W HOLSON, RR AF SOBRIAN, SK ALI, SF SLIKKER, W HOLSON, RR TI INTERACTIVE EFFECTS OF PRENATAL COCAINE AND NICOTINE EXPOSURE ON MATERNAL TOXICITY, POSTNATAL-DEVELOPMENT, AND BEHAVIOR IN THE RAT SO MOLECULAR NEUROBIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine and Methamphetamine, at 14th Biennial Meeting of the International-Society-for-Neurochemistry CY AUG 19-20, 1993 CL NICE, FRANCE SP Int Soc Neurochem, Portuguese Minist Hlth, PROJECTO VIDA Portugal, Med Sch Porto, Portural, Natl Ctr Toxicol Res, US FDA DE POLYDRUG ABUSE; ANIMAL MODEL; PRENATAL COCAINE; PRENATAL NICOTINE; COCAINE PHARMACOKINETICS; MATERNAL FETAL TOXICITY; OFFSPRING BEHAVIOR; DOPAMINE RECEPTORS ID LONG-EVANS RAT; CENTRAL NERVOUS-SYSTEM; RECEPTOR-BINDING; OFFSPRING BEHAVIOR; LOCOMOTOR-ACTIVITY; ACOUSTIC STARTLE; PREGNANCY; BRAIN; FETAL; GESTATION AB Two experiments were performed to investigate the interactive effects of prenatal coadministration of cocaine hydrochloride (C) and nicotine tartrate (N). Experiment I was designed to determine doses of C and N that could be coadministered without altering maternal gestational parameters and/or fetal viability. Exposure of Sprague-Dawley rats to combined high-dose C (20 mg/kg) and high-dose N (5.0 mg/kg) on gestation days 8-21 was not more toxic to dam or fetus than that of exposure to C alone. Experiment II investigated pregnancy outcome, postnatal development, and behavior of the offspring following drug exposure to either high-dose cocaine (20 mg/kg: CS), high-dose nicotine (5.0 mg/kg: NS), or both (NC) on gestation days 8-21. N was administered by osmotic minipump and C by sc injection. Saline-injected dams, fitted with saline-filled pumps (SS), and untreated dams, pair-fed (PF) to NC females, served as controls. Alterations in maternal variables were limited to a 10-15% decrease in food consumption in NC and CS groups. Pregnancy outcome and birth statistics were unaffected by prenatal treatment, as was offspring body weight during the first four postnatal weeks. However, the development of surface righting was delayed in CS pups, and only CS offspring were underresponsive to the stimulatory effects of dopamine agonists on activity and stereotypy. Behavioral responses to N challenge were similar in all groups. In addition, only CS offspring showed altered behavioral responses in a spontaneous alternation task. Treatment effects on dopamine D-1 and D-2 binding in the caudate nucleus were not observed. The combination of N and C did not exacerbate any of the behavioral changes seen in CS offspring. These results support the hypothesis that C is a behavioral teratogen in rodents, and suggest that in the present model, nicotine can mitigate some of the consequences of in utero exposure to cocaine. C1 NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. RP SOBRIAN, SK (reprint author), HOWARD UNIV,COLL MED,DEPT PHARMACOL,WASHINGTON,DC 20059, USA. NR 75 TC 24 Z9 24 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD AUG-DEC PY 1995 VL 11 IS 1-3 BP 121 EP 143 DI 10.1007/BF02740690 PG 23 WC Neurosciences SC Neurosciences & Neurology GA TA780 UT WOS:A1995TA78000012 PM 8561957 ER PT J AU ALI, SF KORDSMEIER, KJ GOUGH, B AF ALI, SF KORDSMEIER, KJ GOUGH, B TI DRUG-INDUCED CIRCLING PREFERENCE IN RATS - CORRELATION WITH MONOAMINE LEVELS SO MOLECULAR NEUROBIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine and Methamphetamine, at 14th Biennial Meeting of the International-Society-for-Neurochemistry CY AUG 19-20, 1993 CL NICE, FRANCE SP Int Soc Neurochem, Portuguese Minist Hlth, PROJECTO VIDA Portugal, Med Sch Porto, Portural, Natl Ctr Toxicol Res, US FDA DE PHENCYCLIDINE; MK-801; METHAMPHETAMINE; COCAINE; APOMORPHINE; 6-HYDROXYDOPAMINE; CIRCLING PREFERENCE; MONOAMINES ID AMPHETAMINE-INDUCED ROTATION; 6-HYDROXYDOPAMINE-LESIONED RATS; INDUCED BEHAVIORS; TURNING BEHAVIOR; DOPAMINE D-1; PHENCYCLIDINE; LESIONS; SCHIZOPHRENIA; INVOLVEMENT; APOMORPHINE AB Drugs of abuse, such as phencyclidine (PCP), methamphetamine (METH), and cocaine (COG) are known to affect several behaviors in rats, such as motor activity, stereotypy, and circling. In this study, we evaluated whether these drugs produce circling preferences in the presence or absence of unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the caudate nucleus. Adult male CD rats were lesioned with 10 mu g 6-OHDA/site. Animals were dosed with PCP (15 mg/kg, ip), its congener, (+) MK-801 (0.15 mg/kg, ip), METH (2 mg/kg, ip), COC (60 mg/kg, ip), or apomorphine (0.2 mg/kg, ip). Circling preference was recorded in control and lesioned rats for 2 h before animals were sacrificed to determine monoamine levels by HPLC/EC. In control animals, administration of these drugs produced 60-70% left circling. In lesioned animals, these drugs produced 78-90% ipsilateral (toward the lesion) circling, except apomorphine, which produced 60-80% contralateral (away from the lesion) circling. Dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations significantly decreased ipsilaterally in lesioned caudate nucleus (CN) and substantia nigra (SN). However, no significant changes were observed in nucleus accumbens (NA) and olfactory tubercles (OT). These data demonstrate that drugs of abuse like PCP, its congener (+) MK-801, METH, and COC produce a greater preference to turn toward the left than the right, a finding similar to that found in human psychosis. Since 6-OHDA lesions enhanced the circling bias and depleted DA and its metabolites DOPAC and HVA, it also suggests that the dopaminergic system may be involved in the circling behavior. C1 US FDA,NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOLEC BIOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. RP ALI, SF (reprint author), US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,JEFFERSON,AR 72079, USA. NR 42 TC 8 Z9 8 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD AUG-DEC PY 1995 VL 11 IS 1-3 BP 145 EP 154 DI 10.1007/BF02740691 PG 10 WC Neurosciences SC Neurosciences & Neurology GA TA780 UT WOS:A1995TA78000013 PM 8561958 ER PT J AU CADET, JL ALI, SF ROTHMAN, RB EPSTEIN, CJ AF CADET, JL ALI, SF ROTHMAN, RB EPSTEIN, CJ TI NEUROTOXICITY, DRUGS OF ABUSE, AND THE CUZN-SUPEROXIDE DISMUTASE TRANSGENIC MICE SO MOLECULAR NEUROBIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine and Methamphetamine, at 14th Biennial Meeting of the International-Society-for-Neurochemistry CY AUG 19-20, 1993 CL NICE, FRANCE SP Int Soc Neurochem, Portuguese Minist Hlth, PROJECTO VIDA Portugal, Med Sch Porto, Portural, Natl Ctr Toxicol Res, US FDA DE TRANSGENIC MICE; SUPEROXIDE DISMUTASE; METHAMPHETAMINE; MPTP; NEUROTOXICITY; FREE RADICALS; STRIATUM; DOPAMINE ID AMYOTROPHIC-LATERAL-SCLEROSIS; TYROSINE-HYDROXYLASE ACTIVITY; OXIDATIVE STRESS; RAT-BRAIN; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE TOXICITY; 1-METHYL-4-PHENYLPYRIDINIUM MPP+; AUTORADIOGRAPHIC DISTRIBUTION; DOPAMINERGIC TOXICITY; LIPID-PEROXIDATION; FREE-RADICALS AB Administration of methamphetamine (METH) to animals causes loss of DA terminals in the brain. The manner by which METH causes these changes in neurotoxicity is not known. We have tested the effects of this drug in copper/zinc (CuZn)-superoxide dismutase transgenic (SOD Tg) mice, which express the human CuZnSOD gene. In nontransgenic (non-Tg) mice, acute METH administration causes significant decreases in DA and dihydroxyphenylacetic acid (DOPAC) in the striata of non-Tg mice. In contrast, there were no significant decreases in striatal DA in the SOD Tg mice. The effects of METH on DOPAC were also attenuated in SOD Tg mice. Chronic METH administration caused decreases in striatal DA and DOPAC in the non-Tg mice, but not in the SOD-Tg mice. Similar studies were carried out with 1-methyl-1,2,3,6-tetrahydropyridine (MPTP), which also causes striatal DA and DOPAC depletion. As in the case of METH, MPTP causes marked depletion of DA and DOPAC in the non-Tg mice, but not in the SOD Tg mice. These results suggest that the mechanisms of toxicity of both METH and MPTP involve superoxide radical formation. C1 US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,JEFFERSON,AR 72079. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. RP CADET, JL (reprint author), NIDA,ADDICT RES CTR,MOLEC NEUROPSYCHIAT SECT,BALTIMORE,MD 21224, USA. FU NIA NIH HHS [AG-08938] NR 49 TC 33 Z9 33 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD AUG-DEC PY 1995 VL 11 IS 1-3 BP 155 EP 163 DI 10.1007/BF02740692 PG 9 WC Neurosciences SC Neurosciences & Neurology GA TA780 UT WOS:A1995TA78000014 PM 8561959 ER PT J AU SHADDOCK, JG FEUERS, RJ CHOU, MW SWENSON, DH CASCIANO, DA AF SHADDOCK, JG FEUERS, RJ CHOU, MW SWENSON, DH CASCIANO, DA TI GENOTOXICITY OF TACRINE IN PRIMARY HEPATOCYTES ISOLATED FROM B6C3F1 MICE AND AGED AD-LIBITUM AND CALORIE-RESTRICTED FISCHER-344 RATS SO MUTATION RESEARCH-GENETIC TOXICOLOGY LA English DT Article DE TACRINE; GENOTOXICITY; DNA REPAIR; HEPATOCYTE; RODENT; AGING; CALORIC RESTRICTION; CYP1A2 ID DNA-REPAIR ASSAY; DRUG-METABOLIZING ENZYMES; ALZHEIMERS-DISEASE; SENILE DEMENTIA; TETRAHYDROAMINOACRIDINE; CARCINOGENS; CHEMICALS AB Tacrine (1,2,3,4-tetrahydro-9-aminoacridine; THA), a reversible centrally acting anticholinesterase, has been shown to be potentially useful for treatment of patients with Alzheimer's disease. However, currently available forms of THA may be therapeutically limited by the fact that high doses have resulted in liver and kidney damage. To determine if THA is hepatotoxic via a genotoxic mechanism, we evaluated its ability to induce unscheduled DNA synthesis (UDS) in primary cultures of rodent hepatocytes. Positive dose-dependent increases in UDS were observed in hepatocytes derived from male B6C3F1 mice and from young, middle-aged, old, and old Aroclor-induced (ARO) male F344 rats maintained on either an ad libitum (AL) or a caloric restricted (CR) diet (60% of AL)and exposed to 0.05-1000.0 mu g/ml of THA. Hepatocytes from old AL rats, treated with THA, exhibited significant age-related decreases in DNA repair compared to young and middle-aged AL rats. By contrast, cultures from CR rats exhibited age- and diet-related decreases in UDS from the AL and young CR animals, respectively. Moreover, ARO-induced old AL- and CR-derived hepatocytes exhibited significant increases in UDS compared to uninduced old AL and CR animals. No cytotoxicity was observed in the uninduced old AL- or any CR-derived hepatocytes. These data indicate that the aged and Cli fed animal is less susceptible to the cytotoxic and genotoxic effects of THA; while the younger AL fed and enzyme induced old AL or CR fed animals were more susceptible. The data suggest that THA may be a genotoxic rodent carcinogen. At present, the relationship of these findings to the clinical use of THA are unclear and further study is required. C1 NATL CTR TOXICOL RES,DIV COMPARAT TOXICOL,JEFFERSON,AR 72079. LOUISIANA STATE UNIV,DEPT PHYSIOL,BATON ROUGE,LA 70803. LOUISIANA STATE UNIV,DEPT PHARMACOL & TOXICOL,BATON ROUGE,LA 70803. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOLEC BIOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT TOXICOL,LITTLE ROCK,AR 72205. RP SHADDOCK, JG (reprint author), NATL CTR TOXICOL RES,DIV GENET TOXICOL,HFT 120,NCTR DR,JEFFERSON,AR 72079, USA. NR 46 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1218 J9 MUTAT RES-GENET TOX JI Mutat. Res.-Genet. Toxicol. PD AUG PY 1995 VL 344 IS 1-2 BP 79 EP 88 DI 10.1016/0165-1218(95)90042-X PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA RV339 UT WOS:A1995RV33900011 PM 7565897 ER PT J AU WYSOWSKI, DK GREEN, L AF WYSOWSKI, DK GREEN, L TI SERIOUS ADVERSE EVENTS IN NORPLANT USERS REPORTED TO THE FOOD-AND-DRUG-ADMINISTRATIONS MEDWATCH SPONTANEOUS REPORTING SYSTEM - REPLY SO OBSTETRICS AND GYNECOLOGY LA English DT Letter RP WYSOWSKI, DK (reprint author), US FDA,OFF EPIDEMIOL & BIOSTAT,DIV EPIDEMIOL & SURVEILLANCE,ROCKVILLE,MD 20857, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD AUG PY 1995 VL 86 IS 2 BP 319 EP 320 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RK505 UT WOS:A1995RK50500035 ER PT J AU DALU, A WARBRITTON, A BUCCI, TJ MEHENDALE, HM AF DALU, A WARBRITTON, A BUCCI, TJ MEHENDALE, HM TI AGE-RELATED SUSCEPTIBILITY TO CHLORDECONE-POTENTIATED CARBON-TETRACHLORIDE HEPATOTOXICITY AND LETHALITY IS DUE TO HEPATIC QUIESCENCE SO PEDIATRIC RESEARCH LA English DT Article ID GROWTH-FACTOR-ALPHA; HEPATOCELLULAR REGENERATION; METABOLIC-ACTIVATION; LIVER-REGENERATION; FEMALE RATS; CCL4; RESILIENCY; PROTECTION; MECHANISM; INJURY AB Previous studies revealed that postnatally developing rats are resilient to the lethal effects of chlordecone (CD) + carbon tetrachloride (CCl4) combination. The objective of this study was to investigate the underlying mechanism. We hypothesized that ongoing cell division and cell cycle progression as well as additional toxicant-induced stimulation of tissue repair help in restraining the progression of injury on the one hand, and in recovery through speedy healing on the other. Postnatally developing (20- and 45-d) and adult (60-d) male Sprague-Dawley rats were challenged with a nontoxic single dose of CCl4 (100 mu L/kg, i.p.) or corn oil after pretreatment with either dietary CD (10 ppm) or normal diet (ND) for 15 d. Hepatocellular injury was assessed by measuring serum enzymes [alanine transaminase (ALT), sorbitol dehydrogenase (SDH)], and bilirubin, as well as by histopathologic examination of liver sections during a time course of 0-96 h after the administration of CCl4 or corn oil. Hepatocellular regeneration was assessed by [H-3]thymidine ([H-3]T) incorporation into hepatic nuclear DNA, in CD + CCl4 treatment, ALT, SDH, and bilirubin levels peaked between 36 and 48 h after CCl4. All 20-d-old rats survived the challenge of CD + CCl4. CD-potentiated hepatotoxicity and lethality of CCl4 begin to be manifested in 45-d-old rats at 48 h and later times (25% mortality), whereas adult rats experience progressive hepatotoxic injury and 100% mortality by 72 h. In contrast, regardless of pretreatment, 20-d-old rats recover fully from injury by 72 h after CCl4 treatment. The rapid recovery of 20-d-old rats was associated with a combination of higher level of ongoing cell division and additional sustained stimulation of [H-3]T incorporation from 24 to 72 h after the administration of CCl4. In the older rats (45- or 60-d-old) this response was significantly delayed and attenuated. Ongoing cell division and CCl4-stimulated regeneration were inversely related to postnatal development (20-, 45-, or 60-d). These biochemical, histopathological, and [H-3]T incorporation studies suggest that the liver of younger rats has greater plasticity for repair after toxic injury whereas adult liver is much more quiescent in this regard. C1 NE LOUISIANA UNIV,COLL PHARM & HLTH SCI,DIV PHARMACOL & TOXICOL,MONROE,LA 71209. NATL CTR TOXICOL RES,PATHOL ASSOCIATES INC,JEFFERSON,AR 72079. NR 34 TC 8 Z9 8 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD AUG PY 1995 VL 38 IS 2 BP 140 EP 148 DI 10.1203/00006450-199508000-00002 PG 9 WC Pediatrics SC Pediatrics GA RK287 UT WOS:A1995RK28700002 PM 7478807 ER PT J AU BACON, CM PETRICOIN, EF ORTALDO, JR REES, RC LARNER, AC JOHNSTON, JA O'SHEA, JJ AF BACON, CM PETRICOIN, EF ORTALDO, JR REES, RC LARNER, AC JOHNSTON, JA O'SHEA, JJ TI INTERLEUKIN-12 INDUCES TYROSINE PHOSPHORYLATION AND ACTIVATION OF STAT4 IN HUMAN-LYMPHOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CYTOKINE SIGNAL TRANSDUCTION; TRANSCRIPTION FACTOR ID DNA-BINDING FACTOR; SIGNAL-TRANSDUCTION PATHWAY; INTERFERON-GAMMA; ANTIGEN RECEPTOR; KILLER CELLS; IFN-GAMMA; PROTEIN; TRANSCRIPTION; AFFINITY; LINE AB Interleukin 12 (IL-12) is an important immunoregulatory cytokine whose receptor is a member of the hematopoietin receptor superfamily, We have recently demonstrated that stimulation of human T and natural killer cells with IL-12 induces tyrosine phosphorylation of the Janus family tyrosine kinases JAK2 and Tyk2, implicating these kinases in the immediate biochemical response to IL-12. Recently, transcription factors known as STATs (signal transducers and activators of transcription) have been shown to be tyrosine phosphorylated and activated in response to a number of cytokines that bind hematopoietin receptors and activate JAK kinases. In this report we demonstrate that IL-12 induces tyrosine phosphorylation of a recently identified STAT family member, STAT4, and show that STAT4 expression is regulated by T-cell activation. Furthermore, we show that IL-12 stimulates formation of a DNA-binding complex that recognizes a DNA sequence previously shown to bind STAT proteins and that this complex contains STAT4. These data, and the recent demonstration of JAK phosphorylation by IL-12, identify a rapid signal-transduction pathway likely to mediate IL-12-induced gene expression. C1 UNIV SHEFFIELD, SCH MED, INST CANC STUDIES, SHEFFIELD S10 2RX, S YORKSHIRE, ENGLAND. US FDA, CTR BIOL EVALUAT & RES, DIV CYTOKINE BIOL, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, EXPTL IMMUNOL LAB, FREDERICK, MD 21702 USA. RP BACON, CM (reprint author), NIAMSD, ARTHRIT & RHEUMATISM BRANCH, LYMPHOCYTE CELL BIOL SECT, BLDG 10, ROOM 9N262, BETHESDA, MD 20892 USA. NR 52 TC 330 Z9 333 U1 1 U2 4 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 AUG 1 PY 1995 VL 92 IS 16 BP 7307 EP 7311 DI 10.1073/pnas.92.16.7307 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RM722 UT WOS:A1995RM72200036 PM 7638186 ER PT J AU KODELL, RL CHEN, JJ GAYLOR, DW AF KODELL, RL CHEN, JJ GAYLOR, DW TI NEUROTOXICITY MODELING FOR RISK ASSESSMENT SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article AB The setting of acceptable exposure levels for neurotoxicants has followed the traditional approach of dividing experimental no-observed-adverse-effect-levels (NOAELs) by safety/uncertainty factors. NOAELs are believed by many toxicologists to represent levels having zero or negligible risk, while uncertainty factors are used to account for a number of sources of variation. Although the use of NOAELs in this manner has been criticized because of their imprecise quantitative definition, NOAELs for nonquantal neurotoxic effects have not been replaced by more precisely defined quantities (e.g., benchmark doses), partly due to the absence of a generally accepted methodology for attaching specific risk levels to low exposures. The present paper describes a quantitative approach to modeling nonquantal neurotoxic effects for risk assessment, which can be used to obtain results similar to the familiar results obtained in risk assessment for carcinogenicity and developmental toxicity. The steps involved in implementing the process are discussed, with particular attention being given to the critical step of defining an adverse neurologic effect. An experimental data set is used to illustrate the methodology. (C) 1995 Academic Press, Inc. RP KODELL, RL (reprint author), US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079, USA. NR 10 TC 30 Z9 30 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 1995 VL 22 IS 1 BP 24 EP 29 DI 10.1006/rtph.1995.1064 PG 6 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA RQ584 UT WOS:A1995RQ58400004 PM 7494899 ER PT J AU GAYLOR, DW GOLD, LS AF GAYLOR, DW GOLD, LS TI QUICK ESTIMATE OF THE REGULATORY VIRTUALLY SAFE DOSE BASED ON THE MAXIMUM TOLERATED DOSE FOR RODENT BIOASSAYS SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID CARCINOGENIC POTENCY DATABASE; NATIONAL-TOXICOLOGY-PROGRAM; ANIMAL BIOASSAYS; CHRONOLOGICAL SUPPLEMENT; RISK AB With a limited subset of National Cancer Institute/National Toxicology Program (NCI/NTP) bioassays, Gaylor (Regul. Toxicol. Pharmacol. 9, 101-108, 1989) showed that the regulatory virtually safe dose (VSD), corresponding to an estimated lifetime cancer risk of less than 10(-6), could be estimated within a factor of 10 simply by dividing the maximum tolerated dose (MTD), estimated from the results of a 90-day study, by 380,000. The purpose of this current study was to extend the analysis to all carcinogens in the Carcinogenic Potency Database (CPDB) utilizing the TD50 (average daily dose rate in mg/kg body wt/day that was estimated to halve the probability of remaining tumor-free at a specified tissue site throughout a a-year study). Using the relationship between the upper bound on the low-dose slope (q(1)*) and the TD50 reported by Krewski et al. (Risk. Anal. 13, 383-398, 1993) and the ratio of the maximum dose tested (Max-D)/TD50 obtained in our present analysis, an estimate of the regulatory VSD was given by the MTD/740,000, for NCI/NTP rodent carcinogens. This was about a factor of two lower than the limited analysis conducted by Gaylor. There was little difference when the chemicals were divided into mutagens and nonmutagens. Ninety-six percent (134 of the 139 NCI/NTP rodent carcinogens) of the regulatory VSDs calculated from the individual TD(50)s obtained from the 2-year bioassays were within a factor of 10 of the MTD/740,000. Gold et al. (Environ. Health Perspect. 79, 259-272, 1989) investigated the distribution of the TD50 among ''near-replicate'' experiments (where the same chemical was tested more than once and was positive in the same strain, sex, and species by the same route). The distribution of TD(50)s from near-replicate experiments is similar to the distribution of the Max-D/TD50. Hence, the estimate of the regulatory VSD based on the Max-D/740,000, for NCI/NTP bioassays, is about as precise as the estimate obtained from a 2-year bioassay. This questions the advisability of conducting a 2-year bioassay for purposes of regulatory risk estimation. Since resources are available to test only a small fraction of chemicals to which humans are exposed, a preliminary estimate of the regulatory VSD can be useful in setting testing priorities. If the expected human exposure level is below the regulatory VSD estimated from the MTD, a chemical may be assigned low priority for testing in a 2-year bioassay. Based on previous work the FDA proposed a ''threshold of regulation'' of a dietary concentration of 0.5 ppb for all substances used in food-contact articles. The results of the present analysis could be used to make the procedure more chemical specific based upon an available MTD. The high correlation between the MTD and estimate of cancer potency (TD50) can be exploited to provide a preliminary, hypothetical upper bound estimate of cancer risk for exposure to a chemical without conducting a 2-year animal bioassay. Thus, the expected level of human exposure relative to the MTD can be used to determine the priority for further research on a chemical, such as mechanistic studies. (C) 1995 Academic Press, Inc. C1 UNIV CALIF BERKELEY, BERKELEY, CA 94720 USA. LAWRENCE BERKELEY LAB, BERKELEY, CA 94720 USA. RP US FDA, NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. NR 16 TC 35 Z9 35 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 EI 1096-0295 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 1995 VL 22 IS 1 BP 57 EP 63 DI 10.1006/rtph.1995.1069 PG 7 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA RQ584 UT WOS:A1995RQ58400009 PM 7494904 ER PT J AU ZHENG, Q AF ZHENG, Q TI ON THE MVK STOCHASTIC CARCINOGENESIS MODEL WITH ERLANG DISTRIBUTED CELL LIFE LENGTHS SO RISK ANALYSIS LA English DT Article DE SURVIVAL FUNCTION; CHARACTERISTIC CURVE; DEVICE OF STAGES; MATHEMATICA PROGRAMMING ID MULTISTAGE MODEL; DNA DAMAGE; REPAIR; CANCER; TUMOR; TIME AB This paper proposes extending the MVK carcinogenesis model by adopting the Erlang distribution for the life length of the intermediate cells. The investigation concentrates on the survival function and the mean value functions. The approach is basically numerical, making use of the Mathematica software system. The paper also provides a closed form expression for the survival function for a variation of the original MVK model, where all the model parameters are piecewise constants. RP ZHENG, Q (reprint author), NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,HFT-20,3900 NCTR DR,JEFFERSON,AR 72079, USA. NR 26 TC 12 Z9 13 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD AUG PY 1995 VL 15 IS 4 BP 495 EP 502 DI 10.1111/j.1539-6924.1995.tb00342.x PG 8 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA TB073 UT WOS:A1995TB07300007 PM 7480949 ER PT J AU FISHER, BR HEREDIA, DJ BROWN, KM AF FISHER, BR HEREDIA, DJ BROWN, KM TI INDUCTION OF HSP72 IN HEAT-TREATED RAT EMBRYOS - A TISSUE-SPECIFIC RESPONSE SO TERATOLOGY LA English DT Article ID SHOCK RESPONSE; SEGMENTAL ANOMALIES; DEVELOPMENT INVITRO; PROTEIN-SYNTHESIS; STRESS PROTEINS; CHICK-EMBRYO; THERMOTOLERANCE; HYPERTHERMIA; EXPOSURE; ABNORMALITIES AB Previous studies have demonstrated that heat exposure on gestation day 10 (GD10) resulted in disrupted somite development in rat embryos 24 hr after exposure and in thoracic skeletal malformations in neonatal rats examined 3 days postpartum. The production of abnormal somites was correlated with the location of skeletal elements that developed from the affected somites. Heat has also been shown to induce changes in genetic expression whereby new proteins are synthesized and the expression of constituent proteins may be repressed. In the present study, heat-induced alterations in protein synthesis during rat organogenesis that may be associated with previously observed malformation was investigated. GD10 rat embryos were exposed in utero to a heat treatment previously demonstrated to produce skeletal malformations; maternal core temperature was raised and maintained at 42-42.4 degrees C for 5 min. In addition, explanted GD10 embryos were cultured in vitro and exposed to temperatures of 42-42.5 degrees C for 15 min. At various times postexposure, embryos were labeled with S-35-methionine and processed for SDS-PAGE. In both in vivo and in vitro heat treated embryos, a transient enhanced de novo synthesis of 70- and 90-kD proteins was observed 1-8 hr after exposure. Actinomycin D studies were conducted to determine whether transcription of new mRNA was required for the enhanced synthesis of the 70- and 90-kD proteins in heat-treated embryos. Results from these studies demonstrated that the expression of these proteins was transcriptionally regulated. The 70-kD protein was identified, using Western blot analysis, as a eukaryotic inducible stress protein (hsp72), and the presence of this protein was detected between 2 and 27 hr post-treatment. Immunohistochemical results indicated that following heat shock, hsp72 accumulates in the neuroectodermal tissues of the embryos. The data demonstrate that although heat-induced expression and accumulation of the hsp72 precedes aberrant somite morphology, the lack of hsp72 accumulation in the somite mesoderm may explain the sensitivity of this tissue to heat. (C) 1995 Wiley-Liss, Inc. C1 BIOCON INC,ROCKVILLE,MD 20851. GEORGE WASHINGTON UNIV,DEPT BIOL SCI,WASHINGTON,DC 20052. RP FISHER, BR (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,DIV LIFE SCI,HLTH SCI BRANCH,HFZ 112,ROCKVILLE,MD 20857, USA. NR 48 TC 15 Z9 16 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD AUG PY 1995 VL 52 IS 2 BP 90 EP 100 DI 10.1002/tera.1420520205 PG 11 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA TB553 UT WOS:A1995TB55300004 PM 8588186 ER PT J AU CHEN, W NICHOLS, J ZHOU, YG CHUNG, KT HART, RW CHOU, MW AF CHEN, W NICHOLS, J ZHOU, YG CHUNG, KT HART, RW CHOU, MW TI EFFECT OF DIETARY RESTRICTION ON GLUTATHIONE-S-TRANSFERASE ACTIVITY SPECIFIC TOWARD AFLATOXIN B-1-8,9-EPOXIDE SO TOXICOLOGY LETTERS LA English DT Article DE RAT; DIETARY RESTRICTION; AFLATOXIN B-1; AFLATOXIN B-1-8,9-EPOXIDE; GLUTATHIONE S-TRANSFERASE; AFLATOXIN B-1-GLUTATHIONE CONJUGATE ID DRUG-METABOLIZING ENZYMES; CALORIC RESTRICTION; FISCHER-344 RATS; LIVER CANCER; DNA; BINDING; CONJUGATE; INVITRO; INVIVO AB Dietary restriction (DR) reduced the metabolic activation of aflatoxin B1 (AFB(1)) in rats, This reduction may be attributed to the decrease of cytochrome P-450-mediated AFB(1) epoxidation and/or increase in the detoxification of AFB(1) catalyzed by hepatic glutathione S-transferase (GST) and other phase II detoxification enzymes. In this study the effect of DR on male rat liver cytosolic GST activity toward AFB(1)-8,9-epoxide was studied. The chemically-synthesized AFB(1)-8,9-epoxide was used as the substrate in this assay, and the formation of AFB(1)-GSH conjugate was analyzed by HPLC. Male Fischer 344 rats fed DR diets (60% of the food consumption of ad libitum (AL)-fed rats) showed a 2.4-fold increase in GST activity when AFB(1)-epoxide was used as the substrate. The results from the enzyme kinetic study showed that DR increased V-max of the liver cytosolic GST but not the K-m. Acute DR has little or no impact on GST activity when 1-chloro-2,4-dinitrobenzene and 2,4-dichloronitrobenzene were used as substrates. The mouse liver GST activity toward AFB(1)-epoxide was 3-fold greater than that of phenobarbital-induced rats, 4.5-fold greater than DR rats, and 14.7-fold greater than the GST activity of AL rats, This direct assay of liver GST activity using AFB(1)-epoxide as the substrate is useful for studying AFB(1)-induced biomarkers, such as AFB(1)-GSH conjugation and AFB(1)-DNA adducts. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. MEMPHIS STATE UNIV,DEPT BIOL,MEMPHIS,TN 38152. GUANGZHOU MED COLL,INST CHEM CARCINOGENESIS,CANTON,PEOPLES R CHINA. SHANGHAI INST LABOUR HYG & OCCUPAT DIS,DEPT OCCUPAT CANC,SHANGHAI,PEOPLES R CHINA. NR 26 TC 10 Z9 12 U1 0 U2 0 PU ELSEVIER SCI PUBL 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 AUG PY 1995 VL 78 IS 3 BP 235 EP 243 DI 10.1016/0378-4274(95)03263-K PG 9 WC Toxicology SC Toxicology GA RJ838 UT WOS:A1995RJ83800009 PM 7624894 ER PT J AU CROUCH, RC MARTIN, GE DICKEY, RW BADEN, DG GAWLEY, RE REIN, KS MAZZOLA, EP AF CROUCH, RC MARTIN, GE DICKEY, RW BADEN, DG GAWLEY, RE REIN, KS MAZZOLA, EP TI BREVETOXIN-3 - TOTAL ASSIGNMENT OF THE H-1 AND C-13 NMR-SPECTRA AT THE SUBMICROMOLE LEVEL SO TETRAHEDRON LA English DT Article ID MICRO INVERSE-DETECTION; GAMBIERDISCUS-TOXICUS; HMQC-TOCSY; SPECTROSCOPY; CONNECTIVITY; CIGUATOXIN; MAITOTOXIN; SIGNALS AB The proton and carbon NMR spectra of the marine polyether toxin, brevetoxin-3, are totally assigned using a series of 2D NMR experiments which included: TOCSY, ROESY, HMQC, HMBC, and IDR-(Inverted Direct Response)-HMQC-TOCSY. All work was performed on a sample consisting of 800 mu g (0.95 mu mole) at 500 MHz. C1 US FDA,GULF COAST SEAFOOD LAB,DAUPHIN ISL,AL 36528. UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,DIV BIOL & LIVING RESOURCES,MIAMI,FL 33101. US FDA,WASHINGTON,DC 20020. RP CROUCH, RC (reprint author), WELLCOME RES LABS,RES TRIANGLE PK,NC 27709, USA. NR 26 TC 15 Z9 17 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD JUL 31 PY 1995 VL 51 IS 31 BP 8409 EP 8422 DI 10.1016/0040-4020(95)00360-K PG 14 WC Chemistry, Organic SC Chemistry GA RL911 UT WOS:A1995RL91100003 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI NEM RULE TO PROTECT IDENTITIES OF REPORTERS OF ADVERSE EVENTS AND PATIENTS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 26 PY 1995 VL 274 IS 4 BP 292 EP 292 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RJ898 UT WOS:A1995RJ89800008 PM 7609246 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI NEW INFORMATION ADDED TO THEOPHYLLINE LABELING SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 26 PY 1995 VL 274 IS 4 BP 292 EP 292 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RJ898 UT WOS:A1995RJ89800009 PM 7609246 ER PT J AU SAKATSUME, M IGARASHI, K WINESTOCK, KD GAROTTA, G LARNER, AC FINBLOOM, DS AF SAKATSUME, M IGARASHI, K WINESTOCK, KD GAROTTA, G LARNER, AC FINBLOOM, DS TI THE JAK KINASES DIFFERENTIALLY ASSOCIATE WITH THE ALPHA AND BETA (ACCESSORY FACTOR) CHAINS OF THE INTERFERON-GAMMA RECEPTOR TO FORM A FUNCTIONAL RECEPTOR UNIT CAPABLE OF ACTIVATING STAT TRANSCRIPTION FACTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASES; SIGNAL TRANSDUCER; HUMAN-MONOCYTES; DOMAIN; PROMOTER; BINDING; REGION; GENE AB Interferon gamma (IFN gamma) induces the expression of early response genes by tyrosine phosphorylation of Jak kinases and transcription factors referred to as STAT proteins. The topology of the IFN gamma receptor is partially understood and the relationship between the alpha chain that binds the ligand and the beta chain that is required for signal transduction is undefined. In a cell line which expresses only the human alpha chain, we show that these cells did not activate Jak kinases or STAT proteins with human IFN gamma, even though Jak1 co-immunoprecipitated with the alpha chain. In cells unexposed to IFN gamma, Jak1 preferentially associated with the alpha chain, while Jak2 associated with the beta chain. There was evidence for Jak1 kinase activity in untreated cells. For Jak2, kinase activity was IFN gamma-dependent. Although the alpha chain was tyrosine-phosphorylated in response to ligand, we found no evidence for tyrosine phosphorylation of the beta chain. These data are consistent with a model of the IFN gamma receptor in which Jak1 associates with the a chain, whereas Jak2 associates with the beta chain, IFN gamma clusters at least two receptor units which results in the tyrosine phosphorylation of Jak1 and Jak2, the activation of Jak2 kinase activity, and the recruitment of STAT1 alpha resulting in its activation by tyrosine phosphorylation. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. F HOFFMANN LA ROCHE & CO LTD,PHARMACEUT RES,NEW TECHNOL,CH-4002 BASEL,SWITZERLAND. NR 31 TC 97 Z9 104 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 21 PY 1995 VL 270 IS 29 BP 17528 EP 17534 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RK689 UT WOS:A1995RK68900074 PM 7615558 ER PT J AU KESSLER, DA AF KESSLER, DA TI NICOTINE ADDICTION IN YOUNG-PEOPLE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material RP KESSLER, DA (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 37 TC 80 Z9 81 U1 1 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 20 PY 1995 VL 333 IS 3 BP 186 EP 189 DI 10.1056/NEJM199507203330311 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA RK917 UT WOS:A1995RK91700011 PM 7791824 ER PT J AU SOMMERS, CL HUANG, K SHORES, EW GRINBERG, A CHARLICK, DA KOZAK, CA LOVE, PE AF SOMMERS, CL HUANG, K SHORES, EW GRINBERG, A CHARLICK, DA KOZAK, CA LOVE, PE TI MURINE TXK - A PROTEIN-TYROSINE KINASE GENE REGULATED BY T-CELL ACTIVATION SO ONCOGENE LA English DT Article DE TXK; PROTEIN TYROSINE KINASE; THYMUS; T LYMPHOCYTES; SIGNAL TRANSDUCTION ID X-LINKED AGAMMAGLOBULINEMIA; LYMPHOCYTES-T; ZETA-CHAIN; RECEPTOR; MOUSE; EXPRESSION; IDENTIFICATION; INTERLEUKIN-2; CLONING; FAMILY AB To identify genes involved in signal transduction pathways that regulate T cell activation and development, murine fetal thymocytes were screened for expression of protein tyrosine kinase family members by the polymerase chain reaction, Using this approach, a nonreceptor protein tyrosine kinase, txk, was identified and cloned. Txk is expressed in thymocytes as early as fetal day 13.5 and its expression at the mRNA level continues throughout development, Txk transcripts are present in thymocytes, peripheral T cells and mast cell lines, but are not detectable in B cell macrophage/monocyte cell lines or in non-hematopoietic fetal or adult tissues, In both thymocytes and T cells, txk transcripts are down-regulated after activation with PMA and ionomycin, concanavalin A or T cell receptor cross-linking, Sequence analysis indicates that txk contains SH2, SH3 and kinase catalytic domains and belongs to the tec family of cytoplasmic protein tyrosine kinases which includes tec, itk and btk, Its unique N-terminus contains a proline-rich region, but unlike the other dec family members, does not contain a pleckstrin homology domain, The restricted expression pattern of txk and its regulation by T cell activation make it an excellent candidate for involvement in signal transduction during thymocyte development. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. RP SOMMERS, CL (reprint author), NICHHD,MAMMALIAN GENES & DEV LAB,BLDG 6B,ROOM 2B-210,6 CTR DR,MSC 2780,BETHESDA,MD 20892, USA. NR 52 TC 36 Z9 37 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 20 PY 1995 VL 11 IS 2 BP 245 EP 251 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RK957 UT WOS:A1995RK95700005 PM 7542761 ER PT J AU HAYES, MP WANG, JH NORCROSS, MA AF HAYES, MP WANG, JH NORCROSS, MA TI REGULATION OF INTERLEUKIN-12 EXPRESSION IN HUMAN MONOCYTES - SELECTIVE PRIMING BY INTERFERON-GAMMA OF LIPOPOLYSACCHARIDE-INDUCIBLE P35 AND P40 GENES SO BLOOD LA English DT Article ID CELL STIMULATORY FACTOR; TUMOR-NECROSIS-FACTOR; FACTOR NKSF/IL-12; IFN-GAMMA; MODULATION; ENDOTOXIN; RESPONSES; INDUCTION; CYTOKINE; BLOOD AB Interleukin-12 (IL-12) is a monocyte/macrophage-derived cytokine that is critical for T lymphocyte and natural killer cell activities and functions. In this study, we examined the regulation of IL-12 expression by human monocytes in response to bacterial lipopolysaccharide (LPS). Several novel aspects of IL-12 induction from monocytes were shown, Optimal expression of IL-12 mRNA and bioactivity required specific priming of monocytes by interferon-gamma (IFN-gamma) before LPS stimulation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) provided an equivalent priming stimulus for LPS-induced tumor necrosis factor (TNF) and IL-12 p40 mRNA, but primed poorly for LPS-inducible p35 message and secreted IL-12 activity, Macrophage colony-stimulating factor (M-CSF), although a potent survival factor for monocytes, showed no priming activity for IL-12 production. Time course experiments demonstrated independent regulation of p40 and p35 by IFN-gamma and LPS, LPS inducibility of p40 expression required only a brief exposure to IFN-gamma (2 hours), while prolonged exposure (+/-24 hours) to IFN-gamma resulted in diminishing levels of p40 mRNA, p35 inducibility (by LPS) required a longer exposure to IFN-gamma (8 to 16 hours), and continued to be inducible up to 40 hours following IFN-gamma priming. Both mRNAs were rapidly induced (1 to 2 hours) in IFN-gamma-primed monocytes; p35 message reached a plateau by 2 hours, while p40 continued to accumulate. Finally, both p40 and p35 were directly induced by LPS in the presence of cycloheximide, These results indicated that both p40 and p35 are LPS-inducible in monocytes following IFN-gamma pretreatment, and that the regulated expression of p35 controls the level of active IL-12 protein in purified human monocytes. The selectivity of priming by IFN-gamma is in accord with a putative role for IL-12 in the initiation and amplification of T-H 1-type responses. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. RP HAYES, MP (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,ROOM 2D20,BLDG 29-A,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 284 Z9 288 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1995 VL 86 IS 2 BP 646 EP 650 PG 5 WC Hematology SC Hematology GA RH801 UT WOS:A1995RH80100026 PM 7605994 ER PT J AU WANG, RF CAO, WW CERNIGLIA, CE AF WANG, RF CAO, WW CERNIGLIA, CE TI PHYLOGENETIC ANALYSIS OF POLYCYCLIC AROMATIC HYDROCARBON-DEGRADING MYCOBACTERIA BY 16S RIBOSOMAL-RNA SEQUENCING SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE PAH-DEGRADING MYCOBACTERIA; 16S RIBOSOMAL-RNA; POLYMERASE CHAIN REACTION; PHYLOGENY ID RIBOSOMAL-RNA SEQUENCES; NUCLEOTIDE-SEQUENCE; PYRENE; MINERALIZATION; IDENTIFICATION; FLUORANTHENE; DEGRADATION; BACTERIUM; SEDIMENT AB Mycobacterium sp. PYR-1 was previously isolated in our laboratory and was shown to be able to mineralize high molecular mass polycyclic aromatic hydrocarbons (PAHs) [Heitkamp and Cerniglia, (1988) Appl. Environ. Microbiol. 54, 1612-1614]. In this research, the 16S rRNA gene (rDNA) of this strain was amplified by polymerase chain reaction (PCR) and directly sequenced by cycle sequencing method. We compared this sequence with all known mycobacterial 16S rDNA sequences available from GenBank and found that Mycobacterium sp. PYR-1 16S rDNA differs from the other mycobacteria, especially in the region of nucleotides 168-200 (in the Escherichia coli numbering system). Using the 16S rDNA sequences of the mycobacteria, a phylogenetic tree was constructed. The data from the phylogenetic tree and similarity values suggest that Mycobacterium sp. PYR-1 is closer to M. aurum and M. vaccae. Using the same approach, we also determined the 16S rDNA from an another PAH-degrading Mycobacterium sp. PAH135, isolated by Grosser and colleagues (1991) (Appl. Environ. Microbiol. 57, 3462-3469). Mycobacterium sp. PAH135 was found to be closer to M. aichiense, and different from our Mycobacterium sp. PYR-1. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. NR 20 TC 26 Z9 26 U1 0 U2 3 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 JUL 15 PY 1995 VL 130 IS 1 BP 75 EP 80 PG 6 WC Microbiology SC Microbiology GA RK806 UT WOS:A1995RK80600013 PM 7557300 ER PT J AU SWEITZER, SM CALVO, S KRAUS, MH FINBLOOM, DS LARNER, AC AF SWEITZER, SM CALVO, S KRAUS, MH FINBLOOM, DS LARNER, AC TI CHARACTERIZATION OF A STAT-LIKE DNA-BINDING ACTIVITY IN DROSOPHILA-MELANOGASTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID RECEPTOR-TYROSINE KINASES; TRANSCRIPTION FACTOR; INTERFERON-ALPHA; PHOSPHORYLATION; ACTIVATION; PROTEIN; GAMMA; ISGF3 AB The cytokine signaling pathways that activate the Janus family of tyrosine kinases (Jaks) and the ''signal transducers and activators of transcription'' (Stats) have been well characterized in mammalian systems. Work shown here provides evidence that an analogous signaling pathway exists in Drosophila melanogaster. Because many of the ligand-receptor pairs in Drosophila have not been fully characterized, it was necessary to bypass the receptor stimulation event that normally triggers intracellular Jak/Stat activation, This was done by treating Drosophila Schneider 2 cells with vanadate/peroxide, which has been shown to closely mimic some signaling events triggered by interferon gamma, including the activation of Jak1, Jak2, and the Stat1 alpha protein. Evidence presented here demonstrates that vanadate/peroxide can induce a gamma response region binding complex in Drosophila Schneider 2 cells, This complex contains two phosphoproteins of 100 and 150 kDa, respectively, and shares many features with the vanadate/peroxide-stimulated binding complex in the mammalian system, Southern blot analysis of genomic DNA using the src homology domain 2 (SH2) of Stat1 alpha confirms the presence of a related gene in the Drosophila genome. C1 US FDA, DIV CYTOKINE BIOL, BETHESDA, MD 20892 USA. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 22 TC 25 Z9 25 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 14 PY 1995 VL 270 IS 28 BP 16510 EP 16513 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RJ347 UT WOS:A1995RJ34700008 PM 7622453 ER PT J AU DEBINSKI, W OBIRI, NI PASTAN, I PURI, RK AF DEBINSKI, W OBIRI, NI PASTAN, I PURI, RK TI A NOVEL CHIMERIC PROTEIN COMPOSED OF INTERLEUKIN-13 AND PSEUDOMONAS EXOTOXIN IS HIGHLY CYTOTOXIC TO HUMAN CARCINOMA-CELLS EXPRESSING RECEPTORS FOR INTERLEUKIN-13 AND INTERLEUKIN-4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA-CHAIN; FUNCTIONAL COMPONENT; SIGNAL-TRANSDUCTION; INVITRO; DOMAIN AB Chimeric proteins provide a unique opportunity to target therapeutic bacterial toxins to a subset of specific cells. We have generated a new recombinant chimeric toxin composed of human interleukin 13 (hIL13) and a Pseudomonas exotoxin A (PE) mutant, PE38QQR. The hIL13-PE38QQR chimera is highly cytotoxic to cell lines derived from several human epithelial carcinomas such as adenocarcinoma of stomach, colon, and skin. The cytotoxic action of hIL13-PE38QQR, which can only occur upon internalization of ligand-receptor complex, is blocked by an excess of hIL13 but not of hIL2. This action is not solely hIL13-specific because an excess of hIL4 also blocks the cytotoxicity of hIL13 toxin. Conversely, hIL13 blocks the cytotoxicity of a hIL4-PE38QQR chimera. Binding studies showed that hIL13 displaces competitively I-126-labeled hIL4-PE38QQR on carcinoma cells. These results indicate that IL4 and IL13 compete for a common binding site on the studied human cell lines. Despite this competition, hIL4 but not hIL13 decreased protein synthesis in malignant cells susceptible to the cytotoxicity of both hIL13- and hIL4-PE38QQR. Our results suggest that a spectrum of human carcinomas express binding sites for IL13. Furthermore, hIL13 and hIL4 compete reciprocally for a form of the receptor that is internalized upon binding a ligand. Thus, cancer cells represent an interesting model fbr studying receptors for these two growth factors. Finally, hIL13-PE38QQR may be a useful agent in the treatment of several malignancies. C1 PENN STATE UNIV,DEPT MICROBIOL & IMMUNOL,HERSHEY,PA 17033. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,MOLEC TUMOR BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. RP DEBINSKI, W (reprint author), PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT SURG,DIV NEUROSURG,HERSHEY,PA 17033, USA. NR 25 TC 140 Z9 141 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 14 PY 1995 VL 270 IS 28 BP 16775 EP 16780 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RJ347 UT WOS:A1995RJ34700050 PM 7622490 ER PT J AU COLAMONICI, OR DOMANSKI, P SWEITZER, SM LARNER, A BULLER, RML AF COLAMONICI, OR DOMANSKI, P SWEITZER, SM LARNER, A BULLER, RML TI VACCINIA VIRUS B18R GENE ENCODES A TYPE-I INTERFERON-BINDING PROTEIN THAT BLOCKS INTERFERON-ALPHA TRANSMEMBRANE SIGNALING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA RECEPTOR; MYXOMA VIRUS; CELLS; REPLICATION; SUBUNIT; KINASE; PHOSPHORYLATION; IDENTIFICATION; SUPERFAMILY; INHIBITION AB Poxviruses encode a large number of proteins that attenuate the inflammatory and immune responses to infection, In this report we demonstrate that a number of orthopoxviruses express a type I interferon (IFN)-binding protein, which is encoded by the Dish open reading frame in the WR strain of vaccinia virus, The B18R protein has significant regions of homology with the alpha subunits of the mouse, human, and bovine type I IFN receptors, bound human IFN alpha 2 with high affinity, and inhibited transmembrane signaling as demonstrated by inhibition of Fc receptor factor gamma 1/gamma 2 and interferon-stimulated gene factor-3 formation as well as inhibition of the IFN alpha antiviral response, Among viral host response modifiers, the B18R protein is unique inasmuch as it exists as a soluble extracellular as well as a cell surface protein and thus should effectively block both autocrine and paracrine functions of IFN. C1 US FDA,BETHESDA,MD 20892. ST LOUIS UNIV,DEPT MOLEC MICROBIOL & IMMUNOL,ST LOUIS,MO 63104. RP COLAMONICI, OR (reprint author), UNIV TENNESSEE,DEPT PATHOL,899 MADISON AVE,M-576,MEMPHIS,TN 38163, USA. FU NCI NIH HHS [CA55079] NR 43 TC 206 Z9 208 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 7 PY 1995 VL 270 IS 27 BP 15974 EP 15978 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RH226 UT WOS:A1995RH22600016 PM 7608155 ER PT J AU FLURER, CL LIN, LA SATZGER, RD WOLNIK, KA AF FLURER, CL LIN, LA SATZGER, RD WOLNIK, KA TI DETERMINATION OF EPHEDRINE COMPOUNDS IN NUTRITIONAL SUPPLEMENTS BY CYCLODEXTRIN-MODIFIED CAPILLARY ELECTROPHORESIS SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article; Proceedings Paper CT 5th Annual Frederick Conference on Capillary Electrophoresis CY OCT 25-26, 1994 CL FREDERICK, MD ID CHIRAL SEPARATION; ZONE ELECTROPHORESIS AB Capillary electrophoresis was utilized for the separation, identification, and quantitation of ten stereoisomers in the ephedrine family; Chiral discrimination was accomplished through the use of hydroxypropyl-P-cyclodextrin, and separation was enhanced at pH 2 in the presence of tetramethylammonium chloride and sodium dodecyl sulfate. Calibration plots of the ephedrines were linear over the range 4-100 mu g/ml. This method was used in the analysis of nutritional supplements that contain Ma Huang, a Chinese herbal preparation that is made from plants in the genus Ephedra. RP FLURER, CL (reprint author), US FDA,NATL FORENS CHEM CTR,1141 CENT PKWY,CINCINNATI,OH 45202, USA. NR 11 TC 58 Z9 64 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD JUL 7 PY 1995 VL 669 IS 1 BP 133 EP 139 DI 10.1016/0378-4347(95)00020-J PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA RK530 UT WOS:A1995RK53000016 PM 7581877 ER PT J AU YU, CL MEYER, DJ CAMPBELL, GS LARNER, AC CARTERSU, C SCHWARTZ, J JOVE, R AF YU, CL MEYER, DJ CAMPBELL, GS LARNER, AC CARTERSU, C SCHWARTZ, J JOVE, R TI ENHANCED DNA-BINDING ACTIVITY OF A STAT3-RELATED PROTEIN IN CELLS TRANSFORMED BY THE SRC ONCOPROTEIN SO SCIENCE LA English DT Article ID TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; INTERFERON-GAMMA; GENE; INDUCIBILITY; ACTIVATION; ELEMENT; KINASE; JAK AB Cytokines and growth factors induce tyrosine phosphorylation of signal transducers and activators of transcription (STATs) that directly activate gene expression. Cells stably transformed by the Src oncogene tyrosine kinase were examined for STAT protein activation. Assays of electrophoretic mobility, DNA-binding specificity, and antigenicity indicated that Stat3 or a closely related STAT family member was constitutively activated by the Src oncoprotein. Induction of this DNA-binding activity was accompanied by tyrosine phosphorylation of Stat3 and correlated with Src transformation. These findings demonstrate that Src can activate STAT signaling pathways and raise the possibility that Stat3 contributes to oncogenesis by Src. C1 UNIV MICHIGAN,SCH MED,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,CTR COMPREHENS CANC,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,DEPT PHYSIOL,ANN ARBOR,MI 48109. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. RI Yu, Chao-Lan/D-1834-2011 OI Yu, Chao-Lan/0000-0002-9381-6011 FU NCI NIH HHS [CA55652]; NIDDK NIH HHS [DK34171, R01 DK034171] NR 29 TC 700 Z9 712 U1 3 U2 31 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 7 PY 1995 VL 269 IS 5220 BP 81 EP 83 DI 10.1126/science.7541555 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RG980 UT WOS:A1995RG98000038 PM 7541555 ER PT J AU LOPEZ, H AF LOPEZ, H TI CHARACTERIZING THE PERFORMANCE OF DIAGNOSTIC-IMAGING SYSTEMS SO ACADEMIC RADIOLOGY LA English DT Note RP LOPEZ, H (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,MAIL CODE HFZ-132,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JUL PY 1995 VL 2 IS 7 BP 634 EP 637 DI 10.1016/S1076-6332(05)80131-X PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RF525 UT WOS:A1995RF52500012 PM 9419616 ER PT J AU VUJCIC, LK QUINNAN, GV AF VUJCIC, LK QUINNAN, GV TI PREPARATION AND CHARACTERIZATION OF HUMAN HIV TYPE-1 NEUTRALIZING REFERENCE SERA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID ACCELERATED DEGRADATION TESTS; HUMAN-IMMUNODEFICIENCY-VIRUS; BIOLOGICAL STANDARDS; ANTIBODIES; STABILITY; ISOLATE; ASSAYS; DESIGN AB Reference neutralizing antibody (NA) reagents are needed for laboratories to be able to compare results of neutralization assays that will be used to monitor HIV-1 vaccine recipients. In an effort to establish such reference reagents two asymptomatic, seropositive patients were identified with medium to high amounts of crossreactive NA activity against a number of HIV-1 strains, Sera obtained from each individual at three or four sequential phlebotomies were pooled, and the two pools were each distributed in >3000 aliquots into glass ampoules and lyophilized, and the ampoules were flame sealed, An HIV-1 antibody-negative reference serum was prepared in a similar fashion after pooling serum from four individuals. Ampoules were tested for uniformity of fill, sterility, moisture content, residual oxygen, stability, infectivity, and presence of antibody, An international collaborative study was conducted to determine the potency of the samples in six laboratories, each using their own neutralization assays and reagents, The results indicated reasonable consistency between laboratories and that both sera have sufficient titers against a variety of strains for use as reference reagents, These reference sera have been included in the World Health Organization (WHO) AIDS Reagent Project and are available through the three AIDS reagent repositories. RP VUJCIC, LK (reprint author), US FDA,CTR BIOL EVALUAT & RES,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 19 TC 53 Z9 56 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL PY 1995 VL 11 IS 7 BP 783 EP 787 DI 10.1089/aid.1995.11.783 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RK462 UT WOS:A1995RK46200003 PM 7546904 ER PT J AU RHEINSTEIN, PH THOMAS, A AF RHEINSTEIN, PH THOMAS, A TI HOME TEST KITS AND MONITORS SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material RP RHEINSTEIN, PH (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD JUL PY 1995 VL 52 IS 1 BP 293 EP 296 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA RH250 UT WOS:A1995RH25000028 PM 7604768 ER PT J AU GLINSMANN, WH PARK, YM AF GLINSMANN, WH PARK, YM TI PERSPECTIVE ON THE 1986 FOOD-AND-DRUG-ADMINISTRATION ASSESSMENT OF THE SAFETY OF CARBOHYDRATE SWEETENERS - UNIFORM DEFINITIONS AND RECOMMENDATIONS FOR FUTURE ASSESSMENTS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Workshop on the Evaluation of the Nutritional and Health Aspects of Sugars CY MAY 02-05, 1994 CL WASHINGTON, D.C. SP ILSI, N Amer Subcomm Sugars & Hlth, ILSI, Europe Oral Hlth Task Force, ILSI Austr DE DEFINITION OF SUGARS; DEFINITION OF SWEETENERS; DIETARY SUGARS; CARBOHYDRATE SWEETENERS; SUGARS INTAKE; UNDERREPORTING OF ENERGY INTAKE; AVAILABILITY OF SUGARS ID ENERGY-INTAKE; FUNDAMENTAL PRINCIPLES; OBESE SUBJECTS; DIET; PHYSIOLOGY; EXERCISE; RECORDS; HEALTH AB Carbohydrate sweeteners in the diet, which are sources of added sugars, have recently undergone changes that vary considerably among countries. The major driving force for these changes is a technological development that permits conversion of corn and other starches to sweeteners. Major changes in the type of sweeteners used in the United States began in the mid-1970s. In 1986 the US Food and Drug Administration comprehensively evaluated exposures and potential health effects of sugars contained in carbohydrate sweeteners. A UK Department of Health report followed in 1989. An overview of issues is provided, terminologies used to describe sugars and sweeteners are defined, the findings of the US and UK reports are reviewed, trends in the availability of added and naturally occurring sugars are evaluated, and recommendations for future assessment of sugars are discussed. The potential problem of underreporting of food intakes in national food consumption surveys is also reviewed. C1 US FDA, OFF SPECIAL NUTR, WASHINGTON, DC 20204 USA. NR 38 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 1995 VL 62 IS 1 SU S BP 161S EP 169S PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RK076 UT WOS:A1995RK07600002 PM 7598073 ER PT J AU PIAZZAHEPP, TD KENNEDY, DL AF PIAZZAHEPP, TD KENNEDY, DL TI REPORTING OF ADVERSE EVENTS TO MEDWATCH SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE DRUGS; DRUGS, ADVERSE REACTIONS; FOOD AND DRUG ADMINISTRATION (US); MEDWATCH; PHARMACISTS; PHYSICIANS; REPORTS AB Trends in the reporting of serious adverse events directly to FDA between 1992 and 1994 and the quality of reports before and after the June 1993 launching of MedWatch were studied. Computerized data were used to assess changes between 1992 and 1944 in the proportion of adverse-event reports to FDA classified as serious. To evaluate the quality of reports, every third report received during April 1993 (sample size, 254) and April 1994 (263) was evaluated for 21 variables and to determine whether the event was serious. For the first analysis, a serious adverse event was defined as one that resulted in death, hospitalization or prolongation of hospitalization, or disability; for the second, the outcome of a threat to life was also included. The proportion of reports that were serious increased from 34% in 1992 to 49% in 1994. The overall quality of the reports made in 1994 was higher than that of the 1993 reports. In particular, significantly higher percentages of reports in 1994 indicated whether the drug was a new molecular entity, indicated whether the event was serious, and gave laboratory and clinical information in support of the event diagnosis. Reports from pharmacists increased both in number and in quality. Physicians' reports were of high quality in both years, but the number of reports they made decreased. The proportion of adverse-event reports classified as serious increased between 1992 and 1994, and the quality of event reporting to FDA improved since the introduction of MedWatch. C1 US FDA,OFF COMMISSIONER,MEDWATCH,ROCKVILLE,MD 20857. US FDA,CTR DRUG EVALUAT & RES,DIV EPIDEMIOL & SURVEILLANCE,ROCKVILLE,MD 20857. NR 4 TC 21 Z9 21 U1 1 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JUL 1 PY 1995 VL 52 IS 13 BP 1436 EP 1439 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RH260 UT WOS:A1995RH26000010 PM 7671043 ER PT J AU MUSKHELISHVILI, L HART, RW TURTURRO, A JAMES, SJ AF MUSKHELISHVILI, L HART, RW TURTURRO, A JAMES, SJ TI AGE-RELATED-CHANGES IN THE INTRINSIC RATE OF APOPTOSIS IN LIVERS OF DIET-RESTRICTED AND AD LIBITUM-FED B6C3F1 MICE SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID CALORIC RESTRICTION; CELL-DEATH; MECHANISMS; CANCER AB Cancer incidence increases progressively with age. This observation suggests that a mechanistic relationship may exist at the cellular level between these two apparently diverse processes. Indirect evidence for this fundamental relationship is derived from the fact that interventions that retard the rate of aging simultaneously retard the incidence of many forms of cancer Dietary restriction of rodents is a noninvasive manipulation that reproducibly retards most physiological indices of aging as well as the incidence of spontaneous and chemically induced tumors. As such, it provides a powerful model in which, to study common mechanistic processes associated with both aging and cancer In a recent study, toe established that chronic dietary restriction induces an increase in the spontaneous rate of apoptotic cell death in hepatocytes of 12-month-old B6C3F1 mice and is associated with a significant reduction in the subsequent development of spontaneous hepatoma in this genetically susceptible strain, The purpose of the present investigation uas to extend and confirm these original observations by determining whether the increased rate of spontaneous apoptosis w,ith chronic dietary restriction is maintained throughout the life span itt this strain. We quantified the spontaneous apoptotic rate by histological examination of liver sections from diet-restricted and ad libitum-fed B6C3F1 mice at age intervals of 12, 18, 24, and 30 months. The incidence of apoptotic bodies was enumerated in non-tumor-bearing mice bq, scoring 50,000 hepatocytes per liver by in situ end-labeling immunohistochemistry and uas expressed as the mean incidence per 100 cells. The rate of apoptotic cell death was found to be elevated with age in both diet groups; however, the rate of apoptosis was significantly and consistently higher in the diet-restricted mice, relative to the ad libitum-fed mice, regardless of age. It has been proposed that apoptosis, or physiological cell death, provides a protective mechanism whereby DNA-damaged or potentially neoplastic cells are selectively eliminated. Thus, infertventions that increase cellular sensitivity to apoptotic cell death would tend to protect genotypic and phenotypic stability with age; on the other hand the failure to initiate or respond to appropriate signals for apoptosis would tend to accelerate the accumulation of age-associated genetic lesions and age-related neoplasia, An increase in the intrinsic rate of apoptotic cell death may contribute, in part, to decreased tumor incidence and increased life span potential with dietary restriction. C1 US FDA,NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. NR 24 TC 83 Z9 83 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1995 VL 147 IS 1 BP 20 EP 24 PG 5 WC Pathology SC Pathology GA RH023 UT WOS:A1995RH02300003 PM 7604880 ER PT J AU TIMBO, BB ALTEKRUSE, SF HEADRICK, M KLONTZ, KC AF TIMBO, BB ALTEKRUSE, SF HEADRICK, M KLONTZ, KC TI RAW SHELLFISH CONSUMPTION IN CALIFORNIA - THE 1932 CALIFORNIA BEHAVIORAL RISK FACTOR SURVEY SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article AB We used the 1992 California Behavioral Risk Factor Surveillance System to study the prevalence of raw shellfish consumption in California and the demographic and behavioral characteristics of raw shellfish consumers. We used the logistic regression analysis of the weighted survey data with PC SAS and SUDAAN to adjust for the effects of age and gender. Twenty-three percent of the respondents in the survey reported that they ate raw shellfish; one third of these reported eating raw shellfish once a month. Higher prevalences of raw shellfish consumption were reported by men, persons 18-49 years old, those with income above $25,000 and education beyond high school than by women, individuals older than 49 years, and those with an income of $25,000 or less per year and 12 or fewer years of school. A higher percentage of persons with liver disease, stomach surgery, and a history of chronic alcohol drinking reported consumption of raw shellfish than did individuals without liver disease, previous stomach surgery, or a history of alcohol abuse. After adjustment for gender and age, those who reported acute (P < .01) and chronic (P < .01) drinking and driving while intoxicated (P < .01) were more likely to report consumption of raw shellfish. Two variables (lack of seat belt usage [P = 2] and cigarette smoking [P = .13]) were not significantly associated statistically with raw shellfish consumption. RP TIMBO, BB (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,EPIDEMIOL BRANCH,HFS-728,200 C ST SW,WASHINGTON,DC 20204, USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL-AUG PY 1995 VL 11 IS 4 BP 214 EP 217 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA RN607 UT WOS:A1995RN60700004 PM 7495596 ER PT J AU JOHNSON, JM WEAGANT, SD JINNEMAN, KC BRYANT, JL AF JOHNSON, JM WEAGANT, SD JINNEMAN, KC BRYANT, JL TI USE OF PULSED-FIELD GEL-ELECTROPHORESIS FOR EPIDEMIOLOGIC-STUDY OF ESCHERICHIA-COLI O157-H7 DURING A FOOD-BORNE OUTBREAK SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Note ID HEMOLYTIC UREMIC SYNDROME; INFECTIONS; STRAINS AB Food and patient isolates from an Escherichia coli O157:H7 outbreak associated with undercooked ground beef were characterized by pulsed-field gel electrophoresis and Shiga-like toxin genotype. Pulsed-field gel electrophoresis confirmed the epidemiologically implicated source of the two-state outbreak and differentiated between outbreak and sporadic strains. C1 US FDA, SEAFOOD PROD RES CTR, BOTHELL, WA 98041 USA. RP JOHNSON, JM (reprint author), US FDA, SEATTLE DIST LAB, BOTHELL, WA 98041 USA. NR 16 TC 38 Z9 39 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 1995 VL 61 IS 7 BP 2806 EP 2808 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA RG334 UT WOS:A1995RG33400063 PM 7618896 ER PT J AU SHUTTLEWORTH, KL CERNIGLIA, CE AF SHUTTLEWORTH, KL CERNIGLIA, CE TI ENVIRONMENTAL ASPECTS OF PAH BIODEGRADATION SO APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY LA English DT Article; Proceedings Paper CT 3rd International Conference on Frontiers in Bioprocessing CY SEP 19-23, 1993 CL BOULDER, CO SP NeXstar, Univ Minnesota, Biol Proc Technol Inst, Bur Mines, Biol Proc Technol Inst, US EPA, NIST, Colorado Inst Res Biotechnol, Colorado Bioproc Ctr, Univ Colorado DE POLYCYCLIC AROMATIC HYDROCARBONS; PAHS; BIODEGRADATION; BIOAVAILABILITY; WATER SOLUBILITY; DEGRADATION KINETICS; TOXICITY ID POLYCYCLIC AROMATIC-HYDROCARBONS; SOIL-WATER SYSTEMS; MICROBIAL-DEGRADATION; MYCOBACTERIUM SP; NONIONIC SURFACTANTS; CONTAMINATED SOIL; PHENANTHRENE; MINERALIZATION; DIFFUSION; KINETICS AB Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants, some of which are on the US Environmental Protection Agency priority pollutant list. Consequently, timely clean-up of contaminated sites is important. The lower-mol-wt PAHs are amenable to bioremediation; however, higher-mol-wt PAHs seem to be recalcitrant to microbial degradation, The rates of biodegradation of PAHs are highly variable and are dependent not only on PAH structure, but also on the physicochemical parameters of the site as well as the number and types of microorganisms present. PAHs sorb to organic matter in soils and sediments, and the rate of their desorption strongly influences the rate at which microorganisms can degrade the pollutants. Much of the current PAH research focuses on techniques to enhance the bioavailability and, therefore, the degradation rates of PAHs at polluted sites. Degradation products of PAHs are, however, not necessarily less toxic than the parent compounds. Therefore, toxicity assays need to be incorporated into the procedures used to monitor the effectiveness of PAH bioremediation. In addition, this article highlights areas of PAH research that require further investigation. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. NR 41 TC 153 Z9 162 U1 7 U2 42 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 0273-2289 J9 APPL BIOCHEM BIOTECH JI Appl. Biochem. Biotechnol. PD JUL-SEP PY 1995 VL 54 IS 1-3 BP 291 EP 302 DI 10.1007/BF02787927 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA RY911 UT WOS:A1995RY91100021 PM 7486983 ER PT J AU FINBLOOM, DS LARNER, AC AF FINBLOOM, DS LARNER, AC TI INDUCTION OF EARLY RESPONSE GENES BY INTERFERONS, INTERLEUKINS, AND GROWTH-FACTORS BY THE TYROSINE PHOSPHORYLATION OF LATENT TRANSCRIPTION FACTORS - IMPLICATIONS FOR CHRONIC INFLAMMATORY DISEASES SO ARTHRITIS AND RHEUMATISM LA English DT Review ID DNA-BINDING PROTEIN; SIGNAL-TRANSDUCTION PATHWAY; COLONY-STIMULATING FACTOR; IFN-GAMMA RECEPTOR; HUMAN-CELLS; ALPHA-INTERFERON; CYTOPLASMIC ACTIVATION; INTRACELLULAR DOMAIN; INVITRO ACTIVATION; RAPID ACTIVATION C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. RP FINBLOOM, DS (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BLDG 29 A,ROOM 3C22,29 LINCOLN DR MSC 4555,BETHESDA,MD 20892, USA. NR 131 TC 21 Z9 21 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 1995 VL 38 IS 7 BP 877 EP 889 DI 10.1002/art.1780380702 PG 13 WC Rheumatology SC Rheumatology GA RJ618 UT WOS:A1995RJ61800001 PM 7541992 ER PT J AU KAYSNER, CA AF KAYSNER, CA TI DOES MANNITOL FERMENTATION CORRELATE WITH VIBRIO-VULNIFICUS VIRULENCE SO ASM NEWS LA English DT Letter C1 US FDA,SEAFOOD PROD RES CTR,BOTHELL,WA 98041. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0044-7897 J9 ASM NEWS JI ASM News PD JUL PY 1995 VL 61 IS 7 BP 321 EP 321 PG 1 WC Microbiology SC Microbiology GA RJ615 UT WOS:A1995RJ61500004 ER PT J AU FERGUSON, SA PAULE, MG AF FERGUSON, SA PAULE, MG TI LACK OF EFFECT OF PREFEEDING ON FOOD-REINFORCED TEMPORAL RESPONSE DIFFERENTIATION AND PROGRESSIVE RATIO RESPONDING SO BEHAVIOURAL PROCESSES LA English DT Article DE MOTIVATION; OPERANT BEHAVIOR; PREFEEDING; PROGRESSIVE RATIO; TEMPORAL RESPONSE DIFFERENTIATION; TIME DISCRIMINATION; RAT ID BEHAVIORAL-TEST BATTERY AB To investigate the effects of various prefeeding intervals on operant performance (time of partial satiation prior to assessment), adult male Sprague-Dawley rats were trained on two operant tasks: a temporal response differentiation (TRD) task thought to measure time discrimination and a progressive ratio (PR) task thought to measure motivation to work for food reinforcers. Endpoints included percent task completed, response rate, accuracy (TRD only) and breakpoint (PR only). During the two week baseline period, subjects were fed their daily allotment of food (9-12 g) 23 h prior to assessment. In subsequent weeks, subjects were partially satiated by prefeeding the daily allotment of food from 0.25 h to 6 h prior to operant assessment. Prefeeding had no significant effects on performance of either operant task. This study extends previous findings by demonstrating no effects of prefeeding interval on two dissimilar operant behaviors. Thus, the results do not support deprivation interval as a measure of hunger. A more accurate measure of hunger might be provided by the use of body weight or percentage thereof. C1 NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. RP FERGUSON, SA (reprint author), NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 17 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0376-6357 J9 BEHAV PROCESS JI Behav. Processes PD JUL PY 1995 VL 34 IS 2 BP 153 EP 160 DI 10.1016/0376-6357(94)00062-L PG 8 WC Psychology, Biological; Behavioral Sciences; Zoology SC Psychology; Behavioral Sciences; Zoology GA RM778 UT WOS:A1995RM77800005 PM 24897515 ER PT J AU BEIJNEN, JH FLORA, KP HALBERT, GW HENRAR, REC SLACK, JA AF BEIJNEN, JH FLORA, KP HALBERT, GW HENRAR, REC SLACK, JA TI CRC/EORTC/NCI JOINT FORMULATION WORKING PARTY - EXPERIENCES IN THE FORMULATION OF INVESTIGATIONAL CYTOTOXIC DRUGS SO BRITISH JOURNAL OF CANCER LA English DT Article DE FORMULATION; INVESTIGATION OF CYTOTOXIC DRUGS; CLINICAL TRIALS; JOINT FORMULATION WORKING PARTY ID DABIS MALEATE; PHASE-I; CARMETHIZOLE HYDROCHLORIDE; ANTITUMOR-ACTIVITY; S-TRIAZINE; TRIMELAMOL; STABILITY; ANALOGS; AGENTS; PHARMACOKINETICS AB The pharmaceutical formulation of a new anti-tumour agent has often been perceived as the bottleneck in anti-cancer drug development. In order to increase the speed of this essential development step, the Cancer Research Campaign (CRC), the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute (NCI) agreed in 1987 to form the Joint Formulation Working Party (JFWP). The main goal of the JFWP is to facilitate the rapid progress of a new drug through pharmaceutical developmental to preclinical toxicology and subsequently to phase I clinical trial, Under the auspices of the JFWP around 50 new agents have been developed or are currently in development. In this report we present our formulation experiences since the establishment of the JFWP with a selected number of agents: aphidicolin glycinate, bryostatin 1, carmethizole, carzelesin, combretastatin A4, dabis maleate, disulphonated aluminium phthalocyanine, E.O.9, 4-hydroxyanisole, pancratistatin, rhizoxin, Springer pro-drug, SRI 62-834, temozolomide, trimelamol and V489. The approaches used and problems presented may be of general interest to scientists in related fields and those considering submitting agents for development. C1 US FDA,DIV RES & TESTING,LAUREL,MD 20708. UNIV STRATHCLYDE,ROYAL COLL,DEPT PHARMACEUT SCI,CRC,FORMULAT UNIT,GLASGOW G1 1XW,LANARK,SCOTLAND. FREE UNIV AMSTERDAM HOSP,EORTC,OFF NEW DRUG DEV,1007 MB AMSTERDAM,NETHERLANDS. ASTON MOLEC LTD,BIRMINGHAM B7 4EJ,W MIDLANDS,ENGLAND. RP BEIJNEN, JH (reprint author), SLOTERVAART HOSP,NETHERLANDS CANC INST,DEPT PHARM,LOUWESWEG 6,1066 EC AMSTERDAM,NETHERLANDS. NR 33 TC 19 Z9 19 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 1995 VL 72 IS 1 BP 210 EP 218 DI 10.1038/bjc.1995.305 PG 9 WC Oncology SC Oncology GA RF100 UT WOS:A1995RF10000038 PM 7599054 ER PT J AU SKIKNE, BS WHITTAKER, P COOKE, A COOK, JD AF SKIKNE, BS WHITTAKER, P COOKE, A COOK, JD TI FERRITIN EXCRETION AND IRON BALANCE IN HUMANS SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE FERRITIN; EXCRETION; IRON BALANCE ID IDIOPATHIC HEMOCHROMATOSIS; TRANSFERRIN RECEPTOR; SERUM FERRITIN; DEFICIENCY; ABSORPTION; CELLS AB Under normal circumstances, most of the lumenal iron taken into the intestinal mucosal cell is stored within the cell as ferritin and subsequently is lost in the faeces when the cell exfoliates at the end of its lifespan, To evaluate whether faecal iron proteins reflect mucosal cell iron as well as whole body iron and to examine further the kinetics of gastrointestinal iron transport, faecal H-rich and L-rich ferritin were measured in normal subjects and patients with iron deficiency and genetic haemochromatosis. In normal and iron-deficient subjects, the concentration of L-rich but not H-rich faecal ferritin correlated closely with body iron status. In genetic haemochromatosis, the faecal L-rich and H-rich ferritin concentrations were lower than expected for their body iron status. The administration of oral iron to normal subjects led to a rise in L-rich ferritin. Administration of oral or parenteral iron to patients with iron deficiency led to a prompt rise in both forms of faecal ferritin, although the relative increase of L-rich ferritin was greater than that of H-rich ferritin with oral iron administration. Faecal ferritin correlated closely with iron stores in normals and patients with iron deficiency but faecal ferritin levels were lower than expected in genetic haemochromatosis, similar to that previously noted in the duodenal mucosal cells of these patients. C1 UNIV KANSAS,MED CTR,DEPT MED,DIV GASTROENTEROL,KANSAS CITY,KS 66160. US FDA,LAUREL,MD. RP SKIKNE, BS (reprint author), UNIV KANSAS,MED CTR,DEPT MED,DIV HEMATOL,3901 RAINBOW BLVD,KANSAS CITY,KS 66160, USA. FU PHS HHS [DF39246] NR 23 TC 18 Z9 19 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1995 VL 90 IS 3 BP 681 EP 687 DI 10.1111/j.1365-2141.1995.tb05600.x PG 7 WC Hematology SC Hematology GA RH703 UT WOS:A1995RH70300027 PM 7647009 ER PT J AU TALL, BD WILLIAMS, HN GEORGE, KS GRAY, RT WALCH, M AF TALL, BD WILLIAMS, HN GEORGE, KS GRAY, RT WALCH, M TI BACTERIAL SUCCESSION WITHIN A BIOFILM IN WATER-SUPPLY LINES OF DENTAL AIR-WATER SYRINGES SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Note DE DENTAL EQUIPMENT; AIR-WATER SYRINGES; BIOFILMS ID DRINKING-WATER; MICROBIAL-CONTAMINATION; HETEROTROPHIC BACTERIA; UNIT WATER AB Biofilms have been implicated as reservoirs for bacterial contamination of water delivered by dental air-water syringes. A B-month study was done of bacterial colonization and biofilm formation in plastic water supply lines connected to dental air-water syringes. Changes in biofilm flora were observed by both scanning electron microscopy and bacteriologic culture. By day 7, many rod- and spiral-shaped bacteria had colonized the ridged surface of the luminal wall of the tubing, as revealed by scanning electron microscopy. By day 30, individual microcolonies were embedded in extracellular polymeric material. By day 120, these microcolonies had begun to coalesce, and by day 180 the biofilm had developed into a multilayered, heterogenous mixture of microcolonies. The mean aerobic plate counts of colony-forming units of planktonic and biofilm populations were: in log(10) values, 5.9 +/- 0.54/mL and 4.2 +/- 0.82/cm(2), respectively. Early colonizers were predominantly Pseudomonas spp., but included Pasteurella, Moraxella, Ochrobactrum, and Aeromonas spp. Flavobacterium and Acinetobacter spp. were observed later. Many of these organisms are opportunistic pathogens. These results demonstrate the longitudinal dynamics of biofilm formation. C1 UNIV MARYLAND, SCH DENT, DEPT MICROBIOL, BALTIMORE, MD 21201 USA. US FDA, CTR FOOD SAFETY & APPL NUTR, DIV MICROBIOL STUDIES, WASHINGTON, DC 20204 USA. US FDA, CTR FOOD SAFETY & APPL NUTR, DIV GEN SCI SUPPORT, WASHINGTON, DC 20204 USA. UNIV MARYLAND, CTR MARINE BIOTECHNOL, BALTIMORE, MD 21202 USA. OI Tall, Ben/0000-0003-0399-3629 NR 15 TC 42 Z9 42 U1 0 U2 4 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4166 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD JUL PY 1995 VL 41 IS 7 BP 647 EP 654 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA RP276 UT WOS:A1995RP27600015 PM 7641146 ER PT J AU NOGUCHI, PD AF NOGUCHI, PD TI CELL TRANSPLANTATION AND FEDERAL-REGULATION SO CELL TRANSPLANTATION LA English DT Article; Proceedings Paper CT 2nd International Congress of the Cell-Transplant-Society CY MAY 01-04, 1994 CL MINNEAPOLIS, MN SP Cell Transplant Soc DE SOMATIC CELL THERAPY; FEDERAL REGULATION; FOOD AND DRUG ADMINISTRATION AB Federal regulation of tissues and organs has proceeded slowly, with main emphasis on safety of the procured material. More recently with the development of somatic cell therapies, the Food and Drug Administration has issued some guidance documents that establish that some classes of cells that are manufactured will be subject to not only safety but efficacy requirements. Cell transplantation presents several aspects that are similar to somatic cell therapies, and the purpose of this presentation is to explore those relationships. RP NOGUCHI, PD (reprint author), US FDA,CTR BIOL EVALUAT & RES,OFF THERAPEUT RES & REV,DIV CELLULAR & GENE THERAPIES,ROCKVILLE,MD 20852, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD JUL-AUG PY 1995 VL 4 IS 4 BP 411 EP 414 DI 10.1016/0963-6897(95)00024-R PG 4 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA RL942 UT WOS:A1995RL94200009 PM 7582572 ER PT J AU ALATRASH, J ZHANG, YJ LIN, DX KADLUBAR, FF SANTELLA, RM AF ALATRASH, J ZHANG, YJ LIN, DX KADLUBAR, FF SANTELLA, RM TI QUANTITATIVE IMMUNOHISTOCHEMICAL ANALYSIS OF 4-AMINOBIPHENYL-DNA IN CULTURED-CELLS AND MICE - COMPARISON TO GAS-CHROMATOGRAPHY MASS-SPECTROSCOPY ANALYSIS SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CARCINOGEN-DNA ADDUCTS; EXFOLIATED UROTHELIAL CELLS; MONOCLONAL-ANTIBODIES; HEPATOCELLULAR-CARCINOMA; URINARY-BLADDER; LIVER-TISSUE; AFLATOXIN-B1; SMOKING AB Two monoclonal antisera, 4C11 and 3C8, recognizing 4-aminobiphenyl (4-ABP)-DNA adducts were developed and characterized by competitive enzyme-linked immunosorbent assay (ELISA). Both antisera are highly specific for 4-ABP-DNA and, at the highest concentration tested, do not recognize the DNA adducts of several other aromatic amines tested including 1-aminopyrene, 8-nitro-1-aminopyrene, and 6-nitro-1-aminopyrene. An immunohistochemical method for detecting adducts was developed in R52 cells, a mouse NIH3T3 cell line expressing high levels of cytochrome P450 1A2. Quantitation of fluorescence labeling indicated a dose-related increase in staining in cells treated with 0, 6, 30, 60, and 300 mu M 4-ABP. To apply the method to tissue samples, Balb/c mice were treated with 0, 4, 10, 20, 40, and 80 mg/kg 4-ABP and liver, bladder, and lung tissue analyzed by immunohistochemical staining of tissue sections. There was a dose-related increase in specific nuclear staining in liver and bladder tissues with no detectable staining in lung tissue. DNA from liver tissue was also analyzed by alkaline hydrolysis of 4-ABP, derivatization with pentafluoropropionic anhydride, and gas chromatography/mass spectroscopy analysis. A good correlation (r = 0.98, p < 0.0001) was found between DNA damage levels determined by the two methods. Based on adduct levels determined by GC/MS in both R52 cells and liver tissue, the immunohistochemical method has a limit of sensitivity of approximately 1 adduct/10(7-8) nucleotides. Immunohistochemistry should be useful for analysis of 4-ABP-DNA adducts in human tissue biopsies as well as exfoliated cells from the oral mucosa and urinary bladder. C1 COLUMBIA UNIV,SCH PUBL HLTH,CTR CANC,DIV ENVIRONM SCI,NEW YORK,NY 10032. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. FU NIEHS NIH HHS [ES05294] NR 20 TC 32 Z9 32 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL-AUG PY 1995 VL 8 IS 5 BP 747 EP 752 DI 10.1021/tx00047a015 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA RJ225 UT WOS:A1995RJ22500015 PM 7548758 ER PT J AU FAIRCHOK, MP ROUSE, JH MORRIS, SL AF FAIRCHOK, MP ROUSE, JH MORRIS, SL TI AGE-DEPENDENT HUMORAL RESPONSES OF CHILDREN TO MYCOBACTERIAL ANTIGENS SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; EASTERN-UNITED-STATES; AVIUM COMPLEX DISEASE; NONTUBERCULOUS MYCOBACTERIA; INTRACELLULARE COMPLEX; INFECTED CHILDREN; SWEDISH CHILDREN; AIDS; EPIDEMIOLOGY; ANTIBODIES AB In the United States, disseminated infection with environmental mycobacteria, including the Mycobacterium avium complex, is the most common opportunistic bacterial infection seen in AIDS patients. However, the source and relative degree of exposure to environmental mycobacteria during childhood are unknown. To examine the age-related exposure to mycobacteria, we obtained serum samples from 150 children ranging in age from 6 months to 18 years, Each sample was tested against both M, avium (serovar 1) sonic extracts and mycobacterial lipoarabinomannan, using an enzyme-linked immunosorbent assay (ELISA). All serum samples were also subjected to immunoblot analysis with the sonic extract antigen. These studies established that elevated ELISA values (P < 0.0901) and increased immunoblot reactivity (P < 0.0001) against mycobacterial antigens were both associated with increasing age. The seroreactivity differences were most striking when comparing the age groups of children below the age of 6,vith the older age groups. Our results suggest that the development of humoral immune responses to mycobacterial antigens in children correlates with increasing age and that there may be an environmental factor predisposing to mycobacterial exposure which is related to advancing age. C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BETHESDA,MD 20892. NR 47 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JUL PY 1995 VL 2 IS 4 BP 443 EP 447 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RJ987 UT WOS:A1995RJ98700011 PM 7583921 ER PT J AU HAYES, MP FREEMAN, SL DONNELLY, RP AF HAYES, MP FREEMAN, SL DONNELLY, RP TI IFN-GAMMA PRIMING OF MONOCYTES ENHANCES LPS-INDUCED TNF PRODUCTION BY AUGMENTING BOTH TRANSCRIPTION AND MESSENGER-RNA STABILITY SO CYTOKINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA-GENE; MURINE PERITONEAL-MACROPHAGES; NF-KAPPA-B; MESSENGER-RNA; INTERFERON-GAMMA; PROTEIN-KINASE; CYCLIC-AMP; MONONUCLEAR PHAGOCYTES; FACTOR CACHECTIN AB The induction of cytokine expression in monocytes/macrophages by bacterial endotoxin or lipopolysaccharide is a critical, highly regulated host defence response. The augmentation of LPS responses by interferon gamma (IFN-gamma), referred to as priming, is weil established. However, the mechanism(s) by which priming occurs is poorly defined. Using tumour necrosis factor (TNF) induction as a model, experiments were designed to analyse in detail the printing effect on the LPS response in human monocytes. Priming by IFN-gamma was primarily manifested at the level of TNF mRNA accumulation. IFN-gamma pre-treatment affected the magnitude rather than the sensitivity of the LPS response. Priming occurred after several hours of treatment, and the primed state was induced by either IFN-gamma or GM-CSF, but not M-CSF. Primed monocytes transcribed TNF mRNA at a higher rate than freshly isolated monocytes upon activation with LPS. The increased transcriptional rate correlated with a marked increase in nuclear factor-kappa B activity in these cells as determined by electrophoretic mobility shift assay using a consensus NF-kappa B oligonucleotide. An additional significant finding was that TNF mRNA induced in primed cells was much more stable than in unprimed cells (T1/2 increased 6-8-fold). Consistent with the increased mRNA stability, the duration of mRNA accumulation was longer following LPS stimulation in primed monocytes, in addition to being of greater magnitude. Finally, primed and unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89. H-89 substantially suppressed LPS-induced TNF mRNA accumulation in unprimed cells, but had no effect on primed monocytes following LPS stimulation. These results demonstrate that priming amplifies LPS-inducible TNF expression by increasing both transcription and mRNA stability. (C) 1995 Academic Press Limited. RP HAYES, MP (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,HFM-508,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 59 TC 78 Z9 79 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUL PY 1995 VL 7 IS 5 BP 427 EP 435 DI 10.1006/cyto.1995.0058 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA RJ230 UT WOS:A1995RJ23000005 PM 7578980 ER PT J AU EPIFANO, O LIANG, LF FAMILARI, M MOOS, MC DEAN, J AF EPIFANO, O LIANG, LF FAMILARI, M MOOS, MC DEAN, J TI COORDINATE EXPRESSION OF THE 3 ZONA-PELLUCIDA GENES DURING MOUSE OOGENESIS SO DEVELOPMENT LA English DT Article DE ZONA PELLUCIDA; ZP1; ZP2; ZP3; OOCYTE-SPECIFIC GENE EXPRESSION; IN SITU HYBRIDIZATION,; RNASE PROTECTION ASSAY; MOUSE ID OOCYTE-SPECIFIC EXPRESSION; SECONDARY SPERM RECEPTOR; DEVELOPMENTAL REGULATION; GAMETE INTERACTION; OVARIAN FOLLICLES; MESSENGER-RNAS; PROTEINS; GLYCOPROTEIN; BINDING; IDENTIFICATION AB The mammalian zona pellucida is an extracellular matrix that surrounds growing oocytes, ovulated eggs and early embryos, The mouse zona is composed of three sulfated glycoproteins: ZP1, ZP2 and ZP3. Each is critically involved in fertilization, the postfertilization block to polyspermy and protection of the preimplantation embryo, We have previously isolated cDNAs encoding mouse ZP2 and ZP3 and now report the isolation of a full-length cDNA encoding ZP1, Mouse ZP1 is composed of a 623 amino acid polypeptide chain with a signal peptide and a carboxyl terminal transmembrane domain, typical of all zona proteins, Sequence comparison demonstrate that mouse ZP1 is an orthologue of a rabbit zona protein, R55, The expression of R55 has been reported previously in both oocytes and granulosa cells, However, by northern analysis and in situ hybridization with P-33-labelled antisense probes to each of the three mouse zona mRNAs, we have determined that the expression of each mouse zona gene is restricted to the oocyte, ZP2 transcripts, but not ZP1 or ZP3, are detected in resting (15 mu m diameter) oocytes, and all three zona transcripts coordinately accumulate as oocytes begin to grow. Together they represent approximately 1.5% of the total poly(A)(+) RNA in 50-60 mu m oocytes, In the latter stages of oogenesis, their abundance declines and each zona transcript is present in ovulated eggs at less than 5% of its maximal level. No zona transcripts were detected above background signal in granulosa cells. We conclude that, in mice, the three zona pellucida genes are expressed in a coordinate, oocyte-specific manner during the growth phase of oogenesis. Our data support the hypothesis that the transcription of the zona genes is controlled, in part, by shared regulatory element(s). C1 CTR BIOL EVALUAT & RES,DEV BIOL LAB,BETHESDA,MD 20892. RP EPIFANO, O (reprint author), NIDDK,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 66 TC 202 Z9 209 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 1995 VL 121 IS 7 BP 1947 EP 1956 PG 10 WC Developmental Biology SC Developmental Biology GA RH141 UT WOS:A1995RH14100001 PM 7635043 ER PT J AU GREEN, MD AF GREEN, MD TI AN FDA PERSPECTIVE ON GENERAL PHARMACOLOGY STUDIES TO DETERMINE ACTIVITY AND SAFETY SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE SCREENS; BIOLOGICS; TOXICITY TESTING AB General pharmacology studies are conducted to determine various pharmacological activities, as part of drug discovery or to define some specific issues which are relevant to safety. Regulatory submissions of biological products, unlike other therapeutics classes of agents, e.g., drugs, are frequently accompanied by extensive information regarding their preclinical aspects of physiology, biochemistry, and pharmacology. Although not true in every instances, biologic products exert their effects in a highly specific manner. Various fundamental aspects of protein chemistry and receptor function combine to restrict the spectrum of pharmacological and toxicological effects likely to occur. General pharmacology studies may be conducted either separately or nested in larger studies assessing general toxicity. Pharmacology studies are used best in an attempt to answer specific questions and are particularly effective when complementing other tests of safety. (C) 1995 Wiley-Liss, Inc. RP GREEN, MD (reprint author), US FDA,OFF THERAPEUT REVIEW & RES,DIV CLIN TRIALS DESIGN & ANAL,1435 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JUL PY 1995 VL 35 IS 3 BP 158 EP 160 DI 10.1002/ddr.430350308 PG 3 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RM267 UT WOS:A1995RM26700007 ER PT J AU SCHENCK, FJ WAGNER, J AF SCHENCK, FJ WAGNER, J TI SCREENING-PROCEDURE FOR ORGANOCHLORINE AND ORGANOPHOSPHORUS PESTICIDE-RESIDUES IN MILK USING MATRIX SOLID-PHASE DISPERSION (MSPD) EXTRACTION AND GAS-CHROMATOGRAPHIC DETERMINATION SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE ORGANOCHLORINE; ORGANOPHOSPHORUS; MILK; PESTICIDE; MATRIX SOLID PHASE DISPERSION AB A rapid technique for the extraction and gas chromatographic determination of five organochlorine and five organophosphorus pesticide residues in milk is described. Milk (5.0 ml) is blended with 2.0 g of C-18 [octadecylsilyl-derivatized silica] and 1.5 ml acetonitrile in a syringe barrel. After the aqueous phase is removed from the column by vacuum aspiration, the pesticide residues are eluted from the C-18/milk matrix with acetonitrile which is then eluted through a Florisil solid phase extraction (SPE) column. The acetonitrile is evaporated under nitrogen and the residue is dissolved in petroleum ether. This extract is directly analysed for organophosphorus pesticides by gas chromatography with flame photometric detection. After further clean-up of the extract on a mini-Florisil column, the organochlorine pesticide residues are determined by gas chromatography with electron capture detection. Grade A homogenized and raw milk samples were fortified with five organochlorine and five organophosphorus pesticide residues. The average recoveries of fortified organochlorine pesticide residues (20-20ppb) ranged from 76.0% to 97.8%. The average recoveries of fortified organophosphorus pesticide residues (10-50ppb) ranged from 75.0% to 104.5%. The MSPD and the AOAC International multiresidue method for pesticides in milk produced comparable results for milk samples containing incurred organochlorine pesticide residues. The use of the MSPD method results in a 90% reduction in organic solvent consumption and a 95% reduction in the hazardous waste generated when compared with the AOAC method. RP SCHENCK, FJ (reprint author), US FDA,BALTIMORE DIST,900 MADISON AVE,BALTIMORE,MD 21201, USA. NR 0 TC 43 Z9 44 U1 1 U2 9 PU TAYLOR & FRANCIS LTD LONDON PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD JUL-AUG PY 1995 VL 12 IS 4 BP 535 EP 541 PG 7 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA RK681 UT WOS:A1995RK68100002 PM 7589717 ER PT J AU LIMM, W HOLLIFIELD, HC AF LIMM, W HOLLIFIELD, HC TI EFFECTS OF TEMPERATURE AND MIXING ON POLYMER ADJUVANT MIGRATION TO CORN-OIL AND WATER SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE ANTIOXIDANT; DIFFUSION COEFFICIENT; MASS TRANSFER; MIGRATION; MIXING; POLYMER ADDITIVES; PARTITION COEFFICIENT; POLYOLEFIN AB The effect of mixing on the migration of Irganox 1010(R) antioxidant from polypropylene and high-density polyethylene to water and corn oil was compared at 77, 100, and 135 degrees C. Irganox 1010 migration to water is enhanced almost five-fold by mixing at 77 degrees C, whereas at 135 degrees C, mixing has only a nominal effect on migration. Irganox 1010 migration to corn oil is virtually unaffected by mixing at the temperatures studied. Migration data indicate a similar trend for Irganox 1076. RP LIMM, W (reprint author), US FDA,DIV PROD MANUFACTURE & USE,200 C ST SW HFS-248,WASHINGTON,DC 20204, USA. NR 0 TC 30 Z9 31 U1 1 U2 16 PU TAYLOR & FRANCIS LTD LONDON PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD JUL-AUG PY 1995 VL 12 IS 4 BP 609 EP 624 PG 16 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA RK681 UT WOS:A1995RK68100009 PM 7589724 ER PT J AU GEORGE, JD PRICE, CJ TYL, RW MARR, MC KIMMEL, CA AF GEORGE, JD PRICE, CJ TYL, RW MARR, MC KIMMEL, CA TI THE EVALUATION OF THE DEVELOPMENTAL TOXICITY OF HYDROCHLOROTHIAZIDE IN MICE AND RATS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID F344 RATS AB Timed-pregnant CD-1 outbred albino Swiss mice and CD Sprague-Dawley rats were administered hydrochlorothiazide (HCTZ, USP) in corn oil by gavage during major organogenesis, Gestational Days (GD) 6 through 15. The doses administered were 0, 300, 1000, or 3000 mg/kg/day for mice and 0, 100, 300, or 1000 mg/kg/day for rats. Maternal clinical status was monitored daily during treatment. At termination (GD 17, mice; GD 20, rats), confirmed pregnant females (20-27 per group, mice; 36-39 per group, rats) were evaluated for clinical status and gestational outcome; each live fetus was examined for external, visceral, and skeletal malformations. In mice, no maternal mortality was observed. However, clinical signs including dehydration, piloerection, lethargy, and single-day weight loss appeared to be dose-related. HCTZ had no effect on maternal weight gain or water consumption, gravid uterine weight, relative maternal liver weight, or relative maternal kidney weight. There was no definitive evidence of embryotoxicity or fetal toxicity for mice on GD 17. Thus, the no observed adverse effect level (NOAEL) for both maternal and developmental toxicity was 3000 mg/kg/day. In rats, HCTZ had no effect on maternal survival, clinical signs, or water consumption. Clinical signs were not dose-related. Maternal weight gain during treatment was depressed at 1000 mg/kg/day. Gravid uterine weight and relative maternal liver weight were unaffected. Relative maternal kidney weight was slightly (7-8%) increased at all dose levels, but there was no evidence of a dose response. Thus, the maternal NOAEL for rats was 300 mg/kg/day, based on decreased maternal weight gain during treatment at 1000 mg/kg/day. HCTZ had no effect on prenatal mortality, fetal growth, or morphological development in rats. The developmental NOAEL was greater than or equal to 1000 mg/kg/day. In summary, oral administration of HCTZ to mice at doses up to 3000 mg/kg/day and rats at doses up to 1000 mg/kg/day during organogenesis produced no evidence of developmental toxicity in either species, in spite of mild maternal toxicity in rats at 1000 mg/kg/day. (C) 1995 Society of Toxicology. C1 NATL CTR TOXICOL RES,DIV TERATOGENESIS,JEFFERSON,AR 72079. RP GEORGE, JD (reprint author), RES TRIANGLE INST,CTR LIFE SCI & TOXICOL,POB 12194,RES TRIANGLE PK,NC 27709, USA. NR 29 TC 3 Z9 3 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JUL PY 1995 VL 26 IS 2 BP 174 EP 180 DI 10.1006/faat.1995.1088 PG 7 WC Toxicology SC Toxicology GA RH911 UT WOS:A1995RH91100003 PM 7589906 ER PT J AU WAYNANT, RW AF WAYNANT, RW TI ICAP/4STUDENTS SO IEEE CIRCUITS AND DEVICES MAGAZINE LA English DT Software Review RP WAYNANT, RW (reprint author), US FDA,1901 CHAPMAN AVE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 8755-3996 J9 IEEE CIRCUIT DEVIC JI IEEE Circuit Devices Mag. PD JUL PY 1995 VL 11 IS 4 BP 48 EP 49 PG 2 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA RH929 UT WOS:A1995RH92900016 ER PT J AU WAYNANT, RW AF WAYNANT, RW TI OMATRIX OBJECTIVE NUMERICAL-ANALYSIS SO IEEE CIRCUITS AND DEVICES MAGAZINE LA English DT Software Review RP WAYNANT, RW (reprint author), US FDA,1901 CHAPMAN AVE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 8755-3996 J9 IEEE CIRCUIT DEVIC JI IEEE Circuit Devices Mag. PD JUL PY 1995 VL 11 IS 4 BP 48 EP 48 PG 1 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA RH929 UT WOS:A1995RH92900015 ER PT J AU WEAR, KA WAGNER, RF GARRA, BS AF WEAR, KA WAGNER, RF GARRA, BS TI A COMPARISON OF AUTOREGRESSIVE SPECTRAL ESTIMATION ALGORITHMS AND ORDER DETERMINATION METHODS IN ULTRASONIC TISSUE CHARACTERIZATION SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID ACOUSTIC BACKSCATTER COEFFICIENTS; DOPPLER ULTRASOUND; DATA REDUCTION; HUMAN-LIVER; FREQUENCY; MYOCARDIUM; DEPENDENCE; INVIVO; SIGNAL; DOGS AB Several autoregressive (AR) methods for spectral estimation were applied toward the task of estimating ultrasonic backscatter coefficients from small volumes of tissue, Data were acquired from a homogeneous tissue-mimicking phantom and from a normal human liver in vivo, AR methods performed better at short record lengths than the traditional DFT (discrete Fourier Transform) approach. The DPT method consistently underestimated backscatter coefficients at small gate lengths, Burg's algorithm, the Modified Covariance algorithm, and the Recursive Maximum Likelihood Estimation algorithm performed comparably. The Yule-Walker algorithm did not perform as well as these but offered a slight improvement over the DFT, Several order determination methods were tested, These included residual variance (RV), final prediction error (FPE), Akaike information criterion (AIC), and Minimum Description Length (MDL). The AIC and MDL produced misleading results at higher orders, The RV and FPE yielded better results. The autoregressive method offers promise for enhanced spatial resolution and accuracy in ultrasonic tissue characterization and nondestructive evaluation of materials. C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. RP WEAR, KA (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,12720 TWINBROOK PKWY,ROCKVILLE,MD 20852, USA. NR 42 TC 28 Z9 29 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD JUL PY 1995 VL 42 IS 4 BP 709 EP 716 DI 10.1109/58.393113 PG 8 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA RJ074 UT WOS:A1995RJ07400024 ER PT J AU KOTHARY, MH CLAVERIE, EF MILIOTIS, MD MADDEN, JM RICHARDSON, SH AF KOTHARY, MH CLAVERIE, EF MILIOTIS, MD MADDEN, JM RICHARDSON, SH TI PURIFICATION AND CHARACTERIZATION OF A CHINESE-HAMSTER OVARY CELL ELONGATION-FACTOR OF VIBRIO-HOLLISAE SO INFECTION AND IMMUNITY LA English DT Article ID THERMOSTABLE DIRECT HEMOLYSIN; HEAT-LABILE ENTEROTOXINS; ESCHERICHIA-COLI; UNITED-STATES; SALMONELLA-TYPHIMURIUM; AEROMONAS-HYDROPHILA; CHOLERA-TOXIN; PARAHAEMOLYTICUS; BINDING; QUANTITIES AB The halophilic bacterium Vibrio hollisae, isolated from patients with diarrhea, produces an extracellular toxin which elongates Chinese hamster ovary (CHO) cells. We purified this toxin to homogeneity by sequential ammonium sulfate precipitation, gel filtration with Sephacryl S-200, hydrophobic interaction chromatography with phenyl-Sepharose CL-4B, ion-exchange chromatography with DEAE-Sephadex A-50, and affinity chromatography, The toxin is heat labile and sensitive to proteases, with an isoelectric point of about 6.5 and molecular weights of about 83,000 and 80,000, as estimated by gel filtration and sodium dodecyl sulfate polyacrylamide gel electrophoresis, respectively, The toxin did not react with immunoaffinity-purified antibodies to cholera toxin in a plate enzyme-linked immunosorbent assay and in a Western blot, and its activity could not be neutralized by anti-cholera toxin serum, Mixed gangliosides and gangliosides G(M1), G(D1a), G(D1b), G(q1b), G(T1b), G(D2), G(D3), G(M2), and G(M3) failed to block its activity. Elongation of CHO cells induced by the toxin was not accompanied by an increase in the levels of cyclic AMP. The toxin induced intestinal fluid accumulation in suckling mice. These results and the lack of homology between V. hollisae DNA and DNA coding for cholera toxin or the heat-labile toxin of Escherichia coli suggest that the V. hollisae toxin is structurally and functionally different from other CHO cell-elongating toxins. C1 WAKE FOREST UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,WINSTON SALEM,NC 27103. RP KOTHARY, MH (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV VIRULENCE ASSESSMENT HFS327,200 C ST SW,WASHINGTON,DC 20204, USA. NR 37 TC 14 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1995 VL 63 IS 7 BP 2418 EP 2423 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RE842 UT WOS:A1995RE84200005 PM 7790052 ER PT J AU ZAITSEVA, MB GOLDING, H BETTS, M YAMAUCHI, A BLOOM, ET BUTLER, LE STEVAN, L GOLDING, B AF ZAITSEVA, MB GOLDING, H BETTS, M YAMAUCHI, A BLOOM, ET BUTLER, LE STEVAN, L GOLDING, B TI HUMAN PERIPHERAL-BLOOD CD4(+) AND CD8(+) T-CELLS EXPRESS TH1-LIKE CYTOKINE MESSENGER-RNA AND PROTEINS FOLLOWING IN-VITRO STIMULATION WITH HEAT-INACTIVATED BRUCELLA-ABORTUS SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; POLYMERASE CHAIN-REACTION; IFN-GAMMA; INTERFERON-GAMMA; INDEPENDENT TYPE-1; GENE-EXPRESSION; INTERLEUKIN-4 PRODUCTION; ANTIVIRAL ACTIVITY; IMMUNE INTERFERON; B-CELLS AB Defining the pattern of lymphokine production associated with Brucella abortus is critical for advancing the development of B. abortus as a vaccine carrier. In the present study we investigated the ability of heat-inactivated B. abortus or lipopolysaccharide from B. abortus to induce lymphokine production from purified human T cells in vitro, Gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-5 induction was assayed by mRNA-specific PCR and by enzyme-linked immunosorbent assay and bioassay for protein production, Following depletion of monocytes and B cells, B. abortus increased IFN-gamma and IL-2 mRNA expression in purified T cells compared with expression in unstimulated cells. In contrast, no IL-5 mRNA expression and only transient low-level IL-4 mRNA expression and no IL-4 protein secretion were detected. Phytohemagglutinin or phorbol myristate acetate plus ionomycin induced mRNA and protein for all these cytokines. Similar results were obtained with LPS purified from B. abortus. Removal of NK cells did not reduce lymphokine production, and enriched NK cells did not express IFN-gamma mRNA or secrete IFN-gamma protein in response to B. abortus, indicating that NK cells were not the responding population, Both CD4(+) and CD8(+) populations produced IFN-gamma and IL-2 in response to B. abortus. Preincubation of resting T cells with B. abortus or LPS from B. abortus for 7 days induced their differentiation into Th1-like cells as judged by their subsequent lymphokine response to phorbol myristate acetate plus ionomycin. These results suggest that B. abortus con induce differentiation of Th0 into Th1-type cells. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,PLASMA DERIVAT LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,RETROVIRUS RES LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELL & GENE THERAPY,CELLULAR IMMUNOL LAB,BETHESDA,MD 20892. NR 54 TC 56 Z9 57 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1995 VL 63 IS 7 BP 2720 EP 2728 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RE842 UT WOS:A1995RE84200046 PM 7790090 ER PT J AU Gunderson, EL AF Gunderson, EL TI Dietary intakes of pesticides, selected elements, and other chemicals: FDA total diet study, June 1984 April 1986 SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FOOD AB The U.S. Food and Drug Administration conducts the Total Diet Study to determine dietary intakes of selected pesticides, industrial chemicals, and elements (including radionuclides). The results reported here reflect the sampling period from June 1984 to April 1986. The study involves retail purchase of foods representative of the total diet of the U.S. population, preparation for table-ready consumption, and individual analyses of 234 items depicting the diets of 8 population groups, The diets were based on 2 nationwide food consumption surveys, The data presented represent 8 food collections (also termed ''market baskets'') in regional metropolitan areas during the 2-year period, Dietary intakes of over 90 analytes are presented for the 8 population groups, which range from infants to elderly adults, Intakes of selected population groups are compared with representative previous findings, As reported previously, average daily intakes are well below acceptable limits. RP Gunderson, EL (reprint author), US FDA,OFF PLANT & DAIRY FOODS & BEVERAGES,DIV PROGRAMS & ENFORCEMENT POLICY,WASHINGTON,DC 20204, USA. NR 19 TC 51 Z9 51 U1 0 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1995 VL 78 IS 4 BP 910 EP 921 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA TV257 UT WOS:A1995TV25700004 PM 7580329 ER PT J AU Roy, RR Albert, RH Wilson, P Laski, RR Roberts, JI Hoffmann, TJ Bong, RL Bohannon, BO Yess, NJ AF Roy, RR Albert, RH Wilson, P Laski, RR Roberts, JI Hoffmann, TJ Bong, RL Bohannon, BO Yess, NJ TI US food and drug administration pesticide program: Incidence level monitoring of domestic and imported pears and tomatoes SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB In 1992-1993, the U.S. Food and Drug Administration (FDA) conducted a statistically based study of pesticide residues in domestic and imported pears and tomatoes, For pears, 710 domestic and 949 imported samples were collected and analyzed; 79% of the domestic and 72% of the imported samples had detectable residues, Thiabendazole, a fungicide with postharvest uses, was found with greatest frequency in both groups of pears, Four domestic and 12 imported samples contained violative residues, mainly of pesticides for which there are no U.S. tolerances on pears. The statistically weighted (by shipment size) violation rates for domestic and imported pears were 1.0 and 0.9%, respectively, For tomatoes, 1219 domestic and 144 imported samples were collected and analyzed; 84% of the domestic and 91% of the imported samples had detectable residues, Methamidophos, an insecticide, had the greatest frequency of occurrence in both groups of tomatoes, Thirty-three domestic and 5 imported samples were violative, nearly all the result of acephate use, for which there is no U.S. tolerance on tomatoes, The statistically weighted violation rates for domestic and imported tomatoes were 1.9 and 7.0%, respectively, The statistically weighted violation rates calculated for domestic and imported pears and domestic tomatoes in this study were lower than those observed under FDA's regulatory monitoring in recent years, The violation rate for imported tomatoes was somewhat higher under statistical monitoring than under regulatory monitoring, The results of the statistically based study show that, as in regulatory monitoring, the levels of pesticide residues found are generally well below U.S. tolerances. C1 US FDA, OFF PLANT & DAIRY FOODS & BEVERAGES, DIV PROGRAMS & ENFORCEMENT POLICY, WASHINGTON, DC 20204 USA. US FDA, OFF FIELD PROGRAMS, DIV FIELD PROGRAM PLANNING & EVALUAT, WASHINGTON, DC 20204 USA. US FDA, OFF SCI ANAL & SUPPORT, DIV MATH, WASHINGTON, DC 20204 USA. US FDA, BUFFALO DIST LAB, BUFFALO, NY 14202 USA. US FDA, MINNEAPOLIS DIST LAB, MINNEAPOLIS, MN 55401 USA. NR 16 TC 14 Z9 16 U1 0 U2 0 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1995 VL 78 IS 4 BP 930 EP 940 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA TV257 UT WOS:A1995TV25700006 PM 7580331 ER PT J AU Cieri, UR AF Cieri, UR TI Determination of ajmalicine in reserpine raw materials by liquid chromatography with fluorescence detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A method is presented for determination of ajmalicine in reserpine raw materials by liquid chromatography (LC) with fluorescence detection. The sample is dissolved in a very small volume of chloroform, and the resulting solution is diluted with methanol. The reference solution of ajmalicine is prepared directly in methanol. For LC, a 30 cm long normal-phase column is used. The mobile phase is methanol containing a small volume of an aqueous solution of 1-pentanesulfonic acid, sodium salt. Detection is by fluorescence with excitation at 280 nm and emission at 360 nm. In 3 samples, the ajmalicine contents ranged from 1.2 to 1.9%. RP Cieri, UR (reprint author), US FDA,PHILADELPHIA,PA 19106, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1995 VL 78 IS 4 BP 944 EP 945 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA TV257 UT WOS:A1995TV25700008 PM 7580333 ER PT J AU Hanna, GM AF Hanna, GM TI Determination of ephedrine, pseudoephedrine, and norephedrine in mixtures (bulk and dosage forms) by proton nuclear magnetic resonance spectroscopy SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; THIN-LAYER CHROMATOGRAPHY; ALKALOIDS; ELECTROPHORESIS; BASES AB A simple, specific, and accurate H-1 nuclear magnetic resonance (NMR) spectroscopic method has been developed for quantitative determination of the Ephedra alkaloids (-)-ephedrine, (+)-pseudoephedrine, and (+/-)-norephedrine, either singly or in mixtures with each other, Determination of individual alkaloids was carried out in D2O solution, with acetamide as internal standard. Although calculations were based on integrals for the C-CH3 protons, those for the N-CH3 and -CH-O- protons may also be useful, depending on the compound, Determination of diastereomeric cross-contamination of ephedrine and pseudoephedrine-or of the concentrations of these alkaloids in the presence or absence of (+/-)-norephedrine-was feasible by using the integrals for the -CH-O- protons after addition of a trace of DCI., Mean recoveries for ephedrine and pseudoephedrine from their respective synthetic mixtures with the internal standard (acet- amide) were greater than or equal to 99.9 +/- 0.6% (n = 10) and 99.6 +/- 0.8% (n = 10) of the amount added. Recovery for pseudoephedrine from diastereomeric mixtures with ephedrine was >99.4 +/- 0.7% (n = 10) of the amount added, with as little as 1.92% still being measurable, Mean recovery of (+/-)-norephedrine from mixtures with ephedrine and pseudoephedrine was >99.7 +/- 2.5% (n = 4) of the amount added, with about 1% still being measurable. Application of the proposed NMR spectroscopic method to commercial dosage forms, including ephedrine sulfate injections and pseudoephedrine hydrochloride tablets, yielded assay results ranging from 97.8 to 100.2% (mean, 99.2%) and from 98.7 to 100.5% (mean, 99.7%) of declared, respectively. RP Hanna, GM (reprint author), US FDA,NE REG LAB,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 27 TC 14 Z9 15 U1 2 U2 8 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1995 VL 78 IS 4 BP 946 EP 954 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA TV257 UT WOS:A1995TV25700009 PM 7580334 ER PT J AU Hanna, GM AF Hanna, GM TI Proton nuclear magnetic resonance spectroscopic detection and determination of ethylene glycol dimethacrylate as a contaminant of methyl methacrylate raw material SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CEMENT AB A simple, specific, and accurate proton nuclear magnetic resonance (H-1 NMR) spectroscopic method is presented for detection and assay of ethylene glycol dimethacrylate dimer as a contaminant of methyl methacrylate monomer. In addition to minimizing exposure of the analyst to the irritant and toxic methacrylic acid esters, the proposed method requires no sample preparation. Quantitations are based on integrals for signals of methylene protons of ethylene glycol dimethacrylate at 4.37 ppm and methyl protons of methyl methacrylate at 3.70 ppm. Analysis of 10 synthetic mixtures of the monomer with 1-11% of dimer yielded a dimer recovery of 100.5 +/- 2.05% (mean +/- standard deviation). Correspondence (correlation coefficient, r = 0.9999) between the amount of dimer added and the amount found was excellent. The proposed method measures as little as 1% of dimer. C1 ST JOHNS UNIV,COLL PHARM & ALLIED HLTH PROFESS,JAMAICA,NY 11439. RP Hanna, GM (reprint author), US FDA,NEW YORK REG LAB,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1995 VL 78 IS 4 BP 954 EP 958 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA TV257 UT WOS:A1995TV25700010 PM 7580335 ER PT J AU Rupp, HS Holland, DC Munns, RK Turnipseed, SB Long, AR AF Rupp, HS Holland, DC Munns, RK Turnipseed, SB Long, AR TI Determination of flunixin in milk by liquid chromatography with confirmation by gas chromatography mass spectrometry and selected ion monitoring SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID INDUCED BOVINE MASTITIS; MEGLUMINE; PLASMA; PHARMACOKINETICS; PHENYLBUTAZONE; ACID AB A liquid chromatographic (LC) method was developed for the determination of flunixin (FNX) in raw bovine milk, The milk was acidified and mixed with silica gel, and the mixture was packed into a chromatographic column, The column was defatted with water-saturated dichloromethane-hexane (30 + 70, v/v), and the analyte was eluted with EtOAc. The EtOAc extract was washed with water at pH 3.5, the water was discarded, and the EtOAc layer was then extracted with 0.1M NaOH. The aqueous layer was drained, passed through a primed C-18 solid-phase extraction (SPE) column, and eluted with EtOAc, The EtOAc layer was dried under Ng, taken up in a solution of MeOH-(5 mM tetrabutylammonium [TBA]-H2PO4 + 2 mM NaOH) (50 + 50), sonicated, and filtered. FNX was determined by LC using a C-18 column (ODS Hypersil), a mobile phase mixture of 58% A (MeOH) and 42% B (5 mM TBA-H2PO4 + 2 mM NaOH), and a diode-array ultraviolet detector at 285 nm, FNX was determined in raw milk at 5 spiking levels (5, 10, 20, 40, and 80 ng drug/mL milk), Absolute recoveries ranged from 69.6 to 74.4%, and relative standard deviations ranged from 1.1 to 6.9%, The limit of quantitation was 1.7 ng drug/mL milk, A lactating cow was dosed intravenously (2.2 mg/kg) with flunixin meglumine (Banamine) to generate incurred milk residues, FNX residues ranged from 7.34 ng/mL at 16 h postdose to 1.74 ng/mL at 24 h postdose, Both levels were obtained with additional beta-glucuronidase treatment (almost no incurred drug was detected at these low levels without the enzyme treatment), The presence of FNX in incurred milk was confirmed by gas chromatography/mass spectrometry with selected ion monitoring. RP Rupp, HS (reprint author), US FDA,ANIM DRUGS RES CTR,DENVER FED CTR,DEN-DO,DENVER,CO 80225, USA. NR 11 TC 21 Z9 21 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1995 VL 78 IS 4 BP 959 EP 967 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA TV257 UT WOS:A1995TV25700011 PM 7580336 ER PT J AU Turnipseed, SB Roybal, JE Hurlbut, JA Long, AR AF Turnipseed, SB Roybal, JE Hurlbut, JA Long, AR TI Gas chromatographic mass spectrometric confirmation of leucomalachite green in catfish (Ictalurus punctatus) tissue SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MALACHITE GREEN; THERMOSPRAY IONIZATION; DYES; RESIDUES; VIOLET AB A gas chromatographic/mass spectrometric (GC/MS) method was developed to confirm the presence of leucomalachite green (LMG), a metabolite of the triphenylmethane dye malachite green (MG), in catfish tissue, Residues were isolated according to a previously described liquid chromatographic (LC)/VIS spectrometric analysis of MG and LMG in fish, In our isolation procedure, analytes are extracted from tissue with acetonitrile-buffer, partitioned into CH2Cl2, and applied to neutral alumina and propylsulfonic acid solid-phase extraction cartridges, Before GC/MS analysis, extracts prepared for the LC determinative method are eluted from a cyano solid-phase extraction cartridge, extracted into organic solvent, and concentrated for GC/MS analysis, Selected ion monitoring was performed by using 5 diagnostic ions (m/z 330, 329, 253, 210, and 165) of LMG, The method was validated by confirming LMG in tissue fortified with mixtures of MG and LMG (5 and 10 ng/g each) and in tissue from fish that had been exposed to low levels of MG. RP Turnipseed, SB (reprint author), US FDA,ANIM DRUGS RES CTR,DENVER FED CTR,POB 25087,DENVER,CO 80225, USA. NR 18 TC 38 Z9 46 U1 0 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1995 VL 78 IS 4 BP 971 EP 977 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA TV257 UT WOS:A1995TV25700013 PM 7580338 ER PT J AU Whitaker, TB Springer, J Defize, PR DeKoe, WJ Coker, R AF Whitaker, TB Springer, J Defize, PR DeKoe, WJ Coker, R TI Evaluation of sampling plans used in the United States, United Kingdom, and the Netherlands to test raw shelled peanuts for aflatoxin SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID EXPORT MARKET; VARIABILITY AB The United States is a large producer and exporter of peanuts, The United Kingdom and The Netherlands are major importers of U.S. peanuts, Each country has a different guideline or legal limit for peanut products containing aflatoxin, Peanuts are tested for aflatoxin in each country by using specifically designed aflatoxin sampling plans to determine if the aflatoxin concentration in a lot of raw shelled peanuts is less than the guideline or legal limit, For raw shelled peanuts, the U.S. plan has the highest sample acceptance limit of 15 ng total aflatoxin/g, the UK plan has a sample acceptance limit of 10 ng total aflatoxin/g, and the Dutch Code of Practice (called the Dutch plan) has the lowest sample acceptance limit at 3 ng aflatoxin B-1/g. The U.S. plan uses a maximum of 3 sampling units, each weighing 21.8 kg; the UK plan uses a single sampling unit of 10 kg; and the Dutch plan uses 4 sampling units, each weighing 7.5 kg, The sampling variance is lowest for the U.S. plan and highest for the Dutch plan. The sample preparation variance is lowest for both the Dutch and UK plans and highest for the U.S. plan, primarily because of the mill type used to comminute the kernels in the sample. For a given distribution among lot concentrations, the U.S. plan accepts the greatest number of lots and the Dutch plan rejects the greatest number of lots, The average aflatoxin concentration among accepted lots is highest for the U.S. plan and lowest for the Dutch plan, The U.S. plan accepts the greatest number of good lots, whereas the Dutch plan rejects the greatest number of bad lots, The Dutch plan rejects the greatest number of good lots, whereas the U.S. plan rejects the lowest number of good lots, The Dutch plan accepts the lowest number of bad lots, whereas the UK plan accepts the greatest number of bad lots. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MATH,WASHINGTON,DC 20204. TNO,INST APPL PHYS,CTR APPL STAT,2600 GA DELFT,NETHERLANDS. HLTH PROTECT,2280 HV RIJSWIJK,NETHERLANDS. NAT RESOURCES INST,FOOD SAFETY SECT,MYCOTOXINS GRP,CHATHAM ME4 4TB,KENT,ENGLAND. RP Whitaker, TB (reprint author), N CAROLINA STATE UNIV,USDA ARS,DEPT BIOL & AGR ENGN,BOX 7625,RALEIGH,NC 27695, USA. NR 20 TC 30 Z9 31 U1 2 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1995 VL 78 IS 4 BP 1010 EP 1018 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA TV257 UT WOS:A1995TV25700019 PM 7580312 ER PT J AU Hopper, ML King, JW Johnson, JH Serino, AA Butler, RJ AF Hopper, ML King, JW Johnson, JH Serino, AA Butler, RJ TI Multivessel supercritical fluid extraction of food items in total diet study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CARBON-DIOXIDE EXTRACTION; SEPARATION; PESTICIDES; FATS AB An off-line, large capacity, multivessel supercritical fluid extractor (SFE) was designed and constructed for extraction of large samples, The extractor can simultaneously process 1-6 samples (15-25 g) by using supercritical carbon dioxide (SC-CO2), which is relatively nontoxic and nonflammable, as the solvent extraction medium, Lipid recoveries for the SFE system were comparable to those obtained by blending or Soxhlet extraction procedures, Extractions at 10 000 psi, 80 degrees C, expanded gaseous CO2 flow rates of 4-5 L/min (35 degrees C), and 1-3 h extraction times gave reproducible lipid recoveries for pork sausage (relative standard deviation [RSD], 1.32%), corn chips (RSD, 0.46%), cheddar cheese (RSD, 1.14%), and peanut butter (RSD, 0.44%), In addition, this SFE system gave reproducible recoveries (>93%) for butter fortified with cis-chlordane and malathion at the 100 ppm and 0.1 ppm levels, Six portions each of cheddar cheese, saltine crackers, sandwich cookies, and ground hamburger also were simultaneously extracted with SC-CO2 and analyzed for incurred pesticide residues, Results obtained with this SFE system were reproducible and comparable with results from organic-solvent extraction procedures currently used in the Total Diet Study; therefore, use and disposal of large quantities of organic solvents can be eliminated. C1 USDA ARS,NATL CTR AGR UTILIZAT RES,FOOD QUAL & SAFETY RES UNIT,PEORIA,IL 61604. US FDA,WINCHESTER ENGN & ANALYT CTR,WINCHESTER,MA 01890. RP Hopper, ML (reprint author), US FDA,TOTAL DIET RES CTR,POB 15905,LENEXA,KS 66285, USA. NR 20 TC 23 Z9 24 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1995 VL 78 IS 4 BP 1072 EP 1079 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA TV257 UT WOS:A1995TV25700028 PM 7580320 ER PT J AU Kaufman, BM Clower, M AF Kaufman, BM Clower, M TI Immunoassay of pesticides: An update SO JOURNAL OF AOAC INTERNATIONAL LA English DT Review ID LINKED-IMMUNOSORBENT-ASSAY; PARTICLE-BASED ELISA; INHIBITION ENZYME-IMMUNOASSAY; S-TRIAZINE HERBICIDES; SURFACE-PLASMON RESONANCE; MONOCLONAL-ANTIBODY; MICROTITER PLATE; METHYL 2-BENZIMIDAZOLECARBAMATE; ORGANOPHOSPHATE FENITROTHION; QUANTITATIVE-DETERMINATION AB Measurement of levels of pesticide residues in foods and crops most often requires extensive cleanup and instrumental techniques such as gas chromatography. Immunoassay measurement techniques, on the other hand, may be used directly on the test portion or require only minimal cleanup. Further refinements of the common antibody-enzyme-based solid-phase assays, such as use of coated magnetic particles, antibody-coated crystals, and continuous-flow devices, have extended the measurement range and applicability of these assays. Likewise, new immunoassays for pesticides have been developed, and existing assays have been refined, optimized, and more completely characterized and validated. In addition to their ability to accurately and reliably measure amounts of residues present in food and crops, immunoassays can be readily used as rapid screening methods for contaminants in field samples. We have previously reviewed much of the work in the area of pesticide immunoassay; this report updates previous information and discusses some new immunoassay techniques. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 111 TC 44 Z9 47 U1 1 U2 10 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1995 VL 78 IS 4 BP 1079 EP 1090 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA TV257 UT WOS:A1995TV25700029 PM 7580321 ER PT J AU Sack, CA AF Sack, CA TI Enhancement of ethylenethiourea recoveries in food analyses by addition of cysteine hydrochloride SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID RESIDUES; PLANTS; WATER; CROPS; SOIL; FATE AB The effectiveness of cysteine hydrochloride (Cys-HCl) as a preservative of ethylenethiourea (ETU) in product matrixes and during analysis was studied, ETU recoveries were adversely affected by certain product matrixes when fortified directly into the product, Recoveries in 8 selected food items were 0-92% when analyzed 30 min after fortification and 0-51% when analyzed after 24 h, When Cys-HCl was added to product prior to fortification, recoveries increased to 71-95% even after frozen storage for 2-4 weeks, Cys-HCl was added during analysis of 53 untreated items, Recoveries improved an average of 15% with Cys-HCl, Without Cys-HCl, recoveries were erratic (20-98%), but with Cys-HCl, recoveries were 68-113%, Other antioxidants (sodium sulfite, butylated hydroxyanisole, butylated hydroxytoluene, and vitamins A and C) also were evaluated as ETU preservatives, When lettuce was treated first with sodium sulfite and then fortified with ETU, recoveries averaged 86%; without sodium sulfite, they averaged 1%. The ether antioxidants were less effective for preserving ETU in lettuce, giving only 8-46% recoveries, The effect of oxidizers (potassium bromate, sodium hypochlorite, and hydrogen peroxide) on ETU recovery was also determined, Recovery of ETU from a baby food product (pears and pineapple) was 82%; with oxidizers, recoveries were 0-8%. RP Sack, CA (reprint author), US FDA,KANSAS CITY DIST OFF,LENEXA,KS 66285, USA. NR 22 TC 1 Z9 1 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1995 VL 78 IS 4 BP 1097 EP 1101 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA TV257 UT WOS:A1995TV25700031 PM 7580323 ER PT J AU Kenyon, AS Black, JC Layloff, TP AF Kenyon, AS Black, JC Layloff, TP TI Quality assurance in weighing SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Weighing is the most used step in any analytical procedure, and the balance is the one essential piece of laboratory equipment in all analyses. Yet weighing is a common source of error in final analytical results and can be difficult to detect, Analysts may become complacent and expect all weighings to be accurate. Our laboratory experienced a problem in weighing and found that the principal error was due to drift. The ensuing investigation into the cause led to a procedure for reducing drift, which, in turn, ensured accurate weighings that have improved quality assurance in our total operations. RP Kenyon, AS (reprint author), US FDA,DIV DRUG ANAL,1114 MARKET ST,ST LOUIS,MO 63101, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1995 VL 78 IS 4 BP 1109 EP 1111 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA TV257 UT WOS:A1995TV25700033 PM 7580325 ER PT J AU Holak, W AF Holak, W TI Determination of methylmercury after supercritical fluid extraction SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A method, using supercritical fluid extraction, for determining methylmercury in seafood has been developed to eliminate use of toxic organic solvents. Seafood samples were treated with 1N NaOH and then acidified with HCl to release CH3HgCl. After mixing the sample with cellulose powder (40 mesh) containing stearic acid modifier at 5 mg/g, the extraction was performed with supercritical CO2 under the following conditions: pressure, 200 atm; temperature, 50 degrees C; time, 20 min; and trap, 0.01N Na2S2O3 in a conical tube immersed in a flask of warm water to prevent freezing. The extract was then analyzed by a suitable method, such as cold-vapor atomic absorption spectrophotometry. The accuracy of the procedure was verified by analyzing biological standard reference materials. Several commercial seafood samples and spikes have been analyzed. RP Holak, W (reprint author), US FDA,NEW YORK REG LAB,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 6 TC 16 Z9 16 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1995 VL 78 IS 4 BP 1124 EP 1125 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA TV257 UT WOS:A1995TV25700035 PM 7580326 ER PT J AU HENRARD, DR SORIANO, V ROBERTSON, E GUTIERREZ, M STEPHENS, J DRONDA, F MILES, F PUJOL, E BUYTENDORP, M CASTRO, A CHAN, E VALLEJO, A LLIBRE, J MOTLEY, C PRILLAMAN, J CALDERON, E LEAL, M TUSET, C MARTINEZZAPICO, R CABALLERO, E ORTIZ, R EIROS, J AGUILERA, A ULLOA, F MARTIN, AM RODRIGUEZIGLESIAS, A RIVERA, A BOUZA, E ESPARZA, B MERINO, F TOR, J ESCUDERO, D RIBERA, J DELROMERO, J RODRIGUEZ, C PEDREIRA, J HEREDIA, A HEWLETT, I GONZALEZLAHOZ, J AF HENRARD, DR SORIANO, V ROBERTSON, E GUTIERREZ, M STEPHENS, J DRONDA, F MILES, F PUJOL, E BUYTENDORP, M CASTRO, A CHAN, E VALLEJO, A LLIBRE, J MOTLEY, C PRILLAMAN, J CALDERON, E LEAL, M TUSET, C MARTINEZZAPICO, R CABALLERO, E ORTIZ, R EIROS, J AGUILERA, A ULLOA, F MARTIN, AM RODRIGUEZIGLESIAS, A RIVERA, A BOUZA, E ESPARZA, B MERINO, F TOR, J ESCUDERO, D RIBERA, J DELROMERO, J RODRIGUEZ, C PEDREIRA, J HEREDIA, A HEWLETT, I GONZALEZLAHOZ, J TI PREVALENCE OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-1 (HTLV-1) AND HTLV-2 INFECTION AMONG SPANISH DRUG-USERS MEASURED BY HTLV-1 ASSAY AND HTLV-1 AND HTLV-2 ASSAY SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID II INFECTION; SEROPREVALENCE; ANTIBODY; SPAIN; I/II AB The prevalence of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infection in 1992 and 1993 was determined by testing 2,152 specimens from injection drug users living in 11 geographic areas of Spain. Results obtained by an authentic HTLV-1 and -2 test were compared with those obtained by an HTLV-1 assay. HTLV infection was identified in 7 of 11 regions, with an overall prevalence of 2.5% (range, 0.4 to 11.5%). Fourty-four (81%) of 54 subjects were infected with HTLV-2; the viral strains in the remaining 10 subjects could not be serologically typed. Underestimation of HTLV infection because of the low sensitivities of HTLV-1 enzyme immunoassays for HTLV-2 antibody was relatively low (<20%). Therefore, previous epidemiologic findings generated with HTLV-1 enzyme immunoassays appear to be reasonably accurate. Our results suggest that the rate of HTLV infection may have been increasing recently among Spanish drug users. C1 ABBOTT LABS,RETROVIRUS RES & DEV,ABBOTT PK,IL 60064. INST SALUD CARLOS 3,MADRID,SPAIN. HOSP PENITENCIARO,MADRID,SPAIN. HOSP JUAN RAMON JIMENEZ,HUELVA,SPAIN. HOSP JUAN CANALEJO,LA CORUNA,SPAIN. HOSP ST JAUME,CALELLA,SPAIN. US FDA,CTR BIOL,RETROVIRUS LAB,BETHESDA,MD 20014. RP HENRARD, DR (reprint author), ABBOTT LABS,RETROVIRUS MED RES,DEPT 9GJ,AP8-B,1 ABBOTT PK RD,ABBOTT PK,IL 60064, USA. RI Vallejo, Alejandro/I-5881-2015; Bouza, Emilio/D-8661-2014 OI Vallejo, Alejandro/0000-0001-5360-878X; Bouza, Emilio/0000-0001-6967-9267 NR 18 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 1995 VL 33 IS 7 BP 1735 EP 1738 PG 4 WC Microbiology SC Microbiology GA RD990 UT WOS:A1995RD99000010 PM 7665638 ER PT J AU ANGIOLILLO, AL SGADARI, C TAUB, DD LIAO, F FARBER, JM MAHESHWARI, S KLEINMAN, HK REAMAN, GH TOSATO, G AF ANGIOLILLO, AL SGADARI, C TAUB, DD LIAO, F FARBER, JM MAHESHWARI, S KLEINMAN, HK REAMAN, GH TOSATO, G TI HUMAN INTERFERON-INDUCIBLE PROTEIN-10 IS A POTENT INHIBITOR OF ANGIOGENESIS IN-VIVO SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ENDOTHELIAL-CELLS; GAMMA-INTERFERON; BASEMENT-MEMBRANE; GROWTH-FACTOR; IDENTIFICATION; CHEMOKINE; IP-10 AB Human interferon-inducible protein 10 (IP-10), a member of the alpha chemokine family, inhibits bone marrow colony formation, has antitumor activity in vivo, is chemoattractant for human monocytes and T cells, and promotes T cell adhesion to endothelial cells. Here we report that IP-10 is a potent inhibitor of angiogenesis in vivo. IP-10 profoundly inhibited basic fibroblast growth factor-induced neovascularization of Matrigel (prepared by H. K. Kleinman) injected subcutaneously into athymic mice. In addition, IP-10, in a dose-dependent fashion, suppressed endothelial cell differentiation into tubular capillary structures in vitro. IP-10 had no effect on endothelial cell growth, attachment, and migration as assayed in vitro. These results document an important biological property of IP-10 and raise the possibility that IP-10 may participate in the regulation of angiogenesis during inflammation and tumorigenesis. C1 CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 30 TC 486 Z9 500 U1 3 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1995 VL 182 IS 1 BP 155 EP 162 DI 10.1084/jem.182.1.155 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RF296 UT WOS:A1995RF29600018 PM 7540647 ER PT J AU JINNEMAN, KC TROST, PA HILL, WE WEAGANT, SD BRYANT, JL KAYSNER, CA WEKELL, MM AF JINNEMAN, KC TROST, PA HILL, WE WEAGANT, SD BRYANT, JL KAYSNER, CA WEKELL, MM TI COMPARISON OF TEMPLATE PREPARATION METHODS FROM FOODS FOR AMPLIFICATION OF ESCHERICHIA-COLI O157 SHIGA-LIKE TOXINS TYPE-I AND TYPE-II DNA BY MULTIPLEX POLYMERASE CHAIN-REACTION SO JOURNAL OF FOOD PROTECTION LA English DT Article DE ESCHERICHIA-COLI O157-H7; SHIGA-LIKE TOXIN; PCR ID HEMOLYTIC UREMIC SYNDROME; REACTION IDENTIFICATION; NUCLEOTIDE-SEQUENCE; CLONING; EPIDEMIOLOGY; OUTBREAK; DIARRHEA; SEROTYPE; GENES AB Escherichia coli O157:H7 has been responsible for several recent food-borne outbreaks in the United States. To protect the public health, it is essential that rapid and sensitive methods be developed for detection of this pathogen in foods. Methods were compared for preparation of template DNA for the polymerase chain reaction (PCR) from enrichments of food homogenates seeded with E. coli O157:H7. Samples were enriched for 6 h at 37 degrees C in modified tryptic soy broth supplemented with vancomycin, cefsulodin, and cefixime. Aliquots of the enrichments (10 ml or 1 ml) were analyzed by either washing twice with physiological saline or incubating with antibodies to O157 coupled to immunomagnetic beads (Dynal(R)) followed by resuspending and boiling the samples. A portion of the preparation was used in a multiplex PCR to amplify a 274-bp fragment from the sltI gene and a 364-bp fragment from the sltII gene. PCR amplification of l-ml portions of enrichment broth was successful at inoculation levels of about 10 cells per g of food. Increasing the test sample volume to 10 ml and/or using an immunomagnetic separation step improved the PCR detection sensitivity to about I cell per g; the entire analysis can be completed within 12 h. C1 US FDA,SEATTLE DIST LAB,BOTHELL,WA 98041. RP JINNEMAN, KC (reprint author), US FDA,SEAFOOD PROD RES CTR,22201 23RD DR SE,POB 3012,BOTHELL,WA 98041, USA. NR 31 TC 37 Z9 40 U1 0 U2 0 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUL PY 1995 VL 58 IS 7 BP 722 EP 726 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA RK693 UT WOS:A1995RK69300001 ER PT J AU RAFII, F HOLLAND, MA HILL, WE CERNIGLIA, CE AF RAFII, F HOLLAND, MA HILL, WE CERNIGLIA, CE TI SURVIVAL OF SHIGELLA-FLEXNERI ON VEGETABLES AND DETECTION BY POLYMERASE CHAIN-REACTION SO JOURNAL OF FOOD PROTECTION LA English DT Article DE SHIGELLA; PCR; SURVIVAL; FRESH VEGETABLES; DETECTION ID ESCHERICHIA-COLI; LISTERIA-MONOCYTOGENES; MODIFIED ATMOSPHERE; DYSENTERIAE TYPE-1; COMMON-SOURCE; TEMPERATURE; PLASMID; INVASION; GROWTH; OUTBREAKS AB Commercially prepared and packaged fresh vegetables were tested to determine the types and levels of indigenous microflora. Sixteen species of bacteria from II genera were identified and titers of up to 1 x 10(10) cells per gram of vegetable were observed. To evaluate the survival of Shigella spp. on packaged vegetables, an avirulent insertion mutant of Shigella flexneri 5 (pHS1059) was added to vegetables. This strain survived in phosphate-buffered saline at pH 7.3 at 5 to 10 degrees C for more than 3 months. It also survived for several days at both ambient and refrigerator temperatures when inoculated onto various commercially prepared vegetables. A rapid method for detecting Shigella spp. on vegetables was developed by using the polymerase chain reaction (PCR) to amplify a 118-base-pair DNA fragment from the 8. flexneri virulence-associated spa region. The PCR also generated the corresponding fragments from 8. sonnei, S. boydii, and Shigella sp. This fragment was also observed when S. flexneri cells were used to artificially contaminate sterile and nonsterile vegetables, but no amplified fragment was observed when the normal microflora of the vegetables were eluted and tested by PCR. C1 US FDA,SEAFOOD PROD RES CTR,BOTHELL,WA 98041. RP RAFII, F (reprint author), US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079, USA. NR 31 TC 16 Z9 18 U1 1 U2 4 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUL PY 1995 VL 58 IS 7 BP 727 EP 732 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA RK693 UT WOS:A1995RK69300002 ER PT J AU HEISICK, JE ROSASMARTY, LI TATINI, SR AF HEISICK, JE ROSASMARTY, LI TATINI, SR TI ENUMERATION OF VIABLE LISTERIA SPECIES AND LISTERIA-MONOCYTOGENES IN FOODS SO JOURNAL OF FOOD PROTECTION LA English DT Article DE LISTERIA MONOCYTOGENES; FOOD-BORNE; DIRECT PLATING PROCEDURE; ENUMERATION ID EPIDEMIC LISTERIOSIS; SPORADIC LISTERIOSIS; DIFFERENTIAL MEDIUM AB A direct plating procedure was developed for the enumeration of Listeria spp. and Listeria monocytogenes in foods. Both naturally contaminated foods and foods spiked with L. innocua, L. seeligeri, and L. monocytogenes were studied. The enhanced hemolysis agar (EHA) developed by Cox and modified in our study resulted in two types of agar, referred to as listeria enumeration agar (LEA) no. 1 and 2, used for products of lighter and heavier background microbial populations, respectively. On LEA plates, total Listeria spp, counts were determined by fluorescence caused by the breakdown of 4-methylumbelliferyl-beta-D-glucoside contained in EHA. L. monocytogenes counts were determined by picking a representative number of hemolytic colonies and stabbing them into a xylose agar plate to distinguish L. monocytogenes from L. seeligeri. Contamination levels of >200 Listeria cells per g of food can be accurately quantified by this procedure with >80% recovery. Counts of <200 Listeria cells per g of food were considered estimates. When the level of contamination was <100 Listeria cells per g of food, the recovery was <58%. Occasionally, with low-level inocula, Listeria was not detected. Nevertheless, when the procedure was combined with incubation of the enrichment mixture (used for the 1:10 direct plating dilution) and subsequent streaking, Listeria contamination could still be detected and the level, therefore, was determined to be between 1 and 150/g. C1 UNIV MINNESOTA,DEPT FOOD SCI & NUTR,ST PAUL,MN 55108. RP HEISICK, JE (reprint author), US FDA,MINNEAPOLIS,MN 55401, USA. NR 17 TC 28 Z9 29 U1 0 U2 0 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUL PY 1995 VL 58 IS 7 BP 733 EP 736 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA RK693 UT WOS:A1995RK69300003 ER PT J AU HEITKEMPER, DT PLATEK, SF WOLNIK, KA AF HEITKEMPER, DT PLATEK, SF WOLNIK, KA TI ELEMENTAL AND MICROSCOPIC ANALYSIS IN THE 1993 SOFT DRINK SYRINGE PRODUCT TAMPERING INCIDENTS SO JOURNAL OF FORENSIC SCIENCES LA English DT Note DE FORENSIC SCIENCE; ELEMENTAL ANALYSIS; PRODUCT TAMPERING; INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY; INDUCTIVELY COUPLED PLASMA ATOMIC EMISSION SPECTROMETRY; STEREOSCOPIC LIGHT MICROSCOPY; SCANNING ELECTRON MICROSCOPY; ENERGY DISPERSIVE X-RAY ANALYSIS ID PLASMA; SPECTROMETRY; GLASS; ZINC AB Throughout the summer of 1993, a large number of alleged product tamperings were reported to the US Food and Drug Administration concerning medical syringes and numerous other items found in carbonated soft drinks. In response to several of these claims, FDA's National Forensic Chemistry Center (NFCC) utilized microscopic and elemental analysis to help establish the veracity of the allegations. The techniques used include inductively coupled plasma atomic emission spectrometry, inductively coupled plasma mass spectrometry, stereoscopic light microscopy, scanning electron microscopy, and energy dispersive X-ray analysis. This report describes, in part, studies which were performed in response to some specific product tampering scenarios. RP HEITKEMPER, DT (reprint author), US FDA,NATL FORENS CHEM CTR,1141 CENT PKWY,CINCINNATI,OH 45202, USA. NR 7 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD JUL PY 1995 VL 40 IS 4 BP 664 EP 669 PG 6 WC Medicine, Legal SC Legal Medicine GA RL472 UT WOS:A1995RL47200031 ER PT J AU HEATON, AW LEVY, AS AF HEATON, AW LEVY, AS TI INFORMATION-SOURCES OF US ADULTS TRYING TO LOSE WEIGHT SO JOURNAL OF NUTRITION EDUCATION LA English DT Article AB This study attempted to determine whether dieters differ from nondieters in how and where they obtain nutrition and health information and whether choice of weight-loss practices is related to use of different information sources. A national telephone survey of a probability sample of 1649 adults provided detailed information on the weight-loss practices of 1431 dieters and comparable background information on 218 nondieters. Dieters were more active readers of nutrition information than were nondieters. However, their choices about type of regimen and about specific products and services were more heavily dependent on word of mouth, commercial sources, and physicians than on written information. Dieters relying on written materials were more likely to engage in healthy weight-loss regimens and less likely to engage in questionable weight-loss practices than were those relying on other sources. The pattern of information-seeking behavior observed for dieters, which indicated seater motivation to seek out written information but reliance on oral sources to inform them of specific weight-loss practices, suggests that if authoritative written information about specific weight-loss practices was available, it would be used and would likely be effective. RP HEATON, AW (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MARKET STUDIES,HFS 727,200 C ST ST SW,WASHINGTON,DC 20204, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON ST, PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0022-3182 J9 J NUTR EDUC JI J. Nutr. Educ. PD JUL-AUG PY 1995 VL 27 IS 4 BP 182 EP 190 PG 9 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA RN302 UT WOS:A1995RN30200005 ER PT J AU BARATTA, EJ AF BARATTA, EJ TI DETERMINATION OF PLUTONIUM-239/240 IN FISH IN LOW-LEVEL RADIOACTIVE OCEAN WASTE DUMP SITES SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY-ARTICLES LA English DT Article; Proceedings Paper CT 3rd International Conference on Methods and Applications of Radioanalytical Chemistry (MARC-III) CY APR 10-16, 1994 CL KAILUA KONA, HI SP Amer Nucl Soc, Div Isotopes & Radiat, Amer Nucl Soc, Div Biol & Med, Amer Nucl Soc, NO Calif Sect AB There was concern that radioactivity might find its way into the food chain, namely fish, via low-level radioactive waste Ocean Dump Sites. This led the U.S. Food and Drug Administration, in collaboration with other Federal Agencies, to the monitoring and determination of radioactivity in fish samples from these Ocean Dump Sites. The radionuclide thought to be of major concern was plutonium-239/240. These sites were monitored at various periods from 1980. The sites were located off the coasts of New Jersey, California (near San Francisco) and Massachusetts Bay. The fish samples selected were shellfish that inhabited the ocean floor and bottom-feeders. The levels of activities required sophisticated measuring techniques since for plutonium-239/240, they were below the range. After a radiochemical procedure is used to separate the plutonium, it was measured using solid-state silicon detectors. These are coupled to a computer based multichannel analyzer system. A plutonium-236 tracer is used to measure the recovery. The levels were found to be at background or in the 10 mBq range. RP BARATTA, EJ (reprint author), US FDA,WINCHESTER,MA 01890, USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU AKADEMIAI KIADO PI BUDAPEST PA PO BOX 245, H-1519 BUDAPEST, HUNGARY SN 0236-5731 J9 J RADIOAN NUCL CH AR JI J. Radioanal. Nucl. Chem.-Artic. PD JUL PY 1995 VL 194 IS 1 BP 157 EP 162 DI 10.1007/BF02037622 PG 6 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA RH446 UT WOS:A1995RH44600016 ER PT J AU ANDERSON, DL CUNNINGHAM, WC AF ANDERSON, DL CUNNINGHAM, WC TI MAPLE SYRUP ANALYSIS FOR CS-137, K, AND B, USING A LOW-BACKGROUND COUNTING SYSTEM AND PGAA SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY-ARTICLES LA English DT Article; Proceedings Paper CT 3rd International Conference on Methods and Applications of Radioanalytical Chemistry (MARC-III) CY APR 10-16, 1994 CL KAILUA KONA, HI SP Amer Nucl Soc, Div Isotopes & Radiat, Amer Nucl Soc, Div Biol & Med, Amer Nucl Soc, NO Calif Sect ID ACTIVATION-ANALYSIS; NEUTRON-ACTIVATION; FOODS AB Fifteen maple syrups were analyzed for Cs-137 and K (via K-40) by using a low-background gamma-ray counting system, and for B and K by using neutron capture prompt gamma-ray activation analysis (PGAA). For low-background gamma-ray counting, 3 sigma limits of detection (24-hour counts) were 0.03 Bq Cs-137/kg and 10 mg K/kg for 3.5-L, portions and 0.08 Bq Cs-137/kg and 20 mg K/kg for 1.0-L portions. K concentrations determined by the two methods (using 2-g portions for PGM) were in excellent agreement. The products were obtained in 1991, with one produced in Maryland, three in New York, four in Pennsylvania, two in New Hampshire, and five in Canada. The average activity concentration for Canadian syrups (2.8 Bq Cs-137/kg) was nearly a factor of 20 greater than the average (0.15 Bq Cs-137/kg) for the other syrups, but all Cs-137 activity concentrations were at least 100 times lower than those for which controls would be recommended according to Federal Radiation Council guidance. The data exhibited distinct groupings related to the sources of the products when The ratios of Cs-137 activity to K content (BqC(s)/mg(K)) were plotted vs. B concentrations. RP ANDERSON, DL (reprint author), US FDA,ELEMENTAL RES BRANCH HFS338,200 C ST SW,WASHINGTON,DC 20204, USA. NR 15 TC 5 Z9 5 U1 0 U2 0 PU AKADEMIAI KIADO PI BUDAPEST PA PO BOX 245, H-1519 BUDAPEST, HUNGARY SN 0236-5731 J9 J RADIOAN NUCL CH AR JI J. Radioanal. Nucl. Chem.-Artic. PD JUL PY 1995 VL 194 IS 2 BP 351 EP 357 DI 10.1007/BF02038434 PG 7 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA RH447 UT WOS:A1995RH44700016 ER PT J AU LEE, JS GIESE, NA ELKINS, KL YETTER, RA HOLMES, KL HARTLEY, JW MORSE, HC AF LEE, JS GIESE, NA ELKINS, KL YETTER, RA HOLMES, KL HARTLEY, JW MORSE, HC TI EFFECTS OF EXOGENOUS, NONLEUKEMOGENIC, ECOTROPIC MURINE LEUKEMIA-VIRUS INFECTIONS ON THE IMMUNE-SYSTEMS OF ADULT C57BL/6 MICE SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; CD4+ T-CELLS; LEISHMANIA-MAJOR; MAIDS; INDUCTION; DISEASE; ACTIVATION; MOUSE; RESISTANCE; EXPRESSION AB Mouse AIDS (MAIDS) develops in mice infected with a mixture of replication-competent ecotropic and mink lung cell focus-inducing murine leukemia viruses and an etiologic replication-defective virus. Helper viruses are not required for induction of MAIDS, but the time course of disease is accelerated in their presence, To understand the possible contributions of ecotropic murine leukemia viruses to MAIDS pathogenesis, we biologically cloned a series of viruses from the MAIDS-inducing LP-BM5 virus mixture, These viruses were examined for replication in tissues of infected mice and for effects on the immune system, All virus stocks replicated efficiently in mice, Infected animals showed slight lymphadenopathy and splenomegaly due primarily to B-cell proliferation associated with differentiation to immunoglobulin secretion resulting in twofold increases in serum immunoglobulin M levels; however, B-cell responses to helper T-cell-independent antigens were increased rather than decreased as in MAIDS, Analyses of CD8(+) T-cell function showed that cytotoxic T-lymphocyte responses to alloantigens were comparable in control and infected mice, Finally, we showed that infection resulted in enhanced expression of transcripts for interleukin-10, interleukin-4, and gamma interferon, These cytokines can ail contribute to B-cell activation and may promote the expansion of a target cell population for the MAIDS defective virus. C1 NIAID, IMMUNOPATHOL LAB, BETHESDA, MD 20892 USA. CBER, DBP, ENTER & SEXUALLY TRANSMITTED DIS LAB, BETHESDA, MD 20892 USA. US FDA, DIV VACCINES & RELATED PROD APPLICAT, ROCKVILLE, MD 20852 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 40 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1995 VL 69 IS 7 BP 4182 EP 4188 PG 7 WC Virology SC Virology GA RC226 UT WOS:A1995RC22600029 PM 7769677 ER PT J AU BURLINGTON, DB AF BURLINGTON, DB TI OPEN-LETTER FROM THE FDA ON PSA TESTS SO LABORATORY MEDICINE LA English DT Letter RP BURLINGTON, DB (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 SN 0007-5027 J9 LAB MED JI Lab. Med. PD JUL PY 1995 VL 26 IS 7 BP 430 EP 431 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RG432 UT WOS:A1995RG43200007 ER PT J AU YURAWECZ, MP HOOD, JK MOSSOBA, MM ROACH, JAG KU, Y AF YURAWECZ, MP HOOD, JK MOSSOBA, MM ROACH, JAG KU, Y TI FURAN FATTY-ACIDS DETERMINED AS OXIDATION-PRODUCTS OF CONJUGATED OCTADECADIENOIC ACID SO LIPIDS LA English DT Article ID LINOLEIC-ACID; DERIVATIVES; FISH; SPECTROMETRY; INHIBITION AB The objective of this study was to identify oxidation products of conjugated linoleic acid (CLA), a series of octadecadienoic acids with conjugated double bonds, which have been reported to have antioxidant and anticarcinogenic properties. Reference materials of CLA were oxidized in different concentrations of water/methanol; for example, 0.5 g octadecadienoic acid was dissolved in 50 mL methanol, and 100 mL water was added; this suspension was heated at 50 degrees C and continuously aerated. Aliquots of 5 mL were taken over time, extracted with ether, treated with diazomethane and examined by gas chromatography/mass spectrometry and/or gas chromatography with flame-ionization detection. Products identified included the following furan fatty acids (FFAs): 8,11-epoxy-8,10-octadecadienoic; 9,12-epoxy-9,11-octadecadienoic; 10,13-epoxy-10,12-octadecadienoic; and 11,14-epoxy-11,13-octadecadienoic. Conjugated dienes should be considered as a possible source of FFAs, and CLA may have products common to furans in their overall oxidative scheme. RP YURAWECZ, MP (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV SCI & APPL TECHNOL,HFS-175,200 C ST SW,WASHINGTON,DC 20204, USA. NR 21 TC 75 Z9 79 U1 1 U2 4 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD JUL PY 1995 VL 30 IS 7 BP 595 EP 598 DI 10.1007/BF02536995 PG 4 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA RK293 UT WOS:A1995RK29300003 PM 7564913 ER PT J AU METZ, CE WAGNER, RF DOI, K BROWN, DG NISHIKAWA, RM MYERS, KJ AF METZ, CE WAGNER, RF DOI, K BROWN, DG NISHIKAWA, RM MYERS, KJ TI TOWARD CONSENSUS ON QUANTITATIVE ASSESSMENT OF MEDICAL IMAGING-SYSTEMS SO MEDICAL PHYSICS LA English DT Article DE DETECTIVE QUANTUM EFFICIENCY (DQE); IDEAL OBSERVER; IMAGE QUALITY; NOISE EQUIVALENT QUANTA (NEQ); RECEIVER OPERATING CHARACTERISTIC (ROC) ANALYSIS ID SCREEN-FILM SYSTEMS; DIGITAL RADIOGRAPHY; ROC METHODOLOGY; EFFICIENCY; QUALITY; MAMMOGRAPHY; PERFORMANCE; SPECTRUM; OBSERVER; DENSITY AB Consensus has been developing over the past few decades on a number of measurements required for the laboratory assessment of medical imaging modalities. Nevertheless, understanding of the connection between these measurements and human observer performance in a broad range of tasks remains far from complete. Focusing primarily on projection radiography to provide concrete examples, this overview indicates areas in which consensus on methodology for physical image-quality measurement has been established. Concepts such as ''noise equivalent quanta'' (NEQ) and ''detective quantum efficiency'' (DQE) have been found useful for normalizing physical measurements on an absolute scale and for relating those measurements to the decision performance of a hypothetical ''ideal observer'' that effectively performs decision tasks from the image data. The connection between ideal observer performance and human performance, as determined by receiver operating characteristic (ROC) analysis, remains to be understood for many clinically relevant tasks. C1 US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,ROCKVILLE,MD 20857. RP METZ, CE (reprint author), UNIV CHICAGO,DEPT RADIOL,KURT ROSSMANN LABS RADIOL IMAGE RES,MC 2026,5841 S MARYLAND AVE,CHICAGO,IL 60637, USA. OI Nishikawa, Robert/0000-0001-7720-9951 FU NCI NIH HHS [CA24806] NR 47 TC 80 Z9 80 U1 0 U2 6 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 1995 VL 22 IS 7 BP 1057 EP 1061 DI 10.1118/1.597511 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RK269 UT WOS:A1995RK26900004 PM 7565380 ER PT J AU MCCARDELL, BA MADDEN, JM KOTHARY, MH SATHYAMOORTHY, V AF MCCARDELL, BA MADDEN, JM KOTHARY, MH SATHYAMOORTHY, V TI PURIFICATION AND CHARACTERIZATION OF A CHO CELL-ELONGATING TOXIN PRODUCED BY AEROMONAS-HYDROPHILA SO MICROBIAL PATHOGENESIS LA English DT Article DE AEROMONAS HYDROPHILA; CELL-ELONGATING TOXIN; CYTOTONIC TOXIN; EFFECT ON CHO CELLS ID CYTOTONIC ENTERO-TOXIN; CHOLERA-TOXIN; FLUID ACCUMULATION; ESCHERICHIA-COLI; CLONING; GENE; INVOLVEMENT; EXPRESSION; HEMOLYSIN; SEQUENCE AB A Chinese hamster ovary (CHO) cell-elongating toxin produced by Aeromonas hydrophila was purified from cell-free supernatant fluids by ammonium sulfate precipitation and fast protein liquid chromatography. The purified toxin had an isolelectric point (pi) of 3.7 and a molecular weight of 70 000 in a single band on isoelectric focusing (IEF) gels and SDS-PAGE gels, respectively. The N-terminal sequence, amino acids 1-20, and the amino acid content were determined from Western blots of the 70 kDa band. No homology with any known microbial toxin was found. CHO cell activity was not neutralized by antiserum to cholera toxin (anti-CT), and the toxin did not react with anti-CT on Western blots. The toxin did not increase cyclic AMP, cyclic GMP, or prostaglandin E(2) levels in CHO cells. No cytotoxic activity was observed. Intragastric administration of purified toxin (5x10(4) and 5x10(8) CHO cell units) induced intestinal fluid accumulation in infant mice. These results suggest that this toxin may be a novel cytotonic toxin distinct from previously described toxins produced by A. hydrophila or A. sobria. (C) 1995 Academic Press Limited RP MCCARDELL, BA (reprint author), US FDA,DIV VIRULENCE ASSESSMENT,WASHINGTON,DC 20204, USA. NR 27 TC 17 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD JUL PY 1995 VL 19 IS 1 BP 1 EP 9 DI 10.1006/mpat.1995.0039 PG 9 WC Immunology; Microbiology SC Immunology; Microbiology GA RZ992 UT WOS:A1995RZ99200001 PM 8559035 ER PT J AU KENNEY, NJ HUANG, RP JOHNSON, GR WU, JX OKAMURA, D MATHENY, W KORDON, E GULLICK, WJ PLOWMAN, G SMITH, GH SALOMON, DS ADAMSON, ED AF KENNEY, NJ HUANG, RP JOHNSON, GR WU, JX OKAMURA, D MATHENY, W KORDON, E GULLICK, WJ PLOWMAN, G SMITH, GH SALOMON, DS ADAMSON, ED TI DETECTION AND LOCATION OF AMPHIREGULIN AND CRIPTO-1 EXPRESSION IN THE DEVELOPING POSTNATAL MOUSE MAMMARY-GLAND SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE EGF-LIKE LIGANDS; POSTNATAL DEVELOPMENT; RT-PCR; IMMUNOCYTOCHEMISTRY; IMMUNOBLOTTING ID EPIDERMAL GROWTH-FACTOR; CARCINOMA CELL-LINE; FACTOR RECEPTOR; DUCTAL MORPHOGENESIS; MITOGENIC ACTIVITY; EPITHELIAL-CELLS; MESSENGER-RNA; FACTOR-ALPHA; FACTOR-BETA; GENE AB Amphiregulin (Ar) and Cripto-1 (Cr-1) are growth promoting peptides that share amino acid sequence homology with epidermal growth factor (EGF). The present study examined Ar and Cr-1 mRNA and protein expression during various stages of C57BL/6 mouse mammary morphogenesis. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect transcripts for Ar and Cr-1 at all stages of mammary development. Immunocytochemical (ICC) localization demonstrated that in virgin 4-week to mature 12-week-old mouse fourth inguinal mammary gland, Ar and Cr-1 are expressed in the stromal cells, luminal epithelial cells, and myoepithelial cells of the branching ducts. Ar, and to lesser extent Cr-1, were also found in the epithelial cap cells and in the luminal epithelial cells of the advancing terminal end bud (TEB) from virgin 4-week and 6-week-old mice. Western blot analysis demonstrated that both Ar (28 and 26 kDa) and Cr-1 (90, 67, 56, and 21 kDa) proteins are expressed in virgin, 13.5 day midpregnant and in the 14 day lactating mammary gland. In addition, Ar and Cr-1 are associated with developing alveolar structures as determined by ICC. These results imply that together with EGF and transforming growth factor alpha (TGF alpha), Ar and Cr-1 may play salient roles as modifiers in the morphogenesis and differentiation of the mammary gland. (C) 1995 Wiley-Liss, Inc. C1 LA JOLLA CANC RES FDN,LA JOLLA,CA 92037. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20014. SUGEN INC,PHARMACEUT,REDWOOD CITY,CA. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. IMPERIAL CANC RES FUND,MOLEC ONCOL LAB,LONDON WC2A 3PX,ENGLAND. FU NCI NIH HHS [CA54233]; NICHD NIH HHS [HD 28427] NR 35 TC 69 Z9 69 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD JUL PY 1995 VL 41 IS 3 BP 277 EP 286 DI 10.1002/mrd.1080410302 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA RE839 UT WOS:A1995RE83900001 PM 8588926 ER PT J AU GOIN, CJ MAYER, VW AF GOIN, CJ MAYER, VW TI INDUCTION OF CHROMOSOME LOSS IN SACCHAROMYCES-CEREVISIAE STRAIN D61.M BY SELECTED BENZIMIDAZOLE COMPOUNDS SO MUTATION RESEARCH-GENETIC TOXICOLOGY LA English DT Article DE CHROMOSOME LOSS; SACCHAROMYCES CEREVISIAE; BENZIMIDAZOLE ID SUSPECTED SPINDLE POISONS; ASPERGILLUS-NIDULANS; ANTHELMINTIC BENZIMIDAZOLES; FUNGAL TUBULIN; ETHYL-ACETATE; ANEUPLOIDY; NOCODAZOLE; MALSEGREGATION; DERIVATIVES; RESISTANCE AB Twenty-two benzimidazole compounds were tested for induction of chromosome loss (CHRL) in the diploid yeast Saccharomyces cerevisiae strain D61.M. Six compounds tested positive for CHRL induction: mebendazole, albendazole, RS-9237-000, fenbendazole, 2-benzimidazolylacetonitrile, and thiabendazole. Mebendazole, albendazole, RS-9237-000, and fenbendazole were strongly positive only after modified testing media were used to enhance solubility. The compounds that tested negative for CHRL were 2-phenylbenzimidazole, 2-(2-pyridyl)benzimidazole, benzimidazole, 2-aminobenzimidazole, 2-amino-5,6-dimethylbenzimidazole, 2-(aminomethyl)benzimidazole dihydrochloride hydrate, 5,6-dimethylbenzimidazole, 2-guanidinobenzimidazole, 2-methylbenzimidazole, 2-(methylmercapto)benzimidazole, 1-methyl-2-phenylbenzimidazole, 2-benzimidazolylurea, RS-65255-000, oxibendazole, and RS-95005-000. One chemical, cambendazole, tested negative or only marginally positive. Modified testing medium was also used to enhance the solubility of 2-phenylbenzimidazole, oxibendazole, and RS-95005-000. Because no toxicity was observed with oxibendazole or RS-95005-000, the negative results obtained with these two compounds could not be considered definitive. RP GOIN, CJ (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MOLEC BIOL RES & EVALUAT,WASHINGTON,DC 20204, USA. NR 38 TC 12 Z9 12 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1218 J9 MUTAT RES-GENET TOX JI Mutat. Res.-Genet. Toxicol. PD JUL PY 1995 VL 343 IS 4 BP 185 EP 199 DI 10.1016/0165-1218(95)90014-4 PG 15 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA RL229 UT WOS:A1995RL22900001 PM 7623873 ER PT J AU HOLSON, RR GOUGH, B SULLIVAN, P BADGER, T SHEEHAN, DM AF HOLSON, RR GOUGH, B SULLIVAN, P BADGER, T SHEEHAN, DM TI PRENATAL DEXAMETHASONE OR STRESS BUT NOT ACTH OR CORTICOSTERONE ALTER SEXUAL-BEHAVIOR IN MALE-RATS SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE CORTICOSTEROIDS; PRENATAL BEHAVIOR; MALE SEXUAL BEHAVIOR ID MATERNAL STRESS; PLASMA TESTOSTERONE; LUTEINIZING-HORMONE; ADULT-RATS; DEHYDROGENASE-ACTIVITY; IMMOBILIZATION STRESS; ANDROGEN BIOSYNTHESIS; PSYCHOLOGICAL STRESS; ENVIRONMENTAL-STRESS; INDUCED SUPPRESSION AB Prenatal maternal stress in rats and mice can demasculinize and feminize the sexual behavior of adult male offspring. Causal mechanisms are unknown, but one attractive hypothesis is that stress activation of maternal adrenal glucocorticoid secretion is the responsible agent. To test this hypothesis, pregnant rats were exposed to a variety of substances which enhance glucocorticoid actions. These included ACTH (20 IU of a gel preparation, SC once daily), corticosterone (CORT; 7 mg/kg SC in oil, three times daily), or dexamethasone (DEX; 0.1 mg/kg, SC once daily). Controls included noninjected dams and a positive stress control group (restraint under bright lights three times daily). All treatments reduced maternal weight gain, DEX most potently. No treatment altered litter size, stillbirths, or sex ratio, but DEX reduced weight at birth, an effect still seen at postnatal day 85. DEX, CORT, and stress reduced male adrenal weight at birth, while DEX and CORT altered sexual differentiation as measured by anogenital distance. Stress impaired adult male sexual performance but not the lordosis quotient following exposure of animals to stud males. DEX affected both measures. No other treatment had any significant effect on sexual behavior. No treatment altered plasma LH levels, either basal or in response to an estrogen challenge in adult gonadectomized males. In adulthood there was no treatment effect on stress reactivity, measured behaviorally or by plasma glucocorticoids. Correlational analysis revealed that weight gain during pregnancy was the single best predictor of subsequent sexual performance. It is concluded that prenatal dexamethasone exposure demasculinizes and feminizes male offspring. Whether the similar effect of stress is mediated solely by adrenal glucocorticoids is less certain; the ACTH and CORT treatments produced maternal plasma corticosterone levels higher than in stressed dams, yet did not affect adult sexual behavior. Because at high doses many drugs elicit a maternal stress response, including glucocorticoid secretion, these findings suggest that there may be a common effect of prenatal drug exposure upon sexual differentiation in the rat. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM,LITTLE ROCK,AR 72205. RP HOLSON, RR (reprint author), NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079, USA. NR 75 TC 84 Z9 86 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 1995 VL 17 IS 4 BP 393 EP 401 DI 10.1016/0892-0362(94)00074-N PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA RK959 UT WOS:A1995RK95900001 PM 7565485 ER PT J AU LINEBACK, D DREHER, M DEVRIES, J SLAVIN, J STEPHEN, A GORDON, D PROSKY, L SCARBOROUGH, E HENDERSON, G LEE, S OLSON, B KRITCHEVSKY, D LANZA, E LI, B VANHORN, L WOLEVER, T VANDERVEEN, J CLYDESDALE, F AF LINEBACK, D DREHER, M DEVRIES, J SLAVIN, J STEPHEN, A GORDON, D PROSKY, L SCARBOROUGH, E HENDERSON, G LEE, S OLSON, B KRITCHEVSKY, D LANZA, E LI, B VANHORN, L WOLEVER, T VANDERVEEN, J CLYDESDALE, F TI COMPLEX CARBOHYDRATES - THE SCIENCE AND THE LABEL SO NUTRITION REVIEWS LA English DT Editorial Material C1 NABISCO INC,PARSIPPANY,NJ. GEN MILLS INC,MINNEAPOLIS,MN. UNIV MINNESOTA,ST PAUL,MN 55108. UNIV SASKATCHEWAN,SASKATOON,SK,CANADA. N DAKOTA STATE UNIV,FARGO,ND 58105. US FDA,WASHINGTON,DC 20204. KRAFT GEN FOODS INC,WHITE PLAINS,NY. KELLOGG CO,BATTLE CREEK,MI. NR 8 TC 5 Z9 5 U1 1 U2 3 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD JUL PY 1995 VL 53 IS 7 BP 186 EP 193 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RU336 UT WOS:A1995RU33600002 ER PT J AU WYSOWSKI, DK GREEN, L AF WYSOWSKI, DK GREEN, L TI SERIOUS ADVERSE EVENTS IN NORPLANT USERS RELATED TO THE FOOD AND DRUG ADMINISTRATIONS MEDWATCH SPONTANEOUS REPORTING SYSTEM - REPLY SO OBSTETRICS AND GYNECOLOGY LA English DT Letter RP WYSOWSKI, DK (reprint author), US FDA,OFF EPIDEMIOL & BIOSTAT,DIV EPIDEMIOL & SURVEILLANCE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 1995 VL 86 IS 1 BP 154 EP 155 DI 10.1016/0029-7844(95)00116-9 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RE544 UT WOS:A1995RE54400031 ER PT J AU BERLIN, CM GORMAN, RL MAY, DG NOTTERMAN, DA WEISMANN, DN WILSON, GS WILSON, JT BENNETT, DR MULINARE, J KAUFMAN, P LICATA, SA TOMICH, P TROENDLE, G YAFFE, SJ COTE, CJ BANNER, W AF BERLIN, CM GORMAN, RL MAY, DG NOTTERMAN, DA WEISMANN, DN WILSON, GS WILSON, JT BENNETT, DR MULINARE, J KAUFMAN, P LICATA, SA TOMICH, P TROENDLE, G YAFFE, SJ COTE, CJ BANNER, W TI TREATMENT GUIDELINES FOR LEAD-EXPOSURE IN CHILDREN SO PEDIATRICS LA English DT Note ID CHELATION-THERAPY; 2,3-DIMERCAPTOSUCCINIC ACID; PENICILLAMINE; MOBILIZATION; MANAGEMENT; EFFICACY; INTOXICATION; PATIENT; HUMANS; CAEDTA C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. DEPT HLTH & WELF,HLTH PROTECT BRANCH,OTTAWA,ON K1A 0L2,CANADA. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC 20024. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. RP BERLIN, CM (reprint author), AMER MED ASSOC,CHICAGO,IL 60610, USA. NR 43 TC 51 Z9 53 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1995 VL 96 IS 1 BP 155 EP 160 PN 1 PG 6 WC Pediatrics SC Pediatrics GA RH182 UT WOS:A1995RH18200030 ER PT J AU BYRN, S PFEIFFER, R GANEY, M HOIBERG, C POOCHIKIAN, G AF BYRN, S PFEIFFER, R GANEY, M HOIBERG, C POOCHIKIAN, G TI PHARMACEUTICAL SOLIDS - A STRATEGIC APPROACH TO REGULATORY CONSIDERATIONS SO PHARMACEUTICAL RESEARCH LA English DT Review DE POLYMORPH; HYDRATE; AMORPHOUS FORM; DESOLVATED SOLVATE ID PHYSICOCHEMICAL PROPERTIES; SOLUTION CALORIMETRY; CRYSTAL-STRUCTURE; 2 POLYMORPHS; NMR-SPECTRA; STABILITY; STATE; FORMS AB This review describes a conceptual approach to the characterization of pharmaceutical solids. Methods. Four flow charts are presented: (1) polymorphs, (2) hydrates, (3) desolvated solvates, and (4) amorphous forms. Results. These flow charts (decision trees) are suggested as tools to develop information on pharmaceutical solids for both scientific and regulatory purposes. Conclusions. It is hoped that this review will lead to a more direct approach to the characterization of pharmaceutical solids and ultimately to faster approval of regulatory documents containing information on pharmaceutical solids. C1 US FDA,DIV ONCOL & PULM,ROCKVILLE,MD 20857. RP BYRN, S (reprint author), PURDUE UNIV,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907, USA. NR 22 TC 289 Z9 296 U1 6 U2 37 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JUL PY 1995 VL 12 IS 7 BP 945 EP 954 DI 10.1023/A:1016241927429 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA RH333 UT WOS:A1995RH33300002 PM 7494814 ER PT J AU HENDELES, L JENKINS, J TEMPLE, R AF HENDELES, L JENKINS, J TEMPLE, R TI REVISED FDA LABELING GUIDELINE FOR THEOPHYLLINE ORAL DOSAGE FORMS SO PHARMACOTHERAPY LA English DT Article C1 UNIV FLORIDA,DIV PEDIAT,GAINESVILLE,FL 32610. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. RP HENDELES, L (reprint author), UNIV FLORIDA,HLTH SCI CTR,COLL PHARM,POB 100486,GAINESVILLE,FL 32610, USA. NR 0 TC 26 Z9 26 U1 1 U2 2 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JUL-AUG PY 1995 VL 15 IS 4 BP 409 EP 427 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RL174 UT WOS:A1995RL17400001 PM 7479193 ER PT J AU GODAR, DE LUCAS, AD AF GODAR, DE LUCAS, AD TI SPECTRAL DEPENDENCE OF UV-INDUCED IMMEDIATE AND DELAYED APOPTOSIS - THE ROLE OF MEMBRANE AND DNA-DAMAGE SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID L5178Y MOUSE LYMPHOMA; CELL-DEATH; CYTOSKELETAL DAMAGE; ULTRAVIOLET-LIGHT; STRAND BREAKS; SUNBURN CELL; RADIATION; CLEAVAGE; PROTEIN; 2,4-DIAMINOTOLUENE AB The phototoxicity of each waveband region of UV radiation (UVR), ie., UVA (320-400 nm), UVB (290-320 nm) and UVC (200-290 nm), was correlated with an apoptotic mechanism using equilethal doses (10% survival) on murine lymphoma L5178Y-R cells. Apoptosis was qualitatively monitored for DNA ''ladder'' formation (multiples of 200 base pair units) using agarose gel electrophoresis, while the percentages of apoptotic and membrane-permeabilized cells were quantified over a postexposure time course using flow cytometry. The UVA1 radiation (340-400 nm) induced both an immediate (<4 h) and a delayed (>20 h) apoptotic mechanism, while UVB or UVC radiation induced only the delayed mechanism. The role of membrane damage was examined using a lipophilic free-radical scavenger, vitamin E. Immediate apoptosis and membrane permeability increased in a UVA1 dose-dependent manner, both of which were reduced by vitamin E. However, vitamin E had little effect on UVR-induced delayed apoptosis. In contrast, the DNA damaging agents 2,4- and 2,6-diaminotoluene exclusively induced delayed apoptosis. Thus, immediate apoptosis can be initiated by UVA1-induced membrane damage, while delayed apoptosis can be initiated by DNA damage. Moreover, the results suggest that immediate and delayed apoptosis are two independent mechanisms that exist beyond the realm of photobiology. RP GODAR, DE (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857, USA. NR 33 TC 92 Z9 94 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL PY 1995 VL 62 IS 1 BP 108 EP 113 DI 10.1111/j.1751-1097.1995.tb05246.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RJ710 UT WOS:A1995RJ71000016 PM 7638254 ER PT J AU CAPUTO, FA SCALLET, AC AF CAPUTO, FA SCALLET, AC TI POSTNATAL MSG TREATMENT ATTENUATES ANGIOTENSIN-II (AII) INDUCED DRINKING IN RATS SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE RAT; CIRCUMVENTRICULAR ORGANS; HYPOTHALAMUS; MSG; ANGIOTENSIN II; ISOPROTERENOL; DRINKING ID MONOSODIUM-L-GLUTAMATE; BRAIN; LESIONS; MICE; OBESITY; WATER AB Exogenous angiotensin II (AII) administration produces a robust drinking response, even in water-satiated rats. AII receptors are located in the hypothalamus and circumventricular organs (CVOs). Early postnatal administration of monosodium glutamate (MSG) produces hypothalamic/CVO damage. Therefore MSG might damage hypothalamic/CVO neurons important for producing the drinking response to AII. Few noninvasive procedures or tests exist to indicate the presence of a MSG lesion. Thus, the present study sought to determine whether altered water consumption after AII administration would signify the presence of a MSG lesion, as well as to demonstrate hypothalamic/CVO involvement in AII-induced drinking. Adult rats (dosed as neonates with MSG or saline) were given various doses of AII and the beta-adrenergic agonist isoproterenol. MSG-treated rats drank significantly less water after 100 ug/kg, sc AII than control rats. MSG-treated rats also had an unexpectedly high mortality after 100 ug/kg, sc isoproterenol. Thus, measurement of the drinking response may be a sensitive, noninvasive method for detecting neurotoxic damage to hypothalamic/CVO sites critical for the central action of AII. C1 US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. NR 26 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD JUL PY 1995 VL 58 IS 1 BP 25 EP 29 DI 10.1016/0031-9384(95)00031-D PG 5 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA RB505 UT WOS:A1995RB50500004 PM 7667423 ER PT J AU STEFANEK, ME HELZLSOUER, KJ WILCOX, PM HOUN, F AF STEFANEK, ME HELZLSOUER, KJ WILCOX, PM HOUN, F TI PREDICTORS OF AND SATISFACTION WITH BILATERAL PROPHYLACTIC MASTECTOMY SO PREVENTIVE MEDICINE LA English DT Article ID BREAST-CANCER; SUBCUTANEOUS MASTECTOMY; RISK; ONSET AB Background. Women with a first-degree relative with breast cancer are at increased risk of developing this disease. The optimal medical management of these women is unclear, with options including close breast cancer screening, bilateral prophylactic mastectomy, or participation in chemoprevention trials. Among women who undergo prophylactic bilateral mastectomy, very little is known about satisfaction with this surgery. Also, we know very little about variables related to prophylactic mastectomy decision making. Methods. Participants were women at increased risk of breast cancer due to family history. These women were categorized by self-report as not interested in prophylactic mastectomy (n = 58), interested but deciding against surgery (n = 92), or subsequently having a bilateral prophylactic mastectomy (n = 14). Information on screening practices, risk. perception, level of depression, and cancer-related worry was collected. Women completing prophylactic mastectomy reported on their satisfaction with the surgery and breast reconstruction. Results. Women selecting surgery reported more breast cancer worry. The group expressing no interest in surgery reported fewer biopsies and lower risk estimates. Women completing surgery were satisfied with their decision, although satisfaction with reconstruction was mixed. Conclusion. Factors influencing surgical decision making may include breast-cancer-related worry, biopsy history, and subjective breast cancer risk. (C) 1995 Academic Press, Inc. C1 JOHNS HOPKINS UNIV HOSP,CTR ONCOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. US FDA,DIV MAMMOG QUAL,ROCKVILLE,MD 20857. US FDA,RADIAT PROGRAM,ROCKVILLE,MD 20857. NR 27 TC 109 Z9 109 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 1995 VL 24 IS 4 BP 412 EP 419 DI 10.1006/pmed.1995.1066 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA RM398 UT WOS:A1995RM39800014 PM 7479633 ER PT J AU Collins, TFX Black, TN Ruggles, DI AF Collins, TFX Black, TN Ruggles, DI TI Developmental toxicity of Orange B given to rats in drinking water SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE Orange B; teratogenesis AB Orange B, a pyrazolone dye used to color frankfurter and sausage casings, was given in distilled drinking water to pregnant Osborne-Mendel rats throughout gestation. Assessed on the basis of fluid consumption, the dose levels of 0, 0.05, 0.1, 0.2, and 0.4% corresponded to daily Orange B consumption of 0, 67.5, 129.6, 266.6, and 532.3 mg/kg body weight, respectively. On gestation day 20, the females were euthanized and cesarean sections were performed. Throughout gestation, the treated animals consumed less fluid than did the controls, but the decreases were not dose-related. Feed consumption and maternal weight gain were not affected. No dose-related changes were seen in maternal clinical findings, implantations, fetal viability, or fetal size (weight and length). No compound-related effects were seen in sternebral development. Ossification of the interparietal bones was reduced at some dose levels, but the decreases were considered random because of absence of dose response. No dose-related effect was seen in the incidence of skeletal variations in fetuses or in the number of litters containing fetuses with skeletal variations. Skeletal development, as measured by the average number of ossified vertebrae, was similar in all groups. Soft-tissue development was not affected by dose levels of 0.05 to 0.2%. In animals treated with 0.4% Orange B, significant increases were seen in the incidence of hydroureters (severe and moderate), in the average numbers of fetuses with at least one and at least two soft-tissue variations per litter, and in the percentage of litters containing fetuses with at least two soft-tissue variations. RP Collins, TFX (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,TOXICOL EFFECTS BRANCH,HFS-507,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUL-AUG PY 1995 VL 11 IS 4 BP 387 EP 397 PG 11 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA TK629 UT WOS:A1995TK62900002 PM 8748420 ER PT J AU Johnson, GR AF Johnson, GR TI The role of heparan sulfate proteoglycan in ligand-induced activation of the epidermal growth factor receptor SO TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY LA English DT Review DE amphiregulin; epidermal growth factor receptor; fibroblast growth factor; heparan sulfate proteoglycan; heparin-binding EGF-like growth factor ID FIBROBLAST GROWTH; CELL-SURFACE; FACTOR FAMILY; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; EPITHELIAL-CELLS; FACTOR-ALPHA; AMPHIREGULIN; BINDING; EXPRESSION AB The class of mammalian biologically active polypeptides called growth factors influence the proliferation, differentiation, motility, maintenance and apoptosis of target cells. Growth factors such as epidermal growth factor(EGF) and fibroblast growth factor (FGF) elicit responses in cells by interacting with the extracellular domain of their receptors. This binding results in the activation of the intrinsic tyrosine kinase activity of the receptor and signaling. It has become apparent that accessory receptors, namely heparan sulfate (HS) proteoglycan, are required for the action of some growth factors. The mechanism of action of the FGFs serves as the prototype for this phenomenon. Amphiregulin and heparin-binding EGF-like growth factor (HB-EGF), two ligands which function via the activation of the EGF receptor have been shown to require extracellular HS proteoglycan for bioactivity. The heparin-binding regions of amphiregulin and HB-EGF have been localized to a basic similar to 20 amino acid segment which lies just adjacent to the EGF-like domain of these mitogens. Based upon experimental data, a mechanism is proposed for amphiregulin action in which the HS proteoglycan is an integral membrane protein which either presents amphiregulin to the receptor or stabilizes the bivalent binding of one molecule of amphiregulin to the activated receptor dimer. C1 US FDA, CTR BIOL EVALUAT & RES, DIV CYTOKINE BIOL, BETHESDA, MD 20892 USA. NR 64 TC 0 Z9 0 U1 0 U2 0 PU GAKUSHIN PUBL CO PI TOKYO PA YUSHOKAIN7F, 1-38-12 NIHONBASHIKAKIGARACHO, CHUO-KU, TOKYO, 103-0014, JAPAN SN 0915-7352 J9 TRENDS GLYCOSCI GLYC JI Trends Glycosci. Glycotechnol. PD JUL PY 1995 VL 7 IS 36 BP 291 EP 302 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UF320 UT WOS:A1995UF32000003 ER PT J AU DOERGE, DR DIVI, RL AF DOERGE, DR DIVI, RL TI PORPHYRIN PI-CATION AND PROTEIN RADICALS IN PEROXIDASE CATALYSIS AND INHIBITION BY ANTITHYROID CHEMICALS SO XENOBIOTICA LA English DT Article; Proceedings Paper CT Symposium on Cation-Radicals in Drug Metabolism: Chemical and Biological Perspectives, at the 6th North-American ISSX Meeting CY OCT, 1994 CL RALEIGH, NC ID CYTOCHROME-C PEROXIDASE; IODINATION; MECHANISM; LACTOPEROXIDASE; INACTIVATION; GOITROGENS; OXIDATION AB 1. Thyroid peroxidase (TPO) catalyses the iodination and phenolic coupling reactions in the biosynthesis of thyroid hormones. 2. The two-electron oxidation of TPO by H2O2 produces an oxoferryl porphyrin pi-cation radical compound I that isomerizes spontaneously to a form of compound I that contains an oxoferryl haem and the second oxidizing equivalent as an amino acid radical. 3. The pi-cation radical compound I is the catalytic species that effects iodide ion oxidation and the protein radical compound I is most likely the catalytic species that catalyses coupling. 4. Methimazole, a therapeutic, anti-hyperthyroid drug, is a suicide substrate for TPO and effects irreversible inactivation by TPO-mediated S-oxygenation to a reactive sulphenic acid that binds covalently to the prosthetic haem. 5. Sulphamethazine and other arylamines containing electron-withdrawing substituents inhibit TPO compound I-mediated reactions by reversible, mixed-type inhibition. 6. Ethylenethiourea, a fungicide metabolite, blocks TPO-mediated iodination by reacting with the catalytic iodinating species as an alternate substrate. 7. Resorcinol and related dietary flavonoids are suicide substrates for TPO and act by covalent binding to amino acid residues, presumably those radical sites present in the compound I isomer. 8. Nitrosobenzene, a known radical-trapping agent, blocks TPO-mediated coupling but not iodination or phenolic oxidations presumably by interception of the 3,5-diiodotyrosyl radical species generated during the coupling reaction. RP DOERGE, DR (reprint author), NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 21 TC 20 Z9 21 U1 0 U2 1 PU TAYLOR & FRANCIS LTD LONDON PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD JUL PY 1995 VL 25 IS 7 BP 761 EP 767 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RP938 UT WOS:A1995RP93800011 PM 7483672 ER PT J AU COHEN, SM CLYDESDALE, FM WINTER, C GRAHAM, JD WEIL, WB KROGER, M PARIZA, MW CRAWFORD, LM AVERY, D SCHEUPLEIN, RJ WEISBERGER, E AF COHEN, SM CLYDESDALE, FM WINTER, C GRAHAM, JD WEIL, WB KROGER, M PARIZA, MW CRAWFORD, LM AVERY, D SCHEUPLEIN, RJ WEISBERGER, E TI DELANEY REFORM SO SCIENCE LA English DT Letter C1 UNIV MASSACHUSETTS,AMHERST,MA 01003. UNIV CALIF DAVIS,COOPERAT EXTENS SERV,DAVIS,CA 95616. HARVARD UNIV,SCH PUBL HLTH,CTR RISK ANAL,BOSTON,MA 02115. MICHIGAN STATE UNIV,E LANSING,MI 48823. PENN STATE UNIV,UNIVERSITY PK,PA 16802. UNIV WISCONSIN,MADISON,WI 53706. ASSOC AMER VET MED COLL,WASHINGTON,DC 20005. HUDSON INST,CHURCHVILLE,VA 24421. US FDA,ROCKVILLE,MD 20857. NCI,BETHESDA,MD 20892. RP COHEN, SM (reprint author), UNIV NEBRASKA,MED CTR,OMAHA,NE 68198, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 30 PY 1995 VL 268 IS 5219 BP 1829 EP 1830 DI 10.1126/science.268.5219.1829-a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF990 UT WOS:A1995RF99000003 PM 7604249 ER PT J AU ABE, S OTA, Y DOI, Y NOMOTO, A NOMURA, T CHUMAKOV, KM HASHIZUME, S AF ABE, S OTA, Y DOI, Y NOMOTO, A NOMURA, T CHUMAKOV, KM HASHIZUME, S TI STUDIES ON NEUROVIRULENCE IN POLIOVIRUS-SENSITIVE TRANSGENIC MICE AND CYNOMOLGUS MONKEYS FOR THE DIFFERENT TEMPERATURE-SENSITIVE VIRUSES DERIVED FROM THE SABIN TYPE-3 VIRUS SO VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCES; VACCINE; GENOMES AB We have studied methods for testing the neurovirulence of live poliovaccine viruses by intraspinal inoculation into mice carrying the human poliovirus receptor gene CTS mice). A comparison of the neurovirulence of Sabin type 3 vaccine virus and related viruses using the 50% paralysis dose determined after intraspinal inoculation into the Tg mice as an index revealed a close correlation between the results of the paralysis dose in Tg mice, the neurovirulence expressed by the histopathological lesion score in monkeys, and the temperature sensitivity of the viruses. The results of experiments in the Tg mice also showed a good correlation with the humber of mutations at position 472 from U to C in the 5' noncoding region in the genomes of the viruses tested. These results strongly suggest that the neurovirulence test for oral poliomyelitis vaccine using the Tg mice is an excellent method and may be used in place of the test using monkeys. (C) 1995 Academic Press, Inc. C1 JAPAN POLIOMYELITIS RES INST,HIGASHIMURAYAMA,TOKYO 189,JAPAN. UNIV TOKYO,INST MED SCI,MINATO KU,TOKYO 108,JAPAN. CENT INST EXPTL ANIM,MIYAMAE KU,KAWASAKI,KANAGAWA 216,JAPAN. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 18 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 20 PY 1995 VL 210 IS 1 BP 160 EP 166 DI 10.1006/viro.1995.1327 PG 7 WC Virology SC Virology GA RE655 UT WOS:A1995RE65500017 PM 7793068 ER PT J AU SORIANO, V HEREDIA, A BRAVO, R GUTIERREZ, M GONZALEZLAHOZ, J AF SORIANO, V HEREDIA, A BRAVO, R GUTIERREZ, M GONZALEZLAHOZ, J TI RAPID PROGRESSION TO AIDS IN A PATIENT WITH INFECTION FROM A STRAIN OF SYNCYTIUM FORMING HIV-1 SO MEDICINA CLINICA LA French DT Note ID IMMUNODEFICIENCY-VIRUS TYPE-1; PHENOTYPE AB A woman who had recently become infected with HIV-1 after sexual relations with a seropositive subject presented a rapid fall in CD4+ T lymphocytes and evolved to AIDS 13 months after primoinfection. The most plausible cause for the rapid disease progression in this patient was the observation of a viral syncytium forming phenotype. The plasmatic viremia was high throughout the follow up despite the administration of antiretroviral drugs. C1 US FDA,MOLEC VIROL LAB,BETHESDA,MD. INST SALUD CARLOS 3,MICROBIOL SERV,E-28010 MADRID,SPAIN. RP SORIANO, V (reprint author), INST SALUD CARLOS 3,SERV ENFERMEDADES INFECCIOSAS,RAFAEL CALVO 72A,E-28010 MADRID,SPAIN. NR 19 TC 2 Z9 2 U1 0 U2 0 PU EDICIONES DOYMA S/A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0025-7753 J9 MED CLIN-BARCELONA JI Med. Clin. PD JUN 17 PY 1995 VL 105 IS 3 BP 99 EP 100 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RG772 UT WOS:A1995RG77200006 PM 7603120 ER PT J AU MYERS, MR KERSCHEN, EJ AF MYERS, MR KERSCHEN, EJ TI INFLUENCE OF INCIDENCE ANGLE ON SOUND GENERATION BY AIRFOILS INTERACTING WITH HIGH-FREQUENCY GUSTS SO JOURNAL OF FLUID MECHANICS LA English DT Article ID FLOWS; ENERGY AB A theoretical model is developed for the sound generated when a convected vortical or entropic gust encounters an airfoil at non-zero angle of attack. The theory is based on a linearization of the Euler equations about the steady subsonic flow past the airfoil. High-frequency gusts, whose wavelengths are short compared to the airfoil chord, but long compared to the displacement of the mean-flow stagnation point from the leading edge, are considered. The analysis utilizes singular-perturbation techniques and involves four asymptotic regions. Local regions, which scale on the gust wavelength, are present at the airfoil leading and trailing edges. Behind the airfoil a 'transition' region, which is similar to the transition zone between illuminated and shadow zones in optical problems, is present. In the outer region, far away from the airfoil edges and wake, the solution has a geometric-acoustics form. The primary sound generation is found to be concentrated in the local leading-edge region. The trailing edge plays a secondary role as a scatterer of the sound generated in the leading-edge region. Parametric calculations are presented which illustrate that moderate levels of airfoil steady loading can significantly affect the sound field produced by airfoil-gust interactions. C1 UNIV ARIZONA,DEPT AEROSP & MECH ENGN,TUCSON,AZ 85721. RP MYERS, MR (reprint author), US FDA,HYDRODYNAM & ACOUST BRANCH,HFZ-132,ROCKVILLE,MD 20817, USA. NR 24 TC 24 Z9 24 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-1120 J9 J FLUID MECH JI J. Fluid Mech. PD JUN 10 PY 1995 VL 292 BP 271 EP 304 DI 10.1017/S0022112095001522 PG 34 WC Mechanics; Physics, Fluids & Plasmas SC Mechanics; Physics GA RF328 UT WOS:A1995RF32800012 ER PT J AU CHU, CC ZHANG, L COYNE, LD AF CHU, CC ZHANG, L COYNE, LD TI EFFECT OF GAMMA-IRRADIATION AND IRRADIATION TEMPERATURE ON HYDROLYTIC DEGRADATION OF SYNTHETIC ABSORBABLE SUTURES SO JOURNAL OF APPLIED POLYMER SCIENCE LA English DT Article ID POLYGLYCOLIC ACID; TENSILE-STRENGTH AB The purpose of this study is to examine the effects of gamma irradiation and the relative magnitude of T-irr to T-g on the physical, mechanical, thermal, morphological, and hydrolytic properties of two types of synthetic absorbable polymers. Polyglycolic acid (PGA) and glycolide-trimethylene carbonate block copolymer fibers in the form of 2/0 size Dexon and Maxon sutures from Davis/Geck were used in this study. In addition, injection-molded PGA disks were also used for determining how different polymer morphology affected the outcomes of gamma irradiation and irradiation temperature. These two types of biomaterials were Co-60 gamma irradiated at two irradiation temperatures (55 and -78 degrees C in dry ice). Both gamma-irradiated and control specimens were immersed in a phosphate buffer solution of pH 7.44 at 37 degrees C for various durations of hydrolysis. After each predetermined duration, the specimens were removed for subsequent testing which included determinations of tensile strength, weight loss, level of crystallinity, melting temperature, intrinsic viscosity, surface morphology, and infrared spectroscopic characteristics. gamma irradiation at both irradiation temperature resulted in a faster hydrolytic degradation of these two biodegradable polymers. There was no apparent irradiation temperature effect in terms of mass loss, intrinsic viscosity, level of crystallinity, and melting temperature. However, irradiation temperature effect was evident in those properties that depended on the tie-chain segments located in the noncrystalline domains, such as tensile strength. The observed effect of irradiation temperature was attributed to chain mobility which could facilitate cage recombination of macromolecular radical pairs at the irradiation temperature lower than the glass transition temperature of the irradiated polymers. (C) 1995 John Wiley and Sons, Inc. C1 US FDA,CTR DEVICES & RADIOL HLTH,DEPT MECH & MAT SCI,ROCKVILLE,MD 20857. RP CHU, CC (reprint author), CORNELL UNIV,DEPT TEXT & APPAREL,ITHACA,NY 14853, USA. NR 38 TC 30 Z9 30 U1 1 U2 9 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-8995 J9 J APPL POLYM SCI JI J. Appl. Polym. Sci. PD JUN 6 PY 1995 VL 56 IS 10 BP 1275 EP 1294 DI 10.1002/app.1995.070561010 PG 20 WC Polymer Science SC Polymer Science GA QY130 UT WOS:A1995QY13000010 ER PT J AU NEURATH, MF MAX, EE STROBER, W AF NEURATH, MF MAX, EE STROBER, W TI PAX5 (BSAP) REGULATES THE MURINE IMMUNOGLOBULIN 3'ALPHA ENHANCER BY SUPPRESSING BINDING OF NF-ALPHA-P, A PROTEIN THAT CONTROLS HEAVY-CHAIN TRANSCRIPTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID B-CELL DIFFERENTIATION; LIGATION-MEDIATED PCR; SWITCH REGIONS; GENE; PROMOTER; ELEMENT; DOMAIN; SITES; LOCUS AB The Pad transcription factor BSAP (B-cell-specific activator protein) is known to bind to and repress the activity of the immunoglobulin heavy chain 3'alpha enhancer, We have detected an element-designated alpha P-that lies approximate to 50 bp downstream of the BSAP binding site 1 and is required for maximal enhancer activity, In vitro binding experiments suggest that the 40-kDa protein that binds to this element (NF-alpha P) is a member of the Ets family present in both B-cell and plasma-cell nuclei. However, in Five footprint analysis suggests that the alpha P site is occupied only in plasma cells, whereas the BSAP site is occupied in B cells but not in plasma cells. When Pax5 binding to the enhancer in B cells Has blocked in vivo by transfection with a triple-helix-forming oligonucleotide, an alpha P footprint appeared and endogenous immunoglobulin heavy chain transcripts increased, The tripie-helix-forming oligonucleotide also increased enhancer activity of a transfected construct in B cells, but only when the alpha P Site was intact. Pax5 thus regulates the 3'alpha enhancer and immunoglobulin gene transcription by blocking activation by NF-alpha P. C1 NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 28 TC 84 Z9 84 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 6 PY 1995 VL 92 IS 12 BP 5336 EP 5340 DI 10.1073/pnas.92.12.5336 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB804 UT WOS:A1995RB80400017 PM 7777508 ER PT J AU BRIGHT, RA TORRENCE, ME GROSS, TP AF BRIGHT, RA TORRENCE, ME GROSS, TP TI A PRELIMINARY-STUDY OF APHERETIC DEVICE AND ACE-INHIBITOR INTERACTION CAUSING ANAPHYLACTOID REACTIONS IN DIALYSIS PATIENTS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20850. RI Bright, Roselie/D-2240-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S10 EP S10 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800036 ER PT J AU DEPAOLA, A PEELER, JT RODRICK, GE AF DEPAOLA, A PEELER, JT RODRICK, GE TI EFFECT OF OXYTETRACYCLINE-MEDICATED FEED ON ANTIBIOTIC-RESISTANCE OF GRAM-NEGATIVE BACTERIA IN CATFISH PONDS SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID TRANSFERABLE R-PLASMIDS; AEROMONAS-HYDROPHILA; ANTIMICROBIAL SUSCEPTIBILITY; EDWARDSIELLA-TARDA; AGENTS; SALMONICIDA; MICROFLORA AB The effect of oxytetracycline-medicated feeds on antibiotic resistance in gram-negative bacteria from fish intestines and water in catfish ponds was investigated, In experiments in the fall and spring, using ponds with no previous history of antibiotic usage, percentages of tetracycline-resistant bacteria in catfish intestines obtained from medicated ponds increased significantly after 10 days of treatment. In the fall, resistance of the intestinal and aquatic bacteria returned to pretreatment Levels within 21 days after treatment, In the spring, resistance declined after treatment but remained higher than pretreatment levels for at least 21 days in intestinal bacteria and for 5 months in aquatic bacteria. Plesiomonas shigelloides, Aeromonas hydrophila, and Citrobacter freundii were isolated frequently in both spring and fall; Escherichia coli, Klebsiella pneumoniae, Edwardsiella tarda, and Enterobacter spp, were isolated primarily in the spring. Oxytetracycline treatment did not affect the distribution of bacterial species in the fall but may have accelerated a shift toward greater prevalence of members of the family Enterobacteriaceae ilo the spring. Multiple antibiotic resistance did not appear to be elicited by oxytetracycline treatment. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. UNIV FLORIDA,DEPT FOOD SCI & HUMAN NUTR,GAINESVILLE,FL 32611. RP DEPAOLA, A (reprint author), US FDA,GULF COAST SEAFOOD LAB,POB 158,DAUPHIN ISL,AL 36528, USA. NR 33 TC 72 Z9 79 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUN PY 1995 VL 61 IS 6 BP 2335 EP 2340 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA RA621 UT WOS:A1995RA62100041 PM 7793953 ER PT J AU FELSON, DT ANDERSON, JJ BOERS, M BOMBARDIER, C FURST, D GOLDSMITH, C KATZ, LM LIGHTFOOT, R PAULUS, H STRAND, V TUGWELL, P WEINBLATT, M WILLIAMS, HJ WOLFE, F KIESZAK, S AF FELSON, DT ANDERSON, JJ BOERS, M BOMBARDIER, C FURST, D GOLDSMITH, C KATZ, LM LIGHTFOOT, R PAULUS, H STRAND, V TUGWELL, P WEINBLATT, M WILLIAMS, HJ WOLFE, F KIESZAK, S TI AMERICAN-COLLEGE-OF-RHEUMATOLOGY PRELIMINARY DEFINITION OF IMPROVEMENT IN RHEUMATOID-ARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CONTROLLED CLINICAL-TRIAL; LOW-DOSE METHOTREXATE; DISEASE-ACTIVITY; PLACEBO; AURANOFIN; EFFICACY; DRUGS AB Objective, Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure, Multiple definitions of improvement are currently in use in different trials, The goal of this study was to promulgate a single definition for use in RA trials. Methods. Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3-step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates, With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement, Results. The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acute-phase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo-treated patients as being improved. Conclusion. We present a definition of improvement which we hope will be used widely in RA trials, C1 BOSTON UNIV,SCH MED,CTR ARTHRITIS,BOSTON,MA 02118. UNIV LIMBURG HOSP,MAASTRICHT,NETHERLANDS. UNIV TORONTO,WELLESLEY HOSP,TORONTO,ON M4Y 1J3,CANADA. VIRGINIA MASON MED CTR,SEATTLE,WA 98101. MCMASTER UNIV,HAMILTON,ON,CANADA. US FDA,ROCKVILLE,MD 20857. UNIV KENTUCKY,LEXINGTON,KY 40506. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. STANFORD UNIV,STANFORD,CA 94305. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV UTAH,SALT LAKE CITY,UT 84112. ARTHRIT CTR,WICHITA,KS. RP FELSON, DT (reprint author), AMER COLL RHEUMATOL,60 EXECUT PK S,SUITE 150,ATLANTA,GA 30329, USA. OI Tugwell, Peter/0000-0001-5062-0556 NR 15 TC 1758 Z9 1825 U1 2 U2 31 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1995 VL 38 IS 6 BP 727 EP 735 DI 10.1002/art.1780380602 PG 9 WC Rheumatology SC Rheumatology GA RC253 UT WOS:A1995RC25300001 PM 7779114 ER PT J AU Ohama, T Jung, JE Park, SI Clouse, KA Lee, BJ Hatfield, D AF Ohama, T Jung, JE Park, SI Clouse, KA Lee, BJ Hatfield, D TI Identification of new selenocysteine tRNA([Ser]Sec) isoacceptors in human cell lines SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article ID TRANSFER-RNA; TRANSFER RNASEC; MAMMALIAN-CELLS; XENOPUS OOCYTES; UGA; ANTICODON AB The selenocysteine tRNA population was examined in a human T-cell line and in a human monocytic cell line for the occurrence of additional species of selenocysteine tRNA. At least three additional (and possibly more) selenocysteine isoacceptors were found which occur in minor levels as compared to the two major selenocysteine isoacceptors previously characterized. The possible significance of these newly observed species are discussed. C1 SEOUL NATL UNIV,INST MOLEC BIOL & GENET,MOLEC GENET LAB,SEOUL 151742,SOUTH KOREA. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP Ohama, T (reprint author), NCI,NIH,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD JUN PY 1995 VL 36 IS 2 BP 421 EP 427 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UG016 UT WOS:A1995UG01600022 PM 7663446 ER PT J AU JamisDow, CA Klecker, RW Katki, AG Collins, JM AF JamisDow, CA Klecker, RW Katki, AG Collins, JM TI Metabolism of taxol by human and rat liver in vitro: A screen for drug interactions and interspecies differences SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE drug metabolism; species differences; drug interactions ID HYPERSENSITIVITY REACTIONS; HUMAN HEPATOCYTES; PHASE-II; KETOCONAZOLE; CYCLOSPORINE; TRIAL; AGENT AB Human liver slices, human liver microsomes, and rat liver microsomes were used to investigate the metabolism of H-3-taxol. The effects of drugs frequently coadministered with taxol and the effects of several cytochrome P450 system probes were studied. In all, 16 compounds were screened. After incubation with liver slices or with microsomal protein, H-3-taxol was converted into several radioactive species resolved by HPLC. There were qualitative and quantitative species differences in the metabolism of taxol. The pattern of metabolism was similar for both human-derived preparations, with 6 alpha-hydroxytaxol being the major metabolite peak. In drug interaction studies performed with human liver microsomes, cimetidine 80 mu M, and diphenhydramine 200 mu M, had little or no effect on 6 alpha-hydroxytaxol formation. Quinidine, ketoconazole, dexamethasone and Cremophor EL inhibited 6 alpha-hydroxytaxol formation with IC50 values of 36 mu M, 37 mu M, 16 mu M and 1 mu l/ml, respectively, but these concentrations exceed the usual clinical range. Cremophor EL also inhibited microsomal metabolism of taxol, but at 2 mu l/ml it had little or no effect on 6 alpha-hydroxytaxol production by human liver slices. These results suggest that: (1) taxol is metabolized by the cytochrome P450 system; (2) taxol metabolism is different in humans than in rats; (3) taxol metabolism in humans is unlikely to be altered by cimetidine, dexamethasone, or diphenhydramine, drugs regularly coadministered with taxol; (4) taxol metabolism can be indirectly affected by Cremophor EL, the formulation vehicle; (5) taxol metabolism may be altered by concentrations of ketoconazole achievable in humans only at very high doses; and (6) taxol metabolism and drug interaction studies of clinical relevance can be performed in vitro with human liver microsomes and human liver slices, but not with rat liver preparations. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD 20892. RP JamisDow, CA (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV CLIN PHARMACOL,OFF RES RESOURCES,4 RES COURT,ROOM 314,ROCKVILLE,MD 20850, USA. NR 30 TC 53 Z9 55 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1995 VL 36 IS 2 BP 107 EP 114 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA QY585 UT WOS:A1995QY58500003 PM 7767945 ER PT J AU SHIM, JS KANG, MH KIM, YH ROH, JK ROBERTS, C LEE, IP AF SHIM, JS KANG, MH KIM, YH ROH, JK ROBERTS, C LEE, IP TI CHEMOPREVENTIVE EFFECT OF GREEN TEA (CAMELLIA-SINENSIS) AMONG CIGARETTE SMOKERS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SISTER-CHROMATID EXCHANGES; BONE-MARROW CELLS; PERIPHERAL-BLOOD LYMPHOCYTES; METHYL-N-NITROSOUREA; DNA ADDUCTS; CHROMOSOME-ABERRATIONS; TANNIC-ACID; A/J MICE; TUMORIGENESIS; SMOKING AB Chemopreventive effects of green tea and coffee among cigarette smokers were examined in 52 clinically healthy male subjects between 20 and 52 years of age, Blood specimens were obtained from nonsmokers (group I), smokers (group II), smokers consuming green tea (group III), and smokers drinking coffee (group IV). The mean number of cigarette smoking years (>10 cigarettes/day) in groups II-IV ranged from 13.4 to 14.7 years, Daily intake of green tea and coffee was 2-3 cups/day for 6 months (groups III and IV), The frequencies of sister-chromatid exchange (SCE) in mitogen-stimulated peripheral lymphocytes from each experimental group were determined and analyzed statistically. SCE rates were elevated significantly in smokers (9.46 +/- 0.46) versus nonsmokers (7.03 +/- 0.33); however, the frequency of SCE in smokers who consumed green tea (7.94 +/- 0.31) was comparable to that of nonsmokers, implying that green tea can block the cigarette-induced increase in SCE frequency. Coffee, in contrast, did not exhibit a significant inhibitory effect on smoking-induced SCE. C1 KOREA RES INST CHEM TECHNOL, TOXICOL RES CTR, DAEDUCK, SOUTH KOREA. HAN NAM UNIV, DEPT FOOD & NUTR, TAEJON, SOUTH KOREA. US SUBST ABUSE & MENTAL HLTH SERV ADM, CTR SUBST ABUSE TREATMENT, ROCKVILLE, MD 20857 USA. US FDA, CTR FOOD & APPL NUTR, DIV TOXICOL RES, MOLEC TOXICOL BRANCH, WASHINGTON, DC 20204 USA. NR 48 TC 36 Z9 36 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 1995 VL 4 IS 4 BP 387 EP 391 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RC372 UT WOS:A1995RC37200013 PM 7655335 ER PT J AU SMITH, BA FULLERTON, NF HEFLICH, RH BELAND, FA AF SMITH, BA FULLERTON, NF HEFLICH, RH BELAND, FA TI DNA ADDUCT FORMATION AND T-LYMPHOCYTE MUTATION-INDUCTION IN F344 RATS IMPLANTED WITH TUMORIGENIC DOSES OF 1,6-DINITROPYRENE SO CANCER RESEARCH LA English DT Article ID ETHYL-N-NITROSOUREA; MOLECULAR DOSIMETRY; DIESEL EXHAUST; ENVIRONMENTAL CARCINOGENS; HEMOGLOBIN ADDUCTS; FISCHER-344 RATS; RISK ASSESSMENT; ANIMAL-MODELS; CANCER RISK; HPRT LOCUS AB Diesel emissions are known to induce tumors in experimental animals and are suspected of being carcinogenic in humans. Of the compounds associated with diesel exhaust, 1,6-dinitropyrene is a particularly potent mutagen and carcinogen. In these experiments, we have investigated the use of DNA adducts and T-lymphocyte mutations of 1,6-dinitropyrene as biomarkers for exposure to diesel emissions. 1,6-Dinitropyrene (0-150 mu g) was applied directly to the lungs of male F344 rats according to a protocol known to induce lung tumors. In target (lung) and surrogate (liver, WBC, and spleen lymphocytes) tissues, one major DNA adduct, N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene, was detected by HPLC and/or P-32-postlabeling analyses. The levels of this adduct reached a maximum 1-7 days following treatment and decreased to 13-50% of the peak values by 28 days after dosing. In the lung, a 2-fold increase in dose resulted in a 2-fold increase in DNA binding up to the 30-mu g dose; in the liver the same relationship was observed up to 10 mu g 1,6-dinitropyrene. At higher doses, the extent of adduct formation still increased, but the rate was much lower than that occurring at lower doses. A limiting dilution clonal assay was used to measure mutation induction at the hypoxanthine-guanine phosphoribosyltranferase locus in spleen T lymphocytes. Following treatment, the mutant frequency increased until 21 weeks, remained constant until week 40, and then began to decrease. Mutant induction was dose related, with the increase in mutant frequency being significant at doses greater than or equal to 1 mu g 1,6-dinitropyrene. These data indicate that 1,6-dinitropyrene, a constituent of diesel emissions, is metabolically activated by nitroreduction to give DNA adducts in target and surrogate tissues. They further suggest that T-lymphocyte mutations may be a more sensitive and longer-lived biomarker than DNA adducts for assessing previous exposures to nitropolycyclic aromatic hydrocarbons. C1 NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. NR 71 TC 28 Z9 28 U1 1 U2 2 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 JUN 1 PY 1995 VL 55 IS 11 BP 2316 EP 2324 PG 9 WC Oncology SC Oncology GA RA145 UT WOS:A1995RA14500020 PM 7757982 ER PT J AU ALLEVA, JJ ALLEVA, FR PESTANER, JF MCINTYRE, JM WILSON, DB AF ALLEVA, JJ ALLEVA, FR PESTANER, JF MCINTYRE, JM WILSON, DB TI IMPORTANCE OF 6 PM IN HAMSTER TIMEKEEPING EVIDENCED BY COMPUTER-ANALYSIS OF WHEEL-RUNNING ACTIVITY SO CHRONOBIOLOGY INTERNATIONAL LA English DT Article DE WHEEL-RUNNING; CLOCK MASKING; HAMSTER ESTRUS ID ESTROUS-CYCLE; CLOCK AB We addressed the question whether the clock signal for hamsters to become active occurs at sundown throughout summer or at some constant time after noon (p.m. time). Ten female golden hamsters housed in wheel cages in a windowless room were exposed to 24-h light/dark (LD) cycles simulating the equinoxes (LD 12:12), when the sun sets at 6 p.m. and rises at 6 a.m., and summer (LD 14:10, 16:8, and 18:6), when the sun sets after 6 p.m. and rises before 6 a.m. The onset of behavioral estrus, a mask-free phase marker of the same clock that controls wheel-running, was observed every 4 days, and wheel revolutions were recorded every 5 min for 52 days. Computer analysis of the 5-min values averaged for all 10 hamsters revealed a clear onset of running for each LD exposure. Time in the windowless room is referenced to mid-L (room ''noon'') of the LD cycles. Although L-off ranged from 6 p.m. in LD 12:12 (6 h after mid-L) to 9 p.m, in LD 18:6, estrus began close to 4 p.m. and running close to 6 p.m. in every LD cycle. In a second study, 13 females not tested for estrus began running closer to 7 p.m. in LD 16:8 (L-off, 8 p.m.), but when L-off was advanced to 4 p.m. they also began running on that day at 6 p.m. Testing for estrus may have made the first group of hamsters less fearful of light and therefore more responsive to a 6 p.m. clock signal to become active. It is conceivable that these nocturnal rodents voluntarily suppress, to varying degrees, overt activity from 6 p.m. standard time to sundown to avoid predators. It is noteworthy that 6 p.m. room time also marks the onset of the clock's 12-h light-sensitive period underlying hamster timekeeping. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,LAUREL,MD 20708. RP ALLEVA, JJ (reprint author), US FDA,CTR DRUG EVALUAT & RES,HFD-472,8301 MUIRKIRK RD MOD-I,LAUREL,MD 20708, USA. NR 11 TC 2 Z9 2 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0742-0528 J9 CHRONOBIOL INT JI Chronobiol. Int. PD JUN PY 1995 VL 12 IS 3 BP 166 EP 175 DI 10.3109/07420529509057262 PG 10 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA RN843 UT WOS:A1995RN84300002 ER PT J AU ALLEVA, JJ AF ALLEVA, JJ TI REPORTING OF TIME IN CHRONOBIOLOGIC STUDIES SO CHRONOBIOLOGY INTERNATIONAL LA English DT Letter RP ALLEVA, JJ (reprint author), US FDA,DIV RES & TESTING,LAUREL,MD 20708, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0742-0528 J9 CHRONOBIOL INT JI Chronobiol. Int. PD JUN PY 1995 VL 12 IS 3 BP 222 EP 224 DI 10.3109/07420529509057269 PG 3 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA RN843 UT WOS:A1995RN84300009 ER PT J AU OHANLON, TP MESSERSMITH, WA DALAKAS, MC PLOTZ, PH MILLER, FW AF OHANLON, TP MESSERSMITH, WA DALAKAS, MC PLOTZ, PH MILLER, FW TI GAMMA-DELTA T-CELL RECEPTOR GENE-EXPRESSION BY MUSCLE-INFILTRATING LYMPHOCYTES IN THE IDIOPATHIC INFLAMMATORY MYOPATHIES SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE GAMMA-DELTA T CELLS; MYOSITIS; T CELL RECEPTORS ID MYOSITIS-SPECIFIC AUTOANTIBODIES; MULTIPLE-SCLEROSIS; PERIPHERAL-BLOOD; RHEUMATOID-ARTHRITIS; CLONAL EXPANSION; GRAVES-DISEASE; SYNOVIAL-FLUID; BRAIN-LESIONS; REPERTOIRE; POLYMYOSITIS AB Autoreactive alpha beta T cells have been implicated as playing a primary pathogenic role in a group of diseases characterized by chronic muscle inflammation known as the idiopathic inflammatory myopathies (IIM). gamma delta T cells, a distinct and enigmatic class of T cells, play a less certain role in a variety of human autoimmune diseases including the IIM. In an attempt to understand the significance of gamma delta T cells in the IIM, we utilized a sensitive polymerase chain reaction (PCR) technique to evaluate gamma delta T cell receptor (TCR) gene expression in 45 muscle biopsies obtained from 42 IIM patients (17 polymyositis, 12 dermatomyositis, and 13 inclusion body myositis). gamma delta TCR gene expression was not detected in 36 specimens, the majority of muscle biopsies surveyed. gamma delta TCR gene expression by muscle-infiltrating lymphocytes was detected among nine clinically heterogeneous patients. We further analysed the junctional sequence composition of the V gamma 3 and V delta 1 transcripts, whose expression was prominent among gamma delta positive patients. DNA sequence analysis of V gamma 3 amplification products from two patients revealed the presence of several productively rearranged transcripts with amino acid sequence similarities within the V gamma 3-N-J gamma junctional domain. No amino acid sequence similarities were evident within the V delta-N-D delta-N-J delta region of V delta 1 transcripts amplified from four patients, although a distinct and dominant clonotype was detected from each patient. Our cumulative data suggest that unlike alpha beta T cells, gamma delta T cells do not play a prominent pathologic role in the IIM. In fact, the sporadic nature of gamma delta TCR gene expression detected among these patients implies that gamma delta T cell infiltration, when it occurs, is a secondary event perhaps resulting from non-specific inflammatory processes. C1 NINCDS,BETHESDA,MD 20892. NIAMSD,BETHESDA,MD 20892. RP OHANLON, TP (reprint author), US FDA,CTR BIOL EVALUAT & RES,MOLEC IMMUNOL LAB,NIH 29B,ROOM 2G11,HFM-521,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Miller, Frederick/0000-0003-2831-9593 NR 58 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUN PY 1995 VL 100 IS 3 BP 519 EP 528 PG 10 WC Immunology SC Immunology GA RB163 UT WOS:A1995RB16300024 PM 7774065 ER PT J AU BALIAN, JD SUKHOVA, N HARRIS, JW HEWETT, J PICKLE, L GOLDSTEIN, JA WOOSLEY, RL FLOCKHART, DA AF BALIAN, JD SUKHOVA, N HARRIS, JW HEWETT, J PICKLE, L GOLDSTEIN, JA WOOSLEY, RL FLOCKHART, DA TI THE HYDROXYLATION OF OMEPRAZOLE CORRELATES WITH S-MEPHENYTOIN METABOLISM - A POPULATION STUDY SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GENETIC-POLYMORPHISM; DRUG-METABOLISM; BLADDER-CANCER; OXIDATION; DEBRISOQUIN; CAUCASIANS; RATIO AB We compared omeprazole and mephenytoin as probes for the CYP2C19 metabolic polymorphism, Single oral doses of omeprazole (20 mg) or mephenytoin (100 mg) were administered at least 1 week apart to 167 healthy volunteers, Mephenytoin metabolism was measured using the amount of 4'-hydroxymephenytoin and the S/R ratio of mephenytoin in an 8-hour urine collection, Omeprazole hydroxylation was measured using the ratio of omeprazole to 5'-hydroxyomeprazole in serum 2 hours after dosing, All three methods separated poor- or extensive-metabolizer phenotypes with complete concordance, Omeprazole hydroxylation correlated with the S/R ratio of mephenytoin in extensive metabolizers (r(2) = 0.681; P < 0.001), Genotyping tests showed that six poor metabolizers of omeprazole were homozygous for a single base pair mutation in exon 5 of CYP2C19. These results support the hypothesis that omeprazole 5'-hydroxylation cosegregates with the CYP2C19 metabolic polymorphism. C1 GEORGETOWN UNIV,MED CTR,DEPT MED,DIV CLIN PHARMACOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,WASHINGTON,DC 20007. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. NIEHS,RES TRIANGLE PK,NC 27709. RI Goldstein, Joyce/A-6681-2012 FU NIGMS NIH HHS [T32-GM 08386] NR 38 TC 135 Z9 141 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 1995 VL 57 IS 6 BP 662 EP 669 DI 10.1016/0009-9236(95)90229-5 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RE818 UT WOS:A1995RE81800008 PM 7781266 ER PT J AU MESSIER, RH DOMKOWSKI, PW ALY, HM JONES, JL HILBERT, SL CRESCENZO, DG ABDELFATTAH, AS WALLACE, RB BASS, BL HOPKINS, RA AF MESSIER, RH DOMKOWSKI, PW ALY, HM JONES, JL HILBERT, SL CRESCENZO, DG ABDELFATTAH, AS WALLACE, RB BASS, BL HOPKINS, RA TI ADENINE-NUCLEOTIDE DEPLETION IN CRYOPRESERVED HUMAN CARDIAC VALVES - THE STUNNED LEAFLET INTERSTITIAL CELL-POPULATION SO CRYOBIOLOGY LA English DT Article ID HEART-VALVES; HOMOGRAFTS; VIABILITY; STEP AB Preparation protocols for human cardiac valves are intended to minimize cytotoxicity because it has been thought that viable leaflet interstitial cells may enhance homograft durability. Preimplantation factors influencing the status of these cells at the time of transplantation include ischemia, disinfection, and cryopreservation freezing programs. In these experiments, ade:nine nucleotide quantitation was undertaken to assess metabolic consequences of preparation; preharvest ischemia served as an independent variable to examine the relationship between time of procurement (postmortem) and high-energy phosphate status of the cryopreserved leaflets at thaw. Nucleotides were measured using high-performance liquid chromatography performed on extracts of semilunar cusps from 25 cryopreserved human valves with documented ischemic times. Results indicate total adenine nucleotides (TAN; [ATP] + [ADP] + [AMP], in nmol TAN/mg leaflet protein) are higher (P < 0.05) after <2 h of harvest ischemia (1.16 +/- 0.36) than with ischemic times of 3-6 h (undetected), 7-12 h (0.18 +/- 0.07), and 13-20 h (0.06 +/- 0.06). Depletion of ATP was similar, with many leaflets devoid of detectable levels. Net utilization of leaflet energy stores demonstrates time dependency when assayed after completed processing. However, relatively elevated catabolites, even with brief ischemia, and infrequently identified ATP, ADP, and AMP, suggest a consumption so accelerated that the following cryopreservation it is virtually independent of procurement-associated ischemia. We conclude resumption of a functional cell population obligates significant de novo, phosphoanhydride boned reformation or a repopulation of dead/dying interstitial cells from a subset surviving the apparently severe rigors of valve preparation. (C) 1995 Academic Press, Inc. C1 GEORGETOWN UNIV,MED CTR,DEPT SURG,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT PHYSIOL,WASHINGTON,DC 20007. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT SURG,RICHMOND,VA 23298. OFF SCI & TECHNOL,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD. US FDA,ROCKVILLE,MD 20857. NR 23 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD JUN PY 1995 VL 32 IS 3 BP 199 EP 208 DI 10.1006/cryo.1995.1019 PG 10 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA RA355 UT WOS:A1995RA35500001 PM 7781324 ER PT J AU Rafii, F Cerniglia, CE AF Rafii, F Cerniglia, CE TI Reduction of azo dyes and nitroaromatic compounds by bacterial enzymes from the human intestinal tract SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE azo dyes; nitroaromatic; azoreductase; nitroreductase; anaerobic bacteria ID CLOSTRIDIUM-PERFRINGENS; AZOREDUCTASE; MICROFLORA; METABOLISM AB Several anaerobic bacteria from the human intestinal tract are capable of reducing azo dyes and nitropolycyclic aromatic hydrocarbons to the corresponding aromatic amines with enzymes that have azoreductase and nitroreductase activities. The majority of bacteria with these activities belong to the genera Clostridium and Eubacterium. The azoreductases and nitroreductases from three Clostridium strains and one Eubacterium strain were studied. Both enzymes were produced constitutively in each of the bacteria; the enzymes from various bacteria had different electrophoretic mobilities. The azoreductases from all of the bacteria had immunological homology, as was evident from the cross-reactivity of an antibody raised against the azoreductase of C. perfringens with azoreductases from other bacteria. Comparison of azoreductases and nitroreductases showed that they both had identical electrophoretic mobilities on polyacrylamide gels and reacted with the antibody against the azoreductase from C. perfringens. Furthermore, the nitroaromatic compounds competitively inhibited the azoreductase activity. The data indicate that the reduction of both nitroaromatic compounds and azo dyes may be carried out by the same enzyme, which is possibly a flavin adenine dinucleotide dehydrogenase that is synthesized throughout the cell and not associated with any organized subcellular structure. 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. NR 15 TC 21 Z9 21 U1 0 U2 16 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1995 VL 103 SU 5 BP 17 EP 19 DI 10.2307/3432471 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA V42AS UT WOS:000202841000005 PM 8565901 ER PT J AU SHAH, VP LESKO, LJ WILLIAMS, RL AF SHAH, VP LESKO, LJ WILLIAMS, RL TI IN-VITRO EVALUATION OF TRANSDERMAL DRUG-DELIVERY SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS LA English DT Article DE IN VITRO RELEASE; TRANSDERMAL IN VITRO RELEASE ID THERAPEUTIC SYSTEMS; SKIN PERMEATION; NITROGLYCERIN; ESTRADIOL; PROFILE; PATCHES AB The article provides an overview of in vitro evaluation of transdermal drug delivery systems. A simple in vitro release methodology applicable to all transdermal systems is described which can be used as a quality control test. C1 US FDA,CTR DRUG EVALUAT & RES,OFF GENER DRUGS,ROCKVILLE,MD 20855. NR 12 TC 5 Z9 5 U1 1 U2 4 PU WISSENSCHAFTLICHE VERLAG GMBH PI STUTTGART 10 PA BIRKENWALDSTRASSE 44 POSTFACH 105339, W-7000 STUTTGART 10, GERMANY SN 0939-6411 J9 EUR J PHARM BIOPHARM JI Eur. J. Pharm. Biopharm. PD JUN PY 1995 VL 41 IS 3 BP 163 EP 167 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RG943 UT WOS:A1995RG94300003 ER PT J AU SHAH, VP DIGHE, SV HUANG, YC FANG, F HARE, DB LESKO, LJ WILLIAMS, RL AF SHAH, VP DIGHE, SV HUANG, YC FANG, F HARE, DB LESKO, LJ WILLIAMS, RL TI NEW AND GENERIC TRANSDERMAL NITROGLYCERIN SYSTEMS - REGULATORY CONSIDERATIONS SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS LA English DT Article DE TRANSDERMAL NITROGLYCERIN; DRUG APPROVAL; GENERIC APPROVAL AB The article provides an overview of recent development at the Food and Drug Administration relative to marketing applications for new and abbreviated applications for transdermal nitroglycerin systems. The article also provides regulatory history and chemistry, manufacturing and control requirements. In addition, in vivo and in vitro requirements for transdermal nitroglycerin patches are also described. C1 US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20855. NR 7 TC 3 Z9 3 U1 0 U2 0 PU WISSENSCHAFTLICHE VERLAG GMBH PI STUTTGART 10 PA BIRKENWALDSTRASSE 44 POSTFACH 105339, W-7000 STUTTGART 10, GERMANY SN 0939-6411 J9 EUR J PHARM BIOPHARM JI Eur. J. Pharm. Biopharm. PD JUN PY 1995 VL 41 IS 3 BP 189 EP 193 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RG943 UT WOS:A1995RG94300007 ER PT J AU BROTMAN, M GIANNELLA, RA ALM, PF BAUMAN, H BENNETT, AR BLACK, RE BRUHN, CM COHEN, MB GORBACH, SL KAPER, JB ROBERTS, MR STANECK, JL TAYLOR, S TROUTT, HF BELL, BP BUCHANAN, RL DURHAM, K FENG, P FORMAN, CT GALLER, RG GRAVANI, RB HALL, RB HANCOCK, DD HOLLINGSWORTH, J KARMALI, MA KEUSCH, GT MARSDEN, JL OSTERHOLM, MT REAGAN, JO ROBERTS, T SIEGLER, RL SWERDLOW, DL TARR, PI COWMAN, GL GOODFELLOW, SJ GRIFFIN, PM HALL, M HAMILTON, F HARRINGTON, RE KARR, KJ LANG, DR MADDEN, JM NORCROSS, MA SAVAGE, K SHANK, F TAYLOR, DN AF BROTMAN, M GIANNELLA, RA ALM, PF BAUMAN, H BENNETT, AR BLACK, RE BRUHN, CM COHEN, MB GORBACH, SL KAPER, JB ROBERTS, MR STANECK, JL TAYLOR, S TROUTT, HF BELL, BP BUCHANAN, RL DURHAM, K FENG, P FORMAN, CT GALLER, RG GRAVANI, RB HALL, RB HANCOCK, DD HOLLINGSWORTH, J KARMALI, MA KEUSCH, GT MARSDEN, JL OSTERHOLM, MT REAGAN, JO ROBERTS, T SIEGLER, RL SWERDLOW, DL TARR, PI COWMAN, GL GOODFELLOW, SJ GRIFFIN, PM HALL, M HAMILTON, F HARRINGTON, RE KARR, KJ LANG, DR MADDEN, JM NORCROSS, MA SAVAGE, K SHANK, F TAYLOR, DN TI CONSENSUS CONFERENCE STATEMENT - ESCHERICHIA-COLI O157-H7 INFECTIONS - AN EMERGING NATIONAL-HEALTH CRISIS, JULY 11-13, 1994 SO GASTROENTEROLOGY LA English DT Editorial Material ID HEMOLYTIC-UREMIC SYNDROME; HEMORRHAGIC COLITIS; 0157-H7; TOXIN; EPIDEMIOLOGY; PATHOGEN; DIARRHEA; CULTURES AB This statement was prepared by a nonadvocate panel of experts based an (1) presentations by investigators working in areas relevant to the consensus questions during a 2-day public session, (2) questions and statements from conference attendees during open discussion periods that are part of the public session, and (3) closed deliberations by the panel during the remainder of the second dat and the morning of the third. This statement is an independent report of the panel and is not a policy statement of the American Gastroenterological Association, the American Gastroenterological Association Foundation (now known as the American Digestive Health Foundation) or the cosponsors listed at the end at this statement. C1 CALIF PACIFIC MED CTR,DEPT MED,SAN FRANCISCO,CA. UNIV CINCINNATI,COLL MED,DEPT INTERNAL MED,DIV DIGEST DIS,CINCINNATI,OH 45267. ALM CONSULTING SERV,SAN ANTONIO,TX. FOX BENNETT & TURNER,WASHINGTON,DC. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT INT HLTH,BALTIMORE,MD. UNIV CALIF DAVIS,CTR CONSUMER RES,DAVIS,CA. CHILDRENS HOSP,MED CTR,DIV PEDIAT GASTROENTEROL & NUTR,CINCINNATI,OH 45229. TUFTS UNIV,SCH MED,BOSTON,MA 02111. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,DEPT MED,BALTIMORE,MD 21201. FLORIDA DEPT AGR & CONSUMER SERV,TALLAHASSEE,FL. UNIV CINCINNATI HOSP,DEPT PATHOL & LAB MED,CINCINNATI,OH. UNIV NEBRASKA,DEPT FOOD SCI & TECHNOL,LINCOLN,NE 68583. UNIV ILLINOIS,DEPT VET CLIN MED,URBANA,IL 61801. WASHINGTON DEPT HLTH,CTR DIS CONTROL & PREVENT,SEATTLE,WA. USDA ARS,EASTERN REG RES CTR,MICROBIAL FOOD SAFETY RES UNIT,PHILADELPHIA,PA 19118. US FDA,CTR FOOD SAFETY & APPL NUTR,OFF CONSTITUENT OPERAT,WASHINGTON,DC 20204. US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204. FOREMAN & HEIDEPRIEM INC,WASHINGTON,DC. LOIS JOY GALLER FDN HEMOLYT UREM SYNDROME INC,VALLEY STREAM,NY. CORNELL UNIV,INST FOOD SCI,DEPT FOOD SCI,DIV FOOD SAFETY EXTENS,ITHACA,NY 14853. US FDA,CTR FOOD SAFETY & APPL NUTR,DIV VIRULENCE ASSESSMENT,WASHINGTON,DC 20204. DEPT VET CLIN SCI,FIELD DIS INVEST UNIT,PULLMAN,WA. USDA,FOOD SAFETY & INSPECT SERV,WASHINGTON,DC 20250. HOSP SICK CHILDREN,DEPT MICROBIOL,TORONTO,ON M5G 1X8,CANADA. TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,DIV GEOG MED & INFECT DIS,BOSTON,MA 02111. AMI FDN,AMER MEAT INST,ARLINGTON,VA. MINNESOTA DEPT HLTH,ACUTE DIS & EPIDEMIOL SECT,MINNEAPOLIS,MN. NATL LIVE STEOCK & MEAT BOARD,DEPT RES MEAT SCI,DIV PROD TECHNOL,CHICAGO,IL. USDA,DIV ECON RES SERV,FOOD SAFETY & REGULAT SECT,WASHINGTON,DC 20250. UNIV UTAH,SCH MED,DEPT PEDIAT,DIV NEPHROL,SALT LAKE CITY,UT. CTR DIS CONTROL & PREVENT,FOODBORNE & DIARRHEAL DIS BRANCH,DIV BACTERIAL & MYCOT DIS,ATLANTA,GA 30341. UNIV WASHINGTON,CHILDRENS HOSP & MED CTR,DEPT PEDIAT,DIV GASTROENTEROL,SEATTLE,WA. UNIV CINCINNATI,COLL MED,DEPT INTERNAL MED,DIV DIGEST DIS,CINCINNATI,OH 45267. CALIF PACIFIC MED CTR,DEPT MED,SAN FRANCISCO,CA. NATL CATTLEMENS ASSOC,ENGLEWOOD,CO. ABC RES CORP,DEPT MICROBIOL,GAINESVILLE,FL. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV BACTERIAL & MYCOT DIS,ATLANTA,GA. AMER GASTROENTEROL ASSOC FDN,BETHESDA,MD. NIDDKD,DIV DIGEST DIS & NUTR,BETHESDA,MD 20892. NATL RESTAURANT ASSOC,TECH SERV,WASHINGTON,DC. NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. FOOD MKT INST,WASHINGTON,DC. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. WALTER REED ARMY INST RES,DEPT BACTERIAL DIS,DIV COMMUNICABLE DIS & IMMUNOL,WASHINGTON,DC. NR 55 TC 39 Z9 39 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 1995 VL 108 IS 6 BP 1923 EP 1934 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RA378 UT WOS:A1995RA37800040 ER PT J AU REEVES, JP LO, CY KLINMAN, DM EPSTEIN, SL AF REEVES, JP LO, CY KLINMAN, DM EPSTEIN, SL TI MOUSE MONOCLONAL-ANTIBODIES TO HUMAN-IMMUNODEFICIENCY-VIRUS GLYCOPROTEIN-120 GENERATED BY REPEATED IMMUNIZATION WITH GLYCOPROTEIN-120 FROM A SINGLE ISOLATE, OR BY SEQUENTIAL IMMUNIZATION WITH GLYCOPROTEIN-120 FROM 3 ISOLATES SO HYBRIDOMA LA English DT Article ID RECOMBINANT VACCINIA VIRUSES; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; TYPE-1; GP120; CD4; SPECIFICITY; RESPONSES; BINDING; GP160 AB Mouse hybridomas were isolated that produce monoclonal antibodies (MAbs) to several regions of the HIV envelope, gp120, which may be used to map immunogenic regions in animal and human immunity, One series of MAbs was generated by repeated immunization with recombinant gp120 (rgp120) from a single isolate, and a second series by sequential immunization with rgp120 from three isolates, All MAbs bound to rgp120(IIIB), but only one bound well to cell surface-expressed gp160, Synthetic peptides spanning much of the length of gp120 were used to map MAb reactivity, Two MAbs were mapped to the C1 region, one to the C2 region, and three to the C5 region by this approach, Six distinct epitopes were detected by competitive binding analysis. One MAb binding in the C1 region blocks binding of CD4 to rgp120(IIIB), binds by ELISA to rgp120(MN) (an isolate not used during immunization), and binds to cell surface-expressed gp160. These hybridomas will be made available to the scientific community through a hybridoma culture facility. C1 US FDA,OFF THERAPEUT RES & REVIEW,DIV CELLULAR & GENE THERAPIES,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. US FDA,OFF VACCINE RES & REVIEW,DIV VIRAL PROD,RETROVIRUS LAB,BETHESDA,MD 20892. NR 22 TC 15 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1995 VL 14 IS 3 BP 235 EP 242 DI 10.1089/hyb.1995.14.235 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA RF575 UT WOS:A1995RF57500004 PM 7590785 ER PT J AU EPSTEIN, S AF EPSTEIN, S TI MONOCLONAL-ANTIBODIES - 46-2, ANTI-GP120 SO HYBRIDOMA LA English DT Note RP EPSTEIN, S (reprint author), US FDA,CBER,OTRR,DCGT,1401 ROCKVILLE PIKE,HFM-521,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1995 VL 14 IS 3 BP 291 EP 291 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA RF575 UT WOS:A1995RF57500013 ER PT J AU EPSTEIN, S AF EPSTEIN, S TI MONOCLONAL-ANTIBODIES - 46-3, ANTI-GP120 SO HYBRIDOMA LA English DT Note RP EPSTEIN, S (reprint author), US FDA,CBER,OTRR,DCGT,1401 ROCKVILLE PIKE,HFM-521,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1995 VL 14 IS 3 BP 292 EP 292 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA RF575 UT WOS:A1995RF57500014 ER PT J AU EPSTEIN, S AF EPSTEIN, S TI MONOCLONAL-ANTIBODIES - 46-4, ANTI-GP120 SO HYBRIDOMA LA English DT Note RP EPSTEIN, S (reprint author), US FDA,CBER,OTRR,DCGT,1401 ROCKVILLE PIKE,HFM-521,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1995 VL 14 IS 3 BP 293 EP 293 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA RF575 UT WOS:A1995RF57500015 ER PT J AU EPSTEIN, S AF EPSTEIN, S TI MONOCLONAL-ANTIBODIES - 46-5, ANTI-GP120 SO HYBRIDOMA LA English DT Note RP EPSTEIN, S (reprint author), US FDA,CBER,OTRR,DCGT,1401 ROCKVILLE PIKE,HFM-521,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1995 VL 14 IS 3 BP 294 EP 294 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA RF575 UT WOS:A1995RF57500016 ER PT J AU EPSTEIN, S AF EPSTEIN, S TI MONOCLONAL-ANTIBODIES - 55-2, ANTI-GP120 SO HYBRIDOMA LA English DT Note RP EPSTEIN, S (reprint author), US FDA,CBER,OTRR,DCGT,1401 ROCKVILLE PIKE,HFM-521,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1995 VL 14 IS 3 BP 295 EP 295 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA RF575 UT WOS:A1995RF57500017 ER PT J AU EPSTEIN, S AF EPSTEIN, S TI MONOCLONAL-ANTIBODIES - 55-6, ANTI-GP120 SO HYBRIDOMA LA English DT Note RP EPSTEIN, S (reprint author), US FDA,CBER,OTRR,DCGT,1401 ROCKVILLE PIKE,HFM-521,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1995 VL 14 IS 3 BP 296 EP 296 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA RF575 UT WOS:A1995RF57500018 ER PT J AU EPSTEIN, S AF EPSTEIN, S TI MONOCLONAL-ANTIBODIES - 55-36, ANTI-GP120 SO HYBRIDOMA LA English DT Note RP EPSTEIN, S (reprint author), US FDA,CBER,OTRR,DCGT,1401 ROCKVILLE PIKE,HFM-521,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1995 VL 14 IS 3 BP 297 EP 297 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA RF575 UT WOS:A1995RF57500019 ER PT J AU EPSTEIN, S AF EPSTEIN, S TI MONOCLONAL-ANTIBODIES - 55-83, ANTI-GP120 SO HYBRIDOMA LA English DT Note RP EPSTEIN, S (reprint author), US FDA,CBER,OTRR,DCGT,1401 ROCKVILLE PIKE,HFM-521,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1995 VL 14 IS 3 BP 298 EP 298 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA RF575 UT WOS:A1995RF57500020 ER PT J AU EPSTEIN, S AF EPSTEIN, S TI MONOCLONAL-ANTIBODIES - 55-100, ANTI-GP120 SO HYBRIDOMA LA English DT Note RP EPSTEIN, S (reprint author), US FDA,CBER,OTRR,DCGT,1401 ROCKVILLE PIKE,HFM-521,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1995 VL 14 IS 3 BP 299 EP 299 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA RF575 UT WOS:A1995RF57500021 ER PT J AU GAZZANOSANTORO, H PARENT, JB CONLON, PJ KASLER, HG TSAI, CM LILLELGHANIAN, DA HOLLINGSWORTH, RI AF GAZZANOSANTORO, H PARENT, JB CONLON, PJ KASLER, HG TSAI, CM LILLELGHANIAN, DA HOLLINGSWORTH, RI TI CHARACTERIZATION OF THE STRUCTURAL ELEMENTS IN LIPID-A REQUIRED FOR BINDING OF A RECOMBINANT FRAGMENT OF BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN RBPI(23) SO INFECTION AND IMMUNITY LA English DT Article ID AMINO-TERMINAL FRAGMENT; GRAM-NEGATIVE BACTERIA; POLYMORPHONUCLEAR LEUKOCYTES; HUMAN NEUTROPHILS; LIPOPOLYSACCHARIDE; ENDOTOXIN; PURIFICATION; RESPONSES; COMPONENT; LPS AB Both human bactericidal/permeability-increasing protein (BPI) and a recombinant amino-terminal fragment of BPI (rBPI(23)) have been shown to bind with high affinity to the lipid A region of lipopolysaccharide (LPS) (H. Gazzano-Santoro, J. B. Parent, L. Grinna, A. Horwitz, T. Parsons, G. Theofan, P. Elsbach, J. Weiss, and P. J. Conlon, Infect. Immun. 60:4754-4761, 1992). In the present study, lipid A preparations derived from bacterial LPS as well as synthetic lipid A's and various lipid A analogs were used to determine the structural elements required for rBPI(23) binding. rBPI(23) bound in vitro to a variety of synthetic and natural lipid A preparations (both mono- and diphosphoryl forms), including lipid A's prepared from Escherichia coli and Salmonella, Neisseria, and Rhizobium species. Binding does not require that the origin of negative charge be phosphate, since rBPI(23) bound with high affinity to lipid A's isolated from Rhizobium species that contain carboxylate (Rhizobium trifolii) or sulfate (Rhizobium meliloti) anionic groups and lack phosphate. Lipid A acyl chains are important, since rBPI(23) did not bind to four synthetic variants of the beta(1-6)-linked D-glucosamine disaccharide lipid A head group, all devoid of acyl chains. rBPI(23) also bound weakly to lipid X, a monosaccharide lipid precursor of LPS corresponding to the reducing half of lipid A. Lipid IVA, a precursor identical to E. coli lipid A except that it lacks the 2' and 3' acyl chains, was the simplest structure identified in this study that rBPI(23) bound with high affinity. These results demonstrate that rBPI(23) has a binding specificity for the lipid A region of LPS and binding involves both electrostatic and hydrophobic components. C1 NEUROCRINE BIOSCI INC,SAN DIEGO,CA 92121. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824. MICHIGAN STATE UNIV,DEPT CHEM,E LANSING,MI 48824. RP GAZZANOSANTORO, H (reprint author), XOMA CORP,SEPSIS RES DEPT,2910 7TH ST,BERKELEY,CA 94710, USA. NR 42 TC 32 Z9 32 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1995 VL 63 IS 6 BP 2201 EP 2205 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RA191 UT WOS:A1995RA19100016 PM 7768599 ER PT J AU Bazaral, MG Ciarkowski, A AF Bazaral, MG Ciarkowski, A TI Food and drug administration regulations and computer-controlled infusion pumps SO INTERNATIONAL ANESTHESIOLOGY CLINICS LA English DT Article ID CLOSED-LOOP CONTROL; ANESTHESIA; ALFENTANIL; DEVICES; DESIGN RP Bazaral, MG (reprint author), US FDA,DCRND,ROCKVILLE,MD 20857, USA. NR 42 TC 4 Z9 4 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-5907 J9 INT ANESTHESIOL CLIN JI Int. Anesthesiol. Clin. PD SUM PY 1995 VL 33 IS 3 BP 45 EP 63 DI 10.1097/00004311-199503330-00005 PG 19 WC Anesthesiology SC Anesthesiology GA TM632 UT WOS:A1995TM63200004 PM 8838751 ER PT J AU LUECKE, RH WOSILAIT, WD YOUNG, JF AF LUECKE, RH WOSILAIT, WD YOUNG, JF TI MATHEMATICAL REPRESENTATION OF ORGAN GROWTH IN THE HUMAN EMBRYO FETUS SO INTERNATIONAL JOURNAL OF BIO-MEDICAL COMPUTING LA English DT Article DE HUMAN; FETAL DEVELOPMENT; ORGAN WEIGHTS; BIOLOGICAL MODEL; GROWTH AND EMBRYONIC DEVELOPMENT; ALLOMETRY ID PHARMACOKINETICS; DEFECTS AB During human pregnancy, there is a huge increase in the total weight of the embryo/fetus from conception to term. The total growth, which is the summation of growth of the various organs and tissues that make up the organism, was analyzed in a previous paper and fitted to the Gompertz equation for growth. In the present study, allometry, the quantitative representation of the consequence of size; was utilized to describe the correlation of individual fetal organ/tissue weights with the total fetal weight. The organ/tissue weight and the total fetal weight data used in the analyses were pooled from various sources that provided data ranging from 25 days to 300 days post-conception. Allometric equations are presented for 16 embryo/fetal organs and tissues. The standard allometric equation gave adequate fits for embryo/fetal adrenal, bone, bone marrow, brain, heart, liver, pancreas, plasma, skeletal muscle, extracellular water, thymus and thyroid; but it was necessary to use a quadratic form of the allometric equation for embryo/fetal fat, kidney, lung and spleen. Parameters were also calculated for crown-to-rump and crown-to-heels for fetal lengths that occur during pregnancy. C1 NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. UNIV MISSOURI,DEPT CHEM ENGN,COLUMBIA,MO 65211. UNIV MISSOURI,DEPT PHARMACOL,COLUMBIA,MO 65211. NR 27 TC 30 Z9 30 U1 0 U2 2 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0020-7101 J9 INT J BIOMED COMPUT JI Int. J. Bio-Med. Comput. PD JUN PY 1995 VL 39 IS 3 BP 337 EP 347 DI 10.1016/0020-7101(95)01115-U PG 11 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA RQ504 UT WOS:A1995RQ50400006 PM 7490167 ER PT J AU HARDY, BJ EGAN, W WIDMALM, G AF HARDY, BJ EGAN, W WIDMALM, G TI CONFORMATIONAL-ANALYSIS OF THE DISACCHARIDE ALPHA-L-RHAP-(1-]2)-ALPHA-L-RHAP-OME - COMPARISON OF DYNAMICS SIMULATIONS WITH NMR EXPERIMENTS SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE STOCHASTIC DYNAMICS SIMULATIONS; NMR SPECTROSCOPY; DISACCHARIDE ID MOLECULAR-DYNAMICS; AQUEOUS-SOLUTION; FORCE-FIELD; D-GLUCOSE; WATER; RELAXATION; OLIGOSACCHARIDES; MOTION; SPECTROSCOPY; CELLOBIOSE AB The conformational behaviour of the disaccharide alpha-L-Rhap-(1 --> 2)-alpha-L-Rhap-(1 --> OMe) has been examined using molecular dynamics (MD) and Langevin dynamics simulations and nuclear magnetic resonance (NMR) spectroscopy; an 800 ps MD trajectory with the explicit inclusion of water was also determined. The results of the MD simulations were found to be sensitive to the choice of dielectric constant and force-field parameters. NOE build-up curves were constructed from the water and vacuum dynamics trajectories and compared with experimental values. Calculation of NOE data sets from the simulations was problematic for several resons, including the similarity in time scales for the internal and overall motions. C1 US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,ROCKVILLE,MD 20852. UNIV STOCKHOLM,ARRHENIUS LAB,DEPT ORGAN CHEM,S-10691 STOCKHOLM,SWEDEN. NR 36 TC 39 Z9 39 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA LINACRE HOUSE JORDAN HILL, OXFORD, OXON, ENGLAND OX2 8DP SN 0141-8130 J9 INT J BIOL MACROMOL JI Int. J. Biol. Macromol. PD JUN PY 1995 VL 17 IS 3-4 BP 149 EP 160 DI 10.1016/0141-8130(95)92681-F PG 12 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA RJ169 UT WOS:A1995RJ16900005 PM 7577813 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI WRITTEN PATIENT INFORMATION ON PRESCRIPTION DRUGS - THE EVOLUTION OF GOVERNMENT AND VOLUNTARY PROGRAMS IN THE UNITED-STATES SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article AB This paper describes the evolution of written patient information on prescription drugs, FDA's patient package insert proposal and its revocation before its implementation in the early 1980s, the status of voluntary and government efforts since that time, and a review of current trends in this area. The burgeoning practice of direct-to-consumer advertising of prescription drugs in the lay press is viewed within the context of these efforts. This paper also reviews the current developments in certain FDA-regulated consumer products - over-the-counter drug labeling and nutrition labeling. The current state of patient information in the United States is reviewed in light of programs to improve prescription drug counseling, and current research in this area is discussed. RP NIGHTINGALE, SL (reprint author), US FDA,ROOM 15-36,HFY-1,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 20 TC 15 Z9 15 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD SUM PY 1995 VL 11 IS 3 BP 399 EP 409 PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA RV238 UT WOS:A1995RV23800004 PM 7591542 ER PT J AU BOOTH, SL SADOWSKI, JA PENNINGTON, JAT AF BOOTH, SL SADOWSKI, JA PENNINGTON, JAT TI PHYLLOQUINONE (VITAMIN K-1) CONTENT OF FOODS IN THE US-FOOD-AND-DRUG-ADMINISTRATION TOTAL DIET STUDY SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE PHYLLOQUINONE; VITAMIN-K-1; FOOD COMPOSITION; TOTAL DIET STUDY ID OSTEOCALCIN AB Two hundred sixty-one foods from the U.S. Food and Drug Administration's Total Diet Study were analyzed for phylloquinone (vitamin K-1) using a high-performance liquid chromatographic method that incorporates postcolumn reduction of the quinone, followed by fluorescence detection of the hydroquinone form of the vitamin. Green, leafy vegetables still appear to be the predominant dietary source of this vitamin (113-440 mu g of phylloquinone/100 g of vegetable), followed by certain vegetable oils that are derived from vegetables or seeds containing large concentrations of phylloquinone. Some mixed dishes contain moderate amounts of phylloquinone that are attributable to the vegetable oils used in their preparation. Other foods, such as certain meats, brewed beverages, soft drinks, and alcoholic beverages, contained negligible amounts of phylloquinone. These data expand and improve the quality and quantity of the phylloquinone food composition table and will be used to prioritize future analyses. C1 US FDA,DIV NUTR,WASHINGTON,DC 20204. RP BOOTH, SL (reprint author), TUFTS UNIV,JEAN MAYER US DEPT AGR,HUMAN NUTR RES CTR AGING,VITAMIN K LAB,711 WASHINGTON ST,BOSTON,MA 02111, USA. NR 16 TC 71 Z9 73 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN PY 1995 VL 43 IS 6 BP 1574 EP 1579 DI 10.1021/jf00054a030 PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA RE380 UT WOS:A1995RE38000030 ER PT J AU JACKSON, LS HARGRAVES, WA AF JACKSON, LS HARGRAVES, WA TI EFFECTS OF TIME AND TEMPERATURE ON THE FORMATION OF MEIQ(X) AND DIMEIQ(X) IN A MODEL SYSTEM CONTAINING THREONINE, GLUCOSE, AND CREATINE SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE AMINOIMIDAZOAZAARENE; PROCESSING; CREATINE; CREATININE ID MUTAGENIC HETEROCYCLIC AMINES; MAILLARD-REACTION-PRODUCTS; FRIED GROUND-BEEF; AROMATIC-AMINES; FOOD-PRODUCTS; COOKING; MEAT; ACIDS; PURIFICATION; PRECURSORS AB This project studied the effects of processing time and temperature on the formation of MeIQ(x) and DiMeIQ(x), two of the most common aminoimidazoazaarenes (AIAs) found in food. Each model system containing threonine, glucose, and creatine (2:1:2 molar ratio) was processed for 2 h at a temperature between 125 and 250 degrees C. Neither MeIQ(x) nor DiMeIQ(x) was found at processing temperatures lower than 150 degrees C. At temperatures between 150 and 200 degrees C, AIA concentrations increased with processing time. However, at 225 and 250 degrees C the concentrations of the two products increased during the initial 15-30 min of processing and then decreased for the remainder of the processing run. MeIQ(x) and DiMeIQ(x) did not appear in the reaction mixture until almost all of the creatine was converted into creatinine. This systematic study suggests that maintaining cooking temperatures below 150 degrees C may reduce the formation of MeIQ(x) and DiMeIQ(x) in food. RP JACKSON, LS (reprint author), US FDA,NATL CTR FOOD SAFETY & TECHNOL,6502 S ARCHER RD,SUMMIT ARGO,IL 60501, USA. NR 41 TC 29 Z9 29 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN PY 1995 VL 43 IS 6 BP 1678 EP 1684 DI 10.1021/jf00054a049 PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA RE380 UT WOS:A1995RE38000049 ER PT J AU AKASAWA, A HSIEH, LS LIN, Y AF AKASAWA, A HSIEH, LS LIN, Y TI SERUM REACTIVITIES TO LATEX PROTEINS (HEVEA-BRASILIENSIS) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE LATER ALLERGENS; IGE-REACTIVE PROTEINS; LATEX PARTICLES; LATEX C-SERUM ID RUBBER ELONGATION-FACTOR; ANTIGENS; IDENTIFICATION; CHILDREN; CONTACT AB Background: In recent years there has been an increasing incidence of allergy to latex among health care workers and children with spina bifida. The allergic response in these individuals can be severe and occasionally fatal Several allergens have been identified with the use of sera from different patient groups. In our effort to identify reagents for in vitro testing and clinical use, we investigated the reactivities of latex proteins to sera collected from a wide range of patients with latex allergy. Methods: Twenty-six serum samples were obtained from adult patients with latex allergy, both hospital workers and non-hospital workers. Serum pools were made either from sera of children with spina bifida or sera of adult patients with Eater allergy. proteins from C-serum and lattex particles of latex sap (nonammoniated) were separated by different gel electrophoresis techniques and evaluated for specific IgE binding by immunoblotting. Results: More than 50% of the sera tested reacted to an 18 kd protein, a 25.6 kd acidic protein with an isoelectric point of 3.5, or to both proteins; whereas only 23% of the individual serum samples tested reacted to the rubber elongation factor which has been reported to be a major Eater allergen. The immunoreactive patterns of children's and adults' serum pools were similar but not identical. Conclusions: With the use of gel electrophoresis and immunoblotting techniques, different immunoreactive proteins were identified in C-serum and particles of latex. Rubber elongation factor, which reacted to only 23% of sera tested, did not appear to cross-react immunologically with other latex allergens. C1 US FDA,CTR BIOL EVALUAT & RES,DIV ALLERGEN PROD & PARASITOL,IMMUNOBIOCHEM LAB,BETHESDA,MD. NR 16 TC 35 Z9 36 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 1995 VL 95 IS 6 BP 1196 EP 1205 DI 10.1016/S0091-6749(95)70076-5 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA RD309 UT WOS:A1995RD30900007 PM 7797788 ER PT J AU YAHIRO, MA GANTENBERG, JB NELSON, R LU, HTC MISHRA, NK AF YAHIRO, MA GANTENBERG, JB NELSON, R LU, HTC MISHRA, NK TI COMPARISON OF THE RESULTS OF CEMENTED, POROUS-INGROWTH, AND THREADED ACETABULAR CUP FIXATION - A METAANALYSIS OF THE ORTHOPEDIC LITERATURE SO JOURNAL OF ARTHROPLASTY LA English DT Review DE TOTAL HIP ARTHROPLASTY; THREADED ACETABULAR CUPS; METAANALYSIS AB A meta-analysis of the orthopaedic literature was performed to evaluate the clinical performance of cementless, threaded acetabular cups. The hypothesis for the study was that the clinical performance of the cementless, threaded acetabular cup is equivalent to that of the cemented and porous-ingrowth acetabular cups. Ninety-five articles were included in the study. There were 1,269 cases in the threaded cup group, 1,979 in the porous control group, and 10,230 in the cemented control group. The primary outcome variable tested was the rate of aseptic loosening of the acetabular components as measured by the revision rates following the index total hip arthroplasty procedure. Other measures of acetabular component loosening that were analyzed included clinical rating scores, pain scores, frequency of radiolucencies according to location and size, frequency of radiolucencies as a separately defined outcome variable, progressive radiolucencies, and component migration. The threaded cup group was found to have a significantly higher rate of revision, clinical and pain score failures, progressive radiolucencies and migrations when compared with the cemented and porous control groups (P < .05). Despite the many limitations of meta-analyses and the poor state of the orthopaedic literature database, this study provides a reasonable comparison of the clinical performance of threaded acetabular cups with that of cemented and porous-ingrowth acetabular cups. RP YAHIRO, MA (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF DEVICE EVALUAT,DGRD,ORDB,,HFZ-410CARD DR,ROCKVILLE,MD 20850, USA. NR 0 TC 41 Z9 41 U1 2 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JUN PY 1995 VL 10 IS 3 BP 339 EP 350 PG 12 WC Orthopedics SC Orthopedics GA RE007 UT WOS:A1995RE00700013 PM 7673913 ER PT J AU GUNDBERG, CM FAWZI, MI CLOUGH, ME CALVO, MS AF GUNDBERG, CM FAWZI, MI CLOUGH, ME CALVO, MS TI A COMPARISON OF THE EFFECTS OF PARATHYROID-HORMONE AND PARATHYROID HORMONE-RELATED PROTEIN ON OSTEOCALCIN IN THE RAT SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID PRIMARY HYPERPARATHYROIDISM; MALIGNANT HYPERCALCEMIA; BONE HISTOMORPHOMETRY; GLA PROTEIN; NUDE-MICE; PEPTIDE; INFUSION; INVIVO; PTH; METABOLISM AB We compared the effects of parathyroid hormone (PTH1-34) and parathyroid hormone-related protein (PTHrp1-34) on osteocalcin release in the isolated rat hindlimb and in intact and thyroparathyroidectomized (TPTX) rats, PTH1-34 suppressed osteocalcin release from perfused rat hindquarters, while PTHrp1-34 had no effect on osteocalcin release, despite comparable stimulation of cAMP production, Similarly, serum osteocalcin declined in the intact and TPTX animals by 5 h after a single dose of PTH1-34, while there was no response to PTHrp1-34, Chronic administration of PTH1-34 or PTHrp1-34 produced comparable hypercalcemia and hypophosphatemia in sham-operated and TPTX animals, Chronic PTH1-34 administration produced significant increases in serum osteocalcin both in the sham-operated rats and in the TPTX animals, However, in animals chronically treated with PTHrp1-34, there was no change at any time point in osteocalcin in either sham-operated or TPTX rats, These differences could be inherent or merely due to potency differences between the two peptides. C1 YALE UNIV,SCH MED,DEPT REHABIL,NEW HAVEN,CT 06510. HARVARD UNIV,SCH DENT MED,BOSTON,MA 02115. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. RP GUNDBERG, CM (reprint author), YALE UNIV,SCH MED,DEPT ORTHOPAED,333 CEDAR ST,NEW HAVEN,CT 06510, USA. FU NIAMS NIH HHS [R01-AR38460, AR01789] NR 31 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 1995 VL 10 IS 6 BP 903 EP 909 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RM876 UT WOS:A1995RM87600010 PM 7572314 ER PT J AU LATHERS, CM SCHRAEDER, PL AF LATHERS, CM SCHRAEDER, PL TI EXPERIENCE-BASED TEACHING OF THERAPEUTICS AND CLINICAL-PHARMACOLOGY OF ANTIEPILEPTIC DRUGS, SUDDEN UNEXPLAINED DEATH IN EPILEPSY - DO ANTIEPILEPTIC DRUGS HAVE A ROLE SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID CARDIAC NEURAL DISCHARGE; EPILEPTOGENIC ACTIVITY; AUTONOMIC DYSFUNCTION; UNEXPECTED DEATH; ARRHYTHMIAS; SEIZURES; DIGITALIS; CAT AB The contents of this paper have been written to be used in a teaching program specifically designed for medical postgraduate education of resident physicians and fellows in training interested in the clinical pharmacology of antiepileptic drugs and their role in the treatment of epilepsy and/or in the prevention of sudden unexpected death associated with this disease. With some modifications, such as a specific lecture to provide an overview of the numerous concepts presented in the text, the article could be used when teaching fourth-year medical students. The format of the paper is a combination of didactic review and eight case reports in a self-learning format. A quiz for self-assessment is included at the end of the article (see Appendix). This material was covered in part in the 1992 Board Review Course for Clinical Pharmacology sponsored by the American College of Clinical Pharmacology. The format or setting of instruction for this material could include small learning groups composed of 10 to 15 students. When used in combination with other topics prepared in similar formats, this could become a take home course for those preparing to take the Boards in Clinical Pharmacology. Each instructor could select specific publications from the reference list for assigned readings depending upon the material emphasized by the instructor. The questions included at the end of the text could be used as either a closed or an open book quiz to assess student learning. C1 US FDA,DIV CARDIO RENAL,ROCKVILLE,MD. NASA,VISITING SCI PROGRAM,HOUSTON,TX. ROBERT WOOD JOHNSON MED SCH,CAMDEN,NJ. NR 72 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUN PY 1995 VL 35 IS 6 BP 573 EP 587 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RD818 UT WOS:A1995RD81800002 PM 7665717 ER PT J AU PEELER, JT GRAHAM, TE MATURIN, LJ AF PEELER, JT GRAHAM, TE MATURIN, LJ TI PRECISION PARAMETERS FOR THE FDA SHELLFISH LABORATORY QUALITY ASSURANCE PROGRAM FOR 1973-1989 SO JOURNAL OF FOOD PROTECTION LA English DT Article DE STAPHYLOCOCCUS AUREUS; MOST PROBABLE NUMBER; SHELLFISH QUALITY ASSURANCE PROGRAM AB Precision parameters from four microbiological analytical methods (coliform most probable number [MPN], fecal coliform MPN, Staphylococcus aureus plate count and standard plate count) were computed for the Shellfish Quality Assurance Program of the U.S. Food and Drug Administration (FDA). The pooled reproducibility variance (S-R(2)) for the four methods from 1973 to 1989 were 0.0778, 0.1181, 0.0137, and 0.0087, respectively. C1 US FDA,QUAL ASSURANCE BRANCH LAB,SUMMIT ARGO,IL 60501. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 12 TC 0 Z9 0 U1 0 U2 0 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 1995 VL 58 IS 6 BP 648 EP 650 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA RF336 UT WOS:A1995RF33600011 ER PT J AU DOERGE, DR BAJIC, S BLANKENSHIP, LR PREECE, SW CHURCHWELL, MI AF DOERGE, DR BAJIC, S BLANKENSHIP, LR PREECE, SW CHURCHWELL, MI TI DETERMINATION OF BETA-AGONIST RESIDUES IN HUMAN PLASMA USING LIQUID-CHROMATOGRAPHY ATMOSPHERIC-PRESSURE CHEMICAL-IONIZATION MASS-SPECTROMETRY AND TANDEM MASS-SPECTROMETRY SO JOURNAL OF MASS SPECTROMETRY LA English DT Article ID CLENBUTEROL AB A multi-residue gradient liquid chromatographic (LC) separation was developed for five beta-agonists (fenoterol, metaproterenol, terbutaline, salbutamol and clenbuterol) in human plasma and detection was made using LC/ atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) in the selected-ion monitoring (SIM) mode. Detection limits for the protonated molecules of the beta-agonists were < 25 ppb in plasma or 100 pg on-column and responses were highly linear over the range 25-50 ppb. A solid-phase extraction (SPE) procedure, yielding recoveries of 67-104% from plasma spiked at 5 ppb with the five analytes, was also developed. In-source collision-indnced dissociation was used to produce mass spectra containing diagnostic fragment ions and a common mechanism of fragmentation for all the beta-agonists was identified. The LC/APCI-MS method was unable to determine salbutamol at levels < 10 ppb in spiked plasma. To determine whether this resulted from low SPE efficiency or matrix interference, LC/APCI-MS/MS was performed in the multiple reaction monitoring (MRM) mode to enhance the selectivity of the analysis. The MRM results showed that high recoveries were obtained for salbutamol, confirming the detrimental effect of co-eluting interferences in the LC/MS analysis. This study demonstrates the feasibility of using SPE, gradient LC separation and highly sensitive/selective detection using LC/APCI-MS and MS/MS for the multi-residue analysis of beta-agonists at low ppb levels in a biological matrix. C1 FISONS INSTRUMENTS BIOTECH MS,ALTRINCHAM WA14 5RZ,CHESHIRE,ENGLAND. RP DOERGE, DR (reprint author), NATL CTR TOXICOL RES,HFT-230,JEFFERSON,AR 72079, USA. NR 5 TC 39 Z9 39 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD JUN PY 1995 VL 30 IS 6 BP 911 EP 916 DI 10.1002/jms.1190300617 PG 6 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA RD737 UT WOS:A1995RD73700016 ER PT J AU MALOZOWSKI, S TANNER, LA WYSOWSKI, DK FLEMING, GA STADEL, BV AF MALOZOWSKI, S TANNER, LA WYSOWSKI, DK FLEMING, GA STADEL, BV TI BENIGN INTRACRANIAL HYPERTENSION IN CHILDREN WITH GROWTH-HORMONE DEFICIENCY TREATED WITH GROWTH-HORMONE SO JOURNAL OF PEDIATRICS LA English DT Article ID PSEUDOTUMOR CEREBRI; FACTOR-I; CHILDHOOD AB We report 13 cases of benign intracranial hypertension (IH) in children with growth hormone (GH) deficiency treated with GH in the United States. The group consisted of eight boys and five girls, 3 to 16 years of age (median, 9 years). The interval from starting GH therapy to diagnosis of IH was 2 weeks or less in six patients, between 2 and 12 weeks in four, 8 months in one, 5 years in one, and unknown in one, Seven patients were not known to have previously described IH risk factors; the other six had at least one factor each. All patients but one had headache, nausea, vomiting, and visual changes. All had papilledema, and cerebrospinal fluid pressures were elevated (>250 mm H2O) in all nine patients tested. The GH dosage range was 0.17 to 0.35 mg per kilogram body weight per week (median, 0.30 mg/kg per week) for the 11 patients with dosage data. After discontinuation of GH and treatment with lumbar punctures and/or medications, signs and symptoms resolved in eight children; in two of these children signs and symptoms reappeared when GH therapy was restarted. In four patients signs and symptoms resolved while GH therapy was continued; one child was treated with a ventriculoperitoneal shunt because of an arachnoid cyst, after which GH was restarted without subsequent IH. In the 12 patients with idiopathic GH deficiency the course of IH was benign, with complete resolution of all signs and symptoms. Because doses and scheduling of GH administration have changed since the introduction of recombinant GH, higher doses and increased frequency of administration may be contributing to the development of IH in some patients. We suggest beginning therapy at the lowest recommended dose, with gradual titration to higher doses, and the performance of routine funduscopic examinations during initiation of GH therapy and whenever signs or symptoms of IH develop. C1 US FDA, CTR DRUG EVALUAT & RES, DIV METAB & ENDOCRINE DRUG PROD, ROCKVILLE, MD 20857 USA. US FDA, CTR DRUG EVALUAT & RES, DIV EPIDEMIOL & SURVEILLANCE, ROCKVILLE, MD 20857 USA. NR 22 TC 65 Z9 67 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 1995 VL 126 IS 6 BP 996 EP 999 DI 10.1016/S0022-3476(95)70232-6 PG 4 WC Pediatrics SC Pediatrics GA RC754 UT WOS:A1995RC75400034 PM 7776116 ER PT J AU FLURER, CL AF FLURER, CL TI THE ANALYSIS OF AMINOGLYCOSIDE ANTIBIOTICS BY CAPILLARY ELECTROPHORESIS SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE AMINOGLYCOSIDE ANTIBIOTICS; BORATE COMPLEXATION; CAPILLARY ELECTROPHORESIS; POTENCY DETERMINATION ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PRE-COLUMN DERIVATIZATION; GENTAMICIN SULFATE; MASS-SPECTROMETRY; SEPARATION; 1-FLUORO-2,4-DINITROBENZENE AB The analyses of aminoglycoside antibiotics by capillary electrophoresis utilizing borate complexation and direct UV detection are discussed. Twelve aminoglycosides were studied and separated to demonstrate identification capabilities, with migration time RSDs from 0.21 to 0.44% (n = 6) for individual components. This buffer system permitted the detection of minor impurities such as precursors; or closely related fermentation products. Quantification of dihydrostreptomycin and streptomycin was accomplished in 160 mM sodium tetraborate decahydrate with linearity over the range 0.050-1.0 mg ml(-1). Determination of the purity of bulk dihydrostreptomycin was possible by the addition of the cationic surfactant myristyltrimethylammonium bromide. This reversed the electroosmotic flow, thereby reversing the migration order, and causing the streptomycin impurity to migrate before the dihydrostreptomycin main peak. Quantification was also demonstrated with the closely related compounds amikacin, bekanamycin, kanamycin A, and tobramycin, using sisomicin as an internal standard. The reproducibility of the method was typically 2-3% over 1 day, and 2% day-to-day. These studies illustrate the use of capillary electrophoresis for the identification and quantification of selected aminoglycosides as potential alternative methods to the assays given by the US Pharmacopeia. RP FLURER, CL (reprint author), US FDA, NATL FOR CHEM CTR, 1141 CENT PKWY, CINCINNATI, OH 45202 USA. NR 18 TC 48 Z9 55 U1 3 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD JUN PY 1995 VL 13 IS 7 BP 809 EP 816 DI 10.1016/0731-7085(95)01502-C PG 8 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA RP053 UT WOS:A1995RP05300002 PM 8562603 ER PT J AU ALTWEIN, DM FOSTER, K DOOSE, G NEWTON, RT AF ALTWEIN, DM FOSTER, K DOOSE, G NEWTON, RT TI THE DETECTION AND DISTRIBUTION OF THE MARINE NEUROTOXIN DOMOIC ACID ON THE PACIFIC COAST OF THE UNITED-STATES 1991-1993 SO JOURNAL OF SHELLFISH RESEARCH LA English DT Article DE DOMOIC ACID; AMNESIC SHELLFISH POISONING (ASP); NEUROTOXIN; RAZOR CLAMS; ANCHOVIES; CRAB ID PSEUDONITZSCHIA-AUSTRALIS; MUSSELS; INTOXICATION; MICE AB Analysis of 2873 samples from a wide variety of domestic as well as import seafoods for domoic acid revealed the presence of the toxin in specimens of anchovies, razor clams, crab, and spiny lobster harvested from the coastal waters of California, Oregon and Washington from 1991 to 1993. Of the 392 razor clam samples investigated, 42% were found to contain the toxin in excess of 20 ppm, a level considered to be unsafe for human consumption by the Food and Drug Administration (FDA). In sharp contrast to the razor clam results, neither mussels nor oysters gathered from the same sampling sites showed any significant sign of domoic acid contamination. Of the total of 397 cooked crab samples harvested from the coastal waters of Washington and Oregon, greater than 65% were found to contain some level of domoic acid and greater than 5% were found to contain levels of the toxin in excess of 20 ppm. These studies also revealed that, in general, crab viscera contained domoic acid at levels 5 to 10 times higher than those found in the meat. While all samples of crab and lobster were analyzed as cooked specimens, all other species investigated were analyzed in the raw state. Of all the species investigated, anchovies were found to be the most highly contaminated. C1 US FDA,ALAMEDA,CA 94502. US FDA,LOS ANGELES,CA 90015. RP ALTWEIN, DM (reprint author), US FDA,22201 23RD DR SE,POB 3012,BOTHELL,WA 98041, USA. NR 17 TC 19 Z9 20 U1 0 U2 3 PU NATL SHELLFISHERIES ASSOC PI SOUTHHAMPTON PA C/O DR. SANDRA E. SHUMWAY, NATURAL SCIENCE DIVISION, SOUTHAMPTON COLLEGE, SOUTHHAMPTON, NY 11968 SN 0730-8000 J9 J SHELLFISH RES JI J. Shellfish Res. PD JUN PY 1995 VL 14 IS 1 BP 217 EP 222 PG 6 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA RH798 UT WOS:A1995RH79800029 ER PT J AU KING, JW JOHNSON, JH TAYLOR, SL ORTON, WL HOPPER, ML AF KING, JW JOHNSON, JH TAYLOR, SL ORTON, WL HOPPER, ML TI SIMULTANEOUS MULTISAMPLE SUPERCRITICAL-FLUID EXTRACTION OF FOOD-PRODUCTS FOR LIPIDS AND PESTICIDE-RESIDUE ANALYSIS SO JOURNAL OF SUPERCRITICAL FLUIDS LA English DT Article DE MULTISAMPLE EXTRACTION; PESTICIDES; LIPIDS; SUPERCRITICAL FLUID ID CARBON-DIOXIDE EXTRACTION; OPTIMIZATION; RECOVERY; CO2 AB Sample preparation for food analysis has traditionally involved the processing of a large number of samples simultaneously. A supercritical-fluid extraction (SFE) apparatus has been designed and tested to facilitate a similar approach, using SC-CO2 as the extraction fluid. The prototype extractor was constructed to allow the extraction of six samples simultaneously, as well as the regulation and balancing of the fluid flow through each of the individual extraction vessels. In addition, procedures were developed to eliminate contamination from the apparatus and the extraction fluid which could interfere with electron capture detection of pesticide residues in meat samples. Rapid extraction of lipid phases from food products (soybeans, frankfurters, poultry) could be achieved within 15 minutes using extraction pressures of 5,000-10,000 psi at 60 degrees and accompanying CO2 flow rates of 5-10 L min(-1) (ambient conditions). Simultaneous multi-extraction of dispersed fat and soybean flake samples yielded lipid recoveries of 98 and 95%, respectively. Initial experiments on spiked frankfurter samples yielded analyte recoveries of 87-118% for a mixture of eight chlorinated pesticides. Additional studies on the coextraction of incurred organo-chlorine pesticide residues from poultry adipose tissue, resulted in 96% or better recoveries of endrin, heptachlor epoxide, and dieldrin, at the 1-3 ppm level in the extracted fat. C1 US FDA,TOTAL DIET RES CTR,LENEXA,KS 66285. RP KING, JW (reprint author), USDA ARS,NATL CTR AGR UTILIZAT RES,FOOD QUAL & SAFETY RES UNIT,1815 N UNIV ST,PEORIA,IL 61604, USA. NR 16 TC 9 Z9 10 U1 3 U2 5 PU PRA PRESS PI CINCINNATI PA POLYMER RES ASSOC INC 9200 MONTGOMERY RD, SUITE 23B, CINCINNATI, OH 45242 SN 0896-8446 J9 J SUPERCRIT FLUID JI J. Supercrit. Fluids PD JUN PY 1995 VL 8 IS 2 BP 167 EP 175 DI 10.1016/0896-8446(95)90030-6 PG 9 WC Chemistry, Physical; Engineering, Chemical SC Chemistry; Engineering GA RU655 UT WOS:A1995RU65500010 ER PT J AU WAGNER, RF WEAR, KA PEREZ, JE MCGILL, JB SCHECHTMAN, KB MILLER, JG AF WAGNER, RF WEAR, KA PEREZ, JE MCGILL, JB SCHECHTMAN, KB MILLER, JG TI QUANTITATIVE ASSESSMENT OF MYOCARDIAL ULTRASOUND TISSUE CHARACTERIZATION THROUGH RECEIVER OPERATING CHARACTERISTIC ANALYSIS OF BAYESIAN CLASSIFIERS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ROC; DESIGN; IMAGES AB Objectives. This work proposes a self-consistent assessment methodology for quantitative evaluation of any combination of diagnostic features, with the immediate goal of quantitatively assessing the discriminating power in diabetic patients of features derived from ultrasound backscatter from myocardium. Background. Four features from analysis of left ventricular myocardial ultrasound backscatter have previously been shown to be sensitive to potentially cardiomyopathic changes in patients with insulin dependent diabetes mellitus who have no overt heart disease. The measured features were significantly different between such patients and normal control subjects, as well as among groups of such patients with and without systemic complications of the disease. The quantitative discriminating potential of the features was not assessed. Methods. Multivariate classifier functions were constructed and analyzed by using the methodology of the receiver operating characteristic curve, which allows quantitative assessment of the discriminating power of these features, alone or in combination. The area under the receiver operating characteristic curve-the true positive rate averaged over all false positive rates-was used as a summary measure of performance. Results. In distinguishing patients with insulin-dependent diabetes mellitus from normal control subjects, the most discriminating combination of ultrasound features for the detection of such changes in these patients yielded receiver operating characteristic curves with area measures of similar to 0.80; for such patients with retinopathy the measure increased to 0.90. This performance is comparable to that of many commonly used diagnostic tests. Conclusions. A self-consistent set of evaluation methodologies has quantitatively demonstrated the sensitivity of four ultrasound backscatter features to otherwise latent changes in myocardial structure that accompany the evolution of insulin-dependent diabetes mellitus. The results are remarkable in themselves and suggest the potential of the features for tbe general field of cardiac ultrasound tissue characterization. C1 UNIV WASHINGTON,DEPT MED,DIV CARDIOVASC,ST LOUIS,MO. UNIV WASHINGTON,DEPT PHYS,BIOMED COMP LAB,ST LOUIS,MO. RP WAGNER, RF (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,HFZ 142,ROCKVILLE,MD 20857, USA. FU NHLBI NIH HHS [HL40302, HL17646] NR 18 TC 27 Z9 31 U1 0 U2 2 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN PY 1995 VL 25 IS 7 BP 1706 EP 1711 DI 10.1016/0735-1097(95)00038-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RA480 UT WOS:A1995RA48000036 PM 7759727 ER PT J AU MOSSOBA, MM YURAWECZ, MP ROACH, JAG LIN, HS MCDONALD, RE FLICKINGER, BD PERKINS, EG AF MOSSOBA, MM YURAWECZ, MP ROACH, JAG LIN, HS MCDONALD, RE FLICKINGER, BD PERKINS, EG TI ELUCIDATION OF CYCLIC FATTY-ACID MONOMER STRUCTURES - CYCLIC AND BICYCLIC RING SIZES AND DOUBLE-BOND POSITION AND CONFIGURATION SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE CYCLIC FATTY ACID MONOMERS; DOUBLE BOND CONFIGURATION; DOUBLE BOND POSITION; INFRARED; MASS SPECTROMETRY ID CHROMATOGRAPHY MASS-SPECTROMETRY; HEAT-TREATMENT; VEGETABLE-OILS; LINSEED OILS; GC-MS; INFRARED SPECTROMETRY; SEED OILS; DERIVATIVES; QUANTITATION; SUNFLOWER AB Gas chromatography (CC)-electron ionization mass spectrometry of 2-alkenyl-4,4-dimethyl-oxazoline derivatives was used to confirm the identities of a complex mixture of C-18 diunsaturated cyclic fatty acid monomers (CFAMs) that were isolated from heated flaxseed (linseed) oil. The positions of double bonds and 1,2-disubstituted unsaturated 5- and 6-membered rings along the fatty acid hydrocarbon chains were established by this method. The oxazoline spectra exhibited a homologous ion series with a pattern of peaks that were 14 u (u = atomic mass unit) apart but interrupted when a double bond (12-u mass interval) or a ring was present along the fatty acid chain. The identity and location of a ring were indicated by a large interval of 68, 82, 66, 80, 78, or 120 u for a saturated 5- or 6-membered ring, monounsaturated 5- or 6-membered ring, diunsaturated 6-membered ring, or monounsaturated bicyclic ring system (fused 5- and 6-membered rings), respectively. The double bond configuration for the methyl ester derivatives of these CFAMs was established by GC-matrix isolation-fourier transform infrared spectroscopy. The elucidated alkenyl structures at C-2 in diunsaturated 2-[alkenyl]-4,4-dimethyloxazolines were 8-(2-but-trans-1-enyl-cyclopentenyl)octyl, 9-(2-propyl-cyclopentenyl)non-trans-8-enyl, 9-(2-propyl-cyclopentenyl)non-cis-7-enyl, 8-(2-but-cis-1-enyl-cyclopentenyl)octyl, 9-(2-propylcyclopentenyl)non-cis-8-enyl, 8-(2-propyl-cyclohex-cis-4-enyl)oct-trans-7-enyl, 8-(prop-trans-1 -enyl-cyclohex-cis-4-enyl)octyl, and 8-(2-propylcyclohexa-cis,cis-3,5-dienyl)octyl. C1 US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. UNIV ILLINOIS,URBANA,IL 61801. RP MOSSOBA, MM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,HFS-717,WASHINGTON,DC 20204, USA. NR 35 TC 22 Z9 22 U1 2 U2 3 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD JUN PY 1995 VL 72 IS 6 BP 721 EP 727 DI 10.1007/BF02635662 PG 7 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA RC944 UT WOS:A1995RC94400018 ER PT J AU GOLDING, B INMAN, J HIGHET, P BLACKBURN, R MANISCHEWITZ, J BLYVEIS, N ANGUS, RD GOLDING, H AF GOLDING, B INMAN, J HIGHET, P BLACKBURN, R MANISCHEWITZ, J BLYVEIS, N ANGUS, RD GOLDING, H TI BRUCELLA-ABORTUS CONJUGATED WITH A GP120 OR V3 LOOP PEPTIDE DERIVED FROM HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-1 INDUCES NEUTRALIZING ANTI-HIV ANTIBODIES, AND THE V3 B-ABORTUS CONJUGATE IS EFFECTIVE EVEN AFTER CD4(+) T-CELL DEPLETION SO JOURNAL OF VIROLOGY LA English DT Article ID INDEPENDENT TYPE-1; IFN-GAMMA; RESPONSES; VACCINES; KINETICS; PROTEINS; CARRIER; INVITRO AB Human immunodeficiency virus type 1 (HIV-1) infection is associated with loss of function and numbers of CD4(+) T-helper cells, In order to bypass the requirement for CD4(+) cells in antibody responses, we have utilized heat-inactivated Brucella abortus as a carrier, In this study we coupled a 14-mer V3 loop peptide (V3), which is homologous to 9 of 11 amino acids from the V3 loop of HIV-1 MN, and gp120 from HIV-1 SF2 to B. abortus [gp120(SF2)-B, abortus]. Our results showed that specific antibody responses, dominated by immunoglobulin G2a in BALB/c mice, were induced by these conjugates, Sera from the immunized mice bound native gp120 expressed on the surfaces of cells infected with a recombinant vaccinia virus gp160 vector (VPE16), Sera from mice immunized with gp120(SF2)-B, abortus inhibited binding of soluble CD4 to gp120, whereas sera from mice immunized with V3-B, abortus were ineffective, Sera from mice immunized with either conjugate were capable of blocking syncytium formation between CD4(+) CEM cells and H9 cells chronically infected dth the homologous virus, Sera from mice immunized with gp120(SF2)-B. abortus were more potent than sera from mice immunized with V3-B. abortus in inhibiting syncytia from heterologous HIV-1 laboratory strains, Importantly, in primary and secondary responses, V3-B. abortus evoked anti-HN MN antibodies in mice depleted of CD4(+) cells, and sera from these mice were able to inhibit syncytia, These findings indicate that B, abortus can provide carrier function for peptides and proteins from HIV-1 and suggest that they could be used for immunization of individuals with compromised CD4(+) T-cell function. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,RETROVIRUS RES LAB,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. USDA,ANIM & PLANT HLTH INSPECT SERV,VET SERV,NATL VET SERV LABS,AMES,IA 50010. RP GOLDING, B (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,PLASMA DERIVAT LAB,8800 ROCKVILLE PK,BETHESDA,MD 20892, USA. NR 26 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1995 VL 69 IS 6 BP 3299 EP 3307 PG 9 WC Virology SC Virology GA QX931 UT WOS:A1995QX93100007 PM 7745677 ER PT J AU ATREYA, CD SINGH, NK NAKHASI, HL AF ATREYA, CD SINGH, NK NAKHASI, HL TI THE RUBELLA-VIRUS RNA-BINDING ACTIVITY OF HUMAN CALRETICULIN IS LOCALIZED TO THE N-TERMINAL DOMAIN SO JOURNAL OF VIROLOGY LA English DT Note ID AUTOANTIGEN; TRANSLATION; SEQUENCE AB The rubella virus RNA 3' cis-acting element, which is essential for viral negative-strand RNA synthesis, is specifically bound by autophosphorylated calreticulin. Autophosphorylation in recombinant human calreticulin occurs on serine and threonine residues. The RNA-binding and autophosphorylation activities were localized to the N-terminal 180 amino acids. Furthermore, N-terminal deletions revealed that the RNA-binding activity of calreticulin is abrogated upon deletion of the first 10 residues, whereas the autophosphorylation activity resides between amino acids 60 and 180. These results indicate that both the rubella virus RNA-binding and autophosphorylation activities of calreticulin are present in the N-terminal domain. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 18 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1995 VL 69 IS 6 BP 3848 EP 3851 PG 4 WC Virology SC Virology GA QX931 UT WOS:A1995QX93100069 PM 7745733 ER PT J AU MOELANS, IIMD COHEN, J MARCHAND, M MOLITOR, C DEWILDE, P VANPELT, JF HOLLINGDALE, MR ROEFFEN, WFG ELING, WMC ATKINSON, CT AIKAWA, M SCHOENMAKERS, JGG KONINGS, RNH AF MOELANS, IIMD COHEN, J MARCHAND, M MOLITOR, C DEWILDE, P VANPELT, JF HOLLINGDALE, MR ROEFFEN, WFG ELING, WMC ATKINSON, CT AIKAWA, M SCHOENMAKERS, JGG KONINGS, RNH TI INDUCTION OF PLASMODIUM-FALCIPARUM SPOROZOITE-NEUTRALIZING ANTIBODIES UPON VACCINATION WITH RECOMBINANT PFS16 VACCINIA VIRUS AND/OR RECOMBINANT PFS16 PROTEIN PRODUCED IN YEAST SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE PLASMODIUM FALCIPARUM; PFS16; RECOMBINANT VACCINIA VIRUS; HETEROLOGOUS PRODUCTION; YEAST; SPOROZOITE-NEUTRALIZING VACCINE ID CIRCUMSPOROZOITE PROTEIN; SACCHAROMYCES-CEREVISIAE; INFECTED HEPATOCYTES; PRIMARY CULTURES; MALARIA VACCINE; SURFACE-ANTIGEN; HEPATOMA-CELLS; MEMBRANE; RESPONSES; IMMUNITY AB Pfs16 is a sexual stage/sporozoite-specific antigen of Plasmodium falciparum and is a potential candidate for a sporozoite-neutralizing vaccine. To obtain more information on the function of Pfs16 and to investigate its role during transmission and hepatocyte invasion, immunization experiments were performed with both a Pfs16-specific recombinant vaccinia virus and virus-like particles produced in yeast composed of the hepatitis B surface antigen (HBsAg) and antigen Pfs16 fused to HBsAg. Upon transformation of yeast cells, harbouring a genomic copy of the HBsAg gene, with a plasmid carrying the fusion gene Pfs16-HBsAg (Pfs16-S) virus-like hybrid particles composed of HBsAg and Pfs16-S were formed of a size similar to those present in human sera after infection with the hepatitis B virus. Cells infected with recombinant Pfs16 vaccinia virus synthesized a polypeptide of approx. 16 kDa that reacted with a Pfs16-specific polyclonal antibody. Animals vaccinated with the yeast hybrid particles and/or recombinant vaccinia virus both produced Pfs16-specific antibodies. These antibodies showed no transmission-blocking activity, but they efficiently diminished or abolished in vitro invasion of sporozoites into human hepatoma cells (HepG2-A16) and primary human hepatocytes. C1 UNIV NIJMEGEN,FAC SCI,DEPT MOLEC BIOL,NIJMEGEN,NETHERLANDS. SMITHKLINE BIOL,DEPT MOLEC & CELLULAR BIOL,RIXENSART,BELGIUM. CATHOLIC UNIV LEUVEN,DEPT MED,DIV LIVER & PANCREAT DIS,LOUVAIN,BELGIUM. US FDA,ROCKVILLE,MD 20857. UNIV NIJMEGEN,FAC MED,INST MED PARASITOL,NIJMEGEN,NETHERLANDS. CASE WESTERN RESERVE UNIV,SCH MED,INST PATHOL,CLEVELAND,OH 44106. RI Roeffen, W.F.G./L-4607-2015 NR 44 TC 15 Z9 16 U1 0 U2 1 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 JUN PY 1995 VL 72 IS 1-2 BP 179 EP 192 DI 10.1016/0166-6851(95)00072-9 PG 14 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA RV618 UT WOS:A1995RV61800017 PM 8538688 ER PT J AU MILLER, CE HUPPI, K SIWARSKI, D KARPAS, A NEWMAN, A MAINHART, C GLAUDEMANS, CPJ AF MILLER, CE HUPPI, K SIWARSKI, D KARPAS, A NEWMAN, A MAINHART, C GLAUDEMANS, CPJ TI A MURINE ANTIBODY TO SHIGELLA-DYSENTERIAE TYPE-1 EMPLOYS V-GENES THAT CONTAIN A REARRANGED CODON FOR THE LAMBDA-LIGHT-CHAIN SO MOLECULAR IMMUNOLOGY LA English DT Note ID INFECTIONS AB The cDNA coding for a hybridoma anti Shigella dysenteriae type 1 antibody (3707 E9) has been cloned, and sequenced. Binding patterns with fragments of the bacterial polysaccharide antigen had already been studied in detail. The VH sequence utilizes the VH441 gene, first identified amongst beta-(1,6)galactan-binding antibodies, while the VL is closely related to the V lambda 1 gene. We found that the VL(3707) (E9) gene employed a VL-J combinatorial joining leading to a rare Trp-->Leu substitution at position L96. C1 NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NCI,GENET LAB,MOLEC GENET SECT,BETHESDA,MD 20892. NIH,US FDA,CTR BIOL RES & REVIEW,BETHESDA,MD 20892. NR 13 TC 3 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUN PY 1995 VL 32 IS 9 BP 679 EP 682 DI 10.1016/0161-5890(95)00072-M PG 4 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA RM056 UT WOS:A1995RM05600009 PM 7643860 ER PT J AU ALAYASH, AI CASHON, RE AF ALAYASH, AI CASHON, RE TI HEMOGLOBIN AND FREE-RADICALS - IMPLICATIONS FOR THE DEVELOPMENT OF A SAFE BLOOD SUBSTITUTE SO MOLECULAR MEDICINE TODAY LA English DT Review ID NITRIC-OXIDE AB The two major concerns in the development of cell-free hemoglobin as a blood substitute (i.e. circulatory retention and oxygen delivery) have been resolved successfully by strategic chemical or genetic modification of the protein. However, the redox reactivity of hemoglobin and its impact on the physiological processes has not been fully understood, nor has it been subject to control by design. This article reviews current research into heme-mediated toxicities that potentially constitute serious impediments to the development of a usable blood substitute. C1 UNIV MAINE,DEPT BIOCHEM MICROBIOL & MOLEC BIOL,ORONO,ME 04469. RP ALAYASH, AI (reprint author), US FDA,CTR BIOL EVALUAT & RES,8800 ROCKVILLE PIKE,BLDG 29,BETHESDA,MD 20892, USA. NR 31 TC 42 Z9 42 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD JUN PY 1995 VL 1 IS 3 BP 122 EP 127 DI 10.1016/S1357-4310(95)80089-1 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RP376 UT WOS:A1995RP37600008 PM 9415147 ER PT J AU MORRIS, SM DEMON, OE MCGARRITY, LJ CHEN, JJ CASCIANO, DA AF MORRIS, SM DEMON, OE MCGARRITY, LJ CHEN, JJ CASCIANO, DA TI PROGRAMMED CELL-DEATH AND MUTATION-INDUCTION IN AHH-1 HUMAN LYMPHOBLASTOID-CELLS EXPOSED TO M-AMSA SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE LYMPHOBLASTOID CELLS; HUMAN; APOPTOSIS; TK MUTATION; HPRT MUTATION; M-AMSA ID MOUSE LYMPHOMA-CELLS; DNA STRAND BREAKS; TOPOISOMERASE-II INHIBITORS; RESISTANT TFT MUTANTS; BCL-2 GENE; B-CELLS; ANTICANCER DRUGS; HL-60 CELLS; C-MYC; CHEMOTHERAPEUTIC DRUGS AB One role of programmed cell death (apoptosis) is the removal of cells with DNA damage from the population. Certain cells, however, ale able to suppress the signals for apoptotic cell death and maintain viability. This suggests that the susceptibility of a cell to either undergo apoptosis or escape from the apoptotic death pathways may be an important factor in chemical mutagenesis. In order to provide insight into the role of apoptosis in the recovery of chemically induced mutants, AHH-1 cells were exposed to the chromosomal mutagen, m-amsa, and the percentage of cells undergoing apoptosis or necrosis quantified by flow cytometry. Logistic regression analysis revealed that the primary manner of cell death was by apoptosis. Two specific-locus mutations assays, the tk and the hprt, were utilized as markers for cells with DNA damage and that retained clonogenicity under conditions known to induce apoptosis. Analysis of variance indicated that the concentration-dependent increase in the mutant fraction at the tk locus was significant and the result of the recovery of clones with the slow-growth phenotype. Because this phenotype is thought to reflect chromosomal mutations, these results are consistent with the survival and clonogenicity of damaged cells. This suggests that the ability to recover mutant cells may be influenced by the suppression of or an escape from the apoptotic death pathways. C1 US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. RP MORRIS, SM (reprint author), US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,DIV GENET TOXICOL,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 103 TC 16 Z9 17 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 JUN PY 1995 VL 329 IS 1 BP 79 EP 96 DI 10.1016/0027-5107(95)00020-J PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA RC495 UT WOS:A1995RC49500009 PM 7770078 ER PT J AU FREDERICK, DL GILLAM, MP ALLEN, RR PAULE, MG AF FREDERICK, DL GILLAM, MP ALLEN, RR PAULE, MG TI ACUTE EFFECTS OF METHYLENEDIOXYMETHAMPHETAMINE (MDMA) ON SEVERAL COMPLEX BRAIN FUNCTIONS IN MONKEYS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE MDMA; ECSTASY; MONKEY; OPERANT BEHAVIOR; LEARNING; SHORT-TERM MEMORY; TIME PERCEPTION; MOTIVATION; COLOR AND POSITION DISCRIMINATION; FOOD REINFORCEMENT; SEROTONIN; AMPHETAMINE; HALLUCINOGEN ID BEHAVIORAL-TEST BATTERY; OPERANT TEST BATTERY; ORALLY-ADMINISTERED MDMA; RHESUS-MONKEYS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; NONHUMAN PRIMATE; RAT-BRAIN; SEROTONIN; PERFORMANCE; DEPLETION AB The effects of MDMA were assessed in rhesus macaques using behavior in an operant test battery (OTB) consisting of five food-reinforced tasks designed to model aspects of time estimation, short-term memory, and attention, motivation, learning, and color and position discrimination. Testing occurred 30 min after intramuscular. injections of MDMA (0.0, 0.1, 0.3, and 1.0 mg/kg). The behavioral endpoints monitored included percent task completed, response rate or latency, and response accuracy. Percent task completed was significantly decreased in the time estimation, learning, and motivation tasks at 1.0 mg/kg as compared to saline controls. Response accuracies in the time estimation and learning tasks were also decreased at 1.0 mg/kg. Response rate was decreased at 1.0 mg/kg in the motivation task but was not significantly affected in any other tasks. No behavioral endpoints were significantly affected in the short-term memory and attention and color and position discrimination tasks at any dose tested. Results indicate that time estimation, motivation, and learning are more sensitive to the acute effects of MDMA than are short-term memory and attention and color and position discrimination. C1 NATL CTR TOXICOL RES,US FDA,COMP BASED SYST INC,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,LITTLE ROCK,AR 72205. RP FREDERICK, DL (reprint author), NATL CTR TOXICOL RES,US FDA,DIV NEUROTOXICOL,HFT-132,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 39 TC 19 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUN-JUL PY 1995 VL 51 IS 2-3 BP 301 EP 307 DI 10.1016/0091-3057(94)00383-T PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA RB491 UT WOS:A1995RB49100021 PM 7667344 ER PT J AU THOMSEN, MS LOFT, S ROBERTS, DW POULSEN, HE AF THOMSEN, MS LOFT, S ROBERTS, DW POULSEN, HE TI CYTOCHROME P4502E1 INHIBITION BY PROPYLENE-GLYCOL PREVENTS ACETAMINOPHEN (PARACETAMOL) HEPATOTOXICITY IN MICE WITHOUT CYTOCHROME P4501A2 INHIBITION SO PHARMACOLOGY & TOXICOLOGY LA English DT Article ID INDUCED HEPATIC NECROSIS; HUMAN LIVER-MICROSOMES; COVALENT BINDING; PROTECTIVE ROLE; METABOLISM; CAFFEINE; OXIDATION; GLUTATHIONE; ACTIVATION; PROTEINS AB Acetaminophen hepatotoxicity is associated with its biotransformation to the reactive metabolite N-acetyl-p-benzoquinone imine that binds to protein. Two forms of cytochrome P450, CYP2E1 and CYP1A2, have been implicated as primarily responsible for the bioactivation. To determine the relative contributions of these P450's, overnight fasted male NMRI mice were pretreated with 10 ml of 50% v/w propylene glycol/kg or fluvoxamine (10 mg/kg) at -80 and -20 min. relative to acetaminophen dosing to inhibit CYP2E1 and CYP1A2, respectively. Mice were sacrificed at 0.5 or 4 hr after a hepatotoxic dose of acetaminophen (300 mg/kg). Propylene glycol or propylene glycol plus fluvoxamine, but not fluvoxamine alone protected against acetaminophen hepatotoxicity as indicated by abolished increase in serum alanine aminotransferase activity, less depletion of hepatic glutathione and lower liver:body weight ratios. Propylene glycol inhibited the activity of CYP2E1 as indicated by 84% reduction in the clearance of 3 mg/kg dose of chlorzoxazone, whereas fluvoxamine inhibited the activity of CYP1A2 as indicated by 40% reduction in the clearance of a 10 mg/kg dose of caffeine. For this animal model, the data are consistent with the notion that hepatotoxicity is associated with bioactivation of acetaminophen by CYP2E1 but not by CYP1A2. C1 UNIV COPENHAGEN,PANUM INST 18548,DEPT PHARMACOL,DK-2200 COPENHAGEN,DENMARK. NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. OI Loft, Steffen/0000-0001-9552-8518 NR 32 TC 32 Z9 32 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0901-9928 J9 PHARMACOL TOXICOL JI Pharmacol. Toxicol. PD JUN PY 1995 VL 76 IS 6 BP 395 EP 399 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RD025 UT WOS:A1995RD02500011 PM 7479582 ER PT J AU WEST, RW ROWLAND, KL MILLER, SA BEER, JZ AF WEST, RW ROWLAND, KL MILLER, SA BEER, JZ TI NEOPLASTIC TRANSFORMATION OF NEONATAL HUMAN FIBROBLASTS EXPOSED IN-VITRO TO RADIATION FROM A QUARTZ-HALOGEN LAMP SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE QUARTZ-HALOGEN LAMP; HUMAN FIBROBLAST; TRANSFORMATION AB The use of unfiltered quartz-halogen lamps exposes human skin to radiation that spans much of the ultraviolet (UV) spectrum. Reports indicate that exposure to quartz-halogen lamps is erythemogenic, mutagenic, and carcinogenic. To compare the carcinogenic potential of quartz-halogen lamps with that of other UV sources, we determined the dose dependence for cytotoxicity and neoplastic transformation in neonatal human fibroblasts exposed in vitro to: a 15 W germicidal lamp (primarily 254 MI radiation), a 15 W Cool White fluorescent lamp, and an unfiltered 20 W quartz-halogen lamp. Fluence-survival relationships were multiphasic with linear dose response below about 40% survival, and all three sources produced fluence-dependent transformation as indicated by induction of anchorage-independent growth. Maximum transformation frequencies were observed at fluences of 5-8 J/m(2) for the germicidal lamp, 6.3 kJ/m(2) for the fluorescent lamp, and 300 J/m(2) for the quartz-halogen lamp. These data confirm the carcinogenic potential of the quartz-halogen lamp. RP WEST, RW (reprint author), US FDA,NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079, USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD JUN PY 1995 VL 11 IS 3 BP 119 EP 123 PG 5 WC Dermatology SC Dermatology GA TC739 UT WOS:A1995TC73900006 PM 8555010 ER PT J AU PROTA, G LAMOREUX, ML MULLER, J KOBAYASHI, T NAPOLITANO, A VINCENSI, MR SAKAI, C HEARING, VJ AF PROTA, G LAMOREUX, ML MULLER, J KOBAYASHI, T NAPOLITANO, A VINCENSI, MR SAKAI, C HEARING, VJ TI COMPARATIVE-ANALYSIS OF MELANINS AND MELANOSOMES PRODUCED BY VARIOUS COAT COLOR MUTANTS SO PIGMENT CELL RESEARCH LA English DT Article DE PIGMENTATION; MELANIN; MELANOSOMES; MELANOGENESIS ID TYROSINASE-RELATED PROTEIN; DOPACHROME CONVERSION; YELLOW MICE; AGOUTI GENE; MOUSE; LOCUS; HAIR; MELANOGENESIS; PIGMENTATION; EXPRESSION AB Pigmentation in the skin, hair, and eyes of animals is influenced by a number of genes that modulate the activity of melanocytes, the intervention of enzymatic controls at different stages of the melanogenic process, and the physico-chemical properties of the final pigment. The results of combined phenotypic, ultrastructural, biochemical, and chemical analyses of hairs of a variety of defined genotypes on a common genetic background performed in this study are consistent with the view that pigmentation of dark to black hairs results from the incorporation of eumelanin pigments whereas that of yellow hairs results from the incorporation of eu- and pheomelanins. It is also clear that relatively minor differences in melanin content can have dramatic effects on visible hair color. A good correlation was found for expression of (and enzyme activities associated with) TRP1 and TRP2 with eumelanin synthesis and eumelanosome production. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. UNIV NAPLES,DEPT ORGAN & BIOL CHEM,I-80134 NAPLES,ITALY. TEXAS A&M UNIV,TEXAS VET MED CTR,DEPT VET PATHOBIOL,COLLEGE STN,TX 77843. US FDA,DIV VIROL,BETHESDA,MD 20892. RI Napolitano, Alessandra /E-9761-2011 NR 51 TC 60 Z9 61 U1 1 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD JUN PY 1995 VL 8 IS 3 BP 153 EP 163 DI 10.1111/j.1600-0749.1995.tb00657.x PG 11 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA RM035 UT WOS:A1995RM03500006 PM 7567792 ER PT J AU LYSIAK, JJ JOHNSON, GR LALA, PK AF LYSIAK, JJ JOHNSON, GR LALA, PK TI LOCALIZATION OF AMPHIREGULIN IN THE HUMAN PLACENTA AND DECIDUA THROUGHOUT GESTATION - ROLE IN TROPHOBLAST GROWTH SO PLACENTA LA English DT Article ID EPITHELIAL-CELLS; FACTOR RECEPTOR; FACTOR FAMILY; EXPRESSION; DIFFERENTIATION; CARCINOMAS; SURFACE; ALPHA; LINE; GENE AB Amphiregulin (AR) is a growth regulatory glycoprotein with significant amino acid homology to members of the epidermal growth factor (EGF) family. Its effects ave mediated via the EGF receptor tyrosine It kinase or through specific nuclear targeting sequences. In this study, the localization of immunoreactive AR was examined in paraformaldehyde-glutaraldehyde fixed, paraffin-embedded human placentae and decidua obtained at various stages from 11 weeks to term pregnancy using the avidin-biotin complex/peroxidase method. In addition, the effects of AR on trophoblast proliferation mere evaluated fi om (3)HTdR uptake by first trimester human trophoblast cells. Results revealed immunolocalization of AR to the nucleus as well as the cytoplasm of the syncytiotrophoblast cell layer of chorionic villi until approximately meek 18 of gestation after which no immunostaining mas detected. Villous and extravillous cytotrophoblast cells as well as decidual tissue mere negative for AR at all gestational ages examined. In the presence of exogenous AR, there was a dose-dependent dependent increase in proliferation of the trophoblast at AR concentrations ranging from 1-100 ng/ml. These results suggest that AR may be an important paracrine or juxtacrine growth stimulatory molecule for cytotrophoblast cells in situ early;ly in gestation. C1 UNIV WESTERN ONTARIO,DEPT ANAT,LONDON,ON N6A 5C1,CANADA. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NR 19 TC 35 Z9 35 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0143-4004 J9 PLACENTA JI Placenta PD JUN PY 1995 VL 16 IS 4 BP 359 EP 366 DI 10.1016/0143-4004(95)90093-4 PG 8 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA RF015 UT WOS:A1995RF01500005 PM 7567798 ER PT J AU SCHEUPLEIN, RJ BOWERS, JC AF SCHEUPLEIN, RJ BOWERS, JC TI DIOXIN - AN ANALYSIS OF THE MAJOR HUMAN STUDIES - COMPARISON WITH ANIMAL-BASED CANCER RISKS SO RISK ANALYSIS LA English DT Article DE DIOXIN; CANCER RISK; PHARMACOKINETICS; DIOXIN BLOOD LEVELS ID TUMOR PROMOTION; ADIPOSE-TISSUE; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; 2,3,7,8-TCDD; WORKERS; MORTALITY; SERUM; POPULATION AB Several major epidemiological studies have reported significant mortality rates (SMRs) for both rare cancers (soft tissue sarcoma, non-Hodgkin's, lymphoma, liver) and the more common cancers (lung, colon, etc), all allegedly caused by TCDD. In this paper, we use the potency of TCDD in animals to establish a plausible worst case cancer risk and ask whether its likely that TCDD is responsible for the epidemiological findings assuming the animal carcinogenic potency is applicable to the conditions of human exposure. Two new features of the technique are the use of measured TCDD blood levels in both animals and humans for dose scale-up and the calculation of an integrated life-time exposure for the exposed workers using measured blood levels. On the basis of the stated assumptions it appears unlikely that any of the major epidemiological studies, with the possible exception of the NIOSH study(1) have adequate power to detect the common cancers potentially caused by TCDD. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SCI ANAL & SUPPORT,WASHINGTON,DC 20204. RP SCHEUPLEIN, RJ (reprint author), WEINBURG CONSULTANT GRP INC,1220 19TH ST NW,SUITE 300,WASHINGTON,DC 20036, USA. NR 38 TC 8 Z9 8 U1 1 U2 5 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD JUN PY 1995 VL 15 IS 3 BP 319 EP 333 DI 10.1111/j.1539-6924.1995.tb00325.x PG 15 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA RF155 UT WOS:A1995RF15500004 PM 7604166 ER PT J AU NAKASHIMA, H LIEBERMAN, R KARATO, A ARIOKA, H OHMATSU, H NOMURA, N SHIRAISHI, J TAMURA, T EGUCHI, K SHINKAI, T SASAKI, Y YAMAMOTO, N HUKUDA, M OSHITA, F OHE, Y SAIJO, N AF NAKASHIMA, H LIEBERMAN, R KARATO, A ARIOKA, H OHMATSU, H NOMURA, N SHIRAISHI, J TAMURA, T EGUCHI, K SHINKAI, T SASAKI, Y YAMAMOTO, N HUKUDA, M OSHITA, F OHE, Y SAIJO, N TI EFFICIENT SAMPLING STRATEGIES FOR FORECASTING PHARMACOKINETIC PARAMETERS OF IRINOTECAN (CPT-11) - IMPLICATION FOR AREA UNDER THE CONCENTRATION-TIME CURVE MONITORING SO THERAPEUTIC DRUG MONITORING LA English DT Article DE CPT-11; PHARMACOKINETIC; BAYESIAN ESTIMATION; OPTIMAL SAMPLING THEORY ID CELL LUNG-CANCER; PHASE-II; CAMPTOTHECIN; MICROCOMPUTER; PROGRAM AB A linear two-compartment Bayesian pharmacokinetic model was developed using a standard two-stage population method for the novel anticancer agent CPT-11 from 11 adult patients with refractory cancer. The accuracy and efficiency of this Bayesian model for estimating pharmacokinetic parameters including the area under the concentration-time curve (AUG) was then evaluated using two different sampling strategies in a new study cohort of 13 patients with cancer. Sampling strategies included either one, two, or three nonsteady-state feedback levels determined empirically and from optimal sampling theory (D-optimality). All 24 patients in this study received CPT-11 (60 mg/m(2)) as a 90-min infusion. Pharmacokinetic parameters derived from the Bayesian model combined with these limited sampling strategies were compared with those parameters obtained from the full sample data sets (n = 10) analyzed by weighted nonlinear least squares regression (reference method). The least-bias and most precise sampling times for estimating AUC were 3.5; 3.5 and 9.5; and 0.5, 3.5, and 9.5 h, respectively. At these times, only marginal improvement in precision of the AUC estimate was observed using two versus three samples. However, the precision of the estimate of clearance was not improved using two versus three samples. The sampling times derived from optimal sampling theory were 0.25, 3.5, 8.5, and 24 h and correlated closely to the actual and best empirical sampling times of 0.5, 3.5, 9.5, and 24 h. These results strongly suggest that Bayesian estimation combined with only two optimally timed samples accurately predicts the AUC of CPT-11 and should be useful for implementing adaptive control dosing for monitoring CPT-11 systemic exposure in patients with cancer. C1 CANC INST HOSP,DEPT MED ONCOL,TOKYO,JAPAN. NATL CANC CTR CENT HOSP,DEPT MED ONCOL,TOKYO,JAPAN. NATL CANC CTR E HOSP,DEPT MED ONCOL,CHIBA,JAPAN. RP NAKASHIMA, H (reprint author), US FDA,CTR DRUG EVALUAT & RES,HFD-006,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 26 TC 10 Z9 11 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD JUN PY 1995 VL 17 IS 3 BP 221 EP 229 DI 10.1097/00007691-199506000-00003 PG 9 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA QZ367 UT WOS:A1995QZ36700003 PM 7624917 ER PT J AU STRICHARTZ, GR HALL, S MAGNANI, B HONG, CY KISHI, Y DEBIN, JA AF STRICHARTZ, GR HALL, S MAGNANI, B HONG, CY KISHI, Y DEBIN, JA TI THE POTENCIES OF SYNTHETIC ANALOGS OF SAXITOXIN AND THE ABSOLUTE STEREOSELECTIVITY OF DECARBAMOYL SAXITOXIN SO TOXICON LA English DT Article ID TETRODOTOXIN-BINDING COMPONENT; RAT SKELETAL-MUSCLE; SODIUM CHANNEL-II; NA+ CHANNELS; SQUID AXON; ELECTROPHORUS-ELECTRICUS; MYELINATED NERVE; PURIFICATION; MEMBRANES; BRAIN AB The potencies of synthetic saxitoxin (+/-STX) and six of its synthetic analogues, including the enantioselectively synthesized unnatural (-)enantiomer of decarbamoyl saxitoxin (dcSTX), were measured and compared to those of natural saxitoxin [(+)STX]. The analogues, ail of which were racemic (+/-) mixtures except for dcSTX, varied in the substituents at the C6 position, the carbamoyl 'moiety', and the C12 position, the hydrated ketone. The ability of the toxins to inhibit the compound action potential (AP) and to displace radiolabeled natural saxitoxin (H-3-STX) from nerve membranes at equilibrium were both used as potency assays. Biological activity of both (+)- and (-)dcSTX was analyzed by the kinetics of block of single Na+ channels reconstituted in planar lipid bilayer membranes, where it was demonstrated that only (+)dcSTX had biological activity. The potency of STX analogues fell markedly as the substituent at the C6 position became smaller; K-i values from the binding competition assay (at 4 degrees C) are: (+/-)6-methanolic-STX, 5 x 10(-10) M; (+/-)6-methyl-STX, 1 x 10(-6) M; (+/-)6-dihydro-STX, 3.5 x 10(-5) M. Replacement of the ketone at the C12 position by a methylene group was accomplished in two derivatives, although both also had substituents at the C6 position. The compound (+/-)6-methyl-12-deoxy-STX was about 0.03 as potent as (+/-)6-methyl-STX and only 10(-5) as potent as racemic (+/-)STX. In synthetic compounds where the benzyloxymethyl (-CH2OCH2C6H5) substituent occurred at the C6 position, the C12-methylene derivative still displayed some binding activity (K-i = 6 x 10(-4) M). However, when the same C6 derivatized compounds also contained a 6-membered heterocyclic group (-C3H3S2-) conjugated to carbon 12, the measured binding affinity was even further decreased (K-i = 2 x 10(-3) M). The findings show that substitutions on the carbon 6 C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. US FDA,DEPT AGR,WASHINGTON,DC 20204. HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02146. RP STRICHARTZ, GR (reprint author), BRIGHAM & WOMENS HOSP,ANESTHESIA RES LABS,BOSTON,MA 02115, USA. FU NIGMS NIH HHS [GM35647]; NINDS NIH HHS [NS12108, NS18467] NR 48 TC 24 Z9 24 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0041-0101 J9 TOXICON JI Toxicon PD JUN PY 1995 VL 33 IS 6 BP 723 EP 737 DI 10.1016/0041-0101(95)00031-G PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RD672 UT WOS:A1995RD67200002 PM 7676464 ER PT J AU TAFFS, RE CHUMAKOV, KM REZAPKIN, GV LU, ZB DOUTHITT, M DRAGUNSKY, EM LEVENBOOK, IS AF TAFFS, RE CHUMAKOV, KM REZAPKIN, GV LU, ZB DOUTHITT, M DRAGUNSKY, EM LEVENBOOK, IS TI GENETIC STABILITY AND MUTANT SELECTION IN SABIN-2 STRAIN OF ORAL POLIOVIRUS VACCINE GROWN UNDER DIFFERENT CELL-CULTURE CONDITIONS SO VIROLOGY LA English DT Article ID POLYMERASE ERROR FREQUENCY; 5' NONCODING REGION; NUCLEOTIDE-SEQUENCE; TYPE-2 POLIOVIRUS; ATTENUATION; RNA; NEUROVIRULENCE; DETERMINANTS; TEMPERATURE; GENOME AB Mutations that consistently accumulated in the attenuated Sabin 2 strain of poliovirus during propagation in cell cultures were identified by sequence heterogeneity assay and quantified by mutant analysis by PCR and restriction enzyme cleavage (MAPREC). Eight additional sites previously identified in stool isolates were also examined by MAPREC in the virus passages. The pattern of selectable mutations and the rate of their accumulation depended on the type and confluence of the cell culture and the temperature of virus growth. Five unstable genomic sites were identified in Sabin 2 virus passaged 10 times at 34 degrees in African green monkey kidney (AGMK) cells, with the mutations accumulating in the range 1 to 24%. Accumulation of these mutations did not appear to result in a loss of attenuated phenotype since the virus passaged under these conditions passed the monkey neurovirulence test (MNVT). The content of the 481-G revertant known to be related to neurovirulence in monkeys did not increase. Thus, our results suggest that upon growth of Sabin 2 virus in AGMK cells at 34 degrees, the key determinant(s) of attenuation remained stable, and the mutations that occurred did not affect monkey neurovirulence. In virus passaged 10 times at 37 degrees in AGMK cells, 4 unstable genomic sites were identified, in some of them accumulating up to 12% of the mutants. This virus sample severely failed the MNVT. Virus passaged in Vero cells at 34 and 37 degrees accumulated mutants at 7 and 14 genomic sites, respectively, including 481-G in both cases, with almost complete substitution of the original nucleotides at some of the sites. We tested 44 commercial monopools of Type 2 OPV and found out that all of them contained 481-G revertants in the range 0.4-1.1%. An increase in the 481-G revertants in passaged viruses to the level of 4% and above correlated with failure of these samples by the MNVT. Since the pattern of selectable mutations differed in viruses grown in the two cell cultures used in this study, specific mutation profiles should be determined for each cell substrate used for vaccine production to assess manufacturing consistency. (C) 1995 Academic Press, Inc. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20852. NR 25 TC 35 Z9 37 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 1 PY 1995 VL 209 IS 2 BP 366 EP 373 DI 10.1006/viro.1995.1268 PG 8 WC Virology SC Virology GA RC351 UT WOS:A1995RC35100010 PM 7778271 ER PT J AU OBIRI, NI TANDON, N PURI, RK AF OBIRI, NI TANDON, N PURI, RK TI UP-REGULATION OF INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) ON HUMAN RENAL-CELL CARCINOMA-CELLS BY INTERLEUKIN-4 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID ACTIVATED KILLER-CELLS; NECROSIS-FACTOR-ALPHA; INTERFERON-GAMMA; DIFFERENTIAL EXPRESSION; LYMPHOCYTE ADHESION; ENDOTHELIAL-CELLS; MEDIATED LYSIS; TUMOR-CELLS; T-CELLS; MELANOMA AB We have previously demonstrated that human renal cell carcinoma (RCC) cells express high-affinity IL-4 receptors (IL-4R). To study the functions of these receptors, we have examined the effect of IL-4 on the expression of intracellular adhesion molecule-I (ICAM-I or CD54) on human RCC cells. Following incubation with various concentrations of IL-4, RCC cells were examined for ICAM-I expression by flow cytometric analysis. The 2 primary RCC cell cultures and the 2 cell lines examined expressed varying basal levels of ICAM-I on the cell surface. IL-4 treatment increased ICAM-I expression in a time-dependent manner and maximum augmentation of ICAM-I expression was observed after a 48 hr incubation. The increase in ICAM-I expression was specific because anti-hIL-4 antibody blocked this effect. No enhancement of ICAM-I expression was observed when RCC cells were incubated with IL-4 in the presence of cycloheximide, indicating that the IL-4 effect requires new protein synthesis. Up-regulation of ICAM-I expression was also observed at the mRNA level and maximum increase in message occurred 8 hr post-IL-4 treatment. Both IL-4 and IFN-gamma also increased soluble ICAM-I levels in WS-RCC culture supernatant. The significance of enhanced soluble and surface ICAM-I expression was investigated by examining the lymphokine activated killer (LAK) cell-mediated lysis of IL-4-treated WS-RCC cells. LAK cells lysed WS-RCC cells very effectively, but lysis observed in target cells pre-treated with IL-4 did not correlate with the increased expression of ICAM-I antigen. Our results indicate a previously unknown function of IL-4 on RCC and further demonstrate that IL-4R on RCC are functional. (C) 1995 Wiley-Liss, Inc.* C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,MOLEC TUMOR BIOL LAB,BETHESDA,MD 20892. NR 30 TC 25 Z9 25 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 29 PY 1995 VL 61 IS 5 BP 635 EP 642 DI 10.1002/ijc.2910610509 PG 8 WC Oncology SC Oncology GA RB283 UT WOS:A1995RB28300008 PM 7768636 ER PT J AU SEMBA, RD MUNASIR, Z BEELER, J AKIB, A MUHILAL AUDET, S SOMMER, A AF SEMBA, RD MUNASIR, Z BEELER, J AKIB, A MUHILAL AUDET, S SOMMER, A TI REDUCED SEROCONVERSION TO MEASLES IN INFANTS GIVEN VITAMIN-A WITH MEASLES VACCINATION SO LANCET LA English DT Article ID IMMUNIZATION; ANTIBODY; CHILDREN AB Administration of 100 000 IU vitamin A at the time of measles immunisation is currently recommended for infants in developing countries. However, the safety and value of giving vitamin A, a potent immune enhancer, with live measles virus vaccines are unknown. We conducted a randomised, double-blind, placebo-controlled clinical trial in Indonesia to evaluate the effect of simultaneous vitamin A supplementation on the immune response to measles immunisation at six months of age. 336 infants received either vitamin A (100 000 IU) or placebo when immunised with standard-titre Schwarz measles vaccine. 82% of infants seroconverted to measles. In a multiple logistic regression model adjusting for maternal antibody titres, vitamin A supplementation was associated with a lower likelihood of seroconversion to measles (odds ratio 0.40, 95% CI 0.19-0.88), and girls were less likely to seroconvert than boys (0.34, 0.15-0.76). Immunisation with standard-titre Schwarz vaccine at six months of age in this study population is characterised by high seroconversion rates. However, simultaneous high-dose vitamin A may interfere with seroconversion to live measles vaccine in infants with maternal antibody. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC MICROBIOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT IMMUNOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DIV HUMAN NUTR,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT OPHTHALMOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MOLEC MICROBIOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT IMMUNOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DIV HUMAN NUTR,BALTIMORE,MD 21287. UNIV INDONESIA,DEPT CHILD HLTH,JAKARTA,INDONESIA. US FDA,DIV VIRAL PROD,BETHESDA,MD 20014. MINIST HLTH,CTR NUTR RES & DEV,BOGOR,INDONESIA. RP SEMBA, RD (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT OPHTHALMOL,BALTIMORE,MD 21287, USA. FU NIAID NIH HHS [AI35143]; NICHD NIH HHS [HD30042] NR 10 TC 60 Z9 61 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD MAY 27 PY 1995 VL 345 IS 8961 BP 1330 EP 1332 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA RA148 UT WOS:A1995RA14800007 PM 7752754 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI VARICELLA VIRUS-VACCINE LIVE LICENSED SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material 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 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 24 PY 1995 VL 273 IS 20 BP 1564 EP 1564 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QY541 UT WOS:A1995QY54100004 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI MAMMOGRAM QUALITY ASSURANCE PROGRAM SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US FDA, OFF HLTH AFFAIRS, PARKLAWN BLDG, 5600 FISHERS LN, ROCKVILLE, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 24 PY 1995 VL 273 IS 20 BP 1564 EP 1564 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QY541 UT WOS:A1995QY54100005 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI LATEX ALLERGY TEST CLEARED FOR MARKETING SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material 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 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 24 PY 1995 VL 273 IS 20 BP 1564 EP 1564 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QY541 UT WOS:A1995QY54100006 ER PT J AU CHAKRAVERTY, M HAY, A SCHILD, G WOOD, J GUST, I HAMPSON, A WEBER, J KIM, J PARK, K CLAAS, E AF CHAKRAVERTY, M HAY, A SCHILD, G WOOD, J GUST, I HAMPSON, A WEBER, J KIM, J PARK, K CLAAS, E TI UPDATE - INFLUENZA ACTIVITY - UNITED-STATES AND WORLDWIDE, 1994-95 SEASON, AND COMPOSITION OF THE 1995-96 INFLUENZA VACCINE (REPRINTED FROM MMWR, VOL 44, PG 282-285, 1995) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 NATL INST MED RES,LONDON NW7 1AA,ENGLAND. NATL INST BIOL STAND & CONTROLS,POTTERS BAR EN6 3QG,HERTS,ENGLAND. COMMONWEALTH SERUM LABS,PARKVILLE,VIC 3052,AUSTRALIA. LAB CTR DIS CONTROL,OTTAWA,ON K1A 0L2,CANADA. NATL INST HLTH,SEOUL,SOUTH KOREA. ERASMUS UNIV ROTTERDAM,ROTTERDAM,NETHERLANDS. WHO,NATL INFLUENZA CTR,PROGRAM BACTERIAL VIRAL DIS & IMMUNOL,CH-1211 GENEVA,SWITZERLAND. CDC,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,INFLUENZA BR,ATLANTA,GA. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,ROCKVILLE,MD. RP CHAKRAVERTY, M (reprint author), CENT PUBL HLTH LAB,LONDON NW9 5HT,ENGLAND. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 24 PY 1995 VL 273 IS 20 BP 1565 EP 1566 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QY541 UT WOS:A1995QY54100007 ER PT J AU ANDERSON, LW LUDEMAN, SM COLVIN, OM GROCHOW, LB STRONG, JM AF ANDERSON, LW LUDEMAN, SM COLVIN, OM GROCHOW, LB STRONG, JM TI QUANTITATION OF 4-HYDROXYCYCLOPHOSPHAMIDE ALDOPHOSPHAMIDE IN WHOLE-BLOOD SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article ID CLINICAL PHARMACOKINETICS; PHOSPHORAMIDE MUSTARD; CYCLOPHOSPHAMIDE; METABOLITES; PLASMA AB There is considerable interest in determining 4-hydroxycylcophosphamide/aldophosphamide (4-HO-CP/AP) blood levels in patients receiving the prodrug, cyclophosphamide (CP). Phosphoramide mustard (PM), the alkylating metabolite of CP, is relatively impermeable to cell membranes and it is generally believed that circulating intermediary metabolites, including aldophosphamide, the immediate precursor of PM, is; transported by circulating blood to tumor tissue. Therefore, circulating 4-HO-CP/AP blood levels should more closely reflect the oncostatic and cytotoxic effects of CP than the parent drug. We have developed a gas chromatographic electron-impact mass spectrometric (GC-EIMS) method suitable for routine monitoring of 4-HO-CP/AP levels in whole blood over the range 0.085 mu M (25 ng/ml) to 34 mu M (10 mu g/ml). The unstable metabolites were derivatized with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine-HCl to form a stable aldophosphamide oxime derivative (PBOX). [H-2(4)]PBOX was used as an internal standard. For clinical samples, tubes were prepared prior to blood drawing, which contained the derivatizing reagent solution and the internal standard. These solutions were stable for up to 3 months when stored at room temperature. Following addition of blood to the reaction tubes, PBOX formation was rapid and the resulting derivative was stable under these conditions for up to 8 days at room temperature. Application of the method was demonstrated by quantitating 4-HO-CP/AP blood levels in patients receiving 4 g/m(2) intravenous infusion of CP over a period of 90 min. C1 US FDA,CDER,ORR,DEPT CLIN PHARMACOL,ROCKVILLE,MD 20850. JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,BALTIMORE,MD 21287. FU NCI NIH HHS [5-PO1-CA15396, 5-RO1-CA16783] NR 18 TC 34 Z9 34 U1 1 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-Biomed. Appl. PD MAY 19 PY 1995 VL 667 IS 2 BP 247 EP 257 DI 10.1016/0378-4347(95)00036-I PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA RC070 UT WOS:A1995RC07000007 PM 7663697 ER PT J AU OHANLON, TP RABEN, N MILLER, FW AF OHANLON, TP RABEN, N MILLER, FW TI A NOVEL GENE ORIENTED IN A HEAD-TO-HEAD CONFIGURATION WITH THE HUMAN HISTIDYL-TRANSFER-RNA SYNTHETASE (HRS) GENE ENCODES AN MESSENGER-RNA THAT PREDICTS A POLYPEPTIDE HOMOLOGOUS TO HRS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TRANSFER-RNA-SYNTHETASE; BIDIRECTIONAL PROMOTER; EVOLUTIONARY RELATIONSHIPS; MESSENGER-RNA; RESTRICTION; ALPHA-1(IV); EXPRESSION; SITE AB The human histidyl-tRNA synthetase (HRS) gene encodes an enzyme that catalyzes the esterification of histidine to its cognate tRNA as an early step in protein biosynthesis. Previous reports have described a bidirectional promoter element which coordinates the transcription of both HRS and an unknown mRNA whose gene is oriented in a head-to-head configuration with HRS. We have isolated and characterized a human genomic DNA clone that encodes portions of these oppositely transcribed mRNAs and a putatively full-length cDNA clone (HO3) corresponding to the gene mapping immediately 5' of HRS. The largest open reading frame within HO3 (1518 bp) shares approximately 75% nucleotide sequence identity with human HRS (1527 bp) and predicts a polypeptide with extensive amino acid sequence homology with the HRS protein (72%). Moreover, amino acid sequence motifs characteristic of class II aminoacyl-tRNA synthetases are conserved within HO3. Despite their similarity, HRS and HO3 have divergent amino-terminal domains which correspond to the first two exons of each gene. RNA blot analysis revealed that HRS (2.0 kb) and HO3 (2.5 kb) exhibit distinct patterns of steady-state mRNA expression among multiple human tissues. (C) 1995 Academic Press, Inc. C1 NIAMSD,BETHESDA,MD 20892. RP OHANLON, TP (reprint author), US FDA,CTR BIOL EVALUAT & RES,MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 25 TC 26 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 16 PY 1995 VL 210 IS 2 BP 556 EP 566 DI 10.1006/bbrc.1995.1696 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QX870 UT WOS:A1995QX87000045 PM 7755634 ER PT J AU MEHROTRA, PT GRANT, AJ SIEGEL, JP AF MEHROTRA, PT GRANT, AJ SIEGEL, JP TI SYNERGISTIC EFFECTS OF IL-7 AND IL-12 ON HUMAN T-CELL ACTIVATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA PRODUCTION; STIMULATORY FACTOR INTERLEUKIN-12; LYMPHOCYTE MATURATION FACTOR; HUMAN PERIPHERAL-BLOOD; NK CELLS; GROWTH-FACTOR; IFN-GAMMA; CYTOTOXIC LYMPHOCYTES; RECEPTOR EXPRESSION; GENE-EXPRESSION AB We have previously demonstrated that human rIL-12 alone can augment the development of cytotoxic activity in stimulated CD8(+) T cells. The present study was undertaken to examine the interactions of rIL-7 and rIL-12 on human peripheral blood T cell activation and CTL differentiation. Purified T lymphocytes were pulsed overnight with immobilized alpha-CD3 and then cultured for 3 additional days with IL-7 and/or IL-12. The combination of IL-7 and IL-12 synergistically enhanced the proliferation of either fresh CD3(+) T cells or an IL-2-dependent CD4(+) T cell line, Kit-225-K6. This synergy was seen on both subsets of T cells; however, CD8(+) T cells were usually more responsive to IL-7 and IL-12 at lower concentrations than were CD4(+) T cells. Furthermore, these cytokines additively/synergistically augmented the cytotoxic activity of CD8(+) T cells. Abs to IL-2 and IL-2R alpha blocked the synergistic effect on proliferation of CD4(+) T cells, but had a minimal effect on the synergistic response of the proliferative and cytotoxic activity of CD8(+) T cells. Examination of the effects of IL-7 and IL-12 on the expression of IL-12 receptor on T cells revealed an increase in the subunit of IL-12R by IL-7 as determined by flow cytometric analysis. We analyzed the effects on IFN-gamma production by CD8(+) T cells and found that IL-7 alone did not induce detectable levels of IFN-gamma production but together with IL-12 it synergistically enhanced the production of IFN-gamma We also found that IFN-gamma was probably not required for enhanced CTL activity of CD8(+) T cells, because Ab to human IFN-gamma did not block additive/synergistic effects of either cytokine. The synergistic stimulatory activity of IL-7 and IL-12 may be of significance in vivo and may provide an alternative mechanism of stimulating T cells for use in immunotherapy. RP MEHROTRA, PT (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,CELLULAR IMMUNOL LAB HFM518,ROCKVILLE,MD 20852, USA. NR 64 TC 81 Z9 85 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1995 VL 154 IS 10 BP 5093 EP 5102 PG 10 WC Immunology SC Immunology GA QW901 UT WOS:A1995QW90100020 PM 7730615 ER PT J AU GRUBER, MF WEIH, KA BOONE, EJ SMITH, PD CLOUSE, KA AF GRUBER, MF WEIH, KA BOONE, EJ SMITH, PD CLOUSE, KA TI ENDOGENOUS MACROPHAGE CSF PRODUCTION IS ASSOCIATED WITH VIRAL REPLICATION IN HIV-1-INFECTED HUMAN MONOCYTE-DERIVED MACROPHAGES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; PRIMARY MONONUCLEAR PHAGOCYTES; LYMPHOBLASTOID CELL-LINE; GROWTH-FACTOR-BETA; PERIPHERAL-BLOOD; HIV-1 INFECTION; FACTOR-ALPHA; TNF-ALPHA AB Human monocyte-derived macrophages (MDM) cultured in medium containing macrophage (M) CSF are more susceptible to infection with HIV-1.M-CSF increases the frequency with which MDM become infected, the level of HIV mRNA expressed per infected cell, and the level of proviral DNA expressed per infected culture. Because of these effects of M-CSF on HIV-1 replication and the reported function of this factor as a survival and differentiation factor for human monocytes, we investigated whether HIV-1 could induce endogenous M-CSF production by MDM and the potential role of endogenous M-CSF on HIV-1 infection in these cells. MDM infected with HIV and maintained in the absence of exogenous M-CSF produced this cytokine endogenously at levels 5- to 24- fold higher than uninfected cells. In contrast, the proinflammatory cytokines IL-1, IL-6, and TNF-alpha and the growth factor granulocyte-macrophage CSF were not detected. The kinetics of M-CSF production following infection paralleled the kinetics of virus replication. Furthermore, enhanced production of M-CSF was dependent on viral entry and active replication of HIV-1. Thus, endogenous M-CSF production may contribute to the survival of HIV-1 infected MDM, enable them to function as a reservoir for HIV, and facilitate the spread of virus in vivo. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. VET ADM MED CTR,BIRMINGHAM,AL 35294. FU NIAID NIH HHS [AI-45218]; NIDDK NIH HHS [DK-47322] NR 47 TC 55 Z9 56 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1995 VL 154 IS 10 BP 5528 EP 5535 PG 8 WC Immunology SC Immunology GA QW901 UT WOS:A1995QW90100067 PM 7537309 ER PT J AU ONEILL, R ROSEN, O DARNE, B DURRLEMAN, S AF ONEILL, R ROSEN, O DARNE, B DURRLEMAN, S TI CONSTRUCTING A BOOTSTRAP CONFIDENCE-INTERVAL FOR THE UNKNOWN CONCENTRATION IN RADIOIMMUNOASSAY - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion C1 TECHNION ISRAEL INST TECHNOL,FAC IND ENGN & MANAGEMENT,IL-32000 HAIFA,ISRAEL. RP ONEILL, R (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV BIOMETR,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 15 PY 1995 VL 14 IS 9-10 BP 953 EP 953 PG 1 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 RC528 UT WOS:A1995RC52800012 ER PT J AU LEWIS, J JONES, B LIU, JP COLMAN, P ONEILL, R AF LEWIS, J JONES, B LIU, JP COLMAN, P ONEILL, R TI CHOOSING THE DESIGN OF A CONFIRMATORY CLINICAL-TRIAL - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion C1 UNIV CANTERBURY,INST MATH & STAT,CANTERBURY CT2 7NF,KENT,ENGLAND. BERLEX LABS INC,DEPT BIOSTAT,WAYNE,NJ 07066. US FDA,CTR DRUG EVALUAT & RES,DIV BIOMETR,ROCKVILLE,MD 20857. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 15 PY 1995 VL 14 IS 9-10 BP 1079 EP 1080 PG 2 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 RC528 UT WOS:A1995RC52800025 ER PT J AU ONEILL, RT AF ONEILL, RT TI STATISTICAL CONCEPTS IN THE PLANNING AND EVALUATION OF DRUG SAFETY FROM CLINICAL-TRIALS IN DRUG DEVELOPMENT - ISSUES OF INTERNATIONAL HARMONIZATION SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 2nd International Meeting on Statistical Methods in Biopharmacy: Choice and Decisions in the Development of Pharmaceutical Products CY SEP 06-07, 1993 CL PARIS, FRANCE SP ASU Biopharmacy, INSERM AB The assessment of the safety of new drugs during pre-marketing clinical studies is an important and integral part of the drug development and regulatory evaluation process. The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is a project that brings together the regulatory decision-makers of Europe, Japan and the United States of America and the experts from the pharmaceutical industry in the three regions to seek ways to eliminate redundant and duplicative technical requirements among the developed countries for registering new medicinal substances and products. The ICH is developing guidelines or position papers to achieve the goal of harmonizing technical standards in three broad areas, namely, drug efficacy, safety and quality. Within the area of drug safety, this paper will discuss three of the safety topics because of their relevant statistical framework, and because these topics have not, to date, received any attention by the statistical community. The three issues under consideration by the International Conference on Harmonization (ICH), are: 1. Dose-response information to support drug registration (especially dose/toxicity relationships).(1) 2. Studies in support of special populations;(2) Geriatrics, A Draft Guideline. 3. ICH Draft Guideline 3 on 'The extent of population exposure required to assess clinical safety for drugs intended for long-term-treatment of non-life-threatening conditions'.(3) The ICH special population guideline concerning studies in geriatric patients is closely related to a recent Food and Drug Administration 'Guideline for the study and evaluation of gender differences in the clinical evaluation of drugs',(4) which is another example of a 'subgroup' for whom specific interest exists to evaluate drug safety and efficacy. RP ONEILL, RT (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV BIOMETR,ROCKVILLE,MD 20857, USA. NR 15 TC 5 Z9 5 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 15 PY 1995 VL 14 IS 9-10 BP 1117 EP 1127 DI 10.1002/sim.4780140932 PG 11 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 RC528 UT WOS:A1995RC52800030 ER PT J AU LARNER, AC FINBLOOM, DS AF LARNER, AC FINBLOOM, DS TI PROTEIN-TYROSINE PHOSPHORYLATION AS A MECHANISM WHICH REGULATES CYTOKINE ACTIVATION OF EARLY RESPONSE GENES SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Review ID GUANYLATE-BINDING PROTEIN; INTERFERON-STIMULATED GENES; SIGNAL-TRANSDUCTION PATHWAY; TRANSCRIPTION FACTOR ISGF3; MACROPHAGE CELL-LINE; GAMMA-INTERFERON; ALPHA-INTERFERON; BETA-INTERFERON; GROWTH-FACTOR; CYTOPLASMIC ACTIVATION AB Two well-defined rapid responses which occur as a consequence of growth factors binding to their cell surface receptors involve tyrosine phosphorylation of cellular proteins and the induction of the transcription of cellular genes. Recent advances have been made in purification and cloning of Src homology 2 and 3 (SH2/SH3) domain-containing transcription factors which are required for the activation of early response genes by interferons. These transcription factors are covalently modified by tyrosine phosphorylation such that they interact with enhancers needed for interferon-stimulated gene expression. The Jak family of tyrosine kinases are also an integral component in these signalling cascades. The information gained concerning interferon signalling has now been extended to include a broad network of cytokine-regulated signalling systems which use tyrosine phosphorylation of a family of structurally related proteins to activate transcription of early response genes. RP LARNER, AC (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 115 TC 53 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD MAY 12 PY 1995 VL 1266 IS 3 BP 278 EP 287 DI 10.1016/0167-4889(95)00015-K PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QZ778 UT WOS:A1995QZ77800009 PM 7539296 ER PT J AU CHOU, MW SHADDOCK, JG KONG, J HART, RW CASCIANO, DA AF CHOU, MW SHADDOCK, JG KONG, J HART, RW CASCIANO, DA TI EFFECT OF DIETARY RESTRICTION ON PARTIAL HEPATECTOMY-INDUCED LIVER-REGENERATION OF AGED F344 RATS SO CANCER LETTERS LA English DT Article DE DIETARY RESTRICTION; PARTIAL HEPATECTOMY; DNA ADDUCT; BENZO[A]PYRENE; AFLATOXIN B-1 ID CALORIC RESTRICTION; CELL-PROLIFERATION; CARBON-TETRACHLORIDE; CARCINOGENESIS; DNA; METABOLISM; CYTOCHROME-P-450; AFLATOXIN-B1; EXPOSURE; BINDING AB Fourteen weeks-old male F344 rats maintained on a reduced calorie diet (60% of ad libitum (AL) food consumption) for 6 weeks or for 14 months did not affect the hepatic cell proliferation in terms of % S phase population, determined by evaluation of DNA synthesis in hepatocytes isolated from either young (5 months) or aged (18 months) rats. However, hepatic basal cellular DNA synthesis estimated by [H-3]thymidine incorporation was reduced through acute dietary restriction (DR) in young rats, but increased in aged animals after 14 months restriction. Partial hepatectomy (PH) on aged rats stimulated hepatocyte regeneration and restored some aging-associated biochemical functions, such as drug metabolizing enzyme-dependent xenobiotic metabolic activation which was determined by measuring the formation of carcinogen-DNA adducts. Forty-eight hours after partial hepatectomy, the % of S phase population and the basal nuclear DNA synthesis of hepatocytes isolated from the partial hepatectomized DR-rats were 4- and 2.8-fold, respectively, greater than those of hepatocytes from AL-animals. DR reduced aflatoxin B-1 (AFB(1)) metabolizing enzyme activity and decreased the AFB(1)-DNA adduct formation in young rats treated with AFB(1). In aged AL-rats, the formation of AFB(1)-DNA adducts diminished to the same level as that of DR-groups and probably was due to the faster decline of drug metabolizing enzymes in aging AL-rats. However, 48 h after PH, the metabolic activation of AFB(1) was restored in AL- and DR-groups which resulted in the increase of AFB(1)-DNA binding by 4.2 and 1.9-fold, respectively. During the liver regeneration of old PH-rats, DR inhibited the AFB(1)-DNA adduct formation after the PH-rats received a single dose of AFB(1). DR increased benzo[a]pyrene (BaP) metabolic activation in both young and aged rats. Aging also decreased BaP-DNA adduct formation in both DR and AL-rats. The increase of BaP-DNA adduct formation in PH-groups was attributed to the restoration of BaP-metabolizing enzyme activity during liver regeneration. The PH-stimulated BaP-DNA adduct formation in AL- and DR-rats was 3.4- and 2.0-fold greater than control aged rats, Our results indicated that the stimulation of PH-induced liver regeneration by DR in aged animals may be attributed to the retardation of aging by DR and the retention of more active biochemical and enzymological functions in old DR-animals, RP CHOU, MW (reprint author), NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 33 TC 14 Z9 16 U1 0 U2 1 PU ELSEVIER SCI PUBL 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 MAY 8 PY 1995 VL 91 IS 2 BP 191 EP 197 DI 10.1016/0304-3835(95)03750-Q PG 7 WC Oncology SC Oncology GA RA705 UT WOS:A1995RA70500006 PM 7767909 ER PT J AU YU, MW MASON, BL GUO, ZP TANKERSLEY, DL NEDJAR, S MITCHELL, FD BISWAS, RM AF YU, MW MASON, BL GUO, ZP TANKERSLEY, DL NEDJAR, S MITCHELL, FD BISWAS, RM TI HEPATITIS-C TRANSMISSION ASSOCIATED WITH INTRAVENOUS IMMUNOGLOBULINS SO LANCET LA English DT Letter C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,BETHESDA,MD 20892. RP YU, MW (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,BETHESDA,MD 20892, USA. NR 5 TC 75 Z9 77 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD MAY 6 PY 1995 VL 345 IS 8958 BP 1173 EP 1174 DI 10.1016/S0140-6736(95)91002-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QW622 UT WOS:A1995QW62200036 PM 7536874 ER PT J AU CRANE, NT WILSON, DB COOK, DA LEWIS, CJ YETLEY, EA RADER, JI AF CRANE, NT WILSON, DB COOK, DA LEWIS, CJ YETLEY, EA RADER, JI TI EVALUATING FOOD FORTIFICATION OPTIONS - GENERAL-PRINCIPLES REVISITED WITH FOLIC-ACID SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB Objectives. This article uses folic acid as an example to illustrate some of the complex issues and general principles that emerge when evaluating fortification of the food supply as one possible means to address a public health recommendation. Methods. Distributions of current daily folate intakes from conventional foods and dietary supplements were estimated. Intakes that might result from fortification of cereal-grain products and ready-to-eat cereals at various levels for eight age-gender groups were also estimated by using the US Department of Agriculture's 1987-1988 Nationwide Food Consumption Survey. Results. The results illustrate that fortification of the US food supply tends to increase folate intakes of consumers at the high end of the intake distribution curves in the general population to a greater extent than it affects consumers at the low end of the intake distribution curves in the target population. Conclusions. The effectiveness of food fortification options for a target population and the safety for the general population impose conflicting challenges that must be considered concurrently when making decisions about fortifying the US food supply. C1 USDA ARS,WASHINGTON,DC 20250. RP CRANE, NT (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF FOOD LABELING HFS165,200 C ST SW,WASHINGTON,DC 20204, USA. NR 30 TC 53 Z9 56 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 1995 VL 85 IS 5 BP 660 EP 666 DI 10.2105/AJPH.85.5.660 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QW839 UT WOS:A1995QW83900012 PM 7733426 ER PT J AU BIENER, L HEATON, A AF BIENER, L HEATON, A TI WOMEN DIETERS OF NORMAL-WEIGHT - THEIR MOTIVES, GOALS, AND RISKS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID BEHAVIOR; OBESITY; ADOLESCENT; OVERWEIGHT; POPULATION; ADULTS AB Using data from a national survey of weight loss practices, this study examined those dieters who were of normal weight. Forty-seven percent of White women, 25% of Black women, and 16% of men currently trying to lose weight had a body mass index under 25. Women's primary motive was health improvement. Among normal-weight female dieters, 12% of Whites and 27% of Blacks were using risky strategies. Dieters were less likely than nondieters to smoke and reported better nutritional practices; however, they were not more likely to exercise, and their maximum weight fluctuation was 50% greater. Additional research on the consequences of dieting among normal-weight individuals is of high priority. C1 US FDA,WASHINGTON,DC 20204. RP BIENER, L (reprint author), UNIV MASSACHUSETTS,SURVEY RES CTR,BOSTON,MA 02125, USA. OI Biener, Lois/0000-0002-4130-8138 NR 28 TC 23 Z9 23 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 1995 VL 85 IS 5 BP 714 EP 717 DI 10.2105/AJPH.85.5.714 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QW839 UT WOS:A1995QW83900021 PM 7733435 ER PT J AU KAZEMPOUR, K AF KAZEMPOUR, K TI IMPACT OF STRATIFICATION IMBALANCE ON PROBABILITY OF TYPE-I ERROR SO AMERICAN STATISTICIAN LA English DT Article DE ANALYSIS OF COVARIANCE; BASE-LINE ADJUSTMENT; PRETEST-POSTTEST ID ANTIHYPERTENSIVE AGENTS; ASSESSING EFFICACY AB The impact of ignoring the stratification effect on the probability of a Type I error is investigated. The evaluation is in a clinical setting where the treatments may have different response rates among the strata. Deviation from the nominal probability of a Type I error, alpha, depends on the stratification imbalance and the heterogeneity in the response rates; it appears that the latter has a larger impact. The probability of a Type I error is depicted for cases in which the heterogeneity in the response rate is present but there is no stratification imbalance. Three-dimensional graphs are used to demonstrate the simultaneous impact of heterogeneity in response rates and of stratification imbalance. RP KAZEMPOUR, K (reprint author), US FDA,DIV BIOMETR,ROCKVILLE,MD 20857, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER STATIST ASSN PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0003-1305 J9 AM STAT JI Am. Stat. PD MAY PY 1995 VL 49 IS 2 BP 170 EP 174 DI 10.2307/2684632 PG 5 WC Statistics & Probability SC Mathematics GA RN994 UT WOS:A1995RN99400008 ER PT J AU BEDFORD, RF PALMISANO, BW AF BEDFORD, RF PALMISANO, BW TI SUCCINYLCHOLINE SO ANESTHESIOLOGY LA English DT Editorial Material RP BEDFORD, RF (reprint author), US FDA,CTR DRUG EVALUAT & RES,WASHINGTON,DC 20204, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 1995 VL 82 IS 5 BP A31 EP A32 PG 2 WC Anesthesiology SC Anesthesiology GA QW587 UT WOS:A1995QW58700002 ER PT J AU ZVILICH, M WILLIAMS, JC WAAG, D RILL, WR BELL, P KENDE, M AF ZVILICH, M WILLIAMS, JC WAAG, D RILL, WR BELL, P KENDE, M TI EFFICACY OF COXIELLA-BURNETII AND ITS CHLOROFORM-METHANOL RESIDUE (CMR) FRACTION AGAINST RIFT-VALLEY FEVER VIRUS-INFECTION IN MICE SO ANTIVIRAL RESEARCH LA English DT Article DE ANTIVIRAL SUBSTANCE; RICKETTSIAL EXTRACT; IMMUNOMODULATOR; RVF VIRUS ID PHASE-I; INTERFERON-ALPHA; POLY(ICLC); RIBAVIRIN; IMMUNITY; VACCINE; BETA AB Strains of Coxiella burnetii phase I and II whole cells (WC-I and WC-II) or whole cell fractions were assessed for their potential to induce long-lasting protection in endotoxin-non-responder C3H/HeJ or CD-1 mice against Rift Valley fever (RVF) virus challenge. Among the whole cell fractions, only the chloroform-methanol residue (CMR), administered as a single dose (100 mu g per mouse) 24 h before viral challenge, effectively protected 100% of the mice from RVF virus; the CMR of the Ohio strain of C. burnetii was not protective. Most of the RVF virus-infected mice treated with other C. burnetii cell fractions died, although their times to death varied. Lipopolysaccharide (LPS) associated with CMR preparations used in these studies, did not protect against RVF virus challenge. A single dose of 100 mu g of CMR given 24 h before viral challenge completely eradicated 4-5 logs of RVF virus in the serum, liver, spleen, and central nervous system. Compared to several other immunomodulators, CMR was an equally effective antiviral agent. Efficacy of CMR of both Henzerling and Ohio,strains disappeared or was marginal when treatment was initiated 2-3 days before RVF viral challenge, even when a second or a third dose of CMR was administered after challenge. A single dose of liposome-encapsulated CMR to RVF virus-infected mice extended the range of therapeutic efficacy of this biologically active component of C. burnetii to 4 days before infection. C1 USA,MED RES INST INFECT DIS,DEPT CLIN IMMUNOL,DIV APPL RES,FT DETRICK,MD 21702. USA,MED RES INST INFECT DIS,DEPT PATHOGENESIS & IMMUNOL,DIV BACTERIOL,FT DETRICK,MD 21702. US FDA,CTR BIOL EVALUAT & RES,OFF VACCINE RES & REVIEW,DIV VACCINES & RELATED PROD APPLICAT,ROCKVILLE,MD 20852. NR 32 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 1995 VL 27 IS 1-2 BP 137 EP 149 DI 10.1016/0166-3542(95)00003-5 PG 13 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA RA073 UT WOS:A1995RA07300011 PM 7486951 ER PT J AU ATLAS, RM CERNIGLIA, CE AF ATLAS, RM CERNIGLIA, CE TI BIOREMEDIATION OF PETROLEUM POLLUTANTS - DIVERSITY AND ENVIRONMENTAL ASPECTS OF HYDROCARBON BIODEGRADATION SO BIOSCIENCE LA English DT Article C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. RP ATLAS, RM (reprint author), UNIV LOUISVILLE,DEPT BIOL,LOUISVILLE,KY 40292, USA. NR 13 TC 134 Z9 144 U1 2 U2 20 PU AMER INST BIOL SCI PI WASHINGTON PA 730 11TH STREET, NW, WASHINGTON, DC 20001-4521 SN 0006-3568 J9 BIOSCIENCE JI Bioscience PD MAY PY 1995 VL 45 IS 5 BP 332 EP 338 DI 10.2307/1312494 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA QU439 UT WOS:A1995QU43900012 ER PT J AU CALVERT, RJ WEGHORST, CM BUZARD, GS AF CALVERT, RJ WEGHORST, CM BUZARD, GS TI PCR AMPLIFICATION OF SILVER-STAINED SSCP BANDS FROM COLD SSCP GELS SO BIOTECHNIQUES LA English DT Note ID CONFORMATION POLYMORPHISM ANALYSIS; NONISOTOPIC SSCP; MUTATIONS; DNA; GENE C1 NCI,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. RP CALVERT, RJ (reprint author), US FDA,MODI LAB,HFS-452,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 14 TC 10 Z9 11 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAY PY 1995 VL 18 IS 5 BP 782 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QX422 UT WOS:A1995QX42200014 PM 7619478 ER PT J AU POGRIBNY, IP BASNAKIAN, AG MILLER, BJ LOPATINA, NG POIRIER, LA JAMES, SJ AF POGRIBNY, IP BASNAKIAN, AG MILLER, BJ LOPATINA, NG POIRIER, LA JAMES, SJ TI BREAKS IN GENOMIC DNA AND WITHIN THE P53 GENE ARE ASSOCIATED WITH HYPOMETHYLATION IN LIVERS OF FOLATE/METHYL-DEFICIENT RATS SO CANCER RESEARCH LA English DT Article ID FED METHYL-DEFICIENT; CHOLINE-DEVOID DIET; ACID-DEFINED DIETS; DOUBLE-STRAND BREAKS; S-ADENOSYLMETHIONINE; MAMMALIAN NUCLEI; METHIONINE; CANCER; CELLS; CARCINOGENESIS AB Male weanling Fischer 344 rats were fed either a semipurified diet deficient in the methyl donors methionine, choline, and folic acid or a supplemented control diet for a period of 9 weeks. At intervals of 2, 5, and 7 days, 3 weeks, and 9 weeks after initiation of the respective diets, the relative level of DNA strand breaks and the degree of cytosine methylation were quantified in high molecular weight DNA and also within the p53 gene in liver samples from these rats. Genome-wide strand break accumulation was associated with progressive genomic hypomethylation and increased DNA methyltransferase activity, With the use of quantitative PCR as a gene-specific DNA strand break assay, unique DNA strand breaks were detected in exon 5 but not in exons 6-8 of the p53 gene, and were accompanied by significant p53 gene hypomethylation. DNA hypomethylation has been shown to alter the conformation and stability of the chromatin structure, rendering affected regions more accessible to DNA-damaging agents. To determine whether methylation status alters the sensitivity of DNA to strand breakage, DNA in isolated nuclei was methylated in vitro and exposed to endogenous calcium/magnesium-dependent endonuclease activated under defined conditions, The incidence of enzyme-induced DNA strand breaks was decreased significantly with increased DNA methylation. In nuclei isolated from livers of methyl-deficient rats, the hypomethylated DNA was found to be more sensitive to enzyme- and oxidant-induced DNA strand break induction, Taken together, these results provide evidence that DNA strand breaks are induced in high molecular weight DNA and also within the p53 gene in Liver tissue from methyl-deficient rats. The increased incidence of these strand breaks in DNA from methyl-deficient rats may be related to alterations in chromatin accessibility associated with DIVA hypomethylation. C1 US FDA,NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. NR 53 TC 235 Z9 243 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1995 VL 55 IS 9 BP 1894 EP 1901 PG 8 WC Oncology SC Oncology GA QV015 UT WOS:A1995QV01500018 PM 7794383 ER PT J AU GREEN, S AF GREEN, S TI VALIDATION AND IN-VITRO NEUROTOXICITY SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Article; Proceedings Paper CT IUPHAR 1994 Satellite Symposium on In Vitro Neurotoxicology CY JUL, 1994 CL VAL MORIN, CANADA DE IN VITRO; NEUROTOXICITY; VALIDATION AB 1. Validation of in vitro systems for studying neurotoxicants generally has not been accomplished, although in vitro tests have been used as screens to identify potential neurotoxic hazards and to study mechanisms. 2. A number of factors need to be taken into account when a test is validated: (i) a rationale for developing the test; (ii) clear biological or pathophysiological relevance of the endpoint to the effect detected in vivo; (iii) a standardized protocol and evidence of intra- and interlaboratory reproducibility; (iv) testing of chemicals representative of the categories of interest, including very toxic, moderately toxic and relatively non-toxic substances; and (v) a method to statistically evaluate the data. 3. Proper validation should lead to methods which can be used by regulatory agencies to make decisions regarding hazard/risk. RP GREEN, S (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV TOXICOL RES,LAUREL,MD 20708, USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL AUSTR PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON 3053, AUSTRALIA SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD MAY PY 1995 VL 22 IS 5 BP 383 EP 384 DI 10.1111/j.1440-1681.1995.tb02026.x PG 2 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA RA297 UT WOS:A1995RA29700019 PM 7554439 ER PT J AU ABDALLAH, HY LUDDEN, TM AF ABDALLAH, HY LUDDEN, TM TI A SPREADSHEET PROGRAM FOR SIMULATION OF BIOEQUIVALENCE AND BIOAVAILABILITY STUDIES SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE BIOAVAILABILITY; BIOEQUIVALENCE; COMPUTER SIMULATIONS; SPREADSHEETS; INTRASUBJECT VARIABILITY AB This paper presents a spreadsheet for Excel for Windows(TM), which simulates bioequivalence (BE) trials. The program incorporates intersubject and intrasubject variability in drug absorption and disposition as well as assay precision and the uniformity of the administered dose. The output provides confidence intervals and a pass/fail code for each study. This program is useful for simulating BE trials using widely available and simple-to-use spreadsheet programs. An example of the application of the program in assessing the influence of intrasubject variability on the outcome of BE testing of two identical formulations is also presented. C1 SYNTEX DEV RES,CTR CLIN PHARMACOL & CLIN PHARMACOKINET,PALO ALTO,CA 94303. US FDA,DIV BIOPHARMACEUT,ROCKVILLE,MD 20857. NR 3 TC 2 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD MAY PY 1995 VL 25 IS 3 BP 349 EP 354 DI 10.1016/0010-4825(95)00015-V PG 6 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA RG252 UT WOS:A1995RG25200004 PM 7554851 ER PT J AU KREITMAN, RJ PURI, RK MCPHIE, P PASTAN, I AF KREITMAN, RJ PURI, RK MCPHIE, P PASTAN, I TI CIRCULARLY PERMUTED INTERLEUKIN-4 RETAINS PROLIFERATIVE AND BINDING-ACTIVITY SO CYTOKINE LA English DT Article DE CYTOKINE; GROWTH FACTOR; MUTEIN ID MAGNETIC-RESONANCE SPECTROSCOPY; 3-DIMENSIONAL SOLUTION STRUCTURE; RECOMBINANT HUMAN INTERLEUKIN-4; RECEPTOR GAMMA-CHAIN; SECONDARY STRUCTURE; CARCINOMA-CELLS; EXPRESSION; PROTEINS; VARIANTS; LYMPHOCYTES AB In human interleukin 4(IL-4), the carboxyl and amino termini of the 129 amino acid hormone are close to each other and this region is believed to be important for binding to the IL-4 receptor (IL-4r). We constructed plasmids encoding circularly permuted IL-4 mutants with the peptide Gly-Gly-Asn-Gly-Gly (GGNGG) joining the carboxyl to the amino terminus and with new amino and carboxyl termini elsewhere. Mutant IL-4(38-37) is composed of IL-4 residues 38-129, GGNGG and 1-37. Mutant IL-4(105-104) is composed of IL-4 residues 105-129, GGNGG and 1-104. IL-4(38-37) and IL-4(105-104) were purified from E. coli to near homogeneity and retained 50-100% of the binding and proliferative activity of IL-4, and in addition retained the ability to upregulate CD23 on Burkitt's lymphoma cells. Circular dichroism studies indicated that the tertiary structures of both IL-4(38-37) and IL-4(105-104) were retained, with the former molecule most similar to native IL-4. We conclude that while both native termini of IL-4 may be near its binding site, neither is required to be free for optimum activity. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NIH,US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR GENE THERAPIES,MOLEC TUMOR BIOL LAB,BETHESDA,MD 20892. NIDDKD,DIV INTRAMURAL RES,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892. NR 44 TC 17 Z9 17 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAY PY 1995 VL 7 IS 4 BP 311 EP 318 DI 10.1006/cyto.1995.0039 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA RB161 UT WOS:A1995RB16100002 PM 8589260 ER PT J AU WAAG, D CHULAY, J MARRIE, T ENGLAND, M WILLIAMS, J AF WAAG, D CHULAY, J MARRIE, T ENGLAND, M WILLIAMS, J TI VALIDATION OF AN ENZYME-IMMUNOASSAY FOR SERODIAGNOSIS OF ACUTE Q-FEVER SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; COXIELLA-BURNETII; PHASE-I; IMMUNOGLOBULIN RESPONSES; ANTIBODY-RESPONSE; IMMUNE-RESPONSE; PARTURIENT CAT; OUTBREAK; PNEUMONIA AB An enzyme immunoassay was validated for the serodiagnosis of acute Q fever. Minimum positive tests were determined for both serial dilutions and a single dilution of patient sera. To establish the specificity of the test, 152 serum samples were tested from individuals with no evidence of past Coxiella burnetii infection. Diagnostic titers were set at greater than or equal to 128 for the IgM and IgG responses to phase I, at greater than or equal to 512 for the IgM response to phase II and at greater than or equal to 1,024 for the IgG response to phase II Coxiella burnetii These titers gave a false-positive rate of less than or equal to 1 %. Alternatively, testing a single dilution of sera (1:128) gave specificities ranging from 97.3 to 98.7 %. Tests with the greatest sensitivities, using serially diluted early convalescent-phase sera, were the IgM (84 %) and IgG (80 %) responses to phase II Coxiella burnetii. At a single serum dilution, 92 % of early convalescent sera had a positive IgG response to phase II Coxiella burnetii With a high specificity and good sensitivity, the EIA can be used to diagnose acute Q fever with a single convalescent serum specimen. The duration of a positive response was greater than five years. C1 BURROUGHS WELLCOME CO,DEPT INFECT DIS & IMMUNOL,RES TRIANGLE PK,NC 27709. VICTORIA GEN HOSP,HALIFAX,NS B3H 2Y9,CANADA. US FDA,DIV VACCINES & RELATED PROD APPLICAT,OFF VACCINE RES & REVIEW,ROCKVILLE,MD 20852. RP WAAG, D (reprint author), USA,MED RES INST INFECT DIS,PATHOGENESIS & IMMUNOL BRANCH,FREDERICK,MD 21702, USA. NR 20 TC 28 Z9 30 U1 0 U2 1 PU FRIEDR VIEWEG SOHN VERLAG GMBH PI WIESBADEN 1 PA PO BOX 5829, W-6200 WIESBADEN 1, GERMANY SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD MAY PY 1995 VL 14 IS 5 BP 421 EP 427 DI 10.1007/BF02114898 PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA RE119 UT WOS:A1995RE11900007 PM 7556231 ER PT J AU VANN, WF AF VANN, WF TI A FILTER ASSAY FOR POLYSIALYLTRANSFERASE SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE SIALYLTRANSFERASE; POLYSIALIC ACID BIOSYNTHESIS; ENZYME ASSAY; ESCHERICHIA COLI ID ESCHERICHIA-COLI K1; POLYSIALIC ACID; COLOMINIC ACID; SIALIC ACIDS; SIALYLTRANSFERASE; POLYSACCHARIDE; BIOSYNTHESIS; POLYMERS AB Polysialic acids occur as capsular polysaccharides of several pathogenic bacteria. An understanding of how polysialyltransferase functions in the synthesis of polysialic acid will require enzyme purification and characterization in concert with genetic analysis. A rapid filter assay has been developed for bacterial polysialyltransferase suitable for enzyme purification. The filter assay and the currently used paper chromatography methods are equivalent in parallel experiments. The Escherichia coli K92 polysialyltransferase exhibited the same pH and temperature optima, Mg2+ dependence and acceptor specificity in both assays. [C-14]Sialic acid bound in filter assays correlates with polymer formed by gel filtration. Specificity may be increased by the addition of exogenous accepters. RP VANN, WF (reprint author), US FDA,CTR BIOL EVALUAT & RES,BACTERIAL POLYSACCHARIDES LAB,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD MAY 1 PY 1995 VL 128 IS 2 BP 163 EP 166 PG 4 WC Microbiology SC Microbiology GA QX543 UT WOS:A1995QX54300011 ER PT J AU IKEDA, GJ SAPIENZA, PP AF IKEDA, GJ SAPIENZA, PP TI DISTRIBUTION, METABOLISM AND EXCRETION OF PENTACHLOROANISOLE IN THE BEAGLE DOG AND MINIATURE PIG SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article AB Tissue distribution, excretion and metabolism studies of pentachloroanisole (PCA), an environmental metabolite of pentachlorophenol (PCP), were conducted in the beagle dog and miniature pig following single oral doses (25 mg/kg) of radiolabelled PCA. PCA was readily demethylated by both species, with a half-life of 5-8 min. The resultant PCP was the major metabolite in dogs and pigs. In the dog, an average of 21.9% of the administered radiolabel was excreted in the urine and 62.3% in the faeces during a 7-day period. Of the tissues analysed, an average of 3.2% of the radiolabel remained in the liver, and blood and muscle accounted for averages of 3.0 and 2.3%, respectively, of the dose. Free and conjugated PCP were found in the urine of dogs; no PCA or tetrachlorohydroquinone (TCH) were found. In dog faeces, PCP and a trace of polar material were observed; no PCA was excreted in dog faeces. In the miniature pig, an average of 25.8% of the administered radiolabel was excreted in the urine and 32.0% in the faeces during a 2-wk period. An average of 4.4% of the radiolabel was found in the liver, 8.8% in the blood, 7.1% in the muscle and 6.4% in the fat. In pig urine, PCP and conjugated PCP were the only metabolites observed; no PCA or TCH was found. Pig faeces contained a trace of unchanged PCA; PCP and polar metabolites were also found. Since pig tissues retained a sizeable residue 2 wk after a single dose of PCA, various agents were used in an attempt to decrease the tissue level of radiolabel in pigs; anion exchange resin was found to be the most effective. RP IKEDA, GJ (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV TOXICOL RES,PHARMACOKINET & METAB BRANCH,8501 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 8 TC 8 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD MAY PY 1995 VL 33 IS 5 BP 409 EP 421 DI 10.1016/0278-6915(95)00001-I PG 13 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA RA543 UT WOS:A1995RA54300009 PM 7759026 ER PT J AU SCARBROUGH, FE BENDER, MM AF SCARBROUGH, FE BENDER, MM TI FDA POLICY ON THE USE OF DATABASES FOR NUTRITION LABELING SO FOOD TECHNOLOGY LA English DT Article RP SCARBROUGH, FE (reprint author), US FDA,OFF FOOD LABELING,200 C ST SW,WASHINGTON,DC 20204, USA. NR 12 TC 0 Z9 0 U1 2 U2 3 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD MAY PY 1995 VL 49 IS 5 BP 142 EP 145 PG 4 WC Food Science & Technology SC Food Science & Technology GA RB226 UT WOS:A1995RB22600015 ER PT J AU ANDERSON, DL DOWNING, RG IYENGAR, GV AF ANDERSON, DL DOWNING, RG IYENGAR, GV TI TRACE-ELEMENTS IN FOOD REFERENCE MATERIALS - COMPOSITIONAL AND ANALYTICAL PERSPECTIVES SO FRESENIUS JOURNAL OF ANALYTICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 6th International Symposium on Biological and Environmental Reference Materials (BERM-6) CY APR 17-21, 1994 CL KONA, HI SP AOAC INT, Promochem GmbH, Wesel Germany, TAMA Chem Co, Japan, NYCOMED, Norway, PROLAB, Denmark, Kellogg, Battle Creek, MI, NIST, Gaithersburg, MD, Int Atom Energy Agcy, Vienna, Austria, Inst Ref Mat Measurements, Geel, Belgium, Measurement & Testing Programme, Brussels, Belgium, Res Ctr Julich, Julich, Germany, USDA, Beltsvile, MD ID BOTANICAL REFERENCE MATERIALS; SILICON; BORON AB Selection criteria for production of food reference materials need to simultaneously consider realistic proximate matrix compositions, emerging trends for the nutritional and toxicological effects of less-emphasized trace elements (e.g., B, Li, Si, and V), chemical speciation (especially for As, Hg, Se, and Sn), and analyte certification requirements from the analyst's point of view. For the most part, currently available Certified Reference Materials (CRMs) do not meet many of these needs. Candidate CRMs with relevant concentrations of trace elements could be chosen from similar foods with different proximate compositions (e.g., fat content of milk products, meat, or soya flour). Explicit guidance must accompany CRMs so that variations in measured trace element concentrations arising from procedural lapses and basis weight are avoided. C1 NATL INST STAND & TECHNOL,GAITHERSBURG,MD 20899. BIOMINERAL SCI INT INC,GAITHERSBURG,MD 20877. RP ANDERSON, DL (reprint author), US FDA,200 C ST SW,WASHINGTON,DC 20204, USA. NR 23 TC 3 Z9 3 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0937-0633 J9 FRESEN J ANAL CHEM JI Fresenius J. Anal. Chem. PD MAY PY 1995 VL 352 IS 1-2 BP 107 EP 110 DI 10.1007/BF00322307 PG 4 WC Chemistry, Analytical SC Chemistry GA RH366 UT WOS:A1995RH36600026 ER PT J AU BARATTA, EJ AF BARATTA, EJ TI REFERENCE MATERIALS FOR USFDAS WHOLE-BODY COUNTING SYSTEM SO FRESENIUS JOURNAL OF ANALYTICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 6th International Symposium on Biological and Environmental Reference Materials (BERM-6) CY APR 17-21, 1994 CL KONA, HI SP AOAC INT, Promochem GmbH, Wesel Germany, TAMA Chem Co, Japan, NYCOMED, Norway, PROLAB, Denmark, Kellogg, Battle Creek, MI, NIST, Gaithersburg, MD, Int Atom Energy Agcy, Vienna, Austria, Inst Ref Mat Measurements, Geel, Belgium, Measurement & Testing Programme, Brussels, Belgium, Res Ctr Julich, Julich, Germany, USDA, Beltsvile, MD AB The U.S. Food and Drug Administration (FDA) operates a whole-body counter at its's Winchester Engineering and Analytical Center (WEAC), Winchester, MA. This counter has been registered with the International Atomic Energy Agency (IAEA) and has been made available to others. The new requirements of the Nuclear Regulatory Commission (NRC) include internal dose exposure, using such a system. The whole-body counter performs thyroid scans for iodine-131 and also for iodine-125 and iodine-123. The latter requires thin-window germanium detectors (X-ray spectrometers). In addition, it has a large sodium iodine (Tl) crystal for whole body scans. One of the problems has been developing reference standards for energy and efficiency calibrations. Up to recently, only phantoms have been available to which the radioactive solution must be added. Lately, the Department of Energy has developed a ''loan'' program of phantoms containing specific radioactive isotopes in various configurations. This is expected to be added to this program to confirm the measurements. Software has also been developed which will calculate a 50 year dose commitment as required by the NRC for exposures. The use of these reference materials to assure that the system is in calibration is discussed. RP BARATTA, EJ (reprint author), US FDA,WINCHESTER,MA 01890, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0937-0633 J9 FRESEN J ANAL CHEM JI Fresenius J. Anal. Chem. PD MAY PY 1995 VL 352 IS 1-2 BP 189 EP 192 DI 10.1007/BF00322324 PG 4 WC Chemistry, Analytical SC Chemistry GA RH366 UT WOS:A1995RH36600043 ER PT J AU HART, RW KEENAN, K TURTURRO, A ABDO, KM LEAKEY, J LYNCOOK, B AF HART, RW KEENAN, K TURTURRO, A ABDO, KM LEAKEY, J LYNCOOK, B TI CALORIC RESTRICTION AND TOXICITY SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Editorial Material ID DRUG-METABOLIZING-ENZYMES; MALE FISCHER-344 RAT; GLUCOCORTICOID REGULATION; FOOD RESTRICTION; CYTOCHROME-P-450; CANCER; SYSTEM; GENE AB The modulatory effects of caloric intake on the rate and extent of both spontaneous and induced disease incidence is well known, but the significance of these effects in the interpretation of testing data has only recently become appreciated. This is especially true relative to the impact of caloric intake on both survival and background incidence for common tumors. In order to enhance the health and survival of animals ongoing chronic toxicity testing it has been suggested that such tests should restrict food consumption. Although this restriction will result in increasing survival of the test animals, it may also effect the expression of toxicity by altering agent metabolism and disease progression. Focus in this symposium is on the necessity to control dietary consumption in toxicity tests (dietary control), and if such a need does exist to what level of consumption should be diet be focused (caloric restriction). C1 MERCK & CO INC,W POINT,PA 19486. NIEHS,RES TRIANGLE PK,NC 27709. RP HART, RW (reprint author), NATL CTR TOXICOL RES,3900 NCTR DR,JEFFERSON,AR 72079, USA. NR 52 TC 57 Z9 58 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1995 VL 25 IS 2 BP 184 EP 195 DI 10.1006/faat.1995.1054 PG 12 WC Toxicology SC Toxicology GA QY808 UT WOS:A1995QY80800003 PM 7665002 ER PT J AU WAYNANT, RW AF WAYNANT, RW TI SUFFICIENTLY PRACTICAL SO IEEE CIRCUITS AND DEVICES MAGAZINE LA English DT Editorial Material RP WAYNANT, RW (reprint author), US FDA,1901 CHAPMAN AVE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 8755-3996 J9 IEEE CIRCUIT DEVIC JI IEEE Circuit Devices Mag. PD MAY PY 1995 VL 11 IS 3 BP 2 EP 2 PG 1 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA QV820 UT WOS:A1995QV82000001 ER PT J AU WAYNANT, R AF WAYNANT, R TI SHEU,BING NEWCAS EDITOR SO IEEE CIRCUITS AND DEVICES MAGAZINE LA English DT Item About an Individual RP WAYNANT, R (reprint author), US FDA,1901 CHAPMAN AVE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 8755-3996 J9 IEEE CIRCUIT DEVIC JI IEEE Circuit Devices Mag. PD MAY PY 1995 VL 11 IS 3 BP 11 EP 11 PG 1 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA QV820 UT WOS:A1995QV82000007 ER PT J AU WAYNANT, RW AF WAYNANT, RW TI SOFTWARE REVIEW SO IEEE CIRCUITS AND DEVICES MAGAZINE LA English DT Software Review RP WAYNANT, RW (reprint author), US FDA,1901 CHAPMAN AVE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 8755-3996 J9 IEEE CIRCUIT DEVIC JI IEEE Circuit Devices Mag. PD MAY PY 1995 VL 11 IS 3 BP 54 EP 56 PG 3 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA QV820 UT WOS:A1995QV82000015 ER PT J AU SAXON, A MAX, EE DIAZSANCHEZ, D ZHANG, K AF SAXON, A MAX, EE DIAZSANCHEZ, D ZHANG, K TI ALTERNATIVE RNA OF EPSILON-TRANSCRIPTS PRODUCES MESSENGER-RNAS ENCODING 2 MEMBRANE AND 4 SECRETED IGE ISOFORMS SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 20th Symposium of the Collegium-Internationale-Allergologicum on Molecular and Clinical Implications for Allergy in the 21st-Century CY SEP 25-29, 1994 CL NANTUCKET, MA SP Collegium Int Allergologicum DE IGE; EPSILON GENE; IMMUNOGLOBULIN ISOFORMS; ALLERGIC ANTIBODY; ALTERNATIVE SPLICING ID IMMUNOGLOBULIN-E AB We elucidated a series of alternatively spliced human epsilon mRNAs by employing a human epsilon-specific RT-PCR strategy. Two mRNA isoforms provide for the expression of distinct membrane IgE proteins, the common form of which contains a novel 56-amino-acid sequence after the last epsilon constant-region domain. Other mRNAs encode, in addition to the classic secreted epsilon chain, at least three novel epsilon secreted proteins that lack a transmembrane domain and possess distinctive C-terminal features. Furthermore, the expression of these epsilon mRNA isoforms is differentially regulated by stimuli such as interleukin-10, Fc epsilon RII cross-linking and aromatic hydrocarbons found in diesel exhaust. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. RP SAXON, A (reprint author), UNIV CALIF LOS ANGELES,SCH MED,CTR HLTH SCI 52175,DEPT MED,DIV CLIN IMMUNOL ALLERGY,LOS ANGELES,CA 90024, USA. FU NCI NIH HHS [CA-30515]; NIAID NIH HHS [AI-34567, AI-15251] NR 6 TC 11 Z9 11 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD MAY-JUL PY 1995 VL 107 IS 1-3 BP 45 EP 47 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA RM261 UT WOS:A1995RM26100010 PM 7613209 ER PT J AU REVELLE, LK RUTTER, AM WILSON, JA AF REVELLE, LK RUTTER, AM WILSON, JA TI SYNTHESIS OF CHLORHEXIDINE DIGLUCONATE IMPURITIES SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE CHLORHEXIDINE DIGLUCONATE; IMPURITIES; SYNTHESIS; ANTIMICROBIAL AB Five new biguanides, found as impurities in chlorhexidine digluconate solutions, were synthesized by addition of amines to aminonitriles. Nonstoichiometric additions required to prepare the unsymmetrical biguanides resulted in low yields of the desired impurities, which were isolated by flash chromatography and characterized by HPLC-UV, HPLC-MS, and H-1 NMR. RP REVELLE, LK (reprint author), US FDA,DIV DRUG ANAL,ROOM 1002,1114 MARKET ST,ST LOUIS,MO 63101, USA. NR 9 TC 4 Z9 4 U1 2 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY PY 1995 VL 43 IS 5 BP 1299 EP 1301 DI 10.1021/jf00053a032 PG 3 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA QY978 UT WOS:A1995QY97800032 ER PT J AU FRIEDMAN, L GAINES, DW NEWELL, RF SMITH, MC BRAUNBERG, RC FLYNN, TJ ODONNELL, MW AF FRIEDMAN, L GAINES, DW NEWELL, RF SMITH, MC BRAUNBERG, RC FLYNN, TJ ODONNELL, MW TI GROWTH-PATTERNS IN SELECTED ORGANS OF THE MINIATURE SWINE AS DETERMINED BY GROSS MACROMOLECULAR-COMPOSITION SO JOURNAL OF ANIMAL SCIENCE LA English DT Article DE MINIATURE PIGS; GROWTH; DNA; RNA; PROTEIN ID PROTEIN-SYNTHESIS; EARLY LIFE; PIG; NUTRITION; INHIBITOR; MUSCLE; TISSUE; RAT AB As part of a larger study designed to characterize the early developmental stages of the Hormel-Hanford strain miniature pig, the brain, kidney, liver, pancreas, and spleen from male animals were examined for changes in RNA, DNA, and protein contents from 1 to 196 d after birth. Distinct patterns were found for changes with age in macromolecular levels. Protein levels increased from d 1 to 56 in all organs except spleen, in which little change was noted. Gel electrophoresis showed little qualitative change in the liver protein profile during this period. A fat-free, non-nucleic acid, protein-containing fraction, insoluble in hot alkali, appeared in the brain after approximately 1 wk following birth. DNA concentrations decreased markedly from d 1 to d 196 for brain, kidney, and spleen but decreased more gradually for liver and pancreas. RNA levels declined slightly or remained the same in all organs except pancreas, where a large increase occurred from d 1 to weaning (56 d). Growth proceeded in all organs by increases in cell number (hyperplasia), as evidenced by increases in total (level or concentration x organ weight) DNA, or by hypertrophy, as evidenced by increases in the ratio of protein to DNA or by a combination of both processes. Hypertrophic growth was attained by d 56 and continued to sexual maturity in all organs except spleen. Hyperplastic growth continued to sexual maturity in all organs except brain. RP FRIEDMAN, L (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,BELTSVILLE RES FACIL,HFS-508,8501 MUIRKIRK RD,LAUREL,MD 20708, USA. OI Flynn, Thomas/0000-0002-7248-0643 NR 38 TC 8 Z9 8 U1 1 U2 4 PU AMER SOC ANIMAL SCIENCE PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 SN 0021-8812 J9 J ANIM SCI JI J. Anim. Sci. PD MAY PY 1995 VL 73 IS 5 BP 1340 EP 1350 PG 11 WC Agriculture, Dairy & Animal Science SC Agriculture GA QW908 UT WOS:A1995QW90800015 PM 7545146 ER PT J AU BACZYNSKYJ, WM YESS, NJ AF BACZYNSKYJ, WM YESS, NJ TI US FOOD-AND-DRUG-ADMINISTRATION MONITORING OF LEAD IN DOMESTIC AND IMPORTED CERAMIC DINNERWARE SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The U.S. Food and Drug Administration (FDA) conducted a survey of domestic and imported ceramic dinnerware from January to February 1992 to determine the status of lead leaching from this ware. Ceramicware was screened at the collection point by using the Quick Color Test(QCT); if the QCT was positive, the ware was analyzed in the laboratory by using atomic absorption spectroscopy (AAS). For imports, 5222 lots were examined using the QCT. Of these lots, 46 exceeded FDA's 1992 guidelines as determined by using AAS. For domestic ware, 676 lots were examined using the QCT, and 17 lots exceeded the 1991 guidelines. The violation rates, 0.9% for imports and 2.5% for domestic ware, were about twice as high as they would have been under the 1980 guidelines. C1 US FDA,DIV FIELD PROGRAM PLANNING & EVALUAT,OFF FIELD PROGRAMS,WASHINGTON,DC 20204. US FDA,DIV PROGRAMS & ENFORCEMENT POLICY,OFF PLANT & DAIRY FOODS & BEVERAGES,WASHINGTON,DC 20204. NR 10 TC 3 Z9 5 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1995 VL 78 IS 3 BP 610 EP 614 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QZ024 UT WOS:A1995QZ02400005 PM 7756873 ER PT J AU ROGERS, WM KENDALL, DC SALMON, GD JOHNSON, RD MELOAN, CE CLINE, JK CRAUN, JC DAFT, JL EGAN, SK FLEMINGJONES, ME GRAHAM, DF GRIFFITT, KR HENSLEY, DD HUDNALL, WP MACTAL, LP PALMER, RE PODREBARAC, DS REED, GD SACK, CA SISK, RL TERRAZAS, DL VALDIVIA, R WELLS, NC WHYTE, WJ AF ROGERS, WM KENDALL, DC SALMON, GD JOHNSON, RD MELOAN, CE CLINE, JK CRAUN, JC DAFT, JL EGAN, SK FLEMINGJONES, ME GRAHAM, DF GRIFFITT, KR HENSLEY, DD HUDNALL, WP MACTAL, LP PALMER, RE PODREBARAC, DS REED, GD SACK, CA SISK, RL TERRAZAS, DL VALDIVIA, R WELLS, NC WHYTE, WJ TI ACCUMULATED PESTICIDE AND INDUSTRIAL-CHEMICAL FINDINGS FROM A 10-YEAR STUDY OF READY-TO-EAT FOODS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TOTAL DIET AB This report lists the pesticide and industrial chemicals found in the ready-to-eat foods tested repetitively for 10 years through the U.S, Food and Drug Administrations's Revised Market Basket Study. The study operated from 1982 to 1991. During that time 37 market baskets, each containing 234 food items that represented about 5000 food types in American diets covering all age groups, including infants and children, were collected. Each food item was individually prepared for eating; that is, it was opened, unwrapped, washed, peeled, sliced, formulated by recipe, or cooked. Each item was then composited and analytically screened for about 300 different chemicals, including chlorphenoxy acids, ethylenethiourea, methyl carbamates, organochlorines, organophosphates, organosulfurs, phenylureas, and pyrethroids. Overall, less than 1% of the potential of 2.5 million findings occurred for the 10-year study period. In total, 138 different chemical residues accounted for 17 050 accumulated findings, Most findings were less than 1 mu g/g, which is considered a low-level finding. Each food item averaged about 2 low-level findings per analysis. RP ROGERS, WM (reprint author), US FDA,KANSAS CITY DIST OFF,POB 15905,LENEXA,KS 66285, USA. NR 5 TC 7 Z9 7 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1995 VL 78 IS 3 BP 614 EP 631 PG 18 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QZ024 UT WOS:A1995QZ02400006 ER PT J AU TRUCKSESS, MW THOMAS, F YOUNG, K STACK, ME FULGUERAS, WJ PAGE, SW AF TRUCKSESS, MW THOMAS, F YOUNG, K STACK, ME FULGUERAS, WJ PAGE, SW TI SURVEY OF DEOXYNIVALENOL IN US 1993 WHEAT AND BARLEY CROPS BY ENZYME-LINKED-IMMUNOSORBENT-ASSAY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID GAS-CHROMATOGRAPHY; NIVALENOL; CEREALS; MYCOTOXINS; VOMITOXIN; PRODUCTS AB Wheat and barley from the 1993 crop year were analyzed for deoxynivalenol (DON). A total of 630 samples were collected by the Federal Grain Inspection Service in 25 states and analyzed using a commercially available, direct competitive, enzyme-linked immunosorbent assay. The limit of determination was about 0.5 mu g/g. DON contamination in the 483 wheat samples averaged 2.0 mu g/g and ranged from <0.5 to 18 mu g/g. DON contamination in the 147 barley samples averaged 4.2 mu g/g and ranged from <0.5 to 26 mu g/g. About 40% of the wheat samples and 57% of the barley samples contained DON levels that were greater than the U.S. Food and Drug Administration 1982 advisory level of 2 mu g/g for DON In wheat designated for milling (human consumption). RP TRUCKSESS, MW (reprint author), US FDA,DIV NAT PROD,WASHINGTON,DC 20204, USA. NR 22 TC 61 Z9 63 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1995 VL 78 IS 3 BP 631 EP 636 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QZ024 UT WOS:A1995QZ02400007 PM 7756875 ER PT J AU CUTTING, JH KIESSLING, WM BOND, FL MCCARRON, JE KREUZER, KS HURLBUT, JA SOFOS, JN AF CUTTING, JH KIESSLING, WM BOND, FL MCCARRON, JE KREUZER, KS HURLBUT, JA SOFOS, JN TI AGAROSE-GEL ELECTROPHORETIC DETECTION OF 6 BETA-LACTAM ANTIBIOTIC RESIDUES IN MILK SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ANIMAL-TISSUES AB An electrophoretic method coupled with bioautography was developed for detection and identification of penicillin G, ampicillin, amoxicillin, cloxacillin, cephapirin, and ceftiofur residues in milk. The method uses a 2% agarose gel for electrophoresis, an overlay of PM indicator agar seeded with Bacillus stearothermophilus var, calidolactis, and incubation at 55 degrees C for 16-18 h. The new method separated and detected residues in milk at the levels of concern for the Food and Drug Administration (FDA) for penicillin G (5 ppb), cephapirin (20 ppb), and ceftiofur (50 ppb). The method also detected ampicillin, amoxicillin, and cloxacillin at 20, 30, and 30 ppb, respectively, but these levels are above those of concern for FDA (10 ppb). C1 METROPOLITAN STATE COLL,DEPT CHEM,DENVER,CO 80217. COLORADO STATE UNIV,DEPT ANIM SCI,FT COLLINS,CO 80523. COLORADO STATE UNIV,DEPT FOOD SCI & HUMAN NUTR,FT COLLINS,CO 80523. RP CUTTING, JH (reprint author), US FDA,DENVER DIST LAB,POB 25087,DENVER,CO 80225, USA. NR 22 TC 11 Z9 12 U1 0 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1995 VL 78 IS 3 BP 663 EP 667 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QZ024 UT WOS:A1995QZ02400013 PM 7756879 ER PT J AU SHERROD, PS AMAGUANA, RM ANDREWS, WH JUNE, GA HAMMACK, TS AF SHERROD, PS AMAGUANA, RM ANDREWS, WH JUNE, GA HAMMACK, TS TI RELATIVE EFFECTIVENESS OF SELECTIVE PLATING AGARS FOR RECOVERY OF SALMONELLA SPECIES FROM SELECTED HIGH-MOISTURE FOODS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID GRID MEMBRANE-FILTER; EF-18 AGAR; ENRICHMENT AB The relative effectiveness of 6 selective plating media were compared for effectiveness in recovery of Salmonella spp, from selected high-moisture foods. Three new plating agars (EF-18, Rambach, and xylose lysine Tergitol-4) and 3 selective plating agars (bismuth sulfite, Hektoen enteric, and xylose lysine desoxycholate) recommended by AOAC INTERNATIONAL and the Bacteriological Analytical Manual (BAM) were compared. The agars were streaked from cultures selectively enriched in selenite cystine broth, tetrathionate broth, and Rappaport-Vassiliadis medium. The high-moisture foods studied were naturally contaminated pork sausage, chicken parts, turkey parts, and frog legs and artificially contaminated shrimp, oysters, egg yolks, and lettuce. The relative effectiveness of each selective plating agar was determined by recovery of Salmonella spp, and enumeration of false-positive and false-negative reactions. Although the new selective plating agars compared favorably with the AOAC/BAM-recommended agars, they offered no advantage, Incubation of selective enrichment broths at elevated temperatures decreased the numbers of false-positive and false-negative reactions for all 6 selective plating agars. RP SHERROD, PS (reprint author), US FDA,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204, USA. NR 23 TC 11 Z9 11 U1 0 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1995 VL 78 IS 3 BP 679 EP 690 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QZ024 UT WOS:A1995QZ02400016 PM 7756882 ER PT J AU TRUCKSESS, MW STACK, ME ALLEN, S BARRION, N AF TRUCKSESS, MW STACK, ME ALLEN, S BARRION, N TI IMMUNOAFFINITY COLUMN COUPLED WITH LIQUID-CHROMATOGRAPHY FOR DETERMINATION OF FUMONISIN B-1 IN CANNED AND FROZEN SWEET CORN SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FUSARIUM-MONILIFORME; FOODS; FEEDS AB A modified liquid chromatographic (LC) method for determining fumonisin B-1 (FB1) in corn was applied to canned and frozen sweet corn. The corn is extracted with methanol-water (8 + 2), and the extract is filtered. The filtrate is diluted with water and passed through an immunoaffinity column. After the column is washed with water, FB1 is eluted with methanol-water (8 + 2). The eluate is evaporated to dryness by using a vacuum concentrator, and the residue is dissolved in acetonitrile-water (1 + 1). FB1 is derivatized with o-phthaldialdehyde. The derivative is separated on a reversed-phase C-18 LC column using acetonitrile-water-acetic acid (50 + 50 + 1) and quantitated with a fluorescence detector. Recoveries of FB1 from canned and frozen corn spiked over the range of 50-200 ng/g were 76-88%. The limit of determination was about 25 ng/g, and the limit of detection was about 4 ng/g. The method was applied to 97 commercial canned and frozen sweet corn samples collected from different areas of the United States. Sixty samples contained no FB1. Low levels (trace-82 ng FB1/g corn) were found in 35 samples; 235 ng FB1/g was found in 1 canned corn sample, and 350 ng FB1/g was found in 1 frozen corn sample. RP TRUCKSESS, MW (reprint author), US FDA,DIV NAT PROD,WASHINGTON,DC 20204, USA. NR 12 TC 54 Z9 54 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1995 VL 78 IS 3 BP 705 EP 710 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QZ024 UT WOS:A1995QZ02400020 PM 7756885 ER PT J AU LEE, SC RODRIGUEZ, F STOREY, M FARMAKALIDIS, E PROSKY, L AF LEE, SC RODRIGUEZ, F STOREY, M FARMAKALIDIS, E PROSKY, L TI DETERMINATION OF SOLUBLE AND INSOLUBLE DIETARY FIBER IN PSYLLIUM-CONTAINING CEREAL PRODUCTS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FOODS AB A method for soluble and insoluble dietary fiber determinations was developed for psyllium-containing food products, which are highly viscous in aqueous solutions. The assay is based on a modification of the AOAC soluble and insoluble dietary fiber method (991.43), which was recommended for nutrition labeling in the final U.S. food labeling regulations. We found that method 991.43 and other existing dietary fiber methods could not be applied to psyllium food products, which exhibit high viscosity in aqueous solutions, because highly viscous solutions could not be filtered easily. In this study, we modified AOAC method 991.43 to accommodate the filtration process of viscous sample solutions. Sonication followed by highspeed centrifugation was used before filtration. The principles of the method ape similar to those for AOAC method 991.43, including the use of the same 3 enzymes (heat-stable alpha-amylase, protease, and amyloglucosidase) as well as similar enzyme incubation conditions. The modification using sonication and high-speed centrifugation did not alter the method performance for analytically normal products such as wheat bran, oat bran, and soy fiber. Yet, the modification allowed the separation of soluble dietary fiber fractions from insoluble fractions for psyllium products with satisfactory precision, This method for psyllium dietary fiber determinations may be applied to other food products that exhibit high viscosity in aqueous solutions. C1 KELLOGG AUSTRALIA,BOTANY,AUSTRALIA. US FDA,WASHINGTON,DC 20204. RP LEE, SC (reprint author), KELLOGG CO,BATTLE CREEK,MI 49016, USA. NR 10 TC 15 Z9 16 U1 6 U2 10 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1995 VL 78 IS 3 BP 724 EP 729 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QZ024 UT WOS:A1995QZ02400023 PM 7756888 ER PT J AU PARDUE, JR AF PARDUE, JR TI MULTIRESIDUE METHOD FOR THE CHROMATOGRAPHIC DETERMINATION OF TRIAZINE HERBICIDES AND THEIR METABOLITES IN RAW AGRICULTURAL PRODUCTS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SOLID-PHASE EXTRACTION; DEGRADATION PRODUCTS; GAS-CHROMATOGRAPHY; SOIL SAMPLES; WATER; ATRAZINE; PESTICIDES; SURFACE; CROPS AB A method is described for the determination of 19 triazine herbicides and 4 metabolites in 6 agricultural products that represent diverse matrixes, In addition, a modification of this method to determine the more water-soluble metabolite, desethyldesisopropylatrazine, is described. In both these procedures, residues are extracted with methanol, and the product coextractives are removed using solvent partition and cation-exchange solid-phase extraction chromatography, A nitrogen phosphorus detector and DB-17 megabore column are used for the temperature-programmed chromatographic determination of samples fortified at 0.02-1.0 ppm levels. Average recoveries ranged from 81.1 to 106.2% for the parent herbicides and from 59.6 to 87.5% for the metabolites on all crops. An average recovery of 101.1% was obtained for desethyldesisopropylatrazine. RP PARDUE, JR (reprint author), US FDA,SE REG LAB,60 8TH ST NE,ATLANTA,GA 30309, USA. NR 23 TC 17 Z9 19 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1995 VL 78 IS 3 BP 856 EP 862 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QZ024 UT WOS:A1995QZ02400039 PM 7756901 ER PT J AU BUNCH, EA ALTWEIN, DM JOHNSON, LE FARLEY, JR HAMMERSMITH, AA AF BUNCH, EA ALTWEIN, DM JOHNSON, LE FARLEY, JR HAMMERSMITH, AA TI HOMOGENEOUS SAMPLE PREPARATION OF RAW SHRIMP USING DRY ICE SO JOURNAL OF AOAC INTERNATIONAL LA English DT Note AB Sample homogeneity is critical to accurate and reproducible analysis of trace residues in foods. A method of uniform sample preparation using dry ice is described for shrimp. Other sample preparation techniques for raw shrimp produce nonhomogeneous samples. Sample homogeneity was determined through analysis of chloramphenicol added to intact tiger or white shrimp prior to sample preparation. Simulated chloramphenicol residue levels were 50, 15, 10, and 5 ppb. No significant differences were noted when analyses of shrimp inoculated with chlor-amphenicol prior to sample preparation with dry ice were compared with analyses of shrimp spiked after grinding with dry ice. Grinding shrimp with dry ice produced samples with homogeneous chloramphenicol residues. This technique should be applicable to other tissues and vegetable products. RP BUNCH, EA (reprint author), US FDA,22201 23RD DR SE,BOTHELL,WA 98021, USA. NR 8 TC 18 Z9 18 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1995 VL 78 IS 3 BP 883 EP 887 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QZ024 UT WOS:A1995QZ02400044 PM 7756906 ER PT J AU PETZINGER, G BARRY, TL ROACH, JAG MUSSER, SM SPHON, J AF PETZINGER, G BARRY, TL ROACH, JAG MUSSER, SM SPHON, J TI GAS-CHROMATOGRAPHIC MASS-SPECTROMETRIC ANALYSES OF UNKNOWN ANALYTICAL RESPONSE IN IMPORTED FAVA BEANS - 4-CHLORO-6-METHOXYINDOLE SO JOURNAL OF AOAC INTERNATIONAL LA English DT Note ID ION AB A halogenated unidentified analytical response (UAR) was encountered in a number of imported Fava bean samples during the Food and Drug Administration's routine pesticide-monitoring program, Gas chromatographic/mass spectrometric (GC/MS) analyses identified the halogenated component as 4-chloro-6-methoxyindole, a naturally occurring promutagen in Fava beans that has been linked to incidents of gastric cancer. Data from electron impact, positive and negative chemical ionization, collision-induced dissociation, and deuteration studies of this compound are presented, along with GC retention time data. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. RP PETZINGER, G (reprint author), US FDA,NE REG LAB,BROOKLYN,NY 11232, USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1995 VL 78 IS 3 BP 888 EP 892 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QZ024 UT WOS:A1995QZ02400045 PM 7756907 ER PT J AU MALEK, A MILLER, RK MATTISON, DR CECKLER, T PANIGEL, M DISANTAGNESE, PA JESSEE, LN AF MALEK, A MILLER, RK MATTISON, DR CECKLER, T PANIGEL, M DISANTAGNESE, PA JESSEE, LN TI CONTINUOUS MEASUREMENT OF ATP BY P-31-NMR IN TERM HUMAN DUALLY PERFUSED PLACENTA IN-VITRO - RESPONSE TO ISCHEMIA SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE PLACENTAL PERFUSION; HUMAN CHORIONIC GONADOTROPIN; HUMAN PLACENTAL LACTOGEN; GLUCOSE; LACTATE; ADENOSINE 5'-TRIPHOSPHATE; P-31 NUCLEAR MAGNETIC RESONANCE ID MAGNETIC-RESONANCE SPECTROSCOPY; INVITRO AB ATP was examined in dually perfused term human placentas by using P-31-nuclear magnetic resonance (NMR) spectroscopy. P-31-NMR spectra were acquired every 30 min starting similar to 30 min after establishing fetal and maternal perfusions, and maternal perfusate samples were obtained to monitor glucose utilization, lactate production, and human chorionic gonadotropin (hCG) and human placental lactogen (hPL) release. In continuous-perfusion experiments, placentas were perfused as long as 10 h. ATP increased and P-i fell after initiation of perfusion. Fetal volume loss was <2 ml/h, and constant production of hCG, hPL, and lactate as well as constant utilization of glucose were observed. In additional experiments, ischemia was produced by halting maternal and fetal perfusion pumps after a 2-h control period. After 2, 3, or 4 h of ischemia, ATP decreased 46 +/- 17, 51 +/- 5, and 85% of control, respectively. When perfusion was reinitiated, ATP increased and was maintained for the duration of the experiment (an additional 2 h). Recovery of ATP after reperfusion was not paralleled by recovery in glucose utilization, lactate production, or hPL and hCG release. However, during the reperfusion period, fetal pressure was <70 mmHg and fetal volume loss was <2 ml/h. These investigations suggest that the dually perfused human placental lobule can maintain ATP for greater than or equal to 10 h. Although the perfused human placenta recovers ATP and maintains fetal perfusion volume after ischemia lasting up to 4 h, utilization of glucose, production of lactate, and production and release of hCG and hPL are impaired. C1 UNIV ROCHESTER,MED CTR,DEPT OBSTET & GYNECOL,ROCHESTER,NY 14642. UNIV ROCHESTER,MED CTR,DEPT ENVIRONM MED,ROCHESTER,NY 14642. UNIV ROCHESTER,MED CTR,DEPT PATHOL & CLIN LAB MED,ROCHESTER,NY 14642. UNIV ARKANSAS MED SCI HOSP,DEPT OBSTET & GYNECOL,LITTLE ROCK,AR 72205. NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. BUCKNELL UNIV,DEPT CHEM,LEWISBURG,PA 17837. DEPT PEDIAT & INFECT DIS,ATLANTA,GA 30303. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU NIEHS NIH HHS [ES-01247, ES-02774] NR 33 TC 21 Z9 21 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 1995 VL 78 IS 5 BP 1778 EP 1786 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA QY605 UT WOS:A1995QY60500023 PM 7649912 ER PT J AU THOMPSON, J GENTRYWEEKS, CR NGUYEN, NY FOLK, JE ROBRISH, SA AF THOMPSON, J GENTRYWEEKS, CR NGUYEN, NY FOLK, JE ROBRISH, SA TI PURIFICATION FROM FUSOBACTERIUM-MORTIFERUM ATCC-25557 OF A 6-PHOSPHORYL-O-ALPHA-D-GLUCOPYRANOSYL-6-PHOSPHOGLUCOHYDROLASE THAT HYDROLYZES MALTOSE 6-PHOSPHATE AND RELATED PHOSPHO-ALPHA-D-GLUCOSIDES SO JOURNAL OF BACTERIOLOGY LA English DT Article ID D-PHOSPHOGALACTOSIDE GALACTOHYDROLASE; SUGAR PHOSPHOTRANSFERASE SYSTEM; BETA-GALACTOSIDASE GENE; GRAM-POSITIVE BACTERIA; ESCHERICHIA-COLI K12; NUCLEOTIDE-SEQUENCE; SUCROSE-6-PHOSPHATE HYDROLASE; STREPTOCOCCUS-MUTANS; BACILLUS-SUBTILIS; BGL OPERON AB 6-Phospholyl-O-alpha-D-glucopyranosyl:6-phosphoglucohydrolase (8-phospho-alpha-glucosidase) has been purified from Fusobacterium mortiferum ATCC 25557, p-Nitrophenyl-alpha-D-glucopyranoside 6-phosphate (pNP alpha Glc6P) served as the chromogenic substrate for detection and assay of enzyme activity, The O-2-sensitive, metal-dependent phospho-alpha-glucosidase was stabilized during purification by inclusion of dithiothreitol and Mn2+ ion in chromatography buffers. Various 6-phosphoryl-O-alpha-linked glucosides, including maltose 6-phosphate, pNP alpha Glc6P, trehalose 6-phosphate, and sucrose 6-phosphate, mere hydrolyzed by the enzyme to yield D-glucose 6-phosphate and aglycone moieties in a 1:1 molar ratio, 6-Phospho-alpha-glucosidase (M(r) of similar to 49,000; pI of similar to 4.9) is activated by Fe2+, Mn2+, Co2+, and Ni2+, and the maximum rate of pNP alpha Glc6P hydrolysis occurs at 40 degrees C within the pH range 7.0 to 7.5, The sequence of the first 32 amino acids of 6-phospho-alpha-glucdsidase exhibits 67% identity (90% similarity) to that deduced for the N terminus of a putative phospho-beta-glucosidase (designated ORF f212) encoded by glvG in Escherichia coli. Western blots involving highly specific polyclonal antibody against 6-phospho-alpha-glucosidase and spectrophotometric analyses with pNP alpha Glc6P revealed only low levels of the enzyme in glucose-, mannose-, or fructose-grown cells of F. mortiferum, Synthesis of 6-phospho-alpha-glucosidase increased dramatically during growth of the organism on alpha-glucosides, such as maltose, alpha-methylglucoside, trehalose, turanose, and palatinose. C1 NIDR, CELLULAR DEV & ONCOL LAB, BETHESDA, MD 20892 USA. US FDA, CTR BIOL EVALUAT & RES, DIV CYTOKINE BIOL, BETHESDA, MD 20892 USA. RP THOMPSON, J (reprint author), NIDR, MICROBIAL ECOL LAB, BLDG 30, RM 528, BETHESDA, MD 20892 USA. NR 53 TC 33 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1995 VL 177 IS 9 BP 2505 EP 2512 PG 8 WC Microbiology SC Microbiology GA QW529 UT WOS:A1995QW52900036 PM 7730284 ER PT J AU MERKEL, TJ STIBITZ, S AF MERKEL, TJ STIBITZ, S TI IDENTIFICATION OF A LOCUS REQUIRED FOR THE REGULATION OF BVG-REPRESSED GENES IN BORDETELLA-PERTUSSIS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GRAM-NEGATIVE BACTERIA; VIRULENCE FACTORS; ESCHERICHIA-COLI; CHROMOSOMAL INSERTION; NUCLEOTIDE-SEQUENCE; MERCURIC-RESISTANCE; CLONING SYSTEM; VIR; DNA; CONSTRUCTION AB In Bordetella pertussis, the coordinate regulation of virulence factor expression is controlled by the products of the bvgAS locus. In the presence of modulating signals such as MgSO4, nicotinic acid, or reduced temperature, the expression of bvg-activated genes is reduced while the expression of bvg-repressed genes is induced. One model for the regulation of bvg-repressed genes predicts the existence of a repressor protein encoded by a bvg-activated gene, Once activated, the product of this bvg-activated gene would bind to and repress transcription from the bvg-repressed genes. We isolated five genetically independent transposon insertion mutants of B. pertussis that have a phenotype consistent,vith the knockout of a putative bvg-regulated repressor. These mutants constitutively expressed a vrg6-phoA transcriptional fusion but demonstrated normal bvgAS function. Genomic mapping and DNA sequence analysis of the sites of transposon insertion demonstrated that these mutants define a locus downstream of bvgAS. Introduction of an in-frame, 12-bp insertion within this locus also conferred the mutant phenotype, confirming that the phenotype seen in the transposon mutants is the result of disruption of a distinct gene, which we have designated bvgR, and is not a consequence of polar effects on bvgAS. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP MERKEL, TJ (reprint author), NIDR,LME,BLDG 30,RM 532,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 46 Z9 48 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1995 VL 177 IS 10 BP 2727 EP 2736 PG 10 WC Microbiology SC Microbiology GA QX752 UT WOS:A1995QX75200016 PM 7751282 ER PT J AU LOOKER, AC JOHNSTON, CC WAHNER, HW DUNN, WL CALVO, MS HARRIS, TB HEYSE, SP LINDSAY, RL AF LOOKER, AC JOHNSTON, CC WAHNER, HW DUNN, WL CALVO, MS HARRIS, TB HEYSE, SP LINDSAY, RL TI PREVALENCE OF LOW FEMORAL BONE-DENSITY IN OLDER US WOMEN FROM NHANES-III SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID HIP FRACTURE; MINERAL DENSITY; RISK; OSTEOPOROSIS; PREDICTION; SITES; RACE AB Data on the number of U.S. women with low femoral bone mineral density (BMD) are currently available only from indirect estimates. We used dual-energy X-ray absorptiometry (DXA) measurements of femoral BMD from phase 1 of the third National Health and Nutrition Examination Survey (NHANES III, 1988-1991) to estimate prevalences of low femoral BMD in women ages 50 years and older using an approach proposed recently by an expert panel of the World Health Organization (WHO). Cutpoints for low BMD were derived from BMD data of 194 non-Hispanic white (NHW) women aged 20-29 years from the NHANES III dataset. The prevalence of older U.S. women with femoral osteopenia (BMD between 1 standard deviation [SD] and 2.5 SD below the mean of young NHW women) ranged from 34-50% in four different femur regions, which corresponds to similar to 12-17 million women. The prevalence with osteoporosis (BMD > 2.5 SD below the mean of young NHW women) ranged from 17-20, or similar to 6-7 million women. Prevalences were 1.3-2.4 times higher in NHW women than non-Hispanic black women (NHB), and 0.8-1.2 times higher in NHW versus Mexican American (MA) women. The estimated numbers of NHW, NHB, and MA women with osteopenia were 10-15 million, 800,000-1.2 million, and 300,000-400,000, respectively; corresponding figures for osteoporosis were 5-6 million, 200,000-300,000, and 100,000 respectively. Thus, the first data on BMD from a nationally representative sample of older women show a substantial number with low femoral BMD. The majority of these women are white, but the number of minority women with low BMD is not trivial. C1 CTR DIS CONTROL & PREVENT,DIV HLTH EXAMINAT STAT,HYATTSVILLE,MD 20782. INDIANA UNIV,MED CTR,INDIANAPOLIS,IN. MAYO CLIN & MAYO FDN,DEPT DIAGNOST RADIOL,ROCHESTER,MN 55905. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NIA,BETHESDA,MD 20892. HELEN HAYES HOSP,REG BONE CTR,W HAVERSTRAW,NY. NIAMSD,BETHESDA,MD 20892. NR 39 TC 295 Z9 298 U1 2 U2 3 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 1995 VL 10 IS 5 BP 796 EP 802 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QU603 UT WOS:A1995QU60300016 PM 7639115 ER PT J AU BURLINGTON, DB AF BURLINGTON, DB TI UNTITLED SO JOURNAL OF CLINICAL MONITORING LA English DT Editorial Material RP BURLINGTON, DB (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,1350 PICCARD DR,HFZ 230,ROCKVILLE,MD 20850, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0748-1977 J9 J CLIN MONITOR JI J. Clin. Monit. PD MAY PY 1995 VL 11 IS 3 BP 212 EP 213 DI 10.1007/BF01617724 PG 2 WC Anesthesiology SC Anesthesiology GA QY370 UT WOS:A1995QY37000010 PM 7623062 ER PT J AU SORIANO, V NEDJAR, S GARCIASAMANIEGO, J BRAVO, R CASTRO, A GONZALEZ, J MARTINEZODRIOZOLA, P PEDREIRA, J DELROMERO, J SUAREZ, D LLIBRE, JM GONZALEZLAHOZ, J AF SORIANO, V NEDJAR, S GARCIASAMANIEGO, J BRAVO, R CASTRO, A GONZALEZ, J MARTINEZODRIOZOLA, P PEDREIRA, J DELROMERO, J SUAREZ, D LLIBRE, JM GONZALEZLAHOZ, J TI HIGH-RATE OF COINFECTION WITH DIFFERENT HEPATITIS-C VIRUS SUBTYPES IN HIV-INFECTED INTRAVENOUS DRUG-ADDICTS IN SPAIN SO JOURNAL OF HEPATOLOGY LA English DT Letter ID GENOTYPES; INTERFERON C1 US FDA,VIRAL HEPATITIS LAB,KENSINGTON,MD. RP SORIANO, V (reprint author), INST SALUD CARLOS III,MADRID,SPAIN. NR 6 TC 14 Z9 14 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0169-5185 J9 J HEPATOL JI J. Hepatol. PD MAY PY 1995 VL 22 IS 5 BP 598 EP 599 DI 10.1016/0168-8278(95)80460-9 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RL114 UT WOS:A1995RL11400017 PM 7650343 ER PT J AU TAGA, H TAGA, K WANG, F CHRETIEN, J TOSATO, G AF TAGA, H TAGA, K WANG, F CHRETIEN, J TOSATO, G TI HUMAN AND VIRAL INTERLEUKIN-10 IN ACUTE EPSTEIN-BARR-VIRUS - INDUCED INFECTIOUS-MONONUCLEOSIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID SERUM INTERLEUKIN-10; HOMOLOGY; IL-10; BCRFI; CELL AB Human interleukin 10 (hIL-10), a product of monocytes, T cells, and B cells, shares extensive structural and functional similarity with viral IL-10 (vIL-10), a product of Epstein-Barr virus (EBV) replication, With two ELISAs, one that recognizes both hIL-10 and vIL-10 and the other specific for vIL-10, IL-10 was measured in serum or plasma and in saliva from 50 patients with acute EBV-induced infectious mononucleosis and from 19 normal subjects, In serum or plasma, 60% of the patients had measurable hIL-10 and/or vIL-10 and 18% had measurable vIL-10, In saliva, 20% of the patients had detectable hIL-10 and/or vIL-10 and none had detectable vIL-10, In contrast, hIL-10 and/or vIL-10 was undetectable in all 19 normal serum or plasma samples (P < .001 vs, patient samples), Among normal saliva samples, 21% had detectable hIL-10 and/or vIL-10 but none had detectable vIL-10, Thus, most patients with acute EBV-induced infectious mononucleosis transiently have abnormally high levels of circulating IL-10. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20852. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. GEORGETOWN UNIV,WASHINGTON,DC. NR 15 TC 32 Z9 32 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1995 VL 171 IS 5 BP 1347 EP 1350 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QU640 UT WOS:A1995QU64000041 PM 7751715 ER PT J AU LAO, NT LU, HTC REGO, A KOSAKOWSKI, RH BURGESS, DJ HUME, RD AF LAO, NT LU, HTC REGO, A KOSAKOWSKI, RH BURGESS, DJ HUME, RD TI INTERLABORATORY COMPARISON OF ANALYTICAL METHODS FOR RESIDUAL ETHYLENE-OXIDE AT LOW CONCENTRATION LEVELS IN MEDICAL DEVICE MATERIALS SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article AB An interlaboratory comparison of two extraction methods and one thermal desorption test method for the quantification of ethylene oxide (EO) by gas chromatography in two common medical device materials, high density polyethylene (HDPE) and plasticized polyvinyl chloride (PVC), was conducted by 15 laboratories. The three procedures included extraction with water, extraction with acetone, and headspace gas analysis, respectively. Materials were processed through an industrial EO cycle and aerated for various periods to achieve target levels of a low (5 mu g/g), medium (10 mu g/g), and high (25 mu g/g) residual determination following extraction or thermal desorption. The results of this study, using only the data from the laboratories that did not deviate from the procedure, showed that the average estimated total coefficient of variation ranged from 3.63 to 12.42% for the three different methods. Each of the methods is suitable for use as a reference test method for determining residual EO in polymeric materials in the concentration range 2.8-42.3 mu g/g. C1 BAXTER HEALTHCARE CORP,VALENCIA,CA 91355. ETHOX CORP,BUFFALO,NY 14204. N AMER SCI ASSOCIATES INC,NORTHWOOD,OH. RP LAO, NT (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,1220 WILKINS AVE,ROCKVILLE,MD 20852, USA. NR 14 TC 1 Z9 1 U1 0 U2 2 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD MAY PY 1995 VL 84 IS 5 BP 647 EP 655 DI 10.1002/jps.2600840524 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA QX151 UT WOS:A1995QX15100023 PM 7658360 ER PT J AU ANDERSON, DL AF ANDERSON, DL TI CERAMIC GLAZE ANALYSIS BY SIMULTANEOUS IN-BEAM PGAA AND XRFS SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY-ARTICLES LA English DT Article; Proceedings Paper CT 3rd International Conference on Methods and Applications of Radioanalytical Chemistry (MARC-III) CY APR 10-16, 1994 CL KAILUA KONA, HI SP Amer Nucl Soc, Div Isotopes & Radiat, Amer Nucl Soc, Div Biol & Med, Amer Nucl Soc, NO Calif Sect ID RAY ACTIVATION-ANALYSIS; NEUTRON AB Twenty-one ready-to-use hobby glazes, of which 18 were labeled ''safe for food containers'' (SFFC), were analyzed for Al, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, Gd, Hf, K, Mn, Na, pb, Si, Sm, Sr, Ti, Zn, and Zr by neutron capture prompt gamma-ray activation analysis (PGAA). Simultaneously, Pb was also determined by X-ray fluorescence spectrometry (XRFS) using Pb K X-rays induced by the gamma-ray component of the neutron beam. The XRFS limits of detection were 200-400 mu g Pb . g(-1) (dry weight), a factor of similar to 100 better than those for PGAA. Pb concentrations (by dry weight; with weight losses ranging from 28 to 49% after air-drying) found were 0.16-27.2% in the SFFC glazes and 0.86-32% in the other glazes. The SFFC glazes contained from <0.6 to 202 mu g Cd . g(-1), and Co, Cr, and Cu (elements which may enhance Pb leaching from fired glazes) were found in concentrations up to 1.2, 2.7, and 5.6%, respectively. Method accuracy was demonstrated with the analysis of soil, fly ash,and glass standard reference materials. RP ANDERSON, DL (reprint author), US FDA,ELEMENTAL RES BRANCH,HFS-338,200 C ST SW,WASHINGTON,DC 20204, USA. NR 13 TC 7 Z9 7 U1 0 U2 1 PU AKADEMIAI KIADO PI BUDAPEST PA PO BOX 245, H-1519 BUDAPEST, HUNGARY SN 0236-5731 J9 J RADIOAN NUCL CH AR JI J. Radioanal. Nucl. Chem.-Artic. PD MAY PY 1995 VL 192 IS 2 BP 281 EP 287 DI 10.1007/BF02041732 PG 7 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA RA209 UT WOS:A1995RA20900012 ER PT J AU BARRETT, HH DENNY, JL WAGNER, RF MYERS, KJ AF BARRETT, HH DENNY, JL WAGNER, RF MYERS, KJ TI OBJECTIVE ASSESSMENT OF IMAGE QUALITY .2. FISHER INFORMATION, FOURIER CROSSTALK, AND FIGURES OF MERIT FOR TASK-PERFORMANCE SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID HOTELLING TRACE CRITERION; OBSERVER PERFORMANCE; IDEAL-OBSERVER; SYSTEMS; NOISE; RECONSTRUCTION; OPTIMIZATION; TOMOGRAPHY; MODEL; SNR AB Figures of merit for image quality are derived on the basis of the performance of mathematical observers on specific detection and estimation tasks. The tasks include detection of a known signal superimposed on a known background, detection of a known signal on a random background, estimation of Fourier coefficients of the object, and estimation of the integral of the object over a specified region of interest. The chosen observer for the detection tasks is the ideal linear discriminant, which we call the Hotelling observer. The figures of merit are based on the Fisher information matrix relevant to estimation of the Fourier coefficients and the closely related Fourier crosstalk matrix introduced earlier by Barrett and Gifford [Phys. Med. Biol. 39, 451 (1994)]. A finite submatrix of the infinite Fisher information matrix is used to set Cramer-Rao lower bounds on the variances of the estimates of the first N Fourier coefficients. The figures of merit for detection tasks are shown to be closely related to the concepts of noise-equivalent quanta (NEQ) and generalized NEQ, originally derived for linear, shift-invariant imaging systems and stationary noise, Application of these results to the design of imaging systems is discussed. C1 UNIV ARIZONA,CTR OPT SCI,TUCSON,AZ 85724. UNIV ARIZONA,DEPT MATH,TUCSON,AZ 85724. US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20852. RP BARRETT, HH (reprint author), UNIV ARIZONA,DEPT RADIOL,TUCSON,AZ 85724, USA. FU NCI NIH HHS [R01 CA52643, P01 CA23417] NR 50 TC 166 Z9 166 U1 0 U2 9 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0740-3232 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD MAY PY 1995 VL 12 IS 5 BP 834 EP 852 DI 10.1364/JOSAA.12.000834 PG 19 WC Optics SC Optics GA QV029 UT WOS:A1995QV02900003 PM 7730951 ER PT J AU WANG, K KRAUSE, PR STRAUS, SE AF WANG, K KRAUSE, PR STRAUS, SE TI ANALYSIS OF THE PROMOTER AND CIS-ACTING ELEMENTS REGULATING EXPRESSION OF HERPES-SIMPLEX VIRUS TYPE-2 LATENCY-ASSOCIATED TRANSCRIPTS SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN TRIGEMINAL GANGLIA; HUMAN SENSORY GANGLIA; IMMEDIATE EARLY GENE; LAT PROMOTER; LOCATED UPSTREAM; RESPONSE ELEMENT; MESSENGER-RNA; CYCLIC-AMP; SEQUENCE; REACTIVATION AB In latently infected neurons, herpes simplex virus type 2 (HSV-2) expresses one abundant family of transcripts, the latency-associated transcripts (LATs). We demonstrate here that the sequence lying about 700 bp upstream of the 5' end of the HSV-2 major LAT acts as a very strong promoter in transient expression assays in both neuronal and nonneuronal cells. Transcription starts about 27 to 32 bp downstream of a functional TATA box. The proximal fragment from -102 to +34 includes the basal promoter and accounts for constitutive transcriptional activity in various cell lines. The distal region from -392 to -103 contributes to particularly strong promoter activity in neuronal cell lines and involves multiple cis-acting elements. A functional activating transcription factor/cyclic AMP (cAMP) response element binding protein motif lies just upstream of the TATA. By DNase I footprint and methylation protection assays, we identified several additional protein-binding sites upstream of the activating transcription factor/cAMP response element binding protein motif. A GC-rich element, termed LAT-3, was located between bases -128 to -102. A 2-bp substitution in LAT-3 markedly reduced promoter activity and abolished protein-binding ability in vitro. Gel retardation assay showed no competition for protein binding to LAT-3 by other GC-rich elements. LAT-3 appears to be a novel cis-acting element that may contribute to the neuronal responsiveness of the HSV-2 LAT promoter. C1 USDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD 20892. RP WANG, K (reprint author), NIAID,CLIN INVEST LAB,MED VIROL SECT,BLDG 10,ROOM 11N228,BETHESDA,MD 20892, USA. NR 42 TC 8 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1995 VL 69 IS 5 BP 2873 EP 2880 PG 8 WC Virology SC Virology GA QR784 UT WOS:A1995QR78400021 PM 7707511 ER PT J AU BRORSON, KA KRASNOKUTSKY, MV STEIN, KE AF BRORSON, KA KRASNOKUTSKY, MV STEIN, KE TI IMMUNOGLOBULIN ISOTYPE SWITCHING IN XID MICE SO MOLECULAR IMMUNOLOGY LA English DT Article DE IMMUNOGLOBULIN; IGG3; ISOTYPE SWITCH; RID; IMMUNODEFICIENCY ID X-LINKED IMMUNODEFICIENCY; CELL SUB-POPULATIONS; B-CELLS; SUBCLASS RESTRICTION; EXPRESSION; ANTIBODIES; ACTIVATION; TRANSCRIPTS; MOUSE; GENE AB Mice with the x-linked immunodeficiency mutation (xid) are unresponsive to polysaccharide antigens, lack a subset of B cells, and have low serum IgM (2-20% of normal) and IgG3 (3% of normal). Because of the disproportionate reduction of IgG3, the ability of B cells from xid mice to switch to gamma 3 was examined. Switching was indirectly measured by comparing IgG3 production and C gamma 3 mRNA steady state levels of purified B cells activated to switch to IgG3 by LPS in bulk culture. Direct measurement of switching was achieved by enumerating on a percentage basis switched cells in a filter disk culture assay and by FAGS analysis. In both bulk culture and the filter disk assay, switching to gamma 3 was equivalent between xid and non-xid B cells. RP BRORSON, KA (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV MONOCLONAL ANTIBODIES,OFF THERAPEUT RES & REVIEW,BETHESDA,MD 20892, USA. NR 43 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAY PY 1995 VL 32 IS 7 BP 487 EP 494 DI 10.1016/0161-5890(95)00015-7 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA RC767 UT WOS:A1995RC76700005 PM 7783751 ER PT J AU FINN, TM STEVENS, LA AF FINN, TM STEVENS, LA TI TRACHEAL COLONIZATION FACTOR - A BOUDETELLA-PERTUSSIS SECRETED VIRULENCE DETERMINANT SO MOLECULAR MICROBIOLOGY LA English DT Article ID BORDETELLA-PERTUSSIS; FILAMENTOUS HEMAGGLUTININ; SEQUENCE; ADHERENCE; CLONING; CELLS; GENE; PRECURSOR; ADHESINS; ANTIGEN AB We report here the identification of a virulence-associated factor, Tcf, (tracheal colonization factor), produced by strains of Bordetella pertussis but not Bordetella parapertussis or Bordetella bronchiseptica. This protein is encoded by the tcfA gene. When a strain of B. pertussis 18323 lacking this protein is used to infect mice with an aerosol challenge, the number of bacteria isolated from the tracheas is decreased 10-fold when compared with the parent 18323. The derived amino acid sequence of tcfA predicts a 68 kDa RGD-containing, proline-rich protein, which after cleavage of a typical prokaryotic signal sequence would be 64 kDa. Amino acid sequence analysis demonstrates that the C-terminal 30 kDa of this protein shows 50% identity to the 30 kDa C-terminus of another Bordetella protein, the pertactin precursor. The N-terminal 34 kDa region contains the three amino-acid motif RGD and is 16.5% proline. Coupled in vitro transcription and translation analysis indicates that the tcfA gene product migrates as two bands of approximately 90 kDa. A fusion protein of the N-terminal, 34 kDa portion of Tcf to maltose-binding protein migrates, on SDS-PAGE, 30 kDa higher than expected from the combined molecular weights. Polyclonal antisera raised against the unique N-terminal portion of Tcf recognizes 90 kDa and 60 kDa bands in immunoblots of whole-cell lysates of strains of B. pertussis; it does not recognize any protein in whole-cell lysates of B. bronchiseptica or B. parapertussis. Supernatants of cultures of B. pertussis 18323 contain the 60 kDa form of the protein. Southern blot analysis of chromosomal DNA from strains of B. bronchiseptica and B. parapertussis, using a probe derived from tcfA, shows strong hybridization only to B. pertussis DNA. Thus, Tcf appears to be a unique virulence factor of B. pertussis. C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. RP FINN, TM (reprint author), US FDA,CTR BIOL EVALUAT & RES,PERTUSSIS LAB,BETHESDA,MD 20892, USA. NR 32 TC 82 Z9 86 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 1995 VL 16 IS 4 BP 625 EP 634 DI 10.1111/j.1365-2958.1995.tb02425.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA RF961 UT WOS:A1995RF96100003 PM 7476158 ER PT J AU CHEN, ML JACKSON, AJ AF CHEN, ML JACKSON, AJ TI THE ROLE OF METABOLITES IN BIOEQUIVALENCY ASSESSMENT .2. DRUGS WITH LINEAR PHARMACOKINETICS AND FIRST-PASS EFFECT SO PHARMACEUTICAL RESEARCH LA English DT Article DE BIOEQUIVALENCE; RATE OF ABSORPTION; RATE OF AVAILABILITY; PARENT DRUG; METABOLITE; LINEAR PHARMACOKINETICS; FIRST-PASS ID LIQUID-CHROMATOGRAPHIC ANALYSIS; GAS-CHROMATOGRAPHY; PLASMA; NORTRIPTYLINE; AMITRIPTYLINE; TRIAMTERENE; DESIPRAMINE; IMIPRAMINE; SERUM AB Simulations were conducted to address the question of whether metabolite data are required for bioequivalence evaluation of immediate release formulations with drugs exhibiting linear pharmacokinetics and first-pass effect. Plasma level-time profiles were generated for parent drug and metabolite using relevant rate constants obtained from a bivariate normal distribution and designated random error. Simulation results showed that the need for metabolite data (C-max) in the assessment of bioequivalence depends on the relative variability between the absorption process of the drug and first-pass route for metabolite(s). The importance of metabolite C-max data ia the evaluation of rate of availability is clearly demonstrated for drugs with a high degree of intra-subject variation in the first-pass metabolism compared to the absorption process of the drug. Under such conditions, a wider confidence interval was found for the metabolite rather than parent drug. Opposite results were obtained when the intra-subject variance was high for drug absorption relative to first-pass effect. Discrepancies were observed for the scenarios in which the elimination pathway of the metabolite is more variable than the absorption process of the drug. The simulation results were in agreement with real bioequivalence data. It is thus recommended that, in the absence of the information on the relative variability of absorption and first-pass process, both parent drug and metabolite data be included for documentation of bioequivalence, should the metabolite(s) play an important role in the determination of efficacy and safety of the drug. C1 US FDA,CTR DRUG EVALUAT & RES,OFF GENER DRUGS,DIV BIOEQUIVALENCE,ROCKVILLE,MD 20855. RP CHEN, ML (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF RES RESOURCES,DIV BIOPHARMACEUT,ROCKVILLE,MD 20857, USA. NR 18 TC 24 Z9 27 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD MAY PY 1995 VL 12 IS 5 BP 700 EP 708 DI 10.1023/A:1016259509257 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA QW831 UT WOS:A1995QW83100012 PM 7479556 ER PT J AU ETTE, EI HOWIE, CA KELMAN, AW WHITING, B AF ETTE, EI HOWIE, CA KELMAN, AW WHITING, B TI EXPERIMENTAL-DESIGN AND EFFICIENT PARAMETER-ESTIMATION IN PRECLINICAL PHARMACOKINETIC STUDIES SO PHARMACEUTICAL RESEARCH LA English DT Article DE POPULATION PHARMACOKINETICS; PRECLINICAL; DESTRUCTIVE (QUANTIC); SIMULATION; EXPERIMENTAL DESIGN; PARAMETER ESTIMATION; DESIGN NUMBER; CONFIDENCE INTERVALS COVERAGE ID POPULATION AB Monte Carlo simulation technique used to evaluate the effect of the arrangement of concentrations on the efficiency of estimation of population pharmacokinetic parameters in the preclinical setting is described. Although the simulations were restricted to the one compartment model with intravenous bolus input, they provide the basis of discussing some structural aspects involved in designing a destructive (''quantic'') preclinical population pharmacokinetic study with a fixed sample size as is usually the case in such studies. The efficiency of parameter estimation obtained with sampling strategies based on the three and four time point designs were evaluated in terms of the percent prediction error, design number, individual and joint confidence intervals coverage for parameter estimates approaches, and correlation analysis. The data sets contained random terms for both inter- and residual intra-animal variability. The results showed that the typical population parameter estimates for clearance and volume were efficiently (accurately and precisely) estimated for both designs, while interanimal variability (the only random effect parameter that could be estimated) was inefficiently (inaccurately and imprecisely) estimated with most sampling schedules of the two designs. The exact location of the third and fourth time point for the three and four time point designs, respectively, was not critical to the efficiency of overall estimation of all population parameters of the model. However, some individual population pharmacokinetic parameters were sensitive to the location of these times. C1 UNIV GLASGOW,WESTERN INFIRM,GARDINER INST,DEPT MED & THERAPEUT,DIV CLIN PHARMACOL,GLASGOW G11 6NT,LANARK,SCOTLAND. W SCOTLAND HLTH BOARDS,DEPT CLIN PHYS & BIOENGN,GLASGOW G4 9LF,LANARK,SCOTLAND. UNIV GLASGOW,FAC MED,DEANS OFF,GLASGOW G12 8QQ,LANARK,SCOTLAND. RP ETTE, EI (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV BIOPHARMACEUT,HFD 426,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 18 TC 31 Z9 31 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD MAY PY 1995 VL 12 IS 5 BP 729 EP 737 DI 10.1023/A:1016267811074 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA QW831 UT WOS:A1995QW83100016 PM 7479560 ER PT J AU KODELL, RL BLACKWELL, BN BUCCI, TJ GREENMAN, DL AF KODELL, RL BLACKWELL, BN BUCCI, TJ GREENMAN, DL TI CAUSE-OF-DEATH ASSIGNMENT AT THE NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH SO TOXICOLOGIC PATHOLOGY LA English DT Article DE RODENT BIOASSAY; CANCER; NEOPLASM; TUMOR; FATAL; INCIDENTAL; CONTEXT OF OBSERVATION; AGE-ADJUSTED AB The system for assigning cause of death in animal studies of carcinogenicity at the National Center for Toxicological Research (NCTR) is described. An empirical study of the NCTR's experience with its current cause-of-death assignment system based on selected representative experiments is reported. Issues investigated include the degree of confidence associated with histologic cause-of-death assignment, potential age-, dose- and sex-related differences in assigned grades of certainty of cause of death, and frequencies of identification of various organ-specific and systemic diagnoses as the cause of death. Implications for age-adjusted statistical tests of carcinogenicity that require cause-of-death data are discussed. RP KODELL, RL (reprint author), NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,HFT-20,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 0 TC 23 Z9 23 U1 0 U2 1 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 1995 VL 23 IS 3 BP 241 EP 247 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA RD372 UT WOS:A1995RD37200001 PM 7659948 ER PT J AU PATRIARCA, PA BEELER, JA AF PATRIARCA, PA BEELER, JA TI MEASLES VACCINATION AND INFLAMMATORY BOWEL-DISEASE SO LANCET LA English DT Editorial Material ID CROHNS-DISEASE; VIRUS RP PATRIARCA, PA (reprint author), US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20205, USA. NR 12 TC 16 Z9 16 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD APR 29 PY 1995 VL 345 IS 8957 BP 1062 EP 1063 DI 10.1016/S0140-6736(95)90810-2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QV411 UT WOS:A1995QV41100002 PM 7715332 ER PT J AU ROGERS, MS RYAN, BB CASHON, RE ALAYASH, AI AF ROGERS, MS RYAN, BB CASHON, RE ALAYASH, AI TI EFFECTS OF POLYMERIZATION ON THE OXYGEN-CARRYING AND REDOX PROPERTIES OF DIASPIRIN CROSS-LINKED HEMOGLOBIN SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE HEMOGLOBIN; BLOOD SUBSTITUTE; POLYMERIZATION; OXIDATION-REDUCTION; KINETICS ID CELL-FREE HEMOGLOBIN; NITRIC-OXIDE; HEME-PROTEINS; ALPHA-CHAINS; BINDING AB Human hemoglobin site specifically cross-linked with bis(3,5-dibromosalicyl)fumarate results in a low oxygen affinity hemoglobin-based red cell substitute (alpha-DBBF). Polymerization of alpha-DBBF by bis(maleoylglycylamide) polyethylene glycol (BMAA-PEG) yields poly alpha-DBBF which offers the added benefits of reduced renal clearance and increased retention in the vascular circulation. Oxygen equilibrium curves for poly alpha-DBBF are slightly left-shifted (higher O-2 affinity) compared to those of alpha-DBBF; with a diminished cooperativity and a reduced Bohr effect. In rapid mixing experiments (oxygen dissociation and carbon monoxide binding), poly alpha-DBBF exhibits a several fold increase in the overall rate of deoxygenation and carbon monoxide binding kinetics over its cross-linked counterpart. The rate of nitric oxide binding to the oxidized form of poly alpha-DBBF shows little or no change compared to the intramolecularly cross-linked derivative. The reduction of cyanomet poly alpha-DBBF by dithionite is several fold faster than that of HbA(0) and alpha-DBBF whereas the slow subsequent cyanide dissociation from the ferrous iron remained unchanged among all proteins. The propensity of poly alpha-DBBF for auto-oxidation is slightly enhanced over alpha-DBBF whereas the extent of oxidative modification by hydrogen peroxide is very similar. Polymerization appears to selectively modify ligand interactions and redox kinetics of the tetrameric cross-linked form which reflects a possibly more open heme pocket. The data suggests that changes in oxygenation properties of hemoglobin brought about by a given modification are not necessarily predictive of other functional changes. C1 UNIV MAINE,DEPT BIOCHEM MICROBIOL & MOLEC BIOL,ORONO,ME 04469. RP ROGERS, MS (reprint author), US FDA,CTR BIOL EVALUAT & RES,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 23 Z9 23 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD APR 27 PY 1995 VL 1248 IS 2 BP 135 EP 142 DI 10.1016/0167-4838(95)00017-O PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QY394 UT WOS:A1995QY39400007 PM 7748895 ER PT J AU BOWYER, JF CLAUSING, P NEWPORT, GD AF BOWYER, JF CLAUSING, P NEWPORT, GD TI DETERMINATION OF D-AMPHETAMINE IN BIOLOGICAL SAMPLES USING HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AFTER PRECOLUMN DERIVATIZATION WITH O-PHTHALDIALDEHYDE AND 3-MERCAPTOPROPIONIC ACID SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article ID AMINO-ACIDS; METHAMPHETAMINE; ULTRAVIOLET; PLASMA; BRAIN AB An HPLC method is described for the determination of amphetamine using fluorometric detection after derivatization with o-phthaldialdehyde and 3-mercaptopropionic acid. This procedure is more sensitive (detection limit 370 fmol in microdialysate buffer standards, 1.5 pmol in extracted plasma and tissue samples) than most of the previous methods described for the determination of amphetamine with HPLC-fluorescence detection. Due to the stability of the derivative it is also suitable for autosampling after manual derivatization. Investigators currently using o-phthaldialdehyde derivatization and fluorometric detection for amino acid determination should be able to rapidly implement this method. RP BOWYER, JF (reprint author), NATL CTR TOXICOL RES,DIV NEUROTOXICOL,3900 NCTR DR,JEFFERSON,AR 72079, USA. NR 25 TC 21 Z9 22 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD APR 21 PY 1995 VL 666 IS 2 BP 241 EP 250 DI 10.1016/0378-4347(94)00573-N PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QW512 UT WOS:A1995QW51200006 PM 7633600 ER PT J AU FIELDS, BA GOLDBAUM, FA YSERN, X POLJAK, RJ MARIUZZA, RA AF FIELDS, BA GOLDBAUM, FA YSERN, X POLJAK, RJ MARIUZZA, RA TI MOLECULAR-BASIS OF ANTIGEN MIMICRY BY AN ANTI-IDIOTOPE SO NATURE LA English DT Article ID 3-DIMENSIONAL STRUCTURE; IDIOTYPIC ANTIBODIES; COMPLEX; LYSOZYME; D1.3 AB IDIOTOPES are antigenic determinants, unique to an antibody or group of antibodies, defined by the reaction of anti-idiotopic antibodies with the antibodies bearing the idiotopes. The ensemble of idiotopes of an antibody constitutes its idiotype. Idiotypes are useful as markers to follow specific antibodies and clones of cells in immune responses and the inheritance of immunoglobulin genes. As external antigens and anti-idiotypic antibodies can competitively bind the combining site of specific antibodies, some antiidiotypic antibodies may resemble the external antigen, thus mimicking its structure. It has been proposed(1-5) that an anti-idiotypic antibody, anti-anti-X, may resemble the external antigen X and thus carry its 'internal image', but this idea is not unequivocally supported by the three-dimensional structures of anti-idiotopic antibodies(6-9), either because the structures of the external antigen(8) or of the anti-idiotopic antibody(7) were unknown, or because the anti-idiotopic antibodies showed no resemblance to the external antigens(6,9) (reviewed in ref. 10). Functional mimicry of ligands of biological receptors by anti-idiotypic antibodies has been described in several systems (reviewed in ref. 11). But how closely can antibodies mimic antigens at the molecular level? Here we present the crystal structure of an idiotope-anti-idiotope complex between the Fv fragments of the anti-lysozyme antibody D1.3 and the anti-D1.3 antibody E5.2. D1.3 contacts the antigen, lysozyme and the anti-idiotopic E5.2 through essentially the same combining-site residues, In addition, E5.2 interacts with D1.3, making contacts similar to those between lysozyme and D1.3. Thus, the anti-idiotopic antibody E5.2 mimics lysozyme in its binding interactions with D1.3. Validating these observations, E5.2, used as an immunogen, induces an anti-lysozyme response. C1 US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. RP FIELDS, BA (reprint author), UNIV MARYLAND,CTR ADV RES BIOTECHNOL,INST BIOTECHNOL,9600 GUDELSKY DR,ROCKVILLE,MD 20850, USA. NR 21 TC 143 Z9 147 U1 1 U2 4 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD APR 20 PY 1995 VL 374 IS 6524 BP 739 EP 742 DI 10.1038/374739a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QU304 UT WOS:A1995QU30400055 PM 7536303 ER PT J AU MEGGS, WJ WEISMAN, R HOFFMAN, RS SHIH, R WEIMER, SM DEANNUNTIS, GJ GOLDFRANK, LR HSU, CK SABO, S LEO, P SHASTRY, D RUBIN, K CONSTANTINE, I SOMWARU, S MUNSHI, A AF MEGGS, WJ WEISMAN, R HOFFMAN, RS SHIH, R WEIMER, SM DEANNUNTIS, GJ GOLDFRANK, LR HSU, CK SABO, S LEO, P SHASTRY, D RUBIN, K CONSTANTINE, I SOMWARU, S MUNSHI, A TI ANTICHOLINERGIC POISONING ASSOCIATED WITH AN HERBAL TEA - NEW-YORK-CITY, 1994 (REPRINTED FROM MMWR, VOL 44, PG 193-195, 1995) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 NEW YORK STATE DEPT HLTH,BUR ENVIRONM INVEST,DIST OFF,NEW YORK,NY. US FDA,REG LAB,NEW YORK,NY. CTR DIS CONTROL,NATL CTR ENVIRONM HLTH,DIV ENVIRONM HAZARDS & HLTH EFFECTS,ATLANTA,GA. RP MEGGS, WJ (reprint author), ELMHURST HOSP,MED CTR,NEW YORK,NY, USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 19 PY 1995 VL 273 IS 15 BP 1166 EP 1167 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QT100 UT WOS:A1995QT10000005 ER PT J AU HOWARD, PC CONSOLO, MC DOOLEY, KL BELAND, FA AF HOWARD, PC CONSOLO, MC DOOLEY, KL BELAND, FA TI METABOLISM OF 1-NITROPYRENE IN MICE - TRANSPORT ACROSS THE PLACENTA AND MAMMARY TISSUES SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE 1-NITROPYRENE; PLACENTA; MAMMARY TISSUES; C-OXIDIZED METABOLITES; NITROREDUCED METABOLITES ID HAMSTER OVARY CELLS; XANTHINE-OXIDASE; CARCINOGEN 1-NITROPYRENE; SALMONELLA-TYPHIMURIUM; MICROSOMAL METABOLITES; OXIDIZED METABOLITES; DNA ADDUCTS; LINE HEPG2; LIVER; MUTAGENICITY AB The distribution and metabolism of the environmental pollutant 1-nitropyrene was studied in C57B1/6N mice following oral or intraperitoneal dosing. When administered by gavage, 1-nitropyrene and its metabolites demonstrated biphasic elimination kinetics from the blood, with half-lives of 0.3 and 1.8 days and a distribution volume of 74 ml. Intraperitoneal administration resulted in similar biphasic elimination, with half-lives of 0.5 and 3 days and a distribution volume of 98 ml. Treating pregnant C57B1/6N (C3H sire) mice by gavage resulted in similar absorption and elimination kinetics of 1-nitropyrene and metabolites, except that the distribution volume increased to 123 ml. 1-Nitropyrene and/or its metabolites (0.7% of the administered dose) crossed the placenta and accumulated in the fetuses and amniotic fluid, with both C-oxidized and nitroreduced metabolites being detected. Suckling neonates accumulated I-nitropyrene and its metabolites when their darns were administered 1-nitropyrene by gavage. Each neonate received approximately 0.1% of the administered dose and demonstrated the presence of both C-oxidized and nitroreduced metabolites. These results demonstrate that this environmental pollutant is capable of crossing the placenta or mammary tissues to expose the offspring to a potentially genotoxic compound. C1 NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. RP HOWARD, PC (reprint author), CASE WESTERN RESERVE UNIV,SCH MED,DEPT ENVIRONM HLTH SCI,CLEVELAND,OH 44106, USA. FU NIEHS NIH HHS [ES-03648] NR 39 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD APR 14 PY 1995 VL 95 IS 3 BP 309 EP 325 DI 10.1016/0009-2797(94)03574-R PG 17 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA QU886 UT WOS:A1995QU88600008 PM 7728900 ER PT J AU OBIRI, NI DEBINSKI, W LEONARD, WJ PURI, RK AF OBIRI, NI DEBINSKI, W LEONARD, WJ PURI, RK TI RECEPTOR FOR INTERLEUKIN-13 - INTERACTION WITH INTERLEUKIN-4 BY A MECHANISM THAT DOES NOT INVOLVE THE COMMON GAMMA-CHAIN SHARED BY RECEPTORS FOR INTERLEUKIN-2, INTERLEUKIN-4, INTERLEUKIN-7, INTERLEUKIN-9 AND INTERLEUKIN-15 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN B-CELLS; FUNCTIONAL COMPONENT; IL-2 RECEPTOR; IGE SYNTHESIS; KILLER-CELLS; EXPRESSION; CYTOKINE; DIFFERENTIATION; PROLIFERATION; ACTIVATION AB Interleukin 13 (IL-13) shares many biological properties with IL-4, and although the receptor for IL-4 (IL-4R) has been characterized, the expression and structure of IL-13 receptor are unknown. We report here that human renal cell carcinoma (RCC) cells express large numbers of functional IL-13R. Human B lymphocytes and monocytes expressed a very small number of IL-13R, while resting or activated human T cells expressed little or no IL-13R, IL-4 did not compete for IL-13 binding, while IL-13 competed for IL-4 binding, even though IL-4R and IL-13R are structurally distinct on human RCC cells. IL-13 cross-linked with one major protein that is similar in size to the gamma(c) subunit of IL-2, -4, -7, -9, and -15 receptors but was not recognized by anti-gamma(c) or anti-IL-4R antibodies. IL-4, on the other hand, cross linked with two major proteins, the smaller of which appears to be similar in size to IL-13R and gamma(c), but (like the IL-13R) it did not react with anti-gamma(c) antibody. Although as shown in this study and in previous studies, gamma(c) is a functional component of IL-4R in lymphoid cells, it does not appear to be associated with IL-4R on RCC cells. Even in the absence of common gamma chain IL-4 and IL-13 were able to up-regulate intracellular adhesion molecule-1 antigen on RCC cells. These data suggest that the interaction of IL-13 with IL-4R does not involve gamma(c) and IL-13R itself may be a novel subunit of the IL-4R. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,MOLEC TUMOR BIOL LAB,BETHESDA,MD 20892. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT SURG,DIV NEUROSURG,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT MICROBIOL & IMMUNOL,HERSHEY,PA 17033. NHLBI,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NR 31 TC 229 Z9 234 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 14 PY 1995 VL 270 IS 15 BP 8797 EP 8804 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT448 UT WOS:A1995QT44800064 PM 7721786 ER PT J AU LABORDE, JB PIPKIN, JL HINSON, WG ANSON, JF SHEEHAN, DM YOUNG, JF HANSEN, DK AF LABORDE, JB PIPKIN, JL HINSON, WG ANSON, JF SHEEHAN, DM YOUNG, JF HANSEN, DK TI RETINOIC ACID-INDUCED STRESS PROTEIN-SYNTHESIS IN THE MOUSE SO LIFE SCIENCES LA English DT Article DE RETINOIC ACID; STRESS PROTEINS; ORGANOGENESIS ID HEAT-SHOCK PROTEINS; POSTIMPLANTATION RAT EMBRYOS; SKELETAL DEVELOPMENT; EXPOSURE; THERMOTOLERANCE; MALFORMATIONS; ACCUMULATION; TERATOGENS; INDUCTION; RESPONSES AB We have previously demonstrated that stress proteins (SPs) are synthesized in tissues in which malformations are later observed following treatment with the developmental toxicant, retinoic acid (RA), on day 11 of gestation (GD 11). These proteins were not synthesized in tissues which did not present with malformations near partuition. The purpose of the present investigation was to determine if this correlation between early SP synthesis and later malformation was present at other times during gestation. CD-1 strain mice were dosed orally with corn oil or 100 mg/kg body weight RA on GD 10 or 13. Some of the mice in each group were given an intraperitoneal injection of H-3-leucine to label embryonic protein synthesis one hour after dosing with RA. These animals were sacrificed 1.5 hour later, and embryonic protein synthesis was determined by two-dimensional gel electrophoresis followed by autoradiography. Other animals in each group were sacrificed on day 17 of gestation, and fetuses were examined for the presence of malformations. Following treatment with RA on day 10 of gestation, malformations were observed in the forelimbs, the hindlimbs and the tail; heart defects were not observed. SPs of 20-25,000 and 90,000 relative molecular mass (Mr) were synthesized in the forelimb bud and tail; in addition, a second low molecular weight (20-25,000) and a 84,000 Mr SPs were synthesized in forelimb buds. No SPs were synthesized in the hindlimb bud or the heart. Following RA treatment on GD 13, cleft palate was observed in 58% of fetuses; no other malformations were found. Proteins of 34,000, 84,000 and 90,000 Mr were synthesized in craniofacial tissue; SPs were not observed in forelimb bud, hindlimb bud, heart or tail tissues at this time. Therefore, it appears that there may be a correlation between tissue-specific SP synthesis early in organogenesis and the presence of a malformation later in gestation. C1 US FDA,NATL CTR TOXICOL RES,DIV GENET TOXICOL,JEFFERSON,AR 72079. RP LABORDE, JB (reprint author), US FDA,NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079, USA. NR 47 TC 21 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 14 PY 1995 VL 56 IS 21 BP 1767 EP 1778 DI 10.1016/0024-3205(95)00148-Y PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA QT787 UT WOS:A1995QT78700003 PM 7739351 ER PT J AU HOBERMAN, D AF HOBERMAN, D TI DRUG PROMOTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP HOBERMAN, D (reprint author), US FDA,ROCKVILLE,MD 20852, USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 13 PY 1995 VL 332 IS 15 BP 1031 EP 1031 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QT737 UT WOS:A1995QT73700013 PM 7885412 ER PT J AU KESSLER, DA ROSE, JL TEMPLE, RJ SCHAPIRO, R GRIFFIN, JP AF KESSLER, DA ROSE, JL TEMPLE, RJ SCHAPIRO, R GRIFFIN, JP TI DRUG PROMOTION - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP KESSLER, DA (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 13 PY 1995 VL 332 IS 15 BP 1033 EP 1033 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QT737 UT WOS:A1995QT73700019 ER PT J AU HERMAN, EH HASINOFF, BB ZHANG, J RALEY, LG ZHANG, TM FUKUDA, Y FERRANS, VJ AF HERMAN, EH HASINOFF, BB ZHANG, J RALEY, LG ZHANG, TM FUKUDA, Y FERRANS, VJ TI MORPHOLOGIC AND MORPHOMETRIC EVALUATION OF THE EFFECT OF ICRF-187 ON BLEOMYCIN-INDUCED PULMONARY TOXICITY SO TOXICOLOGY LA English DT Article DE BLEOMYCIN; BLEOMYCIN IRON COMPLEX; PULMONARY TOXICITY; ICRF-187, PROTECTIVE EFFECTS ID INDUCED LUNG FIBROSIS; DEFEROXAMINE INFUSION; CHELATING-AGENTS; MICE; DNA; (+)-1,2-BIS(3,5-DIOXOPIPERAZINYL-1-YL)PROPANE; CARDIOTOXICITY; DEGRADATION; HYDROLYSIS; ADRIAMYCIN AB Morphologic and morphometric studies were made of the protective effects of ICRF-I87 against the pulmonary damage induced by bleomycin in male and female C57/BL6 mice, Sixty minutes prior to the subcutaneous administration of 15 mg/kg of bleomycin, animals received either saline or ICRF-187 (300 or 150 mg/kg) intraperitoneally, twice a week for 4 weeks, The lungs of animals treated with bleomycin alone showed inflammation, hyperplasia of type II epithelial cells, squamous cell metaplasia and fibrosis. The extent of fibrosis was quantified by means of a color videometric system and histologic sections of lung stained according to a modified Masson trichrome method. The severity of these alterations, particularly of fibrosis, was reduced in all groups of animals pretreated with ICRF-187. The fibrosis was reduced to a similar extent in female mice treated with the 300 mg/kg and the 150 mg/kg doses of ICRF-187, from 39.3% to 17.6% and 13.3%, respectively. ICRF-187 induced significantly different degrees of reduction in fibrosis in the 2 groups of male mice treated with the 150 mg/kg and the 300 mg/kg doses, from 30% to 19.7% and 12.2%, respectively. In vitro studies indicated that both ICRF-187 and its open-ring hydrolysis product (ADR-925) remove iron slowly from the bleomycin-iron complex, This observation provides a basis for the concept that ICRF-187 protects by chelating iron involved in the formation of the bleomycin-Fe3+ complex that generates reactive oxygen radicals capable of causing pulmonary damage. C1 UNIV MANITOBA,FAC PHARM,WINNIPEG,MB R3T 2N2,CANADA. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NIPPON MED COLL,DEPT PATHOL 1,TOKYO,JAPAN. RP HERMAN, EH (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV RES & TESTING,HFD-472 MOD 1,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 44 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD APR 12 PY 1995 VL 98 IS 1-3 BP 163 EP 175 DI 10.1016/0300-483X(94)02987-6 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA QX943 UT WOS:A1995QX94300017 PM 7537925 ER PT J AU KRIEG, AM YI, AK MATSON, S WALDSCHMIDT, TJ BISHOP, GA TEASDALE, R KORETZKY, GA KLINMAN, DM AF KRIEG, AM YI, AK MATSON, S WALDSCHMIDT, TJ BISHOP, GA TEASDALE, R KORETZKY, GA KLINMAN, DM TI CPG MOTIFS IN BACTERIAL-DNA TRIGGER DIRECT B-CELL ACTIVATION SO NATURE LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; BINDING; OLIGONUCLEOTIDES; PHOSPHOROTHIOATE; STIMULATION; LYMPHOCYTES; FRAGMENTS; MICE AB UNMETHYLATED CpG dinucleotides are more frequent in the genomes of bacteria and viruses than of vertebrates. We report here that bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated CPG dinucleotides induce murine B cells to proliferate and secrete immunoglobulin in vitro and in vivo. This activation is enhanced by simultaneous signals delivered through the antigen receptor. Optimal B-cell activation requires a DNA motif in which an unmethylated CpG dinucleotide is flanked by two 5' purines and two 3' py,rimidines. Oligodeoxynucleotides containing this CpG motif induce more than 95% of all spleen B cells to enter the cell cycle. These data suggest a possible evolutionary link between immune defence based on the recognition of microbial DNA and the phenomenon of CpG suppression' in vertebrates. The potent immune activation by CpG oligonucleotides has implications for the design and interpretation of studies using 'antisense' oligonucleotides and points to possible new applications as adjuvants. C1 UNIV IOWA,COLL MED,DEPT PATHOL,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DEPT MICROBIOL,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DEPT PHYSIOL,IOWA CITY,IA 52242. VET AFFAIRS MED CTR,IOWA CITY,IA 52246. US FDA,CTR BIOL EVALUAT & RES,RETROVIRAL IMMUNOL SECT,BETHESDA,MD 20892. RP KRIEG, AM (reprint author), UNIV IOWA,COLL MED,DEPT INTERNAL MED,IOWA CITY,IA 52242, USA. NR 29 TC 2497 Z9 2663 U1 11 U2 87 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD APR 6 PY 1995 VL 374 IS 6522 BP 546 EP 549 DI 10.1038/374546a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR069 UT WOS:A1995QR06900053 PM 7700380 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI PROPOSAL TO REQUIRE EVIDENCE OF EFFECTIVENESS OF SPERMICIDES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), OFF HLTH AFFAIRS,FDA 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 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 5 PY 1995 VL 273 IS 13 BP 982 EP 982 DI 10.1001/jama.273.13.982 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QP890 UT WOS:A1995QP89000008 PM 7897804 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI TREATMENT IND FOR ADVANCED PANCREATIC-CANCER AUTHORIZED SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), OFF HLTH AFFAIRS,FDA 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 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 5 PY 1995 VL 273 IS 13 BP 982 EP 982 DI 10.1001/jama.273.13.982 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QP890 UT WOS:A1995QP89000009 PM 7897804 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI MONOCLONAL-ANTIBODY LICENSED FOR USE IN ANGIOPLASTY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US OFF HLTH AFFAIRS,FDA PARKLAWN BLDG,560 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 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 5 PY 1995 VL 273 IS 13 BP 982 EP 982 DI 10.1001/jama.273.13.982 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QP890 UT WOS:A1995QP89000007 PM 7897804 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI TREATMENT IND FOR AIDS-RELATED WASTING AUTHORIZED SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US OFF HLTH AFFAIRS,FDA 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 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 5 PY 1995 VL 273 IS 13 BP 982 EP 982 DI 10.1001/jama.273.13.982 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QP890 UT WOS:A1995QP89000006 PM 7897804 ER PT J AU LEE, YL HELMAN, L HOFFMAN, T LABORDA, J AF LEE, YL HELMAN, L HOFFMAN, T LABORDA, J TI DLK, PG2 AND PREF-1 MESSENGER-RNAS ENCODE SIMILAR PROTEINS BELONGING TO THE EGF-LIKE SUPERFAMILY - IDENTIFICATION OF POLYMORPHIC VARIANTS OF THIS RNA SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE TRANSMEMBRANE PROTEIN; PROTEIN POLYMORPHISM; EGF-LIKE SUPERFAMILY; CELL DIFFERENTIATION; NEUROENDOCRINE CELL ID NEURAL CREST DERIVATIVES; EPIDERMAL GROWTH-FACTOR; DROSOPHILA-NOTCH; HOMEOTIC GENE; MOUSE HOMOLOG; CELL-LINE; DIFFERENTIATION; SEQUENCE; GLUCOCORTICOIDS; MELANOGASTER AB dlk encodes a transmembrane protein member of the EGF-like family of homeotic proteins, dlk is expressed in the same type of neuroendocrine tissues and tumors as pG2, a gene cloned because of its differential expression in human pheochromocytomas versus neuroblastomas. Human dlk and pG2 cDNAs are around 98% similar in sequence, but the predicted proteins encoded by those genes are apparently unrelated. This fact suggested the existence of polymorphic variants of the same gene. We have sequenced again several pG2 and dlk clones in parallel. We identified a pG2 cDNA species corresponding to an alternatively spliced dlk mRNA, as well as several other variant forms of dlk mRNA. One of the pG2 clones resulted to be identical to human dlk and encode the same EGF-like protein. Pref-1, a cDNA. isolated from 3T3-L1 fibroblasts, encodes a putative protein possessing an extracellular EGF-like domain similar to dlk, but a different intracellular region. Analysis of sequence data from different clones obtained in our laboratory confirmed some of the differences between dlk and Pref-1. However, the putative difference in the intracellular regions of dlk and Pref-1 was due to sequence artifacts. These data suggest that dlk, pG2 and Pref-1 are variant products of the same gene. C1 US FDA,CTR BIOL EVALUAT & RES,DIV MONOCLONAL ANTIBODIES,CELL BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,PEDIAT BRANCH,BETHESDA,MD 20892. RI Laborda, Jorge/L-5726-2014 OI Laborda, Jorge/0000-0002-9210-838X NR 28 TC 49 Z9 53 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD APR 4 PY 1995 VL 1261 IS 2 BP 223 EP 232 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QQ952 UT WOS:A1995QQ95200007 PM 7711066 ER PT J AU SHANK, FR CARSON, KL AF SHANK, FR CARSON, KL TI THE ROLE OF BIOTECHNOLOGY IN THE NEXT MILLENNIUM FROM THE REGULATORS POINT-OF-VIEW SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 1 EP BTEC PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP233 UT WOS:A1995QP23301881 ER PT J AU JERUSSI, RA AF JERUSSI, RA TI THE REVIEW OF DRUG APPLICATIONS BY CHEMISTS AT THE FDA SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20855. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 10 EP CHAL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23201486 ER PT J AU LIPMAN, AL AF LIPMAN, AL TI SAFETY OF XANTHENE DYES ACCORDING TO THE FDA SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR FOOD SAFETY & APPL NUTR,OFF PREMKT APPROVAL,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 10 EP AGRO PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200160 ER PT J AU HATHEWAY, CL FERREIRA, JL AF HATHEWAY, CL FERREIRA, JL TI DETECTION AND IDENTIFICATION OF CLOSTRIDIUM-BOTULINUM NEUROTOXINS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. US FDA,ATLANTA,GA 30309. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 11 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200011 ER PT J AU WEKELL, MM MANGER, RM HADLEY, SW HUNGERFORD, JM AF WEKELL, MM MANGER, RM HADLEY, SW HUNGERFORD, JM TI METHODS FOR THE DETECTION OF MARINE TOXINS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,SEAFOOD PROD RES CTR,BOTHELL,WA 98021. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 25 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200025 ER PT J AU TRUCKSESS, MW AF TRUCKSESS, MW TI COMPARISON OF IMMUNOCHEMICAL AND LIQUID-CHROMATOGRAPHY METHODS FOR DETERMINATION OF FUMONISIN-B1 IN CORN SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,DIV NAT PROD,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 34 EP BTEC PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP233 UT WOS:A1995QP23301914 ER PT J AU SMITH, MJ EPPLEY, RM STACK, ME THOMAS, FS AF SMITH, MJ EPPLEY, RM STACK, ME THOMAS, FS TI FUMONISIN STRUCTURE-ACTIVITY STUDIES - NOVEL IMPLICATIONS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CFSAN,DIV NAT PROD,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 39 EP BTEC PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP233 UT WOS:A1995QP23301919 ER PT J AU WARNER, CR DANIELS, DH JOE, FL DIACHENO, GW AF WARNER, CR DANIELS, DH JOE, FL DIACHENO, GW TI THE USE OF ION-INTERACTION CHROMATOGRAPHY WITH A POSTCOLUMN COLORIMETRIC REACTION TO DETERMINE BROMATE IN WATER SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 44 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200325 ER PT J AU MOORE, ML DOYLE, TD AF MOORE, ML DOYLE, TD TI EFFECT OF MOBILE-PHASE COMPOSITION ON ENANTIOSELECTIVITY IN REVERSE-PHASE AND NORMAL-PHASE HPLC CHIRAL RESOLUTION SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 GALLAUDET UNIV,DEPT CHEM,WASHINGTON,DC 20002. US FDA,DIV RES & TESTING,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 45 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200326 ER PT J AU FIFER, EK ROBERTSON, KS FREEMAN, JP SHAIKH, AU AF FIFER, EK ROBERTSON, KS FREEMAN, JP SHAIKH, AU TI ORTHO-SUBSTITUTED NITROPHENYLFURANS - CHEMISTRY AND MUTAGENICITIES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. UNIV ARKANSAS,LITTLE ROCK,AR 72204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 48 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203241 ER PT J AU CARSON, MC HELLER, DN AF CARSON, MC HELLER, DN TI CONFIRMATION OF MULTIPLE TETRACYCLINE RESIDUES IN MILK BY LIQUID-CHROMATOGRAPHY PARTICLE-BEAM MASS-SPECTROMETRY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR VET MED,BELTSVILLE,MD 20705. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 53 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200053 ER PT J AU POHLAND, AE AF POHLAND, AE TI OCCURRENCE OF FUMONISINS IN THE UNITED-STATES FOOD-SUPPLY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 57 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200057 ER PT J AU SUNDLOF, SF AF SUNDLOF, SF TI HUMAN HEALTH RISKS ASSOCIATED WITH DRUG RESIDUES IN ANIMAL-DERIVED FOODS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR VET MED,ROCKVILLE,MD 20855. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 62 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200062 ER PT J AU ORANGERS, JJ BERKOWITZ, DB AF ORANGERS, JJ BERKOWITZ, DB TI EVALUATION OF ANALYTICAL METHODS WITHIN A CONTEXT OF USE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20855. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 65 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200065 ER PT J AU MUSSER, SM AF MUSSER, SM TI LC/MS ANALYSIS AND IDENTIFICATION OF FUMONISINS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,INSTRUMENTAT & BIOPHYS BRANCH,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 95 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200095 ER PT J AU WILKES, JG CHURCHWELL, MI THOMPSON, HC AF WILKES, JG CHURCHWELL, MI THOMPSON, HC TI DETERMINATION OF UNDERIVATIZED FUMONISINS FB1, FB2 AND RELATED-COMPOUNDS BY HPLC SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NCTR,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 99 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200099 ER PT J AU HENDERSON, TJ VENABLE, RM EGAN, W AF HENDERSON, TJ VENABLE, RM EGAN, W TI CONFORMATIONAL MOBILITY OF THE GROUP-B MENINGOCOCCAL CAPSULAR POLYSACCHARIDE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 105 EP CARB PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200766 ER PT J AU CARSON, MC CHU, PS VONBREDOW, J AF CARSON, MC CHU, PS VONBREDOW, J TI TOWARDS A REGULATORY METHOD - COMPARISON AND VALIDATION OF MULTIRESIDUE PROCEDURES FOR DETERMINATION OF BETA-LACTAM ANTIBIOTICS IN MILK SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 USFDA,CTR VET MED,BELTSVILLE,MD 20705. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 117 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200117 ER PT J AU TOLLESON, WH SHELDON, WG THURMAN, JD BUCCI, TJ HOWARD, PC AF TOLLESON, WH SHELDON, WG THURMAN, JD BUCCI, TJ HOWARD, PC TI THE MYCOTOXIN FUMONISIN INDUCES APOPTOSIS IN CULTURED HUMAN KERATINOCYTES AND IN LIVER AND KIDNEY OF RATS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL CTR TOXICOL RES,FOOD & DRUG ADM,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 122 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200122 ER PT J AU SHAIKH, B AF SHAIKH, B TI DETERMINATION OF DIURETIC DRUGS USED IN FOOD-PRODUCING ANIMALS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,BARC E,BELTSVILLE,MD 20705. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 128 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200128 ER PT J AU ROYBAL, JE PFENNING, AP TURNIPSEED, SB HURLBUT, JA LONG, AR AF ROYBAL, JE PFENNING, AP TURNIPSEED, SB HURLBUT, JA LONG, AR TI DYE RESIDUES IN FOODS FROM ANIMAL ORIGIN SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,ANIM DRUGS RES CTR,DENVER FED CTR,DENVER,CO 80225. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 129 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200129 ER PT J AU JACKSON, LS HLYWKA, J BULLERMAN, LB AF JACKSON, LS HLYWKA, J BULLERMAN, LB TI EFFECT OF TIME, TEMPERATURE AND PH ON THE STABILITY OF FUMONISIN B IN AN AQUEOUS MODEL SYSTEM SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. IIT,NCFST,SUMMIT ARGO,IL 60501. UNIV NEBRASKA,DEPT FOOD SCI & TECHNOL,LINCOLN,NE 68583. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 133 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200133 ER PT J AU HOLDER, CL CHURCHWELL, MI DOERGE, DR THOMPSON, HC AF HOLDER, CL CHURCHWELL, MI DOERGE, DR THOMPSON, HC TI MULTI-RESIDUE METHODS FOR THE DETERMINATION AND CONFIRMATION OF 8 HETEROCYCLIC AMINES IN COOKED MEATS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCTR,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 137 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200137 ER PT J AU ANG, CYW AF ANG, CYW TI INFLUENCE OF COOKING END-POINT TEMPERATURE ON HEADSPACE VOLATILES OF CHICKEN MEAT SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 FDA,DHHS,NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 138 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200138 ER PT J AU THOMPSON, HC AF THOMPSON, HC TI OVERVIEW OF THE ANALYTICAL REQUIREMENTS FOR THE TOXICOLOGICAL EVALUATION OF FUMONISIN B1 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 FDA,NCTR,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 141 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200141 ER PT J AU TROXELL, TC AF TROXELL, TC TI REGULATORY ASPECTS OF FUMONISINS IN THE UNITED-STATES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 143 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200143 ER PT J AU MILLER, MA HONSTEAD, JP LOVELL, RA AF MILLER, MA HONSTEAD, JP LOVELL, RA TI REGULATORY ASPECTS OF FUMONISINS WITH RESPECT TO ANIMAL FEED-ANIMAL DERIVED RESIDUES IN FOODS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR VET MED,ROCKVILLE,MD 20855. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 144 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200144 ER PT J AU ANG, CYW AF ANG, CYW TI CATALATIC ACTIVITY IN CHICKEN MEAT AS AN INDICATOR OF COOKING END-POINT TEMPERATURE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,DHHS,NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72070. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 146 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200146 ER PT J AU LIMM, W BEGLEY, TH HOLLIFIELD, HC AF LIMM, W BEGLEY, TH HOLLIFIELD, HC TI MODELING OF ADDITIVE DIFFUSION IN POLYETHYLENE TEREPHTHALATE (PET) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 382 EP POLY PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP233 UT WOS:A1995QP23301518 ER PT J AU CLOUSE, KA WEIH, KA WEBER, ND DANIEL, S COSENTINO, LM AF CLOUSE, KA WEIH, KA WEBER, ND DANIEL, S COSENTINO, LM TI INTERLEUKIN (IL)-12 CAN FUNCTION ALONE AND IN SYNERGY WITH IL-2 TO SUPPORT HIV-1 REPLICATION IN ACTIVATED HUMAN T-CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 204 EP 204 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500683 ER PT J AU JOSHI, BH EPSTEIN, JS HEWLETT, IK AF JOSHI, BH EPSTEIN, JS HEWLETT, IK TI IMMUNOMAGNETIC CAPTURE LINKED RT-PCR FOR DETECTION OF HIV-1 RNA IN SERUM AND CULTURE FLUIDS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 207 EP 207 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500696 ER PT J AU BOERKOEL, CF EXELBERT, R NICASTRI, C NICHOLS, RC MILLER, FW PLOTZ, PH RABEN, N AF BOERKOEL, CF EXELBERT, R NICASTRI, C NICHOLS, RC MILLER, FW PLOTZ, PH RABEN, N TI LEAKY SPLICING MUTATION IN THE ACID MALTASE GENE IS ASSOCIATED WITH DELAYED-ONSET OF GLYCOGENOSIS TYPE-II SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID LYSOSOMAL ALPHA-GLUCOSIDASE; PROTEIN MESSENGER-RNAS; DISEASE TYPE-II; MISSENSE MUTATION; DNA FRAGMENTS; POMPE DISEASE; ONE ALLELE; GC-CLAMP; DEFICIENCY; EXPRESSION AB An autosomal recessive deficiency of acid alpha-gIucosidase (GAA), type II glycogenosis, is genetically and clinically heterogeneous. The discovery of an enzyme-inactivating genomic deletion of exon 18 in three unrelated genetic compound patients-two infants and an adult-provided a rare opportunity to analyze the effect of the second mutation in patients who displayed dramatically different phenotypes. A deletion of Lys-903 in one patient and a substitution of Arg for Leu-299 in another resulted in the fatal infantile form. In the adult, a T-to-G base change at position -13 of intron 1 resulted in alternatively spliced transcripts with deletion of exon 2, the location of the start codon. The low level of active enzyme (12% of normal) generated from the leakage of normally spliced mRNA sustained the patient to adult life. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. US FDA,ROCKVILLE,MD 20857. OI Miller, Frederick/0000-0003-2831-9593 NR 61 TC 72 Z9 76 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1995 VL 56 IS 4 BP 887 EP 897 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA QP663 UT WOS:A1995QP66300010 PM 7717400 ER PT J AU BROWN, SL AF BROWN, SL TI CHOLESTEROL CONCENTRATIONS AND DEPRESSION IN ELDERLY PEOPLE SO ANNALS OF MEDICINE LA English DT Editorial Material ID SUICIDE RP BROWN, SL (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OSB,EPIDEMIOL BRANCH,5600 FISHERS LANE,HFZ-541,ROCKVILLE,MD 20857, USA. NR 8 TC 3 Z9 3 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0785-3890 J9 ANN MED JI Ann. Med. PD APR PY 1995 VL 27 IS 2 BP 141 EP 142 DI 10.3109/07853899509031950 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QY908 UT WOS:A1995QY90800001 PM 7632405 ER PT J AU POLIS, MA SPOONER, KM BAIRD, BF MANISCHEWITZ, JF JAFFE, HS FISHER, PE FALLOON, J DAVEY, RT KOVACS, JA WALKER, RE WHITCUP, SM NUSSENBLATT, RB LANE, HC MASUR, H AF POLIS, MA SPOONER, KM BAIRD, BF MANISCHEWITZ, JF JAFFE, HS FISHER, PE FALLOON, J DAVEY, RT KOVACS, JA WALKER, RE WHITCUP, SM NUSSENBLATT, RB LANE, HC MASUR, H TI ANTICYTOMEGALOVIRAL ACTIVITY AND SAFETY OF CIDOFOVIR IN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION AND CYTOMEGALOVIRUS VIRURIA SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIVIRAL ACTIVITY; (S)-1-(3-HYDROXY-2-PHOSPHONYLMETHOXYPROPYL)CYTOSINE; AIDS; (S)-1-<3-HYDROXY-2-(PHOSPHONYLMETHOXY)PROPYL>CYTOSINE; 9-(1,3-DIHYDROXY-2-PROPOXYMETHYL)GUANINE; INVITRO; HPMPC AB Cidofovir {HPMPC; (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine} is a nucleotide analog with activity against human (CMV). A phase I/II dose escalation trial was conducted with asymptomatic human immunodeficiency virus (HIV)-infected patients with CMV viruria to determine its pharmacokinetics, maximally tolerated dose, and preliminary antiviral activity against CMV. Qualitative CMV blood and urine cultures were monitored weekly to assess anti-CMV activity. Twenty-one HIV-infected persons with CD4 counts from 0 to 389 cells per mu l (median, 39) were enrolled in six dose-ranging groups. The first five groups enrolled four patients each to receive cidofovir infusions either weekly or biweekly for 4 weeks or every 3 weeks for 12 weeks. The sixth group enrolled one patient who received infusions of 5 mg/kg of body weight every other week. Patients receiving 0.5 or 1.5 mg/kg twice weekly experienced no serious toxicity. The first two patients who received 5 mg/kg twice weekly developed glycosuria and 2+ proteinuria. Subsequent patients received concomitant probenecid to attempt to ameliorate renal toxicity. Seventeen patients experienced proteinuria on one or more occasions; 6 of them experienced at least 2+ proteinuria. Four patients did not complete the study as planned because of renal toxicity. Positive CMV urine cultures reverted to negative in 2 of 8 patients receiving doses of less than or equal to 1.5 mg/kg twice weekly and 11 of 13 patients receiving higher doses. Cidofovir has in vivo anti-CMV activity demonstrated by prolonged clearing of CMV viruria, although this observation is tempered by the fact that clearance of viremia could not be demonstrated. The dose-limiting toxicity is renal; however, concurrent administration of probenecid may be protective. The maximally tolerated weekly intravenous dose with probenecid is approximately 5 mg/kg. Efficacy trials with CMV disease will define the therapeutic utility and optimal dosing interval for cidofovir. C1 NEI,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20014. GILEAD SCI INC,FOSTER CITY,CA. RP POLIS, MA (reprint author), NIAID,LIR,BLDG 10,ROOM 11C103,BETHESDA,MD 20892, USA. OI Polis, Michael/0000-0002-9151-2268 NR 20 TC 99 Z9 103 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 1995 VL 39 IS 4 BP 882 EP 886 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA QQ123 UT WOS:A1995QQ12300016 PM 7785989 ER PT J AU BENJAMIN, MM DATTA, AR AF BENJAMIN, MM DATTA, AR TI ACID TOLERANCE OF ENTEROHEMORRHAGIC ESCHERICHIA-COLI SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Note ID HEMOLYTIC UREMIC SYNDROME; SALMONELLA-TYPHIMURIUM; LISTERIA-MONOCYTOGENES; SHOCK PROTEINS; PH; O157-H7; INFECTION; BACTERIA; SURVIVAL AB Enterohemorrhagic Escherichia coli (EHEC) strains were tested for their ability to survive in acid pH at 37 degrees C. No loss of viability was observed in an O157:H7 EHEC strain (ATCC 43895) at pH levels of 3.0 and 2.5 for at least 5 h. The level of acid tolerance of most EHEC isolates was very high, similar to that of Shigella flexneri strains. The acid tolerance was dependent on the growth phase and pH of the growth medium. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MOLEC BIOL RES & EVALUAT HFS-237,WASHINGTON,DC 20204. NR 24 TC 240 Z9 241 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 1995 VL 61 IS 4 BP 1669 EP 1672 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA QQ362 UT WOS:A1995QQ36200084 PM 7747983 ER PT J AU RAFII, F SELBY, AL NEWTON, RK CERNIGLIA, CE AF RAFII, F SELBY, AL NEWTON, RK CERNIGLIA, CE TI REDUCTION AND MUTAGENIC ACTIVATION OF NITROAROMATIC COMPOUNDS BY A MYCOBACTERIUM SP (VOL 60, PG 4264, 1994) SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Correction, Addition C1 US FDA,NATL CTR TOXICOL RES,DIV GENET TOXICOL,JEFFERSON,AR 72079. RP RAFII, F (reprint author), US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 1995 VL 61 IS 4 BP 1677 EP 1677 PG 1 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA QQ362 UT WOS:A1995QQ36200086 PM 16535012 ER PT J AU SAMOKYSZYN, VM FREEMAN, JP MADDIPATI, KR LLOYD, RV AF SAMOKYSZYN, VM FREEMAN, JP MADDIPATI, KR LLOYD, RV TI PEROXIDASE-CATALYZED OXIDATION OF PENTACHLOROPHENOL SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID PROSTAGLANDIN-H SYNTHASE; HORSERADISH-PEROXIDASE; MICROSOMAL METABOLISM; COVALENT BINDING; SODIUM-AZIDE; TETRACHLOROHYDROQUINONE; PROTEIN; DNA; HEXACHLOROBENZENE; CHLOROPHENOLS AB Pentachlorophenol (PCP) was shown to function as a reducing substrate for horseradish peroxidase (HRP) and to stimulate the HRP-catalyzed reduction of 5-phenyl-4-penten-1-yl hydroperoxide (PPHP) to 5-phenyl-4-penten-1-ol. HRP catalyzed the hydroperoxide-dependent oxidation of PCP, using H2O2, PPHP, or ethyl hydroperoxide as substrates, as evidenced by UV spectroscopic and reverse phase HPLC analysis of reaction mixtures. The major oxidation product was tetrachloro-1,4-benzoquinone which was identified on the basis of electronic absorption spectroscopy, mass spectrometry, and cochromatography with authentic standard. HRP-catalyzed oxidation of PCP yielded relatively stable, ESR-detectable pentachlorophenoxyl radical intermediates whose ESR spectra consisted of a symmetrical single line without hyperfine structure. Substitution of natural abundance isotopically-labeled PCP with C-13-labeled PCP resulted in broadening of the ESR signal line width from 6.1 G to 13.5 CT. ESR spin trapping studies, with alpha-(1-oxy-4-pyridyl)-N tert-butylnitrone (4-POBN) as the spin trap demonstrated identical spectra using natural abundance isotopically-labeled PCP versus C-13-labeled PCP, suggesting oxyl addition, rather than carbon-centered radical addition to 4-POBN. The computer simulation of the observed spectra is consistent with two distinct 4-POBN adducts, with relative abundances of similar to 3:1, and hyperfine coupling constants of alpha(N) = (14.61 G)/alpha(H) = 1.83 G and alpha(N) = (14.76 G)/alpha(H) = 5.21 G, respectively. Mechanisms for the hydroperoxide-dependent, HRP-catalyzed oxidation of PCP are presented that are consistent with these results. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. CAYMAN CHEM CORP,ANN ARBOR,MI 48108. MEMPHIS STATE UNIV,DEPT CHEM,MEMPHIS,TN 38152. RP SAMOKYSZYN, VM (reprint author), UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,MAIL SLOT 638,4301 W MARKHAM,LITTLE ROCK,AR 72205, USA. OI Maddipati, Krishna Rao/0000-0003-1445-791X NR 40 TC 37 Z9 40 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD APR-MAY PY 1995 VL 8 IS 3 BP 349 EP 355 DI 10.1021/tx00045a005 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA QU473 UT WOS:A1995QU47300005 PM 7578920 ER PT J AU LUDDEN, LK STRONG, JM KOHN, EC COLLINS, JM AF LUDDEN, LK STRONG, JM KOHN, EC COLLINS, JM TI SIMILARITY OF METABOLISM FOR CAI (NSC-609974) IN HUMAN LIVER-TISSUE IN-VITRO AND IN HUMANS IN-VIVO SO CLINICAL CANCER RESEARCH LA English DT Article ID CYTOCHROMES-P450; L651582; CALCIUM; AGENT AB Metabolism of a new antitumor agent, CAI (NSC 609974), was investigated in human liver tissue in vitro and in plasma and urine of patients receiving CAI. Metabolites identified by HPLC following C-14-labeled CAI incubation with human liver microsomes and reported as percentage of total metabolites formed were M1 (0-3.4%), M2 (4.5-33%), M3 (60-79%), and M4 (7.2-19%). Ketoconazole, an inhibitor of cytochrome P450 3A4, prevented formation of M1, M3, and M4 (concentration of drug that inhibited metabolite formation by 50% when compared to maximum uninhibited activity, 3.0 mu M), but only weakly inhibited formation of M2 (concentration of drug that inhibited metabolite formation by 50% when compared to maximum uninhibited activity, > 50 mu M). CAI incubated with recombinant human P450 3A4 microsomes produced metabolites M3 and M4. Conjugation of M3, most likely a glucuronide, was observed after incubation of C-14-labeled CAI and UDP-glucuronic acid with human liver 13,000 x g supernatant. Plasma samples from patients receiving CAI contained CAI (3.1-5.0 mu g/ml), M1 (0.9-2.6 mu g/ml), and M2 (1.0-2.2 mu g/ml). CAI and M3 but not M4 were observed in the urine samples, After incubation of the urine samples with beta-glucuronidase, CAI concentrations increased 67%, M3 increased up to 9-fold, and M4 was detected. CAI is metabolized in vitro and in vivo by both Phase I and Phase II enzymes and is metabolized to M3 and M4 by P450 3A4. These studies suggest that elevated levels of CAI may result from P450 3A4 inhibition by ketoconazole if these two drugs are coadministered. Correlation between CAI metabolism in vitro and results obtained in patients demonstrates the usefulness of liver metabolism studies in vitro in the early stages of drug development. C1 NCI,PATHOL LAB,SIGNAL TRANSDUCT & PREVENT UNIT,BETHESDA,MD 20892. RP LUDDEN, LK (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV CLIN PHARMACOL,OFF RES RESOURCES,4 RES COURT,ROOM 314,ROCKVILLE,MD 20850, USA. NR 15 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 1995 VL 1 IS 4 BP 399 EP 405 PG 7 WC Oncology SC Oncology GA RJ530 UT WOS:A1995RJ53000005 ER PT J AU LIN, DX LANG, NP KADLUBAR, FF AF LIN, DX LANG, NP KADLUBAR, FF TI SPECIES-DIFFERENCES IN THE BIOTRANSFORMATION OF THE FOOD-BORNE CARCINOGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE BY HEPATIC MICROSOMES AND CYTOSOLS FROM HUMANS, RATS, AND MICE SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID METABOLIC-ACTIVATION; GLUTATHIONE TRANSFERASES; COLORECTAL-CARCINOMA; HETEROCYCLIC AMINES; LIVER-MICROSOMES; COVALENT BINDING; PYRIDINE PHIP; COOKED FOOD; DNA; ENZYMES AB A comparative study on the metabolic activation and detoxification of the food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP), by human, rat, and mouse hepatic subcellular fractions was conducted to elucidate the mechanism of the interspecies and organ-specific differences in genotoxicity and carcinogenesis. Incubation of PhlP with human, rat, and mouse hepatic microsomes each generated two metabolites, which were identified as N-hydroxy-PhlP and 4'-hydroxy-PhlP. However, the rates of formation of these metabolites differed significantly between species. Human hepatic microsomes had the highest capacity to convert PhlP to the genotoxic metabolite, N-hydroxy-PhlP, with a mean rt SD value (9.69 +/- 5.15 nmol/mg protein/30 min, N = 3) that was 1.8-fold and 1.4-fold higher than that of rats (5.25 +/- 1.63, N = 3) and mice (6.89 +/- 0.55, N = 3) p < 0.05), respectively. Rodent microsomes were also able to convert PhlP to its nongenotoxic 4'-hydroxy derivative; however, this detoxification pathway was negligible in human hepatic microsomes. The ratio of N-hydroxylation to 4'-hydroxylation was 97:1, 3.3:1, and 1.7:1 for humans, rats, and mice, respectively. The capacities for the further metabolic activation of N-hydroxy-PhlP by cytosolic O-acetyltransferase, sulfotransferase, L-prolyl-tRNA synthetase, and an ATP-dependent kinase(s) were examined using PhlP-DNA binding as a measure of bioactivation. Acetyl coenzyme A-dependent DNA binding of N-hydroxy-PhlP was detected with both human and rodent hepatic cytosols, and showed a significant interspecies difference. The enzyme activity in rats (65.5 +/- 9.7 pmol bound/mg DNA/30 min, N = 3) was similar to that in human rapid acetylators (59.9 +/- 6.2, N = 3), but was 2.6-fold higher than that in human slow acetylators (25.5 +/- 5.7, N = 7; p < 0.01). Mice had the lowest O-acetyltransferase activity for the activation of N-hydroxy-PhlP (7.3 +/- 0.3, N = 3), which was only 11% of that in rats and 12% and 29% of that in human rapid and slow acetylators, respectively. In contrast to O-acetylation, mouse hepatic cytosols were found to have the highest sulfotransferase activity for the activation of N-hydroxy-PhlP (101.4 +/- 9.1 pmol bound/mg DNA/30 min, N = 3), which was 4.9-fold and 2.3-fold higher than that in rats (20.8 +/- 3.2, N = 3) and in humans (45.0 +/- 20.2, N = 3), respectively. The ATP-dependent activation of N-hydroxy-PhlP was also detected in all three sources of cytosols, and the mean values (N = 3) were 131.1 +/- 12.6, 84.2 +/- 11.4, and 31.5 +/- 9.4 pmol bound/mg DNA/30 min for mice, rats, and humans, respectively. Neither human nor rodent hepatic cytosol-catalyzed DNA binding of N-hydroxy-PhlP was stimulated upon the addition of L-proline, suggesting that L-prolyl-tRNA synthetase was not involved in this reaction. Human and rat hepatic cytosols exhibited high revers of glutathione S-transferase activity that significantly inhibited the acetyltransferase-mediated DNA binding of N-hydroxy-PhlP; no such effect was observed with mouse hepatic cytosols. Moreover, the glutathione S-transferases had no inhibitory effect on sulfotransferase-mediated or ATP-dependent DNA binding of N-hydroxy-PhlP. These results suggest that: the differential metabolic activation and detoxification of PhlP in rats and mice are likely to be critical factors in determining the species differences and organ-specificity to PhlP genotoxicity and carcinogenesis. Because human hepatic microsomes seem to catalyze exclusively the N-hydroxylation of PhlP and the capacities of further metabolic activation of N-hydroxy-PhlP are comparable with the rodents, humans may be at relatively higher risk for developing cancers upon exposure to this carcinogen. C1 NATL CTR TOXICOL RES,OFF RES HFT100,JEFFERSON,AR 72079. JOHN L MCCLELLAN MEM VET ADM MED CTR,LITTLE ROCK,AR 72205. NR 48 TC 57 Z9 58 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD APR PY 1995 VL 23 IS 4 BP 518 EP 524 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QT058 UT WOS:A1995QT05800014 PM 7600922 ER PT J AU FENG, P AF FENG, P TI ESCHERICHIA-COLI SEROTYPE O157-H7 - NOVEL VEHICLES OF INFECTION AND EMERGENCE OF PHENOTYPIC VARIANTS SO EMERGING INFECTIOUS DISEASES LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; SEROLOGICAL CROSS-REACTIONS; HEMORRHAGIC COLITIS; O-157 INFECTIONS; APPLE CIDER; STRAINS; EPIDEMIOLOGY; DIARRHEA; OUTBREAK; FOOD AB Escherichia coli serotype O157:H7 was only recognized as a human pathogen a little more than a decade ago, yet it has become a major foodborne pathogen. In the United States, the severity of serotype O157:H7 infections in the young and the elderly has had a tremendous impact on human health, the food industry, and federal regulations regarding food safety. The implication of acidic foods as vehicles of infection has dispelled the concept that low-pH foods are safe. Further, the association of nonbovine products with outbreaks suggests that other vehicles of transmission may exist for this pathogen. In laboratory diagnosis, most microbiologic assays rely on a single phenotype to selectively isolate this pathogen. However the increasing evidence that phenotypic variations exist among isolates in this serogroup may eventually necessitate modifications in assay procedures to detect them. RP FENG, P (reprint author), US FDA,200 C ST SW,HFS-516,WASHINGTON,DC 20204, USA. NR 44 TC 104 Z9 110 U1 0 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD APR-JUN PY 1995 VL 1 IS 2 BP 47 EP 52 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TD318 UT WOS:A1995TD31800002 PM 8903158 ER PT J AU CETRON, MS JERNIGAN, DB BREIMAN, RF BIRKHEAD, G BUTLER, JC CARTTER, ML CHESNEY, JP CRAIG, W GAYNES, RP GILCHRIST, MJR HOFFMAN, RE JORGENSEN, J KLEIN, D OBRIEN, T SCHWARTZ, B SHELDON, A SPITALNY, KC TENOVER, FC TIMPERI, RJ AF CETRON, MS JERNIGAN, DB BREIMAN, RF BIRKHEAD, G BUTLER, JC CARTTER, ML CHESNEY, JP CRAIG, W GAYNES, RP GILCHRIST, MJR HOFFMAN, RE JORGENSEN, J KLEIN, D OBRIEN, T SCHWARTZ, B SHELDON, A SPITALNY, KC TENOVER, FC TIMPERI, RJ TI ACTION PLAN FOR DRUG-RESISTANT STREPTOCOCCUS-PNEUMONIAE SO EMERGING INFECTIOUS DISEASES LA English DT Note C1 NEW YORK STATE DEPT HLTH,ALBANY,NY 12237. COUNCIL STATE & TERR EPIDEMIOLOGISTS,AUSTIN,TX. CONNECTICUT DEPT PUBL HLTH & ADDICT SERV,HARTFORD,CT 06106. AMER ACAD PEDIAT,ELK GROVE VILLAGE,IL 60007. COLORADO DEPT PUBL HLTH & ENVIRONM,DENVER,CO 80222. NATL COMM CLIN LAB STAND,VILLANOVA,PA 19085. NIAID,BETHESDA,MD 20892. WHO,COLLABORATING CTR ANTIBIOT RESISTANCE,BOSTON,MA. US FDA,ROCKVILLE,MD 20857. NEW JERSEY STATE DEPT HLTH,TRENTON,NJ 08625. ASSOC STATE & TERR PUBL HLTH LAB DIRECTORS,WASHINGTON,DC. RP CETRON, MS (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,1600 CLIFTON RD,MAILSTOP C-12,ATLANTA,GA 30333, USA. NR 9 TC 12 Z9 12 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD APR-JUN PY 1995 VL 1 IS 2 BP 64 EP 65 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TD318 UT WOS:A1995TD31800008 PM 8903164 ER PT J AU MALOZOWSKI, S PARMER, TG TROJAN, S MERRIAM, GR GIBORI, G ROBERTS, CT LEROITH, D WERNER, H ZILBERSTEIN, M AF MALOZOWSKI, S PARMER, TG TROJAN, S MERRIAM, GR GIBORI, G ROBERTS, CT LEROITH, D WERNER, H ZILBERSTEIN, M TI GROWTH-HORMONE (GH) MODULATES INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) AND TYPE-I IGF RECEPTOR MESSENGER-RNA LEVELS IN THE OVARY OF PREPUBERTAL GH-DEFICIENT RATS SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; MONOSODIUM GLUTAMATE; GENE-EXPRESSION; SOMATOMEDIN-C; GONADOTROPIN TREATMENT; OVULATION INDUCTION; GRANULOSA-CELLS; FOLLICLE; DIFFERENTIATION; SECRETION AB In order to explore the potential role of growth hormone (GH) in modulating insulin-like growth factor I (IGF-I) gene expression in the prepubertal rat ovary, female rats were rendered GH deficient by neonatal administration of monosodium glutamate (MSG). One group of rats received vehicle and served as the control. At 21 days of age, MSG-treated rats received either GH or vehicle for 2 weeks. On days 21, 24, 28 and 31 animals were weighed and subsets were sacrificed for liver RNA extraction. The remaining animals were sacrificed at day 35 when livers and ovaries were collected, and serum was obtained for GH determinations. The IGF-I mRNA levels were estimated by Northern blots and corroborated further by slot-blot analysis. The MSG-treated rats had lower body weights (p < 0.01) and GH levels (p < 0.05) than controls. Growth hormone replacement significantly accelerated the weight gain of MSG-treated rats. At day 24 and thereafter, three RNA IGF-I species (7.5, 1.8 and 0.8-1.2 kB) were seen in the liver. in the ovary, at age 35 days, two major IGF-I mRNA species (7.5 and 0.8-1.2 kb) were seen. The MSG treatment consistently reduced the levels of both IGF-I mRNA species in the ovary. Growth hormone administration partially restored their expression, both in the liver and in the ovary. In addition, ovarian type I IGF receptor mRNA levels were increased in the MSG-treated rats when compared to controls. This trend was reversed by GH replacement. In summary, we have found that in prepubertal female rats rendered GH deficient with MSG, ovarian IGF-I gene expression is reduced while type I IGF receptor mRNA levels are increased. These findings are reversed with GH replacement. These results suggest a physiological role for GH in modulating IGF-I and type I IGF receptor genes in the ovary. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. US FDA,DIV METAB & ENDOCRINE DRUG PROD,ROCKVILLE,MD 20857. UNIV ILLINOIS,DEPT PHYSIOL & BIOPHYS,CHICAGO,IL 60612. AMER LAKE VET AFFAIRS MED CTR,SEATTLE,WA 98195. UNIV WASHINGTON,DIV ENDOCRINOL,SEATTLE,WA 98195. NIDDK,DIABET BRANCH,BETHESDA,MD 20892. FU NICHD NIH HHS [HD 11119] NR 35 TC 5 Z9 5 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD APR PY 1995 VL 132 IS 4 BP 497 EP 501 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QQ673 UT WOS:A1995QQ67300019 PM 7711889 ER PT J AU DIGNAN, DM AF DIGNAN, DM TI GOING ONLINE WITH FDA SO FOOD TECHNOLOGY LA English DT Article; Proceedings Paper CT Symposium on Information Management for the 90s, at the Annual Meeting of the Institute-of-Food-Technologists CY JUN 25-29, 1994 CL ATLANTA, GA SP INST FOOD TECHNOLOGISTS, FRUIT & VEGETABLE PROD DIV, INST FOOD TECHNOLOGISTS, FOOD ENGN DIV RP DIGNAN, DM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF FIELD PROGRAMS,DIV HACCP PROGRAMS,WASHINGTON,DC 20204, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD APR PY 1995 VL 49 IS 4 BP 87 EP & PG 0 WC Food Science & Technology SC Food Science & Technology GA QV219 UT WOS:A1995QV21900015 ER PT J AU SENNERT, S VOLMER, D LEVSEN, K WUNSCH, G AF SENNERT, S VOLMER, D LEVSEN, K WUNSCH, G TI MULTIRESIDUE ANALYSIS OF POLAR PESTICIDES IN SURFACE AND DRINKING-WATER BY ONLINE ENRICHMENT AND THERMOSPRAY LC-MS SO FRESENIUS JOURNAL OF ANALYTICAL CHEMISTRY LA English DT Article ID CHROMATOGRAPHIC PRECONCENTRATION TECHNIQUES; AQUEOUS ENVIRONMENTAL-SAMPLES; LIQUID-CHROMATOGRAPHY; ORGANIC-COMPOUNDS; TRACE AMOUNTS; SPECTROMETRY; EXTRACTION AB In the search for a fast and robust sample handling and preparation step to analyse various pesticides at trace levels in aqueous samples, an on-line trace enrichment has been combined with our thermospray LC-MS method [1] allowing both selective identification and a quantification down to the lower ng/L level. 51 polar pesticides were investigated by applying solid phase extraction to 50-100 ml aqueous samples using small cartridges filled with 40 mg adsorbent. Prior to their liquid chromatographic separation, the enriched analytes were eluted from the solid phase with the initial methanol/water gradient composition of the HPLC onto the analytical column using column switching techniques. A base-deactivated C-18 material and the two styrene-divinylbenzene copolymers PLRP-S and PRP-1 were tested for enrichment in combination with a C-8-bonded silica analytical column. The method developed was evaluated with respect to recoveries, precision, limits of detection and linearity. Furthermore, it was applied to various environmental samples. Apart from a few compounds of higher polarity, most of the pesticides show recoveries > 60% (often > 80%) with relative standard deviations between 1-15%. Overall method detection limits are in the range of 1-100 ng/L allowing, with one exception, a ready verification of the pesticide limit of 100 ng/L set in the EU drinking water guideline [2]. C1 FRAUNHOFER INST TOXICOL & AEROSOL RES,D-30625 HANNOVER,GERMANY. UNIV HANNOVER,INST INORGAN & ANALYT CHEM,D-30167 HANNOVER,GERMANY. US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RI Volmer, Dietrich/G-7900-2012 OI Volmer, Dietrich/0000-0003-2820-1480 NR 20 TC 43 Z9 43 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0937-0633 J9 FRESEN J ANAL CHEM JI Fresenius J. Anal. Chem. PD APR PY 1995 VL 351 IS 7 BP 642 EP 649 DI 10.1007/BF00323341 PG 8 WC Chemistry, Analytical SC Chemistry GA RH363 UT WOS:A1995RH36300011 ER PT J AU GREENMAN, DL CRONIN, GM DAHLGREN, R ALLEN, R ALLABEN, W AF GREENMAN, DL CRONIN, GM DAHLGREN, R ALLEN, R ALLABEN, W TI CHRONIC FEEDING STUDY OF PYRILAMINE IN FISCHER-344 RATS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Review ID MONONUCLEAR CELL LEUKEMIA; METHAPYRILENE HYDROCHLORIDE; TUMOR-INCIDENCE; BODY-WEIGHT; ANTIHISTAMINES; MALEATE; ASSAY; TESTS; MICE AB The antihistamine, pyrilamine maleate, was fed for up to 2 years to groups of 57 Fischer 344 (F344) rats of each sex at dietary levels of 0, 300, 1500, or 3000 ppm (free base), Eight or nine of these rats per sex and dose group were killed at 65 weeks to analyze hematology and clinical chemistry in all groups and histopathology of control and high-dose animals, Histopathology also was performed on all dead or moribund rats and on all that survived for 2 years, Average daily exposures were 11 to 150 mg/kg pyrilamine compared to human dosages up to 3 mg/kg, Pyrilamine treatment did not reduce survival. Final body weights were reduced relative to controls (mid-dose males, 93%, females, 82%: high-dose males, 82%, females, 70%). The incidences of inflammation of the nasolacrimal duct (chronic in females; suppurative in males), liver cytoplasmic vacuolization (males), and the combination of animals with either liver basophilic or clear cell foci (males) tended to significantly increase with dose. Adrenal pheochromocytomas, mammary gland fibroadenomas, and neoplasms of the clitoral gland, thyroid c-cell, and pituitary gland all tended to decrease with increasing dose in females, In males only preputial gland neoplasms exhibited a similar negative trend, While two ovarian granulosatheca cell benign tumors occurred in high-dose females, these were thought to be a random occurrence, There was no evidence for the carcinogenicity of pyrilamine in F344 rats in the current study. C1 NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,PATHOL ASSOCIATES INC,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,COMP BASED SYST INC,JEFFERSON,AR 72079. RP GREENMAN, DL (reprint author), NATL CTR TOXICOL RES,OFF ASSOCIATE DIRECTOR SCI COORDINAT,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 29 TC 12 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD APR PY 1995 VL 25 IS 1 BP 1 EP 8 DI 10.1006/faat.1995.1034 PG 8 WC Toxicology SC Toxicology GA QQ799 UT WOS:A1995QQ79900001 PM 7601318 ER PT J AU GREENMAN, DL SHELDON, W SCHIEFERSTEIN, G ALLEN, R ALLABEN, WT AF GREENMAN, DL SHELDON, W SCHIEFERSTEIN, G ALLEN, R ALLABEN, WT TI CHRONIC STUDY OF TRIPROLIDINE FOR ONCOGENICITY IN MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID METHAPYRILENE HYDROCHLORIDE; PSEUDOEPHEDRINE; RATS AB Triprolidine hydrochloride was fed to groups of 60 B6C3F1 mice per sex at dietary levels of 0, 500, 2000, or 4000 ppm (as the free base) for up to 2 years. Up to 12 mice of each sex and dose group were terminated after 65 weeks for hematology and clinical chemistry. The control and high-dose groups were examined histologically. A complete histopathological examination was performed on the remaining 48 mice from each dose group when removed from study due to moribund condition, early death, or terminal euthanization at 105 weeks. Triprolidine did not significantly alter the survival of either sex. High-dose male and mid- and high-dose female body weights were significantly less than controls at the end of the study. Significant trends toward lower frequency with increasing dose were noted in females for fatty change in the liver and lymphomas (combination of lymphocytic, mixed, and histiocytic lymphomas). Similar negative trends in males were for lymphocytic cellular infiltration in multiple organs and lung alveolar/bronchiolar adenomas or the combination of alveolar/bronchiolar adenomas or carcinomas. Significant trends toward increased frequency with increasing dose were found in female mice for lymphocytic infiltration in multiple organs and cytoplasmic alterations of the acinar cells of the parotid gland. Similar positive trends were found in males for cytoplasmic alterations of the parotid gland and various hepatocellular changes (e.g., hypertrophy and altered foci). While there was a positive dose-response trend for hepatocellular adenomas in males the combination of these and hepatocellular carcinomas eliminated the significant trend, and it was concluded that there was no evidence of a carcinogenic response to triprolidine in B6C3F1 mice. No effects considered to be adverse were observed in either sex at 500 ppm. Body weight depression was noted in females and liver toxicity was indicated in males at 2000 and 4000 ppm. C1 NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,PATHOL ASSOCIATES INC,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,COMP BASED SYST INC,JEFFERSON,AR 72079. RP GREENMAN, DL (reprint author), NATL CTR TOXICOL RES,OFF ASSOCIATE DIRECTOR SCI COORDINAT,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 19 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD APR PY 1995 VL 25 IS 1 BP 138 EP 145 DI 10.1006/faat.1995.1047 PG 8 WC Toxicology SC Toxicology GA QQ799 UT WOS:A1995QQ79900014 PM 7601321 ER PT J AU MONTAGUE, DC CARTER, CA RAYFORD, PL CHOWDHURY, P AF MONTAGUE, DC CARTER, CA RAYFORD, PL CHOWDHURY, P TI NICOTINE AND ITS METABOLITES DISRUPT F-ACTIN AND ALTER RAS LOCALIZATION IN CULTURED RAT PANCREATIC-CELLS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,DEPT SURG,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PHYSIOL,LITTLE ROCK,AR 72205. NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A510 EP A510 DI 10.1016/0016-5085(95)26353-5 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302028 ER PT J AU LIN, JX MIGONE, TS TSANG, M FRIEDMANN, M WEATHERBEE, JA ZHOU, L YAMAUCHI, A BLOOM, ET MIETZ, J JOHN, S LEONARD, WJ AF LIN, JX MIGONE, TS TSANG, M FRIEDMANN, M WEATHERBEE, JA ZHOU, L YAMAUCHI, A BLOOM, ET MIETZ, J JOHN, S LEONARD, WJ TI THE ROLE OF SHARED RECEPTOR MOTIFS AND COMMON STAT PROTEINS IN THE GENERATION OF CYTOKINE PLEIOTROPY AND REDUNDANCY BY IL-2, IL-4, IL-7, IL-13, AND IL-15 SO IMMUNITY LA English DT Article ID BETA-CHAIN GENE; INTERLEUKIN-2 RECEPTOR; GAMMA-CHAIN; FUNCTIONAL COMPONENT; SIGNAL-TRANSDUCTION; ACTIVATION; PROLIFERATION; LYMPHOCYTES; REQUIREMENT; EXPRESSION AB To understand the molecular bases for cytokine redundancy and pleiotropy, we have compared the Stat proteins activated In peripheral blood lymphocytes (PBLs) by cytokines with shared and distinct actions. Interleukin-2 (IL-2) rapidly activated Stat5 in fresh PBL, and Stat3 and Stat5 in preactivated PBL. IL-7 and IL-15 induced the same complexes as IL-2, a feature explained by the existence of similar tyrosine-phosphorylated motifs in the cytoplasmic domains of IL-PRP and IL-7R that can serve as docking sites for Stat proteins. IL-13 induced the same complexes as IL-4, a finding explained by our studies implicating IL-4R as a shared component of the receptors. These studies demonstrate that a single cytokine can activate different combinations of Stat proteins under different physiological conditions, and also indicate two mechanisms by which distinct cytokines can activate the same Stat protein. C1 R & D SYST,MINNEAPOLIS,MN 55413. US FDA,CTR BIOL EVALUAT & RES,DIV CELL & GENE THERAPY,BETHESDA,MD 20892. RP LIN, JX (reprint author), NHLBI,MOLEC IMMUNOL LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 53 TC 591 Z9 593 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 1995 VL 2 IS 4 BP 331 EP 339 DI 10.1016/1074-7613(95)90141-8 PG 9 WC Immunology SC Immunology GA QU616 UT WOS:A1995QU61600003 PM 7719938 ER PT J AU KLINMAN, DM STEINBERG, AD AF KLINMAN, DM STEINBERG, AD TI INQUIRY INTO MURINE AND HUMAN LUPUS SO IMMUNOLOGICAL REVIEWS LA English DT Review ID B-CELL REPERTOIRE; REACTIVE LYMPHOCYTES-B; ANTI-DNA ANTIBODIES; T-HELPER CELLS; ENDOGENOUS RETROVIRAL EXPRESSION; RECOMBINANT INBRED LINES; MRL-LPR/LPR MICE; LPR-LPR MICE; SYSTEMIC LUPUS; AUTOIMMUNE-DISEASE C1 MITRE CORP,MCLEAN,VA 22102. US FDA,BETHESDA,MD 20892. NR 165 TC 102 Z9 112 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 1995 VL 144 BP 157 EP 193 PG 37 WC Immunology SC Immunology GA QZ594 UT WOS:A1995QZ59400007 PM 7590812 ER PT J AU PU, Y BERNSTEIN, JA BERNSTAM, LI BRONAUGH, RL AF PU, Y BERNSTEIN, JA BERNSTAM, LI BRONAUGH, RL TI GROWING A STRATIFIED, CORNIFIED PRIMARY CULTURE OF RAT KERATINOCYTES WITH EPIDERMIS-LIKE WATER PERMEATION BARRIER FUNCTION SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE WATER PERMEATION BARRIER; KERATINOCYTE CULTURE; PSEUDO-EPIDERMIS ID AIR-LIQUID INTERFACE; INVITRO PERCUTANEOUS-ABSORPTION; DIFFERENTIATION AB The culture of cutaneous keratinocytes grown on a Puropore nylon microporous membrane at the air-liquid interface has been shown to be similar to the epidermis in a number of molecular and morphologic characteristics but to exhibit a significantly greater degree of tritiated water permeation. Various culture conditions have been altered in an effort to improve the water barrier properties. A Kp value in the range of 5.5 +/- 1.6 X 10(-3) has been obtained for 79% of the cultures a) by plating 0.9 X 10(6) viable basal cells on a piece (13-mm diameter) of membrane for 7 days of submerged growth, b) by placing two membranes on two stacked glass fiber filters (47-mm extra-thick) in a culture dish (60 mm) for 14 days of growth at the air-liquid interface, c) by replacing the growth medium, i.e., 1 mi of complete minimum essential medium (CMEM) every 24 h after lifting, d) by using 10% fetal bovine serum (FBS) in the CMEM during the submerged culture period and 15% FBS in the CMEM during the lifted culture period, and e) by adding a dialysis membrane on top and a Puropore nylon membrane below the culture when the cultures were inserted in the permeation cell for testing. The percentage of cultures with this value for kp can be increased to 90% if only cultures with yellow, smooth, and shiny surfaces are tested. This system should be useful as a replacement for skin in testing the cutaneous permeation of some chemicals. C1 UNIV MICHIGAN, SCH PUBL HLTH, DEPT ENVIRONM & IND HLTH, TOXICOL PROGRAM, ANN ARBOR, MI 48109 USA. US FDA, LAUREL, MD 20708 USA. FU PHS HHS [223-88-2147] NR 19 TC 7 Z9 7 U1 0 U2 1 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD APR PY 1995 VL 31 IS 4 BP 283 EP 287 PG 5 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA QP273 UT WOS:A1995QP27300009 PM 7795847 ER PT J AU SHAHIN, R LEEF, M ELDRIDGE, J HUDSON, M GILLEY, R AF SHAHIN, R LEEF, M ELDRIDGE, J HUDSON, M GILLEY, R TI ADJUVANTICITY AND PROTECTIVE IMMUNITY ELICITED BY BORDETELLA-PERTUSSIS ANTIGENS ENCAPSULATED IN POLY(DL-LACTIDE-CO-GLYCOLIDE) MICROSPHERES SO INFECTION AND IMMUNITY LA English DT Article ID ISLET-ACTIVATING PROTEIN; ENTEROTOXIGENIC ESCHERICHIA-COLI; VACCINE DELIVERY SYSTEM; BIODEGRADABLE MICROSPHERES; FILAMENTOUS HEMAGGLUTININ; RESPIRATORY-INFECTION; COLONIZATION FACTOR; ORAL IMMUNIZATION; MEMBRANE-PROTEIN; ANTIBODY AB Purified Bordetella pertussis antigens, encapsulated in biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) microspheres, were evaluated for their immunogenicity and ability to elicit a protective immune response against B. pertussis respiratory infection, Microencapsulated pertussis toroid, filamentous hemagglutinin, and pertactin all retained their immunogenicity when administered parenterally, Intranasal immunization with a low dose (1 mu g) of encapsulated filamentous hemagglutinin, pertussis toroid, or pertactin elicited strong specific immunoglobulin G and immunoglobulin A antibody responses in respiratory secretions that were greater in magnitude than the responses elicited by the same doses of unencapsulated antigen. Intranasal immunization with as little as 1 mu g of encapsulated pertussis antigen prior to infection reduced the bacterial recovery by 3 log(10) CFU. However, intranasal immunization with the same low doses of unencapsulated antigens did not reduce infection. Intranasal administration of a combination of 1 mu g of each of the microencapsulated pertussis antigens was more effective in reducing bacterial infection than administration of any single microencapsulated antigen, Intranasal administration of microencapsulated B. pertussis antigens elicits high levels of specific antibody coinciding with protection against infection when these microspheres are administered to the respiratory tract, These data provide evidence of the respiratory adjuvanticity of three different DL-PLG microsphere preparations, each of which contains a unique B. pertussis antigen, C1 UNIV ALABAMA,BIRMINGHAM,AL. SO RES INST,BIRMINGHAM,AL 35255. RP SHAHIN, R (reprint author), US FDA,CBER,PERTUSSIS LAB,HFM-434,BLDG 29,ROOM 414,29 LINCOLN DR MSC 4555,BETHESDA,MD 20892, USA. NR 32 TC 79 Z9 83 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1995 VL 63 IS 4 BP 1195 EP 1200 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QP134 UT WOS:A1995QP13400009 PM 7890372 ER PT J AU ROUSE, DA MORRIS, SL AF ROUSE, DA MORRIS, SL TI MOLECULAR MECHANISMS OF ISONIAZID RESISTANCE IN MYCOBACTERIUM-TUBERCULOSIS AND MYCOBACTERIUM-BOVIS SO INFECTION AND IMMUNITY LA English DT Article ID NUCLEOTIDE-SEQUENCE ANALYSIS; CATALASE-PEROXIDASE; ESCHERICHIA-COLI; GENE; INTRACELLULARE; MUTATIONS; STRAINS AB Genetic and biochemical studies have suggested a link between reduced catalase activity and resistance to isoniazid in Mycobacterium tuberculosis. In this study, we examined the molecular mechanisms of resistance to isoniazid with six in vitro mutants of the M. tuberculosis complex (Mycobacterium bovis and M. tuberculosis), Five of six mutants resistant to isoniazid were negative by catalase assays. Immunoblot analyses using a polyclonal antibody against the katG gene product (catalase-peroxidase) demonstrated that the enzyme is not produced in four of these isoniazid-resistant strains. A complete deletion of the katG gene was detected in only one of these isoniazid-resistant M. tuberculosis complex strains by Southern blot analyses, In two other resistant strains, partial deletions of the katC gene were identified, A point mutation which resulted in the insertion of a termination codon in the katG coding sequence caused a catalase-negative phenotype in a fourth strain, Of the two resistant strains which produce the enzyme, one was shown to be negative by a catalase assay. Single-stranded conformational polymorphism and DNA sequence analyses identified a mutation in the katC gene of this strain which may contribute to reduced enzymatic activity and subsequent isoniazid resistance. These data demonstrate that genetic alterations to the katG gene other than complete deletions are prevalent and may contribute significantly to the number of cases of isoniazid-resistant tuberculosis. RP ROUSE, DA (reprint author), US FDA,CTR BIOL EVALUAT & RES,MYCOBACTERIA LAB,800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 46 Z9 50 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1995 VL 63 IS 4 BP 1427 EP 1433 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QP134 UT WOS:A1995QP13400045 PM 7890405 ER PT J AU BASH, MC LESIAK, KB BANKS, SD FRASCH, CE AF BASH, MC LESIAK, KB BANKS, SD FRASCH, CE TI ANALYSIS OF NEISSERIA-MENINGITIDIS CLASS-3 OUTER-MEMBRANE PROTEIN GENE VARIABLE REGIONS AND TYPE IDENTIFICATION USING GENETIC TECHNIQUES SO INFECTION AND IMMUNITY LA English DT Article ID POLYMERASE CHAIN-REACTION; EXPRESSION; CLONING; SEROTYPES; ANTIGENS; SEQUENCE; STRAINS; PORINS AB The class 3 porin proteins of Neisseria meningitidis stimulate bactericidal antibodies and express serotype-specific antigenic epitopes. Sequence analysis of porB genes for the class 3 proteins revealed regions of variability that map to surface-exposed loops, To evaluate the relationship between serotype and variable-region (VR) genotype, sequences from the 11 class 3-expressing serotype strains and 3 additional serotype 3 strains were analyzed by molecular techniques, Multiple-sequence alignment revealed a limited number of unique sequences at each of four VRs (VR1 to VR4), ranging from four unique sequences at VR1 to seven sequence patterns at VR2 and VR4, Serotype-specific VR sequences were found in each of the four VRs, suggesting that each VR has immunologic importance, Five serotypes had at least one VR sequence that was unique. Three serotypes which had sequences in common with other serotypes at each VR were distinguished by examining multiple VRs, Serotype 3 was identical to serotype 19 at each VR, and serotype 8 was identical to serotype 18 at each VR, Serotypes 4 and 21 were identical at VR1 and significantly different at VR3 and VR4, A subpopulation of serotype 4 strains with a unique VR2 sequence was identified, The serotypes which were grouped with closely related or identical sequences at one VR were grouped with different serotypes at other VRs consistent with the pattern of genetic mosaicism described for the porA (class 1 protein) gene. Hybridization assays demonstrated the ability to identify VR genotypes and distinguish serotypes using biotin-labelled oligonucleotide probes, This information may be useful in strain selection for vaccine development, in epidemiologic studies to determine the prevalence of the individual VR genotype (especially among nonserotypeable strains) and, combined with PCR, in the identification of culture-negative suspected meningococcal cases. C1 CTR BIOL EVALUAT & RES,DIV ALLERGEN PROD & PARASITOL,ROCKVILLE,MD 20852. RP BASH, MC (reprint author), CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,HFM-428,1401 ROCKVILLE PK,ROCKVILLE,MD 20852, USA. NR 28 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1995 VL 63 IS 4 BP 1484 EP 1490 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QP134 UT WOS:A1995QP13400054 PM 7890414 ER PT J AU KOCH, WH HENRIKSON, E EISENSTADT, E CEBULA, TA AF KOCH, WH HENRIKSON, E EISENSTADT, E CEBULA, TA TI SALMONELLA-TYPHIMURIUM LT7 AND LT2 STRAINS CARRYING THE IMP OPERON ON COLIA SO JOURNAL OF BACTERIOLOGY LA English DT Note ID UV PROTECTION; PLASMIDS; MUTATION; MUTAGENESIS AB The imp operon is carried on a transmissible plasmid, Colla, in original isolates of Salmonella typhimurium LT7. LT2 strain recipients of F' factors from LT7 strains harboring Colla can acquire Colla and imp under nonselective conditions. Thus, S. typhimurium LT2 strains that have received plasmids by conjugal transfer from LT7 strains might be inadvertently harboring Coll factors. C1 OFF NAVAL RES,DIV BIOL SCI & TECHNOL,ARLINGTON,VA 22217. US FDA,MOLEC BIOL BRANCH,WASHINGTON,DC 20204. NR 25 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 1995 VL 177 IS 7 BP 1903 EP 1905 PG 3 WC Microbiology SC Microbiology GA QP810 UT WOS:A1995QP81000038 PM 7896721 ER PT J AU CEBULA, TA PAYNE, WL FENG, P AF CEBULA, TA PAYNE, WL FENG, P TI SIMULTANEOUS IDENTIFICATION OF STRAINS OF ESCHERICHIA-COLI SEROTYPE O157-H7 AND THEIR SHIGA-LIKE TOXIN TYPE BY MISMATCH AMPLIFICATION MUTATION ASSAY-MULTIPLEX PCR (VOL 33, PG 249, 1995) SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Correction, Addition RP CEBULA, TA (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 1 TC 10 Z9 10 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 1995 VL 33 IS 4 BP 1048 EP 1048 PG 1 WC Microbiology SC Microbiology GA QM888 UT WOS:A1995QM88800065 ER PT J AU PISCITELLI, SC THIBAULT, A FIGG, WD TOMPKINS, A HEADLEE, D LIEBERMANN, R SAMID, D MYERS, CE AF PISCITELLI, SC THIBAULT, A FIGG, WD TOMPKINS, A HEADLEE, D LIEBERMANN, R SAMID, D MYERS, CE TI DISPOSITION OF PHENYLBUTYRATE AND ITS METABOLITES, PHENYLACETATE AND PHENYLACETYLGLUTAMINE SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID WASTE NITROGEN-EXCRETION; DIFFERENTIATION; UREA; ACID AB Phenylacetate, an inducer of tumor cytostasis and differentiation, shows promise as a relatively nontoxic antineoplastic agent, Phenylacetate, however, has an unpleasant odor that might limit patient acceptability. Phenylbutyrate, an odorless compound that also has activity in tumor models, is known to undergo rapid conversion to phenylacetate by beta-oxidation in vivo. This phase I study examined the pharmacokinetics of phenylbutyrate and characterized the disposition of the two metabolites, phenylacetate and phenylacetylglutamine, Fourteen patients with cancer (aged 51.8 +/- 13.8 years) received a 30-minute infusion of phenylbutyrate at 3 dose levels (600, 1200, and 2000 mg/m(2)), Serial blood samples and 24-hour urine collections were obtained. Samples were assayed by high-performance liquid chromatography. A model to simultaneously describe the pharmacokinetics of all three compounds was developed using ADAPT II. Data were modeled as molar equivalents. The model Ft the data well os shown by mean (+/-SD) coefficients of determination (r(2)) for phenylbutyrate, phenylacetate, and phenylacetylglutamine, which were 0.96 +/- 0.07, 0.88 +/- 0.10, and 0.92 +/- 0.06, respectively. The intrapatient coefficient of variation percentage (CV%) around the parameter estimates were small (range 7.2-33.5%). Phenylbutyrate achieved peak concentrations in the range of in vitro tumor activity (500-2000 mu mol/L) and exhibited saturable elimination (K-m = 34.1 +/- 18.1 mu g/mL and V-max = 18.1 +/- 18 mg/h/kg). Metabolism was rapid; the rimes to maximum concentration for phenylacetate and phenylacetylglutamine were 1 and 2 hours, respectively. The conversion of phenylbutyrate to phenylacetate was extensive (80 +/- 12.6%), but serum concentrations of phenylacetate were low owing to rapid, subsequent conversion to phenylacetylglutamine. The ratio of phenylbutyrate AUC to phenylacetate AUC was 2.66. Thus, phenylbutyrate may not be a prodrug for phenylacetate and should be pursued as an independent antitumor agent. C1 NCI,CLIN PHARMACOL BRANCH,CLIN PHARMACOKINET SECT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT PHARM,CLIN PHARMACOKINET RES LAB,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. RI Figg Sr, William/M-2411-2016 NR 17 TC 58 Z9 61 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD APR PY 1995 VL 35 IS 4 BP 368 EP 373 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QT480 UT WOS:A1995QT48000006 PM 7650225 ER PT J AU BURD, PR THOMPSON, WC MAX, EE MILLS, FC AF BURD, PR THOMPSON, WC MAX, EE MILLS, FC TI ACTIVATED MAST-CELLS PRODUCE INTERLEUKIN-13 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NECROSIS-FACTOR-ALPHA; FC-EPSILON-RI; TNF-ALPHA; IGE; MOUSE; CHROMOSOME-11; MODULATION; CYTOKINE; IL-13; LINE AB When mast cells are activated through their immunoglobulin (Ig)E receptors, release of low molecular weight mediators like histamine is followed by secretion of multiple cytokines, including interleukin (IL)-3, IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor. Here we report that stimulated mast cells also synthesize IL-13 mRNA and protein; secretion of this cytokine may be of particular importance because of its ability to stimulate IgE expression. IL-13 transcripts detected by a semiquantitative reverse transcriptase-mediated polymerase chain reaction assay were induced within 30 min after stimulation of mast cells by dinitrophenyl plus monoclonal IgE anti-dinitrophenyl, and peaked at about 1 h. Within 3 h of IgE stimulation, secreted IL-13 bioactivity, estimated by proliferation of an IL-13-dependent cell line, reached levels equivalent to 1-2 ng/ml of IL-13. When added to human B lymphocytes, the mast cell-derived IL-13 activity (like bone fide IL-13) induced Ig C epsilon transcripts, DNA recombination characteristic of the isotype switch to C epsilon, and the secretion of IgE protein. These results suggest a model of local positive feedback interactions between mast cells and B cells, which could play a role in the pathogenesis of atopy. C1 US FDA,DIV HEMATOL PROD,ROCKVILLE,MD 20852. RP BURD, PR (reprint author), US FDA,CBER,DCGT,LCI,HFM-518,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 32 TC 257 Z9 257 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 1 PY 1995 VL 181 IS 4 BP 1373 EP 1380 DI 10.1084/jem.181.4.1373 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QQ192 UT WOS:A1995QQ19200012 PM 7535336 ER PT J AU KALLANDER, KD ROMER, JC SOFOS, JN KREUZER, KS SINGLETON, ER AF KALLANDER, KD ROMER, JC SOFOS, JN KREUZER, KS SINGLETON, ER TI DETECTION OF HEATED BACTERIAL-SPORES WITH FLUID THIOGLYCOLATE AND SOYBEAN CASEIN DIGEST BROTHS CONTAINING VARIABLE CONCENTRATIONS OF SOLIDS SO JOURNAL OF FOOD PROTECTION LA English DT Article DE BACTERIAL SPORES; INJURY; RECOVERY ID BACILLUS-STEAROTHERMOPHILUS; RECOVERY; MEDIA AB Spore suspensions of Bacillus stearothermophilus (ATCC 7953, 10149, 12980), Bacillus subtilis (ATCC 6633), Bacillus subtilis var. niger (ATCC 9372), Bacillus pumilus (ATCC 27142, and a wild strain) and Bacillus cereus (ATCC 11778) were heated (20 min at 121 degrees C for thermophiles, and 2.5-20 min at 100 degrees C, 105 degrees C, or 107 degrees C for mesophiles) in 1 mi sealed ampoules. Surviving spores were recovered by a 5-tube most probable number (MPN) procedure with soybean casein digest (SCD) or fluid thioglycollate (FTH) broths containing variable concentrations of solids, Numbers of heated thermophilic spores (ATCC 7953) recovered with SCD broths were approximately 1.5 log MPN/ml higher at the 100% broth solids concentration than numbers recovered with FTH broth. Increasing the solids of SCD broth to twice the recommended amount (200%) reduced recovery of heated thermophilic spores compared to regular (100%) strength broth. Recovery of heated thermophilic spores with SCD or FTH broths was higher (P < 0.05) when their content of solids was reduced to as low as 0.391% compared to regular concentrations (100%). Broths with concentrations of solids at 10% of the manufacturer's recommended levels resulted in maximum recovery of heated thermophilic spores. In contrast, reduction of solids in SCD broth to 10% did not (P > 0.05) influence recovery of heated mesophilic spores compared to SCD broth with regular concentration of solids. Broths with reduced as well as regular concentrations of solids were equally effective in recovering unheated spores. These results should be useful in future modifications of methodology for sterility testing. C1 COLORADO STATE UNIV,DEPT ANIM SCI,FT COLLINS,CO 80523. COLORADO STATE UNIV,DEPT FOOD SCI & HUMAN NUTR,FT COLLINS,CO 80523. RP KALLANDER, KD (reprint author), US FDA,DENVER FED CTR,DENVER DIST LAB,BLDG 20,POB 25087,DENVER,CO 80225, USA. NR 17 TC 2 Z9 2 U1 0 U2 1 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 1995 VL 58 IS 4 BP 421 EP 425 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA QV770 UT WOS:A1995QV77000013 ER PT J AU MORRIS, S BAI, GH SUFFYS, P PORTILLOGOMEZ, L FAIRCHOK, M ROUSE, D AF MORRIS, S BAI, GH SUFFYS, P PORTILLOGOMEZ, L FAIRCHOK, M ROUSE, D TI MOLECULAR MECHANISMS OF MULTIPLE-DRUG RESISTANCE IN CLINICAL ISOLATES OF MYCOBACTERIUM-TUBERCULOSIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; STREPTOMYCIN RESISTANCE; ESCHERICHIA-COLI; POINT MUTATIONS; S12 GENE; MUTANTS; SINGLE AB The molecular mechanisms of resistance to streptomycin, rifampin, and isoniazid in 53 Mycobacterium tuberculosis clinical isolates were examined, Twenty-five of 44 streptomycin-resistant strains had mutations in the rpsL gene and 5 of these had rus gene perturbations, The region of the rpoB gene that is associated with resistance to rifampin was altered in 28 of 29 rifampin-resistant strains, Mutations in known genetic markers of isoniazid resistance were detected in 25 of 42 isoniazid-resistant isolates: 20 strains had katG gene alterations and 5 had perturbations in the inhA operon. Of the 20 multiply resistant strains with reduced sensitivity to streptomycin, rifampin, and isoniazid, 11 had mutations in genetic markers associated with resistance to each of these three drugs, These studies suggest that the primary mechanism of multiple drug resistance in tuberculosis is the accumulation of mutations in individual drug target genes. C1 KOREAN NATL INST TB,SEOUL,SOUTH KOREA. UNIV GUADALAJARA,GUADALAJARA 44430,JALISCO,MEXICO. OSWALDO CRUZ FDN,RIO JANEIRO,BRAZIL. WALTER REED ARMY MED INST,WASHINGTON,DC. RP MORRIS, S (reprint author), US FDA,CTR BIOL EVALUAT & RES,HFM-431,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI suffys, philip/E-3009-2013 NR 30 TC 182 Z9 221 U1 0 U2 9 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1995 VL 171 IS 4 BP 954 EP 960 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QP912 UT WOS:A1995QP91200028 PM 7706824 ER PT J AU MALOZOWSKI, S STADEL, BV AF MALOZOWSKI, S STADEL, BV TI PREPUBERTAL GYNECOMASTIA DURING GROWTH-HORMONE THERAPY SO JOURNAL OF PEDIATRICS LA English DT Note ID HUMAN-BREAST-CANCER AB We report 22 cases of prepubertal gynecomastia diagnosed during growth hormone (GH) treatment. The age and dose range were 2 to 12 years and 1.8 to 0.3 mg/kg per week, respectively. In most of the patients, gynecomastia appeared between 0.5 and 7 months after GH was started. Three boys were using drugs other than GH. This condition appears to be self-limited and benign. RP MALOZOWSKI, S (reprint author), US FDA, CTR DRUG EVALUAT & RES, DIV METAB & ENDOCRINE DRUG PROD, HFD-510, ROOM 14B-03, ROCKVILLE, MD 20857 USA. NR 16 TC 27 Z9 27 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 1995 VL 126 IS 4 BP 659 EP 661 DI 10.1016/S0022-3476(95)70372-1 PG 3 WC Pediatrics SC Pediatrics GA QR212 UT WOS:A1995QR21200029 PM 7699552 ER PT J AU LUDEMAN, SM SHULMANROSKES, EM WONG, KKT HAN, SY ANDERSON, LW STRONG, JM COLVIN, OM AF LUDEMAN, SM SHULMANROSKES, EM WONG, KKT HAN, SY ANDERSON, LW STRONG, JM COLVIN, OM TI OXIME DERIVATIVES OF THE INTERMEDIARY ONCOSTATIC METABOLITES OF CYCLOPHOSPHAMIDE AND IFOSFAMIDE - SYNTHESIS AND DEUTERIUM LABELING FOR APPLICATIONS TO METABOLITE QUANTIFICATION SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID PHOSPHORAMIDE MUSTARD; ISOPHOSPHORAMIDE MUSTARD; ANTITUMOR-ACTIVITY; MASS-SPECTROMETRY; 4-HYDROXYCYCLOPHOSPHAMIDE; IMINOCYCLOPHOSPHAMIDE; ALDOPHOSPHAMIDE; TRANS-4-HYDROXYCYCLOPHOSPHAMIDE; CIS-4-HYDROXYCYCLOPHOSPHAMIDE; CHROMATOGRAPHY AB There is ongoing interest in the selective, quantitative analysis of the cyclophosphamide metabolites 4-hydroxycyclophosphamide (2a) and aldophosphamide (3a) because these tautomers are generally believed to play a key role in oncostatic selectivity and metabolite transport. O-(2,3,4,5,6-Pentafluorobenzyl)hydroxylamine (C(6)F5CH(2)ONH(2), 1 equiv) provided for the complete conversion (by P-31 NMR, 60% reaction within 15 min at 20 degrees C) of 2a/3a (17 mM in H2O/CH3OH) to E/Z-aldophosphamide O-(2,3,4,5,6-pentafluorobenzyl)oxime [C6F5CH2ON=CHCH2CH2OP(O)(NH2)N(CH2CH2Cl)(2); E:Z = 54:46 (+/-3% average deviation)]. Under these conditions, the oxime exhibited little (6%) decomposition over 3 weeks. Parallel studies showed th at 4-hydroxyifosfamide/aldoifosfamide reacted completely to give the analogous aldoifosfamide oxime [C6F5CH2ON=CHCH2CH2OP(O)(NHCH2CH2Cl)2; E:Z = 52:48 (+/-1% average deviation)] with 50% reaction within 15 min at 20 degrees C with no product decomposition over 3 weeks. In aqueous methanol and with 2 equiv C6F5CH2ONH2, clinically useful 4-hydroperoxycyclophosphamide (10 mM; tau(1/2) = 10 min, 37 degrees C) and its isomer 4-hydroperoxyifosfamide (10 mM; tau(1/2) = 25 min, 20 degrees C) underwent complete conversion to the corresponding aldehyde oximes. Each oxime was synthesized with deuterium in the chloroethyl moieties for use as internal standards in GC/MS applications. C1 JOHNS HOPKINS UNIV,DEPT CHEM,BALTIMORE,MD 21218. US FDA,CTR DRUG EVALUAT & RES,DIV CLIN PHARMACOL,ROCKVILLE,MD 20850. RP LUDEMAN, SM (reprint author), JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,DIV PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21287, USA. FU NCI NIH HHS [5-R01-CA16783, CA09243-14, 5-P01-CA15396] NR 35 TC 20 Z9 20 U1 0 U2 3 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD APR PY 1995 VL 84 IS 4 BP 393 EP 398 DI 10.1002/jps.2600840403 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA QR366 UT WOS:A1995QR36600002 PM 7629726 ER PT J AU Ludden, TM Gillespie, WR Bachman, WJ AF Ludden, TM Gillespie, WR Bachman, WJ TI Physiologically based pharmacokinetic modeling as a tool for drug development - Commentary SO JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS LA English DT Article ID FLOW MODELS RP Ludden, TM (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV BIOPHARMACEUT,5600 FISHERS LANE HFD-426,ROCKVILLE,MD 20857, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0090-466X J9 J PHARMACOKINET BIOP JI J. Pharmacokinet. Biopharm. PD APR PY 1995 VL 23 IS 2 BP 231 EP 235 DI 10.1007/BF02354274 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TM200 UT WOS:A1995TM20000007 PM 8719239 ER PT J AU GREENMAN, DL ALLEN, R DAHLGREN, R CRONIN, GM ALLABEN, WT AF GREENMAN, DL ALLEN, R DAHLGREN, R CRONIN, GM ALLABEN, WT TI CHRONIC TOXICITY/CARCINOGENICITY STUDY OF PYRILAMINE IN B6C3F1 MICE SO JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY LA English DT Article DE PYRILAMINE; CHRONIC TOXICITY; CARCINOGENICITY; MICE ID METHAPYRILENE HYDROCHLORIDE; RATS; ANTIHISTAMINES; TOXICITY; ASSAY; TESTS AB The chronic toxicity and carcinogenicity of pyrilamine maleate were evaluated in B6C3F1 mice by feeding for up to 2 years to groups of 60 male or female mice at dietary levels of 0, 150, 750, or 1,500 ppm (as the free base). Up to 12 mice per sex and dose group were killed after 65 weeks for clinical chemistry, hematology, and histopathologic evaluation of control and high-dose animals. Histopathology was performed on all animals that were dead or moribund or lived until the study was terminated at 2 years. Daily exposures to pyrilamine ranged from similar to 16 to 176 mg/kg, compared with maximum human exposure of 3 mg/kg. Regarding longevity, pyrilamine-treated male mice tended to survive longer than controls, whereas no differences among treated and control female mice were noted. Body weights did not differ among treated and control male groups, but final body weight average of treated female mice was 6-10% lower than that for controls. Although no dose-response trends were noted in male mice for histopathologic end points, liver/body and liver/ brain weight ratios were significantly greater in high-dose male mice than in controls. Chronic liver inflammation exhibited a positive dose-response trend in female mice, but there was no evidence for a carcinogenic response to pyrilamine by either sex. C1 NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,PATHOL ASSOCIATES INC,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,COMP BASED SYST INC,JEFFERSON,AR 72079. RP GREENMAN, DL (reprint author), NATL CTR TOXICOL RES,OFF ASSOCIATE DIRECTOR SCI COORDINAT,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 20 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0730-0913 J9 J AM COLL TOXICOL JI J. Am. Coll. Toxicol. PD APR PY 1995 VL 14 IS 2 BP 148 EP 157 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA QR173 UT WOS:A1995QR17300006 ER PT J AU BRANCO, PS CHIARELLI, MP LAY, JO BELAND, FA AF BRANCO, PS CHIARELLI, MP LAY, JO BELAND, FA TI LOW-ENERGY TANDEM MASS-SPECTROMETRY OF DEOXYNUCLEOSIDE ADDUCTS OF POLYCYCLIC AROMATIC HYDROCARBON DIHYDRODIOL-EPOXIDES SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID FAST-ATOM-BOMBARDMENT; BENZOPYRENE DIOL EPOXIDE; CARCINOGEN-DNA ADDUCTS; IDENTIFICATION; NUCLEOSIDES; INVITRO; BINDING; SPECTRA; RAT AB The use of fast-atom bombardment ionization-tandem mass spectrometry approaches, with collision energies on the order of 30-50 eV, was developed for the analysis of low picomole quantities of polycyclic aromatic hydrocarbon dihydrodiol-epoxide deoxynucleoside adducts. This strategy combines three experimental techniques: (1) product ion scans, (2) constant neutral loss scans, and (3) precursor ion scans. Product ion scans of the protonated molecule or the BH: ion that results from loss of the deoxyribose were dominated by fragments associated with cleavage of the sigma bond between the dihydrodiol-epoxide moiety and the nucleobase. Constant neutral loss scans were based upon the loss of deoxyribose (116 u) or the combined loss of the deoxynucleoside, water, and carbon monoxide (313 u); precursor ion scans utilized the latter fragment. The formation of trimethylsilyl derivatives increased the sensitivity of analysis, which allowed the simultaneous detection of DNA adducts in a mixture. C1 NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079. UNIV ARKANSAS,LITTLE ROCK,AR. UNIV NOVA LISBOA,FAC CIENCIAS & TECNOL,DEPT QUIM,SECCAO QUIM APLICADA,P-2825 MONTE DE CAPARICA,PORTUGAL. RI Lay, Jackson/G-1007-2011; Branco, Paula/I-6567-2012; REQUIMTE, ORG/M-4578-2013; REQUIMTE, LAQV/N-9835-2013 OI Lay, Jackson/0000-0003-3789-2527; Branco, Paula/0000-0002-7312-8596; NR 28 TC 10 Z9 10 U1 1 U2 3 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD APR PY 1995 VL 6 IS 4 BP 248 EP 256 DI 10.1016/1044-0305(94)00162-S PG 9 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA QV778 UT WOS:A1995QV77800004 PM 24214170 ER PT J AU VEITH, FJ ABBOTT, WM YAO, JST GOLDSTONE, J WHITE, RA ABEL, D DAKE, MD ERNST, CB FOGARTY, TJ JOHNSTON, KW MOORE, WS VANBREDA, A SOPKO, G DIDISHEIM, P RUTHERFORD, RB KATZEN, BT MILLER, DC AF VEITH, FJ ABBOTT, WM YAO, JST GOLDSTONE, J WHITE, RA ABEL, D DAKE, MD ERNST, CB FOGARTY, TJ JOHNSTON, KW MOORE, WS VANBREDA, A SOPKO, G DIDISHEIM, P RUTHERFORD, RB KATZEN, BT MILLER, DC TI GUIDELINES FOR DEVELOPMENT AND USE OF TRANSLUMINALLY PLACED ENDOVASCULAR PROSTHETIC GRAFTS IN THE ARTERIAL SYSTEM SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ABDOMINAL AORTIC-ANEURYSM; VASCULAR-SURGERY; ANGIOPLASTY; RECOMMENDATIONS; FEASIBILITY; STANDARDS; DISEASE C1 SOC VASC SURG,MANCHESTER,MA. INT SOC CARDIOVASC SURG,MANCHESTER,MA. US FDA,ROCKVILLE,MD 20857. NHLBI,BETHESDA,MD 20892. RP VEITH, FJ (reprint author), MONTEFIORE MED CTR,DEPT SURG,111 E 210TH ST,BRONX,NY 10467, USA. NR 37 TC 80 Z9 83 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD APR PY 1995 VL 21 IS 4 BP 670 EP 685 DI 10.1016/S0741-5214(95)70198-2 PG 16 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA QT922 UT WOS:A1995QT92200013 PM 7707571 ER PT J AU SHAIKH, B JACKSON, J THAKER, NH AF SHAIKH, B JACKSON, J THAKER, NH TI NEOMYCIN RESIDUES IN KIDNEYS OF ORALLY DOSED NON-RUMINATING CALVES DETERMINED BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC AND MICROBIOLOGICAL ASSAY-METHODS SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Note C1 USDA,FOOD SAFETY & INSPECT SERV,DIV MICROBIOL,BELTSVILLE,MD 20705. RP SHAIKH, B (reprint author), US FDA,BARC E,CTR VET MED,BELTSVILLE,MD 20705, USA. NR 12 TC 1 Z9 1 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Therapeutics PD APR PY 1995 VL 18 IS 2 BP 150 EP 152 DI 10.1111/j.1365-2885.1995.tb00569.x PG 3 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA QR796 UT WOS:A1995QR79600011 PM 7629930 ER PT J AU RODERIQUEZ, G ORAVECZ, T YANAGISHITA, M BOUHABIB, DC MOSTOWSKI, H NORCROSS, MA AF RODERIQUEZ, G ORAVECZ, T YANAGISHITA, M BOUHABIB, DC MOSTOWSKI, H NORCROSS, MA TI MEDIATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 BINDING BY INTERACTION OF CELL-SURFACE HEPARAN-SULFATE PROTEOGLYCANS WITH THE V3 REGION OF ENVELOPE GP120-GP41 SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING MONOCLONAL-ANTIBODIES; GLYCOPROTEIN GP120; SOLUBLE CD4; SYNCYTIUM FORMATION; HIV-1 VIRIONS; AIDS VIRUS; INFECTION; DOMAIN; RETROVIRUS; GENERATION AB The mechanism of heparan sulfate (HS)-mediated human immunodeficiency virus type 1 (HIV-1) binding to and infection of T cells was investigated with a clone (H9h) of the T-cell line H9 selected on the basis of its high level of cell surface CD4 expression. Semiquantitative PCR analysis revealed that enzymatic removal of cell surface HS by heparitinase resulted in a reduction of the amount of HIV-1 DNA present in H9h cells 4 h after exposure to virus. Assays of the binding of recombinant envelope proteins to H9h cells demonstrated a structural requirement for an oligomeric form of gp120/gp41 for HS-dependent binding to the cell surface, The ability of the HIV-1 envelope to bind simultaneously to HS and CD4 was shown by immunoprecipitation of HS with either antienvelope or anti-CD4 antibodies from (SO42-)-S-35-labeled H9h cells that had been incubated with soluble gp140. Soluble HS blocked the binding of monoclonal antibodies that recognize the V3 and C4 domains of the envelope protein to the surface of H9 cells chronically infected with HIV-1(IIIB). The V3 domain was shown to be the major site of envelope-HS interaction by examining the effects of both antienvelope monoclonal antibodies and heparitinase on the binding of soluble gp140 to H9h cells. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NR 50 TC 185 Z9 186 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1995 VL 69 IS 4 BP 2233 EP 2239 PG 7 WC Virology SC Virology GA QL683 UT WOS:A1995QL68300030 PM 7884870 ER PT J AU BATTEGAY, M FIKES, J DIBISCEGLIE, AM WENTWORTH, PA SETTE, A CELIS, E CHING, WM GRAKOUL, A RICE, CM KUROKOHCHI, K BERZOFSKY, JA HOOFNAGLE, JH FEINSTONE, SM AKATSUKA, T AF BATTEGAY, M FIKES, J DIBISCEGLIE, AM WENTWORTH, PA SETTE, A CELIS, E CHING, WM GRAKOUL, A RICE, CM KUROKOHCHI, K BERZOFSKY, JA HOOFNAGLE, JH FEINSTONE, SM AKATSUKA, T TI PATIENTS WITH CHRONIC HEPATITIS-C HAVE CIRCULATING CYTOTOXIC T-CELLS WHICH RECOGNIZE HEPATITIS-C VIRUS-ENCODED PEPTIDES BINDING TO HLA-A2.1 MOLECULES SO JOURNAL OF VIROLOGY LA English DT Article ID TERM FOLLOW-UP; LYMPHOCYTE-T; ANTIGENIC SITES; CTL RESPONSES; NON-A; GENOME; SEQUENCE; INTERFERON; INFECTION; INDUCTION AB Antiviral cytotoxic T lymphocytes (CTL) may play a role in clearance of hepatitis C virus (HCV)-infected cells and thereby cause hepatocellular injury during acute and chronic HCV infection. The aim of this study was to identify HLA-A2.1-restricted HCV T-cell epitopes and to evaluate whether anti-HCV-specific CTL are present during chronic hepatitis C. Peripheral blood mononuclear cells from four HLA-A2-positive patients with chronic hepatitis C and from two individuals after recovery from HCV infection were tested against a panel of HCV-encoded peptides derived from different regions of the genome, including some peptides containing HLA-A2.1 binding moths. HLA-A2-negative patients,vith chronic hepatitis C as well as healthy HLA-A2-positive (anti-HCV-negative) donors served as controls. Peripheral blood mononuclear cells stimulated repeatedly with several HCV-encoded peptides (three in core, one in NS4B, and one in NS5B) yielded cytolytic responses. All four HLA-A2-positive patients with active infection had CTL specific for at least one of the identified epitopes, whereas two patients who had recovered from HCV infection had almost no CTL responses. Monoclonal antibody blocking experiments performed for two epitopes demonstrated a class I- and HLA-A2-restricted CTL response. CTL epitopes could partially be predicted by HLA-AZ, binding motifs and more reliably by quantitative HLA-A2.1 molecule binding assays. Most of the identified epitopes could also be produced via the endogenous pathway. Specific CTL against multiple, mostly highly conserved epitopes of HCV were detected during chronic HCV infection. This finding may be important for further investigations of the immunopathogenesis of HCV, the development of potential therapies against HCV on the basis of induction or enhancement of cellular immunity, and the design of vaccines. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,HEPATITIS RES LAB,BETHESDA,MD 20892. USN,MED RES INST,BETHESDA,MD. NIDDKD,LIVER DIS SECT,BETHESDA,MD. NCI,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD. CYTEL CORP,SAN DIEGO,CA. WASHINGTON UNIV,SCH MED,DEPT MOLEC MICROBIOL,ST LOUIS,MO. RI Yang, Chen/G-1379-2010 FU NCI NIH HHS [CA57973] NR 68 TC 199 Z9 203 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1995 VL 69 IS 4 BP 2462 EP 2470 PG 9 WC Virology SC Virology GA QL683 UT WOS:A1995QL68300059 PM 7884894 ER PT J AU GARDNER, DJ DAVIS, JA WEINA, PJ THEUNE, B AF GARDNER, DJ DAVIS, JA WEINA, PJ THEUNE, B TI COMPARISON OF TRIBROMOETHANOL, KETAMINE ACETYLPROMAZINE, TELAZOL(TM) XYLAZINE, PENTOBARBITAL, AND METHOXYFLURANE ANESTHESIA IN HSD-ICR MICE SO LABORATORY ANIMAL SCIENCE LA English DT Article ID FENTANYL-DROPERIDOL DROPERIDOL; ADULT MALE-RATS; BODY-TEMPERATURE; COMBINATION; DIAZEPAM AB Variation in the duration of surgical anesthesia in mice prompted an evaluation of various commonly used anesthetics, Using biotelemetric technology, we evaluated the effects of six anesthetic regimens (tribromoethanol, ketamine and acetylpromazine in combination, Telazol(TM) and xylazine in two combinations, pentobarbital, and methoxyflurane) on temperature and activity. Six groups of four male HSD:ICR mice received one of the anesthetic regimens or an equivalent volume of saline, Induction time (time from anesthetic administration until righting reflex loss) and duration of anesthesia (loss of response to interdigital toe pinch) were evaluated, Methoxyflurane and both doses of Telazol(TM) combinations resulted in the shortest and most repeatable induction times. None of the mice in the ketamine/acetylpromazine- and pentobarbital-treated groups lost the interdigital toe pinch reflex. Duration of anesthesia was superior in the two Telazol(TM)/xylazine-treated groups, A direct correlation existed between duration of anesthesia and magnitude and duration of temperature reduction, Duration of anesthesia can be used to predict extent of hypothermia. C1 WALTER REED ARMY INST RES,DIV VET MED,WASHINGTON,DC 20307. WALTER REED ARMY INST RES,DIV EXPTL THERAPEUT,WASHINGTON,DC 20307. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20889. RP GARDNER, DJ (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV VET SERV,BETHESDA,MD 20892, USA. NR 16 TC 33 Z9 33 U1 0 U2 3 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD APR PY 1995 VL 45 IS 2 BP 199 EP 204 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA QU962 UT WOS:A1995QU96200015 PM 7603025 ER PT J AU DEPAOLA, A HWANG, GC AF DEPAOLA, A HWANG, GC TI EFFECT OF DILUTION, INCUBATION-TIME, AND TEMPERATURE OF ENRICHMENT ON CULTURAL AND PCR DETECTION OF VIBRIO-CHOLERAE OBTAINED FROM THE OYSTER CRASSOSTREA-VIRGINICA SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE VIBRIO CHOLERAE; RECOVERY; OYSTER; CRASSOSTREA VIRGINICA; POLYMERASE CHAIN REACTION ID POLYMERASE CHAIN-REACTION; EPIDEMIC; COAST AB The recovery of Vibrio cholerae O1 by culture from the oyster Crassostrea virginica and detection of the cholera toxin gene by polymerase chain reaction were evaluated using various enrichment procedures in alkaline peptone water. The effects of dilutions (1:10 and 1:100), incubation times (6-8 and 18-21 h), and incubation-temperatures (35 and 42 degrees C) were determined. Recovery of V. cholerae was significantly greater (P<0.05) from oyster homogenates diluted 1:100 in alkaline peptone water and incubated at 42 degrees C for 18-21 h. This enrichment procedure also provided the best detection of the cholera toxin gene by polymerase chain reaction. C1 NATL FISHERIES RES & DEV AGCY,YANGSAN GUN 626900,SOUTH KOREA. RP DEPAOLA, A (reprint author), US FDA,GULF COAST SEAFOOD LAB,POB 158,DAUPHIN ISL,AL 36528, USA. NR 23 TC 21 Z9 23 U1 1 U2 1 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD APR PY 1995 VL 9 IS 2 BP 75 EP 81 DI 10.1016/S0890-8508(95)80031-X PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA QU663 UT WOS:A1995QU66300001 PM 7603474 ER PT J AU KITT, CA WILCOX, BJ AF KITT, CA WILCOX, BJ TI PRELIMINARY EVIDENCE FOR NEURODEGENERATIVE CHANGES IN THE SUBSTANTIA-NIGRA OF RETT-SYNDROME SO NEUROPEDIATRICS LA English DT Article; Proceedings Paper CT International Rett Symposium - Molecular and Neurobiology Aspects of Rett Syndrome CY OCT 01, 1994 CL PORTLAND, OR DE RETT SYNDROME; NEUROPATHOLOGY; SUBSTANTIA NIGRA ID POSTMORTEM BRAIN; BIOGENIC-AMINES; CELL-DEATH; NEURONS; INSITU; DNA AB Rett syndrome (RS), which affects similar to 1 in 10,000 young females, is characterized by cognitive deterioration, ataxia, apraxia, rigidity, and stereotyped hand movements. Neuropathological features include reduction in brain size and hypopigmentation of neurons of the substantia nigra pars compacta (SNpc). Neurochemical and imaging studies support nigrostriatal involvement. The results of our preliminary studies show abnormalities in neurons of the substantia nigra (SN), including decreased numbers of neurons, ubiquitin-stained neuronal inclusion bodies, decreased immunostaining for transmitter markers, and evidence of cell death using terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-biotin nick end labeling (TUNEL), which labels fragmented intranucleosomal DNA. These preliminary data represent the first evidence for cell death in RS. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,ROCKVILLE,MD 20857. RP KITT, CA (reprint author), JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,558 ROSS RES BLDG,720 RUTLAND AVE,BALTIMORE,MD 21205, USA. FU NIA NIH HHS [AG 05146]; NICHD NIH HHS [HD 24448]; NINDS NIH HHS [NS 20471] NR 22 TC 46 Z9 46 U1 0 U2 1 PU HIPPOKRATES VERLAG GMBH PI STITTGART PA PO BOX 30 05 04 RUDIGERSTRASSE 14, 70469 STITTGART, GERMANY SN 0174-304X J9 NEUROPEDIATRICS JI Neuropediatrics PD APR PY 1995 VL 26 IS 2 BP 114 EP 118 DI 10.1055/s-2007-979739 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA RE344 UT WOS:A1995RE34400018 PM 7566448 ER PT J AU WYSOWSKI, DK GREEN, L AF WYSOWSKI, DK GREEN, L TI SERIOUS ADVERSE EVENTS IN NORPLANT USERS REPORTED TO THE FOOD AND DRUG ADMINISTRATIONS MEDWATCH SPONTANEOUS REPORTING SYSTEM SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID IDIOPATHIC INTRACRANIAL HYPERTENSION AB Objective: To describe serious adverse events in Norplant users from reports submitted to the Food and Drug Administration's (FDA) MedWatch Spontaneous Reporting System. Methods: Reports of certain serious adverse events in Norplant users in the United States from February 1998 to December 1993 were reviewed and analyzed. Results: From the introduction of Norplant in the United States in February 1991 to December 1993, the FDA received reports of 24 women hospitalized for infections at the insertion site, 14 hospitalized or disabled because of difficulties removing the capsules, 14 hospitalized for stroke, three for thrombotic thrombocytopenia purpura, six for thrombocytopenia, and 39 for pseudotumor cerebri. The comparison of reported rates with expected rates and the relationship of some of these disorders with oral contraceptives raises the suspicion of a causal association with Norplant. Conclusions: The FDA has received reports of hospitalization or disability for infections, capsule removal difficulties, stroke, thrombotic thrombocytopenia purpura, thrombocytopenia, and pseudotumor cerebri in Norplant users. Health care professionals need to be trained in Norplant insertion and removal to ensure the proper technique. Studies are needed to determine if stroke, thrombocytopenia, and pseudotumor cerebri are causally related to Norplant use. RP WYSOWSKI, DK (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV EPIDEMIOL & SURVEILLANCE,ROCKVILLE,MD 20857, USA. NR 10 TC 42 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 1995 VL 85 IS 4 BP 538 EP 542 DI 10.1016/0029-7844(94)00457-O PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QN352 UT WOS:A1995QN35200010 PM 7898829 ER PT J AU SAUBERMAN, HR AF SAUBERMAN, HR TI APPROVAL PROCESS FOR IMPLANTS IN OTOLARYNGOLOGY SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article AB The United States Federal Food, Drug, and Cosmetic Act, embodied under Title 21 of the US Code and amended by the Medical Device Amendments of 1976 and the Safe Medical Device Act of 1990, granted authority to the US Food and Drug Administration to permit clinical studies for the purpose of compiling safety and efficacy data. A new or modified otolaryngologic implant may be required to undergo a clinical study before marketing approval can be given. A study approval permits an implant to be lawfully investigated in human subjects. The data collected from the study may then be used to support a request for marketing approval via premarket notification in accordance with Section 510(k) of the Medical Device Amendments, or via premarket approval application in accordance with the amendments. This article examines the approval process as it applies to otolaryngologic implants. RP SAUBERMAN, HR (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF DEVICE EVALUAT,9200 CORP RD,ROCKVILLE,MD 20850, USA. NR 7 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD APR PY 1995 VL 28 IS 2 BP 235 EP 244 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA QT544 UT WOS:A1995QT54400003 PM 7596604 ER PT J AU SAVARY, WE AF SAVARY, WE TI DACNE PICTA CROTCH - A RECENTLY INTRODUCED REST OF STORED, DRIED SHIITAKE MUSHROOMS (COLEOPTERA, EROTYLIDAE) SO PAN-PACIFIC ENTOMOLOGIST LA English DT Article DE INSECTA; COLEOPTERA; EROTYLIDAE; STORED PRODUCTS; INTRODUCED PESTS; MUSHROOMS AB A major infestation of the dacnine erotylid beetle Dacne picta Crotch was found in dried shiitake mushrooms (Lentinula edodes (Berkeley) Pegler) stored in a warehouse in San Francisco, California. The mushrooms were imported from the People's Republic of China, via Hong Kong, in June 1990, six months prior to the discovery of the infestation. The spread of the infestation within the warehouse was documented. RP SAVARY, WE (reprint author), US FDA,1431 HARBOR BAY PKWY,ALAMEDA,CA 94502, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU PACIFIC COAST ENTOMOL SOC PI SAN FRANCISCO PA CALIFORNIA ACAD OF SCIENCES GOLDEN GATE PARK, SAN FRANCISCO, CA 94118 SN 0031-0603 J9 PAN-PAC ENTOMOL JI Pan-Pacific Entomol. PD APR PY 1995 VL 71 IS 2 BP 87 EP 91 PG 5 WC Entomology SC Entomology GA TA182 UT WOS:A1995TA18200004 ER PT J AU POGUE, GP KOUL, S LEE, NS DWYER, DM NAKHASI, HL AF POGUE, GP KOUL, S LEE, NS DWYER, DM NAKHASI, HL TI IDENTIFICATION OF INTRASPECIFIC AND INTERSPECIFIC LEISHMANIA GENETIC - POLYMORPHISMS BY ARBITRARY PRIMED POLYMERASE CHAIN-REACTIONS AND USE OF POLYMORPHIC DNA TO IDENTIFY DIFFERENTIALLY REGULATED GENES SO PARASITOLOGY RESEARCH LA English DT Article ID INFANTUM NICOLLE; KINETOPLAST DNA; DONOVANI; AMPLIFICATION; EVOLUTION; PROTOZOA; MARKERS; STRAINS; STOCKS; TOOL AB Arbitrary primed polymerase chain reactions (AP-PCR) were used to amplify different polymorphic genomic DNA fragments from various Old World Leishmania species. Using four 10-mer AP primers, geographic isolates of L. donovani and various Old World species of Leishmania could be readily distinguished from one another by the pattern of amplified DNA products. Our studies confirmed two important characteristics of AP-PCR: its abilities to amplify a consistent pattern of DNA fragments from the genomes of different isolates of a single species and to identify genetic polymorphisms between the species isolates. We selected three polymerphic DNA fragments that differentiate L. donovani geographic isolates for further analysis. Sequence analysis of the clones derived from these three polymorphic fragments revealed eight unique sequences. Six of eight unique clones hybridized to distinct RNAs upon Northern-blot analysis. Three of these six clones hybridized to RNAs expressed differentially in in vitro grown L. donovani pro- and ''amastigotes.'' One of the differentially expressed clones, LdE-6-1, exhibited restriction length polymorphisms that distinguished L. donovani from L. tropica and L. major. Comparative Northern blotting revealed that LdE-6-1 was differentially expressed in some members of the L. donovani species complex but not in L. major or L. tropica. These results demonstrate that AP-PCR can be used to generate products reflecting particular genes in organisms with low-complexity genomes. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NR 28 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0044-3255 J9 PARASITOL RES JI Parasitol. Res. PD APR PY 1995 VL 81 IS 4 BP 282 EP 290 DI 10.1007/BF00931531 PG 9 WC Parasitology SC Parasitology GA QT555 UT WOS:A1995QT55500003 PM 7624284 ER PT J AU TREANOR, JJ CLARK, HF PICHICHERO, M CHRISTY, C GOUVEA, V SHRAGER, D PALAZZO, S OFFIT, P AF TREANOR, JJ CLARK, HF PICHICHERO, M CHRISTY, C GOUVEA, V SHRAGER, D PALAZZO, S OFFIT, P TI EVALUATION OF THE PROTECTIVE EFFICACY OF A SEROTYPE-1 BOVINE-HUMAN ROTAVIRUS REASSORTANT VACCINE IN INFANTS SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE ROTAVIRUS; VACCINES; CLINICAL TRIALS; REASSORTANTS; LIVE ATTENUATED VACCINES ID POLYMERASE CHAIN-REACTION; RHESUS-ROTAVIRUS; YOUNG-CHILDREN; VENEZUELAN INFANTS; HEALTHY INFANTS; WC3 VACCINE; FIELD TRIAL; STRAIN WC3; DIARRHEA; GASTROENTERITIS AB The objective of this study was to evaluate the efficacy of a live, attenuated bovine (strain WC3) x human (strain WI79, serotype G1) rotavirus reassortant (WI79-9) virus vaccine for prevention of symptomatic rotavirus gastroenteritis in infants. The study was a prospective, randomized, double-blind, placebo-controlled trial, conducted over a single rotavirus season in 325 infants who were 2 to 8 months old at enrollment. Subjects were randomized to receive either placebo or WI79-9 virus vaccine at 10(7.3) plaque-forming units in three oral doses each separated by 2 months, Subjects were followed for 7 days after each dose for occurrence of adverse events and during the subsequent winter for development of rotavirus gastroenteritis. Administration of WI79-9 virus vaccine was well-tolerated, and the rates of low grade fever after each dose were no higher in vaccine recipients (8 to 21%) than in placebo recipients (14 to 19%), The protective efficacy of tbe WI79-9 vaccine during a subsequent epidemic of predominantly serotype G1 rotavirus was 87.0% (95% confidence limits, 62.6 to 95.5%) against relatively severe rotavirus gastroenteritis (rotavirus gastroenteritis with a clinical severity score of >8) and was 64.1% (95% confidence limits 35.9 to 79.9%) against all symptomatic rotavirus episodes. The WI79-9 vaccine was safe and effective in prevention of homotypic human rotavirus infection in infants. Further studies of reassortant vaccines based on the bovine WC3 rotavirus should be performed. C1 UNIV ROCHESTER,DEPT PEDIAT,ROCHESTER,NY 14642. CHILDRENS HOSP PHILADELPHIA,INFECT DIS SECT,PHILADELPHIA,PA 19104. US FDA,DIV MICROBIOL,WASHINGTON,DC 20204. RP TREANOR, JJ (reprint author), UNIV ROCHESTER,SCH MED,DEPT MED,INFECT DIS UNIT,BOX 689,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. FU NIAID NIH HHS [N01-AI-05049] NR 33 TC 40 Z9 40 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD APR PY 1995 VL 14 IS 4 BP 301 EP 307 DI 10.1097/00006454-199504000-00010 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA QT556 UT WOS:A1995QT55600010 PM 7603812 ER PT J AU HINSON, RM SHACTER, E AF HINSON, RM SHACTER, E TI INDUCTION OF INTERLEUKIN-6 SYNTHESIS BY PROSTAGLANDINS IN INFLAMMATORY PERITONEAL-MACROPHAGES SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 US FDA, CBER, DHP, IMMUNOL LAB, BETHESDA, MD 20014 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT PEDIAT, BETHESDA, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A9 EP A9 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08200037 ER PT J AU KOLLER, EA STADEL, BV MALOZOWSKI, SN AF KOLLER, EA STADEL, BV MALOZOWSKI, SN TI PAPILLEDEMA IN 13 RENAL PATIENTS TREATED WITH GH FOR IMPAIRED GROWTH SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 US FDA, DIV METAB & ENDOCRINE DRUG PROD, ROCKVILLE, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A364 EP A364 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08202169 ER PT J AU SPADY, DW CARSON, MM KREZOLEK, M GRIMSRUD, K BEELER, J PABST, HF AF SPADY, DW CARSON, MM KREZOLEK, M GRIMSRUD, K BEELER, J PABST, HF TI INFLUENCE OF GENDER AND MODE OF FEEDING ON THE IMMUNE-RESPONSE SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 UNIV ALBERTA, EDMONTON BOARD HLTH, DEPT PEDIAT, EDMONTON, AB T6G 2E1, CANADA. US FDA, CTR BIOL EVALUAT & RES, BETHESDA, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A10 EP A10 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08200048 ER PT J AU FREDERICK, DL SCHULZE, GE GILLAM, MP PAULE, MG AF FREDERICK, DL SCHULZE, GE GILLAM, MP PAULE, MG TI ACUTE EFFECTS OF PHYSOSTIGMINE ON COMPLEX OPERANT-BEHAVIOR IN RHESUS-MONKEYS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE MONKEYS; PHYSOSTIGMINE; OPERANT BEHAVIOR; LEARNING; INCREMENTAL REPEATED ACQUISITION; MEMORY; DELAYED MATCHING-TO-SAMPLE; TIME PERCEPTION; TEMPORAL RESPONSE DIFFERENTIATION; MOTIVATION; PROGRESSIVE RATIO; COLOR AND POSITION DISCRIMINATION; CONDITIONED POSITION RESPONDING ID TEST BATTERY; CHOLINERGIC AGENTS; SAMPLE PERFORMANCE; NONHUMAN-PRIMATES; SQUIRREL-MONKEY; FIMBRIA-FORNIX; MEMORY; SCOPOLAMINE; ATROPINE; RATS AB The effects of physostigmine were assessed in rhesus macaques using behavior in several complex tasks designed to model aspects of time estimation [temporal response differentiation (TRD)], short-term memory [delayed matching-to-sample (DMTS)], motivation [progressive ratio (PR)], learning [incremental repeated acquisition (IRA)], and color and position discrimination [conditioned position responding (CPR)]. The endpoints monitored included percent task completed, response rate, and accuracy. Physostigmine sulphate (0.001-0.056 mg/kg) significantly decreased the percentage of task completed and response rate in each task at 0.03 and 0.056 mg/kg. Accuracy in the TRD task was significantly decreased at 0.03 and 0.056 mg/kg, whereas accuracy in the CPR and IRA tasks was significantly decreased only at 0.056 mg/kg. DMTS accuracy was not significantly affected at any dose tested. A significant increase in accuracy was noted in learning task performance at the 0.01 mg/kg dose, although only for one-lever response sequences. Performance enhancements were not seen in any other task. These results indicate that in monkeys, low doses of physostigmine may facilitate acquisition or learning of simple one-lever spatial tasks while not significantly altering the acquisition of similar but more complex tasks. Impaired task performance at high doses may be more reflective of cholinomimetic side effects (tremor and hypothermia) that affect response rate than a central or ''cognitive'' impairment. C1 BRISTOL MYERS SQUIBB CO,DEPT TOXICOL,EVANSVILLE,IN 47721. UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,DEPT PHARMACOL & INTERDISCIPLINARY TOXICOL,LITTLE ROCK,AR 72205. RP FREDERICK, DL (reprint author), US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,HFT-132,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 42 TC 19 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD APR PY 1995 VL 50 IS 4 BP 641 EP 648 DI 10.1016/0091-3057(94)00358-0 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA QN046 UT WOS:A1995QN04600024 PM 7617713 ER PT J AU WAMER, WG TIMMER, WC WEI, RR MILLER, SA KORNHAUSER, A AF WAMER, WG TIMMER, WC WEI, RR MILLER, SA KORNHAUSER, A TI FUROCOUMARIN-PHOTOSENSITIZED HYDROXYLATION OF GUANOSINE IN RNA AND DNA SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID PSORALENS; MECHANISMS; 3-CARBETHOXYPSORALEN; PHOTOREACTIVITY; INVITRO; DAMAGE; INVIVO AB Guanosine hydroxylation was used as a marker for assessing photooxidation of DNA and RNA sensitized by monofunctional and bifunctional furocoumarins. DNA or RNA, treated with sensitizer and UVA light, was enzymatically hydrolyzed, dephosphorylated and then analyzed by reversed-phase HPLC with electrochemical detection. Hydroxylated guanosine, i.e. 8-hydroxy-2'-deoxyguanosine (8-OHdG) or 8-hydroxyguanosine (8-OHG), was quantitated. 3-Carbethoxypsoralen (3-CP) was found to be an efficient photosensitizer for oxidation of guanosine in DNA, resulting in conversion of up to 0.4% of guanosine residues to 8-OHdG. In contrast, dramatically lower levels of guanosine hydroxylation were observed in 3-CP-photosensitized RNA. Psoralen was found to be a more efficient photosensitizer than angelicin in both DNA and RNA. Additional studies of oxidation of 3-CP-photosensitized DNA indicated that double-stranded DNA is 10 times more susceptible to photooxidation than single-stranded DNA, implicating 3-CP binding to DNA as an important mechanistic step in photooxidation of guanosine. The effects of D2O and degassing with argon on photooxidation of guanosine in DNA sensitized by 3-CP were inconsistent with a mechanism involving O-2. In addition, chelation of adventitious metal ions present in preparations of DNA photosensitized by 3-CP had no effect on hydroxylation of guanosine. C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. RP WAMER, WG (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 24 TC 11 Z9 14 U1 0 U2 3 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD APR PY 1995 VL 61 IS 4 BP 336 EP 340 DI 10.1111/j.1751-1097.1995.tb08618.x PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QQ294 UT WOS:A1995QQ29400005 PM 7537887 ER PT J AU CEBULA, TA HENRIKSON, EN HARTMAN, PE BIGGLEY, WH AF CEBULA, TA HENRIKSON, EN HARTMAN, PE BIGGLEY, WH TI REVERSION PROFILES OF COOLWHITE FLUORESCENT LIGHT COMPARED WITH FAR-ULTRAVIOLET LIGHT - HOMOLOGIES AND DIFFERENCES SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; SQUAMOUS-CELL CARCINOMA; SALMONELLA-TYPHIMURIUM; TARGET SEQUENCES; P53 MUTATIONS; RADIATION; EXPOSURE; SUNLIGHT; SKIN; LAMPS AB General Electric and Sylvania 15 W coolwhite fluorescent lamps emit roughly 6% of their total irradiance as light in the UV spectrum. Illumination of sensitive Salmonella tester strains results in both lethal and mutagenic activities. In contrast, comparable Philips lamps emit lower levels of UV light, especially UVB, and exhibit no detectable lethal or mutagenic effects. The spectra of mutations induced by General Electric coolwhite lamps in histidine-requiring base substitution mutants hisG46 and hisG428 (''reversion profiles'') resemble mutagenesis by far UV light (UVC) and differ quite markedly from the spectra of mutations that occur spontaneously. Coolwhite and UVC reversion profiles are not identical, however. The percentage of C to A transversion mutations induced in hisG46 are elevated over those found after UVC treatment, and a strong bias for one particular class of tandem base substitutions (TAA --> TGT) prevails after treatment of hisG428 with coolwhite light, a bias not observed with UVC. Increased attention needs to be given to minimization of exposure to UV light from fluorescent lamps commonly used in homes and workplaces. C1 JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. US FDA,CTR FOOD SAFETY & APPL NUTR,MOLEC BIOL BRANCH HFS235,WASHINGTON,DC 20204. NR 46 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD APR PY 1995 VL 61 IS 4 BP 353 EP 359 DI 10.1111/j.1751-1097.1995.tb08622.x PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QQ294 UT WOS:A1995QQ29400009 PM 7740078 ER PT J AU BAILEY, JE AF BAILEY, JE TI DAY-ONE - JANUARY 31, 1994 - SESSION-1 - INTRODUCTION - OVERVIEW - SCOPE OF THE WORKSHOP SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Editorial Material RP BAILEY, JE (reprint author), US FDA,PUBL HLTH SERV,OFF COSMET & COLORS,200 C ST SW,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 1995 VL 21 IS 2 BP 216 EP 217 DI 10.1006/rtph.1995.1031 PG 2 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA QY863 UT WOS:A1995QY86300004 ER PT J AU GILBERTSON, WE AF GILBERTSON, WE TI THE REGULATORY STATUS OF TALC SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT International-Society-of-Regulatory-Toxicology-and-Pharmacology/US-FDA Workshop on Talc - Consumer Uses and Health Perspectives CY JAN 31-FEB 01, 1994 CL NIH, BETHESDA, MD SP NIH HO NIH RP GILBERTSON, WE (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF OVER COUNTER DRUG EVALUAT,7520 STANDISH PL HFD-810,ROCKVILLE,MD 20855, USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 1995 VL 21 IS 2 BP 230 EP 232 DI 10.1006/rtph.1995.1033 PG 3 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA QY863 UT WOS:A1995QY86300006 PM 7644710 ER PT J AU ROSA, F AF ROSA, F TI HOLOPROSENCEPHALY AND ANTIEPILEPTIC EXPOSURES SO TERATOLOGY LA English DT Letter RP ROSA, F (reprint author), US FDA,CTR DRUG EVALUAT & RES,HFD-733,ROCKVILLE,MD 20857, USA. NR 1 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD APR PY 1995 VL 51 IS 4 BP 230 EP 230 DI 10.1002/tera.1420510405 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA RJ394 UT WOS:A1995RJ39400004 PM 7570362 ER PT J AU WILKES, JG SUTHERLAND, JB CHURCHWELL, MI WILLIAMS, AJ AF WILKES, JG SUTHERLAND, JB CHURCHWELL, MI WILLIAMS, AJ TI DETERMINATION OF FUMONISINS B-1, B-2, B-3 AND B-4 BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH EVAPORATIVE LIGHT-SCATTERING DETECTION SO JOURNAL OF CHROMATOGRAPHY A LA English DT Note ID FUSARIUM-MONILIFORME; FLUORESCENCE DETECTION; MASS-SPECTROMETRY; MYCOTOXINS; CORN; CANCER; HPLC; B1 AB Fumonisins B-1, B-2, B-3 and B-4 (FB1-FB4), a group of mycotoxins produced by the fungus Fusarium moniliforme, were separated by HPLC using an analytical-scale, base-deactivated C-8 column and a gradient of trifluoroacetic acid buffer (pH 2.7) and acetonitrile. An evaporative light-scattering detector was used to detect the fumonisin peaks. A semi-preparative-scale, base-deactivated C-8 column with a 1:14 mobile phase split facilitated the purification of analytical standards of FB1. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. RP WILKES, JG (reprint author), US FDA,NATL CTR TOXICOL RES,DIV CHEM,JEFFERSON,AR 72079, USA. NR 22 TC 30 Z9 31 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAR 31 PY 1995 VL 695 IS 2 BP 319 EP 323 DI 10.1016/0021-9673(95)00064-T PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QR529 UT WOS:A1995QR52900016 PM 7757206 ER PT J AU AOKI, I KINZER, C SHIRAI, A PAUL, WE KLINMAN, DM AF AOKI, I KINZER, C SHIRAI, A PAUL, WE KLINMAN, DM TI IGE - RECEPTOR-POSITIVE NON-B/NON-T CELLS DOMINATE THE PRODUCTION OF INTERLEUKIN-4 AND INTERLEUKIN-6 IN IMMUNIZED MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SPLENIC NON-B; INTERFERON-GAMMA; FC-EPSILON; MURINE LEISHMANIASIS; STIMULATING FACTOR; CROSS-LINKAGE; IL-4; LYMPHOKINES; EXPRESSION; BASOPHILS AB The phenotype and antigenic specificity of cells secreting interleukin (IL) 4, IL-6, and interferon gamma was studied in mice during primary and secondary immune responses. T lymphocytes were the major source of interferon gamma, whereas non-B/non-T cells were the dominant source of IL-4 and IL-6 in the spleens of immunized animals. Cytokine-secreting non-B/non-T cells expressed surface receptors for IgE and/or IgG types II/III. Exposing these cells to antigen-specific IgE or IgG in vivo (or in vitro) ''armed'' them to release IL-4 and IL-6 upon subsequent antigenic challenge. These findings suggest that non-B/non-T cells may represent the ''natural immunity'' analogue of CD4(+) T helper type 2 cells and participate in a positive feedback loop involved in the perpetuation of T helper type 2 cell responses. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP AOKI, I (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,RETROVIRAL IMMUNOL SECT,BETHESDA,MD 20892, USA. NR 39 TC 37 Z9 37 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 1995 VL 92 IS 7 BP 2534 EP 2538 DI 10.1073/pnas.92.7.2534 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QP889 UT WOS:A1995QP88900026 PM 7708680 ER PT J AU KOGA, M WILK, A MOORE, MF SCREMIN, CL ZHOU, L BEAUCAGE, SL AF KOGA, M WILK, A MOORE, MF SCREMIN, CL ZHOU, L BEAUCAGE, SL TI SYNTHESIS AND PHYSICOCHEMICAL PROPERTIES OF ALTERNATING ALPHA,BETA-OLIGODEOXYRIBONUCLEOTIDES WITH ALTERNATING (3'-]3')-INTERNUCLEOTIDIC AND (5'-]5')-INTERNUCLEOTIDIC PHOSPHODIESTER LINKAGES SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SULFUR-TRANSFER REAGENT; GENE-EXPRESSION; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; DEOXYNUCLEOSIDE PHOSPHORAMIDITES; ANTISENSE OLIGONUCLEOTIDES; FORMING-OLIGONUCLEOTIDES; MESSENGER-RNA; DNA; DEOXYOLIGONUCLEOTIDES AB A simple and straightforward synthesis of alpha-2'-deoxycytidine and alpha-2'-deoxyadenosine derivatives 6a,b has been achieved from commercial N-4-benzoyl-beta-2'-deoxycytidine and N-6-benzoyl-beta-2'-deoxyadenosine, respectively. Properly protected alpha-2'-deoxyribonucleosides 8a-d were converted to the corresponding 5'-phosphoramidite derivatives 9a-d. These and commercial beta-2'-deoxyribonucleoside 3'-phosphoramidites were readily incorporated into alternating alpha,beta-oligodeoxyribonucleotides with alternating (3'-->3')- and (5'-->5')-internucleotidic phosphodiester linkages by standard solid-phase synthesis methods. The alpha,beta-oligodeoxyribonucleotide 12 (Scheme 3) was considerably more resistant to hydrolysis catalyzed by snake venom phosphodiesterase, calf spleen phosphodiesterase, and S1 nuclease than the parent unmodified oligonucleotide 17 (Table 2). Thermal stability of the complex composed of 12 and complementary unmodified beta-oligomer 18 was comparable to that measured for the hybrid composed of the beta-oligodeoxyribonucleoside phosphorothioate 20 and 18 but less than that of the native DNA duplex 17:18 (Table 3). The differences in thermal stability (Delta T-m) and free energy of dissociation (Delta Delta G(37)degrees) observed between the duplex 12:18 and the singly mismatched complex 12:19 (9 degrees C and -2.5 kcal/mol, respectively) (Tables 3 and 4) suggest that the sequence specificity;of 12 toward a complementary unmodified beta-DNA oligomer is comparable to that of 17. In addition, the CD spectrum of 12:18 at 22 degrees C resembles more closely that of the natural DNA duplex 17:18 than that of the alpha,beta-DNA duplex 12:13 (Figure 3). These findings indicate that the duplex 12:18 exhibits, at least to some extent, a B-type helicity. The alpha,beta-oligodeoxyribonucleotide 12 formed also a complex with the complementary beta-oligoribonucleotide 23 but with much reduced affinity (T-m = 35 degrees C) than that measured with the complementary DNA sequence 18 (T-m = 54 degrees C). CD spectroscopy indicated that the complex 12:23 adopted a conformation similar to that observed for duplex 17:23 at 22 degrees C. Unlike the DNA-RNA heteroduplex 17:23, the complex 12:23 was not a substrate for E. coli RNase H. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV ALLERGEN PROD & PARASITOL,BETHESDA,MD 20892. UNIV CALIF BERKELEY,CANC RES LAB,BERKELEY,CA 94720. NR 56 TC 33 Z9 33 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD MAR 24 PY 1995 VL 60 IS 6 BP 1520 EP 1530 DI 10.1021/jo00111a009 PG 11 WC Chemistry, Organic SC Chemistry GA QN888 UT WOS:A1995QN88800009 ER PT J AU MATHERS, PH JAMRICH, M AF MATHERS, PH JAMRICH, M TI INDUCTION OF A NOVEL HOMEODOMAIN GENE, RX, IN THE ANTERIOR NEURAL PLATE AND ITS ROLE IN RETINAL PROLIFERATION SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20014. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1995 VL 36 IS 4 BP S213 EP S213 PG 1 WC Ophthalmology SC Ophthalmology GA QM915 UT WOS:A1995QM91500975 ER PT J AU SHELDON, WG WARBRITTON, AR BUCCI, TJ TURTURO, A AF SHELDON, WG WARBRITTON, AR BUCCI, TJ TURTURO, A TI PRIMARY GLAUCOMA IN FOOD RESTRICTED AND AD-LIBITUM FED DBA/2NNIA MICE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 PATHOL ASSOCIATES INC,JEFFERSON,AR. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1995 VL 36 IS 4 BP S968 EP S968 PG 1 WC Ophthalmology SC Ophthalmology GA QM915 UT WOS:A1995QM91504457 ER PT J AU EGAN, W FRASCH, CE ANTHONY, BF AF EGAN, W FRASCH, CE ANTHONY, BF TI LOT-RELEASE CRITERIA, POSTLICENSURE QUALITY-CONTROL, AND THE HAEMOPHILUS-INFLUENZAE TYPE-B CONJUGATE VACCINES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HBOC VACCINE; POPULATION; EFFICACY; CHILDREN; INFANTS; DISEASE RP EGAN, W (reprint author), US FDA,CTR BIOL EVALUAT & RES,OFF VACCINES RES & REVIEW,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 13 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 15 PY 1995 VL 273 IS 11 BP 888 EP 889 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QL402 UT WOS:A1995QL40200029 PM 7869562 ER PT J AU HAHN, DW EDIGER, MN PETTIT, GH AF HAHN, DW EDIGER, MN PETTIT, GH TI ABLATIAN PLUME PARTICLE DYNAMICS DURING EXCIMER-LASER ABLATION OF POLYIMIDE SO JOURNAL OF APPLIED PHYSICS LA English DT Article ID FLAMES; SPECTROSCOPY; POLYMERS; PRODUCTS; FILMS C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. NR 32 TC 13 Z9 13 U1 0 U2 2 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-8979 J9 J APPL PHYS JI J. Appl. Phys. PD MAR 15 PY 1995 VL 77 IS 6 BP 2759 EP 2766 DI 10.1063/1.358745 PG 8 WC Physics, Applied SC Physics GA QN148 UT WOS:A1995QN14800081 ER PT J AU SHIRAI, M ARICHI, T NISHIOKA, M NOMURA, T IKEDA, K KAWANISHI, K ENGELHARD, VH FEINSTONE, SM BERZOFSKY, JA AF SHIRAI, M ARICHI, T NISHIOKA, M NOMURA, T IKEDA, K KAWANISHI, K ENGELHARD, VH FEINSTONE, SM BERZOFSKY, JA TI CTL RESPONSES OF HLA-A2.1-TRANSGENIC MICE SPECIFIC FOR HEPATITIS-C VIRAL PEPTIDES PREDICT EPITOPES FOR CTL OF HUMANS CARRYING HLA-A2.1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NON-B-HEPATITIS; CYTOTOXIC LYMPHOCYTES-T; MAJOR HISTOCOMPATIBILITY COMPLEX; NON-A; CELL RECOGNITION; TRANSGENIC MICE; ANTIGEN PRESENTATION; MONOCLONAL-ANTIBODY; SYNTHETIC PEPTIDES; VIRUS-REPLICATION AB Vaccine development in animal models depends on ability to recognize epitopes seen by human T cells. In this work, we show that CTL responses in transgenic mice expressing human HLA-A2.1 prospectively predict the same four of 11 hepatitis C virus (HCV) structural protein-derived peptides, expressing a sequence motif for HLA-A2.1 binding, that are actually recognized by human A2.1-restricted CTLs. The CTLs also recognized targets endogenously expressing these proteins. Human CTLs from HCV-infected patients, tested by using the same peptides, revealed a virtually identical response repertoire. A highly conserved HCV core peptide was the most immunogenic, and may be a valuable component of a vaccine against a broad range of HCV isolates in HLA-A2-positive patients. These results suggest that, in spite of species differences, the T cell repertoire is plastic enough to allow a similar response when the same class I MHC molecule is presenting the peptide. Thus, the HLA molecule plays the primary role in determining which peptides are recognized by CTLs. This transgenic mouse model is important for the study of HLA-restricted CTL determinants and for an approach to design a potential HCV vaccine. C1 NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. KAGAWA MED SCH,DEPT INTERNAL MED 3,KAGAWA 76107,JAPAN. KAGAWA MED SCH,DEPT TRANSFUS MED,KAGAWA 76107,JAPAN. UNIV VIRGINIA,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,HEPATITIS RES LAB,BETHESDA,MD 20892. RI Yang, Chen/G-1379-2010 FU NIAID NIH HHS [R01 AI21393] NR 68 TC 151 Z9 154 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1995 VL 154 IS 6 BP 2733 EP 2742 PG 10 WC Immunology SC Immunology GA QL084 UT WOS:A1995QL08400020 PM 7533182 ER PT J AU BERKOWER, I BRIDGEWATER, J SHIH, M AF BERKOWER, I BRIDGEWATER, J SHIH, M TI NOVEL CROSS-LINKERS FORM GP120 GLYCOCONJUGATES WHICH RETAIN BIOLOGICAL-ACTIVITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,OVRR,BETHESDA,MD 20892. CORNELL UNIV,ITHACA,NY. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A1051 EP A1051 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40602470 ER PT J AU BOWYER, JF SLIKKER, W SCHMUED, L CLAUSING, P AF BOWYER, JF SLIKKER, W SCHMUED, L CLAUSING, P TI COMPARISON OF THE EXPRESSION OF AMPHETAMINE (AMPH) NEUROTOXICITY IN DEVELOPING VERSUS ADULT-RATS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A665 EP A665 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40600238 ER PT J AU BRAUNBERG, RC FRIEDMAN, L RABBANI, I GATES, D AF BRAUNBERG, RC FRIEDMAN, L RABBANI, I GATES, D TI BIOCHEMICAL EFFECTS OF ACETAMINOPHEN (A) AND ETHANOL (E) ON INCUBATED PRECISION-CUT RAT-LIVER SLICES (PCS) - PRELIMINARY FINDINGS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,DIV TOXICOL RES,LAUREL,MD 20708. NR 1 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 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 QM406 UT WOS:A1995QM40601843 ER PT J AU BRORSON, KA BRUNSWICK, M STEIN, KE AF BRORSON, KA BRUNSWICK, M STEIN, KE TI XID B-CELLS - AN ANALYSIS OF ACTIVATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DMA,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A813 EP A813 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40601091 ER PT J AU CALVERT, RJ TASHIRO, Y SATCHITHANANDAM, S TEPPER, SA KRITCHEVSKY, D AF CALVERT, RJ TASHIRO, Y SATCHITHANANDAM, S TEPPER, SA KRITCHEVSKY, D TI FRUCTOOLIGOSACCHARIDE (FOS) FEEDING DECREASES SERUM-CHOLESTEROL LEVELS IN NON-HYPERCHOLESTEROLEMIC RATS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,LAUREL,MD 20708. MEIJI SEIKA KAISHA LTD,TOKYO 104,JAPAN. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A739 EP A739 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40600665 ER PT J AU CASSIDY, MM KRAMER, MG SATCHITHANANDAM, S AF CASSIDY, MM KRAMER, MG SATCHITHANANDAM, S TI MODULATION OF GLUCOSE-ABSORPTION AND INSULIN-RESPONSE BY DIETARY-FIBERS IN THE NEONATE RAT SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,LAUREL,MD 20708. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A703 EP A703 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40600459 ER PT J AU CASTERLINE, JL OLES, C KU, Y AF CASTERLINE, JL OLES, C KU, Y TI PRODUCTION OF SHIRT CHAIN FATTY-ACIDS IN-VITRO FROM VARIOUS FIBERS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A740 EP A740 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40600668 ER PT J AU ELLWOOD, KC JOHANNESSEN, JN BHATHENA, SJ AF ELLWOOD, KC JOHANNESSEN, JN BHATHENA, SJ TI BIOMARKERS USED TO ASSESS THE EFFECTS OF DIETARY SUGAR ALCOHOLS IN RATS SO FASEB JOURNAL LA English DT Meeting Abstract C1 USDA,CSREES,WASHINGTON,DC 20250. US FDA,LAUREL,MD 20708. USDA ARS,BELTSVILLE,MD 20705. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A999 EP A999 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40602176 ER PT J AU FRAZIERJESSEN, M CHRIST, M PANEK, RB MCCARTNEYFRANCIS, N KATONA, I BAUER, S KULKARNI, A WARD, J WAHL, S AF FRAZIERJESSEN, M CHRIST, M PANEK, RB MCCARTNEYFRANCIS, N KATONA, I BAUER, S KULKARNI, A WARD, J WAHL, S TI ABERRANT B-LYMPHOCYTE FUNCTION IN TGF-BETA-1(-/-) NULL MICE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A814 EP A814 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40601095 ER PT J AU KOSAKA, T WANG, T LEE, C AF KOSAKA, T WANG, T LEE, C TI MATERNAL IMMUNIZATION, HORMONE EFFECT, AND IMMUNE-RESPONSE OF YOUNG MICE TO PNEUMOCOCCAL TYPE 9V PS CONJUGATE SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A809 EP A809 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40601066 ER PT J AU MILLS, FC BURD, PR THOMPSON, WC MAX, EE AF MILLS, FC BURD, PR THOMPSON, WC MAX, EE TI ACTIVATED MAST-CELLS PRODUCE INTERLEUKIN-13 SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A802 EP A802 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40601028 ER PT J AU OHANLON, TP RABEN, N MILLER, FW AF OHANLON, TP RABEN, N MILLER, FW TI THE HUMAN HISTIDYL-TRANSFER-RNA SYNTHETASE LOCUS BIDIRECTIONAL PROMOTER DIRECTS THE SYNTHESIS OPPOSITE-STRAND MESSENGER-RNA THAT PREDICTS A POLYPEPTIDE HOMOLOGOUS WITH HRS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NIAMS,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A857 EP A857 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40601349 ER PT J AU PEDERSOLI, WM JACKSON, JD FROBISH, RA AF PEDERSOLI, WM JACKSON, JD FROBISH, RA TI DEPLETION OF GENTAMICIN IN THE MILK OF HOLSTEIN COWS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CVM,BELTSVILLE,MD 20705. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A691 EP A691 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40600387 ER PT J AU PERRIN, PJ RACKE, MK DAVIS, TA JUNE, CH SCOTT, DE AF PERRIN, PJ RACKE, MK DAVIS, TA JUNE, CH SCOTT, DE TI DIFFERENTIAL ROLES OF THE CTLA-4 LIGANDS CD80(B7-1) AND CD86(B7-2) IN THE INDUCTION OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS SO FASEB JOURNAL LA English DT Meeting Abstract C1 WASHINGTON UNIV,ST LOUIS,MO. USN,MED RES INST,BETHESDA,MD. US FDA,BETHESDA,MD 20014. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A788 EP A788 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40600943 ER PT J AU RHEE, HM PARK, DH AF RHEE, HM PARK, DH TI PLASMA-CATECHOLAMINE CONCENTRATIONS AND CENTRAL CATECHOLAMINE METABOLIZING ENZYME (CME) ACTIVITIES AFTER OPIOID ANTAGONISTS IN SPRAGUE-DAWLEY RATS - INTERACTION OF OPIOID AND SYMPATHETIC NERVOUS SYSTEMS FOR BLOOD-PRESSURE REGULATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A903 EP A903 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40601621 ER PT J AU SCHOLL, PF MUSSER, S KENSLER, TW GROOPMAN, JD AF SCHOLL, PF MUSSER, S KENSLER, TW GROOPMAN, JD TI CHARACTERIZATION OF AFLATOXIN-B1 MERCAPTURATE AS A BIOMARKER OF CHEMOPROTECTION STATUS SO FASEB JOURNAL LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. US FDA,WASHINGTON,DC 20204. RI Kensler, Thomas/D-8686-2014 OI Kensler, Thomas/0000-0002-6676-261X 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A943 EP A943 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40601855 ER PT J AU SCOTT, DE GOLDING, B AF SCOTT, DE GOLDING, B TI BRUCELLA-ABORTUS DIVERTS AN ANTIGEN-SPECIFIC OVALBUMIN ALUM IMMUNIZATION FROM AN ALLERGIC TH2-LIKE RESPONSE TO A TH1-LIKE RESPONSE SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A802 EP A802 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40601025 ER PT J AU VARRICCHIO, F GILL, P PURI, R AF VARRICCHIO, F GILL, P PURI, R TI INTERLEUKIN-4 RECEPTOR EXPRESSION IN HUMAN AIDS-RELATED KAPOSIS-SARCOMA IN-VIVO SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CBER,DIV EPIDEMIOL & BIOSTAT,ROCKVILLE,MD 20852. US FDA,CBER,DIV CELLULAR & GENE THERAPY,ROCKVILLE,MD 20852. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A832 EP A832 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40601203 ER PT J AU YAMAUCHI, A TAGA, K BLOOM, ET AF YAMAUCHI, A TAGA, K BLOOM, ET TI TARGET CELL-INDUCED APOPTOSIS OF IL-2-ACTIVATED HUMAN NK CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 10 PY 1995 VL 9 IS 4 BP A794 EP A794 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QM406 UT WOS:A1995QM40600977 ER PT J AU RAMACHANDRA, S MARTI, GE METCALF, RA RAVECHE, ES AF RAMACHANDRA, S MARTI, GE METCALF, RA RAVECHE, ES TI TYPE OF IMMUNOGLOBULIN JUNCTION PREDICTS CLONAL DEVELOPMENT OF B-1 CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 UMDNJ,GRAD SCH BIOMED SCI,DEPT PATHOL,NEWARK,NJ 07103. FDA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 10 PY 1995 SU 21A BP 128 EP 128 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT864 UT WOS:A1995QT86400458 ER PT J AU VACCHIO, MS ASHWELL, JD AF VACCHIO, MS ASHWELL, JD TI INFLUENCE OF THYMIC-DERIVED STEROIDS ON POSITIVE SELECTION OF THYMOCYTES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CBER,DIV HEMATOL PROD,BETHESDA,MD 20892. NCI,IMMUNE CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 10 PY 1995 SU 21A BP 132 EP 132 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT864 UT WOS:A1995QT86400473 ER PT J AU CALABRESI, PA MCFARLAND, PA COWAN, HF AF CALABRESI, PA MCFARLAND, PA COWAN, HF TI INDUCTION OF BOTH CONTROL AND CYTOKINE GENES IN RELATIVE RT-PCR ANALYSIS OF ACTIVATED LYMPHOCYTES FROM MULTIPLE-SCLEROSIS PATIENTS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 10 PY 1995 SU 21A BP 137 EP 137 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT864 UT WOS:A1995QT86400494 ER PT J AU SMITH, MJ AF SMITH, MJ TI VV/IV/III-METABOLISM IN ASCIDIAN HOMEOSTASIS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CFSAN,DIV NAT PROD,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 10 PY 1995 SU 21A BP 262 EP 262 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT864 UT WOS:A1995QT86400944 ER PT J AU KOCH, WH WOODGATE, R AF KOCH, WH WOODGATE, R TI IDENTIFICATION OF NEW UMUC HOMOLOGS BY DEGENERATE PRIMER PCR AMPLIFICATION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,MOLEC BIOL BRANCH,WASHINGTON,DC 20204. NICHHD,DNA REPLICAT REPAIR & MUTAGENESIS SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 10 PY 1995 SU 21A BP 333 EP 333 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT864 UT WOS:A1995QT86401205 ER PT J AU BERLIN, E BHATHENA, SJ MCCLURE, D PETERS, RC AF BERLIN, E BHATHENA, SJ MCCLURE, D PETERS, RC TI EFFECTS OF DIETARY MENHADEN AND CORN OILS ON RED-BLOOD-CELL MEMBRANE FLUIDITY IN HYPERCHOLESTEROLEMIC AND NORMOCHOLESTEROLEMIC MINIATURE SWINE SO FASEB JOURNAL LA English DT Meeting Abstract C1 USDA ARS,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. US FDA,DIV TOXICOL RES,LAUREL,MD 20708. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A463 EP A463 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98702708 ER PT J AU BOOTH, SL PENNINGTON, JAT SADOWSKI, JA AF BOOTH, SL PENNINGTON, JAT SADOWSKI, JA TI PRIMARY FOOD SOURCES AND ESTIMATED DIETARY INTAKES OF DIHYDRO-PHYLLOQUINONE IN THE AMERICAN DIET SO FASEB JOURNAL LA English DT Meeting Abstract C1 TUFTS UNIV,USDA,JEAN MAYER HUMAN NUTR RES CTR AGING,VITAMIN K LAB,BOSTON,MA 02111. US FDA,DIV NUTR,WASHINGTON,DC 20204. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A474 EP A474 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98702772 ER PT J AU DESAI, VG FREEMAN, JE DUFFY, LM COLLINS, JB HART, RW FEUERS, RJ AF DESAI, VG FREEMAN, JE DUFFY, LM COLLINS, JB HART, RW FEUERS, RJ TI THE EFFECT OF DIETARY RESTRICTION (DR) ON ELECTRON-TRANSPORT IN AGING SO FASEB JOURNAL LA English DT Meeting Abstract C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A173 EP A173 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701035 ER PT J AU GOLDING, B GOLDING, H INMAN, J SCOTT, DE AF GOLDING, B GOLDING, H INMAN, J SCOTT, DE TI HIV V3 PEPTIDE CONJUGATED TO BRUCELLA-ABORTUS IS IMMUNOGENIC IN CD4+ T-CELL DEFICIENT MICE SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A207 EP A207 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701229 ER PT J AU KELLEHER, JK KHARROUBI, AT ALDAGHLAS, TA HOLLERAN, AL SATCHITHANANDAM, S AF KELLEHER, JK KHARROUBI, AT ALDAGHLAS, TA HOLLERAN, AL SATCHITHANANDAM, S TI EVALUATING CARBON-SOURCES FOR RAT CHYLOMICRON TRIGLYCERIDES USING ISOTOPOMER SPECTRAL-ANALYSIS (ISA) AND C-13 SUBSTRATES SO FASEB JOURNAL LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. US FDA,WASHINGTON,DC 20037. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A470 EP A470 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98702745 ER PT J AU LEE, SC VINCENT, RW PROSKY, L JIA, MY MIN, DB AF LEE, SC VINCENT, RW PROSKY, L JIA, MY MIN, DB TI DEFINITION AND ANALYSIS OF COMPLEX CARBOHYDRATES SO FASEB JOURNAL LA English DT Meeting Abstract C1 KELLOGG CO,BATTLE CREEK,MI 49017. US FDA,WASHINGTON,DC 20204. OHIO STATE UNIV,COLUMBUS,OH 43210. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A454 EP A454 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98702652 ER PT J AU MORRIS, P GILLAM, MP ALLEN, RR PAULE, MG AF MORRIS, P GILLAM, MP ALLEN, RR PAULE, MG TI ACUTE EFFECTS OF NALOXONE ON OPERANT BEHAVIORS IN THE RHESUS-MONKEY SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A101 EP A101 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98700588 ER PT J AU NEURATH, MF STUBER, ER MAX, EE STROBER, W AF NEURATH, MF STUBER, ER MAX, EE STROBER, W TI THE TRANSCRIPTION FACTOR BSAP REPRESSES THE IMMUNOGLOBULIN HEAVY-CHAIN 3'ALPHA ENHANCER IN-VIVO BY INHIBITION OF BINDING OF NF-ALPHA-P, AN ETS-LIKE PROTEIN THAT CONTROLS IG GENE-TRANSCRIPTION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,LCI,MIS,BETHESDA,MD 20892. US FDA,CYBER,CELL & VIRAL REGULAT LAB,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A196 EP A196 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701169 ER PT J AU POGRIBNY, IP POIRIER, LA JAMES, SJ AF POGRIBNY, IP POIRIER, LA JAMES, SJ TI NONRANDOM ALTERATIONS IN P53 GENE METHYLATION ARE INDUCED BY DIETARY METHYL DEFICIENCY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A178 EP A178 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701062 ER PT J AU PRAVDENKOVA, SV BASNAKIAN, AG JAMES, SJ ANDERSEN, BJ AF PRAVDENKOVA, SV BASNAKIAN, AG JAMES, SJ ANDERSEN, BJ TI DNA FRAGMENTATION IN RAT-BRAIN AFTER SEVERE CLOSED-HEAD INJURY SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A381 EP A381 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98702229 ER PT J AU SATCHITHANANDAM, S TASHIRO, Y WIESENFELD, P FLYNN, T CALVERT, RJ KRITCHEVSKY, D AF SATCHITHANANDAM, S TASHIRO, Y WIESENFELD, P FLYNN, T CALVERT, RJ KRITCHEVSKY, D TI EFFECT OF PEANUT OIL (PNO) AND RANDOMIZED PEANUT OIL (RPNO) IN THE TRANSPORT OF CHOLESTEROL IN THE LYMPH OF RAT SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,LAUREL,MD. MEIJI SEIKA KAISHA LTD,KAWASAKI,KANAGAWA,JAPAN. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A194 EP A194 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701153 ER PT J AU STOLOFF, L AF STOLOFF, L TI SPERM COUNT EXPLANATION SO CHEMICAL & ENGINEERING NEWS LA English DT Letter C1 US FDA,DELRAY BEACH,FL. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0009-2347 J9 CHEM ENG NEWS JI Chem. Eng. News PD MAR 6 PY 1995 VL 73 IS 10 BP 5 EP 5 PG 1 WC Chemistry, Multidisciplinary; Engineering, Chemical SC Chemistry; Engineering GA QK256 UT WOS:A1995QK25600006 ER PT J AU RHEINSTEIN, PH AF RHEINSTEIN, PH TI SIGNIFICANT FDA APPROVALS IN 1994 SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material RP RHEINSTEIN, PH (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD MAR PY 1995 VL 51 IS 4 BP 888 EP 890 PG 3 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA QM003 UT WOS:A1995QM00300023 PM 7887364 ER PT J AU JACOBSON, ED AF JACOBSON, ED TI UNTITLED SO AMERICAN INDUSTRIAL HYGIENE ASSOCIATION JOURNAL LA English DT Letter RP JACOBSON, ED (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,1390 PICCARD DR,ROCKVILLE,MD 20850, USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 SN 0002-8894 J9 AM IND HYG ASSOC J JI Am. Ind. Hyg. Assoc. J. PD MAR PY 1995 VL 56 IS 3 BP 295 EP 295 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA QN023 UT WOS:A1995QN02300012 PM 7717273 ER PT J AU BYRD, JC HERTLER, AA WEISS, RB FREIMAN, J KWEDER, SL DIEHL, LF AF BYRD, JC HERTLER, AA WEISS, RB FREIMAN, J KWEDER, SL DIEHL, LF TI FATAL RECURRENCE OF AUTOIMMUNE HEMOLYTIC-ANEMIA FOLLOWING PENTOSTATIN THERAPY IN A PATIENT WITH A HISTORY OF FLUDARABINE-ASSOCIATED HEMOLYTIC-ANEMIA SO ANNALS OF ONCOLOGY LA English DT Note DE AUTOIMMUNE HEMOLYTIC ANEMIA; FLUDARABINE; PENTOSTATIN; CHRONIC LYMPHOCYTIC LEUKEMIA; ADVERSE DRUG REACTION ID CHRONIC LYMPHOCYTIC-LEUKEMIA; DEOXYCOFORMYCIN C1 UNIFORMED SERV UNIV HLTH SCI,WASHINGTON,DC. PS,DEPT HEMATOL ONCOL,ROCKWOOD CLIN,SPOKANE,WA. US FDA,CTR DRUG EVALUAT & RES,EPIDEMIOL BRANCH,ROCKVILLE,MD 20857. RP BYRD, JC (reprint author), WALTER REED ARMY MED CTR,DEPT MED,HEMATOL ONCOL SERV,WASHINGTON,DC 20307, USA. NR 13 TC 29 Z9 29 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 1995 VL 6 IS 3 BP 300 EP 301 PG 2 WC Oncology SC Oncology GA QX057 UT WOS:A1995QX05700019 PM 7612497 ER PT J AU FARRINGTON, JK MARTZ, EL WELLS, SJ ENNIS, CC HOLDER, J LEVCHUK, JW AVIS, KE HOFFMAN, PS HITCHINS, AD MADDEN, JM AF FARRINGTON, JK MARTZ, EL WELLS, SJ ENNIS, CC HOLDER, J LEVCHUK, JW AVIS, KE HOFFMAN, PS HITCHINS, AD MADDEN, JM TI ABILITY OF LABORATORY METHODS TO PREDICT IN-USE EFFICACY OF ANTIMICROBIAL PRESERVATIVES IN AN EXPERIMENTAL COSMETIC (VOL 60, PG 4553, 1994) SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Correction, Addition C1 UNIV TENNESSEE,DEPT PHARMACEUT,MEMPHIS,TN 38163. UNIV TENNESSEE,DEPT MICROBIOL & IMMUNOL,MEMPHIS,TN 38163. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. RP FARRINGTON, JK (reprint author), SCHERING PLOUGH HLTH CARE PROD,MEMPHIS,TN 38151, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAR PY 1995 VL 61 IS 3 BP 1169 EP 1169 PG 1 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA QJ889 UT WOS:A1995QJ88900055 PM 16534967 ER PT J AU WHITE, B BAUER, EA GOLDSMITH, LA HOCHBERG, MC KATZ, LM KORN, JH LACHENBRUCH, PA LEROY, EC MITRANE, MP PAULUS, HE POSTLETHWAITE, AE STEEN, VD AF WHITE, B BAUER, EA GOLDSMITH, LA HOCHBERG, MC KATZ, LM KORN, JH LACHENBRUCH, PA LEROY, EC MITRANE, MP PAULUS, HE POSTLETHWAITE, AE STEEN, VD TI GUIDELINES FOR CLINICAL-TRIALS IN SYSTEMIC-SCLEROSIS (SCLERODERMA) .1. DISEASE-MODIFYING INTERVENTIONS SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ARTHRITIS; INVOLVEMENT; PHYSICIANS; THERAPY AB Objective. To develop guidelines for therapeutic trials designed to improve the overall course of systemic sclerosis (SSc), that is, to reduce the development of significant organ damage or death, Methods, A committee developed general guidelines for patient inclusion and exclusion criteria, randomization, blinding of patients and physicians, controls, duration of the trial, investigator training, responses, samples size, study dropouts, statistical analyses, data management, and safety monitoring, Delphi and nominal group techniques were used. Results. Briefly, patients with diffuse cutaneous SSc of less than 24 months' duration should be included because they are at greatest risk for the development of severe organ damage and death, Patients should be excluded if they have other connective tissue diseases, SSc-like illnesses related to exposures or ingestions, severe existing internal organ damage, an unacceptable risk of side effects, dr concurrent therapies that might independently influence the outcome, Randomized, double-blind, placebo-controlled trials are preferred, The treatment and followup period must be long enough to permit observation of any disease modification, which is likely to require 18-36 months, unless an extraordinarily effective therapy is identified, Responses selected should be quantitative, consistently add accurately reflect activity of SSc in major target organs (not solely the skin), be sensitive to change, and be standardized, with limited variability, An example of a set of responses is given, Surrogate responses are desirable, but none have been validated as correlating with organ damage. Conclusion, Guidelines have been established for trials of disease-modifying interventions in SSc, These guidelines will need to be altered as additional information becomes available. Any given protocol will be individualized based on the nature of the intervention and objectives of the study, Nonetheless, each study team should develop a protocol that meets the spirit of these guidelines. C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. VET ADM MED CTR,BALTIMORE,MD 21218. STANFORD UNIV,MED CTR,STANFORD,CA 94305. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. US FDA,PILOT DRUG EVALUAT STAFF,ROCKVILLE,MD 20857. BOSTON UNIV,SCH MED,BOSTON,MA 02118. BOSTON VA MED CTR,BOSTON,MA. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. MED UNIV S CAROLINA,CHARLESTON,SC 29425. US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. UNIV TENNESSEE,SCH MED,MEMPHIS,TN. VET ADM MED CTR,MEMPHIS,TN 38104. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA. RP WHITE, B (reprint author), AMER COLL RHEUMATOL,60 EXECUT PK S,SUITE 150,ATLANTA,GA 30329, USA. NR 25 TC 97 Z9 99 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 1995 VL 38 IS 3 BP 351 EP 360 DI 10.1002/art.1780380309 PG 10 WC Rheumatology SC Rheumatology GA QL615 UT WOS:A1995QL61500008 PM 7880189 ER PT J AU TOSATO, G TAGA, K ANGIOLILLO, AL SGADARI, C AF TOSATO, G TAGA, K ANGIOLILLO, AL SGADARI, C TI EPSTEIN-BARR-VIRUS AS AN AGENT OF HEMATOLOGICAL DISEASE SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; LINKED LYMPHOPROLIFERATIVE SYNDROME; NON-HODGKINS-LYMPHOMA; REED-STERNBERG CELLS; INDUCED INFECTIOUS-MONONUCLEOSIS; BONE-MARROW TRANSPLANTATION; LATENT MEMBRANE-PROTEIN; C-MYC ONCOGENE; MOLECULAR GENETIC-ANALYSIS; AFRICAN BURKITTS-LYMPHOMA C1 KANAZAWA UNIV,SCH MED,DEPT PEDIAT,KANAZAWA,ISHIKAWA 920,JAPAN. CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. UNIV ROMA LA SAPIENZA,SCH MED,INST HEMATOL,I-00161 ROME,ITALY. RP TOSATO, G (reprint author), US FDA,CTR BIOL RES & REVIEW,DIV HEMATOL PROD,OFF THERAPEUT RES & REVIEW,29A-2D16,ROCKVILLE,MD 20852, USA. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 312 TC 19 Z9 21 U1 0 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD MAR PY 1995 VL 8 IS 1 BP 165 EP 199 DI 10.1016/S0950-3536(05)80237-9 PG 35 WC Hematology SC Hematology GA QW108 UT WOS:A1995QW10800009 PM 7663046 ER PT J AU WOOD, DJ HEATH, AB SAWYER, LA AF WOOD, DJ HEATH, AB SAWYER, LA TI A WHO COLLABORATIVE STUDY ON ASSAYS OF THE ANTIGENIC CONTENT OF INACTIVATED POLIOVIRUS VACCINES SO BIOLOGICALS LA English DT Article ID QUANTITATION AB In the first phase of a two part WHO Collaborative study, fourteen laboratories from ten countries estimated the antigenic content of six trivalent inactivated poliovirus vaccine preparations using in vitro methods. All laboratories used a candidate standard method for D antigen assay (method A) and eight contributed results from established 'in-house' methods (method B). All methods assayed D antigen in an antigen capture ELISA format. Monoclonal antibodies were used as detector reagents in method A and in some laboratories for method B. The average difference in potency estimates for duplicate preparations A and C was used to assess within assay variation. Overall this was found to be 22% and 19% for methods A and B respectively. Within laboratory variation was measured as the geometric coefficient of variation for between assay repeatability. Results for methods A and B, 28% and 26% respectively were again very similar. Variation in potency estimates between laboratories was in the range 2- to 5-fold for most samples and most laboratories irrespective of the method used. However, a maximum 24-fold difference occurred when ail results were taken into account. Method A gave significantly enhanced potency estimates for the type 3 component of preparation B, a vaccine shown to be immunogenic in humans in clinical trials, compared to method B. Method A also failed to assay the type 3 component of preparation F which was prepared by inactivation of the Sabin 3 strain of poliovirus. Further work is required to identify monoclonal antibodies, or combinations of monoclonal antibodies, suitable for universal application in D antigen assays of inactivated poliovirus vaccines. Further work is also required to improve control of the antigen-capture ELISA in some laboratories. The second phase of this WHO Collaborative Study evaluated the proficiency of in vivo potency assays. These results together with an evaluation of the correlation of immunogenicity and antigenic assay plus assessment of candidate reference materials will be reported separately. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. RP WOOD, DJ (reprint author), NATL INST BIOL STAND & CONTROLS,BLANCHE LANE,POTTERS BAR EN6 3QG,HERTS,ENGLAND. NR 4 TC 22 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 1995 VL 23 IS 1 BP 83 EP 94 DI 10.1016/1045-1056(95)90017-9 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA QR822 UT WOS:A1995QR82200017 PM 7619442 ER PT J AU SZABO, G WEAVER, JL PINE, PS RAO, PE ASZALOS, A AF SZABO, G WEAVER, JL PINE, PS RAO, PE ASZALOS, A TI CROSS-LINKING OF CD4 IN A TCR/CD3-JUXTAPOSED INHIBITORY STATE - A PFRET STUDY SO BIOPHYSICAL JOURNAL LA English DT Article ID T-CELL RECEPTOR; TYROSINE-PROTEIN-KINASE; PHYSICAL ASSOCIATION; ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; MOLECULES CD4; LYMPHOCYTES-T; ACTIVATION; P56LCK AB Instances when T cell activation via the T cell receptor/CD3 complex is suppressed by anti-CD4 Abs are generally attributed either to the topological separation of CD4-p56(kk) from CD3, or their improper apposition. Photobleaching fluorescence resonance energy transfer measurements permitted direct analysis of these alternatives on human peripheral blood lymphocytes. Distinction between changes of relative antigen densities or positioning was made possible by simultaneously recording donor and acceptor fluorescence in the energy transfer experiment performed on homogeneous populations of flow-sorted cells. We show here that CD4 stays in the molecular vicinity of CD3, while anti-CD3 stimulation is suppressed by anti-CD4 or cross-linked HIV gp120. Our data suggest that cross-linking of CD4 through particular epitopes is capable of inhibiting activation driven by Abs binding to specific sites on CD3 without major topological sequestration of the Ags, in such a way that additional positive signals will also be affected. Thus, these and other related cases of negative signaling via CD4 may be interpreted in terms of functional uncoupling rather than a wide physical separation of CD4 from the T cell receptor-CD3 complex. C1 US FDA,CTR DRUG EVALUAT & RES,WASHINGTON,DC 20204. ORTHO DIAGNOST SYST INC,RARITAN,NJ 08869. RP SZABO, G (reprint author), DEBRECEN UNIV MED,SCH MED,DEPT BIOPHYS,NAGYERDEI KRT 98,H-4012 DEBRECEN,HUNGARY. NR 36 TC 16 Z9 16 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 1995 VL 68 IS 3 BP 1170 EP 1176 PG 7 WC Biophysics SC Biophysics GA QH944 UT WOS:A1995QH94400045 PM 7538802 ER PT J AU HERRENOSAENZ, D EVANS, FE BELAND, FA FU, PP AF HERRENOSAENZ, D EVANS, FE BELAND, FA FU, PP TI IDENTIFICATION OF 2 N-2-DEOXYGUANOSINYL DNA-ADDUCTS UPON NITROREDUCTION OF THE ENVIRONMENTAL MUTAGEN 1-NITROPYRENE SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID SPRAGUE-DAWLEY RATS; METABOLIC-ACTIVATION; SALMONELLA-TYPHIMURIUM; P-32-POSTLABELING ANALYSIS; AROMATIC-HYDROCARBONS; A/J MICE; INVITRO; BINDING; CARCINOGEN; TISSUES AB 1-Nitropyrene, the most abundant nitro-polycyclic aromatic hydrocarbon in the environment, is a known mammalian and bacterial mutagen and a tumorigen in animals. Early studies on DNA adduct characterization for 1-nitropyrene identified N-(deoxyguanosin-8-y1)-1-aminopyrene as the major product from the modification of calf thymus DNA with N-hydroxy-1-aminopyrene, the activated metabolite from nitroreduction of l-nitropyrene. In this paper, we report the identification of two N-2-deoxyguanosinyl adducts, in addition to N-(deoxyguanosin-8-y1)-1-aminopyrene, formed from the reaction of N-hydroxy-1-aminopyrene, prepared in situ, with calf thymus DNA. These DNA adducts were identified as 6-(deoxyguanosin-N-2-yl)-1-aminopyrene and 8-(deoxyguanosin-N-2-yl)-1-aminopyrene. The two N-2-deoxyguanosinyl adducts were also identified in an ascorbic acid-catalyzed activation of 1-nitrosopyrene and in the mammary gland of female Sprague-Dawley rats administered 1-nitropyrene. The DNA adducts were also formed when 1-nitropyrene was metabolized by xanthine oxidase in the presence of calf thymus DNA, and when 1-nitropyrene was activated by rat liver microsomes and cytosols, as well as from DNA isolated from Salmonella typhimurium suspension cultures incubated with 1-nitropyrene. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 45 TC 27 Z9 27 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 1995 VL 8 IS 2 BP 269 EP 277 DI 10.1021/tx00044a600 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA QK539 UT WOS:A1995QK53900013 PM 7766811 ER PT J AU WAAG, DM MCKEE, KT SANDSTROM, G PRATT, LLK BOLT, CR ENGLAND, MJ NELSON, GO WILLIAMS, JC AF WAAG, DM MCKEE, KT SANDSTROM, G PRATT, LLK BOLT, CR ENGLAND, MJ NELSON, GO WILLIAMS, JC TI CELL-MEDIATED AND HUMORAL IMMUNE-RESPONSES AFTER VACCINATION OF HUMAN VOLUNTEERS WITH THE LIVE VACCINE STRAIN OF FRANCISELLA-TULARENSIS SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID POLYACRYLAMIDE GELS; HUMAN TULAREMIA; DIAGNOSIS; AGGLUTININS; STIMULATION; INFECTION; PROTEINS; DISEASE AB The specific humoral and cell-mediated immune responses of human volunteers vaccinated with the Francisella tularensis live vaccine strain (LVS) were evaluated. In the search for an optimal antigen to measure the immunogenicity of the vaccine in an enzyme-linked immunosorbent assay, we tested irradiation-killed LVS, an aqueous ether extract of the LVS (EEx), lipopolysaccharide (LPS) from LVS, and a virulent strain (SCHU4). Volunteers were immunized with LVS by scarification. Immunoglobulin G (IgG) responses to LVS and LPS gave the highest background titers when tested with sera from unimmunized volunteers, whereas IgA, IgG, and IgM background titers to EEx and SCHU4 were low. Vaccination caused a significant rise (P < 0.01) in IgA, IgG, and IgM titers to all antigens tested, except for the IgG response to LPS. Eighty percent of vaccinated volunteers developed a positive IgG response to EEx 14 days postvaccination, while 50% were positive to LVS. By day 14 after vaccination, 70% of immunized volunteers exhibited a positive response to EEx in an in vitro peripheral blood lymphocyte proliferation assay. EEx, a specific and sensitive antigen for evaluating immune responses of vaccinated volunteers, may be a superior antigen for the diagnosis of tularemia. C1 USA,MED RES INST INFECT DIS,DIV MED,FT DETRICK,MD 21702. USA,MED RES INST INFECT DIS,DIV BIOMETR & INFORMAT MANAGEMENT,FT DETRICK,MD 21702. US FDA,CTR BIOL EVALUAT & RES,OFF VACCINES RES & REVIEW,DIV VACCINES & RELATED PROD APPLICAT,BETHESDA,MD 20892. UMEA UNIV,DEPT INFECT DIS,S-90185 UMEA,SWEDEN. NATL DEF RES ESTAB,DEPT MICROBIOL,S-90182 UMEA,SWEDEN. RP WAAG, DM (reprint author), USA,MED RES INST INFECT DIS,DIV BACTERIOL,PATHOGENESIS & IMMUNOL BRANCH,FT DETRICK,MD 21702, USA. NR 24 TC 30 Z9 31 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAR PY 1995 VL 2 IS 2 BP 143 EP 148 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QK802 UT WOS:A1995QK80200004 PM 7697521 ER PT J AU NDIMBIE, OK NEDJAR, S KINGSLEY, L RIDDLE, P RINALDO, C AF NDIMBIE, OK NEDJAR, S KINGSLEY, L RIDDLE, P RINALDO, C TI LONG-TERM SEROLOGIC FOLLOW-UP OF HEPATITIS-C VIRUS-SEROPOSITIVE HOMOSEXUAL MEN SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; POLYMERASE CHAIN-REACTION; MULTICENTER AIDS COHORT; NON-B-HEPATITIS; BLOOD-DONORS; IGM ANTIBODY; NON-A; INFECTION; ASSAY; RNA AB Hepatitis C virus (HCV) infection may go undiagnosed and continue to present a source of community-acquired or transfusion-associated infection because of shortcomings in sensitivity, specificity, and reproducibility of serologic tests. This project was designed to longitudinally study persons who were HCV seropositive or were at risk for seroconversion to characterize the course of infection. Sequential serum samples obtained semiannually from 617 homosexual male volunteers were available for study from the Pittsburgh site of the Multicenter AIDS Cohort Study. Testing by anti-HCV enzyme immunoassay (ELA) was performed on baseline (1984 to 1985) and most-recent (censor date, August 1992) samples. Selected samples were also assayed for alanine aminotransferase and by recombinant immunoblot (RIBA II) and nested PCR, A total of 17 of 617 (2.8%) men were HCV seropositive at entry, Of the 600 seronegative men, 9 converted to HCV seropositive during the study interval. Parenteral sources of exposure could be identified in 6 of these 26 HCV-seropositive men. Four men were HCV seropositive at baseline and seronegative at;their most recent visit. Of the 26 HCV seropositive men, 12 were also seropositive for human immunodeficiency virus, EIA analysis of 298 longitudinal samples from the 26 men revealed three patterns of HCV seropositivity: persistent, intermittent, and rare, Nine men (35%) showed intermittent or rare seropositivity with periods of over 1 year between some seropositive samples, PCR was positive in 76% of the HCV EIA-positive and 84% of the RIBA-positive samples, Thus, a low but significant number of homosexual men were HCV seropositive with variable positivity over several years of follow-up. A portion of these men become HCV seronegative, Individuals who exhibit intermittent or rare seropositivity are a challenge to diagnosis. C1 UNIV PITTSBURGH,MED CTR,DEPT PATHOL,PITTSBURGH,PA. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15213. US FDA,DIV TRANSFUS SCI,KENSINGTON,MD 20895. RP NDIMBIE, OK (reprint author), INST TRANSFUS MED,VIRAL TESTING LAB,3636 BLVD ALLIES,PITTSBURGH,PA 15213, USA. FU NIAID NIH HHS [U01-AI-35041, N01-AI-72632] NR 18 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAR PY 1995 VL 2 IS 2 BP 219 EP 224 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QK802 UT WOS:A1995QK80200018 PM 7697532 ER PT J AU DIGGS, CL HINES, F WELLDE, BT AF DIGGS, CL HINES, F WELLDE, BT TI PLASMODIUM-FALCIPARUM - PASSIVE-IMMUNIZATION OF AOTUS-LEMURINUS GRISEIMEMBRA WITH IMMUNE SERUM SO EXPERIMENTAL PARASITOLOGY LA English DT Article AB Owl monkeys (Aotus lemurinus griseimembra) were immunized against Plasmodium falciparum by infection and drug cure. After challenge, 3 of 4 monkeys developed extended prepatent periods and low grade parasitemias followed by self cure. The fourth monkey did not develop a patent infection. Immune monkey serum passively transferred at the time of challenge conferred immunity to 20 naive monkeys. Immunity was characterized by extended prepatent periods in 19 monkeys, low levels of parasitemia (less than or equal to 1%) followed by self cure in 12 animals, and lack of detectable infection in 3 recipient monkeys, Immune serum collected from monkeys undergoing repeated challenges afforded more protection than serum from singly infected monkeys. However, single doses of hyperimmune serum appeared to be as effective as multiple doses. Normal serum had no effect on the course of infection in 12 monkeys. These studies confirm that owl monkeys can be immunized by infection and cure and demonstrate that this immunity can, in large part, be transferred to nonimmune recipients with serum from immune donors. (C) 1995 Academic Press, Inc. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SCI ANAL & SUPPORT,DIV GEN SCI SUPPORT,WASHINGTON,DC 20204. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT IMMUNOL,WASHINGTON,DC 20307. RP DIGGS, CL (reprint author), JOHNS HOPKINS UNIV,DEPT INT HLTH,103 E MT ROYAL AVE,2B,BALTIMORE,MD 21202, USA. NR 16 TC 8 Z9 9 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD MAR PY 1995 VL 80 IS 2 BP 291 EP 296 DI 10.1006/expr.1995.1035 PG 6 WC Parasitology SC Parasitology GA QP934 UT WOS:A1995QP93400015 PM 7895839 ER PT J AU LAMBERT, LA HINES, FA EPPLEY, RM AF LAMBERT, LA HINES, FA EPPLEY, RM TI LACK OF INITIATION AND PROMOTION POTENTIAL OF DEOXYNIVALENOL FOR SKIN TUMORIGENESIS IN SENCAR MICE SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID FUSARIUM MYCOTOXINS; MOUSE SKIN; VOMITOXIN; ZEARALENONE; WHEAT; TOXICITY; LESIONS; TOXINS; CELLS; CORN AB The mycotoxin deoxynivalenol (DON; vomitoxin) was tested for its potential to initiate or promote skin tumours through a two-stage treatment regimen in female Sencar mice. DON's capability for initiation was tested by applying a single topical dose (200 mu g) followed by multiple treatments of the promoter phorbol 12-myristate 13-acetate (PMA). The test for promotion involved initiation with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) followed by multiple DON treatments (50 mu g). Appropriate control groups were included in the study design. Mice were observed for 26 wk and skin tumours were counted. Results of the study showed that DON was not an initiator or a promoter. When DON was tested as an initiator, there were no statistically significant differences in the number of cumulative tumours or the number of tumour-bearing mice between the DON-initiated/PMA-promoted group and its control, the vehicle-initiated/PMA-promoted group. When DON was administered as a promoter, no tumours were observed. Histopathology of the skin revealed that DON induced a mild diffuse squamous hyperplasia, but there was no progression of the lesion to neoplasia. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV GEN SCI SUPPORT,PATHOL BRANCH,WASHINGTON,DC 20204. US FDA,CTR FOOD SAFETY & APPL NUTR,DIV NAT PROD,BIOANALYT CHEM BRANCH,WASHINGTON,DC 20204. RP LAMBERT, LA (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV SCI & APPL TECHNOL,COSMET TOXICOL BRANCH,WASHINGTON,DC 20204, USA. NR 24 TC 9 Z9 10 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD MAR PY 1995 VL 33 IS 3 BP 217 EP 222 DI 10.1016/0278-6915(94)00132-8 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA QQ765 UT WOS:A1995QQ76500007 PM 7896232 ER PT J AU LIPNICK, RL COTRUVO, JA HILL, RN BRUCE, RD STITZEL, KA WALKER, AP CHU, I GODDARD, M SEGAL, L SPRINGER, JA MYERS, RC AF LIPNICK, RL COTRUVO, JA HILL, RN BRUCE, RD STITZEL, KA WALKER, AP CHU, I GODDARD, M SEGAL, L SPRINGER, JA MYERS, RC TI COMPARISON OF THE UP-AND-DOWN, CONVENTIONAL LD(50), AND FIXED-DOSE ACUTE TOXICITY PROCEDURES SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID LD50 TEST; VALIDATION; ANIMALS; NUMBER AB The up-and-down procedure (UDP), fixed-dose procedure (FDP) and conventional LD(50) tests were compared to determine their consistency in chemical hazard classification for acute oral toxicity according to the European Economic Community (EEC) system. There was consistent classification for 23 out of 25 cases between the UDP and the conventional LD(50) results, in 16 out of 20 cases between the FDP and the conventional LD(50), and in seven out of 10 cases between the UDP and the FDP. The UDP needed only between six and 10 animals of one sex (fewer than either the LD(50) or the FDP). Available literature indicates that the sexes are usually similar in their acute toxicity responses and that of females are often more sensitive than males when acute toxicity differences do exist, thus obviating the need for both sexes to be tested in most cases. Unlike the FDP, the UDP also estimates an LD(50), thus providing data directly applicable to all current hazard classification systems based on acute oral toxicity. C1 PROCTER & GAMBLE CO,MIAMI VALLEY LABS,CINCINNATI,OH 45239. HLTH & WELF CANADA,HLTH PROTECT BRANCH,OTTAWA,ON K1A 0L2,CANADA. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. UNION CARBIDE CORP,BUSHY RUN RES CTR,EXPORT,PA 15632. RP LIPNICK, RL (reprint author), US EPA,OFF PREVENT PESTICIDES & TOX SUBSTANCES,WASHINGTON,DC 20460, USA. NR 38 TC 68 Z9 77 U1 0 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD MAR PY 1995 VL 33 IS 3 BP 223 EP 231 DI 10.1016/0278-6915(94)00136-C PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA QQ765 UT WOS:A1995QQ76500008 PM 7896233 ER PT J AU HORWITZ, W ALBERT, R AF HORWITZ, W ALBERT, R TI PRECISION IN ANALYTICAL MEASUREMENTS - EXPECTED VALUES AND CONSEQUENCES IN GEOCHEMICAL ANALYSES SO FRESENIUS JOURNAL OF ANALYTICAL CHEMISTRY LA English DT Article ID FOODS AB Over the years the authors have developed an empirical formula for the relative standard deviation among laboratories (RSD(R), %) as a function of concentration C, expressed as a decimal fraction: RSD(R) = 2((1-0.51og) (C)) approximate to) 2C((-0.1505)). This formula predicts that starting with a concentration of 100% (pure materials; C = 1.00), RSD(R) will be 2%, increasing by a factor of 2 for each decrease in C of 2 orders of magnitude. It has been a useful guide to acceptable precision in the fields of agricultural, pharmaceutical, and nutritional chemical analysis. It has now been found that this formula is also useful for interpreting the quality of reported analyses of various reference materials available to geochemists. If a ratio is calculated of the found RSD(R) value to the RSD(R) value calculated from the formula, an easily interpreted limiting parameter is generated. A ratio > 2 provides a rational reference point for interpreting the uncertainty of the analytical portion of the total variability of geochemical concentration estimates. Such a high ratio indicates excessive among-laboratories precision, reflecting large systematic errors on the part of one or more laboratories. The formula quantitates the concept of the transformation of the individual systematic errors of the laboratories into the random error of the group. RP HORWITZ, W (reprint author), US FDA,WASHINGTON,DC 20204, USA. NR 10 TC 19 Z9 21 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0937-0633 J9 FRESEN J ANAL CHEM JI Fresenius J. Anal. Chem. PD MAR PY 1995 VL 351 IS 6 BP 507 EP 513 DI 10.1007/BF00322724 PG 7 WC Chemistry, Analytical SC Chemistry GA RH362 UT WOS:A1995RH36200006 ER PT J AU WAYNANT, RW AF WAYNANT, RW TI UNTITLED SO IEEE CIRCUITS AND DEVICES MAGAZINE LA English DT Editorial Material RP WAYNANT, RW (reprint author), US FDA,1901 CHAPMAN AVE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 8755-3996 J9 IEEE CIRCUIT DEVIC JI IEEE Circuit Devices Mag. PD MAR PY 1995 VL 11 IS 2 BP 2 EP 2 PG 1 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA QL797 UT WOS:A1995QL79700001 ER PT J AU WAYNANT, RW AF WAYNANT, RW TI MATLAB FOR WINDOWS SO IEEE CIRCUITS AND DEVICES MAGAZINE LA English DT Software Review RP WAYNANT, RW (reprint author), US FDA,1901 CHAPMAN AVE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 8755-3996 J9 IEEE CIRCUIT DEVIC JI IEEE Circuit Devices Mag. PD MAR PY 1995 VL 11 IS 2 BP 56 EP 58 PG 3 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA QL797 UT WOS:A1995QL79700015 ER PT J AU CAO, XQ SHORES, EW HULI, J ANVER, MR KELSALL, BL RUSSELL, SM DRAGO, J NOGUCHI, M GRINBERG, A BLOOM, ET PAUL, WE KATZ, SI LOVE, PE LEONARD, WJ AF CAO, XQ SHORES, EW HULI, J ANVER, MR KELSALL, BL RUSSELL, SM DRAGO, J NOGUCHI, M GRINBERG, A BLOOM, ET PAUL, WE KATZ, SI LOVE, PE LEONARD, WJ TI DEFECTIVE LYMPHOID DEVELOPMENT IN MICE LACKING EXPRESSION OF THE COMMON CYTOKINE RECEPTOR-GAMMA CHAIN SO IMMUNITY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; EPIDERMAL T-CELLS; IL-2 RECEPTOR; BETA-CHAIN; FUNCTIONAL COMPONENT; MONOCLONAL-ANTIBODY; GENE; DISEASE; REQUIREMENT; ACTIVATION AB The common gamma chain (gamma(c)) of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors is defective in hu mans with XSCID. Mice lacking gamma(c) expression had hypoplastic thymuses; the thymocytes responded to gamma(c)-independent mitogens, but not gamma(c)-dependent stimuli. Splenic T cells were diminished at 3 weeks of age, but CD4+ T cells markedly increased by 4 weeks. B cells were greatly diminished, in contrast with the situation in XSCID. NK cells, gamma delta intestinal intraepithelial lymphocytes, dendritic epidermal T cells, peripheral lymph nodes, and gut-associated lymphoid tissue were absent. These findings underscore the importance of gamma(c) in lymphoid development. Moreover, differences in humans and mice lacking ye expression indicate species-specific differences in the roles of gamma(c)-dependent cytokines or in the existence of redundant pathways. These mice provide an important model for studying the pathophysiology of and gene therapy for human XSCID. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,DIV HEMATOL PROD,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,CELLULAR IMMUNOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP INC,PROGRAM RESOURCES,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. RP CAO, XQ (reprint author), NHLBI,MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. RI Russell, Sarah/B-9341-2009 OI Russell, Sarah/0000-0001-5826-9641 NR 62 TC 683 Z9 691 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 1995 VL 2 IS 3 BP 223 EP 238 DI 10.1016/1074-7613(95)90047-0 PG 16 WC Immunology SC Immunology GA QP276 UT WOS:A1995QP27600002 PM 7697543 ER PT J AU DEVELASCO, EA MERKUS, D ANDERTON, S VERHEUL, AFM LIZZIO, EF VANDERZEE, R VANEDEN, W HOFFMAN, T VERHOEF, J SNIPPE, H AF DEVELASCO, EA MERKUS, D ANDERTON, S VERHEUL, AFM LIZZIO, EF VANDERZEE, R VANEDEN, W HOFFMAN, T VERHOEF, J SNIPPE, H TI SYNTHETIC PEPTIDES REPRESENTING T-CELL EPITOPES ACT AS CARRIERS IN PNEUMOCOCCAL POLYSACCHARIDE CONJUGATE VACCINES SO INFECTION AND IMMUNITY LA English DT Article ID HEAT-SHOCK PROTEINS; INFLUENZAE TYPE-B; STREPTOCOCCUS-PNEUMONIAE; ANTIBODY-RESPONSE; INTERFERON-GAMMA; HELPER ACTIVITY; CLONES; VIRUS; SEQUENCE; TH1 AB Improvement of antibody responses to polysaccharides through their linkage to proteins is thought to be mediated by protein-specific T helper (Th) cells. To investigate whether the carrier protein of a conjugate could be substituted by a Th epitope, Streptococcus pneumoniae type 17F polysaccharide (PS) was bromoacetylated and coupled to different peptides via their carboxy-terminal cysteines. Two peptides, one from the mycobacterial 65-kDa heat shock protein (hsp65) and the other from influenza virus hemagglutinin, are well-known Th epitopes. Two other peptides were selected from the pneumolysin sequence by Th epitope prediction methods; one of them was synthesized with cysteine either at the carboxy or the amino terminus. Three conjugates consistently elicited in mice anti-PS immunoglobulin M (IgM) and IgG responses that were not observed upon immunization with derivatized PS without peptide. The same conjugates induced no anti-PS antibody responses in athymic (nu/nu) mice, whereas clear responses were elicited in euthymic (nu/+) controls, demonstrating the thymus-dependent character of these conjugates. Only the three conjugates inducing anti-PS responses were capable of eliciting antipeptide antibodies. One of the immunogenic conjugates was studied in more detail. It induced significant protection and an anti-PS IgG response comprising all subclasses. Od the basis of these results and proliferation studies with peptide and conjugate-primed cells, it is concluded that linkage of Th epitopes to PS in the right orientation enhances its immunogenicity in a thymus-dependent manner. Future possibilities for using peptides as carriers for inducing antibody responses to poorly immunogenic saccharide antigens are discussed. C1 UNIV UTRECHT,EIJKMAN WINKLER INST MED & CLIN MICROBIOL,3584 CL UTRECHT,NETHERLANDS. UNIV UTRECHT,FAC VET,DEPT INFECT DIS & IMMUNOL,3584 CL UTRECHT,NETHERLANDS. US FDA,CTR BIOL EVALUAT & RES,CELL BIOL LAB,BETHESDA,MD 20892. RI Merkus, Daphne/C-6539-2011; van der Zee, Ruurd/O-5256-2015; OI van der Zee, Ruurd/0000-0002-4331-2755; Merkus, Daphne/0000-0002-4852-831X NR 49 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 1995 VL 63 IS 3 BP 961 EP 968 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QJ524 UT WOS:A1995QJ52400032 PM 7532630 ER PT J AU YOKOYAMA, M EBERT, M FUNATOMI, H FRIESS, H BUCHLER, MW JOHNSON, GR KORC, M AF YOKOYAMA, M EBERT, M FUNATOMI, H FRIESS, H BUCHLER, MW JOHNSON, GR KORC, M TI AMPHIREGULIN IS A POTENT MITOGEN IN HUMAN PANCREATIC-CANCER CELLS - CORRELATION WITH PATIENT SURVIVAL SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE AMPHIREGULIN; EGF RECEPTOR; HUMAN PANCREATIC CANCER ID EPIDERMAL GROWTH-FACTOR; FACTOR RECEPTOR; ENHANCED EXPRESSION; EPITHELIAL-CELLS; FACTOR FAMILY; CARCINOMA; OVEREXPRESSION; GENE; ADENOCARCINOMAS; INHIBITION AB The epidermal growth factor (EGF) receptor (EGFR) is activated by EGF and other EGF-like growth factors, including amphiregulin (AR). We characterized the localization and mitogenic action of AR in T3M4 and COLO-357 human pancreatic cancer cell lines and determined whether the presence of AR in human pancreatic cancers correlates with patient survival. Both T3M4 and COLO-357 cells were found to be extremely sensitive to AR, one-half maximal stimulation occurring at a concentration of 70 and 50 pM, respectively. The magnitude of the stimulatory effect was greater with AR than with EGF. Both cell lines exhibited AR immunostaining, which was present in a variable manner in the cytoplasm, nucleus and nucleoli. Immunohistochemical analysis of 62 pancreatic cancer tissues revealed the presence of nuclear and/or cytoplasmic AR immunoreactivity in the cancer cells. Cytoplasmic, but not nuclear localization of AR in the pancreatic cancer cells was associated with a statistically significant decrease in the post-operative survival period. The presence of EGFR alone in the cancer cells did not correlate with decreased survival, whereas coexpression of cytoplasmic AR and EGFR was associated with shorter survival. Distant metastases did not always exhibit cytoplasmic AR immunoreactivity. These findings point to the existence of an EGFR: AR autocrine loop in human pancreatic cancer which may contribute to its biological aggressiveness. C1 UNIV CALIF IRVINE,DEPT MED,DIV ENDOCRINOL DIABET & METAB,IRVINE,CA 92717. UNIV CALIF IRVINE,DEPT BIOL CHEM,IRVINE,CA 92717. UNIV BERN,INSELSPITAL,DEPT VISCERAL & TRANSPLANTAT SURG,CH-3010 BERN,SWITZERLAND. US FDA,DIV CYTOKINE BIOL,CELL BIOL LAB,BETHESDA,MD 20892. NR 36 TC 25 Z9 25 U1 1 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 1995 VL 6 IS 3 BP 625 EP 631 PG 7 WC Oncology SC Oncology GA QJ135 UT WOS:A1995QJ13500016 PM 21556580 ER PT J AU ROSSDEGNAN, D SOUMERAI, SB AVORN, J BOHN, RL BRIGHT, R ALEDORT, LM AF ROSSDEGNAN, D SOUMERAI, SB AVORN, J BOHN, RL BRIGHT, R ALEDORT, LM TI HEMOPHILIA HOME TREATMENT - ECONOMIC-ANALYSIS AND IMPLICATIONS FOR HEALTH-POLICY SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article ID DUTCH HEMOPHILIACS; FACTOR-VIII; CARE; MORTALITY; PROGRAM AB This analysis describes the development of technology for home self-infusion of factor VIII in the treatment of hemophilia and its clinical, economic, and social consequences, and uses the case study of such home care treatment to illustrate the potentials and pitfalls of formal economic analyses of programs to treat chronically ill children. A comprehensive review of all original data on hemophilia programs, their related costs, and outcomes, conducted from 1966 through 1993, examined the economic outcomes for two hypothetical cohorts, one aged 0-4 years and the other aged 30-34 years. Including the measurement of treatment effects on the productivity of parental caregivers substantially increases the benefit-cost relationship of an intervention directed at chronically ill children. Increased economic productivity and societal return resulting from such a program for young adults exceeds those for a cohort of children, primarily due to assumptions related to discounting. However, estimation of quality-adjusted life years favors the younger age cohort, since children survive for a longer period of time and with each year survived comes a higher quality of life. Unlike simpler instances in which economic benefits can be shown to outweigh resource costs, policy decisions concerning services for chronically ill children raise an additional set of complex analytic issues. Inclusion of the benefits in productivity experienced by family caregivers provides an important added dimension to such analyses. The development of cost-benefit or cost-effectiveness analyses of these programs illustrates the importance of careful measurement of outcomes and explicit statements of underlying assumptions. Such an analysis of home care for children with hemophilia therefore demonstrates both the strengths and the limitations of this approach. C1 HARVARD COMMUNITY HLTH PLAN,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,PROGRAM ANAL CLIN STRATEGIES,BOSTON,MA 02115. US FDA,OFF SCI & TECHNOL,ROCKVILLE,MD 20852. MT SINAI MED CTR,DEPT MED,NEW YORK,NY 10029. RP ROSSDEGNAN, D (reprint author), HARVARD UNIV,SCH MED,DEPT AMBULATORY MED & PREVENT,126 BROOKLINE AVE,BOSTON,MA 02215, USA. RI Bright, Roselie/D-2240-2016 NR 49 TC 26 Z9 26 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD SPR PY 1995 VL 11 IS 2 BP 327 EP 344 PG 18 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA QZ406 UT WOS:A1995QZ40600016 PM 7790175 ER PT J AU WOLNIK, KA HEITKEMPER, DT CROWE, JB BARNES, BS BRUEGGEMEYER, TW AF WOLNIK, KA HEITKEMPER, DT CROWE, JB BARNES, BS BRUEGGEMEYER, TW TI APPLICATION OF INDUCTIVELY-COUPLED PLASMA-ATOMIC EMISSION AND MASS-SPECTROMETRY TO FORENSIC ANALYSIS OF SODIUM GAMMA-HYDROXY BUTYRATE AND EPHEDRINE HYDROCHLORIDE SO JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY LA English DT Article; Proceedings Paper CT 7th Biennial National-Atomic-Spectroscopy-Society Meeting CY JUL 20-22, 1994 CL KINGSTON HULL, ENGLAND SP NATL ATOMIC SPECT SOC DE INDUCTIVELY COUPLED PLASMA ATOMIC EMISSION SPECTROMETRY; INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY; EPHEDRINE HYDROCHLORIDE; GAMMA HYDROXY BUTYRATE; SODIUM OXYBATE; FORENSIC ANALYSIS ID GLASS SAMPLES; COCAINE; CHROMATOGRAPHY AB The identity and relative amounts of various elements in samples of two compounds, sodium gamma hydroxy butyrate (GHB) and ephedrine hydrochloride (ephedrine), have been used to compare items of evidence, GHB, unapproved for use in the United States, and ephedrine, used in the illicit manufacture of methamphetamine, are currently of interest to law enforcement authorities. In this paper, the analysis of the elemental impurities in GHB by inductively coupled plasma atomic emission spectrometry (ICP-AES) has been used to further the investigation of clandestine manufacturing sources. The following elements were detected in samples of GHB: Ba,Ca, Cd, Fe; K, Mg, Ni, P, Pb, Si, Sr, and Zn. Results were used to demonstrate an association between samples of unknown origin. Analysis of samples of ephedrine of known origin from legitimate manufacturers by ICP-mass spectrometry showed that Al, Ba, Mn, Pt, Rb, and Sr were the most useful for discriminating between sources and making direct comparisons. Interpretation of results with respect to the intended use of conclusions derived from those results is discussed. RP WOLNIK, KA (reprint author), US FDA,NATL FORENS CHEM CTR,CINCINNATI,OH 45221, USA. NR 19 TC 2 Z9 2 U1 0 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0267-9477 J9 J ANAL ATOM SPECTROM JI J. Anal. At. Spectrom. PD MAR PY 1995 VL 10 IS 3 BP 177 EP 181 DI 10.1039/ja9951000177 PG 5 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA QN125 UT WOS:A1995QN12500002 ER PT J AU GEHRING, TA COOPER, WM HOLDER, CL THOMPSON, HC AF GEHRING, TA COOPER, WM HOLDER, CL THOMPSON, HC TI LIQUID-CHROMATOGRAPHIC DETERMINATION OF THIAMINE IN RODENT FEED BY POSTCOLUMN DERIVATIZATION AND FLUORESCENCE DETECTION SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID RIBOFLAVIN; FOOD AB A liquid chromatographic method was developed for determination of the essential nutrient thiamine (vitamin B-1) in rodent feed. Thiamine was extracted with hydrochloric acid, separated by reversed-phase liquid chromatography, derivatized postcolumn to thiochrome with potassium hydroxide and potassium ferricyanide, and detected by fluorescence. Excitation and emission wavelengths were 370 and 430 nm, respectively. Detector response was linear in the range of 2.58 to 15.5 ng of thiamine injected. Instrument detection limit was 5 pg of thiamine injected. RP GEHRING, TA (reprint author), US FDA,NATL CTR TOXICOL RES,DIV CHEM,HPT-230,JEFFERSON,AR 72079, USA. NR 4 TC 9 Z9 9 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 307 EP 309 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400006 PM 7756846 ER PT J AU FARAG, SA AF FARAG, SA TI LIQUID-CHROMATOGRAPHIC ASSAY OF DIATRIZOIC ACID AND ITS DIIODO DEGRADATION PRODUCTS IN RADIO-OPAQUE SOLUTIONS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A liquid chromatographic method is described for the analysis of diatrizoic acid (2,4,6-triiodo-3,5-diacetamidobenzoic acid) and its 2,4- and 2,6-diiodo degradation products in radio-opaque injection solutions. The method is accurate, precise, and linear at a concentration range of 5-50 ppm. RP FARAG, SA (reprint author), US FDA,DIV DRUG ANAL,1114 MARKET ST,ROOM 1002,ST LOUIS,MO 63101, USA. NR 12 TC 6 Z9 6 U1 1 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 328 EP 333 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400009 PM 7756847 ER PT J AU LEHR, GJ YUEN, SM LAWRENCE, GD AF LEHR, GJ YUEN, SM LAWRENCE, GD TI LIQUID-CHROMATOGRAPHIC DETERMINATION OF ATROPINE IN NERVE-GAS ANTIDOTES AND OTHER DOSAGE FORMS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TROPIC ACID; SULFATE AB A simple and specific liquid chromatographic method was developed for the determination of atropine in nerve gas antidotes and several other dosage forms. The method is also used simultaneously to quantitate phenol, an antimicrobial agent present in nerve gas antidotes, and to monitor the level of tropic acid, a principal degradation product of atropine, The system uses a Spherisorb CN column and a mobile phase of acetonitrile-0.05M sodium phosphate monobasic (10 + 90), pH 4.0, The detection wavelength is 220 nm. The method was validated by testing for accuracy, linearity, reproducibility and precision. In addition, the proposed method was applied to 8 commercial preparations of atropine, including injectables, ophthalmic solutions, and ointments, and was found to be satisfactory and free from interferences from preservatives, such as benzyl alcohol, methylparaben, benzalkonium chloride and chlorobutanol, that are present in these formulations. RP LEHR, GJ (reprint author), US FDA,NEW YORK REG LAB,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 339 EP 343 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400011 PM 7756848 ER PT J AU MUNNS, RK TURNIPSEED, SB PFENNING, AP ROYBAL, JE HOLLAND, DC LONG, AR PLAKAS, SM AF MUNNS, RK TURNIPSEED, SB PFENNING, AP ROYBAL, JE HOLLAND, DC LONG, AR PLAKAS, SM TI DETERMINATION OF RESIDUES OF FLUMEQUINE AND NALIDIXIC, OXOLINIC, AND PIROMIDIC ACIDS IN CATFISH BY LIQUID-CHROMATOGRAPHY WITH FLUORESCENCE AND UV DETECTION SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CULTURED FISH; ANTIBACTERIALS; EXTRACTION; TISSUES AB A liquid chromatographic (LC) method is described for determining residues of flumequine (FLU) and nalidixic (NAL), oxolinic (OXO), and piromidic (PIR) acids in catfish muscle, The identities of 3 of these residues are confirmed by gas chromatography-mass spectrometry (GO-MS), The extraction and cleanup procedures are the same for both determination and identification, Analyte isolation involves homogenizing the tissue with acetone, defatting the acetone extract with hexane, and extracting the compounds into chloroform, The extract is further purified by first partitioning into base and subsequently back-extracting into chloroform after acidifying the aqueous phase. After the solvent is evaporated, the residue is dissolved in mobile phase, and the analytes are determined by LC with fluorescence detection, excitation at 325 nm and emission at 365 nm, Catfish muscle was fortified with each quinolone at 5, 10, 20, 40, and 80 ng/g. Overall average recoveries were 83-94%, with relative standard deviations (RSDs) of 5-7%, The method was evaluated also by a second analyst, who determined 4 quinolones added in combination. Average recoveries of quinolones from catfish fortified at 5, 10, and 20 ng/g were 78-90%, with RSDs of 3-6%, The presence in catfish muscle of incurred OXO, FLU, and NAL at the 10 ng/g level was confirmed by analyzing the decarboxylated quinolones by GO-MS, The relative abundances of all 5 major ions for OXO, FLU, and NAL were within 10% of those observed in spectra of standard compounds decarboxylated by the same method. C1 US FDA,DIV SEAFOOD RES,DAUPHIN ISL,AL 36528. RP MUNNS, RK (reprint author), US FDA,ANIM DRUGS RES CTR,DENVER FED CTR,DENVER,CO 80225, USA. NR 11 TC 36 Z9 36 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 343 EP 352 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400012 ER PT J AU REVELLE, LK DAVIGNON, DA REEPMEYER, JC ZERFING, RC AF REVELLE, LK DAVIGNON, DA REEPMEYER, JC ZERFING, RC TI STABILITY-INDICATING PROTON NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPIC METHOD FOR DETERMINATION OF S-ADENOSYL-L-METHIONINE IN TABLETS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LANTHANIDE SHIFT-REAGENT; TRANYLCYPROMINE SULFATE; DOUBLE-BLIND; ADENOSYLMETHIONINE; INSTABILITY; DEPRESSION; PURITY; TRIAL AB We present a simple, accurate, stability-indicating nuclear magnetic resonance (NMR) method for determining active (S,S) and inactive (R,S) epimers of S-adenosyl-L-methionine (SAM) in tablets, The SCH3 resonances of SAM epimers were well resolved at 300 MHz. Individual assays of 5 SAM tablets gave SAM values of 101.3 +/- 1.7% of declared amounts, Tablet solutions were assayed at a level of 8.0 mg/mL, but the method was linear for SAM concentrations ranging from 64 to 1 mg/mL(correlation coefficient, 0.9996), Reproducibility was indicated by a relative standard deviation of 0.33% for 6 replicate assays for total SAM at a concentration of 8 mg/mL. In contrast to the propietary liquid chromatographic (LC) method, which requires SAM as an external standard, the NMR method uses sodium trimethylsilylpropionate-d(4) (TSP) both as an internal standard and as a chemical shift reference, The method was used to test the stability of SAM analytes under various pH levels and temperatures, We found 8% inactivation of SAM due to epimerization over a 24 h period at room temperature and pH 5, SAM solutions showed no detectable inactivation after 14 days when stored below 0 degrees C. RP REVELLE, LK (reprint author), US FDA,DIV DRUG ANAL,1114 MARKET ST,ROOM 1002,ST LOUIS,MO 63101, USA. NR 16 TC 11 Z9 11 U1 0 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 353 EP 358 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400013 PM 7756849 ER PT J AU JUNE, GA SHERROD, PS HAMMACK, TS AMAGUANA, RM ANDREWS, WH AF JUNE, GA SHERROD, PS HAMMACK, TS AMAGUANA, RM ANDREWS, WH TI RELATIVE EFFECTIVENESS OF SELENITE CYSTINE BROTH, TETRATHIONATE BROTH, AND RAPPAPORT-VASSILIADIS MEDIUM FOR THE RECOVERY OF SALMONELLA FROM RAW FLESH AND OTHER HIGHLY CONTAMINATED FOODS - PRECOLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ABBREVIATED SELECTIVE ENRICHMENT; RAPID IMMUNODIFFUSION METHOD; GREEN BROTH; PRODUCTS; GROWTH AB The effectiveness of selenite cystine (SC) broth, tetrathionate (TT) broth, and Rappaport-Vassiliadis (RV) medium for recovery of Salmonella spp, from 8 highly contaminated foods was determined, RV medium prepared from individual ingredients and incubated at 42 degrees and 43 degrees C was compared with 2 commercial (Difco and Oxoid) media incubated at 42 degrees C, Naturally and artificially contaminated foods were tested under 2 protocols, For Protocol 1, each food was preenriched in the appropriate medium, After incubation, serial 10 fold dilutions of the preenriched foods were inoculated into selective enrichment media and incubated at 35 degrees, 42 degrees, or 43 degrees C. Effectiveness of these conditions was evaluated by most probable number determination of Salmonella spp, recovered, Productivity of selective enrichments did not differ significantly with this protocol, except that with Oxoid RV medium the number of Salmonella cells recovered from most of the foods was significantly reduced, For Protocol 2, twenty 25 g test portions from artificially inoculated foods were examined qualitatively for Salmonella spp, The effectiveness of the broth/temperature combinations was determined by the number of positive tests under each condition, RV medium prepared from individual ingredients and TT broth incubated at 43 degrees C yielded significantly more Salmonella-positive tests from frog legs and lettuce than did SC and TT broths incubated at 35 degrees C or commercial RV medium incubated at 42 degrees C, With pork sausage and ground beef, significantly fewer Salmonella-positive tests were found with Oxoid RV medium incubated at 42 degrees C and SC incubated at 35 degrees C than from other selective enrichments. With chicken, fewer Salmonella-positive tests were found from SC and TT broths incubated at 35 degrees C and Oxoid RV medium incubated at 42 degrees C than from other selective enrichments. There were no significant differences among selective enrichments in the recovery of Salmonella spp, from the remaining foods, Overall, RV prepared from individual ingredients and incubated at 42 degrees C yielded the highest number of Salmonella-positive tests. RP JUNE, GA (reprint author), US FDA,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204, USA. NR 27 TC 22 Z9 24 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 375 EP 380 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400016 PM 7756852 ER PT J AU NOAH, CW POTEET, SS RAMOS, NC PEREZ, JC HUANG, SY AF NOAH, CW POTEET, SS RAMOS, NC PEREZ, JC HUANG, SY TI PRODUCTION OF MONOCLONAL-ANTIBODIES SPECIFIC TO CLOSTRIDIUM-BOTULINUM TYPE-B NEUROTOXIN SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TOXIN; IMMUNOASSAY AB Four monoclonal antibodies were produced for use in a rapid method to detect Clostridium botulinum type B neurotoxin, Cells of mouse myeloma cell line SP2/0 were fused with splenocytes of immunized BALB/c mice, An immunoblot assay of semipurified commercial neurotoxins of C. botulinum types A, B, C, D, E, and F was used to show specificity, All the monoclonal antibodies reacted with-type B neurotoxin but did not cross-react with the other types, The monoclonal antibodies, separately and combined, did not neutralize the toxin in mice, and all showed specificity to the whole neurotoxin molecule and the heavy-chain component by immunoblot, No evidence of specific binding to the hemagglutinin molecule was noted, When tested against concentrated cultured supernatants of C. botulinum types A, B, E, and F, the 4 monoclonal antibodies reacted only against type B strains, They will be incorporated into a rapid assay with other specific monoclonal antibodies to detect C. botulinum neurotoxins from pure cultures or suspect foods. C1 TEXAS A&I UNIV,DEPT BIOL,KINGSVILLE,TX 78363. RP NOAH, CW (reprint author), US FDA,3032 BRYAN ST,DALLAS,TX 75204, USA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 381 EP 385 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400017 PM 7756853 ER PT J AU MCNEAL, TP HOLLIFIELD, HC DIACHENKO, GW AF MCNEAL, TP HOLLIFIELD, HC DIACHENKO, GW TI SURVEY OF TRIHALOMETHANES AND OTHER VOLATILE CHEMICAL CONTAMINANTS IN PROCESSED FOODS BY PURGE-AND-TRAP CAPILLARY GAS-CHROMATOGRAPHY WITH MASS-SELECTIVE DETECTION SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID RESIDUES AB A limited number of soft drinks, juices, beers, and waters from processed vegetables were analyzed for trihalomethanes (THMs), benzene, and toluene by a modified Environmental Protection Agency (EPA) Method 524.2. The THMs, which include chloroform, bromodichloromethane, dibromochloromethane, and bromoform, are reaction by-products of water disinfection by chlorination. EPA Method 524.2 is a purge-and-trap capillary gas chromatographic method based on mass spectrometric detection which identifies and simultaneously measures purgeable volatile organic compounds in drinking water. Chloroform was present at concentrations ranging from none detected to 94 ng/g in the 44 foods analyzed, Bromoform was not found in any of the products at a detection limit of 0.1 ng/g. Residue levels of the other THMs ranged from none detected to highs of 12 and 2 ng/g for bromodichloromethane and dibromochloromethane, respectively, Benzene residues were typically <5 ng/g, except for 7 and 9 ng/g in 2 foods, Toluene residues were typically less than or equal to 3 ng/g except for 23, 29, and 75 ng/g in 3 canned foods. RP MCNEAL, TP (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 12 TC 20 Z9 20 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 391 EP 397 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400019 PM 7756854 ER PT J AU ANDERSON, DL CUNNINGHAM, WC LINDSTROM, TR OLMEZ, I AF ANDERSON, DL CUNNINGHAM, WC LINDSTROM, TR OLMEZ, I TI IDENTIFICATION OF LEAD AND OTHER ELEMENTS IN CERAMIC GLAZES AND HOUSEWARES BY CD-109-INDUCED X-RAY-FLUORESCENCE EMISSION-SPECTROMETRY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Radioisotope x-ray fluorescence spectrometry was investigated as a potential screening method for Pb and other elements in housewares. Thirty-six commercial houseware items and 87 ceramic test tiles (85 fired with hobby glazes and 2 blank bisques) were examined qualitatively for the presence of Pb by using Cd-109-induced L x-ray fluorescence emission spectrometry. For the housewares, the technique provided fast, nondestructive analysis of areas with about 10 cm diameters (general regions) to about 4 mm diameters (isolated design regions). Pb was found in 25 of 28 ceramicware items, in all 8 other housewares, and in all the test-tile glazes above the limit of detection of 1 count per second (cps) for Pb L beta x-rays. For housewares, Pb identification did not always correspond to Pb leachability. For 68 test-tile glazes labeled as containing Pb (39 of which were also labeled 'dinnerware safe' or 'safe for food containers'), count rates ranged from 290 to 730 cps, whereas for the other 17 glazes labeled (with one exception) 'nontoxic,' much lower count rates (5-61 cps) were obtained. Other elements found in the housewares or test glazes were As, Au, Ca, Co, Cr, Cu, Fe, Mn, Nb, Ni, Rb, Sr, Y, Zn, and Zr. C1 MIT,NUCL REACTOR LAB,CAMBRIDGE,MA 02139. RP ANDERSON, DL (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,ELEMENTAL RES BRANCH,WASHINGTON,DC 20204, USA. NR 11 TC 6 Z9 6 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 407 EP 412 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400022 PM 7756857 ER PT J AU BARRY, TL PETZINGER, G LEHR, G SPECCHIO, JJ AF BARRY, TL PETZINGER, G LEHR, G SPECCHIO, JJ TI PURGE-AND-TRAP GAS-CHROMATOGRAPHIC MASS-SPECTROMETRIC DETERMINATION OF BENZENE IN DENTURE ADHESIVES SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID VOLATILE ORGANIC-COMPOUNDS; HUMAN-BLOOD; MIGRATION; FOODS AB A purge-and-trap gas chromatographic-mass spectrometric procedure is presented for determination of trace levels of benzene in denture adhesives and their raw materials. The limit of quantitation is 10 ppb, reproducibility is +/- 10%, and recoveries of d(6)-benzene are 70-85%. Results of a nationwide survey of 109 finished products and their raw materials representing 32 brand name products from 17 manufacturers are reported. C1 MONTCLAIR STATE COLL,MONTCLAIR,NJ 07403. RP BARRY, TL (reprint author), US FDA,NEW YORK REG LAB,BROOKLYN,NY 11232, USA. NR 25 TC 4 Z9 4 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 413 EP 418 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400023 PM 7756858 ER PT J AU GILLESPIE, AM DALY, SL GILVYDIS, DM SCHNEIDER, F WALTERS, SM AF GILLESPIE, AM DALY, SL GILVYDIS, DM SCHNEIDER, F WALTERS, SM TI MULTICOLUMN SOLID-PHASE EXTRACTION CLEANUP OF ORGANOPHOSPHORUS AND ORGANOCHLORINE PESTICIDE-RESIDUES IN VEGETABLE-OILS AND BUTTERFAT SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID GAS-CHROMATOGRAPHY; COLUMN; FAT; CARTRIDGES; FRACTIONATION; SEPARATION; PARTITION; LIPIDS AB Diatomaceous earth columns used with reversed and normal solid phase extraction (SPE) cartridges were evaluated for the quantitative determination of a number of organophosphorus (OP) and organochlorine (OC) pesticide residues in edible vegetable oils and butterfat, An oil or fat sample (about 2 g) in hexane was passed through a diatomaceous earth (Extrelut QE) column and a C-18 bonded silica (ODS) SPE cartridge, resulting in the separation of the pesticides from about 98% of the lipids, The eluate was split in half, with the first portion concentrated into acetone for the determination of OP pesticides by gas chromatography with flame photometric detection (GC-FPD), The other half was passed through an Alumina-N SPE cartridge for additional cleanup of lipid matrix to determine OC pesticides by GC with electron-capture detection (GC-ECD), Average recoveries from fortified samples were greater than 89% for the pesticides studied. RP GILLESPIE, AM (reprint author), US FDA,PESTICIDES & IND CHEM RES CTR,1560 E JEFFERSON AVE,DETROIT,MI 48207, USA. NR 17 TC 35 Z9 37 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 431 EP 437 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400026 PM 7756860 ER PT J AU ROYBAL, JE PFENNING, AP MUNNS, RK HOLLAND, DC HURLBUT, JA LONG, AR AF ROYBAL, JE PFENNING, AP MUNNS, RK HOLLAND, DC HURLBUT, JA LONG, AR TI DETERMINATION OF MALACHITE GREEN AND ITS METABOLITE, LEUCOMALACHITE GREEN, IN CATFISH (ICTALURUS-PUNCTATUS) TISSUE BY LIQUID-CHROMATOGRAPHY WITH VISIBLE DETECTION SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID GENTIAN-VIOLET AB To determine residues of malachite green (MG) and its metabolite, leucomalachite green (LMG), in catfish tissue, analytes are extracted with acetonitrile-buffer and the extract is partitioned into methylene chloride, Final cleanup and isolation are performed on neutral alumina solid-phase extraction (SPE) and propylsulfonic acid cation-exchange SPE columns before analysis by liquid chromatography with visible detection, PbO2 postcolumn oxidation is performed by isocratic elution with a buffered mobile phase from a cyano column, Recoveries and relative standard deviations (RSDs) from fortified catfish tissues were 72.9% (RSD, 1.92%; 23 ppb), 75.5% (RSD, 6.85%; 11 ppb), and 69.6% (RSD, 6.93%; 5.7 ppb) for MG and 87.4% (RSD, 2.92%; 21 ppb), 88.1% (RSD, 5.94%; 10 ppb), and 82.6% (RSD, 11.5%; 5.3 ppb) for LMG,The method was applied to MG-incurred catfish at depuration times of 0, 2, 4, 8, and 24 h, Average levels of residual MG and LMG in the 24 h depuration catfish tissue were 73.4 and 289 ppb, respectively. RP ROYBAL, JE (reprint author), US FDA,DENVER FED CTR,ANIM DRUGS RES CTR,POB 25087,DENVER,CO 80225, USA. NR 10 TC 57 Z9 73 U1 0 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 453 EP 457 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400029 PM 7756862 ER PT J AU LAWRENCE, JF HUNGERFORD, J AF LAWRENCE, JF HUNGERFORD, J TI AOAC SYMPOSIUM - ANALYTICAL METHODS FOR SEAFOOD TOXINS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Editorial Material C1 US FDA,SEAFOOD PROD RES CTR,BOTHELL,WA 98041. RP LAWRENCE, JF (reprint author), HLTH & WELF CANADA,HLTH PROTECT BRANCH,FOOD DIRECTORATE,BUR CHEM SAFETY,DIV FOOD RES,OTTAWA,ON K1A 0L2,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 497 EP 498 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400037 ER PT J AU MANGER, RL LEJA, LS LEE, SY HUNGERFORD, JM HOKAMA, Y DICKEY, RW GRANADE, HR LEWIS, R YASUMOTO, T WEKELL, MM AF MANGER, RL LEJA, LS LEE, SY HUNGERFORD, JM HOKAMA, Y DICKEY, RW GRANADE, HR LEWIS, R YASUMOTO, T WEKELL, MM TI DETECTION OF SODIUM-CHANNEL TOXINS - DIRECTED CYTOTOXICITY ASSAYS OF PURIFIED CIGUATOXINS, BREVETOXINS, SAXITOXINS, AND SEAFOOD EXTRACTS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT Symposium on Analytical Methods for Seafood Toxins, at the 107th AOAC International Annual Meeting CY JUL 26-29, 1993 CL WASHINGTON, DC SP ASSOC OFFICIAL ANALYT CHEMISTS ID GAMBIERDISCUS-TOXICUS; CIGUATERA; NEUROTOXINS; ACTIVATION; JAVANICUS; BIOASSAY; MANNITOL; FISH AB Neuroblastoma cells in culture were used to detect sodium channel-specific marine toxins based on an end-point determination of mitochondrial dehydrogenase activity, The assay responds in a dose-dependent manner to ciguatoxins, brevetoxins, and saxitoxins, and delineates the toxic activity as either sodium channel enhancing or sodium channel blocking, The assay responds rapidly to sodium channel activating toxins, allowing dose dependent detection in 4 to 6 h, Brevetoxins can be detected at 250 pg, and purified ciguatoxins are detected in the low picogram and subpicogram levels, The results obtained from cell bioassay of ciguatoxic finfish extracts correlates with those obtained from mouse bioassays, Sodium channel blocking toxins can also be detected with an approximate sensitivity of 20 pg in 24 to 48 h, This cell-based technique is simple, sensitive, demonstrates potential as an alternative to animal testing for sodium channel activating and blocking toxins, and can be automated. RP MANGER, RL (reprint author), US FDA,SEAFOOD PROD RES CTR,22201 23RD DR SE,POB 3012,BOTHELL,WA 98041, USA. RI Lewis, Richard/E-8674-2013 OI Lewis, Richard/0000-0003-3470-923X NR 32 TC 165 Z9 183 U1 1 U2 10 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 521 EP 527 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400041 PM 7756868 ER PT J AU JAN, LR YANG, CS TRENT, DW FALGOUT, B LAI, CJ AF JAN, LR YANG, CS TRENT, DW FALGOUT, B LAI, CJ TI PROCESSING OF JAPANESE ENCEPHALITIS-VIRUS NONSTRUCTURAL PROTEINS - NS2B-NS3 COMPLEX AND HETEROLOGOUS PROTEASES SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID NONSTRUCTURAL PROTEINS; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; VACCINIA VIRUS; POLYPROTEIN; CLEAVAGE; NS3; IDENTIFICATION; DOMAIN; FLAVIVIRUSES AB Processing of Japanese encephalitis (JE) virus nonstructural (NS) proteins expressed by recombinant vaccinia viruses was analysed to characterize the responsible viral protease. Analysis of the processing of polyprotein NS2A-2B-3' containing the N-terminal 322 amino acids of NS3 revealed products consistent with cleavages at the predicted intergenic junctions as well as at one or possibly two sites within NS2A, Cleavage at the alternate site(s) containing the cleavage sequence motif within NS2A could possibly explain the production of the NS1' protein in JE virus-infected cells. Polyprotein NS2A-d2B-3' containing a large deletion within NS2B was cleavage-defective, despite the presence of the proposed NS3 protease domain. Cleavage of NS2A-d2B-3' was restored if NS2B or NS2A-2B was supplied in trans, providing evidence that NS2B is strictly required for NS3 proteolytic activity. NS2B- or NS3-specific sera raised against the bacterial TrpE fusion protein co-precipitated NS2B and NS3 or NS3'from the lysate of JE virus or recombinant virus-infected cells. Thus both protease components are associated as a complex, presumably representing the active JE virus protease. JE virus and the analogous dengue 4 (DEN-4) protease components were employed to examine the activity of heterologous proteases. The defective cleavage of JE virus NS2A-d2B-3' was complemented by heterologous DEN-4 NS2B, whereas the defective cleavage of DEN-4 NS2A-d2B-3' was not corrected by heterologous JE virus NS2B. This suggests that the heterologous JE virus NS2B-DEN-4 NS3 protease is not active, despite the considerable sequence conservation of NS2B and NS3 between the two viruses. The cleavage activity was restored by replacement of the C-terminal 80 amino acids of JE virus NS2B with the corresponding DEN-4 sequence, consistent with the notion that the C-terminal region contains amino acid residues for interaction with DEN-4 NS3. C1 NIAID,INFECT DIS LAB,MOLEC VIRAL BIOL SECT,BETHESDA,MD 20892. NATL TAIWAN UNIV,COLL MED,INST MICROBIOL,TAIPEI 10764,TAIWAN. NATL INST PREVENT MED,TAIPEI 11513,TAIWAN. CTR DIS CONTROL & PREVENT,FT COLLINS,CO 80522. US FDA,CTR BIOL EVALUAT & RES,VECTOR BORNE DIS LAB,BETHESDA,MD 20892. NIAID,INFECT DIS LAB,MOLEC VIRAL BIOL SECT,BETHESDA,MD 20892. NR 28 TC 44 Z9 47 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD MAR PY 1995 VL 76 BP 573 EP 580 DI 10.1099/0022-1317-76-3-573 PN 3 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA QL246 UT WOS:A1995QL24600009 PM 7897348 ER PT J AU YETLEY, EA PARK, YK AF YETLEY, EA PARK, YK TI DIET AND HEART-DISEASE - HEALTH CLAIMS SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 1st International Symposium on the Role of Soy in Preventing and Treating Chronic Disease CY FEB 20-23, 1994 CL MESA, AZ SP UNITED SOYBEAN BOARD, PROTEIN TECHNOL INT DE DIET AND HEALTH; HEALTH CLAIM; SODIUM AND HYPERTENSION; LIPIDS AND CORONARY HEART DISEASE; FIBER-RICH FOODS AND CORONARY HEART DISEASE AB The Nutrition Labeling and Education Act of 1990 states, in part, that a product is misbranded if it bears a claim that characterizes the relationship of a nutrient to a disease or health-related condition (health claim), unless the claim is made in accordance with Food and Drug Administration (FDA) regulations. In response to the new law, on January 6, 1993, the FDA promulgated regulations that described general requirements for health claims on foods in conventional food forms and specific requirements for seven authorized health claim topics. Three authorized claims are related to heart disease: dietary saturated fat and cholesterol and coronary heart disease; fruits, vegetables and grain products that contain fiber, particularly soluble fiber, and risk of coronary heart disease and sodium and hypertension. The general requirements regulation specifies the scientific standard for assessing the validity of claims, criteria for the qualification of claims, conditions for disqualification and general labeling requirements for health claims. Approval for health claims is based on the totality of publicly available scientific evidence and significant agreement among experts qualified by scientific training and experience to evaluate the relationship. On January 4, 1994, the FDA finalized similar requirements for health claims on dietary supplements. C1 US FDA,WASHINGTON,DC 20204. NR 23 TC 13 Z9 13 U1 1 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAR PY 1995 VL 125 IS 3 SU S BP S679 EP S685 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA QM161 UT WOS:A1995QM16100019 PM 7884551 ER PT J AU FINTOR, L ALCIATI, MH FISCHER, R AF FINTOR, L ALCIATI, MH FISCHER, R TI LEGISLATIVE AND REGULATORY MANDATES FOR MAMMOGRAPHY QUALITY ASSURANCE SO JOURNAL OF PUBLIC HEALTH POLICY LA English DT Article ID SCREEN-FILM MAMMOGRAPHY; ACCREDITATION; EQUIPMENT AB The current practice of screening mammography in the United States has been the focus of numerous legislative and regulatory mandates at the state and federal levels, both in terms of increasing access to age-eligible women and elevating the quality of mammographic imaging. Several parameters have emerged as central to a comprehensive mammography quality assurance program: (I) equipment specifications, (2) equipment performance testing including radiation dose limits, (3) facility quality assurance procedures, and (4) personnel qualifications. In 1992, Congress enacted the Mammography Quality Standards Act (MQSA) (P. L. 102-539) to address the problem of differences in mandated standards across states. By October 1994, all facilities will be required to comply with interim MQSA regulations which were released in December 1993. However, depending upon the specific requirements of applicable state standards, the extent and nature of modifications of existing quality assurance procedures will differ for facilities across states as they attempt to come into compliance with uniform Federal standards. In addition, because some provisions within state standards are likely to be more stringent than Federal standards, some level of variation will persist. This paper reviews the components of mandated standards established by states and the standards established by other organizations, including the Federal Government, prior to the MQSA interim regulations. This review will provide an understanding of the highly technical and complicated requirements surrounding mammography quality assurance. C1 NCI,DIV CANC PREVENT & CONTROL,CANC CONTROL SCI PROGRAM,PUBL HLTH APPLICAT RES BRANCH,ROCKVILLE,MD 20892. US FDA,CTR DEVICES & RADIOL HLTH,DIV MAMMOG QUAL,ROCKVILLE,MD 20857. US FDA,CTR DEVICES & RADIOL HLTH,RADIAT PROGRAM,ROCKVILLE,MD 20857. RP FINTOR, L (reprint author), NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,APPL RES BRANCH,EXECUT PLAZA N,BETHESDA,MD 20892, USA. OI Alciati, Marianne/0000-0001-6294-1090 NR 46 TC 8 Z9 8 U1 0 U2 0 PU JOURNAL PUBLIC HEALTH POLICY PI S BURLINGTON PA 208 MEADOWOOD DR, S BURLINGTON, VT 05403 SN 0197-5897 J9 J PUBLIC HEALTH POL JI J. Public Health Policy PD SPR PY 1995 VL 16 IS 1 BP 81 EP 107 DI 10.2307/3342978 PG 27 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA QR236 UT WOS:A1995QR23600005 PM 7738160 ER PT J AU Kenney, GE Sakr, A Lichtin, JL Chou, H Bronaugh, RL AF Kenney, GE Sakr, A Lichtin, JL Chou, H Bronaugh, RL TI In vitro skin absorption and metabolism of Padimate-O and a nitrosamine formed in Padimate-O-containing cosmetic products SO JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS LA English DT Article ID INVITRO PERCUTANEOUS-ABSORPTION; AMINOBENZOIC ACID AB 2-Ethylhexyl p-(N,N-dimethylamino) benzoic acid (Padimate-O) has been a popular sunscreen agent In 1988 it was reported by the U.S. Food and Drug Administration to sometimes contain a nitrosamine contaminant, 2-ethylhexyl p-(N-methyl-N-nitrosamino) benzoic acid (NMPABAO). The nitrosamine was initially reported to be mutagenic in the Ames test, but this finding was not confirmed by others. The in vitro percutaneous absorption and metabolism of NMPABAO and Padimate-O were determined in hairless guinea pig and human skin. The viability of excised skin was maintained for 24 h in flow-through diffusion cells. The percutaneous absorption of Padimate-O was almost fourfold greater from a volatile vehicle (ethanol) than from a lotion vehicle. Substantial amounts of the absorbed compound were hydrolyzed by esterase enzymes in skin. The percentages of the applied dose of NMPABAO absorbed (lotion vehicle) were 5.2 (hairless guinea pig) and 2.3 (human skin). About 26% (hairless guinea pig) and 85% (human) of the NMPABAO absorbed into the receptor fluid were hydrolyzed to p-(N-methyl-N-nitrosamino) benzoic acid (NMPABA). In some experiments, NMPABAO applied to hairless guinea pig skin was immediately irradiated with UVA and UVB light from a solar simulator. The amount of NMPABAO absorbed was reduced 17-fold as a result of the instability of the nitrosamine in UV light. However, UV instability generally cannot be considered a safety factor because many sunscreen users apply these products on a regular basis regardless of whether exposure to the sun is expected. C1 US FDA,OFF COSMET & COLORS,LAUREL,MD 20708. UNIV CINCINNATI,COLL PHARM,CINCINNATI,OH 45221. HILL TOP RES,MIAMIVILLE,OH 45147. NR 15 TC 12 Z9 12 U1 1 U2 2 PU SOC COSMETIC CHEMISTS PI NEW YORK PA 120 WALL STREET SUITE 2400, NEW YORK, NY 10005-4088 SN 0037-9832 J9 J SOC COSMET CHEM JI J. Soc. Cosmet. Chem. PD MAR-APR PY 1995 VL 46 IS 2 BP 117 EP 127 PG 11 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA TW798 UT WOS:A1995TW79800005 ER PT J AU BERKOWITZ, D BISHOP, D PASTORET, PP PERVIKOV, Y SMITH, H SORENSEN, IK AF BERKOWITZ, D BISHOP, D PASTORET, PP PERVIKOV, Y SMITH, H SORENSEN, IK TI WORKING GROUP-V - RABIES RECOMBINANT VACCINE AS AN EXAMPLE OF WHAT MIGHT BE REQUIRED BY REGULATORY AUTHORITIES SO MICROBIAL ECOLOGY IN HEALTH AND DISEASE LA English DT Editorial Material ID ORAL VACCINATION; VIRUS; FOXES; WILDLIFE C1 NERC,INST VIROL & ENVIRONM MICROBIOL,OXFORD OX1 3SR,ENGLAND. UNIV LIEGE,FAC VET MED,DEPT VIROL IMMUNOL,B-4000 LIEGE,BELGIUM. WHO,MICROBIOL SUPPORT SERV,CH-1211 GENEVA,SWITZERLAND. WHO,IMMUNOL SUPPORT SERV,CH-1211 GENEVA,SWITZERLAND. UNIV BIRMINGHAM,SCH MED,BIRMINGHAM B15 2TJ,W MIDLANDS,ENGLAND. NATL FOOD AGCY,INST TOXICOL,DK-2860 SOBORG,DENMARK. RP BERKOWITZ, D (reprint author), US FDA,OFF BIOTECHNOL HF6,5600 FISHERS LANE,ROOM 11-34,ROCKVILLE,MD 20857, USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0891-060X J9 MICROB ECOL HEALTH D JI Microb. Ecol. Health Dis. PD MAR PY 1995 VL 8 SU 1 BP S37 EP S40 PG 4 WC Ecology; Immunology; Microbiology SC Environmental Sciences & Ecology; Immunology; Microbiology GA RE184 UT WOS:A1995RE18400010 ER PT J AU BERKOWITZ, D CONTREPOIS, M DEGREVE, H GUNDERSEN, WB HOFFJORGENSEN, R KLEM, P KROGFELDT, KA LINTERMANNS, P MORTENSEN, S PERVIKOV, Y SMITH, H SORENSEN, IK VUUST, J AF BERKOWITZ, D CONTREPOIS, M DEGREVE, H GUNDERSEN, WB HOFFJORGENSEN, R KLEM, P KROGFELDT, KA LINTERMANNS, P MORTENSEN, S PERVIKOV, Y SMITH, H SORENSEN, IK VUUST, J TI WORKING GROUP-VI - REPORT FROM THE WORKSHOP ON GENETICALLY-MODIFIED VACCINES SO MICROBIAL ECOLOGY IN HEALTH AND DISEASE LA English DT Editorial Material C1 INRA AGRON,CTR RECH CLERMONT FERRARD,MICROBIOL LAB,F-63122 CEYRAT,FRANCE. FREE UNIV BRUSSELS,INST MOLEC BIOL,VIRAL GENET LAB,B-1640 RHODE ST GENESE,BELGIUM. UNIV OSLO,RIKSHOSP,INST BACTERIOL,N-0027 OSLO,NORWAY. NATL VET LAB,DK-1790 COPENHAGEN V,DENMARK. TECH UNIV DENMARK,DEPT MICROBIOL,DK-2800 LYNGBY,DENMARK. STATENS SERUM INST,DEPT BACTERIOL,DK-2300 COPENHAGEN S,DENMARK. NATL INST VET RES,B-1180 BRUSSELS,BELGIUM. FEDERAT DANISH PIG PROD & SLAUGHTER HOUSES,DIV VET,DK-1609 COPENHAGEN V,DENMARK. WHO,MICROBIOL SUPPORT SERV,CH-1211 GENEVA,SWITZERLAND. WHO,IMMUNOL SERV SERV,CH-1211 GENEVA,SWITZERLAND. UNIV BIRMINGHAM,SCH MED,BIRMINGHAM B15 2TJ,W MIDLANDS,ENGLAND. NATL FOOD AGCY,INST TOXICOL,DK-2860 SOBORG,DENMARK. STATENS SERUM INST,DEPT INFECT & IMMUNOL,DK-2300 COPENHAGEN S,DENMARK. RP BERKOWITZ, D (reprint author), US FDA,OFF BIOTECHNOL HF6,5600 FISHERS LANE,ROOM 11-34,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0891-060X J9 MICROB ECOL HEALTH D JI Microb. Ecol. Health Dis. PD MAR PY 1995 VL 8 SU 1 BP S41 EP S42 PG 2 WC Ecology; Immunology; Microbiology SC Environmental Sciences & Ecology; Immunology; Microbiology GA RE184 UT WOS:A1995RE18400011 ER PT J AU RHEE, HM LEE, SY LES, SM VALENTINE, JL AF RHEE, HM LEE, SY LES, SM VALENTINE, JL TI CARDIOVASCULAR EFFECTS OF TROPACOCAINE IN CONSCIOUS AND ANESTHETIZED RABBITS - LACK OF EVIDENCE FOR NEURO-CARDIAC INTERACTIONS AND ACUTE NEUROTOXICITY SO NEUROTOXICOLOGY LA English DT Article DE TROPACOCAINE; COCAINE; NEURO-CARDIAC EFFECTS; BLOOD PRESSURE; HEART RATE; RESPIRATORY RATE; SYMPATHETIC NERVE ACTIVITY ID MYOCARDIAL-INFARCTION; CORONARY-ARTERIES; COCAINE; SEIZURES; RATS AB The cardiovascular effects of tropacocaine, a structural analog of cocaine, were investigated in both conscious and anesthetized New Zealand white rabbits to determine if such effects were mediated through the CNS as had been demonstrated with cocaine, i.e., did a neuro-cardiac pathway exist? To facilitate the requisite cardiovascular measurements in both urethane- and pentobarbital-anesthetized animals, the right femoral artery and vein were cannulated for the measurement of arterial blood pressure and subsequent delivery of drugs, respectively. In addition, urethane-anesthetized animals had a branch of the left renal nerve isolated and multiunit renal nerve activity was monitored to obtain measures of sympathetic nerve activity originating from the CNS. Animals utilized in conscious experiments were surgically prepared 3 days prior to drug administration by placing canulae in the femoral artery and vein that were tunneled subcutaneously to the back between the scapulae. ECG and respiratory activity were also monitored in each animal. Doses of 0.3, 1, 3, and 10 mg/kg of tropacocaine were administered in both an ascending and descending fashion at 15 min intervals to 5 animals in each group, i.e., conscious, urethane, and pentobarbital-anesthetized. In urethane-anesthetized animals a comparison was made between sympathetic renal nerve activity, systolic and diastolic blood pressure, respiratory rate, and heart rate. No presser effects were observed and the changes in renal nerve activity could not be assigned as the cause of the observed depressor effects at the higher doses. A comparison was also made between results obtained with tropacocaine and those previously obtained with cocaine (Rhee, Valentine and Lee, Neurotoxicology 1990; 11:361-6) and demonstrated that tropacocaine did not produce cardiovascular effects like those seen with cocaine, such as an increase in sympathetic renal nerve activity immediately prior to a presser effect on blood pressure. Rather, tropacocaine produced effects in conscious and urethane-anesthetized animals similar to those seen with cocaine when the CNS outflow was essentially ablated by pentobarbital-anesthesia. Tropacocaine also had no effect on CNS mediated respiratory rate except when there was a precipitous fall in blood pressure observed with higher doses (attributed to a compensatory mechanism). Mean blood pressure was compared in conscious and anesthetized animals and demonstrated that conscious animals were more resistant to the apparent peripherally-mediated cardiovascular effects of tropacocaine as the dose was increased. No seizures were noted in any animals administered tropacocaine. Results from this study suggest that the cardiovascular actions of tropacocaine are not mediated through the CNS. The lack of tropacocaine-induced seizures also suggests a lack of acute neurotoxicity with this tropane alkaloid. (C) 1995 Inter Press, Inc. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,PEDIAT CLIN PHARMACOL SECT,LITTLE ROCK,AR 72202. US FDA,CTR DRUG EVALUAT & RES,DIV METAB ENDOCRINE DRUG PROD,HFD510,ROCKVILLE,MD 20857. IL YANG PHARMACEUT CO LTD,YONGIN KYUNGKI,SOUTH KOREA. ARKANSAS CHILDRENS HOSP,LITTLE ROCK,AR 72202. NR 20 TC 1 Z9 1 U1 0 U2 2 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SPR PY 1995 VL 16 IS 1 BP 145 EP 151 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA QV617 UT WOS:A1995QV61700016 PM 7603635 ER PT J AU SANDBERG, JA MURPHEY, LJ OLSEN, GD AF SANDBERG, JA MURPHEY, LJ OLSEN, GD TI PHARMACOKINETICS AND METABOLISM OF COCAINE IN MATERNAL AND FETAL GUINEA-PIGS SO NEUROTOXICOLOGY LA English DT Article DE COCAINE; GUINEA PIG; PHARMACOKINETICS; DEVELOPMENT; CYTOCHROME P450 ID LIQUID-CHROMATOGRAPHY; TISSUE DISTRIBUTION; BENZOYLECGONINE; PREGNANCY; DISPOSITION; HUMANS; RATS; BIOTRANSFORMATION; EXPOSURE; INVITRO AB The pharmacokinetics and metabolism of cocaine (COC) were determined in late gestation maternal and fetal guinea pigs. After a single i.v. dose of 2-12 mg/kg, the average +/- SD total body clearance of COC was 59 +/- 16 ml/min/kg and was not dose dependent. However, volume of distribution was 2.1 and 3.9 l/kg, mean resident time (MRT) was 42 and 57 min, and elimination half-life was 34 and 49 min at the 2 and 4 mg/kg dose of COC, respectively. With the exception of an increased MRT, the pharmacokinetics were similar after s.c. COC administration. Benzoylecgonine (BE) and benzoylnorecgonine (BN) were major and persistent metabolites. Norcocaine (NOR) concentrations were low and transient After chronic maternal administration of 6 mg/kg COC s. c., there was no difference between maternal and fetal plasma COC concentrations one hour after the last injection, but COC and BN accumulated in amniotic fluid. Examination of in vitro metabolism of COC in fetal and maternal guinea pig hepatic microsomes demonstrated minimal fetal N-demethylation and induction of maternal N-demethylation by chronic COC exposure. The minimal fetal N-demethylation tion suggests BN seen previously in vivo after chronic maternal COC administration resulted from maternal formation of NOR and subsequent maternal and/or fetal hydrolysis to BN. (C) 1995 Intox Press, inc. C1 US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. RP SANDBERG, JA (reprint author), OREGON HLTH SCI UNIV,SCH MED,DEPT PHARMACEUT L221,PORTLAND,OR 97201, USA. FU NIDA NIH HHS [DA04905, DA05516, DA05489] NR 35 TC 7 Z9 7 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SPR PY 1995 VL 16 IS 1 BP 169 EP 177 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA QV617 UT WOS:A1995QV61700019 PM 7603638 ER PT J AU RHEE, HM SONG, BJ CUSHMAN, S SHOAF, SE AF RHEE, HM SONG, BJ CUSHMAN, S SHOAF, SE TI VASCULAR REACTIVITY IN ALCOHOLIC RAT AORTAS - IN-VITRO INTERACTIONS BETWEEN CATECHOLAMINES AND ALCOHOL SO NEUROTOXICOLOGY LA English DT Article DE ALCOHOL; NOREPINEPHRINE; VASCULAR REACTIVITY; DIABETES MELLITUS; AORTIC RINGS ID BLOOD-PRESSURE; HYPERTENSION; CONSUMPTION; ETHANOL AB To understand the nature of vascular problems of hypertensive and alcoholic subjects, an in vitro interaction between catecholamine and alcohol was investigated in male Sprague-Dawley rats. The decending aortas were isolated from either the control or alcohol treated rats. The aortic strips were cooled rapidly in ice-chilled Krebs-Henseleit (K-H)solution and the aorta was cut into a series of rings of approximately 1 mm width. The rings were fixed under 1 g of resting tension between a force-displacement transducer and anchoring electrodes at 37 degrees C. The rings were equilibrated for an hour with frequent changes of the K-H solution before testing. There was norepinephrine (NE) dose-dependent contraction of the rings, which showed the maximum tension with 1 mu M NE. Acetylcholine or carbachol produced slow relaxation. Pretreatment of the rings with 10 mu M prazocin prevent the contraction induced by 1 mu M NE. Even in the presence of prazocin, 60 mM KCI was able to generate the maximum tension. NE-induced contraction was analyzed in the control K-H solution or in the presence of 1.5, 3.0 and 5.0% of ethanol. Ethanol (1.5%) slowed the rate of rise of the aortic tension without a remarkable compromise of the maximum tension. But, there was a significant reduction in contraction with 3% ethanol. A complete inhibition of contraction was not-ed with 5% ethanol. However, the effect of ethanol was fully reversible upon washings the aortic rings with K-H solution. Aortic rings prepared from the rats that were fed with alcohol for 30 days were not able to generate the maximum tension with 1 mu M NE. The data suggest that alcohol modifies the vascular reactivity to sympathetic responses. (C) 1995 Intox Press, Inc. C1 NIAAA,ROCKVILLE,MD 20852. NIDDKD,BETHESDA,MD 20892. RP RHEE, HM (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV METAB & ENDOCRINE DRUG PROD,ROCKVILLE,MD 20857, USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SPR PY 1995 VL 16 IS 1 BP 179 EP 185 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA QV617 UT WOS:A1995QV61700020 PM 7603639 ER PT J AU KIM, CS SLIKKER, W BINIENDA, Z GARGAS, ML ANDERSEN, ME AF KIM, CS SLIKKER, W BINIENDA, Z GARGAS, ML ANDERSEN, ME TI DEVELOPMENT OF A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL FOR 2,4-DICHLOROPHENOXYACETIC ACID DOSIMETRY IN DISCRETE AREAS OF THE RABBIT BRAIN SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE PHARMACOKINETIC MODELING; 2,4-DICHLOROPHENOXYACETIC ACID (2,4-D); ORGANIC ACID; NEUROTOXICITY RISK ASSESSMENT ID RISK ASSESSMENT; RATS; 2,4-D; HERBICIDE AB A basic PBPK model for the dosimetry of organic acids in discrete areas of the brain was constructed using 2,4-D as a model compound. The PBPK model describes distribution of 2,4-D throughout the body and within discrete areas of the brain. The brain compartments in the model were the hypothalamus, caudate nucleus, hippocampus, forebrain, brainstem, and cerebellum. The remainder of the model consisted of two-body compartments and venous and arterial blood compartments. In the model, chemical uptake by the brain was membrane-limited by the blood-brain barrier (BBB) with saturable clearance from the cerebrospinal fluid (CSF) into the venous blood by the choroid plexus. The body has both a central and a deep compartment with saturable clearance from the central compartment. The model was used to examine the brain and CSF concentrations of 2,4-D as a function of plasma 2,4-D, as well as plasma time-course behavior using experimental data from rabbits given 2,4-D 40 or 100 mg/kg,IP or Na-2,4-D 40 mg/kg, IV administration. Model parameters were adjusted to fit the observed 2,4-D concentrations in blood and brain regions over a 2-h time frame. PBPK models could be a useful tool for evaluating the safety of this class of organic acids. C1 NATL CTR TOXICOL RES,DIV NEUROTOXICOL HFT132,JEFFERSON,AR 72079. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. RP KIM, CS (reprint author), US FDA,DIV TOXICOL RES HFS506,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. OI Andersen, Melvin/0000-0002-3894-4811 NR 27 TC 12 Z9 12 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 1995 VL 17 IS 2 BP 111 EP 120 DI 10.1016/0892-0362(94)00059-M PG 10 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA QG587 UT WOS:A1995QG58700004 PM 7760772 ER PT J AU PETTIT, GH EDIGER, MN WEIBLINGER, RP AF PETTIT, GH EDIGER, MN WEIBLINGER, RP TI EXCIMER-LASER ABLATION OF THE CORNEA SO OPTICAL ENGINEERING LA English DT Article DE OPHTHALMOLOGY; PHOTOABLATION; PHOTOREFRACTIVE KERATECTOMY; LASER INDUCED FLUORESCENCE; INCUBATION ID TIME-RESOLVED REFLECTIVITY; ULTRAVIOLET-RADIATION; ORGANIC POLYMERS; UV-RADIATION; DYNAMICS; SURGERY; LENS; NM; METHACRYLATE; FLUORESCENCE AB Pulsed ultraviolet laser ablation is being extensively investigated clinically to reshape the optical surface of the eye and correct vision defects. Current knowledge of the laser/tissue interaction and the present state of the clinical evaluation are reviewed. In addition, the principal findings of internal Food and Drug Administration research are described in some detail, including a risk assessment of the laser-induced-fluorescence and measurement of the nonlinear optical properties of cornea during the intense UV irradiation. Finally, a survey is presented of the alternative laser technologies being explored for this ophthalmic application. RP PETTIT, GH (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,MAIL STOP HFZ-134,ROCKVILLE,MD 20857, USA. NR 60 TC 21 Z9 24 U1 1 U2 6 PU SOC PHOTO-OPT INSTRUM ENG PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 SN 0091-3286 J9 OPT ENG JI Opt. Eng. PD MAR PY 1995 VL 34 IS 3 BP 661 EP 667 DI 10.1117/12.190408 PG 7 WC Optics SC Optics GA QL475 UT WOS:A1995QL47500003 ER PT J AU MOSTAFA, MH BADAWI, AF OCONNOR, PJ AF MOSTAFA, MH BADAWI, AF OCONNOR, PJ TI BLADDER-CANCER ASSOCIATED WITH SCHISTOSOMIASIS SO PARASITOLOGY TODAY LA English DT Editorial Material ID PROMUTAGENIC METHYLATION DAMAGE; MECHANISMS; MICE; DNA C1 NATL CTR TOXICOL RES,PUBL HLTH SERV FOOD & DRUG ADM,JEFFERSON,AR 72079. CHRISTIE HOSP & HOLT RADIUM INST,PATERSON INST CANC RES,DEPT CARCINOGENESIS,CANC RES CAMPAIGN,MANCHESTER M20 9BX,LANCS,ENGLAND. RP MOSTAFA, MH (reprint author), UNIV ALEXANDRIA,INST GRAD STUDIES & RES,CHATBY 21526,ALEXANDRIA,EGYPT. NR 14 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD MAR PY 1995 VL 11 IS 3 BP 87 EP 89 DI 10.1016/0169-4758(95)80160-X PG 3 WC Parasitology SC Parasitology GA QH307 UT WOS:A1995QH30700001 ER PT J AU DHAWAN, S HEREDIA, A WAHL, LM EPSTEIN, JS MELTZER, MS HEWLETT, IK AF DHAWAN, S HEREDIA, A WAHL, LM EPSTEIN, JS MELTZER, MS HEWLETT, IK TI INTERFERON-GAMMA-INDUCED DOWN-REGULATION OF CD4 INHIBITS THE ENTRY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN PRIMARY MONOCYTES SO PATHOBIOLOGY LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS TYPE-1; PATHOGENESIS; MONOCYTES; INTERFERON-GAMMA; TUMOR NECROSIS FACTOR-ALPHA ID IFN-GAMMA; MONONUCLEAR PHAGOCYTES; INFECTED-CELLS; MACROPHAGES; AIDS; REPLICATION; ACTIVATION; MECHANISM; NITRITE; ALPHA AB We have previously shown that the treatment of monocytes with interferon-gamma (IFN-gamma) prior to exposure with human immunodeficiency virus type-1 (HIV) results in complete inhibition of HIV infection of monocytes. In the present report, we have extended this study to obtain information on the mechanism(s) underlying IFN-gamma-induced inhibition of HIV infection of monocytes. To examine the effect of IFN-gamma on HIV entry, the first event in the infectious cycle of the virus, we amplified HIV-gag sequences in the genomic DNA and RNA of IFN-gamma treated monocytes, and found no evidence for the presence of either proviral DNA or HIV RNA sequences. These results were consistent with the absence of intracellular HIV particles either in the latent or actively replicating state as determined by flow-cytometric analysis of these cells. Furthermore, no HIV-induced cytopathic effects, such as multinucleated giant cell formation or cell death, were observed in IFN-gamma-treated monocytes after their exposure to HIV. Stimulation of IFN-gamma-treated monocytes 6 days postinfection with tumor necrosis factor-alpha(TNF-alpha), which is known to augment HIV replication in the infected cells, did not result in the induction of the HIV indicating the absence of latent HIV infection in IFN-gamma-treated monocytes. Treatment of monocytes with IFN-gamma, TNF-alpha, or with a combination of the two agents which is known to induce antimicrobial free radical nitric oxide (NO2- in the murine system did not induce NO(2)(-)production human monocytes suggesting the antiviral activity of IFN-gamma to be independent of NO(2)(-)mediated killing of HIV or HIV-infected monocytes. Interestingly, CD4 expression on the surface of monocytes was substantially downregulated by IFN-gamma treatment, and was directly related to intracellular HIV-p24 levels. These results indicate that IFN-gamma-mediated inhibition of HIV infection of monocytes was not due to virus latency or killing of these cells, but was primarily due to downregulation of CD4 expression resulting in the inhibition of HIV entry into monocytes. C1 NIDR,IMMUNOL LAB,BETHESDA,MD 20892. WALTER REED ARMY INST RES,DEPT CELLULAR IMMUNOL,WASHINGTON,DC. RP DHAWAN, S (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,MOLEC VIROL LAB,ROCKVILLE,MD 20852, USA. NR 23 TC 28 Z9 30 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD MAR-APR PY 1995 VL 63 IS 2 BP 93 EP 99 DI 10.1159/000163939 PG 7 WC Cell Biology; Pathology SC Cell Biology; Pathology GA RY038 UT WOS:A1995RY03800006 PM 8554705 ER PT J AU AMIDON, GL LENNERNAS, H SHAH, VP CRISON, JR AF AMIDON, GL LENNERNAS, H SHAH, VP CRISON, JR TI A THEORETICAL BASIS FOR A BIOPHARMACEUTIC DRUG CLASSIFICATION - THE CORRELATION OF IN-VITRO DRUG PRODUCT DISSOLUTION AND IN-VIVO BIOAVAILABILITY SO PHARMACEUTICAL RESEARCH LA English DT Article DE BIOAVAILABILITY; DRUG ABSORPTION; MATHEMATICAL MODELING; IN VITRO IN VIVO CORRELATION; INTESTINAL PERMEABILITY ID INTESTINAL-MEMBRANE PERMEABILITY; REGIONAL JEJUNAL PERFUSION; ORAL ABSORPTION; PARTICLE-SIZE; DOSAGE FORMS; MODEL; TRANSIT; HUMANS AB A biopharmaceutics drug classification scheme for correlating in vitro drug product dissolution and in vivo bioavailability is proposed based on recognizing that drug dissolution and gastrointestinal permeability are the fundamental parameters controlling rate and extent of drug absorption. This analysis uses a transport model and human permeability results for estimating in vivo drug absorption to illustrate the primary importance of solubility and permeability on drug absorption. The fundamental parameters which define oral drug absorption in humans resulting from this analysis are discussed and used as a basis for this classification scheme. These Biopharmaceutic Drug Classes are defined as: Case 1. High solubility-high permeability drugs, Case 2. Low solubility-high permeability drugs, Case 3. High solubility-low permeability drugs, and Case 4. Low solubility-low permeability drugs. Based on this classification scheme, suggestions are made for setting standards for in vitro drug dissolution testing methodology which will correlate with the in vivo process. This methodology must be based on the physiological and physical chemical properties controlling drug absorption. This analysis points out conditions under which no in vitro-in vivo correlation may be expected e.g. rapidly dissolving low permeability drugs. Furthermore, it is suggested for example that for very rapidly dissolving high solubility drugs, e.g. 85% dissolution in less than 15 minutes, a simple one point dissolution test, is all that may be needed to insure bioavailability. For slowly dissolving drugs a dissolution profile is required with multiple time points in systems which would include low pH, physiological pH, and surfactants and the in vitro conditions should mimic the in vivo processes. This classification scheme provides a basis for establishing in vitro-in vivo correlations and for estimating the absorption of drugs based on the fundamental dissolution and permeability properties of physiologic importance. C1 UNIV UPPSALA,SCH PHARM,S-75123 UPPSALA,SWEDEN. US FDA,HFD 602,ROCKVILLE,MD 20857. TSRL INC,ANN ARBOR,MI 48108. RP AMIDON, GL (reprint author), UNIV MICHIGAN,COLL PHARM,428 CHURCH ST,ANN ARBOR,MI 48109, USA. FU FDA HHS [FD01462]; NIGMS NIH HHS [GM37188] NR 33 TC 2377 Z9 2509 U1 39 U2 303 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD MAR PY 1995 VL 12 IS 3 BP 413 EP 420 DI 10.1023/A:1016212804288 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA QM376 UT WOS:A1995QM37600016 PM 7617530 ER PT J AU KENYON, AS LAYLOFF, TP AF KENYON, AS LAYLOFF, TP TI ELIMINATION OR REDUCTION OF THE USE OF MERCURY, MERCURY-COMPOUNDS, AND CHROMIC-ACID CLEANING SOLUTION IN THE USP PROCEDURES SO PHARMACOPEIAL FORUM LA English DT Article RP KENYON, AS (reprint author), US FDA,DIV DRUG ANAL,1114 MARKET ST,ROOM 1002,ST LOUIS,MO 63101, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU US PHARMACOPEIAL CONVENTION PI ROCKVILLE PA 12601 TWINBROOK PKWY, ROCKVILLE, MD 20852 SN 0363-4655 J9 PHARMACOPEIAL FORUM JI Pharmacop. Forum PD MAR-APR PY 1995 VL 21 IS 2 BP 485 EP 489 PG 5 WC Medicine, Legal; Pharmacology & Pharmacy SC Legal Medicine; Pharmacology & Pharmacy GA QM369 UT WOS:A1995QM36900002 ER PT J AU TORRENCE, ME BECK, AM GLICKMAN, LT PEREZ, CM SAMUELS, ML AF TORRENCE, ME BECK, AM GLICKMAN, LT PEREZ, CM SAMUELS, ML TI RACCOON RABIES IN THE MID-ATLANTIC (EPIDEMIC) AND SOUTHEASTERN STATES (ENDEMIC), 1970-1986 - AN EVALUATION OF REPORTING METHODS SO PREVENTIVE VETERINARY MEDICINE LA English DT Article DE RACCOON; RABIES; EPIDEMIC; ENDEMIC; USA ID UNITED-STATES; SURVEILLANCE AB This study evaluates the current method of rabies reporting in the United States to assess its ability to reflect temporal trends of animal rabies transmission as epidemiologic patterns change. Currently, the Centers for Disease Control and Prevention report only the numbers of animals confirmed rabid in each state. The reported data from three states that experienced a raccoon rabies epidemic and three states that had experienced endemic raccoon rabies from 1970 to 1986 were analyzed by calculating the percent of animals that tested positive for rabies from state records and plotting them, using modified smoothing splines. These data were compared with the number of animals that tested positive for rabies. The findings indicated that the reported numbers of positive animals by themselves should not be used to assess changes in rabies frequency. The percent rabies positive of the total tested was more reflective of temporal changes of rabies occurrence in the population and of the known patterns of rabies transmission between raccoons and other terrestrial species. Reporting the percent positive of those examined for rabies requires not collecting new data, but rather the reporting of total number of animals tested, and a simple calculation of information reported. C1 PURDUE UNIV,SCH SCI,DEPT STAT,W LAFAYETTE,IN 47907. PURDUE UNIV,SCH VET MED,DEPT VET PATHOBIOL,W LAFAYETTE,IN 47907. PURDUE UNIV,SCH VET MED,DEPT VET PATHOBIOL,CTR APPL ETHOL & HUMAN ANIM INTERACT,W LAFAYETTE,IN 47907. RP TORRENCE, ME (reprint author), US FDA,CTR VET MED,DIV SURVEILLANCE,ROCKVILLE,MD 20855, USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-5877 J9 PREV VET MED JI Prev. Vet. Med. PD MAR PY 1995 VL 22 IS 3 BP 197 EP 211 DI 10.1016/0167-5877(94)00410-K PG 15 WC Veterinary Sciences SC Veterinary Sciences GA QR331 UT WOS:A1995QR33100004 ER PT J AU MEDLOCK, KL BRANHAM, WS SHEEHAN, DM AF MEDLOCK, KL BRANHAM, WS SHEEHAN, DM TI THE EFFECTS OF PHYTOESTROGENS ON NEONATAL RAT UTERINE GROWTH AND DEVELOPMENT SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID COUMESTROL; UTERUS; ESTROGEN; MICE; DIETHYLSTILBESTROL; ZEARALANOL; RECEPTOR; HORMONE; BINDING; CLOVER AB Phytoestrogens found in clover, alfalfa, and soybeans have caused reproductive toxicity in several mammalian species. Other estrogens, such as diethylstilbestrol (DES), are developmental toxicants, reducing uterine estrogen receptor (ER) concentration, altering uterine growth, and eliciting reproductive tract abnormalities in the rat. The present study examines the effects of the phytoestrogens coumestrol and equol on the developing rat uterus. Various doses of these compounds were injected sc on postnatal days (PND) 1-5 or 1-10 to ascertain their effects on uterine weight and ER levels, and on PND 10-14 to determine their effects on uterine weight and gland genesis. Coumestrol (PND 1-5) was about 10(-3) as potent as DES in increasing uterine weight (wet or dry) while equol increased dry weight only, with a potency of 10(-5) that of DES. Although the 10 and 100 mu g doses of coumestrol (PND 1-5 or 1-10) initially increased uterine wet weight, by PND 20 uterine weights either equaled or fell significantly below controls. The 100-mu g dose of coumestrol (PND 1-5 or 1-10) reduced ER levels at all ages, while the 10-mu g dose was not as effective. Equol (PND 1-5 or 1-10) did not affect ER levels. Premature uterine gland genesis occurred by PND 9 for the PND 1-5 100-mu g coumestrol dose. When given on PND 10-14 (the critical period of gland genesis), 10 mu g and 100 mu g of coumestrol and 10 mu g DES greatly increased uterine weight, while no effect was elicited by equol. Although coumestrol and equol inhibited uterine gland genesis in a dose-dependent manner, neither abolished gland genesis as did 10 mu g of DES or tamoxifen. These data demonstrate that coumestrol elicits uterine biochemical and morphological toxicity much like DES. Equol decreased uterine gland number without increasing uterine wet weight or luminal epithelial hypertrophy, which is inconsistent with either an estrogenic or antiestrogenic action in the uterus. C1 UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. RP MEDLOCK, KL (reprint author), US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,DIV REPROD & DEV TOXICOL,HFT-130,JEFFERSON,AR 72079, USA. NR 29 TC 45 Z9 46 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD MAR PY 1995 VL 208 IS 3 BP 307 EP 313 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QK568 UT WOS:A1995QK56800012 PM 7878071 ER PT J AU VANDENBOOGAART, JE HUIGE, CJM BOAL, JH EGAN, W ALTONA, C AF VANDENBOOGAART, JE HUIGE, CJM BOAL, JH EGAN, W ALTONA, C TI AN ABASIC SITE INDUCES A BULGED CONFORMATION IN THE SINGLE-STRANDED-DNA TRIMER D(AP(AB)PA) - AN NMR AND MODEL-BUILDING STUDY SO RECUEIL DES TRAVAUX CHIMIQUES DES PAYS-BAS-JOURNAL OF THE ROYAL NETHERLANDS CHEMICAL SOCIETY LA English DT Article DE CONFORMATIONAL ANALYSIS; DNA DERIVATIVES; MULTIDIMENSIONAL NMR ID MOLECULAR MECHANICS CALCULATIONS; NUCLEIC-ACID CONSTITUENTS; SPIN COUPLING-CONSTANTS; PROTON-NMR; MAGNETIC-RESONANCE; DEOXYADENOSINE STACKS; AQUEOUS-SOLUTION; HELIX OPPOSITE; SUGAR RING; SPECTROSCOPY AB 1',2'-Dideoxy-D-ribofuranose (ab), its 5'- and 3'-phosphorylated analogues (ab5 and ab3), and the DNA trimer d(Ap(ab)pA) have been studied by means of proton NMR spectroscopy. These fragments are of interest as model compounds for abasic lesions occurring in vivo. All abasic sugars exhibit similar S-type sugar conformations with populations of S-conformer varying from 75% (in ab and ab5) to 83% (in ab3 and dab(2)), P-s approximate to 144 degrees and Phi(s) in the range from 30 to 33 degrees. Having established the presence of mainly S-type sugar, we could assign the H1' and H1'' protons of all abasic residues stereospecifically on the basis of their respective vicinal coupling constants. The trimer exhibits considerable flexibility in the backbone. Moreover, chemical shifts as a function of temperature and chemical-shift differences between abasic sugar protons in the trimer and in the abasic monomers point to the presence of a structure in which dab(2) is bulged out of the helix and the terminal residues stack on top of each other. Several models which fit the experimental data are presented. C1 US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,BETHESDA,MD 20892. RP VANDENBOOGAART, JE (reprint author), LEIDEN UNIV,GORLAEUS LABS,LEIDEN INST CHEM,POB 9502,2300 RA LEIDEN,NETHERLANDS. NR 50 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0513 J9 RECL TRAV CHIM PAY B JI Recl. Trav. Chim. Pays-Bas-J. Roy. Neth. Chem. Soc. PD MAR PY 1995 VL 114 IS 3 BP 79 EP 86 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA QX848 UT WOS:A1995QX84800001 ER PT J AU KESSLER, DA FEIDEN, KL AF KESSLER, DA FEIDEN, KL TI FASTER EVALUATION OF VITAL DRUGS SO SCIENTIFIC AMERICAN LA English DT Article ID TRIALS RP KESSLER, DA (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD MAR PY 1995 VL 272 IS 3 BP 48 EP 54 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QG731 UT WOS:A1995QG73100026 PM 7871409 ER PT J AU HARDEMAN, S NELSON, T BEIRNE, D DESILVA, M HESKETH, PJ MACLAY, GJ GENDEL, SM AF HARDEMAN, S NELSON, T BEIRNE, D DESILVA, M HESKETH, PJ MACLAY, GJ GENDEL, SM TI SENSITIVITY OF NOVEL ULTRATHIN PLATINUM FILM IMMUNOSENSORS TO BUFFER IONIC-STRENGTH SO SENSORS AND ACTUATORS B-CHEMICAL LA English DT Article; Proceedings Paper CT 5th International Meeting on Chemical Sensors CY JUL 11-14, 1994 CL ROME, ITALY DE BUFFER IONIC STRENGTH; IMMUNOSENSORS; PLATINUM ID BIOSENSORS AB The direct detection of antibody/antigen binding is demonstrated with a conductivity-based sensor. The sensor consists of an ultrathin Nm of platinum 25 Angstrom thick deposited onto an insulating silicon dioxide or silicon nitride substrate. The film has a metal island structure, as demonstrated by atomic force microscope images of the surface. The impedance response at 20 Hz to 1 MHz measured in buffers of differing pH and ionic strength indicates that the conductivity of the solution is a dominant factor in defining the response of the sensor. C1 IIT,DEPT CHEM,CHICAGO,IL 60616. US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT,IL 60501. RP HARDEMAN, S (reprint author), UNIV ILLINOIS,DEPT ELECT ENGN & COMP SCI,MICROFABRICAT APPLLICAT LAB,CHICAGO,IL 60607, USA. NR 7 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0925-4005 J9 SENSOR ACTUAT B-CHEM JI Sens. Actuator B-Chem. PD MAR PY 1995 VL 24 IS 1-3 BP 98 EP 102 DI 10.1016/0925-4005(95)85021-X PG 5 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA RM959 UT WOS:A1995RM95900019 ER PT J AU DEGEORGE, JJ AF DEGEORGE, JJ TI FOOD-AND-DRUG-ADMINISTRATION VIEWPOINTS ON TOXICOKINETICS - THE VIEW FROM REVIEW SO TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT 13th International Symposium of the Society-of-Toxicologic-Pathologists, Role of Drug Metabolism and Pharmacokinetics in Toxicologic Pathology CY JUN 05-09, 1994 CL CHARLESTON, SC SP SOC TOXICOL PATHOLOGISTS DE PHARMACOKINETICS; TOXICOLOGY; DRUG DEVELOPMENT AB The importance of drug kinetics for interpretation of toxicity findings and for cross-species toxicity assessment has been long recognized. Recently, an international effort was initiated to standardize guidance on the kinetic data to be collected in conjunction with toxicity studies. The guidance addresses the kinetic data to be included in studies on carcinogenicity, reproduction toxicity, genotoxicity, and single- and repeat-dose toxicity. In various stages of development or implementation, the guidance is intentionally nondetailed regarding the specific kinetic assessments to be performed. This is to allow flexibility in study design and ensures that scientific judgment is used to determine the appropriate kinetic endpoints to achieve study- and drug-specific goals. Some examples of how kinetics have been used at the Food and Drug Administration in review of toxicity studies submitted in drug applications are presented. The examples discussed demonstrate successful and unsuccessful integration of kinetics into study design and interpretation and highlight the impact on the drug development program from a regulatory perspective. RP DEGEORGE, JJ (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV ONCOL & PULM DRUG PROD,5600 FISHERS LANE,HFD-150,ROCKVILLE,MD 20857, USA. NR 0 TC 5 Z9 6 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAR-APR PY 1995 VL 23 IS 2 BP 220 EP 225 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA QU178 UT WOS:A1995QU17800017 PM 7569678 ER PT J AU KIM, CS GARGAS, ML ANDERSEN, ME AF KIM, CS GARGAS, ML ANDERSEN, ME TI PHARMACOKINETIC MODELING OF 2,4-DICHLOROPHENOXYACETIC ACID (2,4-D) IN RAT AND IN RABBIT BRAIN FOLLOWING SINGLE-DOSE ADMINISTRATION (VOL 74, PG 189, 1994) SO TOXICOLOGY LETTERS LA English DT Correction, Addition C1 CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. RP KIM, CS (reprint author), US FDA,DIV TOXICOL RES HFS506,WASHINGTON,DC 20204, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD MAR PY 1995 VL 76 IS 2 BP 185 EP 185 DI 10.1016/0378-4274(95)95696-L PG 1 WC Toxicology SC Toxicology GA QT009 UT WOS:A1995QT00900012 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI METFORMIN APPROVED FOR NON-INSULIN-DEPENDENT DIABETES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US FDA, OFF HLTH AFFAIRS, FDA PARKLAWN BLDG, 5600 FISHERS LN, ROCKVILLE, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 22 PY 1995 VL 273 IS 8 BP 613 EP 613 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QG748 UT WOS:A1995QG74800008 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI NALTREXONE APPROVED AS ADJUNCT IN ALCOHOLISM-TREATMENT SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US FDA, OFF HLTH AFFAIRS, FDA 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 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 22 PY 1995 VL 273 IS 8 BP 613 EP 613 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QG748 UT WOS:A1995QG74800007 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI ORAL FLUID SPECIMEN TEST SYSTEM FOR HIV-1 APPROVED SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US FDA, OFF HLTH AFFAIRS, FDA PARKLAWN BLDG, 5600 FISHERS LN, ROCKVILLE, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 22 PY 1995 VL 273 IS 8 BP 613 EP 613 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QG748 UT WOS:A1995QG74800006 ER PT J AU GOLDEN, L STADEL, B AF GOLDEN, L STADEL, B TI ESTROGEN REPLACEMENT THERAPY IN BREAST-CANCER SURVIVORS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP GOLDEN, L (reprint author), US FDA,ROCKVILLE,MD, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 22 PY 1995 VL 273 IS 8 BP 620 EP 621 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QG748 UT WOS:A1995QG74800021 PM 7844869 ER PT J AU JAYATILAKA, A POOLE, SK POOLE, CF CHICHILA, TMP AF JAYATILAKA, A POOLE, SK POOLE, CF CHICHILA, TMP TI SIMULTANEOUS MICRO STEAM DISTILLATION SOLVENT-EXTRACTION FOR THE ISOLATION OF SEMIVOLATILE FLAVOR COMPOUNDS FROM CINNAMON AND THEIR SEPARATION BY SERIES COUPLED-COLUMN GAS-CHROMATOGRAPHY SO ANALYTICA CHIMICA ACTA LA English DT Article DE GAS CHROMATOGRAPHY; MICRO STEAM DISTILLATION; CINNAMON; FLAVOR COMPOUNDS ID TUBULAR CAPILLARY COLUMNS; SAMPLE PREPARATION; ORGANIC-COMPOUNDS; SELECTIVITY; OPTIMIZATION; OIL AB Simultaneous micro steam distillation/solvent extraction is an efficient method of extracting semivolatile flavor and fragrance compounds from cinnamon for subsequent separation by series coupled-column gas chromatography. With pentane as the extraction solvent and an extraction time of 1.5 h clean extracts requiring no further sample preparation prior to gas chromatographic analysis are obtained. It is shown that adulteration of cinnamon inner bark oil with leaf oil can be recognized by an elevated concentration of eugenol with respect to the concentration of trans-cinnamaldehyde and the presence of eugenol acetate and safrole in amounts exceeding trace quantities. The principal Cinnamomum species of commerce can be identified in powdered samples based on differences in their characteristic chromatographic profiles. True cinnamon (Cinnamomum zeylanicum Nees) can be distinguished from cassia by the presence of eugenol and benzyl benzoate, and the absence of coumarin and delta-cadinene, all minor components, referenced to the extracted amount of trans-cinnamaldehyde. Multivariate analysis of 16 semivolatile compounds commonly found in powdered cinnamon samples is used to classify samples of cinnamon purchased in seven countries. C1 WAYNE STATE UNIV,DEPT CHEM,DETROIT,MI 48202. US FDA,PESTICIDE & IND CHEM RES CTR,DETROIT,MI 48207. NR 36 TC 46 Z9 52 U1 2 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD FEB 20 PY 1995 VL 302 IS 2-3 BP 147 EP 162 DI 10.1016/0003-2670(94)00445-R PG 16 WC Chemistry, Analytical SC Chemistry GA QH032 UT WOS:A1995QH03200002 ER PT J AU SIEGEL, JP AF SIEGEL, JP TI ANTIENDOTOXIN ANTIBODIES SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP SIEGEL, JP (reprint author), US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852, USA. NR 2 TC 7 Z9 7 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 15 PY 1995 VL 122 IS 4 BP 315 EP 315 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QF769 UT WOS:A1995QF76900017 PM 7825773 ER PT J AU HOWARD, OMZ KIRKEN, RA GARCIA, GG HACKETT, RH FARRAR, WL AF HOWARD, OMZ KIRKEN, RA GARCIA, GG HACKETT, RH FARRAR, WL TI STRUCTURAL DOMAINS OF INTERLEUKIN-2 RECEPTOR-BETA CRITICAL FOR SIGNAL-TRANSDUCTION - KINASE ASSOCIATION AND NUCLEAR COMPLEX-FORMATION SO BIOCHEMICAL JOURNAL LA English DT Article ID PROTEIN-TYROSINE KINASES; COLONY-STIMULATING FACTOR; GROWTH-HORMONE RECEPTOR; HUMAN IL-2 RECEPTOR; HUMAN T-CELLS; GAMMA-CHAIN; CYTOPLASMIC REGIONS; PHOSPHORYLATION; SUBUNIT; ACTIVATION AB The structural domains of interleukin-2 receptor beta (IL-2R beta) were examined, characterizing the protein domains, associated phosphoproteins and nuclear complexes of IL-2-induced signal transduction. A series of IL-2R beta cytoplasmic deletion mutants were constructed and transfected into a murine pre-B-cell line, Ba/F3. The proliferative response of characterized clones was determined. A minimal linear cytoplasmic sequence required for proliferation and a sequence motif (PQPLXP) needed along with Box1-Box2 for IL-2-induced proliferation were identified, Anti-phosphotyrosine Western-blot analysis of a stimulated biologically active clone showed several IL-2-induced tyrosylphosphorylated proteins with molecular masses ranging from 45 to 116 kDa. In vitro kinase studies of biologically active clone-receptor complexes showed a 116 kDa protein (p116) to be the major tyrosine-phosphorylated component. The presence of the p116 kinase in the receptor complex correlates with IL-2-induced proliferation. An IL-2-inducible p116 kinase has recently been characterized as a Jak kinase family member and named Jak3. Nuclear complexes were formed with the GRR oligomer only when the IL-2R beta mutant supported proliferation. This led us to conclude that Box1-Box2 and PQPLXP motifs associate with Jak3 and that this association is an essential element in the IL-2 signal-transduction pathway culminating in the formation of a nuclear complex. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. RP HOWARD, OMZ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 50 TC 21 Z9 22 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD FEB 15 PY 1995 VL 306 BP 217 EP 224 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QH166 UT WOS:A1995QH16600032 PM 7532397 ER PT J AU GORDON, AW PEGUES, JC JOHNSON, GR KANNAN, B AUERSPERG, N STROMBERG, K AF GORDON, AW PEGUES, JC JOHNSON, GR KANNAN, B AUERSPERG, N STROMBERG, K TI MESSENGER-RNA PHENOTYPING OF THE MAJOR LIGANDS AND RECEPTORS OF THE EGF SUPERGENE FAMILY IN HUMAN OVARIAN EPITHELIAL-CELLS SO CANCER LETTERS LA English DT Article DE EGF; TGF-ALPHA; AMPHIREGULIN; EGF-R; ERBB-2; OVARIAN CARCINOMA CELLS ID EPIDERMAL GROWTH-FACTOR; FACTOR-ALPHA; SURFACE EPITHELIUM; SMALL NUMBERS; EXPRESSION; CANCER; AUTOCRINE; AMPHIREGULIN; CARCINOMA; HER-2/NEU AB mRNA amplification phenotyping (MAPPing) was used to determine the level of mRNA expression of the major EGF-related ligands (EGF, TGF-alpha, and Amphiregulin) and receptors (EGF-receptor and erbB-2) of the EGF supergene family in three ovarian carcinoma lines (OVCA 429 and 433, and NIH:OVCAR-8) under serum-supplemented and reduced serum (minimal medium with 2% fetuin) growth conditions. mRNA levels of TGF-alpha, EGF-R, and erbB-2 were particularly high, and increased approximately 2-3 orders of magnitude when grown in serum, consistent with an autocrine involvement of these genes in ovarian epithelial growth in vitro. Moreover, even when grown without serum, OVCA 429 and NIH:OVCAR-8 expressed elevated levels of mRNA for erbB-2. C1 US FDA,CTR BIOL EVALUAT & RES,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. UNIV BRITISH COLUMBIA,DEPT ANAT,VANCOUVER,BC V6T 1Z3,CANADA. NR 38 TC 26 Z9 26 U1 0 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 10 PY 1995 VL 89 IS 1 BP 63 EP 71 DI 10.1016/0304-3835(95)90159-0 PG 9 WC Oncology SC Oncology GA QP339 UT WOS:A1995QP33900010 PM 7882303 ER PT J AU MALOZOWSKI, S HUNG, W SCOTT, DC STADEL, BV AF MALOZOWSKI, S HUNG, W SCOTT, DC STADEL, BV TI ACUTE-PANCREATITIS ASSOCIATED WITH GROWTH-HORMONE THERAPY FOR SHORT STATURE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. RP MALOZOWSKI, S (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 5 TC 25 Z9 25 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 9 PY 1995 VL 332 IS 6 BP 401 EP 402 DI 10.1056/NEJM199502093320618 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QF300 UT WOS:A1995QF30000027 PM 7824013 ER PT J AU BYRNES, GA CHANG, B LOOSE, I MILLER, SA BENSON, WE AF BYRNES, GA CHANG, B LOOSE, I MILLER, SA BENSON, WE TI PROSPECTIVE INCIDENCE OF PHOTIC MACULOPATHY AFTER CATARACT-SURGERY SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Note AB PURPOSE/METHODS: To determine the incidence of photic retinal injury during cataract surgery, we studied 37 consecutive patients with intravenous fluorescein angiography within ten days after cataract surgery. The microscope irradiance was standardized for all cases. RESULTS/CONCLUSIONS: Fluorescein evidence of photic retinal injury did not develop in any of the 37 cataract patients. Incidence rates for photic retinal injury induced by the surgical microscope vary considerably among ophthalmologists and most likely reflect differences in microscope brightness, surgical duration, and surgical technique. C1 WILLS EYE HOSP & RES INST,DEPT RETINAL SURG,PHILADELPHIA,PA 19107. US FDA,ELECTROOPT BRANCH,WASHINGTON,DC 20204. NR 3 TC 23 Z9 23 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 1995 VL 119 IS 2 BP 231 EP 232 PG 2 WC Ophthalmology SC Ophthalmology GA QE782 UT WOS:A1995QE78200016 PM 7832232 ER PT J AU LYTLE, CD ROUTSON, LB AF LYTLE, CD ROUTSON, LB TI MINIMIZED VIRUS BINDING FOR TESTS OF BARRIER MATERIALS SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SURROGATE VIRUSES; MEMBRANE FILTERS; POLIOVIRUS AB Viruses are used to test the barrier properties of materials. Binding of virus particles during passage through holes in the material may yield misleading test results. The choices of challenge virus and suspending medium may be important for minimizing confounding effects that might arise from such binding. In this study, different surrogate viruses, as well as different support media, were evaluated to determine optimal test parameters. Two membranes with high-binding properties (nitrocellulose and cationic polysulfone) were used as filters to compare binding activities of different surrogate challenge viruses (MS2, phi X174, T7, PRD1, and phi 6) in different media. The media consisted of buffered saline with surfactants, serum, or culture broth as additives. In addition, elution rates of viruses that bound to the membranes were determined. The results suggest that viruses can bind by hydrophobic and electrostatic interactions, with phi X174 displaying the lowest level of binding by either process. The nonionic detergents Triton X-100 and Tween 80 (0.1%) equally minimized hydrophobic interactions. Neither anionic nor cationic surfactants were as effective at nontoxic levels. Serum was effective at reducing both hydrophobic and electrostatic binding, with 2% being sufficient for eliminating binding under our test conditions. Thus, phi X174 remains the best choice as a surrogate virus to test barrier materials, and Triton X-100 (0.1%) remains a good choice for reducing hydrophobic binding. In addition, binding of viruses by barrier materials is unlikely to prevent passage of blood-borne pathogens. C1 BIOCON INC,ROCKVILLE,MD 20857. RP LYTLE, CD (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,DIV LIFE SCI,HFZ-112,12709 TWINBROOK PKWY,ROCKVILLE,MD 20857, USA. NR 16 TC 40 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD FEB PY 1995 VL 61 IS 2 BP 643 EP 649 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA QF428 UT WOS:A1995QF42800037 PM 7574603 ER PT J AU LEBEDEVA, LG ALEXANDROVA, SS VOTRIN, II BASNAKIAN, AG AF LEBEDEVA, LG ALEXANDROVA, SS VOTRIN, II BASNAKIAN, AG TI IN-VITRO PROTEOLYSIS OF ENDONUCLEASES IN RAT-LIVER NUCLEI EXTRACTS SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article ID GRANULE SERINE PROTEASES; DNA FRAGMENTATION; PURIFICATION; APOPTOSIS; THYMOCYTES; PROTEIN; IDENTIFICATION; CALCIUM AB DNA endonucleases in rat liver nuclei extracts were examined by SDS-polyacrylamide gel electrophoresis followed by zymogram analysis. Four polypeptides of 120, 54, 31 and 28 kDa, which have DNA endonuclease activity, were shown to occur in the extract isolated in the presence of phenylmethanesulfonyl fluoride (PMSF), a proteinase inhibitor. Isolation without PMSF, as well as storage at -20 degrees C, or autodigestion, resulted in multiplication of active polypeptides in the extracts. Trypsin digestion led to the appearance of an active >140 kDa polypeptide, indicating the existence of a potential endonuclease precursor in the nuclear extract. C1 US FDA,NATL CTR TOXICOL RES,DEPT NUTR TOXICOL,JEFFERSON,AR 72079. RUSSIAN ACAD MED SCI,INST BIOL & MED CHEM,MOSCOW 119832,RUSSIA. NR 29 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD FEB PY 1995 VL 35 IS 2 BP 433 EP 440 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QX927 UT WOS:A1995QX92700025 PM 7663399 ER PT J AU JANZ, S GAWRISCH, K LESTER, DS AF JANZ, S GAWRISCH, K LESTER, DS TI TRANSLOCATION AND ACTIVATION OF PROTEIN-KINASE-C BY THE PLASMA-CELL TUMOR-PROMOTING ALKANE PRISTANE SO CANCER RESEARCH LA English DT Article ID PROMYELOCYTIC LEUKEMIA-CELLS; HEMATOPOIETIC-CELLS; DIFFERENTIATION; INVITRO; 2,6,10,14-TETRAMETHYLPENTADECANE; EXPRESSION; BILAYERS; ACID; DNA; SPECTROSCOPY AB Pristane (2,6,10,14-tetramethylpentadecane) is a C-19-isoalkane that promotes the development of plasmacytomas in genetically susceptible BALB/c mice. Similarities between the effects of pristane and protein kinase C (PKC)-activating phorbol esters suggested that the tumor promoting activity of pristane might involve the activation of PKC. Here we show that up to 5 mol% of pristane can be homogeneously incorporated into phosphatidylcholine/phosphatidylserine bilayers. Membrane incorporated pristane partially activated PKC and increased phorbol ester binding to the bilayer by more than 50%. Pristane (50 mu M) delivered as an inclusion complex with beta-cyclodextrin to promyelocytic HL-60 leukemia cells induced a partial Long-term translocation of PKC to the cell membrane. This was accompanied by differentiation of HL-60 cells into macrophage-like cells. It is concluded that activation of PKC may comprise an important aspect of the tumor promoting potential of pristane. C1 NIAAA,MEMBRANE BIOCHEM & BIOPHYS LAB,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,DIV RES & TESTING,LAUREL,MD 20708. RP JANZ, S (reprint author), NCI,GENET LAB,BLDG 37,ROOM 2B09,BETHESDA,MD 20892, USA. NR 47 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1995 VL 55 IS 3 BP 518 EP 524 PG 7 WC Oncology SC Oncology GA QD717 UT WOS:A1995QD71700016 PM 7834620 ER PT J AU CHOU, HC LANG, NP KADLUBAR, FF AF CHOU, HC LANG, NP KADLUBAR, FF TI METABOLIC-ACTIVATION OF N-HYDROXY ARYLAMINES AND N-HYDROXY HETEROCYCLIC AMINES BY HUMAN SULFOTRANSFERASE(S) SO CANCER RESEARCH LA English DT Article ID PLATELET PHENOL SULFOTRANSFERASE; HUMAN-LIVER; AROMATIC-AMINES; DNA; PHENOLSULFOTRANSFERASE; POLYMORPHISM; PURIFICATION; ACETYLATION; CARCINOGENS; OXIDATION AB Several N-hydroxy metabolites of carcinogenic arylamines and heterocyclic amines were examined as substrates for bioactivation by human Liver sulfotransferases (STs). Among the N-hydroxy derivatives studied, N-hydroxy-2-acetylaminofluorene, N-hydroxy-2-aminofluorene, N-hydroxy-4,4'-methylene-bis(2-chloroaniline), N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, and N-hydroxy-2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole were each metabolically activated by 3'-phosphoadenosine-5'-phosphosulfate-dependent human liver STs. No ST-mediated DNA binding of N-hydroxy-2-amino-3-methylimidazo[4,5-f]quinoline or N-hydroxy-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline was detected under our assay conditions. In the 12 human hepatic cytosols studied, the extent of 3'-phosphoadenosine-5'-phosphosulfate-dependent DNA binding of the N-hydroxy derivatives were all significantly correlated with levels of thermostable phenol ST (TS-PST) activity but not with thermolabile phenol ST or dehydroepiandrosterone ST activities. The propensity of these N-hydroxy arylamines and N-hydroxy heterocyclic amines to serve as selective substrates for human TS-PST was further confirmed by inhibition with 2,6-dichloro-4-nitrophenol and by thermostability studies. N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and N-hydroxy-4,4'-methylene-bis(2-chloroaniline) were also used as substrates to study ST-dependent metabolic activation in other human tissue preparations. 3'-phosphoadenosine-5'-phosphosulfate-dependent DNA binding activity was detected in human liver and colon cytosols but not in pancreas, larynx, or urinary bladder epithelial cytosols. Since the TS-PST appears to be expressed polymorphically in human populations, the funding that human TS-PST is capable of metabolically activating N-hydroxy metabolites of several carcinogenic arylamines and heterocyclic amines suggests that TS-PST may have an important role in determining interindividual susceptibility to these environmental and dietary carcinogens. C1 NATL CTR TOXICOL RES,RES OFF,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT SURG,LITTLE ROCK,AR 72205. NR 44 TC 136 Z9 138 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1995 VL 55 IS 3 BP 525 EP 529 PG 5 WC Oncology SC Oncology GA QD717 UT WOS:A1995QD71700017 PM 7834621 ER PT J AU CHOU, HC LANG, NP KADLUBAR, FF AF CHOU, HC LANG, NP KADLUBAR, FF TI METABOLIC-ACTIVATION OF THE N-HYDROXY DERIVATIVE OF THE CARCINOGEN 4-AMINOBIPHENYL BY HUMAN TISSUE SULFOTRANSFERASES SO CARCINOGENESIS LA English DT Article ID HUMAN-PLATELET PHENOLSULFOTRANSFERASE; SULFURIC-ACID ESTERS; HUMAN-LIVER; PHENOL SULFOTRANSFERASE; B6C3F1 MICE; PARTIAL-PURIFICATION; AROMATIC-AMINES; DNA-BINDING; SULFATION; N-HYDROXY-2-ACETYLAMINOFLUORENE AB The role of human sulfotransferase(s) in the bioactivation of the N-hydroxy (N-OH) metabolite of the human bladder carcinogen 4-aminobiphenyl (ABP) was investigated in vitro with human tissue cytosols. Using an enzymatic assay consisting of a PAPS-regenerating system, [H-3]N-OH-ABP, calf thymus DNA and tissue cytosols, the sulfotransferase-mediated metabolic activation of N-OH-ABP was determined as the PAPS-dependent covalent binding of the N-OH substrate to DNA. With cytosols prepared from various tissues, we found that the sulfotransferase(s) in human liver, and to a lesser extent colon, can readily metabolize N-OH-ABP. No PAPS-dependent metabolic activation was detected with cytosols prepared from human pancreas or from the carcinogen target tissue, the urinary bladder epithelium. The N-OH-ABP sulfotransferase activities of liver and colon cytosols from different individuals were highly correlated with their thermostable phenol sulfotransferase (TS-PST) activity (liver, r = 0.99, P < 0.01; colon, r = 0.88, P < 0.01), but not with activities for the thermolabile phenol sulfotransferase (TL-PST; liver, r = 0.29; colon, r = 0.53), or for the dehydroepiandrosterone sulfotransferase DHEA-ST; liver, r = 0.32; colon, negligible activity). N-OH-ABP sulfotransferase activity was highly sensitive to inhibition by a selective TS-PST inhibitor, 2,6-dichloro-4-nitrophenol (IC50 = 0.7 mu M), and by p-nitrophenol, but was unaffected by competitive inhibitors of TL-PST (dopamine) or DHEA-ST (DHEA, DHEA-sulfate). The N-OH-ABP sulfotransferase activity also exhibited thermostability properties similar to that of the TS-PST. From these data, we conclude that human liver TS-PST but not TL-PST or DHEA-ST can metabolically activate the proximate human carcinogen N-OH-ABP to a reactive sulfuric acid ester intermediate that binds covalently to DNA. In addition, in view of the putative role of N-OH-ABP as a major transport form of the carcinogen to the urinary bladder and of the absence of sulfotransferase activity in this tissue, we hypothesize that sulfotransferase activation in the liver may actually decrease the bioavailability of N-OH-ABP toward extrahepatic tissues and thus serve as an important overall detoxification mechanism for the urinary bladder. C1 NATL CTR TOXICOL RES,OFF RES HFT100,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. JOHN L MCCLELLAN MEM VET ADM MED CTR,LITTLE ROCK,AR 72205. NR 37 TC 48 Z9 49 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1995 VL 16 IS 2 BP 413 EP 417 DI 10.1093/carcin/16.2.413 PG 5 WC Oncology SC Oncology GA QH261 UT WOS:A1995QH26100035 PM 7859374 ER PT J AU HILLMAN, GG YOUNES, E VISSCHER, D ALI, E LAM, JS MONTECILLO, E PONTES, JE HAAS, GP PURI, RK AF HILLMAN, GG YOUNES, E VISSCHER, D ALI, E LAM, JS MONTECILLO, E PONTES, JE HAAS, GP PURI, RK TI SYSTEMIC TREATMENT WITH INTERLEUKIN-4 INDUCES REGRESSION OF PULMONARY METASTASES IN A MURINE RENAL-CELL CARCINOMA MODEL SO CELLULAR IMMUNOLOGY LA English DT Article ID ASIALO GM1; NATURAL-KILLER; CANCER; IMMUNOTHERAPY; LYMPHOCYTES; THERAPY; GROWTH; MOUSE; IL-4; MICE AB Advanced metastatic renal cell carcinoma has been shown to be responsive to immunotherapy but the response rate is still limited. We have investigated the therapeutic potential of systemic interleukin-4 (IL-4) administration for the treatment of pulmonary metastases in the murine Renca renal adenocarcinoma model. Renca cells were injected iv in Balb/c mice to induce multiple pulmonary tumor nodules. From Day 5, Renca-bearing mice were treated with two daily injections of recombinant murine IL-4 for 5 consecutive days. IL-4 treatment induced a significant reduction in the number of lung metastases in a dose-dependent manner and significantly augmented the survival of treated animals. Immunohistochemistry studies, performed on lung sections, showed macrophage and CD8(+) T cell infiltration in the tumor nodules 1 day after the end of IL-4 treatment. The CD8 infiltration increased by Day 7 after IL-4 treatment. Granulocyte infiltration was not detectable. To clarify further the role of the immune system in IL-4 anti-tumor effect, mice were depleted of lymphocyte subpopulations by in vivo injections of specific antibodies prior to treatment with IL-4. Depletion of CD8(+) T cells or AsGM1(+) cells abrogated the effect of IL-4 on lung metastases, whereas depletion of CD4(+) T cells had no impact. These data indicate that CD8(+) T cells and AsGM1(+) cells are involved in IL-4-induced regression of established renal cell carcinoma. (C) 1995 Academic Press, Inc. C1 WAYNE STATE UNIV,SCH MED,DEPT PATHOL,DETROIT,MI 48201. HARPER GRACE HOSP,DETROIT,MI 48201. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,MOLEC TUMOR BIOL LAB,BETHESDA,MD 20892. RP HILLMAN, GG (reprint author), WAYNE STATE UNIV,SCH MED,DEPT UROL,DETROIT,MI 48201, USA. FU NCI NIH HHS [CA 22453] NR 23 TC 26 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD FEB PY 1995 VL 160 IS 2 BP 257 EP 263 DI 10.1016/0008-8749(95)80036-I PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA QH401 UT WOS:A1995QH40100014 PM 7720087 ER PT J AU YETLEY, EA RADER, JI AF YETLEY, EA RADER, JI TI FOLATE FORTIFICATION OF CEREAL GRAIN PRODUCTS - FDA POLICIES AND ACTIONS SO CEREAL FOODS WORLD LA English DT Article ID NEURAL-TUBE DEFECTS; ACID; SUPPLEMENTATION; PREVENTION; COBALAMIN; VITAMIN C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV SCI & APPL TECHNOL,OFF FOOD LABELING,WASHINGTON,DC 20204. RP YETLEY, EA (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SPECIAL NUTR,WASHINGTON,DC 20204, USA. NR 29 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CEREAL CHEMISTS PI ST PAUL PA 3340 PILOT KNOB RD, ST PAUL, MN 55121-2097 SN 0146-6283 J9 CEREAL FOOD WORLD JI Cereal Foods World PD FEB PY 1995 VL 40 IS 2 BP 67 EP & PG 0 WC Food Science & Technology SC Food Science & Technology GA QK533 UT WOS:A1995QK53300008 ER PT J AU ALLEVA, JJ ALLEVA, FR AF ALLEVA, JJ ALLEVA, FR TI SYNERGISTIC INHIBITION BY BENZODIAZEPINE AND BARBITURATE DRUGS OF THE CLOCK CONTROL OF OVULATION IN HAMSTERS SO CHRONOBIOLOGY INTERNATIONAL LA English DT Article DE BENZODIAZEPINE DRUGS; BARBITURATE DRUGS; GABA; BIOLOGICAL CLOCK; LUTEINIZING HORMONE; OVULATION ID GABA; RECEPTORS AB A surge of pituitary luteinizing hormone (LH) into the bloodstream occurs in hamsters every 4 days between 1:30 p.m. and 3 p.m. in response to a signal from a biological clock. This surge initiates behavioral estrus similar to 2 h later and ovulation similar to 12 h later Phenobarbital at a dose greater than or equal to 100 mg/kg consistently blocks LH release. Barbiturate and benzodiazepine drugs have separate binding sites in the GABA(A) receptor/chloride channel complex. Binding of either drug increases GABA-mediated chloride conductance, which suppresses the postsynaptic neuron. Barbiturate binding also increases benzodiazepine binding. This suggested that these drugs might synergize to inhibit LH release. A combination of triazolam and phenobarbital at doses of 10 mg/kg injected s.c. at 1:30 p.m. inhibited ovulation and extended the 4-day vaginal cycle in all treated hamsters. Either drug dose injected alone at 1:30 p.m., or the combination at 3 p.m., was completely ineffective. Bicuculline prevented inhibition by the combination at 1:30 p.m. The clock signal for LH release may act by antagonizing GABA transmission, which may be chronically inhibiting LH release, The combination delimited a 75-min period (1:30-2:45 p.m.) within which the clock signal for LH release occurred in all individuals (ET(50) = 2:08 p.m.). This period appears to arise from individuals with different but constant clock settings rather than from a 75-min variation in the clock setting of the individual. C1 US FDA,CTR DRUG EVALUAT & RES,WASHINGTON,DC 20204. NR 24 TC 4 Z9 4 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0742-0528 J9 CHRONOBIOL INT JI Chronobiol. Int. PD FEB PY 1995 VL 12 IS 1 BP 1 EP 7 DI 10.3109/07420529509064494 PG 7 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA QK004 UT WOS:A1995QK00400001 PM 7750153 ER PT J AU WOLFE, EJ CAVACINI, LA POSNER, MR SAMORE, MH SPINO, C KETTER, N TRAPNELL, C HAMMER, S GAMBERTOGLIO, JG AF WOLFE, EJ CAVACINI, LA POSNER, MR SAMORE, MH SPINO, C KETTER, N TRAPNELL, C HAMMER, S GAMBERTOGLIO, JG TI PHARMACOKINETICS OF F105, A HUMAN MONOCLONAL-ANTIBODY FOR THE TREATMENT OF HIV-INFECTION - A PHASE-I STUDY SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA. NIAID,BETHESDA,MD. US FDA,ROCKVILLE,MD. 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 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 143 EP 143 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200033 ER PT J AU STRONG, JM MOODY, DE PARKER, RJ ALBURGES, ME COLLINS, JM AF STRONG, JM MOODY, DE PARKER, RJ ALBURGES, ME COLLINS, JM TI PROTOCOL FOR INVESTIGATING P450 METABOLISM OF L-ALPHA-ACETYLMETHADOL (LAAM) IN HUMAN LIVER-TISSUE IN-VITRO SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,CDER,ORR,DIV CLIN PHARMACOL,ROCKVILLE,MD 20857. UNIV UTAH,CTR HUMAN TOX,SALT LAKE CITY,UT. 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 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 148 EP 148 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200052 ER PT J AU PRADHAN, RS LUDDEN, TM KORTHBRADLEY, J AF PRADHAN, RS LUDDEN, TM KORTHBRADLEY, J TI POPULATION PHARMACOKINETICS OF IV AMIODARONE - RAPID SCREENING OF COVARIATES SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 WYETH AYERST RES,RADNOR,PA. US FDA,DIV BIOPHARM,ROCKVILLE,MD. 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 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 156 EP 156 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200083 ER PT J AU SCHEINBAUM, ML PERMUTT, T AF SCHEINBAUM, ML PERMUTT, T TI DOSING HYPOTHESIS FOR NASAL STEROIDS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD. 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 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 170 EP 170 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200141 ER PT J AU SINGH, GJP LESKO, LJ SHAH, VP ADAMS, WP MOLZON, JA WILLIAMS, RL PERSHING, LK AF SINGH, GJP LESKO, LJ SHAH, VP ADAMS, WP MOLZON, JA WILLIAMS, RL PERSHING, LK TI PHARMACODYNAMIC (PD) MODELING TO DEVELOP BIOEQUIVALENCE (BE) METHODOLOGY FOR DERMATOLOGICAL CORTICOSTEROIDS (DCS) SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,CDER,OFF GENER DRUGS,ROCKVILLE,MD 20857. UNIV UTAH,SCH MED,DIV DERMATOL,SALT LAKE CITY,UT. 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 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 181 EP 181 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200182 ER PT J AU ETTE, EI SUN, H AF ETTE, EI SUN, H TI SAMPLE-SIZE AND POPULATION PHARMACOKINETIC (PPK) STUDIES SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,DIV BIOPHARM,ROCKVILLE,MD 20857. 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 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 188 EP 188 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200212 ER PT J AU SPYKER, DA CANTILENA, LR AF SPYKER, DA CANTILENA, LR TI CARDIOVASCULAR AND CNS ADVERSE EVENTS FOR ANTIDEPRESSANTS REPORTED TO THE FDA SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,CDER,ROCKVILLE,MD 20857. UNIFORMED SERV UNIV HLTH SCI,DIV CLIN PHARM,BETHESDA,MD. 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 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 190 EP 190 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200220 ER PT J AU NAKASHIMA, H LIEBERMAN, R KARATO, A SAIJO, N AF NAKASHIMA, H LIEBERMAN, R KARATO, A SAIJO, N TI BAYESIAN-ESTIMATION (BE) AND LIMITED SAMPLING METHODS (LSM) ARE COST-EFFECTIVE (CE) MONITORING STRATEGIES FOR ANTICANCER DRUGS (ACD) SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,CDER,ROCKVILLE,MD 20857. NATL CANC CTR,TOKYO 104,JAPAN. NR 1 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 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 192 EP 192 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200226 ER PT J AU STEIN, RA LEUNG, HM AF STEIN, RA LEUNG, HM TI COMPARABLE DRUG EFFICACY SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. 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 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 195 EP 195 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200237 ER PT J AU BEDFORD, R SPYKER, D WRIGHT, C AF BEDFORD, R SPYKER, D WRIGHT, C TI PROPOSED DESCRIPTORS FOR MUSCLE-RELAXANT ONSET AND DURATION SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,CDER,PILOT DRUG EVALUAT STAFF,ROCKVILLE,MD 20857. 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 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 196 EP 196 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200241 ER PT J AU HOUGH, DW FERGUSON, CL WEINTRAUB, M CANTILENA, LR AF HOUGH, DW FERGUSON, CL WEINTRAUB, M CANTILENA, LR TI AN ASSESSMENT OF CRITERIA FOR INAPPROPRIATE PRESCRIBING OF PSYCHOTROPIC MEDICATIONS IN THE ELDERLY SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 UNIFORMED SERV UNIV HLTH SCI,DIV CLIN PHARMACOL,BETHESDA,MD. US FDA,CDER,OTC,ROCKVILLE,MD 20857. 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 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 199 EP 199 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200253 ER PT J AU PARKER, RJ COLLINS, JM STRONG, JM AF PARKER, RJ COLLINS, JM STRONG, JM TI METABOLISM OF LIDOCAINE IN HUMAN LIVER SLICES AND LIVER-MICROSOMES - IDENTIFICATION OF 2,6-XYLIDINE AS A MAJOR METABOLITE SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA,CTR DRUG EVALUAT & RES,ORR,DIV CLIN PHARMACOL,ROCKVILLE,MD 20857. 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 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 211 EP 211 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200303 ER PT J AU STAGNI, G SHEPHERD, AMM LIU, Y GILLESPIE, WR AF STAGNI, G SHEPHERD, AMM LIU, Y GILLESPIE, WR TI BIOAVAILABILITY (BA) ASSESSMENT FROM PHARMACOLOGICAL DATA - METHOD AND CLINICAL-EVALUATION SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 UNIV TEXAS,COLL PHARM,AUSTIN,TX 78712. UNIV TEXAS,HLTH SCI CTR,DIV CLIN PHARMACOL,SAN ANTONIO,TX. US FDA,DIV BIOPHARMACEUT,ROCKVILLE,MD 20857. 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 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 214 EP 214 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200313 ER PT J AU BADAWI, AF MOSTAFA, MH PROBERT, A OCONNOR, PJ AF BADAWI, AF MOSTAFA, MH PROBERT, A OCONNOR, PJ TI ROLE OF SCHISTOSOMIASIS IN HUMAN BLADDER-CANCER - EVIDENCE OF ASSOCIATION, ETIOLOGIC FACTORS, AND BASIC MECHANISMS OF CARCINOGENESIS SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Review DE BETA-GLUCURONIDASE; BLADDER CANCER; DNA ADDUCTS; N-NITROSO COMPOUNDS; SCHISTOSOMIASIS; TRYPTOPHAN METABOLISM ID RAT URINARY-BLADDER; PROMUTAGENIC METHYLATION DAMAGE; ALKYLTRANSFERASE ACTIVITY; HAEMATOBIUM INFECTION; ALKYLATING-AGENTS; FASCIOLA-HEPATICA; UNITED-STATES; HIGH-GRADE; DNA; CARCINOMA AB Several epidemiological, clinical and experimental studies have been carried out to determine whether there is an aetiological role for schistosomiasis in the multi-stage process of bladder carcinogenesis. Lines of evidence supporting the association between bladder cancer and schistosomiasis include indications from the geographical correlation between the two conditions, the distinctive patterns of gender and age at diagnosis, the clinicopathological identity of schistosome-associated bladder cancer and the extensive experimental evidence in infected laboratory animals. Although the causative role of schistosomiasis is now accepted, various associated factors have been proposed in the induction of this particular type of cancer. While all may contribute to the carcinogenic process taking place in the infected bladder, none of these has yet been confirmed. Most attention has been directed at theories proposing possible roles for urinary chemical carcinogens, particularly tryptophan metabolites, N-nitroso compounds and of beta-glucuronidase, as factors that are primarily involved in the initiation of bladder carcinogenesis in areas endemic for schistosomiasis. C1 UNIV ALEXANDRIA,INST GRAD STUDIES & RES,DEPT ENVIRONM STUDIES,ALEXANDRIA,EGYPT. UNIV COLL N WALES,SCH BIOL SCI,BANGOR,GWYNEDD,WALES. CHRISTIE HOSP & HOLT RADIUM INST,PATERSON INST CANC RES,DEPT CARCINOGENESIS,CRC,MANCHESTER M20 9BX,LANCS,ENGLAND. RP BADAWI, AF (reprint author), NATL CTR TOXICOL RES,OFF RES HFT 100,JEFFERSON,AR 72079, USA. NR 136 TC 66 Z9 68 U1 1 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD FEB PY 1995 VL 4 IS 1 BP 45 EP 59 DI 10.1097/00008469-199502000-00004 PG 15 WC Oncology SC Oncology GA RQ178 UT WOS:A1995RQ17800004 PM 7728097 ER PT J AU ALAYASH, AI AF ALAYASH, AI TI EFFECTS OF INTRAMOLECULAR AND INTERMOLECULAR CROSS-LINKING ON THE FREE-RADICAL REACTIONS OF BOVINE HEMOGLOBINS SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE BOVINE HEMOGLOBIN; FREE RADICALS; BLOOD SUBSTITUTES ID LIPID-PEROXIDATION; ACTIVATED METMYOGLOBIN; OXYGEN; BINDING; OXYHEMOGLOBIN; DERIVATIVES; CHAINS AB Chemical modifications of human or bovine hemoglobins are designed to produce proteins that can act as oxygen-carrying blood substitutes. Concerns about the redox reactivity of cell-free hemoglobin and its contribution to tissue-damaging oxygen free radicals has not been fully established. We determined that bovine hemoglobins intra- or intermolecularly crosslinked differ in their ability to generate or interact with reactive oxygen species. These differences do not correlate with their oxygen affinities. We compared HbBv-FMDa, produced by the reaction of bovine hemoglobin with fumaryl-monodiaspirin and Poly HbBv, a glutaraldehyde polymerized bovine hemoglobin, with unmodified bovine hemoglobin (HbBv). Superoxide radicals are produced during the spontaneous oxidation of hemoglobin. Relative to the other two proteins, Poly HbBv was found to be more susceptible to autoxidation. Spectral changes indicative of protein modification and ferrylhemoglobin formation during the enzymatic peroxidation of these hemoglobins differ qualitatively and occur at an increasing order, poly HbBv > HbBv > HbBv-FMDA. The proteins also differ in the rate of hemoglobin catalyzed NADPH oxidation and aniline hydroxylation, reactions mediated by reactive oxygen species. Taken together, our results and those reported previously on modified human hemoglobins, suggest that redox and oxygen-carrying functions of hemoglobin can be experimentally manipulated as independently selectable parameters that may ultimately aid in the design of a safer reperfusion agent. RP ALAYASH, AI (reprint author), US FDA,CTR BIOL EVALUAT & RES,8800 ROCKVILLE PIKE,BLDG 29,ROOM B-10,BETHESDA,MD 20892, USA. NR 32 TC 24 Z9 25 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD FEB PY 1995 VL 18 IS 2 BP 295 EP 301 DI 10.1016/0891-5849(94)E0142-6 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA QF074 UT WOS:A1995QF07400020 PM 7744314 ER PT J AU CHANDA, S MANGIPUDY, RS WARBRITTON, A BUCCI, TJ MEHENDALE, HM AF CHANDA, S MANGIPUDY, RS WARBRITTON, A BUCCI, TJ MEHENDALE, HM TI STIMULATED HEPATIC TISSUE-REPAIR UNDERLIES HETEROPROTECTION BY THIOACETAMIDE AGAINST ACETAMINOPHEN-INDUCED LETHALITY SO HEPATOLOGY LA English DT Article ID CARBON-TETRACHLORIDE; HEPATOCELLULAR REGENERATION; HALOMETHANE HEPATOTOXICITY; CCL4 AUTOPROTECTION; COVALENT BINDING; TREATED RATS; NECROSIS; CHLORDECONE; POTENTIATION; GLUTATHIONE AB Acetaminophen (APAP) is a widely used analgesia and antipyretic drug that causes massive centrilobular hepatic necrosis at high doses, leading to death. The objectives of this study were to test our working hypothesis that preplaced cell division and hepatic tissue repair by prior thioacetamide (TA) administration provides protection against APAP-induced lethality and to investigate the underlying mechanism. Male Sprague-Dawley rats were treated with a low dose of TA (50 mg/kg, intraperitoneally [i.p.]) before challenge with a 90% lethal dose (1,800 mg/kg, i.p.) of APAP. This protocol resulted in a 100% protection against the lethal effect of APAP. Because TA caused a 23% decrease of hepatic microsomal cytochromes P-450, the possibility that TA protection may be caused by decreased bioactivation of APAP was examined. A 30% decrease in cytochromes P-450 induced by cobalt chloride failed to provide protection against APAP lethality. Time course of serum enzyme elevations (alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase) indicated that actual indiction of liver injury by APAP peaked between 12 to 24 hours after the administration of APAP, whereas the ultimate outcome of that injury depended on the biological events thereafter. Although liver injury progressed in rats receiving only APAP, it regressed in rats pretreated with TA. Acetaminophen t(1/2) was not altered in TA-treated rats, indicating that significant changes in APAP disposition and bioactivation are unlikely. Moreover, hepatic glutathione was decreased to a similar extent regardless of TA pretreatment, suggesting that decreased bioactivation of APAP is unlikely to be the mechanism underlying TA protection, [H-3]Thymidine incorporation studies confirmed the expected stimulation of S-phase synthesis, and proliferating cell nuclear antigen studies showed a corresponding stimulation of cell division through accelerated cell cycle progression. Intervention with TA induced cell division by colchicine antimitosis ended the TA protection in the absence of significant changes in the time course of serum enzyme elevations during the inflictive phase of APAP hepatotoxicity. These studies suggest that hepatocyte division and tissue repair induced by TA facilitate sustained hepatic tissue repair after subsequent APAP-induced liver injury, producing recovery from fiver injury and protection against APAP lethality. C1 NE LOUISIANA UNIV,COLL PHARM & HLTH SCI,DIV PHARMACOL & TOXICOL,MONROE,LA 71209. NATL CTR TOXICOL RES,PATHOL ASSOCIATES INC,JEFFERSON,AR 72079. NR 43 TC 80 Z9 80 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 1995 VL 21 IS 2 BP 477 EP 486 DI 10.1016/0270-9139(95)90110-8 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RB789 UT WOS:A1995RB78900031 PM 7843722 ER PT J AU BURKS, AW COCKRELL, G CONNAUGHTON, C KARPAS, A HELM, RM AF BURKS, AW COCKRELL, G CONNAUGHTON, C KARPAS, A HELM, RM TI EPITOPE SPECIFICITY OF THE MAJOR PEANUT ALLERGEN, ARA-H-II SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE PEANUT; EPITOPE SPECIFICITY; MONOCLONAL ANTIBODIES; IGE ID ATOPIC-DERMATITIS; ELECTROPHORETIC TRANSFER; ANAPHYLACTIC REACTIONS; MONOCLONAL-ANTIBODIES; POLYACRYLAMIDE GELS; P-I; FOOD; DERMATOPHAGOIDES; IDENTIFICATION; ANTIGENS AB The antigenic and allergenic structure of Ara h II, a major allergen of peanuts, was investigated with the use of four monoclonal antibodies obtained from BALB/c mice immunized with purified Ara h II. Our previous studies with monoclonal antibodies generated to peanut allergens showed this method to be useful for epitope mapping. When used as a solid phase in an ELISA, these monoclonal antibodies captured peanut antigen, which bound human IgE from patients with positive peanut challenge responses. The Ara h II monoclonal antibodies were found to be specific for peanut antigens when binding for other legumes was examined. In ELISA inhibition studies with the monoclonal antibodies, we identified two different antigenic sites on Ara h II. In similar studies with pooled human IgE serum from patients with positive challenge responses to peanuts, we identified two closely related IgE-binding epitopes. These characterized monoclonal antibodies to Ara h II will be useful for future studies to immunoaffinity purify the Ara h II allergen and to use in conjunction with recombinant technology for determining structure-function relationships. C1 US FDA,ALLERGY & IMMUNOCHEM LAB,ROCKVILLE,MD. RP BURKS, AW (reprint author), UNIV ARKANSAS MED SCI HOSP,ARKANSAS CHILDRENS HOSP,DEPT PEDIAT,800 MARSHALL ST,LITTLE ROCK,AR 72202, USA. FU NIAID NIH HHS [R29AI26629-04] NR 19 TC 31 Z9 32 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 1995 VL 95 IS 2 BP 607 EP 611 DI 10.1016/S0091-6749(95)70323-3 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA QH697 UT WOS:A1995QH69700013 PM 7531731 ER PT J AU SCHOENEMANN, HM MCCORMACK, JF SMEDLEY, KO AF SCHOENEMANN, HM MCCORMACK, JF SMEDLEY, KO TI THE RESPONSIBILITIES OF INVESTIGATORS, MONITORS, AND SPONSORS OF CLINICAL-STUDIES SUPPORTING NEW ANIMAL DRUG APPLICATIONS SO JOURNAL OF ANIMAL SCIENCE LA English DT Article DE NEW ANIMAL DRUG APPLICATION; CLINICAL TRIALS; INVESTIGATOR; MONITOR; SPONSOR; FDA AB Clinical studies evaluating the effectiveness of investigational new animal drugs are conducted to support approval of a new animal drug application. These studies must be conducted in a manner that ensures the integrity and validity of the collected data. On November 2, 1992, the Center for Veterinary Medicine announced the availability of a guideline entitled ''Conduct of Clinical Investigations: Responsibilities of Clinical Investigators and Monitors for Investigational New Animal Drug Studies.'' This guideline, which provides recommendations on the conduct of clinical investigations and the responsibilities of monitors and investigators, is presented in this manuscript. Additionally, the responsibilities of sponsors as delineated by the Food and Drug Administration's laws and regulations are also summarized. RP SCHOENEMANN, HM (reprint author), US FDA,CTR VET MED,ROCKVILLE,MD 20855, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC ANIMAL SCIENCE PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 SN 0021-8812 J9 J ANIM SCI JI J. Anim. Sci. PD FEB PY 1995 VL 73 IS 2 BP 606 EP 613 PG 8 WC Agriculture, Dairy & Animal Science SC Agriculture GA QF442 UT WOS:A1995QF44200038 PM 7601797 ER PT J AU FINN, TM LI, ZM KOCSIS, E AF FINN, TM LI, ZM KOCSIS, E TI IDENTIFICATION OF A BORDETELLA-PERTUSSIS BVG-REGULATED PORIN-LIKE PROTEIN SO JOURNAL OF BACTERIOLOGY LA English DT Note ID VIRULENCE FACTORS; FILAMENTOUS HEMAGGLUTININ; ANTIGENIC MODULATION; SEQUENCES; CLONING; GENE; VIR; NUCLEOTIDE; MUTATIONS AB Bordetella pertussis 18323 produces a bvg-regulated 39.1-kDa porin-like protein, OmpQ. OmpQ had 61% similarity to the major porin of B. pertussis and contains conserved regions common to both the neisserial and enteric porin families. The results of Southern blot analysis indicate that strains of Bordetella parapertussis and Bordetella bronchiseptica but not Bordetella avium contain this gene. C1 US FDA,CTR BIOL EVALUAT & RES,PERTUSSIS LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,MYCOBACTERIAL DIS & CELLULAR IMMUNOL LAB,BETHESDA,MD 20892. NIAMS,STRUCT BIOL LAB,BETHESDA,MD 20892. NR 26 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 1995 VL 177 IS 3 BP 805 EP 809 PG 5 WC Microbiology SC Microbiology GA QD435 UT WOS:A1995QD43500043 PM 7836316 ER PT J AU CALVEY, EM BEGLEY, TH ROACH, JAG AF CALVEY, EM BEGLEY, TH ROACH, JAG TI SFC-FTIR SPECTROSCOPY AND SFC-MS OF NONVOLATILE EXTRACTANTS OF MICROWAVE SUSCEPTOR PACKAGING SO JOURNAL OF CHROMATOGRAPHIC SCIENCE LA English DT Article ID SUPERCRITICAL FLUID CHROMATOGRAPHY; POLYMER ADDITIVES; QUANTITATIVE-ANALYSIS; MIGRATION; FOOD; ANTIOXIDANTS; LIQUID RP CALVEY, EM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 14 TC 11 Z9 11 U1 1 U2 2 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0021-9665 J9 J CHROMATOGR SCI JI J. Chromatogr. Sci. PD FEB PY 1995 VL 33 IS 2 BP 61 EP 65 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QE349 UT WOS:A1995QE34900001 ER PT J AU PAULI, GH TARANTINO, IM AF PAULI, GH TARANTINO, IM TI FDA REGULATORY ASPECTS OF FOOD IRRADIATION SO JOURNAL OF FOOD PROTECTION LA English DT Article DE FOOD IRRADIATION; FOOD SAFETY; FDA AB The Federal Food, Drug, and Cosmetic Act requires that a food that has been irradiated may not be sold in the United States unless the Department of Health and Human Services finds that the food is safe and issues a regulation specifying safe conditions of irradiation. This presentation briefly outlines the types of information needed to issue an authorizing regulation, describes the conditions under which food may currently be irradiated, and discusses the basis for current regulations. RP PAULI, GH (reprint author), US FDA,DIV PROD POLICY,HFS 205,200 C ST SW,WASHINGTON,DC 20204, USA. NR 0 TC 16 Z9 18 U1 2 U2 2 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD FEB PY 1995 VL 58 IS 2 BP 209 EP 212 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA QP353 UT WOS:A1995QP35300014 ER PT J AU PERRIN, PJ SCOTT, D QUIGLEY, L ALBERT, PS FEDER, O GRAY, GS ABE, R JUNE, CH RACKE, MK AF PERRIN, PJ SCOTT, D QUIGLEY, L ALBERT, PS FEDER, O GRAY, GS ABE, R JUNE, CH RACKE, MK TI ROLE OF B7/CD28 CTLA-4 IN THE INDUCTION OF CHRONIC RELAPSING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TRANSFORMING GROWTH FACTOR-BETA-1; BRAIN-BARRIER BREAKDOWN; T-CELL ACTIVATION; MULTIPLE-SCLEROSIS; CLONAL ANERGY; LYMPHOCYTE-T; GUINEA-PIG; EXPRESSION AB T cell activation requires both Ag/MHC recognition and costimulatory signals. The present studies were designed to test whether the loss of tolerance to myelin basic protein (MBP) requires costimulation by members of the B7 receptor family. CTLA-4Ig, a fusion protein ligand for B7-1 and B7-2, was used to assess the role of B7-mediated costimulation in chronic relapsing experimental allergic encephalomyelitis (EAE) induced by the transfer of MBP specific T cell lines. In adoptively transferred EAE, administering CTLA-4Ig to donor mice or during in vitro activation of MBP specific-T cells resulted in diminution of clinical disease. The presence of CTLA-4Ig during both the immunization and in vitro activation stages was most effective in preventing clinical signs of disease. This diminution in clinical disease was paralleled by a decreased proliferative response and reduced production of IL-2 and IL-4, but not IFN-gamma, after antigenic stimulation of encephalitogenic T cells in vitro. In contrast, CTLA-4Ig treatment of recipient animals after the transfer of MBP-activated T cells affected neither disease course nor severity. These results indicate that additional costimulatory pathways may be involved in established EAE, or that some cells are independent of costimulation or, alternatively, that CTLA-4Ig does not enter brain parenchyma in therapeutic concentrations. Thus, we conclude that costimulation provided by B7 molecules plays a major role in the development of encephalitogenic T cells and in the establishment of chronic relapsing EAE, a prototypic CD4(+) T cell-mediated autoimmune disease. C1 GEOCENTERS INC,FT WASHINGTON,MD. US FDA,BETHESDA,MD 20892. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. REPLIGEN CORP,CAMBRIDGE,MA 02139. RP PERRIN, PJ (reprint author), USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,MAIL STOP 06,BETHESDA,MD 20889, USA. NR 51 TC 139 Z9 140 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1995 VL 154 IS 3 BP 1481 EP 1490 PG 10 WC Immunology SC Immunology GA QC546 UT WOS:A1995QC54600054 PM 7529805 ER PT J AU PYRAMIDES, G ROBINSON, JW ZITO, SW AF PYRAMIDES, G ROBINSON, JW ZITO, SW TI THE COMBINED USE OF DSC AND TGA FOR THE THERMAL-ANALYSIS OF ATENOLOL TABLETS SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE THERMAL ANALYSIS; THERMOGRAVIMETRIC ANALYSIS; DIFFERENTIAL SCANNING CALORIMETRY; ATENOLOL TABLETS AB The New York Regional Laboratory's forensic pharmaceutical group used thermal analysis (TA) to ensure adherence to batch formulations by drug manufacturers. TA in our laboratory consisted of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). DSC and TGA were used to analyse finished dosage forms and their components. In this study the components of atenolol formulations were qualitatively identified by analysing individual components and comparing with the finished product. DSC and TGA were used together to develop a profile of batch formulations, with each analytical technique giving complementary types of information. For example, the excipient sodium starch glycolate was identified by DSC and confirmed by TGA. These experimental results demonstrated the use of TA for the characterization of finished dosage forms and the qualitative identification of some of the individual components in batch formulations. C1 ST JOHNS COLL,DEPT PHARMACEUT SCI,QUEENS,NY. RP PYRAMIDES, G (reprint author), US FDA,NE REG LAB,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 12 TC 26 Z9 28 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD FEB PY 1995 VL 13 IS 2 BP 103 EP 110 DI 10.1016/0731-7085(94)00112-F PG 8 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA QH921 UT WOS:A1995QH92100003 PM 7766716 ER PT J AU CONTRERA, JF JACOBS, AC PRASANNA, HR MEHTA, M SCHMIDT, WJ DEGEORGE, J AF CONTRERA, JF JACOBS, AC PRASANNA, HR MEHTA, M SCHMIDT, WJ DEGEORGE, J TI SYSTEMIC EXPOSURE-BASED ALTERNATIVE TO THE MAXIMUM TOLERATED DOSE FOR CARCINOGENICITY STUDIES OF HUMAN THERAPEUTICS SO JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY LA English DT Article DE MAXIMUM TOLERATED DOSE; CARCINOGENICITY STUDY; HUMAN THERAPEUTICS; SYSTEMIC EXPOSURE (AREA UNDER PLASMA CONCENTRATION-TIME CURVE) ID HUMAN HEALTH AB A systemic exposure-based alternative to the maximum tolerated dose (MTD) for high-dose selection in carcinogenicity studies for human therapeutics was accepted at the Second International Conference on Harmonization (ICH-2). The systemic exposure-based alternative to the MTD is suitable for nongenotoxic compounds with low rodent toxicity that are metabolized similarly in rodents and humans. This is the first product of an evaluation of current standards for rodent carcinogenicity studies of therapeutics. The relative systemic exposure is the ratio of the rat plasma area under the plasma concentration-time curve (AUC) at the MTD/human plasma AUC at the maximum recommended daily dose. An appropriate systemic exposure ratio for high-dose selection in carcinogenicity studies was empirically derived from the distribution of systemic exposure ratios attained by 35 compounds from 11 therapeutic categories in a Food and Drug Administration (FDA) database. Approximately one-third achieved a relative systemic exposure ratio <1 and two-thirds attained an exposure ratio of 10 or less, at the MTD. A systemic exposure ratio of at least 25 was accepted for high-dose selection in carcinogenicity studies at ICH-2, This ratio is high enough to detect all compounds with positive studies in the FDA database and would detect IARC 1 and 2A carcinogenic drugs. A ratio of 25 exceeds the systemic exposure ratio attained by 75% of drugs tested at the MTD in the FDA database and represents an adequate margin of safety which can be attained by a significant proportion of drugs. C1 US FDA,CTR DRUG EVALUAT & RES,OFF RES RESOURCES,DIV BIOPHARMACEUT,ROCKVILLE,MD 20857. US FDA,CTR DRUG EVALUAT & RES,OFF RES RESOURCES,DIV ONCOL & PULM DRUG PROD,ROCKVILLE,MD 20857. RP CONTRERA, JF (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF RES RESOURCES,DIV ANTIVIRAL DRUG PROD,HFD-400,ROCKVILLE,MD 20857, USA. NR 20 TC 20 Z9 21 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0730-0913 J9 J AM COLL TOXICOL JI J. Am. Coll. Toxicol. PD FEB PY 1995 VL 14 IS 1 BP 1 EP 10 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA QC832 UT WOS:A1995QC83200001 ER EF