FN Thomson Reuters Web of Science™ VR 1.0 PT J AU LUHTALA, TA ROECKER, EB PUGH, T FEUERS, RJ WEINDRUCH, R AF LUHTALA, TA ROECKER, EB PUGH, T FEUERS, RJ WEINDRUCH, R TI DIETARY RESTRICTION ATTENUATES AGE-RELATED INCREASES IN RAT SKELETAL-MUSCLE ANTIOXIDANT ENZYME-ACTIVITIES SO JOURNALS OF GERONTOLOGY LA English DT Article ID EXTENSOR DIGITORUM LONGUS; FOOD RESTRICTION; DIFFERENTIAL CHANGES; OLD RATS; MITOCHONDRIAL; LIVER; DNA; METABOLISM; CATALASE; MUTATIONS AB Dietary restriction (DR) retards aging in rodents, but its mechanism of action remains unclear. Free radicals have been hypothesized to be involved in aging and in DR's actions. We investigated the influences of age and DR on the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in skeletal muscle from 11-, 26- and 34-mo-old (BN x Fischer 344) F-1 rats fed either ad libitum (AL) or subjected to a 30% DR from 14 weeks of age. The mass of the upper hindlimb muscles recoverable in 34-mo-old AL rats was only 52% that of Ii-mo-old AL rats, whereas rats on DR showed a stable, intermediate value at both ages. CAT and GPX activities increased progressively and markedly in muscle of AL animals with aging. The increase in CAT activity,was partially attenuated by DR, while that of GPX was entirely prevented. These effects of aging and DR were more profound in 12,000 x g pellets than in cytosolic fractions. SOD activities were more variable and not clearly influenced by age or DR, These data agree with prior reports of an age-related increase in skeletal muscle antioxidant enzyme activities. Further, DR attenuates this alteration and does so most profoundly in the 12,000 x g pellet, the fraction which is enriched in mitochondria. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,DEPT NUTR SCI,MADISON,WI 53706. UNIV WISCONSIN,DEPT BIOSTAT,MADISON,WI. VER ADM GERIATR RES,CTR EDUC & CLIN,JEFFERSON,AR. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 56 TC 56 Z9 58 U1 0 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD SEP PY 1994 VL 49 IS 5 BP B231 EP B238 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA PE106 UT WOS:A1994PE10600012 PM 8056935 ER PT J AU ARCHER, BR FEWELL, TR CONWAY, BJ QUINN, PW AF ARCHER, BR FEWELL, TR CONWAY, BJ QUINN, PW TI ATTENUATION PROPERTIES OF DIAGNOSTIC-X-RAY SHIELDING MATERIALS SO MEDICAL PHYSICS LA English DT Article DE RADIATION PROTECTION; SHIELDING; X RAYS ID GYPSUM WALLBOARD AB Single- and three-phase broad-beam x-ray attenuation data I;ave been obtained using lead, steel, plate glass, gypsum wallboard, lead acrylic, and wood. Tube voltages of 50, 70, 100, 125, and 150 kVp were employed and the resulting curves were compared to transmission data found in the literature. To simplify computation of barrier requirements, all data sets were parametrized by nonlinear least-squares fit to a previously described mathematical model. High attenuation half value layers and the lead equivalence of the alternate materials were also determined. C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. RP ARCHER, BR (reprint author), BAYLOR COLL MED,DEPT RADIOL SCI,HOUSTON,TX 77030, USA. FU PHS HHS [7952570089RW00] NR 25 TC 40 Z9 40 U1 0 U2 8 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 SEP PY 1994 VL 21 IS 9 BP 1499 EP 1507 DI 10.1118/1.597408 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PH393 UT WOS:A1994PH39300017 PM 7838062 ER PT J AU MAX, EE JAHAN, N YI, HF MCBRIDE, WO AF MAX, EE JAHAN, N YI, HF MCBRIDE, WO TI A PROCESSED J CHAIN PSEUDOGENE ON HUMAN-CHROMOSOME-8 THAT IS SHARED BY SEVERAL PRIMATE SPECIES SO MOLECULAR IMMUNOLOGY LA English DT Article DE EVOLUTION; IMMUNOGLOBULIN; GENE MAPPING; GENETIC LINKAGE ANALYSIS; DNA POLYMORPHISM; CHROMOSOMAL LOCALIZATION; RFLP ID IMMUNOGLOBULIN J-CHAIN; GENES; DNA; POLYMORPHISMS; LOCALIZATION; SEQUENCES; FAMILY; CELLS; SITE AB Human DNA contains two sequences that hybridize to a human J chain gene probe: the J chain gene itself and a second previously uncharacterized sequence. By cloning and sequence analysis we now show this related sequence to be a processed pseudogene, which we have localized using somatic hybrids to chromosome 8 (distinct from the functional gene on chromosome 4) and mapped by linkage analysis to 8q13-q21. The pseudogene provides evidence of an additional DNA insertion event as it contains an AluI element embedded in sequence corresponding to the 3' untranslated region of the gene. The extent of sequence divergence between the pseudogene and the functional J chain gene suggests that the pseudogene was created roughly 40-50 million years ago; consistent with this estimate, Southern blots suggest that the pseudogene is shared by great apes as well as Old World monkeys. C1 NCI,DIV CANC TREATMENT,BIOL CHEM LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RP MAX, EE (reprint author), US FDA,CTR BIOL EVALUAT & RES,HFM-541,BETHESDA,MD 20892, USA. NR 26 TC 4 Z9 5 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 SEP PY 1994 VL 31 IS 13 BP 1029 EP 1036 DI 10.1016/0161-5890(94)90097-3 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA PH391 UT WOS:A1994PH39100008 PM 7916122 ER PT J AU PINTO, JC POTIE, F RICE, KC BORING, D JOHNSON, MR EVANS, DM WILKEN, GH CANTRELL, CH HOWLETT, AC AF PINTO, JC POTIE, F RICE, KC BORING, D JOHNSON, MR EVANS, DM WILKEN, GH CANTRELL, CH HOWLETT, AC TI CANNABINOID RECEPTOR-BINDING AND AGONIST ACTIVITY OF AMIDES AND ESTERS OF ARACHIDONIC-ACID SO MOLECULAR PHARMACOLOGY LA English DT Article ID ADENYLATE-CYCLASE; RAT-BRAIN; ANANDAMIDE; IDENTIFICATION; INHIBITORS; MEMBRANES; HYDROLASE AB The cannabinoid receptor in brain (CB1) specifically binds Delta(9)-tetrahydrocannabinol, the predominant central nervous system-active component of marijuana. An eicosanoid found in brain, N-(2-hydroxyethyl)arachidonylamide (anandamide), binds to CB1 with similar affinity. This report considers structure-activity requirements for a series of novel amides and rigid hairpin conformations typified by N-(2-hydroxyethyl)prostaglandin amides, assayed with phenylmethylsulfonyl fluoride inactivation of esterases/amidases. Arachidonyl esters were 30-fold less potent than N-(2-hydroxyethyl)arachidonylamide, showing a rank order of potency of methyl = ethyl > propyl = isopropyl, Within the N-(hydroxyalkyl)arachidonylamide series, a one-carbon increase in chain length increased the potency e-fold, but continued extension decreased affinity. Substituting the amide for the N-(2-hydroxyethylamide function produced a 4-fold loss of affinity. The N-(propyl)-, N-(butyl)-, and N-(Benzyl)arachidonylamide derivatives exhibited a 3-fold increase, no change, and a 5-fold decrease, respectively, in affinity, Compared with N-(2-hydroxyethyl)arachidonylamide. Both the methoxy ether and the formamide derivatives suffered > 20-fold loss of potency, compared with N-(2-hydroxyethyl)arachidonylamide. N-(2-Aminoethyl)arachidonylamide interacted poorly with CB1. At 100 mu M, N-(2-hydroxyethyl)amide analogs of prostaglandin E(2), A(2), B-2, and B-1 failed to alter [H-3]CP55940 binding to CB1. N-(2-Hydroxyethyl)arachidonylamide inhibited adenylate cyclase with lesser potency but with similar efficacy, compared with desacetyllevon-antradol. Extending the length of the hydroxyalkyl moiety by one carbon increased the apparent potency by 1 order of magnitude. The N-(propyl) derivative exhibited a 5-fold greater potency than did the N-(2-hydroxyethyl) analog. It appears that the bulk and length of the moiety appended to arachidonic acid are more important determinants of affinity for CB1 than is hydrogen-bonding capability. C1 ST LOUIS UNIV,SCH MED,DEPT PHARMACOL & PHYSIOL SCI,ST LOUIS,MO 63104. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. US FDA,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. OI Howlett, Allyn/0000-0002-2810-0164 FU NIDA NIH HHS [K05-DA00182, R01-DA03690, R01-DA06912] NR 22 TC 108 Z9 112 U1 1 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1994 VL 46 IS 3 BP 516 EP 522 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PJ601 UT WOS:A1994PJ60100016 PM 7935333 ER PT J AU DUHL, DMJ VRIELING, H MILLER, KA WOLFF, GL BARSH, GS AF DUHL, DMJ VRIELING, H MILLER, KA WOLFF, GL BARSH, GS TI NEOMORPHIC AGOUTI MUTATIONS IN OBESE YELLOW MICE SO NATURE GENETICS LA English DT Article ID A-PARTICLE GENES; COAT COLOR; MOUSE; SEQUENCES; ELEMENTS; PROTEIN AB Several dominant mutations of the mouse agouti coat colour gene have pleiotropic effects that include obesity and a yellow coat. The A(y) allele is caused by a large deletion that affects the expression of several contiguous genes. We show that three other obesity-associated agouti mutations, A(iy), A(sy) and A(vy), are due to different molecular alterations that result in ubiquitous expression of a chimaeric RNA that encodes a normal agouti protein. The A(iy) and A(vy) alleles are caused by insertion of an intracisternal A particle element 1 kb or 100 kb, respectively, upstream of agouti coding sequences. These results provide a model for other genes that show allele-specific imprinting, and demonstrate that molecular mechanisms typically responsible for activation of proto-oncogenes can also lead to other disease phenotypes. C1 STANFORD UNIV,SCH MED,DEPT PEDIAT,STANFORD,CA 94305. STANFORD UNIV,SCH MED,HOWARD HUGHES MED INST,STANFORD,CA 94305. US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. FU NHGRI NIH HHS [HG-00377] NR 42 TC 286 Z9 293 U1 2 U2 14 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1994 VL 8 IS 1 BP 59 EP 65 DI 10.1038/ng0994-59 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA PE157 UT WOS:A1994PE15700016 PM 7987393 ER PT J AU BADAWI, AF AF BADAWI, AF TI O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY IN TISSUES OF MICE TREATED WITH ANTISCHISTOSOMAL AGENTS SO ONCOLOGY REPORTS LA English DT Article DE SCHISTOSOMIASIS; HYCANTHONE; METRIFONATE; OXAMINIQUINE; BLADDER CANCER; DNA METHYLATION DAMAGE; DNA REPAIR ID PROMUTAGENIC METHYLATION DAMAGE; ALKYLATING-AGENTS; BLADDER-CANCER; DNA; REPAIR; N-METHYL-N'-NITRO-N-NITROSOGUANIDINE; METHYLTRANSFERASE; CARCINOGENESIS; SCHISTOSOMES; MECHANISMS AB The activity of O-6-alkylguanine-DNA alkyl transferase (ATase), the enzyme responsible for repairing promutagenic methylation damage in DNA, was measured at various time intervals in tissue extracts of mice administered (in vivo) a single therapeutic dose of the antischistosomal agents hycanthone, oxaminiquine and metrifonate. In control animals, liver contained the highest levels of ATase activity (15.8+/-1.8 fmole ATase/mu g DNA) followed by spleen (11.0+/-1.7 fmole/mu g DNA), intestine (2.3+/-0.3 fmole/mu g DNA) and bladder (0.22+/-0.04 fmole/mu g DNA). With hycanthone, ATase activity was reduced by 6 and 24 h post treatment to 74% and 27% below the control value, respectively. Bladder exhibited a 25% inactivation in the ATase level at 6 h time point. Spleen and bladder did not show any alteration in the ATase activity. In animals administered oxaminiquine, liver and bladder had a near identical pattern to that observed for hycanthone. Spleen and intestine, however, revealed activation in ATase by 50% and 42%, respectively after 6 h of treatment. This activation was also observed in the bladder of metrifonate-treated mice. In a previous study (Badawi et al, Cancer Lett 75: 167, 1993), DNA-alkylation damage (O-6-methyldeoxyguanosine; O-6-MedG) was evaluated in these tissues and there was an inverse correlation between the levels of methylation damage and ATase activity in liver (r=-0.85, p<0.01), intestine (r=-0.62, p<0.01) and bladder (r=-0.59, p<0.05). RP BADAWI, AF (reprint author), NATL CTR TOXICOL RES,OFF RES HFT100,JEFFERSON,AR 72079, USA. NR 32 TC 2 Z9 2 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD SEP-OCT PY 1994 VL 1 IS 5 BP 1023 EP 1027 PG 5 WC Oncology SC Oncology GA PW228 UT WOS:A1994PW22800031 PM 21607486 ER PT J AU HALL, CB CHESNEY, PJ GROMISCH, DS HALSEY, NA KOHL, S MARCY, SM MARKS, MI NANKERVIS, GA OVERALL, JC PICKERING, LK STEELE, RW YOGEV, R PETER, G BERKELMAN, RL HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, NR ROBBINS, A AF HALL, CB CHESNEY, PJ GROMISCH, DS HALSEY, NA KOHL, S MARCY, SM MARKS, MI NANKERVIS, GA OVERALL, JC PICKERING, LK STEELE, RW YOGEV, R PETER, G BERKELMAN, RL HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, NR ROBBINS, A TI UPDATE ON TIMING OF HEPATITIS-B VACCINATION FOR PREMATURE-INFANTS AND FOR CHILDREN WITH LAPSED IMMUNIZATION - COMMITTEE ON INFECTIOUS-DISEASES SO PEDIATRICS LA English DT Editorial Material C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. US FDA,ROCKVILLE,MD 20857. CANADIAN PAEDIAT SOC,OTTAWA,ON,CANADA. NIH,BETHESDA,MD 20892. NATL VACCINE PROGRAM,ROCKVILLE,MD. NR 11 TC 16 Z9 16 U1 0 U2 0 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 SEP PY 1994 VL 94 IS 3 BP 403 EP 404 PG 2 WC Pediatrics SC Pediatrics GA PE782 UT WOS:A1994PE78200024 ER PT J AU ELTAHTAWY, AA JACKSON, AJ LUDDEN, TM AF ELTAHTAWY, AA JACKSON, AJ LUDDEN, TM TI COMPARISON OF SINGLE AND MULTIPLE-DOSE PHARMACOKINETICS USING CLINICAL BIOEQUIVALENCE DATA AND MONTE-CARLO SIMULATIONS SO PHARMACEUTICAL RESEARCH LA English DT Article DE BIOEQUIVALENCE; ABSORPTION RATE; STEADY-STATE BIOAVAILABILITY; MONTE CARLO SIMULATIONS ID HEALTHY-VOLUNTEERS; EQUIVALENCE AB The purpose of this study was to evaluate the relative performance and usefulness of single dose (SD) and multiple dose (MD) regimens for bioequivalence (BE) determination. Drugs such as indomethacin, procainamide, erythromycin, quinidine, nifedipine were tested for BE under SD and MD dose regimens. Drugs characterized by low accumulation indices (AI) showed virtually no change in the 90% confidence interval (CI) of AUC and CMAX upon multiple dosing. On the other hand, drugs with higher AI appeared to have smaller CI at steady-state. For example, the CI range of AUC and CMAX of quinidine (AI of 1.54) decreased from 26 to 12 and from 22 to 12, respectively, upon multiple dosing. A Monte Carlo simulation study of SD and MD bioequivalence trials was performed. The probability of failing the bioequivalence test was evaluated for several situations defined by different levels of variability and correlation in ka constants, presence or absence of inter- and/or intra-individual variability in clearance (CL) and volume of distribution (V), and different degrees of accumulation. All the possible combinations of these factors were tested with SD and MD study designs. All simulations used 1000 data sets with 30 subjects in each data set for a total of 144 unique designs (total of 144,000 simulations of bioequivalence trials). Upon multiple dosing, narrowing of CI ranges was observed for drugs simulated to have high AI, high variability and a large difference in absorption constants (ka) between test and reference formulations. The mean AUC and CMAX CI ranges for this situation decreased from 15 to 6 and from 16 to 10, respectively, in going from SD to MD design. Thus, there was concordance between simulated and experimental data. The probability of failing the bioequivalence test is shown to dramatically decrease upon multiple dosing due to the changes (range and shift) in the confidence interval. RP ELTAHTAWY, AA (reprint author), US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857, USA. NR 10 TC 24 Z9 24 U1 0 U2 1 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 SEP PY 1994 VL 11 IS 9 BP 1330 EP 1336 PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA PE511 UT WOS:A1994PE51100018 PM 7816765 ER PT J AU MATSUMOTO, A FUJIWARA, Y ELESPURU, RK HANAWALT, PC AF MATSUMOTO, A FUJIWARA, Y ELESPURU, RK HANAWALT, PC TI PHOTOACTIVATED GILVOCARCIN-V INDUCES DNA-PROTEIN CROSS-LINKING IN GENES FOR HUMAN RIBOSOMAL-RNA AND DIHYDROFOLATE-REDUCTASE SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ANTI-TUMOR ANTIBIOTICS; TOPOISOMERASE-I; CELLS; LIGHT; INDUCTION; REPAIR AB The nature of DNA interactions with photoactivated gilvocarcin V has been analyzed at the gene level in both rRNA and dihydrofolate reductase genes of human fibroblasts, utilizing a modified Southern hybridization technique. Neither interstrand DNA crosslinking nor RNA linkage to DNA was detected. However, we consistently observed in both genes retarded DNA bands appearing in a dose-dependent fashion following exposure to photoactivated gilvocarcin V. These retarded bands were enhanced when genomic DNA was prepared without proteinase K treatment, suggesting involvement of protein in this DNA interaction. Because these bands disappear following proteinase K treatment, it is probable that photoactivated gilvocarcin V induces DNA-protein crosslinking. C1 US FDA,CTR DEVICES & RADIOL HLTH,DLS,MOLEC BIOL BRANCH,ROCKVILLE,MD 20857. STANFORD UNIV,DEPT BIOL SCI,STANFORD,CA 94305. RP MATSUMOTO, A (reprint author), KOBE UNIV,SCH MED,DEPT RADIAT BIOPHYS & GENET,CHUO KU,KUSUNOKI CHO 7-5-1,KOBE 650,JAPAN. NR 25 TC 14 Z9 14 U1 1 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 SEP PY 1994 VL 60 IS 3 BP 225 EP 230 DI 10.1111/j.1751-1097.1994.tb05095.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PG816 UT WOS:A1994PG81600007 PM 7972373 ER PT J AU VALENTINE, CR HEINRICH, MJ CHISSOE, SL ROE, BA AF VALENTINE, CR HEINRICH, MJ CHISSOE, SL ROE, BA TI DNA-SEQUENCE OF DIRECT REPEATS OF THE SULI GENE OF PLASMID PSA SO PLASMID LA English DT Note ID SULFONAMIDE RESISTANCE GENES; SITE-SPECIFIC INTEGRATION; GRAM-NEGATIVE BACTERIA; NUCLEOTIDE-SEQUENCE; STREPTOMYCIN-SPECTINOMYCIN; TRIMETHOPRIM RESISTANCE; TN21; INTEGRONS; TRANSPOSONS; ELEMENTS AB The restriction enzyme and genetic map ofthe antibiotic-resistance region of plasmid pSa is related to Tn21 integrons by the insertion of 5.4 kb containing a chloramphenicol resistance gene (calm) and a 1.1-kb direct repeat. We report here the nucleotide sequences of both copies of the repeat with adjoining sequences. They were identical for 1065 bp and contained the entire coding sequence ofthe sulfanilamide resistance gene, sulI. Since only the first copy of the repeat confers sulfonamide resistance, this leads to the conclusion that no promoter was available for the second copy. The sequence of the pSa sulI gene was identical to several published sulI sequences from other plasmids. The first junction point ofthe catII-containing insert was identical to the sequence for pDG0100; the second junction occurred farther into the 3'-conserved segment of integrons than does that of pDG0100. A recent report of these junction sequences for pSa and pDG0100 differs from our sequences by one nucleotide. Two additional differences were an insert of 41 bases and a single base insertion between sulI and ORF341 in our sequence. Our sequenced regions have been assigned GenBank Accession Nos. UO4277 and UO4278 for the first and second sulI genes of pSa, respectively. (C) 1994 Academic Press, Inc. C1 GOOD SAMARITAN REG MED CTR,DEPT OBSTET & GYNECOL,PHOENIX,AZ 85006. UNIV OKLAHOMA,DEPT CHEM & BIOCHEM,NORMAN,OK 73019. RP VALENTINE, CR (reprint author), NATL CTR TOXICOL RES,DGT,HFT 120,3900 NCTR RD,JEFFERSON,AR 72079, USA. FU NHGRI NIH HHS [2R01HG00313] NR 29 TC 25 Z9 29 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0147-619X J9 PLASMID JI Plasmid PD SEP PY 1994 VL 32 IS 2 BP 222 EP 227 DI 10.1006/plas.1994.1059 PG 6 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA PK825 UT WOS:A1994PK82500009 PM 7846147 ER PT J AU HORWITZ, W AF HORWITZ, W TI NOMENCLATURE OF INTERLABORATORY ANALYTICAL STUDIES (IUPAC RECOMMENDATIONS 1994) SO PURE AND APPLIED CHEMISTRY LA English DT Article AB There are three major types of interlaboratory studies in which a group of laboratories analyzes identical test portions from a homogeneous, stable test sample. Each type is characterized by a self-defining designation according to its purpose: (1) Method-performance study.-A study in which all laboratories follow the same written protocol and use the same test method to measure a property (usually concentration of an analyte) in order to assess the performance parameters of a method. (2) Laboratory-performance study.-A study in which laboratories use the method of their choice to measure a property in order to assess the performance of the laboratory or analyst, usually to evaluate or improve performance. (3) Material-certification study.-A study that assigns a reference value to a characteristic in the test material, usually with a stated uncertainty, using the ''best'' laboratories and the least-biased methods. Vague terms such as ''round-robins,'' ''intercalibrations,'' ''ring tests,'' etc., should not be used. RP HORWITZ, W (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,HFS-500,WASHINGTON,DC 20204, USA. NR 2 TC 27 Z9 27 U1 1 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD SEP PY 1994 VL 66 IS 9 BP 1903 EP 1911 DI 10.1351/pac199466091903 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA PG509 UT WOS:A1994PG50900013 ER PT J AU ALI, SF DAVID, SN NEWPORT, GD CADET, JL SLIKKER, W AF ALI, SF DAVID, SN NEWPORT, GD CADET, JL SLIKKER, W TI MPTP-INDUCED OXIDATIVE STRESS AND NEUROTOXICITY ARE AGE-DEPENDENT - EVIDENCE FROM MEASURES OF REACTIVE OXYGEN SPECIES AND STRIATAL DOPAMINE LEVELS SO SYNAPSE LA English DT Article DE AGING; DOPAMINE; MPTP; NEUROTOXICITY; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES; STRIATUM ID HYDROXYL RADICAL GENERATION; MONOAMINE OXIDASE-B; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; 1-METHYL-4-PHENYLPYRIDINIUM MPP+; INTRACRANIAL MICRODIALYSIS; CATECHOLAMINE NEURONS; SUBSTANTIA NIGRA; TOXICITY; MICE; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE AB 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes marked depletion of dopamine (DA) levels and reduction in the activity of tyrosine hydroxylase (TH) in the nigrostriatal DA pathway. In the brain, the enzyme monoamine oxidase B converts MPTP to 1-methyl-4-phenylpyridinium (MPP(+)) which enters DA terminals via DA uptake sites. Within the DA terminals, MPP(+) blocks the mitochondrial complex I and causes ATP depletion. This is thought to be the main cause of MPTP-induced terminal degeneration. In addition, reactive oxygen species (ROS) generated after blockade of the complex I as well as those generated due to DA oxidation may participate in MPTP-induced dopaminotoxicity. The present study sought to determine if a single injection of a large dose of MPTP generates ROS. We also sought to determine if these changes as well as changes in DA levels were correlated and age-dependent. Toward that end, we have used C57/B6N male mice that were 22 days or 12 months old. These animals were injected with a single dose of MPTP (40 mg/kg, ip). Animals were sacrificed at various times after drug administration. MPTP produced no significant increase in ROS nor decreases in DA or HVA concentrations in the striatum of the younger mice. However, DOPAC concentrations were significantly decreased from 15-120 min after drug administration. In the older mice, MPTP caused significant increases in ROS from the beginning to the end of the study period. DA concentrations were decreased from 60 min onward. DOPAC concentrations were decreased significantly after 15-120 min while HVA concentrations were significantly increased after 60 and 120 min. These data demonstrate that in older mice, a single dose of MPTP can cause increases of ROS which were associated with subsequent decreases in DA concentrations. Younger mice were not similarly affected. These results suggest that MPTP-induced neurotoxicity is age-dependent and may be mediated by oxidative stress. (C) 1994 Wiley-Liss, Inc. C1 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. ARKANSAS STATE UNIV,DEPT SCI BIOL,STATE UNIV,AR 72467. NIDA,ADDICT RES CTR,MOLEC NEUROPSYCHIAT SECT,BALTIMORE,MD 21224. RP ALI, SF (reprint author), NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,HFT-132,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 40 TC 93 Z9 93 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP PY 1994 VL 18 IS 1 BP 27 EP 34 DI 10.1002/syn.890180105 PG 8 WC Neurosciences SC Neurosciences & Neurology GA PE144 UT WOS:A1994PE14400004 PM 7825121 ER PT J AU FRICKE, W AF FRICKE, W TI FDA PERSPECTIVE ON AND RESPONSE TO THE RISK OF HEPATITIS-A FROM BLOOD PRODUCTS SO VOX SANGUINIS LA English DT Article; Proceedings Paper CT Symposium on Viral Safety of Plasma-Derived Replacement Factors for Hemophilia: How Safe is Safe, held Preceding the 35th Annual Meeting of the American-Society-of-Hematology CY DEC 03, 1993 CL ST LOUIS, MO SP AMER SOC HEMATOL ID VIRAL SAFETY; HEMOPHILIA AB The clinical and laboratory data available on hepatitis A virus infections reported in Europe were reviewed by the Blood Pro ducts Advisory Committee of the Food and Drug Administration. The panel's consensus was that the clotting factor concentrates currently available in the United States are safe with respect to viral diseases, hepatitis A transmissions do not appear to be a significant health problem, and there is a paucity of epidemiologic data on hepatitis A in patients with hemophilia in the United States. C1 US FDA,BETHESDA,MD 20014. RP FRICKE, W (reprint author), UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201, USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD SEP PY 1994 VL 67 SU 4 BP 16 EP 18 PG 3 WC Hematology SC Hematology GA PK900 UT WOS:A1994PK90000005 PM 7831864 ER PT J AU MOSLEY, JW LEMON, SM FRICKE, W VERMYLEN, J PURCELL, RH MANNUCCI, PM HOROWITZ AF MOSLEY, JW LEMON, SM FRICKE, W VERMYLEN, J PURCELL, RH MANNUCCI, PM HOROWITZ TI VIRAL SAFETY OF PLASMA-DERIVED REPLACEMENT FACTORS FOR HEMOPHILIA - HOW SAFE IS SAFE - PROCEEDINGS OF A SYMPOSIUM HELD PRECEDING THE 35TH ANNUAL-MEETING AND EXPOSITION OF THE AMERICAN-SOCIETY-OF-HEMATOLOGY, DECEMBER 3, 1993, ST-LOUIS, MO - DISCUSSION SO VOX SANGUINIS LA English DT Discussion C1 NIAID,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. MAGGIORE HOSP,IRCCS,INST INTERNAL MED,MILAN,ITALY. MAGGIORE HOSP,IRCCS,ANGELO BIANCHI BONOMI HEMOPHILIA & THROMBOSIS CTR,MILAN,ITALY. UNIV MILAN,MILAN,ITALY. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. US FDA,BETHESDA,MD 20014. CATHOLIC UNIV LEUVEN,CTR MOLEC & VASC BIOL,B-3000 LOUVAIN,BELGIUM. CATHOLIC UNIV LEUVEN,DIV BLEEDING & VASC DISORDERS,B-3000 LOUVAIN,BELGIUM. RP MOSLEY, JW (reprint author), CALIF STATE UNIV LOS ANGELES,SCH MED,DEPT MED,1840 N SOTO ST EDM 108,LOS ANGELES,CA 90032, USA. RI Mannucci, Pier/C-3102-2014 FU NHLBI NIH HHS [N01-HB-4-7002, N01-HB-4-7003, N01-HB-9-7074] NR 0 TC 9 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD SEP PY 1994 VL 67 SU 4 BP 24 EP 26 PG 3 WC Hematology SC Hematology GA PK900 UT WOS:A1994PK90000007 PM 8091731 ER PT J AU SNAWDER, JE ROE, AL BENSON, RW ROBERTS, DW AF SNAWDER, JE ROE, AL BENSON, RW ROBERTS, DW TI LOSS OF CYP2E1 AND CYP1A2 ACTIVITY AS A FUNCTION OF ACETAMINOPHEN DOSE - RELATION TO TOXICITY SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN LIVER-MICROSOMES; METABOLIZING ENZYMES; HEPATIC NECROSIS; PROTEIN; HEPATOTOXICITY; ACTIVATION; OXIDATION; INHIBITION; ASSAY; MOUSE AB The effect of acetaminophen (APAP) dose on the cytochrome P450s responsible for its bioactivation was examined in control mice and mice treated with acetone to induce CYP2E1, or beta-napthaflavone to induce CYP1A2. In non-induced mice, 150 mg/kg APAP caused minimal hepatotoxicity and loss of CYP2E1- but not CYP1A2-dependent activity. In contrast, 400 mg/kg APAP was hepatotoxic and diminished both CYP2E1 and CYP1A2 activities. In acetone-pretreated mice, the 150 and 400 mg/kg APAP doses caused similar depletion of CYP2E1 activity and similar levels of covalent binding of APAP to liver proteins. In beta-napthaflavone-pretreated mice, CYP1A2 activity was decreased only by the high dose of APAP, and covalent binding was > 2-fold higher at the high APAP dose. The data indicate CYP2E1 is important in the bioactivation of APAP at the low dose with little additional contribution at the high dose, whereas CYP1A2 contributes more to the bioactivation and toxicity APAP at high doses. (C) 1994 Academic Press, Inc. C1 US FDA,NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. UNIV KENTUCKY,GRAD CTR TOXICOL,LEXINGTON,KY 40536. NR 30 TC 60 Z9 62 U1 1 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 30 PY 1994 VL 203 IS 1 BP 532 EP 539 DI 10.1006/bbrc.1994.2215 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PD473 UT WOS:A1994PD47300076 PM 8074700 ER PT J AU CARAYANNOPOULOS, L MAX, EE CAPRA, JD AF CARAYANNOPOULOS, L MAX, EE CAPRA, JD TI RECOMBINANT HUMAN-IGA EXPRESSED IN INSECT CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BACULOVIRUS; GLYCOSYLATION; IMMUNOGLOBULIN A RECEPTOR; J CHAIN ID IMMUNOGLOBULIN-A; MONOCLONAL-ANTIBODIES; HEAVY-CHAIN; RECEPTORS; SECRETION; BINDING; GENE; TRANSPORT; PROTEINS AB IgA serves as the first line of humoral defense at all mucosal surfaces and is present in large quantities in serum. To map the sites of interaction of immune effector molecules with the IgA constant region (C-alpha), we have expressed soluble, chimeric human IgA in insect cells using recombinant baculoviruses. This antibody is correctly assembled into heavy chain/light chain heterodimers, N-glycosylated, and secreted by the insect cells; further, when coexpressed with a human J chain, the antibodies can assemble into dimers. The recombinant protein is authentic by a number of criteria, including antigen-binding, recognition by monoclonal antibodies, complement fixation via the alternative pathway, and specific binding to the monocyte IgA Fc receptor. We have also constructed viruses which encode structurally altered IgA heavy chains. Using one of these variant viruses, we have shown that glycosylation of the second domain of C-alpha is required for interaction with the monocyte IgA Fc receptor. This system should prove useful in further characterization of the structure-function relationships in human C-alpha. C1 UNIV TEXAS,SW MED CTR,DEPT MICROBIOL,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,DEPT INTERNAL MED,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,PROGRAM MOLEC BIOPHYS,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,MED SCIENTIST TRAINING PROGRAM,DALLAS,TX 75235. US FDA,CTR BIOL,CELL & VIRAL REGULAT LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI12127, AI32413]; NIGMS NIH HHS [GM08203] NR 49 TC 56 Z9 59 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 AUG 30 PY 1994 VL 91 IS 18 BP 8348 EP 8352 DI 10.1073/pnas.91.18.8348 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE388 UT WOS:A1994PE38800009 PM 8078886 ER PT J AU SHINDO, M DIBISCEGLIE, AM AKATSUKA, T FONG, TL SCAGLIONE, L DONETS, M HOOFNAGLE, JH FEINSTONE, SM AF SHINDO, M DIBISCEGLIE, AM AKATSUKA, T FONG, TL SCAGLIONE, L DONETS, M HOOFNAGLE, JH FEINSTONE, SM TI THE PHYSICAL STATE OF THE NEGATIVE STRAND OF HEPATITIS-C VIRUS-RNA IN SERUM OF PATIENTS WITH CHRONIC HEPATITIS-C SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLYMERASE CHAIN-REACTION; NON-B HEPATITIS; NON-A; VIRAL-RNA; GENOME; ORGANIZATION; REPLICATION; SEQUENCES; INFECTION; REGION AB Negative strands of the hepatitis C virus (HCV) genome (a positive-stranded RNA virus) have been found in a nuclease-resistant form in the serum of patients with HCV infections. We determined whether a complete negative-strand copy is present in the serum, whether the negative strand is particle-associated, and finally, whether it is virion-associated and encapsidated like the positive (genomic) strand. Isopyknic sucrose and cesium chloride density ultracentrifugation followed by a strand-specific reverse transcription-polymerase chain reaction on the collected fractions was performed to determine whether both positive and negative strands were associated with similar particles. Both strands comigrated to approximately the same density (1.11-1.16 g/cm(3)) in sucrose. After treatment of the plasma with detergent (0.1% Nonidet P-40) to remove the viral envelope and centrifugation on cesium chloride gradients, the positive strands shifted to a density of 1.35 g/cm(3), and the negative strands were not detected. By using antibodies specific for the HCV core or envelope glycoproteins E1 or E2 coated onto the wells of a microtiter plate, it was possible to specifically bind HCV or viral cores to the solid phase. Pelleted virus particles were resuspended in either PBS or PBS with 0.1% Nonidet P-40 to expose the core. These pellets were then incubated in antibody-coated microtiter wells. RNA extracted from the bound and unbound fractions was tested for HCV RNA. The anti-core antibody was able to bind positive strands but not negative strands only in detergent-treated samples. In the nondetergent-treated pellets, the anti-E1 and -E2 bound the positive strand, but only anti-E1 bound the negative strands. These findings indicate that while both strands of HCV RNA can be detected in serum, the positive strand is encapsidated within the enveloped core, and the negative strand appears to be in a membrane particle associated with the viral envelope protein E1 but does not appear to be within the HCV core of circulating virions. C1 NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,HEPATITIS RES LAB,BETHESDA,MD 20892. NR 25 TC 31 Z9 31 U1 1 U2 3 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 AUG 30 PY 1994 VL 91 IS 18 BP 8719 EP 8723 DI 10.1073/pnas.91.18.8719 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE388 UT WOS:A1994PE38800084 PM 8078948 ER PT J AU WEISZ, A ANDRZEJEWSKI, D ITO, Y AF WEISZ, A ANDRZEJEWSKI, D ITO, Y TI PREPARATIVE SEPARATION OF COMPONENTS OF THE COLOR ADDITIVE D-AND-C RED NO-28 (PHLOXINE B) BY PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article ID STANDARDIZATION; PURIFICATION; PERFORMANCE; DERIVATIVES; STAINS; DYES AB A pH-zone-refining counter-current chromatographic method was developed for the preparative (multigram) separation and purification of components of the commercial color additive D&C Red No. 28 (phloxine B). The chromatography of 3 and 6 g of color additive yielded 1.07 and 4.06 g, respectively, of pure 2',4',5',7'-tetrabromo-4,5,6,7-tetrachlorofluorescein, the principal component of D&C Red No. 28. The importance of the quantity of retainer acid (trifluoroacetic acid) relative to the amount of salt in the color additive is discussed. C1 US FDA,OFF SCI ANAL & SUPPORT,WASHINGTON,DC 20204. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP WEISZ, A (reprint author), US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204, USA. NR 20 TC 28 Z9 28 U1 0 U2 3 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 AUG 26 PY 1994 VL 678 IS 1 BP 77 EP 84 DI 10.1016/0021-9673(94)87076-4 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PE486 UT WOS:A1994PE48600009 PM 7921192 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI ADVERSE DRUG-REACTIONS - GETTING INFORMATION BACK FROM MEDWATCH - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP NIGHTINGALE, SL (reprint author), US FDA,ROCKVILLE,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 24 PY 1994 VL 272 IS 8 BP 590 EP 591 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PC398 UT WOS:A1994PC39800016 ER PT J AU MARYANSKI, JH AF MARYANSKI, JH TI FDAS POLICY FOR FOODS DEVELOPED BY BIOTECHNOLOGY 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 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 10 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100010 ER PT J AU JERUSSI, RA AF JERUSSI, RA TI THE REVIEW OF DRUG APPLICATIONS AT THE FOOD-AND-DRUG-ADMINISTRATION 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 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 13 EP CHAL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101015 ER PT J AU ROBERTSON, DE AF ROBERTSON, DE TI CONTRIBUTION OF FDAS NON-LABORATORY CHEMISTS TO FOOD SAFETY 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 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 14 EP CHAL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101016 ER PT J AU SHANK, FR CARSON, KL AF SHANK, FR CARSON, KL TI HYPERNUTRITIOUS FOODS - POLICY ISSUES 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 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 15 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100015 ER PT J AU ZHANG, YH AF ZHANG, YH TI MOLECULAR-DYNAMICS SIMULATIONS OF LIQUID ALKANES AND THE ALKANE-WATER INTERFACE 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 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 16 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101323 ER PT J AU BLOOM, RA AF BLOOM, RA TI BIODEGRADATION OF COMPLEX ORGANIC-COMPOUNDS - UPDATING FDA TECHNICAL ASSISTANCE DOCUMENTS 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 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 20 EP ENVR PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101527 ER PT J AU DUSOLD, LR AF DUSOLD, LR TI WHAT CHEMISTS SHOULD KNOW ABOUT COMPUTERS AT FDA/CFSAN SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,TELECOMMUN & SCI COMP SUPPORT 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 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 24 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101331 ER PT J AU KUZNESOF, PM VANDERVEER, MC AF KUZNESOF, PM VANDERVEER, MC TI RECYCLED PLASTICS FOR FOOD-CONTACT APPLICATIONS - SCIENCE, POLICY, AND REGULATION SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR FOOD SAFETY & APPL NUTR,OFF PREMARKET APPROVAL,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 26 EP MACR PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26902047 ER PT J AU HOLAK, W AF HOLAK, W TI SUPERCRITICAL-FLUID EXTRACTION AND DETERMINATION OF SACCHARIN IN FOODS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NE REG LAB,BROOKLYN,NY 11232. NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 37 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100316 ER PT J AU THORSHEIM, HR AF THORSHEIM, HR TI FDA ACTIONS ON THE USE OF RECYCLED PLASTICS IN CONTACT WITH FOOD SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR FOOD SAFETY & APPL NUTR,OFF PREMARKET APPROVAL,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 43 EP MACR PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26902064 ER PT J AU BEGLEY, TH HOLLIFIELD, HC AF BEGLEY, TH HOLLIFIELD, HC TI FOOD-PACKAGING MADE FROM RECYCLED POLYMERS - FUNCTIONAL BARRIER CONSIDERATIONS 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 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 44 EP MACR PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26902065 ER PT J AU KOMOLPRASERT, V LAWSON, A AF KOMOLPRASERT, V LAWSON, A TI RESIDUAL CONTAMINANTS IN RECYCLED POLYETHYLENE TEREPHTHALATE (PET) - EFFECTS OF WASHING AND DRYING SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT AGRO,IL 60501. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 46 EP MACR PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26902067 ER PT J AU VENABLE, RM AF VENABLE, RM TI COMPUTER-SIMULATION OF A DPPC BILAYER SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 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 AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 47 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101354 ER PT J AU KOMOLPRASERT, V LAWSON, A HARGRAVES, W AF KOMOLPRASERT, V LAWSON, A HARGRAVES, W TI AN ANALYTICAL METHOD FOR QUANTIFYING POLAR CONTAMINANTS IN RECYCLED POLYETHYLENE TEREPHTHALATE (PET) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 51 EP MACR PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26902072 ER PT J AU WILKES, JG CHURCHWELL, MI FREEMAN, JP AF WILKES, JG CHURCHWELL, MI FREEMAN, JP TI FUMONISIN IMPURITIES QUANTIFIED USING HPLC WITH A NONLINEAR EVAPORATIVE LIGHT-SCATTERING DETECTOR AND IDENTIFIED BY OFFLINE FAB/MS 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 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 68 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100068 ER PT J AU FU, TJ AF FU, TJ TI KINETICS OF THE FORMATION AND DECOMPOSITION OF 1,1'-ETHYLIDENEBIS[L-TRYPTOPHAN], AN EOSINOPHILIA MYALGIA SYNDROME-ASSOCIATED COMPOUND SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 72 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100072 ER PT J AU WEISZ, A SCHER, AL ANDRZEJEWSKI, D ITO, Y AF WEISZ, A SCHER, AL ANDRZEJEWSKI, D ITO, Y TI PREPARATIVE SEPARATION OF 4'-BROMO-4,5,6,7-TETRACHLOROFLUORESCEIN BY PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY WITH COMPUTERIZED SCANNING UV-VIS DETECTION AND CONTINUOUS PH MONITORING SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204. US FDA,OFF SCI ANAL & SUPPORT,WASHINGTON,DC 20204. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 77 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100356 ER PT J AU NGUYENPHO, AAN BRUNNER, CA ROSCHER, NM DOYLE, TD AF NGUYENPHO, AAN BRUNNER, CA ROSCHER, NM DOYLE, TD TI ENANTIOMERIC RESOLUTION ON HPLC CHIRAL STATIONARY PHASES - INFLUENCE OF AROMATIC INTERACTIONS ON ELUTION ORDER SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,DIV RES & TESTING,WASHINGTON,DC 20204. AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 85 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100364 ER PT J AU CONTE, ED CONWAY, SC MILLER, DW AF CONTE, ED CONWAY, SC MILLER, DW TI DETERMINATION OF METHYLISOBORNEOL IN DRINKING-WATER AND CHANNEL CATFISH POND WATER BY SOLID-PHASE EXTRACTION FOLLOWED BY CAPILLARY GAS-CHROMATOGRAPHY WITH DETECTION BY MASS-SPECTROMETRY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. UNIV ARKANSAS,PINE BLUFF,AR 71601. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 87 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100366 ER PT J AU WELSH, WJ TONG, W ZIELINSKI, W AF WELSH, WJ TONG, W ZIELINSKI, W TI MOLECULAR SIMULATIONS OF CHROMATOGRAPHIC SEPARATIONS OF GEOMETRIC ISOMERS BY LIQUID-CRYSTAL STATIONARY PHASES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV MISSOURI,DEPT CHEM,ST LOUIS,MO 63121. US FDA,DIV DRUG ANAL,ST LOUIS,MO 63101. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 96 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101403 ER PT J AU LUDEMAN, SM ANDERSON, LW COLVIN, OM STRONG, JM GROCHOW, LB AF LUDEMAN, SM ANDERSON, LW COLVIN, OM STRONG, JM GROCHOW, LB TI A NEW METHOD FOR THE QUANTITATIVE-ANALYSIS OF CYCLOPHOSPHAMIDE METABOLITES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 JOHNS HOPKINS ONCOL CTR,PHARMACOL LAB,BALTIMORE,MD 21287. US FDA,ROCKVILLE,MD 20850. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 100 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102895 ER PT J AU MILLER, DW LEE, ME TAKENAKA, NE CONTE, E AF MILLER, DW LEE, ME TAKENAKA, NE CONTE, E TI SEAFOOD DECOMPOSITION - THE COLORIMETRIC METHOD FOR INDOLE FROM THE DECOMPOSITION OF SHRIMP REVISITED SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NCTR,DIV CHEM,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 145 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100145 ER PT J AU KAMBHAMPATI, RVB BLUMENSTEIN, JJ CHI, WC AF KAMBHAMPATI, RVB BLUMENSTEIN, JJ CHI, WC TI REGULATORY CONCERNS FOR THE SYNTHESIS, CHARACTERIZATION, AND CONTROLS OF OLIGONUCLEOTIDE THERAPEUTICS FOR USE IN CLINICAL-STUDIES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 157 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100436 ER PT J AU FELLER, SE MCQUARRIE, DA AF FELLER, SE MCQUARRIE, DA TI VARIATIONAL SOLUTIONS TO INTEGRAL-EQUATION THEORIES OF THE ELECTRICAL DOUBLE-LAYER 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. UNIV CALIF DAVIS,DEPT CHEM,DAVIS,CA 95616. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 207 EP COLL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101265 ER PT J AU ROBBINS, JD BORING, DL TANG, WJ SHANK, R SEAMON, KB AF ROBBINS, JD BORING, DL TANG, WJ SHANK, R SEAMON, KB TI MAPPING OF ADENYLYL-CYCLASE ISOFORM ACTIVATION AND BINDING REQUIREMENTS WITH FORSKOLIN CARBAMATES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DBB,LMP,BETHESDA,MD 20014. DAVDP,CTR DRUG EVALUAT & RES,ODE 2,ROCKVILLE,MD. UNIV TEXAS,SW MED CTR,DALLAS,TX 75235. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 248 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26103041 ER PT J AU DAVIS, C SMITH, A WALDEN, R BOWER, G CUMMINGS, K DEAN, B RIGSBY, J JUSTICE, P ANDERSON, C BROWN, N MINOR, J GEIGER, EF LAXTON, V CROCKETT, L MCDOUGAL, W HLADY, WG HOPKINS, RS AF DAVIS, C SMITH, A WALDEN, R BOWER, G CUMMINGS, K DEAN, B RIGSBY, J JUSTICE, P ANDERSON, C BROWN, N MINOR, J GEIGER, EF LAXTON, V CROCKETT, L MCDOUGAL, W HLADY, WG HOPKINS, RS TI VIRAL GASTROENTERITIS ASSOCIATED WITH CONSUMPTION OF RAW OYSTERS - FLORIDA, 1993 (REPRINTED FROM MMWR, VOL 43, PG 446-448, 1994) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 JACKSON CTY PUBL HLTH UNIT,MARIANNA,AR. WASHINGTON CTY PUBL HLTH UNIT,CHIPLEY,FL. DIST 1 HLTH OFF,PENSACOLA,FL. DIST 2 HLTH OFF,TALLAHASSEE,FL. US FDA,FLORIDA DEPT HLTH & REHABIL SERV,STATE HLTH OFF,TALLAHASSEE,FL. CTR DIS CONTROL,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,VIRAL GASTROENTERITIS SECT,ATLANTA,GA 30333. CTR DIS CONTROL,EPIDEMIOL PROGRAM OFF,DIV FIELD EPIDEMIOL,ATLANTA,GA. RP DAVIS, C (reprint author), BAY CTY PUBL HLTH UNIT,PANAMA CITY,FL, USA. NR 7 TC 3 Z9 3 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 AUG 17 PY 1994 VL 272 IS 7 BP 510 EP 511 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PB229 UT WOS:A1994PB22900008 ER PT J AU DIVI, RL DOERGE, DR AF DIVI, RL DOERGE, DR TI MECHANISM-BASED INACTIVATION OF LACTOPEROXIDASE AND THYROID PEROXIDASE BY RESORCINOL DERIVATIVES SO BIOCHEMISTRY LA English DT Article ID CYTOCHROME-C PEROXIDASE; THIOCARBAMIDE GOITROGENS; HORSERADISH-PEROXIDASE; HYDROGEN-PEROXIDE; INHIBITION; THYROGLOBULIN; SUBSTANCES; IODINATION; OXIDATION; COMPOUND AB Humans are exposed to resorcinol derivatives in the environment through ground water, foods, food additives, drugs, and hair dyes. Epidemiological studies have linked human exposure to phenolic compounds with the thyroid disorder, goiter. The results presented here demonstrate the suicide (mechanism-based) inactivation of thyroid peroxidase (TPO) and the closely related lactoperoxidase (LPO) by resorcinol derivatives. The evidence for this mechanism includes irreversible, hydrogen peroxide-dependent loss of enzymatic activity by kinetics consistent with a suicide mechanism, concomitant with changes in the visible spectrum of the prosthetic heme group and covalent binding of resorcinol (ca. 10 mol/mol of lactoperoxidase inactivated). The inactivation was specific for thyroid peroxidase and lactoperoxidase since the activity of horseradish peroxidase, myeloperoxidase, chloroperoxidase, or the pseudoperoxidase, metmyoglobin, was unaffected by incubation with resorcinol. The enzymatic oxidation of resorcinol by lactoperoxidase was linked to inactivation since the same products were observed spectrally, albeit at a much lower level, as were observed with horseradish peroxidase. The results are consistent with thyroid peroxidase- and lactoperoxidase-catalyzed oxidation of resorcinol derivatives to reactive radical species that covalently bind to amino acid residues unique to these two enzymes. The oxidation of thyroid peroxidase and lactoperoxidase by hydrogen peroxide produces catalytic intermediates containing unpaired electron density on amino acid residues similar to that seen with cytochrome c peroxidase. These results provide an explanation for the potency of resorcinol derivatives in the inhibition of LPO and TPO and the goitrogenic responses observed in humans and animals. The widespread occurrence of resorcinol derivatives in the environment suggests that exposure to these compounds may cause thyroid dysfunction in humans. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 34 TC 64 Z9 67 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 16 PY 1994 VL 33 IS 32 BP 9668 EP 9674 DI 10.1021/bi00198a036 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC545 UT WOS:A1994PC54500036 PM 8068644 ER PT J AU SCRIBNER, CL KAPIT, RM PHILLIPS, ET RICKLES, NM AF SCRIBNER, CL KAPIT, RM PHILLIPS, ET RICKLES, NM TI ASEPTIC-MENINGITIS AND INTRAVENOUS IMMUNOGLOBULIN THERAPY SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID IDIOPATHIC THROMBOCYTOPENIC PURPURA; IMMUNE GLOBULIN; CHILDHOOD RP SCRIBNER, CL (reprint author), US FDA,OFF BLOOD RES & REVIEW,HFM-370,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 15 TC 37 Z9 37 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 AUG 15 PY 1994 VL 121 IS 4 BP 305 EP 306 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PB102 UT WOS:A1994PB10200014 PM 8037414 ER PT J AU HARTMANN, F HORAK, EM GARMESTANI, K WU, CC BRECHBIEL, MW KOZAK, RW TSO, J KOSTEINY, SA GANSOW, OA NELSON, DL WALDMANN, TA AF HARTMANN, F HORAK, EM GARMESTANI, K WU, CC BRECHBIEL, MW KOZAK, RW TSO, J KOSTEINY, SA GANSOW, OA NELSON, DL WALDMANN, TA TI RADIOIMMUNOTHERAPY OF NUDE-MICE BEARING A HUMAN INTERLEUKIN-2 RECEPTOR ALPHA-EXPRESSING LYMPHOMA UTILIZING THE ALPHA-EMITTING RADIONUCLIDE-CONJUGATED MONOCLONAL-ANTIBODY BI-212-ANTI-TAC SO CANCER RESEARCH LA English DT Article ID BETA-CHAIN; TAC; THERAPY; CELLS; IMMUNOTHERAPY; ANTIFERRITIN; LEUKEMIA; CANCER; TARGET; BI-212 AB The efficacy, specificity, and toxicity of bismuth (Bi-212) alpha particle-mediated radioimmunotherapy was evaluated in nude mice bearing a murine lymphoma transfected with the human CD25 [human Tac; interleukin 2 receptor alpha (IL-2R alpha)] gene, The therapeutic agent used was the tumor-specific humanized monoclonal antibody anti-Tac conjugated to Bi-212. The human IL-2R alpha-expressing cell line was produced by transfecting the gene encoding human Tac into the murine plasmacytoma cell line SP2/0. The resulting cell line, SP2/Tac, expressed approximately 18,000 human IL-2R alpha molecules/cell. Following s.c. or i.p. injection of 2 x 10(6) SP2/Tac cells into nude mice, rapidly growing tumors developed in all animals after a mean of 10 and 13 days, respectively. The bifunctional chelate cyclohexyldiethylenetriaminepentaacetic acid was used to couple Bi-212 to the humanized anti-Tac monoclonal antibody. This immunoconjugate was shown to be stable in vivo. Specifically, in pharmacokinetic studies in nude mice, the blood clearance patterns of i.v. administered Bi-205/206-anti-Tac and coinjected I-125-anti-Tac were comparable. The toxicity and therapeutic efficacy of Bi-212-anti-Tac were evaluated in nude mouse ascites or solid tumor models wherein SP2/Tac cells were administered either i.p. or s.c., respectively. The i.p. administration of Bi-212-anti-Tac, 3 days following i.p. tumor inoculation, led to a dose-dependent, significant prolongation of tumor-free survival. Doses of 150 or 200 mu Ci prevented tumor occurrence in 75% (95% confidence interval, 41-93%) of the animals. In the second model, i.v. treatment with Bi-212-anti-Tac 3 days following s.c. tumor inoculation also resulted in a prolongation of the period before tumor development. However, prevention of tumor occurrence decreased to 30% (95% confidence interval, 11-60%). In both the i.p. and s.c. tumor trials, Bi-212-anti-Tac was significantly more effective for i.p. (P2 = 0.0128 50/100 mu Ci Bi-212-anti-Tac versus 50/100 mu Ci Mik beta; P2 = 0.0142 150/200 mu Ci anti-Tac versus 150/200 mu Ci Mik beta) and for s.c. tumors (P2 = 0.0018 100 mu Ci anti-Tac versus 100 mu Ci Mik beta; P2 = 0.0042 200 mu Ci anti-Tac versus 200 mu Ci Mik beta 1) than the control antibody Mik beta 1 coupled to Bi-212 at comparable dose levels. In contrast to the efficacy observed in the adjuvant setting, therapy of large, established s.c. SP-2/ Tac-expressing tumors with i.v. administered Bi-212-anti-Tac (at doses up to 200 mu Ci/animal) failed to induce tumor regression. Pharmacokinetic and tissue distribution studies of radiolabeled anti-Tac in this particular therapeutic situation provided an explanation for this observation. Only 5-6% of the injected dose of radiolabeled antibody was present per g of tumor at 2 h following injection at a time when 75% of the administered Bi-212 radioactivity had decayed. Furthermore, at this time point, there was no greater uptake of Bi-anti-Tac into Tac-expressing tumors than was observed with Tac-nonexpressing variants of SP2/0. Finally, the specific antibody Bi-212/206-anti-Tac was not enriched in the tumor when compared to the irrelevant monoclonal antibody Bi-205/206-Mik beta 1. Although specific enrichment of radiolabeled Bi-anti-Tac was not seen at 2 h, such enrichment in the tumor was observed at 5 and 24 h postinjection with up to 15.6% injected dose present per g of tumor. The dose limiting acute toxicity following i.v. administration of Bi-212 anti-Tac was bone marrow suppression, which was observed at doses above 200 mu Ci. In summary, Bi-212-anti-Tac as a complete antibody may be of only limited value in the therapy of bulky solid tumors due to the short physical half-life of Bi-212 and the time required to achieve a useful tumor:normal tissue ratio of the radionuclide following administration of the radiolabeled antibody. However, this radionuclide may be useful in select situations such as adjuvant or intracavitary therapy, strategies that target the vascular endothelial cells of tumors, or in the treatment of leukemias. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,INORGAN & RADIOIMMUNE CHEM SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV MONOCLONAL ANTIBODIES,BETHESDA,MD 20892. PROT DESIGN LABS INC,MT VIEW,CA 94043. NR 41 TC 63 Z9 65 U1 0 U2 3 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 AUG 15 PY 1994 VL 54 IS 16 BP 4362 EP 4370 PG 9 WC Oncology SC Oncology GA PB502 UT WOS:A1994PB50200022 PM 8044783 ER PT J AU PURI, RK LELAND, P KREITMAN, RJ PASTAN, I AF PURI, RK LELAND, P KREITMAN, RJ PASTAN, I TI HUMAN NEUROLOGICAL CANCER-CELLS EXPRESS INTERLEUKIN-4 (IL-4) RECEPTORS WHICH ARE TARGETS FOR THE TOXIC EFFECTS OF IL4-PSEUDOMONAS EXOTOXIN CHIMERIC PROTEIN SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID PSEUDOMONAS EXOTOXIN; HIGH-AFFINITY; CARCINOMA-CELLS; TUMOR-CELLS; GAMMA-CHAIN; GROWTH; INHIBITION; IDENTIFICATION; THERAPY; INVIVO AB Glioblastoma, glioma or neuroblastoma cells were examined for the expression of IL-4 receptors (IL-4R) by now cytometric analysis and I-125-IL-4 binding. These cancer cell lines expressed IL-4R which were of high affinity (K-D = 700 x 10(-12) M) on glioblastoma cells. To investigate the function of these receptors and to target potent cytotoxic antitumor agents to human neurological cancers, we utilized IL4-PE4E, which is composed of IL-4 and mutant Pseudomonas exotoxin (IL4-PE4E). This chimeric molecule was cytotoxic toward human glioblastoma, neuroblastoma and glioma tumor cells in a dose-dependent manner. The cytotoxicity of IL4-PE4E was specific, since it was neutralized by excess IL-4, and by an anti-IL-4 monoclonal antibody in all types of brain tumor tested. IL2-PE4E and IL6-PE4E were not cytotoxic, nor was an IL4-PE4E mutant lacking ADP-ribosylating activity, indicating the IL4-PE4E-mediated cytotoxicity of the brain tumor cells required both IL-4R binding and enzymatic toxin activity. These data indicate that human neurological cancer cells express IL-4R which are targets for the cytotoxic effects of IL4-toxin. In addition, our data also suggest that IL4-PE4E should be studied further as a potential treatment for human neurological cancers. (C) 1994 Wiley-Liss, Inc. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. RP PURI, RK (reprint author), NIH,US FDA,CBER,DIV CELLULAR & GENE THERAPIES,MOLEC TUMOR BIOL LA,BLDG 29A,ROOM 2B23,BETHESDA,MD 20892, USA. NR 29 TC 94 Z9 98 U1 1 U2 2 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 AUG 15 PY 1994 VL 58 IS 4 BP 574 EP 581 DI 10.1002/ijc.2910580421 PG 8 WC Oncology SC Oncology GA PB589 UT WOS:A1994PB58900020 PM 8056454 ER PT J AU SHIRAI, A AOKI, I OTANI, M MOND, JJ KLINMAN, DM AF SHIRAI, A AOKI, I OTANI, M MOND, JJ KLINMAN, DM TI TREATMENT WITH DEXTRAN-CONJUGATED ANTI-IGD DELAYS THE DEVELOPMENT OF AUTOIMMUNITY IN MRL LPR/LPR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; MOUSE IMMUNOGLOBULIN ANTIBODIES; B-CELL ACTIVATION; SECRETING CELLS; BACTERIAL LIPOPOLYSACCHARIDES; AUTOANTIBODY PRODUCTION; DNA ANTIBODIES; T-CELLS; MICE; LPR AB The onset of clinical disease in autoimmune MRL-Ipr/Ipr mice is preceded by a switch from predominantly IgM production to IgG production. Previous studies have shown that IgG autoantibodies play a central role in the development of life-threatening glomerulonephritis in this strain. Delaying or preventing the switch from IgM to IgG production might therefore be of therapeutic benefit. We previously documented similarities in the B cell repertoire expressed by young MRL-Ipr/Ipr mice and normal mice treated with the polyclonal activator LPS. Recent in vivo studies indicate that cross-linking membrane IgM or IgD can suppress LPS-dependent IgG production in normal animals. These observations led us to examine whether membrane cross-linking could also lower serum IgG levels in MRL-Ipr/Ipr mice. Lupus-prone animals were treated with multivalent anti-IgD conjugated to high m.w. dextran. This anti-IgD dextran conjugate was previously shown to reduce IgG production in LPS-stimulated normal animals. Treatment of young lupus-prone MRL-Ipr/Ipr mice resulted in a significant reduction in the total number of B cells secreting IgG and lower serum titers of IgG anti-DNA and IgG anti-histone autoantibodies. Anti-IgD dextran treatment also delayed the development of glomerulonephritis and improved survival. Thus, anti-IgD dextran interfered with autoantibody-dependent disease progression, perhaps by inhibiting the switch from IgM to IgG autoantibody production. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,RETROVIRAL IMMUNOL SECT,BETHESDA,MD 20892. TOHO UNIV,SCH MED,DEPT PATHOL 2,TOKYO,JAPAN. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. NR 37 TC 8 Z9 8 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 15 PY 1994 VL 153 IS 4 BP 1889 EP 1894 PG 6 WC Immunology SC Immunology GA PB406 UT WOS:A1994PB40600049 PM 7519219 ER PT J AU ELLENBERG, JH GAIL, MH SIMON, RH AF ELLENBERG, JH GAIL, MH SIMON, RH TI NATIONAL-INSTITUTES-OF-HEALTH CONFERENCE ON CURRENT TOPICS IN BIOSTATISTICS (VOL 13, PG 1600, 1994) SO STATISTICS IN MEDICINE LA English DT Correction, Addition C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892. RP ELLENBERG, JH (reprint author), US FDA,CBER,OELPS,DIV BIOSTAT & EPIDEMIOL,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 1 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 AUG 15 PY 1994 VL 13 IS 15 BP 1600 EP 1600 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 PF482 UT WOS:A1994PF48200009 ER PT J AU BARTMAN, T MURASKO, DM SIECK, TG TURTURRO, A HART, R BLANK, KJ AF BARTMAN, T MURASKO, DM SIECK, TG TURTURRO, A HART, R BLANK, KJ TI A MURINE LEUKEMIA-VIRUS EXPRESSED IN AGED DBA/2 MICE IS DERIVED BY RECOMBINATION OF THE EMV-3 LOCUS AND ANOTHER ENDOGENOUS GAG SEQUENCE SO VIROLOGY LA English DT Article ID ECOTROPIC PROVIRUSES; NUCLEOTIDE-SEQUENCE; LYMPHOCYTES-T; AKR MICE; DNA; ACTIVATION; INFECTION; PROTEIN; GENOME AB Although most inbred strains of mice contain endogenous retroviral sequences, these sequences are usually not capable of producing infectious retroviruses. In some cases, the retroviral sequences are small fragments of viral genomes. In a few cases the sequences for complete retroviruses exist, but contain small defects which prevent the production of infectious virus. While the ability of reversions of these defects to produce retroviruses has been studied by site-directed mutagenesis and chemical-mediated mutagenesis, the presence of spontaneously occurring reversions has not been completely evaluated. We characterized an infectious ecotropic retrovirus spontaneously expressed in aged DBA/2 mice, which carries the complete but defective Emv-3. Although this endogenously produced retrovirus was related to the endogenous Emv-3 sequence, it had undergone recombination with another retroviral sequence to correct the defect which resided in the gag of Emv-3. Thus, recombination of endogenous ecotropic retroviral sequences may be a mechanism to produce infectious retroviruses in adult animals that contributes to pathologic disease. (C) 1994 academic Press, Inc. C1 TEMPLE UNIV,SCH MED,GRAD PROGRAM MOLEC BIOL & GENET,MD PHD PROGRAM,PHILADELPHIA,PA 19140. HAHNEMANN UNIV,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19102. MED COLL PENN,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19129. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 32 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 15 PY 1994 VL 203 IS 1 BP 1 EP 7 DI 10.1006/viro.1994.1448 PG 7 WC Virology SC Virology GA NZ236 UT WOS:A1994NZ23600001 PM 8030264 ER PT J AU SCHNEIDER, L GEHA, R AF SCHNEIDER, L GEHA, R TI OUTBREAK OF HEPATITIS-C ASSOCIATED WITH INTRAVENOUS IMMUNOGLOBULIN ADMINISTRATION - UNITED-STATES, OCTOBER-1993 JUNE-1994 (REPRINTED FROM MMWR, VOL 43, PG 505-509, 1994) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID INFECTION C1 WALTER REED ARMY INST RES,WASHINGTON,DC. US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITED DIS,WASHINGTON,DC. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,OFF BLOOD RES & REVIEW,WASHINGTON,DC. NIDDKD,DIV DIGEST DIS & NUTR,BETHESDA,MD. NHLBI,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD. CTR DIS CONTROL,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA. RP SCHNEIDER, L (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 6 TC 9 Z9 9 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 AUG 10 PY 1994 VL 272 IS 6 BP 424 EP 425 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PA278 UT WOS:A1994PA27800006 ER PT J AU MAKHOV, AM HANNAH, JH BRENNAN, MJ TRUS, BL KOCSIS, E CONWAY, JF WINGFIELD, PT SIMON, MN STEVEN, AC AF MAKHOV, AM HANNAH, JH BRENNAN, MJ TRUS, BL KOCSIS, E CONWAY, JF WINGFIELD, PT SIMON, MN STEVEN, AC TI FILAMENTOUS HEMAGGLUTININ OF BORDETELLA-PERTUSSIS - A BACTERIAL ADHESIN FORMED AS A 50-NM MONOMERIC RIGID-ROD BASED ON A 19-RESIDUE REPEAT MOTIF RICH IN BETA-STRANDS AND BETA-TURNS SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE PERTUSSIS; FILAMENTOUS HEMAGGLUTININ; ADHESIN; LEUCINE-RICH REPEATS; BETA-HELIX PROTEINS ID RESPIRATORY-EPITHELIAL-CELLS; MONOCLONAL-ANTIBODIES; ELECTRON-MICROSCOPY; SECONDARY STRUCTURE; TAIL-FIBER; MOLECULAR-STRUCTURE; ESCHERICHIA-COLI; ADENOVIRUS FIBER; PROMOTING FACTOR; SHEET STRUCTURE AB The filamentous hemagglutinin (FHA) of Bordetella pertussis is an adhesin that binds the bacteria to cells of the respiratory epithelium in whooping-cough infections. Mature FNA is a 220 kDa secretory protein that is highly immunogenic and has been included in acellular vaccines. We have investigated its structure by combining electron microscopy and circular dichroism spectroscopy (CD) with computational analysis of its amino acid sequence. The FHA molecule is 50 nm in length and has the shape of a horseshoe nail: it has a globular head that appears to consist of two domains; a 35 nm-long shaft that averages 4 nm in width, but tapers slightly from the head end; and a small, flexible, tail. Mass measurements by scanning transmission electron microscopy establish that FHA is a monomer. Its sequence contains two regions of tandem 19-residue pseudo-repeats: the first, of 38 cycles, starts at residue 344; the second, of 13 cycles, starts at residue 1440. The repeat motifs are predicted to consist of short beta-strands separated by beta-turns, and secondary structure measurements by CD support this prediction. We propose a hairpin model for FHA in which the head is composed of the terminal domains; the shaft consists mainly of the repeat regions conformed as amphipathic, hyper-elongated beta-sheets, with their hydrophobic faces apposed and the tail is composed of the intervening sequence. Further support for the model was obtained by immuno-labeling electron microscopy. The 19-residue repeats of FHA have features in common with the leucine-rich repeats (LRRs) that are present in many eukaryotic proteins, including some adhesion factors. The model is also compared with the two other classes of filamentous proteins that are rich in beta-structure, i.e. viral adhesins and two beta-helical secretory proteins. Our proposed structure implies how the functionally important adhesion sites and epitopes of PHB are distributed: its tripeptide (RGD) integrin-binding site is assigned to the tail; the putative hemagglutination site forms part of the head. and two classes of immunodominant epitopes are assigned to opposite ends of the molecule. Possible mechanisms are discussed for two modes of FHA-mediated adhesion. C1 NIH,US FDA,DIV BACTERIAL PROD,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,COMPUTAT BIOL & ENGN LAB,BETHESDA,MD 20892. NIH,OFF DIRECTOR,PROT EXPRESS LAB,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. NIAMSD,STRUCT BIOL RES LAB,BETHESDA,MD 20892. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 78 TC 79 Z9 81 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 5 PY 1994 VL 241 IS 1 BP 110 EP 124 DI 10.1006/jmbi.1994.1478 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA947 UT WOS:A1994PA94700012 PM 7519681 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI FDA TO SPONSOR WORKSHOP ON HIV DETECTION DURING WINDOW PERIOD IN DONOR SCREENING 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 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 3 PY 1994 VL 272 IS 5 BP 344 EP 344 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NY903 UT WOS:A1994NY90300006 PM 8028152 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI POSSIBLE ELECTROMAGNETIC-INTERFERENCE PROBLEMS WITH WHEELCHAIRS AND OTHER MEDICAL DEVICES 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 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 3 PY 1994 VL 272 IS 5 BP 344 EP 344 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NY903 UT WOS:A1994NY90300005 PM 8028152 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI COMBINATION TUBERCULOSIS DRUG APPROVED 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 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 3 PY 1994 VL 272 IS 5 BP 344 EP 344 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NY903 UT WOS:A1994NY90300004 PM 8028152 ER PT J AU MICHELSON, D MISIEWICZPOLTORAK, B RAYBOURNE, RB GOLD, PW STERNBERG, EM AF MICHELSON, D MISIEWICZPOLTORAK, B RAYBOURNE, RB GOLD, PW STERNBERG, EM TI IMIPRAMINE REDUCES THE LOCAL INFLAMMATORY RESPONSE TO CARRAGEENAN SO AGENTS AND ACTIONS LA English DT Article DE ANTIDEPRESSANTS; IMIPRAMINE; CRH; CORTISOL; INFLAMMATION ID CORTICOTROPIN-RELEASING HORMONE; WALL-INDUCED ARTHRITIS; LEWIS RATS; SUSCEPTIBILITY; EXPRESSION; SECRETION AB Imipramine was administered chronically to LEW/N, outbred and F344/N rats which were then exposed to the aseptic irritant carrageenin in order to determine whether the decreased hypothalamic expression of CRH m-RNA previously shown to be associated with imipramine affects peripheral immune processes. Both LEW/N and outbred but not F344/N rats had vigorous inflammatory responses to carrageenin, and imipramine was associated with significant decreases in the local cellular inflammatory response to carrageenin. Imipramine was also associated with changes in the expression of peripheral blood cell MHC class II expression in LEW/N and outbred rats. These results suggest that at doses comparable to those used clinically imipramine has significant effects on response to an inflammatory stimulus. C1 US FDA,LAUREL,MD 20708. RP MICHELSON, D (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BLDG 10 ROOM 3S231,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 17 Z9 19 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA PO BOX 133 KLOSTERBERG 23, CH-4010 BASEL, SWITZERLAND SN 0065-4299 J9 AGENTS ACTIONS JI Agents Actions PD AUG PY 1994 VL 42 IS 1-2 BP 25 EP 28 DI 10.1007/BF02014295 PG 4 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA PE662 UT WOS:A1994PE66200007 PM 7847180 ER PT J AU BERMAN, PW NAKAMURA, GR HASTINGS, R WILKES, D FOX, J BYRN, R SCHWARTZ, D BELSHE, R MATTHEWS, T NORCROSS, MA AF BERMAN, PW NAKAMURA, GR HASTINGS, R WILKES, D FOX, J BYRN, R SCHWARTZ, D BELSHE, R MATTHEWS, T NORCROSS, MA TI ANALYSIS OF THE IMMUNOGENICITY OF RECOMBINANT GP120 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 GENENTECH INC,DEPT IMMUNOL,S SAN FRANCISCO,CA. GENENTECH INC,DEPT PHARMACOL,S SAN FRANCISCO,CA. NEW ENGLAND DEACONESS HOSP,DEPT HEMATOL & ONCOL,BOSTON,MA. US FDA,NAIAD,AIDS VACCINE EVALUAT NETWORK,BETHESDA,MD. US FDA,DIV VIROL,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S46 EP S46 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600102 ER PT J AU BROWNING, PJ SECHLER, JMG ENSOLI, B KAPLAN, M WASHINGTON, RH GENDELMAN, R YARCHOAN, R GALLO, RC AF BROWNING, PJ SECHLER, JMG ENSOLI, B KAPLAN, M WASHINGTON, RH GENDELMAN, R YARCHOAN, R GALLO, RC TI IDENTIFICATION AND CULTURE OF KS-LIKE SPINDLE CELLS FROM THE PERIPHERAL-BLOOD OF HIV-1-INFECTED INDIVIDUALS AND NORMAL CONTROLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,MED BRANCH,LTCB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. N SHORE UNIV HOSP,DEPT INTERNAL MED,DIV INFECT DIS & IMMUNOL,MANHASSET,NY 11030. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S51 EP S51 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600121 ER PT J AU COWAN, EP LEHKY, TJ ELLER, NL TSUCHIDA, T BIDDISON, WE LAMPSON, LA JACOBSON, S AF COWAN, EP LEHKY, TJ ELLER, NL TSUCHIDA, T BIDDISON, WE LAMPSON, LA JACOBSON, S TI HLA CLASS-II EXPRESSION ON NEUROBLASTOMAS INFECTED WITH HTLV-I SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 US FDA,CBER,DIV TRANSFUS TRANSMITTED DIS,ROCKVILLE,MD. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD. HARVARD UNIV,SCH MED,DEPT NEUROL,CAMBRIDGE,MA 02138. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S118 EP S118 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600356 ER PT J AU DIMITROV, D LITTMAN, D MANISCHEWITZ, J BLUMENTHAL, R GOLDING, H AF DIMITROV, D LITTMAN, D MANISCHEWITZ, J BLUMENTHAL, R GOLDING, H TI KINETICS OF CELL-FUSION, MEDIATED BY THE HIV-1 ENVELOPE GLYCOPROTEIN INTERACTION WITH A HYBRID CD4.CD8 MOLECULE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S72 EP S72 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600196 ER PT J AU GOLDING, H ZAITSEVA, M GOLDING, B AF GOLDING, H ZAITSEVA, M GOLDING, B TI DESIGN OF HIV-1 PEPTIDE-CARRIER VACCINE WHICH DIFFERENTIALLY ACTIVATES TH1 LYMPHOKINES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,RETROVIRUS RES LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S46 EP S46 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600100 ER PT J AU HEREDIA, A WEISS, SH JOSHI, B POFFENBERGER, KL LEE, S MULLER, J SORIANO, V EPSTEIN, JS HEWLETT, IK AF HEREDIA, A WEISS, SH JOSHI, B POFFENBERGER, KL LEE, S MULLER, J SORIANO, V EPSTEIN, JS HEWLETT, IK TI LACK OF EVIDENCE OF RETROVIRAL INFECTION IN 5 PATIENTS WITH IDIOPATHIC CD4+ T-LYMPHOCYTOPENIA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,BETHESDA,MD. US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD. UNIV MED & DENT NEW JERSEY,SCH MED,NEWARK,NJ 07103. INST SALUD CARLOS 3,MADRID,SPAIN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S80 EP S80 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600228 ER PT J AU HEWLETT, IK JOSHI, J EPSTEIN, JS AF HEWLETT, IK JOSHI, J EPSTEIN, JS TI A NOVEL, PCR BASED VIRAL CAPTURE ASSAY FOR THE DETECTION OF HIV-1 IN SERUM AND CULTURE FLUIDS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S67 EP S67 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600178 ER PT J AU JORDAN, EK FRANK, JA GRIMLEY, P SNOY, PJ HEYES, MP STONE, G POSSE, S LEBIHAN, D CUENOD, C TORNATORE, G AF JORDAN, EK FRANK, JA GRIMLEY, P SNOY, PJ HEYES, MP STONE, G POSSE, S LEBIHAN, D CUENOD, C TORNATORE, G TI NEUROLOGICAL AIDS IN THE RHESUS-MONKEY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NINCDS,AHCS,BETHESDA,MD. US FDA,DOQC,CBER,ROCKVILLE,MD. NIMH,LCS,BETHESDA,MD. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NIH,OD,LDR,BETHESDA,MD. NINCDS,LCNSS,BETHESDA,MD. NIH,BEIP,BETHESDA,MD. NIH,CC,DR,BETHESDA,MD. NINCDS,LVMP,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S80 EP S80 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600227 ER PT J AU JOSHI, B CHANG, P MAYERS, D LEE, S EPSTEIN, JS HEWLETT, IK AF JOSHI, B CHANG, P MAYERS, D LEE, S EPSTEIN, JS HEWLETT, IK TI INHIBITION OF METHYLATION IN HIV REPLICATION - POTENTIAL USE AS NOVEL ANTI-HIV DRUGS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 US FDA,CBER,DTTD,BETHESDA,MD. WALTER REED ARMY INST RES,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S24 EP S24 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600027 ER PT J AU LUNARDIISKANDAR, Y BRYANT, J LAM, VH ZEMAN, RA GESSAIN, A VARRICCHIO, F GALLO, RC AF LUNARDIISKANDAR, Y BRYANT, J LAM, VH ZEMAN, RA GESSAIN, A VARRICCHIO, F GALLO, RC TI A MODEL OF TROPICAL SPASTIC PARAPARESIS HTLV-I-ASSOCIATED MYELOPATHY (TSP/HAM) DISEASE IN IMMUNODEFICIENT MICE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NIDR,BETHESDA,MD 20892. INST PASTEUR,PARIS,FRANCE. US FDA,CBER,ROCKVILLE,MD. 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 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S120 EP S120 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600362 ER PT J AU NORCROSS, MA RODERIQUEZ, G YANAGISHITA, M BOUHABIB, D PATEL, M ORAVECZ, T AF NORCROSS, MA RODERIQUEZ, G YANAGISHITA, M BOUHABIB, D PATEL, M ORAVECZ, T TI CELL-SURFACE HEPARAN-SULFATE INTERACTS WITH THE V3 REGION ON GP120/41 OLIGOMERS TO MEDIATE HIV-1 BINDING AND INFECTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20014. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S75 EP S75 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600206 ER PT J AU POFFENBERGER, KL RIORDAN, G LEE, S EPSTEIN, J HEWLETT, I AF POFFENBERGER, KL RIORDAN, G LEE, S EPSTEIN, J HEWLETT, I TI TRIPLE-HELIX TARGETED OLIGONUCLEOTIDES SUPPRESS HIV-1 INFECTION IN-VITRO SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,MOLEC VIROL LAB,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S31 EP S31 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600052 ER PT J AU SAVILLE, MW TOSATO, G TAGA, K FOLI, A BRODER, S YARCHOAN, R AF SAVILLE, MW TOSATO, G TAGA, K FOLI, A BRODER, S YARCHOAN, R TI INHIBITION OF HIV REPLICATION IN MONOCYTE/MACROPHAGES (M/M) BY INTERLEUKIN-10 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,OFF DIRECTOR,BETHESDA,MD 20892. US FDA,CBER,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S27 EP S27 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600038 ER PT J AU WEISS, SH CLARICI, M MAYUR, RK DENNY, TN QUIRINALE, JE HEWLETT, IK EPSTEIN, J PALUMBO, PE BERZOFSKY, JA SHEARER, GM AF WEISS, SH CLARICI, M MAYUR, RK DENNY, TN QUIRINALE, JE HEWLETT, IK EPSTEIN, J PALUMBO, PE BERZOFSKY, JA SHEARER, GM TI IMMUNOLOGICAL AND VIROLOGICAL RESPONSES TO HIV EXPOSURE AMONG A HIGH-RISK BUT LONG-TERM HIV ANTIBODY NEGATIVE COHORT OF DRUG-USERS, AND INTERACTIONS WITH HTLV-II SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,NEWARK,NJ 07103. US FDA,BETHESDA,MD 20014. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S106 EP S106 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600314 ER PT J AU HSU, HH WRIGHT, TL TSAO, SC COMBS, C DONETS, M FEINSTONE, SM GREENBERG, HB AF HSU, HH WRIGHT, TL TSAO, SC COMBS, C DONETS, M FEINSTONE, SM GREENBERG, HB TI ANTIBODY-RESPONSE TO HEPATITIS-C VIRUS-INFECTION AFTER LIVER-TRANSPLANTATION SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID NON-B HEPATITIS; POLYMERASE CHAIN-REACTION; EPSTEIN-BARR-VIRUS; NON-A; ORGAN DONORS; RECIPIENTS; CYTOMEGALOVIRUS; PREVALENCE; DIAGNOSIS; SYSTEMS AB Objective: To determine whether liver transplantation and the subsequent immunosuppression affect the antibody response to hepatitis C virus (HCV) infection. Methods: Sera from 46 patients were compared before and after liver transplantation for markers of HCV infection. Serum HCV RNA was determined by polymerase chain reaction (PCR). Anti-HCV antibody was determined by first- and second-generation immunoassays as well as a quantitative assay of the titer of anti-HCV core antibody. Results: Among individuals who acquired hepatitis C infection in association with liver transplantation, only 15% (3/12) developed antibody to the core antigen and only 25% (3/12) reacted to any antigen present on the second-generation recombinant immunoblot assay after a mean follow-up period of 18 months. Thirty-eight percent (5/13) were positive, by the second-generation enzyme immunoassay (EIA-2). Whereas 94% (16/17) of the individuals who had detectable anti-HCV core antibodies pretransplant continued to have such antibodies after transplant, the titer of these antibodies declined an average of 4-fold. No significant change was seen in the antibody titer toward rotavirus, a common viral pathogen. Patients who acquired HCV infection or in whom the allograft became reinfected had a significantly increased incidence of posttransplant hepatitis (61% vs. 33%, respectively). Conclusions: Liver transplantation and posttransplant immunosuppression lead to an attenuated antibody response to hepatitis C viral infection. Currently available assays for anti-HCV antibodies may be unreliable in the posttransplant setting. C1 STANFORD UNIV,MED CTR,DEPT MED,STANFORD,CA 94305. VET ADM MED CTR,DEPT MED,SAN FRANCISCO,CA 94121. US FDA,DIV VIROL,BETHESDA,MD 20014. RP HSU, HH (reprint author), VET ADM MED CTR,DEPT MED,3801 MIRANDA AVE,PALO ALTO,CA 94304, USA. NR 21 TC 23 Z9 23 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD AUG PY 1994 VL 89 IS 8 BP 1169 EP 1174 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PB410 UT WOS:A1994PB41000009 PM 7519818 ER PT J AU NEWMAN, NJ TORRONI, A BROWN, MD LOTT, MT FERNANDEZ, MM WALLACE, DC AF NEWMAN, NJ TORRONI, A BROWN, MD LOTT, MT FERNANDEZ, MM WALLACE, DC TI EPIDEMIC NEUROPATHY IN CUBA NOT ASSOCIATED WITH MITOCHONDRIAL-DNA MUTATIONS FOUND IN LEBERS HEREDITARY OPTIC NEUROPATHY PATIENTS SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID TOBACCO-ALCOHOL AMBLYOPIA; CLINICAL MANIFESTATIONS; COMPLEX-I; CYANIDE; AFFINITIES; DEFICIENCY; PEDIGREES; DISEASES; SEQUENCE; ATROPHY AB An epidemic neuropathy in Cuba has caused bilateral optic neuropathies in more than 26,000 people during the past three years. Various pathogenetic factors have been proposed, including toxins, nutritional deficiencies, and an underlying genetic predisposition involving mitochondrial DNA. As part of a case-control collaborative investigation, 135 Cuban blood samples were analyzed for the most common mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy. None of the participants tested were found to have the mitochondrial DNA mutations at nucleotide positions 11778, 3460, 14484, 7444, or 9804. Of 57 definite case subjects and 69 normal control subjects, three case and three control subjects had the mutation at nucleotide position 9438, three different case and three different control subjects had the mutation at position 13708, and one case and one control subject had the mutation at position 15257 in association with the mutation at position 13708. The most common mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy do not appear to be contributing factors in the epidemic neuropathy in Cuba. We also identified a large Cuban family with maternally related members who experienced visual loss consistent with the diagnosis of Leber's hereditary optic neuropathy. Maternal family members harbored the highly pathogenetic mutation at nucleotide position 11778. C1 EMORY UNIV,SCH MED,DEPT OPHTHALMOL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT NEUROL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT NEUROSURG,ATLANTA,GA. HOSP AMEIJEIRAS,HAVANA,CUBA. CUBAN MINIST PUBL HLTH,HAVANA,CUBA. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. PAN AMER HLTH ORG,WASHINGTON,DC. PAN AMER HLTH ORG,HAVANA,CUBA. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. RP NEWMAN, NJ (reprint author), EMORY UNIV,SCH MED,DEPT GENET & MOLEC MED,1462 CLIFTON RD NE,ROOM 403,ATLANTA,GA 30322, USA. RI Torroni, Antonio/E-1557-2011 OI Torroni, Antonio/0000-0002-4163-4478 FU NEI NIH HHS [P30 EY06360]; NINDS NIH HHS [NS21468, NS30164] NR 54 TC 44 Z9 46 U1 1 U2 1 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 AUG PY 1994 VL 118 IS 2 BP 158 EP 168 PG 11 WC Ophthalmology SC Ophthalmology GA PA910 UT WOS:A1994PA91000003 PM 8053461 ER PT J AU SHEPPARD, BS HEITKEMPER, DT GASTON, CM AF SHEPPARD, BS HEITKEMPER, DT GASTON, CM TI MICROWAVE DIGESTION FOR THE DETERMINATION OF ARSENIC, CADMIUM AND LEAD IN SEAFOOD PRODUCTS BY INDUCTIVELY-COUPLED PLASMA-ATOMIC EMISSION AND MASS-SPECTROMETRY SO ANALYST LA English DT Article DE MICROWAVE DIGESTION; FISH; SHELLFISH; INDUCTIVELY COUPLED PLASMA ATOMIC EMISSION AND MASS SPECTROMETRY ID TRACE-ELEMENT ANALYSIS; FOODS AB A single microwave digestion procedure was developed for use with a variety of seafood products. Inductively coupled plasma atomic emission and mass spectrometry were used to determine the levels of As, Cd and Pb in samples of tuna, salmon, shrimp, walleye, clams, oysters and lobster. The precision for ten replicate analyses of clams was 2.1% for As at the 10.0 mu g g(-1) level, 5.6% for Pb at the 0.067 mu g g(-1) level and 2.5% for Cd at the 0.079 mu g g(-1) level. Acceptable spike recoveries in each of the sample types were achieved using both detection methods. Results for two standard reference materials were in good agreement with certified values RP SHEPPARD, BS (reprint author), US FDA,NATL FORENS CHEM CTR,1141 CENT PKWY,CINCINNATI,OH 45202, USA. NR 17 TC 44 Z9 48 U1 0 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0003-2654 J9 ANALYST JI Analyst PD AUG PY 1994 VL 119 IS 8 BP 1683 EP 1686 DI 10.1039/an9941901683 PG 4 WC Chemistry, Analytical SC Chemistry GA PE574 UT WOS:A1994PE57400006 ER PT J AU KAYSNER, CA ABEYTA, C TROST, PA WETHERINGTON, JH JINNEMAN, KC HILL, WE WEKELL, MM AF KAYSNER, CA ABEYTA, C TROST, PA WETHERINGTON, JH JINNEMAN, KC HILL, WE WEKELL, MM TI UREA HYDROLYSIS CAN PREDICT THE POTENTIAL PATHOGENICITY OF VIBRIO-PARAHAEMOLYTICUS STRAINS ISOLATED IN THE PACIFIC-NORTHWEST SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Note ID GASTROENTERITIS; WASHINGTON AB The ability of some strains of Vibrio parahaemolyticus to hydrolyze urea (uh(+)) can be used as a marker to predict which strains isolated from molluscan shellfish harvested in the Pacific Northwest are potentially pathogenic. The thermostable direct hemolysin-producing (TDH+) characteristic is a marker that is correlated with potential pathogenicity, and all of the TDH+ strains that we have isolated have been found to be uh(+) Most of the uh(+) strains belong to somatic antigen groups 03, 04, and 05. TDH+ strains are usually members of groups 04 and 05. The strains most often associated with human illness are members of the uh(+), 04 group. The test for urease production is a simple screening test that can be helpful in predicting which strains are potentially pathogenic. RP KAYSNER, CA (reprint author), US FDA,SEAFOOD PROD RES CTR,POB 3012,BOTHELL,WA 98041, USA. NR 11 TC 30 Z9 32 U1 2 U2 3 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 AUG PY 1994 VL 60 IS 8 BP 3020 EP 3022 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA NZ703 UT WOS:A1994NZ70300052 PM 8085837 ER PT J AU WIDMALM, G VENABLE, RM AF WIDMALM, G VENABLE, RM TI MOLECULAR-DYNAMICS SIMULATION AND NMR-STUDY OF A BLOOD GROUP-H TRISACCHARIDE SO BIOPOLYMERS LA English DT Article ID OVERHAUSER EFFECT SPECTROSCOPY; CONFORMATIONAL-ANALYSIS; GROUP DETERMINANTS; D-GALACTOSE; OLIGOSACCHARIDES; RELAXATION; DIFUCOSYLLACTOSES; MONOSYLLACTOSES; DISTANCES; MOBILITY AB Molecular dynamics simulations in vacuum and solution have been carried out on 2'-alpha-L-fucosyllactitol, a model for blood group H in conjunction with two-dimensional nmr measurements on the same compound. Three independent starting conformations for the dynamics were chosen from low energy conformations obtained by a phi/psi grid search. Nine 5 ns vacuum simulations of the trisaccharide were performed, employing three different ways to treat electrostatic interactions for each starting conformation: distance-dependent dielectric with epsilon = r, constant dielectric with epsilon = 1, or constant dielectric with epsilon = 80. In vacuum, transitions of phi and psi for the alpha-L-Fuc-(1 --> 2)-beta-D-Gal element occur in a cooperative manner. The virtual distance obtained for H1 in fucose to H2 in galactose from nuclear Overhauser effect spectroscopy experiments agree with one of the conformations of the trisaccharide in one of the three 100 ps aqueous simulations (phi/psi ca. -100 degrees /150 degrees), indicating this may be a dominant solution conformation. The rms fluctuations of the phi- and psi-dihedral angles were similar to 10 degrees for a conformational state, both in the vacuum and the aqueous simulations. For the simulations in vacuum, the agreement with experimental NOE data is reasonable when a constant dielectric of 1 is used (major conformers having phi/psi ca. -100 degrees/150 degrees and -140 degrees/100 degrees), whereas the agreement was poor with a constant dielectric of 80. Translational diffusion coefficients calculated from the simulation of the oligosaccharides were 0.12-0.18 X 10(-5) cm(2)/s and from nmr measurements 0.27 X 10(-5) cm(2)/s. (C) John Wiley & Sons, Inc. C1 US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,BETHESDA,MD 20892. RP WIDMALM, G (reprint author), UNIV STOCKHOLM,DEPT ORGAN CHEM,ARRHENIUS LAB,STOCKHOLM,SWEDEN. NR 36 TC 19 Z9 19 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD AUG PY 1994 VL 34 IS 8 BP 1079 EP 1088 DI 10.1002/bip.360340811 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NY408 UT WOS:A1994NY40800010 PM 8075388 ER PT J AU EBERT, M YOKOYAMA, M KOBRIN, MS FRIESS, H LOPEZ, ME BUCHLER, MW JOHNSON, GR KORC, M AF EBERT, M YOKOYAMA, M KOBRIN, MS FRIESS, H LOPEZ, ME BUCHLER, MW JOHNSON, GR KORC, M TI INDUCTION AND EXPRESSION OF AMPHIREGULIN IN HUMAN PANCREATIC-CANCER SO CANCER RESEARCH LA English DT Note ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR; DIFFERENTIAL EXPRESSION; ENHANCED EXPRESSION; FACTOR-ALPHA; CELL-LINE; CARCINOMA; OVEREXPRESSION; TUMORS AB The epidermal growth factor receptor is activated by a family of polypeptides that includes the growth factor amphiregulin (AR). Using Northern blot analysis and the polymerase chain reaction, we now report that AR mRNA is expressed in human pancreatic cancer cell lines, and that this expression is enhanced in several of these cell lines by tetradecanoyl phorbol acetate and transforming growth factor alpha. AR was also expressed in normal and malignant pancreatic tissues. However, in the normal pancreas, AR immunostaining was most evident in the nuclei of ductal cells. In contrast, in many carcinomas, AR was also present in the cytoplasm of the ductal-like cancer cells. Cytoplasmic localization of AR was associated with a more advanced clinical stage. These findings suggest that AR may contribute to aberrant activation of the epidermal growth factor receptor in human pancreatic cancer, and may enhance disease progression. C1 UNIV CALIF IRVINE,DEPT MED,DIV ENDOCRINOL & 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. FU NCI NIH HHS [CA-40162] NR 24 TC 141 Z9 142 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 AUG 1 PY 1994 VL 54 IS 15 BP 3959 EP 3962 PG 4 WC Oncology SC Oncology GA NZ246 UT WOS:A1994NZ24600002 PM 8033121 ER PT J AU HARRIS, JW RAHMAN, A KIM, BR GUENGERICH, FP COLLINS, JM AF HARRIS, JW RAHMAN, A KIM, BR GUENGERICH, FP COLLINS, JM TI METABOLISM OF TAXOL BY HUMAN HEPATIC MICROSOMES AND LIVER SLICES - PARTICIPATION OF CYTOCHROME-P450 3A4 AND AN UNKNOWN P450 ENZYME SO CANCER RESEARCH LA English DT Article ID OXIDATIVE DRUG-METABOLISM; GENETIC-POLYMORPHISM; CATALYTIC ACTIVITY; ESCHERICHIA-COLI; GRAPEFRUIT JUICE; OVARIAN-CANCER; EXPRESSION; PURIFICATION; RAT; MECHANISM AB Incubation of taxol with human hepatic microsomal fractions or freshly isolated human liver slices yields three metabolite high performance liquid chromatography peaks, metabolite A, metabolite B, and 6 alpha-hydroxytaxol. These metabolites are formed in patients given taxol, with 6 alpha-hydroxytaxol formation representing the principal biotransformation pathway. Metabolite B and 6 alpha-hydroxytaxol are shown to be products of different, highly regioselective cytochrome P-450 (P450) enzymes, while metabolite A results from stepwise metabolism by each of these enzymes. Correlation of metabolite B formation with P450 3A markers was good (r(2) = 0.91-0.94), but the correlation of 6 alpha-hydroxytaxol formation with markers for several P450 enzymes was poor. Chemical inhibitors that selectively inhibited metabolite B formation (troleandomycin, cyclosporine), that selectively inhibited 6 alpha-hydroxytaxol formation (naringenin, quercetin), or that nonselectively inhibited both pathways (felodipine, ketoconazole) were found. Metabolite B formation was selectively reduced by anti-P450 3A4 antibodies. Expressed human P450 3A4 preparations were efficient catalysts of metabolite B formation; no expressed P450 preparation tested showed a capacity for catalyzing taxane 6 alpha-hydroxylation reactions. The combined results of several experimental approaches show that p450 3A4 is the major catalyst of metabolite B formation and that the identity of the P450 enzyme or enzymes responsible for 6 alpha-hydroxytaxol formation cannot be assigned with certainty. C1 US FDA,CTR DRUG EVALUAT & RES,DIV CLIN PHARMACOL,ROCKVILLE,MD 20857. VANDERBILT UNIV,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. FU NCI NIH HHS [CA44353]; NIEHS NIH HHS [ES00267] NR 43 TC 256 Z9 262 U1 2 U2 4 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 AUG 1 PY 1994 VL 54 IS 15 BP 4026 EP 4035 PG 10 WC Oncology SC Oncology GA NZ246 UT WOS:A1994NZ24600017 PM 7913410 ER PT J AU PLUZNIK, DH LEE, NS SAWADA, T AF PLUZNIK, DH LEE, NS SAWADA, T TI TAXOL INDUCES THE HEMATOPOIETIC GROWTH-FACTOR GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN MURINE B-CELLS BY STABILIZATION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR NUCLEAR-RNA SO CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; BACTERIAL LIPOPOLYSACCHARIDE; ANTINEOPLASTIC AGENT; MESSENGER-RNA; PHASE-I; ESTABLISHMENT; INTERLEUKIN-4; MICROTUBULES; RECEPTORS; MOUSE AB Taxol, a microtubule-stabilizing agent, has been shown to have antineoplastic activity against various tumors. In addition, it has been shown that taxol resembles bacterial lipopolysaccharide in its ability to activate macrophages. Recently we have shown that lipopolysaccharide induces the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) in murine B-cell lines. In light of the similarity of taxol and lipopolysaccharide in their effects on macrophages, we tested whether taxol could also induce the expression of GM-CSF in B-cell lines. In the present study we used the murine B-lymphoma cell line M12.4.1. In unstimulated cells, no GM-CSF mRNA was detected, whereas in taxol-stimulated cells at a concentration of 30 mu M, GM-CSF mRNA was induced 4-8 h after stimulation. This induction of GM-CSF mRNA was down-regulated by 10 ng/ml of interleukin 4. Actinomycin D chase experiments revealed that interleukin 4 did not affect the half-life of the taxol-induced GM-CSF cytoplasmic mRNA, nor did it alter GM-CSF gene transcription. Polymerase chain reaction analysis of nuclear RNA, utilizing probes specific for sequences in the first intron of GM-CSF, indicated that taxol enhances accumulation of nuclear precursor RNA and that interleukin 4 decreases this accumulation. The present study shows a novel activity of taxol in inducing the release of the hematopoietic growth factor GM-CSF from B-cells. Since GM-CSF is known to recruit macrophages and enhance their cytotoxicity against tumor cells, our observations suggest that part of the known antitumor activity of taxol may be due to synergistic effects of GM-CSF activity together with direct cytotoxic actions through microtubule stabilization. RP PLUZNIK, DH (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,HFM-547,BLDG 29A,ROOM 3B-19,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 33 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 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1994 VL 54 IS 15 BP 4150 EP 4154 PG 5 WC Oncology SC Oncology GA NZ246 UT WOS:A1994NZ24600035 PM 7913412 ER PT J AU KADERLIK, KR MULDER, GJ TURESKY, RJ LANG, NP TEITEL, CH CHIARELLI, MP KADLUBAR, FF AF KADERLIK, KR MULDER, GJ TURESKY, RJ LANG, NP TEITEL, CH CHIARELLI, MP KADLUBAR, FF TI GLUCURONIDATION OF N-HYDROXY HETEROCYCLIC AMINES BY HUMAN AND RAT-LIVER MICROSOMES SO CARCINOGENESIS LA English DT Article ID FOOD-BORNE CARCINOGEN; METABOLIC-ACTIVATION; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; AROMATIC-AMINES; COOKED FOOD; PYROLYSIS PRODUCTS; DNA ADDUCTS; IDENTIFICATION; ACETYLATION; 2-AMINO-3,8-DIMETHYLIMIDAZO<4,5-F>QUINOXALINE AB The food-borne carcinogenic and mutagenic heterocyclic aromatic amines undergo bioactivation to the corresponding N-hydroxy (OH)-arylamines and the subsequent N-glucuronidation of these metabolites is regarded as an important detoxification reaction. In this study, the rates of glucuronidation for the N-OH derivatives of 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhlP), 2-amino-6-methyl-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino-3,8-dimethylimidazo[4,5-f-]quinoxaline (MeIQx) by liver microsomal glucuronosyltransferase were compared to that of the proximate human urinary bladder carcinogen, N-OH-aminobiphenyl (N-OH-ABP) and the proximate rat colon carcinogen N-OH-3,2'-dimethyl-4-amino-biphenyl (N-OH-DMABP). Human liver microsomes catalyzed the uridine 5'-diphosphoglucuronic acid (UDPGA)-dependent glucuronidation of N-OH-IQ, N-OH-PhIP, N-OH-Glu-P-1 and N-OH-MeIQx at rates of 59%, 42%, 35% and 27%, respectively, of that measured for N-OH-ABP (11.5 nmol/ min/mg). Rat liver microsomes also catalyzed the UDPGA-dependent glucuronidation of N-OH-PhIP, N-OH-Glu-P-1 and N-OH-IQ at rates of 30%, 20% and 10%, respectively of that measured for N-OH-DMABP (11.2 nmol/min/mg); activity towards N-OH-MEIQx was not detected. Two glucuronide(s) of N-OH-PhIP, designated I and II, were separated by HPLC. Conjugate II was found to be chromatographically and spectrally identical with a previously reported major biliary metabolite of PhIP in the rat, while conjugate I was identical with a major urinary metabolite of PhIP in the dog. Hepatic microsomes from rat, dog and human were found to catalyze the formation of both conjugates. The rat preferentially formed conjugate II (I to LT ratio of 1:15), while the dog and human formed higher relative amounts of conjugate I (I to II ratio of 2.5:1.0 and 1.3:1.0 respectively). Fast atom bombardment mass spectrometry of conjugates I and II gave the corresponding molecular ions and showed nearly identical primary spectra. However, collision-induced spectra were distinct and were consistent with the identity of conjugates I and II as structural isomers. Moreover, the UV spectrum of conjugate I exhibited a lambda(max) at 317 mn and was essentially identical to that of N-OH-PhIP, while conjugate II was markedly different with a lambda(max) of 331 nm. Both conjugates were stable in 0.1 N HCl and were resistant to hydrolysis by rat, dog and human liver microsomal beta-glucuronidases. In contrast, conjugate H, but not conjugate I, was readily cleaved by Esherichia coli beta-glucuronidase to yield N-OH-PhIP, On comparison of these properties with those of the known N-2-and N3-glucuronides of PhIP, conjugates I and II were judged to be N-OH-PhIP N-2-glucuronide and N-OH-PhIP N3-glucuronide, respectively. These results indicate that both human and rat liver microsomes catalyze the glucuronidation of several N-OH heterocyclic amines and, in the case of N-OH-PhIP, two microsomal N-glucuronide metabolites were formed with distinct chemical acid enzymatic properties. C1 NESTEC LTD,NESTLE RES CTR,CH-1000 LAUSANNE 26,SWITZERLAND. JOHN A MCCLELLAN MEM VET ADM HOSP,LITTLE ROCK,AR 72205. LEIDEN UNIV,SYLVIUS LABS,CTR BIOPHARMACEUT SCI,DIV TOXICOL,2300 RA LEIDEN,NETHERLANDS. RP KADERLIK, KR (reprint author), NATL CTR TOXICOL RES,HFT 100,JEFFERSON,AR 72079, USA. NR 45 TC 76 Z9 77 U1 1 U2 2 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 AUG PY 1994 VL 15 IS 8 BP 1695 EP 1701 DI 10.1093/carcin/15.8.1695 PG 7 WC Oncology SC Oncology GA PC325 UT WOS:A1994PC32500035 PM 8055651 ER PT J AU KADERLIK, KR MINCHIN, RF MULDER, GJ ILETT, KF DAUGAARDJENSON, M TEITEL, CH KADLUBAR, FF AF KADERLIK, KR MINCHIN, RF MULDER, GJ ILETT, KF DAUGAARDJENSON, M TEITEL, CH KADLUBAR, FF TI METABOLIC-ACTIVATION PATHWAY FOR THE FORMATION OF DNA-ADDUCTS OF THE CARCINOGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE (PHIP) IN RAT EXTRAHEPATIC TISSUES SO CARCINOGENESIS LA English DT Article ID FOOD MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; HETEROCYCLIC AROMATIC-AMINES; CHEMICAL CARCINOGENESIS; LIVER-MICROSOMES; IDENTIFICATION; ACETYLATION; SULFATION; COLON; 2'-DEOXYGUANOSINE; GLUCURONIDATION AB The food-borne mutagen 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) induces tumors in colon of male rats and has been implicated in the etiology of human cancers, particularly colorectal cancer. This study was conducted to examine: (1) the biliary and/or circulatory transport of N-hydroxy-PhIP and its N-glucuronides, N-sulfonyloxy-PhIP and N-acetoxy-PhIP; (2) their role as proximate and ultimate carcinogenic metabolites of PhIP; (3) the potential role of glutathione in modulating PhIP-DNA adduct formation. PhIP-DNA adducts, measured by the P-32-postlabeling method, were highest in the pancreas (361 adducts/10(8) nucleotides or 100%), followed by colon (56%), lung (28%), heart (27%) and liver (2%), at 24 h after a single oral dose of PhIP (220 mu mol/kg) to male rats. In each tissue examined, we observed two major adducts, each of which accounted for 35-45% of the total, and one minor adduct, which represented about 10-20% of the total. One of the major adducts was identified as N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine by chromatographic comparisons with an authentic standard. The major urinary metabolites of PhIP in these rats were 4'-hydroxy-PhIP and its glucuronide and sulfate conjugates, followed by N-hydroxy-PhIP N3-glucuronide, N-hydroxy-PhIP N-2-glucuronide and unchanged PhIP. In bile duct-ligated rats, the urinary excretion of the N-OH-PhIP N3-glucuronide was increased two-fold, but there was no effect on PhIP-DNA adduct formation in the colon, heart, lung, pancreas or liver. 2,6-Dichloro-4-nitrophenol, which strongly inhibits arylsulfotransferase-mediated DNA binding in vivo, had no effect on PhIP-DNA adduct levels in liver or in extrahepatic tissues. Pretreatment of rats with buthionine sulfoximine, which results in hepatic glutathione depletion, caused a five-fold increase in adduct formation in the liver. Intravenous administration (10 mu mol/kg) of N-hydroxy-PhIP and N-acetoxy-PhIP each led to high levels of PhIP-DNA adducts in each of the extrahepatic tissues examined. Adduct levels ranged from two- to six-fold higher (for N-hydroxy-PhIP and four- to 28-fold higher (for N-acetoxy-PhIP) as compared to that after an i.v. dose of the parent compound, indicating that these two bioactivated derivatives of PhIP are sufficiently stable to be transported through the circulation to extrahepatic tissues. Analyses of whole blood obtained at 2-8 h after oral administration of [H-3]PNP failed to detect N-hydroxy-PhIP (<0.1% of the radioactivity), however, a decomposition product of N-acetoxy-PhIP was found to account for about 80% of the total radioactivity in the blood. These results suggest that transport of N-acetoxy-PhIP, and perhaps N-hydroxy-PhIP, via the bloodstream and not biliary transport and deconjugation of N-hydroxy-PhIP N-glucuronides is primarily responsible for PhIP-DNA adduct formation in rat colon and other extrahepatic tissues. C1 UNIV WESTERN AUSTRALIA,QUEEN ELIZABETH II MED CTR,DEPT PHARMACOL,NEDLANDS,WA 6009,AUSTRALIA. LEIDEN UNIV,SYLVIUS LABS,CTR BIOPHARMACEUT SCI,DIV TOXICOL,2300 PA LEIDEN,NETHERLANDS. RP KADERLIK, KR (reprint author), NATL CTR TOXICOL RES,HFT 100,JEFFERSON,AR 72079, USA. NR 41 TC 141 Z9 142 U1 1 U2 4 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 AUG PY 1994 VL 15 IS 8 BP 1703 EP 1709 DI 10.1093/carcin/15.8.1703 PG 7 WC Oncology SC Oncology GA PC325 UT WOS:A1994PC32500036 PM 8055652 ER PT J AU KADERLIK, KR MULDER, GJ SHADDOCK, JG CASCIANO, DA TEITEL, CH KADLUBAR, FF AF KADERLIK, KR MULDER, GJ SHADDOCK, JG CASCIANO, DA TEITEL, CH KADLUBAR, FF TI EFFECT OF GLUTATHIONE DEPLETION AND INHIBITION OF GLUCURONIDATION AND SULFATION ON 2-AMINO-1-METHYL-6-PHENYLIMIDAZO [4,5-B]PYRIDINE (PHIP) METABOLISM, PHIP-DNA ADDUCT FORMATION AND UNSCHEDULED DNA-SYNTHESIS IN PRIMARY RAT HEPATOCYTES SO CARCINOGENESIS LA English DT Article ID FOOD MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; BORNE CARCINOGEN 2-AMINO-3,8-DIMETHYLIMIDAZO<4,5-F>QUINOXALINE; HETEROCYCLIC AROMATIC-AMINES; LIVER; ACTIVATION; IDENTIFICATION; BINDING; COLON; N-HYDROXY-2-ACETYLAMINOFLUORENE; ACETYLTRANSFERASE AB The potent rat colon carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), unlike other food-borne heterocyclic amines, does not induce tumors in rat liver. This correlates with an extremely low level of PhIP-DNA adducts formed in this tissue, and together these observations suggest that PhLP is efficiently detoxified in the liver. In order to identify possible detoxification mechanisms, we assessed the effect of inhibition of glucuronidation, glutathione (GSH) conjugation and sulfation on PhIP metabolism and PhTP-induced DNA damage in rat hepatocytes. Hepatocytes isolated from rats pretreated with Aroclor 1254 metabolized PhIP to the same products found in vivo. N-Hydroxy-PhIP N3-glucuronide and N-hydroxy-PhIP N-2-glucuronide were major and minor metabolites respectively. P-32-Postlabeling analysis of DNA from the PhIP-treated hepatocytes indicated the presence of two major adducts, one of which was identified as N-(deoxyguanosin-8-yl)-PhIP, and one minor adduct. There was no unscheduled DNA synthesis (UDS) in these cells. However, pretreatment of the hepatocytes with 1-bromoheptane and buthionine sulfoximine, which depletes GSH and prevents its resynthesis, resulted in a 15-fold increase in the formation of PhIP-DNA adducts, as well as ire a high level of UDS. GSH depletion had no effect on the formation of detectable PhIP metabolites. Hepatocyte pretreatment with D-galactosamine, which inhibits glucuronidation, increased the formation of DNA adducts two-fold and UDS was increased similarly. D-Galactosamine decreased the formation of the two N-glucuronides of N-hydroxy-PhIP by 50-60%, but had no effect on other metabolites. Pentachlorophenol, which strongly inhibits sulfotransferases, decreased adduct formation slightly, but had essentially no effect on UDS or on the formation of PhIP metabolites. These results indicate that metabolic conjugation pathways involving GSH and glucuronidation may play an important role in protecting rat liver against PhIP carcinogenesis. C1 LEIDEN UNIV,SYLVIUS LABS,CTR BIOPHARMACEUT SCI,DIV TOXICOL,2300 RA LEIDEN,NETHERLANDS. RP KADERLIK, KR (reprint author), NATL CTR TOXICOL RES,HFT 100,JEFFERSON,AR 72079, USA. NR 44 TC 58 Z9 58 U1 1 U2 3 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 AUG PY 1994 VL 15 IS 8 BP 1711 EP 1716 DI 10.1093/carcin/15.8.1711 PG 6 WC Oncology SC Oncology GA PC325 UT WOS:A1994PC32500037 PM 8055653 ER PT J AU THADANI, U LIPICKY, RJ AF THADANI, U LIPICKY, RJ TI SHORT AND LONG-ACTING ORAL NITRATES FOR STABLE ANGINA-PECTORIS SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Review DE STABLE ANGINA PECTORIS; ISOSORBIDE DINITRATE; EXERCISE; ISOSORBIDE-5-MONONITRATE; ORAL NITROGLYCERIN; BUCCAL NITROGLYCERIN; PENTAERYTHRITOL TETRANITRATE; COMBINATION TREATMENT ID DOSE-RESPONSE RELATION; CONGESTIVE-HEART-FAILURE; CONTROLLED-RELEASE ISOSORBIDE-5-MONONITRATE; ADMINISTERED ISOSORBIDE DINITRATE; CORONARY-ARTERY DISEASE; ORGANIC NITRATES; INTRAVENOUS NITROGLYCERIN; N-ACETYLCYSTEINE; ACUTE THERAPY; DOUBLE-BLIND AB Nitroglycerin (NTG) spray and sublingual tablets rapidly relieve an established attack of angina, and their infrequent use is not associated with the development of tolerance. Although, following a suitable nitrate-free interval, the first dose of oral, long-acting nitrates produces significant hemodynamic effects, increases angina free walking, and decreases exercise-induced ischemia, during continued longterm therapy tolerance limits their usefulness. Appropriate dosing regimens of controlled-release formulations of isosorbide dinitrate (ISDN) and controlled-release NTG during long-term therapy have not been established. Use of immediate-release formulation of 15-120 mg of ISDN in a old regimen lead to a marked reduction in the size and duration of antianginal effects compared to the initial dose. Asymmetric tid therapy with 30 mg of ISDN (7 a.m., 1 p.m, and 6 p.m.) is also associated with the development of partial tolerance and appears to provide antianginal prophylaxis for only a period of 6 hours each day. Asymmetric bid therapy with ISDN at 7 a.m. and noon mag give sustained effect but is supported by only a single, small study that did not examine effectiveness after the noon dose in long-term use. Isosorbide-5-mononitrate (IS-5-MN) has been the subject of more recent studies than other nitrates because of attempts to bring a number of products into the U.S. market. IS-5-MN in old, tid, and standard bid (8 a.m. and 8 p.m.) dosing regimens produce tolerance. Asymmetric regimens of immediate release IS-5-MN (10 and 20 mg) given bid (once in the morning and again 7 hours later) decrease the development of tolerance compared to symmetric regimens and produce an increased exercise duration after each dose of the day; the 20 mg bid dosing is more effective. Similarly, once-daily 120 and 240 mg controlled-release IS-5-MN does not produce tolerance and gives a sustained increase in daytime exercise duration. Both asymmetric bid immediate-release and once-daily controlled-release IS-5-MN preparations do not produce deterioration in exercise performance prior to the administration of the medication in the morning (i.e., no zero-hour effect). Further studies are needed to establish useful dosing regimens for ISDN, for controlled-release ISDN, and for controlled-release nitroglycerin. None of the dosing regimens of any oral, long-acting nitrate (including IS-5-MN) provide 24 hour antianginal and antiischemic effects. Although it is intuitively attractive to add an agent (beta-blocker or calcium channel blocker) that exerts 24 hour antianginal and antiischemic effects, which appear to depend on mechanisms different from those of nitrates, there are no studies that allow an evaluation of the usefulness of adding beta-blockers or calcium channel blockers to nitrate therapy (or vice versa). C1 UNIV OKLAHOMA,HLTH SCI CTR,DEPT MED,DIV CARDIOL,OKLAHOMA CITY,OK. US FDA,CTR DRUG RES & REV,OFF DRUG EVALUAT 1,DIV CARDIORENAL DRUG PROD,BETHESDA,MD 20014. NR 99 TC 34 Z9 34 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD AUG PY 1994 VL 8 IS 4 BP 611 EP 623 DI 10.1007/BF00877415 PG 13 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA PL410 UT WOS:A1994PL41000004 PM 7848896 ER PT J AU THADANI, U LIPICKY, RJ AF THADANI, U LIPICKY, RJ TI OINTMENTS AND TRANSDERMAL NITROGLYCERIN PATCHES FOR STABLE ANGINA-PECTORIS SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Article DE NITROGLYCERIN OINTMENT; NITROGLYCERIN PATCHES; ISOSORBIDE DINITRATE CREAM; ANGINA PECTORIS; TOLERANCE; CONTINUOUS VERSUS INTERMITTENT TREATMENT ID LONG ANTIANGINAL EFFECTIVENESS; ORAL ISOSORBIDE DINITRATE; ANTI-ISCHEMIC EFFICACY; GLYCERYL TRINITRATE; DOUBLE-BLIND; EXERCISE CAPACITY; DOSE-TITRATION; NITRODERM TTS; SUSTAINED THERAPY; NITRATE TOLERANCE AB Nitroglycerin (NTG) ointment is used for the prophylaxis against angina pectoris, but there are no data to support its effectiveness during long-term therapy. Continuous, once-daily application of isosorbide dinitrate cream produces tolerance with complete loss of efficacy within 1 week. Nitroglycerin patches are very popular and continuous once-daily application is still claimed by some investigators to provide 24 hour antiischemic and antianginal efficacy. This claim is based on data from postmarketing studies in a very large number of patients and placebo-controlled studies in smaller groups of patients from Italy, Yugoslavia, Greece, and Germany. In contrast, studies from the United States, Canada, England, and some centers in Germany have failed to show superiority of patches over placebo during continuous therapy. This controversy was addressed by the NTG cooperative study group, in which a total of 562 patients who were responders to sublingual nitroglycerin were studied. Patients received either placebo or NTG patches delivering low (15-30 mg/24 hr), moderate (45-60 mg/24 hr), or large (75 and 105 mg/24 hr) amounts of NTG. Four hours after the initial application, NTG patches increased exercise duration compared to placebo, but this beneficial effect had disappeared by 24 hours. Furthermore, after 8 weeks of continuous therapy, none of the NTG patches were superior to placebo, whether patients were or were not taking concomitant beta-blockers. Therefore, current opinion is that continous therapy with NTG patches produces pharmacologic tolerance acid is ineffective. Pharmacologic tolerance can be minimized when patches are applied every morning and removed after 10-12 hours at night. However, patches delivering > 15 mg NTG/24 hr are required to maintain an increased exercise duration for up to hour 8 after the patch application. Intermittent therapy with patches, however, may lead to rebound nocturnal angina in some patients. Also, intermittent therapy with patches has been associated with worsening of exercise performance in the morning prior to the patch renewal, compared to therapy with placebo patches. This has been referred to as the zero-hour effect and probably represents a rebound phenomenon following nitrate withdrawal. Patients experiencing either nocturnal or early morning angina during intermittent therapy with patches should either be switched to oral long-acting nitrates or should in addition be treated with a beta-blocker, provided there are no contraindications to beta-blocker treatment. C1 UNIV OKLAHOMA,HLTH SCI CTR,DEPT MED,DIV CARDIOL,OKLAHOMA CITY,OK. US FDA,CTR DRUG RES & REV,OFF DRUG EVALUAT 1,DIV CARDIORENAL DRUG PROD,BETHESDA,MD 20014. NR 86 TC 22 Z9 22 U1 1 U2 8 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD AUG PY 1994 VL 8 IS 4 BP 625 EP 633 DI 10.1007/BF00877416 PG 9 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA PL410 UT WOS:A1994PL41000005 PM 7848897 ER PT J AU ASZALOS, A PINE, PS WEAVER, JL RAO, PE AF ASZALOS, A PINE, PS WEAVER, JL RAO, PE TI CYTOCHALASIN-D MODULATES CD4 CROSS-LINKING SENSITIVE MITOGENIC SIGNAL IN T-LYMPHOCYTES SO CELLULAR IMMUNOLOGY LA English DT Article ID ANTIGEN RECEPTOR; ALPHA-INTERFERON; ENERGY-TRANSFER; CYCLOSPORINE-A; CELL RECEPTOR; ACTIVATION; CALCIUM; PROLIFERATION; ASSOCIATION; INDUCTION AB It has previously been shown that crosslinking of the CD4 molecule, either with anti-Leu3a mAb or with gp 120 (the HIV coat protein) plus anti-gp120 mAb, suppresses activation induced by wt31, a TcR/CD3-specific mAb. This suppression was associated with hindrance of the necessary association of the p56(lck) kinase bearing CD4 molecule with the TcR/CD3 complex. In this paper we demonstrate that this crosslinking-induced suppression can be bypassed by perturbing the microfilament system of CD4(+) cells by pretreatment with 1 mu M cytochalasin D. Using the fluorescence resonance energy transfer method, we have shown that the cytochalasin D-affected increase of mitogenesis is not due to changes in the TcR/CD3 to CD4 distance. Likewise, other membrane biophysical parameters, membrane potential and lateral diffusion of surface receptors, cannot be associated with these cytochalasin D-affected mitogenic changes. Cytochalasin D treatment elevates intracellular Ca2+ levels induced by wt31 mAb plus crosslinking and generates a TcR/CD3-dependent signal which is cyclosporin sensitive. (C) 1994 Academic Press, Inc. C1 IMMUNOL PHARMACEUT CORP,WALTHAM,MA 02154. RP ASZALOS, A (reprint author), US FDA,CTR DRUG EVALUAT & RES,200 C ST SW,WASHINGTON,DC 20204, USA. NR 36 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD AUG PY 1994 VL 157 IS 1 BP 81 EP 91 DI 10.1006/cimm.1994.1207 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA NZ093 UT WOS:A1994NZ09300008 PM 7913666 ER PT J AU BREUNINGER, L GOONEWARDENE, IM DEMPSEY, WL MURASKO, DM AF BREUNINGER, L GOONEWARDENE, IM DEMPSEY, WL MURASKO, DM TI MONOCYTE CULTURE AND ADHERENCE MODIFIES LPS-INDUCED IL-6 PRODUCTION AND INHIBITION BY HYDROCORTISONE SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; MOUSE PERITONEAL-MACROPHAGES; HUMAN-BLOOD MONOCYTES; LIPOPOLYSACCHARIDE LPS; HOMOTYPIC ADHESION; TNF-ALPHA; EXPRESSION; DIFFERENTIATION; INTERLEUKIN-1; INDUCTION AB The effect of hydrocortisone (HC) on IL-6 production by monocytes (Mo) that were cultured under either adherent or limited-adherent culture conditions was determined. Although freshly isolated Mo produced more IL-6 in response to LPS than Mo cultured 24 hr, culture had little effect on inhibition of IL-6 by HC. In contrast, the conditions of Mo culture had a significant impact on the kinetics of IL-6 production and inhibition by HC. Adherent Mo produced significantly higher levels of IL-6 4 hr after LPS compared to limited-adherent Mo. By 12 hr of LPS stimulation, comparable quantities of IL-6 were produced by both cultures. HC inhibition was complete 4 hr after LPS stimulation of adherent Mo, while 12 hr was required for maximum inhibition of limited-adherent Mo. Production of an IL-6 inhibitor was not responsible for the increased inhibition by HC with adherence, because both IL-6 protein and bioactivity were comparably decreased. The kinetics of inhibition of TNF alpha and IL-1 beta production by HC were similarly affected by adherence. Phenotypic analysis of cultured vs freshly isolated Mo showed a decrease in Mo expressing CD14, but not CD11b, which paralleled a decrease in IL-6 production by the cultured Mo. However, there were no phenotypic differences between adherent and limited-adherent Mo. The results demonstrate that the time of Mo culture, as well as adherence, may serve to alter LPS-induced IL-6 production and its inhibition by HC. (C) 1994 Academic Press, Inc. C1 US FDA,DIV ANTIVIRAL PROD,ROCKVILLE,MD 20852. RP BREUNINGER, L (reprint author), MED COLL PENN,DEPT MICROBIOL & IMMUNOL,3300 HENRY AVE,PHILADELPHIA,PA 19129, USA. FU NIA NIH HHS [AG03934]; NIMH NIH HHS [NIMH MH19129] NR 35 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD AUG PY 1994 VL 72 IS 2 BP 264 EP 272 DI 10.1006/clin.1994.1140 PG 9 WC Immunology; Pathology SC Immunology; Pathology GA PB324 UT WOS:A1994PB32400021 PM 8050200 ER PT J AU WU, TC AF WU, TC TI ON THE DEVELOPMENT OF ANTIFUNGAL AGENTS - PERSPECTIVE OF THE US FOOD-AND-DRUG-ADMINISTRATION SO CLINICAL INFECTIOUS DISEASES LA English DT Article AB As medical advances have prolonged the lives of patients with cancer, recipients of organ transplants, and patients with AIDS, there has been a marked increase in the number of fungal infections. Because of the known toxicity associated with amphotericin B, which has been the mainstay of therapy for systemic fungal infections, there has been a pressing need for regimens that are more effective and less toxic and that are more easily complied with by patients. This article provides a brief overview of the regulatory process of drug approval and discusses issues specific to the design of clinical trials for the treatment of systemic fungal diseases. RP WU, TC (reprint author), US FDA,DIV ANTIVIRAL DRUG PROD,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 4 TC 7 Z9 7 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1994 VL 19 SU 1 BP S54 EP S58 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PC397 UT WOS:A1994PC39700009 PM 7948572 ER PT J AU PASTOR, RW AF PASTOR, RW TI MOLECULAR-DYNAMICS AND MONTE-CARLO SIMULATIONS OF LIPID BILAYERS SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID SODIUM OCTANOATE MICELLE; STOCHASTIC BOUNDARY-CONDITIONS; COMPUTER-SIMULATION; PHOSPHOLIPID MONOLAYER; CRYSTAL-STRUCTURES; AQUEOUS-SOLUTION; CHAIN MOLECULES; LIQUID-CRYSTAL; WATER-SYSTEM; MODEL AB Molecular dynamics simulations of lipid bilayer/water systems have been reported by a number of groups, and are generally in good agreement with experimental results and with each other. The bilayer interior has been found closely to resemble an alkane melt although, because the chains are oriented, diffusion of benzene and water is more rapid in the center than near the surface. The waters at the interface are oriented for several layers, with the polarization profile monotonic and possibly a stretched exponential. Stochastic dynamics simulations have been extended to unsaturated lipids, and recently developed Monte Carlo methods have been used to sample a variety of lipid systems efficiently. RP PASTOR, RW (reprint author), US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 82 TC 152 Z9 154 U1 2 U2 17 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD AUG PY 1994 VL 4 IS 4 BP 486 EP 492 DI 10.1016/S0959-440X(94)90209-7 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QB256 UT WOS:A1994QB25600002 ER PT J AU PROAKIS, AC AF PROAKIS, AC TI REGULATORY CONSIDERATIONS ON THE ROLE OF GENERAL PHARMACOLOGY STUDIES IN THE DEVELOPMENT OF THERAPEUTIC AGENTS SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT Inaugural Conference on General Pharmacology/Safety Pharmacology CY OCT 05, 1993 CL FAIRFIELD, NJ DE INVESTIGATIONAL NEW DRUG APPLICATION (IND); NEW DRUG APPLICATION (NDA); NONCLINICAL PHARMACOLOGY AB In contrast to the well-defined regulatory requirements for the conduct of animal toxicology studies, FDA regulations and guidelines for nonclinical pharmacodynamic studies are relatively general and do not require that any specific studies be conducted. General pharmacology studies are conducted to identify actions of a new agent in addition to those associated with the primary therapeutic utility. General pharmacology studies aimed at determining drug effects on cardiovascular, central nervous system, gastrointestinal, respiratory and pulmonary, renal, endocrine and metabolism, autonomic nervous system, and drug-receptor functions were among the types of general pharmacology studies included in a sample of recent investigational new drug application (IND) and new drug application (NDA) submissions. Assessment of drug effects on cardiovascular, autonomic nervous system, and drug-receptor interactions were given the greatest individual importance in identifying drug effects relevant to the assessment of a product's safety at the initial IND stage. At the NDA stage, general pharmacology studies find their greatest value in predicting drug-drug interactions, defining mechanisms of action, characterizing the pharmacological correlates of drug-overdose, identifying dose-limiting effects for the chronic toxicity studies, and associating animal toxicity findings with known pharmacotoxic effects. General pharmacology studies provide valuable information to complement animal toxicity studies for evaluating a drug's potential risk to humans. (C) 1994 Wiley-Liss, Inc. RP PROAKIS, AC (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 1 TC 5 Z9 5 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD AUG PY 1994 VL 32 IS 4 BP 233 EP 236 DI 10.1002/ddr.430320407 PG 4 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PB459 UT WOS:A1994PB45900006 ER PT J AU KHAMBATY, FM BENNETT, RW SHAH, DB AF KHAMBATY, FM BENNETT, RW SHAH, DB TI APPLICATION OF PULSED-FIELD GEL-ELECTROPHORESIS TO THE EPIDEMIOLOGIC CHARACTERIZATION OF STAPHYLOCOCCUS-INTERMEDIUS IMPLICATED IN A FOOD-RELATED OUTBREAK SO EPIDEMIOLOGY AND INFECTION LA English DT Article ID STAPHYLOCOCCUS-INTERMEDIUS; INFECTIONS; STRAINS AB Bn outbreak of food intoxication involving over 265 cases in western United States occurred in October 1991. Staphylococcus intermedius was implicated as the aetiologic agent. Representative outbreak isolates (five clinical and ten from foods) produced type A enterotoxin. DNA fragments generated by four restriction endonucleases and analysed by pulsed-field gel electrophoresis (PFGE) provided definitive evidence that all isolates from nine different counties in California and Nevada were derived from a single strain. The PFGE pattern of these outbreak isolates was distinct from those of a heterogeneous collection of seven S. intermedius strains of veterinary origin and five unrelated S. aureus laboratory strains. The data show a significant PFGE pattern heterogeneity not only among members of different Staphylococcus species but also within members of the same species and even the same enterotoxin type. The results indicate that PFGE is a valuable strain-specific discriminator for the epidemiological characterization of S. intermedius. To our knowledge, this represents the first documented foodborne outbreak caused by S. intermedius. These findings suggest that the presence of S. intermedius and other species such as S. hyicus in food should be reason for concern. C1 US FDA,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204. NR 17 TC 68 Z9 73 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD AUG PY 1994 VL 113 IS 1 BP 75 EP 81 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA PE014 UT WOS:A1994PE01400009 PM 8062882 ER PT J AU PLUZNIK, DH LEE, NS SAWADA, T DOUGHERTY, SF AF PLUZNIK, DH LEE, NS SAWADA, T DOUGHERTY, SF TI MICROTUBLE STABILIZATION BY TAXOL INDUCES GM-CSF EXPRESSION IN MURINE B-CELL AND MACROPHAGE LINES SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL ONCOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD 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 1994 VL 22 IS 8 BP 686 EP 686 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800033 ER PT J AU FREASLUTZ, DL CORRELL, PH DOUGHERTY, SF XU, LC PLUZNIK, DH KARLSSON, S AF FREASLUTZ, DL CORRELL, PH DOUGHERTY, SF XU, LC PLUZNIK, DH KARLSSON, S TI EXPRESSION OF HUMAN GLUCOCEREBROSIDASE IN MURINE MACROPHAGES - IDENTIFICATION OF EFFICIENT RETROVIRAL VECTORS SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE GENE TRANSFER; MACROPHAGES; M1 CELLS; GLUCOCEREBROSIDASE ID HEMATOPOIETIC STEM-CELLS; MYELOID-LEUKEMIA CELLS; MEDIATED GENE-TRANSFER; BONE-MARROW TRANSPLANTATION; TERM RECONSTITUTED MICE; MOLECULAR-CLONING; GAUCHER DISEASE; DIFFERENTIATION; INTERLEUKIN-6; THERAPY AB Gaucher's disease is an autosomal recessive disorder characterized by a functional deficiency in beta-glucocerebrosidase enzymatic activity and the resultant accumulation of the glycolipid glucocerebroside in macrophages. Due to the nature of the affected cells, Gaucher's disease is an excellent candidate for gene therapy of hematopoietic stem cells and autologous bone marrow transplantation of transduced cells using retroviral vectors containing the glucocerebrosidase (GC) gene. In order to identify a retroviral vector capable of high levels of expression of the GC gene in macrophages, we have used the murine myeloid leukemia cell line, M1, a cell line that can be differentiated with interleukin-6 (IL-6) from blasts to macrophages. Two vectors use the Moloney murine leukemia virus (MoMLV) enhancer/promoter (LG vector) or the myeloproliferative sarcoma virus (MPSV) enhancer/MoMLV promoter (MG vector), both located in the viral long-terminal repeat (LTR); the third vector uses the phosphoglycerate kinase (PGK) promoter located internally in the vector (PG vector). The amphotropic PA317 and GP+am12 packaging cell lines were used as virus producer cells, and the GP+am12 cell line demonstrated higher titers, higher levels of GC protein expression, and specific GC enzymatic activity as well as higher transduction efficiencies for all three vectors. The LG retroviral vector was the most efficient in transducing the M1 cells. On average, higher levels of RNA and protein expression were seen in the M1 clones transduced with the LG vector, and these levels increased after differentiation. Thus, the LG retroviral vector in which the expression of the GC gene is driven by the MoMLV LTR enhancer/promoter is the best vector of the three studied for future studies for gene therapy of Gaucher's disease and other hematopoietic disorders that involve macrophages. C1 NINCDS,DEV & METAB NEUROL BRANCH,MOLEC & MED GENET SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NR 45 TC 8 Z9 8 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD 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 1994 VL 22 IS 9 BP 857 EP 865 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB177 UT WOS:A1994PB17700001 PM 8062885 ER PT J AU SZABO, G PINE, PS WEAVER, JL RAO, PE ASZALOS, A AF SZABO, G PINE, PS WEAVER, JL RAO, PE ASZALOS, A TI THE L-SELECTIN (LEU8) MOLECULE IS ASSOCIATED WITH THE TCR/CD3 RECEPTOR - FLUORESCENCE ENERGY-TRANSFER MEASUREMENTS ON LIVE CELLS SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article DE FLUORESCENCE ENERGY TRANSFER; L-SELECTIN; TCR/CD3 ID LYMPHOCYTE-T ACTIVATION; NODE HOMING RECEPTOR; CD4; SURFACE; CALCIUM; INDUCTION; COMPLEX; EVENTS AB Several accessory molecules were shown to play important roles in T cell functions and be in close proximity to the T cell receptor (TcR/CD3). The L-selectin molecule (Leu8, LAM1-1, LECAM1) also plays an important role in lymphocyte homing and proliferation. We were interested in determining the proximity of this molecule to the TcR/CD3 complex on live peripheral human T cells. Using a fluorescence energy transfer method, designed to study individual cells, we could show that L-selectin is within 170 A of the TcR/CD3 complex. Monoclonal antibody directed against the LAM1-1 (Leu8) epitope of the L-selectin molecule suppressed the mitogenic activity of antibodies specific for various CD3 epitopes in vitro. Intracellular Ca2+ mobilization obtained with wt31 followed by cross-linking antibody or with anti-CD3 was not influenced by anti-leu8 antibody. Also antibody directed against the LAM1-1 epitope did not influence the binding of the mitogenic antibodies, as shown by fluorescence-based flow cytometry. Therefore, we suggest that binding of TcR/CD3 bound mitogenic antibodies to accessory cell Fc receptors may be hindered by antibodies bound to the close proximity L-selectin molecules. C1 DEBRECEN UNIV MED,SCH MED,DEPT BIOPHYS,H-4012 DEBRECEN,HUNGARY. CTR DRUG EVALUAT & RES,WASHINGTON,DC. ORTHO DIAGNOST SYST INC,RARITAN,NJ. NR 26 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD AUG PY 1994 VL 72 IS 4 BP 319 EP 325 DI 10.1038/icb.1994.48 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA PC199 UT WOS:A1994PC19900007 PM 7528722 ER PT J AU RHINEHARTJONES, TR FORTIER, AH ELKINS, KL AF RHINEHARTJONES, TR FORTIER, AH ELKINS, KL TI TRANSFER OF IMMUNITY AGAINST LETHAL MURINE FRANCISELLA INFECTION BY SPECIFIC ANTIBODY DEPENDS ON HOST GAMMA-INTERFERON AND T-CELLS SO INFECTION AND IMMUNITY LA English DT Article ID FRANCISELLA-TULARENSIS LVS; POLYMORPHONUCLEAR LEUKOCYTES; PROTECTIVE IMMUNITY; RESISTANCE; GLOBULIN; MICE; MACROPHAGES; DESTRUCTION; GENERATION; ACTIVATION AB Both serum and spleen cells from mice immune to Francisella tularensis transfer protection to naive recipients. Here we characterize the mechanism of protection induced by transfer of immune mouse serum (IMS). IMS obtained 4 weeks after intradermal infection with 10(3) bacteria of the live vaccine strain (LVS) contained high levels of immunoglobulin G2 (IgG2a) and IgM (end point titers, 1:16,600 and 1:7,200, respectively) and little IgG1, IgG2b, or IgG3. LVS-specific antibodies were detected 5 days after intradermal infection, and reached peak levels by 2 weeks postinfection. Only sera obtained 10 days or more after sublethal infection, when IgG titers peaked, transferred protection against a challenge of 100 50% lethal doses (LD(50)s). Purified high-titer IgG anti LVS antibody but not IgM anti-LVS antibody was responsible for transfer of protection against an intraperitoneal challenge of up to 3,000 LD(50)s. IMS had no direct toxic effects on LVS and did not affect uptake or growth of bacteria in association with peritoneal cells. One day after LVS infection, liver, spleen, and lung tissue from mice treated with IMS contained 1 to 2 log units fewer bacteria than did tissue from mice treated with normal mouse serum or phosphate-buffered saline. Between 2 and 4 days after infection, however, bacterial growth rates in tissues were similar in both serum-protected mice and unprotected mice. Bacterial burdens in IMS-treated, LVS-infected mice declined in infected tissues after day 5, whereas control animals died. This lag phase suggested that development of a host response was involved in complete bacterial clearance. In fact, transfer of IMS into normal recipients that were simultaneously treated with anti-gamma interferon and challenged with LVS did not protect mice from death. Further, transfer of IMS into athymic nu/nu mice did not protect against LVS challenge; protection was, however, reconstituted by transfer of normal T cells into nu/nu mice. Thus, ''passive'' transfer of protection against LVS with specific antibody is not passive but depends on a host T cell response to promote clearance of systemic infection and protection against lethal disease. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,ENTER & SEXUALLY TRANSMITTED DIS LAB,BETHESDA,MD 20852. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT CELLULAR IMMUNOL,ROCKVILLE,MD 20850. NR 35 TC 85 Z9 86 U1 1 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 1994 VL 62 IS 8 BP 3129 EP 3137 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NY872 UT WOS:A1994NY87200013 PM 8039881 ER PT J AU SAEKI, T SALOMON, D NORMANNO, N JOHNSON, GR GULLICK, WJ MANDAI, K MORIWAKI, S TAKASHIMA, S KUNIYASU, M TAHARA, E KAWAMI, H NISHIYAMA, M TOGE, T AF SAEKI, T SALOMON, D NORMANNO, N JOHNSON, GR GULLICK, WJ MANDAI, K MORIWAKI, S TAKASHIMA, S KUNIYASU, M TAHARA, E KAWAMI, H NISHIYAMA, M TOGE, T TI IMMUNOHISTOCHEMICAL DETECTION OF CRIPTO-1, AMPHIREGULIN AND TRANSFORMING GROWTH-FACTOR-ALPHA IN HUMAN GASTRIC CARCINOMAS AND INTESTINAL METAPLASIAS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE CRIPTO; AMPHIREGULIN; EPIDERMAL GROWTH FACTOR RECEPTOR; ERBB-2; TGF-ALPHA; P53 ID FACTOR-RECEPTOR; CELL-LINE; COLORECTAL TUMORS; EPITHELIAL-CELLS; FACTOR FAMILY; EXPRESSION; GENE; CANCER; INDUCTION; RATS AB The expression and localization of cripto-1 (CR-1), amphiregulin (AR) and transforming growth factor alpha (TGFalpha) were assessed by immunocytochemistry in 37 primary human gastric tumors, 30 noninvolved gastric mucosa samples that were adjacent to carcinoma but exhibited intestinal metaplasia and 37 adjacent, noninvolved gastric mucosa samples. Seventeen (46%), nineteen (51%) and twenty-one (57%) carcinomas showed staining for CR-1, AR and TGFalpha, respectively; whereas sixteen (53%), eight (26%) and five (17%) intestinal metaplasias were reactive with the anti-CR-1, anti-AR and anti-TGFalpha antibodies, respectively. In contrast, none of the normal, noninvolved gastric mucosa samples reacted with the TGFalpha antibody and only 1 (3%) of these samples showed weak staining with the anti-CR-1 antibody. However, 8 (21%) of the normal gastric mucosa samples showed moderate levels of staining with the AR antibody. Within the carcinomas, there was a slight trend for association between TGFalpha and CR-1 expression (p<0.05), but no correlation was found between epidermal growth factor receptor and CR-1 expression. Staining for p53 was observed in 26 (70%) of the carcinomas, 3 (10%) intestinal metaplasias and none of the gastric mucosa samples. This data demonstrate that CR-1, like TGFalpha, may be a tumor marker for a subset of gastric carcinomas in addition to being an important factor in the early stages of gastric cancer development. C1 HAMMERSMITH HOSP,IMPERIAL CANC RES FUND,MOLEC ONCOL UNIT,LONDON W12 0HS,ENGLAND. HIROSHIMA UNIV,SCH MED,DEPT PATHOL,HIROSHIMA 730,JAPAN. HIROSHIMA UNIV,NUCL MED & BIOL RES INST,DEPT SURG,HIROSHIMA 730,JAPAN. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20014. NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTOR SECT,BETHESDA,MD 20892. RP SAEKI, T (reprint author), NATL SHIKOKU CANC CTR HOSP,DEPT CLIN RES,ONCOGENE SECT,HORINOUCHI 13,MATSUYAMA 790,JAPAN. OI Normanno, Nicola/0000-0002-7158-2605 NR 40 TC 23 Z9 23 U1 0 U2 0 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 AUG PY 1994 VL 5 IS 2 BP 215 EP 223 PG 9 WC Oncology SC Oncology GA NY136 UT WOS:A1994NY13600012 PM 21559578 ER PT J AU HAHN, DW PETTIT, GH EDIGER, MN AF HAHN, DW PETTIT, GH EDIGER, MN TI OPTICAL-PROPERTIES OF POLYIMIDE DURING ARF EXCIMER-LASER ABLATION SO JOURNAL OF APPLIED PHYSICS LA English DT Article ID TIME-RESOLVED REFLECTIVITY; ORGANIC POLYMERS; DYNAMICS AB Reflectivity measurements of the backsurface of thin polyimide films indicate a transient decrease in reflectivity during ArF (193 nm) excimer laser ablation. The posterior surface reflectivity is decreased by 20%-40% over the range of incident laser fluences from 75 to 175 mJ/cm2, respectively. The results are discussed within the framework of a theoretical model of saturable absorption, and calculations are presented which are in good agreement with the experimental' results. It is concluded that the observed decrease in reflectivity is the result of transient changes in the optical properties within the solid polymer material which occur during ultraviolet laser ablation. RP HAHN, DW (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,HFZ-134,1901 CHAPMAN AVE,ROCKVILLE,MD 20857, USA. NR 14 TC 4 Z9 4 U1 0 U2 1 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 AUG 1 PY 1994 VL 76 IS 3 BP 1830 EP 1832 DI 10.1063/1.357702 PG 3 WC Physics, Applied SC Physics GA PA305 UT WOS:A1994PA30500068 ER PT J AU GANGULI, S ZAPATA, G WALLIS, T REID, C BOULNOIS, G VANN, WF ROBERTS, IS AF GANGULI, S ZAPATA, G WALLIS, T REID, C BOULNOIS, G VANN, WF ROBERTS, IS TI MOLECULAR-CLONING AND ANALYSIS OF GENES FOR SIALIC-ACID SYNTHESIS IN NEISSERIA-MENINGITIDIS GROUP-B AND PURIFICATION OF THE MENINGOCOCCAL CMP-NEUNAC SYNTHETASE ENZYME SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI K1; N-ACETYLNEURAMINIC ACID; CAPSULE BIOSYNTHESIS GENES; POLYSIALIC ACID; POLYSACCHARIDE CAPSULE; EXPRESSION; CLUSTER; K5; SEQUENCE; ANTIGENS AB The gene encoding for the CMP-NeuNAc synthetase enzyme of Neisseria meningitidis group B was cloned by complementation of a mutant of Escherichia coli defective for this enzyme. The gene (neuA) was isolated on a 4.1-kb fragment of meningococcal chromosomal DNA. Determination of the nucleotide sequence of this fragment revealed the presence of three genes, termed neuA, neuB, and neuC, organized in a single operon. The presence of a truncated ctr A gene at one end of the cloned DNA and a truncated gene encoding for the meningococcal sialyltransferase at the other confirmed that the cloned DNA corresponded to region A and part of region C of the meningococcal capsule gene cluster. The predicted amino acid sequence of the meningococcal NeuA protein was 57% homologous to that of NeuA, the CMP-NeuNAc synthetase encoded by E. coli K1. The predicted molecular mass of meningococcal NeuA protein was 24.8 kDa, which was 6 kDa larger than that formerly predicted (U. Edwards and M. Frosch, FEMS Microbiol. Lett, 96:161-166, 1992). Purification of the recombinant meningococcal NeuA protein together with determination of the N-terminal amino acid sequence confirmed that this 24.8-kDa protein was indeed the meningococcal CMP-NeuNAc synthetase. The predicted amino acid sequences of the two other encoded proteins were homologous to those of the NeuC and NeuB proteins of E. coli K1, two proteins involved in the synthesis of NeuNAc. These results indicate that common steps exist in the biosynthesis of NeuNAc in these two microorganisms. C1 UNIV LEICESTER,DEPT MICROBIOL,LEICESTER LE1 7RH,ENGLAND. US FDA,CTR BIOL EVALUAT & RES,BACTERIAL POLYSACCHARIDES LAB,BETHESDA,MD 20892. NR 51 TC 45 Z9 46 U1 1 U2 3 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 AUG PY 1994 VL 176 IS 15 BP 4583 EP 4589 PG 7 WC Microbiology SC Microbiology GA NY398 UT WOS:A1994NY39800015 PM 8045888 ER PT J AU JOHNSON, VG NICHOLLS, PJ AF JOHNSON, VG NICHOLLS, PJ TI IDENTIFICATION OF A SINGLE AMINO-ACID SUBSTITUTION IN THE DIPHTHERIA-TOXIN A CHAIN OF CRM-228 RESPONSIBLE FOR THE LOSS OF ENZYMATIC-ACTIVITY SO JOURNAL OF BACTERIOLOGY LA English DT Note ID NAD BINDING-SITE; CORYNEBACTERIOPHAGE-BETA; NUCLEOTIDE-SEQUENCE; ASPARTIC-ACID; FRAGMENT-A; TRANSLOCATION; MUTATIONS; MUTANTS; DOMAIN; GENE AB CRM 228 (T. Uchida, A. M. Pappenheimer, and R. Greany, J. Biol. Chem. 248:3838-3844, 1973), a mutant form of diphtheria toxin which completely lacks ADP-ribosyltransferase activity, contains five amino acid substitutions. The two amino acid changes that fall within the A chain of the toxin (G79D and E162K) were separately analyzed by substituting a variety of other amino acids at these sites. The substitution at position 79 (G79D) singularly appears to account for the loss of enzymatic activity found in CRM 228. C1 NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. RP JOHNSON, VG (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BACTERIAL TOXINS LAB,BLDG 29,RM 103,BETHESDA,MD 20892, USA. NR 34 TC 6 Z9 6 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 AUG PY 1994 VL 176 IS 15 BP 4766 EP 4769 PG 4 WC Microbiology SC Microbiology GA NY398 UT WOS:A1994NY39800039 PM 8045910 ER PT J AU WOODGATE, R SINGH, M KULAEVA, OI FRANK, EG LEVINE, AS KOCH, WH AF WOODGATE, R SINGH, M KULAEVA, OI FRANK, EG LEVINE, AS KOCH, WH TI ISOLATION AND CHARACTERIZATION OF NOVEL PLASMID-ENCODED UMUC MUTANTS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DNA POLYMERASE-III; SINGLE-STRANDED VECTOR; ESCHERICHIA-COLI; RECA PROTEIN; UV MUTAGENESIS; ULTRAVIOLET-LIGHT; SOS MUTAGENESIS; CHEMICAL MUTAGENESIS; CYCLOBUTANE DIMER; GROE MUTANTS AB Most inducible mutagenesis in Escherichia coli is dependent upon the activity of the UmuDC proteins. The role of UmuC in this process is poorly understood, possibly because of the limited number of genetically characterized umuC mutants. To better understand the function of the UmuC protein in mutagenic DNA repair, we have isolated several novel plasmid-encoded umuC mutants. A multicopy plasmid that expressed UmuC at physiological levels was constructed and randomly mutagenized in vitro by exposure to hydroxylamine. Mutated plasmids were introduced into the umu tester strain RW126, and 16 plasmids that were unable to promote umuC-dependent spontaneous mutator activity were identified by a colorimetric papillation assay. Interestingly, these plasmid mutants fell into two classes: (i) 5 were expression mutants that produced either too little or too much wild-type UmuC protein, and (ii) 11 were plasmids with structural changes in the UmuC protein. Although hydroxylamine mutagenesis was random, most of the structural mutants identified in the screen were localized to two regions of the UmuC protein; four mutations were found in a stretch of 30 amino acids (residues 133 to 162) in the middle of the protein, while four other mutations (three of which resulted in a truncated UmuC protein) were localized in the last 50 carboxyl-terminal amino acid residues. These new plasmid umuC mutants, together with the previously identified chromosomal umuC25, umuC36, and umuC104 mutations that we have also cloned, should prove extremely useful in dissecting the genetic and biochemical activities of UmuC in mutagenic DNA repair. C1 US FDA,MOLEC BIOL BRANCH,WASHINGTON,DC 20204. RP WOODGATE, R (reprint author), NICHHD,DNA REPLICAT REPAIR & MUTAGENESIS,BLDG 6,ROOM 1A13,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Studitskaia, Olga/D-8551-2014 OI Studitskaia, Olga/0000-0001-5417-9964 NR 58 TC 34 Z9 35 U1 1 U2 1 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 AUG PY 1994 VL 176 IS 16 BP 5011 EP 5021 PG 11 WC Microbiology SC Microbiology GA PA426 UT WOS:A1994PA42600029 PM 8051014 ER PT J AU FRANCIOSA, G FERREIRA, JL HATHEWAY, CL AF FRANCIOSA, G FERREIRA, JL HATHEWAY, CL TI DETECTION OF TYPE-A, TYPE-B, AND TYPE-E BOTULISM NEUROTOXIN GENES IN CLOSTRIDIUM-BOTULINUM AND OTHER CLOSTRIDIUM SPECIES BY PCR - EVIDENCE OF UNEXPRESSED TYPE-B TOXIN GENES IN TYPE-A TOXIGENIC ORGANISMS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; NUCLEOTIDE-SEQUENCE ANALYSIS; AMINO-ACID-SEQUENCE; ENCODING GENE; F NEUROTOXIN; BUTYRICUM; STRAIN; CLONING; BARATI; INFANT AB We studied the effectiveness of the PCR in detecting the type A, B, and E botulism neurotoxin genes in 209 strains of Clostridium botulinum and 29 strains of other Clostridium spp. All 79 strains that produced type A toxin, 77 strains that produced type B toxin, and 51 organisms that produced type E toxin (46 C. botulinum and 5 C. butyricum) were PCR positive in reactions with primers targeting sequences specific for their respective toxin genes. The PCR for type A toxin was positive for one type B toxin-producing strain that produced a small amount of type A toxin in addition to a large amount of type B toxin. Surprisingly, the type B toxin gene was detected in addition to the type A toxin gene in 43 type A toxin producing strains, only 1 of which could be shown by bioassay to produce biologically active type E toxin in culture. The type B gene was also detected in two strains of C. subterminale, which were determined to be nontoxigenic by bioassay. While the PCR was sensitive and specific in detecting the neurotoxin genes, the discovery of unexpressed toxin genes indicates that PCR results may not be adequate for establishing type B neurotoxigenicity. C1 CTR DIS CONTROL & PREVENT,BDMD,ATLANTA,GA 30333. IST SUPER SANITA,ALIMENTI LAB,I-00161 ROME,ITALY. US FDA,ATLANTA,GA 30309. RI FRANCIOSA, GIOVANNA/C-7040-2015 OI FRANCIOSA, GIOVANNA/0000-0003-1520-4826 NR 30 TC 105 Z9 109 U1 0 U2 4 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 AUG PY 1994 VL 32 IS 8 BP 1911 EP 1917 PG 7 WC Microbiology SC Microbiology GA NX414 UT WOS:A1994NX41400016 PM 7989542 ER PT J AU PEELER, JT BUNNING, VK AF PEELER, JT BUNNING, VK TI HAZARD ASSESSMENT OF LISTERIA-MONOCYTOGENES IN THE PROCESSING OF BOVINE-MILK SO JOURNAL OF FOOD PROTECTION LA English DT Article DE LISTERIA MONOCYTOGENES; MILK; PROCESSING; PASTEURIZATION ID CONTAMINATED RAW-MILK; HEAT-TREATED MILK; THERMAL-RESISTANCE; YERSINIA-ENTEROCOLITICA; MICROBIOLOGICAL SAFETY; GROWTH; CHEESE; CAMPYLOBACTER; INACTIVATION; PHAGOCYTES AB The steps in Grade A production of bovine milk for human consumption were assessed. A cumulative distribution of values, based on published data, was used to evaluate steps for milking, storage, transportation and pasteurization. Conservative estimates of parameters in the distributions were used to compute concentrations and probabilities. Under normal operations, the probability was less than 2 in 100 that one Listeria monocytogenes cell occurs in every 2 gallons of milk processed at exactly 71.7 degrees C for 15 s. The probability was less than 2 in 100 that one cell occurs in 3.8 x 10(10) gallons processed at 74.4 degrees C for 20 s. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 64 TC 26 Z9 27 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 1994 VL 57 IS 8 BP 689 EP 697 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA PF223 UT WOS:A1994PF22300007 ER PT J AU JONES, JD CALLAHAN, TJ ALPERT, S BARNETT, M AF JONES, JD CALLAHAN, TJ ALPERT, S BARNETT, M TI A FOOD-AND-DRUG-ADMINISTRATION REQUEST FOR COOPERATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material RP JONES, JD (reprint author), US FDA,DIV CARDIOVASC RESP & NEUROL DEVICES,OFF DEVICE EVALUAT,1390 PICCARD DR,ROCKVILLE,MD 20857, USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE 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 1994 VL 24 IS 2 BP 413 EP 413 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH376 UT WOS:A1994PH37600020 PM 8034876 ER PT J AU UDAYKUMAR HEREDIA, A SORIANO, V BRAVO, R EPSTEIN, JS HEWLETT, IK AF UDAYKUMAR HEREDIA, A SORIANO, V BRAVO, R EPSTEIN, JS HEWLETT, IK TI ENHANCED DIAGNOSTIC EFFICIENCY OF THE POLYMERASE CHAIN-REACTION BY COAMPLIFICATION OF MULTIPLE REGIONS OF HIV-1 AND HIV-2 SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV-1; HIV-2; POLYMERASE CHAIN REACTION; PCR; COAMPLIFICATION; COINFECTIONS ID DNA; SENSITIVITY; INFECTIONS AB A method for co-amplification of multiple viral sequences of HIV-1 and HIV-2 by polymerase chain reaction was designed. The technique resulted in the specific detection of each type of virus and allowed the amplification of as few as two copies of target DNA. The amplification of multiple regions of the viral genome offers the advantage of detecting multiple target sequences, which may be essential for some viruses, such as HIV, that exhibit a high degree of variability in their gene sequences. In addition, the method permitted the detection of both virus types in the same reaction, allowing for greater utility in geographic areas where coinfections with both viruses occur and cross-reactivity in Western blots is observed. This method was applied successfully to the detection of viral DNA in clinical specimens. C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS & TRANSMITTED DIS,MOLEC VIROL LAB,ROCKVILLE,MD 20852. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI 48109. INST SALUD CARLOS 3,SERV INFECT DIS MICROBIOL & IMMUNOL,E-28010 MADRID,SPAIN. NR 19 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD AUG PY 1994 VL 49 IS 1 BP 37 EP 46 DI 10.1016/0166-0934(94)90053-1 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA PF136 UT WOS:A1994PF13600004 PM 7829590 ER PT J AU LAVIGNON, M WALKER, JL PERRYMAN, SM MALIK, FG KHAN, AS THEODORE, TS EVANS, LH AF LAVIGNON, M WALKER, JL PERRYMAN, SM MALIK, FG KHAN, AS THEODORE, TS EVANS, LH TI CHARACTERIZATION OF EPITOPES DEFINING 2 MAJOR SUBCLASSES OF POLYTROPIC MURINE LEUKEMIA VIRUSES (MULVS) WHICH ARE DIFFERENTIALLY EXPRESSED IN MICE INFECTED WITH DIFFERENT ECOTROPIC MULVS SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; FOCUS-FORMING VIRUSES; ENV GENE; MONOCLONAL-ANTIBODIES; SPONTANEOUS LYMPHOMAS; NUCLEOTIDE-SEQUENCE; ENVELOPE GENE; MCF VIRUSES; AKR/J MICE; CELL LINES AB Polytropic murine leukemia viruses (MuLVs) arise in mice by recombination of ecotropic MuLVs with endogenous retroviral envelope genes and have been implicated in the induction of hematopoietic proliferative diseases. Inbred mouse strains contain many endogenous sequences which are homologous to the polytropic env genes; however, the extent to which particular sequences participate in the generation of the recombinants is unknown, Previous studies have established antigenic heterogeneity among the env genes of polytropic MuLVs, which may reflect recombination with distinct endogenous genes. In the present study, we have examined many polytropic MuLVs and found that nearly all isolates fall into two mutually exclusive antigenic subclasses on the basis of the ability of their SU proteins to react with one of two monoclonal antibodies, termed Hy 7 and MAb 516. Epitope-mapping studies revealed that reactivity to the two antibodies is dependent on the identity of a single amino acid residue encoded in a variable region of the receptor-binding domain of the env gene. This indicated that the two antigenic subclasses of MuLVs arose by recombination with distinct sets of endogenous genes. Evaluation of polytropic MuLVs in mice revealed distinctly different ratios of the two subclasses after inoculation of different ecotropic MuLVs, suggesting that individual ecotropic MuLVs preferentially recombine with distinct sets of endogenous polytropic env genes. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. US FDA,CTR BIOL EVALUAT & RES,RETROVIRUS RES LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 53 TC 10 Z9 10 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 AUG PY 1994 VL 68 IS 8 BP 5194 EP 5203 PG 10 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800054 PM 7518532 ER PT J AU FENG, P LAMPEL, KA AF FENG, P LAMPEL, KA TI GENETIC-ANALYSIS OF UIDA EXPRESSION IN ENTEROHEMORRHAGIC ESCHERICHIA-COLI SEROTYPE O157-H7 SO MICROBIOLOGY-SGM LA English DT Article DE ESCHERICHIA COLI O157,H7; UIDA EXPRESSION; BETA-GLUCURONIDASE ID HEMOLYTIC-UREMIC SYNDROME; BETA-GLUCURONIDASE; IDENTIFICATION; SEQUENCE; GROWTH AB Isolates of enterohaemorrhagic Escherichia coli serotype O157:H7 do not exhibit beta-glucuronidase (GUD) activity; however, they carry nucleotide sequences for the uidA gene that encodes the GUD enzyme. Polymerase chain reaction analysis using uidA-specific primers confirmed that a genetic region homologous in size to the E. coli uidA structural gene, including the regulatory region, was present in E. coli O157:H7 isolates. DNA sequencing analysis of the regulatory region and the 5' terminus of the uidA gene of E. coli O157:H7 showed a base substitution in the putative -10 promotor region and at 93 bases downstream from the initiation codon. Neither base alteration, however, appeared to affect uidA allele gene expression in the O157:H7 isolates. Immunoblotting of cell extracts with an anti-GUD antibody showed that E. coli O157:H7 isolates produced an antibody-reactive protein that was homologous in site to E. coli CUD, but no CUD activity was observed in cell-free extracts of these isolates. These results suggest that the antibody-reactive protein produced by E. coli O157:H7 may be an inactive GUD enzyme. Sequencing of the uidA structural gene in O157:H7 showed the presence of 18 additional nucleotide base substitutions. but only six altered the amino acid sequence. Also, there were two frame shift mutations, 18 bases apart, that altered the sequence of six consecutive amino acids. These genetic alterations in the uidA structural gene of O157:H7 may account for the absence of CUD activity in this serotype. C1 US FDA, DIV MOLEC BIOL RES & EVALUAT, WASHINGTON, DC 20204 USA. RP FENG, P (reprint author), US FDA, DIV MICROBIOL STUDIES, WASHINGTON, DC 20204 USA. NR 21 TC 45 Z9 46 U1 1 U2 5 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD AUG PY 1994 VL 140 BP 2101 EP 2107 PN 8 PG 7 WC Microbiology SC Microbiology GA PC693 UT WOS:A1994PC69300035 PM 7921260 ER PT J AU MORRIS, DI GREENBERGER, LM BRUGGEMANN, EP CARDARELLI, C GOTTESMAN, MM PASTAN, I SEAMON, KB AF MORRIS, DI GREENBERGER, LM BRUGGEMANN, EP CARDARELLI, C GOTTESMAN, MM PASTAN, I SEAMON, KB TI LOCALIZATION OF THE FORSKOLIN LABELING SITES TO BOTH HALVES OF P-GLYCOPROTEIN - SIMILARITY OF THE SITES LABELED BY FORSKOLIN AND PRAZOSIN SO MOLECULAR PHARMACOLOGY LA English DT Article ID MULTIDRUG-RESISTANT CELLS; BACTERIAL TRANSPORT PROTEINS; MEMBRANE GLYCOPROTEIN; PHOTOACTIVE ANALOGS; CHEMICAL-PROPERTIES; FUNCTIONAL-ANALYSIS; GLUCOSE-TRANSPORT; ADENYLATE-CYCLASE; BINDING-SITE; MOUSE MDR1 AB An iodinated derivative of forskolin, 6-O-[[2-[3-(4-azido-3-[I-125]iodophenyl)propionamido]ethyl]carbamyl]forskolin ([I-125]6-AIPP-Fsk), photolabels the multidrug efflux pump P-glycoprotein in membranes prepared from the multidrug-resistant cell lines KB-V1 and KB-C1. The labeling site for [I-125]6-AIPP-Fsk was localized by immunoprecipitation of tryptic fragments of P-glycoprotein labeled in KB-C1 membranes. A 6-kDa, photolabeled, tryptic fragment was immunoprecipitated by antiserum raised against residues 348-419 of P-glycoprotein, PEPG9, but not by antisera raised against flanking regions PEPG7 and PEPG11. A peptide that corresponds to residues 343-359 of P-glycoprotein inhibited immunoprecipitation of the 6-kDa fragment by antiserum against PEPG9 but had no effect on the immunoprecipitation of photolabeled fragments by antiserum against PEPG7. A second peptide, corresponding to residues 360-376, had no effect on the immunoprecipitation by antiserum against PEPG9. [I-125]6-AIPP-Fsk labels the carboxyl-terminal half of P-glycoprotein, because low molecular mass tryptic fragments were immunoprecipitated by three carboxyl-terminal antisera. Therefore, [I-125]6-AlPP-Fsk labels both halves of P-glycoprotein, and labeling in the aminoterminal half can be localized to residues 291-359, which span proposed transmembrane regions 5 and 6. KB-V1 membranes photolabeled with [I-125]6-AIPP-Fsk and [I-125]iodoarylazidoprazosin were digested with either Staphlyococcus aureus V8 protease or chymotrypsin and had similar digestion patterns, suggesting that the two drugs label the same sites on P-glycoprotein. C1 US FDA,DIV BIOCHEM & BIOPHYS,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965. NICHHD,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NR 52 TC 98 Z9 98 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1994 VL 46 IS 2 BP 329 EP 337 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PE364 UT WOS:A1994PE36400014 PM 7915819 ER PT J AU CHUMAKOV, KM AF CHUMAKOV, KM TI REVERSE-TRANSCRIPTASE CAN INHIBIT PCR AND STIMULATE PRIMER-DIMER FORMATION SO PCR-METHODS AND APPLICATIONS LA English DT Note ID POLIOVIRUS VACCINE; SEQUENCE RP CHUMAKOV, KM (reprint author), US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20852, USA. NR 5 TC 23 Z9 23 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 PCR METH APPL JI PCR-Methods Appl. PD AUG PY 1994 VL 4 IS 1 BP 62 EP 64 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA RM625 UT WOS:A1994RM62500014 PM 9018322 ER PT J AU BOEHNLEIN, J SAKR, A LICHTIN, JL BRONAUGH, RL AF BOEHNLEIN, J SAKR, A LICHTIN, JL BRONAUGH, RL TI CHARACTERIZATION OF ESTERASE AND ALCOHOL-DEHYDROGENASE ACTIVITY IN SKIN - METABOLISM OF RETINYL PALMITATE TO RETINOL (VITAMIN-A) DURING PERCUTANEOUS-ABSORPTION SO PHARMACEUTICAL RESEARCH LA English DT Article DE PERCUTANEOUS ABSORPTION; METABOLISM; RETINYL PALMITATE; HAIRLESS GUINEA PIG ID BENZYL ACETATE; MOUSE EPIDERMIS; BENZYL ACETATE; ACID; INVITRO; INDUCTION; DIFFERENTIATION; XENOBIOTICS; VEHICLE; CELL AB Retinyl palmitate, a widely used ingredient in cosmetic products, is promoted for its beneficial effects on the appearance of skin. Previous studies suggest that enzymes are available in skin to metabolize this ingredient during skin absorption. Esterase activity hydrolyzes retinyl palmitate to retinol (vitamin A), which is oxidized in many tissues to retinoic acid primarily by alcohol dehydrogenase. The activities of esterase and alcohol dehydrogenase were characterized in hairless guinea pig skin by using flow-through diffusion cells and radiolabeled model compounds (methyl salicylate and benzyl alcohol) previously shown to be metabolized by these enzymes. Methyl salicylate was hydrolyzed by esterase to a greater extent in viable skin than in nonviable skin. Glycine conjugation of salicylic acid and benzoic acid occurred only in viable skin. The metabolism of methyl salicylate and benzyl alcohol occurred to a greater extent in male guinea pig skin than in female guinea pig skin. The percutaneous absorption of both radiolabeled compounds was similar in viable and nonviable skin. About 30 and 18% of topically applied retinyl palmitate were absorbed from an acetone vehicle by hairless guinea pig skin and human skin, respectively. Less than 1% of the applied dose of this lipophilic compound diffused from skin into the receptor fluid. Retinol was the only detectable metabolite of retinyl palmitate in both hairless guinea pig and human skin. In human skin, 44% of the absorbed retinyl palmitate was hydrolyzed to retinol. The use of retinyl palmitate in cosmetic formulations may result in significant delivery of retinol into the skin. C1 US FDA,COSMET TOXICOL BRANCH,LAUREL,MD 20708. UNIV CINCINNATI,COLL PHARM,CINCINNATI,OH 45221. NR 29 TC 60 Z9 62 U1 0 U2 15 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 AUG PY 1994 VL 11 IS 8 BP 1155 EP 1159 DI 10.1023/A:1018941016563 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA NZ366 UT WOS:A1994NZ36600015 PM 7971717 ER PT J AU BUFFALO, EA GILLAM, MP ALLEN, RR PAULE, MG AF BUFFALO, EA GILLAM, MP ALLEN, RR PAULE, MG TI ACUTE BEHAVIORAL-EFFECTS OF MK-801 IN RHESUS-MONKEYS - ASSESSMENT USING AN OPERANT TEST BATTERY SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE MK-801; MACACA MULATTA; OPERANT BEHAVIOR; TIME ESTIMATION; INCREMENTAL REPEATED ACQUISITION; LEARNING; COLOR AND POSITION DISCRIMINATION; TEMPORAL RESPONSE DIFFERENTIATION; DELAYED MATCHING-TO-SAMPLE; SHORT-TERM MEMORY; MOTIVATION; ATTENTION; FOOD REINFORCEMENT ID RECEPTOR ANTAGONISTS; MARIJUANA SMOKE; PERFORMANCE; PHENCYCLIDINE; RAT AB The acute effects of MK-801, a selective, noncompetitive NMDA receptor antagonist, were assessed using an operant test battery (OTB) of complex food-reinforced tasks that are thought to depend upon relatively specific brain functions such as motivation to work for food (progressive ratio, PR), learning (incremental repeated acquisition, IRA), color and position discrimination (conditioned position responding, CPR), time estimation (temporal response differentiation, TRD), and short-term memory and attention (delayed matching-to-sample, DMTS). Endpoints included response rates (RR), accuracies (ACC), and percent task completed (PTC). MK-801 (0.003-0.075 mg/kg, IV), given 15 min pretesting, produced significant dose-dependent decreases in measures of IRA and TRD performance at doses greater than or equal to 0.03 mg/kg. In both tasks, MK-801 produced significant decreases in accuracy at doses lower than those required to affect response rate. MK-801 also produced statistically significant decreases in PR, CPR, and DMTS measures, but only at higher doses (greater than or equal to 0.056 mg/kg) that caused significant decreases in both response rates and accuracies. These results indicate that, in monkeys, performance of operant tasks designed to model learning and time estimation is more sensitive to the disruptive effects of MK-801 than performance of tasks that model motivation, color, and position discrimination, and short-term memory and attention. C1 NATL CTR TOXICOL RES, DIV NEUROTOXICOL, JEFFERSON, AR 72079 USA. NATL CTR TOXICOL RES, COMP BASED SYST INC, JEFFERSON, AR 72079 USA. UNIV ARKANSAS MED SCI HOSP, DEPT PHARMACOL & TOXICOL, LITTLE ROCK, AR 72205 USA. UNIV ARKANSAS MED SCI HOSP, DEPT PEDIAT, LITTLE ROCK, AR 72205 USA. NR 28 TC 42 Z9 42 U1 1 U2 3 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 AUG PY 1994 VL 48 IS 4 BP 935 EP 940 DI 10.1016/0091-3057(94)90203-8 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA PA431 UT WOS:A1994PA43100014 PM 7972299 ER PT J AU DOERGE, DR HOWARD, PC BAJIC, S PREECE, S AF DOERGE, DR HOWARD, PC BAJIC, S PREECE, S TI DETERMINATION OF FUMONISINS USING ONLINE LIQUID-CHROMATOGRAPHY COUPLED TO ELECTROSPRAY MASS-SPECTROMETRY SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID FUSARIUM-MONILIFORME; FLUORESCENCE DETECTION; HPLC; B1 AB Fumonisin (FB) mycotoxins are produced by Fusarium monoliforme, which grows primarily on yellow corn. Ingestion of FB1-contaminated food causes leukoencephalomalacia in horses, pulmonary edema in pigs, and is suspected in the etiology of human esophageal cancer. Chromatographic separation and detection of underivatized fumonisins has been hampered because these compounds are nonvolatile, thermally labile, and devoid of chromophoric functional groups. We report here a simple liquid chromatography/mass spectrometry method employing chromatographic separation on a polymer-based column coupled with sensitive detection using positive-ion electrospray mass spectrometry for the quantification of fumonisins B1, B2 and B3 in extracts of commercial corn meal. C1 FISONS INSTRUMENTS ORGAN ANAL,ALTRINCHAM WA14 5RZ,CHESHIRE,ENGLAND. RP DOERGE, DR (reprint author), NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 17 TC 22 Z9 23 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD AUG PY 1994 VL 8 IS 8 BP 603 EP 606 DI 10.1002/rcm.1290080807 PG 4 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA PE081 UT WOS:A1994PE08100006 ER PT J AU HOLSON, RR WEBB, PJ GRAFTON, TF HANSEN, DK AF HOLSON, RR WEBB, PJ GRAFTON, TF HANSEN, DK TI PRENATAL NEUROLEPTIC EXPOSURE AND GROWTH STUNTING IN THE RAT - AN IN-VIVO AND IN-VITRO EXAMINATION OF SENSITIVE PERIODS AND POSSIBLE MECHANISMS SO TERATOLOGY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; BRAIN-DEVELOPMENT; POSTNATAL-DEVELOPMENT; INSITU HYBRIDIZATION; PSYCHOTROPIC-DRUGS; NEURITE OUTGROWTH; GENE-EXPRESSION; DNA-SYNTHESIS; HALOPERIDOL; ONTOGENY AB There is increasing evidence that a number of neurotransmitters can play a trophic role in the development of the central nervous system. Dopamine is one candidate for this role. In a series of papers, Lewis, Patel, and colleagues have demonstrated that exposure to compounds which interfere with dopaminergic neurotransmission (''neuroleptics'') can block cell proliferation in the brains of 11-day-old rat pups for at least 24 hr. More recently our laboratory has reported that prenatal exposure to haloperidol (HAL), a neuroleptic which binds to and blocks dopamine receptor sites in the adult brain, permanently stunts body and brain growth when that exposure extends throughout postimplantation pregnancy. Reported here are the results of two experiments conducted to further examine this phenomenon. The first experiment attempted to identify sensitive gestational periods for the HAL effect on growth in vivo. This experiment also assessed the effect of exposure to reserpine (RES), a compound which in the adult blocks dopaminergic neurotransmission by rupturing monoamine storage vesicles, an effect which is quite distinct from the HAL mechanism of action. In a second experiment, gestational day (GD) 9 embryos were exposed in vitro for 48 hr to either HAL, RES, or one of two specific blockers of dopamine receptor subtypes. Schering 23390 (SCH) was used as the D1 blocker, and sulpiride (SULP) as the D2 blocker. The in vivo experiment showed that twice-daily exposure to subcutaneous injections of HAL (5 mg/kg for each of the 2 injections) or RES (0.1 mg/kg for each injec tion) permanently stunted brain growth when injections were given in midpregnancy (GD 12-16), but not in late pregnancy (GD 16-20). RES was substantially more fetotoxic than HAL, especially late in pregnancy. The growth stunting produced by either compound with GD 12-16 exposure was not restricted to dopamine-rich areas of the brain, or indeed to the brain itself, in that body weight was also depressed. Pair-fed controls did not show the same magnitude or duration of stunting, indicating that this effect was not due to drug-induced maternal hypophagia. The in vitro experiment revealed that exposure to micromolar concentrations of any of the 4 neuroleptics reduced embryonic GD 11 DNA and protein content and delayed development. HAL and SCH had the most pronounced effects at concentrations close to blood levels reportedly produced by exposure to doses used in the in vivo experiments. RES was less potent, and SULP still less potent than RES. It is concluded that neuroleptics acting through a variety of mechanisms can permanently stunt growth. There is a sensitive period for this stunting in midgestation. These effects are probably the result of direct drug action on the fetus, at least in the case of HAL, in that direct embryonic exposure to HAL in vitro at levels similar to those probably attained in vivo likewise slowed growth and development. Furthermore, the HAL effect on growth may be due in part to a direct effect on a D1-like receptor, in that equimolar exposure to SCH had a very similar depressive effect on embryonic growth and differentiation. (C) 1994 Wiley-Liss, Inc. C1 NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. NR 53 TC 23 Z9 24 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 1994 VL 50 IS 2 BP 125 EP 136 DI 10.1002/tera.1420500207 PG 12 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA PE960 UT WOS:A1994PE96000006 PM 7801300 ER PT J AU FRATANTONI, JC AF FRATANTONI, JC TI POINTS TO CONSIDER ON EFFICACY EVALUATION OF HEMOGLOBIN-BASED AND PERFLUOROCARBON-BASED OXYGEN CARRIERS SO TRANSFUSION LA English DT Editorial Material RP FRATANTONI, JC (reprint author), CTR BIOL EVALUAT & RES,DIV HEMATOL,HFM-330,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 40 Z9 40 U1 1 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 1994 VL 34 IS 8 BP 712 EP 713 PG 2 WC Hematology SC Hematology GA PD361 UT WOS:A1994PD36100014 ER PT J AU LEE, CJ LOCK, RA ANDREW, PW MITCHELL, TJ HANSMAN, D PATON, JC AF LEE, CJ LOCK, RA ANDREW, PW MITCHELL, TJ HANSMAN, D PATON, JC TI PROTECTION OF INFANT MICE FROM CHALLENGE WITH STREPTOCOCCUS-PNEUMONIAE TYPE 19F BY IMMUNIZATION WITH A TYPE 19F POLYSACCHARIDE PNEUMOLYSOID CONJUGATE SO VACCINE LA English DT Article DE STREPTOCOCCUS PNEUMONIAE; PNEUMOCOCCUS; PNEUMOLYSIN; POLYSACCHARIDE; CONJUGATE VACCINE ID ANTIBODY-RESPONSE; VACCINE; VIRULENCE; CHILDREN; IMMUNITY; PROTEINS; AGE AB The immunogenicity and protective efficacy of a conjugate of Streptococcus pneumoniae type 19F polysaccharide and a genetically toxoided derivative,e of the pneumococcal toxin pneumolysin was investigated in an infant mouse model. The conjugate was administered to Balb/c mice during pregnancy and/or lactation, and to their offspring during early infancy. The anti-polysaccharide and anti-pneumolysin titres of the immunized infant mice were significantly higher than those of non-immunized controls. When the infant mice were challenged with type 19F pneumococci, the bacteria were cleared more effectively from the blood of immunized mice than front that of control mice. The survival rate for the immunized mice was also significantly higher than that for the control group. These results indicate that highly protective anti-pneumococcal responses can be induced in infant mice by immunization with the conjugate during gestation or early infancy, and suggest a possible role for pneumolysoid-polysaccharide conjugates as human vaccine components. C1 WOMENS & CHILDRENS HOSP,DEPT MICROBIOL,ADELAIDE,SA 5006,AUSTRALIA. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. UNIV LEICESTER,DEPT MICROBIOL,LEICESTER LE1 9HN,ENGLAND. RI Paton, James/A-9920-2008 NR 14 TC 30 Z9 30 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD AUG PY 1994 VL 12 IS 10 BP 875 EP 878 DI 10.1016/0264-410X(94)90028-0 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NW195 UT WOS:A1994NW19500003 PM 7975828 ER PT J AU KESSLER, DA MERKATZ, RB SCHAPIRO, R AF KESSLER, DA MERKATZ, RB SCHAPIRO, R TI SILICONE GEL BREAST IMPLANTS - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP KESSLER, DA (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 27 PY 1994 VL 272 IS 4 BP 273 EP 274 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NX806 UT WOS:A1994NX80600019 ER PT J AU ELLENBERG, SS EPSTEIN, JS FRATANTONI, JC SCOTT, D ZOON, KC AF ELLENBERG, SS EPSTEIN, JS FRATANTONI, JC SCOTT, D ZOON, KC TI A TRIAL OF RSV IMMUNE GLOBULIN IN INFANTS AND YOUNG-CHILDREN - THE FDAS VIEW SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID RESPIRATORY SYNCYTIAL VIRUS RP ELLENBERG, SS (reprint author), US FDA,ROCKVILLE,MD 20852, USA. NR 2 TC 10 Z9 10 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 JUL 21 PY 1994 VL 331 IS 3 BP 203 EP 204 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NW797 UT WOS:A1994NW79700027 PM 8054049 ER PT J AU POTTER, M MORRISON, S WIENER, F ZHANG, XKK MILLER, FW AF POTTER, M MORRISON, S WIENER, F ZHANG, XKK MILLER, FW TI INDUCTION OF PLASMACYTOMAS WITH SILICONE GEL IN GENETICALLY SUSCEPTIBLE STRAINS OF MICE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PRISTANE-INDUCED ARTHRITIS; BREAST IMPLANTS; TRANSLOCATIONS; GROWTH; WOMEN; AUTOANTIBODIES; INTERLEUKIN-6; REQUIREMENT; PROTEINS; MYELOMA AB Background: Plasmacytomas can be induced in high frequency in susceptible strains of mice by the intraperitoneal introduction of plastics or paraffin oils, including the chemically defined oil pristane (2,6,10,14-tetramethglpentadecane). These materials persist in the peritoneal cavity, where they induce chronic inflammation during the long periods before plasmacytomas develop. Such plasmacytomas appear to arise from B cells carrying chromosomal translocations that affect c-myc transcription. Purpose: Because silicone gels are in widespread medical use and share many of the characteristics of other materials known to be inducers of plasmacytomas, we wished to determine their capacity to induce plasmacytomas in mice. Methods: In a series of parallel experiments, corn oil, pristane, silicone oil (dimethylpolysiloxane), or silicone gel from commercially obtained mammary implants was injected intraperitoneally into plasmacytoma-susceptible BALB/cAnPt-A and congenic BALB/cAnPt.DB A/2-Idhl-Pep3 mice, as well as into plasmacytoma-resistant C57BL/6N, C3H/HeJ, DBA/2N, and (BALB/c x DBA/2)F1 mice. Mice were examined at least once every 2 weeks for signs of abdominal tumor or weight loss and screened every 4-6 weeks for; peritoneal-plasmacytoma cells by peritoneal lavage. Tissues were examined by histologic and immunohistechemical techniques. Metaphase chromosome spreads were made from ascitic plasmacytomas without Colcemid treatment, and metaphase plates were G-banded according to standard techniques. The t(12;15) or t(6;15) translocation chromosomes were identified under the microscope in at least five metaphase plates of high banding quality. Mice were autopsied 125-400 days after the injection of test material. Gas chromatography and mass spectrometry were utilized to determine the composition of the silicone oil and silicone gel used in the injections. Results: The silicone gels tested induced plasmacytomas in BALB/cAnPt-A and BALB/cAnPt.DBA/2-Idhl-Pep3 mice. Neither corn oil used as a control nor 1000-centistoke or 12500-centistoke dimethylpolysiloxane induced plasmacytomas in these mice. The plasmacytomas were transplantable in syngeneic hosts. Cytogenetic studies of 41 silicone-induced plasmacytomas showed that 30 had t(12;15) translocations, eight had t(6;15) translocations, and three had no translocations. Conclusions: The silicone gels used in mammary implants, which contain a complex mixture of different siloxanes, induced peritoneal plasmacytomas in genetically susceptible mice. Silicone gels provide new chemically defined materials that are effective inducers of plasmacytomas in BALB/cAnPt-A and BALB/cAnPt.DBA/2-Idh1-Pep3 mice. Further studies will be required to determine which of the components of these gels are the active materials. C1 KAROLINSKA INST,DEPT TUMOR BIOL,S-10401 STOCKHOLM,SWEDEN. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,MOLEC IMMUNOL LAB,BETHESDA,MD. RP POTTER, M (reprint author), NCI,DIV CANC BIOL DIAG & CTR,BLDG 37,RM 2B04,BETHESDA,MD 20892, USA. NR 40 TC 89 Z9 89 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 20 PY 1994 VL 86 IS 14 BP 1058 EP 1065 DI 10.1093/jnci/86.14.1058 PG 8 WC Oncology SC Oncology GA NW605 UT WOS:A1994NW60500009 PM 8021954 ER PT J AU KREITMAN, RJ PURI, RK PASTAN, I AF KREITMAN, RJ PURI, RK PASTAN, I TI A CIRCULARLY PERMUTED RECOMBINANT INTERLEUKIN-4 TOXIN WITH INCREASED ACTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IMMUNOTOXIN; GROWTH FACTOR; PSEUDOMONAS TOXIN; RECOMBINANT DNA; CYTOKINE ID 3-DIMENSIONAL SOLUTION STRUCTURE; MAGNETIC-RESONANCE SPECTROSCOPY; COLONY-STIMULATING FACTOR; PSEUDOMONAS EXOTOXIN; FUSION PROTEIN; GENETIC CONSTRUCTION; DIPHTHERIA-TOXIN; RECEPTOR-BINDING; ESCHERICHIA-COLI; GROWTH-FACTORS AB Fusion of ligands such as growth factors to other proteins often dramatically reduces the affinity of the ligand for its receptor. With recombinant DNA techniques, the attachment point between the two proteins has until now been restricted to either the amino or the carboxyl terminus of the ligand. However, binding may be greatly compromised if both ends are close to the site at which the ligand binds to its receptor. To construct a single-chain growth factor fusion protein with the connection at a new site on the growth factor, we constructed a DNA fragment encoding circularly permuted interleukin 4 (IL4), termed IL4(38-37). This was accomplished by placing a start codon before position 38, connecting codons 1 and 129 with a sequence encoding a; peptide linker, and placing a stop codon after codon 37 of IL4. IL4(38-37) was fused via its new carboxyl terminus, Lys(37), to a truncated form of Pseudomonas exotoxin. The purified circularly permuted IL4-toxin bound to the IL4 receptor with 10-fold higher affinity than an IL4-toxin in which the toxin was fused to the carboxyl terminus of IL4. Circular permuteins of growth factors can improve the effectiveness of recombinant fusion proteins, because the junction can be moved to a site on the growth factor which allows it to bind with higher affinity. C1 NCI,DIAGNOSIS & CTRS,DIV CANC BIOL,MOLEC BIOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR GENE THERAPIES,MOLEC TUMOR BIOL LAB,BETHESDA,MD 20892. NR 41 TC 94 Z9 97 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 JUL 19 PY 1994 VL 91 IS 15 BP 6889 EP 6893 DI 10.1073/pnas.91.15.6889 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800030 PM 8041715 ER PT J AU ADAMS, DH HARVATH, L BOTTARO, DP INTERRANTE, R CATALANO, G TANAKA, Y STRAIN, A HUBSCHER, SG SHAW, S AF ADAMS, DH HARVATH, L BOTTARO, DP INTERRANTE, R CATALANO, G TANAKA, Y STRAIN, A HUBSCHER, SG SHAW, S TI HEPATOCYTE GROWTH-FACTOR AND MACROPHAGE INFLAMMATORY PROTEIN 1-BETA - STRUCTURALLY DISTINCT CYTOKINES THAT INDUCE RAPID CYTOSKELETAL CHANGES AND SUBSET-PREFERENTIAL MIGRATION IN T-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SCATTER FACTOR; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; EXTRACELLULAR-MATRIX; FACTOR-RECEPTOR; RAT-TISSUES; EXPRESSION; LYMPHOCYTES; MOTILITY; ACTIN AB T-cell migration into tissue depends on a cascade of rapid and selective adhesive interactions with endothelium. ''Triggering'' is a step in that cascade required to activate T-cell integrins. Hepatocyte growth factor (HGF) may be a physiologically relevant trigger, since we demonstrate that HGF can induce both adhesion and migration of human T-cell subsets and can be detected immunohistochemically on inflamed endothelium. HGF preferentially induces responses from T cells of memory phenotype, in contrast to macrophage inflammatory protein 1 beta (MIP-1 beta), a chemokine which acts preferentially on naive cells. HGF, like the chemokines, binds to heparin, and HGF retained in extracellular matrix is efficient in promoting migration. Further, both MIP-1 beta and HGF induce actin polymerization within seconds, kinetics that approach those required to contribute to physiologic triggering. HGF is a member of a structural family distinct from the chemokines, whose only known receptor is the tyrosine kinase c-Met. HGF induces tyrosine phosphorylation on T cells apparently via a distinct receptor, since no c-Met is detectable by surface staining, PCR, or anti-phosphotyrosine immunoprecipitation. Thus, promotion of T-cell adhesion and migration are previously undescribed functions of HGF that we propose are relevant to selective T-cell recruitment. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,BETHESDA,MD 20892. UNIV ROME,DEPT HEMATOL,ROME,ITALY. UNIV BIRMINGHAM,DEPT BIOCHEM,BIRMINGHAM B15 2TT,ENGLAND. UNIV BIRMINGHAM,DEPT PATHOL,BIRMINGHAM B15 2TT,ENGLAND. RP ADAMS, DH (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. RI Bottaro, Donald/F-8550-2010; Adams, David/C-9092-2009 OI Bottaro, Donald/0000-0002-5057-5334; NR 43 TC 107 Z9 107 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 JUL 19 PY 1994 VL 91 IS 15 BP 7144 EP 7148 DI 10.1073/pnas.91.15.7144 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800082 PM 8041760 ER PT J AU DAVID, M PETRICOIN, EF IGARASHI, K FELDMAN, GM FINBLOOM, DS LARNER, AC AF DAVID, M PETRICOIN, EF IGARASHI, K FELDMAN, GM FINBLOOM, DS LARNER, AC TI PROLACTIN ACTIVATES THE INTERFERON-REGULATED P91 TRANSCRIPTION FACTOR AND THE JAK2 KINASE BY TYROSINE PHOSPHORYLATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; DNA-BINDING PROTEINS; GAMMA-INTERFERON; INVITRO ACTIVATION; LYMPHOMA-CELLS; GENE PROMOTER; GROWTH-FACTOR; FACTOR ISGF3; IFN-GAMMA; FACTOR-I AB The prolactin (PRL) receptor is a member of the family of cytokine receptors that lack intrinsic tyrosine kinase activity but contain two conserved cysteines in their N-terminal regions and a WSXWS moth adjacent to their transmembrane domains. In a manner similar to the interferons (IFNs), exposure of cells to PRL results in tyrosine phosphorylation of several cellular proteins and the rapid transcriptional induction of the IFN regulatory factor 1 gene. In this communication, we demonstrate that treatment of rat Nb2 lymphoma cells with PRL activates a latent protein factor so that it binds to an enhancer in the IFN regulatory factor 1 gene. This enhancer has been shown to be required for IFN-gamma-activated expression of this gene. PRL-induced assembly of the DNA binding complex, PRL-stimulated factor, required tyrosine phosphorylation. PRL-stimulated factor contained at least one protein that was antigenically similar to the p91 transcription factor, a component of several transcription complexes required for cytokine-activated gene expression. PRL not only induced the tyrosine phosphorylation of p91 but also induced tyrosine phosphorylation of Jak2, a tyrosine kinase required for IFN-gamma-activated gene expression. These results provide evidence for a signaling mechanism, some of whose components are shared by both PRL and IFN-gamma receptors, that results in the expression of early response genes. RP DAVID, M (reprint author), CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 44 TC 83 Z9 83 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 JUL 19 PY 1994 VL 91 IS 15 BP 7174 EP 7178 DI 10.1073/pnas.91.15.7174 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800088 PM 7518927 ER PT J AU MASOOD, R LUNARDIISKANDAR, Y MOUDGIL, T ZHANG, Y LAW, RE HUANG, CL PURI, RK LEVINE, AM GILL, PS AF MASOOD, R LUNARDIISKANDAR, Y MOUDGIL, T ZHANG, Y LAW, RE HUANG, CL PURI, RK LEVINE, AM GILL, PS TI IL-10 INHIBITS HIV-1 REPLICATION AND IS INDUCED BY TAT SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS FACTOR-ALPHA; LYMPHOBLASTOID CELL-LINE; GENE-EXPRESSION; INFECTION; TRANSCRIPTION; ACTIVATION; TYPE-1; AIDS AB Interleukin 10 (IL-10) is produced by T(H)2 lymphocytes and regulates both lymphoid and myeloid cells. In the present study we demonstrate that IL-10 is expressed and produced spontaneously in the peripheral blood mononuclear cells (PBMCs) of all HIV-1 infected individuals tested, 3 of 19 cases of HIV-negative lymphoma and none of five healthy controls. IL-10 mRNA was detectable in both monocytes/macrophages and T lymphocytes isolated from PBMCs of HIV infected patients. We have also shown that infection of promonocytic (U937) and T (H9) cell lines with HIV stimulates IL-10 secretion. Furthermore, a T cell line (H9) stably transfected with a HIV tat expression-vector secreted higher levels of IL-10. We have also demonstrated that rhIL-10 inhibited HIV-1 replication in infected monocytes and PBMCs in a dose dependent manner. IL-10 may thus participate in long latency between HIV-1 infection and development of AIDS. (C) 1994 Academic Press, Inc. C1 UNIV SO CALIF,DEPT MED,LOS ANGELES,CA 90033. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. ADV BIOSCI LAB INC,KENSINGTON,MD 20895. US FDA,DIV CELLULAR & GENE THERAPIES,BETHESDA,MD 20014. FU NCI NIH HHS [CA51621, CA55510]; NHLBI NIH HHS [HL48499] NR 23 TC 60 Z9 60 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 15 PY 1994 VL 202 IS 1 BP 374 EP 383 DI 10.1006/bbrc.1994.1938 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NX142 UT WOS:A1994NX14200054 PM 8037735 ER PT J AU FLURER, CL WOLNIK, KA AF FLURER, CL WOLNIK, KA TI CHEMICAL PROFILING OF PHARMACEUTICALS BY CAPILLARY ELECTROPHORESIS IN THE DETERMINATION OF DRUG ORIGIN SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article ID MICELLAR ELECTROKINETIC CHROMATOGRAPHY; ZONE ELECTROPHORESIS; ANTIBIOTICS; SEPARATION; BENZYLPENICILLIN AB Capillary electrophoresis has been utilized to detect trace components in bulk pharmaceutical products, with emphasis on the identification of differences among manufacturers that can be used for source verification in suspect/counterfeit cases. Micellar electrokinetic capillary chromatography with sodium dodecyl sulfate was used in the analyses of beta-lactam antibiotics. The aminoglycoside clindamycin phosphate and the macrolide erythromycin stearate were analyzed using berate buffers with direct UV detection. Methyl-beta-cyclodextrin was used as a buffer additive in the erythromycin studies, Determination of product potency using peak area ratios has been demonstrated for ampicillin and clindamycin phosphate. RP FLURER, CL (reprint author), US FDA,NATL FORENS CHEM CTR,1141 CENT PKWY,CINCINNATI,OH 45202, USA. NR 24 TC 36 Z9 36 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 15 PY 1994 VL 674 IS 1-2 BP 153 EP 163 DI 10.1016/0021-9673(94)85223-5 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NZ413 UT WOS:A1994NZ41300011 PM 8075768 ER PT J AU KAINE, LA WOLNIK, KA AF KAINE, LA WOLNIK, KA TI FORENSIC INVESTIGATION OF GENTAMICIN SULFATES BY ANION-EXCHANGE ION CHROMATOGRAPHY WITH PULSED ELECTROCHEMICAL DETECTION SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; COMPONENT RATIO AB Many methods exist for the separation of gentamicin C complex components, C-1, C-1a, C-2 and C-2a. In an investigation of possible counterfeit suppliers of gentamicin sulfate, a new method utilized high-pH anion-exchange separation on a carbohydrate column, with pulsed electrochemical detection on a gold electrode. Component ratios and the presence and/or absence of additional peaks were used to link or dissociate forensic samples. RP KAINE, LA (reprint author), US FDA,NATL FORENS CHEM CTR,1141 CENT PKWY,CINCINNATI,OH 45202, USA. NR 14 TC 24 Z9 25 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 15 PY 1994 VL 674 IS 1-2 BP 255 EP 261 DI 10.1016/0021-9673(94)85231-6 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NZ413 UT WOS:A1994NZ41300019 PM 8075773 ER PT J AU SCIACCHITANO, CJ MOPPER, B SPECCHIO, JJ AF SCIACCHITANO, CJ MOPPER, B SPECCHIO, JJ TI IDENTIFICATION AND SEPARATION OF 5 CEPHALOSPORINS BY MICELLAR ELECTROKINETIC CAPILLARY CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article; Proceedings Paper CT 4th Annual Frederick Conference on Capillary Electrophoresis CY OCT 19-20, 1993 CL FREDERICK, MD ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ANTIBIOTICS; CEFOTAXIME; SODIUM AB The cephalosporins are a group of structurally related, broad spectrum beta-lactam antibiotics isolated from the mold Cephalosporium. Methods of analysis of cephalosporin antibiotics include microbiological, titrimetric and chromatographic assays. Chromatographic techniques, including high-performance liquid chromatography, have been extensively utilized for specific and sensitive assays of beta-lactam antibiotics in a variety of matrices, i.e. clinical and pharmaceutical. Several of the drawbacks of HPLC in the analysis of cephalosporins in food and biological samples include matrix interferences and low resolution due to column adsorption. Recently, the applicability of capillary electrophoresis to the resolution of beta-lactam antibiotics has been demonstrated in the literature. In this paper we employed sodium berate and an anionic surfactant, sodium dodecyl sulfate (SDS), in a separation technique called micellar electrokinetic capillary chromatography with UV detection, to resolve a mixture of five cephalosporins-cefuroxime, cephalexin, cephapirin, cefamandole nafate and cephalothin. The presence of SDS in the running buffer above the critical micelle concentration, creates a pseudostationary phase enabling high-efficiency chromatographic separations. The effect of the ion-pairing reagent, pentanesulfonic acid sodium salt, on the resolution of the cephalosporin mixture in conjunction with SDS was also examined. RP SCIACCHITANO, CJ (reprint author), US FDA,NE REG LAB,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 16 TC 41 Z9 44 U1 1 U2 7 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 15 PY 1994 VL 657 IS 2 BP 395 EP 399 DI 10.1016/0378-4347(94)00355-6 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PA243 UT WOS:A1994PA24300017 PM 7952104 ER PT J AU TESKE, RH AF TESKE, RH TI UNTITLED SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Editorial Material RP TESKE, RH (reprint author), US FDA,CTR VET MED,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JUL 15 PY 1994 VL 205 IS 2 BP 191 EP 192 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA NW866 UT WOS:A1994NW86600019 ER PT J AU MITCHELL, B AF MITCHELL, B TI COMPLIANCE POLICY GUIDELINE ENFORCEMENT ISSUES SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article RP MITCHELL, B (reprint author), US FDA,CTR VET MED,OFF SURVEILLANCE & COMPLIANCE,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JUL 15 PY 1994 VL 205 IS 2 BP 201 EP 202 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA NW866 UT WOS:A1994NW86600025 PM 7928574 ER PT J AU GLOYD, J MITCHELL, B POWERS, T BARROWS, T NASH, D SIEGNER, W ROGERS, M TESKE, R DUDLEY, S SHELDON, J LENZ, T OELLER, D GEYER, RE BAGLEY, C AF GLOYD, J MITCHELL, B POWERS, T BARROWS, T NASH, D SIEGNER, W ROGERS, M TESKE, R DUDLEY, S SHELDON, J LENZ, T OELLER, D GEYER, RE BAGLEY, C TI COMPOUNDING FOR TREATMENT OF TOXICOSIS - DISCUSSION SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Discussion C1 OHIO STATE UNIV,DEPT VET PHYSIOL & PHARMACOL,COLUMBUS,OH 43210. HYMAN PHELPS & MCNAMARA PC,WASHINGTON,DC 20005. VET ADM MED CTR,WORTHINGTON,MN 56187. AMER ASSOC EQUINE PRACTITIONERS,LEXINGTON,KY 40511. US FDA,CTR VET MED,OFF SURVEILLANCE & COMPLIANCE,ROCKVILLE,MD 20855. UTAH STATE UNIV,DEPT ANIM DAIRY & VET SCI,LOGAN,UT 84322. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JUL 15 PY 1994 VL 205 IS 2 BP 217 EP 220 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA NW866 UT WOS:A1994NW86600032 ER PT J AU GUSHEE, J AF GUSHEE, J TI WHEN DOES COMPOUNDING BECOME MANUFACTURING SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article RP GUSHEE, J (reprint author), US FDA,DEPT HLTH & HUMAN SERV,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JUL 15 PY 1994 VL 205 IS 2 BP 235 EP 236 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA NW866 UT WOS:A1994NW86600037 PM 7928585 ER PT J AU GEYER, RE AF GEYER, RE TI LEGAL RESTRICTIONS ON COMPOUNDING SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article RP GEYER, RE (reprint author), US FDA,CTR VET MED,OFF SURVEILLANCE & COMPLIANCE,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JUL 15 PY 1994 VL 205 IS 2 BP 241 EP 242 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA NW866 UT WOS:A1994NW86600040 PM 7928588 ER PT J AU BALLITCH, EJ AF BALLITCH, EJ TI LABELING AND RECORD-KEEPING FOR COMPOUNDED DRUGS SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article RP BALLITCH, EJ (reprint author), US FDA,CTR VET MED,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JUL 15 PY 1994 VL 205 IS 2 BP 249 EP 250 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA NW866 UT WOS:A1994NW86600043 PM 7928591 ER PT J AU TESKE, R BARROWS, T GEYER, RE SIEGNER, W TERRY, M NEWTON, D SEARS, JE GLOYD, J RIVIERE, J HARDEE, GE POWERS, T SHELDON, J AF TESKE, R BARROWS, T GEYER, RE SIEGNER, W TERRY, M NEWTON, D SEARS, JE GLOYD, J RIVIERE, J HARDEE, GE POWERS, T SHELDON, J TI LABELING AND RECORD-KEEPING FOR COMPOUNDED DRUGS - DISCUSSION SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Discussion C1 US FDA,CTR VET MED,OFF SURVEILLANCE & COMPLIANCE,ROCKVILLE,MD 20855. HYMAN PHELPS & MCNAMARA PC,WASHINGTON,DC 20005. ALBANY COLL PHARM,DEPT PHARMACEUT,ALBANY,NY 12208. N CAROLINA STATE UNIV,COLL VET MED,CTR CUTANEOUS PHARMACOL & TOXICOL,RALEIGH,NC 27606. UPJOHN CO,DRUG DELIVERY RES & DEV,VET PROD,KALAMAZOO,MI 49001. OHIO STATE UNIV,DEPT VET PHYSIOL & PHARMACOL,COLUMBUS,OH 43210. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JUL 15 PY 1994 VL 205 IS 2 BP 250 EP 253 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA NW866 UT WOS:A1994NW86600044 ER PT J AU MITCHELL, B AF MITCHELL, B TI ANTICIPATED REGULATORY ENFORCEMENT SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article RP MITCHELL, B (reprint author), US FDA,CTR VET MED,OFF SURVEILLANCE & COMPLIANCE,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JUL 15 PY 1994 VL 205 IS 2 BP 299 EP 299 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA NW866 UT WOS:A1994NW86600063 PM 7928608 ER PT J AU ELLENBERG, S AF ELLENBERG, S TI SURROGATE MARKERS IN AIDS AND CANCER TRIALS - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion ID HUMAN-IMMUNODEFICIENCY-VIRUS; PLACEBO-CONTROLLED TRIAL; HOMOSEXUAL MEN; HIV-INFECTION; DOUBLE-BLIND; ZIDOVUDINE; LYMPHOCYTES; EFFICACY; COMPLEX; COUNTS RP ELLENBERG, S (reprint author), US FDA,CBER,OELPS,DIV BIOSTAT & EPIDEMIOL,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 12 TC 5 Z9 5 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 JUL 15 PY 1994 VL 13 IS 13-14 BP 1437 EP 1440 DI 10.1002/sim.4780131319 PG 4 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PA168 UT WOS:A1994PA16800017 ER PT J AU BURKE, G AF BURKE, G TI EARLY STOPPING RULES - CLINICAL PERSPECTIVES AND ETHICAL CONSIDERATIONS - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion RP BURKE, G (reprint author), US FDA,DIV ONCOL,ROCKVILLE,MD 20857, USA. NR 0 TC 2 Z9 2 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 JUL 15 PY 1994 VL 13 IS 13-14 BP 1471 EP 1472 DI 10.1002/sim.4780131323 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 PA168 UT WOS:A1994PA16800021 ER PT J AU ONEILL, RT AF ONEILL, RT TI THE RELATIONSHIP BETWEEN CLINICAL-TRIALS AND CLINICAL-PRACTICE - THE RISKS OF UNDERESTIMATING ITS COMPLEXITY .2. SO STATISTICS IN MEDICINE LA English DT Editorial Material AB I have been asked to take an overall view of the presentations in this 'Early stopping rules' workshop and to extract some messages from them. In attempting to meet the charge to summarize what I have heard and what I have concluded over the last two days, I will focus on the following issues: the underlying theme of the workshop concerns whether the statistical strategies proposed for monitoring trials are a help or a hindrance to the successful completion of clinical trials; how much of a problem is this and what should be done about it; whether the current diversity in practical operational aspects of data monitoring and analysis is responsible for some trials being stopped earlier than planned and thus should we begin to develop some consensus on 'good practices and procedures' in this area; and finally to place this topic within the broader public health framework of clinical trials of treatments for any life-threatening disease, what are the regulatory impacts and consequences of early stopping, especially when decisions regarding the licensure and marketing of treatments depends upon results from monitored clinical trials that might be stopped early. RP ONEILL, RT (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV BIOMETR,ROCKVILLE,MD 20857, USA. NR 0 TC 12 Z9 12 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 JUL 15 PY 1994 VL 13 IS 13-14 BP 1493 EP 1499 DI 10.1002/sim.4780131327 PG 7 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 PA168 UT WOS:A1994PA16800025 ER PT J AU FENICHEL, RR LIPICKY, RJ AF FENICHEL, RR LIPICKY, RJ TI COMBINATION PRODUCTS AS FIRST-LINE PHARMACOTHERAPY SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material RP FENICHEL, RR (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD HFD110,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 0 TC 31 Z9 32 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 11 PY 1994 VL 154 IS 13 BP 1429 EP 1430 DI 10.1001/archinte.154.13.1429 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NW090 UT WOS:A1994NW09000001 PM 7880229 ER PT J AU BASNAKIAN, AG JAMES, SJ AF BASNAKIAN, AG JAMES, SJ TI A RAPID AND SENSITIVE ASSAY FOR THE DETECTION OF DNA FRAGMENTATION DURING EARLY PHASES OF APOPTOSIS SO NUCLEIC ACIDS RESEARCH LA English DT Note ID CELLS; DEATH RP BASNAKIAN, AG (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 12 TC 46 Z9 47 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 11 PY 1994 VL 22 IS 13 BP 2714 EP 2715 DI 10.1093/nar/22.13.2714 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NZ215 UT WOS:A1994NZ21500042 PM 8041637 ER PT J AU GRASELA, TH WALAWANDER, CA JOLSON, HM KENNEDY, DL AF GRASELA, TH WALAWANDER, CA JOLSON, HM KENNEDY, DL TI ALTERNATIVES TO INTRAVENOUS TETRACYCLINE HYDROCHLORIDE FOR MALIGNANT PLEURAL EFFUSIONS SO ANNALS OF PHARMACOTHERAPY LA English DT Letter C1 US FDA,DIV ANTIVIRAL DRUG PROD,CTR DRUG EVALUAT & RES,OFF DRUG EVALUAT 2,ROCKVILLE,MD 20857. RP GRASELA, TH (reprint author), SUNY BUFFALO,CTR PHARMACOEPIDEMIOL RES,319 COOKE HALL,BUFFALO,NY 14260, USA. FU FDA HHS [FD-U-000741-01] NR 5 TC 1 Z9 1 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUL-AUG PY 1994 VL 28 IS 7-8 BP 968 EP 969 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PB270 UT WOS:A1994PB27000038 PM 7524817 ER PT J AU MCCARTHY, SA KHAMBATY, FM AF MCCARTHY, SA KHAMBATY, FM TI INTERNATIONAL DISSEMINATION OF EPIDEMIC VIBRIO-CHOLERAE BY CARGO SHIP BALLAST AND OTHER NONPOTABLE WATERS SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID STATES GULF-COAST; UNITED-STATES; TOXIGENIC VIBRIO-CHOLERAE-O1; MOLECULAR EPIDEMIOLOGY; AMERICA AB In 1991 and 1992, toxigenic Vibrio cholerae 01, serotype Inaba, biotype Fl Tor, was recovered from nonpotable (ballast, bilge, and sewage) water from five cargo ships docked in ports of the U.S. Gulf of Mexico. Four of these ships had taken on ballast water in cholera-infected countries; the fifth took on ballast in a noninfected country. Isolates examined by pulsed-field gel electrophoresis were indistinguishable from the Latin American epidemic strain, C6707; however, they differed significantly from the endemic Gulf Coast strain (VRL 1984), the sixth-pandemic strain (569-B), and a V. cholerae non-01 strain isolated from a ship arriving from a foreign port. On the basis of our findings, the Food and Drug Administration recommended that the U.S. Coast Guard issue an advisory to shipping agents and captains requesting that ballast waters be exchanged on the high seas before entry of ships into U.S. ports. C1 US FDA,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204. RP MCCARTHY, SA (reprint author), US FDA,GULF COAST SEAFOOD LAB,POB 158,DAUPHIN ISL,AL 36528, USA. NR 32 TC 127 Z9 135 U1 0 U2 10 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 1994 VL 60 IS 7 BP 2597 EP 2601 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA NV572 UT WOS:A1994NV57200056 PM 8074532 ER PT J AU HAREWOOD, P RIPPEY, S MONTESALVO, M AF HAREWOOD, P RIPPEY, S MONTESALVO, M TI EFFECT OF GAMMA-IRRADIATION ON SHELF-LIFE AND BACTERIAL AND VIRAL LOADS IN HARD-SHELLED CLAMS (MERCENARIA-MERCENARIA) SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Note ID ESCHERICHIA-COLI; ENUMERATION AB The feasibility of using Co-60 gamma irradiation to inactivate total coliforms, fecal coliforms, Escherichia coli, Clostridium perfringens, and F-coliphage in hard-shelled clams, Mercenaria mercenaria, was investigated. The results of three trials indicated average D-10 values of 1.32 kGy for total coliforms, 1.39 kGy for fecal coliforms, 1.54 kGy for E. coli, 2.71 kGy for C. perfringens, and 13.50 kGy for F-coliphage. Irradiation doses of >0.5 kGy were significantly lethal to the shellfish. C1 US FDA,NE SEAFOOD LAB,N KINGSTOWN,RI 02852. UNIV LOWELL,RADIAT LAB,LOWELL,MA 01854. NR 16 TC 18 Z9 19 U1 0 U2 8 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 1994 VL 60 IS 7 BP 2666 EP 2670 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA NV572 UT WOS:A1994NV57200069 PM 8074539 ER PT J AU FERGUSON, SA HOLSON, RR PAULE, MG AF FERGUSON, SA HOLSON, RR PAULE, MG TI EFFECTS OF METHYLAZOXYMETHANOL-INDUCED MICRENCEPHALY ON TEMPORAL RESPONSE DIFFERENTIATION AND PROGRESSIVE RATIO RESPONDING IN RATS SO BEHAVIORAL AND NEURAL BIOLOGY LA English DT Note ID TEST BATTERY; DEFICITS; LESIONS AB Micrencephalic Sprague-Dawley rats were produced by an injection of 20 mg/kg methylazoxymethanol acetate on gestational Day 14. Brain weights of the offspring were 70% of controls while weights of frontal cortex and hippocampus were approximately 58% (Ferguson, Racey, Paule, and Holson, 1993). Operant performance was measured with particular emphasis on assessment of time estimation. The temporal response differentiation (TRD) and the progressive ratio (PR) tasks, previously used in the NCTR operant test battery for monkeys, were chosen for evaluation. The TRD schedule is notably different from other temporal tasks in that it requires subjects to initiate and maintain a lever press for 10-14 s. The PR task was included as a measure of motivation to work for food reinforcers. Micrencephalics acquired and performed both tasks comparably to controls. During extinction, however, micrencephalics exhibited an increased TRD lever hold duration. This suggests an atypical response perseveration, that is, perseverating the previously correct response. Previously, frontal cortical alterations were suggested to contribute heavily to micrencephalic-induced behavioral alterations (Ferguson et al., 1993). This study provides further evidence that response perseveration, a hallmark of frontal cortical lesions, is expressed in micrencephalic rats. (C) 1994 Academic Press, Inc. 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,HFT 130,JEFFERSON,AR 72079, USA. NR 18 TC 20 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0163-1047 J9 BEHAV NEURAL BIOL JI Behav. Neural Biol. PD JUL PY 1994 VL 62 IS 1 BP 77 EP 81 DI 10.1016/S0163-1047(05)80062-7 PG 5 WC Behavioral Sciences; Neurosciences; Psychology SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA NW114 UT WOS:A1994NW11400011 PM 7945149 ER PT J AU MCLAUGHLIN, LG HENION, JD KIJAK, PJ AF MCLAUGHLIN, LG HENION, JD KIJAK, PJ TI MULTI-RESIDUE CONFIRMATION OF AMINOGLYCOSIDE ANTIBIOTICS AND BOVINE KIDNEY BY ION-SPRAY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY TANDEM MASS-SPECTROMETRY SO BIOLOGICAL MASS SPECTROMETRY LA English DT Article ID SOLID-PHASE DISPERSION; CHEMICAL IONIZATION; REVERSED-PHASE; TISSUE; GENTAMICIN; THERMOSPRAY; EXTRACTION; IVERMECTIN; INHIBITOR; CRITERIA AB An ion spray high-performance liquid chromatographic/tandem mass spectrometric (HPLC/MS/MS) method capable of determining the following six aminoglycosides in bovine kidney is presented: spectinomycin, hygromycin B, streptomycin, dihydrostreptomycin, gentamicin C complex and neomycin B. Tobramycin was used as an internal standard. This method uses an improved matrix solid-phase dispersion (MSPD) method for tissue extraction. A gradient HPLC separation was developed with mobile phases consisting of aqueous 20 mM pentafluoropropionic acid and acetonitrile. Protonated molecules served as precursor ions for collision-induced dissociation (CID) and three product ions were chosen for each analyte for selected reaction monitoring (SRM) where possible. A validation study was conducted for the confirmation of dihydrostreptomycin, neomycin B and four major components of the gentamicin C complex through SRM HPLC/MS/MS analysis of negative control, fortified and incurred bovine kidney samples. All of the samples analyzed could be confirmed with ion ratios within 15% of the daily mean of fortified standards and 90% of the samples had ion ratios within 10%. All compounds except spectinomycin could be detected (while monitoring three ions by SRM) in bovine kidney tissue at or below the regulatory level of concern. MSPD recoveries were aceptable with the exception of the 27% value observed for spectinomycin. C1 CORNELL UNIV,NEW YORK STATE COLL VET MED,ANALYT TOXICOL DIAGNOST LAB,ITHACA,NY 14850. US FDA,CTR VET MED,DIV RESIDUE CHEM,BELTSVILLE,MD 20705. FU FDA HHS [FD-U-000577-02] NR 51 TC 87 Z9 93 U1 2 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1052-9306 J9 BIOL MASS SPECTROM JI Biol. Mass Spectrom. PD JUL PY 1994 VL 23 IS 7 BP 417 EP 429 DI 10.1002/bms.1200230706 PG 13 WC Biophysics; Spectroscopy SC Biophysics; Spectroscopy GA NW622 UT WOS:A1994NW62200005 PM 8068737 ER PT J AU TOYODA, M SAITO, Y UCHIYAMA, M TROY, AL TRUCKSESS, MW PAGE, SW AF TOYODA, M SAITO, Y UCHIYAMA, M TROY, AL TRUCKSESS, MW PAGE, SW TI FORMATION OF A 3-(PHENYLAMINO)ALANINE CONTAMINANT IN EMS-ASSOCIATED L-TRYPTOPHAN SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY LA English DT Note ID EOSINOPHILIA-MYALGIA-SYNDROME; TOXIC OIL SYNDROME; 1,1'-ETHYLIDENEBIS(L-TRYPTOPHAN) AB Chemical studies were conducted to determine the origin of the 3-(phenylamino)alanine (PAA) contaminant in EMS-associated L-tryptophan samples. Anthranilic acid, a biosynthetic precursor of the L-tryptophan, was heated at 80 degrees C for 6 h under acidic conditions to produce 140 mu g of aniline/g of anthranilic acid. The presence of aniline was verified by HPLC-UV and GC-MS. PAA (160 mu g of PAA/g of aniline) was produced by heating aniline and serine at 80 degrees C for 6h under basic conditions. PAA was confirmed by HPLC-UV and LC-MS. These results suggest that PAA could be formed under the fermentation and purification conditions used to produce L-tryptophan on an industrial scale. C1 US FDA, CTR FOOD SAFETY & APPL NUTR, WASHINGTON, DC 20204 USA. RP TOYODA, M (reprint author), NATL INST HLTH SCI, SETAGAYA KU, 1-18 KAMIYOGA 1 CHOME, TOKYO 158, JAPAN. NR 12 TC 7 Z9 7 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0916-8451 EI 1347-6947 J9 BIOSCI BIOTECH BIOCH JI Biosci. Biotechnol. Biochem. PD JUL PY 1994 VL 58 IS 7 BP 1318 EP 1320 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA NZ263 UT WOS:A1994NZ26300027 ER PT J AU NAKAJIMA, M YOKOI, T MIZUTANI, M SHIN, S KADLUBAR, FF KAMATAKI, T AF NAKAJIMA, M YOKOI, T MIZUTANI, M SHIN, S KADLUBAR, FF KAMATAKI, T TI PHENOTYPING OF CYP1A2 IN JAPANESE POPULATION BY ANALYSIS OF CAFFEINE URINARY METABOLITES - ABSENCE OF MUTATION PRESCRIBING THE PHENOTYPE IN THE CYP1A2 GENE SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN HEPATIC MICROSOMES; CIGARETTE-SMOKING; CYTOCHROME-P-450 MONOOXYGENASES; CARCINOGENIC ARYLAMINES; THEOPHYLLINE METABOLISM; PHENACETIN METABOLISM; LIVER-MICROSOMES; XANTHINE-OXIDASE; MESSENGER-RNA; OXIDATION AB Caffeine has been used as a metabolic probe to determine the relative levels of CYPlA2 activity in different individuals, since this compound is specifically 3-demethylated by CYPlA2. Urine specimen obtained at a 4-5-h interval after caffeine ingestion from 205 Japanese were analyzed using the [1,7-dimethyluric acid + 1,7-dimethylxanthinel/caffeine (1,3,7-trimethylxanthine) ratio, which better correlated with the rate constant for caffeine 3-demethylation than other ratios. The probit analyses of nonsmokers (n = 147) and smokers (n = 58) suggested that the CYP1A2 activity was not normally distributed and appeared bimodal. The breakpoints were at 5.0 and 6.0 of (1,7-dimethyluric acid + 1,7-dimethylxanthine)/1,3,7-trimethylxanthine ratio in nonsmokers and smokers, respectively. The bimodal probit plot suggested the existence of poor and extensive phenotypes. The percentage of individuals with the poor phenotype in Japanese was 14.1%. Induction of CYP1A2 by cigarette smoking was confirmed by the higher molar ratio observed in smokers (P < 0.0001). The CYP1A2 ratio was also higher in males than in females (P = 0.04). A reproducibility study of 12 subjects in an 11 month interval period showed that intraindividual variability did not alter this CYPlA2 phenotypic classification. Family study in eight pedigrees suggested that the poor phenotype of CYPlA2 inherited as an autosomal recessive trait. The sequences of CYP1A2 gene from poor and extensive metabolizers were analyzed. Although no differences of nucleotide sequence were observed in exons, exon-intron junctions and 5'-flanking regions (up to -2.6 kilobases) of CYP1A2 gene between each phenotype, there were some sequences which differed from the previous reported data. This is the first report in which the CYP1A2 phenotype and a genetic polymorphism in the CYP1A2 gene were comparably investigated. C1 HOKKAIDO UNIV,FAC PHARMACEUT SCI,DIV DRUG METAB,N12W6,KITA KU,SAPPORO,HOKKAIDO 060,JAPAN. OTSUKA PHARMACEUT CO LTD,OTSUKA ASSAY LABS,TOKUSHIMA 77101,JAPAN. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RI Nakajima, Miki/C-3990-2015; yokoi, tsuyoshi/I-7115-2014 NR 47 TC 135 Z9 140 U1 0 U2 1 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 JUL-AUG PY 1994 VL 3 IS 5 BP 413 EP 421 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NX376 UT WOS:A1994NX37600008 PM 7920209 ER PT J AU LI, EE HEFLICH, RH BUCCI, TJ MANJANATHA, MG BLAYDES, BS DELCLOS, KB AF LI, EE HEFLICH, RH BUCCI, TJ MANJANATHA, MG BLAYDES, BS DELCLOS, KB TI RELATIONSHIPS OF DNA ADDUCT FORMATION, K-RAS ACTIVATING MUTATIONS AND TUMORIGENIC ACTIVITIES OF 6-NITROCHRYSENE AND ITS METABOLITES IN THE LUNGS OF CD-1 MICE SO CARCINOGENESIS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; HAMSTER OVARY CELLS; NEWBORN MOUSE ASSAY; LIVER-TUMORS; P-32-POSTLABELING ASSAY; ADENOMA BIOASSAY; P53 MUTATIONS; GENE; CARCINOGENICITY; INDUCTION AB 6-Nitrochrysene (6-NC), an environmental pollutant and a potent mouse lung carcinogen, is activated by two major metabolic pathways to yield DNA adducts derived from either trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene (1,2-DHD-6-AC) or N-hydroxy-6-aminochrysene (N-OH-6-AC). While the former pathway has been shown to be the major activation pathway leading to DNA adducts in mice treated with 6-NC, the potential contribution of the minor nitroreduction pathway to tumorigenicity in this system is not clear. To evaluate the roles of these activation pathways and the resulting DNA adducts in mouse lung tumorigenesis, we studied DNA adduct formation, the induction of tumors and tumor K-ras mutational spectra in the lungs of male CD-1 mice treated with 6-NC and its metabolites. 6-NC, 6-AC and 1,2-DHD-6-AC produced predominantly a single chromatographically identical dG adduct, and 6-nitrosochrysene (6-NOC) gave a single major adduct that was most likely derived from reaction at the C8 position of deoxyadenosine. 6-NC-, 1,2-DHD-6-AC- and 6-NOC-treated mice developed both adenomas and adenocarcinomas in the lung, whereas only lung adenomas were observed in 6-AC-treated animals. K-ras mutations in adenomas resulting from 6-NC and its metabolites were primarily at G:C basepairs in codons 12 and 13, while adenocarcinomas had K-ras mutations distributed between codons 12, 13 and 61, and involved both G:C and A:T basepairs. The K-ras mutational spectra in codons 12 and 13 were similar in both adenomas and adenocarcinomas, whereas a higher percentage of mutations at A:T in codon 61 was found in adenocarcinomas. These results support the conclusion that the 1,2-DHD-6-AC-derived adduct is associated with both adenoma and adenocarcinoma formation and is the primary lesion involved in the induction of mouse lung tumors by 6-NC. The major adduct detected after 6-NOC treatment, which is derived from N-OH-6-AC, is apparently less efficient as an inducer of mouse lung tumors and is associated more specifically with adenocarcinoma formation. C1 NATL CTR TOXICOL RES,DIV BIOCHEM,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,DIV GENET TOXICOL,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,PATHOL ASSOCIATES INC,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. NR 42 TC 32 Z9 33 U1 0 U2 0 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 JUL PY 1994 VL 15 IS 7 BP 1377 EP 1385 DI 10.1093/carcin/15.7.1377 PG 9 WC Oncology SC Oncology GA NW755 UT WOS:A1994NW75500013 PM 8033314 ER PT J AU JAMES, SJ MILLER, BJ MCGARRITY, LJ MORRIS, SM AF JAMES, SJ MILLER, BJ MCGARRITY, LJ MORRIS, SM TI THE EFFECT OF FOLIC-ACID AND/OR METHIONINE DEFICIENCY ON DEOXYRIBONUCLEOTIDE POOLS AND CELL-CYCLE DISTRIBUTION IN MITOGEN-STIMULATED RAT LYMPHOCYTES SO CELL PROLIFERATION LA English DT Article ID DNA STRAND BREAKS; MAMMALIAN-CELLS; METHYL-DONOR; FOLATE; METABOLISM; REPAIR; DAMAGE; RIBONUCLEOTIDES; ACCUMULATION; TOXICITY AB Folate deficiency will induce abnormal deoxynucleoside triphosphate (dNTP) metabolism because folate-derived one-carbon groups are essential for de novo synthesis of purines and the pyrimidine, thymidylate. Under conditions of methionine deprivation, a functional folate deficiency for deoxynucleoside triphosphate synthesis is induced as a result of the irreversible diversion of available folates toward endogenous methionine resynthesis from homocysteine. The purpose of the present study was to examine the effect of nutritional folate and/or methionine deprivation in vitro on intracellular dNTP pools as related to DNA synthesis activity and cell cycle progression. Primary cultures of mitogen-stimulated rat splenic T-cells were incubated in complete RPMI 1640 medium or in custom-prepared RPMI 1640 medium lacking in folic acid and/or methionine. Parallel cultures, initiated from the same cell suspension, were analysed for deoxyribonucleotide pool levels and for cell proliferation. The distribution of cells within the cell cycle was quantified by dual parameter flow cytometric bromodeoxyuridine/propidium iodide DNA analysis which allows more accurate definition of DNA synthesizing S-phase cells than the traditional DNA-specific staining with propidium iodide alone. Relative to cells cultured in complete RPMI 1640 media, the cells cultured in media deficient in folate, methionine or in both nutrients manifested increases in the deoxythymidylate pool and an apparent depletion of the deoxyguanosine triphosphate pool. Both adenosine triphosphate and nicotinamide adenine diphosphate levels were significantly reduced with single or combined deficiencies of folate and methionine. These nucleotide pool alterations were associated with a decrease in the proportion of cells actively synthesizing DNA and an increase in cells in G(2) +M phase of the cell cycle. Folate deprivation in the presence of adequate methionine produced a moderate decrease in DNA synthesizing cells over the 68 h incubation. However, methionine deprivation, in the presence or absence of folate, severely compromised DNA synthesis activity. These results are consistent with the established 'methyl trap' diversion of available folates towards the resynthesis of methionine from homocysteine and away from nucleotide synthesis. The data confirm the metabolic interdependence of folic acid and methionine and emphasize the pivotal role of methionine on the availability of folate one-carbon groups for deoxynucleotide synthesis. The decrease in DNA synthesis activity under nutrient conditions that negatively affect nucleotide biosynthesis suggest a possible role for abnormal dNTP metabolism in the regulation of cell cycle progression and DNA synthesis. RP JAMES, SJ (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 35 TC 25 Z9 25 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7722 J9 CELL PROLIFERAT JI Cell Prolif. PD JUL PY 1994 VL 27 IS 7 BP 395 EP 406 DI 10.1111/j.1365-2184.1994.tb01471.x PG 12 WC Cell Biology SC Cell Biology GA NW285 UT WOS:A1994NW28500003 ER PT J AU SCHWIETERMAN, WD MANOUSSAKIS, M KLINMAN, DM STEINBERG, AD AF SCHWIETERMAN, WD MANOUSSAKIS, M KLINMAN, DM STEINBERG, AD TI STUDIES OF MARROW PROGENITOR ABNORMALITIES IN LUPUS-PRONE MICE .2. FURTHER-STUDIES OF NZB THY 1(NEG)LIN(NEG) BONE-MARROW CELLS SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; LEUKEMIA INHIBITORY FACTOR; ENDOGENOUS RETROVIRAL EXPRESSION; SYSTEMIC AUTOIMMUNE-DISEASE; COLONY-FORMING CELLS; ZEALAND BLACK MICE; LONG-TERM CULTURE; LYMPHOCYTE-B; APOPTOSIS GENE; MURINE LUPUS AB Bone marrow cells from NZB mice were fractionated and enriched in cells lacking surface markers characteristic of mature lineages, termed Thy 1(neg) Lineage(neg) cells. These cells represent approximately 1% of all marrow cells and constitute a much greater fraction of the bone marrow than do Thy 1(lo) Lineage(neg) cells. The NZB Thy 1(neg) Lineage(neg) cells were able to protect nonautoimmune, histocompatible DBA/2 recipients from lethal doses of irradiation, suggesting that this subpopulation contained progenitor cells. Consistent with this observation, fractioned Lip 6(+) Thy 1(neg) Lineage(neg) cells, representing early B lineage cells, were less effective than Lip 6(neg) Thy 1(neg) Lineage(neg) cells in radioprotection. NZB marrow contains a great many more CFU-S than does marrow from nonautoimmune strains. DBA/2 mice transplanted with Thy 1(neg) Lineage(neg) cells from NZB marrow had substantial numbers of CFU-S, much greater than controls. This CFU-S potential was found primarily in the Lip 6(neg) Thy 1(neg) Lineage(neg) fractionated marrow, suggesting that that population contained early progenitor cells that had not yet differentiated into B lineage cells. Both radioprotection and increased CFU-S were transmitted serially by bone marrow from DBA/2 recipients of Thy 1(neg) Lineage(neg) NZB marrow to secondary and tertiary (irradiated) DBA/2 recipients. Also serially transplanted were precursors of antibody forming cells. These findings suggest that NZB Thy 1(neg) Lineage (neg) marrow cells play a critical role in the development of the abnormal phenotype of NZB mice. However, because this probably is not a homogeneous population, additional work will be necessary to define the surface and molecular properties of the cell or cells within the NZB Thy 1(neg) Lineage (neg) marrow population which serve as progenitors of the cells which mediate NZB disease. (C) 1994 Academic Press, Inc. C1 MITRE CORP,MCLEAN,VA 22102. NIAMDSK,ARTHRITIS RHEUMATISM BRANCH,BETHESDA,MD. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. NR 51 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD JUL PY 1994 VL 72 IS 1 BP 114 EP 120 DI 10.1006/clin.1994.1114 PG 7 WC Immunology; Pathology SC Immunology; Pathology GA NV074 UT WOS:A1994NV07400016 PM 8020184 ER PT J AU SHVEDOVA, AA KRAMARIK, JA KEOHAVONG, P CHUMAKOV, KM KAROL, MH AF SHVEDOVA, AA KRAMARIK, JA KEOHAVONG, P CHUMAKOV, KM KAROL, MH TI USE OF ANTI-TNF-ALPHA ANTISERUM TO INVESTIGATE TOXIC ALVEOLITIS ARISING FROM COTTON DUST EXPOSURE SO EXPERIMENTAL LUNG RESEARCH LA English DT Article DE ALVEOLITIS; COTTON DUST; INFLAMMATION; MESSENGER-RNA MOUSE; TUMOR NECROSIS FACTOR ID TUMOR-NECROSIS-FACTOR; IDIOPATHIC PULMONARY FIBROSIS; BRONCHOALVEOLAR LAVAGE; GUINEA-PIGS; MACROPHAGES; CELLS; LUNG; RELEASE; INJURY; SILICA AB Cotton dust has been associated with byssinosis and toxic alveolitis. A murine animal model has been developed with which to investigate the pathogenesis of these disorders. Studies with the model have reproduced the neutrophilic inflammation characteristic of the alveolitis, and have shown the presence of tumor necrosis factor-alpha (TNF-alpha) in the bronchoalveolar lavage (BAL) fluid. The current study investigated the role of TNF-alpha in the inflammatory response by use of a polyclonal antiserum to recombinant murine TNF-alpha. Following a 4-h exposure to cotton dust, experimental animals showed a 40-fold increase in BAL cells with 92% neutrophils. There was a 24-fold increase in TNF-alpha in the BAL fluid. Up regulation of TNF-alpha mRNA expression was detected in BAL cells. Mice pretreated with anti-TNA-alpha antiserum displayed a marked attenuation of the neutrophilic inflammation; however, the level of TNF-alpha mRNA expression was not reduced in these mice. These studies support a major role of TNF-alpha in the toxic alveolitis induced by cotton dust inhalation. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. RP SHVEDOVA, AA (reprint author), UNIV PITTSBURGH,DEPT ENVIRONM & OCCUPAT HLTH,PITTSBURGH,PA 15238, USA. OI Keohavong, Phouthone/0000-0001-7812-4925 FU NIEHS NIH HHS [ES 05651] NR 49 TC 9 Z9 9 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD JUL-AUG PY 1994 VL 20 IS 4 BP 297 EP 315 DI 10.3109/01902149409064389 PG 19 WC Respiratory System SC Respiratory System GA PD765 UT WOS:A1994PD76500003 PM 7988494 ER PT J AU SHEU, CW DOBRAS, SN RODRIGUEZ, I LEE, JK FU, PP AF SHEU, CW DOBRAS, SN RODRIGUEZ, I LEE, JK FU, PP TI TRANSFORMING ACTIVITY OF SELECTED POLYCYCLIC AROMATIC-HYDROCARBONS AND THEIR NITRO-DERIVATIVES IN BALB/3T3 A31-1-1 CELLS SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID HAMSTER EMBRYO CELLS; MORPHOLOGICAL TRANSFORMATION; NEOPLASTIC TRANSFORMATION; CHEMICAL CARCINOGENS; 6-NITROBENZOPYRENE; 6-NITROCHRYSENE; 1-NITROPYRENE; GENOTOXICITY; MUTAGENICITY; INDUCTION AB The transforming activities of four polycyclic aromatic hydrocarbons and six of their nitro-derivatives were studied using BALB/3T3 clone A31-1-1 cells in the absence of exogenous metabolic activation. Each compound was assayed two to four times to its maximal level of solubility. A transformation response was induced by 1-nitropyrene, 2-nitropyrene, 4-nitropyrene and benzo[a]pyrene in the BALB/3T3 mouse embryo cells. Pyrene and 7-nitrobenz[a]anthracene produced questionable responses, and benz[a]anthracene, chrysene, 6-nitrobenzo[a]pyrene and 6-nitrochrysene produced negative responses. The capacity of the assay system to indicate tumorigenicity of the test compounds is discussed. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MATH,BIOMETR & RISK ASSESSMENT BRANCH,WASHINGTON,DC 20204. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP SHEU, CW (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MOLEC BIOL RES & EVALUAT,GENET TOXICOL BRANCH,HFS-236,WASHINGTON,DC 20204, USA. NR 23 TC 8 Z9 8 U1 2 U2 2 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 JUL PY 1994 VL 32 IS 7 BP 611 EP 615 DI 10.1016/0278-6915(94)90004-3 PG 5 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA PB008 UT WOS:A1994PB00800004 PM 8045474 ER PT J AU ROSENSTEIN, M WEBSTER, EW AF ROSENSTEIN, M WEBSTER, EW TI EFFECTIVE DOSE TO PERSONNEL WEARING PROTECTIVE APRONS DURING FLUOROSCOPY AND INTERVENTIONAL RADIOLOGY SO HEALTH PHYSICS LA English DT Letter C1 MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA 02114 USA. RP ROSENSTEIN, M (reprint author), CTR DEVICES & RADIOL HLTH, OFF HLTH PHYS, ROCKVILLE, MD 20850 USA. NR 8 TC 34 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUL PY 1994 VL 67 IS 1 BP 88 EP 89 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA NT232 UT WOS:A1994NT23200012 PM 8200807 ER PT J AU ELKINS, KL ENNIST, DL WINEGAR, RK WEIR, JP AF ELKINS, KL ENNIST, DL WINEGAR, RK WEIR, JP TI IN-VIVO DELIVERY OF INTERLEUKIN-4 BY A RECOMBINANT VACCINIA VIRUS PREVENTS TUMOR-DEVELOPMENT IN MICE SO HUMAN GENE THERAPY LA English DT Article ID STIMULATORY FACTOR-I; IMMUNODEFICIENT MICE; NECROSIS-FACTOR; GAMMA-INTERFERON; GENE-THERAPY; CELL-GROWTH; VECTOR; EXPRESSION; INFECTION; INVIVO AB To study the immunotherapeutic potential of interleukin-4 (IL-4) delivered in vivo via a recombinant vaccinia virus, a thymidine kinase-negative (TK-) vaccinia virus that expressed the murine IL-4 gene (VV1/IL-4) was constructed. When mice were inoculated with 10(7) plaque-forming units (pfu) of VV1/IL-4 subcutaneously (s.c.), 10(5) pfu/cm(2) were found in skin, and smaller numbers in liver and kidney between 1 and 7 days after infection; few viral pfu were found in spleen and lung, or in any organ after intravenous infection. This suggested that recombinant vaccinia viruses might be most efficient at delivery of cytokine genes to the skin. Because IL-4 has recently been found to have potent anti-tumor activity, the effect of recombinant virus infection on the development of s.c. tumors was studied. A single s.c. inoculation with VV1/IL-4 delayed the development of NCTC 2472 tumors, but when VV1/IL-4 was inoculated s.c. weekly for 8 weeks, turner development was completely prevented in 93% of mice. Similarly, the development of M-3 melanoma tumors was also prevented by weekly s.c. inoculations of VV1/IL-4. About 40% of mice treated with control VV2/beta gal by the same regimen also failed to develop tumors. Weekly virus treatment did not prevent NCTC 2472 tumor development in athymic nu/nu mice, suggesting that mature T cells are required for expression of VV1/IL-4 induced antitumor activity. Thus, recombinant vaccinia viruses may be especially well suited for convenient therapeutic delivery of immunomodulator genes to skin-related sites. C1 WALTER REED ARMY INST RES,DEPT CELLULAR IMMUNOL,ROCKVILLE,MD 20852. NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. RP ELKINS, KL (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,ENTER & SEXUALY TRANSMITTED DIS LAB,BETHESDA,MD 20852, USA. NR 48 TC 28 Z9 29 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL PY 1994 VL 5 IS 7 BP 809 EP 820 DI 10.1089/hum.1994.5.7-809 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA NY715 UT WOS:A1994NY71500004 PM 7981307 ER PT J AU LU, CH LEE, CJ KIND, P AF LU, CH LEE, CJ KIND, P TI IMMUNE-RESPONSES OF YOUNG MICE TO PNEUMOCOCCAL TYPE 9V POLYSACCHARIDE-TETANUS TOXOID CONJUGATE SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; STREPTOCOCCUS-PNEUMONIAE; CAPSULAR POLYSACCHARIDE; ANTIBODY-RESPONSE; NEISSERIA-MENINGITIDIS; PROTEIN CONJUGATE; VACCINE; IMMUNIZATION; INFECTION; INFANTS AB Pneumococcal type 9V polysaccharide (PS), contained in the current pneumococcal vaccine, induces only a weak antibody response in young children and therefore is not an effective vaccine for young children. To increase its immunogenicity, a conjugate of PS to a protein carrier, tetanus toroid (TT), was prepared. To quantify the immune response, mouse anti-9V PS immunoglobulin G (IgG) and IgM reference standards were established. Young mice immunized at 2 weeks of age produced IgM antibody in response to 9V PS alone or 9V PS conjugated to TT. However, only the 9V PS-TT conjugate induced an IgG antibody response and an anamnestic effect. Thus, a covalent linkage between TT and 9V PS was required for isotype switching from IgM to IgG. 9V PS-TT adsorbed with aluminum hydroxide adjuvant resulted in a fivefold or greater increase in the IgG antibody level. We also studied the effect of maternal immunization on the immune response of young mice to 9V PS-TT. Maternal immunization before mating or before mating and during gestation primed 2-week-old progeny given two injections of 9V PS-TT to produce more IgM antibody than progeny from unimmunized mothers. The IgG antibody level of neonates at birth was similar to that observed in the mothers and was probably passive antibody. These results indicate that maternal immunization with an optimum dose of a PS-protein conjugate before and/or during pregnancy, followed by immunization of the offspring with the conjugate, could provide young children with an enhanced IgM antibody response to pneumococcal PSs. C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20037. CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 46 TC 20 Z9 20 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 1994 VL 62 IS 7 BP 2754 EP 2760 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NU014 UT WOS:A1994NU01400014 PM 8005665 ER PT J AU UMEHARA, H MINAMI, Y DOMAE, N BLOOM, ET AF UMEHARA, H MINAMI, Y DOMAE, N BLOOM, ET TI INCREASED PROCESSING OF LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 IN HUMAN NATURAL-KILLER-CELLS STIMULATED WITH IL-2 SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE ADHESION MOLECULE; CELL SURFACE; CYTOTOXIC LYMPHOCYTES; IL-2; INTEGRIN; LAK; LFA-1; NATURAL KILLER ID LEUKOCYTE ADHESION DEFICIENCY; LARGE GRANULAR LYMPHOCYTES; COMMON BETA-SUBUNIT; HUMAN-NEUTROPHILS; INTERLEUKIN-2 RECEPTOR; MONOCLONAL-ANTIBODIES; CROSS-LINKING; MESSENGER-RNA; NK ACTIVITY; LFA-1 AB Previously we reported that surface expression of lymphocyte function-associated antigen-1 (LFA-1), the primary leukocyte integrin on human natural killer (NK) and lymphokine-activated killer (LAK) cells, does not differ between NK and LAK cells. In contrast to surface expression, we now report that much higher levels of both precursor and mature forms of LFA-1 molecules were found relative to MHC class I, another membrane glycoprotein, with metabolic labeling of IL-2-stimulated LAK cells compared with native NK cells. An 85 - 90 kDa glycoprotein, found in much higher quantities in LAK compared with NK cells, appeared to be a precursor of the 95 kDa beta chain of the beta2 integrin family in human LAK cells because: (i) pulse-chase experiments using LAK cells demonstrated decreased S-35-labeling of the 85 - 90 kDa molecule with a concomitant increase in the radioactivity of the mature 95 kDa LFA-1 beta chain, (ii) results of protease treatment revealed that the two molecules share virtually identical peptide maps, and (iii) endoglycosaminidase F treatment of LAK cell lysates immunoprecipitated with antibody against LFA-1beta resulted in the disappearance of both the 85-90 and 96 kDa LFA-1 beta signals, and appearance of a signal at approximately 76 kDa. Digestion of the same immunoprecipitates with neuraminidase resulted in the disappearance of the 95 kDa signal and revealed a single molecular weight signal corresponding to 85 - 90 kDa. These data suggest that a core protein of approximately 76 kDa becomes N-glycosylated, perhaps terminally with sialic acid residues, to mature into the 95 kDa form. Moreover, the rate of maturation of LFA-1 was more rapid in LAK than NK cells, with half times of 0.8 versus 1.5 h for the alpha chain and 3.7 versus 4.9 h for the beta chain for LAK versus NK cells respectively. IL-2 treatment of NK cells therefore alters the processing of LFA-1 molecules during the transition to LAK cells, providing a larger intracellular reservoir with which to replenish the surface molecule. Together with our previous observation that LFA-1 is phosphorylated and transduces signal more effectively in LAK than NK cells, the findings support the notion that adhesion molecules contribute to the increased function of LAK cells. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES HEM518,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. OSAKA DENT UNIV,CHUO KU,OSAKA 540,JAPAN. OSAKA UNIV,INST MOLEC & CELLULAR BIOL,SUITA,OSAKA 565,JAPAN. NR 46 TC 15 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUL PY 1994 VL 6 IS 7 BP 1071 EP 1080 DI 10.1093/intimm/6.7.1071 PG 10 WC Immunology SC Immunology GA NY685 UT WOS:A1994NY68500017 PM 7947458 ER PT J AU BARKER, SA LONG, AR AF BARKER, SA LONG, AR TI PREPARATION OF MILK SAMPLES FOR IMMUNOASSAY AND LIQUID-CHROMATOGRAPHIC SCREENING USING MATRIX SOLID-PHASE DISPERSION SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID 9 CHLORINATED PESTICIDES; MULTIRESIDUE METHOD; MSPD EXTRACTION; SULFONAMIDES AB The use of drugs to maintain the health and maximize the output of dairy cattle has made the monitoring of milk for such agents essential. Screening tests based on immunological, microbial inhibition, and bacterial receptor assays have been developed for the detection of violative levels of therapeutic substances. However, such assays are not infallible, and false positive or negative results can occur when contaminants bind receptors or compete for the binding of the target residues. Such effects may arise from dietary sources, diseases, or other variables. Thus, a violation by such a test is not definitive until further confirmation is obtained. Our laboratory has developed extraction procedures for several drugs used in dairy production. Our method uses matrix solid-phase dispersion (MSPD) to isolate drugs away from contaminants and to eliminate many possible interferences. MSPD can also be used to enhance the specificity of such assays by fractionating various classes of drugs that may cross-react. Similarly, such methods may be used for liquid chromatographic screening and confirmation of a suspect sample. C1 US FDA,ANIM DRUG RES CTR,DENVER FED CTR,DENVER,CO 80225. RP BARKER, SA (reprint author), LOUISIANA STATE UNIV,SCH VET MED,DEPT PHYSIOL PHARMACOL & TOXICOL,RESIDUE STUDIES LAB,BATON ROUGE,LA 70803, USA. FU FDA HHS [FDA FD-U-000235, FDA 5U01-FD-01319, FDA FD-U-000581] NR 17 TC 10 Z9 11 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 1994 VL 77 IS 4 BP 848 EP 854 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NY376 UT WOS:A1994NY37600012 PM 8069113 ER PT J AU MOPPER, B SCIACCHITANO, CJ AF MOPPER, B SCIACCHITANO, CJ TI CAPILLARY ZONE ELECTROPHORETIC DETERMINATION OF HISTAMINE IN FISH SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; BIOGENIC-AMINES; HPLC AB Histamine, the principal causative agent in scombroid food poisoning, was analyzed in seafood by a new, rapid, and sensitive method using capillary zone electrophoresis (CZE) with UV detection at 210 nm. Incurred histamine in methanolic fish extracts migrated within 4 min in a fused silica capillary filled with 0.02 M citrate buffer, pH 2.5, under an applied potential of 375 V/cm. The analytical response was linear from 0.5 to 100 ppm histamine (correlation coefficient, r = 0.999). The coefficients of variation for migration time and peak area response were <1 and <3%, respectively. Recovery of histamine in fortified fish composites was satisfactory. CZE was considered for alternative application in seafood speciation. RP MOPPER, B (reprint author), US FDA,NE REG LAB,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 13 TC 29 Z9 29 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 1994 VL 77 IS 4 BP 881 EP 884 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NY376 UT WOS:A1994NY37600018 PM 8069116 ER PT J AU STEHLY, GR PLAKAS, SM ELSAID, KR AF STEHLY, GR PLAKAS, SM ELSAID, KR TI LIQUID-CHROMATOGRAPHIC DETERMINATION OF FURAZOLIDONE IN SHRIMP SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TISSUE AB A liquid chromatographic (LC) method was developed for the quantitation of furazolidone residues in shrimp muscle. The shrimp homogenate (1.0 g) is extracted with acetonitrile, and the extract is taken to dryness. The residue is dissolved in acetonitrile, and the solution is passed through alumina and C18 cleanup columns. The eluate is taken to dryness and reconstituted in a suitable solvent for reversed-phase (C18) LC with UV detection at 365 nm. Recoveries of furazolidone from shrimp homogenates spiked from 5 to 80 ng/g ranged from 74.3 to 79.7%, and relative standard deviations (RSDs) were 5.0-8.9%. RSDs for incurred furazolidone quantitated at 5.9 and 9.2 ng/g were 6.6 and 7.6%, respectively. C1 US FDA,GULF COAST SEAFOOD LAB,DAUPHIN ISL,AL 36528. NR 7 TC 4 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 JUL-AUG PY 1994 VL 77 IS 4 BP 901 EP 904 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NY376 UT WOS:A1994NY37600022 PM 8069120 ER PT J AU ANDREWS, WH AF ANDREWS, WH TI UPDATE ON VALIDATION OF MICROBIOLOGICAL METHODS BY AOAC-INTERNATIONAL SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB An update is presented of the microbiological methods validated by AOAC since 1983. A sequential listing of the microbiological methods adopted first action between 1939 and 1993 gives the permanent new numbers of each, as introduced in Official Methods of Analysis, 15th Edition. Consideration is given to the expanded applicability of approved methods with respect to food matrix; the predominance of methods for the detection, identification, and serological testing of Salmonella spp.; and the procedures for coliforms and Escherichia coli, which were most frequently approved between 1973 and 1993. The substantial increase in validation of test kits is discussed, and categories of methods for the modification of test kits already approved are defined. RP ANDREWS, WH (reprint author), US FDA,DIV MICROBIOL STUDIES,200 C ST SW,WASHINGTON,DC 20204, USA. NR 9 TC 2 Z9 2 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 JUL-AUG PY 1994 VL 77 IS 4 BP 925 EP 931 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NY376 UT WOS:A1994NY37600026 PM 8069124 ER PT J AU FIRESTONE, D AF FIRESTONE, D TI DIRECT GRAPHITE-FURNACE ATOMIC-ABSORPTION METHOD FOR DETERMINATION OF LEAD IN EDIBLE OILS AND FATS - SUMMARY OF COLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The IUPAC Commission on Oils, Fats, and Derivatives undertook development of a method and collaborative study for the determination of lead in oils and fats by direct graphite furnace-atomic absorption spectrophotometric method. Various types of graphite furnaces were used with or without platform. Twenty-three collaborators from 12 countries participated in the study. The materials tested were edible oils (soybean oil) and fats (cocoa butter) containing lead at 3 concentration levels (low, medium, and high). Each level was represented by 2 batches provided in duplicate (blind coded), so that each collaborator received a total of 24 test samples. Collaborators were instructed to analyze each in duplicate and report both results. Twenty collaborators returned the results of the study. After data from laboratories that did not follow the instructions were excluded, only 16 sets of data were evaluated statistically. The method for determination of lead in oils and fats by direct graphite furnace-atomic absorption spectrophotometry has been adopted first action by AOAC INTERNATIONAL as an IUPAC-AOCS-AOAC method. RP FIRESTONE, D (reprint author), US FDA,DIV PESTICIDES & IND CHEM,HFS-336,200 C ST SW,WASHINGTON,DC 20204, USA. NR 5 TC 10 Z9 10 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 1994 VL 77 IS 4 BP 951 EP 954 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NY376 UT WOS:A1994NY37600031 PM 8069126 ER PT J AU FIRESTONE, D AF FIRESTONE, D TI LIQUID-CHROMATOGRAPHIC METHOD FOR DETERMINATION OF TRIGLYCERIDES IN VEGETABLE-OILS IN TERMS OF THEIR PARTITION NUMBERS - SUMMARY OF COLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The IUPAC Commission on Oils, Fats and Derivatives undertook development of a method and collaborative study for the determination of triglycerides in vegetable oils by liquid chromatography. Three collaborative studies were conducted from 1985 to 1987. Refinements were made in the method after the first collaborative study, and the second and third collaborative studies demonstrated that the method produces acceptable results. Materials studied were soybean oil, almond oil, sunflower oil, olive oil, rapeseed oil, and blends of palm and sunflower oils, and almond and sunflower oils. Six test samples were analyzed by 18 laboratories from 11 countries in the second study; 4 test samples were analyzed by 16 laboratories from 12 countries in the third study. The method for determination of triglycerides (by partition numbers) in vegetable oils by liquid chromatography was adopted first action by AOAC INTERNATIONAL as an IUPAC-AOCS-AOAC method. RP FIRESTONE, D (reprint author), US FDA,DIV PESTICIDES & IND CHEM,HFS-336,200 C ST SW,WASHINGTON,DC 20204, USA. NR 3 TC 12 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 JUL-AUG PY 1994 VL 77 IS 4 BP 954 EP 957 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NY376 UT WOS:A1994NY37600032 PM 8069127 ER PT J AU FIRESTONE, D AF FIRESTONE, D TI GEL-PERMEATION LIQUID-CHROMATOGRAPHIC METHOD FOR DETERMINATION OF POLYMERIZED TRIGLYCERIDES IN OILS AND FATS - SUMMARY OF COLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The IUPAC Commission on Oils, Fats and Derivatives undertook development of a method and collaborative study for determination of polymerized triglycerides in oils and fats. Two collaborative studies were carried out by IUPAC in 1985 and 1986. Both studies consisted of 4 materials, including animal fat, frying oil with average content of polymers, and blends of frying oil containing varying amounts of polymers. Thirteen and 17 laboratories were included in the first and second IUPAC collaborative studies, respectively. Another collaborative study conducted by Inspectorate for Health Protection, Food Inspection Service, The Netherlands, included 13 laboratories. Six heat-processed fat samples (3 pairs of split samples) containing 14-28% (w/w) of polymerized triglycerides were studied. The method was adopted by AOAC INTERNATIONAL as an IUPAC-AOCS-AOAC method. RP FIRESTONE, D (reprint author), US FDA,DIV PESTICIDES & IND CHEM,HFS-336,200 C ST SW,WASHINGTON,DC 20204, USA. NR 3 TC 6 Z9 6 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 1994 VL 77 IS 4 BP 957 EP 960 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NY376 UT WOS:A1994NY37600033 PM 8069128 ER PT J AU MINDAK, WR AF MINDAK, WR TI DETERMINATION OF LEAD IN TABLE WINES BY GRAPHITE-FURNACE ATOMIC-ABSORPTION SPECTROMETRY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MATRIX INTERFERENCES; ALCOHOLIC BEVERAGES; ASCORBIC-ACID; MODIFIER; BLOOD; TEMPERATURE; PALLADIUM; PLATFORM; CADMIUM; COPPER AB A quick, easy method was developed for the analysis of table wines for lead quantitated at greater-than-or-equal-to 14 ng Pb/mL wine. The method uses graphite furnace atomic absorption spectrometry with Zeeman background correction and a L'vov pyrolytic graphite platform. Ammonium dihydrogen phosphate is used as a matrix modifier. Wines are diluted by a factor of 10 with 1% HNO3 and analyzed directly. Their absorbances are compared with those of a standard curve prepared with 1% HNO3. Analytical results obtained by comparison with a standard curve agreed with those obtained by the method of standard additions. Four white, 4 red, and 2 rose wines were studied. Pb concentrations varied from 15 to 135 ng Pb/mL. Wines fortified with 100 ng Pb/mL had an average recovery of 94%. The average short-term relative standard deviation (RSD) was 2.1%; the average long-term RSD was 7.4%. The estimated detection (3 sigma) and quantitation (10 sigma) limits were 4 and 14 ng Pb/mL, respectively. RP MINDAK, WR (reprint author), US FDA,ELEMENTAL RES BRANCH,200 C ST SW,WASHINGTON,DC 20204, USA. NR 52 TC 13 Z9 13 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 1994 VL 77 IS 4 BP 1023 EP 1030 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NY376 UT WOS:A1994NY37600042 PM 8069109 ER PT J AU SCHENCK, FJ WAGNER, R HENNESSY, MK OKRASINSKI, JL AF SCHENCK, FJ WAGNER, R HENNESSY, MK OKRASINSKI, JL TI SCREENING-PROCEDURE FOR ORGANOCHLORINE AND ORGANOPHOSPHORUS PESTICIDE-RESIDUES IN EGGS USING A SOLID-PHASE EXTRACTION CLEANUP AND GAS-CHROMATOGRAPHIC DETECTION SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A solid-phase extraction (SPE) screening procedure for the isolation and gas chromatographic (GC) determination of organochlorine and organophosphorus pesticide residues in eggs is described. Eggs are extracted with acetonitrile. The extract is subjected to a cleanup on tandem C18 and Florisil SPE columns. Organochlorine and organophosphorus pesticide residues are determined by GC with electron capture and flame photometric detection, respectively. Because the injected extracts are free from matrix interferences, the amount of residue present is easy to calculate. The average recoveries of 9 spiked organochlorine pesticide residues (0.01-1.0 ppm) ranged from 80.9 to 91.1%. The average recoveries of 7 spiked organophosphorus pesticide residues (0.02-0.50 ppm) ranged from 80.3 to 89.5%. The SPE method results in a 90% reduction in organic solvent consumption and an 85% reduction in hazardous waste production compared with the AOAC methodology. RP SCHENCK, FJ (reprint author), US FDA,BALTIMORE DIST,900 MADISON AVE,BALTIMORE,MD 21201, USA. NR 7 TC 30 Z9 34 U1 1 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 1994 VL 77 IS 4 BP 1036 EP 1040 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NY376 UT WOS:A1994NY37600044 PM 8069110 ER PT J AU DAY, TL TATANI, SR NOTERMANS, S BENNETT, RW AF DAY, TL TATANI, SR NOTERMANS, S BENNETT, RW TI A COMPARISON OF ELISA AND RPLA FOR DETECTION OF BACILLUS-CEREUS DIARRHEAL ENTEROTOXIN SO JOURNAL OF APPLIED BACTERIOLOGY LA English DT Article ID TOXIN PRODUCTION; DIARRHEAL; MILK; PURIFICATION AB Fourteen strains of Bacillus cereus isolated from different sources were examined for their ability to produce diarrhoeal enterotoxin by two commercial immunoassay kits (Oxoid BCET-RPLA and Tecra ELISA) and the microslide immunodiffusion assay. One strain that was positive in monkey feedings, as well as a number of other strains isolated from diarrhoeal outbreaks, gave positive results in the ELISA and negative results in the RPLA test systems. When tested in the microslide assay, these strains produced only one antigen which formed a line of identity with the reference toxin. The results of the control toxins provided with the kits substantiated that the two commercial assays did not detect the same antigen. Cultures positive with both assay kits were shown to produce diarrhoeal enterotoxin (by a line of identity) and other antigens in the microslide immunodiffusion assay. C1 UNIV MINNESOTA,DEPT FOOD SCI & NUTR,ST PAUL,MN 55108. RIVM,BILTHOVEN,NETHERLANDS. US FDA,WASHINGTON,DC 20204. NR 18 TC 22 Z9 23 U1 2 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0021-8847 J9 J APPL BACTERIOL JI J. Appl. Bacteriol. PD JUL PY 1994 VL 77 IS 1 BP 9 EP 13 DI 10.1111/j.1365-2672.1994.tb03037.x PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA NW732 UT WOS:A1994NW73200002 PM 7928785 ER PT J AU WUNDER, DE AARONSON, W HAYES, SF BLISS, JM SILVER, RP AF WUNDER, DE AARONSON, W HAYES, SF BLISS, JM SILVER, RP TI NUCLEOTIDE-SEQUENCE AND MUTATIONAL ANALYSIS OF THE GENE ENCODING KPSD, A PERIPLASMIC PROTEIN INVOLVED IN TRANSPORT OF POLYSIALIC ACID IN ESCHERICHIA-COLI K1 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CAPSULAR POLYSACCHARIDE; MOLECULAR ANALYSIS; MEMBRANE-PROTEINS; SUICIDE VECTOR; RNA-POLYMERASE; GROUP-B; EXPRESSION; CONSTRUCTION; BACTERIA; CLUSTER AB The 17-kb kps gene cluster encodes proteins necessary for the synthesis, assembly, and translocation of the polysialic acid capsule of Escherichia coli K1. We previously reported that one of these genes, kpsD, encodes a 60-kDa periplasmic protein that is involved in the translocation of the polymer to the cell surface. The nucleotide sequence of the 2.4-kb BamHI-PstI fragment accommodating the kpsD gene was determined. Sequence analysis showed an open reading frame for a 558-amino-acid protein,vith a typical N-terminal prokaryotic signal sequence corresponding to the first 20 amino acids. KpsD was overexpressed, partially purified, and used to prepare polyclonal antiserum. A chromosomal insertion mutation was generated in the kpsD gene and results in loss of surface expression of the polysialic acid capsule. Immunodiffusion analysis and electron microscopy indicated that polysaccharide accumulates in the periplasmic space of mutant cells. A wild-type copy of kpsD supplied in trans complemented the chromosomal mutation, restoring extracellular expression of the K1 capsule. However, a kpsD deletion derivative (kpsD Delta C11), which results in production of a truncated KpsD protein lacking its 11 C-terminal amino acids, was nonfunctional. Western blot (immunoblot) data from cell fractions expressing KpsD Delta C11 suggest that the truncated protein was inefficiently exported into the periplasm and localized primarily to the cytoplasmic membrane. C1 UNIV ROCHESTER, MED CTR, DEPT MICROBIOL & IMMUNOL, ROCHESTER, NY 14642 USA. CTR BIOL EVALUAT & RES, BETHESDA, MD 20892 USA. NIAID, ROCKY MT LABS, VECTORS & PATHOGENS LAB, HAMILTON, MT 59840 USA. RI Bliss, Joseph/C-7446-2013 FU NIAID NIH HHS [AI26655] NR 60 TC 34 Z9 39 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 1994 VL 176 IS 13 BP 4025 EP 4033 PG 9 WC Microbiology SC Microbiology GA NU758 UT WOS:A1994NU75800024 PM 8021185 ER PT J AU HEIKES, DL AF HEIKES, DL TI SFE WITH GC AND MS DETERMINATION OF SAFROLE AND RELATED ALLYLBENZENES IN SASSAFRAS TEAS SO JOURNAL OF CHROMATOGRAPHIC SCIENCE LA English DT Article ID SUPERCRITICAL-FLUID EXTRACTION; POLYCYCLIC AROMATIC-HYDROCARBONS; PERFORMANCE LIQUID-CHROMATOGRAPHY; POLYCHLORINATED-BIPHENYLS; CARBON-DIOXIDE; ENVIRONMENTAL-ANALYSIS; GAS-CHROMATOGRAPHY; TRANS-ANETHOLE; SAMPLES; SOLIDS RP HEIKES, DL (reprint author), US FDA,TOTAL DIET RES CTR,POB 15905,LENEXA,KS 66285, USA. NR 49 TC 23 Z9 23 U1 0 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 JUL PY 1994 VL 32 IS 7 BP 253 EP 258 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NW808 UT WOS:A1994NW80800001 PM 8063885 ER PT J AU TAGA, K CHRETIEN, J CHERNEY, B DIAZ, L BROWN, M TOSATO, G AF TAGA, K CHRETIEN, J CHERNEY, B DIAZ, L BROWN, M TOSATO, G TI INTERLEUKIN-10 INHIBITS APOPTOTIC CELL-DEATH IN INFECTIOUS-MONONUCLEOSIS T-CELLS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE EPSTEIN-BARR VIRUS; PROGRAMMED CELL DEATH; BCRF-1; CELL SURVIVAL; DNA FRAGMENTATION ID EPSTEIN-BARR-VIRUS; AUTOCRINE GROWTH-FACTOR; CYTOKINE SYNTHESIS; LYMPHOCYTES-T; B-CELLS; DIFFERENTIATION FACTOR; STIMULATORY FACTOR; INTERFERON-GAMMA; FLOW-CYTOMETRY; IL-10 AB T lymphocytes from patients with acute EBV-induced infectious mononucleosis rapidly die by apoptosis in vitro. Because human and viral IL-10 are likely to be induced during acute EBV infection and display a variety of functions on human T cells, we examined IL-10 effects on infectious mononucleosis T cell death. After 12 h of incubation in medium alone, only 35.6 (+/-8.2%) of the originally seeded infectious mononucleosis T cells were viable. Addition of human IL-10 (100 U/ml) to T cell cultures significantly improved recovery of viable cells (71.3+/-6.2%, P = 0.0156). Viral IL-10 had comparable effects to human IL-10 in this system. Protection from death by human and viral IL-10 (100 U/ml) was dose dependent and continued over a 6-d culture period. The human IL-10 effect was neutralized by the anti-human IL-10 mAb 19F1. Morphology and analysis of DNA after separation on agarose gels showed that IL-10 inhibits loss of cell volume, chromatin condensation, and DNA fragmentation, characteristics of death by apoptosis. As assessed by [H-3]thymidine incorporation, the T cells were not induced to proliferate by IL-10 above the level exhibited when first removed from blood. T cells protected from death by IL-10 proliferated to IL-2 and spontaneously killed sensitive targets as effectively as medium-precultured T cells. Thus, IL-10 promotes the survival of infectious mononucleosis T cells otherwise destined to die by apoptosis and may be critical for the establishment of immunologic memory after resolution of the illness. C1 GEORGETOWN UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20007. NIH,BETHESDA,MD 20892. RP TAGA, K (reprint author), US FDA,CTR BIOL EVALUAT & RES,IMMUNOL LAB,BLDG 29A,ROOM 2D06,ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 60 TC 69 Z9 69 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1994 VL 94 IS 1 BP 251 EP 260 DI 10.1172/JCI117315 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NW496 UT WOS:A1994NW49600033 PM 8040267 ER PT J AU CAMERON, DN KHAMBATY, FM WACHSMUTH, IK TAUXE, RV BARRETT, TJ AF CAMERON, DN KHAMBATY, FM WACHSMUTH, IK TAUXE, RV BARRETT, TJ TI MOLECULAR CHARACTERIZATION OF VIBRIO-CHOLERAE O1 STRAINS BY PULSED-FIELD GEL-ELECTROPHORESIS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID STATES GULF-COAST; UNITED-STATES; TOXIGENIC VIBRIO-CHOLERAE-O1; EPIDEMIOLOGIC APPLICATION; LATIN-AMERICA; TOXIN GENES; COLI; DNA AB Pulsed-field gel electrophoresis (PFGE) was performed on 180 isolates of Vibrio cholerae serogroup 01 representing 6 different multilocus enzyme electrophoresis (MEE) types and 27 rRNA restriction fragment length polymorphism types (ribotypes). Isolates were digested with the restriction enzyme NotI and were separated into 63 patterns on the basis of differences in band arrangements. In general, strains which were different by MEE or ribotyping also had different PFGE patterns. PFGE identified individual strains within a single MEE type or ribotype; isolates with one PFGE pattern were less frequently distinguished by ribotyping. All V. cholerae 01 isolates tested from the Latin American epidemic were indistinguishable by their MEE, ribotype, or PFGE patterns. PFGE could further distinguish strains of this same ribotype isolated in Africa, Europe, the South Pacific, or Southeast Asia. Although both MEE and PFGE could identify the strain from the Latin American epidemic, PFGE was more rapid and less labor intensive. PFGE also distinguished nontoxigenic isolates endemic to the U.S. Gulf Coast from unrelated nontoxigenic isolates. In the present study PFGE was more discriminating than other previously described subtyping assays for V. cholerae 01 and appears to be a useful epidemiologic tool. C1 US FDA,DIV MICROBIOL STUDIES,MICROBIAL ECOL BRANCH,WASHINGTON,DC 20204. RP CAMERON, DN (reprint author), CTR DIS CONTROL & PREVENT,FDDB,DBMD,NATL CTR INFECT DIS,DIV BACTERIAL & MYCOT DIS,ATLANTA,GA 30333, USA. NR 25 TC 120 Z9 126 U1 0 U2 1 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 1994 VL 32 IS 7 BP 1685 EP 1690 PG 6 WC Microbiology SC Microbiology GA NR924 UT WOS:A1994NR92400013 PM 7929758 ER PT J AU DECASTRO, VGL TIMENETSKY, MD GREENBERG, H SANTOS, N AF DECASTRO, VGL TIMENETSKY, MD GREENBERG, H SANTOS, N TI ROTAVIRUS SEROTYPE-G5 ASSOCIATED WITH DIARRHEA IN BRAZILIAN CHILDREN (VOL 32, PG 1408, 1994) SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Correction, Addition C1 INST ADOLFO LUTZ REGISTRO,VIROL LAB,SAO PAULO,BRAZIL. US FDA,DIV MICROBIOL,WASHINGTON,DC 20204. STANFORD UNIV,DIV GASTROENTEROL,STANFORD,CA 94305. RP DECASTRO, VGL (reprint author), INST OSWALDO CRUZ,DEPT VIROL,RIO JANEIRO,BRAZIL. RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 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 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 1994 VL 32 IS 7 BP 1834 EP 1834 PG 1 WC Microbiology SC Microbiology GA NR924 UT WOS:A1994NR92400046 ER PT J AU WEAGANT, SD BRYANT, JL BARK, DH AF WEAGANT, SD BRYANT, JL BARK, DH TI SURVIVAL OF ESCHERICHIA-COLI O157-H7 IN MAYONNAISE AND MAYONNAISE-BASED SAUCES AT ROOM AND REFRIGERATED TEMPERATURES SO JOURNAL OF FOOD PROTECTION LA English DT Note DE ESCHERICHIA-COLI O157-H7; MAYONNAISE; MAYONNAISE-BASED SAUCES; ROOM AND REFRIGERATED TEMPERATURES ID HEMOLYTIC UREMIC SYNDROME; APPLE CIDER; SEROTYPE AB Three Escherichia coli O157:H7 (EHEC) strains were inoculated separately into portions of commercially prepared mayonnaise held at 25 or 7-degrees-C, then examined periodically for survival of detectable EHEC. Four mayonnaise-based sauces including: a) mayonnaise-mustard sauce, b) blue cheese dressing, c) thousand island dressing and d) seafood sauce, were each inoculated with one EHEC strain. Samples of these sauces were held at 5-degrees-C, and assayed periodically for survival of detectable EHEC. Both direct plate count and selective enrichment recovery were employed as assay procedures. Escherichia coli O157:H7 strains, when inoculated and mixed into mayonnaise and stored at 25-degrees-C, became undetectable after 72 h storage when assayed by direct plating or by selective enrichment. The same strains inoculated into mayonnaise and stored at 7-degrees-C were detectable up to 35 days when assayed by direct plating or by selective enrichment. Escherichia coli O157:H7 inoculated into mayonnaise-based sauces and held at 5-degrees-C were detectable past 35 days in three of the four sauces. Loss of EHEC culturability occurred within 3 days in mayonnaise-mustard sauce. RP WEAGANT, SD (reprint author), US FDA,SEATTLE DIST LAB,BOTHELL,WA 98041, USA. NR 12 TC 159 Z9 161 U1 1 U2 10 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 1994 VL 57 IS 7 BP 629 EP 631 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA NZ593 UT WOS:A1994NZ59300014 ER PT J AU SKINNER, GE LARKIN, JW RHODEHAMEL, EJ AF SKINNER, GE LARKIN, JW RHODEHAMEL, EJ TI MATHEMATICAL-MODELING OF MICROBIAL-GROWTH - A REVIEW SO JOURNAL OF FOOD SAFETY LA English DT Review ID NONPROTEOLYTIC CLOSTRIDIUM-BOTULINUM; TEMPERATURE FUNCTION INTEGRATION; CONCENTRATION WATER ACTIVITY; RESPONSE-SURFACE MODELS; PASTEURIZED PORK SLURRY; MODIFIED ATMOSPHERES; SODIUM-CHLORIDE; BACTERIAL-GROWTH; TOXIN PRODUCTION; LAG PHASE AB The use of mathematical modeling of microbiological behavior to predict and evaluate food safety or shelf life is receiving considerable interest. Researchers are attempting to use mathematical equations that incorporate such critical growth factors as pH, a(w) and NaCl content to predict microbial growth and/or toxin production in order to replace traditional time-intensive challenge studies. Predictive equations can be divided into probabilistic, regression, Arrhenius, and square root models. Models vary greatly in theory and complexity. Predictive models are used to monitor processes ranging from temperature during distribution to inventory control. They have been shown to be useful in product development and shelf-life estimation when safety is not an issue. Most models are generated by regression analysis of data obtained from laboratory experiments. Statistically based models, even when conservatively derived, are not appropriate as the only criterion for evaluating food safety. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV HACCP PROGRAMS,WASHINGTON,DC 20204. RP SKINNER, GE (reprint author), US FDA,NATL CTR FOOD SAFETY & TECHNOL,DIV FOOD PROC & PACKAGING,FOOD PROC HAZARD ANAL BRANCH,SUMMIT ARGO,IL 60501, USA. NR 113 TC 64 Z9 67 U1 2 U2 11 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD JUL PY 1994 VL 14 IS 3 BP 175 EP 217 DI 10.1111/j.1745-4565.1994.tb00594.x PG 43 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA PA297 UT WOS:A1994PA29700001 ER PT J AU SANTOS, N GOUVEA, V TIMENETSKY, MD CLARK, HF RIEPENHOFFTALTY, M GARBARGCHENON, A AF SANTOS, N GOUVEA, V TIMENETSKY, MD CLARK, HF RIEPENHOFFTALTY, M GARBARGCHENON, A TI COMPARATIVE-ANALYSIS OF VP8(ASTERISK) SEQUENCES FROM ROTAVIRUSES POSSESSING M37-LIKE VP4 RECOVERED FROM CHILDREN WITH AND WITHOUT DIARRHEA SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; NUCLEOTIDE-SEQUENCE; UNIQUE VP4; NEUTRALIZATION EPITOPES; STRAIN K8; 4TH GENE; INFECTIONS; NEWBORN; INFANTS; IDENTIFICATION AB Rotavirus strains belonging to G types 1 to 4 and having a P3 genotype (M37-1ike VP4) were recovered from children with symptomatic and asymptomatic infections. Partial sequences of their VP4 genes were determined in an attempt to characterize these strains further. The genomic regions encoding VP8*, the connecting and putative fusion peptides and three other regions in VP5* were sequenced. The deduced amino acid sequences were compared with rotavirus strains belonging to different P genotypes that had been previously reported. High degrees of identity were found between the VP8* fragment of all human P3 strains (92.7 to 99.7%) suggesting that they belong to the same genotype, regardless of differences in their virulence. Furthermore, based on comparative sequence analysis, we did not identify any amino acid(s) that differ appreciably between symptomatic and asymptomatic strains and could therefore be associated with virulence. The results suggest that the P3 genotype, although frequently associated with asymptomatic infections, may not be the single determining factor in attenuation of symptoms. C1 US FDA,DIV MOLEC BIOL RES & EVALUAT,WASHINGTON,DC 20204. INST ADOLFO LUTZ REGISTRO,BR-01246900 SAO PAULO,BRAZIL. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. CHILDRENS HOSP BUFFALO,BUFFALO,NY 14222. HOP ENFANTS ARMAND TROUSSEAU,F-75012 PARIS,FRANCE. RI Garbarg- Chenon, antoine/B-3397-2010; TIMENETSKY, MARIA/I-7593-2013; OI Garbarg- Chenon, antoine/0000-0003-2940-6672; Santos, Norma/0000-0002-5123-9172 NR 29 TC 27 Z9 27 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 JUL PY 1994 VL 75 BP 1775 EP 1780 DI 10.1099/0022-1317-75-7-1775 PN 7 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA NV175 UT WOS:A1994NV17500028 PM 8021606 ER PT J AU MEADE, BD BOLLEN, A AF MEADE, BD BOLLEN, A TI RECOMMENDATIONS FOR USE OF THE POLYMERASE CHAIN-REACTION IN THE DIAGNOSIS OF BORDETELLA-PERTUSSIS INFECTIONS SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID LINKED IMMUNOSORBENT-ASSAY; DNA; AMPLIFICATION; CULTURE; IDENTIFICATION; SWABS C1 FREE UNIV BRUSSELS,B-1400 NIVELLES,BELGIUM. RP MEADE, BD (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,HFM-490,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 16 TC 73 Z9 76 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD JUL PY 1994 VL 41 IS 1 BP 51 EP 55 PG 5 WC Microbiology SC Microbiology GA NV922 UT WOS:A1994NV92200009 PM 7911841 ER PT J AU DIGENIS, GA GOLD, TB SHAH, VP AF DIGENIS, GA GOLD, TB SHAH, VP TI CROSS-LINKING OF GELATIN CAPSULES AND ITS RELEVANCE TO THEIR IN-VITRO IN-VIVO PERFORMANCE SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Review ID PHENYTOIN SODIUM CAPSULES; DOSAGE FORMS; DISSOLUTION; FORMALDEHYDE; BIOAVAILABILITY; CROSSLINKING; HUMIDITY AB The present review deals with the chemistry of gelatin cross-linking under conditions that are relevant to pharmaceutical situations. Mechanistic rationalizations are offered to explain gelatin cross-linking under ''stress'' conditions. These include elevated temperature and high humidity conditions. In addition, the chemical interactions between gelatin and aldehydes, such as formaldehyde and other formulation excipients, are discussed. The literature on the in vitro and in vivo dissolution and bioavailability of a drug from stressed gelatin capsules and gelatin-coated tablets is reviewed. Cross-linking phenomena, occurring in stressed hard gelatin capsules and gelatin-coated tablets, could cause considerable changes in the in vitro dissolution profiles of drugs. However, in a few cases, the bioavailability of the drug from the stressed capsules is not significantly altered when compared to that obtained from freshly packed capsules. It is concluded that, as with other drug-delivery systems, careful attention should be paid to the purity and chemical reactivity of all excipients that are to be encapsulated in a gelatin shell. It is suggested that in vitro dissolution tests of hard gelatin-containing dosage forms be conducted in two stages, one in a dissolution medium without enzymes and secondly in dissolution media containing enzymes (pepsin at pH 1.2 or pancreatin at pH 7.2, representing gastric and intestinal media, respectively) prior to in vivo evaluation. Such in vitro tests may constitute a better indication of the in vivo behavior of gelatin-an capsulated formulations. Furthermore, testing for contamination with formaldehyde as well as low molecular weight aldehydes should be a standard part of excipient evaluation procedures. C1 US FDA,CDER,OFF GENET DRUGS,ROCKVILLE,MD 20855. RP DIGENIS, GA (reprint author), UNIV KENTUCKY,COLL PHARM,DIV MED CHEM & PHARMACEUT,LEXINGTON,KY 40536, USA. NR 43 TC 176 Z9 181 U1 7 U2 52 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 JUL PY 1994 VL 83 IS 7 BP 915 EP 921 DI 10.1002/jps.2600830702 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA NX390 UT WOS:A1994NX39000001 PM 7965669 ER PT J AU WELCH, RA AF WELCH, RA TI HIGH-RISK INDIVIDUALS NEED V-VULNIFICUS EDUCATION SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Letter RP WELCH, RA (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 1 TC 1 Z9 1 U1 1 U2 1 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUL PY 1994 VL 94 IS 7 BP 716 EP 716 DI 10.1016/0002-8223(94)91926-7 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PC112 UT WOS:A1994PC11200005 PM 8021408 ER PT J AU GOUVEA, V SANTOS, N TIMENETSKY, MD ESTES, MK AF GOUVEA, V SANTOS, N TIMENETSKY, MD ESTES, MK TI IDENTIFICATION OF NORWALK VIRUS IN ARTIFICIALLY SEEDED SHELLFISH AND SELECTED FOODS SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE GASTROENTERITIS; NORWALK VIRUS; VIRAL RNA RECOVERY; RT-PCR ID POLYMERASE CHAIN-REACTION; MOUNTAIN AGENT GASTROENTERITIS; CAPSID ANTIGEN; SNOW MOUNTAIN; STOOL SPECIMENS; ANTIBODIES; ROTAVIRUS; OUTBREAK AB A rotavirus dsRNA. purification protocol was adapted to extract Norwalk ssRNA from artificially contaminated shellfish, and a sensitive reverse transcription-polymerase chain reaction assay for Norwalk virus was devised to identify an estimated 20-200 genomic copies. The technique includes deproteinization with guanidinium isothiocyanate, adsorption of RNA to hydroxyapatite, and sequential precipitation with cetyltrimethylammonium bromide and ethanol. The protocol allows high recovery of viral RNA free of enzymatic inhibitors from oysters, clams, and a variety of food matrices. Norwalk virus sequences were copied and amplified by using primers selected from the polymerase gene. Digestion of the amplified products with restriction enzymes ensured the specificity of the test. This rapid and sensitive assay may significantly improve the prospect for the routine screening of the uncultivatable Norwalk virus in food stuffs. C1 INST ADOLFO LUTZ REGISTRO,VIROL LAB,SAO PAULO,BRAZIL. BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030. RP GOUVEA, V (reprint author), US FDA,DIV MOLEC BIOL RES & EVALUAT,WASHINGTON,DC 20204, USA. RI TIMENETSKY, MARIA/I-7593-2013; Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 FU NIAID NIH HHS [AI30448] NR 35 TC 34 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD JUL PY 1994 VL 48 IS 2-3 BP 177 EP 187 DI 10.1016/0166-0934(94)90117-1 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA PA011 UT WOS:A1994PA01100006 PM 7989435 ER PT J AU MANJANATHA, MG LINDSEY, LA MITTELSTAEDT, RA HEFLICH, RH AF MANJANATHA, MG LINDSEY, LA MITTELSTAEDT, RA HEFLICH, RH TI LOW HPRT MESSENGER-RNA LEVELS AND MULTIPLE HPRT MESSENGER-RNA SPECIES IN 6-THIOGUANINE-RESISTANT CHINESE-HAMSTER CELL MUTANTS POSSESSING NONSENSE MUTATIONS SO MUTATION RESEARCH LA English DT Article DE HPRT MESSENGER-RNA LEVELS; MESSENGER-RNA LEVELS; 6-THIOGUANINE-RESISTANT; NONSENSE MUTATIONS; CHO CELL HPRT MUTANTS; POINT MUTATIONS ID OVARY CELLS; FRAMESHIFT MUTATIONS; SEQUENCE-ANALYSIS; DNA-SEQUENCE; GENE; MOUSE; CDNA AB Previous studies suggested that many Chinese hamster ovary (CHO) cell hprt mutants having point mutations in the protein coding region also have low steady-state hprt mRNA concentrations. In addition, polymerase-chain reaction (PCR) amplification of hprt cDNA synthesized from some of these mutants results in multiple products containing deleted exons indicating that these mutants possess multiple species of hprt mRNA. In this study, we have used northern blot analysis to quantify the concentrations of hprt mRNA in 86 mutants known to possess point mutations leading to either missense or nonsense mutations. 28 of 35 nonsense mutants (80%), but only 7 of 51 missense mutants (14%), had < 50% of the hprt mRNA concentration found in parental CHO cells. Furthermore, all the nonsense mutants with premature termination codons in the internal exons of the gene (i.e., exons 3, 4, 5, 6 and 7) showed a significant reduction (averages < 16% of parental) in the steady-state levels of hprt mRNA, while nonsense mutants with termination codons situated in the extreme 5' and 3' regions of the gene had near parental hprt mRNA levels. In the same collection of mutants, the proportion of mutants producing multiple cDNA PCR products was much greater (18/35) for mutants having nonsense mutations than for mutants with missense mutations (2/51). All nonsense mutants with mutations in exons 3, 4 and 5 produced multiple species, while all those with mutations in exons 7, 8 and 9 produced a single PCR product. These results suggest that sequence changes in mammalian genes that affect protein chain length can also affect mRNA concentration and the splicing of pre-mRNA molecules. RP MANJANATHA, MG (reprint author), NATL CTR TOXICOL RES,DIV GENET TOXICOL,HFT-120,NCTR DR,JEFFERSON,AR 72079, USA. RI Lindsey-Boltz, Laura/A-3121-2010 NR 20 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUL 1 PY 1994 VL 308 IS 1 BP 65 EP 75 DI 10.1016/0027-5107(94)90199-6 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA NU644 UT WOS:A1994NU64400007 PM 7516487 ER PT J AU ALI, SF NEWPORT, GD BRACHA, HS AF ALI, SF NEWPORT, GD BRACHA, HS TI PHENCYCLIDINE AND (+)-MK-801-INDUCED CIRCLING PREFERENCE - CORRELATION WITH MONOAMINE LEVELS IN STRIATUM OF THE RAT-BRAIN SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE PHENCYCLIDINE; (+)-MK-801; CIRCLING PREFERENCE; DOPAMINE; STRIATUM; GLOBUS PALLIDUS; SCHIZOPHRENIA PSYCHOSIS ID INDUCED BEHAVIORS; INDUCED ROTATION; ANTICONVULSANT MK-801; SCHIZOPHRENIA; ASYMMETRY; RECEPTOR; AMPHETAMINE; ANTAGONIST; DOPAMINE; LESIONS AB Phencyclidine (PCP; angel dust) is a drug of abuse known to produce a behavioral state in humans resembling schizophrenia/psychosis. PCP is a noncompetitive NMDA receptor antagonist and produces a variety of behaviors in rats including circling. The behavioral effects of other noncompetitive NMDA receptor antagonists such as (+)-MK-801 are still being elucidated. Here, adult female rats were dosed with PCP (10 mg/kg, IP), or (+)-MK-801 (0.1 mg/kg, IP) and circling preference was recorded for 2 h before sacrifice to determine monoamine levels by HPLC/EC. Animals injected with PCP or (+)-MK-801 showed a preference to turn to the left (65% and 72%, respectively). PCP and (+)-MK-801 also produced a significant increase of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in whole striatum on both sides of the brain. Further dissection of the striatum into medioventral and dorsolateral regions revealed that HVA was increased bilaterally except in globus pallidus where we found significant increases in dopamine (DA), DOPAC, and HVA only on the left side after PCP and (+)-MK-801 administration. These data suggest that PCP and (+)-MK-801 produce a greater preference to turn left than right, a finding similar to that found in human psychosis. Furthermore, it is possible that this preference to turn toward the left hemispace is due to an asymmetry in dopamine function found in the globus pallidus after administration of PCP and similar drugs. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOLEC BIOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PSYCHIAT & BEHAV SCI,LITTLE ROCK,AR 72205. VET ADM MED CTR,PSYCHIAT SERV,N LITTLE ROCK,AR 72114. RP ALI, SF (reprint author), US FDA,NATL CTY TOXICOL RES,DIV NEW NEUROCHEM LAB,HFT-132,JEFFERSON,AR 72079, USA. FU NIMH NIH HHS [MH-43537] NR 38 TC 19 Z9 19 U1 0 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 JUL-AUG PY 1994 VL 16 IS 4 BP 335 EP 342 DI 10.1016/0892-0362(94)90021-3 PG 8 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA PB306 UT WOS:A1994PB30600001 PM 7968937 ER PT J AU KAUFFMAN, RE BANNER, W BERLIN, CM BLUMER, JL GORMAN, RL LAMBERT, GH WILSON, GS BENNETT, DR MULINARE, J KAUFMAN, P LICATA, SA TOMICH, P TROENDLE, G YAFFE, SJ COTE, CJ TEMPLE, AR AF KAUFFMAN, RE BANNER, W BERLIN, CM BLUMER, JL GORMAN, RL LAMBERT, GH WILSON, GS BENNETT, DR MULINARE, J KAUFMAN, P LICATA, SA TOMICH, P TROENDLE, G YAFFE, SJ COTE, CJ TEMPLE, AR TI CAMPHOR REVISITED - FOCUS ON TOXICITY SO PEDIATRICS LA English DT Editorial Material ID DATA-COLLECTION-SYSTEM C1 AMER MED ASSOC,CHICAGO,IL 60610. CTR DIS CONTROL & PREVENT,ATLANTA,GA. PHARMACEUT MANUFACTURERS ASSOC,WASHINGTON,DC. HLTH PROTECT BRANCH,OTTAWA,ON,CANADA. AMER COLL OBSTET GYNECOL,WASHINGTON,DC. US FDA,WASHINGTON,DC. NIH,BETHESDA,MD 20892. AMER ACAD PEDIAT,ANESTHESIOL SECT,ELK GROVE VILLAGE,IL. NR 11 TC 14 Z9 14 U1 0 U2 0 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 1994 VL 94 IS 1 BP 127 EP 128 PG 2 WC Pediatrics SC Pediatrics GA NU544 UT WOS:A1994NU54400031 ER PT J AU BOIS, FY TOZER, TN HAUCK, WW CHEN, ML PATNAIK, R WILLIAMS, RL AF BOIS, FY TOZER, TN HAUCK, WW CHEN, ML PATNAIK, R WILLIAMS, RL TI BIOEQUIVALENCE - PERFORMANCE OF SEVERAL MEASURES OF RATE OF ABSORPTION SO PHARMACEUTICAL RESEARCH LA English DT Article AB The highest point of the plasma concentration-time profile, C-max, is currently used by regulatory agencies to assess the rate of drug absorption after single dose administration of oral products. It is, however, quite insensitive, and a number of new measures of rate have been proposed. Using simulations, several approaches toward measuring rate were tested. A set of model scenarios for drugs with typical mean characteristics and statistical distributions was investigated. Using different kinetic models of disposition, the time course of the concentration in plasma was simulated. Intraindividual and interindividual variability and assay error were modeled using Monte Carlo techniques. The accuracy, precision, and ease of use of the various measures of rate were evaluated by simulating crossover design clinical trials and then determining the probability of declaring bioequivalence as a function of differences in rates of absorption between test and reference formulations. All of the rate measures tested showed a degree of insensitivity to changes in rate and no universally superior measure was found. Indeed, the main conclusion is that the choice of a measure should be based on simulations of the particular situation in a bioequivalence trials. C1 UNIV CALIF SAN FRANCISCO,SCH PHARM,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL & BIOSTAT,SAN FRANCISCO,CA 94143. US FDA,CTR DRUG EVALUAT & RES,OFF GENER DRUGS,ROCKVILLE,MD 20855. RP BOIS, FY (reprint author), UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,INDOOR ENVIRONM PROGRAM,MAIL STOP 90-3058,BERKELEY,CA 94720, USA. RI Bois, Frederic/E-9241-2012 OI Bois, Frederic/0000-0002-4154-0391 FU PHS HHS [224-91-3007] NR 11 TC 52 Z9 52 U1 0 U2 4 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 1994 VL 11 IS 7 BP 966 EP 974 DI 10.1023/A:1018970901116 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA NW467 UT WOS:A1994NW46700006 PM 7937556 ER PT J AU LAYLOFF, TP AF LAYLOFF, TP TI ANALYTICAL CHEMICAL CONSIDERATIONS IN PHARMACEUTICAL REGULATION SO PHARMACOPEIAL FORUM LA English DT Article RP LAYLOFF, TP (reprint author), US FDA,DIV DRUG ANAL,1114 MKT ST,ST LOUIS,MO 63101, USA. NR 4 TC 1 Z9 1 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 JUL-AUG PY 1994 VL 20 IS 4 BP 7865 EP 7869 PG 5 WC Medicine, Legal; Pharmacology & Pharmacy SC Legal Medicine; Pharmacology & Pharmacy GA NX870 UT WOS:A1994NX87000001 ER PT J AU YU, MYW MASON, BL TANKERSLEY, DL AF YU, MYW MASON, BL TANKERSLEY, DL TI DETECTION AND CHARACTERIZATION OF HEPATITIS-C VIRUS-RNA IN IMMUNE GLOBULINS SO TRANSFUSION LA English DT Article ID NON-B-HEPATITIS; NON-A-HEPATITIS; INTRAVENOUS IMMUNOGLOBULIN; CENTRIFUGATION; FRACTIONATION; ANTIBODIES; INFECTION; PLASMA; DONORS AB Background: Hepatitis C virus (HCV) RNA was measured in immune globulins and its chemical and physical properties were characterized. Study Design and Methods: The study examined 69 immune globulin lots from 7 manufacturers, including 44 intravenous and 25 intramuscular immune globulin preparations. In addition, 8 experimental intravenous immune globulin preparations were investigated. Detection and quantitation of HCV RNA were achieved by reverse transcription and nested polymerase chain reaction at limiting dilution. A multi-antigen anti-HCV enzyme immunoassay was also used to test these immune globulins. Results: The highest level of HCV RNA was found in an experimental immune globulin lot derived from a plasma pool made up of 186 anti-c100-3-reactive units. HCV RNA was detected only in 1 of 7 manufacturers' experimental intravenous immune globulin preparations derived from a pool made up of 2887 anti-c100-3-negative units. It was also detected in commercial intravenous immune globulin lots prepared by the same manufacturer from source plasma, but not from recovered plasma. More than half of the commercial intramuscular immune globulin lots, including specific immune globulin products, were HCV RNA positive. All immune globulin products examined were reactive for anti-HCV. Certain similarities were found for HCV RNA present in an immune globulin product and plasma. Ethanol at 20 or 25 percent had no effect upon the buoyant density of HCV RNA. Conclusion: Many immune globulin preparations contained HCV RNA, with levels depending upon both the type of starting plasma and the manufacturing process. Exposure to ethanol did not appear to affect the physical characteristics of HCV RNA. RP YU, MYW (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,PLASMA DERIVAT LAB,HFM-345,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 27 TC 40 Z9 40 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 1994 VL 34 IS 7 BP 596 EP 602 DI 10.1046/j.1537-2995.1994.34794330014.x PG 7 WC Hematology SC Hematology GA PC356 UT WOS:A1994PC35600009 PM 7519795 ER PT J AU SAWYER, LA MCINNIS, J PATEL, A HORNE, AD ALBRECHT, P AF SAWYER, LA MCINNIS, J PATEL, A HORNE, AD ALBRECHT, P TI DELETERIOUS EFFECT OF THIMEROSAL ON THE POTENCY OF INACTIVATED POLIOVIRUS VACCINE SO VACCINE LA English DT Article DE INACTIVATED POLIOVIRUS VACCINE; THIMEROSAL; STORAGE TEMPERATURE; COMBINATION VACCINE; POTENCY ID QUANTITATION AB High-potency inactivated poliovirus vaccine (eIPV) was combined with diptheria-tetanus-pertussis (DTP) vaccine containing thimerosal as a preservative to simulate the performance of a potential tetravalent vaccine. Neither type 1 nor type 3 poliovirus antigens appeared to be affected by thimerosal after exposure for 1 h at 37 degrees C as measured by enzyme-linked immunosorbent assay (ELISA). One epitope on the type 2 antigen was damaged within 5 min of exposure, however, the overall potency was unchanged when measured using a polyclonal antibody preparation. Exposure to thimerosal at 37 degrees C decreased the potency of all three poliovirus types to well below the level caused by heat deterioration alone in 1-2 days and to 0% after 16-17 days. At 25 degrees C, the potency of type 1 poliovirus decreased by 46% in 1 day, whereas poliovirus types 2 and 3 were stable for I week. Storage of eIPV at 4 degrees C in the presence of thimerosal reduced the potency of type 1 poliovirus antigen to undetectable levels after 4-6 months. Type 2 and 3 antigens were less markedly affected by 8 months of exposure to thimerosal at 4 degrees C. The loss of potency of type 1 as measured by ELISA was paralleled by a reduced level of neutralizing antibodies in mice injected with these preparations. The results obtained from testing eIPV in combination with DTP and thimerosal were generally similar to those obtained using eIPV with thimerosal. It remains to be seen to what extent thimerosal will affect the immunogenicity of eIPV in humans when injected as combined eIPY-DTP vaccine. RP SAWYER, LA (reprint author), US FDA,DIV VIRAL PROD,PEDIAT DIS LAB,BETHESDA,MD 20014, USA. NR 9 TC 21 Z9 21 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD JUL PY 1994 VL 12 IS 9 BP 851 EP 856 DI 10.1016/0264-410X(94)90296-8 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NQ622 UT WOS:A1994NQ62200014 PM 7526574 ER PT J AU REZAPKIN, GV CHUMAKOV, KM LU, ZB RAN, YX DRAGUNSKY, EM LEVENBOOK, IS AF REZAPKIN, GV CHUMAKOV, KM LU, ZB RAN, YX DRAGUNSKY, EM LEVENBOOK, IS TI MICROEVOLUTION OF SABIN-1 STRAIN IN-VITRO AND GENETIC STABILITY OF ORAL POLIOVIRUS VACCINE SO VIROLOGY LA English DT Article ID POLYMERASE ERROR FREQUENCY; RNA-POLYMERASE; NONCODING REGION; NEUROVIRULENCE; ATTENUATION; MUTATIONS; GENOME; DETERMINANTS; REVERSION; SEQUENCE AB Mutants consistently accumulating in Sabin 1 poliovirus during serial passaging in vitro were identified by sequence heterogeneity assay and quantitated using mutant analysis by PCR and restriction enzyme cleavage (MAPREC). Only four unstable genomic sites were identified in virus passaged 10 times in African green monkey kidney (AGMK) cells, and eight sites in virus passaged in Vero cells. Mutations accumulated both in untranslated regions of RNA (nucleotides 480, 525 and 7441) and in coding sequences, as missense (nucleotides 1449, 4944, and 6203) or silent (nucleotides 1123 and 1141) mutations. The most prominent selectable mutations were found at complementary nucleotides 480 and 525 of the 5'-untranslated region (5'-UTR) of the Sabin strain, changing the G:U pair in F-domain to either A:U or G:C variants. These two variants have been shown previously to have an increased neurovirulence in monkeys. The G:C variant accumulated during passage in Vero cells, while A:U variant accumulated in CV-1 cells. Virus passaged in AGMK cells accumulated both variants. Higher temperature (37 instead of 34 degrees) strongly favored selection of mutants in Vero cells, had a smaller effect on mutant accumulation in AGMK cells, and had no effect in CV-1 cells. Monopools of type 1 oral poliovirus vaccine (OPV) made by seven manufacturers were found to contain both 480-A and 525-C revertants at a combined level of 1.1-2.7%. Viral samples with increased amounts of these revertants had higher neurovirulence in monkeys. Our results suggest that quantitation of these reversions by MAPREC may be prognostic for results of the monkey neurovirulence test (MNVT) and can be used for monitoring type 1 OPV consistency. (C) 1994 Academic Press, Inc. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 30 TC 45 Z9 46 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL PY 1994 VL 202 IS 1 BP 370 EP 378 DI 10.1006/viro.1994.1353 PG 9 WC Virology SC Virology GA NQ858 UT WOS:A1994NQ85800038 PM 8009849 ER PT J AU SADAIE, MR HAGER, GL AF SADAIE, MR HAGER, GL TI INDUCTION OF DEVELOPMENTALLY PROGRAMMED CELL-DEATH AND ACTIVATION OF HIV BY SODIUM-BUTYRATE SO VIROLOGY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; GLOBIN GENE-EXPRESSION; T-CELLS; INFECTION; APOPTOSIS; DIFFERENTIATION; RNA; REPLICATION; PROMOTER; GROWTH AB Apoptosis is an important regulatory process during normal development and maturation. We find that the proliferation-arresting and differentiation-inducing compound sodium n-butyrate (NaB) triggers a marked host chromatin degradation. This apoptotic process is independent of, but commensurate with, a rapid increase in viral mRNA synthesis and subsequent release of HIV-1 virus in transformed human cell lines harboring tat(-) (HLM1) or tat(+) (U1,ACH-2) dormant HIV-1 proviruses. This compound stimulates a reversible accumulation of the characteristic viral mRNAs at a much faster rate than two other DNA degradation inducers such as tumor necrosis factor-alpha and phorbol 12-myristate 13-acetate. The transcriptional activator butyrate analogue, alpha-amino-n-butyrate, failed to cause similar phenotypic changes. These results suggest that common regulatory signals may be involved in activation of apoptosis genes and latent provirus by NaB. (C) 1994 Academic Press, Inc. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. RP SADAIE, MR (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,HFM-310,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 37 TC 23 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL PY 1994 VL 202 IS 1 BP 513 EP 518 DI 10.1006/viro.1994.1372 PG 6 WC Virology SC Virology GA NQ858 UT WOS:A1994NQ85800057 PM 8009866 ER PT J AU PACKARD, BZ AF PACKARD, BZ TI UP-REGULATION OF THE SURFACE EXPRESSION OF 2 INTEGRINS AND INDUCTION OF CHEMOTACTIC ACTIVITY IN A HUMAN LEUKEMIC-CELL LINE BY ONCOIMMUNIN-M SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE INTEGRIN; CHEMOTAXIS; ONCOIMMUNIN-M; HL-60 ID LEUKOCYTE DIFFERENTIATION; CHEMOATTRACTANT RECEPTORS; ADOPTIVE IMMUNOTHERAPY; ADHESION; FAMILY; MAC-1; LFA-1; MACROPHAGES; NEUTROPHILS; PEPTIDE AB Previously, it was shown that Oncoimmunin-M (OI-M), a recently identified tumor cell-derived 36 kDa protein, is able both to inhibit the proliferation of the human promyelocytic leukemic cell line HL-60 while maintaining viability in culture and to induce a bimodal distribution of CD11b, the alpha chain of the integrin MAC-1, on the cell surface (Packard, B.Z. and Komoriya, A. (1993) J. Biol. Chem. 268, 6356-6363). Now, data which reveal that exposure of HL-60 cells to this factor also brings about an increase in the mean level of surface expression of CD11c, the cu chain of another leukocyte integrin (p150,95), but leaves CD11a, the alpha chain of the third leukointegrin (LFA-1), virtually unchanged (<10%) are presented. Comparison of motility studies of OI-M-treated HL-60 bulk populations with control bulk populations demonstrates coinduction of CD11b and CD11c surface upregulation with chemotactic responsiveness to a gradient of the chemoattractant human C5a. Separation of motile from nonmotile cell subpopulations after exposure to C5a further reveals that individual cells which respond to this chemoattractant express increased levels of both CD11b and CD11c relative to unresponsive cells. These data correlate the upregulation of leukointegrins MAC-1 and p150,95 by a tumor cell-derived protein on a preterminally differentiated myeloid cell with chemotactic responsiveness to human C5a. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NR 35 TC 4 Z9 4 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 JUN 30 PY 1994 VL 1222 IS 2 BP 159 EP 163 DI 10.1016/0167-4889(94)90164-3 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NV851 UT WOS:A1994NV85100004 PM 8031851 ER PT J AU DHAWAN, S HEREDIA, A LA, RB WAHL, LM EPSTEIN, JS HEWLETT, IK AF DHAWAN, S HEREDIA, A LA, RB WAHL, LM EPSTEIN, JS HEWLETT, IK TI INTERFERON-GAMMA INDUCES RESISTANCE IN PRIMARY MONOCYTES AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NECROSIS-FACTOR-ALPHA; HIV REPLICATION; T-CELLS; RESTRICTION; MACROPHAGES AB Treatment of monocytes with interferon-gamma 1 day before, or at the time of infection with human immunodeficiency virus type-1 (HIV-1) induced complete resistance in monocytes against HIV-1 infection. There was no evidence of viral RNA, proviral DNA, p24 antigen, or reverse transcriptase activity through 2 weeks after inoculation. Ultrastructural examination of these cells showed no detectable virus particles. When interferon-gamma was added to monocytes 1 to 3 days post-infection, virus integration occurred, but the viral expression was either ablated (1 day postinfection) or significantly inhibited (3 days post-infection). Treatment of monocytes with interferon-gamma before or after infection with HIV-1 produced significantly higher levels of tumor necrosis factor-alpha and interleukin-8 than untreated or uninfected monocytes. These results suggest that altered regulation of cytokines may mediate antiviral activity of interferon-gamma in monocytes. (C) 1994 Academic Press, Inc. C1 CTR DIS CONTROL,RETROVIRUS DIS BRANCH,ATLANTA,GA 30333. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. RP DHAWAN, S (reprint author), US FDA,CTR BIOL EVALUAT & RES,MOLEC VIROL LAB,HFM-310,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 18 TC 12 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 15 PY 1994 VL 201 IS 2 BP 756 EP 761 DI 10.1006/bbrc.1994.1765 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NQ805 UT WOS:A1994NQ80500038 PM 8003012 ER PT J AU SAVILLE, MW TAGA, K FOLI, A BRODER, S TOSATO, G YARCHOAN, R AF SAVILLE, MW TAGA, K FOLI, A BRODER, S TOSATO, G YARCHOAN, R TI INTERLEUKIN-10 SUPPRESSES HUMAN IMMUNODEFICIENCY VIRUS-1 REPLICATION IN-VITRO IN CELLS OF THE MONOCYTE/MACROPHAGE LINEAGE SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; GROWTH-FACTOR-BETA; RETROVIRUS-INDUCED IMMUNODEFICIENCY; INHIBITS CYTOKINE PRODUCTION; T-CELL; B-CELLS; ACTIVATED MACROPHAGES; STIMULATORY FACTOR; HUMAN-MONOCYTES; DOWN-REGULATION C1 NCI,OFF DIRECTOR,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,IMMUNOL LAB,BETHESDA,MD. RP SAVILLE, MW (reprint author), NCI,MED BRANCH,RETROVIRAL DIS SECT,BLDG 10,ROOM 12N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 65 TC 72 Z9 72 U1 0 U2 0 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 JUN 15 PY 1994 VL 83 IS 12 BP 3591 EP 3599 PG 9 WC Hematology SC Hematology GA NR905 UT WOS:A1994NR90500022 PM 7911340 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI NEW RULE ON LABELING FOODS AS HEALTHY ISSUED 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 2 Z9 2 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 JUN 15 PY 1994 VL 271 IS 23 BP 1818 EP 1818 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NP959 UT WOS:A1994NP95900004 PM 7910857 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI TREATMENT IND FOR ADVANCED NON-SMALL-CELL LUNG-CANCER 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 2 Z9 2 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 JUN 15 PY 1994 VL 271 IS 23 BP 1818 EP 1818 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NP959 UT WOS:A1994NP95900007 PM 7910857 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI NEW DEVICE APPROVED FOR USE BY PARAPLEGICS 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 2 Z9 2 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 JUN 15 PY 1994 VL 271 IS 23 BP 1818 EP 1818 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NP959 UT WOS:A1994NP95900006 PM 7910857 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI PACLITAXEL APPROVED FOR TREATMENT OF CERTAIN BREAST-CANCER 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 2 Z9 2 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 JUN 15 PY 1994 VL 271 IS 23 BP 1818 EP 1818 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NP959 UT WOS:A1994NP95900005 PM 7910857 ER PT J AU CREEDON, KA RATHOD, PK WELLEMS, TE AF CREEDON, KA RATHOD, PK WELLEMS, TE TI PLASMODIUM-FALCIPARUM S-ADENOSYLHOMOCYSTEINE HYDROLASE - CDNA IDENTIFICATION, PREDICTED PROTEIN-SEQUENCE, AND EXPRESSION IN ESCHERICHIA-COLI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID L-HOMOCYSTEINE HYDROLASE; ADENOSYL-L-HOMOCYSTEINE; AMINO-ACID SEQUENCE; RAT-LIVER; NEPLANOCIN-A; ANTIMALARIAL ACTIVITY; CHEMICAL MODIFICATION; GENOMIC ORGANIZATION; NUCLEOTIDE-SEQUENCE; MALARIA PARASITES AB Compounds that specifically inhibit S-adenosylhomocysteine hydrolase (SAHH; EC 3.3.1.1) interfere with the proliferation of Plasmodium malarial parasites, but efforts to identify the enzyme directly in parasite extracts have been unsuccessful. Here we report genetic and biochemical evidence for the presence of a gene encoding P. falciparum SAHH. The gene is transcribed as a 2.8-kilobase mRNA in erythrocytic stage parasites. Analysis of the open reading frame predicts a 53.9-kDa protein having conserved regions thought to be involved in NAD binding. The cDNA sequence has been incorporated into an Escherichia coli expression construct to confirm the function of the sahh product. Transformed E. coli cells produce a protein with a relative molecular weight of 56,000 which possesses SAHH activity as evidenced by the conversion of 3-deazaadenosine to S-3-deazaadenosylhomocysteine. Several amino acid residues that have been suggested to be at the SAHH active site in other organisms show nonconserved replacements in P. falciparum, suggesting that some current proposals for the enzyme mechanism may need to be revised. The structural differences between the P. falciparum and mammalian SAHH enzymes may foster innovative strategies for drug development against malaria. C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. CATHOLIC UNIV AMER,INST BIOMOLEC STUDIES,DEPT BIOL,WASHINGTON,DC 20064. FU NIAID NIH HHS [NIAID AI26912, AI01112] NR 66 TC 47 Z9 48 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 JUN 10 PY 1994 VL 269 IS 23 BP 16364 EP 16370 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NQ729 UT WOS:A1994NQ72900063 PM 8206944 ER PT J AU HEITKEMPER, DT KAINE, LA JACKSON, DS WOLNIK, KA AF HEITKEMPER, DT KAINE, LA JACKSON, DS WOLNIK, KA TI PRACTICAL APPLICATIONS OF ELEMENT-SPECIFIC DETECTION BY INDUCTIVELY-COUPLED PLASMA-ATOMIC EMISSION-SPECTROSCOPY AND INDUCTIVELY-COUPLED PLASMA-MASS SPECTROMETRY TO TON CHROMATOGRAPHY OF FOODS SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 6th International Ion Chromatography Symposium CY SEP 12-15, 1993 CL BALTIMORE, MD SP DIONEX CORP, MILLIPORE, WATERS CHROMATOG DIV ID LIQUID-CHROMATOGRAPHY AB Three practical examples are presented to demonstrate the utility of element-selective detection for ion chromatography (IC). The determination of As species in a liquid health food supplement by IC with inductively coupled plasma atomic emission spectroscopy (IC-ICP-AES) is shown to confirm results obtained for total As. IC-ICP-AES is also used to investigate the identity of an unknown peak in a sample of shrimp commercially treated with tripolyphosphate. Finally, results are presented for the determination of residual bromate in baked goods by IC with inductively coupled plasma mass spectrometry detection. RP HEITKEMPER, DT (reprint author), NATL FORENS CHEM CTR,US FDA,1141 CENT PKWY,CINCINNATI,OH 45202, USA. NR 13 TC 31 Z9 34 U1 0 U2 3 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 JUN 10 PY 1994 VL 671 IS 1-2 BP 101 EP 108 DI 10.1016/0021-9673(94)80227-0 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NT177 UT WOS:A1994NT17700016 PM 8049760 ER PT J AU KAINE, LA HEITKEMPER, DT JACKSON, DS WOLNIK, KA AF KAINE, LA HEITKEMPER, DT JACKSON, DS WOLNIK, KA TI USE OF ION CHROMATOGRAPHY FOR THE VERIFICATION OF DRUG AUTHENTICITY SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 6th International Ion Chromatography Symposium CY SEP 12-15, 1993 CL BALTIMORE, MD SP DIONEX CORP, MILLIPORE, WATERS CHROMATOG DIV AB Investigations of drug authenticity focus on both bulk drugs and finished products. Excipients and contaminants from manufacturing processes may be used as ''chemical fingerprints'' to track drug sources. This paper describes the ion chromatographic determination of sodium lauryl sulfate, chloride, phosphate and citrate in drug formulations as applied to drug authenticity cases. RP KAINE, LA (reprint author), US FDA,NATL FORENS CHEM CTR,1141 CENTRAL PARKWAY,CINCINNATI,OH 45202, USA. NR 5 TC 6 Z9 6 U1 1 U2 2 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 JUN 10 PY 1994 VL 671 IS 1-2 BP 303 EP 308 DI 10.1016/0021-9673(94)80254-8 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NT177 UT WOS:A1994NT17700043 ER PT J AU HEITKEMPER, DT JACKSON, DS KAINE, LA MULLIGAN, KA WOLNIK, KA AF HEITKEMPER, DT JACKSON, DS KAINE, LA MULLIGAN, KA WOLNIK, KA TI DETERMINATION OF SACCHARIN IN SHRIMP BY ION CHROMATOGRAPHY AND CAPILLARY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 6th International Ion Chromatography Symposium CY SEP 12-15, 1993 CL BALTIMORE, MD SP DIONEX CORP, MILLIPORE, WATERS CHROMATOG DIV ID PERFORMANCE LIQUID-CHROMATOGRAPHY; FOOD-ADDITIVES; PRESERVATIVES AB A procedure is described for the detection, identification and determination of saccharin in shrimp. Undeclared use of this regulated substance has been noted. Shrimp is extracted with water, and the extract is treated with a C-18 solid-phase extraction cartridge and a chloride removal cartridge. The method detection limit is 2 mu g/g saccharin in shrimp. Recovery of a 16 mu g/g saccharin spike averaged 91 +/- 6%. The identity of saccharin is confirmed by gas chromatography-mass spectrometry of the methyl derivative which is prepared using an on-column methylating agent. RP HEITKEMPER, DT (reprint author), US FDA,NATL FORENS CHEM CTR,CINCINNATI,OH 45202, USA. NR 14 TC 6 Z9 6 U1 0 U2 3 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 JUN 10 PY 1994 VL 671 IS 1-2 BP 323 EP 329 DI 10.1016/0021-9673(94)80257-2 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NT177 UT WOS:A1994NT17700046 ER PT J AU FORTESDIAS, CL LIN, Y EWELL, J DINIZ, CR LIU, TY AF FORTESDIAS, CL LIN, Y EWELL, J DINIZ, CR LIU, TY TI A PHOSPHOLIPASE A(2) INHIBITOR FROM THE PLASMA OF THE SOUTH-AMERICAN RATTLESNAKE (CROTALUS-DURISSUS-TERRIFICUS) - PROTEIN-STRUCTURE, GENOMIC STRUCTURE, AND MECHANISM OF ACTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRIMERESURUS-FLAVOVIRIDIS; ANTIHEMORRHAGIC FACTOR; SNAKE-VENOM; ERINACEUS-EUROPAEUS; OPOSSUM SERUM; BLOOD-PLASMA; PURIFICATION; CROTOXIN; HEDGEHOG; SEQUENCE AB The lethal toxicity of the South American rattlesnake (Crotalus durissus terrificus) venom can be attributed mainly to the presence of a pre-synaptic neurotoxin, crotoxin, with phospholipase A(2) activity. Crotoxin is a heterodimer of an acidic protein (CA) and a basic phospholipase A(2) (CB). An anti-toxic protein of subunit molecular mass 23.6 kDa that neutralizes both lethal and PLA(2) activity of crotalid venom and crotoxin has been previously purified from the plasma of this snake (Fortes-Dias, C., Fonseca, B. C. B., Kochva, E., and Diniz, C. R. (1991) Toxicon 29, 997-1008). The protein has been named CNF for Crotalus neutralizing factor. In the present study, we have shown that CNF exists as an oligomeric aggregate of (CNF)(n), where n = 6-8, and when it interacts with crotoxin, it replaces the acidic protein CA of crotoxin to form a stable near stoichiometric complex of CNF.CB. The CNF.CB complex no longer exhibits PLA(2) activity and is inert in vivo, Thus, the exchange reaction between CA.CB of crotoxin and CNF to form CNF.CB and free CA is reminiscent of the interaction of crotoxin with its target receptor at the neuromuscular transmission site in the presynaptic cells. A cDNA encoding CNF has been isolated from a liver cDNA library using an appropriate nucleotide probe. The nucleotide sequence codes for a 19-residue signal peptide, followed by a 181-residue protein of which 16 are half-cystines. Calculated molecular mass is 20.06 kDa, and there is a putative N-linked carbohydrate site at Asn(157). C1 US FDA,CTR BIOL EVALUAT & RES,DIV ALLERGEN PROD & PARASITOL,BETHESDA,MD 20892. RP FORTESDIAS, CL (reprint author), FDN EZEQUIEL DIAS,CTR PESQUISA & DESENVOLVIMENTO,BELO HORIZONT,MG,BRAZIL. RI Fortes-Dias, Consuelo/I-4896-2012 OI Fortes-Dias, Consuelo/0000-0002-4494-5108 NR 33 TC 61 Z9 64 U1 1 U2 1 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 JUN 3 PY 1994 VL 269 IS 22 BP 15646 EP 15651 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP513 UT WOS:A1994NP51300042 PM 8195214 ER PT J AU GOLDING, H DSOUZA, MP BRADAC, J MATHIESON, B FAST, P AF GOLDING, H DSOUZA, MP BRADAC, J MATHIESON, B FAST, P TI MEETING REPORT - NEUTRALIZATION OF HIV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; GP120 MOLECULES; ASSAY; INFECTION; CELL; SITE; SUSCEPTIBILITY; QUANTITATION; PEPTIDES AB A Workshop on Neutralization of HIV-1: Technology and reagents for analysis of prophylactic vaccines clinical trials, sponsored by the Food and Drug Administration (FDA) and the Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), was held on April 19-20, 1993, in Bethesda, Maryland. This workshop brought together researchers who are involved in the development, testing, and evaluation of HIV-1 prophylactic vaccines. The major objectives were (1) to discuss critically the different neutralization and binding assays that are currently used in the evaluation of immune sera; (2) to identify assays that will measure the ''most relevant'' antibodies, which are likely to predict neutralization of primary isolates; and (3) to identify well-characterized reference reagents, which could be used to standardize neutralization assays used in laboratories around the world. C1 NIAID,DIV AIDS,PATHOGENESIS BRANCH,BRDP,ROCKVILLE,MD 20852. NIAID,DIV AIDS,VACCINE RES & DEV BRANCH,BRDP,ROCKVILLE,MD 20852. RP GOLDING, H (reprint author), US FDA,CBER,DIV VIRAL PROD,RETROVIRUS RES LAB,8800 ROCKVILLE PIKE,HFM-457,BLDG 29A,BETHESDA,MD 20892, USA. NR 41 TC 52 Z9 52 U1 0 U2 0 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 JUN PY 1994 VL 10 IS 6 BP 633 EP 643 DI 10.1089/aid.1994.10.633 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NU496 UT WOS:A1994NU49600002 PM 8074927 ER PT J AU HOFFMAN, FA RHEINSTEIN, PH HOUN, F AF HOFFMAN, FA RHEINSTEIN, PH HOUN, F TI THE MAMMOGRAPHY QUALITY STANDARDS ACT OF 1992 SO AMERICAN FAMILY PHYSICIAN LA English DT Article RP HOFFMAN, FA (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 3 Z9 3 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 JUN PY 1994 VL 49 IS 8 BP 1965 EP 1970 PG 6 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA NP750 UT WOS:A1994NP75000025 PM 8203325 ER PT J AU GROSS, TP SCHLESSELMAN, JJ AF GROSS, TP SCHLESSELMAN, JJ TI THE ESTIMATED EFFECT OF ORAL-CONTRACEPTIVE USE ON THE CUMULATIVE RISK OF EPITHELIAL OVARIAN-CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD. UNIV PITTSBURGH,PITTSBURGH,PA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1994 VL 139 IS 11 SU S BP S13 EP S13 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NP863 UT WOS:A1994NP86300041 ER PT J AU MARINACDABIC, D KRULEWITCH, CJ MOORE, RM AF MARINACDABIC, D KRULEWITCH, CJ MOORE, RM TI BIRTH-WEIGHT IN RELATION TO FREQUENT PRENATAL ULTRASOUND EXPOSURES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20852. CDC,DRH,PIHB,ATLANTA,GA. OASH,OIH,WASHINGTON,DC 20201. NR 0 TC 3 Z9 3 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1994 VL 139 IS 11 SU S BP S62 EP S62 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NP863 UT WOS:A1994NP86300207 ER PT J AU LUMPKIN, MM BURLINGTON, DB AF LUMPKIN, MM BURLINGTON, DB TI SAFETY ALERT - HAZARDS OF PRECIPITATION ASSOCIATED WITH PARENTERAL-NUTRITION SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Article C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. RP LUMPKIN, MM (reprint author), US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857, USA. NR 1 TC 61 Z9 64 U1 0 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD JUN 1 PY 1994 VL 51 IS 11 BP 1427 EP 1428 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NT181 UT WOS:A1994NT18100004 PM 7942876 ER PT J AU CURRIE, LA HORWITZ, W AF CURRIE, LA HORWITZ, W TI IUPAC RECOMMENDATIONS FOR DEFINING AND MEASURING DETECTION AND QUANTIFICATION LIMITS SO ANALUSIS LA English DT Article AB For many years, the international chemical community has recognised the importance of defining objective criteria for: 1) judging whether an experimental outcome indicates presence or absence of an analyte; and 2) defining the inherent detection and quantification capabilities of a chemical measurement process (CMP). C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. RP CURRIE, LA (reprint author), NATL INST STAND & TECHNOL,CHEM SCI & TECHNOL LAB,GAITHERSBURG,MD 20899, USA. NR 8 TC 18 Z9 19 U1 1 U2 4 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0365-4877 J9 ANALUSIS JI Analusis PD JUN PY 1994 VL 22 IS 5 BP M24 EP M26 PG 3 WC Chemistry, Analytical SC Chemistry GA NV562 UT WOS:A1994NV56200007 ER PT J AU TIFFANY, LJ DOBBS, D GARMESTANI, K RAUBITSCHEK, A TINUBU, A BRECHBIEL, MW GOFFMAN, T GANSOW, OA WALDMANN, TA KOZAK, RW AF TIFFANY, LJ DOBBS, D GARMESTANI, K RAUBITSCHEK, A TINUBU, A BRECHBIEL, MW GOFFMAN, T GANSOW, OA WALDMANN, TA KOZAK, RW TI RADIOLABELED CHX(B)-2E4 IS STABLE IN-VIVO AND IS A SUITABLE IMMUNOCONJUGATE FOR TESTING ALPHA-PARTICLE-EMITTING BISMUTH RADIONUCLIDES IN INTERLEUKIN-2 RECEPTOR TARGETED IMMUNOTHERAPY SO ANTIBODY IMMUNOCONJUGATES AND RADIOPHARMACEUTICALS LA English DT Article ID TAC MONOCLONAL-ANTIBODY; T-CELLS; RADIOIMMUNOTHERAPY; TRANSPLANTATION; STREPTAVIDIN; EXPRESSION; SURVIVAL; SUBUNIT; TUMOR; MICE AB A murine model system has been established to assess immunotherapeutic approaches to treating interleukin-2 receptor (IL-2R) expressing malignancies. A rat IgG(2c) anti-murine p55 lL-2R monoclonal antibody (2E4) was successfully chelate coupled and radiolabelled with either Indium-lll or Bismuth-206 while retaining full immunoreactivity. The chelating agent used in these studies was p(SCNBZ) CHX(B) DTPA. Indium-111 labeled 2E4 was used to test the in vivo behavior of the immunoconjugate and pre-select murine tumor lines based on in vivo radiolabel uptake. The CHX(B)-2E4 MAb was labelled with either Bismuth-206 or iodine-131 and the two independently radiolabelled antibodies given simultaneously to tumor-bearing nude mice. Both isotopes were found to have equivalent blood clearance and tissue distributions. In addition, 100 percent of the bismuth activity in 1 and 4 hour postinjection serum samples was able to bind to IL-2R expressing cells, while 3 percent bound to an equivalent number of IL-2R negative cells. The time course of in vivo tumor targeting indicated that 25-35 percent of the i.v. injected dose per gram tissue (ID/g) was taken up by a subcutaneous IL-2R positive murine solid tumor (EL4J3.4) by 24 h post-injection. In contrast, 8 percent (ID/g) was taken up by the IL-2R receptor negative parental tumor (EL4J). Hence, radiolabeled CHX(B)-2E4 is stable in vivo and is a suitable immunoconjugate for testing alpha-emitting bismuth radionuclides in anti-IL-2R immunotherapy. C1 US FDA,CTR BIOL EVALUAT & RES,DIV MONOCLONAL ANTIBODIES,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. NR 23 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0892-7049 J9 ANTIBODY IMMUNOCONJ JI Antib. Immunoconjug. Radiopharm. PD SUM PY 1994 VL 7 IS 2 BP 99 EP 115 PG 17 WC Immunology; Radiology, Nuclear Medicine & Medical Imaging SC Immunology; Radiology, Nuclear Medicine & Medical Imaging GA NW260 UT WOS:A1994NW26000001 ER PT J AU PETTIT, GH EDIGER, MN HAHN, DW BRINSON, BE SAUERBREY, R AF PETTIT, GH EDIGER, MN HAHN, DW BRINSON, BE SAUERBREY, R TI TRANSMISSION OF POLYIMIDE DURING PULSED ULTRAVIOLET-LASER IRRADIATION SO APPLIED PHYSICS A-MATERIALS SCIENCE & PROCESSING LA English DT Article ID ABLATION AB Experiments that demonstrate quantitatively the importance of laser absorption dynamics for ultraviolet laser ablation of organic materials are presented. Laser pulse transmission measurements have been performed on 0.1 mum spin-coated polyimide films at three ultraviolet wavelengths (193 nm, 248 nm, and 355 nm) over the fluence range 10(-3)-10 J/cm2. Target transmission is observed to increase with increasing fluence by a factor of approximately 5 at 193 nm, and a factor of approximately 10 at 248 nm. In contrast, transmission decreases by approximately one half during 355 nm target irradiation. These results are analyzed theoretically with a two-level model of chromophore absorption. This theory is also applied to reported pulsed UV-laser polyimide ablation data. It is shown that an accurate description of the fluence-dependent film absorption leads to a prediction of the etch depth versus pulse fluence relationship in good agreement with experimental data. C1 RICE UNIV,DEPT ELECT & COMP ENGN,HOUSTON,TX 77251. RICE UNIV,RICE QUANTUM INST,HOUSTON,TX 77251. RP PETTIT, GH (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,MAIL STOP HFZ-134,ROCKVILLE,MD 20857, USA. NR 14 TC 25 Z9 25 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0947-8396 J9 APPL PHYS A-MATER JI Appl. Phys. A-Mater. Sci. Process. PD JUN PY 1994 VL 58 IS 6 BP 573 EP 579 DI 10.1007/BF00348168 PG 7 WC Materials Science, Multidisciplinary; Physics, Applied SC Materials Science; Physics GA NR641 UT WOS:A1994NR64100005 ER PT J AU PERSHING, LK LAMBERT, L WRIGHT, ED SHAH, VP WILLIAMS, RL AF PERSHING, LK LAMBERT, L WRIGHT, ED SHAH, VP WILLIAMS, RL TI TOPICAL 0.050-PERCENT BETAMETHASONE DIPROPIONATE - PHARMACOKINETIC AND PHARMACODYNAMIC DOSE-RESPONSE STUDIES IN HUMANS SO ARCHIVES OF DERMATOLOGY LA English DT Article ID CORTICOSTEROID PREPARATIONS; SKIN; BIOAVAILABILITY; ASSAY AB Background and Design: Effective topical drug therapy requires drug delivery into the skin to produce the desired pharmacodynamic response. For topical corticosteroids, the visual skin-blanching assay has been used to rank the potency of the corticosteroids and their overall efficacy. While vehicles have been shown to influence the resulting blanching response, the dose of drug applied has not always produced proportional differences in the blanching assay. The mechanism of the nonproportional pharmacodynamic response to the corticosteroid dose is unclear. We describe four methods for assessing the dose-response relationship of topical betamethasone dipropionate on the ventral forearm of six human subjects: duration, concentration, film thickness, and surface area. Drug uptake analysis in human stratum corneum and the resulting pharmacodynamic response, measured visually and with a chromameter, were performed with each method to quantify the dose-response relationship. Results: Only the concentration and duration methods demonstrated an increase in mean drug uptake with increasing dose. The maximal mean pharmacodynamic response reflected the mean drug uptake with all four methods. Application conditions for maximal pharmacodynamic activity of topical betamethasone dipropionate in the skin include short duration of treatment (less than or equal to 2 hours), a lower concentration than commercially marketed, and thin film thicknesses (1 to 5 mu m). Conclusion: A dose response can be produced by increasing the drug concentration or the duration of application time. Achievement of steady-state betamethasone dipropionate uptake into the stratum corneum was not commensurate with the maximal pharmacodynamic response. Very small amounts of this potent corticosteroid within the skin appear to maximize the receptor response to drug. C1 US FDA,OFF GENER DRUGS,ROCKVILLE,MD 20857. RP PERSHING, LK (reprint author), UNIV UTAH,SCH MED,DEPT MED,DIV DERMATOL,50 N MED DR,SALT LAKE CITY,UT 84132, USA. FU PHS HHS [223-91-1801] NR 15 TC 18 Z9 18 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 1994 VL 130 IS 6 BP 740 EP 747 DI 10.1001/archderm.130.6.740 PG 8 WC Dermatology SC Dermatology GA NQ995 UT WOS:A1994NQ99500006 PM 8002644 ER PT J AU RIDER, LG BUYON, JP SHERRY, DD AF RIDER, LG BUYON, JP SHERRY, DD TI POSTNATAL TREATMENT OF COMPLETE CONGENITAL HEART-BLOCK WITH GLUCOCORTICOIDS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. NYU,HOSP JOINT DIS,MED CTR,NEW YORK,NY 10003. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1994 VL 37 IS 6 SU S BP R17 EP R17 PG 1 WC Rheumatology SC Rheumatology GA NP830 UT WOS:A1994NP83000058 ER PT J AU MILLER, H AF MILLER, H TI CLINTONS MALIGN NEGLECT BATTERS BIOTECHNOLOGY SO BIO-TECHNOLOGY LA English DT Editorial Material C1 US FDA,ROCKVILLE,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0733-222X J9 BIO-TECHNOL JI Bio-Technology PD JUN PY 1994 VL 12 IS 6 BP 571 EP 573 DI 10.1038/nbt0694-571 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA NP637 UT WOS:A1994NP63700015 ER PT J AU WEST, RW HINSON, WG LYLE, DB SWICORD, ML AF WEST, RW HINSON, WG LYLE, DB SWICORD, ML TI ENHANCEMENT OF ANCHORAGE-INDEPENDENT GROWTH IN JB6 CELLS EXPOSED TO 60 HERTZ MAGNETIC-FIELDS SO BIOELECTROCHEMISTRY AND BIOENERGETICS LA English DT Article ID FREQUENCY ELECTROMAGNETIC-FIELDS; CALCIUM REQUIREMENTS; MOUSE CELLS; PROLIFERATION; INVITRO; PROMOTER; HZ AB Extremely low frequency electromagnetic fields (EMFs) are implicated in the genesis of childhood leukemias and lymphomas after residential exposure, and of tumors in adults after occupational exposure. Experiments in vitro have demonstrated biochemical changes with cultured cells including modulation of signal transduction pathways. We examined the ability of 60 Hz sinusoidal EMFs to alter the growth of a promotion-sensitive mouse epidermal cell line (JB6) under anchorage-independent conditions. Cells (10(4) per dish) were suspended in 0.3% agar in 60 mm dishes and exposed to a 1.1 X 10(-3) T field generated by a Helmholtz coil held in an incubator at 37 degrees C, 5% CO2 and 90%-97% relative humidity. Growth of colonies more than 60 mu m in diameter was scored after 10-14 days. Exposure to the EMF significantly increased the colony-forming efficiency, by 40%-70% compared with control cells(> 95% confidence level), suggesting interaction with a growth control/signal transduction pathway. C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. RP WEST, RW (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 23 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0302-4598 J9 BIOELECTROCH BIOENER JI Bioelectrochem. Bioenerg. PD JUN PY 1994 VL 34 IS 1 BP 39 EP 43 DI 10.1016/0302-4598(94)80007-3 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NT998 UT WOS:A1994NT99800007 ER PT J AU YUH, L BEAL, S DAVIDIAN, M HARRISON, F HESTER, A KOWALSKI, K VONESH, E WOLFINGER, R AF YUH, L BEAL, S DAVIDIAN, M HARRISON, F HESTER, A KOWALSKI, K VONESH, E WOLFINGER, R TI POPULATION PHARMACOKINETIC-PHARMACODYNAMIC METHODOLOGY AND APPLICATIONS - A BIBLIOGRAPHY SO BIOMETRICS LA English DT Review DE NONLINEAR MIXED EFFECTS MODEL; POPULATION PHARMACOKINETICS/PHARMACODYNAMICS ID ROUTINE CLINICAL-DATA; MIXED-EFFECTS MODELS; MAXIMUM-LIKELIHOOD-ESTIMATION; PHARMACOKINETIC DATA-ANALYSIS; UNBALANCED REPEATED-MEASURES; PARAMETER-ESTIMATION; LONGITUDINAL DATA; THERAPEUTIC TRIALS; NONLINEAR-REGRESSION; NONMEM ANALYSIS AB This bibliography lists all published methodological works (statistical methodology, implementation methodology, review papers, descriptions of software) in the area of population pharmacokinetics/pharmacodynamics up to 1993 and all published works describing applications of population pharmacokinetics/pharmacodynamics up to 1992. C1 UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. N CAROLINA STATE UNIV,DEPT STAT,RALEIGH,NC 27695. US FDA,DIV BIOMETR,ROCKVILLE,MD 20857. CIBA GEIGY CORP,PHARMACEUT,DEPT DEV,SUMMIT,NJ 07901. GD SEARLE & CO,CLIN PHARMACOKINET & BIOAVAILABIL,SKOKIE,IL 60077. BAXTER HLTHCARE CORP,CTR APPL STAT,ROUND LAKE,IL 60073. SAS INST INC,DEPT APPLICAT,CARY,NC 27513. RP YUH, L (reprint author), WARNER LAMBERT PARKE DAVIS,DIV PHARMACEUT RES,DEPT BIOMETR,2800 PLYMOUTH RD,ANN ARBOR,MI 48105, USA. NR 133 TC 55 Z9 55 U1 0 U2 4 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1994 VL 50 IS 2 BP 566 EP 575 DI 10.2307/2533402 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA NX428 UT WOS:A1994NX42800027 PM 8068854 ER PT J AU BAO, JZ DAVIS, CC SWICORD, ML AF BAO, JZ DAVIS, CC SWICORD, ML TI MICROWAVE DIELECTRIC MEASUREMENTS OF ERYTHROCYTE SUSPENSIONS SO BIOPHYSICAL JOURNAL LA English DT Article ID ENDED COAXIAL LINE; COMPLEX PERMITTIVITY; POLAR LIQUIDS; RELAXATION; SPECTROSCOPY; TISSUES AB Complex dielectric constants of human erythrocyte suspensions over a frequency range from 45 MHz to 26.5 GHz and a temperature range from 5 to 40 degrees C have been determined with the open-ended coaxial probe technique using an automated vector network analyzer (HP 8510). The spectra show two separate major dispersions (beta and gamma) and a much smaller dispersion between them. The two major dispersions are analyzed with a dispersion equation containing two Cole-Cole functions by means of a complex nonlinear least squares technique. The parameters of the equation at different temperatures have been determined. The low frequency behavior of the spectra suggests that the dielectric constant of the cell membrane increases when the temperature is above 35 degrees C. The real part of the dielectric constant at similar to 3.4 GHz remains almost constant when the temperature changes. The dispersion shifts with temperature in the manner of a thermally activated process, and the thermal activation enthalpies for the beta- and gamma-dispersions are 9.87 +/- 0.42 kcal/mol and 4.80 +/- 0.06 kcal/mol, respectively. C1 UNIV MARYLAND,DEPT ELECT ENGN,COLL PK,MD 20742. US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. NR 33 TC 38 Z9 39 U1 1 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1994 VL 66 IS 6 BP 2173 EP 2180 PG 8 WC Biophysics SC Biophysics GA NN129 UT WOS:A1994NN12900046 PM 8075351 ER PT J AU BRUNSWICK, M JUNE, CH MOND, JJ AF BRUNSWICK, M JUNE, CH MOND, JJ TI B-LYMPHOCYTE IMMUNOGLOBULIN RECEPTOR DESENSITIZATION IS DOWNSTREAM OF TYROSINE KINASE ACTIVATION SO CELLULAR IMMUNOLOGY LA English DT Note ID PHOSPHOLIPASE-C; MEMBRANE IMMUNOGLOBULIN; MONOCLONAL-ANTIBODIES; CROSS-LINKING; SIGNAL TRANSDUCTION; PHOSPHORYLATION; CELLS; SRC; IG; STIMULATION AB Resting mature B cells have two classes of immunoglobulin receptors on their surface, IgD and IgM. Activation of a cell by crosslinking one of these receptors leads to homologous and heterologous receptor anergy as judged by the inability to induce a second calcium signal 2 hr after the initial activation step. The mechanism for this anergy is not known. In this report we show that this receptor anergy is downstream of tyrosine kinase activation in that cells pretreated with anti-IgM, when stimulated with anti-IgD, showed tyrosine phosphorylation comparable to that of naive cells, but had no calcium response. (C) 1994 Academic Press, Inc. C1 NMRI,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. RP BRUNSWICK, M (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV MONOCLONAL ANTIBODIES,MOLEC & DEV IMMUNOL LAB,HFM 561,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [R01 AI27465] NR 25 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUN PY 1994 VL 156 IS 1 BP 240 EP 244 DI 10.1006/cimm.1994.1168 PG 5 WC Cell Biology; Immunology SC Cell Biology; Immunology GA NP117 UT WOS:A1994NP11700021 PM 8200038 ER PT J AU VANDERVEEN, JE AF VANDERVEEN, JE TI SHOULD HACCP BE REQUIRED FOR THE CEREAL INDUSTRY SO CEREAL FOODS WORLD LA English DT Article RP VANDERVEEN, JE (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CEREAL CHEMISTS PI ST PAUL PA 3340 PILOT KNOB RD, ST PAUL, MN 55121-2097 SN 0146-6283 J9 CEREAL FOOD WORLD JI Cereal Foods World PD JUN PY 1994 VL 39 IS 6 BP 458 EP 458 PG 1 WC Food Science & Technology SC Food Science & Technology GA NU411 UT WOS:A1994NU41100008 ER PT J AU YEROKUN, T LYNCOOK, BD RINGER, DP AF YEROKUN, T LYNCOOK, BD RINGER, DP TI HYPOMETHYLATION OF THE RAT ARYL SULFOTRANSFERASE-IV GENE AND AMPLIFICATION OF A DNA-SEQUENCE DURING MULTISTAGE 2-ACETYLAMINOFLUORENE HEPATOCARCINOGENESIS SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT 2nd International Workshop on Sulfation of Xenobiotics and Endogenous Compounds CY JUN 03-06, 1993 CL SAMUEL ROBERTS NOBLE FDN, ARDMORE, OK SP SAMUEL ROBERTS NOBLE FDN HO SAMUEL ROBERTS NOBLE FDN DE ARYL SULFOTRANSFERASE IV (AST IV); 2-ACETYLAMINOFLUORENE (AAF); CHINESE HAMSTER OVARY CELLS (CHO CELLS); RESTRICTION FRAGMENT LENGTH POLYMORPHISM (RFLP) ID N-HYDROXY-2-ACETYLAMINOFLUORENE SULFOTRANSFERASE; ARYLSULFOTRANSFERASE-IV; LIVER; CELLS; CARCINOGENESIS; METHYLATION; 5-METHYLCYTOSINE; ONCOGENE; CANCER AB Rat hepatic aryl sulfotransferase IV (AST IV), which catalyses sulfuric acid esterification of N-hydroxy-2-acetylaminofluorene to its ultimate carcinogenic form, is differentially expressed during multistep 2-acetylaminofluorene (AAF) hepatocarcinogenesis. Two molecular mechanisms associated with this effect involve modulation of mRNA translational capacity at the early stages, and gene transcription at the late stages of the carcinogenic process. To characterize further the molecular mechanisms that may be involved in the transient regulation of the enzyme expression, an AST IV cDNA was used to assess the change in methylation profile and restriction fragment length polymorphism (RFLP) in the gene domain of genomic DNA derived from rats at different stages of carcinogenesis. The onset of hypomethylation of the AST IV gene domain and amplification of a 5.3-kb DNA sequence was found to correlate with the stage in AAF hepatocarcinogenesis, where rats begin to exhibit irreversible loss in hepatic enzyme expression and the liver becomes committed to hepatoma formation. This represents the first observation of both altered methylation status of AST IV gene domain and amplification of a DNA sequence whose expression may play a role in the genesis and/or progression of neoplastic transformation of initiated cells during AAF hepatocarcinogenesis. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. OKLAHOMA MED RES FDN,NOBLE CTR BIOMED RES,OKLAHOMA CITY,OK 73104. RP YEROKUN, T (reprint author), UNIV ARKANSAS,DEPT BIOL,PINE BLUFF,AR 71601, USA. NR 28 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JUN PY 1994 VL 92 IS 1-3 BP 363 EP 370 DI 10.1016/0009-2797(94)90077-9 PG 8 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA PD138 UT WOS:A1994PD13800031 PM 7913417 ER PT J AU HILLMAN, GG PURI, RK KUKURUGA, MA PONTES, JE HAAS, GP AF HILLMAN, GG PURI, RK KUKURUGA, MA PONTES, JE HAAS, GP TI GROWTH AND MAJOR HISTOCOMPATIBILITY ANTIGEN EXPRESSION REGULATION BY IL-4, INTERFERON-GAMMA (IFN-GAMMA) AND TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) ON HUMAN RENAL-CELL CARCINOMA SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE RENAL CELL CARCINOMA; IL-4; INTERFERON-GAMMA; TUMOR NECROSIS FACTOR-ALPHA ID INTERLEUKIN-4 RECEPTOR EXPRESSION; TRANSFORMED-CELLS; MELANOMA-CELLS; LINES; THERAPY; IMMUNOTHERAPY; MODULATION; INHIBITION; CANCER; HLA-A,B,C AB We have recently shown that human renal cell carcinoma (RCC) tumour lines express high-affinity IL-4 receptors. Binding of IL-4 to RCC cells induced a growth inhibition in the range of 20-68%. To enhance the growth inhibitory effect of IL-4, we have tested the effects of two additional cytokines capable of directly affecting tumour cell growth. IFN-gamma caused a significant inhibition of RCC tumour cell growth (up to 70%) in a dose-dependent manner, whereas the effect of TNF-alpha was more limited (0-20% inhibition). The addition of IL-4 to IFN-gamma on RCC cells sensitive to IL-4 induced a greater inhibition of cell growth than that seen with each cytokine alone. IL-4 and IFN-gamma rendered RCC cells more responsive to the inhibitory effect mediated by TNF-alpha. The combination of TNF-alpha with IL-4 and IFN-gamma induced an optimal growth inhibition (up to 90-98%) of RCC cells. In addition to a direct anti-proliferative effect, we have demonstrated that these cytokines can also enhance the expression of MHC antigens on the surface of RCC tumour cell lines which may render the cells more immunogenic. All RCC lines tested expressed class I antigens, but not class II antigens. IFN-gamma induced class II expression and up-regulated the expression of class I antigens on RCC cells. Class II antigen expression was detectable following 48 h incubation, and greater after 72 h with IFN-gamma. IL-4 minimally affected class I expression, whereas TNF-alpha up-regulated class I antigen expression. IL-4 or TNF-alpha did not induce class II expression. The combination of the three cytokines slightly augmented the up-regulation of class I and class II antigens observed with IFN-gamma alone. These observations confirm the direct interaction of IL-4, IFN-gamma and TNF-alpha with RCC tumour cells, both at the level of growth regulation and MHC antigen expression, and suggest a therapeutic potential of the combination of the three cytokines for renal cell carcinoma. C1 WAYNE STATE UNIV,SCH MED,DIV HAEMATOL & ONCOL,DETROIT,MI. HARPER GRACE HOSP,DETROIT,MI 48201. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,MOLEC TUMOUR BIOL LAB,BETHESDA,MD. RP HILLMAN, GG (reprint author), WAYNE STATE UNIV,SCH MED,DEPT UROL,LANDE BLDG ROOM 150,550 CANFIELD ST,DETROIT,MI 48201, USA. FU NCI NIH HHS [CA 22453] NR 33 TC 21 Z9 21 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 1994 VL 96 IS 3 BP 476 EP 483 PG 8 WC Immunology SC Immunology GA NP376 UT WOS:A1994NP37600018 PM 8004818 ER PT J AU BLUM, MD GRAHAM, DJ MCCLOSKEY, CA AF BLUM, MD GRAHAM, DJ MCCLOSKEY, CA TI TEMAFLOXACIN SYNDROME - REVIEW OF 95 CASES SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HEMOLYTIC UREMIC SYNDROME; ANTIBODIES; ANEMIA; DRUGS; CELL AB Four months after its approval in the United States, temafloxacin was withdrawn from the market worldwide because of frequent reports of serious hemolysis with or without other organ system dysfunction. We describe this ''temafloxacin syndrome'' on the basis of a review of 95 spontaneous reports of hemolysis sent to the Food and Drug Administration, Patients typically presented with fever, chills, and jaundice a mean of 6.4 days after starting therapy. A moderate degree of hemolysis was reflected by the mean drop in hemoglobin level (by 42 g/L) and by the mean lowest concentration of hemoglobin (97 g/L). New-onset renal dysfunction was noted in 54 cases (57%), and dialysis was required in 34 cases (63%). Congulopathy was noted in 33 cases (35%), and 48 cases (51%) met the criteria for hepatic dysfunction. Four patients developed central nervous system complications, and to patients died. Prior quinolone use was more common among patients who developed hemolysis after only one dose as opposed to two or more doses (P < .001). These data suggest that temafloxacin causes immune hemolytic anemia, most likely secondary to immune complex formation. RP BLUM, MD (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV ANTIINFECT DRUG PROD,HFD-520,5600 FISHERS LANE,ROOM 12B-45,ROCKVILLE,MD 20857, USA. NR 18 TC 94 Z9 96 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1994 VL 18 IS 6 BP 946 EP 950 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NQ826 UT WOS:A1994NQ82600017 PM 8086558 ER PT J AU TAIRA, M OTANI, H JAMRICH, M DAWID, IB AF TAIRA, M OTANI, H JAMRICH, M DAWID, IB TI EXPRESSION OF THE LIM CLASS HOMEOBOX GENE XLIM-1 IN PRONEPHROS AND CNS CELL LINEAGES OF XENOPUS-EMBRYOS IS AFFECTED BY RETINOIC ACID AND EXOGASTRULATION SO DEVELOPMENT LA English DT Article DE XENOPUS LAEVIS; NOTOCHORD; PRONEPHROS; CENTRAL NERVOUS SYSTEM; RETINOIC ACID; EXOGASTRULATION; HOMEOBOX GENE; LIM DOMAIN; XLIM-1 ID CENTRAL-NERVOUS-SYSTEM; TOUCH RECEPTOR NEURONS; CAENORHABDITIS-ELEGANS; LAEVIS EMBRYOS; PROTEIN ISL-1; DEVELOPING FOREBRAIN; SPEMANN ORGANIZER; NEURAL INDUCTION; EARLY RESPONSE; INSULIN GENE AB The LIM class homeobox gene Xlim-1 is expressed in Xenopus embryos in the lineages leading to (i) the notochord, (ii) the pronephros, and (iii) certain cells of the central nervous system (CNS). In its first expression phase, Xlim-1 mRNA arises in the Spemann organizer region, accumulates in prechordal mesoderm and notochord during gastrulation, and decays in these tissues during neurula stages except that it persists in the posterior tip of the notochord. In the second phase, expression in lateral mesoderm begins at late gastrula, and converges to the pronephros at tailbud stages. Expression in a central location of the neural plate also initiates at late gastrula, expands anteriorly and posteriorly, and becomes established in the lateral regions of the spinal cord and hindbrain at tailbud stages. Thus Xlim-1 expression precedes morphogenesis, suggesting that it may be involved in cell specification in these lineages. Enhancement of Xlim-1 expression by retinoic acid (RA) was first detectable in the dorsal mesoderm at initial gastrula. During gastrulation and early neurulation, RA strongly enhanced Xlim-1 expression in all three lineages and also expanded its expressing domains; this overexpression correlated well with RA phenotypes such as enlarged pronephros and hindbrain-like structure. Exogastrulation reduced Xlim-1 expression in the lateral mesoderm and ectoderm but not in the notochord, suggesting that the second phase of Xlim-1 expression requires mesoderm/ectoderm interactions. RA treatment of exogastrulae did not revert this reduction. C1 US FDA,CTR BIOL EVALUAT & RES,DEV BIOL LAB,BETHESDA,MD 20892. RP TAIRA, M (reprint author), NICHHD,GENET MOLEC LAB,BETHESDA,MD 20892, USA. FU NICHD NIH HHS [NICHD N01-HD-2-3144] NR 69 TC 116 Z9 117 U1 0 U2 0 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 JUN PY 1994 VL 120 IS 6 BP 1525 EP 1536 PG 12 WC Developmental Biology SC Developmental Biology GA NT555 UT WOS:A1994NT55500015 PM 7914163 ER PT J AU NAWAZ, MS FRANKLIN, W CERNIGLIA, CE AF NAWAZ, MS FRANKLIN, W CERNIGLIA, CE TI DEGRADATION OF ALIPHATIC AMIDE MIXTURE BY IMMOBILIZED AND NONIMMOBILIZED CELLS OF PSEUDOMONAS SP SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID BOUND PESTICIDE-RESIDUES; MICROBIAL-DEGRADATION; ACRYLAMIDE; BIODEGRADATION; ACETONITRILE; METABOLISM; TOXICITY; KINETICS; SOIL; RATS AB A strain of Pseudomonas sp. capable of utilizing acrylamide as the sole source of carbon and nitrogen was tested for its ability to degrade an aliphatic amide mixture containing acrylamide, propionamide, butyramide, and methacrylamide. Batch cultures of Pseudomonas sp. degraded butyramide and propionamide at the rate of 115 mumol/h and at the rate of 127 mumol/h to butyric and propionic acids and ammonia in 48 h. Acrylamide and methacrylamide were degraded to acrylic acid and methacrylic acid in 72 h at the rate of 97 and 78 mumol/h, respectively. Faster rates of degradation could be obtained when the bacteria was immobilized. Calcium alginate-immobilized cells of the isolate degraded the mixture of butyramide, propionamide, acrylamide, and methacrylamide within 2 h at the rate of 2750, 3050, 3500, and 2800 mumol/h, respectively, to their corresponding carboxylic acids and ammonia. Higher amidase activity of 14.3, 14.0, and 17.3 were obtained with acetamide, acrylamide, and isobutyramide, and lower amidase activity of 9.3, 9.4, and 10.2 were obtained with methacrylamide, propionamide, and butyramide, respectively. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. NR 28 TC 13 Z9 17 U1 3 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD JUN PY 1994 VL 28 IS 6 BP 1106 EP 1109 DI 10.1021/es00055a020 PG 4 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA NP277 UT WOS:A1994NP27700024 PM 22176236 ER PT J AU ROSENBERG, AS SECHLER, JMG HORVATH, JA MANIERO, TG BLOOM, ET AF ROSENBERG, AS SECHLER, JMG HORVATH, JA MANIERO, TG BLOOM, ET TI ASSESSMENT OF ALLOREACTIVE T-CELL SUBPOPULATIONS OF AGED MICE IN-VIVO - CD4+ BUT NOT CD8+ T-CELL-MEDIATED REJECTION RESPONSE DECLINES WITH ADVANCED AGE SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE ALLOGRAFTS; AGING; CD4+; T CELLS; T CELLS; CYTOTOXIC T LYMPHOCYTES ID LYMPHOCYTES-T; INTERLEUKIN-2 RECEPTOR; AGING MICE; PRECURSOR FREQUENCY; MURINE LYMPHOCYTES; CYTO-TOXICITY; OLD MICE; CLASS-I; EXPRESSION; SUBSETS AB The present investigation explored age-related alterations in T cell populations mediating allospecific responses in vivo. Healthy aged and young H-2(b) and H-2(b)xH-2(k) mice were engrafted with major histocompatibility complex (MHC) class II-disparate bm12 skin, rejection of which requires CD4(+) T cells, and MHC class I-disparate bm1 skin, rejection of which requires CD8(+) T cells. Aged mice of both genders exhibited prolonged survival of bm12 skin grafts relative to their young counterparts but rejected bm1 skin grafts at a rate equivalent to that of young mice. Consistent with prolonged survival of bm12 skin grafts, markedly diminished levels of Ia(bm12) CTL activity were elicited from T cells of aged mice in vitro. However, no such decline was observed in the level of K-bm1 CTL from T cells of aged mice. The alterations in Ia(bm12) allospecific responses were not attributable to quantitative changes in CD4(+) T cells of aged mice, and addition of soluble T cell helper factors to response cultures of aged mice did not augment Ia(bm12) cytotoxic T lymphocytes activity These data demonstrate that aging fundamentally affects CD4(+) T cell-mediated allospecific responses particularly in vivo, and that deficient generation of soluble T cell helper factors alone cannot explain this deficit. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,BETHESDA,MD. RP ROSENBERG, AS (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD HFM-535,8800 ROCKVILLE IKE,BETHESDA,MD 20892, USA. NR 42 TC 13 Z9 13 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 1994 VL 24 IS 6 BP 1312 EP 1316 DI 10.1002/eji.1830240611 PG 5 WC Immunology SC Immunology GA NT243 UT WOS:A1994NT24300010 PM 7911422 ER PT J AU TANKERSLEY, DL AF TANKERSLEY, DL TI DIMER FORMATION IN IMMUNOGLOBULIN PREPARATIONS AND SPECULATIONS ON THE MECHANISM OF ACTION OF INTRAVENOUS IMMUNE GLOBULIN IN AUTOIMMUNE-DISEASES SO IMMUNOLOGICAL REVIEWS LA English DT Review ID GAMMA-GLOBULIN; THROMBOCYTOPENIC PURPURA; ANTIHEMOPHILIC-FACTOR; AUTOANTIBODIES; ANTIIDIOTYPES; INFUSION; IGG RP TANKERSLEY, DL (reprint author), CTR BIOL EVALUAT & RES,DIV HEMATOL,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 30 TC 58 Z9 59 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 JUN PY 1994 VL 139 BP 159 EP 172 DI 10.1111/j.1600-065X.1994.tb00861.x PG 14 WC Immunology SC Immunology GA NW397 UT WOS:A1994NW39700008 PM 7927410 ER PT J AU BLOOM, ET MOSTOWSKI, HS HORVATH, JA AF BLOOM, ET MOSTOWSKI, HS HORVATH, JA TI DOES THE AGE-RELATED CHANGE IN CD44-DEFINED T-CELL SUBSETS HAVE FUNCTIONAL-SIGNIFICANCE FOR CYTOTOXIC T-LYMPHOCYTE GENERATION SO IMMUNOLOGY LETTERS LA English DT Article DE AGING; CYTOTOXIC T LYMPHOCYTES; CD44; T CELL; MEMORY T CELL; CYTOTOXIC T CELL ID OLD MICE; MEMORY; CD44; ACTIVATION; EXPRESSION; PGP-1; PROLIFERATION; MOLECULE; RECEPTOR; CALCIUM AB CD44 or Pgp-1 is a transmembrane leukocyte adhesion-related glycoprotein which is often expressed in greater density on the membranes of memory T lymphocytes (CD44(hi)) compared to naive T cells (CD44(lo)). The proportion of Pgp(hi) or CD44(hi) cells among T cells is increased with advancing age. We examined the relevance of this alteration for the age-related decrease in the generation of allospecific CTL activity. The findings confirm the age-related increase in the frequency of CD44(hi) cells in spleens of aged mice of several strains, but also show interstrain variability in the magnitude of the increase (bml > C57BL/6 > BALB/c). In contrast, we found that after allo-stimulation, the proportion of cells bearing the memory phenotype is decreased in cells from aged mice, particularly within the CD8(+) T cell subset. To determine if these observations reflected an alteration in the frequency or responsiveness of naive T cells, enriched populations of spleen cells depleted of CD44(hi) cells were prepared from spleen cells of young and aged mice, and stimulated in mixed lymphocyte culture. Enrichment for cells expressing the naive phenotype did not restore the ability of T cells is from aged mice to generate allospecific CTL. Together, these findings suggest that (1) the age-related increase in frequency of splenic T cells expressing memory phenotype and concordant decrease in phenotypically naive cells, does not explain the age-related decrease in the ability to generate primary allo-CTL, and (2) naive cells from aged mice exhibit intrinsically compromised ability to generate CTL in response to primary alloantigenic stimulation. RP BLOOM, ET (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CELL & GENE THERAPY,CELLULAR IMMUNOL LAB HFM518,BETHESDA,MD 20892, USA. NR 26 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JUN 1 PY 1994 VL 40 IS 3 BP 251 EP 258 DI 10.1016/0165-2478(94)00072-7 PG 8 WC Immunology SC Immunology GA PB029 UT WOS:A1994PB02900010 PM 7525465 ER PT J AU KESSLER, DA AF KESSLER, DA TI INTRODUCING MEDWATCH - A NEW APPROACH TO REPORTING MEDICATION AND DEVICE ADVERSE-EFFECTS AND PRODUCT PROBLEMS, (REPRINTED FROM JAMA, VOL 269, 1993) SO JOURNAL OF ADOLESCENT HEALTH LA English DT Reprint ID DRUG EVENTS; CONSEQUENCES; SAFETY RP KESSLER, DA (reprint author), US FDA,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD JUN PY 1994 VL 15 IS 4 BP 281 EP 285 PG 5 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA NU129 UT WOS:A1994NU12900002 ER PT J AU ADAMS, WP POOCHIKIAN, G TAYLOR, AS PATEL, RM BURKE, GP WILLIAMS, RL AF ADAMS, WP POOCHIKIAN, G TAYLOR, AS PATEL, RM BURKE, GP WILLIAMS, RL TI REGULATORY ASPECTS OF MODIFICATIONS TO INNOVATOR BRONCHODILATOR METERED-DOSE INHALERS AND DEVELOPMENT OF GENERIC SUBSTITUTES SO JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG LA English DT Review DE REGULATORY REVIEW; METERED DOSE INHALERS; MDIS; INHALATION AEROSOLS; BETA-ADRENERGIC AGONISTS; REFORMULATION OF APPROVED PRODUCTS; SAFETY AND EFFECTIVENESS TESTING, CMC ISSUES; GENERIC PRODUCTS; CMC ISSUES; IN-VITRO BIOEQUIVALENCE, IN-VIVO BIOEQUIVALENCE AB Regulatory requirements for modifications to an approved innovator metered dose inhaler (pressurized MDI; USP nomenclature: inhalation aerosol) and for development of a new generic product are discussed. Although many of the requirements apply generally to MDI's, they are discussed with specific reference to albuterol. Changes to the container and closure system may impact on the dosimetry of the redesigned product, as well as upon toxicologic and chemistry, manufacturing and controls (CMC) concerns. Changes to the formulation, including the use of alternate propellants, may raise issues requiring both clinical and in vitro performance evaluation. In view of the level of interest of a number of firms in approval requirements for generic Albuterol Inhalation Aerosol products, the article discusses in considerable detail the CMC and bioequivalence requirements for a generic product. Similarities in the CMC. requirements for innovator and generic products are evident. Three comparative in vitro bioequivalence tests, particle size distribution, spray pattern and plume geometry, and unit spray content, established by the Division of Bioequivalence are discussed. Similarities and differences in the in vivo requirements' for innovator and generic products are evident. Differences are the result of U.S. statute, which requires safety and efficacy testing for a product approved under a new drug application (NDA), but documentation of bioequivalence for a product approved under an abbreviated new drug application (ANDA). The advantages and disadvantages of three pharmacodynamic study designs which have potential usefulness for documentation of in vivo bioequivalence are discussed. RP ADAMS, WP (reprint author), US FDA,DIV BIOEQUIVALENCE,OFF GENER DRUGS HFD 658,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 0 TC 19 Z9 19 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0894-2684 J9 J AEROSOL MED JI J. Aerosol Med.-Depos. Clear. Eff. Lung PD SUM PY 1994 VL 7 IS 2 BP 119 EP 134 DI 10.1089/jam.1994.7.119 PG 16 WC Public, Environmental & Occupational Health; Respiratory System SC Public, Environmental & Occupational Health; Respiratory System GA NV797 UT WOS:A1994NV79700002 PM 10147277 ER PT J AU CALVEY, EM MATUSIK, JE WHITE, KD BETZ, JM BLOCK, E LITTLEJOHN, MH NAGANATHAN, S PUTMAN, D AF CALVEY, EM MATUSIK, JE WHITE, KD BETZ, JM BLOCK, E LITTLEJOHN, MH NAGANATHAN, S PUTMAN, D TI OFF-LINE SUPERCRITICAL-FLUID EXTRACTION OF THIOSULFINATES FROM GARLIC AND ONION SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article ID CHROMATOGRAPHY-MASS-SPECTROMETRY; CARBON-DIOXIDE EXTRACTION; GAS-CHROMATOGRAPHY; ALLIUM CHEMISTRY; CHINESE CHIVE; HPLC ANALYSIS; PESTICIDES; SCALLION; PRODUCTS; SHALLOT AB Supercritical fluid (SF) extracts of fresh garlic (Allium sativum) and fresh onion (Allium cepa) were analyzed by liquid chromatography, gas chromatography (GC), and mass spectrometry (MS). Allicin (2-propene-1-sulfinothioic acid S-2-propenyl ester), the major thiosulfinate found in fresh garlic, was readily extracted by using Supercritical CO2 (SC-CO2). Under SF extraction conditions using a solvent trap, the yield of allicin from a water homogenate of fresh garlic was 98.2%; however, when a solid-phase trap (i.e., condensation on glass beads) was used, the yield of allicin was 124.6% relative to yields obtained with methylene chloride extraction. An increase in the quantity of thermal decomposition products with respect to allicin was evident when the garlic was extracted at temperatures greater than 36 degrees C. The identity of allicin in the garlic SF extracts was confirmed by thermospray MS. The SF extraction of yellow onion was ca. 69% as efficient as the extraction with diethyl ether, as determined by GC-MS. C1 SUNY ALBANY,DEPT CHEM,ALBANY,NY 12222. RP CALVEY, EM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. RI Block, Eric/D-3989-2014 NR 30 TC 30 Z9 37 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN PY 1994 VL 42 IS 6 BP 1335 EP 1341 DI 10.1021/jf00042a017 PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA NT867 UT WOS:A1994NT86700017 ER PT J AU OHANLON, TP DALAKAS, MC PLOTZ, PH MILLER, FW AF OHANLON, TP DALAKAS, MC PLOTZ, PH MILLER, FW TI THE ALPHA-BETA-T-CELL RECEPTOR REPERTOIRE IN INCLUSION-BODY MYOSITIS - DIVERSE PATTERNS OF GENE-EXPRESSION BY MUSCLE-INFILTRATING LYMPHOCYTES SO JOURNAL OF AUTOIMMUNITY LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; MULTIPLE-SCLEROSIS; RHEUMATOID-ARTHRITIS; POLYMYOSITIS; DISEASE; PROTEIN; RECOGNITION; USAGE; DERMATOMYOSITIS; AUTOANTIBODIES C1 NINCDS,BETHESDA,MD 20892. NIAMSD,BETHESDA,MD 20892. RP OHANLON, TP (reprint author), US FDA,CTR BIOL EVALUAT & RES,MOLEC IMMUNOL LAB,BLDG 29,ROOM 507,HFM-521,BETHESDA,MD 20205, USA. NR 51 TC 33 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD JUN PY 1994 VL 7 IS 3 BP 321 EP 333 DI 10.1006/jaut.1994.1023 PG 13 WC Immunology SC Immunology GA NP269 UT WOS:A1994NP26900003 PM 7916906 ER PT J AU MISHRA, N YAHIRO, M MORREY, BF AF MISHRA, N YAHIRO, M MORREY, BF TI THE FOOD-AND-DRUG-ADMINISTRATIONS REGULATION OF ORTHOPEDIC DEVICES SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article C1 US FDA,DIV GEN & RESTORAT DEVICES,ROCKVILLE,MD 20850. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. RP MISHRA, N (reprint author), US FDA,2092 GAITHER RD,OAKGROVE RM 149,ROCKVILLE,MD 20918, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUN PY 1994 VL 76A IS 6 BP 919 EP 922 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA NR372 UT WOS:A1994NR37200018 PM 8200902 ER PT J AU GHEESLING, LL CARLONE, GM PAIS, LB HOLDER, PF MASLANKA, SE PLIKAYTIS, BD ACHTMAN, M DENSEN, P FRASCH, CE KAYHTY, K MAYS, JP NENCIONI, L PEETERS, C PHIPPS, DC POOLMAN, JT ROSENQVIST, E SIBER, GR THIESEN, B TAI, J THOMPSON, CM VELLA, PP WENGER, JD AF GHEESLING, LL CARLONE, GM PAIS, LB HOLDER, PF MASLANKA, SE PLIKAYTIS, BD ACHTMAN, M DENSEN, P FRASCH, CE KAYHTY, K MAYS, JP NENCIONI, L PEETERS, C PHIPPS, DC POOLMAN, JT ROSENQVIST, E SIBER, GR THIESEN, B TAI, J THOMPSON, CM VELLA, PP WENGER, JD TI MULTICENTER COMPARISON OF NEISSERIA-MENINGITIDIS SEROGROUP-C ANTI-CAPSULAR POLYSACCHARIDE ANTIBODY-LEVELS MEASURED BY A STANDARDIZED ENZYME-LINKED-IMMUNOSORBENT-ASSAY SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INFLUENZAE TYPE-B; RADIOANTIGEN BINDING ASSAY; GROUP-A; MENINGOCOCCAL DISEASE; ELISA; VACCINES; CHILDREN; RADIOIMMUNOASSAY; IMMUNIZATION; QUANTITATION AB A standardized enzyme-linked immunosorbent assay (ELISA) was used by 11 laboratories to measure levels of total serum antibody to Neisseria meningitidis serogroup C capsular polysaccharide in 16 unpaired pre- and postvaccination serum samples. Twelve serum samples were from adults, and four were from children aged 2, 3, 5, and 9. The between-laboratory coefficient of variation for pre- and postvaccination sera ranged from 16 to 59% and 11 to 21%, respectively. The average percent difference (absolute value) from the between laboratory means for all prevaccination sera measured by each laboratory was 24%, whereas the average percent difference was 13% for all postvaccination sera. A postvaccination quality control serum was diluted three times to give optical densities on the high, middle, and low portions of the standard reference curve. The three dilutions were assayed by the II laboratories a total of 241 times and yielded an overall coefficient of variation of 20%. Antibody-binding inhibition curves showed that the standardized ELISA was specific for N. meningitidis serogroup C capsular polysaccharide antibody. Fifty percent inhibition of seven serum samples was obtained after reaction with an average concentration of 0.9 mu g of meningococcal serogroup C polysaccharide per mi; an average of 93% inhibition was obtained with 50 pg of polysaccharide per mt The acceptance and use of this standardized ELISA will reduce between-laboratory assay variability and ensure a more accurate and reproducible assessment of immunogenicity for vaccines under development. C1 CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,CHILDHOOD & RESP DIS BRANCH,ATLANTA,GA 30333. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,BIOSTAT & INFORMAT MANAGEMENT BRANCH,ATLANTA,GA 30333. MAX PLANCK INST MOLEC GENET,W-1000 BERLIN,GERMANY. UNIV IOWA,IOWA CITY,IA 52242. US FDA,BETHESDA,MD 20892. NATL PUBL HLTH INST,HELSINKI,FINLAND. CONNAUGHT LABS INC,SWIFTWATER,PA 18370. BIOCINE SCLAVO SPA,SIENA,ITALY. NATL INST PUBL HLTH & ENVIRONM PROTECT,3720 BA BILTHOVEN,NETHERLANDS. LEDERLE PRAXIS BIOL INC,W HENRIETTA,NY 14586. NATL INST PUBL HLTH,OSLO,NORWAY. DANA FARBER CANC INST,BOSTON,MA 02115. AMERICAN VACCINE CORP,AMVAX,BELTSVILLE,MD 20705. MERCK SHARP & DOHME LTD,RES LABS,W POINT,PA 19484. NR 32 TC 138 Z9 143 U1 0 U2 1 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 JUN PY 1994 VL 32 IS 6 BP 1475 EP 1482 PG 8 WC Microbiology SC Microbiology GA NL918 UT WOS:A1994NL91800011 PM 8077392 ER PT J AU UHAA, IJ FISHBEIN, DB OLSON, JG RIVES, CC WAAG, DM WILLIAMS, JC AF UHAA, IJ FISHBEIN, DB OLSON, JG RIVES, CC WAAG, DM WILLIAMS, JC TI EVALUATION OF SPECIFICITY OF INDIRECT ENZYME-LINKED-IMMUNOSORBENT-ASSAY FOR DIAGNOSIS OF HUMAN Q-FEVER SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HEAT-SHOCK PROTEINS; INDIRECT FLUORESCENT-ANTIBODY; COXIELLA-BURNETII; COMPLEMENT-FIXATION; ESCHERICHIA-COLI; PHASE-I; IMMUNOGLOBULIN RESPONSES; SEROLOGICAL DIAGNOSIS; IMMUNE-RESPONSE; UNITED-STATES AB Ninety-five acute- and convalescent-phase serum specimens from 48 patients suspected of having rickettsial or Legionella infections were assayed for antibodies to Coxiella burnetii, the causative agent of Q fever. To evaluate the specificity of the indirect enzyme-linked immunosorbent assay (ELISA) for human Q fever, we compared the ELISA results with those of the indirect immunofluorescence antibody (IFA) test. The ELISA data were analyzed by two different criteria for a positive test. The first criterion for positive results by ELISA was based upon diagnostic titers established in a study of 150 subjects who had no demonstrable cellular or humoral immune responses to C. burnetii phase I or phase II whole cells or phase I lipopolysaccharide. The second criterion was based upon diagnostic antibody titers in a study of 51 subjects who had been diagnosed as having clinical Q fever and had fourfold or greater rises in humoral immune responses to C. burnetii phase I and phase II whole-cell antigens. A comparison of the ELISA and IFA test results of the 95 serum specimens indicated excellent agreement between the tests (Kappa = 92.9%; P < 0.05). None of the 38 patients whose etiologies were confirmed serologically as Legionnaires' disease or rickettsial diseases other than Q fever were classified as positive for C. burnetii by the ELISA. Only one patient identified by the IFA test as having Q fever was not scored positive by the ELISA. These results suggest that the ELISA is useful for epidemiologic screening and as a diagnostic test for human Q fever. C1 US PHS,CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333. US PHS,CTR DIS CONTROL & PREVENT,EPIDEMIOL PROGRAM OFF,DIV FIELD EPIDEMIOL,INT BRANCH,ATLANTA,GA 30333. USA,MED RES INST INFECT DIS,DIV BACTERIOL,PATHOGENESIS & IMMUNOL BRANCH,FREDERICK,MD 21702. US FDA,CTR BIOL EVALUAT & RES,DIV VACCINE & RELATED PROD APPLICAT,OFF VACCINE RES & REVIEW,ROCKVILLE,MD 20852. NR 47 TC 26 Z9 26 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 JUN PY 1994 VL 32 IS 6 BP 1560 EP 1565 PG 6 WC Microbiology SC Microbiology GA NL918 UT WOS:A1994NL91800027 PM 8077404 ER PT J AU LATHERS, CM CHARLES, JB SCHNEIDER, VS FREY, MAB FORTNEY, S AF LATHERS, CM CHARLES, JB SCHNEIDER, VS FREY, MAB FORTNEY, S TI USE OF LOWER-BODY NEGATIVE-PRESSURE TO ASSESS CHANGES IN HEART-RATE RESPONSE TO ORTHOSTATIC LIKE STRESS DURING 17 WEEKS OF BED REST SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 12th Frontiers of Clinical Pharmacology Symposium, Pharmacology Beyond Earths Boundaries CY MAY 06-08, 1992 CL HOUSTON, TX ID SPACE-FLIGHT; ZERO-GRAVITY; UP TILT; INTOLERANCE; ASTRONAUTS; IMMERSION; BEDREST; SHIFTS AB This study examined the heart rate response to lower body negative pressure (LBNP) during 17 weeks of horizontal bed rest to estimate the development and duration of orthostatic instability elicited by this model for space flight. Based on data from Skylab, the authors hypothesized that orthostatic (LBNP) instability would appear during the first 3 to 4 weeks, and would then remain constant for the duration of bed rest. Heart rates of four healthy adult male subjects were monitored at rest and during LBNP for 1 week of ambulatory control, 17 weeks of horizontal bed rest, and 5 weeks of recovery. The LBNP protocol consisted of 10 minutes of control (atmospheric pressure) and 5 minutes each at 5, 10, 20, 30, 40, and 50 mm Hg decompression, followed by a 10-minute recovery period; this protocol was repeated weekly to document the progressive changes in heart rate response to LBNP. Lower body negative pressure was terminated early if symptoms compatible with the onset of syncope occurred. Throughout the study, heart rate was unchanged at 5, 10, and 20 mm Hg, but it increased at 30, 40, and 50 mm Hg LBNP. During the pre-bed rest period, peak heart rate was 97 +/- 10 beats/min (mean +/- SE), occurring at 50 mm Hg for all four subjects. After 3 days of bed rest, all monitored heart rate responses, including values after release of LBNP, were only slightly elevated (NS) above pre-bed rest level. Peak heart rate was 118 +/- 21 beats/min at 50 mm Hg decompression (NS; N = 3). After 3 weeks of bed rest, peak heart rare was 110 +/- 16 beats/min at 50 mm Hg decompression (NS; N = 4). The slight increase (NS) in heart rate persisted throughout the 17 weeks of bed rest. In three subjects, the duration of tolerance to LBNP decreased; in two subjects, decompression was ended before completion of the full 5-minute period at 50 mm Hg; and in one subject, decompression was ended before completion of the full 5-minute period at 40 mm Hg. This indicates a decrease in orthostatic tolerance in three subjects. The heart rate responses after 1 day of reambulation appeared no different than those for weeks 1 through 17 of bed rest. After 3 days of reambulation, the heart rate response during LBNP was similar to that recorded before bed rest (NS). After 32 days of reambulation, the heart rate was slightly lower (NS) than before bed rest at all levels of LBNP and recovery. The data are similar to those obtained during Skylab, including the increase in heart rate response after 1 week of space flight, which was maintained throughout the period of weightlessness. The data indicate that the heart rate changes associated with orthostatic instability develop early (after as few as 3 days of bed rest) and persist throughout the entire 17 weeks of horizontal bed rest. C1 US FDA,DIV CARDIORENAL HFD110,ROCKVILLE,MD. SPACE BIOMED RES INST,HOUSTON,TX. UNIV TEXAS,SCH MED,HLTH SCI CTR,DEPT MED,HOUSTON,TX. LOCKHEED ENGN & SCI CO,WASHINGTON,DC. KRUG LIFE SCI,HOUSTON,TX. NASDA,HOUSTON,TX. NR 62 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUN PY 1994 VL 34 IS 6 BP 563 EP 570 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NQ189 UT WOS:A1994NQ18900004 PM 8083387 ER PT J AU CHARLES, JB LATHERS, CM AF CHARLES, JB LATHERS, CM TI SUMMARY OF LOWER-BODY NEGATIVE-PRESSURE EXPERIMENTS DURING SPACE-FLIGHT SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 12th Frontiers of Clinical Pharmacology Symposium, Pharmacology Beyond Earths Boundaries CY MAY 06-08, 1992 CL HOUSTON, TX ID HEAD-UP TILT; RESPONSES; BEDREST AB This paper summarizes the lower body negative pressure experiments performed in space, beginning with the experiments conducted on Skylab, because this program provided the most cardiovascular physiology data for United States space flight. Data obtained during studies of lower body negative pressure for use as a countermeasure after months of Russian space flight are also presented. Lower body negative pressure experiments conducted aboard Space Shuttle flights provide data about the deadaptation response of the cardiovascular system to orthostatic stress occurring during periods of zero gravity, and about protection against postflight orthostatic intolerance. Data obtained using Russian and American lower body negative pressure devices indicate that, when a crew member stands, as opposed to being supported by a seat or saddle as in the American device, there may be a slight detrimental effect in terms of the cardiovascular response to this orthostatic stress. Comparison of heart rate and blood pressure response to entry and landing of the Shuttle indicate that, although lower body negative pressure is a different stress and is applied in a different manner, the maximum heart rates during lower body negative pressure are reached at approximately the same point that the maximum heart rates are reached during entry and landing. Thus, the use of a lower body negative pressure stress in flight is a fairly good predictor of the cardiovascular response to the actual entry and landing of the Shuttle. C1 US FDA,DIV CARDIORENAL PROD,ROCKVILLE,MD. RP CHARLES, JB (reprint author), NASA,LYNDON B JOHNSON SPACE CTR,SPACE BIOMED RES INST,MAIL CODE SD5,HOUSTON,TX 77058, USA. NR 15 TC 16 Z9 20 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUN PY 1994 VL 34 IS 6 BP 571 EP 583 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NQ189 UT WOS:A1994NQ18900005 PM 8083388 ER PT J AU VICK, JA AF VICK, JA TI MEDICAL STUDIES OF POISONOUS LAND AND SEA-SNAKES SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 12th Frontiers of Clinical Pharmacology Symposium, Pharmacology Beyond Earths Boundaries CY MAY 06-08, 1992 CL HOUSTON, TX AB The comparative toxicity and pathophysiology of thirteen (13) of poisonous snakes indigenous to the area in and around Saudi Arabia were determined. Four snakes from the Viperidae family, six from the Elapidae family, and three representative sea snakes from the family Hydrophiodae were included. Anesthetized adult Beagle dogs and anesthetized monkeys were used in the study. Vital physiologic functions were recorded continuously as were changes in the blood coagulation system and any tissue damage produced by the venom at the site of envenomation. venom was administered intravenously or by an actual bite. Venom from the snakes of the family Viperidae produced death in an average of 3 hours. The average lethal dose was 1.13 mg/kg. Depression of 1st and 2nd stage clotting factors and a decrease in fibrinogen levels and in platelet counts were observed with these venoms. Findings suggestive of intravascular coagulation also were observed with moderate hemolysis of the formed elements. Some local hemorrhage was seen at the site of envenomation. venom from the Elapidae family of snakes produced death at an average of 1.7 hours. The average lethal dose was 0.70 mg/kg. Death appeared to be primarily due to respiratory paralysis after blockade at the neuromuscular junction. Only moderate hemolysis was seen with these venoms. No intravascular coagulation or tissue damage was seen. The venom of the family Hydrophiodae consistently produced death in less than 30 minutes at an average dose of 0.06 mg/kg. Tissue damage was not observed, and changes were not observed in the hematologic parameters monitored. Death in these studies was due primarily to respiratory paralysis; however, the breakdown of muscle tissue was observed. The area in and around Saudi Arabia has a number of snakes that are dangerous to humans. C1 WALTER REED ARMY INST RES,WASHINGTON,DC. RP VICK, JA (reprint author), US FDA,200 C ST SW,WASHINGTON,DC 20204, USA. NR 9 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUN PY 1994 VL 34 IS 6 BP 709 EP 712 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NQ189 UT WOS:A1994NQ18900024 PM 8083405 ER PT J AU HOLLINGWORTH, TA HUNGERFORD, JM BARNETT, JD WEKELL, MM AF HOLLINGWORTH, TA HUNGERFORD, JM BARNETT, JD WEKELL, MM TI TOTAL VOLATILE ACIDS - TEMPERATURE-DEPENDENT DECOMPOSITION INDICATOR IN HALIBUT DETERMINED BY FLOW-INJECTION ANALYSIS SO JOURNAL OF FOOD PROTECTION LA English DT Article DE TOTAL VOLATILE ACIDS; FLOW INJECTION ANALYSIS; SENSORY ANALYSIS; DECOMPOSITION; HALIBUT ID SURIMI; CRAB AB Total volatile acids (TVA) is a well known indicator for the decomposition of seafood products. A flow injection analysis (FIA) method, using a gas diffusion cell at elevated temperature, was developed for the determination of TVA in fish and applied to halibut. The FIA method is simple and rapid. The results of this study indicate that the correlation between levels of TVA and degree of decomposition is temperature dependent. C1 US FDA,SEATTLE DIST LAB,BOTHELL,WA 98021. RP HOLLINGWORTH, TA (reprint author), US FDA,SEAFOOD PROD RES CTR,22201 23RD DR SE,BOTHELL,WA 98021, USA. NR 17 TC 5 Z9 5 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 1994 VL 57 IS 6 BP 505 EP 508 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA NR987 UT WOS:A1994NR98700010 ER PT J AU HARVATH, L BROWNSON, NE FIELDS, GB SKUBITZ, APN AF HARVATH, L BROWNSON, NE FIELDS, GB SKUBITZ, APN TI LAMININ PEPTIDES STIMULATE HUMAN NEUTROPHIL MOTILITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASEMENT-MEMBRANE COMPONENTS; CELL-ADHESION; MONOCLONAL-ANTIBODIES; POLYMORPHONUCLEAR LEUKOCYTES; MULTIDOMAIN PROTEIN; FIBRONECTIN PROMOTE; RECEPTOR EXPRESSION; SYNTHETIC PEPTIDE; GLOBULAR DOMAIN; IV COLLAGEN AB Laminin, isolated from Engelbreth-Holm-Swarm tumor, and 10 chemically synthesized peptides, corresponding to various regions of the laminin A and B1 chains, were compared for their abilities to stimulate human peripheral blood polymorphonuclear leukocyte (PMN) chemotaxis and chemokinesis through polycarbonate membrane filters in a 48-well microchemotaxis assay. Peptides F-9, F-ll, F-12, and F-13 were derived from the B1 chain of laminin at the intersection of the cross, and six peptides were derived from the laminin A chain: peptide TG-1 from the amino-terminal top globule; peptides GD-1, CD-3, CD-6, and CD-7 from the carboxyl-terminal globular domain; and peptide AG-1 from above the carboxyl-terminal globular domain. Laminin and the peptides were evaluated over a concentration range of 1 to 200 mu g/ml in motility assays. Six of the peptides, F-9, F-12, GD-1, GD-3, GD-6, and TG-1, stimulated human PMN migration in the absence of a gradient (chemokinesis). A fluorescein conjugate of the most active laminin peptide, GD-1, exhibited nonspecific, nonsaturable binding to PMN. Intact laminin and the other peptides failed to stimulate human PMN migration. In contrast, intact Engelbreth-Holm-Swarm laminin stimulated rabbit peripheral blood PMN chemokinesis. These results demonstrate that rabbit and human peripheral blood PMNs have divergent migratory responses to intact laminin. These findings suggest that intact basement membrane laminin does not directly stimulate human blood PMN motility in vivo, but that selected laminin peptide sequences, which may be generated during proteolytic digestion of laminin, can activate human PMN migration. C1 UNIV MINNESOTA,SCH MED,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH MED,CTR BIOMED ENGN,MINNEAPOLIS,MN 55455. RP HARVATH, L (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,BIOL CELLULAIRE HEMATOL LAB,BLDG 29,ROOM 321,BETHESDA,MD 20892, USA. NR 50 TC 22 Z9 22 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 JUN 1 PY 1994 VL 152 IS 11 BP 5447 EP 5456 PG 10 WC Immunology SC Immunology GA NM615 UT WOS:A1994NM61500033 PM 8189064 ER PT J AU FONG, TL DIBISCEGLIE, AM BISWAS, R WAGGONER, JG WILSON, L CLAGGETT, J HOOFNAGLE, JH AF FONG, TL DIBISCEGLIE, AM BISWAS, R WAGGONER, JG WILSON, L CLAGGETT, J HOOFNAGLE, JH TI HIGH-LEVELS OF VIRAL REPLICATION DURING ACUTE HEPATITIS-B INFECTION PREDICT PROGRESSION TO CHRONICITY SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HEPATITIS B VIRUS; CHRONIC HEPATITIS B; HEPATITIS B VIRUS DNA; SEROLOGY OF HEPATITIS B ID ANTIGEN-POSITIVE HEPATITIS; VIRUS-INFECTION; SERUM; DNA AB To assess the pattern of development of sero9logic markers during acute hepatitis B, levels of HBsAg, HBeAg, and hepatitis B virus (HBV) DNA were assayed in stored serum samples obtained sequentially from 12 subjects infected with HBV during experimental studies conducted in the 1950s. Six patients developed acute self-limited hepatitis, three developed chronic hepatitis, and three had an asymptomatic infection with out HBsAg. HBsAg was the first serologic marker detected (mean = 52 days after exposure), followed by HBeAg (62 days) and HBV DNA (72 days). Peak HBsAg levels occurred before onset of symptoms and correlated with peak titers of HBeAg and HBV DNA. Patients who developed chronic hepatitis had higher peak levels of viral markers than those with self-limited disease: HBsAg (30 versus 5.4 mu g/ml), HBeAg (1:2,000 versus 1:60 titer) and HBV DNA (3,192 versus 444 pg/ml). Thus, chronic HBV infection is characterized by high levels of viral replication appearing early during the acute phase of infection. (C) 1994 Wiley-Liss, Inc.* C1 NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS SCI,HEPATATIS LAB,BETHESDA,MD. NR 19 TC 45 Z9 47 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 1994 VL 43 IS 2 BP 155 EP 158 DI 10.1002/jmv.1890430210 PG 4 WC Virology SC Virology GA NM387 UT WOS:A1994NM38700009 PM 8083663 ER PT J AU ELLWOOD, KC ROEBUCK, BD HATHCOCK, JN AF ELLWOOD, KC ROEBUCK, BD HATHCOCK, JN TI MARGINAL ZINC STATUS DOES NOT EXACERBATE PANCREATIC CARCINOGENESIS ASSOCIATED WITH DIETARY SOYBEAN TRYPSIN-INHIBITOR CONCENTRATE IN RATS SO JOURNAL OF NUTRITION LA English DT Article DE ZINC; PANCREATIC CANCER; RATS; SOYBEAN TRYPSIN INHIBITOR CONCENTRATE ID SOY PRODUCTS; SECRETION; PROTEIN; CANCER; DEFICIENCY; AZASERINE; MODEL; FLOUR; FOCI AB Although the etiology of pancreatic cancer is largely unknown, diet-associated factors may play a role. Male Sprague-Dawley rats (14 d of age) were given a single injection of either saline or azaserine and were weaned (21 d) to diets with either adequate (30 mu g/g) or low (9 mu g/g) zinc, with or without 1.0 g/100 g active trypsin inhibitor in the form of soybean trypsin inhibitor concentrate. Experimental diets were fed for 14 wk. Regardless of dietary zinc status, diets with soybean trypsin inhibitor concentrate caused hyperplasia and/or hypertrophy of the pancreas. Pancreatic zinc content was not different among groups. Low dietary zinc levels did not affect total body growth rate or serum zinc concentration. Tibia zinc was also used as an indicator of zinc status. Tibia zinc concentration was lower in rats fed diets low in zinc relative to adequate zinc diets. Azaserine-induced acidophilic foci were larger and more numerous when soybean trypsin inhibitor concentrate was present in the diet regardless of dietary zinc level. Thus, low zinc does not exacerbate the soybean trypsin inhibitor concentrate effects that promote pancreatic cancer. C1 DARTMOUTH COLL,SCH MED,DEPT PHARMACOL & TOXICOL,HANOVER,NH 03755. RP ELLWOOD, KC (reprint author), US FDA,OFF SPECIAL NUTR,DIV SCI & APPL TECHNOL,HFS-465,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 35 TC 4 Z9 4 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD JUN PY 1994 VL 124 IS 6 BP 894 EP 900 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NP543 UT WOS:A1994NP54300017 PM 8207548 ER PT J AU SISTARE, FD ROSENZWEIG, BA CONTRERA, JG JORDAN, B AF SISTARE, FD ROSENZWEIG, BA CONTRERA, JG JORDAN, B TI SEPARATE P-2T AND P-2U PURINERGIC RECEPTORS WITH SIMILAR 2ND-MESSENGER SIGNALING PATHWAYS IN UMR-106 OSTEOBLASTS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INTRACELLULAR FREE CALCIUM; HUMAN-PLATELETS; PARATHYROID-HORMONE; CYTOSOLIC CALCIUM; ADENOSINE-DIPHOSPHATE; P2-PURINERGIC RECEPTORS; TRANSDUCTION SYSTEMS; EXPRESSION CLONING; ATP RECEPTOR; CELL-LINE AB UMR-106 rat osteogenic sarcoma cells express two calcium signaling Pp purinergic receptors. One is a P-2U receptor with EC(50),S for adenosine triphosphate (ATP) and uridine triphosphate (UTP) of 2.6 and 2.4 mu M, respectively. The other is a novel P-2T receptor for adenosine diphosphate (ADP) (EC(50) 0.4 mu M), adenosine 5'-O-(2-thiodiphosphate). (EC(50) 5 mu M), 2-methylthio ATP (EC(50) 0.2 mu M), and 2-methylthio ADP (EC(50) 0.04 mu gM). Responses to these ligands are desensitized by ADP but not by UTP. Responses to UTP and ATP are desensitized by UTP but not by ADP or adenosine 5'-O-(2-thiodiphosphate). 2-ChloroATP interacts with both receptors at high concentrations but with only the P-2T receptor at low concentrations (EC(50) 0.05 mu M). The weak platelet P-2T receptor antagonist AMP blocks this P-2T and not the P-2U receptor. Addition of ATP after UTP desensitization of P-2U receptors inhibits subsequent responsiveness to ADP but evidence for rapid conversion of ATP to ADP complicates interpretation of this apparent antagonism of P-2T receptors by ATP. A subpassage of UMR-106.P135 cells lose P-2U but retain P-2T ligand responsiveness. Activation of either P-2 receptor increases cellular IP3 concentrations in UMR-106 cells. Neither receptor can activate divalent cation entry as evidenced by their lack of effect on Mn++ quenching of fura-2 fluorescence. Neither receptor can modify parathyroid hormone receptor-mediated elevation of cellular cyclic AMP. This receptor for ADP demonstrates many of the same characteristics of the ADP receptor which we have previously reported as a P-2T receptor expressed in K562 and Dami cells. RP SISTARE, FD (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF RES RESOURCES,DIV RES & TESTING,MOD 1,RM 2007,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 53 TC 23 Z9 23 U1 0 U2 0 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 JUN PY 1994 VL 269 IS 3 BP 1049 EP 1061 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PB548 UT WOS:A1994PB54800021 PM 8014849 ER PT J AU POTHULURI, JV EVANS, FE HEINZE, TM CERNIGLIA, CE AF POTHULURI, JV EVANS, FE HEINZE, TM CERNIGLIA, CE TI FUNGAL METABOLISM OF 3-NITROFLUORANTHENE SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; CUNNINGHAMELLA-ELEGANS; DETOXIFICATION; TRANSFORMATION; 1-NITROPYRENE; FLUORANTHENE AB We investigated the metabolism of 3-nitrofluoranthene by filamentous fungus, Cunninghamella elegans ATCC 36112. Cunninghamella elegans metabolized about 72% of the 3-nitro[3,4-C-14]fluoranthene added during 144 h of incubation to 2 major metabolites. These metabolites were separated by reversed-phase high-performance liquid chromatography and identified as 3-nitronuoranthene-8-sulfate and 3-nitrofluoranthene-9-sulfate by H-1 nuclear magnetic resonance, UV-visible, and mass spectral techniques. These results, in conjunction with previous studies on the fungal metabolism of fluoranthene, indicate that the nitro substituent at the C-3 position of fluoranthene sterically hinders epoxidation and shifts metabolism to the C-8 and C-9 positions. Since the phenolic microsomal metabolites of 3-nitrofluoranthene are mutagenic, the formation oi sulfate conjugates of 8- and 9-hydroxy-3-nitrofluoranthene by C. elegans suggests that the fungal metabolic pathways may be beneficial for detoxification of this ubiquitous pollutant. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. NR 17 TC 11 Z9 11 U1 0 U2 3 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD JUN PY 1994 VL 42 IS 2 BP 209 EP 218 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NT046 UT WOS:A1994NT04600007 PM 8207756 ER PT J AU WANG, JH JONES, C NORCROSS, M BOHNLEIN, E RAZZAQUE, A AF WANG, JH JONES, C NORCROSS, M BOHNLEIN, E RAZZAQUE, A TI IDENTIFICATION AND CHARACTERIZATION OF A HUMAN HERPESVIRUS-6 GENE SEGMENT CAPABLE OF TRANSACTIVATING THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 LONG TERMINAL REPEAT IN AN SP1 BINDING SITE-DEPENDENT MANNER (VOL 68, PG 1707, 1994) SO JOURNAL OF VIROLOGY LA English DT Correction, Addition C1 UNIV NEBRASKA,CTR BIOTECHNOL,DEPT VET SCI,LINCOLN,NE 68583. UNIV VIENNA,VIENNA INT RES COOPERAT CTR,VIENNA,AUSTRIA. RP WANG, JH (reprint author), CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 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 1994 VL 68 IS 6 BP 4108 EP 4108 PG 1 WC Virology SC Virology GA NL349 UT WOS:A1994NL34900082 ER PT J AU GATEHOUSE, D HAWORTH, S CEBULA, T GOCKE, E KIER, L MATSUSHIMA, T MELCION, C NOHMI, T OHTA, T VENITT, S ZEIGER, E AF GATEHOUSE, D HAWORTH, S CEBULA, T GOCKE, E KIER, L MATSUSHIMA, T MELCION, C NOHMI, T OHTA, T VENITT, S ZEIGER, E TI RECOMMENDATIONS FOR THE PERFORMANCE OF BACTERIAL MUTATION ASSAYS SO MUTATION RESEARCH LA English DT Article DE BACTERIAL MUTATION ASSAYS; RECOMMENDATIONS; STANDARDIZATION; GENOTOXICITY TEST PROCEDURES ID SALMONELLA-TYPHIMURIUM TA97A; MAMMALIAN-MICROSOME TEST; RODENT CARCINOGENICITY; 300 CHEMICALS; AMES TEST; MUTAGENICITY; TA102; REVERSION; NITROSAMINES; STRAINS AB At the International Workshop on the Standardisation of Genotoxicity Test Procedures, in Melbourne (27-28 February 1993), the current international guidelines for the correct conduct of bacterial mutation assays were considered, and the major differences between them were examined. An attempt was made to construct a scientifically based, internationally harmonised protocol. The main points of agreement were as follows. The consensus opinion was that there are currently insufficient data to justify a preference for either the preincubation or plate-incorporation methodologies as the initial test. Whichever method is used there was consensus agreement that the bacterial test battery should consist of S. typhimurium TA1537, TA1535, TA98 and TA100. There was also consensus that the 3 strains TA97a, TA97 and TA1537 could be used interchangeably. Although it was not possible to achieve a consensus, the majority of the working group members agreed that strains for the detection of mutagens acting specifically on AT base pairs should be routinely included within the test battery. These strains may be S. typhimurium TA102 or E. coli WP2 strains (WP2 pKM101 and WP2 uvrA or WP2 uvrA pkM101). With regard to study design it was universally agreed that 5 doses of test compound should be used in each experiment, and a majority agreement was obtained for 3 plates per dose. The use of 2 plates per dose is acceptable ONLY if the experiment is repeated. It is recommended that the negative controls may consist of solvent control alone provided that historical data are available to demonstrate lack of effect of the solvent in question. Positive control compounds should be included in all experiments, although the nature of these control compounds need not be specified in the guidelines. There was consensus agreement that for non-toxic freely soluble test agents, an upper limit of 5 mg/plate should be tested (5 mu l per plate for liquids). For insoluble or toxic compounds, the recommendations were the same as those for other in vitro tests (see appropriate paper). A consensus agreement was reached on the need to carry out further tests if equivocal results are obtained in the initial test, although it was generally agreed that the design of the repeat study should be left flexible. As there are little or no data to support the use of an exact repeat assay, a majority of the group recommended that negative results in the first test should be further investigated by either conducting a modified repeat (e.g. S9 titration) or by conducting the alternative methodology. If a preincubation assay is carried out, an incubation time within the range 20-60 min is recommended, usually at a temperature of 37 degrees C. Lastly, a consensus agreement on the acceptable criteria for a positive or negative result could not be reached. There was majority agreement that a reproducible dose-response was necessary for a chemical to be classified as positive. A number of limitations of the proposed test methodology were recognised and included the adequate testing of specific chemical classes or groups, (i.e. ate-dyes and diazo compounds, gases, volatile chemicals and glycosides). Such 'special cases' should be evaluated using alternative published procedures. C1 BIOTRACE LABS, SALT LAKE CITY, UT 84119 USA. US FDA, HFF 235, MOLEC BIOL BRANCH, WASHINGTON, DC 20204 USA. F HOFFMANN LA ROCHE & CO LTD, CH-4002 BASEL, SWITZERLAND. MONSANTO CO, ENVIRONM HLTH LAB, ST LOUIS, MO 63110 USA. JAPAN BIOASSAY LAB, KANAGAWA 257, JAPAN. RHONE POULENC RORER, F-92165 ANTONY, FRANCE. NATL INST HYG SCI, TOKYO 158, JAPAN. INST CANC RES, HADDOW LABS, SUTTON, SURREY, ENGLAND. NIEHS, ENVIRONM TOXICOL PROGRAM, RES TRIANGLE PK, NC 27709 USA. RP GATEHOUSE, D (reprint author), GLAXO GRP RES LTD, DEPT GENET & REPROD TOXICOL, PARK RD, WARE SG12 0DP, HERTS, ENGLAND. NR 43 TC 120 Z9 129 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES JI Mutat. Res. PD JUN PY 1994 VL 312 IS 3 BP 217 EP 233 DI 10.1016/0165-1161(94)90037-X PG 17 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA NQ875 UT WOS:A1994NQ87500005 PM 7514736 ER PT J AU DAIN, JG COLLINS, JM ROBINSON, WT AF DAIN, JG COLLINS, JM ROBINSON, WT TI A REGULATORY AND INDUSTRIAL PERSPECTIVE OF THE USE OF C-14 AND TRITIUM ISOTOPES IN HUMAN ADME STUDIES SO PHARMACEUTICAL RESEARCH LA English DT Article C1 US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. SANDOZ PHARMACEUT CORP,SANDOZ RES INST,DRUG SAFETY,E HANOVER,NJ 07936. RP DAIN, JG (reprint author), SANDOZ PHARMACEUT CORP,SANDOZ RES INST,DEPT DRUG METAB & PHARMACOKINET DRUG SAFETY,E HANOVER,NJ 07936, USA. NR 7 TC 20 Z9 20 U1 0 U2 0 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 JUN PY 1994 VL 11 IS 6 BP 925 EP 928 DI 10.1023/A:1018958631158 PG 4 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA NR166 UT WOS:A1994NR16600026 PM 7937538 ER PT J AU BEER, JZ OLVEY, KM LEE, W ZMUDZKA, BZ AF BEER, JZ OLVEY, KM LEE, W ZMUDZKA, BZ TI REASSESSMENT OF THE DIFFERENTIAL-EFFECTS OF ULTRAVIOLET AND IONIZING-RADIATION ON HIV PROMOTER - THE USE OF CELL-SURVIVAL AS THE BASIS FOR COMPARISONS SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; HEME OXYGENASE GENE; C-JUN GENE; TRANSGENIC MICE; UVA RADIATION; INVIVO ACTIVATION; DNA DAMAGE; KAPPA-B; EXPRESSION AB Effects of different radiation treatments on the human immunodeficiency virus-1 (HIV) promoter were reassessed for exposures comparable to those encountered in clinical or cosmetic practice, using survival of the host cell as a basis for comparisons. The exposures were performed with two ultraviolet radiation sources commonly used as medical or cosmetic devices (UVASUN 2000 and FS20 lamps), a germicidal(G15T8) lamp and an X-ray machine. The UVC component of the FS20 lamp was filtered out. The emission spectra of the lamps were determined. The characteristics of these sources allowed us to discriminate among effects of UVA1 (340-400 nm), UVB + UVA2 (280-340 nm) and UVC (254 nm) radiations. Effects of irradiation were ascertained using cultures of HeLa cells stably transfected with the HIV promoter linked to a reporter-chloramphenicol acetyl transferase-gene. The exposures used caused at least two logs of cell killing. In this cytotoxicity range, UVA1 or X radiations had no effect on the HIV promoter, whereas UVB + UVA2 or UVC radiations activated the HIV promoter in a fluence-dependent manner. Survivals following exposure to UVB + UVA2 or UVC radiation were (1) at the lowest measurable HIV promoter activation, 30 and 20%, respectively, (2) at one-half maximal activation, 6 and 3%, respectively and (3) at the maximal activation, 0.5 and 0.2%, respectively. The results suggest that, among the radiations studied, UVB is the most important modality from the viewpoint of its potential effects on HIV-infected individuals, since(l) UVA1 or X radiations have no effects on the HIV promoter, (2) human exposure to UVC radiation is infrequent and (3) human UVB exposure is very common. RP BEER, JZ (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,RADIAT BIOL BRANCH,HFZ-114,ROCKVILLE,MD 20857, USA. NR 47 TC 26 Z9 25 U1 0 U2 0 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 JUN PY 1994 VL 59 IS 6 BP 643 EP 649 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NU563 UT WOS:A1994NU56300011 PM 8066124 ER PT J AU ZHANG, YH BULL, TE AF ZHANG, YH BULL, TE TI NONLINEARLY COUPLED GENERALIZED FOKKER-PLANCK EQUATION FOR ROTATIONAL RELAXATION SO PHYSICAL REVIEW E LA English DT Article ID EXTENDED DIFFUSION-MODELS; QUANTUM BROWNIAN-MOTION; INTERNAL-ROTATION; MOLECULES; LANGEVIN AB We have investigated the stochastic dynamics of a one dimensional rotor with C3 symmetry and zero barrier to rotation about the symmetry axis. Angular momentum correlation functions derived from various stochastic dynamics models were compared to the corresponding correlation functions obtained from a molecular dynamics simulation [G. Widmalm, R. W. Pastor, and T. E. Bull, J. Chem. Phys. 94, 4097 (1991)]. None of the existing classical models agrees with the simulation; and we have shown in general that no linearly coupled generalized Langevin equation with Gaussian random noise can reproduce the simulation results. A quantum stochastic dynamics model [T. E. Bull, Chem. Phys. 143, 381 (1990)] extrapolated to the classical limit does, however, agree with the computer simulations. But this model is limited to very small molecules because the matrices involved become prohibitively large for even moderately sized molecules. In order to address some of these limitations, we have constructed a nonlinearly coupled rotor-bath model for the rotor. The form of the nonlinear coupling between the rotor and bath is determined by the symmetry of the rotor. A classical nonlinearly coupled generalized Langevin equation and its corresponding nonlinearly coupled Fokker-Planck equation were derived from this microscopic rotor-bath model using the projection operator formalism. In the limit of white noise, these equations reduce to the standard equations derived with linear coupling. With colored noise, however, the linearly and nonlinearly coupled equations are distinct. Angular momentum correlation functions calculated with this nonlinearly coupled Fokker-Planck equation are in excellent agreement with the simulations both in terms of the short time Gaussian decay and long time exponential tail and in terms of the magnitudes of the correlation functions. Collision operators derived from this model should therefore provide a more accurate connection between experimentally measured quantities and the underlying microscopic dynamics. RP US FDA, CTR BIOL EVALUAT & RES, BIOPHYS LAB, 8800 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2470-0045 EI 2470-0053 J9 PHYS REV E JI Phys. Rev. E PD JUN PY 1994 VL 49 IS 6 BP 4886 EP 4902 DI 10.1103/PhysRevE.49.4886 PN A PG 17 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA NW029 UT WOS:A1994NW02900024 ER PT J AU WARBRITTON, A GILL, AM YEN, TT BUCCI, T WOLFF, GL AF WARBRITTON, A GILL, AM YEN, TT BUCCI, T WOLFF, GL TI PANCREATIC-ISLET CELLS IN PREOBESE YELLOW A(VY)/- MICE - RELATION TO ADULT HYPERINSULINEMIA AND OBESITY SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID MOUSE; INSULIN; SYSTEM AB Plasma insulin levels in yellow A(vy)/- mice begin to increase before the animals are overtly obese. Are the elevated insulin levels in yellow mice primary or secondary to the subsequent obesity? Elevated blood insulin levels in young preobese mice, due to synthesis and release of insulin by increased number of beta cells, would stimulate lipogenesis, resulting in excess lipid deposition and subsequent peripheral insulin resistance. Examination of this possibility was the objective of this study. The beta, alpha, and delta cells in the pancreata of 7-, 14-, and 21-day-old male yellow A(vy)/A and agouti Ala (BALB/c x VY)F-1 hybrid mice were counted with immunohistochemical/ morphometric techniques. The insulin and glucagon concentrations in pancreata from male and female mice of the same ages and genotypes were also assayed. In the 21-day-old male mice, the mean number of beta cells/pancreas was significantly greater in the yellow mice than in the agouti mice; however, insulin content and body weight were the same. This suggests that increased beta cell proliferation in yellow mice precedes any detectable genotype-specific increase in pancreatic insulin content or body weight. C1 US FDA,NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. PATHOL ASSOC INC,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS,INDIANAPOLIS,IN 46285. NR 16 TC 35 Z9 36 U1 0 U2 0 PU BLACKWELL SCIENCE INC 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 JUN PY 1994 VL 206 IS 2 BP 145 EP 151 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NQ948 UT WOS:A1994NQ94800008 PM 8208738 ER PT J AU KODELL, RL CHEN, JJ AF KODELL, RL CHEN, JJ TI REDUCING CONSERVATISM IN RISK-ESTIMATION FOR MIXTURES OF CARCINOGENS SO RISK ANALYSIS LA English DT Article; Proceedings Paper CT Conference on the Risk Assessment Paradigm After Ten Years: Policy and Practice Then, Now, and in the Future CY APR 05-08, 1993 CL WRIGHT PATTERSON AFB, OH SP USAF, ARMSTRONG LAB, TOXICOL DIV, USN, NAVAL MED RES INST DETACHMENT, USA, ARMY BIOMED RES & DEV LAB, US EPA, ENVIRONM CRITERIA & ASSESSMENT OFF, NATL RES COUNCIL, COMM TOXICOL DE BIOASSAY; BOOTSTRAP; LINEAR EXTRAPOLATION; SUMMING UPPER BOUNDS AB The excess cancer risk that might result from exposure to a mixture of chemical carcinogens usually must be estimated using data from experiments conducted with individual chemicals. In estimating such risk, it is commonly assumed that the total risk due to the mixture is the sum of the risks of the individual components, provided that the risks associated with individual chemicals at levels present in the mixture are low. This assumption, while itself not necessarily conservative, has led to the conservative practice of summing individual upper-bound risk estimates in order to obtain an upper bound on the total excess cancer risk for a mixture. Less conservative procedures are described here and are illustrated for the case of a mixture of four carcinogens. RP KODELL, RL (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 19 TC 13 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 JUN PY 1994 VL 14 IS 3 BP 327 EP 332 DI 10.1111/j.1539-6924.1994.tb00248.x PG 6 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA NR536 UT WOS:A1994NR53600014 PM 8029505 ER PT J AU GAYLOR, DW SLIKKER, W AF GAYLOR, DW SLIKKER, W TI MODELING FOR RISK ASSESSMENT OF NEUROTOXIC EFFECTS SO RISK ANALYSIS LA English DT Article; Proceedings Paper CT Conference on the Risk Assessment Paradigm After Ten Years: Policy and Practice Then, Now, and in the Future CY APR 05-08, 1993 CL WRIGHT PATTERSON AFB, OH SP USAF, ARMSTRONG LAB, TOXICOL DIV, USN, NAVAL MED RES INST DETACHMENT, USA, ARMY BIOMED RES & DEV LAB, US EPA, ENVIRONM CRITERIA & ASSESSMENT OFF, NATL RES COUNCIL, COMM TOXICOL DE RISK ESTIMATION; NEUROTOXICITY; BENCHMARK DOSE; CONTINUOUS DATA ID MDMA AB The regulation of noncancer toxicants, including neurotoxicants, has usually been based upon a reference dose (allowable daily intake). A reference dose is obtained by dividing a no-observed-effect level by uncertainty (safety) factors to account for intraspecies and interspecies sensitivities to a chemical. It is assumed that the risk at the reference dose is negligible, but no attempt generally is made to estimate the risk at the reference dose. A procedure is outlined that provides estimates of risk as a function of dose. The first step is to establish a mathematical relationship between a biological effect and the dose of a chemical. Knowledge of biological mechanisms and/or pharmacokinetics can assist in the choice of plausible mathematical models. The mathematical model provides estimates of average responses as a function of dose. Secondly, estimates of risk require selection of a distribution of individual responses about the average response given by the mathematical model. In the case of a normal or lognormal distribution, only an estimate of the standard deviation is needed. The third step is to define an adverse level for a response so that the probability (risk) of exceeding that level can be estimated as a function of dose. Because a firm response level often cannot be established at which adverse biological effects occur, it may be necessary to at least establish an abnormal response level that only a small proportion of individuals would exceed in an unexposed group. That is, if a normal range of responses can be established, then the probability (risk) of abnormal responses can be estimated. In order to illustrate this process, measures of the neurotransmitter serotonin and its metabolite 5-hydroxyindoleacetic acid in specific areas of the brain of rats and monkeys are analyzed after exposure to the neurotoxicant methylene-dioxymethamphetamine. These risk estimates are compared with risk estimates from the quantal approach in which animals are classified as either abnormal or not depending upon abnormal serotonin levels. RP GAYLOR, DW (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 12 TC 12 Z9 13 U1 0 U2 1 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 1994 VL 14 IS 3 BP 333 EP 338 DI 10.1111/j.1539-6924.1994.tb00249.x PG 6 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA NR536 UT WOS:A1994NR53600015 PM 7518093 ER PT J AU EPSTEIN, JS AF EPSTEIN, JS TI CONTROVERSY IN TRANSFUSION MEDICINE - USE OF EXTERNAL CONTROLS IN TRANSMISSIBLE DISEASE TESTING - CON SO TRANSFUSION LA English DT Editorial Material RP EPSTEIN, JS (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,OFF BLOOD RES & REVIEW,HFM-300,ROCKVILLE,MD 20852, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 1994 VL 34 IS 6 BP 552 EP 553 DI 10.1046/j.1537-2995.1994.34694295076.x PG 2 WC Hematology SC Hematology GA NV575 UT WOS:A1994NV57500020 PM 8023401 ER PT J AU TSAI, CM GU, XX BYRD, RA AF TSAI, CM GU, XX BYRD, RA TI QUANTIFICATION OF POLYSACCHARIDE IN HAEMOPHILUS-INFLUENZAE TYPE-B CONJUGATE AND POLYSACCHARIDE VACCINES BY HIGH-PERFORMANCE ANION-EXCHANGE CHROMATOGRAPHY WITH PULSED AMPEROMETRIC DETECTION SO VACCINE LA English DT Article DE HAEMOPHILUS INFLUENZAE; POLYSACCHARIDE; QUANTIFICATION ID HEMOPHILUS-INFLUENZAE; CAPSULAR POLYSACCHARIDES; HBOC VACCINE; INFANTS; CHILDREN; EFFICACY; OLIGOSACCHARIDES; IMMUNOGENICITY; EPIDEMIOLOGY; IMMUNIZATION AB A sensitive method for the quantification of polysaccharide (PS) in Haemophilus influenzae type b (Hib) conjugate and PS vaccines has been developed. It is based on measurement of the Hib PS subunit after depolymerization of the PS in sodium hydroxide to produce the subunit, which is characterized by chemical composition and P-31 n.m.r. analyses as ribitol-ribose-phosphate. The Hib vaccines were first treated with 0.1 M sodium hydroxide. The Hib PS subunit in the treated vaccines was then analysed directly by high-performance anion-exchange chromatography using a CarboPak PA-1 column, and quantified by pulsed amperometric detection. The PS contents of three conjugate vaccines and three PS vaccines from different manufacturers were determined. Their values were in the expected ranges. This method is particularly useful for vaccines with a sugar stabilizer such as lactose which would interfere with the colorimetric orcinol assay currently used for determination of the PS. The method can measure 0.1 mu g of PS and its sensitivity is at least 30-fold higher than that of the orcinol assay. It may be used for stability studies of conjugate vaccines since a breakdown as low as 5% of the PS from the PS-protein conjugates would be detected. RP TSAI, CM (reprint author), US FDA,CTR BIOL EVALUAT & RES,OFF VACCINE RES & REVIEW,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Byrd, R. Andrew/F-8042-2015 OI Byrd, R. Andrew/0000-0003-3625-4232 NR 28 TC 26 Z9 29 U1 0 U2 4 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD JUN PY 1994 VL 12 IS 8 BP 700 EP 706 DI 10.1016/0264-410X(94)90219-4 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NN325 UT WOS:A1994NN32500005 PM 8091847 ER PT J AU BARILE, MF GRABOWSKI, MW KAPATAISZOUMBOIS, K BROWN, B HU, PC CHANDLER, DKF AF BARILE, MF GRABOWSKI, MW KAPATAISZOUMBOIS, K BROWN, B HU, PC CHANDLER, DKF TI PROTECTION OF IMMUNIZED AND PREVIOUSLY INFECTED CHIMPANZEES CHALLENGED WITH MYCOPLASMA-PNEUMONIAE SO VACCINE LA English DT Article DE MYCOPLASMA PNEUMONIAE; CHIMPANZEES; FORMALIN-INACTIVATED VACCINE; ACELLULAR EXTRACT VACCINE ID EPIDEMIOLOGY; ANTIBODIES; DISEASE; EXTRACT; ADULTS AB Following immunization, peak geometric mean serum metabolism inhibition antibody (MIT) titres were 1.13 and 1.16 for groups of three chimpanzees each that received either the formalin-inactivated OSU-1A or experimental acellular extract vaccine, respectively. Following challenge, the mean titres for chimpanzees given the acellular vaccine peaked at 1:256 in 4 weeks and was 1.48 at 10 weeks. Chimpanzees given the OSU-1A vaccine peaked at 1.80 in 4 weeks and remained at 1:80 at 10 weeks. There was no direct correlation between the serum MIT response and the severity of disease or colonization, and thus the MIT response was not a reliable measurement of protection. The two non-immunized chimpanzees showed significant signs of disease, including cough, pharyngitis, rhinitis, fever and abnormal X-ray findings, for about 5 weeks. The chimpanzees immunized with either vaccine were less colonized and showed far less disease than non-immunized controls. Protection afforded the chimpanzees was similar to that of vaccinees in the human clinical trial given the same OSU-1A vaccine (Wenzel et al., 1977). The two previously infected chimpanzees were most protected against colonization and disease on challenge. C1 PRIMATE RES INST,HOLLOMAN AFB,NM 88330. UNIV N CAROLINA,SCH MED,DEPT PEDIAT,CHAPEL HILL,NC 27514. RP BARILE, MF (reprint author), US FDA,CTR BIOL EVALUAT & RES,MYCOPLASMA LAB,BETHESDA,MD 20892, USA. NR 41 TC 8 Z9 8 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD JUN PY 1994 VL 12 IS 8 BP 707 EP 714 DI 10.1016/0264-410X(94)90220-8 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NN325 UT WOS:A1994NN32500006 PM 8091848 ER PT J AU STEIN, W GORHAM, JR AF STEIN, W GORHAM, JR TI NEW RESULTS ABOUT STORED-PRODUCT PROTECTION (ANIMAL PESTS) .6. SO ZEITSCHRIFT FUR PFLANZENKRANKHEITEN UND PFLANZENSCHUTZ-JOURNAL OF PLANT DISEASES AND PROTECTION LA English DT Review DE STORED-PRODUCT PROTECTION; ANIMAL PESTS; DAMAGE; FAUNA; COMPETITION; ARTHROPODS AND FUNGI; DETECTION; SUBSTRATE RESISTANCE; BIOLOGICAL CONTROL; PHYSICAL CONTROL; CHEMICAL CONTROL; INSECTICIDE RESISTANCE ID PROSTEPHANUS-TRUNCATUS HORN; TRIBOLIUM-CASTANEUM HERBST; CALLOSOBRUCHUS-MACULATUS F; OBTECTUS SAY COLEOPTERA; PHASEOLUS-VULGARIS L; INTERPUNCTELLA HUBNER LEPIDOPTERA; SUBINNOTATUS PIC COLEOPTERA; SITOPHILUS-ZEAMAIS MOTSCH; RUSTY GRAIN BEETLE; RED FLOUR BEETLE C1 US FDA,DEPT HLTH & HUMAN SERV,WASHINGTON,DC 20204. RP STEIN, W (reprint author), JUSTUS LIEBIG UNIV,INST PHYTOPATHOL & ANGEW ZOOL VORRATSSCHUTZ,ALTER STEINBACHER WEG 44,D-35394 GIESSEN,GERMANY. NR 80 TC 0 Z9 0 U1 0 U2 1 PU EUGEN ULMER GMBH CO PI STUTTGART 70 PA POSTFACH 700561 WOLLGRASWEG 41, W-7000 STUTTGART 70, GERMANY SN 0340-8159 J9 Z PFLANZENK PFLANZEN JI Z. Pflanzenk. Pflanzens.-J. Plant Dis. Prot. PD JUN PY 1994 VL 101 IS 3 BP 321 EP 335 PG 15 WC Plant Sciences SC Plant Sciences GA NZ105 UT WOS:A1994NZ10500011 ER PT J AU BURTON, JD BAMFORD, RN PETERS, C GRANT, AJ KURYS, G GOLDMAN, CK BRENNAN, J ROESSLER, E WALDMANN, TA AF BURTON, JD BAMFORD, RN PETERS, C GRANT, AJ KURYS, G GOLDMAN, CK BRENNAN, J ROESSLER, E WALDMANN, TA TI A LYMPHOKINE, PROVISIONALLY DESIGNATED INTERLEUKIN-T AND PRODUCED BY A HUMAN ADULT T-CELL LEUKEMIA LINE, STIMULATES T-CELL PROLIFERATION AND THE INDUCTION OF LYMPHOKINE-ACTIVATED KILLER-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID I-ASSOCIATED MYELOPATHY; RECEPTOR GAMMA-CHAIN; VIRUS TYPE-I; GROWTH-FACTOR; LYMPHOCYTES AB In early phases of human T-cell lymphotropic virus I induced adult T-cell leukemia (ATL), the malignant cell proliferation is associated with an autocrine process involving coordinate expression of interleukin (IL) 2 and its receptor. However, during late-phase ATL, leukemic cells no longer produce IL-2 yet continue to express high affinity IL-2 receptors. During studies to define pathogenic mechanisms that underlie this IL-2-independent proliferation, we demonstrated that the ATL cell line HuT-102 secretes a lymphokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Conditioned medium from HuT-102, when added to the IL-2-dependent CTLL-2 line, yielded a stimulation index of 230. Since CTLL-2 was purported to be IL 2-specific, we performed a number of studies to exclude IL-2 production by HuT-102. Stimulation of CTLL-2 cells by HuT-102-conditioned medium was not meaningfully inhibited by addition of an antiserum to IL-2. Furthermore, uninduced HuT-102 cells did not express mRNA encoding IL-2 as assessed by Northern blot analysis. No biological activity on CTLL-2 cells was mediated by purified IL-1, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, or granulocyte/macrophage colony-stimulating factor, thus differentiating these factors from IL-T. Based on preliminary biochemical data, IL-T is a protein with a pI value of 4.5 and a molecular mass in SDS gels of 14 kDa. In addition to its action on CTLL-2 cells, 3200-fold-purified IL-T stimulated proliferation of the human cytokine-dependent T-cell line Kit-225. Furthermore, addition of IL-T enhanced cytotoxic activity of large granular lymphocytes (i.e., induced lymphokine-activated killer cells). Thus, IL-T is a lymphokine that plays a role in T-cell proliferation and induction of lymphokine activated killer cells. Furthermore, IL-T may contribute to IL-2-independent proliferation of select ATL cells and lines. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPY,CELLULAR IMMUNOL LAB,ROCKVILLE,MD 20852. NR 22 TC 283 Z9 295 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 MAY 24 PY 1994 VL 91 IS 11 BP 4935 EP 4939 DI 10.1073/pnas.91.11.4935 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400069 PM 8197160 ER PT J AU BAMFORD, RN GRANT, AJ BURTON, JD PETERS, C KURYS, G GOLDMAN, CK BRENNAN, J ROESSLER, E WALDMANN, TA AF BAMFORD, RN GRANT, AJ BURTON, JD PETERS, C KURYS, G GOLDMAN, CK BRENNAN, J ROESSLER, E WALDMANN, TA TI THE INTERLEUKIN (IL)-2 RECEPTOR-BETA CHAIN IS SHARED BY IL-2 AND A CYTOKINE, PROVISIONALLY DESIGNATED IL-T, THAT STIMULATES T-CELL PROLIFERATION AND THE INDUCTION OF LYMPHOKINE-ACTIVATED KILLER-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GAMMA-CHAIN; MONOCLONAL-ANTIBODY; FUNCTIONAL COMPONENT; EXPRESSION; LEUKEMIA; TAC; P75; LYMPHOCYTES; COMPLEX; FIBROBLASTS AB Late-phase human T-cell lymphotropic virus I-associated adult T-cell leukemia cells express IL-2 receptors (IL-2R) but no longer produce IL-2. We have reported that the IL-2-independent adult T-cell leukemia line HuT-102 secretes a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and lymphokine-activated killer cell activity. Stimulation of proliferation of the cytokine-dependent human T-cell line Kit-225 mediated by HuT-102 conditioned medium or by 3200-fold purified IL-T was not blocked by the addition of antibodies against IL-2 or IL-2R alpha submit. However, IL-T-mediated stimulation of this human T-cell line was inhibited by addition of Mik-beta-1, an antibody that binds specifically to IL-2R beta subunit. In addition, the activation of large granular lymphocytes to lymphokine-activated killer cells mediated by IL-T-containing conditioned medium was not blocked by antibodies directed toward IL-2 or IL-2 alpha but was inhibited by an antibody to IL-2R beta, suggesting the requirement of this receptor subunit for IL-T action. This conclusion was confirmed using an IL-3-dependent murine myeloid precursor cell line, 32D, that expresses H-2R alpha and IL-2R gamma, but not IL-2R beta Neither IL-2 nor IL-T stimulated 32D cell proliferation. However, after transfection with the gene encoding human IL-2R beta, 32D beta cells proliferated on addition of either cytokine. The IL-T-mediated stimulation of 32D beta proliferation was inhibited by an anti-IL2R beta antibody but not by an anti-IL-2 antibody. Thus, the IL-T-mediated stimulation of T-cell and lymphokine-activated killer cell activation requires the expression of the IL-2R beta subunit. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPY,CELLULAR IMMUNOL LAB,ROCKVILLE,MD 20852. NR 39 TC 326 Z9 336 U1 1 U2 3 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 MAY 24 PY 1994 VL 91 IS 11 BP 4940 EP 4944 DI 10.1073/pnas.91.11.4940 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400070 PM 8197161 ER PT J AU IGARASHI, K GAROTTA, G OZMEN, L ZIEMIECKI, A WILKS, AF HARPUR, AG LARNER, AC FINBLOOM, DS AF IGARASHI, K GAROTTA, G OZMEN, L ZIEMIECKI, A WILKS, AF HARPUR, AG LARNER, AC FINBLOOM, DS TI INTERFERON-GAMMA INDUCES TYROSINE PHOSPHORYLATION OF INTERFERON-GAMMA RECEPTOR AND REGULATED ASSOCIATION OF PROTEIN-TYROSINE KINASES, JAK1 AND JAK2, WITH ITS RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID SIGNAL TRANSDUCER; DOMAIN AB Interferon-gamma (IFN-gamma) induces the expression of a set of early response genes by tyrosine phosphorylation of latent transcription factors such as p91. Although the tyrosine kinases, Jak1 and Jak2, have recently been shown to be critical for signal transduction by IFN-gamma, evidence is lacking for both tyrosine phosphorylation of the IFN-gamma receptor (IFN-gamma R) and the interaction between Jak1, Jak2, and the IFN-gamma R. In this report, we show that binding of IFN-gamma to HeLa cells initiated a series of events that resulted in the extremely rapid (15 s) tyrosine phosphorylation of not only Jak1, Jak2, and p91 but also the IFN-gamma R. Coimmunoprecipitation experiments revealed that Jak1 was associated with the IFN-gamma R prior to ligand binding, whereas Jak2 became part of the IFN-gamma R Jak1 complex immediately after ligand binding. H2O2/vanadate treatment of cells for 15 min resulted in only the tyrosine phosphorylation of Jak1 and IFN-gamma R. Only after 60 min of this treatment did we observe tyrosine phosphorylation of Jak2 and p91 and assembly of the transcription factor complex FcRF gamma that binds to the promoter of the fcgr1 gene. These data suggest that JAK1 associates with the IFN-gamma R prior to ligand binding. IFN-gamma treatment of cells results in recruitment of JAK2 into the IFN-gamma R-Jak1 complex followed by assembly of the transcription factor FcRF gamma complex. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. HOFFMANN LA ROCHE AG,PHARMACEUT RES NEW TECHNOL,CH-4002 BASEL,SWITZERLAND. UNIV BERN,INST CLIN & EXPTL CANC RES,CH-3004 BERN,SWITZERLAND. LUDWIG INST CANC RES,MELBOURNE TUMOUR BIOL BRANCH,MELBOURNE,VIC 3050,AUSTRALIA. NR 22 TC 193 Z9 198 U1 2 U2 3 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 MAY 20 PY 1994 VL 269 IS 20 BP 14333 EP 14336 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM065 UT WOS:A1994NM06500002 PM 7514165 ER PT J AU KASHANCHI, F THOMPSON, J SADAIE, MR DONIGER, J DUVALL, J BRADY, JN ROSENTHAL, LJ AF KASHANCHI, F THOMPSON, J SADAIE, MR DONIGER, J DUVALL, J BRADY, JN ROSENTHAL, LJ TI TRANSCRIPTIONAL ACTIVATION OF MINIMAL HIV-I PROMOTER BY ORF-I PROTEIN EXPRESSED FROM THE SA/I-L FRAGMENT OF HUMAN HERPESVIRUS-6 SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERMINAL REPEAT; HUMAN CYTOMEGALO-VIRUS; HUMAN LYMPHOCYTES-T; EPSTEIN-BARR-VIRUS; TRANS-ACTIVATION; EXANTHEM-SUBITUM; CELL-LINE; HTLV-I; TRANSACTIVATION AB The Sall-L fragment of human herpesvirus 6 (HHV-6) strain U1102 transformed rodent cells and transactivated the HIV-1 LTR 10- to 15-fold in both monkey fibroblasts and human T-lymphocytes. In this report, the Sall-L transactivator of the HIV-1 LTR was localized to ORF-I which codes for a protein of 357 amino acids. To determine if ORF-I required functional Spl binding sites or the TATA box element of HIV-1 LTR for transactivation, 5'-deletion mutants of the HIV-I LTR were employed. Plasmids pBS/Sall-L, pBS/Sall-L-SH, and pC6/ORF-1(S), a mammalian expression vector containing ORF-1, all transactivated a deletion mutant of HIV-1 LTR lacking functional Spl binding sites (CD-54). These studies demonstrate that transactivation occurred in the absence of Spl binding sites and required only a minimal HIV-1 promoter which contains the TATA box element. The specificity of the Sall-L transactivator for HIV-1 LTR was demonstrated by its inability to transactivate the human papillomavirus type 16 or 18 early promoters. The ORF-1 gene was cloned into and expressed from the pET17b bacterial expression vector. Purified ORF-I protein was obtained by ammonium sulfate precipitation, Mono-S chromatography, and anti-T7.Tag immunoaffinity chromatography. Transactivation of the HIV-l LTR by ORF-1 protein was demonstrated by electroporation studies in vivo and by transcription studies in vitro. To substantiate the putative biological role of ORF-1, pBS/Sall-L, pBS/Sall-L-SH, and pCG/ORF-1 all reactivated tat-defective HIV-1 provirus from latently infected cells expressing CD4. Thus, the data presented suggest that HHV-6 infection could have a cofactor role in the progression of AIDS. (C) 1994 Academic Press, Inc. C1 GEORGETOWN UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20007. US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,ROCKVILLE,MD 20852. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 81 TC 29 Z9 31 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 15 PY 1994 VL 201 IS 1 BP 95 EP 106 DI 10.1006/viro.1994.1269 PG 12 WC Virology SC Virology GA NK296 UT WOS:A1994NK29600011 PM 8178493 ER PT J AU YSERN, X FIELDS, BA BHAT, TN GOLDBAUM, FA DALLACQUA, W SCHWARZ, FP POLJAK, RJ MARIUZZA, BA AF YSERN, X FIELDS, BA BHAT, TN GOLDBAUM, FA DALLACQUA, W SCHWARZ, FP POLJAK, RJ MARIUZZA, BA TI SOLVENT REARRANGEMENT IN AN ANTIGEN-ANTIBODY INTERFACE INTRODUCED BY SITE-DIRECTED MUTAGENESIS OF THE ANTIBODY COMBINING SITE SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE 3-DIMENSIONAL STRUCTURE; SITE-DIRECTED MUTAGENESIS; ANTIGEN-ANTIBODY REACTION; ENTHALPY-ENTROPY; HYDROPHOBIC EFFECT ID BINDING C1 UNIV MARYLAND,MARYLAND BIOTECHNOL INST,CTR ADV RES BIOTECHNOL,ROCKVILLE,MD 20850. NATL INST STAND & TECHNOL,ROCKVILLE,MD 20850. NCI,FREDERICK CANC RES & DEV CTR,CTR BIOMED SUPERCOMP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21202. RP YSERN, X (reprint author), US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857, USA. NR 17 TC 58 Z9 58 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 13 PY 1994 VL 238 IS 4 BP 496 EP 500 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM066 UT WOS:A1994NM06600002 PM 8176740 ER PT J AU VINEIS, P BARTSCH, H CAPORASO, N HARRINGTON, AM KADLUBAR, FF LANDI, MT MALAVEILLE, C SHIELDS, PG SKIPPER, P TALASKA, G TANNENBAUM, SR AF VINEIS, P BARTSCH, H CAPORASO, N HARRINGTON, AM KADLUBAR, FF LANDI, MT MALAVEILLE, C SHIELDS, PG SKIPPER, P TALASKA, G TANNENBAUM, SR TI GENETICALLY BASED N-ACETYLTRANSFERASE METABOLIC POLYMORPHISM AND LOW-LEVEL ENVIRONMENTAL EXPOSURE TO CARCINOGENS SO NATURE LA English DT Article ID EXFOLIATED UROTHELIAL CELLS; HEMOGLOBIN ADDUCTS; DNA ADDUCTS; URINARY MUTAGENICITY; CIGARETTE SMOKERS; SMOKING; ACETYLATION; PHENOTYPE; CANCER AB THE metabolic activation or inactivation of carcinogens varies considerably in human populations, and is partly genetically determined(1,2). Inter-individual variability in the susceptibility to carcinogens may be particularly important at low degrees of environmental exposure. Examples of probable human carcinogens that present widespread low-dose exposures are environmental tobacco smoke and diesel exhaust(3,4). We have determined levels of DNA adducts in bladder cells and of 4-aminobiphenyl-haemoglobin adducts in 97 volunteers, together with the N-acetylation non-inducible phenotype, the corresponding genotype, and the levels of nicotine-cotinine in the urine. We find that among the slow acetylators, 4-aminobiphenyl adducts were higher than in rapid acetylators at low or null nicotine-cotinine levels, whereas the difference between slow and rapid acetylators was less evident at increasing nicotine-cotinine levels. The N-acetyltransferase genotype is highly predictive of the acetylation phenotype. Our results indicate that the clearance of low-dose carcinogens is decreased in the genetically based slow-acetylator phenotype. Such genetic modulation of low-dose environmental risks is relevant to 'risk assessment' procedures. C1 MAIN HOSP,I-10126 TURIN,ITALY. GERMAN CANC RES CTR,D-69120 HEIDELBERG,GERMANY. NCI,GENET EPIDEMIOL BRANCH,ROCKVILLE,MD 20892. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. UNIV MILAN,IST MED LAVORO,I-20122 MILAN,ITALY. INT AGCY RES CANC,F-69372 LYON,FRANCE. MIT,DEPT CHEM,CAMBRIDGE,MA 02139. UNIV CINCINNATI,DEPT ENVIRONM HLTH,CINCINNATI,OH. RP VINEIS, P (reprint author), UNIV TURIN,DIPARTIMENTO SCI BIOMED & ONCOL UMANA,CANC EPIDEMIOL UNIT,I-10126 TURIN,ITALY. RI Shields, Peter/I-1644-2012; Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 NR 15 TC 262 Z9 266 U1 0 U2 5 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 12 PY 1994 VL 369 IS 6476 BP 154 EP 156 DI 10.1038/369154a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NK971 UT WOS:A1994NK97100051 PM 7909916 ER PT J AU NARANG, PK TRAPNELL, CB SCHOENFELDER, JR LAVELLE, JP BIANCHINE, JR AF NARANG, PK TRAPNELL, CB SCHOENFELDER, JR LAVELLE, JP BIANCHINE, JR TI FLUCONAZOLE AND ENHANCED EFFECT OF RIFABUTIN PROPHYLAXIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA,ROCKVILLE,MD 20892. GEORGETOWN UNIV,WASHINGTON,DC 20007. RP NARANG, PK (reprint author), PHARMACIA ADRIA,COLUMBUS,OH 43017, USA. NR 3 TC 48 Z9 48 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 MAY 5 PY 1994 VL 330 IS 18 BP 1316 EP 1317 DI 10.1056/NEJM199405053301817 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NJ512 UT WOS:A1994NJ51200021 PM 7695673 ER PT J AU AZIZ, KJ AF AZIZ, KJ TI TUMOR-MARKERS - FDA REVIEW AND EVALUATION SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Editorial Material RP AZIZ, KJ (reprint author), CTR DEVICES & RADIOL HLTH,OFF DEVICE EVALUAT,DIV CLIN LAB DEVICES,FOOD & DRUG ADM,ROCKVILLE,MD 20850, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU INST CLINICAL SCIENCE INC PI PHILADELPHIA PA 1833 DELANCEY PLACE, PHILADELPHIA, PA 19103 SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD MAY-JUN PY 1994 VL 24 IS 3 BP 282 EP 283 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA NH280 UT WOS:A1994NH28000011 PM 8048801 ER PT J AU LUONG, H WINESTOCK, KD FINBLOOM, DS AF LUONG, H WINESTOCK, KD FINBLOOM, DS TI INHIBITORS OF SERINE/THREONINE PHOSPHATASES ENHANCE PHOSPHORYLATION OF THE INTERFERON-GAMMA RECEPTOR WHILE SELECTIVELY ATTENUATING INTERFERON-GAMMA-INDUCED GENE-EXPRESSION IN HUMAN PERIPHERAL-BLOOD MONOCYTES SO BIOCHEMICAL JOURNAL LA English DT Article ID TUMOR-NECROSIS-FACTOR; IFN-GAMMA; BINDING; PROTEIN; INTERLEUKIN-1; PROMOTER AB Since many events following ligand-induced receptor clustering are controlled by serine and threonine (Ser/Thr) phosphorylation, we initiated an investigation into the role of Ser/Thr phosphatases in both phosphorylation of the interferon-gamma (IFN gamma) receptor and IFN gamma-induced gene expression in human peripheral-blood monocytes. Whereas IFN gamma alone did not enhance phosphorylation of the IFN gamma receptor, treatment of monocytes with the Ser/Thr phosphatase inhibitors, okadaic acid and calyculin A, resulted in increased phosphorylation of the IFN gamma receptor. However, when these cells were analysed for IFN gamma-induced IP-10 gene expression, there was profound inhibition. Using three IFN gamma-induced early-response genes, IP-10, the Fc gamma receptor type I (Fc gamma RI) and ISG-54, we found selective sensitivity to pretreatment with okadaic acid and calyculin A. Whereas IFN gamma induction of IP-10 was blocked by both inhibitors, only calyculin A prevented Fc gamma RI-gene expression. Neither inhibitor prevented ISG-54 induction by IFN gamma. IFN-gamma-activated formation of the DNA-binding-protein complex FcRF gamma (which binds to the promoter of the Fc gamma RI gene) remained unaffected by okadaic acid or calyculin A. Therefore these data suggest that Ser/Thr phosphatases have no major part in IFN gamma-initiated signal transduction across the membrane, but selectively control the ultimate transcription of a set of early-response genes. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NR 25 TC 6 Z9 6 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 MAY 1 PY 1994 VL 299 BP 799 EP 803 PN 3 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK092 UT WOS:A1994NK09200030 PM 8192669 ER PT J AU QI, CF LISCIA, DS NORMANNO, N MERLO, G JOHNSON, GR GULLICK, WJ CIARDIELLO, F SAEKI, T BRANDT, R KIM, N KENNEY, N SALOMON, DS AF QI, CF LISCIA, DS NORMANNO, N MERLO, G JOHNSON, GR GULLICK, WJ CIARDIELLO, F SAEKI, T BRANDT, R KIM, N KENNEY, N SALOMON, DS TI EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA, AMPHIREGULIN AND CRIPTO-1 IN HUMAN BREAST CARCINOMAS SO BRITISH JOURNAL OF CANCER LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; MAMMARY EPITHELIAL-CELLS; P53 TUMOR SUPPRESSOR; FACTOR RECEPTOR; TGF-ALPHA; GASTROINTESTINAL CARCINOMAS; COLORECTAL TUMORS; CANCER; GENE; PROTEIN AB The expression of three epidermal growth factor (EGF)-related peptides, transforming growth factor alpha (TGF-alpha), amphiregulin (AR) and cripto-1 (CR-1), was examined by immunocytochemistry (ICC) in 68 primary infiltrating ductal (IDCs) and infiltrating lobular breast carcinomas (ILCs), and in 23 adjacent non-involved human mammary tissue samples. Within the 68 IDC and ILC specimens, 54 (79%) expressed immunoreactive TGF-alpha, 52 (77%) expressed AR and 56 (82%) expressed CR-1. Cytoplasmic staining was observed with all of the antibodies, and this staining could be eliminated by preabsorption of the antibodies with the appropriate peptide immunogen. Cytoplasmic staining with all of the antibodies was confined to the carcinoma cells, since no specific immunoreactivity could be detected in the surrounding stromal or endothelial cells. In addition to cytoplasmic reactivity, the AR antibody also exhibited nuclear staining in a number of the carcinoma specimens. No significant correlations were found between the percentage of carcinoma cells that were positive for TGF-alpha, AR or CR-1 and oestrogen receptor status, axillary lymph node involvement, histological grade, tumour size, proliferative index, loss of heterozygosity on chromosome 17p or overall patient survival. However, a highly significant inverse correlation was observed between the average percentage of carcinoma cells that expressed AR in individual tumours and the presence of a point-mutated p53 gene. Likewise, a significantly higher percentage of tumour cells in the ILC group expressed AR as compared with the average percentage of tumour cells that expressed AR in the IDC group. Of the 23 adjacent, non-involved breast tissue samples, CR-1 could be detected by ICC in only three (13%), while TGF-alpha was found in six (26%) and AR in ten (43%) of the non-involved breast tissues. These data demonstrate that breast carcinomas express multiple EGF-related peptides and show that the differential expression of CR-1 in malignant breast epithelial cells may serve as a potential tumour marker for breast cancer. C1 NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTOR SECT,DIV CANC BIOL DIAG & CTR,BETHESDA,MD 20892. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. HAMMERSMITH HOSP,IMPERIAL CANC RES FUND,MOLEC ONCOL LAB,LONDON W12 0HS,ENGLAND. UNIV NAPLES,FAC MED & CHIRURG 2,CATTEDRA ONCOL MED,I-80131 NAPLES,ITALY. NATL SHIKOKU CANC CTR HOSP,MATSUYAMA,EHIME,JAPAN. OSPED SAN GIOVANNI VECCHIO,SERV ANAT PATOL,USL 1,I-10123 TURIN,ITALY. OI Ciardiello, Fortunato/0000-0002-3369-4841 NR 60 TC 104 Z9 106 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 1994 VL 69 IS 5 BP 903 EP 910 DI 10.1038/bjc.1994.174 PG 8 WC Oncology SC Oncology GA NJ831 UT WOS:A1994NJ83100018 PM 8180021 ER PT J AU KLEINOW, KM JARBOE, HH SHOEMAKER, KE GREENLESS, KJ AF KLEINOW, KM JARBOE, HH SHOEMAKER, KE GREENLESS, KJ TI COMPARATIVE PHARMACOKINETICS AND BIOAVAILABILITY OF OXOLINIC ACID IN CHANNEL CATFISH (ICTALURUS-PUNCTATUS) AND RAINBOW-TROUT (ONCORHYNCHUS-MYKISS) SO CANADIAN JOURNAL OF FISHERIES AND AQUATIC SCIENCES LA English DT Article ID SALMO-SALAR L; FISH; TEMPERATURE; OXYTETRACYCLINE; ABSORPTION; RESIDUES; ELIMINATION; YELLOWTAIL; METABOLISM; EXCRETION AB The pharmacokinetics, bioavailability, and disposition of oxolinic acid (OA), a quinolone antibacterial drug, were examined in a warmwater (channel catfish (Ictalurus punctatus)) and coldwater fish species (rainbow trout (Oncorhynchus mykiss)). Studies were performed at 24 and 14-degrees-C for catfish and at 14-degrees-C for trout to compare temperature- and species-related differences. Analysis of OA pharmacokinetics when determined by HPLC provided elimination half-life (t1/2beta), volume of distribution (V(ss)), and clearance (Cl(b)) estimates for 24-degrees-C catfish, 14-degrees-C catfish, and 14-degrees-C trout of 40.9, 69.3, and 81.3 h, 939, 880, and 1817 mL/kg, and 16.3, 8.9, and 16.9 mL.kg-1.h-1, respectively. Following oral administration, OA plasma concentrations peaked between 8 and 24 h for all treatments; however, 14-degrees-C trout and 14-degrees-C catfish sustained peak concentrations for a longer duration than 24-degrees-C catfish. Oral OA bioavailabilities were 56.0, 91.8, and 90.7% for 24-degrees-C catfish, 14-degrees-C catfish, and 14-degrees-C trout, respectively. OA distribution data for muscle of 14-degrees-C catfish demonstrated an inordinately high peak concentration and delayed time to peak relative to other treatments. Elimination half-lives of OA in muscle were 33.1, 54.3, and 141 h for 24-degrees-C catfish, 14-degrees-C catfish, and 14-degrees-C trout, respectively. C1 US FDA,CTR VET MED,ROCKVILLE,MD 20857. RP KLEINOW, KM (reprint author), LOUISIANA STATE UNIV,SCH VET MED,DEPT PHARMACOL,BATON ROUGE,LA 70803, USA. NR 37 TC 46 Z9 48 U1 1 U2 2 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0706-652X J9 CAN J FISH AQUAT SCI JI Can. J. Fish. Aquat. Sci. PD MAY PY 1994 VL 51 IS 5 BP 1205 EP 1211 DI 10.1139/f94-120 PG 7 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA PA367 UT WOS:A1994PA36700022 ER PT J AU MELCHIOR, WB MARQUES, MM BELAND, FA AF MELCHIOR, WB MARQUES, MM BELAND, FA TI MUTATIONS INDUCED BY AROMATIC AMINE DNA-ADDUCTS IN PBR322 SO CARCINOGENESIS LA English DT Article ID M13 VIRAL-DNA; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; HUMAN-CELLS; PLASMID DNA; 1ST BASE; MUTAGENESIS; AMINOFLUORENE; 1-NITROPYRENE; INVITRO AB A 276 bp region from the tetracycline resistance gene of the plasmid pBR322 was modified with 2-acetylaminofluorene (AAF), 2-aminofluorene (AF), 4-aminobiphenyl (ABP), N'-acetylbenzidine or 1-aminopyrene (AP) in order to determine the effect of adduct structure upon mutation induction. Each modification reaction gave one major adduct and these adducts had chromatographic properties, as determined by P-32-postlabeling, identical to those in which substitution had occurred at C8 of deoxyguanosine through the amine or amide nitrogen. The types and distribution of mutations were then characterized following introduction of the modified plasmids into SOS-induced Escherichia coli using Hanahan et al.'s procedure (Methods Enzymol., 204, 63-113, 1991). With AAF-modified plasmid, 60% of the mutations were deletions or additions, and these were detected primarily at NarI sites or in repetitive G sequences. Modification with AF gave -G deletions, primarily in runs of Gs, and base substitution mutations, which were mainly G to T transversions. Substitution with ABP or N'-acetylbenzidine resulted in G to T and G to C transversions, the latter being a mutation not detected with AF; in addition, -G deletions were detected at only very low frequency. AP modification gave both -G frameshift and base substitution mutations, of which G to T transversions predominated. A comparison of the mutation frequencies per adduct indicated that the mutagenic efficiencies of the adducts decreased in the order AP > AF > AAF similar to ABP similar to N'-acetylbenzidine. AAF- and ABP-modified pBR322 were also introduced with a CaCl2 method. The mutation frequency per adduct increased with this transformation procedure, and this appeared to be a reflection of a greater percentage of frameshift mutations. These data indicate that a series of structurally related aromatic amines will induce both base substitution and frameshift mutations when incorporated into pBR322, but that frameshift mutations occur almost exclusively with the planar derivatives. Furthermore, the ability to induce frameshift mutations increases the mutagenic efficiency of an adduct. C1 Univ Tecn Lisboa, CTR QUIM ESTRUTURAL, INST SUPER TECN, P-1096 LISBON, PORTUGAL. RP NATL CTR TOXICOL RES, DIV BIOCHEM TOXICOL, JEFFERSON, AR 72079 USA. RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 55 TC 67 Z9 67 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1994 VL 15 IS 5 BP 889 EP 899 DI 10.1093/carcin/15.5.889 PG 11 WC Oncology SC Oncology GA NP072 UT WOS:A1994NP07200017 PM 8200092 ER PT J AU EVANS, FE DECK, J HOWARD, PC AF EVANS, FE DECK, J HOWARD, PC TI STRUCTURE OF PHENOLIC ISOMERS OF 2-NITROFLUORANTHENE AND 3-NITROFLUORANTHENE STUDIED BY ONE-DIMENSIONAL AND 2-DIMENSIONAL H-1-NMR SPECTROSCOPY - COMPARATIVE-ANALYSIS OF MUTAGENICITY SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; SALMONELLA-TYPHIMURIUM; MAGNETIC-RESONANCE; NITROFLUORANTHENES; METABOLITES; 2-NITROFLUORANTHENE; H-1-NMR AB The structures of selected phenolic metabolites of 2- and 3-nitrofluoranthene have been analyzed. H-1 NMR spectral analysis at 500 MHz using one- and two-dimensional methods proves that the site of hydroxy substitution in two metabolites previously reported as 3-nitrofluoranthen-8-ol and 3-nitrofluoranthen-9-ol had been reversed. A third and previously unidentified metabolite is shown to be 3-nitrofluoranthen-7-ol. Complete analyis of NMR spectral data on 2- and 3-nitrofluoranthene enabled confirmation of the previously reported structures of 2-nitrofluoranthen-8-ol and 2-nitrofluoranthen-9-ol from derived chemical shift substituent effects. Chemical shift data suggest that the nitro group is not strictly coplanar with the aromatic ring system in solution and that metabolism at a distant site can alter the conformation about the C-N bond of the nitro group. Reported mutagenicity data are analyzed relative to imine quinone formation, chemical shift substituent effects, electronegativity effects, and conformation in an attempt to explain the large differences in mutagenicity between the C8 and C9 hydroxy isomers of 2- and 3-nitrofluoranthene. RP EVANS, FE (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 25 TC 16 Z9 16 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY-JUN PY 1994 VL 7 IS 3 BP 352 EP 357 DI 10.1021/tx00039a012 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA NL680 UT WOS:A1994NL68000012 PM 8075366 ER PT J AU BARILE, MF KAPATAISZOUMBOS, K SNOY, P GRABOWSKI, MW SNELLER, M MILLER, L CHANDLER, DKF AF BARILE, MF KAPATAISZOUMBOS, K SNOY, P GRABOWSKI, MW SNELLER, M MILLER, L CHANDLER, DKF TI EXPERIMENTALLY-INDUCED SEPTIC ARTHRITIS IN CHIMPANZEES INFECTED WITH MYCOPLASMA-HOMINIS, MYCOPLASMA-PNEUMONIAE, AND UREAPLASMA-UREALYTICUM SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IMMUNE-COMPLEXES; INFLAMMATORY POLYARTHRITIS; RHEUMATOID-ARTHRITIS; URETHRAL INFECTION; SYRIAN-HAMSTERS; SYNOVIAL-FLUID; HYPOGAMMAGLOBULINEMIA; PATIENT; PATHOGENICITY; GENITALIUM AB Mycoplasma hominis was isolated in pure culture from septic synovial aspirates from an individual (patient A) during 16 different bouts of exacerbation over a 70-month period of observation. Two isolates, 10(7) and also 10(6) color-changing units (CCU) of the 1620 isolate and 5 X 10(4) CCU of the 1628 isolate, caused inflammation in chimpanzees inoculated intraarticularly. Inflammation was also induced with 10(7) CCU of the 2010B isolate, serovar VII of Ureaplasma urealyticum, recovered from an agammaglobulinemic individual (patient B) with septic polyarthritis and with 3 X 10(6) CCU of the PI-1428 isolate of Mycoplasma pneumoniae. Inflammation persisted for up to 36 days and was self-limiting. The aspirates contained up to 220,000 white blood cells/mm(3) and up to 10(7) CCU/mL. There was good correlation between the severity of inflammation and the numbers of organisms, but antibody was not detected in aspirates during the peak severity of disease. As the numbers of organisms decreased, detectable levels of antibody increased, thus suggesting that antibody may have been bound to antigen. Chimpanzees previously infected with either the 1628 isolate of M. hominis or the 2010B isolate of U. urealyticum were protected on challenge with > 100 times the minimal dose causing arthritis. Chimpanzees showed little or no inflammation when inoculated intraarticularly with 5 X 10(8) CCU of the type strain PG-21 of M. hominis or with the type strain CO of U. urealyticum or when inoculated intravenously with 3 X 10(8) CCU of the arthrogenic 1620 isolate of M. hominis. C1 US FDA,CTR BIOL EVALUAT & RES,MYCOPLASMA LAB,BETHESDA,MD. US FDA,CTR BIOL EVALUAT & RES,PATHOBIOL & PRIMATOL LAB,PRIMATE UNIT,BETHESDA,MD. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 70 TC 14 Z9 14 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1994 VL 18 IS 5 BP 694 EP 703 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NL167 UT WOS:A1994NL16700003 PM 8075258 ER PT J AU SHIRAI, A SIERRA, V KELLY, CI KLINMAN, DM AF SHIRAI, A SIERRA, V KELLY, CI KLINMAN, DM TI INDIVIDUAL CELLS SIMULTANEOUSLY PRODUCE BOTH IL-4 AND IL-6 IN-VIVO SO CYTOKINE LA English DT Article DE IL-4; IL-6; IN VIVO; SIMULTANEOUS; SINGLE CELL ID STIMULATORY FACTOR-I; SYSTEMIC LUPUS-ERYTHEMATOSUS; CYTOKINE-SECRETING CELLS; MOUSE BONE-MARROW; T-CELL; B-CELLS; ANTIBODY-FORMATION; LYMPHOCYTES-B; HEMATOPOIETIC PROGENITORS; IMMUNE INTERFERON C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,RETROVIRAL IMMUNOL SECT,BETHESDA,MD 20892. NR 59 TC 27 Z9 27 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 MAY PY 1994 VL 6 IS 3 BP 329 EP 336 DI 10.1016/1043-4666(94)90030-2 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA NL164 UT WOS:A1994NL16400015 PM 8054489 ER PT J AU PIPKIN, JL HINSON, WG LYNCOOK, LE LABORDE, J ANSON, JF FEUERS, RJ DUFFY, PH HART, RW CASCIANO, DA AF PIPKIN, JL HINSON, WG LYNCOOK, LE LABORDE, J ANSON, JF FEUERS, RJ DUFFY, PH HART, RW CASCIANO, DA TI THE HOMOLOGY OF A NOVEL POLYPEPTIDE WITH STRESS PROTEIN-CHARACTERISTICS IN EMBRYONIC MICE BRAIN AND IN THE HYPOTHALAMUS OF CALORIC RESTRICTED RATS AS DETERMINED BY ULTRAMICRO WESTERN BLOTTING SO ELECTROPHORESIS LA English DT Article ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; SODIUM DODECYL-SULFATE; HEAT-SHOCK PROTEINS; CELL-CYCLE; NUCLEAR-PROTEIN; LIMITED PROTEOLYSIS; HL-60 CELLS; INDUCTION; PHOSPHORYLATION; ARSENITE AB A novel protein (p34) was observed in polyacrylamide gel fluorographs of gestation day 13 embryonic mouse brain following retinoic acid dosing of dams. Another p34 polypeptide with identical gel migratory characteristics was seen in the hypothalamus of old caloric restricted rats after ''food deprivation stress''. Western blotting, employing an ultramicro trans-blot cell developed in our laboratory, detected identical immunochemical determinants between these proteins, verifying their homology. Peptide mapping and Western blotting further validated the uniqueness of p34 compared with other stress proteins including heme oxygenase. RP PIPKIN, JL (reprint author), US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,DIV GENET TOXICOL,HFT-120,JEFFERSON,AR 72079, USA. NR 54 TC 9 Z9 9 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAY PY 1994 VL 15 IS 5 BP 677 EP 684 DI 10.1002/elps.1150150196 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NU199 UT WOS:A1994NU19900022 PM 7925248 ER PT J AU YEN, TT GILL, AM FRIGERI, LG BARSH, GS WOLFF, GL AF YEN, TT GILL, AM FRIGERI, LG BARSH, GS WOLFF, GL TI OBESITY, DIABETES, AND NEOPLASIA IN YELLOW A(VY)/- MICE - ECTOPIC EXPRESSION OF THE AGOUTI GENE SO FASEB JOURNAL LA English DT Review DE OBESITY; DIABETES; NEOPLASIA; YELLOW MOUSE; AGOUTI LOCUS ID VY F1-HYBRID MICE; BODY-WEIGHT; AVY/A MICE; GLUCOSE-TOLERANCE; ADIPOSE-TISSUE; COAT COLOR; INSULIN; MOUSE; THERMOGENESIS; CIGLITAZONE AB The viable yellow A(vy) mutation results in a mottled yellow mouse that is obese, slightly larger than its nonyellow sibs, and more susceptible to tumor formation in those tissues sensitized by the strain genome. The mutation exhibits variable expressivity resulting in a continuum of coat color phenotypes, from clear yellow to pseudoagouti. The mouse agouti protein is a paracrine signaling molecule that induces hair follicle melanocytes to switch from the synthesis of black pigment to yellow pigment. Molecular cloning studies indicate that the obesity and growth effects of the A(vy) mutation result from ectopic expression of the normal agouti gene product. This review seeks to summarize the current state of knowledge regarding the obesity, stimulation of somatic growth, and enhancement of tumor formation caused by the A(vy) mutation, and to interpret these pleiotropic effects in terms of the normal function of the agouti protein. C1 US FDA, NATL CTR TOXICOL RES, DIV NUTR TOXICOL, JEFFERSON, AR 72079 USA. ELI LILLY & CO, LILLY CORP CTR, LILLY RES LABS, INDIANAPOLIS, IN 46285 USA. SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA. STANFORD UNIV, SCH MED, DEPT PEDIAT, STANFORD, CA 94305 USA. STANFORD UNIV, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USA. UNIV ARKANSAS MED SCI HOSP, DEPT BIOCHEM MOLEC BIOL, LITTLE ROCK, AR 72205 USA. UNIV ARKANSAS MED SCI HOSP, DEPT PHARMACOL TOXICOL, LITTLE ROCK, AR 72205 USA. NR 74 TC 242 Z9 248 U1 3 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 1994 VL 8 IS 8 BP 479 EP 488 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NM364 UT WOS:A1994NM36400004 PM 8181666 ER PT J AU PATTON, CA HARRIS, GR PHILLIPS, RA AF PATTON, CA HARRIS, GR PHILLIPS, RA TI OUTPUT LEVELS AND BIOEFFECTS INDEXES FROM DIAGNOSTIC ULTRASOUND EXPOSURE DATA REPORTED TO THE FDA SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article AB As part of the Section 510(k) requirements of the 1976 Medical Device Amendments to the Federal Food, Drug, and Cosmetic Act, manufacturers of diagnostic ultrasound devices submit acoustic output data to the U.S. Food and Drug Administration. Because this information is pertinent to the assessment of any potential bioeffects due to ultrasound exposure, we have summarized the measurement data processed during 1990 and 1991. Exposure data were summarized for real-time B-mode and M-mode, general pulsed Doppler, peripheral vascular (PV) pulsed Doppler, and color flow Doppler. Exposure quantities included peak rarefactional and compressional pressures, spatial-peak pulse-average and spatial-peak temporal-average intensities (both water and derated values), and power. Also, where data permitted, mechanical and thermal indices were calculated. Ranges, means, medians, and standard deviations were categorized for the exposure quantities and indices. In general the temporal-average values (including indices) were higher in Doppler modes than in B/M imaging modes. Differences among the temporal-peak exposure quantities and indices were less distinct, although values tended to be higher in the PV and color flow Doppler categories. These data, along with comparable results collected by others, provide a means to relate the output of current devices to levels of exposure relevant to ultrasound-induced biological effects. RP PATTON, CA (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,MS HFZ 132,ROCKVILLE,MD 20857, USA. NR 13 TC 39 Z9 39 U1 0 U2 4 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 MAY PY 1994 VL 41 IS 3 BP 353 EP 359 DI 10.1109/58.285470 PG 7 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA NM302 UT WOS:A1994NM30200008 ER PT J AU ANSHER, S THOMPSON, W WATSON, R AF ANSHER, S THOMPSON, W WATSON, R TI ALTERATIONS OF HEPATIC DRUG-METABOLISM IN MICE FOLLOWING INFECTION WITH THE MURINE RETROVIRUS LP-BM5 SO IMMUNOPHARMACOLOGY LA English DT Article DE MAIDS; DRUG METABOLISM; INFECTION; CYTOKINE ID INTERFERON-INDUCING AGENTS; INDUCED IMMUNODEFICIENCY; CYTOCHROME-P-450; COCAINE; LIVER; ENDOTOXIN; DISEASE; SYSTEMS; ALPHA; MAIDS AB Infection of mice with the murine retrovirus mixture LP-BM5 caused a retrovirai infection with many similarities to human HIV infection, We have reported alterations in hepatic drug metabolism which progressed during the course of this infection. Hexobarbital-induced sleep time increased 1.5-2.2-fold above uninfected controls after 10 to 19 weeks post infection. Inhibition of spectral cytochrome P-450 levels by 25 to 30% was observed between 15 and 17 weeks postinfection, and there were changes in specific microsomal enzyme activities. The microsomal cocaine demethylase activity was reduced by 40%, whereas cytosolic enzyme activities were increased by 1.5-2.0-fold. These alterations may contribute to the altered metabolism of drugs of abuse reported in MAIDS mice. The mechanism for these alterations is not known, although the effects correspond temporally to reported infiltration of the liver with immunoblasts and plasma cells. This suggests a role for the immune system or for mediators released by cells of the immune system which could account for these observations. An understanding of the effects of infection on drug metabolism is important because of their impact on the efficacy and safety of drugs for use in AIDS patients. C1 UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT FAMILY & COMMUNITY MED,TUCSON,AZ 85724. RP ANSHER, S (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BACTERIAL TOXINS LAB,BLDG 29,ROOM 528,HFM-437,BETHESDA,MD 20892, USA. NR 42 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0162-3109 J9 IMMUNOPHARMACOLOGY JI Immunopharmacology PD MAY-JUN PY 1994 VL 27 IS 3 BP 215 EP 223 DI 10.1016/0162-3109(94)90018-3 PG 9 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA NL126 UT WOS:A1994NL12600006 PM 8071061 ER PT J AU GARCIARODRIGUEZ, JA PETERSON, LR FILE, TM GOLDBERGER, MJ PHILLIPS, I AF GARCIARODRIGUEZ, JA PETERSON, LR FILE, TM GOLDBERGER, MJ PHILLIPS, I TI QUINOLONE RESISTANCE IN INTRACELLULAR AND OTHER PATHOGENS - PANEL DISCUSSION SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Discussion C1 NW MEM HOSP,DEPT PATHOL,CHICAGO,IL 60611. NW MEM HOSP,DEPT MED,CHICAGO,IL 60611. AKRON CITY HOSP,INFECT DIS SERV,AKRON,OH. US FDA,ROCKVILLE,MD 20857. ST THOMAS HOSP,DEPT MICROBIOL,LONDON SE1 7EH,ENGLAND. RP GARCIARODRIGUEZ, JA (reprint author), UNIV SALAMANCA,HOSP CLIN,FAC MED,SALAMANCA,SPAIN. 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 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD MAY-JUN PY 1994 VL 3 SU 3 BP S136 EP S137 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NT413 UT WOS:A1994NT41300006 ER PT J AU RUBINSTEIN, E BERGAN, T BALL, AP BEAM, TR GOLDBERGER, MJ REINHART, H ROLSTON, KVI AF RUBINSTEIN, E BERGAN, T BALL, AP BEAM, TR GOLDBERGER, MJ REINHART, H ROLSTON, KVI TI FUTURE-ROLE AND USES OF QUINOLONES - PANEL DISCUSSION SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Discussion C1 NATL HOSP,INST MED MICROBIOL,OSLO,NORWAY. CAMERON HOSP,INFECT DIS UNIT,FIFE,SCOTLAND. VET ADM MED CTR,BUFFALO,NY 14215. US FDA,ROCKVILLE,MD 20857. MILES INC,W HAVEN,CT. UNIV TEXAS,MD ANDERSON HOSP & TUMOR INST,INFECT DIS SECT,HOUSTON,TX 77030. RP RUBINSTEIN, E (reprint author), CHAIM SHEBA MED CTR,DIV INFECT DIS,IL-52621 TEL HASHOMER,ISRAEL. 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 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD MAY-JUN PY 1994 VL 3 SU 3 BP S215 EP S218 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NT413 UT WOS:A1994NT41300025 ER PT J AU SCHWARTZ, DH COSENTINO, LM SHIRAI, A CONOVER, J DANIEL, S KLINMAN, DM AF SCHWARTZ, DH COSENTINO, LM SHIRAI, A CONOVER, J DANIEL, S KLINMAN, DM TI LACK OF CORRELATION BETWEEN THE NUMBER OF CIRCULATING B-CELLS AND THE CONCENTRATION OF SERUM ANTIBODIES REACTIVE WITH THE HIV-1 ENVELOPE GLYCOPROTEIN SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV-1; GP160; B CELLS; IMMUNE RESPONSE; SERUM ANTIBODIES ID HUMAN-IMMUNODEFICIENCY-VIRUS; MARROW STROMAL CELLS; BONE-MARROW; MONOCLONAL-ANTIBODY; IMMUNE-RESPONSE; LYMPHOCYTES-B; ACTIVATION; INFECTION; NEUTRALIZATION; INDIVIDUALS AB Cells obtained from the peripheral blood of HIV-infected patients and volunteers immunized with HIV-I vaccines are commonly used to study anti-viral responses, since lymphocytes from the central lymphoid organs are difficult to obtain. Analyses involving PBMC implicitly assume that circulating B cells provide an accurate reflection of the systemic humoral response induced by the HIV antigens. We examined this assumption by comparing the number of B cells secreting IgG anti-gp160/120 antibodies in the peripheral circulation with serum antibody titers. Results indicate that neither the magnitude nor duration of the serologic response detected in HIV-infected patients or gp160/gp 120-immunized volunteers reproducibly correlates with the number of B cells secreting anti-envelope antibodies in the blood. C1 CBER,FDA,DIV VIROL,RETROVIRAL RES LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT IMMUNOL & INFECT DIS,BALTIMORE,MD. FU NIAID NIH HHS [N01-AI-05061] NR 57 TC 4 Z9 4 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD MAY PY 1994 VL 7 IS 5 BP 447 EP 453 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NG413 UT WOS:A1994NG41300004 PM 8158537 ER PT J AU KIRCHHOEFER, RD AF KIRCHHOEFER, RD TI NIACIN .2. IDENTIFICATION OF ISONICOTINIC-ACID IN NIACIN BY LIQUID-CHROMATOGRAPHY WITH DIODE-ARRAY DETECTION SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID WATER-SOLUBLE VITAMINS; PAIR; RIBOFLAVIN; SEPARATION; PYRIDOXINE; THIAMIN AB Isonicotinic acid impurity in bulk niacin was detected and identified by comparison with a reference material by liquid chromatography with a diode array detector. The niacin was dissolved in dilute hydrochloric acid and chromatographed on an amine column with a mobile phase of methanol and water acidified with formic acid. Isonicotinic acid has a relative retention time of 1.5 compared with niacin (nicotinic acid), and the wavelengths of maximum ultraviolet (UV) absorbance for isonicotinic acid and niacin are 270 and 260 nm, respectively. The amount of impurity found in the niacin sample was 0.3%. Twelve formulations, including sustained-release products, one bulk material, and the United States Pharmacopeia (USP) reference standard were tested. The impurity was detected in only the bulk and USP reference material samples. RP KIRCHHOEFER, RD (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV DRUG ANAL,1114 MARKET ST,ROOM 1002,ST LOUIS,MO 63101, USA. NR 19 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 1994 VL 77 IS 3 BP 587 EP 590 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NP559 UT WOS:A1994NP55900007 PM 8012205 ER PT J AU MUNNS, RK HOLLAND, DC ROYBAL, JE STOREY, JM LONG, AR STEHLY, GR PLAKAS, SM AF MUNNS, RK HOLLAND, DC ROYBAL, JE STOREY, JM LONG, AR STEHLY, GR PLAKAS, SM TI GAS-CHROMATOGRAPHIC DETERMINATION OF CHLORAMPHENICOL RESIDUES IN SHRIMP - INTERLABORATORY STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ANIMAL-TISSUES; MILK; CONFIRMATION; TROUT AB An interlaboratory study of a gas chromatographic method for determining chloramphenicol (CAP) residues in shrimp was conducted. An internal standard (I(std)), the meta isomer of CAP, was added to the shrimp, and the treated shrimp were homogenized with ethyl acetate. The ethyl acetate extract was defatted with hexane, and the CAP was partitioned into ethyl acetate from an aqueous salt solution. The ethyl acetate was evaporated, and the dried residue was treated with Sylon, a trimethylsilyl derivatizing agent, to yield the trimethylsilyl derivative of CAP. A portion of the solution containing the derivative was injected into a gas chromatograph equipped with an electron capture detector. Levels of fortified and incurred CAP were calculated from the peak area ratio of standard CAP to I(std). Recoveries of CAP from tissue directly fortified at 5 ppb were 102% (within-laboratory relative standard deviation [RSD(r)] = 5.6%),104% (RSD(r) = 5.5%), and 108% (RSD(r) = 6.3%) from Laboratories 1, 2, and 3, respectively. Incurred-CAP residues at 5 and 10 ppb levels were also determined, with the following results: Laboratory 1: composite A, 4.56 ppb (RSD(r) = 14.0%); composite B, 8.38 ppb (RSD(r) = 11.6%); Laboratory 2: composite A, 4.17 ppb (RSD(r) = 12.5%); composite B, 8.90 ppb (RSD(r) = 5.60%); Laboratory 3: composite A, 4.66 ppb (RSD(r) = 14.9%); composite B, 11.0 ppb (RSD(r) = 11.8%). C1 US FDA,DIV SEAFOOD RES,DAUPHIN ISL,AL 36528. RP MUNNS, RK (reprint author), US FDA,ANIM DRUGS RES CTR,POB 25087,DENVER FED CTR,DENVER,CO 80225, USA. NR 14 TC 33 Z9 39 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 MAY-JUN PY 1994 VL 77 IS 3 BP 596 EP 601 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NP559 UT WOS:A1994NP55900009 PM 8012207 ER PT J AU FERNANDEZ, C STACK, ME MUSSER, SM AF FERNANDEZ, C STACK, ME MUSSER, SM TI DETERMINATION OF DEOXYNIVALENOL IN 1991 UNITED-STATES WINTER AND SPRING WHEAT BY HIGH-PERFORMANCE THIN-LAYER CHROMATOGRAPHY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CORN AB A thin-layer chromatographic (TLC) method was modified for determination of deoxynivalenol (DON) in 1991 U.S. winter and spring wheat. After extraction with acetonitrile-water (84 + 16) and cleanup on a charcoal-alumina-Celite (7 + 5 + 3) column, acetonitrile was used instead of ethyl acetate to transfer the concentrated extract containing DON. After the extract was evaporated to dryness, the residue was dissolved in methanol and an aliquot was spotted on a high-performance TLC plate. After development with chloroform-acetone-2-propanol (8 + 1 + 1), the plates were sprayed with aluminum chloride solution and heated; DON was quantitated by fluorodensitometry. Average recoveries of DON added to duplicate test portions of wheat at 200, 400, and 800 ng/g were 83, 82, and 72%, respectively. The detection limit was 40 ng/g. The method was applied to 81 test samples of spring and winter wheat. The wheat contained DON levels that ranged from nondetectable to 9330 ng/g (average 1570 ng/g). The results indicate that DON levels were higher in wheat from Missouri, North Dakota, and Tennessee than in wheat from 7 other states. The identity of DON, which was isolated from 21 of the extracts by preparatory TLC, was confirmed by gas chromatography/mass spectrometry in all 21 test samples. RP FERNANDEZ, C (reprint author), US FDA,DIV CONTAMINANTS CHEM,WASHINGTON,DC 20204, USA. NR 8 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 MAY-JUN PY 1994 VL 77 IS 3 BP 628 EP 630 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NP559 UT WOS:A1994NP55900013 PM 8012211 ER PT J AU PARK, DL TRUCKSESS, MW NESHEIM, S STACK, M NEWELL, R AF PARK, DL TRUCKSESS, MW NESHEIM, S STACK, M NEWELL, R TI SOLVENT-EFFICIENT THIN-LAYER CHROMATOGRAPHIC METHOD FOR THE DETERMINATION OF AFLATOXIN-B1, AFLATOXIN-B2, AFLATOXIN-G1, AND AFLATOXIN-G2 IN CORN AND PEANUT PRODUCTS - COLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID BUTTER AB An interlaboratory study of a solvent-efficient thin-layer chromatographic (TLC) method for the determination of aflatoxins B1, B2, G1, and G2 was conducted in laboratories located in the United States, France, Tunisia, and Denmark. Eighteen artificially contaminated samples plus blanks of raw peanuts and peanut butter and corn containing varying amounts of aflatoxins B1, B2, G1, and G2 were distributed to participating laboratories. The method consists of elements of the U.S. Food and Drug Administration (FDA), Contaminants Branch (CB) (AOAC Method 968.22) and FDA, Best Foods (BF) (AOAC Method 970.45) methods with reduced requirements for solvents. Participating laboratories used either visual or densitometric techniques during the final determinative step. Statistical analysis of the data was performed to determine or confirm outliers and to compute repeatability and reproducibility of the method using either visual or densitometric techniques for the determinative step. Reported results from laboratories using a densitometer showed that, for corn, the relative standard deviation for repeatability (RSD(r)) for aflatoxin B1 ranged from 56.6 to 41.7% for contamination levels ranging from 5 to 50 ng/g. For raw peanuts and peanut butter, the RSD, values for aflatoxin B1 ranged from 21.3 to 37.3% and 65.9 to 42.1%, respectively, for the contamination levels ranging from 5 to 25 ng/g. RSD(r) ranges for aflatoxins B2, G1, and G2 were similar. For reproducibility (R), the RSD(R) ranges for aflatoxin B1 were 41.7-56.6%, 56.6-84.8%, and 26.4-37.3% for corn, peanut butter, and raw peanuts, respectively. Average recoveries for all aflatoxins at all levels were 95.3, 139.0, and 95.6% for corn, peanut butter, and raw peanuts, respectively. When analysts determined aflatoxin concentrations in corn by visual comparison to standards, the RSD(r) values for aflatoxin B1 were 47.8-11.4% for contamination levels ranging from 5 to 50 ng/g. For raw peanuts and peanut butter, the RSD, values for aflatoxin B1 were 76.3-12.6% and 33.4-8.8%, respectively, for the contamination levels ranging from 5 to 25 ng/g. RSD(r) values for aflatoxins B2, G1, and G2 Were similar. The RSD(R) values for aflatoxin B1 were 34.6-90.2%, 45.5-59.3%, and 31.8-78.3% for corn, peanut butter, and raw peanuts, respectively. Average recoveries for all aflatoxins at all levels were 111.0, 157.6, and 92.3% for corn, peanut butter, and raw peanuts, respectively. High recoveries were noted for aflatoxins in peanut butter determined by either a densitometer or comparison to standards. Generally, increased precision was observed with the method at higher contamination levels. On the basis of the results obtained in this AOAC/IUPAC collaborative study, the solvent-efficient TLC method using densitometry for the quantitative step was adopted first action by AOAC for the determination of aflatoxins B1, B2, G1, and G2 in com at levels within the range of 5-50 ng/g, 3-15 ng/g, 10-50 ng/g, and 3-15 ng/g, respectively, by densitometry; for aflatoxins B1 and B2 in raw peanuts at levels ranging from 5 to 25 ng/g and from 1.5 to 7.5 ng/g, respectively, by densitometry; and for aflatoxins B1 and G1 in corn at 10-50 and 50 ng/g, respectively, and aflatoxins B1, B2, and G1 in raw peanuts at 10-25 ng/g, 7.5 ng/g, and 10-25 ng/g, respectively. Because of high recovery values, additional study is recommended for peanut butter. The solvent-efficient TLC method for determination of aflatoxins B1, B2, G1, and G2 in corn and peanuts has been adopted first action by AOAC INTERNATIONAL. RP PARK, DL (reprint author), US FDA,DIV CONTAMINANTS CHEM,WASHINGTON,DC 20204, USA. NR 13 TC 18 Z9 18 U1 1 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 1994 VL 77 IS 3 BP 637 EP 646 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NP559 UT WOS:A1994NP55900015 PM 8012213 ER PT J AU THOMPSON, DW AF THOMPSON, DW TI DETERMINATION OF VOLATILE ORGANIC CONTAMINANTS IN BULK OILS (EDIBLE, INJECTABLE, AND OTHER INTERNAL MEDICINAL) BY PURGE-AND-TRAP GAS-CHROMATOGRAPHY MASS-SPECTROMETRY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Purge-and-trap gas chromatography/mass spectrometry is evaluated for the quantitation of part-per-billion levels of volatile organic contaminants in bulk vegetable oils. Results using 2 purge techniques (direct purging of the heated oil and purging after dispersing the oil on an aluminum oxide powder) and 2 quantitative methods (standard curve and deuterium-labeled internal standard addition) are reported. Twenty volatile compounds and 8 vegetable oils were investigated. Recovery data and estimated detection limits for each compound are reported for each purge technique. Generally acceptable recoveries (70-130% for more than 90% of the analyte spikes) and acceptable detection levels (approximately 4-10 ppb) were obtained for all compounds using either the external standard curve or the deuterium-isotope-labeled internal standard. The use of a dispersant (such as alumina) for sample purging resulted in poor recoveries of the highly volatile contaminants. RP THOMPSON, DW (reprint author), US FDA,SE REG LAB,60 8TH ST,ATLANTA,GA 30309, USA. NR 16 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 MAY-JUN PY 1994 VL 77 IS 3 BP 647 EP 654 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NP559 UT WOS:A1994NP55900016 PM 8012214 ER PT J AU TRUCKSESS, MW STACK, ME AF TRUCKSESS, MW STACK, ME TI ENZYME-LINKED-IMMUNOSORBENT-ASSAY OF TOTAL AFLATOXIN-BU, AFLATOXIN-B2, AND AFLATOXIN-G1 IN CORN - FOLLOW-UP COLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A direct competitive enzyme-linked immunosorbent assay screening method for aflatoxins at 20 ng/g in corn was studied by 15 collaborating laboratories. Test samples of corn were extracted by blending with methanol-water (8 + 2). The extracts were filtered and the filtrates were diluted with buffer to a final methanol concentration of <30%. Each diluted filtrate was applied to a test device containing a filter with immobilized polyclonal antibodies specific to aflatoxins B1, B2, and G1. Aflatoxin B1-peroxidase conjugate was added, the test device was washed with water, and a mixture of hydrogen peroxide and tetramethylbenzidine was added. A test sample was judged to contain greater-than-or-equal-to 20 ng aflatoxins/g when, after exactly 1 min, no color was observed on the filter; if a blue or gray color developed, the test sample was judged to contain <20 ng aflatoxins/g. All laboratories correctly identified naturally contaminated com test samples. Only one false positive was found for controls containing no aflatoxins. The correct responses for positive test samples spiked at levels of 10, 20, and 30 ng aflatoxins/g (the ratio of B1:B2:G1 was 15:1:3) were 67, 97, and 100%, respectively. This method was adopted first action by AOAC INTERNATIONAL as a change in method for 990.34 for screening for aflatoxins B1, B2, and G1 in corn at total aflatoxin concentrations of greater-than-or-equal-to 20 ng/g. RP TRUCKSESS, MW (reprint author), US FDA,DIV CONTAMINANTS CHEM,WASHINGTON,DC 20204, USA. NR 3 TC 12 Z9 12 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 1994 VL 77 IS 3 BP 655 EP 659 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NP559 UT WOS:A1994NP55900017 PM 8012215 ER PT J AU FIRESTONE, D AF FIRESTONE, D TI DETERMINATION OF THE IODINE VALUE OF OILS AND FATS - SUMMARY OF COLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Two collaborative studies were conducted using the Wijs method for determining the iodine value in a wide range of vegetable and animal oils and fats. The results obtained when using carbon tetrachloride were compared to those obtained when using a substitute solvent mixture of cyclohexane and glacial acetic acid. The values reported for the iodine values indicate that the cyclohexane and acetic acid mixture can be used in place of carbon tetrachloride without loss of precision. The method has been adopted first action by AOAC INTERNATIONAL as an IUPAC/AOCS/AOAC method. RP FIRESTONE, D (reprint author), US FDA,DIV PESTICIDE & IND CHEM,200 C ST SW,WASHINGTON,DC 20204, USA. NR 1 TC 7 Z9 7 U1 2 U2 21 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 1994 VL 77 IS 3 BP 674 EP 676 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NP559 UT WOS:A1994NP55900021 PM 8012219 ER PT J AU FIRESTONE, D AF FIRESTONE, D TI GAS-CHROMATOGRAPHIC DETERMINATION OF MONOGLYCERIDES AND DIGLYCERIDES IN FATS AND OILS - SUMMARY OF COLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A collaborative study was conducted on a capillary gas chromatographic method for the determination of mono- and diglycerides in fats and oils. Other components of fats and oils such as glycerol, fatty acids, and sterols may be analyzed by this method. Six materials used in the study consisted of 2 commercial mono- and diglyceride emulsifiers, 2 synthetic compositions with known amounts of mono- and diglycerides in the presence of an excess of triglycerides, and 2 refined sunflower oils spiked with mono- and diglycerides. Eight laboratories participated in the study. On the basis of the collaborative study results, the method has been adopted first action by AOAC INTERNATIONAL as an IUPAC/AOCS/AOAC method. RP FIRESTONE, D (reprint author), US FDA,DIV PESTICIDE & IND CHEM,200 C ST SW,WASHINGTON,DC 20204, USA. NR 1 TC 5 Z9 5 U1 1 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 1994 VL 77 IS 3 BP 677 EP 680 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NP559 UT WOS:A1994NP55900022 PM 8012220 ER PT J AU PROSKY, L ASP, NG SCHWEIZER, TF DEVRIES, JW FURDA, I LEE, SG AF PROSKY, L ASP, NG SCHWEIZER, TF DEVRIES, JW FURDA, I LEE, SG TI DETERMINATION OF SOLUBLE DIETARY FIBER IN FOODS AND FOOD-PRODUCTS - COLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A collaborative study was conducted to determine the soluble dietary fiber (SDF) content of foods and food products by using a combination of enzymatic and gravimetric procedures. The method was basically the same as that employed for determining total dietary fiber (TDF), 985.29, and the method for insoluble dietary fiber (IDF), 991.42. Ten laboratories were each sent 13 test samples (6 blind duplicates and 1 standard [green beans] containing 29-33% TDF, 19-23% IDF, and 8-13% SDF) and were instructed to assay for IDF, SDF, and TDF independently. Included in the package were the 3 enzymes, namely alpha-amylase, amyloglucosidase, and protease, and the filter aid Celite, which was thought to be the major cause of high reproducibility relative standard deviation (RSD(R)) values for SDF obtained in a previous collaborative study. The foods to be analyzed were apricots, carrots, chickpeas, onions, raisins, and the sugar beet fiber Fibrex(TM). IDF, TDF, and SDF were calculated as the weight of residue minus the weight of protein and ash on a dry weight basis. RSD(R) values of the IDF results averaged 8.02%, with only 1 food having an RSD(R) >10%. The RSD(R) values for the TDF results averaged 4.97%, and all foods had an RSD(R) <7%. Although the RSD(R) values for SDF averaged 14.17%, 4 of the 6 foods had an RSD(R) <10%, and 1 of the 2 remaining foods that had a high RSD(R) had an SDF content of only 1.2%. In all cases, the RSD(R) values of the SDF content of the foods were less than the values for the same foods analyzed in a previous collaborative trial. The enzymatic-gravimetric method for the determination of SDF was adopted first action by AOAC INTERNATIONAL. C1 LUND UNIV,DEPT APL NUTR & FOOD CHEM,S-22100 LUND,SWEDEN. NESTEC LTD,CH-1000 LAUSANNE 26,SWITZERLAND. GEN MILLS INC,MINNEAPOLIS,MN 55427. KELLOGGS,BATTLE CREEK,MI 49016. RP PROSKY, L (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,LAUREL,MD 20708, USA. NR 7 TC 47 Z9 49 U1 1 U2 16 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 1994 VL 77 IS 3 BP 690 EP 694 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NP559 UT WOS:A1994NP55900025 PM 8012222 ER PT J AU DOLAN, SP AF DOLAN, SP TI RAPID ABRASION TEST TO INDICATE LEAD ON THE SURFACE OF CERAMICWARE SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A rapid abrasion test (RAT) was developed for screening ceramicware for Pb. A Pb-sensitive chromogen (rhodizonic acid) reacts to form a persistent colored complex, indicating the presence of Pb. RAT takes 2-5 min to complete; a positive test is easily discernible. RAT, which provides only qualitative information, is useful for screening large numbers of ceramicware items for the presence of Pb at greater-than-or-equal-to 0.05 mug/mL. RP DOLAN, SP (reprint author), US FDA,ELEMENTAL RES BRANCH,200 C ST SW,WASHINGTON,DC 20204, USA. NR 12 TC 2 Z9 2 U1 1 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 1994 VL 77 IS 3 BP 718 EP 722 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NP559 UT WOS:A1994NP55900030 PM 8012226 ER PT J AU CIERI, UR AF CIERI, UR TI DETERMINATION OF RESERPINE IN TABLETS BY LIQUID-CHROMATOGRAPHY WITH FLUORESCENCE DETECTION - REVISED PROCEDURE SO JOURNAL OF AOAC INTERNATIONAL LA English DT Note AB A procedure is presented for the determination of reserpine in tablets by liquid chromatography (LC) that is a slight modification of a method presented in a previous publication. The sample is extracted with methanol, and solutions are filtered through filter paper. For LC, a 7.5 cm column is used; the mobile phase is methanol containing a small volume of an aqueous solution of the sodium salt of 1-pentanesulfonic acid. Detection is by fluorescence with 280 nm excitation and 360 nm emission. Two commercial samples containing 0.1 and 0.25 mg reserpine were analyzed. For each sample, 2 determinations were made on a ground composite. Ten tablets were also analyzed individually. A linearity study was conducted, with solutions ranging in concentration from 80 to 120% of the amount present in the reference solution. RP CIERI, UR (reprint author), US FDA,2ND & CHESTNUT ST,PHILADELPHIA,PA 19106, USA. NR 1 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 MAY-JUN PY 1994 VL 77 IS 3 BP 758 EP 760 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NP559 UT WOS:A1994NP55900038 PM 8012230 ER PT J AU GOUVEA, V SANTOS, N TIMENETSKY, MD AF GOUVEA, V SANTOS, N TIMENETSKY, MD TI VP4 TYPING OF BOVINE AND PORCINE GROUP-A ROTAVIRUSES BY PCR SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; OUTER CAPSID PROTEIN-VP4; SEROTYPES; IDENTIFICATION; PROBES; STRAINS; ACID AB A PCR typing assay was developed to identify rotavirus P types (VP4 specificity) of bovine NCDV, UK, and B223 strains and porcine OSU and Gottfried strains. Thirty-nine human and animal strains representing all known, and some undefined, rotavirus P types were used to develop and evaluate the specificity of the method. No cross-amplification was observed. The PCR results agreed with previous characterizations by monoclonal antibodies, sequence analysis, and hybridization assays, except for the Gottfried strain, which showed a P type distinct from the human asymptomatic strains. Analysis of a small number of field specimens suggested a high level of VP4 polymorphism among porcine strains. The assay should be of value in typing field isolates and tracing interspecies infections. C1 US FDA,DIV MOLEC BIOL RES & EVALUAT,WASHINGTON,DC 20204. INST ADOLFO LUTZ REGISTRO,VIROL LAB,SAO PAULO,BRAZIL. RI TIMENETSKY, MARIA/I-7593-2013; Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 NR 31 TC 119 Z9 122 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 MAY PY 1994 VL 32 IS 5 BP 1333 EP 1337 PG 5 WC Microbiology SC Microbiology GA NG217 UT WOS:A1994NG21700034 PM 8051262 ER PT J AU GOUVEA, V SANTOS, N DOCARMOTIMENETSKY, M AF GOUVEA, V SANTOS, N DOCARMOTIMENETSKY, M TI IDENTIFICATION OF BOVINE AND PORCINE ROTAVIRUS-G TYPES BY PCR SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID G-SEROTYPE; SUBGROUP-I; SPECIFICITY; DIFFERENTIATION; THAILAND; STRAINS; PROBES; GENE AB A new seminested PCR typing assay has been extended to identify the important veterinary rotavirus serotypes G5, G6, G10, and G11, as well as the rare human serotype G8. The specificity of the method was evaluated with 30 standard laboratory strains of the G1 to G6 and G8 to G11 types. Rotavirus strain types G6 and G8, not previously recognized in pigs, were identified in field specimens of porcine origin. C1 US FDA,DIV MOLEC BIOL RES & EVALUAT,WASHINGTON,DC 20204. INST ADOLFO LUTZ REGISTRO,VIROL LAB,SAO PAULO,BRAZIL. RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 NR 22 TC 209 Z9 213 U1 0 U2 6 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 MAY PY 1994 VL 32 IS 5 BP 1338 EP 1340 PG 3 WC Microbiology SC Microbiology GA NG217 UT WOS:A1994NG21700035 PM 8051263 ER PT J AU GOUVEA, V DECASTRO, L TIMENETSKY, MD GREENBERG, H SANTOS, N AF GOUVEA, V DECASTRO, L TIMENETSKY, MD GREENBERG, H SANTOS, N TI ROTAVIRUS SEROTYPE-G5 ASSOCIATED WITH DIARRHEA IN BRAZILIAN CHILDREN SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID NUCLEIC-ACID; ANTIBODIES AB Rotavirus serotype G5 in fecal specimens of 38 Brazilian children with diarrhea was identified by PCR and enzyme immunoassays. The strains exhibited long RNA electropherotypes and either subgroup II or nonsubgroup I-nonsubgroup II specificities. Serotype G5 has been found in piglets and horses but not yet in humans. C1 FIOCRUZ MS,INST OSWALDO CRUZ,DEPT VIROL,RIO JANEIRO,BRAZIL. INST ADOLFO LUTZ REGISTRO,VIROL LAB,SAO PAULO,BRAZIL. US FDA,DIV MICROBIOL,WASHINGTON,DC 20204. STANFORD UNIV,DIV GASTROENTEROL,STANFORD,CA 94305. RI TIMENETSKY, MARIA/I-7593-2013; Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 NR 13 TC 161 Z9 167 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 MAY PY 1994 VL 32 IS 5 BP 1408 EP 1409 PG 2 WC Microbiology SC Microbiology GA NG217 UT WOS:A1994NG21700057 PM 8051281 ER PT J AU LATHERS, CM CHARLES, JB PUTCHA, L AF LATHERS, CM CHARLES, JB PUTCHA, L TI THE 12TH-FRONTIERS-SYMPOSIUM - PHARMACOLOGY BEYOND EARTHS BOUNDARIES SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Editorial Material C1 NASA,LYNDON B JOHNSON SPACE CTR,CARDIOPULM GRP,HOUSTON,TX 77058. RP LATHERS, CM (reprint author), US FDA,DIV CARDIORENAL,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 1994 VL 34 IS 5 BP 361 EP 362 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NL960 UT WOS:A1994NL96000001 ER PT J AU LATHERS, CM CHARLES, JB AF LATHERS, CM CHARLES, JB TI ORTHOSTATIC HYPOTENSION IN PATIENTS, BED REST SUBJECTS, AND ASTRONAUTS SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 12th Frontiers Symposium: Pharmacology Beyond Earths Boundaries CY MAY 06, 1992 CL NASA, JOHNSON SPACE CTR, HOUSTON, TX HO NASA, JOHNSON SPACE CTR ID SHY-DRAGER SYNDROME; MIDODRINE; AGENT; INTOLERANCE; MANAGEMENT; SPACE AB Orthostatic hypotension after even short space flights has affected a significant number of astronauts. Given the need for astronauts to function at a high level of efficiency during and after their return from space, the application of pharmacologic and other treatments is strongly indicated. This report addresses the clinical problem of orthostatic hypotension and its treatments to ascertain whether pharmacologic or physiologic treatment may be useful in the prevention of orthostatic hypotension associated with space flight. Treatment of orthostatic hypotension in patients now includes increasing intravascular volume with high sodium intake and mineralocorticoids, or increasing vascular resistance through the use of drugs to stimulate alpha or block beta vascular receptors. Earlier treatment used oral sympathomimetic ephedrine hydrochloride alone or with ''head-up'' bed rest.(1) Then long-acting adrenocortical steroid desoxycorticosterone preparations with high-salt diets were used to expand volume. Fludrocortisone was shown to prevent the orthostatic drop in blood pressure.(2) The combination of the sympathomimetic amine hydroxyamphetamine and a monoamine oxidase inhibitor tranylcypromine(3) has been used, as has indomethacin alone.(4) Davies et al.(5) used mineralocorticoids at low doses concomitantly with alpha-agonists to increase vasocontrictor action. Schirger et al(6) used tranylcypromine and methylphenidate with or without a Jobst elastic leotard garment or the alpha-adrenergic agonist midodrine (which stimulates both arterial and venous systems without direct central nervous system or cardiac effects). Vernikos et al(7) established that the combination of fludrocortisone, dextroamphetamine, and atropine exhibited a beneficial effect on orthostatic hypotension induced by 7-day 6 degrees head-down bed rest (a model used to simulate the weightlessness of space Fight), Thus, there are numerous drugs that, in combination with mechanical techniques, including lower body negative pressure to elevate transmural pressure, could be studied to treat orthostatic hypotension after space flight. C1 NASA,LYNDON B JOHNSON SPACE CTR,INST BIOMED RES,HOUSTON,TX 77058. RP LATHERS, CM (reprint author), US FDA,DIV CARDIORENAL PROD,HFD 110,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 37 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 1994 VL 34 IS 5 BP 403 EP 417 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NL960 UT WOS:A1994NL96000006 PM 7522239 ER PT J AU SCHRAEDER, PL LATHERS, CM CHARLES, JB AF SCHRAEDER, PL LATHERS, CM CHARLES, JB TI THE SPECTRUM OF SYNCOPE SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 12th Frontiers Symposium: Pharmacology Beyond Earths Boundaries CY MAY 06, 1992 CL NASA, JOHNSON SPACE CTR, HOUSTON, TX HO NASA, JOHNSON SPACE CTR ID DEATH AB Syncope is a loss of consciousness and postural tone. Although arising suddenly from prolonged recumbency or returning from weightlessness to Earth's gravity con result in syncope from orthostatic or vasovagal effects, there are many other possible causes. These causes can be divided into several groups. Causes listed in the cardiovascular category, especially cardiac causes, are more likely to occur in the elderly; noncardiac causes are more common in the younger population. The cases described herein illustrate the often unexpected mechanisms of syncope in otherwise healthy individuals. Two of the cases emphasize the usefulness of prolonged combined EEG/EKG monitoring. The categories of loss of consciousness experienced by air crew members are reviewed. The most important screening tool in identifying the mechanism(s) of syncope is a detailed history emphasizing a search for underlying disease, the specific associated circumstances, and pre- and post-event symptoms. The type of diagnostic studies, i.e., cardiac or neurologic, undertaken should be based on the historical data. Seizures must be considered as a possible mechanism of otherwise unexplained loss of consciousness in nonelderly persons, including air crew members. C1 US FDA,DIV CARDIORENAL,ROCKVILLE,MD 20857. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,CAMDEN,NJ 08103. NASA,LYNDON B JOHNSON SPACE CTR,SPACE BIOMED RES INST,HOUSTON,TX 77058. NR 21 TC 6 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 1994 VL 34 IS 5 BP 454 EP 459 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NL960 UT WOS:A1994NL96000012 PM 8089256 ER PT J AU MUKAI, CN LATHERS, CM CHARLES, JB BENNET, BS AF MUKAI, CN LATHERS, CM CHARLES, JB BENNET, BS TI CARDIOVASCULAR-RESPONSES TO REPETITIVE EXPOSURE TO HYPERGRAVITY AND HYPOGRAVITY STATES PRODUCED BY PARABOLIC FLIGHT SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 12th Frontiers Symposium: Pharmacology Beyond Earths Boundaries CY MAY 06, 1992 CL NASA, JOHNSON SPACE CTR, HOUSTON, TX HO NASA, JOHNSON SPACE CTR ID ACUTE HEMODYNAMIC-RESPONSES; WEIGHTLESSNESS AB Physiologic changes to repetitive hyper- and hypogravity stresses occurring during eight to ten parabolas on NASA's KC-135 aircraft were studied. Hemodynamic responses in 11 subjects in 4 different postures (supine, standing, sitting, and semisupine Space Shuttle launch position) were determined using noninvasive impedance cardiography. Five seconds of heart rate, cardiac index, thoracic fluid index, stroke index, ejection velocity index, and ventricular ejection time data were averaged during four different gravity (g) states: 1.3g (before parabola onset); 1.9g (parabola entry); Og (parabola peak); and 1.7g (parabola exit) for each subject. The standing position was associated with the largest changes in the cardiovascular response to hypo- and hypergravity. The thoracic fluid index did not indicate a headward redistribution during transition from a simulated launch position to weightlessness. Analysis of the eight to ten parabolas revealed that, in general, values obtained at 1.8g differed from 1.6g, Og differed from 1.6 and 1.3g, and 1.6g differed from 1.3g. The factors of gravity, thoracic fluid index, and cardiac index exhibited significant differences that were most likely to occur between parabola 1 versus parabolas 6, 7, and 8, and parabola 2 versus parabolas 4 through 8. Only the parameter of thoracic fluid index exhibited significance for parabolas 3 versus parabolas 6 and 7. C1 US FDA,DIV CARDIORENAL,ROCKVILLE,MD. KRUG LIFE SCI INC,HOUSTON,TX. RP MUKAI, CN (reprint author), NASA,LYNDON B JOHNSON SPACE CTR,SPACE BIOMED RES INST,MAIL CODE KN-NASDA,2101 NASA RD 1,HOUSTON,TX 77058, USA. NR 8 TC 15 Z9 15 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 1994 VL 34 IS 5 BP 472 EP 479 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NL960 UT WOS:A1994NL96000015 PM 8089258 ER PT J AU LATHERS, CM CHARLES, JB AF LATHERS, CM CHARLES, JB TI COMPARISON OF CARDIOVASCULAR FUNCTION DURING THE EARLY HOURS OF BED REST AND SPACE-FLIGHT SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 12th Frontiers Symposium: Pharmacology Beyond Earths Boundaries CY MAY 06, 1992 CL NASA, JOHNSON SPACE CTR, HOUSTON, TX HO NASA, JOHNSON SPACE CTR ID HEAD-DOWN TILT; ZERO GRAVITY; ORTHOSTATIC INTOLERANCE; UP TILT; BEDREST; ADAPTATION; RESPONSES AB This paper reviews the cardiovascular responses of six healthy male subjects to 6 hours in a 5 degrees head-down bed rest model of weightlessness, and compares these responses to those obtained when subjects were positioned in head-up tilts of 10 degrees, 20 degrees, and 42 degrees, simulating 1/6, 1/3, and 2/3 G, respectively. Thoracic fluid index, cardiac output, stroke volume, and peak flow were measured using impedance cardiography. Cardiac dimensions and volumes were determined from two-dimensional guided M-mode echocardiograms in the left lateral decubitus position at 0, 2, 4, and 6 hours. Cardiovascular responses to a stand test were compared before and after bed rest. The impedance values were related to tilt angle for the first 2 hours of tilt; however, after 3 hours, at all four angles, values began to converge, indicating that cardiovascular homeostatic mechanisms seek a common adapted state, regardless of effective gravity level (tilt angle) up to 2/3 G. Echocardiography revealed that left ventricular end-diastolic and end-systolic volume, stroke volume, ejection fraction, heart rate, and cardiac output had returned to control values by hour 6 for all tilt angles. The lack of a significant immediate change in left ventricular end-diastolic volume, despite decrements in stroke volume (P <.05) and heart rate (not significant), indicates that multiple factors may play a role in the adaptation to simulated hypogravity. The echocardiography data indicated that no angle of tilt, whether head-down or head-up for 4 to 6 hours, mimicked exactly the changes in cardiovascular function recorded after 4 to 6 hours of space flight. Changes in left ventricular end-diastolic volume during space flight and tilt may be similar, but follow a different time course. Nevertheless, head-down tilt at 5 degrees for a hours mimics some (stroke volume, systolic and diastolic blood pressure, mean arterial blood pressure, and total resistance), but not all, of the changes occurring in an equivalent time of space flight. The magnitude of the change in the mean heart rate response to standing was greater after six hours of tilt at -5 degrees or 10 degrees. Thus, results from the stand test after 6 hours of bed rest at -5 degrees and 10 degrees, but not at 20 degrees or 42 degrees, are similar to those obtained after space flight. C1 NASA,LYNDON B JOHNSON SPACE CTR,SPACE BIOMED RES INST,HOUSTON,TX 77058. RP LATHERS, CM (reprint author), US FDA,DIV CARDIORENAL PROD,5600 FISHERS LANE,HFD 110,ROCKVILLE,MD 20857, USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 1994 VL 34 IS 5 BP 489 EP 499 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NL960 UT WOS:A1994NL96000018 PM 8089261 ER PT J AU HAGEN, CJ SLOAN, EM LANCETTE, GA PEELER, JT SOFOS, JN AF HAGEN, CJ SLOAN, EM LANCETTE, GA PEELER, JT SOFOS, JN TI ENUMERATION OF VIBRIO-PARAHAEMOLYTICUS AND VIBRIO-VULNIFICUS IN VARIOUS SEAFOODS WITH 2 ENRICHMENT BROTHS SO JOURNAL OF FOOD PROTECTION LA English DT Article DE VIBRIO-PARAHAEMOLYTICUS; VIBRIO-VULNIFICUS; SALT POLYMYXIN-B BROTH; ALKALINE PEPTONE WATER ID UNITED-STATES; CHESAPEAKE BAY; MARINE VIBRIO; CHOLERAE; OYSTERS; GASTROENTERITIS; IDENTIFICATION; ENVIRONMENT; WASHINGTON; INFECTIONS AB This study compares recoveries of Vibrio parahaemolyticus and Vibrio vulnifIcus with salt-polymyxin B broth (SPB) and alkaline peptone water (APW) from samples of crab legs, oysters, shrimp, lobster and shark, which were inoculated at three levels (approximately 10(1) to 10(2), 10(2) to 10(3) and 10(4) to 10(5)/g) with each of the pathogens. Six samples of each product were analyzed (3-tube most probable number (MPN)] with each broth. Inoculated samples of oysters and slurries of crab and lobster were also tested after cold stress (refrigerated at 2 to 4-degrees-C, 3 or 7 days, or frozen at -15-degrees-C for 21 or 28 days). For each seafood, geometric means of cells recovered with APW were significantly (P < 0.05) higher than the corresponding means of recovery with SPB. In addition, 12 of 15 calculated estimates of 50% relative detectable levels (RDL50) were lower (P < 0.05) for APW than for SPB. In these samples, the level of detection by APW was found to be 40 to 32,000 and 6- to 42-fold lower for V. parahaemolyticus and V vulnificus, respectively, than the level of detection by SPB. In cold-stored samples, overall detection of the pathogens was greatly reduced, but APW was also more efficient than SPB in recovering stressed cells. C1 COLORADO STATE UNIV,DEPT FOOD SCI & HUMAN NUTR,FT COLLINS,CO 80523. US FDA,CFSAN,DIV HACCP PROGRAMS,WASHINGTON,DC 20204. COLORADO STATE UNIV,DEPT ANIM SCI,FT COLLINS,CO 80523. US FDA,ATLANTA,GA 30309. RP HAGEN, CJ (reprint author), US FDA,DENVER FED CTR,BLDG 20,POB 25087,DENVER,CO 80225, USA. NR 46 TC 4 Z9 5 U1 0 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 MAY PY 1994 VL 57 IS 5 BP 403 EP 409 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA NN281 UT WOS:A1994NN28100008 ER PT J AU ABRISHAMI, SH TALL, BD BRUURSEMA, TJ EPSTEIN, PS SHAH, DB AF ABRISHAMI, SH TALL, BD BRUURSEMA, TJ EPSTEIN, PS SHAH, DB TI BACTERIAL ADHERENCE AND VIABILITY ON CUTTING BOARD SURFACES SO JOURNAL OF FOOD SAFETY LA English DT Article ID CAMPYLOBACTER-JEJUNI; TOXINS; STAGE AB The adherence and viability of Escherichia coli inoculated onto the surfaces of plastic cutting boards and new and used wood cutting boards were evaluated. Most of the inoculum was recovered from all surfaces after resident drying times of 5 min and from plastic surfaces at 24 h. When the exposure time was extended to 2 h, > 90% of the cells placed on new and used dry wood surfaces were not recovered after vigorous rinsing. Scanning electron microscopy showed that the bacteria resided within the structural xylem fibers and vegetative elements of the wood. After resident drying times of up to 2 h, almost 75 % of the adherent bacteria on the wood surfaces were viable, as defined by a nalidixic acid direct viable count procedure. Microcosm studies showed no intrinsic growth-supporting or toxic properties of the cutting board materials. Bacteria that adhered to plastic surfaces were more easily removed by low-temperature washing than were cells that adhered to wood surfaces. These studies demonstrated that bacteria adhering to wood surfaces resided within the structural and vegetative elements of the wood's xylem tissues and were viable; wood was more retentive than plastic; penetration of the inoculum liquid promoted cell adherence to the wood matrix; and conditioning of wood with water before inoculation interfered with bacterial adherence. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204. RP ABRISHAMI, SH (reprint author), NSF INT,DEPT MICROBIOL,ANN ARBOR,MI 48113, USA. OI Tall, Ben/0000-0003-0399-3629 NR 20 TC 52 Z9 52 U1 0 U2 5 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD MAY PY 1994 VL 14 IS 2 BP 153 EP 172 DI 10.1111/j.1745-4565.1994.tb00591.x PG 20 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA NM375 UT WOS:A1994NM37500005 ER PT J AU BATEMAN, RC ELDRIGE, DB WADE, S MCCOYMESSER, J JESTER, ELE MOWDY, DE AF BATEMAN, RC ELDRIGE, DB WADE, S MCCOYMESSER, J JESTER, ELE MOWDY, DE TI COPPER CHELATION ASSAY FOR HISTAMINE IN TUNA SO JOURNAL OF FOOD SCIENCE LA English DT Article DE COPPER; TUNA; CHELATION; HISTAMINE; ANALYSIS ID FISH AB A reported copper chelation method for histamine determination was modified for use in decomposing yellowfin tuna steaks. The assay consisted of histamine extraction with hot methanol, purification by rapid cation exchange chromatography, and addition of copper and a dye to the purified sample to form an easily visualized red complex with the histamine. This method detected histamine in the low mg% range in yellowfin tuna steaks with an accuracy comparable to the standard fluorometric histamine assay. It is an alternative to the standard assay when a visual test is desirable or a fluorometer is not available. C1 US FDA,GULF COAST SEAFOOD LABS,DAUPHIN ISL,AL 36528. RP BATEMAN, RC (reprint author), UNIV SO MISSISSIPPI,DEPT CHEM & BIOCHEM,HATTIESBURG,MS 39406, USA. NR 10 TC 11 Z9 11 U1 0 U2 2 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD MAY-JUN PY 1994 VL 59 IS 3 BP 517 EP & DI 10.1111/j.1365-2621.1994.tb05551.x PG 0 WC Food Science & Technology SC Food Science & Technology GA NW348 UT WOS:A1994NW34800015 ER PT J AU BLOOM, ET HORVATH, JA AF BLOOM, ET HORVATH, JA TI CELLULAR AND MOLECULAR MECHANISMS OF THE IL-12-INDUCED INCREASE IN ALLOSPECIFIC MURINE CYTOLYTIC T-CELL ACTIVITY - IMPLICATIONS FOR THE AGE-RELATED DECLINE IN CTL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTE MATURATION FACTOR; INTERFERON-GAMMA-PRODUCTION; LARGE GRANULAR LYMPHOCYTES; STIMULATORY FACTOR NKSF; PORE-FORMING PROTEIN; KILLER-CELLS; EFFECTOR-CELLS; CYTO-TOXICITY; AGING MICE; HETERODIMERIC CYTOKINE AB The mechanism(s) by which IL-12 augments CTL generation and the potential for IL-12 to alter the age-related decline in CTL activity were assessed using primary CTL stimulated by allogeneic cells. IL-12 at 2 U/ml enhanced the generation of allospecific CTL response in young adult mice by 1.5- to 5-fold, and optimal augmentation was achieved and maintained with as low as 0.1 U/ml IL-12. In contrast to the enhancement of MHC-unrestricted lytic activity, which was most efficient when IL-12 was added near the end of the 5 day culture period, nearly equivalent augmentation of Ag-specific CTL was induced when IL-12 was added from 1 to 5 days before harvest. The augmentation of CTL by IL-12 was not associated with increased incorporation of [H-3]TdR. Increased IFN-gamma production was not required for IL-12 to augment CTL activity because when three different Abs against mouse IFN-gamma were each included in the MLC at concentrations abolishing recoverable lFN-gamma protein, they did not inhibit the IL-12 effect but, under some conditions, further increased CTL activity. Ab to IL-2 also did not alter the IL-12 effect. Depletion of ASGM(1) (+) cells from the responding population before stimulation did not significantly alter the response to IL-12. However, depletion of CD8(+) T cells from effector cells obtained after stimulation substantially reduced the IL-12-induced augmentation of CTL. Thus, the results suggested that IL-12 augments CTL activity primarily through an effect on T cells, and the augmentation was associated with an approximate doubling of perforin levels, which was not caused by a significantly increased proportion of CD8(+) cells. Finally, IL-12 was effective for moderating the age-related decrease in CTL activity, suggesting a potential role for immunomodulation by IL-12. RP BLOOM, ET (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,CELLULAR IMMUNOL LAB HFM 518,BETHESDA,MD 20892, USA. NR 62 TC 85 Z9 86 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 1 PY 1994 VL 152 IS 9 BP 4242 EP 4254 PG 13 WC Immunology SC Immunology GA NG719 UT WOS:A1994NG71900002 PM 7908914 ER PT J AU BOURNE, N STANBERRY, LR CONNELLY, BL KURAWADWALA, J STRAUS, SE KRAUSE, PR AF BOURNE, N STANBERRY, LR CONNELLY, BL KURAWADWALA, J STRAUS, SE KRAUSE, PR TI QUANTITY OF LATENCY-ASSOCIATED TRANSCRIPT PRODUCED BY HERPES-SIMPLEX VIRUS IS NOT PREDICTIVE OF THE FREQUENCY OF EXPERIMENTAL RECURRENT GENITAL HERPES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID HUMAN TRIGEMINAL GANGLIA; GUINEA-PIGS; PATHOGENESIS; INFECTION; HYBRIDIZATION; REACTIVATION; INSITU AB The role of the latency-associated transcript (LAT) in control of recurrent herpes simplex virus type 2 (HSV-2) infection was investigated by examining whether LAT concentration in vitro during productive infection or in ganglia during latency correlated with the frequency of recurrent genital herpes. Clinical HSV-2 isolates from frequent or infrequent recurrent genital disease produced comparable amounts of glycoprotein D and infected cell polypeptide 0 RNA, but the isolate from frequent disease produced about seven times more LAT. The guinea pig model of genital herpes was used to determine whether the quantity of LAT produced during acute infection in vitro correlated with recurrence phenotype; the frequency of recurrent disease was similar for the 2 clinical isolates. Likewise, there was no correlation between the recurrence phenotype of individual animals and LAT concentration in their ganglia. Thus, while absence of LAT may impair HSV reactivation and recurrence, once a threshold concentration is exceeded, LAT has no further effect on recurrence frequency. C1 UNIV CINCINNATI,COLL MED,DEPT PEDIAT,CHILDRENS HOSP RES FDN,DIV INFECT DIS,CINCINNATI,OH 45229. NIAID,CLIN INVEST LAB,BETHESDA,MD. US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD. FU NIAID NIH HHS [AI-22667, AI-29687] NR 15 TC 19 Z9 19 U1 0 U2 2 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 1994 VL 169 IS 5 BP 1084 EP 1087 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NW346 UT WOS:A1994NW34600022 PM 8169396 ER PT J AU GILMAN, SC BONNER, MJ PELLMAR, TC AF GILMAN, SC BONNER, MJ PELLMAR, TC TI FREE-RADICALS ENHANCE BASAL RELEASE OF D-[H-3]ASPARTATE FROM CEREBRAL CORTICAL SYNAPTOSOMES SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE HYDROXYL FREE RADICALS; AMINO ACIDS; NEUROTRANSMITTER; PEROXIDE; SYNAPTOSOME; IRON; GLUTAMATE; ASPARTATE ID ISOLATED NERVE-TERMINALS; PIG HIPPOCAMPUS INVITRO; ALTERS NEURONAL EXCITABILITY; CEREBELLAR GRANULE CELLS; GAMMA-AMINOBUTYRIC ACID; GUINEA-PIG; LIPID-PEROXIDATION; RAT-BRAIN; GLUTAMATE RELEASE; D-ASPARTATE AB Excessive generation of free radicals has been implicated in several pathological conditions. We demonstrated previously that peroxide-generated free radicals decrease calcium-dependent high K+-evoked L-[H-3]glutamate release from synaptosomes while increasing calcium-independent basal release. The present study evaluates the nonvesicular release of excitatory amino acid neurotransmitters, using D-[H-3]aspartate as an exogenous label of the cytoplasmic pool of L-glutamate and L-aspartate. Isolated presynaptic nerve terminals from the guinea pig cerebral cortex were used to examine the actions and interactions of peroxide, iron, and desferrioxamine. Pretreatment with peroxide, iron alone, or peroxide with iron significantly increased the calcium-independent basal release of D-[H-3]aspartate. Pretreatment with desferrioxamine had little effect on its own but significantly limited the enhancement by peroxide. High K+-evoked release in the presence of Ca2+ was enhanced by peroxide but not by iron. These data suggest that peroxide increases nonvesicular basal release of excitatory amino acids through Fenton-generated hydroxyl radicals. This release could cause accumulation of extracellular excitatory amino acids and contribute to the excitotoxicity associated with some pathologies. C1 US FDA,DIV TOXICOL REVIEW,WASHINGTON,DC. RP GILMAN, SC (reprint author), ARMED FORCES RADIOBIOL RES INST,DEPT PHYSIOL,8901 WISCONSIN AVE,BETHESDA,MD 20889, USA. NR 56 TC 57 Z9 57 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1994 VL 62 IS 5 BP 1757 EP 1763 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA NG694 UT WOS:A1994NG69400013 PM 8158126 ER PT J AU WU, C BRECHBEIL, MW KOZAK, RW GANSOW, OA AF WU, C BRECHBEIL, MW KOZAK, RW GANSOW, OA TI PREPARATION AND CHARACTERIZATION OF DENDRIMER-BASED POLY-METAL CHELATES AND MONOCLONAL-ANTIBODIES CONJUGATES SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NR 0 TC 1 Z9 1 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P62 EP P62 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900242 ER PT J AU BETZ, JM EPPLEY, RM TAYLOR, WC ANDREZEJEWSKI, D AF BETZ, JM EPPLEY, RM TAYLOR, WC ANDREZEJEWSKI, D TI DETERMINATION OF PYRROLIZIDINE ALKALOIDS IN COMMERCIAL COMFREY PRODUCTS (SYMPTHYTUM SP) SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID VENO-OCCLUSIVE DISEASE; RUSSIAN COMFREY; RATS; DERIVATIVES; TOXICITY; HERB AB The presence of hepatotoxic pyrrolizidine alkaloids in comfrey (Symphytum sp.) and the widespread use of decoctions of this plant as a beverage (herbal tea) are of increasing concern. A method for the extraction and solid-phase concentration and capillary gas chromatographic determination of these alkaloids and their N-oxides in botanical materials has been developed and was applied to eleven comfrey-containing products purchased from retail health-food outlets in the Washington, DC, area during May-June 1989. Nine of the 11 products were found to contain measurable quantities of one or more of the alkaloids, in ranges from 0.1 to 400.0 ppm. Products containing comfrey leaf in combination with one or more other ingredients were found to contain the lowest alkaloid levels. Highest levels were found in bulk comfrey root, followed by bulk comfrey leaf. The species of the bulk material was verified by thin-layer chromatography and other means. RP BETZ, JM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 47 TC 59 Z9 59 U1 0 U2 7 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 1994 VL 83 IS 5 BP 649 EP 653 DI 10.1002/jps.2600830511 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA NJ868 UT WOS:A1994NJ86800010 PM 8071814 ER PT J AU TRUCKSESS, MW THOMAS, FS PAGE, SW AF TRUCKSESS, MW THOMAS, FS PAGE, SW TI HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF 1,1'-ETHYLIDENEBIS(L-TRYPTOPHAN) IN L-TRYPTOPHAN PREPARATIONS SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID EOSINOPHILIA-MYALGIA-SYNDROME; EMS AB In studies to determine the cause or causes of the eosinophilia myalgic syndrome (EMS) and to monitor the purity of L-tryptophan preparations, an HPLC method has been developed for determining 1,1'-ethylidenebis(L-tryptophan) (EBT) in L-tryptophan (W) preparations. The W preparations are extracted with 0.1% trifluoroacetic acid (TFA) and filtered, and the EBT is purified by passage through a Sep-Pak C-18 cartridge. The cartridge is washed with water and 6% acetonitrile in water, and EBT is eluted with methanol. The water-diluted eluate is then chromatographed on a silica-based, reversed-phase HPLC column with a gradient of water and 80% acetonitrile, both solvents containing 0.1% TFA. EBT absorbance is measured at 280 nm. The average recovery of EBT from L-tryptophan powder, spiked over the range 1.2-4.8 mu g/g, was 91%. The limit of determination was similar to 0.6 mu g/g. Sixteen test samples of W products manufactured by the company to which most of the cases of EMS have been traced contained >70 mu g of EBT/g. Three nonpatient-related test samples either did not contain EBT or contained <2 mu g of EBT/g. RP TRUCKSESS, MW (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. NR 10 TC 9 Z9 9 U1 0 U2 0 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 1994 VL 83 IS 5 BP 720 EP 722 DI 10.1002/jps.2600830525 PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA NJ868 UT WOS:A1994NJ86800024 PM 8071828 ER PT J AU FRENI, SC AF FRENI, SC TI EXPOSURE TO HIGH FLUORIDE CONCENTRATIONS IN DRINKING-WATER IS ASSOCIATED WITH DECREASED BIRTH-RATES SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID ADENYLATE-CYCLASE; REPRODUCTION; PERFORMANCE; COMPONENT; ALUMINUM; BLOOD AB A review of fluoride toxicity showed decreased fertility in most animal species studied. The current study was to see whether fluoride would also affect human birth rates. A U.S. database of drinking water systems was used to identify index counties with water systems reporting fluoride levels of at least 3 ppm. These and adjacent counties were grouped in 30 regions spread over 9 states. For each county, two conceptionally different exposure measures were defined, and the annual total fertility rate (TFR) for women in the age range 10-49 yr was calculated for the period 1970-1988. For each region separately, the annual TFR was regressed on the fluoride measure and sociodemographic covariables. Most regions showed an association of decreasing TFR with increasing fluoride levels. Metaanalysis of the region-specific results confirmed that the combined result was a negative TFR/fluoride association with a consensus combined p value of .0002-.0004, depending an the analytical scenario. There is no evidence that this outcome resulted from selection bias, inaccurate data, or improper analytical methods. However, the study is one that used population means rather than data on individual women. Whether or not the fluoride effect on the fertility rate found at the county level also applies to individual women remains to be investigated. RP FRENI, SC (reprint author), US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,BIOMETRY HFT 20,JEFFERSON,AR 72079, USA. NR 38 TC 77 Z9 82 U1 1 U2 6 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD MAY PY 1994 VL 42 IS 1 BP 109 EP 121 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NL676 UT WOS:A1994NL67600006 PM 8169995 ER PT J AU SHIRAI, M OKADA, H NISHIOKA, M AKATSUKA, T WYCHOWSKI, C HOUGHTEN, R PENDLETON, CD FEINSTONE, SM BERZOFSKY, JA AF SHIRAI, M OKADA, H NISHIOKA, M AKATSUKA, T WYCHOWSKI, C HOUGHTEN, R PENDLETON, CD FEINSTONE, SM BERZOFSKY, JA TI AN EPITOPE IN HEPATITIS-C VIRUS CORE REGION RECOGNIZED BY CYTOTOXIC T-CELLS IN MICE AND HUMANS SO JOURNAL OF VIROLOGY LA English DT Article ID NON-B-HEPATITIS; HUMAN-IMMUNODEFICIENCY-VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; TOXIC LYMPHOCYTES-T; NON-A-HEPATITIS; SYNTHETIC PEPTIDES; TRANSPLANTATION ANTIGENS; INFLUENZA NUCLEOPROTEIN; ENVELOPE PROTEIN; CYTO-TOXICITY AB Several cytotoxic T-lymphocyte (CTL) epitopes have been defined in hepatitis C virus (HCV) proteins. CTL may play an important role in the control of infection by HCV. Here, we identify a highly conserved antigenic site in the HCV core recognized by both murine and human CTL. Spleen cells from mice immunized with a recombinant vaccinia virus expressing the HCV core gene were restimulated in vitro with 11 peptides from the core protein. CTL from H-2(d) mice responded to a single 16-residue synthetic peptide (HCV 129-144). This conserved epitope was presented by a murine class I major histocompatibility molecule (H-2D(d)) to conventional CD4(-) CD8(+) CTL mapped by using transfectants expressing D-d, L(d), or K-d, but was not seen by CTL restricted by H-2(b). The murine epitope was mapped to the decapeptide LMGYIPLVGA. The same 16-residue peptide was recognized by CTL from two HCV-seropositive patients but not by CTL from any seronegative donors. CTL from two HLA-A2-positive patients with acute and chronic hepatitides C recognized a 9-residue fragment (DLMGYIPLV) of the peptide presented by BLA-A2 and containing an HLA-A2-binding motif, extending only 1 residue beyond the murine epitope. Therefore, this conserved peptide, seen with murine CTL and human CTL with a very prevalent HLA class I molecule, may be a valuable component of an HCV vaccine against a broad range of HCV isolates. This study demonstrates that the screening: for CTL epitopes in mice prior to human study may be useful. C1 NCI, METAB BRANCH, MOLEC IMMUNOGENET & VACCINE RES SECT, BETHESDA, MD 20892 USA. KAGAWA MED SCH, DEPT INTERNAL MED 3, KAGAWA 76107, JAPAN. US FDA, CTR BIOL EVALUAT & RES, HEPATITIS RES LAB, BETHESDA, MD 20892 USA. TORREY PINES INST MOLEC STUDIES, SAN DIEGO, CA 92121 USA. NR 73 TC 139 Z9 142 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3334 EP 3342 PG 9 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200060 PM 7512163 ER PT J AU BLOOM, ET AF BLOOM, ET TI NATURAL-KILLER-CELLS, LYMPHOKINE-ACTIVATED KILLER-CELLS, AND CYTOLYTIC T-LYMPHOCYTES - COMPARTMENTALIZATION OF AGE-RELATED-CHANGES IN CYTOLYTIC LYMPHOCYTES SO JOURNALS OF GERONTOLOGY LA English DT Review ID MEDIATED CYTO-TOXICITY; PERIPHERAL SOMATIC EXPANSION; LARGE GRANULAR LYMPHOCYTES; CALCIUM SIGNAL GENERATION; OLD MICE; AGING MICE; NK-CELLS; PRECURSOR CELL; LAK CELLS; CYTOTOXIC LYMPHOCYTES RP US FDA, CTR BIOL EVALUAT & RES, DIV CELLULAR & GENE THERAPIES, CELLULAR IMMUNOL LAB, BLDG 29A, BETHESDA, MD 20892 USA. NR 135 TC 15 Z9 15 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD MAY PY 1994 VL 49 IS 3 BP B85 EP B92 PG 8 WC Gerontology SC Geriatrics & Gerontology GA NJ544 UT WOS:A1994NJ54400021 PM 8169331 ER PT J AU BOIS, FY TOZER, TN HAUCK, WW CHEN, ML PATNAIK, R WILLIAMS, RL AF BOIS, FY TOZER, TN HAUCK, WW CHEN, ML PATNAIK, R WILLIAMS, RL TI BIOEQUIVALENCE - PERFORMANCE OF SEVERAL MEASURES OF EXTENT OF ABSORPTION SO PHARMACEUTICAL RESEARCH LA English DT Note DE PHARMACOKINETICS; BIOEQUIVALENCE; EXTENT OF ABSORPTION; POWER ANALYSIS AB The determination of the area under the concentration-time curve (AUC) is the method most commonly used by regulatory agencies to assess extent of drug absorption after single-dose administration of oral products. Using simulations, several approaches toward measuring the actual area, in whole or part, were tested. In addition, the performance of the peak concentration (C-max), usually taken as a measure of the rate of absorption was assessed evaluating extent. Model scenarios for drugs with typical mean characteristics and statistical distributions were investigated. Using different kinetic models of disposition, the time course of the drug concentration in plasma was simulated. Intraindividual and interindividual variability and assay error were modeled using Monte Carlo techniques. The accuracy, precision, and ease of use of the various measures of extent were evaluated, and statistical power analyses were performed. Among the measures tested, the most reliable were the AUC computed up to the time of the last quantifiable concentration, without extrapolation, and C-max. However, being also sensitive to rate, C-max as a measure of extent is of limited potential. C1 UNIV CALIF SAN FRANCISCO,SCH PHARM,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL & BIOSTAT,SAN FRANCISCO,CA 94143. US FDA,CTR DRUG EVALUAT & RES,OFF GENER DRUGS,ROCKVILLE,MD 20855. RP BOIS, FY (reprint author), UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,INDOOR ENVIRONM PROGRAM,MAIL STOP 90-3058,BERKELEY,CA 94720, USA. RI Bois, Frederic/E-9241-2012 OI Bois, Frederic/0000-0002-4154-0391 FU PHS HHS [224-91-3007] NR 6 TC 47 Z9 47 U1 1 U2 3 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 1994 VL 11 IS 5 BP 715 EP 722 DI 10.1023/A:1018932430733 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA NJ623 UT WOS:A1994NJ62300017 PM 8058642 ER PT J AU SISTARE, FD ROSENZWEIG, BA AF SISTARE, FD ROSENZWEIG, BA TI DEVELOPMENT OF A SIMPLE, PRECISE, NONRADIOACTIVE IN-VITRO CELLULAR BIOASSAY FOR HPTH 1-34 AND COMPARISON TO THE CHICK HYPERCALCEMIC BIOASSAY SO PHARMACOPEIAL FORUM LA English DT Article ID RAT OSTEO-SARCOMA; INTRACELLULAR FREE CALCIUM; PARATHYROID-HORMONE; BONE-RESORPTION; CYTOSOLIC CALCIUM; ADENYLATE-CYCLASE; MOUSE CALVARIA; PROTEIN-KINASE; CELLS; CAMP AB While focusing our efforts on validating a chick hypercalcemic assay proposed for assessing human parathyroid hormone fragment 1-34 (hPTH 1-34) biological potency, we concurrently sought to develop and test an alternative assay that did not involve animal sacrifice or the use of radiochemicals. The assay proposed by a manufacturer involves a 2 X 2 statistical analysis of the serum calcium concentration one hour following subcutaneous injection of two carefully selected doses of hPTH 1-34 standard versus sample in a calcium chloride-gelatin vehicle to 4 groups of 8 chicks (one dose per group). Basal serum calcium concentrations of approximately 10.5 mg/dL increased by 40% to approximately 14.5 mg/dL with maximal doses of hPTH 1-34. Results from three successful 2 X 2 assays using carefully selected intermediate doses of a sample and standard lot indicate that the sample has an overall mean potency of 1.30 times that of the standard with 95% confidence limits that ranged from 1.01 to 1.67. The index of precision for this assay averaged across 4 pairs of dosings was 0.25. This assay is concluded to be acceptable for regulatory purposes; however, the alternative cellular assay we developed was found to have greater precision and accuracy. The cellular assay involves the nonradioactive measurement of cyclic adenosine monophosphate (cAMP) generated in UMR-106 rat osteoblastic sarcoma cells following incubation of cell cultures with a spectrum of hPTH 1-34 sample or standard concentrations, which are carefully selected to bracket the EC50. Basal cellular cAMP concentrations of approximately 10 pmol per well (of a 24-well plate) increase 50-fold at maximal hPTH concentrations to over 500 pmol per well. Non-linear regression analyses were used to evaluate the potency ratio of sample to standard hPTH 1-34. Test dilutions of standard of 50% to 80% of full potency assayed to within 10% to 30% of the true reduced potency. The same sample lot used for the chick assay when assayed against the same standard lot according to this method was found to have an overall mean potency of 1.12 with 95% confidence limits of 1.09 to 1.16. The index of precision for the cellular assay averaged 0.14. We propose that this cellular hPTH 1-34 assay be offered for use as an acceptable regulatory assay to meet quality control and surveillance requirements. RP SISTARE, FD (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV RES & TESTING,HFD 470,MOD I,ROOM 2007,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 37 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 MAY-JUN PY 1994 VL 20 IS 3 BP 7509 EP 7520 PG 12 WC Medicine, Legal; Pharmacology & Pharmacy SC Legal Medicine; Pharmacology & Pharmacy GA NQ089 UT WOS:A1994NQ08900004 ER PT J AU CONWAY, BJ SULEIMAN, OH RUETER, FG ANTONSEN, RG SLAYTON, RJ AF CONWAY, BJ SULEIMAN, OH RUETER, FG ANTONSEN, RG SLAYTON, RJ TI NATIONAL SURVEY OF MAMMOGRAPHIC FACILITIES IN 1985, 1988, AND 1992 SO RADIOLOGY LA English DT Article DE BREAST RADIOGRAPHY, QUALITY ASSURANCE; BREAST RADIOGRAPHY, RADIATION DOSE; BREAST RADIOGRAPHY, TECHNOLOGY; RADIATIONS, EXPOSURE TO PATIENTS AND PERSONNEL ID SCREEN-FILM MAMMOGRAPHY AB PURPOSE: To determine trends in mammography in the United States. MATERIALS AND METHODS: A sample of mammographic facilities was selected for each year of the Nationwide Evaluation of X-ray Trends. The same protocol was followed for the 1985, 1988, and 1992 surveys. Data were collected with use of the same imaging phantom for all three surveys and also with a different phantom in the 1988 and 1992 surveys. RESULTS: Of the 356 facilities surveyed in 1992, 59% claimed to be in compliance with the Health Care Financing Administration (HCFA) mammography requirements, 42% were accredited by the American College of Radiology (ACR), and 23% did not hold credentials from either the HCFA or the ACR. Since 1985, there has been a 34% improvement in acceptable phantom image quality score and a 20% decrease in the mean glandular dose. CONCLUSION: Mammography as practiced today is essentially a screen-film technique. Mammographic phantom image quality has improved considerably. The overall mean glandular dose has decreased primarily because of the elimination of xeroradiography. RP CONWAY, BJ (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,CDRH HFZ-240,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 19 TC 41 Z9 41 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 1994 VL 191 IS 2 BP 323 EP 330 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NG955 UT WOS:A1994NG95500009 PM 8153301 ER PT J AU TOYOKUNI, S SAGRIPANTI, JL AF TOYOKUNI, S SAGRIPANTI, JL TI INCREASED 8-HYDROXYDEOXYGUANOSINE IN KIDNEY AND LIVER OF RATS CONTINUOUSLY EXPOSED TO COPPER SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID DNA DAMAGE; HYDROGEN-PEROXIDE; FERRIC NITRILOTRIACETATE; CARCINOGENESIS; CARCINOMA; STRAND; BASES; MODEL; ACID; ION AB Copper is a ubiquitous metal in the environment, it is a component of dental casting gold alloys and dental amalgams, and it is a main component in some intrauterine contraceptive devices (IUDs). Since copper materials implanted in the human body corrode and release ions into the surrounding tissue, the potential toxicity caused by contact of this metal with bodily fluids needs to be evaluated. We implanted male Wistar rats with osmotic mini pumps that continuously administered saline, CuCl2, or a copper chelate, cupric nitrilotriacetate (Cu-NTA), at a rate of 4 mg copper/kg body wt/day. This experimental design maintained serum copper concentrations at a level 30-70% (CuCl2) or 100-120% (Cu-NTA) higher than in untreated controls. At different times postimplantation, we measured the levels of 8-hydroxydeoxyguanosine (8-OHdG) in DNA of kidney, liver, and tissue surrounding the pump implant, since production of 8-OHdG has been associated with mutagenesis and carcinogenesis. Hepatic and renal levels of 8-OHdG in CuCl2- or Cu-NTA-treated animals were significantly higher than in control animals. In contrast, histopathologic changes in kidneys and livers of rats exposed to CuCl2 and Cu-NTA were limited to mild changes involving hepatic focal necrosis and slightly increased mitotic activity in the renal proximal tubules. These observations suggest that levels of 8-OHdG could be an early marker of copper toxicity. It is unlikely that the high levels of copper at which we observed DNA modification will be encountered after occupational or environmental exposure. A different situation could be found around medical devices that include copper, particularly IUDs, where the amount of copper administered in our experiments could be released in the uterus of women after a few months of continued IUD use. (C) 1994 Academic Press, Inc. C1 US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,DIV LIFE SCI,MOLEC BIOL BRANCH,ROCKVILLE,MD 20857. RI Toyokuni, Shinya/C-1358-2010 OI Toyokuni, Shinya/0000-0002-5757-1109 NR 30 TC 26 Z9 26 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY PY 1994 VL 126 IS 1 BP 91 EP 97 DI 10.1006/taap.1994.1094 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA NL854 UT WOS:A1994NL85400012 PM 8184438 ER PT J AU CHEN, RT RASTOGI, SC MULLEN, JR HAYES, SW COCHI, SL DONLON, JA WASSILAK, SG AF CHEN, RT RASTOGI, SC MULLEN, JR HAYES, SW COCHI, SL DONLON, JA WASSILAK, SG TI THE VACCINE-ADVERSE-EVENT-REPORTING-SYSTEM (VAERS) SO VACCINE LA English DT Article DE VACCINATION; IMMUNIZATION; ADVERSE REACTIONS; PRODUCT SURVEILLANCE; POSTMARKETING ID TETANUS-PERTUSSIS-VACCINE; INFANT DEATH SYNDROME; WHOOPING-COUGH; IMMUNIZATION; MUMPS; RISK; EPIDEMIOLOGY; ERADICATION; LITIGATION; CHILDREN AB Immunizations against most vaccine-preventable diseases will be needed indefinitely unless the disease is eradicated. Public acceptance of immunizations may be threatened as vaccine coverage increases and disease decreases, however, due to the increase in both causally and coincidentally related vaccine adverse events. The post-marketing surveillance for such events in the USA in response to the mandatory reporting requirements of the National Childhood Injury Act of 1986. While VAERS has many methodological limitations intrinsic to such systems, it can play an important role in helping to monitor vaccine safety and maintain public confidence in immunizations. C1 US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. RP CHEN, RT (reprint author), CTR DIS CONTROL & PREVENT,NATL IMMUNIZAT PROGRAM E61,ATLANTA,GA 30341, USA. NR 70 TC 240 Z9 243 U1 1 U2 8 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD MAY PY 1994 VL 12 IS 6 BP 542 EP 550 DI 10.1016/0264-410X(94)90315-8 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NE606 UT WOS:A1994NE60600013 PM 8036829 ER PT J AU CHUNG, BC KIM, DH JUNG, BH EOM, K SLIKKER, W PARK, J AF CHUNG, BC KIM, DH JUNG, BH EOM, K SLIKKER, W PARK, J TI IDENTIFICATION OF URINARY METABOLITES OF PYRILAMINE AFTER ORAL-ADMINISTRATION TO MAN SO XENOBIOTICA LA English DT Article ID MALEATE; ANTIHISTAMINES; TRIPELENNAMINE; DRUGS; ASSAY; RAT AB 1. The metabolism of pyrilamine, 2-[4-methoxybenzyl-(2-dimethylaminoelhyl) amino] pyridine, was studied in adult male volunteers after a single oral dose of 50 mg. 2. Solvent extracts of urine obtained with or without enzyme hydrolysis were analysed by gc/ms after derivatization with MSTFA/TM SCI (N-methyl-N-trimethylsilyl-trifluoroacetamidel-trimethyl chlorosilane). The structure of metabolites were determined based on EI mass spectra and confirmed with those of authentic standards. 3. Conjugated metabolites identified in the urine were pyrilamine, O-desmethylpyril amine, and ring hydroxylated derivatives of pyrilamine. O-desmethylpyrilamine was also detected in low abundance as a free form. 4. These metabolites observed in human urine were quite different from those previously reported in rat. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP CHUNG, BC (reprint author), KOREA ADV INST SCI & TECHNOL,DOPING CONTROL CTR,POB 131,SEOUL,SOUTH KOREA. NR 18 TC 8 Z9 8 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD MAY PY 1994 VL 24 IS 5 BP 451 EP 459 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA NN029 UT WOS:A1994NN02900007 PM 8079504 ER PT J AU TAKIMOTO, CH KLECKER, RW DAHUT, WL YEE, LK STRONG, JM ALLEGRA, CJ GREM, JL AF TAKIMOTO, CH KLECKER, RW DAHUT, WL YEE, LK STRONG, JM ALLEGRA, CJ GREM, JL TI ANALYSIS OF THE ACTIVE LACTONE FORM OF 9-AMINOCAMPTOTHECIN IN PLASMA USING SOLID-PHASE EXTRACTION AND HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article ID XENOGRAFTS; CAMPTOTHECIN; INHIBITION; CANCER; MICE AB We have developed a sensitive HPLC assay to quantitate the active lactone form of 9-aminocamptothecin (9AC) in human plasma over the concentration range 10-0.25 nM (0.091 ng/ml). Solid-phase extraction separated 9AC lactone from its less active metabolite, 9AC carboxylate, allowing samples to be stored for up to two months prior to reversed-phase HPLC analysis. An acidic (pH 2.55) isocratic HPLC mobile phase was used to enhance 9AC fluorescence resulting in an over 50-fold increase in assay sensitivity compared to previous methods. This assay was able to measure steady-state 9AC lactone concentrations even at the lowest dose level of 9AC used in our Phase I clinical trial. C1 US FDA,CTR DRUG EVALUAT & RES,OFF RES RESOURCES,DIV CLIN PHARMACOL,ROCKVILLE,MD 20850. RP TAKIMOTO, CH (reprint author), USN,NATL MED CTR,NCI,DIV CANC TREATMENT,MED ONCOL BRANCH,BETHESDA,MD 20889, USA. NR 9 TC 60 Z9 61 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD APR 22 PY 1994 VL 655 IS 1 BP 97 EP 104 DI 10.1016/0378-4347(94)00051-4 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NJ139 UT WOS:A1994NJ13900013 PM 8061838 ER PT J AU SCREMIN, CL ZHOU, L SRINIVASACHAR, K BEAUCAGE, SL AF SCREMIN, CL ZHOU, L SRINIVASACHAR, K BEAUCAGE, SL TI STEPWISE REGENERATION AND RECOVERY OF DEOXYRIBONUCLEOSIDE PHOSPHORAMIDITE MONOMERS DURING SOLID-PHASE OLIGONUCLEOTIDE SYNTHESIS SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Letter ID GENE-EXPRESSION; ANTISENSE OLIGONUCLEOTIDES; DEOXYNUCLEOSIDE PHOSPHORAMIDITES; CHEMISTRY; VIRUS; COMPLEMENTARY; OPPORTUNITIES; INHIBITORS; TETRAZOLE; REAGENTS AB Deoxyribonucleoside phosphoramidites 1a-d have been regenerated, in a stepwise manner, during solid-phase oligonucleotide synthesis and have been efficiently reutilized in the solid-phase synthesis of polydeoxyribonucleotides. The activator 1H-tetrazole has also been recovered and recycled. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,DIV METAB & ENDOCRINE DRUG PROD,ROCKVILLE,MD 20857. NR 38 TC 17 Z9 17 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD APR 22 PY 1994 VL 59 IS 8 BP 1963 EP 1966 DI 10.1021/jo00087a005 PG 4 WC Chemistry, Organic SC Chemistry GA NJ137 UT WOS:A1994NJ13700005 ER PT J AU CHANG, J IHRIG, T VANN, WF SLIWKOWSKI, MB WARNER, TG AF CHANG, J IHRIG, T VANN, WF SLIWKOWSKI, MB WARNER, TG TI CHARACTERIZATION OF NON-SIALYLATING CHINESE-HAMSTER OVARY (CHO) CELLS TRANSFECTED WITH GLYCOPROTEIN GENES SO FASEB JOURNAL LA English DT Meeting Abstract ID SIALIC-ACID; DEFICIENT C1 US FDA,CBER,BETHESDA,MD 20892. GENENTECH INC,S SAN FRANCISCO,CA 94080. NR 3 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1425 EP A1425 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601182 ER PT J AU FUJIMURA, RK BOCKSTAHLER, L BRACKWERNER, R AF FUJIMURA, RK BOCKSTAHLER, L BRACKWERNER, R TI ANALYSIS OF THE RATIO OF HIV GENOMES TO HUMAN GENOMES IN BRAIN-TISSUES DERIVED FROM AIDS PATIENTS USING A PCR METHOD SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. GSF MUNICH,INST MOLEC VIROL,NEUHERBERG,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1300 EP A1300 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600459 ER PT J AU HAMMONS, GJ MILTON, D GUENGERICH, FP TUKEY, RH KADLUBAR, FF AF HAMMONS, GJ MILTON, D GUENGERICH, FP TUKEY, RH KADLUBAR, FF TI HUMAN CYTOCHROME-P450 1A2-CATALYZED N-HYDROXYLATION OF CARCINOGENIC HETEROCYCLIC AMINES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. VANDERBILT UNIV,MED CTR,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1381 EP A1381 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600924 ER PT J AU KENNEY, NJ HUANG, RP JOHNSON, G OKAMURA, D MATHENY, W PLOWMAN, G SMITH, GH SALOMON, DS ADAMSON, ED AF KENNEY, NJ HUANG, RP JOHNSON, G OKAMURA, D MATHENY, W PLOWMAN, G SMITH, GH SALOMON, DS ADAMSON, ED TI HETEROGENEOUS EXPRESSION OF AMPHIREGULIN (AR) AND CRIPTO (CR-1) IN THE DEVELOPING MOUSE MAMMARY-GLAND SO FASEB JOURNAL LA English DT Meeting Abstract C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. US FDA,CELL BIOL LAB,BETHESDA,MD 20892. LA JOLLA CANC RES FDN,LA JOLLA,CA 92027. NCI,TUMOR IMMUNOL & BIOL,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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1419 EP A1419 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601146 ER PT J AU KOIZUMI, M LEE, C AF KOIZUMI, M LEE, C TI ISOLATION AND CHARACTERIZATION OF AUTOLYSIN IN STREPTOCOCCUS-PNEUMONIAE SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1452 EP A1452 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601341 ER PT J AU LIGHTFOOTE, MM AF LIGHTFOOTE, MM TI EXPRESSION OF HOST CELLULAR CYTOKINES CORRELATES WITH REVERSE-TRANSCRIPTASE ACTIVITY OF HIV SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CDRH DLS,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1311 EP A1311 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600524 ER PT J AU LIU, SY KOMORIYA, A AF LIU, SY KOMORIYA, A TI THE DISULFIDE BOND CONNECTIVITY OF THE SOLUBLE EGF RECEPTOR SUPPORTS INTERNAL FOLDED STRUCTURE DUPLICATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CBER,DIV CYTOKINE BIOL,CELL BIOL LAB,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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1352 EP A1352 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600758 ER PT J AU PACKARD, BZ KOMORIYA, A AF PACKARD, BZ KOMORIYA, A TI ONCOIMMUNIN-L, A 45-KILODALTON PROTEIN WITH LYMPHOID IMMUNOMODULATORY ACTIVITY - MITOGENIC STIMULATION OF HUMAN TUMOR-INFILTRATING LYMPHOCYTES SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CBER,DCB,BETHESDA,MD 20014. NR 2 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1460 EP A1460 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601383 ER PT J AU VANN, WF CROWLEY, J BANKS, S TAVAREZ, JJ SILVER, RP AF VANN, WF CROWLEY, J BANKS, S TAVAREZ, JJ SILVER, RP TI SYNTHESIS OF N-ACETYLNEURAMINIC ACID IN ESCHERICHIA-COLI-K1 BY THE NEU-B GENE-PRODUCT SO FASEB JOURNAL LA English DT Meeting Abstract C1 CTR BIOL EVALUAT & RES,BACTERIAL POLYSACCHARIDES LAB,BETHESDA,MD. UNIV ROCHESTER,MED CTR,DEPT MICROBIOL & IMMUNOL,ROCHESTER,NY 14642. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1454 EP A1454 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601348 ER PT J AU MILLER, MW DUHL, DMJ WINKES, BM ARREDONDOVEGA, F WOLFF, GL EPSTEIN, CJ HERSHFIELD, MS BARSH, GS SAXON, PJ AF MILLER, MW DUHL, DMJ WINKES, BM ARREDONDOVEGA, F WOLFF, GL EPSTEIN, CJ HERSHFIELD, MS BARSH, GS SAXON, PJ TI THE MOUSE LETHAL NONAGOUTI (A(X)) MUTATION DELETES THE S-ADENOSYLHOMOCYSTEINE HYDROLASE (AHCY) GENE SO EMBO JOURNAL LA English DT Article DE S-ADENOSYLHOMOCYSTEINE HYDROLASE; AGOUTI; METHYLTRANSFERASE; MOUSE DEVELOPMENT ID L-HOMOCYSTEINE HYDROLASE; AMINO-ACID SEQUENCE; COAT COLOR LOCUS; ADENOSINE-DEAMINASE; AGOUTI LOCUS; MOLECULAR MARKERS; CDNA SEQUENCE; STEM-CELLS; EXPRESSION; MICE AB The lethal nonagouti (a(x)) mutation is a hypomorphic allele of the agouti coat color locus which, when homozygous, also leads to embryonic death around the time of implantation. To understand the molecular basis of these phenotypes, we identified and cloned a deletion breakpoint junction present in the a(x) chromosome. Long range restriction mapping demonstrated a simple deletion of similar to 100 kb, which does not affect agouti coding sequences, but begins only 4 kb 3' of the last exon, and thus may affect coat color by removing an agouti 3' enhancer. The Ahcy gene, which codes for the enzyme S-adenosylhomocysteine hydrolase (SAHase), is contained within a 20 kb region within the a(x) deletion. SAHase RNA and protein were detectable in early blastocysts and in embryonic stem cells, respectively, and analysis of embryos derived from an a(x)/a x a(x)/a embryo intercross indicated that a(x)/a embryos die between the late blastocyst and early implantation stages. Treatment of cultured embryos with an SAHase inhibitor, 3-deaza-aristeromycin, or with metabolites that can result in elevated levels of cellular SAH, resulted in an inhibition of inner cell mass development, suggesting that loss of SAHase activity in a(x)/a(x) embryos is sufficient to explain their death around the time of implantation. C1 STANFORD UNIV,SCH MED,DEPT PEDIAT,STANFORD,CA 94305. STANFORD UNIV,SCH MED,HOWARD HUGHES MED INST,STANFORD,CA 94305. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT BIOCHEM,DURHAM,NC 27710. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. FU NHGRI NIH HHS [HG-00377]; NICHD NIH HHS [HD-03132]; NIDDK NIH HHS [DK-20902] NR 69 TC 88 Z9 89 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD APR 15 PY 1994 VL 13 IS 8 BP 1806 EP 1816 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NH082 UT WOS:A1994NH08200006 PM 8168479 ER PT J AU QIAN, JH BOURS, V MANISCHEWITZ, J BLACKBURN, R SIEBENLIST, U GOLDING, H AF QIAN, JH BOURS, V MANISCHEWITZ, J BLACKBURN, R SIEBENLIST, U GOLDING, H TI CHEMICALLY SELECTED SUBCLONES OF THE CEM CELL-LINE DEMONSTRATE RESISTANCE TO HIV-1 INFECTION RESULTING FROM A SELECTIVE LOSS OF NF-KAPPA-B DNA-BINDING PROTEINS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; LONG TERMINAL REPEAT; HUMAN T-CELLS; FACTOR-ALPHA; KINASE-C; GENE-EXPRESSION; ACTIVATION; TYPE-1; TRANSCRIPTION AB To delineate cellular genes that are required for optimal HIV-1 infection, CEM cells were subjected to treatment with the chemical mutagen ethylmethanesulfonate (EMS) and subclones were selected based on their increased resistance to HIV-1 infection and reduced syncytium formation, despite relatively normal CD4 expression (20,000 to 25,000 receptors/cell). Two subclones with this phenotype demonstrated a diminished capacity of HIV-1 long terminal repeat-chloramphenicol acetyl transferase expression either after treatment with the protein kinase C activator PMA, or through Tat-mediated transactivation. In this study, we show that the cellular levels of the NF-kappa B DNA binding proteins (but not AP1 or SP1) are markedly reduced in these cell mutants both at the mRNA and protein levels, resulting in reduced nuclear localization of p50/p65 after PMA induction or treatment with the lymphokine TNF-alpha. Transient reconstitution with a plasmid expressing p50 resulted in partial recovery of PMA-inducible LTR-chloramphenicol acetyl transferase expression. These data suggest that, at least in the CEM T cell line, a selective reduction in the NF-kappa B DNA binding proteins is sufficient to curtail HIV-1 infection. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,RETROVIRUS RES LAB,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 40 TC 28 Z9 28 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 APR 15 PY 1994 VL 152 IS 8 BP 4183 EP 4191 PG 9 WC Immunology SC Immunology GA NF018 UT WOS:A1994NF01800052 PM 8144979 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI NEW FOOD CODE PUBLISHED 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 16 Z9 16 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 13 PY 1994 VL 271 IS 14 BP 1067 EP 1067 DI 10.1001/jama.271.14.1067 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NE228 UT WOS:A1994NE22800006 PM 8151837 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI FLUOXETINE LABELING REVISED TO IDENTIFY PHENYTOIN INTERACTION AND TO RECOMMEND AGAINST USE IN NURSING MOTHERS 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 16 Z9 16 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 13 PY 1994 VL 271 IS 14 BP 1067 EP 1067 DI 10.1001/jama.271.14.1067 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NE228 UT WOS:A1994NE22800007 PM 8151837 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI PUBLIC HEARING ON PROPOSED SWITCH OF ACYCLOVIR FROM PRESCRIPTION TO OVER-THE-COUNTER 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 16 Z9 16 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 13 PY 1994 VL 271 IS 14 BP 1067 EP 1067 DI 10.1001/jama.271.14.1067 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NE228 UT WOS:A1994NE22800005 PM 8151837 ER PT J AU CHAKRAVERTY, M SKEHEL, J HAY, A SCHILD, G WOOD, J GUST, I HAMPSON, A AF CHAKRAVERTY, M SKEHEL, J HAY, A SCHILD, G WOOD, J GUST, I HAMPSON, A TI UPDATE - INFLUENZA ACTIVITY - UNITED-STATES AND WORLDWIDE, 1993-94 SEASON, AND COMPOSITION OF THE 1994-95 INFLUENZA VACCINE (REPRINTED FROM MMWR, VOL 43, PG 179-183, 1994) 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,HERTFORD,HERTS,ENGLAND. COMMONWEALTH SERUM LABS,PARKVILLE,AUSTRALIA. WHO,NATL INFLUENZA CTR,MICROBIOL & IMMUNOL SUPPORT SERV,CH-1211 GENEVA 27,SWITZERLAND. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,BETHESDA,MD 20014. CTR DIS CONTROL,NATL CTR INFECT DIS,WHO,COLLABORATING CTR SURVEILLANCE EPIDEMIOL,ATLANTA,GA 30333. RP CHAKRAVERTY, M (reprint author), CENT PUBL HLTH LAB,LONDON NW9 5HT,ENGLAND. NR 8 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 APR 13 PY 1994 VL 271 IS 14 BP 1070 EP 1071 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NE228 UT WOS:A1994NE22800009 ER PT J AU FELDMAN, GM PETRICOIN, EF DAVID, M LARNER, AC FINBLOOM, DS AF FELDMAN, GM PETRICOIN, EF DAVID, M LARNER, AC FINBLOOM, DS TI CYTOKINES THAT ASSOCIATE WITH THE SIGNAL TRANSDUCER GP130 ACTIVATE THE INTERFERON-INDUCED TRANSCRIPTION FACTOR P91 BY TYROSINE PHOSPHORYLATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKEMIA-INHIBITORY FACTOR; DNA-BINDING PROTEIN; FC-GAMMA RECEPTOR; ONCOSTATIN-M; STIMULATED TRANSCRIPTION; CYTOPLASMIC ACTIVATION; RESPONSE ELEMENTS; IFN-GAMMA; CELLS; ALPHA AB Interleukin-6, leukemia inhibitory factor, and oncostatin M exert a broad range of similar biological activities through association of their receptors with the signal-transducing component gp130. Although it is known that these cytokines trigger rapid tyrosine phosphorylation of a common set of cellular proteins as well as induction of several of the same early response genes, the mechanisms by which these genes are activated is not well understood. In this report, we show that interleukin-6 leukemia inhibitory factor, and oncostatin M stimulate the assembly of protein complexes that recognize conserved sequences within the enhancers of two genes (interferon regulatory factor 1 and Fc gamma receptor type I) that are rapidly activated by these cytokines. These enhancers are known to be required for transcriptional induction of these genes by interferon-gamma. Assembly of the DNA-binding protein complexes occurs within minutes after ligand addition and depends upon tyrosine phosphorylation. These complexes contain the p91 transcription factor, which is tyrosine-phosphorylated in response to these cytokines. An additional tyrosine-phosphorylated protein of 93 kDa can be coimmunoprecipitated with antibodies against p91. These findings further expand the network of cytokines known to activate p91 and, in addition, support the concept that sets of tyrosine-phosphorylated proteins may be responsible for the cytokine-regulated expression of early response genes. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NR 51 TC 33 Z9 33 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 APR 8 PY 1994 VL 269 IS 14 BP 10747 EP 10752 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NF017 UT WOS:A1994NF01700083 PM 8144663 ER PT J AU PIPKIN, JL HINSON, WG FEUERS, RJ LYNCOOK, LE BURNS, ER DUFFY, PH HART, R CASCIANO, DA AF PIPKIN, JL HINSON, WG FEUERS, RJ LYNCOOK, LE BURNS, ER DUFFY, PH HART, R CASCIANO, DA TI THE TEMPORAL RELATIONSHIPS OF SYNTHESIS AND PHOSPHORYLATION IN STRESS PROTEINS 70 AND 90 IN AGED CALORIC RESTRICTED RATS EXPOSED TO BLEOMYCIN SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE CALORIC RESTRICTION; RATS; STRESS PROTEINS 70 AND 90 AB A single intraperitoneal injection of the human therapeutic drug bleomycin (BL) was administered to three groups of male Fischer 344 rats at time 0, and the incorporation of [S-35]methionine (''synthesis'') and phosphorylation patterns of stress proteins (sps/hsps) from bone marrow cells were analyzed over time by two-dimensional electrophoresis and fluorography. Two groups of rats, young ad libitum (Y/AL - 3 months) and old ad libitum (O/AL - 28 months), had free access to rat chow, and a third group of old rats (O/CR - 28 months) were maintained on a caloric restricted intake (60% of the AL diet). The administration of BL in Y/AL, O/AL and O/CR animals activated the S-35-labeling of sp 90 which reached a peak at 4 hours. Labeling of sp 90 was significantly greater in Y/AL compared to O/AL, and the incorporation pattern of O/CR was intermediate to Y/AL and O/AL animals. All labeling of sp 90 in each group had disappeared by 10 hours after BL administration. Stress protein 70x (inducible form) in these three animal groups displayed a similar pattern of S-35-incorporation, but the amount of labeling was less than that of sp 90. No labeling of sp 70x remained by 13 hours after BL administration. Phosphorylation ([P-32] phosphate incorporation) of sp 90 reached a maximum level at 2 hours in all animals, and P-32-labeling in Y/AL was significantly increased over O/AL and O/CR with an intermediate level found in O/CR animals. The turnover rate (phosphorylation/dephosphorylation) of sp 90 induced by BL was significantly suppressed and temporarily extended in O/AL as compared with O/CR, which implied that CR not only increased incorporation of sp 90, but also enhanced a utilization of the phosphate pool very similar to that seen in Y/AL animals. RP PIPKIN, JL (reprint author), US FDA,NATL CTR TOXICOL RES,DIV GENET TOXICOL,DGT,HFT 120,JEFFERSON,AR 72079, USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD APR PY 1994 VL 6 IS 2 BP 121 EP 131 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA NJ446 UT WOS:A1994NJ44600008 PM 7522579 ER PT J AU WEISS, SH DENNY, TN QUIRINALE, J MAYUR, RK PALUMBO, PE HEREDIA, A COWAN, EP HEWLETT, I MCCREEDY, BJ AF WEISS, SH DENNY, TN QUIRINALE, J MAYUR, RK PALUMBO, PE HEREDIA, A COWAN, EP HEWLETT, I MCCREEDY, BJ TI HTLV-II SCREENING ISSUES - FALSE-NEGATIVE HTLV ELISA RESULTS WITHIN A HIGH-RISK IDU COHORT SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 UMDNJ,NEW JERSEY SCH MED,NEWARK,NJ. US FDA,ROCKVILLE,MD 20857. ROCHE BIOMED LABS,RES TRIANGLE PK,NC. NR 0 TC 3 Z9 3 U1 0 U2 0 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 APR PY 1994 VL 10 IS 4 BP 451 EP 451 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NK470 UT WOS:A1994NK47000052 ER PT J AU COWAN, EP LEHKY, TJ TSUCHIDA, T BIDDISON, WE JACOBSON, S AF COWAN, EP LEHKY, TJ TSUCHIDA, T BIDDISON, WE JACOBSON, S TI HLA-CLASS-II EXPRESSION ON HTLV-I-INFECTED NEUROBLASTOMAS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,BETHESDA,MD 20014. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 1994 VL 10 IS 4 BP 452 EP 452 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NK470 UT WOS:A1994NK47000056 ER PT J AU LUNARDIISKANDAR, Y BRYANT, JL LAM, VH ZEMAN, RA GESSAIN, A GILL, P VARRICCHIO, F GALLO, RC AF LUNARDIISKANDAR, Y BRYANT, JL LAM, VH ZEMAN, RA GESSAIN, A GILL, P VARRICCHIO, F GALLO, RC TI A MODEL OF SEVERAL ASPECTS OF TROPICAL SPASTIC PARAPARESIS HTLV-I-ASSOCIATED MYELOPATHY (TSP/HAM) DISEASE IN IMMUNODEFICIENT MICE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NIDR,ANIM CARE UNIT,BETHESDA,MD 20892. US FDA,NIH,CBER,BETHESDA,MD 20892. INST PASTEUR,PARIS,FRANCE. UNIV SO CALIF,SCH MED,LOS ANGELES,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 1994 VL 10 IS 4 BP 455 EP 455 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NK470 UT WOS:A1994NK47000066 ER PT J AU HEREDIA, A SORIANO, V WEISS, SH UDAYKUMAR EPSTEIN, JS HEWLETT, IK AF HEREDIA, A SORIANO, V WEISS, SH UDAYKUMAR EPSTEIN, JS HEWLETT, IK TI DETECTION AND DISCRIMINATION OF HTLV-I, HTLV-II, HIV-1 AND HIV-1 IN A SINGLE PCR TEST UTILIZING A COAMPLIFICATION REACTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. INST SALUD CARLOS 3,MADRID,SPAIN. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,NEWARK,NJ 07103. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 1994 VL 10 IS 4 BP 495 EP 495 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NK470 UT WOS:A1994NK47000212 ER PT J AU DONG, YL HERNDON, DN YAN, TZ WAYMACK, JP AF DONG, YL HERNDON, DN YAN, TZ WAYMACK, JP TI EFFECT OF PGE IN MULTIPLE EXPERIMENTAL-MODELS .9. IN-VIVO EFFECTS OF PGE ON IMMUNE-RESPONSE OF LEUKOCYTES TO WOUNDS SO BURNS LA English DT Article AB There have been conflicting results obtained when comparing the in vitro with in vivo effects of prostaglandin E (PGE) on immune function. The in vitro studies have demonstrated immune suppression with PGE administration while the in vivo studies demonstrated improved survival when utilizing infected models. To attempt to resolve this discrepancy, we evaluated the in vivo effect of PGE on host immune function utilizing multiple rat models. PGE was found to have no effect on the ability of leucocytes to infiltrate a sponge matrix wound over a 2-week period of study. PGE also failed to alter the percentage of T-lymphocyte subset populations infiltrating the sponge matrix model. There was noted to be no effect of PGE on the ability of neutrophils to chemiluminesce, or on metabolic function of lymphocytes. In conclusion, PGE does not appear to have immunosuppressive properties when studied using certain in vivo models. C1 US FDA,DIV MED IMAGING SURG DENT PROD,HFD-160,5600 FISHERS LANE,ROCKVILLE,MD 20857. NR 0 TC 5 Z9 5 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0305-4179 J9 BURNS JI Burns PD APR PY 1994 VL 20 IS 2 BP 132 EP 135 DI 10.1016/S0305-4179(06)80010-0 PG 4 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA NC315 UT WOS:A1994NC31500008 PM 8198717 ER PT J AU HELZLSOUER, KJ BLOCK, G BLUMBERG, J DIPLOCK, AT LEVINE, M MARNETT, LJ SCHULPLEIN, RJ SPENCE, JT SIMIC, MG AF HELZLSOUER, KJ BLOCK, G BLUMBERG, J DIPLOCK, AT LEVINE, M MARNETT, LJ SCHULPLEIN, RJ SPENCE, JT SIMIC, MG TI SUMMARY OF THE ROUND-TABLE DISCUSSION ON STRATEGIES FOR CANCER PREVENTION - DIET, FOOD, ADDITIVES, SUPPLEMENTS, AND DRUGS SO CANCER RESEARCH LA English DT Article ID LARGE-BOWEL CANCER; BETA-CAROTENE; ASCORBIC-ACID; COLON CANCER; ASPIRIN USE; VITAMIN-E; RISK; SAFETY; FOLATE AB A Round Table Discussion was held at the Fourth International Conference on Anticarcinogenesis and Radiation Protection. Scientists from government and academia were brought together to discuss the evidence for the preventive effect of foods, specific nutrients and drugs against cancer, and the most appropriate methods of initiating nutritional cancer prevention activities to improve the health of the public. The panel reviewed the epidemiological evidence of the role of diet and specific micronutrients for the prevention of cancer, the doses of specific micronutrients required for preventive effects and their safety, the evidence for aspirin as a chemopreventive agent, the issue of foods versus specific micronutrients in the prevention of cancer, food safety, and approaches to prevention such as food fortification or dietary supplements. The remarks of the panel members are summarized. C1 UNIV LONDON, GUYS HOSP, DIV BIOCHEM & MOLEC BIOL, FREE RAD RES GRP, LONDON SE1 9RJ, ENGLAND. NIDDKD, CELL BIOL & GENET, BETHESDA, MD USA. VANDERBILT UNIV, MED CTR,SCH MED,DEPT BIOCHEM, AB HANCOCK JR MEM LAB CANC RES, NASHVILLE, TN 37232 USA. US FDA, CTR FOOD SAFETY & APPL NUTR, WASHINGTON, DC 20204 USA. USDA, BELTSVILLE HUMAN NUTR RES CTR, BELTSVILLE, MD 20705 USA. UNIV PENN, DEPT RADIAT ONCOL, PHILADELPHIA, PA 19104 USA. UNIV CALIF BERKELEY, SCH PUBL HLTH, DEPT SOCIAL & ADM HLTH SCI, BERKELEY, CA 94720 USA. TUFTS UNIV, USDA, HUMAN NUTR RES CTR AGING, BOSTON, MA 02111 USA. RP HELZLSOUER, KJ (reprint author), JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT EPIDEMIOL, 615 N WOLFE ST, BALTIMORE, MD 21205 USA. RI Block, Gladys/E-3304-2010 NR 38 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1994 VL 54 IS 7 SU S BP S2044 EP S2051 PG 8 WC Oncology SC Oncology GA NE168 UT WOS:A1994NE16800037 ER PT J AU LITTEFIELD, NA HASS, BS JAMES, SJ POIRIER, LA AF LITTEFIELD, NA HASS, BS JAMES, SJ POIRIER, LA TI PROTECTIVE EFFECT OF MAGNESIUM ON DNA STRAND BREAKS INDUCED BY NICKEL OR CADMIUM SO CELL BIOLOGY AND TOXICOLOGY LA English DT Article DE CADMIUM; DNA DAMAGE; LYMPHOCYTES; MAGNESIUM; NICKEL ID ESSENTIAL DIVALENT METALS; A MICE; CALCIUM; RATS; CARCINOGENICITY; METABOLISM; INVITRO; DAMAGE; TRANSFORMATION; ANTAGONISM AB Magnesium, an essential metal that is important in the normal functioning of DNA, has been shown to interact with some of the toxic heavy metals in respect to biochemical and molecular mechanisms and in altering the tumorigenic process. This study examined the influence of magnesium in combination with nickel and cadmium in respect to damage of the DNA molecule. The purpose of this study was to evaluate the influence of magnesium on the amelioration of the toxic metals nickel and cadmium in respect to sustaining DNA damage. Two types of lymphocytes were used, i.e., primary Fischer 344 rat splenocytes and AHH-1 TK+/-, a human B-lymphoblastoid cell line that has been spontaneously transformed. These cells were grown in either a magnesium-free or magnesium-supplemented RPMI 1640 medium that was specifically formulated for this study. A 2 x 2 factorial design was employed with magnesium and either nickel or cadmium serving as the two factors. The experimental groups were as follows: +Mg+Ni, +Mg-Ni, -Mg+Ni, -Mg-Ni, with cadmium alternating for the nickel in the subsequent studies. The nickel or cadmium was added at a concentration of 50 mumol/L. The presence of double-stranded DNA was determined in each of the respective treatment groups with the two types of cell lines. Based on the results of this study, nickel is not directly toxic to DNA, whereas cadmium produces damage directly on the DNA molecule. The magnesium has little or no direct influence on the occurrence of DNA damage from nickel since the toxicity of nickel appears to be manifested in areas other than the DNA molecule, such as ia the heterochromatin. The presence of cadmium in the treatment group resulted in DNA damage, which in turn was reduced significantly by the presence of magnesium. RP LITTEFIELD, NA (reprint author), US PHS,US FDA,NATL CTR & TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079, USA. NR 31 TC 16 Z9 17 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0742-2091 J9 CELL BIOL TOXICOL JI Cell Biol. Toxicol. PD APR PY 1994 VL 10 IS 2 BP 127 EP 135 DI 10.1007/BF00756493 PG 9 WC Cell Biology; Toxicology SC Cell Biology; Toxicology GA NR877 UT WOS:A1994NR87700003 PM 7953910 ER PT J AU PURI, RK DEBINSKI, W OBIRI, N KREITMAN, R PASTAN, I AF PURI, RK DEBINSKI, W OBIRI, N KREITMAN, R PASTAN, I TI HUMAN RENAL CELL-CARCINOMA CELLS ARE SENSITIVE TO THE CYTOTOXIC EFFECT OF A CHIMERIC PROTEIN COMPOSED OF HUMAN INTERLEUKIN-4 AND PSEUDOMONAS EXOTOXIN SO CELLULAR IMMUNOLOGY LA English DT Article ID FACTOR-I RECEPTOR; HIGH-AFFINITY; FUSION PROTEIN; UP-REGULATION; EXPRESSION; ALPHA AB We have previously demonstrated that functional high-affinity interleukin-4 receptors (IL-4R) are expressed on human renal cell carcinoma (RCC) cells (N. I. Obiri et al., J. Clin. Invest. 91, 88, 1993). In the present study, we examined the cytotoxic effect (determined by inhibition of protein synthesis) of a chimeric protein composed of human IL-4 and Pseudomonas exotoxin (PE) on human RCC tumor samples obtained from patients undergoing nephrectomy. The chimeric gene encoding hIL4-PE4E was constructed by fusing a cDNA clone for human IL-4 to the 5' end of a mutated cDNA encoding a full-length PE molecule. This gene was expressed in Escherichia coli, and large quantities of this recombinant protein were isolated to more than 95% purity. This chimeric protein, hIL4-PE4E, was highly cytotoxic to all six RCC cell lines examined. The concentration of hIL4-PE4E at which 50% inhibition of protein synthesis was obtained ranged from <1 ng/ml (12 pM) to 10 ng/ml (120 pM) in five of the six isolates of RCC and 40-70 ng/ml in one other. A mutant chimeric protein which can bind to IL-4R but lacks the ADP ribosylation activity of PE was not cytotoxic to the RCC cells. The cytotoxic effect of hIL4-PE4E was IL-4R mediated because a fourfold molar excess of IL-4 abrogated the cytotoxic effect of hIL4-PE4E. A neutralizing monoclonal antibody to IL-4 also abrogated the cytotoxic effect of hIL4-PE4E. hIL4-PE4E showed very little cytotoxic activity to a normal human umbilical vein endothelial cell line (ID50 = 1000 ng/ml) and a human fibroblast cell line (ID50 similar to 400 ng/ml). Nonactivated human peripheral blood lymphocytes (PBL) were also insensitive to hlL4-PE4E (ID50 similar to 500 ng/ml), whereas phytohemagglutinin-activated PBL were highly susceptible to the cytotoxic effect of hIL4-PE4E (ID50 similar to 4 ng/ml). These data indicate that hIL4-PE4E may be a useful agent for the treatment of human RCC without affecting normal and resting immune cells. (C) 1994 Academic Press, Inc. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RP PURI, RK (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,MOLEC TUMOR BIOL LAB,NIH BLDG 29A,BETHESDA,MD 20892, USA. NR 22 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD APR 1 PY 1994 VL 154 IS 2 BP 369 EP 379 DI 10.1006/cimm.1994.1084 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA NB455 UT WOS:A1994NB45500010 PM 8131209 ER PT J AU TROXELL, T AF TROXELL, T TI GOVERNMENT, CHEMISTRY, AND FOOD SO CHEMTECH LA English DT Article RP TROXELL, T (reprint author), US FDA,DIV PROGRAMS & ENFORCEMENT POLICY,OFF PLANT & DAIRY FOODS & BEVERAGES,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0009-2703 J9 CHEMTECH JI Chemtech PD APR PY 1994 VL 24 IS 4 BP 54 EP 59 PG 6 WC Chemistry, Applied SC Chemistry GA NG971 UT WOS:A1994NG97100009 ER PT J AU SAPIRSTEIN, W ALPERT, S CALLAHAN, TJ AF SAPIRSTEIN, W ALPERT, S CALLAHAN, TJ TI THE ROLE OF CLINICAL-TRIALS IN THE FOOD-AND-DRUG-ADMINISTRATION APPROVAL PROCESS FOR CARDIOVASCULAR DEVICES SO CIRCULATION LA English DT Editorial Material RP SAPIRSTEIN, W (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,1390 PICCARD DR,ROCKVILLE,MD 20850, USA. NR 8 TC 19 Z9 19 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD APR PY 1994 VL 89 IS 4 BP 1900 EP 1902 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NG469 UT WOS:A1994NG46900051 PM 8149556 ER PT J AU WILSON, JT KEARNS, GL MURPHY, D YAFFE, SJ AF WILSON, JT KEARNS, GL MURPHY, D YAFFE, SJ TI PEDIATRIC LABELING REQUIREMENTS - IMPLICATIONS FOR PHARMACOKINETIC STUDIES SO CLINICAL PHARMACOKINETICS LA English DT Review ID EXTENDED LEAST-SQUARES; PEDIATRIC CLINICAL-PHARMACOLOGY; HEPATIC DRUG CLEARANCE; FEBRILE CHILDREN; PHARMACODYNAMIC INTERFACE; POPULATION ANALYSIS; VIRUS-INFECTION; INFANTS; ACETAMINOPHEN; DISPOSITION AB The US Food and Drug Administration (FDA) has proposed new labelling regulations that describe alternative approaches for providing additional information to support labelling a drug, already approved for use in adults, for use in children. Therefore, the study of drugs in paediatric populations may now be encouraged. Paediatric pharmacokinetic studies are an important part of these trials. This action by the FDA may help resolve the ethical and technological concerns about the performance of clinical trials in children, and may render paediatric clinical trials more feasible. Most investigations in children are opportunistic in nature and their design is often constrained by a requisite noninvasive approach. Appropriately applied population-based techniques for both pharmacokinetic and pharmacodynamic data analysis may represent the most robust approach for generating a sufficiently large and accurate database for the use of new or old drugs in paediatric patients. Accordingly, this information, which is crucial for paediatric labelling of any drug product, must be obtained in infants and children if we are to truly individualise therapy for paediatric patients. The funding of 6 Pediatric Pharmacology Research Units by the US National Institutes of Health, and guidelines for application of pharmacokinetic methods to children may further contribute to the performance of paediatric clinical trials. C1 LOUISIANA STATE UNIV,MED CTR,DEPT PEDIAT,SHREVEPORT,LA 71105. UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,LITTLE ROCK,AR. US FDA,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD. NIH,CTR RES MOTHERS & CHILDREN,BETHESDA,MD 20892. RP WILSON, JT (reprint author), LOUISIANA STATE UNIV,MED CTR,DEPT PHARMACOL,CLIN PHARMACOL SECT,1501 KINGS HIGHWAY,SHREVEPORT,LA 71130, USA. NR 112 TC 30 Z9 30 U1 0 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PD APR PY 1994 VL 26 IS 4 BP 308 EP 325 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NF533 UT WOS:A1994NF53300006 PM 8013163 ER PT J AU CHUANG, EJ FELDMAN, GM FINBLOOM, DS AF CHUANG, EJ FELDMAN, GM FINBLOOM, DS TI IGG IMMUNE-COMPLEXES INHIBIT INTERFERON-GAMMA-INDUCED TRANSCRIPTION OF THE HIGH-AFFINITY FC-GAMMA RECEPTOR GENE BY PREVENTING THE TYROSINE PHOSPHORYLATION OF THE P91 TRANSCRIPTION FACTOR SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A308 EP A308 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02001115 ER PT J AU PINTO, JM WILSON, KC FINBLOOM, DS AF PINTO, JM WILSON, KC FINBLOOM, DS TI HOMOLOGOUS DESENSITIZATION OF HUMAN MONOCYTES TO INTERFERON-GAMMA SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A137 EP A137 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000147 ER PT J AU WOODRUFF, T WOLFF, MS DAVIS, DL HAYWARD, D AF WOODRUFF, T WOLFF, MS DAVIS, DL HAYWARD, D TI ORGANOCHLORINE EXPOSURE ESTIMATION IN THE STUDY OF CANCER ETIOLOGY SO ENVIRONMENTAL RESEARCH LA English DT Article ID ADIPOSE-TISSUE; BREAST-CANCER; POLYCHLORINATED-BIPHENYLS; SERUM; PESTICIDES; LIPIDS; DDT; DIBENZOFURANS; HYDROCARBONS; CHEMICALS AB This paper discusses sampling and design considerations relevant to the estimation of exposure to organochlorine compounds in epidemiological studies. We consider exposures measured directly via biomarkers of exposure in the body. It is critical for the design, implementation, and evaluation of studies that epidemiologists and biostatisticians be familiar with methodological issues relevant to the direct measure of exposure. Etiologic, toxicokinetic, quality control and quality assurance, and statistical sampling are discussed. Finally, the limitations of these studies and the need for complete reporting of methods are discussed. (C) 1994 Academic Press,Inc. C1 CUNY MT SINAI SCH MED,NEW YORK,NY 10029. US DEPT HHS,OFF ASSISTANT SECRETARY HLTH,WASHINGTON,DC 20204. US FDA,WASHINGTON,DC 20204. RP WOODRUFF, T (reprint author), US EPA,WASHINGTON,DC 20460, USA. NR 41 TC 43 Z9 44 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD APR PY 1994 VL 65 IS 1 BP 132 EP 144 DI 10.1006/enrs.1994.1026 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA NH586 UT WOS:A1994NH58600010 PM 8162880 ER PT J AU WHITBY, KE COLLINS, TFX WELSH, JJ BLACK, TN FLYNN, T SHACKELFORD, M WARE, SE ODONNELL, MW SUNDARESAN, PR AF WHITBY, KE COLLINS, TFX WELSH, JJ BLACK, TN FLYNN, T SHACKELFORD, M WARE, SE ODONNELL, MW SUNDARESAN, PR TI DEVELOPMENTAL EFFECTS OF COMBINED EXPOSURE TO ETHANOL AND VITAMIN-A SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID FETAL ALCOHOL SYNDROME; RETINOIC ACID; RAT; IDENTIFICATION; POTENTIATION; INGESTION; GESTATION; UPDATE AB The potential for ethanol (EtOH) to influence the developmental toxicity of vitamin A was investigated. 11 groups of approximately 31 FDA-bred Osborne-Mendel rats received either a control or isocaloric 6.4% EtOH liquid diet (containing 4000 IU vitamin A/litre) ad lib. The vehicle control, EtOH and pair-fed (pair-fed against the EtOH group) groups received corn oil (the vehicle) by gavage. Vitamin A was administered by gavage without EtOH at 40,000, 80,000, 120,000 or 160,000 IU/kg daily. Vitamin A was administered by gavage at 10,000, 20,000, 40,000 or 80,000IU/kg with EtOH ad lib., daily throughout the study. Combined EtOH and vitamin A resulted in significant reductions in maternal diet consumption and body weight when doses of vitamin A were as low as 10,000 IU/kg. The most severe effects on overall (days 0-20) maternal body weight gain were observed in the groups receiving 120,000 or 160,000 IU vitamin A/kg alone or EtOH in combination with 80,000 IU vitamin A/kg. The overall diet consumption (days 0-20) paralleled the overall weight gain. In general, pups exposed to ethanol and vitamin A had a tendency to weigh less than those exposed to vitamin A alone, but to weigh more than those exposed to EtOH alone. EtOH combined with vitamin A at 80,000 IU/kg resulted in an increased incidence of cleft palate relative to the vehicle control or either treatment alone. The incidence of exencephaly and protruding tongue was significantly greater in the group given vitamin A at 160,000 IU/kg, compared with the vehicle control group. The most consistent statistically significant skeletal finding in the groups receiving combined treatment was a treatment-related increased incidence of supernumerary ribs [14th rib (C7), 14th rib bud (L1) and 15 ribs]. In addition, the incidence of misshapen zygomatic arch was also significantly increased in the group exposed to EtOH and vitamin A at 80,000 IU/kg. The incidence of moderately enlarged renal pelvis and severely enlarged ureter proximal to the kidney was increased in the group exposed to EtOH and vitamin A at 80,000 IU/kg relative to the vehicle control, or either treatment alone. Therefore, for some of the endpoints examined in this investigation, it would appear that ethanol potentiates the developmental effects of vitamin A. C1 US EPA,OFF PESTICIDE PROGRAMS,WASHINGTON,DC 20460. RP WHITBY, KE (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,200 C ST SW,WASHINGTON,DC 20204, USA. OI Flynn, Thomas/0000-0002-7248-0643 NR 24 TC 10 Z9 10 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 APR PY 1994 VL 32 IS 4 BP 305 EP 320 DI 10.1016/0278-6915(94)90069-8 PG 16 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA NQ428 UT WOS:A1994NQ42800002 PM 8206426 ER PT J AU BUNNING, VK AF BUNNING, VK TI UNTITLED SO FOOD MICROBIOLOGY LA English DT Editorial Material RP BUNNING, VK (reprint author), US FDA,CFSAN,ODFB,DVA,IMMUNOBIOL BRANCH HFS-326,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD APR PY 1994 VL 11 IS 2 BP 87 EP 87 DI 10.1006/fmic.1994.1012 PG 1 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA NL287 UT WOS:A1994NL28700001 ER PT J AU BUNNING, VK AF BUNNING, VK TI IMMUNOPATHOGENIC ASPECTS OF FOODBORNE MICROBIAL DISEASE SO FOOD MICROBIOLOGY LA English DT Article ID STAPHYLOCOCCAL ENTEROTOXIN-B; LISTERIA-MONOCYTOGENES; SODIUM-CHLORIDE; BOVINE-MILK; HEAT-SHOCK; TEMPERATURE; PROTEINS; GROWTH; CELLS; MICE RP BUNNING, VK (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,IMMUNOBIOL BRANCH HFS326,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 58 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD APR PY 1994 VL 11 IS 2 BP 89 EP 95 DI 10.1006/fmic.1994.1013 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA NL287 UT WOS:A1994NL28700002 ER PT J AU DATTA, AR AF DATTA, AR TI FACTORS CONTROLLING EXPRESSION OF VIRULENCE GENES IN LISTERIA-MONOCYTOGENES SO FOOD MICROBIOLOGY LA English DT Article ID STRESS PROTEINS; GROWTH; IDENTIFICATION; ACTIN; TUBERCULOSIS; HEMOLYSIN; BACTERIA; SPREAD; CELLS; IRON RP DATTA, AR (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MOLEC BIOL RES & EVAL,200 C ST SW,WASHINGTON,DC 20204, USA. NR 35 TC 18 Z9 18 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD APR PY 1994 VL 11 IS 2 BP 123 EP 129 DI 10.1006/fmic.1994.1016 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA NL287 UT WOS:A1994NL28700005 ER PT J AU MAHANEY, K TEDESCHI, V DIBISCEGLIE, AM MAERTENS, G SALLIE, R AF MAHANEY, K TEDESCHI, V DIBISCEGLIE, AM MAERTENS, G SALLIE, R TI A NOVEL AND RAPID METHOD OF GENOTYPING HEPATITIS-C VIRUS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH,LIVER DIS SECT,BETHESDA,MD 20892. CBER,HEPATITIS RES LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1994 VL 106 IS 4 SU S BP A936 EP A936 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NH909 UT WOS:A1994NH90903724 ER PT J AU MONTAGUE, DC LYNCOOK, BD CHANG, L RAYFORD, PL CHOWDHURY, P AF MONTAGUE, DC LYNCOOK, BD CHANG, L RAYFORD, PL CHOWDHURY, P TI EXPOSURE TO NICOTINE INDUCES H-RAS MUTATIONS IN RAT PANCREATIC ACINAR-CELLS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,DEPT PHYSIOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PATHOL,LITTLE ROCK,AR 72205. US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1994 VL 106 IS 4 SU S BP A1040 EP A1040 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NH909 UT WOS:A1994NH90904138 ER PT J AU SHAKIL, AO CONRYCANTILENA, C MELPOLDER, J ALTER, HJ HOOFNAGLE, JH KRAWCZYNSKI, K TADESCHI, V DIBISCEGLIE, AM AF SHAKIL, AO CONRYCANTILENA, C MELPOLDER, J ALTER, HJ HOOFNAGLE, JH KRAWCZYNSKI, K TADESCHI, V DIBISCEGLIE, AM TI LIVER HISTOPATHOLOGY IN BLOOD-DONORS WITH HEPATITIS-C AND NORMAL SERUM ALT LEVELS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. CTR DIS CONTROL,ATLANTA,GA 30333. 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 1994 VL 106 IS 4 SU S BP A981 EP A981 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NH909 UT WOS:A1994NH90903901 ER PT J AU KANTOR, G AF KANTOR, G TI ON A MEMBERSHIP DIRECTORY SO IEEE ANTENNAS AND PROPAGATION MAGAZINE LA English DT Letter RP KANTOR, G (reprint author), US FDA,CDRH,HFZ-133,12721 TWINBROOK PKWY,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 1045-9243 J9 IEEE ANTENNAS PROPAG JI IEEE Antennas Propag. Mag. PD APR PY 1994 VL 36 IS 2 BP 89 EP 89 PG 1 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA PT610 UT WOS:A1994PT61000016 ER PT J AU WEN, J WANG, J KUIPERS, JG HUANG, F WILLIAMS, KM RAYBOURNE, RB YU, DTY AF WEN, J WANG, J KUIPERS, JG HUANG, F WILLIAMS, KM RAYBOURNE, RB YU, DTY TI ANALYSIS OF HLA-B(ASTERISK)2705 PEPTIDE MOTIF, USING T2 CELLS AND MONOCLONAL-ANTIBODY ME1 SO IMMUNOGENETICS LA English DT Note C1 UNIV CALIF LOS ANGELES,CTR REHABIL,DEPT MED,DIV RHEUMATOL,LOS ANGELES,CA 90024. US FDA,DIV MICROBIOL,LAUREL,MD 20708. FU NIAMS NIH HHS [NIAMS P01 AR 40919] NR 5 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD APR PY 1994 VL 39 IS 6 BP 444 EP 446 PG 3 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA NJ599 UT WOS:A1994NJ59900012 PM 7910590 ER PT J AU BINIENDA, Z FOGLE, CM SLIKKER, W ALI, SF AF BINIENDA, Z FOGLE, CM SLIKKER, W ALI, SF TI ACUTE EFFECTS OF PERINATAL HYPOXIC INSULT ON CONCENTRATIONS OF DOPAMINE, SEROTONIN, AND METABOLITES IN FETAL MONKEY BRAIN SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE MONKEY; HYPOXIA; FETUS; BRAIN; DOPAMINE; SEROTONIN ID EXCITATORY AMINO-ACIDS; EXTRACELLULAR CONCENTRATIONS; UMBILICAL-CORD; ISCHEMIA; INJURY; TERM; RAT; GLUTAMATE; NEWBORN; INVIVO AB Seven monkeys (Macaca mulatta) were laparotomized under general anesthesia (halothane, nitrous oxide, oxygen). Fetal hypoxia was induced in four monkeys by occlusion of the umbilical cord with a hydraulic occluder for 5-6 min. Three sham-operated fetuses served as controls. After unclamping, the fetuses were allowed to reperfuse for 20-30 min. To monitor hypoxia, the fetal electrocardiogram was recorded continuously. Hypoxic insult was associated with a decrease in fetal heart rate during the occlusion. After reperfusion, fetuses were immediately sacrificed and neocortex regions dissected on ice, frozen on dry ice and stored at -70 degrees C. Dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, serotonin, and 5-hydroxyindoleacetic acid were assayed by high performance liquid chromatography with electrochemical detection (HPLC/EC) in hippocampus, caudate nucleus and cortical regions. In the hippocampus, there was a significant increase in 5-hydroxyindoleacetic acid concentration. In prefrontal cortex, there was a trend toward an increase in serotonin but no effects on dopamine and homovanillic acid concentrations. Dopamine, serotonin and metabolites were not altered in the caudate nucleus. These data demonstrate that fetal hypoxia followed by reperfusion produced an increase in serotonin concentration measured within the hippocampus and selected cortical areas known to be targets of hypoxic injury. RP BINIENDA, Z (reprint author), US FDA,NATL CTR TOXICOL RES,PRIMATE RES FACIL,DIV NEUROTOXICOL,HFT-132,3900 NCTR DR,JEFFERSON,AR 72079, USA. NR 24 TC 3 Z9 3 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD APR PY 1994 VL 12 IS 2 BP 127 EP 131 DI 10.1016/0736-5748(94)90005-1 PG 5 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA NN353 UT WOS:A1994NN35300005 PM 7524270 ER PT J AU TOMAZIC, VJ SHAMPAINE, EL LAMANNA, A WITHROW, TJ ADKINSON, NF HAMILTON, RG AF TOMAZIC, VJ SHAMPAINE, EL LAMANNA, A WITHROW, TJ ADKINSON, NF HAMILTON, RG TI CORNSTARCH POWDER ON LATEX PRODUCTS IS AN ALLERGEN CARRIER SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE LATEX; NATURAL RUBBER; CORNSTARCH; ALLERGEN; TYPE I ALLERGIC REACTION; IGE ANTIBODIES ID SURGICAL GLOVE POWDER; CONTACT URTICARIA; ANAPHYLACTOID REACTION; OCCUPATIONAL ASTHMA; RUBBER; HYPERSENSITIVITY; ANTIGENS; SURGERY AB Allergic reactions of the upper respiratory tract during use of powdered latex rubber gloves have been recently associated with sensitivity to latex. We have studied the ability of cornstarch powder to bind latex proteins and evaluated allergenic properties of the bound protein. Allergenicity was determined by competitive inhibition of human anti-latex IgE binding to solid-phase latex antigen. Cornstarch extracted from powdered latex products and clean cornstarch exposed to latex protein extracts were evaluated in comparison with clean unexposed cornstarch. Both exposed cornstarch preparations inhibited specific binding of anti-latex IgE antibodies to latex proteins in a dose-response manner. Latex-exposed cornstarch diluted 50% vol/vol produced complete inhibition, whereas greater dilutions exhibited variable levels of inhibition, depending on the source of cornstarch-bound proteins, insolubilized latex proteins, and IgE antibody-containing human serum used. Cornstarch not exposed to latex had no inhibitory activity. The study demonstrates that cornstarch indeed binds allergenic latex proteins and supports the causative relationship between allergic reactions in individuals with latex sensitivity and the exposure to airborne particles from powdered latex products. C1 JOHNS HOPKINS UNIV,CTR ASTHMA & ALLERGY,BALTIMORE,MD 21224. RP TOMAZIC, VJ (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,DIV LIFE SCI,HLTH SCI BRANCH,12709 TWINBROOK PKWY,ROCKVILLE,MD 20852, USA. NR 26 TC 110 Z9 113 U1 1 U2 2 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 APR PY 1994 VL 93 IS 4 BP 751 EP 758 DI 10.1016/0091-6749(94)90255-0 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA NH497 UT WOS:A1994NH49700008 PM 8163784 ER PT J AU HERWALDT, BL LEW, JF MOE, CL LEWIS, DC HUMPHREY, CD MONROE, SS PON, EW GLASS, RI AF HERWALDT, BL LEW, JF MOE, CL LEWIS, DC HUMPHREY, CD MONROE, SS PON, EW GLASS, RI TI CHARACTERIZATION OF A VARIANT STRAIN OF NORWALK VIRUS FROM A FOOD-BORNE OUTBREAK OF GASTROENTERITIS ON A CRUISE SHIP IN HAWAII SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IMMUNE ELECTRON-MICROSCOPY; IDENTIFICATION AB A gastroenteritis outbreak affecting at least 217 (41%) of 527 passengers on a cruise ship was caused by a variant strain of Norwalk virus (NV) that is related to but distinct from the prototype NV strain. Consumption of fresh-cut fruit served at two buffets was significantly associated with illness (P less-than-or-equal-to 0.01), and a significant dose-response relationship was evident between illness and the number of various fresh-cut fruit items eaten. Seven (58%) of 12 paired serum specimens from ill persons demonstrated at least fourfold rises in antibody response to recombinant NV capsid antigen. A 32-nm small round-structured virus was visualized by electron microscopy in 4 (29%) of 14 fecal specimens, but none of the 8 specimens that were examined by an enzyme immunoassay for NV antigen demonstrated antigen. Four (40%) of 10 fecal specimens were positive by reverse transcriptase-PCR by using primer pairs selected from the polymerase region of NV. In a 145-bp region, the PCR product shared only 72% nucleotide sequence identity with the reference NV strain and 77% nucleotide sequence identity with Southampton virus but shared 95% nucleotide sequence identity with UK2 virus, a United Kingdom reference virus strain. In addition, the outbreak virus was serotyped as UK2 virus by solid-phase immune electron microscopy. The genetic and antigenic divergence of the outbreak strain from the reference NV strain highlights the need for more broadly reactive diagnostic assays and for improved understanding of the relatedness of the NV group of agents. C1 CTR DIS CONTROL,NATL CTR INFECT DIS,DIV PARASIT DIS,ATLANTA,GA 30333. CTR DIS CONTROL,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333. US FDA,DIV MICROANALYT EVALUAT,OFF PLANT & DAIRY FOODS & BEVERAGES,WASHINGTON,DC 20204. PUBL HLTH LAB,LEEDS,ENGLAND. HAWAII DEPT HLTH,HONOLULU,HI 96813. OI Monroe, Stephan/0000-0002-5424-716X NR 34 TC 63 Z9 64 U1 0 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 1994 VL 32 IS 4 BP 861 EP 866 PG 6 WC Microbiology SC Microbiology GA NB469 UT WOS:A1994NB46900001 PM 8027335 ER PT J AU SCHLESSER, JE STROUP, WH MCKINSTRY, JA AF SCHLESSER, JE STROUP, WH MCKINSTRY, JA TI VOLUMETRIC FLOW-RATE COMPARISONS FOR WATER AND PRODUCT ON PASTEURIZATION SYSTEMS SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE PASTEURIZATION; FLOW RATES; PUMPS; CONVERSION FACTOR AB A flow calibration tube system was assembled to determine the volumetric flow rates for water and various dairy products through a holding tube, using three different flow promotion methods. With the homogenizer, the volumetric flow rates of water and reconstituted skim milk were within 1.5% of each other. With the positive displacement pump, the flow rate for reconstituted skim milk increased compared with that for water as the pressure increased or temperature decreased. The largest increase in flow rate was at 310-kPa gauge and 20-degrees-C. On a magnetic flow meter system, the volumetric flow rates of water and reconstituted skim milk were within .5% of the flow rate measured from the volume collected in a calibrated tank. The flow rate of whole milk was similar to that of skim milk on the three flow promoters evaluated. Ice milk mix increased the flow rate of the positive displacement pump, but not the homogenizer and magnetic flow meter system. RP SCHLESSER, JE (reprint author), NATL CTR FOOD SAFETY & TECHNOL,FOOD & DRUG ADM,SUMMIT ARGO,IL 60501, USA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU AMER DAIRY SCIENCE ASSN PI CHAMPAIGN PA 309 W CLARK ST, CHAMPAIGN, IL 61820 SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PD APR PY 1994 VL 77 IS 4 BP 950 EP 957 DI 10.3168/jds.S0022-0302(94)77031-4 PG 8 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA ND265 UT WOS:A1994ND26500008 PM 8201053 ER PT J AU KESSLER, DA AF KESSLER, DA TI INTRODUCING MEDWATCH - A NEW APPROACH TO REPORTING MEDICATION AND DEVICE ADVERSE-EFFECTS AND PRODUCT PROBLEMS SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Editorial Material RP KESSLER, DA (reprint author), US FDA,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD APR-JUN PY 1994 VL 8 IS 2 BP 71 EP 76 DI 10.1016/1056-8727(94)90054-X PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PM349 UT WOS:A1994PM34900002 ER PT J AU WAKATSUKI, Y NEURATH, MF MAX, EE STROBER, W AF WAKATSUKI, Y NEURATH, MF MAX, EE STROBER, W TI THE B-CELL-SPECIFIC TRANSCRIPTION FACTOR BSAP REGULATES B-CELL PROLIFERATION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DNA-BINDING PROTEIN; SWITCH REGIONS; LYMPHOCYTES-B; ANTISENSE RNA; GENE; DIFFERENTIATION; PROMOTER; GROWTH; ELECTROPORATION; EXPRESSION AB The B cell-specific activator protein (BSAP) is a DNA-binding transcription factor expressed in pro-B, pre-B, and mature B cells, but not in plasma cells. In this study, we explored the role of BSAP in B cell function by assessing how the content of this protein varies in cells driven by proliferative stimuli and, conversely, how artificial manipulation of BSAP activity affects cell proliferation. We found that BSAP activity of nuclear extracts increased when B cells were activated by mitogen (lipopolysaccharide [LPS]), antigen receptor-mediated signaling (surface immunoglobulin D [IgD] cross-linking) or T cell-dependent stimulation (CD40 cross-linking). We could suppress BSAP activity by exposure of B cells to phosphorothioate oligonucleotides antisense to the BSAP translation initiation start site, whereas control oligonucleotides were virtually inactive. Antisense-induced BSAP suppression was associated with a striking reduction in LPS-induced proliferation of splenic B cells and in the spontaneous proliferation of B lymphoma cells (CH12.LX), but the antisense oligonucleotide had virtually no effect on proliferation of two cell lines lacking BSAP: the T lymphoma line EL-4 and the plasma cell line MOPC-315. Overexpression of BS.AP in splenic B cells or de novo expression in MOPC-315 plasma cells induced by transfection of a BSAP expression plasmid stimulated cell proliferation. Taken together, these results suggest that BSAP activity is a rate-limiting regulator of B cell proliferation. We also found that treatment with the antisense BSAP oligonucleotide downregulated Ig class switching induced by interleukin 4 plus LPS. This effect may be secondary to reduced proliferation or could be mediated through BSAP binding sites in the IgH locus. C1 US FDA,CTR BIOL EDUC & RES,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NR 38 TC 130 Z9 132 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 1 PY 1994 VL 179 IS 4 BP 1099 EP 1108 DI 10.1084/jem.179.4.1099 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NC777 UT WOS:A1994NC77700003 PM 7511679 ER PT J AU ADAMS, AM LEJA, LL JINNEMAN, K BEEH, J YUEN, GA WEKELL, MM AF ADAMS, AM LEJA, LL JINNEMAN, K BEEH, J YUEN, GA WEKELL, MM TI ANISAKID PARASITES, STAPHYLOCOCCUS-AUREUS AND BACILLUS-CEREUS IN SUSHI AND SASHIMI FROM SEATTLE AREA RESTAURANTS SO JOURNAL OF FOOD PROTECTION LA English DT Article DE ANISAKID PARASITES; STAPHYLOCOCCUS-AUREUS; BACILLUS CEREUS; SUSHI; SASHIMI ID SURVIVAL; SALMON AB Samples of salmon, tuna, mackerel, and rockfish sushi were analyzed for parasites from 32 of the approximately 50 restaurants in the Seattle area that prepare sushi. The restaurants were sampled up to three times over a 19-month period. Some specialty grocery stores providing restaurants and consumers with sashimi were also sampled. Salmon sushi was most commonly affected with almost 10% of pieces infected with a maximum of 3 nematodes per piece. Only single infections were present in mackerel sushi with frequency of 5%; and tuna and rockfish sushi were free of nematodes. All nematodes were third-stage juveniles of the genus Anisakis. Except for two moribund nematodes, all juveniles from sushi were dead, most likely the result of the practice of using fish that have been previously frozen. The two moribund nematodes were present in one salmon sushi sample, indicating that incompletely frozen product had been used. For the sashimi, no parasites were found in tuna; however, a live anisakid was found in one collection of rockfish sashimi. Efforts to detect anisakid nematodes with nondestructive methods were generally unsuccessful. Neither inspection per ultraviolet light nor by candling was effective for salmon sushi. Candling was also ineffective for mackerel but was useful for rockfish and appears to be appropriate for the analysis of tuna sushi. Results of analyses of rice from sushi samples from 19 of the restaurants indicated that the pH levels were at 4.6 or below, and no fecal coliforms were detected. Most of the aerobic plate counts were below log 6, with only 2 between log 6 and log 7. Bacillus cereus and Staphylococcus aureus were detected in rice from six restaurants each, but in no samples were these two organisms found together, and levels were well below those of public health importance. C1 SEATTLE KING CTY DEPT PUBL HLTH,KENT,WA 98032. RP ADAMS, AM (reprint author), US FDA,SEAFOOD PROD RES CTR,22201 23RD DR SE,POB 3012,BOTHELL,WA 98041, USA. NR 39 TC 16 Z9 21 U1 0 U2 11 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 1994 VL 57 IS 4 BP 311 EP 317 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA NE880 UT WOS:A1994NE88000007 ER PT J AU ZHANG, K MILLS, FC SAXON, A AF ZHANG, K MILLS, FC SAXON, A TI SWITCH CIRCLES FROM IL-4-DIRECTED EPSILON-CLASS SWITCHING FROM HUMAN B-LYMPHOCYTES - EVIDENCE FOR DIRECT, SEQUENTIAL, AND MULTIPLE STEP SEQUENTIAL SWITCH FROM MU TO EPSILON IG HEAVY-CHAIN GENE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CIRCULAR DNA; CD40 ANTIGEN; CELLS; RECOMBINATION; INTERLEUKIN-4; DELETION; REGIONS; LIPOPOLYSACCHARIDE; INDUCTION; MECHANISM AB Ig isotype switch via deletional recombination is accompanied by excision of the intervening DNA between the two switch regions. The excised DNA is looped out as extrachromosomal circular DNA or switch circle. Such switch circles have been isolated and characterized in mice. We investigated deletional recombination in human B cells undergoing Ig isotype switching to demonstrate whether switch circles are also excised, and to thereby gain insight into the processes involved in human isotype switching. We characterized the deleted switch circular DNA from IL-4 directed mu to epsilon switching in polycional human B lymphocytes. By using two sets of specially designed PCR primers, we amplified switch circle fragments representing switch circles resulting from mu to epsilon direct switching and mu-gamma-epsilon sequential switching. The PCR-amplified products were subcloned by a TA cloning strategy and resulting clones were screened by hybridization with a 5'S epsilon probe. Sequence analysis of the positive clones revealed that all clones representing mu to epsilon direct switching indeed had 5' S epsilon directly joined to 3' S mu. Most clones representing mu-gamma-epsilon sequential switching showed 5' S epsilon joined to 3' S mu as expected. However, two clones contained S mu and S alpha 1 sequences interposed between 5' S epsilon and 3' S gamma, respectively. These data demonstrate that switch circles are excised during human B cell isotype switching, and that IL-4 directed epsilon class switching is accomplished by 1) direct mu to epsilon switching, 2) sequential mu-gamma-epsilon switching, and 3) double sequential mu-alpha-gamma-epsilon switching. C1 US FDA, CTR BIOL EVALUAT & RES, BETHESDA, MD 20892 USA. RP ZHANG, K (reprint author), UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, DIV CLIN IMMUNOL ALLERGY, HART & LOUISE LYON LAB, LOS ANGELES, CA 90024 USA. FU NCI NIH HHS [CA-12800]; NIAID NIH HHS [AI-34567, AI-15251] NR 29 TC 76 Z9 79 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1994 VL 152 IS 7 BP 3427 EP 3435 PG 9 WC Immunology SC Immunology GA NC609 UT WOS:A1994NC60900020 PM 8144926 ER PT J AU PURI, RK MEHROTRA, PT LELAND, P KREITMAN, RJ SIEGEL, JP PASTAN, I AF PURI, RK MEHROTRA, PT LELAND, P KREITMAN, RJ SIEGEL, JP PASTAN, I TI A CHIMERIC PROTEIN COMPRISED OF IL-4 AND PSEUDOMONAS EXOTOXIN IS CYTOTOXIC FOR ACTIVATED HUMAN-LYMPHOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HIGH-AFFINITY; FUSION PROTEIN; TUMOR-CELLS; T-CELLS; INTERLEUKIN-4; EXPRESSION; RECEPTORS; IL-2-PE40; BINDING; GROWTH AB IL4-Pseudomonas exotoxin (IL4-PE4E) is a chimeric molecule in which human IL-4 is genetically fused to the mutated binding domain of Pseudomonas exotoxin. This molecule binds specifically to human IL-4 receptor-bearing cells. IL4-PE4E was extremely cytotoxic to highly purified anti-CD3-activated CD8(+) T lymphocytes. The cytotoxic activity of this molecule was dependent on the activation state of CD8(+) T cells: 3- and 4-day activated T cells were very susceptible to the cytotoxic activity of IL4-PE4E compared with 0- to 2-day activated cells. PHA-activated lymphocytes and PBL activated in mixed lymphocyte reaction were also highly sensitive to IL4-PE4E. CD16(+) and/or CD56(+) highly purified NK cells or highly purified, Ii-a-activated NK cells were also very sensitive to the cytotoxic effect of IL4-PE4E. IL-2-activated LAK cells had little susceptibility after 1 day but were very sensitive to IL4-PE4E after 3 days. The cytotoxic effects of IL4-PE4E were mediated through a ligand receptor interaction because excess rIL-4 abrogated these effects as did a neutralizing Ab to human IL-4. A chimeric mutant protein that can bind to IL-4 receptors but lacks the ability to inhibit protein synthesis was not cytotoxic to activated lymphocytes. The IL4-PE4E-mediated cytotoxicity of activated T cells correlated with the level of expression of IL-4 receptors on these cells. CD8+ T cells activated for 3 days expressed the highest density of IL-4 receptors compared with 1- or 2-day activated cells. Among two chimeric toxins tested only IL4-PE4E was cytotoxic to 2-day anti-CD3-activated CD8+ T lymphocytes, whereas IL6-PE4E was not active at all. These studies suggest that human IL4 toxin could be a potent agent for the elimination of activated lymphocytes in allograft rejection, some autoimmune diseases, or treatment of lymphomas and leukemias. C1 NCI, DIV CANC BIOL DIAG & CTR, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. RP PURI, RK (reprint author), US FDA, NIH,CBER,DIC CELLULAR & GENE THERAPIES, MOLEC TUMOR BIOL LAB, BLDG 29A, BETHESDA, MD 20892 USA. NR 43 TC 11 Z9 13 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1994 VL 152 IS 7 BP 3693 EP 3700 PG 8 WC Immunology SC Immunology GA NC609 UT WOS:A1994NC60900049 PM 8144944 ER PT J AU BEER, LZ LIGHTFOOTE, MM ZMUDZKA, BZ AF BEER, LZ LIGHTFOOTE, MM ZMUDZKA, BZ TI ACTIVATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) BY ULTRAVIOLET-B (UVB) RADIATION AND PUVA TREATMENT - EVALUATION OF CLINICAL AND COSMETIC EXPOSURES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1994 VL 102 IS 4 BP 544 EP 544 PG 1 WC Dermatology SC Dermatology GA NF406 UT WOS:A1994NF40600144 ER PT J AU LIEU, TS ZAPPI, E CAPRA, JD SONTHEIMER, RD NAKHASI, HL AF LIEU, TS ZAPPI, E CAPRA, JD SONTHEIMER, RD NAKHASI, HL TI AN AUTOANTIGENIC FORM OF HUMAN CALRETICULIN IS AN HY RNA AND RUBELLA RNA-BINDING PROTEIN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,SW MED CTR,DALLAS,TX 75235. US FDA LABS,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1994 VL 102 IS 4 BP 590 EP 590 PG 1 WC Dermatology SC Dermatology GA NF406 UT WOS:A1994NF40600421 ER PT J AU TIMMER, WC WEI, RR WAMER, WG KORNHAUSER, A AF TIMMER, WC WEI, RR WAMER, WG KORNHAUSER, A TI BIOCHEMICAL AND GENETIC-MARKERS AS END-POINTS FOR MEASURING DNA-DAMAGE IN 8-METHOXYPSORALEN PLUS UV-A TREATED SKIN FIBROBLASTS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1994 VL 102 IS 4 BP 649 EP 649 PG 1 WC Dermatology SC Dermatology GA NF406 UT WOS:A1994NF40600775 ER PT J AU ZMUDZKA, BZ BEER, JZ AF ZMUDZKA, BZ BEER, JZ TI EFFECTS OF HUMAN UVB OR PUVA EXPOSURE ON HIV SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1994 VL 102 IS 4 BP 665 EP 665 PG 1 WC Dermatology SC Dermatology GA NF406 UT WOS:A1994NF40600823 ER PT J AU ZMUDZKA, BZ BEER, JZ OLVEY, KM STRICKLAND, AG GODAR, DE AF ZMUDZKA, BZ BEER, JZ OLVEY, KM STRICKLAND, AG GODAR, DE TI PHOTOSENSITIZER-INDEPENDENT CELL-DAMAGE INDUCED BY UV DOSE USED IN EXTRACORPOREAL PUVA THERAPY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1994 VL 102 IS 4 BP 667 EP 667 PG 1 WC Dermatology SC Dermatology GA NF406 UT WOS:A1994NF40600834 ER PT J AU RAO, SP OGATA, K MORRIS, SL CATANZARO, A AF RAO, SP OGATA, K MORRIS, SL CATANZARO, A TI IDENTIFICATION OF A 68 KD SURFACE-ANTIGEN OF MYCOBACTERIUM-AVIUM THAT BINDS TO HUMAN MACROPHAGES SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HEAT-SHOCK PROTEIN; COMPLEX INFECTION; ESCHERICHIA-COLI; 65-KILODALTON ANTIGEN; HUMAN-MONOCYTES; CELL-SURFACE; BOVIS BCG; LEPRAE; TUBERCULOSIS AB Infection caused by Mycobacterium avium is the major cause of bacteremia in patients with AIDS. A critical event in the initiation of a variety of bacterial infections is the adherence of bacteria to host cell surfaces, which is often brought about by the interaction of specific molecules on the bacterial surface with host cell surface receptors. In the present study, a sonicate of M. avium was used to isolate monocyte-binbing proteins by affinity chromatography with CNBr-Sepharose-4B coupled to extracts of monocytes. A 68 kd protein present on the surface of M. avium was identified as one of nine monocyte-binding proteins. This protein was isolated and further characterized. The N-terminal amino acid sequence (22 residues) of the protein was determined and was found to exhibit strong homology with the 65 kd heat shock proteins of M. tuberculosis, M. leprae, and M. bovis. However, a previously characterized monoclonal antibody directed against a 66 kd antigen of M. avium was found to cross-react with the 68 kd protein from M. avium but not with the 65 kd proteins from M. leprae and M. bovis, suggesting that the 68 kd antigen may differ from the 65 kd proteins of M. leprae and M. bovis with respect to certain epitopes. In an in vitro inhibition assay, the 68 kd protein was found to compete with the attachment of intact fluorescein isothiocyanate-labeled M. avium to monocyte-derived macrophages, inhibiting this attachment in a dose-dependent manner up to 42%. The 65 kd proteins of M. leprae and M. bovis, on the other hand, did not appear to inhibit this attachment substantially (13.9% and 14.6%, respectively). These results suggest that the 68 kd protein of M. avium may be involved in binding to receptors on macrophages and help in the attachment of the organism to its host cell. C1 UNIV CALIF SAN DIEGO,MED CTR,DEPT MED,DIV PULM & CRIT CARE,SAN DIEGO,CA 92103. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. FU NIAID NIH HHS [5RO1AI33827-02] NR 39 TC 21 Z9 21 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD APR PY 1994 VL 123 IS 4 BP 526 EP 535 PG 10 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA NE676 UT WOS:A1994NE67600011 PM 8145001 ER PT J AU LYTLE, CD ROUTSON, LB PRODOUZ, KN AF LYTLE, CD ROUTSON, LB PRODOUZ, KN TI HERPES-VIRUS INFECTION AND REPAIR IN CELLS PRETREATED WITH GILVOCARCIN-V OR MEROCYANINE-540 AND RADIATION SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE GILVOCARCIN V; HERPES VIRUS; MEROCYANINE 540; ENHANCED VIRUS REACTIVATION; HOST CAPACITY ID MONKEY KIDNEY-CELLS; CYTOPLASMIC FREE CALCIUM; ENHANCED REACTIVATION; MAMMALIAN-CELLS; 540-MEDIATED PHOTOSENSITIZATION; INDUCTION; SURVIVAL; INACTIVATION; MUTAGENESIS; INHIBITION AB Pretreatment of mammalian cells with certain genotoxic agents decreases the ability of the cell monolayers to support virus plaque formation but enhances repair of UV-irradiated virus. This study was made to determine whether these phenomena extend to pretreatments with light and photosensitizers, including one dye that primarily affects cell membranes. Confluent CV-1 monkey kidney fibroblast monolayers were pretreated with either gilvocarcin V (GV) or merocyanine 540 (MC540) and light of appropriate wavelengths and infected with control or UV-irradiated herpes simplex virus (HSV). GV phototreatment is known to affect cells at the DNA level, and MC540 at the membrane level. UV radiation served as a positive control pretreatment. Phototoxic concentrations of GV and MC540 were determined via the capacity of pretreated cell monolayers to support plaque formation by unirradiated HSV. Parallel monolayer pretreatment and subsequent infection by UV-irradiated HSV demonstrated that both types of phototreatments enhanced virus survival, but the dose responses and time courses were different. The DNA-damaging GV phototreatment mimicked the effect of UV-irradiating the cells and produced delayed enhanced repair of UV-irradiated virus. However, the MC540-phototreatment produced enhancement of virus survival with a bimodal dose response pattern for immediate infection, suggesting a different route for affecting repair of damaged virus. C1 BIOCON INC,ROCKVILLE,MD 20855. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP LYTLE, CD (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857, USA. NR 35 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD APR PY 1994 VL 23 IS 1 BP 57 EP 62 DI 10.1016/1011-1344(93)06980-H PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NG929 UT WOS:A1994NG92900008 PM 8021752 ER PT J AU JACOBSON, ED AF JACOBSON, ED TI REGULATORY ISSUES IN DENTISTRY - HOW DENTISTS CAN PARTICIPATE SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article AB The FDA's twofold purpose of surveillance and facilitation is defined. For a successful dental program, the FDA welcomes practitioner input in reporting problems in use or performance of dental devices. RP JACOBSON, ED (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,1390 PICCARD DR,ROCKVILLE,MD 20850, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD APR PY 1994 VL 125 IS 4 BP 444 EP & PG 0 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA NF256 UT WOS:A1994NF25600016 PM 8176080 ER PT J AU MARTINEZ, MN RIVIERE, JE AF MARTINEZ, MN RIVIERE, JE TI REVIEW OF THE 1993 VETERINARY DRUG BIOEQUIVALENCE WORKSHOP - PREFACE SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Editorial Material ID SIDED TESTS PROCEDURE; COMPARATIVE PHARMACOKINETICS; INJECTION SITE; BIOAVAILABILITY; ABSORPTION; TIME; FORMULATIONS; GENTAMICIN; PENICILLIN; HORSES C1 N CAROLINA STATE UNIV,COLL VET MED,RALEIGH,NC 27606. RP MARTINEZ, MN (reprint author), US FDA,CTR VET MED,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. RI Riviere, Jim/A-9210-2008 OI Riviere, Jim/0000-0001-8412-9650 NR 88 TC 11 Z9 11 U1 0 U2 0 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. Ther. PD APR PY 1994 VL 17 IS 2 BP 85 EP 119 DI 10.1111/j.1365-2885.1994.tb00220.x PG 35 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA NH062 UT WOS:A1994NH06200001 ER PT J AU DIRKSEN, ML MORASSO, MI SARGENT, TD JAMRICH, M AF DIRKSEN, ML MORASSO, MI SARGENT, TD JAMRICH, M TI DIFFERENTIAL EXPRESSION OF A DISTAL-LESS HOMEOBOX GENE XDLL-2 IN ECTODERMAL CELL LINEAGES SO MECHANISMS OF DEVELOPMENT LA English DT Article DE ACTIVIN; DISTAL-LESS; EPIDERMIS; NEURAL INDUCTION; SKIN; XENOPUS ID MESODERM-INDUCING FACTOR; DNA-BINDING DOMAIN; XENOPUS-LAEVIS; DEVELOPING FOREBRAIN; RESTRICTED EXPRESSION; PROSPECTIVE AREAS; LIMB DEVELOPMENT; ACTIVIN-A; EMBRYOS; HOMEODOMAIN AB Neural induction in Xenopus requires the activation of new sets of genes that are necessary for cellular and regional specification of the neural tube. It has been reported earlier that members of the Distal-less homeobox gene family are specifically activated in distinct regions of the central nervous system (CNS) of Xenopus embryos (Dirksen et al., 1993; Papalopulu and Kintner, 1993). In this paper we describe in detail a-Xenopus homeobox containing gene Xdll-2, which belongs to the Distal-less gene Family. In contrast to other previously described Xenopus family members, Xdll-2 Is expressed in the embryonic ectoderm and is specifically repressed in the CNS. This repression can be mimicked in isolated animal caps by treatment with activin. Expression of Xdll-2 persists in the epidermis and some neural crest cells. Because of its spatial and temporal expression pattern this gene is a good candidate to have a regulatory function in the initial formation of the epidermis. Its high level of expression in adult skin indicates that its Function is continuously required in this tissue. C1 US FDA,CBER,DIV CELLULAR & GENE THERAPY,DEV BIOL LAB,ROCKVILLE,MD 20852. NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 60 TC 53 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD APR PY 1994 VL 46 IS 1 BP 63 EP 70 DI 10.1016/0925-4773(94)90038-8 PG 8 WC Developmental Biology SC Developmental Biology GA NP827 UT WOS:A1994NP82700006 PM 7915132 ER PT J AU WANG, RF CAO, WW FRANKLIN, W CAMPBELL, W CERNIGLIA, CE AF WANG, RF CAO, WW FRANKLIN, W CAMPBELL, W CERNIGLIA, CE TI A 16S RDNA-BASED PCR METHOD FOR RAPID AND SPECIFIC DETECTION OF CLOSTRIDIUM-PERFRINGENS IN FOOD SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE POLYMERASE CHAIN REACTION; CLOSTRIDIUM-PERFRINGENS; FOOD ID HUMAN INTESTINAL MICROFLORA; LISTERIA-MONOCYTOGENES; OUTBREAK; METABOLISM; BACTERIA; GENE; ENTEROTOXIN; PROBE; RAT C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. NR 28 TC 54 Z9 55 U1 2 U2 4 PU ACADEMIC PRESS 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 1994 VL 8 IS 2 BP 131 EP 138 DI 10.1006/mcpr.1994.1018 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA NR070 UT WOS:A1994NR07000006 PM 7935511 ER PT J AU MORRIS, SM MCGARRITY, LJ DOMON, OE CHEN, JJ HINSON, WG BUCCI, TJ WARBRITTON, AR CASCIANO, DA AF MORRIS, SM MCGARRITY, LJ DOMON, OE CHEN, JJ HINSON, WG BUCCI, TJ WARBRITTON, AR CASCIANO, DA TI THE ROLE OF PROGRAMMED CELL-DEATH IN THE TOXICITY OF THE MUTAGENS, ETHYL METHANESULFONATE AND N-ETHYL-N'-NITROSOUREA, IN AHH-1 HUMAN LYMPHOBLASTOID-CELLS SO MUTATION RESEARCH LA English DT Article DE LYMPHOBLASTOID CELLS, HUMAN; ETHYLATING AGENTS, SIMPLE; FLOW CYTOMETRY; CELL VIABILITY; APOPTOSIS ID HAMSTER OVARY CELLS; SISTER-CHROMATID EXCHANGES; MAMMALIAN-CELLS; DNA DAMAGE; TOPOISOMERASE INHIBITORS; MOLECULAR ANALYSIS; CYCLE PROGRESSION; NITROGEN-MUSTARD; PROPIDIUM IODIDE; FLOW-CYTOMETRY AB In order to determine the pathway for cell death in alkylating agent-exposed human lymphoblastoid cells, AHH-1 cells were exposed to either ethyl methanesulfonate (EMS) or ethyl nitrosourea (ENU) and the effect on relative cell growth and plating efficiency quantified. Flow cytometric (FCM) assays were utilized to quantify cell viability and to determine if cell death occurred through necrosis or apoptosis. As expected, exposure to the simple ethylating agents resulted in concentration-dependent decreases in plating efficiencies at each time interval after exposure (Days 0, 2, 3 and 7). EMS exposure did not significantly affect the relative cell growth, in contrast to ENU exposure, which inhibited cell growth. The FCM viability assay, based on light scatter characteristics, revealed that exposure to either alkylating agent resulted in a significant reduction in the percentage of viable cells. The results of the FCM dye-exclusion assays revealed that while necrosis occurred in EMS- and ENU-exposed cells, the primary manner of cell death was apoptosis. AHH-1 cells were stained with propidium iodide and fluorescein diacetate, the population of cells sorted electronically and the cell type (necrotic, apoptotic or viable) confirmed morphologically. Our results clearly indicate that exposure to EMS or ENU results in the movement of AHH-1 cells into the pathway for apoptosis and cell death. C1 US FDA,NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESMENT,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,OFF MANAGEMENT,JEFFERSON,AR 72079. PATHOL ASSOCIATES INC,JEFFERSON,AR 72079. RP MORRIS, SM (reprint author), NCTR,DGT,DIV GENET TOXICOL,HFT-120,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 55 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD APR 1 PY 1994 VL 306 IS 1 BP 19 EP 34 DI 10.1016/0027-5107(94)90164-3 PG 16 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA ND637 UT WOS:A1994ND63700003 PM 7512200 ER PT J AU BOCKSTAHLER, LE AF BOCKSTAHLER, LE TI OVERVIEW OF INTERNATIONAL PCR STANDARDIZATION EFFORTS SO PCR-METHODS AND APPLICATIONS LA English DT Review ID POLYMERASE CHAIN-REACTION; QUALITY-CONTROL; HIV DNA; VIRUS RP BOCKSTAHLER, LE (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,DIV LIFE SCI,ROCKVILLE,MD 20857, USA. NR 11 TC 11 Z9 11 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 PCR METH APPL JI PCR-Methods Appl. PD APR PY 1994 VL 3 IS 5 BP 263 EP 267 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA NM560 UT WOS:A1994NM56000001 PM 8038694 ER PT J AU SPADY, DW CARSON, MM BEELER, J KREZOLEK, M PABST, HF AF SPADY, DW CARSON, MM BEELER, J KREZOLEK, M PABST, HF TI SUCCESSFUL MEASLES VACCINATION OF 6-MONTH (MO) INFANTS OF VACCINATED MOTHERS SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20014. UNIV ALBERTA,DEPT PEDIAT,EDMONTON T6G 2E1,ALBERTA,CANADA. 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 1994 VL 35 IS 4 BP A196 EP A196 PN 2 PG 1 WC Pediatrics SC Pediatrics GA NG779 UT WOS:A1994NG77901161 ER PT J AU HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, NR SIBER, G FINLAYSON, J WATSON, JC AF HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, NR SIBER, G FINLAYSON, J WATSON, JC TI RECOMMENDED TIMING OF ROUTINE MEASLES IMMUNIZATION FOR CHILDREN WHO HAVE RECENTLY RECEIVED IMMUNE GLOBULIN PREPARATIONS SO PEDIATRICS LA English DT Article ID ANTIBODY-RESPONSE; VACCINE; POLIOVIRUS; EFFICACY; INFANTS C1 CANADIAN PAEDIAT SOC,OTTAWA,ON,CANADA. AMER ACAD PEDIAT,COMM INFECT DIS,EVANSTON,IL 60204. CTR DIS CONTROL & PREVENT,ATLANTA,GA. US FDA,BETHESDA,MD 20014. AMER THORAC SOC,NEW YORK,NY. NIH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 17 TC 5 Z9 6 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 1994 VL 93 IS 4 BP 682 EP 685 PG 4 WC Pediatrics SC Pediatrics GA ND363 UT WOS:A1994ND36300030 ER PT J AU BEER, JZ SZUMIEL, I AF BEER, JZ SZUMIEL, I TI SLOW CLONES, REDUCED CLONOGENICITY, AND INTRACLONAL RECOVERY IN X-IRRADIATED L5178Y-S CELL-CULTURES SO RADIATION AND ENVIRONMENTAL BIOPHYSICS LA English DT Article ID COLONY-FORMING ABILITY; DELAYED REPRODUCTIVE DEATH; LIVE MAMMALIAN-CELLS; HAMSTER OVARY CELLS; LETHAL MUTATIONS; GAMMA-IRRADIATION; LYMPHOMA-CELLS; RADIATION; DAMAGE; PROGENY AB Profound, long-lasting growth disturbances and reduced viability and clonogenicity were observed in suspension cultures of L5178Y-S (LY-S) murine leukemic lymphoblasts exposed to 0.25-6 Gy of X rays. In most cases, uncloned cultures grew at a reduced rate for periods corresponding to at least 100 cell generations, even when viability of such cultures returned to the normal level. These disturbances were analyzed in clones isolated using agar-supplemented medium. A slow phenotype was much more frequent among surviving clones isolated from LY-S cell cultures irradiated with 3 Gy of X rays than among clones isolated from nonirradiated controls. Growth of individual LY-S clones was affected to different extents, regardless of the clone's viability. The slowest clones had doubling time twice as long (22 h) as that of the control (10-12 h). More than 100 slow clones isolated from irradiated and nonirradiated cultures were followed for prolonged times, and some of them were further subcloned. The slow clones showed a high degree of heterogeneity, and selection for the slowest clone produced clones with increasing proliferative impairment and decreasing cloning efficiency. These results showed that progeny of X-irradiated LY-S cells contained many slowly growing cells, and that their presence affected the growth rate for scores of cell generations. The prolonged impairment of growth rate, viability, and clonogenicity appeared to depend on heritable lesions that were overcome as a result of intraclonal recovery. All slow clones were capable of such recovery, which for clones derived from irradiated cultures typically required periods corresponding to several scores of, but in some cases > 200, cell generations. Intraclonal recovery was much more rapid in slow clones isolated from nonirradiated cultures. This finding indicated that either slow phenotype depended on different cellular changes in the two groups of clones or mechanisms of intraclonal recovery were affected by radiation. C1 INST NUCL CHEM & TECHNOL,PL-03195 WARSAW,POLAND. RP BEER, JZ (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,HFZ-114,ROCKVILLE,MD 20857, USA. NR 41 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-634X J9 RADIAT ENVIRON BIOPH JI Radiat. Environ. Biophys. PD APR PY 1994 VL 33 IS 2 BP 125 EP 139 DI 10.1007/BF01219336 PG 15 WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging GA NP682 UT WOS:A1994NP68200003 PM 7938436 ER PT J AU RAHEJA, KL JORDAN, A AF RAHEJA, KL JORDAN, A TI FDA RECOMMENDATIONS FOR PRECLINICAL TESTING OF GONADOTROPIN-RELEASING-HORMONE (GNRH) ANALOGS SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID ANTAGONIST; SECRETION; LHRH AB Gonadotropin-releasing hormone (GnRH) agonists and antagonists are synthetic analogues synthesized by modifications of the naturally occurring hypothalamic decapeptide GnRH. These modifications significantly increase the biological potency and duration of action of GnRH agonists as well as the solubility, potency, and duration of action of GnRH antagonists while decreasing GnRH antagonists toxicity. The field of GnRH analogues has expanded significantly during the past few years in terms of the number of analogues, therapeutic indications, formulations, and mode of administration. This paper provides recommendations for nonclinical testing of GnRH analogues and reflects the type and degree of toxicity testing expected by the Division. However, these recommendations are not formal guidelines in that alternative testing methods will be considered. Furthermore, these recommendations should not be used as guidance for testing of other new drugs. (C) 1994 Academic Press, Inc. RP RAHEJA, KL (reprint author), US FDA,DIV METAB & ENDOCRINE DRUG PROD,ROOM 14B-04,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 1994 VL 19 IS 2 BP 168 EP 175 DI 10.1006/rtph.1994.1015 PG 8 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA NH670 UT WOS:A1994NH67000003 PM 8041914 ER PT J AU WEST, RW ROWLAND, KL AF WEST, RW ROWLAND, KL TI IN-VITRO TRANSFORMATION POTENTIAL OF N-POLYCYCLIC AROMATIC-HYDROCARBONS IN RAT TRACHEAL EPITHELIAL-CELLS SO TOXICOLOGY IN VITRO LA English DT Article ID BENZOPYRENE; CULTURE; CARCINOGENS; METABOLISM; HAMSTERS; SYSTEM; 1,6-DINITROPYRENE; MUTAGENICITY; RESPONSES; MODEL AB Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are environmental contaminants and potential human airway carcinogens. Agents of this class show a wide range of potencies for toxicity, mutagenicity and carcinogenicity that are associated with the structure of the PAH and the position of the nitro group. In order to evaluate the effect of nitro substitution on in vitro biological activity, the cytotoxicity and transformation potential of two parent PAHs, pyrene and chrysene, and a series of nitro derivatives were examined in the rat tracheal epithelial (RTE) cell system. The nitro derivatives, but not pyrene or chrysene, produced dose-dependent decreases in the colony forming efficiency of the RTE cells. The most cytotoxic agents were 1,6-dinitropyrene and 6-nitrochrysene with ED(50)s of 1.6 mu M and 5.9 mu M, respectively, followed by 4-nitropyrene and 1-nitropyrene with ED(50)s of 26.3 mu M and 44.5 mu M, respectively. These compounds were evaluated for transformation potential at three treatment levels that spanned the cytotoxic range, and the assays were scored for morphologically transformed preneoplastic colonies. The control or spontaneous transformation frequency in this series of experiments was 1.79 +/- 0.47 (x 10(-4)). 6-Nitrochrysene and 1,6-dinitropyrene were the only compounds that produced transformation frequencies (12.17 x 10(-4) and 9.68 x 10(-4), respectively) that were statistically different from control. The maximum transformation frequencies of the compounds were compared with published data for liver tumorigenicity in the newborn mouse assay. The orders for tumorigenicity and transformation were the same (1,6-dinitropyrene > 4-nitropyrene > 1-nitropyrene U pyrene and 6-nitrochrysene > chrysene), and the relative potencies of the compounds were similar in the two assays. These results suggest that RTE cells are capable of metabolizing nitro-PAHs to reactive products, and that, within this limited class of compounds, in vitro transformation data in the RTE cell system may be correlated with tumorigenicity in animal studies. RP WEST, RW (reprint author), NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079, USA. NR 26 TC 1 Z9 1 U1 4 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD APR PY 1994 VL 8 IS 2 BP 301 EP 307 DI 10.1016/0887-2333(94)90197-X PG 7 WC Toxicology SC Toxicology GA NK547 UT WOS:A1994NK54700022 PM 20692920 ER PT J AU NORMANNO, N SELVAM, MP QI, CF SAEKI, T JOHNSON, G KIM, N CIARDIELLO, F SHOYAB, M PLOWMAN, G BRANDT, R TODARO, G SALOMON, DS AF NORMANNO, N SELVAM, MP QI, CF SAEKI, T JOHNSON, G KIM, N CIARDIELLO, F SHOYAB, M PLOWMAN, G BRANDT, R TODARO, G SALOMON, DS TI AMPHIREGULIN AS AN AUTOCRINE GROWTH-FACTOR FOR C-HA-RAS-TRANSFORMED AND C-ERBB-2-TRANSFORMED HUMAN MAMMARY EPITHELIAL-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HA-RAS; C-NEU; BREAST CANCER ID HUMAN-BREAST CANCER; FACTOR-ALPHA; EXPRESSION; LINE; RECEPTOR; GENE; ESTROGEN; PROTEIN AB Amphiregulin (AR), a member of the epidermal growth factor (EGF) family, was found to be as potent as EGF in stimulating the anchorage-dependent growth (ADG) of immortalized, nontransformed human mammary epithelial MCF-10A cells. MCF-10A cells transformed by either an activated human c-Ha-ras protooncogene (MCF-10A ras) or by overexpression of a nonactivated rat c-neu gene (MCF-10A neu) exhibited a 35% reduction in the response to AR in ADG when compared to MCF-10A cells, but AR was still as potent as EGF in these transformants. Exogenous AR exhibited only 15-20% of the activity of EGF in stimulating the anchorage-independent growth, a response that is normally dependent upon exogenous EGF, of the oncogene-transformed MCF-10A cells. MCF-10A cells express low levels of a 1.4-kb AR mRNA transcript, while MCF-10A ras and MCF-10A neu cells display a 15- to 30-fold increase in the levels of AR mRNA and endogenous AR protein as determined by Western blot analysis. Exogenous EGF was found to induce both AR mRNA and protein in the MCF-10A parental and transformed cells. A 20-mer phosphorothioate antisense deoxyoligonucleotide complementary to the 5' sequence of AR mRNA was able to significantly reduce the levels of endogenous AR protein and to inhibit the EGF-stimulated ADG and anchorage-independent growth of MCF-10A ras and MCF-10A neu cells. These data suggest that AR may function as an EGF-dependent autocrine growth factor in mammary epithelial cells that have been transformed by either a point-mutated c-Ha-ras or c-neu. C1 NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTOR SECT,BLDG 10,BETHESDA,MD 20892. IST NAZL STUDIO & CURA TUMORI FDN PASCALE,I-80131 NAPLES,ITALY. US FDA,CTR BIOL EVALUAT & RES,DIV BLOOD APPLICAT,BETHESDA,MD 20892. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. UNIV NAPOLI FEDERICO II,FAC MED & CHIRURG 2,CATTEDRA ONCOL MED,I-80131 NAPLES,ITALY. BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,SEATTLE,WA 98121. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RI PLOWMAN, Greg/E-2012-2011; OI Normanno, Nicola/0000-0002-7158-2605 NR 33 TC 97 Z9 97 U1 1 U2 4 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 29 PY 1994 VL 91 IS 7 BP 2790 EP 2794 DI 10.1073/pnas.91.7.2790 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ND602 UT WOS:A1994ND60200083 PM 7908443 ER PT J AU HILL, JC FLANNERY, GM FRASER, BA AF HILL, JC FLANNERY, GM FRASER, BA TI HPLC PURIFICATION AND SEPARATION OF 5,5'-SUBSTITUTED-2,4-IMIDAZOLIDINEDITHIONES SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article AB Several 5,5'-substituted-2,4-imidazolidinedithiones, synthesized from aldehydes or ketones, have been purified by HPLC using poly(styrene-divinylbenzene) packings. Purified 5,5'-substituted-2,4-imidazolidinedithiones have been identified in column effluent by UV absorbance and corroborated by mass spectrometry. Several silica-based, polymeric, and poly(styrene-divinylbenzene)-based packings were evaluated as matrices for resolution of a mixture of purified 5,5'-substituted-2,4-imidazolidinedithiones. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAR 25 PY 1994 VL 664 IS 1 BP 63 EP 70 DI 10.1016/0021-9673(94)80629-2 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ND651 UT WOS:A1994ND65100008 PM 8012550 ER PT J AU BABU, US BUNNING, VK RAYBOURNE, RB ODONNELL, MW AF BABU, US BUNNING, VK RAYBOURNE, RB ODONNELL, MW TI EFFECT OF DIETARY FLAXSEED ON FUNCTIONS OF PERITONEAL-MACROPHAGES FROM YOUNG MALE AND FEMALE RATS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,LAUREL,MD 20708. 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 18 PY 1994 VL 8 IS 5 BP A951 EP A951 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19702118 ER PT J AU BALA, S KOVACS, J STEVENS, R BASELER, M WAHL, L SHER, A GAZZINELLI, RT AF BALA, S KOVACS, J STEVENS, R BASELER, M WAHL, L SHER, A GAZZINELLI, RT TI SPECIFIC AND NONSPECIFIC CYTOKINE RESPONSES TO TOXOPLASMA-GONDII OF PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM NORMAL AND HIV-INFECTED HUMANS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,CCM,CCS,BETHESDA,MD 20892. NIDR,BETHESDA,MD 20892. US FDA,DAVDP,ROCKVILLE,MD 20857. PRI DYNCORP,FREDERICK,MD 21701. 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 18 PY 1994 VL 8 IS 5 BP A973 EP A973 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19702244 ER PT J AU BLACK, PL BROUD, DD WOOD, OL USSERY, MA AF BLACK, PL BROUD, DD WOOD, OL USSERY, MA TI FLUORESCENT LABELING AND HIV-INFECTION OF HUMAN PBMC IN SCID MICE AS AN IN-VIVO MODEL FOR ANTIVIRAL DRUG DEVELOPMENT SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CDER,ROCKVILLE,MD 20857. 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 18 PY 1994 VL 8 IS 5 BP A754 EP A754 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19700978 ER PT J AU BOSWELL, C STEIN, K AF BOSWELL, C STEIN, K TI IG GENE SEQUENCE-ANALYSIS OF STRAIN-DEPENDENT FINE SPECIFICITY DIFFERENCES IN ANTIBACTERIAL LEVAN (BL) MONOCLONAL-ANTIBODIES (MAB) SO FASEB JOURNAL LA English DT Meeting Abstract C1 CBER,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 18 PY 1994 VL 8 IS 5 BP A983 EP A983 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19702298 ER PT J AU ELLWOOD, KC NEWELL, RF MCLAUGHLIN, MA AF ELLWOOD, KC NEWELL, RF MCLAUGHLIN, MA TI LIPOGENIC AND GLUCONEOGENIC ENZYME RESPONSE IN RATS FED XYLITOL OR SORBITOL SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,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 18 PY 1994 VL 8 IS 5 BP A954 EP A954 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19702135 ER PT J AU GAINES, DW FRIEDMAN, L AF GAINES, DW FRIEDMAN, L TI IN-VITRO EFFECTS OF IRON (FE) SALTS ON ORNITHINE DECARBOXYLASE (ODC) ACTIVITY (ACT) IN RAT-LIVER PREPARATIONS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CFSAN,LAUREL,MD 20708. 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 18 PY 1994 VL 8 IS 5 BP A712 EP A712 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19700738 ER PT J AU HERMAN, EH ZHANG, J CHADWICK, DP FERRANS, VJ AF HERMAN, EH ZHANG, J CHADWICK, DP FERRANS, VJ TI COMPARISON OF THE CARDIOPROTECTIVE EFFECT OF DEFEROXAMINE (DFO) AND ICRF-187 ON CHRONIC DOXORUBICIN (DXR) CARDIOMYOPATHY IN SPONTANEOUSLY HYPERTENSIVE RATS (SHR) SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,LAUREL,MD. NIH,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 18 PY 1994 VL 8 IS 5 BP A885 EP A885 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19701738 ER PT J AU LEE, C KARPAS, A WANG, T KOSAKA, T AF LEE, C KARPAS, A WANG, T KOSAKA, T TI IMMUNITY AND PRODUCTION OF MONOCLONAL-ANTIBODY TO PNEUMOCOCCAL TYPE 9V PS-PROTEIN 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 18 PY 1994 VL 8 IS 5 BP A756 EP A756 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19700993 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 COCAINE ON OPERANT-BEHAVIOR IN RHESUS-MONKEY OFFSPRING EXPOSED TO COCAINE IN-UTERO 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 18 PY 1994 VL 8 IS 5 BP A631 EP A631 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19700270 ER PT J AU POIRIER, LA JAMES, SJ MILLER, BJ WISE, C VILLANUEVA, J HALSTED, CH AF POIRIER, LA JAMES, SJ MILLER, BJ WISE, C VILLANUEVA, J HALSTED, CH TI ALTERATIONS IN HEPATIC ONE-CARBON COMPOUNDS BY CHRONIC ETHANOL-CONSUMPTION IN MICROPIGS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. UNIV CALIF DAVIS,DEPT INTERNAL MED,DAVIS,CA 95616. 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 18 PY 1994 VL 8 IS 5 BP A952 EP A952 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19702124 ER PT J AU RHEE, H SONG, B CUSHMAN, S SHOAF, S AF RHEE, H SONG, B CUSHMAN, S SHOAF, S TI DIFFERENTIAL RESPONSES TO NOREPINEPHRINE (NE) IN ALCOHOLIC AND DIABETIC RAT AORTA SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NIAAA,ROCKVILLE,MD 20852. NIDDKD,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 18 PY 1994 VL 8 IS 5 BP A952 EP A952 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19702120 ER PT J AU SISTARE, FD JORDAN, B ROSENZWEIG, BA AF SISTARE, FD JORDAN, B ROSENZWEIG, BA TI A DUAL MECHANISM FOR P(2Z) PURINERGIC RECEPTOR-MEDIATED EXTRACELLULAR CALCIUM INFLUX IN GH(3) CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CDER,LAUREL,MD 20708. 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 18 PY 1994 VL 8 IS 5 BP A878 EP A878 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19701697 ER PT J AU VARGAS, FF VINET, R CALVO, S AF VARGAS, FF VINET, R CALVO, S TI VOLTAGE-GATED CA++ CHANNELS IN ADRENAL-MEDULLA ENDOTHELIAL-CELLS AND THEIR LOSS DURING CELL-CULTURE SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,DIV CARDIORENAL DRUGS,BETHESDA,MD 20892. NIH,CELL BIOL & GENET LAB,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 18 PY 1994 VL 8 IS 5 BP A1061 EP A1061 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19702753 ER PT J AU WEN, J WANG, J KUIPERS, J HUANG, F WILLIAMS, K RAYBOURNE, R YU, D AF WEN, J WANG, J KUIPERS, J HUANG, F WILLIAMS, K RAYBOURNE, R YU, D TI ANALYSIS OF HLA-B-ASTERISK-2705 PEPTIDE MOTIF USING T2 CELLS AND ME1 MONOCLONAL-ANTIBODY SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,DIV RHEUMATOL,LOS ANGELES,CA 90024. US FDA,DIV MICROBIOL,LAUREL,MD 20708. 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 18 PY 1994 VL 8 IS 5 BP A776 EP A776 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19701112 ER PT J AU WILLIAMS, N AIDOO, A MUSEY, PI AF WILLIAMS, N AIDOO, A MUSEY, PI TI EVALUATION OF THE GENOTOXIC CYTOGENETIC EFFECTS OF THE CHLORINATED PESTICIDE (CHLORDANE) ON RAT LYMPHOCYTES TREATED IN-VITRO SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCTR,DIV GENET TOXICOL,JEFFERSON,AR 72079. CLARK ATLANTA UNIV,DEPT BIOL SCI,ATLANTA,GA 30314. 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 18 PY 1994 VL 8 IS 5 BP A649 EP A649 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19700373 ER PT J AU ZHANG, J HERMAN, EH YAMAMOTO, A WENTHOLD, RJ FERRANS, VJ AF ZHANG, J HERMAN, EH YAMAMOTO, A WENTHOLD, RJ FERRANS, VJ TI PULMONARY TOXICITY OF HUMAN RECOMBINANT INTERLEUKIN-2 IN RATS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,LAUREL,MD 20708. 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 18 PY 1994 VL 8 IS 5 BP A809 EP A809 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND197 UT WOS:A1994ND19701302 ER PT J AU BARTELS, F BERGEL, H BIGALKE, H FREVERT, J HALPERN, J MIDDLEBROOK, J AF BARTELS, F BERGEL, H BIGALKE, H FREVERT, J HALPERN, J MIDDLEBROOK, J TI SPECIFIC ANTIBODIES AGAINST THE ZN2+-BINDING DOMAIN OF CLOSTRIDIAL NEUROTOXINS RESTORE EXOCYTOSIS IN CHROMAFFIN CELLS TREATED WITH TETANUS OR BOTULINUM A NEUROTOXIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IONIC-STRENGTH SOLUTION; LIGHT CHAIN; NEUROTRANSMITTER RELEASE; INHIBITS EXOCYTOSIS; TOXIN; PROTEINS; GANGLIOSIDES; ZINC AB Although tetanus and botulinum A neurotoxins are ineffective in cultured chromaffin cells, they will inhibit carbachol-induced release of noradrenaline provided they gain access to the cytosol either through artificial pores generated in the plasma membrane or by binding to incorporated exogenous gangliosides. The block of exocytosis persists for weeks followed by a slow recovery of cell function. When specific anti-botulinum A toxin antibodies are introduced into cells through pores after manifestation of the block by botulinum A neurotoxin, restoration of exocytotic function is accelerated and fully reestablished within 4 days. The same time course of restoration is seen with anti-tetanus toxin antibodies in cells poisoned by tetanus toxin. Since the light chains of the toxins are enzymatically active, we have introduced polyclonal and monoclonal anti-light chain antibodies into the cytosol. Of all light chain antibodies tested, only those directed against the peptide homologous to the zinc-binding sequence, which is present in both neurotoxins, restored exocytosis regardless of which toxin caused the block. These results indicate that the zinc-binding domain is directly involved in the interaction of the light chains with their substrates and that the toxins have to be present continuously to maintain the block. C1 MED SCH HANNOVER,INST TOXICOL,D-30625 HANNOVER,GERMANY. PHARMATEC,D-60486 FRANKFURT,GERMANY. US FDA,PUBL HLTH SERV,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,DIV TOXICOL,FREDERICK,MD 21701. NR 34 TC 37 Z9 39 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 MAR 18 PY 1994 VL 269 IS 11 BP 8122 EP 8127 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NB409 UT WOS:A1994NB40900046 PM 8132537 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI NEW SEAFOOD SAFETY INITIATIVE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 16 PY 1994 VL 271 IS 11 BP 812 EP 812 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MZ498 UT WOS:A1994MZ49800040 PM 8114223 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI FDA PROPOSES 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), FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 16 PY 1994 VL 271 IS 11 BP 812 EP 812 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MZ498 UT WOS:A1994MZ49800039 PM 8114223 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI NEW REGULATION REQUIRES IMPRINTING ON SOLID ORAL DOSAGE FORM-DRUG PRODUCTS 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 LANE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 16 PY 1994 VL 271 IS 11 BP 812 EP 812 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MZ498 UT WOS:A1994MZ49800004 PM 8114223 ER PT J AU MACLEOD, MC EVANS, FE LAY, J CHIARELLI, P GEACINTOV, NE POWELL, KL DAYLONG, A LUNA, E HARVEY, RG AF MACLEOD, MC EVANS, FE LAY, J CHIARELLI, P GEACINTOV, NE POWELL, KL DAYLONG, A LUNA, E HARVEY, RG TI IDENTIFICATION OF A NOVEL, N7-DEOXYGUANOSINE ADDUCT AS THE MAJOR DNA ADDUCT FORMED BY A NON-BAY-REGION DIOL EPOXIDE OF BENZO[A]PYRENE WITH LOW MUTAGENIC POTENTIAL SO BIOCHEMISTRY LA English DT Article ID COVALENT NUCLEOSIDE ADDUCTS; EMBRYO CELL-CULTURES; DOUBLE-STRANDED DNA; OPTICAL ENANTIOMERS; MAMMALIAN-CELLS; CHO CELLS; BINDING; CARCINOGEN; BENZO(A)PYRENE; CONFORMATION AB A metabolite of benzo[a]pyrene, 9-r,10-t-dihydroxy-7,8-c-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-III), that is not thought to be involved in carcinogenesis has nevertheless been shown to bind extensively to DNA in vitro. The adducts formed by this non-bay-region diol epoxide in Chinese hamster ovary cells are much less mutagenic than those formed by an isomeric diol epoxide that is carcinogenic. We have isolated and characterized three major adducts formed by in vitro reaction of BPDE-III with DNA. The major adduct, accounting for over half of the total is formed by reaction of BPDE-III with the N7 position of dGuo and is recovered after enzymatic digestion as an N7-Gua adduct. A second major adduct involves the N-2 position of dGuo, while the third adduct is tentatively identified as a C8-substituted dGuo. Little or no reaction with deoxyadenosine residues is detected. The N7 adduct is unstable in DNA at 37 degrees C and is released as the modified base with a half-life of about 24 h. This adduct lability apparently leads to single-strand breaks and alkali-sensitive sites in the DNA and may account in part for some of the biological properties of BPDE-III adducts. This represents the first description of an N7-dGuo adduct that is formed in DNA as the major adduct by a diol epoxide derived from a carcinogenic polycyclic aromatic hydrocarbon. C1 NATL CTR TOXICOL RES,DEPT BIOCHEM TOXICOL,JEFFERSON,AR 72079. NYU,DEPT CHEM,NEW YORK,NY 10003. UNIV CHICAGO,BEN MAY INST,CHICAGO,IL 60637. UNIV CHICAGO,CANC RES CTR,CHICAGO,IL 60637. RP MACLEOD, MC (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CARCINOGENESIS,SMITHVILLE,TX 78957, USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 FU NCI NIH HHS [CA35581]; NIEHS NIH HHS [ES03602] NR 79 TC 15 Z9 15 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 15 PY 1994 VL 33 IS 10 BP 2977 EP 2987 DI 10.1021/bi00176a030 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NA886 UT WOS:A1994NA88600030 PM 8130212 ER PT J AU MISPLON, JA WOOD, T HARVATH, L EPSTEIN, SL AF MISPLON, JA WOOD, T HARVATH, L EPSTEIN, SL TI ANTIBODY REPERTOIRE IN THE RESPONSE TO A PROTEIN ANTIGEN - INTERRELATED IDIOTYPIC FAMILIES IN THE RESPONSE TO IA.7 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL ANTI-H-2 ANTIBODIES; ANTI-IA.7 ANTIBODIES; MOUSE IMMUNOGLOBULIN; IMMUNE-RESPONSES; SOMATIC MUTATION; LIGHT-CHAINS; EXPRESSION; SPECIFICITY; INVIVO; DETERMINANTS AB Mouse alloantibodies to Ia.7 display a cross-reactive idiotype (CRI) recognized by xenogeneic anti-idiotypes. The CRI is expressed on serum Abs in all responding individuals and on all anti-Ia.7 mAbs, from mice of appropriate genetic types. In addition, both xenogeneic and allogeneic anti-idiotypes in this system have a striking ability to induce Ia.7-specific responses in mice never exposed to the Ag. Because of these unusual features, we have investigated the biologic and structural basis of the idiotypic sharing in this system. Ia.7-specific Ab populations induced by eight different Ab2 mAbs were analyzed for expression of each of the set of idiotopes. Two obvious explanations for the unusual properties of the system do not appear to be correct. 1) The induction of Ag-specific immunity was not caused by internal imagery; and 2) the Ab2s do not simply recognize the same idiotope, because they induce populations that were found to be distinct in idiotope expression. The biologic properties of the system are instead caused by a pattern of expression of idiotope sets on distinct but related Ab families, and a remarkable linkage of a series of different idiotopes to Ia.7-specific activity. Mouse anti-idiotypic responses failed to recognize the widely shared CRI site, even when sequential immunizations were performed. To examine the structural basis of Id sharing, light chains of three CRI(+) mAbs were sequenced. They were found to be extremely homologous to each other and to the germ-line V kappa 21E gene, and they used either J1 or J2. A model containing families of distinct but related V regions is proposed for the anti-Ia.7 repertoire. C1 US FDA,CBER,OTRR,DCGT,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. PROGRAM RESOURCES INC,FREDERICK,MD 21702. US FDA,CBER,DIV HEMATOL,CELLULAR HEMATOL LAB,BETHESDA,MD 20892. RI Wood, Thomas/B-6172-2012 NR 48 TC 1 Z9 1 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 MAR 15 PY 1994 VL 152 IS 6 BP 2778 EP 2787 PG 10 WC Immunology SC Immunology GA NC773 UT WOS:A1994NC77300016 PM 7511627 ER PT J AU SIMON, R THALL, PF ELLENBERG, SS AF SIMON, R THALL, PF ELLENBERG, SS TI NEW DESIGNS FOR THE SELECTION OF TREATMENTS TO BE TESTED IN RANDOMIZED CLINICAL-TRIALS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID BINARY OUTCOMES; 2-STAGE DESIGN AB The most important aspect of phase III randomized clinical trials is the selection of the experimental treatments to be tested. Often this decision is based on uncontrolled phase II trials. Substantial statistical attention has been focused on the design of phase III trials and for simple phase II trials, which determine whether a new drug has any anti-disease activity. Much less statistical effort has been devoted to the design and analysis of phase II trials for screening active experimental treatments to determine whether they are sufficiently active, relative to standard treatments, to warrant the conduct of a large randomized phase III trial. This problem is particularly acute in the development of drug combinations where many regimens are possible. We review several designs for such screening trials which we have developed. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOMATH,HOUSTON,TX 77030. US FDA,CTR BIOL EVALUAT & RES,DIV BIOSTAT & EPIDEMIOL,OFF ESTAB LICENSING & PROD SURVEILLANCE,ROCKVILLE,MD 20852. RP SIMON, R (reprint author), NCI,DIV CANC TREATMENT,BIOMETR RES BRANCH,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 16 TC 34 Z9 34 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 MAR 15 PY 1994 VL 13 IS 5-7 BP 417 EP 429 DI 10.1002/sim.4780130506 PG 13 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 NE525 UT WOS:A1994NE52500005 PM 8023026 ER PT J AU JACKSON, LS HARGRAVES, WA AF JACKSON, LS HARGRAVES, WA TI THE EFFECT OF PROCESSING TIME AND TEMPERATURE ON THE FORMATION OF MEIQX AND DIMEIQX IN A MODEL SYSTEM SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 11 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95400011 ER PT J AU PAULI, GH AF PAULI, GH TI ISSUES CONCERNING REGULATORY APPROVAL OF MACROINGREDIENTS IN FOOD SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,OFF PREMARKET APPROVAL,WASHINGTON,DC 20204. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 45 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95400044 ER PT J AU WEISZ, A SCHER, AL ANDRZEJEWSKI, D ITO, Y AF WEISZ, A SCHER, AL ANDRZEJEWSKI, D ITO, Y TI PREPARATIVE SEPARATION OF BROMINATED TETRACHLOROFLUORESCEINS BY PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY WITH COMPUTERIZED SCANNING UV/VIS DETECTION AND CONTINUOUS PH MONITORING SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204. US FDA,OFF SCI ANAL & SUPPORT,WASHINGTON,DC 20204. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 58 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95400334 ER PT J AU CAIRNS, T SIEGMUND, EG CHIU, KS NAVARRO, D AF CAIRNS, T SIEGMUND, EG CHIU, KS NAVARRO, D TI MULTIPESTICIDE RESIDUE ANALYSIS USING ISOTOPE-DILUTION ANALYSIS VIA ION-TRAP TECHNOLOGY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,LOS ANGELES,CA 90015. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 102 EP ENVR PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95402009 ER PT J AU LIU, DTY AF LIU, DTY TI CRITICAL ISSUES IN DOWNSTREAM PROCESSING - ISSUES RELATED TO PROCESS CHANGES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,CBER,OVRR,DIV ALLERGEN PROD & PARASITOL,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 106 EP BTEC PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY955 UT WOS:A1994MY95501849 ER PT J AU TRUCKSESS, MW AF TRUCKSESS, MW TI EVALUATION AND APPLICATION OF IMMUNOCHEMICAL METHODS FOR MYCOTOXINS IN FOOD 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. USDA,FED GRAINS INSPECT SERV,KANSAS CITY,KS. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 190 EP AGRO PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95400263 ER PT J AU ROBBINS, JD BORING, DL TANG, WJ SHANK, R SEAMON, KB AF ROBBINS, JD BORING, DL TANG, WJ SHANK, R SEAMON, KB TI SYNTHESIS AND BIOLOGICAL EVALUATION OF FORSKOLIN CARBAMATES AS POTENTIAL ADENYLYL-CYCLASE ISOFORM SELECTIVE LIGANDS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SW MED SCH,DALLAS,TX 75235. US FDA,CTR BIOL EVALUAT & RES,DBB,LMP,BETHESDA,MD 20892. DAVDP,ODE 2,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20890. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 248 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95403553 ER PT J AU FLURER, CL WOLNIK, KA AF FLURER, CL WOLNIK, KA TI QUANTITATION OF GENTAMICIN SULFATE IN INJECTABLE SOLUTIONS BY CAPILLARY ELECTROPHORESIS SO JOURNAL OF CHROMATOGRAPHY A LA English DT Note ID CHROMATOGRAPHY AB The results presented in this communication establish the use of capillary electrophoresis as a tool in the analysis of injectable solutions containing the antibiotic complex gentamicin sulfate. The utilization of a berate buffer leads to the separation of the individual components and their visualization by direct UV detection. This rapid and straightforward procedure yields qualitative and quantitative information simultaneously, and could be utilized as an alternative to the multiple assays required by current US Pharmacopeia protocols. RP FLURER, CL (reprint author), US FDA,NATL FORENS CHEM CTR,1141 CENT PKWY,CINCINNATI,OH 45202, USA. NR 10 TC 42 Z9 43 U1 1 U2 3 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 11 PY 1994 VL 663 IS 2 BP 259 EP 263 DI 10.1016/0021-9673(94)85253-7 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NB429 UT WOS:A1994NB42900014 PM 8173668 ER PT J AU AHN, HY SHIU, GK TRAFTON, WF DOYLE, TD AF AHN, HY SHIU, GK TRAFTON, WF DOYLE, TD TI RESOLUTION OF THE ENANTIOMERS OF IBUPROFEN - COMPARISON STUDY OF DIASTEREOMERIC METHOD AND CHIRAL STATIONARY-PHASE METHOD SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PLASMA; SEPARATION; DERIVATIVES; HUMANS; ASSAY; DRUGS AB In this study, an indirect diastereomeric method and a direct method utilizing a chiral stationary phase (CSP) were investigated for the resolution of ibuprofen enantiomers. In the indirect method, ethylchloroformate (ECF) and 2-ethoxy-1-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) were utilized as first-step derivatizing reagents in acetonitrile or toluene. In the direct CSP method, ibuprofen enantiomers were derivatized to p-nitrobenzyl ureides and then resolved on an (R)-(-)-(1-naphthyl)ethylurea CSP column. The derivatization procedure took place in 10 min with an overall inversion efficiency of 90.3%. Racemization was not observed under the derivatization conditions used. The HPLC-CSP method was utilized to study the pharmacokinetics of ibuprofen enantiomers in dog plasma after a single oral administration of 200 mg of ibuprofen racemate. C1 US FDA,CTR DRUG EVALUAT & RES,DIV RES & TESTING,WASHINGTON,DC 20204. GALLAUDET UNIV,WASHINGTON,DC 20002. RP AHN, HY (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV BIOPHARMACEUT,BIOPHARMACEUT RES BRANCH,WASHINGTON,DC 20204, USA. NR 14 TC 19 Z9 19 U1 4 U2 7 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 MAR 4 PY 1994 VL 653 IS 2 BP 163 EP 169 DI 10.1016/0378-4347(93)E0425-P PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ND225 UT WOS:A1994ND22500007 PM 8205243 ER PT J AU HARRIS, JW KATKI, A ANDERSON, LW CHMURNY, GN PAUKSTELIS, JV COLLINS, JM AF HARRIS, JW KATKI, A ANDERSON, LW CHMURNY, GN PAUKSTELIS, JV COLLINS, JM TI ISOLATION, STRUCTURAL DETERMINATION, AND BIOLOGICAL-ACTIVITY OF 6-ALPHA-HYDROXYTAXOL, THE PRINCIPAL HUMAN METABOLITE OF TAXOL SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Note ID ESTABLISHMENT; INVITRO AB The principal biotransformation product of taxol was found to be identical for human hepatic microsomes, human liver slices, and patient bile samples. We have isolated this metabolite from the bile of a patient given taxol, and we report its structure and its cytotoxicity relative to taxol. The NMR and SIMS data presented here indicate that, in humans, taxol is regiospecifically hydroxylated at the 6-position on the taxane ring and that this hydroxyl is stereospecifically placed trans to the hydroxyl at position 7, yielding 6(alpha-hydroxytaxol. This metabolite is apparently not formed in rats. Tests of the growth inhibition potential of 6 alpha-hydroxytaxol versus taxol in two human tumor cell lines showed that the metabolite was approximately 30-fold less cytotoxic than taxol. Thus the cytochrome P-450-mediated biotransformation of taxol to 6 alpha-hydroxytaxol can be classified as a detoxification reaction. C1 US FDA,CTR DRUG EVALUAT & RES,DIV CLIN PHARMACOL,ROCKVILLE,MD 20857. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP INC,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. NR 18 TC 79 Z9 81 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 4 PY 1994 VL 37 IS 5 BP 706 EP 709 DI 10.1021/jm00031a022 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA MZ388 UT WOS:A1994MZ38800022 PM 7907372 ER PT J AU ILETT, KF INGRAM, DM CARPENTER, DS TEITEL, CH LANG, NP KADLUBAR, FF MINCHIN, RF AF ILETT, KF INGRAM, DM CARPENTER, DS TEITEL, CH LANG, NP KADLUBAR, FF MINCHIN, RF TI EXPRESSION OF MONOMORPHIC AND POLYMORPHIC N-ACETYLTRANSFERASES IN HUMAN COLON SO BIOCHEMICAL PHARMACOLOGY LA English DT Note DE N-ACETYLTRANSFERASES; HUMAN COLON; ACETYLATION PHENOTYPE/GENOTYPE; SULFAMETHAZINE; P-AMINOBENZOIC ACID ID AROMATIC AMINE ACETYLTRANSFERASE; COLORECTAL-CANCER; ACETYLATOR GENOTYPE; HUMAN LIVER; CARCINOGENS; EXTRACTION; PHENOTYPE AB The metabolism of sulfamethazine (SMZ) and p-aminobenzoic acid (PABA) by N-acetyltransferase (NAT) was measured in human colorectal cytosols from 12 slow and 11 rapid acetylators whose genotype was determined independently by a specific polymerase chain reaction. SMZ metabolism was significantly greater in the rapid than in the slow phenotype (192 +/- 22 versus 94 +/- 11 pmol N-acetylsulfamethazine/min/mg protein), while PABA metabolism was similar in both phenotypes (23.7 +/- 4.4 versus 23.0 +/- 3.9 nmol N-acetyl-p-aminobenzoic acid/min/mg protein). Both monomorphic and polymorphic NAT mRNAs were detected by the polymerase chain reaction in the colorectal mucosa of most samples. The finding that polymorphic NAT is expressed in a phenotype-dependent manner in colorectal mucosa indicates that this tissue has the capacity to participate in local bioactivation of dietary and environmental aryl- or heterocyclic amine carcinogens and may explain, in part, the phenotype-dependent occurrrence of colorectal cancer. C1 UNIV WESTERN AUSTRALIA,DEPT SURG,NEDLANDS,WA 6009,AUSTRALIA. NATL CTR TOXICOL RES,OFF RES,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,ARKANSAS CANC RES CTR,DEPT SURG,LITTLE ROCK,AR 72205. RP ILETT, KF (reprint author), UNIV WESTERN AUSTRALIA,DEPT PHARMACOL,NEDLANDS,WA 6009,AUSTRALIA. NR 22 TC 57 Z9 58 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 2 PY 1994 VL 47 IS 5 BP 914 EP 917 DI 10.1016/0006-2952(94)90493-6 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NA068 UT WOS:A1994NA06800021 PM 8135868 ER PT J AU BENOIT, V RAICHE, P SMITH, MG GUTHRIE, J DONNELLY, EF JULIAN, EM LEE, R DIMAIO, S RITTMANN, M MATYAS, BT AF BENOIT, V RAICHE, P SMITH, MG GUTHRIE, J DONNELLY, EF JULIAN, EM LEE, R DIMAIO, S RITTMANN, M MATYAS, BT TI FOODBORNE OUTBREAKS OF ENTEROTOXIGENIC ESCHERICHIA-COLI - RHODE-ISLAND AND NEW-HAMPSHIRE, 1993 (REPRINTED FROM MMWR, VOL 43, PG 81, 87-89, 1994) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 UNIV RHODE ISL INFIRM,KINGSTON,RI. RHODE ISL DEPT HLTH,PROVIDENCE,RI 02908. US FDA,ATLANTA DIST OFF,ATLANTA,GA. US FDA,DIV EMERGENCY & EPIDEMIOL OPERAT,ATLANTA,GA. CDC,NATL CTR INFECT DIS,DIV FIELD EPIDEMIOL,EPIDEMIOL PROGRAM OFF,ATLANTA,GA. CDC,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,RESP & ENTEROVIRUS BRANCH,ATLANTA,GA. CDC,NATL CTR INFECT DIS,DIV BACTERIAL & MYCOT DIS,ATLANTA,GA. RP BENOIT, V (reprint author), NEW HAMPSHIRE DIV PUBL HLTH SERV,CONCORD,NH 03301, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 2 PY 1994 VL 271 IS 9 BP 652 EP 654 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA MX570 UT WOS:A1994MX57000011 ER PT J AU MANDEL, HG KUSMIERZ, JJ DICKENS, BF ANDERSON, LW AF MANDEL, HG KUSMIERZ, JJ DICKENS, BF ANDERSON, LW TI QUANTITATION OF URINARY 7-METHYLADENINE BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY USING ISOTOPICALLY LABELED INTERNAL STANDARDS SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID METHYLATING CARCINOGENS; EXPOSURE; ALKYLATION AB We have developed a procedure for isolating and quantifying 7-methyladenine from rat urine following the administration to the rat of methylating agents, such as dimethylnitrosamine. Urinary 7-methyladenine and its trideutero isomer, added as an internal standard, were precipitated with silver nitrate, the precipitate was extracted with HCl, and the extract was further purified by C-18-Sep-Pak chromatography. The recovered 7-methyladenine was then derivatized with pentafluorobenzyl bromide at alkaline pH for analysis by gas chromatography-mass spectrometry, indicating a bis(pentafluorobenzyl) conjugate, m/z 509. The mass spectrum of this derivative shows a major fragmentation ion at mit 328 (and 331 for the trideutero derivative) resulting from the loss of one pentafluorobenzyl group. Levels of urinary 7-methyladenine above 150 pg could be detected from the ratio of the gas chromatography peak areas for these ions, using selective-ion monitoring. The method was selective for the 7-methyl isomer. The procedures developed for the syntheses of deuterated and tritiated 7-methyladenine, which were required for these studies, are also described. (C) 1994 Academic Press, Inc. C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT EXPTL MED,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,DEPT PHYSIOL,WASHINGTON,DC 20037. US FDA,CTR DRUG EVALUAT & RES,DIV CLIN PHARMACOL,ROCKVILLE,MD 20850. RP MANDEL, HG (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT PHARMACOL,2300 EYE ST NW,WASHINGTON,DC 20037, USA. NR 13 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAR PY 1994 VL 217 IS 2 BP 292 EP 297 DI 10.1006/abio.1994.1121 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA MY312 UT WOS:A1994MY31200017 PM 8203758 ER PT J AU DEPAOLA, A CAPERS, GM ALEXANDER, D AF DEPAOLA, A CAPERS, GM ALEXANDER, D TI DENSITIES OF VIBRIO-VULNIFICUS IN THE INTESTINES OF FISH FROM THE US GULF-COAST SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID INDICATOR BACTERIA; UNITED-STATES; OYSTERS; ENVIRONMENT; SHELLSTOCK AB Densities of Vibrio vulnificus in the intestinal contents of various finfish, oysters, and crabs and in sediment and waters of the U.S. Gulf Coast were determined by the most probable number procedure. Species were identified by enzyme immunoassay. During the winter, densities of V. vulnificus were low, and the organism was isolated more frequently from sheepshead fish than from sediment and seawater. From April to October, V. vulnificus densities were considerably higher (2 to 5 logs) in estuarine fish than in surrounding water, sediment, or nearby oysters and crustacea. Highest densities were found in the intestinal contents of certain bottom-feeding fish (10(8)/100 g), particularly those that consume mollusks and crustaceans. Densities of V. vulnificus in fish that feed primarily on plankton and other finfish were similar to those in oysters, sediment, and crabs (10(5)/100 g). V. vulnificus was found infrequently in offshore fish. The presence of high densities of V. vulnificus in the intestines of common estuarine fish may have both ecological (grown th and transport) and public health (food and wound infections) implications. C1 UNIV SO ALABAMA,DEPT MARINE SCI,MOBILE,AL 36688. UNIV ALABAMA,DEPT BIOL SCI,HUNTSVILLE,AL 35899. RP DEPAOLA, A (reprint author), US FDA,GULF COAST SEAFOOD LAB,POB 158,DAUPHIN ISL,AL 36528, USA. NR 31 TC 118 Z9 120 U1 1 U2 2 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 1994 VL 60 IS 3 BP 984 EP 988 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA MZ137 UT WOS:A1994MZ13700032 PM 8161189 ER PT J AU BERKOWITZ, DB KRYSPINSORENSEN, I AF BERKOWITZ, DB KRYSPINSORENSEN, I TI TRANSGENIC FISH - SAFE TO EAT - A LOOK AT THE SAFETY CONSIDERATIONS REGARDING FOOD TRANSGENICS SO BIO-TECHNOLOGY LA English DT Article ID PRODUCE TETRODOTOXIN; RESISTIBILITY; PUFFERFISH C1 NATL FOOD AGCY DENMARK,INST TOXICOL,DK-2860 SOBORG,DENMARK. RP BERKOWITZ, DB (reprint author), US FDA,OFF SMALL BUSINESS SCI & TRADE AFFAIRS,HF-50,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 33 TC 20 Z9 21 U1 0 U2 4 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0733-222X J9 BIO-TECHNOL JI Bio-Technology PD MAR PY 1994 VL 12 IS 3 BP 247 EP 252 DI 10.1038/nbt0394-247 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA MZ550 UT WOS:A1994MZ55000018 ER PT J AU HUNG, HMJ AF HUNG, HMJ TI TESTING FOR THE EXISTENCE OF A DESIRABLE DOSE COMBINATION SO BIOMETRICS LA English DT Letter RP HUNG, HMJ (reprint author), US FDA,DIV BIOMETR,ROOM 18B-45,HFD-713,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1994 VL 50 IS 1 BP 307 EP 308 PG 2 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA NH265 UT WOS:A1994NH26500035 PM 8086612 ER PT J AU MURGO, AJ CONTRERA, JG SISTARE, FD AF MURGO, AJ CONTRERA, JG SISTARE, FD TI EVIDENCE FOR SEPARATE CALCIUM-SIGNALING P-2T AND P-2U PURINOCEPTORS IN HUMAN MEGAKARYOCYTIC DAMI CELLS SO BLOOD LA English DT Article ID INDUCED PLATELET ACTIVATION; ADENYLATE-CYCLASE; ADENOSINE 5'-DIPHOSPHATE; GLYCOPROTEIN-IIB; IP3 FORMATION; BINDING-SITE; SHAPE CHANGE; ADP; RECEPTORS; INHIBITION C1 US FDA,CTR DRUG EVALUAT & RES,OFF RES RESOURCES,DIV RES & TESTING,LAUREL,MD 20708. NR 37 TC 31 Z9 31 U1 0 U2 0 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 MAR 1 PY 1994 VL 83 IS 5 BP 1258 EP 1267 PG 10 WC Hematology SC Hematology GA MZ289 UT WOS:A1994MZ28900014 PM 8118030 ER PT J AU DOERGE, DR DECKER, CJ AF DOERGE, DR DECKER, CJ TI INHIBITION OF PEROXIDASE-CATALYZED REACTIONS BY ARYLAMINES - MECHANISM FOR THE ANTITHYROID ACTION OF SULFAMETHAZINE SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HORSERADISH-PEROXIDASE; OXIDATION; LACTOPEROXIDASE; RATS; IDENTIFICATION; SULFONAMIDES; INACTIVATION; GLUTATHIONE; REDUCTION; TYROSINE AB Sulfonamide antibotics, typified by sulfamethazine (SMZ), are widely sed in veterinary practice. Sulfonamide residues in milk and meat products are of regulatory concern since SMZ is a thyroid carcinogen in rodents and sulfonamide-induced hypersensitivity reactions, including hypothyroidism, have been reported in humans. SMZ and other primary arylamines inhibited iodination reactions catalyzed by thyroid peroxidase (TPO) and the closely related lactoperoxidase (LPO). Inhibition of LPO-catalyzed triiodide ion formation by SMZ and other primary arylamines was complex as both apparent K(m) and V(max) values were affected, but consistent with a rapid equilibrium binding mechanism. The apparent K(i) for SMZ inhibition of TPO- and LPO-catalyzed iodide ion oxidation was approximately 0.42 and 0.11 mM, respectively. The corresponding K(i) values for a series of para-substituted anilines correlated with the ease of one-electron N-oxidation as measured by ionization potentials determined from semiempirical molecular orbital calculations. The aniline derivatives containing electron-donating substituents (e.g., p-CH3, p-OEt, p-Cl) were converted by LPO to colored products characteristic of one-electron oxidation. However, sulfonamides were not consumed in such reactions nor were any N-oxygenated derivatives formed in the absence of ascorbate (e.g., hydroxylamino, nitroso, nitro, azoxy). These observations suggest that the primary mechanism for sulfonamide-induced hypothyroidism is reversible inhibition of TPO-mediated thyroid hormone synthesis and not the formation and covalent binding of reactive N-oxygenated metabolites. These results are consistent with a hormonal mechanism for SMZ-induced thyroid carcinogenesis mediated by thyroid-stimulating hormone (TSH). This nongenotoxic mechanism predicts that a threshold dose exists for carcinogenic effects in the thyroid and suggests that minimal carcinogenic risks are associated with consumption of trace amounts of sulfonamide antibiotics in current food supplies. C1 BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. RP DOERGE, DR (reprint author), NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079, USA. NR 40 TC 37 Z9 38 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR-APR PY 1994 VL 7 IS 2 BP 164 EP 169 DI 10.1021/tx00038a008 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA ND492 UT WOS:A1994ND49200008 PM 8199304 ER PT J AU GROSS, PA LEVANDOWSKI, RA RUSSO, C WEKSLER, M BONELLI, J DRAN, S MUNK, G DEICHMILLER, S HILSEN, R PANUSH, RF AF GROSS, PA LEVANDOWSKI, RA RUSSO, C WEKSLER, M BONELLI, J DRAN, S MUNK, G DEICHMILLER, S HILSEN, R PANUSH, RF TI VACCINE IMMUNE-RESPONSE AND SIDE-EFFECTS WITH THE USE OF ACETAMINOPHEN WITH INFLUENZA VACCINE SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID ADVERSE REACTIONS; ASPIRIN AB The purpose of this study was to determine whether acetaminophen impairs the immune response to influenza vaccine. Influenza vaccine is an under-utilized preventive measure, partly because of the unfounded perception that fever and myalgias frequently follow vaccination. While acetaminophen may decrease these infrequent side effects, it may also alter the immune response to vaccination. We compared the effect of acetaminophen with placebo on the humoral immune response to the 1991-1992 commercially available influenza vaccine. We studied 60 healthy, elderly subjects from a geriatric clinic and 20 infirm, elderly subjects from a nursing home. The subjects were randomly assigned to receive placebo or acetaminophen (1,000 mg every 6 h) for 2 days. Acetaminophen did not depress or enhance the immune development of serum hemagglutination inhibition antibody to the three vaccine antigens. The systemic side effects of fever and myalgia were uncommon in both groups. The healthy elderly subjects mounted a significantly better immune response to the influenza virus A/Taiwan/1/86 (H1N1) vaccine strain than did the infirm elderly subjects (geometric mean titer, 115 versus 51; P = 0.003). The functional activity score obtained by using the chronic healthy evaluation component of the Acute Physiology and Chronic Health Evaluation system could be used to distinguish the healthy from the infirm elderly (scores of 1.27 versus 3.75, P < 0.001). Acetaminophen neither depressed nor enhanced the serum antibody response to the vaccine in the healthy and infirm elderly subjects studied. C1 UNIV MED & DENT NEW JERSEY,NEWARK,NJ. CORNELL UNIV,SCH MED,NEW YORK,NY 10021. WOODCREST CTR,NEW MILFORD,NJ. ST BARNABAS HOSP,LIVINGSTON,NJ. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. RP GROSS, PA (reprint author), HACKENSACK MED CTR,DEPT INTERNAL MED,30 PROSPECT AVE,HACKENSACK,NJ 07061, USA. FU PHS HHS [223-90-1102] NR 22 TC 9 Z9 9 U1 0 U2 2 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 1994 VL 1 IS 2 BP 134 EP 138 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PT562 UT WOS:A1994PT56200002 PM 7496933 ER PT J AU JORDAN, A AF JORDAN, A TI TOXICOLOGY OF DEPOT MEDROXYPROGESTERONE ACETATE SO CONTRACEPTION LA English DT Article DE DMPA; PROGESTOGENS; TOXICOLOGY; CARCINOGENICITY ID CONTRACEPTIVE STEROIDS; MAMMARY-TUMORS; GROWTH-HORMONE; MPA; EMBRYOTOXICITY; PROGESTERONE; PROLACTIN; MICE; RAT AB Depo-Provera (depot-medroxyprogesterone acetate or DMPA), administered either subcutaneously or intramuscularly, has undergone a thorough toxicological evaluation in a number of animal species. DMPA has been tested in short- and long-term toxicity studies in rodents, rabbits, and monkeys. It has been examined for its effects on reproduction in mice, rats, and rabbits, and for carcinogenic potential in rats, mice, beagle dogs, and rhesus monkeys. Genotoxicity tests have been performed in vitro and in vivo. This paper describes the toxicology data submitted to the US FDA in support of the New Drug Application (NDA) for Depo-Provera as well as data published in the literature. When interpreted in the light of the available pharmacokinetic information, these data demonstrate that DMPA is not significantly different from other contraceptive progestogens in its toxic and tumorigenic potential. RP JORDAN, A (reprint author), US FDA,DIV METAB & ENDOCRINE DRUG PROD,WASHINGTON,DC 20204, USA. NR 39 TC 11 Z9 11 U1 1 U2 5 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0010-7824 J9 CONTRACEPTION JI Contraception PD MAR PY 1994 VL 49 IS 3 BP 189 EP 201 DI 10.1016/0010-7824(94)90037-X PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA NC848 UT WOS:A1994NC84800002 PM 8200213 ER PT J AU MORASSO, MI JAMRICH, M SARGENT, TD AF MORASSO, MI JAMRICH, M SARGENT, TD TI THE HOMEODOMAIN GENE XENOPUS DISTAL-LESS-LIKE-2 (XDLL-2) IS REGULATED BY A CONSERVED MECHANISM IN AMPHIBIAN AND MAMMALIAN EPIDERMIS SO DEVELOPMENTAL BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR AP-2; DISTAL-LESS; LIMB DEVELOPMENT; RESTRICTED EXPRESSION; DEVELOPING FOREBRAIN; DROSOPHILA EMBRYO; LAEVIS EMBRYOS; HOMEOBOX GENES; KERATIN GENE; DIFFERENTIATION AB Xenopus Distal-less-like-2 (Xdll-2) is a gene encoding a homeodomain protein expressed predominantly in the epidermis of frog embryos. We report here that this epidermal expression is specified by a regulatory 5' flanking DNA region located within 933 bp of the start of transcription. This regulatory DNA also confers upon a globin reporter gene calcium-inducible expression in cultured murine keratinocytes and induction-dependent repression in frog ectodermal cells treated in vitro with activin A. These results reveal a new example of phylogenetically conserved, tissue-specific transcriptional regulation of a homeodomain gene. (C) 1994 Academic Press, Inc. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. US FDA,DIV CELLULAR & GENE THERAPY,DEV BIOL LAB,BETHESDA,MD 20892. NR 71 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR PY 1994 VL 162 IS 1 BP 267 EP 276 DI 10.1006/dbio.1994.1084 PG 10 WC Developmental Biology SC Developmental Biology GA MZ920 UT WOS:A1994MZ92000024 PM 7907299 ER PT J AU HONIG, PK WORTHAM, DC ZAMANI, K CANTILENA, LR AF HONIG, PK WORTHAM, DC ZAMANI, K CANTILENA, LR TI COMPARISON OF THE EFFECT OF THE MACROLIDE ANTIBIOTICS ERYTHROMYCIN, CLARITHROMYCIN AND AZITHROMYCIN ON TERFENADINE STEADY-STATE PHARMACOKINETICS AND ELECTROCARDIOGRAPHIC PARAMETERS SO DRUG INVESTIGATION LA English DT Article ID LONG QT SYNDROME; ANTIMICROBIAL ACTIVITY; CYTOCHROME-P-450; QUINIDINE; EFFICACY AB Terfenadine is a nonsedating histamine H-1-antagonist that, when given with ketoconazole, results in accumulation of parent terfenadine and altered cardiac repolarisation in susceptible individuals. This prospective cohort study, designed to assess macrolide effects on terfenadine pharmacokinetics and electrocardiogram (ECG) parameters, evaluated 18 healthy male and female volunteers who received terfenadine to steady-state. Equal numbers (6) were randomised to receive either erythromycin, clarithromycin or azithromycin at recommended doses while continuing terfenadine. Macrolide monotherapy effects on the ECG were also investigated. Pharmacokinetic profiles for terfenadine were performed before and after the addition of macrolide therapy, and ECGs were obtained at baseline and predose on days of blood sampling. Erythromycin and clarithromycin significantly affected the pharmacokinetics of terfenadine. Three of 6 volunteers receiving erythromycin and 4 of 6 receiving clarithromycin demonstrated accumulation of quantifiable unmetabolised terfenadine that was associated with altered cardiac repolarisation. Azithromycin had no effect on terfenadine pharmacokinetics or cardiac pharmacodynamics. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,DIV CLIN PHARMACOL,4301 JONES BRIDGE RD,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. WALTER REED ARMY MED CTR,DIV CARDIOL,WASHINGTON,DC 20307. US FDA,ROCKVILLE,MD 20857. RI Zamani, Kaveh/A-9182-2011 NR 27 TC 73 Z9 73 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-2402 J9 DRUG INVEST PD MAR PY 1994 VL 7 IS 3 BP 148 EP 156 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NB881 UT WOS:A1994NB88100005 ER PT J AU KLECKER, RW JAMISDOW, CA EGORIN, MJ ERKMEN, K PARKER, RJ STEVENS, R COLLIN, JM AF KLECKER, RW JAMISDOW, CA EGORIN, MJ ERKMEN, K PARKER, RJ STEVENS, R COLLIN, JM TI EFFECT OF CIMETIDINE, PROBENECID, AND KETOCONAZOLE ON THE DISTRIBUTION, BILIARY-SECRETION, AND METABOLISM OF [H-3] TAXOL IN THE SPRAGUE-DAWLEY RAT SO DRUG METABOLISM AND DISPOSITION LA English DT Article AB Male Sprague-Dawley rats had their bile ducts cannulated and were dosed with [H-3]taxol (2 mg/kg, 68-77 mu Ci/mg) as a continuous intravenous infusion for 6 hr so that the plasma concentrations, tissue distribution, metabolism, and biliary secretion of taxol could be studied. Defining potential drug-drug interactions of taxol with cimetidine (90 mg/kg), probenecid (360 mg/kg), and ketoconazole (50 mg/kg) was motivated by frequent concomitant clinical use or the potential to reduce clearance of taxol so that lower doses could be used. At 6 hr, rats were killed. Samples of blood (plasma), lung, spleen, liver, kidney, heart, skeletal muscle, brain, testes, and fat were obtained. Taxol and metabolites were measured by total radioactivity counting and HPLC separation using on-line radioactivity detection. Concentrations of taxol in plasma increased to 0.19 mu M in the control rats and did not reach steady-state by 6 hr. Lung, spleen, liver, and kidneys had the greatest tissue taxol concentrations [4.7-5.7 nmol/g (mu M)] and were > 25-fold higher than the simultaneous 6-hr plasma taxol concentration. Taxol concentrations in brain and testes were negligible, 0.06 and 0.07 nmol/g, respectively. Radioactive metabolites were not found in plasma or most tissues. Only liver had appreciable concentrations of taxol and metabolites; however, > 80% of hepatic radioactivity was parent taxol. Through 6 hr of collection, 24% of the dose was secreted in the bile similar to 38% of which was as parent taxol. Cimetidine had no effect on the distribution, metabolism, or elimination of [H-3]taxol. Probenecid did not effect tissue distribution or plasma concentrations of (axel. Probenecid decreased the biliary secretion of taxol and metabolites by 50%. Rats pretreated with ketoconazole had biliary secretion of taxol, and metabolites decreased to 25% of control with a concomitant increase in plasma taxol concentration. C1 NCI, BETHESDA, MD 20892 USA. UNIV MARYLAND, CTR CANC, BALTIMORE, MD 21201 USA. UNIV MARYLAND, SCH MED, DEPT MED, BALTIMORE, MD 21201 USA. RP KLECKER, RW (reprint author), US FDA, 4 RES COURT, ROOM 314, ROCKVILLE, MD 20850 USA. NR 12 TC 34 Z9 36 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 EI 1521-009X J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAR-APR PY 1994 VL 22 IS 2 BP 254 EP 258 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NB520 UT WOS:A1994NB52000012 PM 7912177 ER PT J AU BANKS, MA PETERS, RC JOHNSON, WA BERLIN, E AF BANKS, MA PETERS, RC JOHNSON, WA BERLIN, E TI EFFECT OF AGE ON SUBCELLULAR-DISTRIBUTION OF VITAMIN-E AND LIPID-PEROXIDATION SUSCEPTIBILITY IN HEARTS FROM MINIATURE SWINE SO FASEB JOURNAL LA English DT Meeting Abstract C1 USDA,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. US FDA,DIV TOXICOL RES,LAUREL,MD 20708. 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 PY 1994 VL 8 IS 4 BP A188 EP A188 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601087 ER PT J AU BERKOWER, I MURPHY, D MOSTOWSKI, H BULL, TE AF BERKOWER, I MURPHY, D MOSTOWSKI, H BULL, TE TI CRITICAL BINDING LEVEL OF CD4 FOR HIV INACTIVATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 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 PY 1994 VL 8 IS 4 BP A495 EP A495 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602866 ER PT J AU BERLIN, E BANKS, MA MCCLURE, D PETERS, RC AF BERLIN, E BANKS, MA MCCLURE, D PETERS, RC TI HEART AND LIVER VITAMIN-E STATUS AND FATTY-ACID PROFILES IN MINIATURE SWINE FED MENHADEN OIL AND CORN-OIL SO FASEB JOURNAL LA English DT Meeting Abstract C1 USDA ARS,BELTSVILLE AGR RES CTR,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. US FDA,DIV TOXICOL RES,LAUREL,MD 20708. 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 PY 1994 VL 8 IS 4 BP A189 EP A189 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601095 ER PT J AU BERN, C AF BERN, C TI THE USE OF RETROSPECTIVE DIET ASSESSMENT IN A FIELD INVESTIGATION OF EPIDEMIC NEUROPATHY SO FASEB JOURNAL LA English DT Meeting Abstract C1 CTR DIS CONTROL,ATLANTA,GA 30333. MINIST SALUD PUBL,HAVANA,CUBA. PAN AMER HLTH ORG,WASHINGTON,DC 20037. NIH,BETHESDA,MD 20892. US FDA,WASHINGTON,DC 20204. EMORY UNIV,ATLANTA,GA 30322. 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 PY 1994 VL 8 IS 4 BP A441 EP A441 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602553 ER PT J AU BLAKELY, SR BROWN, ED BABU, U GRUNDEL, E MITCHELL, GV AF BLAKELY, SR BROWN, ED BABU, U GRUNDEL, E MITCHELL, GV TI BIOAVAILABILITY OF CAROTENOIDS IN TOMATO PASTE AND DRIED SPINACH AND THEIR INTERACTIONS WITH CANTHAXANTHIN SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. NR 0 TC 1 Z9 1 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 PY 1994 VL 8 IS 4 BP A192 EP A192 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601108 ER PT J AU BRORSON, KA KRASNOKUTSKY, MV TIFFANY, LJ STEIN, KE AF BRORSON, KA KRASNOKUTSKY, MV TIFFANY, LJ STEIN, KE TI ISOTYPE SWITCHING IN XID MICE SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CBER,DIV MONOCLONAL ANTIBODIES,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 PY 1994 VL 8 IS 4 BP A471 EP A471 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602724 ER PT J AU CASSIDY, M SATCHITHANANDAM, S CALVERT, RJ KLURFELD, D AF CASSIDY, M SATCHITHANANDAM, S CALVERT, RJ KLURFELD, D TI CHRONIC FEEDING OF PSYLLIUM FIBER INCREASES MUCUS AVAILABILITY AND SECRETION IN RAT COLON SO FASEB JOURNAL LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,DEPT PHYSIOL,WASHINGTON,DC 20052. US FDA,LAUREL,MD. WAYNE STATE UNIV,DETROIT,MI 48202. 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 PY 1994 VL 8 IS 4 BP A566 EP A566 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19603274 ER PT J AU CASTERLINE, JL OLES, C KU, Y AF CASTERLINE, JL OLES, C KU, Y TI IN-VITRO FERMENTATION OF DIETARY FIBER ISOLATES 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 PY 1994 VL 8 IS 4 BP A186 EP A186 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601075 ER PT J AU DONNELLY, RP FREEMAN, SL AF DONNELLY, RP FREEMAN, SL TI COORDINATE REGULATION OF NF-KAPPA-B AND I-KAPPA-B SYNTHESIS IN LIPOPOLYSACCHARIDE (LPS)-STIMULATED MONOCYTIC CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CBER,DIV CYTOKINE BIOL,BETHESDA,MD 20205. 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 PY 1994 VL 8 IS 4 BP A214 EP A214 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601233 ER PT J AU GALLO, L SUBRAMANIAN, S TOUB, R AF GALLO, L SUBRAMANIAN, S TOUB, R TI ROLE OF CHOLESTEROL ESTERASE (CEASE) AND ACAT ON CHOLESTEROL (C) ABSORPTION IN RATS FED INCREASING CHOLESTEROL LOADS SO FASEB JOURNAL LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. US FDA,BELTSVILLE,MD 20708. 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 PY 1994 VL 8 IS 4 BP A452 EP A452 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602614 ER PT J AU HOHE, DF BLOOM, ET AF HOHE, DF BLOOM, ET TI IL-12 AND IL-2 SYNERGIZE TO INCREASE PERFORIN AND SERINE ESTERASE GENE-TRANSCRIPTION BY FRESH HUMAN NK CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CBER,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,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 PY 1994 VL 8 IS 4 BP A512 EP A512 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602965 ER PT J AU LATHERS, CM SCHRAEDER, PL AF LATHERS, CM SCHRAEDER, PL TI CLINICAL-PHARMACOLOGY PROBLEM-SOLVING (CPPS) UNIT, CLINICAL-PHARMACOLOGY OF ANTIEPILEPTIC DRUG (AED) USE, CLINICAL PEARLS ABOUT THE PERILS OF PATTY SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. UMDNJ,ROBERT WOOD JOHNSON MED SCH,CAMDEN,NJ 08103. 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 PY 1994 VL 8 IS 4 BP A564 EP A564 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19603267 ER PT J AU LAVU, S SRIVASTAVA, M KORNHAUSER, A SRIVASTAVA, S AF LAVU, S SRIVASTAVA, M KORNHAUSER, A SRIVASTAVA, S TI ANALYSIS OF THE TUMOR-SUPPRESSOR GENE P53 IN XERODERMA-PIGMENTOSUM FIBROBLASTS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDKO,BETHESDA,MD 20814. USUHSI,BETHESDA,MD 20814. US FDA,LAUREL,MD 20814. 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 PY 1994 VL 8 IS 4 BP A391 EP A391 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602263 ER PT J AU MYERS, MJ FARRELL, DE HENDERSON, M COPE, C EVOCKCLOVER, CM STEELE, NC AF MYERS, MJ FARRELL, DE HENDERSON, M COPE, C EVOCKCLOVER, CM STEELE, NC TI ENDOTOXIN-INDUCED CHANGES IN BLOOD-GLUCOSE, TNF-ALPHA AND IL-6 IN DOMESTIC SWINE SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,BELTSVILLE,MD 20705. USDA,BELTSVILLE,MD 20705. NR 0 TC 0 Z9 0 U1 2 U2 2 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 PY 1994 VL 8 IS 4 BP A222 EP A222 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601282 ER PT J AU PERRIN, PJ SCOTT, D QUIGLY, L FEDER, O DAVIS, T GRAY, G JUNE, CH RACKE, M AF PERRIN, PJ SCOTT, D QUIGLY, L FEDER, O DAVIS, T GRAY, G JUNE, CH RACKE, M TI ROLE OF B7-1/B7-2-CD28/CTLA-4 INTERACTION IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS SO FASEB JOURNAL LA English DT Meeting Abstract C1 USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20814. US FDA,BETHESDA,MD 20014. NINCDS,BETHESDA,MD 20892. REPLIGEN CORP,CAMBRIDGE,MA. 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 PY 1994 VL 8 IS 4 BP A198 EP A198 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601141 ER PT J AU PINE, PS ASZALOS, A AF PINE, PS ASZALOS, A TI COMPARISON OF SUBSTRATE BEHAVIOR OF DAUNORUBICIN AND ITS N-ACYL DERIVATIVES IN MULTIDRUG-RESISTANT CELL-LINES SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,DIV RES & TESTING,WASHINGTON,DC 20204. 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 PY 1994 VL 8 IS 4 BP A97 EP A97 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600561 ER PT J AU SATCHITHANANDAM, S WIESENFELD, P FLYNN, T TASHIRO, Y CALVERT, RJ KRITCHEVSKY, D AF SATCHITHANANDAM, S WIESENFELD, P FLYNN, T TASHIRO, Y CALVERT, RJ KRITCHEVSKY, D TI ABSORPTION OF DIETARY-CHOLESTEROL AND OLEIC-ACID IN THE PRESENCE OF PEANUT OIL OR RANDOMIZED PEANUT OIL SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,LAUREL,MD. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. 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 PY 1994 VL 8 IS 4 BP A451 EP A451 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602607 ER PT J AU SOWELL, A AF SOWELL, A TI NUTRITIONAL-STATUS IN THE CUBA OPTIC NEUROPATHY STUDY SO FASEB JOURNAL LA English DT Meeting Abstract C1 CTR DIS CONTROL,ATLANTA,GA 30333. MINIST SALUD PUBL,HAVANA,CUBA. PAN AMER HLTH ORG,WASHINGTON,DC 20037. EMORY UNIV,ATLANTA,GA 30322. US FDA,WASHINGTON,DC 20204. 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 PY 1994 VL 8 IS 4 BP A441 EP A441 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602550 ER PT J AU SUNDARESAN, PR AF SUNDARESAN, PR TI SEX-DIFFERENCES IN EFFECTS OF DIETARY FLAXSEED ON VITAMIN-A STATUS IN WEANLING SPRAGUE-DAWLEY RATS FED NRC REQUIREMENT LEVELS OF VITAMIN-A SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,LAUREL,MD 20708. 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 PY 1994 VL 8 IS 4 BP A445 EP A445 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602576 ER PT J AU TASHIRO, Y SATCHITHANDAM, S CERNIGLIA, C CALVERT, RJ AF TASHIRO, Y SATCHITHANDAM, S CERNIGLIA, C CALVERT, RJ TI EFFECT OF FRUCTOOLIGOSACCHARIDES ON GASTROINTESTINAL FUNCTION SO FASEB JOURNAL LA English DT Meeting Abstract C1 MEIJI SEIKA KAISHA LTD,TOKYO 104,JAPAN. US FDA,LAUREL,MD 20708. 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 PY 1994 VL 8 IS 4 BP A185 EP A185 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601069 ER PT J AU WIESENFELD, P YAMINI, S CHANDERBAHN, R AF WIESENFELD, P YAMINI, S CHANDERBAHN, R TI COMPARISON OF ADRENAL PHOSPHOLIPID FATTY-ACID PROFILES IN OBESE AND LEAN SHR/N-CP MALE-RATS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,LAUREL,MD. UNIV MARYLAND,COLL PK,MD 20742. 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 PY 1994 VL 8 IS 4 BP A169 EP A169 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600979 ER PT J AU SCHWARTZ, PS AF SCHWARTZ, PS TI UPDATE ON MIGRATION RESEARCH AND REGULATORY INITIATIVES SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article; Proceedings Paper CT 6th International Symposium on Migration in Food Packaging Plastics CY MAY 19-20, 1992 CL AMSTERDAM, NETHERLANDS SP ICI WILTON RES CTR, PIRA INT DE MIGRATION; FOOD ADDITIVE; HEAT SUSCEPTOR; THRESHOLD OF REGULATION AB The Food and Drug Administration's (FDA) current research programme on migration from food packaging materials focuses on high-temperature packaging applications. Results from two studies conducted by Arthur D. Little, Inc., under contract to the FDA, are presented as well as highlights of the FDA's research programme on migration from microwave heat susceptor packaging. Some regulatory policy issues affecting the FDA's future regulation of food packaging materials are also examined. RP SCHWARTZ, PS (reprint author), US FDA,WASHINGTON,DC 20204, USA. NR 0 TC 3 Z9 3 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD MAR-APR PY 1994 VL 11 IS 2 BP 261 EP 270 PG 10 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA NK173 UT WOS:A1994NK17300014 PM 8039586 ER PT J AU WEST, RW SHELDON, WG GAYLOR, DW ALLEN, RR KADLUBAR, FF AF WEST, RW SHELDON, WG GAYLOR, DW ALLEN, RR KADLUBAR, FF TI STUDY OF SODIUM SACCHARIN CO-CARCINOGENICITY IN THE RAT SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID URINARY-BLADDER CARCINOGENESIS; METHYL-N-NITROSOUREA; DOSE-RESPONSE; INDUCTION; N-<4-(5-NITRO-2-FURYL)-2-THIAZOLYL>FORMAMIDE; CANCER; TOXICOLOGY; TRYPTOPHAN; CYCLAMATE; PROMOTION AB A co-carcinogenicity experiment was conducted with female Sprague-Dawley rats in which the effects of short-term sodium saccharin dosing and initiation with a direct-acting carcinogen were examined in the urinary bladder. All initiated animals were administered 0.5 mg N-methyl-N-nitrosourea (MNU) by instillation into the bladder at 8 wk of age. The animals were also given saccharin at one of four levels in the diet (0, 1.0, 2.5 or 5%) for 4 wk either (1) just before treatment with MNU (4-8 wk of age), (2) centred on treatment with MNU (6-10 wk of age) or (3) after MNU treatment (8-12 wk of age). Additionally, a group of animals was exposed to saccharin through the milk for 3 wk by dosing the mothers, starting on the day of parturition. The animals were held on control diet until interim killing of 20 animals per group at about 590 days of age, removal for morbidity, or terminal killing of the remainder of 60 animals per treatment around 780 days of age. A histopathological examination was made of the urinary tract and the relationship of saccharin dose to bladder tumour prevalence analysed statistically. A consistent increase (with very weak statistical significance) in tumour rate at interim killing, and for the pathology data overall, was shown by the 2.5% dose group given saccharin from 8 to 12 wk of age. Tumour prevalences of 47.6 and 40.7% v. control prevalences of 21.1 and 25.4% were observed for the two time periods (P values <0.076 and <0.0853, respectively). All groups given saccharin neonatally showed increased tumour prevalence for both time periods, but none of the differences was statistically significant at the 95% confidence level. No consistent increase in tumour prevalence was seen in the groups given saccharin from 4 to 8 or 6 to 10 wk of age; thus, these data suggest that saccharin does not act as a strong cocarcinogen in the MNU-treated rat bladder. C1 NATL CTR TOXICOL RES,PATHOL ASSOCIATES INC,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,BIOMETRY STAFF,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,COMP BASED SYST INC,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,RES OFF,JEFFERSON,AR 72079. RP WEST, RW (reprint author), NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079, USA. NR 24 TC 5 Z9 5 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 1994 VL 32 IS 3 BP 207 EP 213 DI 10.1016/0278-6915(94)90192-9 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA NG419 UT WOS:A1994NG41900001 PM 8157214 ER PT J AU SUNDARESAN, PR COLLINS, TFX WHITBY, KE WELSH, JJ BLACK, TN SHACKELFORD, M FLYNN, T NEWELL, RF ODONNELL, MW AF SUNDARESAN, PR COLLINS, TFX WHITBY, KE WELSH, JJ BLACK, TN SHACKELFORD, M FLYNN, T NEWELL, RF ODONNELL, MW TI EFFECT OF ETHANOL AND VITAMIN-A EXCESS ON VITAMIN-A STATUS IN THE LIVER, PLASMA AND FETUSES OF PREGNANT RATS SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID BETA-CAROTENE; RETINOIC ACID; FAT DIET; METABOLISM; CONSUMPTION; MICROSOMES; MODERATE; ALCOHOL AB The effect of maternal consumption of dietary ethanol and high doses of vitamin A by gavage was investigated by evaluating plasma, liver and foetal vitamin A in Osborne-Mendel pregnant rats with a view to assessing whether ethanol modulated the potential toxicity of excess vitamin A. All groups received 4000 IU vitamin A/litre in a liquid diet. Ethanol-exposed groups also received 6.4% (v/v) ethanol in the liquid diet. Vitamin A was administered by gavage once per day in corn oil in doses ranging from 10,000 to 160,000 IU/kg body weight. Plasma vitamin A levels in ethanol-exposed groups were similar to levels in a pair-fed group. Plasma vitamin A levels were similar in the group given ethanol plus 40,000 IU vitamin A/kg and the group given 40,000 IU vitamin A/kg only, but were higher in the group receiving ethanol plus 80,000 IU vitamin A/kg than in the group given 80,000 IU vitamin A/kg only. Retinyl esters were present in the plasma of animals receiving 160,000 IU vitamin A/kg only, indicating possible saturation of the liver with vitamin A. Retinyl palmitate levels in female foetuses of the group administered ethanol plus 80,000 IU vitamin A/kg were significantly higher than those of the group administered 80,000 IU vitamin A/kg only; no significant differences in levels of retinyl palmitate in male foetuses were observed between these two groups. This observation suggests a possible sex difference in the modulation of vitamin A toxicity by ethanol in the foetus. C1 US EPA,OFF PESTICIDE PROGRAMS,WASHINGTON,DC 20460. RP SUNDARESAN, PR (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,HFS-465,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 20 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD MAR PY 1994 VL 32 IS 3 BP 247 EP 254 DI 10.1016/0278-6915(94)90197-X PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA NG419 UT WOS:A1994NG41900006 PM 8157219 ER PT J AU SHACKELFORD, ME COLLINS, TFX BLACK, TN AMES, MJ DOLAN, S SHEIKH, NS CHI, RK ODONNELL, MW AF SHACKELFORD, ME COLLINS, TFX BLACK, TN AMES, MJ DOLAN, S SHEIKH, NS CHI, RK ODONNELL, MW TI MINERAL INTERACTIONS IN RATS FED AIN-76A DIETS WITH EXCESS CALCIUM SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID FEMALE RATS; INTRANEPHRONIC CALCULOSIS; NEPHROCALCINOSIS; ZINC; ABSORPTION; METABOLISM; PHOSPHORUS; MAGNESIUM AB The effects of moderate increases in dietary calcium on maternal and foetal mineral interactions were studied in Charles River CD/VAF Plus rats. Female rats were given 0.50, 0.75, 1.00 or 1.25% dietary calcium as calcium carbonate in AIN-76A diets for 6 wk before mating, during mating and for 20 days of gestation. Inductively coupled argon plasma-atomic emission spectrometry was used to determine mineral levels in the tissues of non-pregnant rats after 42 days on the diets, in the tissues of pregnant rats on day 20 of gestation and in the whole body of day-20 foetuses. The femurs of the non-pregnant and pregnant rats had a dose-related linear increase in calcium content. In livers of the non-pregnant rats, dose-related linear increases in the phosphorus, zinc and magnesium content were observed, but there was a dose-related decrease in the iron content. There were dose-related linear decreases in the iron and copper contents of the kidneys from the non-pregnant rats. In pregnant rats dose-related linear decreases were observed in the iron content of the liver and in the zinc, iron and magnesium contents of the kidney. The foetuses from rats given a moderate increase in dietary calcium had dose-related decreases in the whole-body contents of phosphorus, iron, copper and magnesium. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 35 TC 13 Z9 13 U1 0 U2 0 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 1994 VL 32 IS 3 BP 255 EP 263 DI 10.1016/0278-6915(94)90198-8 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA NG419 UT WOS:A1994NG41900007 PM 8157220 ER PT J AU KESSLER, DA NATANBLUT, S KENNEDY, D LAZAR, E RHEINSTEIN, P ANELLO, C BARASH, D BERNSTEIN, I BOLGER, R COOK, K COUIG, MP DONLON, J JOHNSON, J LORRAINE, C MCGINNIS, T NAZARIO, J NIGHTINGALE, S PECK, C PENDERGAST, M RASTOGI, S REYNOLDS, C SCHAPIRO, R TOLLEFSON, L WION, A AF KESSLER, DA NATANBLUT, S KENNEDY, D LAZAR, E RHEINSTEIN, P ANELLO, C BARASH, D BERNSTEIN, I BOLGER, R COOK, K COUIG, MP DONLON, J JOHNSON, J LORRAINE, C MCGINNIS, T NAZARIO, J NIGHTINGALE, S PECK, C PENDERGAST, M RASTOGI, S REYNOLDS, C SCHAPIRO, R TOLLEFSON, L WION, A TI A NEW APPROACH TO REPORTING MEDICATION AND DEVICE ADVERSE-EFFECTS AND PRODUCT PROBLEMS SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID DRUG EVENTS; SAFETY RP KESSLER, DA (reprint author), US FDA,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 18 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAR PY 1994 VL 16 IS 2 BP 96 EP 101 DI 10.1016/0163-8343(94)90051-5 PG 6 WC Psychiatry SC Psychiatry GA NL442 UT WOS:A1994NL44200005 PM 8039699 ER PT J AU KASSIS, JA AF KASSIS, JA TI UNUSUAL PROPERTIES OF REGULATORY DNA FROM THE DROSOPHILA ENGRAILED GENE - 3 PAIRING-SENSITIVE SITES WITHIN A 1.6-KB REGION SO GENETICS LA English DT Article ID WHITE GENE; TRANSPOSABLE ELEMENT; TRANSCRIPTION UNIT; ZESTE PROTEIN; BINDING SITES; TRANSVECTION; MELANOGASTER; PATTERN; TRANSFORMATION; EXPRESSION AB We have previously shown that a 2-kb fragment of engrailed DNA can suppress expression of a linked marker gene, white, in the P element vector CaSpeR. This suppression is dependent on the presence of two copies of engrailed DNA-containing P elements (P[en]) in proximity in the Drosophila genome (either in cis or in trans). In this study, the 2-kb fragment was dissected and found to contain three fragments of DNA which could mediate while suppression [called ''pairing-sensitive sites'' (PS)]. A PS site was also identified in regulatory DNA from the Drosophila escargot gene. The eye colors of six different P[en] insertions in the escargot gene suggest an interaction between P[en]-encoded and genome-encoded PS sites. I hypothesize that white gene expression from P[en] is repressed by the formation of a protein complex which is initiated at the engrailed PS sites and also requires interactions with flanking genomic DNA. Genes were sought which influence the function of PS sites. Mutations in some Polycomb and trithorax group genes were found to affect the eye color from some P[en] insertion sites. However, different mutations affected expression from different P[en] insertion sites and no one mutation was found to affect expression from all P[en] insertion sites examined. These results suggest that white expression from P[en] is not directly regulated by members of the Polycomb and trithorax group genes, but in some cases can be influenced by them. I propose that engrailed PS sites normally act to promote interactions between distantly located engrailed regulatory sites and the engrailed promoter. RP KASSIS, JA (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,DEV BIOL LAB,BETHESDA,MD 20892, USA. OI Kassis, Judith/0000-0001-9268-3213 NR 49 TC 132 Z9 134 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD MAR PY 1994 VL 136 IS 3 BP 1025 EP 1038 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA MZ474 UT WOS:A1994MZ47400029 PM 8005412 ER PT J AU MOMENAN, R WAGNER, RF GARRA, BS LOEW, MH INSANA, MF AF MOMENAN, R WAGNER, RF GARRA, BS LOEW, MH INSANA, MF TI IMAGE STAINING AND DIFFERENTIAL-DIAGNOSIS OF ULTRASOUND SCANS BASED ON THE MAHALANOBIS DISTANCE SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article ID PATTERN-RECOGNITION; LIVER-DISEASE; CLASSIFICATION; PERFORMANCE; TEXTURE; SPECKLE AB We have previously reported on the ability to detect and discriminate among several diffuse disease states in human liver using a four-dimensional feature space derived from the statistical physics of ultrasound B-scan speckle. No image resulted from this method of supervised classification. In the present work the covariance matrices associated with each state of health or disease from that study are used as the basis of an image staining display technique for aid in quantitative differential diagnosis. A state of health or disease is chosen by the clinician: this selects the covariance matrix from the data base. A region of interest (ROI) is then scrolled through an abdominal B-scan. For each position of the ROI a point in the four-dimensional feature space is calculated. A natural measure of the distance of this point from the center of mass (multivariate mean) of the disease class is calculated in terms of the covariance matrix of this class; this measure is the Mahalanobis distance. The confidence level for acceptance or rejection of the hypothesized disease class is obtained from the probability distribution of this distance, the T2 probability law. This confidence level is color coded and used as a color stain that overlays the original scan at that position. The variability of the calculated features is studied as a function of ROI size, or the spatial resolution of the color coded image, and it is found that for an ROI in the neighborhood of 4 cm2 most of the variability due to the finite number of independent samples (speckles) is averaged out, leaving the ''noise floor'' associated with inter- and intra-patient variability. ROIs on the order of 1 cm2 may result with technical advances in B-scan resolution. A small number of points on organ boundaries are entered by the user, to fit with arcs of ellipses to be used to switch between organ (liver and kidney) data bases as the ROI encounters the boundary. By selecting in turn various state-of-health or state-of-disease databases, such images of confidence levels may be used for quantitative differential diagnosis. The method is not limited to ultrasound, being applicable in principle to features obtained from any modality or multimodality combination. C1 GEORGE WASHINGTON UNIV,DEPT ELECT ENGN & COMP SCI,WASHINGTON,DC 20052. FDA,OFF SCI & TECHNOL,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD. GEORGETOWN UNIV,MED CTR,DEPT ABDOMINAL IMAGING,WASHINGTON,DC 20007. UNIV KANSAS,MED CTR,DEPT DIAGNOST RADIOL,KANSAS CITY,KS 66103. NR 23 TC 12 Z9 13 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAR PY 1994 VL 13 IS 1 BP 37 EP 47 DI 10.1109/42.276143 PG 11 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA NE807 UT WOS:A1994NE80700005 PM 18218482 ER PT J AU MENOZZI, FD MUTOMBO, R RENAULD, G GANTIEZ, C HANNAH, JH LEININGER, E BRENNAN, MJ LOCHT, C AF MENOZZI, FD MUTOMBO, R RENAULD, G GANTIEZ, C HANNAH, JH LEININGER, E BRENNAN, MJ LOCHT, C TI HEPARIN-INHIBITABLE LECTIN ACTIVITY OF THE FILAMENTOUS HEMAGGLUTININ ADHESIN OF BORDETELLA-PERTUSSIS SO INFECTION AND IMMUNITY LA English DT Article ID RESPIRATORY-EPITHELIAL-CELLS; FIBROBLAST GROWTH-FACTOR; VIRULENCE FACTORS; MAMMALIAN-CELLS; PROTEIN; BINDING; SEQUENCE; SURFACE; TOXIN; PURIFICATION AB Bordetella pertussis, the etiologic agent of whooping cough, produces an outer membrane-associated filamentous hemagglutinin (FHA) which is the major adhesin of this organism. FHA exhibits a lectin-like activity for heparin and dextran sulfate. By using in vitro adherence assays to cultured epithelial cells, the attachment of B. pertussis was reduced in the presence of sulfated polysaccharides such as heparin and dextran sulfate but not in the presence of dextran, indicating the crucial role of polysaccharide sulfation. In addition, inhibition of cellular sulfation by chlorate treatment of the cells resulted in a reduction of B. pertussis adherence, suggesting that epithelial cell surface-exposed sulfated glycoconjugates may serve as receptors for the microorganism. B. pertussis mutant strains deficient in FHA production expressed residual adherence that was no longer inhibited by sulfated polysaccharides. In addition, purified FHA displayed heparin-inhibitable binding to epithelial cells. Mapping experiments of the heparin-binding site of FHA indicated that this site is different from the RGD site and the recently proposed carbohydrate-binding site involved in the interaction of PHA with lactosylceramide. This result demonstrates that FHA contains at least three different binding sites, a feature unusual for bacterial adhesins but similar to features of eukaryotic adhesins and extracellular matrix proteins. C1 INST PASTEUR,MICROBIOL GENET & MOLEC LAB,INSERM,CJF 9109,F-59019 LILLE,FRANCE. INST PASTEUR,CTR IMMUNOL & BIOL PARASITAIRE,CNRS 624,INSERM 167,F-59019 LILLE,FRANCE. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 56 TC 118 Z9 120 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 MAR PY 1994 VL 62 IS 3 BP 769 EP 778 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MX798 UT WOS:A1994MX79800001 PM 8112848 ER PT J AU FRANZOSO, G HU, PC MELONI, GA BARILE, MF AF FRANZOSO, G HU, PC MELONI, GA BARILE, MF TI IMMUNOBLOT ANALYSES OF CHIMPANZEE SERA AFTER INFECTION AND AFTER IMMUNIZATION AND CHALLENGE WITH MYCOPLASMA-PNEUMONIAE SO INFECTION AND IMMUNITY LA English DT Article ID RESPIRATORY EPITHELIUM; MONOCLONAL-ANTIBODIES; MEMBRANE-PROTEIN; P1 OPERON; ATTACHMENT; IDENTIFICATION; HEMADSORPTION; GENITALIUM; STRAINS; EPIDEMIOLOGY AB Consecutive weekly or biweekly serum specimens obtained during a 3- or 4-month study from 16 chimpanzees were examined by immunoblot analyses to identify the immunogenic components of Mycoplasma pneumoniae. Six experimentally infected chimpanzees showed significant signs of overt disease, including cough, pharyngitis, rhinitis, fever, and loss of appetite. The sera of these infected chimpanzees recognized from 17 to 20 protein bands. Two control chimpanzees that were not inoculated were included in the study. Three chimpanzees immunized with a formalin-inactivated OSU-1A vaccine and three chimpanzees immunized with an experimental acellular vaccine showed minimal signs of disease on challenge. After challenge, the serum immunoblot responses of the immunized chimpanzees were similar to those of the infected chimpanzees. Before challenge, the sera of two previously infected chimpanzees recognized protein bands of 169 (which comigrated with the P1 adhesin), 148, 130, 117, 86, 61, 44, 35, 30, and 29 kDa. After challenge, the previously infected chimpanzees showed the most intense serum immunoblot responses and were most protected against colonization and disease. The sera from each of the 16 chimpanzees examined recognized a large number of immunogenic components, and the serum immunoblot responses were virtually identical to those of patients. Sera from each chimpanzee and patient recognized 169-, 148-, 130-, 117-, 86-, 44-, and 35-kDa bands and many of them recognized 67-, 63-, 61-, 56-, 32-, 30-, and 29-kDa protein hands. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,MYCOPLASMA LAB,BETHESDA,MD 20892. UNIV N CAROLINA,SCH MED,DEPT PEDIAT,CHAPEL HILL,NC 27599. UNIV PADUA,IST MICROBIOL,PADUA,ITALY. NR 58 TC 9 Z9 9 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 1994 VL 62 IS 3 BP 1008 EP 1014 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MX798 UT WOS:A1994MX79800036 PM 8112834 ER PT J AU MINK, CM OBRIEN, CH WASSILAK, S DEFOREST, A MEADE, BD AF MINK, CM OBRIEN, CH WASSILAK, S DEFOREST, A MEADE, BD TI ISOTYPE AND ANTIGEN-SPECIFICITY OF PERTUSSIS AGGLUTININS FOLLOWING WHOLE-CELL PERTUSSIS VACCINATION AND INFECTION WITH BORDETELLA-PERTUSSIS SO INFECTION AND IMMUNITY LA English DT Note ID CHILDREN; ANTIBODY; PROTEIN AB Elevated agglutinin titers have been shown to correlate with protection from disease following whole-cell pertussis vaccination, but the isotype and antigen specificity of human agglutinating antibodies is unknown. In 13 immunoassays, immunoglobulin G antifimbria antibodies had the strangest correlation with agglutinin titers following culture-proven infection with Bordetella pertussis (R' = 0.79; P < 0.0001) and following whole-cell pertussis vaccination (R' = 0.87, P < 0.0001). C1 CTR DIS CONTROL & PREVENT,DIV IMMUNIZAT,ATLANTA,GA. TEMPLE UNIV,ST CHRISTOPHERS HOSP CHILDREN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA. US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,PERTUSSIS LAB,BETHESDA,MD 20892. NR 16 TC 23 Z9 23 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 MAR PY 1994 VL 62 IS 3 BP 1118 EP 1120 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MX798 UT WOS:A1994MX79800050 PM 7509316 ER PT J AU SHEPPARD, BS CARUSO, JA AF SHEPPARD, BS CARUSO, JA TI PLASMA-MASS SPECTROMETRY - CONSIDER THE SOURCE INVITED LECTURE SO JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY LA English DT Article; Proceedings Paper CT XXVIII Colloquium Spectroscopicum Internationale and Post-Symposia on Glow Discharge Techniques, Plasma Source Mass Spectrometry and Graphite Atomizer Techniques CY JUN 29-JUL 07, 1993 CL YORK, ENGLAND DE INDUCTIVELY COUPLED PLASMA; MICROWAVE-INDUCED PLASMA; MASS SPECTROMETRY ID INDUCTIVELY-COUPLED PLASMA; MICROWAVE-INDUCED PLASMA; POLYATOMIC-ION INTERFERENCES; MIXED-GAS PLASMAS; ATMOSPHERIC-PRESSURE; CONCOMITANT ELEMENTS; HALOGENATED COMPOUNDS; IONIZATION SOURCE; AQUEOUS-SOLUTIONS; MOLECULAR GASES AB The use of mixed-gas, helium and nitrogen plasmas as alternative sources for plasma mass spectrometry is discussed in this paper. These plasmas are used to alleviate some of the problems inherent in argon inductively coupled plasma mass spectrometry (ICP-MS). Spectroscopic and non-spectroscopic interferences as well as sensitivities for high ionization potential elements are addressed. Reduced-pressure plasmas are used for the determination of P and S. In addition, applications of chromatographic techniques such as gas, supercritical-fluid and high-performance liquid chromatography with alternative plasma sources are included. Some problems found in the application of argon ICP-MS can be reduced or eliminated with alternative sources and sub-ng to sub-pg levels of detection for halogens can be achieved. C1 UNIV CINCINNATI,DEPT CHEM,CINCINNATI,OH 45221. RP SHEPPARD, BS (reprint author), US FDA,NATL FORENS CHEM CTR,1141 CENT PKWY,CINCINNATI,OH 45202, USA. NR 62 TC 17 Z9 17 U1 0 U2 5 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 1994 VL 9 IS 3 BP 145 EP 149 DI 10.1039/ja9940900145 PG 5 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA NK962 UT WOS:A1994NK96200008 ER PT J AU RUPP, HS MUNNS, RK LONG, AR PLAKAS, SM AF RUPP, HS MUNNS, RK LONG, AR PLAKAS, SM TI SIMULTANEOUS DETERMINATION OF NITROFURAZONE, NITROFURANTOIN, AND FURAZOLIDONE IN CHANNEL CATFISH (ICTALURUS-PUNCTATUS) MUSCLE-TISSUE BY LIQUID-CHROMATOGRAPHY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ANTIBACTERIALS AB A liquid chromatographic (LC) method was developed for the simultaneous determination of nitrofurazone (NFZ), nitrofurantoin (NFT), and furazolidone (FZD) in catfish muscle tissue. The drugs were extracted from the tissue with acetonitrile, and the lipids were removed from the extract with hexane. The acetonitrile extract was evaporated by rotary evaporation, and the resultant drug residues were dissolved with LC mobile phase. The mixture was sonicated, centrifuged, and filtered. The drugs were determined by using LC with a C-18 reversed-phase (ODS Hypersil) column, a mobile phase of acetonitrile-1% aqueous acetic acid (25 + 75), and a photodiode array ultraviolet detector at 375 nm. NFZ, NFT, and FZD were each determined in catfish tissue at 5 fortification levels (80, 40, 20, 10, and 5 ng drug/g tissue). Average recoveries of each of the 3 drugs at each level ranged from 70.7 to 101.5%, and relative standard deviations ranged from 2.2 to 18.6%. The limit of detection of each drug was approximately 1 ng drug/g tissue, and the limit of quantitation was 5 ng drug/g tissue. In the second part of the study, the method was used to determine nitrofuran residues incurred in catfish tissue. Live channel catfish were intravascularly dosed (10 mg/kg body wt) with NFZ to generate drug-incurred fish muscle tissue. Incurred NFZ levels exceeded 400 ng drug/g tissue at 2 h after dosing but decreased rapidly to approximately 1 ng drug/g tissue by 8 h after dosing, as determined by this method. C1 US FDA,DIV SEAFOOD RES,DAUPHIN ISL,AL 36528. RP RUPP, HS (reprint author), US FDA,DENVER FED CTR,ANIM DRUGS RES CTR,POB 25087,DENVER,CO 80225, USA. NR 13 TC 12 Z9 12 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 1994 VL 77 IS 2 BP 344 EP 350 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NF078 UT WOS:A1994NF07800008 PM 8199469 ER PT J AU ABEYTA, C WETHERINGTON, JH AF ABEYTA, C WETHERINGTON, JH TI IRON MILK MEDIUM METHOD FOR RECOVERING CLOSTRIDIUM-PERFRINGENS FROM SHELLFISH - COLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MEMBRANE-FILTER; ENUMERATION AB Eleven laboratories participated in a collaborative study analyzing shellfish (oysters, Crassostrea gigas) for the detection and enumeration of Clostridium perfringens by the iron milk medium (IMM) method. The IMM method was compared to AOAC Official Method 976.30. Shellfish were artificially inoculated with C. perfringens cells (vegetative and spores) at low(1 x 10(3) colony forming units [cfu]/g), medium (1 x 10(4) cfu/g), and high (1 x 10(6) cfu/g) levels. Negative controls (zero level) were analyzed by each laboratory. C. perfringens FD-1,the strain involved in a foodborne illness, was used. Blind duplicates of each inoculum level were analyzed, giving a total of 16 samples per laboratory. The selectivity of IMM relies solely on the rapid growth of C. perfringens at 45 degrees C indicated by stormy fermentation reaction within 18 h. C. perfringens is detected and enumerated using the most probable number technique. A statistical evaluation of the data found no significant differences between the estimates from the 2 methods. The IMM method for detection of C. perfringens from shellfish has been adopted first action by AOAC INTERNATIONAL. RP ABEYTA, C (reprint author), US FDA,SEAFOOD PROD RES CTR,22201 23RD DR SE,BOTHELL,WA 98041, USA. NR 18 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 1994 VL 77 IS 2 BP 351 EP 356 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NF078 UT WOS:A1994NF07800009 PM 8199470 ER PT J AU BENNETT, RW MCCLURE, F AF BENNETT, RW MCCLURE, F TI VISUAL SCREENING WITH ENZYME-IMMUNOASSAY FOR STAPHYLOCOCCAL ENTEROTOXINS IN FOODS - COLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LINKED IMMUNOSORBENT-ASSAY AB Selected foods containing 4-10 ng each of a mixture of Staphylococcus aureus enterotoxin serotypes A-E were tested by 15 collaborators. An enzyme-linked immunosorbent assay (EIA) was used with polyvalent antisera to these serotypes in a polyclonal antibody double ''sandwich'' configuration. Controls were free of toxin. Foods (25 g test samples) were homogenized with Tris (0.25M, pH 8.0) and centrifuged. The food extract was filtered through cotton and mixed with sample additive. For the EIA, 200 mu L aliquots of the treated extracts were added to previously washed microtiter wells coated with antibody to staphylococcal enterotoxin serotypes A-E. Wells were washed and treated with the polyvalent antisera (A-E)-enzyme conjugate, and then washed again. Substrate was added, and wells were incubated. After incubation, stop solution was added. Results were determined visually and by measuring absorbance using a microtiter plate reader. In foods containing enterotoxin, bluish-green color was developed (positive result). Test solutions with absorbances >0.200 were considered positive; those with absorbances less than or equal to 0.200 were negative. The method is sensitive and specific, and allows the rapid assay of staphylococcal enterotoxins in foods without differentiating their serotypes. The method has been adopted first action by AOAC INTERNATIONAL. C1 US FDA,DIV MATH,WASHINGTON,DC 20204. RP BENNETT, RW (reprint author), US FDA,DIV MICROBIOL,200 C ST,WASHINGTON,DC 20204, USA. NR 16 TC 19 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 MAR-APR PY 1994 VL 77 IS 2 BP 357 EP 364 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NF078 UT WOS:A1994NF07800010 PM 8199471 ER PT J AU TWEDT, RM HITCHINS, AD PRENTICE, GA AF TWEDT, RM HITCHINS, AD PRENTICE, GA TI DETERMINATION OF THE PRESENCE OF LISTERIA-MONOCYTOGENES IN MILK AND DAIRY-PRODUCTS - IDF COLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MEDIA AB A collaborative study was conducted on the recovery of viable Listeria monocytogenes from milk and dairy products (Camembert cheese, Limburger cheese, skim milk powder, and ice cream). Test portions were homogenized with Listeria-selective liquid enrichment medium and cultured at 30 degrees C for 48 h. The enrichment culture was then subcultured onto a solid isolation medium at 37 degrees C for 48 h. Suspected Listeria colonies were identified by appropriate conventional morphological, physiological, and biochemical tests. Five kinds of dairy matrixes were spiked with L. monocytogenes at 2 levels: 12 and 120 colony forming units (cfu)/25 g. Each of the 18 collaborating laboratories analyzed 15 blind test portions from each matrix, comprising 5 replicates at each spiking level and 5 uninoculated controls, for a total of 1350 analyses. The specificity of the method was 100%; its sensitivity was 94-100% at the high spiking level and 89-98% at the low spiking level, except for Limburger cheese, which was only 68%. No specificity or sensitivity differences were observed between laboratories for all matrixes at the high spiking level and for all except Limburger cheese at the low spiking level. The calculated 50% detection limit for all products except Limburger cheese was 1.6 cfu/25 g; the 50% detection limit for Limburger cheese itself was 4.1 cfu/25 g. The method was adopted first action by AOAC INTERNATIONAL. C1 MILK MKT BOARD,THAMES DITTON KT7 0EL,SURREY,ENGLAND. RP TWEDT, RM (reprint author), US FDA,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204, USA. NR 13 TC 20 Z9 20 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 1994 VL 77 IS 2 BP 395 EP 402 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NF078 UT WOS:A1994NF07800013 PM 8199474 ER PT J AU BRYCE, JR AF BRYCE, JR TI IDENTIFICATION OF HAIRS OF 3 ASIAN COMMENSAL MAMMALS - SUNCUS-MURINUS, BANDICOTA-BENGALENSIS, AND RATTUS-EXULANS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Hairs of 3 major Asian commensal mammals, Suncus murinus(L.), Bandicota bengalensis (Gray and Hardwicke), and Rattus exulans (Peale), were studied, identified, and compared with those of better-known commensal species to provide an overview of their hair morphologies. Techniques were developed for authentic hair specimen collection and rapid slide mounting to aid in the timely analysis of food products. The study showed that hairs of B. bengalensis and R. exulans are easily identified to the regulatory category of ''rat or mouse hair,'' whereas identification of S murinus contaminant hairs is possible to the species level. C1 US FDA,LOS ANGELES,CA 90015. FU PHS HHS [124-82] NR 28 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 MAR-APR PY 1994 VL 77 IS 2 BP 403 EP 410 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NF078 UT WOS:A1994NF07800014 PM 8199475 ER PT J AU DOLAN, SP CAPAR, SG JACOBS, RM PLUNKETT, RJ HAWKINS, GS AF DOLAN, SP CAPAR, SG JACOBS, RM PLUNKETT, RJ HAWKINS, GS TI SENSITIVITY OF THE QUICK COLOR TEST FOR INDICATING LEAD RELEASE FROM CERAMICWARE SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A quick color test (QCT) for indicating the presence of leachable Pb on ceramicware was evaluated as a screening tool. Fourteen sets of cups and mugs (197 pieces) of undecorated glazed ceramicware were tested. The QCT indicated the presence of leachable Pb on 95% of the cups and mugs at or above approximately 2 mu g/mL. The QCT is an inexpensive and rapid qualitative test for Pb that can be conducted with a portable kit. C1 US FDA,SAN FRANCISCO,CA 94102. RP DOLAN, SP (reprint author), US FDA,ELEMENTAL RES BRANCH,200 C ST SW,WASHINGTON,DC 20204, USA. NR 13 TC 3 Z9 3 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 1994 VL 77 IS 2 BP 454 EP 457 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA NF078 UT WOS:A1994NF07800023 PM 8199482 ER PT J AU LUU, HMD BILES, J WHITE, KD AF LUU, HMD BILES, J WHITE, KD TI CHARACTERIZATION OF POLYESTERURETHANE DEGRADATION PRODUCTS SO JOURNAL OF APPLIED BIOMATERIALS LA English DT Article ID COVERED BREAST IMPLANTS; POLYURETHANE; TOLUENEDIAMINES; PATIENT; FOAM AB Microthane foam, a poly(ester)urethane, used as a covering of some breast implants (Meme or Replicon by Surgitek) degrades readily in phosphate buffer pH 7.4 producing multiple unknown products in addition to 2,4 and 2,6 toluenediamine (TDA). The cumulative weight loss of the foam in buffer was 1.5% at 1 week and 2% at 2 weeks. Multiple peak molecular weights from 105 to 665000 were found in the aqueous foam extracts following 2 weeks of incubation at 37 degrees C using size exclusion chromatography (SEC). TDA was measured in the foam buffer extracts by high pressure liquid chromatography (HPLC) and confirmed by gas chromatography/mass spectroscopy (GC/MS). The total cumulative levels of 2,4 TDA and 2,6 TDA measured were 3 +/- 0.65 mu g/g of foam and 1.13 +/- 0.19 mu g/g of foam following 36 days of incubation at 37 degrees C. Higher amounts, 8.96 mu g/g of 2,4 TDA and 3.3 mu g/g of 2,6 TDA, were obtained at 50 degrees C. The cumulative release of TDA in aqueous extracts was found to correlate linearly with time suggesting a slow but continuous production of TDA under neutral conditions. However, less than 0.2 mu g/g of TDA was detected as residual TDA in the methylene chloride extracts following up to 60 days at 37 degrees C. PU foam extracted with methylene chloride under similar conditions showed higher foam weight loss, 4.4 and 5% at 1 and 2 weeks, respectively. The results presented in this study provide further evidence that Microthane undergoes hydrolysis under neutral conditions in aqueous solutions producing TDA and other unknown low molecular weight components and oligomers. (C) 1994 John Wiley and Sons, Inc. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV PROD MANUFACTURE & USE TECHNOL,WASHINGTON,DC 20204. US FDA,CTR FOOD SAFETY & APPL NUTR,DIV GEN SCI SUPPORT,WASHINGTON,DC 20204. RP LUU, HMD (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,DIV MECH & MAT SCI,ROCKVILLE,MD 20852, USA. NR 25 TC 9 Z9 9 U1 1 U2 10 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-4861 J9 J APPL BIOMATER JI J. Appl. Biomater. PD SPR PY 1994 VL 5 IS 1 BP 1 EP 7 DI 10.1002/jab.770050102 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA MX223 UT WOS:A1994MX22300001 ER PT J AU CALVEY, EM ROACH, JAG BLOCK, E AF CALVEY, EM ROACH, JAG BLOCK, E TI SUPERCRITICAL-FLUID CHROMATOGRAPHY OF GARLIC (ALLIUM-SATIVUM) EXTRACTS WITH MASS-SPECTROMETRIC IDENTIFICATION OF ALLICIN SO JOURNAL OF CHROMATOGRAPHIC SCIENCE LA English DT Article ID GAS-CHROMATOGRAPHY; PRODUCTS; HPLC C1 SUNY ALBANY,DEPT CHEM,ALBANY,NY 12222. RP CALVEY, EM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. RI Block, Eric/D-3989-2014 NR 15 TC 22 Z9 22 U1 1 U2 1 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 MAR PY 1994 VL 32 IS 3 BP 93 EP 96 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA MY486 UT WOS:A1994MY48600005 PM 8200919 ER PT J AU MOE, CL GENTSCH, TJ ANDO, T GROHMANN, G MONROE, SS JIANG, X WANG, J ESTES, MK SETO, Y HUMPHREY, C STINE, S GLASS, RI AF MOE, CL GENTSCH, TJ ANDO, T GROHMANN, G MONROE, SS JIANG, X WANG, J ESTES, MK SETO, Y HUMPHREY, C STINE, S GLASS, RI TI APPLICATION OF PCR TO DETECT NORWALK VIRUS IN FECAL SPECIMENS FROM OUTBREAKS OF GASTROENTERITIS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IMMUNE ELECTRON-MICROSCOPY; POLYMERASE CHAIN-REACTION; REVERSE-TRANSCRIPTASE; AUSTRALIA; ANTIGEN AB Norwalk virus (NV) and other small round-structured viruses (SRSVs) are frequent causes of gastroenteritis outbreaks. The recent cloning and sequencing of the NV genome has made it possible to detect NV and Norwalk-related viruses from fecal specimens by reverse transcription (RT)-PCR. We applied this technique to the examination of a total of 139 fecal specimens from 19 outbreaks characterized by NV serology, including 56 samples from 7 NV outbreaks, 36 from 6 Norwalk-related virus outbreaks, and 47 from 6 outbreaks with SRSVs visualized by electron microscopy that were serologically unrelated to NV. Three primer pairs mere evaluated: two pairs in the polymerase region of NV and one pair near the 3' end of the genome. When one set of primers (primer pair 51-3) from the polymerase region was used, 40% of all samples were positive by RT-PCR and specimens from the NV outbreaks were more likely to be positive (64%) than those from outbreaks associated with Norwalk-related viruses (44%) or SRSVs (8%). To determine the relationship of the outbreak strains to NV, we compared the sequences of a 145-base portion of the polymerase gene from 10 specimens obtained from five different outbreaks characterized as NV by serology. No two outbreak strains had the same sequence in this 145-base portion of the polymerase gene, and the identities of the nucleotide and amino acid sequences of these products compared crith the sequences of the corresponding region of NV ranged from 62 to 79% and 69 to 90%, respectively. Because of sequence diversity in the polymerase region, the successful application of RT-PCR to investigations of outbreaks of suspected NV-associated gastroenteritis will depend on the use of either multiple primer pairs or primers made against regions of the genome that are more conserved. C1 CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333. US FDA,OFF PLANT & DAIRY FOODS & BEVERAGES,DIV MICROANALYT EVALUAT,WASHINGTON,DC 20204. AUSTRALIAN WATER TECHNOL,WATER BOARD,SYDNEY,NSW,AUSTRALIA. BAYLOR COLL MED,HOUSTON,TX 77030. OSAKA INST PUBL HLTH & ENVIRONM SCI,OSAKA,OSAKA,JAPAN. OI Monroe, Stephan/0000-0002-5424-716X FU NIAID NIH HHS [AI30448] NR 30 TC 139 Z9 143 U1 0 U2 4 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 MAR PY 1994 VL 32 IS 3 BP 642 EP 648 PG 7 WC Microbiology SC Microbiology GA MW516 UT WOS:A1994MW51600011 PM 8195372 ER PT J AU LI, ZM JANSEN, DL FINN, TM HALPERIN, SA KASINA, A OCONNOR, SP AOYAMA, T MANCLARK, CR BRENNAN, MJ AF LI, ZM JANSEN, DL FINN, TM HALPERIN, SA KASINA, A OCONNOR, SP AOYAMA, T MANCLARK, CR BRENNAN, MJ TI IDENTIFICATION OF BORDETELLA-PERTUSSIS INFECTION BY SHARED-PRIMER PCR SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; DIAGNOSIS; DNA; AMPLIFICATION; SEROLOGY; CLONING; PROBE; GENE AB A shared-primer PCR method for the detection of infection was developed by using primers derived from DNA sequences upstream of the structural genes for the porin proteins of Bordetella pertussis and Bordetella parapertussis. This method resulted in a 159-bp PCR product specific for B. pertussis and a 121-bp DNA fragment specific for B. parapertussis and allowed for the simultaneous detection of these pathogens. The PCR procedure was shown to be very specific since no PCR product was obtained from 36 non-Bordetella bacterial DNAs. Nasopharyngeal aspirates (NPAs) from children suspected of having pertussis were evaluated by the PCR method, culture, and the Chinese hamster ovary (CHO) cell assay, which detects pertussis toxin. B. pertussis was cultured from 119 of 205 NPAs assayed, and the presence of pertussis toxin was detected in 69 of the NPAs by the CHO cell assay. When ethidium bromide staining was used to detect PCR products, 100 NPAs gave positive results by shared-primer PCR; 94 of these NPAs were also positive by culture. The result indicated a sensitivity of 79% for PCR when culture was used as the standard. The sensitivity of PCR was increased to 95% when a digoxigenin immunoblot system was used. An additional 20 NPAs from patients with suspected pertussis that were culture negative also gave positive results by PCR. The specific and sensitive PCR method described here should be useful for both the clinical diagnosis of pertussis and case identification in vaccine trials. C1 DALHOUSIE UNIV,HALIFAX B3J 3G9,NS,CANADA. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV BACTERIAL & MYCOT DIS,ATLANTA,GA 30333. KAWASAKI MUNICIPAL HOSP,KAWASAKI,KANAGAWA,JAPAN. RP LI, ZM (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,PERTUSSIS LAB,BETHESDA,MD 20892, USA. NR 22 TC 67 Z9 69 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 MAR PY 1994 VL 32 IS 3 BP 783 EP 789 PG 7 WC Microbiology SC Microbiology GA MW516 UT WOS:A1994MW51600035 PM 8195394 ER PT J AU DONOGHUE, DJ HAIRSTON, H COPE, CV BARTHOLOMEW, MJ WAGNER, DD AF DONOGHUE, DJ HAIRSTON, H COPE, CV BARTHOLOMEW, MJ WAGNER, DD TI INCURRED ARSENIC RESIDUES IN CHICKEN EGGS SO JOURNAL OF FOOD PROTECTION LA English DT Article ID LAYING HENS; MEDICATION; ELEMENTS; TRACE AB Arsanilic acid and roxarsone were fed to laying hens at elemental arsenic concentrations of 14, 28, 56 or 112 ppm for 10 weeks followed by a 2-week withdrawal period. Arsenic residues in egg components of laying hens that were fed either control or diets treated with organic arsenicals were determined weekly by atomic absorption. Arsenic concentrations in eggs were also determined after either 0, 2 or 4 weeks of refrigerated storage (4-degrees-C). Arsenic residues in both yolk and albumen increased in a dose-dependent manner although the amount of arsenic was much higher (95% of total) in yolk. Arsenic concentrations increased within 1 week of treatment, and the highest amounts were obtained between the second and fourth week for yolk samples and by the first week for albumen samples, except in the 14-ppm doses where highest amounts were reached by the middle of the treatment period. Hens treated with 112 ppm arsenic from arsanilic acid produced eggs with arsenic residues exceeding the 500 ppb Food and Drug Administration whole egg tolerance level. Eggs subjected to refrigerated storage did not have increased arsenic concentrations in yolk, although, for a few treatments, residues increased in albumen. C1 US FDA,AGR RES CTR,CTR VET MED,BIOMETR BRANCH,BELTSVILLE,MD 20705. RP DONOGHUE, DJ (reprint author), US FDA,AGR RES CTR,PHARMACOL & BIOCHEM BRANCH,BLDG 328-A,BELTSVILLE,MD 20705, USA. NR 29 TC 15 Z9 16 U1 1 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 MAR PY 1994 VL 57 IS 3 BP 218 EP 223 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA NA079 UT WOS:A1994NA07900007 ER PT J AU MURAKAMI, EG AF MURAKAMI, EG TI THERMAL-PROCESSING AFFECTS PROPERTIES OF COMMERCIAL SHRIMP AND SCALLOPS SO JOURNAL OF FOOD SCIENCE LA English DT Article DE SHRIMP; SCALLOPS; THERMAL PROCESSING; CONDUCTIVITY; EXPANSION ID DIFFUSIVITY; FOODS AB Commercial shrimp and scallops were blanched, cooked and canned and their thermal conductivity, density and volumetric expansion were measured. Thermal conductivity was measured with a line-heat source technique while density and volumetric expansion were determined with a gravimetric method. Shrimp and scallops lost moisture and shrunk by <30 and 50%, respectively. Thermal conductivities decreased by <5%, whereas densities increased by less than or equal to 4%. RP MURAKAMI, EG (reprint author), US FDA, NAT CTR FOOD SAFETY & TECHNOL, SUMMIT ARGO, IL 60501 USA. NR 24 TC 15 Z9 16 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD MAR-APR PY 1994 VL 59 IS 2 BP 237 EP 241 DI 10.1111/j.1365-2621.1994.tb06938.x PG 5 WC Food Science & Technology SC Food Science & Technology GA NJ330 UT WOS:A1994NJ33000001 ER PT J AU REDDY, NR SCHREIBER, CL BUZARD, KS SKINNER, GE ARMSTRONG, DJ AF REDDY, NR SCHREIBER, CL BUZARD, KS SKINNER, GE ARMSTRONG, DJ TI SHELF-LIFE OF FRESH TILAPIA FILLETS PACKAGED IN HIGH BARRIER FILM WITH MODIFIED ATMOSPHERES SO JOURNAL OF FOOD SCIENCE LA English DT Article DE FISH; TILAPIA; HIGH BARRIER; MODIFIED ATMOSPHERE; SPOILAGE ID CARBON-DIOXIDE; CLOSTRIDIUM-BOTULINUM; TOXIN PRODUCTION; SNAPPER FILLETS; STORAGE; GROWTH; FISH AB The effect of modified atmospheres (MAs) (75% CO2:25% N-2; 50% CO2: 50% N-2; and 25% CO2: 75% N-2) and 100% air on shelf life of fresh tilapia fillets packaged in high barrier film bags was evaluated at refrigeration temperature (4.0 degrees C). Fillets packaged in 100% air spoiled after 9 days, as indicated by sensory characteristics, and had increased surface pH, TMA content, K-value and high microbial counts. When levels of CO2 were increased from 25 to 75% in the package atmosphere, the shelf life of MA-packaged tilapia fillets was extended 4-21 days more than that of fillets packaged under 100% air. Although fillets packaged under 75% CO2:25% N-2 were judged by sensory characteristics to be acceptable for more than 25 days, their K-value was high (93.1%). K-values were independent of spoilage and correlated only with length of storage of the MA-packaged fillets. C1 LIQUID CARBON IND CORP,CTR TECH,CHICAGO,IL 60629. RP REDDY, NR (reprint author), US FDA,NATL CTR FOOD SAFETY & TECHNOL,DIV FOOD PROCESSING & PACKAGING,6502 S ARCHER RD,SUMMIT ARGO,IL 60501, USA. NR 34 TC 41 Z9 43 U1 0 U2 1 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD MAR-APR PY 1994 VL 59 IS 2 BP 260 EP 264 DI 10.1111/j.1365-2621.1994.tb06943.x PG 5 WC Food Science & Technology SC Food Science & Technology GA NJ330 UT WOS:A1994NJ33000006 ER PT J AU OHANLON, TP DALAKAS, MC PLOTZ, PH MILLER, FW AF OHANLON, TP DALAKAS, MC PLOTZ, PH MILLER, FW TI PREDOMINANT TCR-ALPHA-BETA VARIABLE AND JOINING GENE-EXPRESSION BY MUSCLE-INFILTRATING LYMPHOCYTES IN THE IDIOPATHIC INFLAMMATORY MYOPATHIES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; MYELIN BASIC-PROTEIN; TRANSFER-RNA-SYNTHETASE; MONOCLONAL-ANTIBODY ANALYSIS; SIGNAL RECOGNITION PARTICLE; V-BETA; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; MONONUCLEAR-CELLS; ANTIGEN RECOGNITION AB The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases in which autoreactive T cells are thought to play a pathogenetic role. We have determined the pattern of TCR-alpha beta gene expression by muscle-infiltrating lymphocytes within clinically and serologically defined groups of IIM patients. We utilized the PCR to study TCR V gene expression in muscle biopsies from nine polymyositis (PM) and eight dermatomyositis (DM) patients, all of whom had autoantibodies directed against histidyl-transfer RNA synthetase (anti-Jo-1 autoantibodies). While the TCR repertoire in DM patients was generally polyclonal, an oligoclonal profile characterized PM patients. Certain V gene families were predominantly expressed; V alpha 1 and V beta 6 gene families were detected in 82 and 91% of PM biopsies, respectively. TCR expression was characterized further by analyzing J gene usage from four PM patients expressing the V beta 6 gene. Sequence analysis of 40 independent recombinants (10 per patient) identified only seven V beta 6 clonotypes and restricted usage of the related J beta 2.1, -2.3, and -2.7 genes. These data, describing predominant TCR V and I gene usage by muscle-infiltrating lymphocytes in myositis patients, suggest that Ag-driven T cell responses may play a primary role in mediating some forms of the IIM. C1 US FDA,CTR BIOL EVALUAT & RES,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. NIAMSD,BETHESDA,MD 20892. NR 54 TC 71 Z9 72 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 1 PY 1994 VL 152 IS 5 BP 2569 EP 2576 PG 8 WC Immunology SC Immunology GA NB988 UT WOS:A1994NB98800057 PM 8133064 ER PT J AU HAN, SY SHULMANROSKES, EM MISIURA, K ANDERSON, LW SZYMAJDA, E GAMCSIK, MP CHANG, YH LUDEMAN, SM AF HAN, SY SHULMANROSKES, EM MISIURA, K ANDERSON, LW SZYMAJDA, E GAMCSIK, MP CHANG, YH LUDEMAN, SM TI SYNTHESIS OF O-17 (AND O-18) LABELED ISOPHOSPHORAMIDE MUSTARD SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE O-17-ISOPHOSPHORAMIDE MUSTARD; BENZYL ALCOHOL-O-17; N,N'-BIS-(2-CHLOROETHYL)PHOSPHORODIAMIDIC-O-17 ACID PHENYLMETHYL ESTER; O-18-ISOPHOSPHORAMIDE MUSTARD ID PHOSPHORAMIDE MUSTARD; CYCLOPHOSPHAMIDE ANALOGS; IFOSFAMIDE; METABOLITE AB The ifosfamide metabolite isophosphoramide mustard (IPM) was synthesized with isotopic enrichment at oxygen. Labelled benzaldehyde was made by exchange with isotopically enriched water (13.4 atom % O-17, 25.5 atom % O-18) and this was then reduced with sodium borohydride to give labelled benzyl alcohol (72% yield). Triethylamine and labelled benzyl alcohol were added to POCl3/CHCl3 at -23-degrees-C. Subsequent addition of 2-chloroethylamine hydrochloride (2 equiv) and then triethylamine (4.4 equiv) (-15-degrees-C) provided O-17/O-18 enriched N,N'-bis-(2-chloroethyl)phosphorodiamidic acid phenylmethyl ester [61%, BzOP(O)(NHCH2CH2Cl)2] . Catalytic (10% Pd/C) hydrogenation of this ester at atmospheric pressure gave IPM (22%). GC/MS was used to determine mole percent enrichments of 9.3% O-17 and 17.9% O-18 for IPM (single labelling within one molecule). C1 JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,DIV PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21287. POLISH ACAD SCI,CTR MOLEC & MACROMOLEC STUDIES,PL-90363 LODZ,POLAND. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,DIV NMR RES,BALTIMORE,MD 21287. KOREA ADV INST SCI & TECHNOL,DEPT CHEM,TAEJON,SOUTH KOREA. JOHNS HOPKINS UNIV,DEPT CHEM,BALTIMORE,MD 21218. US FDA,CTR DRUG EVALUAT & RES,DIV CLIN PHARMACOL,ROCKVILLE,MD 20857. RI Misiura, Konrad/H-6197-2014 NR 13 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 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD MAR PY 1994 VL 34 IS 3 BP 247 EP 254 DI 10.1002/jlcr.2580340307 PG 8 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA NB145 UT WOS:A1994NB14500006 ER PT J AU DENNIS, JE AF DENNIS, JE TI AMENDING THE CDRH PERFORMANCE STANDARD FOR LASER PRODUCTS SO JOURNAL OF LASER APPLICATIONS LA English DT Article DE LASERS; LASER SAFETY; SAFETY STANDARDS AB The most recent amendments to the Federal performance standard for laser products became effective in 1985 and 1986. At this time, the Center for Devices and Radiological Health (CDRH) is making public its intention to amend the standard again and is inviting suggestions and comments. The amendments that are now under consideration are based upon advances in the sciences of photobiology and hazard evaluation. They are also intended to harmonize with developments in international standards for similar products, and to clarify and facilitate administration of the CDRH standard. Many of them were developed in cooperation with representatives of industry, professional societies, trade associations, and representatives on national and international standards committees. This discussion will explain the amendment process, provide a brief history of what has transpired thus far, and explain in some detail many of the amendments that are being considered. Among these are reduction of the emission durations for the classification of some laser products depending on their intended application, extension of Class IIIa to include invisible laser radiation products, revision of the applicability requirements for safety interlocks, revision of the tables of accessible emission limits for the laser product classes, increase in the class levels for which certain performance requirements are applicable, allowance of more flexibility in labeling, delegation of some approval authorities to a lower level of management, and new requirements for the higher classes of medical laser products. Many of the amendments are being considered to achieve a higher degree of consistency with the standards of the International Electrotechnical Commission (IEC) standards 825 and 601-2-22. RP DENNIS, JE (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF COMPLIANCE & SURVEILLANCE,SILVER SPRING,MD, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU LASER INST AMER PI ORLANDO PA 12424 RESEARCH PARKWAY SUITE 125, ORLANDO, FL 32826 SN 1042-346X J9 J LASER APPL JI J. Laser Appl. PD MAR PY 1994 VL 6 IS 1 BP 49 EP 53 PG 5 WC Materials Science, Multidisciplinary; Optics; Physics, Applied SC Materials Science; Optics; Physics GA PA088 UT WOS:A1994PA08800009 ER PT J AU BOWYER, JF DAVIES, DL SCHMUED, L BROENING, HW NEWPORT, GD SLIKKER, W HOLSON, RR AF BOWYER, JF DAVIES, DL SCHMUED, L BROENING, HW NEWPORT, GD SLIKKER, W HOLSON, RR TI FURTHER-STUDIES OF THE ROLE OF HYPERTHERMIA IN METHAMPHETAMINE NEUROTOXICITY SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID D-ASPARTATE RECEPTORS; DOPAMINERGIC NERVE-TERMINALS; RAT-BRAIN; D-AMPHETAMINE; RELEASE; TEMPERATURE; SYNAPTOSOMES; MICROGLIA; GLUTAMATE; STRIATUM AB The depletion of striatal dopamine (DA) that can occur after methamphetamine (METH) administration has been linked to METH-induced hyperthermia. The relationship between METH-induced hyperthermia, neurotoxicity (striatal DA depletions) and compounds that protect against METH neurotoxicity was further investigated in this study. Typically, rats exposed to METH die when their body temperatures exceed 41.3 degrees C but such hyperthermic rats can be saved by hypothermic intervention. Subsequently, rats saved by hypothermic intervention have greater depletion of striatal DA at an earlier time of onset (18 hr or less post-METH) than do METH-exposed rats that do not attain such high temperatures. Striatal damage was present 3 days post-METH in these hyperthermic rats, as assessed by silver degeneration of terminals and increases in the astrocytes that express glial fibrillary acidic protein immunoreactivity. By contrast, alterations in the number of [H-3]dizoclipine (MK-801) binding sites in cortical or striatal membranes at 1, 3 or 14 days post-METH were not detected. The experiments showed that mean and maximal body temperature correlated well with striatal DA concentrations 3 days post-METH (r = -0.77, n = 58), which suggests a role for hyperthermia in METH neurotoxicity. However, hyperthermia (alone or with haloperidol present) induced by high ambient temperatures did not deplete striatal DA in the absence of METH. Haloperidol, diazepam and MK-801 all reduced METH-induced striatal DA depletion to a degree predicted by their inhibition of hyperthermia and increased ambient temperature abolished their neuroprotection. Although an interleukin-1 receptor antagonist reduced maximal body temperature enough to lower the lethality rate, it did not reduce the temperature sufficiently to block METH neurotoxicity. It was concluded that short- and long-term decreases in striatal DA levels depend on the degree of hyperthermia produced during METH exposure but cannot be produced by hyperthermia alone. In addition, several agents that block DA depletions do so by inhibiting METH-induced hyperthermia. Finally, the results suggested a role for interleukin-1 in the extreme hyperthermia and lethality produced by METH. C1 NATL CTR TOXICOL RES, DIV REPROD & DEV TOXICOL, JEFFERSON, AR 72079 USA. UNIV ARKANSAS MED SCI HOSP, DEPT ANAT, LITTLE ROCK, AR USA. RP BOWYER, JF (reprint author), NATL CTR TOXICOL RES, DIV NEUROTOXICOL, HFT-132, JEFFERSON, AR 72079 USA. NR 62 TC 331 Z9 332 U1 1 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 1994 VL 268 IS 3 BP 1571 EP 1580 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NB406 UT WOS:A1994NB40600064 PM 8138969 ER PT J AU WANG, JH JONES, C NORCROSS, M BOHNLEIN, E RAZZAQUE, A AF WANG, JH JONES, C NORCROSS, M BOHNLEIN, E RAZZAQUE, A TI IDENTIFICATION AND CHARACTERIZATION OF A HUMAN HERPESVIRUS-6 GENE SEGMENT CAPABLE OF TRANSACTIVATING THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 LONG TERMINAL REPEAT IN AN SP1 BINDING SITE-DEPENDENT MANNER SO JOURNAL OF VIROLOGY LA English DT Article ID TRIPLE-HELIX FORMATION; LYMPHOCYTES-T; TRANSCRIPTION FACTOR; EXANTHEM SUBITUM; HIV-1 INFECTION; ACTIVATION; PROMOTER; DNA; SEQUENCE; CELLS AB The human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) is transactivated by various extracellular signals and viral cofactors that include human herpesviruses. These transactivators are capable of transactivating the HIV-1 LTR through the transactivation response element, NF-kappa B, or other regulatory binding elements. Human herpesvirus 6 (HHV-6) is a potential cofactor of HIV-1. Here, we report that an HHV-6 gene segment, ZVH14, which can neoplastically transform NIH 3T3 and human keratinocytes, is capable of transactivating HIV-1 LTR chloramphenicol acetyltransferase constructs in an Sp1 binding site-dependent manner. Transactivation increased synergistically in the presence of multiple Sp1 sites and was dramatically reduced by cotransfection with oligomers designed to form tripler structures with HIV-1 LTR Sp1 binding sites. HIV-1 LTR NF-kappa B sites were not essential for ZVH14-mediated transactivation. A putative open reading frame in ZVH14, B115, which may encode a highly basic peptide consisting of 115 amino acid residues, showed transactivation capacity similar to that of ZVH14. This open reading frame also transactivated the HIV-1 LTR in an Sp1 site-dependent fashion in African green monkey kidney cells and human T cells. These data suggest that HHV-6 may stimulate HIV-1 replication via transactivation of Sp1 binding sites present in the HIV-1 promoter. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD 20892. UNIV NEBRASKA,CTR BIOTECHNOL,LINCOLN,NE 68583. UNIV VIENNA,VIENNA INT RES COOPERAT CTR,VIENNA,AUSTRIA. NR 46 TC 23 Z9 25 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 MAR PY 1994 VL 68 IS 3 BP 1706 EP 1713 PG 8 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600052 PM 8107231 ER PT J AU GOLDING, H MANISCHEWITZ, J VUJCIC, L BLUMENTHAL, R DIMITROV, DS AF GOLDING, H MANISCHEWITZ, J VUJCIC, L BLUMENTHAL, R DIMITROV, DS TI THE PHORBOL ESTER PHORBOL-MYRISTATE ACETATE INHIBITS HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE-MEDIATED FUSION BY MODULATING AN ACCESSORY COMPONENT(S) IN CD4-EXPRESSING CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUSES; HTLV-III/LAV ENVELOPE; SYNCYTIUM FORMATION; CD4-MEDIATED FUSION; BINDING-PROTEIN; T-CELLS; GLYCOPROTEIN; HIV-1; CD4; INFECTION AB The phorbol ester phorbol myristate acetate (PMA) strongly inhibits human immunodeficiency virus type 1 (HIV-1)-induced syncytium formation; it has been suggested that this inhibitory effect is due to the transient downmodulation of the surface-associated CD4 receptors by PMA (I. H. Chowdhury, Y. Koyanagi, S. Kobayashi, Y. Hamamoto, H. Yoshiyama, T. Yoshida, and N. Yamamoto, Virology 176:126-132, 1990). Surprisingly, PMA treatment of cells expressing truncated (A2.01.CD4.401) and hybrid (A2.01.CD4.CD8) CD4 molecules, which are not downmodulated (P. Bedinger, A. Moriarty, R. C. von Borstel II, N. J. Donovan, K. S. Steimer, and D. R. Littman, Nature [London] 331:162-165, 1988), inhibited their fusion with CD4(-) (12E1) cells expressing vaccinia virus-encoded HIV-1 envelope glycoprotein (gp120-gp41) and with chronically HIV-1-infected H9 (MN, IIIB, or RF) cells. PMA pretreatment of T (12E1) and non-T (HeLa, U937.3, and Epstein-Barr virus-transformed B) cell lines expressing vaccinia virus-encoded CD4 also blocked fusion with 12E1 cells expressing vaccinia virus-encoded gp120-gp41. Interestingly, pretreatment of the gp120-gp41-expressing 12E1 cells with PMA did not alter their fusion with untreated CD4-expressing cells. Although the inhibitory effect of PMA was rapid and treatment for 1.5 h with 5 ng of PMA per ml was sufficient to reduce fusion by more than 50%, the recovery after treatment was slow and more than 40 h was needed before the cells regained half of their fusion potential. The inhibitory effect of PMA was blocked by staurosporine in a dose-dependent fashion, suggesting that it is mediated by protein kinase C. PMA treatment of A2.01.CD4.401 cells reduced the number of infected cells 6.7-fold, as estimated by a quantitative analysis of the HIV-1 MN infection kinetics, probably by affecting the stage of virus entry into cells. CD26 surface expression was not significantly changed by PMA treatment. We conclude that PMA inhibits the CD4-gp120-gp41-mediated fusion by modulating an accessory component(s), different from CD26, in the target CD4-expressing cells. These findings suggest a novel approach for identification of accessory molecules involved in fusion and may have implications for the development of antiviral agents. C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. US FDA,CBER,DIV VIROL,BETHESDA,MD 20892. NR 31 TC 33 Z9 33 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 MAR PY 1994 VL 68 IS 3 BP 1962 EP 1969 PG 8 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600081 PM 7906314 ER PT J AU SMITH, WT AF SMITH, WT TI IDENTIFICATION OF TOXIC HERBS USING TLC ACTIVE CONSTITUENT FINGERPRINTS SO JPC-JOURNAL OF PLANAR CHROMATOGRAPHY-MODERN TLC LA English DT Article DE TLC; TLC FINGERPRINT; TOXIC HERBS; PLANT DRUGS; IDENTIFICATION AB In recent years the US Food and Drug Administration has found it necessary to make positive identification of various herbs and herbal products. Because each herb contains a unique combination of active principles (alkaloids, glycosides, essential oils, etc.) the fastest method of identification is to produce a thin layer chromatographic ''finger-print'' of these components. Positive identification is achieved by comparing the fingerprint from an extract of the suspect sample to that of an authentic botanical product. This article describes the successful identification of several products using this method and outlines the TLC systems used for each product. Problems associated with some of these products are discussed along with other difficulties of which the analyst should be aware before attempting to make positive identification using this procedure. RP SMITH, WT (reprint author), US FDA,ROOM 900,US CUSTOMSHOUSE,2ND & CHESTNUT ST,PHILADELPHIA,PA 19106, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER HUNGARICA KIADO KFT PI BUDAPEST PA WESSELENYI U 28, H-1075 BUDAPEST, HUNGARY SN 0933-4173 J9 JPC-J PLANAR CHROMAT JI JPC-J. Planar Chromatogr.-Mod. TLC PD MAR-APR PY 1994 VL 7 IS 2 BP 95 EP 97 PG 3 WC Chemistry, Analytical SC Chemistry GA NX387 UT WOS:A1994NX38700002 ER PT J AU VARGAS, FF CAVIEDES, PF GRANT, DS AF VARGAS, FF CAVIEDES, PF GRANT, DS TI ELECTROPHYSIOLOGICAL CHARACTERISTICS OF CULTURED HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS SO MICROVASCULAR RESEARCH LA English DT Article ID ELECTRICAL-PROPERTIES; CALCIUM CURRENTS; IONIC CURRENTS; CHANNELS; POTASSIUM; VESSELS AB Electrophysiological characteristics of cultured human umbilical vein endothelial cells (HUVEC) were determined using the patch-clamp technique in the whole cell configuration. In isolated cells, membrane potential, capacitance, and input resistance were (Mean +/- SD) - 16.3 +/- 12.7 mV, 53.9 +/- 26 pF, and 2.3 +/- 1.3 Gn Omega respectively (N = 26); and in confluent cells - 23.6 +/- 5.5 mV, 127 +/- 59 pF, and 0.254 +/- 0.077 G Omega, respectively (N = 6). The almost 10 times higher input resistance, and smaller capacitance of isolated Versus confluent cells, indicated that the latter were in electrical communication, presumably through open gap junctions, which was confirmed by intercellular diffusion of Lucifer Yellow. Whole-cell currents of isolated cells were made up of at least three components: First, two outward currents, an early transient one with activation-inactivation kinetics and a small delayed sustained component with 6.75 +/- 4.8 and 0.73 +/- 0.089 nS conductance, respectively. Second, an inward component which was rectified and had 1.58 +/- 1.2 nS conductance. In contrast to a reported lack of voltage-gated channels in HUVEC, the above currents were voltage dependent. Inhibition of the whole-cell currents by external Ba-2, internal Cs, and other K+ blockers indicates that the three observed currents are carried by K+. This was confirmed by changes of outside K+ concentrations shifting the I-V curve intercept in the direction expected for K+-selective channels. Voltage-gated Ca2+ currents were not apparent in the whole-cell current records. HUVEC membrane potential was as low as that of microvascular cells, while inward current rectification at normal external K+ was like that in arterial endothelial cells. This mixed phenotypic expression and multipotential behavior suggests that the electrical features of HUVEC may be primarily determined by embryonic origin and the local effect of the microenvironment rather than strictly by vessel size. (C) 1994 Academic Press, Inc. C1 NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP VARGAS, FF (reprint author), CDER,ODEI,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857, USA. NR 42 TC 31 Z9 31 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAR PY 1994 VL 47 IS 2 BP 153 EP 165 DI 10.1006/mvre.1994.1012 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NB271 UT WOS:A1994NB27100001 PM 7517490 ER PT J AU TOLLEFSON, L AF TOLLEFSON, L TI HEALTH CLAIMS ON FOOD LABELS SO MILITARY MEDICINE LA English DT Article AB Food and drug law requires that the ingredients in most foods be disclosed on their labels, but until recently there was no requirement that nutrition information be provided. The Nutrition Labeling and Education Act of 1990 (NLEA), passed on November 8, 1990, mandated the Food and Drug Administration to establish regulations requiring most foods to have a uniform nutrition label showing the amount of calories, calories from fat, total fat, saturated fatty acids, cholesterol, total carbohydrates, complex carbohydrates, sugars, fiber, protein, and sodium. The Act also establishes the circumstances under which content claims and disease claims may be made about nutrients in food. This paper briefly discusses recent changes in the food label brought about by the NLEA and focuses on health claims on food labels. RP TOLLEFSON, L (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,EPIDEMIOL BRANCH,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0026-4075 J9 MIL MED JI Milit. Med. PD MAR PY 1994 VL 159 IS 3 BP 213 EP 217 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA NJ938 UT WOS:A1994NJ93800014 PM 8041466 ER PT J AU FINBLOOM, DS PETRICOIN, EF HACKETT, RH DAVID, M FELDMAN, GM IGARASHI, K FIBACH, E WEBER, MJ THORNER, MO SILVA, CM LARNER, AC AF FINBLOOM, DS PETRICOIN, EF HACKETT, RH DAVID, M FELDMAN, GM IGARASHI, K FIBACH, E WEBER, MJ THORNER, MO SILVA, CM LARNER, AC TI GROWTH-HORMONE AND ERYTHROPOIETIN DIFFERENTIALLY ACTIVATE DNA-BINDING PROTEINS BY TYROSINE PHOSPHORYLATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INTERFERON-ALPHA; TRANSCRIPTION FACTOR; STIMULATED TRANSCRIPTION; CYTOPLASMIC ACTIVATION; IFN-GAMMA; RECEPTOR; PROMOTER; DESIGN; ISGF3 AB Binding of growth hormone (GH) and erythropoietin (EPO) to their respective receptors results in receptor clustering and activation of tyrosine kinases that initiate a cascade of events resulting not only in the rapid tyrosine phosphorylation of several proteins but also in the induction of early-response genes. In this report, we show that GH and EPO induce the tyrosine phosphorylation of cellular proteins with molecular masses of 93 kDa and of 91 and 84 kDa, respectively, and that these proteins form DNA-binding complexes which recognize an enhancer that has features in common with several rapidly induced genes such as c-fos. Assembly of the protein complexes required tyrosine phosphorylation, which occurred within minutes after addition of ligand. The activated complexes translocated from the cytoplasm to the nucleus. The protein activated by GH is antigenically similar to p91, a protein common to several transcription complexes that are activated by interferons and other cytokines. In contrast, the proteins activated by EPO are distinct from p91. These findings establish the outlines for a cytokine-induced intracellular signaling pathway, which begins with ligand-induced receptor clustering that activates one or more tyrosine kinases. These data are the first to demonstrate that GH- and EPO-activated tyrosine-phosphorylated proteins can specifically recognize a well-defined enhancer and therefore provide a mechanism for rapidly transducing signals from the membrane to the nucleus. C1 NIDDKD,CHEM BIOL LAB,BETHESDA,MD 20892. UNIV VIRGINIA,HLTH SCI CTR,DEPT MED,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. RP FINBLOOM, DS (reprint author), CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [DK08942] NR 35 TC 87 Z9 87 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1994 VL 14 IS 3 BP 2113 EP 2118 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MX640 UT WOS:A1994MX64000060 PM 7509451 ER PT J AU SLIKKER, W AF SLIKKER, W TI PRINCIPLES OF DEVELOPMENTAL NEUROTOXICOLOGY SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 10th International Neurotoxicology Conference: Mechanisms of Developmental Neurotoxicity CY SEP 28-OCT 01, 1992 CL LITTLE ROCK, AR SP MARCH DIMES, US EPA, HLTH EFFECTS RES LAB, US FDA, NATL CTR TOXICOL RES, NATL INST ENVIRONM HLTH SCI, INT NEUROTOXICOL ASSOC, EASTMAN KODAK CO, DU PONT & CO, HASKELL LAB TOXICOL & IND MED, ARKANSAS CHILDRENS HOSP, UNIV ARKANSAS MED SCI DE DEVELOPMENT; BEHAVIOR; NEUROCHEMISTRY; NEUROPATHOLOGY; RISK ASSESSMENT ID QUANTITATIVE RISK ANALYSIS; VOLATILE ORGANIC-SOLVENTS; BEHAVIORAL-TOXICOLOGY AB With 4-8 percent of U.S. children exhibiting anatomical and/or functional deficits, and the occurrence of several tragic clinical syndromes resulting from developmental exposure to such agents as ethanol, lead and methylmercury, there is good reason to focus attention on the principles of developmental neurotoxicology. Various animal models have been used to confirm the developmental neurotoxicity that results from exposure to these agents, and along with clinical evidence, have implicated several other chemical classes such as antimitotics, insecticides, polyhalogenated hydrocarbons, psychoactive drugs, solvents and vitamins as specific agents with developmental neurotoxic potential. As for developmental toxicity in general, the nature and extent of neurotoxic effects are often dependent on the timing of exposure, and because stages of nervous system development can vary significantly between species in relation to the time of birth, variations in neurotoxic outcome across species are expected. There are several instances in which functional alterations (e.g., neuromotor development, locomotor activity, reactivity and/or habituation, learning and memory and sensory system modulation) have been observed at doses below those needed to produce other indicators of developmental toxicity. Neuroanatomical/neurohistological, neurochemical and neurophysiological endpoints have been used to substantiate these functional deficits and/or to describe adverse nervous system effects in the absence of functional data. As knowledge about the toxicological mechanisms underlying the expression of developmental neurotoxicity is in creased, the ability to conduct quantitative risk assessments and protect human health will be enhanced. (C) 1994 Intox Press, Inc. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR. UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,LITTLE ROCK,AR. RP SLIKKER, W (reprint author), NATL CTR TOXICOL RES,DIV NEUROTOXICOL,3900 NCTR DR,HFT-132,JEFFERSON,AR 72079, USA. NR 27 TC 14 Z9 16 U1 0 U2 1 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 1994 VL 15 IS 1 BP 11 EP 16 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA NP624 UT WOS:A1994NP62400003 PM 8090351 ER PT J AU GROSS, TP SCHLESSELMAN, JJ AF GROSS, TP SCHLESSELMAN, JJ TI THE ESTIMATED EFFECT OF ORAL-CONTRACEPTIVE USE ON THE CUMULATIVE RISK OF EPITHELIAL OVARIAN-CANCER SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID WOMEN AB Objective: To determine the effect of oral contraceptive (OC) use on the cumulative incidence of epithelial ovarian cancer from ages 20-40, 20-50, and 20-55 years among four groups of women: positive family history, negative family history, parous, and nulliparous. Methods: Cancer and Steroid Hormone Study data were combined with data from the Surveillance, Epidemiology, and End Results Network to provide estimates of the age-specific incidence rates of epithelial ovarian cancer among never-users of OCs in the four specified groups of women. These rates provided the basis for calculating cumulative incidences. The rates in women using OCs were estimated from meta-analyses of the epidemiologic literature, using regression equations expressing the log-relative rate of epithelial ovarian cancer as a function of duration of use and recency. Results: In all four groups, the cumulative number of epithelial ovarian cancer cases estimated to occur per 100,000 OC users, compared to never-users, decreased with increasing duration of OC use. Our results suggest that 5 years of OC use by nulliparous women can reduce their ovarian cancer risk to the level seen in parous women who never use OCs, and that 10 years of OC use by women with a positive family history can reduce their risk to a level below that for women whose family history is negative and who never use OCs. Conclusion: These data represent the first published estimates of the effect of OC use on the cumulative incidence of epithelial ovarian cancer by family history and by parity. The demonstrated substantial noncontraceptive benefit from OCs justifies their judicious use as a potentially powerful resource for primary prevention in women at high risk of ovarian cancer. C1 UNIV PITTSBURGH,DEPT CLIN EPIDEMIOL & FAMILY MED,PITTSBURGH,PA. UNIV PITTSBURGH,PITTSBURGH CANC INST,PITTSBURGH,PA. RP GROSS, TP (reprint author), US FDA,CDRH,OST,OBS,EB,DIV BIOMETR SCI,HFZ-161,1801 ROCKVILLE PIKE,SUITE 405,ROCKVILLE,MD 20852, USA. FU NCI NIH HHS [CA50913] NR 30 TC 75 Z9 75 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 1994 VL 83 IS 3 BP 419 EP 424 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA MX857 UT WOS:A1994MX85700018 PM 8127536 ER PT J AU ACRI, JB MORSE, DE POPKE, EJ GRUNBERG, NE AF ACRI, JB MORSE, DE POPKE, EJ GRUNBERG, NE TI NICOTINE INCREASES SENSORY GATING MEASURED AS INHIBITION OF THE ACOUSTIC STARTLE REFLEX IN RATS SO PSYCHOPHARMACOLOGY LA English DT Article DE NICOTINE; ACOUSTIC STARTLE REFLEX (ASR); SENSORY GATING; PRE-PULSE INHIBITION (PPI) ID PREPULSE INHIBITION; D-AMPHETAMINE; AUTORADIOGRAPHIC DISTRIBUTION; ALZHEIMERS-DISEASE; DOPAMINE; SCHIZOPHRENICS; FACILITATION; APOMORPHINE; PERFORMANCE; STIMULATION AB Chronic nicotine administration has been reported to increase acoustic startle response (ASR) amplitude in rats, which has been offered as evidence that some dosages of nicotine can enhance attention. The present experiments examined effects of acutely administered nicotine on amplitude and pre-pulse inhibition (PPI) of acoustic startle in rats. PPI, the decrease in ASR amplitude by a stimulus preceding the startle-eliciting event, reflects pre-attentive neural processes underlying sensory gating. Nicotine had a biphasic dose effect on startle amplitude, with increases at lower dosages (0.01 mg/kg) and decreases at higher dosages (0.5-5.0 mg/kg SC). Lower dosages of nicotine (0.001-0.01 mg/kg) increased PPI and the increase at 0.001 mg/kg occurred independently of changes in ASR amplitude. These results confirm that increases in PPI are not dependent upon changes in ASR amplitude. Results are consistent with nicotine's enhancements of performance on cognitive tasks in humans and are the first reported use of the PPI paradigm to model such effects. These findings indicate that ASR paradigms are useful to study effects of nicotine. C1 US FDA,DIV ANTIVIRAL DRUP PROD,ROCKVILLE,MD 20857. UNIFORMED SERV UNIV HLTH SCI,DEPT MED PSYCHOL,BETHESDA,MD 20814. NR 46 TC 100 Z9 101 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 1994 VL 114 IS 2 BP 369 EP 374 DI 10.1007/BF02244861 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NA384 UT WOS:A1994NA38400026 PM 7838931 ER PT J AU NAIR, PP KESSIE, G PATNAIK, R GUIDRY, C AF NAIR, PP KESSIE, G PATNAIK, R GUIDRY, C TI ISOLATION AND HPLC OF N-EPSILON-LITHOCHOLYL LYSINE AS ITS FLUORESCAMINE AND DIMETHYLAMINOAZOBENZENE ISOTHIOCYANATE DERIVATIVES SO STEROIDS LA English DT Article DE LITHOCHOLIC ACID; TISSUE-BOUND LITHOCHOLIC ACID; BILE ACID CONJUGATE; BILE ACID ID PROTEINS; ASSAY; ACID AB N-epsilon-lithocholyl lysine (NELL) is a component of tissue-bound lithocholic acid (TBL). The isolation of NELL from native protein sources was simulated by hydrolysis of lithocholyl-bovine serum alburmin (BSA) (synthesized by coupling lithocholyl-N-hydroxysuccinimide to fatty acid-free BSA) by digestion with a mixture of 6N HCl-propionic acid at 70 C for 3 h under partial vacuum. NELL was isolated on a reversed phase Sep-Pak C-18 column and converted to either a fluorophor with fluorescamine or to a chromophor with dimethylaminoazobenzene isothiocyanate for subsequent HPLC using appropriate fluorescence or UV/visible absorption detectors. The procedure described here is quantitative, highly sensitive, and not dependent upon the use of Clostridial choranoylamino acid hydrolase, the activity of which is sometimes blocked by steric hindrance on the substrate. Using this procedure we have demonstrated the presence of TBL in native histones. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOCHEM,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT INT HLTH,DIV NUTR,BALTIMORE,MD 21205. US FDA,ROCKVILLE,MD 20857. RP NAIR, PP (reprint author), USDA,BELTSVILLE HUMAN NUTR RES CTR,LIPID NUTR LAB,BLDG 308,BELTSVILLE,MD 20705, USA. NR 14 TC 12 Z9 12 U1 2 U2 3 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0039-128X J9 STEROIDS JI Steroids PD MAR PY 1994 VL 59 IS 3 BP 212 EP 216 DI 10.1016/0039-128X(94)90030-2 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA NA826 UT WOS:A1994NA82600007 PM 8048154 ER PT J AU FLYNN, T GIBSON, R JOHANNESSEN, J AF FLYNN, T GIBSON, R JOHANNESSEN, J TI UNTITLED SO TERATOLOGY LA English DT Letter ID HANDEDNESS; ASYMMETRY RP FLYNN, T (reprint author), US FDA,MOD-1,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 6 TC 2 Z9 2 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 MAR PY 1994 VL 49 IS 3 BP 179 EP 180 DI 10.1002/tera.1420490312 PG 2 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA ND258 UT WOS:A1994ND25800011 ER PT J AU CONTRERA, JF AF CONTRERA, JF TI EMERGING TRENDS IN NONCLINICAL SAFETY ASSESSMENT FOR THERAPEUTICS SO TOXICOLOGIC PATHOLOGY LA English DT Article RP CONTRERA, JF (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF RES RESOURCES,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 1 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 1994 VL 22 IS 2 BP 89 EP 94 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA NY189 UT WOS:A1994NY18900002 PM 7973374 ER PT J AU MEYER, DJ CAMPBELL, GS COCHRAN, BH ARGETSINGER, LS LARNER, AC FINBLOOM, DS CARTERSU, C SCHWARTZ, J AF MEYER, DJ CAMPBELL, GS COCHRAN, BH ARGETSINGER, LS LARNER, AC FINBLOOM, DS CARTERSU, C SCHWARTZ, J TI GROWTH-HORMONE INDUCES A DNA-BINDING FACTOR-RELATED TO THE INTERFERON-STIMULATED 91-KDA TRANSCRIPTION FACTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID PROTEIN-TYROSINE KINASES; SERUM RESPONSE ELEMENT; C-FOS; ALPHA; GENE; PHOSPHORYLATION; REGION; ACTIVATION; INDUCTION; SECRETION AB Signaling mechanisms leading to regulation of gene transcription by growth hormone (GH) and other molecules that signal via the cytokine receptor family have been elusive. Based upon recent findings that GH and interferons activate JAK family tyrosine kinases, we have identified a novel signaling pathway leading from the GH receptor to the nucleus. We report that in 3T3-F442A fibroblasts, GH stimulates tyrosyl phosphorylation of a protein recognized by antibody to p91, a component of DNA-binding complexes that are activated by tyrosyl phosphorylation in response to interferons alpha and gamma. In addition, a GH-inducible DNA binding factor (GHIF) is identified that binds to the c-sis-inducible element of the c-fos promoter. GHIF contains a protein antigenically related to p91 and is tyrosyl-phosphorylated. These findings indicate that in signaling between their receptors and the nucleus, GH and interferons utilize related or identical components, including JAK family tyrosine kinases and proteins in the p91 family. When combined with recent findings that many members of the cytokine receptor family activate JAK kinases, including some cytokines that activate p91-related proteins, these findings suggest that signaling pathways involving JAB kinases and p91 family members may be broadly distributed. C1 UNIV MICHIGAN,SCH MED,DEPT PHYSIOL,ANN ARBOR,MI 48109. TUFTS UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02111. CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. FU NCI NIH HHS [P01-CA42063]; NIDDK NIH HHS [R01 DK034171, DK34171]; NIGMS NIH HHS [T32 GM007315, GM07315] NR 41 TC 166 Z9 166 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 FEB 18 PY 1994 VL 269 IS 7 BP 4701 EP 4704 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MX571 UT WOS:A1994MX57100003 PM 7508925 ER PT J AU PARCHMENT, RE VOLPE, DA LORUSSO, PM ERICKSONMILLER, CL MURPHY, MJ GRIESHABER, CK AF PARCHMENT, RE VOLPE, DA LORUSSO, PM ERICKSONMILLER, CL MURPHY, MJ GRIESHABER, CK TI IN-VIVO-IN-VITRO CORRELATION OF MYELOTOXICITY OF 9-METHOXYPYRAZOLOACRIDINE (NSC-366140, PD115934) TO MYELOID AND ERYTHROID HEMATOPOIETIC PROGENITORS FROM HUMAN, MURINE, AND CANINE MARROW SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELLS-INVITRO; SOLID TUMORS; BONE-MARROW; PYRAZOLOACRIDINES; ASSAYS AB Background: 9-Methoxypyrazoloacridine (PZA) is an anticancer agent that shows selectivity of action for carcinomas over leukemias. It also has nearly equal potency against cycling and quiescent or hypoxic and normoxic target cells. Phase I trials of PZA in humans are nearing completion. Purpose: This study was conducted to determine (a) if PZA is directly inhibitory to hematopoietic cells and, if it is, to characterize the inhibition pharmacodynamically, (b) whether species-specific differences in direct toxicity could explain differences in myelosuppression in mice, dogs, and humans, and (c) whether in vitro data correlate with in vivo myelosuppression data. Methods: In vitro clonogenic assays of hematopoietic progenitors of myeloid and erythroid lineages from human, canine, and murine femoral marrow were used to measure the direct toxicity of PZA. Results from these assays were compared on an area-under-the-curve (AUC) basis to clinical myelosuppression data. Results: On the basis of maximum tolerated concentrations, canine hematopoietic progenitors are most susceptible to PZA, followed by human and then murine progenitors. We found no difference in susceptibility to PZA toxicity between the human progenitors of myeloid and erythroid lineages. Both concentration and duration of exposure contribute to the in vitro toxicity of PZA. In contrast to antimetabolites, the in vitro toxicity of PZA could be minimized at a given AUC by lowering drug concentration and prolonging the period of exposure. On an AUC basis, the in vitro data are consistent with limited in vivo myelosuppression data from preclinical models and correlate with neutropenia data from a phase I trial. Conclusions: PZA directly inhibits hematopoietic progenitors, an action that is responsible for the myelosuppression observed in humans. Human marrow appears able to compensate for the loss of up to 35% of its myeloid progenitors, in that peripheral neutrophil counts remain unchanged at that level of loss. Although in vivo studies show that prolonged infusion reduces myelosuppression at a given total dose in both rodent and canine models, pharmacokinetic differences make it unlikely that this approach will benefit human patients. Implications: The in vitro data quantitatively predict the AUCs at maximum tolerated dose in preclinical models and human patients. Thus, in vitro clonogenic assays of myelotoxic agents can provide data that make both preclinical toxicology testing and clinical trial planning and interpretation more efficient and accurate. C1 HIPPLE CANC RES CTR,DIV PHARMACOL & TOXICOL,DAYTON,OH. WAYNE STATE UNIV,DIV HEMATOL ONCOL,DETROIT,MI 48202. SMITHKLINE BEECHAM PHARMACEUT,DEPT MOLEC VIROL & HOST DEF,KING OF PRUSSIA,PA. RP PARCHMENT, RE (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF RES RESOURCES,DIV RES & TESTING MOD-1,RM 2023,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. FU NCI NIH HHS [CM07361] NR 16 TC 50 Z9 51 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 16 PY 1994 VL 86 IS 4 BP 273 EP 280 DI 10.1093/jnci/86.4.273 PG 8 WC Oncology SC Oncology GA MV706 UT WOS:A1994MV70600012 PM 8158681 ER PT J AU CHO, BP BELAND, FA MARQUES, MM AF CHO, BP BELAND, FA MARQUES, MM TI NMR STRUCTURAL STUDIES OF A 15-MER DNA DUPLEX FROM A RAS PROTOONCOGENE MODIFIED WITH THE CARCINOGEN 2-AMINOFLUORENE - CONFORMATIONAL HETEROGENEITY SO BIOCHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; PROTON RESONANCES; 1ST BASE; ADDUCT; 4-AMINOBIPHENYL; ACETYLAMINOFLUORENE; SPECTROSCOPY; BINDING; MODEL; 2-ACETYLAMINOFLUORENE AB Proton NMR studies were conducted on the complementary 15-mer DNA duplex, d(5'-TACTCTTCTT[AF]GACCT)-d(5'-AGGTCAAGAAGAGTA) (designated as the AF-modified duplex). The sequence represents a portion of the mouse c-Ha-ras protooncogene and was selectively modified to contain a single N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF) adduct at the deoxyguanosine corresponding to the first base of codon 61. The AF-modified duplex was found to exist in multiple conformations, with one being predominant (similar to 60%). The exchangeable and nonexchangeable protons belonging to the major conformer were sufficiently well-resolved to allow the assignment of the majority of the base and sugar protons. The one-dimensional proton spectra, as well as the NOE cross-peak patterns associated with this conformer of the AF-modified duplex both in H2O and D2O spectra, were strikingly similar to those observed for the major conformer of an analogous duplex containing N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP) in the same position [Cho, B. P., Beland, F. A., & Marques, M. M. (1992) Biochemistry 31, 9587-9602]. The experimental results suggest that the AF- and ABP-modified duplexes adopt essentially identical major conformations, with each arylamine moiety being positioned in the major groove of a slightly disturbed B-type DNA duplex. Nonetheless, the absence of specific NOE cross peaks in the vicinity of the modification site indicates that the local structural perturbation is more severe in the AF-modified duplex. Although insufficient data precluded a detailed characterization of the minor conformers of the AF-modified duplex, the observation of significant shielding of the AF aromatic protons suggests a more dramatic structural alteration at the adduct site, possibly involving extensive stacking with the neighboring bases. The higher content (30-40%) of the minor conformers observed for the AF-modified duplex contrasted with the low contribution (5-10%) of similar structures in the ABP-modified duplex and may be attributed to a better overlapping efficiency of the planar AF ring with the nearby bases. Since the significant local perturbation observed in the minor conformers could provide a possible mechanism for mutations, our results support the view that the structural differences in the arylamine fragments of otherwise identical adducts have a direct influence on the conformational heterogeneities, which in turn may play a significant role in arylamine carcinogenesis. C1 NATL CTR TOXICOL RES, DIV BIOCHEM TOXICOL, JEFFERSON, AR 72079 USA. CTR QUIM ESTRUT, P-1096 LISBON, PORTUGAL. RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 40 TC 88 Z9 88 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 15 PY 1994 VL 33 IS 6 BP 1373 EP 1384 DI 10.1021/bi00172a013 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MX208 UT WOS:A1994MX20800013 PM 8312255 ER PT J AU TAFURI, SR FINK, D WOLFFE, AP AF TAFURI, SR FINK, D WOLFFE, AP TI CHARACTERIZATION OF THE RNA-BINDING PROPERTIES OF THE XENOPUS TRANSCRIPTION FACTOR, FRGY2 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 WARNER LAMBERT PARKE DAVIS,SIGNAL TRANSDUCT,ANN ARBOR,MI 48105. US FDA,DIV CELL BIOL,BETHESDA,MD 20892. NIH,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 13 PY 1994 SU 18C BP 139 EP 139 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500497 ER PT J AU TAKAO, M OTRIN, VR ABRAMIC, M MOOS, M WOOTON, JC MCLENIGAN, M LEVINE, AS PROTIC, M AF TAKAO, M OTRIN, VR ABRAMIC, M MOOS, M WOOTON, JC MCLENIGAN, M LEVINE, AS PROTIC, M TI CLONING A CDNA-ENCODING A 127 KDA PROTEIN OF THE UV-DAMAGED DNA-BINDING COMPLEX SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract ID PRIMATE CELLS C1 NICHHD,BETHESDA,MD 20892. NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892. US FDA,DIV CELLULAR & GENE THERAPY,DEV BIOL LAB,BETHESDA,MD 20892. RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 3 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 FEB 13 PY 1994 SU 18C BP 150 EP 150 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500536 ER PT J AU AKSAMIT, RR BACKLUND, PS MOOS, M CARYK, T GOMI, T OGAWA, H FUJIOKA, M CANTONI, GL AF AKSAMIT, RR BACKLUND, PS MOOS, M CARYK, T GOMI, T OGAWA, H FUJIOKA, M CANTONI, GL TI THE ROLE OF CYSTEINE-78 IN FLUOROSULFONYLBENZOYLADENOSINE INACTIVATION OF RAT-LIVER S-ADENOSYLHOMOCYSTEINE HYDROLASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID L-HOMOCYSTEINE HYDROLASE; AMINO-ACID SEQUENCE; SITE-DIRECTED MUTAGENESIS; DICTYOSTELIUM-DISCOIDEUM; COENZYME BINDING; CDNA SEQUENCE; PROTEINS; PURIFICATION; RESIDUES; ENZYME AB Inactivation of rat liver S-adenosylhomocysteine hydrolase by the site-directed reagent 5'-p-fluorosulfonyl-benzoyladenosine (FSBA) is associated with the formation of a disulfide bond between Cys-78 and Cys-112 (Takata, Y., and Fujioka, M. (1984) Biochemistry 23, 4357-4362; Gomi, T., Ogawa,H., and Fujioka, M. (1986) J. Biol. Chem. 261, 13422-13425). To characterize the inactivation mechanism more precisely, the properties of four hydrolase proteins mutated at Cys-78 or Cys-112 were compared to those of the wild-type enzyme. When Cys-78 was mutated to either a serine or an alanine, proteins with greatly reduced enzymatic activity were obtained, large effects on kinetic constants were observed, and enzymatic activity was not affected by incubation with FSBA. When Cys-112 was mutated to either a serine or an alanine, the activity was similar to the wild-type protein, only small changes in the kinetic constants were observed, and the enzyme was inactivated more rapidly upon incubation with FSBA. FSBA inactivation of the C112A mutant protein was accompanied by the formation of a disulfide between Cys-78 and Cys-52. The data indicate that FSBA initially reacts with Cys-78 and that Cys-78 has an important role in the structure of the enzyme. C1 US FDA,CTR BIOL EVALUAT & RES,DEV BIOL LAB,BETHESDA,MD 20892. TOYAMA MED & PHARMACEUT UNIV,FAC MED,DEPT BIOCHEM,SUGITANI,TOYAMA 93001,JAPAN. RP AKSAMIT, RR (reprint author), NIMH,GEN & COMPARAT BIOCHEM LAB,BLDG 36,RM 3D06,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 43 TC 20 Z9 20 U1 0 U2 3 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 FEB 11 PY 1994 VL 269 IS 6 BP 4084 EP 4091 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MW989 UT WOS:A1994MW98900031 PM 8307967 ER PT J AU JOHNSON, VG NICHOLLS, PJ AF JOHNSON, VG NICHOLLS, PJ TI HISTIDINE-21 DOES NOT PLAY A MAJOR ROLE IN DIPHTHERIA-TOXIN CATALYSIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLTRANSFERASE ACTIVITY; AERUGINOSA EXOTOXIN-A; NAD BINDING-SITE; ESCHERICHIA-COLI; ASPARTIC-ACID; FULL-LENGTH; MUTANT; FRAGMENT; TRANSLATION; EXPRESSION AB It has been proposed that the histidine at position 21 (H21) of the diphtheria toxin A subunit (DTA) plays an important role in the ADP-ribosyltransferase (ADPRT) activity of the toxin. The region of DT encompassing H21 demonstrates sequence similarity with other toxins exhibiting ADPRT activity, is located along the catalytic cleft of DTA, and when H21 is chemically modified, ADPRT activity is abolished. H21 was mutagenized by a polymerase chain reaction-based system whereby all alternative amino acids were substituted in place of the histidine. The majority of the substitutions virtually abolished enzymatic activity, the exception being a mutant in which H21 was replaced with asparagine (DTA-H21N). This mutant demonstrated only a slight increase in K-m and relatively small decreases in both reaction rate (k(cat)) and catalytic efficiency (k(cat)/K-m). Asparagine is a sterically conserved substitution, but its side-chain is unable to replace the imidazole group of histidine in general acid-base mechanisms or to participate in electrostatic interactions. This suggests that H21 is important in maintaining a steric conformation required for catalysis rather than in participating in an electrostatic or acid-base type of exchange. C1 NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. RP JOHNSON, VG (reprint author), US FDA,CBER,DIV BACTERIAL PROD,BACTERIAL TOXINS LAB,BLDG 29,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 24 Z9 24 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 FEB 11 PY 1994 VL 269 IS 6 BP 4349 EP 4354 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MW989 UT WOS:A1994MW98900071 PM 8308004 ER PT J AU WU, CC BRECHBIEL, MW KOZAK, RW GANSOW, OA AF WU, CC BRECHBIEL, MW KOZAK, RW GANSOW, OA TI METAL-CHELATE-DENDRIMER-ANTIBODY CONSTRUCTS FOR USE IN RADIOIMMUNOTHERAPY AND IMAGING SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID MONOCLONAL-ANTIBODIES; CONJUGATION; DTPA; POLYMERS; REAGENT; AGENTS; PROTEINS; ACIDS AB Polyamidoamine dendrimers were modified chemically by reaction with DOTA and DTPA type bifunctional metal chelators and were coupled to monoclonal antibody 2E4 without loss of protein immunoreactivity. Both the DTPA- and DOTA-dendrimer-antibody constructs were easily labeled with Y-90, In-111, Bi-212 or cold Gd(III) suggesting use of this dendrimer-macrocycle for mAb guided radiotherapy or imaging. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP WU, CC (reprint author), NIH,RADIAT ONCOL BRANCH,CHEM SECT,BETHESDA,MD 20892, USA. NR 34 TC 128 Z9 132 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD FEB 10 PY 1994 VL 4 IS 3 BP 449 EP 454 DI 10.1016/0960-894X(94)80014-6 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA MY646 UT WOS:A1994MY64600013 ER PT J AU WOOLF, GM ROJTER, SE VILLAMIL, FG VIERLING, JM KATKOV, W STERMITZ, FR BECK, JJ AF WOOLF, GM ROJTER, SE VILLAMIL, FG VIERLING, JM KATKOV, W STERMITZ, FR BECK, JJ TI JIN-BU-HUAN TOXICITY IN ADULTS - LOS-ANGELES, 1993 (REPRINTED FROM MMWR, VOL 42, PG 920-922, 1993) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 ST JOHNS HOSP,SANTA MONICA,CA. COLORADO STATE UNIV,DEPT CHEM,FT COLLINS,CO 80523. COLORADO STATE UNIV,AGR EXPT STN,FT COLLINS,CO 80523. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. CTR DIS CONTROL,NATL CTR ENVIRONM HLTH,DIV ENVIRONM HAZARDS & HLTH EFFECTS,ATLANTA,GA 30333. RP WOOLF, GM (reprint author), CEDARS SINAI MED CTR,HEPATOL SECT,LOS ANGELES,CA 90048, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 9 PY 1994 VL 271 IS 6 BP 423 EP 424 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MU491 UT WOS:A1994MU49100007 ER PT J AU THUN, MJ ALTEKRUSE, SF NAMBOODIRI, MM CALLE, EE MYERS, DG HEATH, CW AF THUN, MJ ALTEKRUSE, SF NAMBOODIRI, MM CALLE, EE MYERS, DG HEATH, CW TI HAIR DYE USE AND RISK OF FATAL CANCERS IN UNITED-STATES WOMEN SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BREAST-CANCER; MULTIPLE-MYELOMA; BLADDER-CANCER; LUNG-CANCER; HAIRDRESSERS; BEAUTICIANS; COSMETOLOGISTS; LEUKEMIA; MEN AB Background: Permanent hair dyes are used by about one third of adult American women. Several epidemiologic studies associate hair dye use with increased risk of non-Hodgkin's lymphoma and multiple myeloma. In one study, risk increased with more prolonged exposure to darker, more concentrated, permanent dyes. Purpose: The purpose of our study was to examine the relationship between hair dye use and development of certain cancers associated with hair dye use in previous studies. Methods: We examined prospectively the relationship between the use of permanent hair dyes and selected fatal cancers in 573369 women. The participants provided information in 1982 on the frequency and duration of hair dye use and the color of hair dye used. Death rates were measured through 1989. Relative risks (RRs) were computed with subjects who had not used hair dyes serving as the referent group, and 95% confidence intervals (CIs) were calculated on the basis of approximate-variance formulas. Results: Women who had ever used permanent hair dyes showed decreased risk of all fatal cancers combined (RR = 0.93; 95% CI = 0.89-0.98) and of urinary system cancers (RR = 0.65; 95% CI = 0.49-0.87) and no increase in risk of any type of hematopoietic cancer. Women who had used black hair dyes for 20 years (0.6% of women hair dyers) or more had increased risk of fatal non-Hodgkin's lymphoma (RR = 4.37; 95% CI = 1.3-15.2) and multiple myeloma (RR = 4.39, 95% CI = 1.1-18.3). These positive findings are based on three cases of non-Hodgkin's lymphoma and two cases of multiple myeloma. We found no relationship between use of permanent hair dyes and fatal cancers of the mouth, breast, lung, bladder, or cervix, areas that were of interest as the result of earlier studies. Conclusions: Women using permanent hair dyes are not generally at increased risk of fatal cancer. Women with prolonged use of dark, particularly black, hair dyes may have increased risk of fatal non-Hodgkin's lymphoma and multiple myeloma, but these women are a small fraction of hair dye users. Nonetheless, the removal of carcinogens from hair dyes and appropriate labeling of hair-coloring products would help reduce this potential risk. C1 US FDA,EPIDEMIOL BRANCH,WASHINGTON,DC 20204. RP THUN, MJ (reprint author), AMER CANC SOC,1599 CLIFTON RD NE,ATLANTA,GA 30329, USA. NR 43 TC 83 Z9 87 U1 1 U2 10 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 2 PY 1994 VL 86 IS 3 BP 210 EP 215 DI 10.1093/jnci/86.3.210 PG 6 WC Oncology SC Oncology GA MT437 UT WOS:A1994MT43700012 PM 8283493 ER PT J AU DSOUZA, MP GEYER, SJ HANSON, CV HENDRY, RM MILMAN, G CHAMOW, S FUNG, M GEYER, S HAIGWOOD, N HANSON, C HENDRY, M HATTORI, T HUISMAN, H SCHUITEMAKER, H KATINGER, H KLIKS, S LEVY, J LAMAN, J LANGEDIJK, H MELOEN, R MCPHEE, D MITCHELL, W NARA, P PAGE, M LING, C PINTER, A POSNER, M POTTS, B FIELD, K RICHMAN, D ROBINSON, J STEIMER, K STOTT, J CORCORAN, T THIRIART, C WAHREN, B WAINBERG, M WEBER, J ZOLLAPAZNER, S BUCHINDER, A AF DSOUZA, MP GEYER, SJ HANSON, CV HENDRY, RM MILMAN, G CHAMOW, S FUNG, M GEYER, S HAIGWOOD, N HANSON, C HENDRY, M HATTORI, T HUISMAN, H SCHUITEMAKER, H KATINGER, H KLIKS, S LEVY, J LAMAN, J LANGEDIJK, H MELOEN, R MCPHEE, D MITCHELL, W NARA, P PAGE, M LING, C PINTER, A POSNER, M POTTS, B FIELD, K RICHMAN, D ROBINSON, J STEIMER, K STOTT, J CORCORAN, T THIRIART, C WAHREN, B WAINBERG, M WEBER, J ZOLLAPAZNER, S BUCHINDER, A TI EVALUATION OF MONOCLONAL-ANTIBODIES TO HIV-1 ENVELOPE BY NEUTRALIZATION AND BINDING ASSAYS - AN INTERNATIONAL COLLABORATION SO AIDS LA English DT Article DE HIV-1; MONOCLONAL ANTIBODIES; IMMUNOADHESIN; NEUTRALIZATION ASSAYS; BINDING ASSAYS ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 GP120; GLYCOPROTEIN GP120; PASSIVE-IMMUNIZATION; INFECTED-CELLS; EPITOPES; IDENTIFICATION; CHIMPANZEES; DOMAIN; PROTECTION AB Objective: To characterize a purified panel of monoclonal antibodies (MAb) to epitopes in HIV-1 envelope V3, CD4-binding region, C4 and gp41. Design: Neutralization and/or binding activity data were obtained from 21 laboratories on a coded panel consisting of seven human MAb, seven mouse MAb, recombinant human CD4 immunoadhesin [CD4-immunoglobulin G (IgG)], normal human and normal murine Ig. Methods: Laboratories performed a variety of neutralization assays and antigen binding assays with HIVIIIB, HIVMN and other laboratory strains of HIV-1. Results: For a single MAb, there was up to a 10(3) range of neutralizing antibody titers between laboratories. The range in titers appeared to depend on the sensitivity of the neutralization assay. Two methods were used to consolidate the data from all laboratories, the geometric mean titer (GMT) and the median neutralizing titer (MNT). The panel of MAb were also analyzed by a variety of assays that measure binding activity to native or denatured epitopes. The relative binding activity of the MAb did not appear to correlate with neutralizing activity. Conclusion: Neutralization results from any single laboratory did not correlate with the collective data. The relative potency (rank order) of the MAb in the panel were equivalent when determined by GMT or MNT. These values may be useful to individual laboratories for estimating the sensitivity of their neutralization assays. The study also identified potential reference reagents with which neutralizing activity could be compared. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. CALIF DEPT HLTH SERV,VIRAL & RICKETTSIAL LAB,BERKELEY,CA. CHIRON CORP,EMERYVILLE,CA 94608. KYOTO UNIV,KYOTO,JAPAN. NETHERLANDS RED CROSS,AMSTERDAM,NETHERLANDS. UNIV CALIF BERKELEY,BERKELEY,CA. TNO,MED BIOL LAB,AMSTERDAM,NETHERLANDS. CENT DIERGENEESKUNDIG INST,AMSTERDAM,NETHERLANDS. VANDERBILT UNIV,NASHVILLE,TN 37240. NCI,BETHESDA,MD 20892. NATL INST BIOL STAND & CONTROLS,POTTERS BAR EN6 3QG,HERTS,ENGLAND. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. UNIV CONNECTICUT,MED CTR,STORRS,CT. NATL BACTERIOL LAB,STOCKHOLM,SWEDEN. MCGILL UNIV,AIDS CTR,MONTREAL,PQ,CANADA. RP DSOUZA, MP (reprint author), NIAID,DIV AIDS,6003 EXECUT BLVD,SOLAR BLDG,ROOM 2835,BETHESDA,MD 20892, USA. NR 60 TC 30 Z9 30 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD FEB PY 1994 VL 8 IS 2 BP 169 EP 181 PG 13 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NA433 UT WOS:A1994NA43300004 PM 7519019 ER PT J AU HEREDIA, A MULLER, J SORIANO, V LEE, SF CASTRO, A PEDREIRA, J POFFEMBERGER, KL EPSTEIN, J HEWLETT, IK AF HEREDIA, A MULLER, J SORIANO, V LEE, SF CASTRO, A PEDREIRA, J POFFEMBERGER, KL EPSTEIN, J HEWLETT, IK TI ABSENCE OF EVIDENCE OF RETROVIRAL INFECTION IN IDIOPATHIC CD4+ T-LYMPHOCYTOPENIA SYNDROME SO AIDS LA English DT Letter C1 US FDA,CTR BIOL EVALUAT & RES,OFF VACCINES,DIV VIRAL PROD,ROCKVILLE PIKE,MD 20852. INST SALUD CARLOS III,SERV INFECT DIS MICROBIOL & IMMUNOL,MADRID,SPAIN. HOSP JUAN CANALEJO,SERV INTERNAL MED,LA CORUNA,SPAIN. RP HEREDIA, A (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS & TRANSMITTED DIS,MOLEC VIROL LAB,ROCKVILLE PIKE,MD 20852, USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD FEB PY 1994 VL 8 IS 2 BP 267 EP 268 DI 10.1097/00002030-199402000-00017 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NA433 UT WOS:A1994NA43300017 PM 7519021 ER PT J AU BALAYAN, M BHAMARAPRAVATI, N BURKE, D CHANDLER, DK DESROSIERS, R SCHILD, G SCHULTZ, A SHAW, GM STOTT, J WEISS, R WIGZELL, H DOWDLE, WR GIRARD, M GOUDSMIT, J GUIMARAES, CS KIENY, MP MBIDDE, EK ROSCAMABBING, EW ESPARZA, J HEYMANN, DL HEYWARD, WL KALLINGS, LO MERSON, MH OSMANOV, S SABA, J AF BALAYAN, M BHAMARAPRAVATI, N BURKE, D CHANDLER, DK DESROSIERS, R SCHILD, G SCHULTZ, A SHAW, GM STOTT, J WEISS, R WIGZELL, H DOWDLE, WR GIRARD, M GOUDSMIT, J GUIMARAES, CS KIENY, MP MBIDDE, EK ROSCAMABBING, EW ESPARZA, J HEYMANN, DL HEYWARD, WL KALLINGS, LO MERSON, MH OSMANOV, S SABA, J TI FEASIBILITY OF DEVELOPING LIVE ATTENUATED HIV VACCINES - CONCLUSIONS AND RECOMMENDATIONS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID GENE C1 MOSCOW POLIOMYELITIS & VIRUS ENCEPHALITIS INST,MOSCOW,RUSSIA. MAHIDOL UNIV,BANGKOK 10700,THAILAND. WALTER REED ARMY INST,ROCKVILLE,MD. US FDA,ROCKVILLE,MD 20857. HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. NATL INST BIOL STAND & CONTROLS,POTTERS BAR EN6 3QG,HERTS,ENGLAND. NIAID,DIV AIDS,BETHESDA,MD 20892. UNIV ALABAMA,BIRMINGHAM,AL. INST CANC RES,CHESTER BEATTY LABS,LONDON SW3 6JB,ENGLAND. KAROLINSKA INST,STOCKHOLM,SWEDEN. CTR DIS CONTROL & PREVENT,ATLANTA,GA. INST PASTEUR,PARIS,FRANCE. UNIV AMSTERDAM,AMSTERDAM,NETHERLANDS. INST MED TROP,SAO PAULO,SP,BRAZIL. WHO,STEERING COMM VACCINE DEV,GENEVA,SWITZERLAND. TRANSGENE SA,STRASBOURG,FRANCE. MULAGO HOSP,KAMPALA,UGANDA. WHO,GLOBAL PROGRAMME AIDS,CH-1211 GENEVA 27,SWITZERLAND. OI /0000-0002-5704-8094 NR 9 TC 6 Z9 6 U1 0 U2 0 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 FEB PY 1994 VL 10 IS 2 BP 221 EP 222 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MZ149 UT WOS:A1994MZ14900016 ER PT J AU KAHN, JO GORELICK, KJ GATTI, G ARRI, CJ LIFSON, JD GAMBERTOGLIO, JG BOSTROM, A WILLIAMS, R AF KAHN, JO GORELICK, KJ GATTI, G ARRI, CJ LIFSON, JD GAMBERTOGLIO, JG BOSTROM, A WILLIAMS, R TI SAFETY, ACTIVITY, AND PHARMACOKINETICS OF GLQ223 IN PATIENTS WITH AIDS AND AIDS-RELATED COMPLEX SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POKEWEED ANTIVIRAL PROTEIN; HUMAN MONOCYTE-MACROPHAGES; HIV REPLICATION; CELLS; INHIBITION; AZIDOTHYMIDINE; TRICHOSANTHIN; ANTIBODIES; INFECTION AB GLQ223 is a highly purified single-chain ribosome-inactivating protein with selective effects against a variety of cells, including macrophages infected with human immunodeficiency virus. We evaluated the safety, pharmacokinetics, and immunologic effects of multiple doses of GLQ223 in 22 patients with AIDS or AIDS-related complex; CD4(+) T-cell counts were between 100 and 350/mm(3). GLQ223 was administered intravenously at doses of 8, 16, 24, 36, and 50 mu g/kg of body weight; the drug was administered by constant infusion over 3 h to achieve a concentration in serum of 50 ng/ml; this concentration is known to be associated with anti-HIV effects in vitro. All patients reported a flu-like syndrome characterized by muscle and joint aches and an increase in creatinine kinase levels; symptoms were controlled easily. For patients who received 36 and 50 mu g/kg, target concentrations in serum were achieved and an increase in CD4(+) and CD8(+) T cells was sustained; this sustained increase persisted for at least 28 days after the last infusion. beta(2)-Microglobulin levels increased during the infusions and then declined when the infusions ended. Repeat infusions of GLQ223 were safe and relatively well tolerated. The target concentration of GLQ223 in serum was achieved and sustained. Our results suggest that GLQ223 may have activity in treating patients with human immunodeficiency virus infection. C1 UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94110. GENELABS TECHNOL INC,REDWOOD CITY,CA 94063. CRUNCH SOFTWARE,OAKLAND,CA 94621. US FDA,WASHINGTON,DC 20204. UNIV CALIF SAN FRANCISCO,DEPT CLIN PHARM,SAN FRANCISCO,CA 94110. NR 27 TC 59 Z9 67 U1 1 U2 2 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 FEB PY 1994 VL 38 IS 2 BP 260 EP 267 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA MU932 UT WOS:A1994MU93200020 PM 7910722 ER PT J AU ASZALOS, A PINE, PS WEAVER, JL SCHOENLEIN, PV GOTTESMAN, MM SZABO, G AF ASZALOS, A PINE, PS WEAVER, JL SCHOENLEIN, PV GOTTESMAN, MM SZABO, G TI BEHAVIOR OF N-ACYLATED DAUNORUBICINS IN MULTIDRUG-RESISTANT AND PARENTAL CANCER-CELLS SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 US FDA,CDER,DIV RES & TESTING,WASHINGTON,DC 20204. NCI,CELL BIOL LAB,BETHESDA,MD 20892. MED SCH DEBRECEN,DEBRECEN,HUNGARY. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A121 EP A121 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46200702 ER EF