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Biomedical subjects

B A Smith

Publications and source records attributed to B A Smith.

At least 163 records · Page 9Linked to original sources
PubMed1985

DNA repair and replication in human fibroblasts treated with (+/-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene .

DNA repair and replication were examined in diploid human fibroblasts after treatment with (+/-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-I). Unscheduled DNA synthesis exhibited a linear response to BPDE-I concentrations up to 1.5 microM and a saturation plateau after higher concentrations. Maximal unscheduled DNA synthesis was observed in the first hour after treatment with synthesis diminishing progressively thereafter. Half-maximal unscheduled DNA synthesis was seen within 4-6 h after treatment with 0.7 microM BPDE-I. DNA replication was inhibited by BPDE-I in a dose- and time-dependent fashion. The mechanisms of this inhibition were characterized by velocity sedimentation of pulse-labeled nascent DNA in alkaline sucrose gradients. Very low concentrations of BPDE-I (0.03 and 0.07 microM) were found to inhibit replicon initiation by up to 50% within 30-60 min after treatment. Recovery of initiation following these low concentrations was evident within 3 h after treatment. Higher concentrations of carcinogen inhibited DNA synthesis in active replicons. This effect was manifested by a reduction in incorporation of precursor into replication intermediates of greater than 1 X 10(7) Da with the concurrent production of abnormally small nascent DNA. When viewed 45 min after treatment with 0.17 microM BPDE-I the combination of these two effects partially masked the inhibition of replicon initiation. However, even after treatment with 0.33 microM BPDE-I an effect on initiation was evident. These results reveal a pattern of response to BPDE-I that is quite similar to that produced by 254 nm radiation.

Benzopyrenes↗
PubMed1985

An estimate of unique DNA sequence heterozygosity in the human genome.

Fifteen different restriction fragment length polymorphisms (RFLPs) were detected in the human genome using 19 cloned DNA segments, derived from flow-sorted metaphase chromosomes or total genomic DNA, as hybridization probes. Since these clones were selected at random with respect to their coding potential, their analysis permitted an unbiased estimate of single-copy DNA sequence heterozygosity in the human genome. Since our estimate (h = 0.0037) is an order of magnitude higher than previous estimates derived from protein data, most of the polymorphic variation present in the genome must occur in non-coding sequences. In addition, it was confirmed that enzymes containing the dinucleotide CpG in their recognition sequence detect more polymorphic variation than those that do not contain CpG.

Base Sequence↗
PubMed1985

Mechanical properties of a new facial prosthetic material.

The tensile strength, tear resistance, and hardness of four silicone elastomers were compared. Results suggest that Cosmesil has improved mechanical properties over commonly used facial prosthetic silicone elastomers.

Chemical Phenomena↗
PubMed1985

Interaction of nucleophiles with the enzymatically-activated carcinogen, N-hydroxy-2-acetylaminofluorene, and with the model ester, N-acetoxy-2-acetylaminofluorene.

A new method was devised to study adduct formation of N-acetyl-L-methionine (N-Ac-met) with activated species of the carcinogen N-hydroxy-2-acetylaminofluorene (N-OH-2-AAF). Following degradation of the adducts, the isomeric methylthio derivatives of 2-acetylaminofluorene (2-AAF) and 2-aminofluorene (2-AF) were separated and quantified by h.p.l.c. With the use of this method the nucleophilicity of N-Ac-met toward enzymatically produced N-acetoxy and N-sulfonoxy derivatives of 2-AF and 2-AAF, respectively, and toward the synthetic model ester, N-acetoxy-2-acetylaminofluorene (N-OAc-2-AAF), was determined. For comparison, the interaction of tRNA and polyguanylic acid (poly G) with the above compounds was measured by standard procedures. tRNA was an efficient acceptor of enzymatically formed N-acetoxy and N-sulfonoxy derivatives as well as of N-OAc-2-AAF. The nucleophilicity of N-Ac-met toward enzymatically formed N-sulfonoxy-2-AAF was comparable with that of tRNA. However, its reactivity with N-OAc-2-AAF and enzymatically generated N-acetoxy-2-aminofluorene (N-OAc-2-AF) was only 20% of that of tRNA. Poly G was as reactive as tRNA toward synthetic N-OAc-2-AAF and enzymatically generated N-OAc-2-AF but was only 25% as efficient as tRNA or N-Ac-met in accepting enzymatically formed N-sulfonoxy-2-AAF. The difference in the interaction of the three nucleophiles with N-OAc-2-AAF and N-OAc-2-AF compared with N-sulfonoxy-2-AAF indicate that N-OAc-2-AAF is not a general model of the ultimate electrophilic metabolites of 2-AAF. Studies of the kinetics of the interaction of N-OAc-2-AAF with N-Ac-met, tRNA and poly G demonstrated dependence of adduct formation on nucleophile concentration, indicative of a bimolecular mechanism. Arylamidonium or nitrenium ions are therefore not necessarily the ultimate electrophilic metabolites of 2-AAF obligatory for interaction with cellular nucleophiles. There was no evidence that nitrenium ions are intermediates in the cytosolic reduction of N-OH-2-AAF to 2-AAF.

2-Acetylaminofluorene↗
PubMed1984

Differential effect of chronic ethanol consumption by the rat on microsomal oxidation of hepatocarcinogens and their activation to mutagens.

The effect of chronic ethanol consumption by rats on hepatic microsomal activation of the hepatocarcinogens dimethylnitrosamine (DMN) and 2-acetylaminofluorene (2-AAF) was investigated. There was a marked increase in the rate of the oxidative demethylation of DMN and its activation to a mutagen by microsomes following ethanol intake. N- and C-hydroxylation of 2-AAF were measured at substrate concentrations ranging from 2 to 70 microM. The ratio of formation of N-hydroxy-2-acetylaminofluorene to C-hydroxy-2-acetylaminofluorenes increased with decreasing substrate concentration, suggesting enhanced carcinogenic potential of 2-AAF with diminishing levels of carcinogen. Kinetic analysis indicated that N-hydroxylation as well as 7-, 5- and 3-hydroxylation of 2-AAF do not follow Michaelis-Menten kinetics. In contrast to the marked inductive effect of ethanol consumption on the metabolic activation of DMN, only a minimal random effect on the N-hydroxylation of 2-AAF was demonstrable in two separate experiments. Furthermore, N-hydroxylation of 2-AAF by microsomes from control and ethanol-treated rats followed similar kinetics. While ethanol consumption enhanced the mutagenic activation of DMN by hepatic microsomes, no such effect of ethanol consumption on the conversion of 2-AAF to a mutagen was observed. The data indicate that chronic ethanol consumption does not have a general inductive effect on the microsomal activation of hepatocarcinogens.

2-Acetylaminofluorene↗
PubMed1984

Tracheal rupture during anaesthesia.

Tracheal rupture as a direct complication of tracheal intubation is rare. We report a case where this occurred during oesophageal surgery. The literature describing eight previous cases is reviewed and recommendations are made to reduce the possibility of such an occurrence.

Aged↗
PubMed1984

High volume milk feeds for preterm infants.

Fifty nine preterm infants of between 1.0 and 2.0 kg birthweight who were fed 250 ml/kg/day of breast milk or standard formulas gained weight at the intrauterine rate without complications. It is suggested that high volume feeding is a satisfactory alternative to low birthweight formula milks and is more desirable in infants who are to be breast fed.

Animals↗
PubMed1984

Interstitial deletion of the short arm of chromosome 5 in a mother and three children.

An interstitial deletion (5) (p13p15.1) was found in a mentally retarded woman and three of her four children. The variable manifestation of this chromosomal defect and the relevance of this particular deletion to the cri du chat syndrome are discussed. To our knowledge the only other reported case of inherited 5p deletion from an affected parent involved the terminal segment of the 5p15.3 band.

Adult↗
PubMed1982

Relationship between Vital Staining and Subculture Growth during the Senescence of Plant Tissue Cultures.

The vital staining properties of rose cultures (Rosa cv Paul's Scarlet) of increasing age were compared with their ability to be subcultured. At 4-day intervals beginning on day 14, after cell division and expansion had stopped, cells were stained separately with Evans blue, fluorescein diacetate, and phenosafranine. The degree to which parent cultures stained with each of these dyes was compared to the dry weight of their subcultures harvested after 9 and 21 days of growth.Staining with either Evans blue or fluorescein diacetate was demonstrated to be a good means of establishing when senescing cells died. However, the staining properties of aging cultures did not correlate well with their ability to be subcultured, because an increasing proportion of the living cells appeared to lose their ability to divide as senescence progressed.

Journal Article↗
PubMed1981

Ribonucleic acid synthesis during fruiting body formation in Myxococcus xanthus.

A method has been devised that allowed us, for the first time, to pulse-label M. xanthus cells with precursors for ribonucleic acid biosynthesis while they were undergoing fruiting body formation. Using this method, we examined patterns of ribonucleic acid (RNA) accumulation throughout the process of fruiting body formation. As development proceeded, the rate of RNA accumulation increased at two periods of the developmental cycle: once just before aggregation and once late in the cycle, when sporulation was essentially completed. In contrast to vegetatively growing cells, in which only stable RNA species are labeled during a 30-min pulse, the majority of radioactivity found in RNA from 30-min pulse-labeled developing cells was found in an unstable heterodisperse fraction that migrated to the 5S to 16S region of sucrose density gradients and sodium dodecyl sulfate-polyacrylamide gels. This pattern of incorporation could not be induced (i) by a shift down of vegetatively growing cells to a nutritionally poor medium, in which the generation time was increased to that of developing cells during the growth phase, or (ii) by plating of vegetative cells onto the same solid-surface environment as that of developing cells, but which surface supported vegetative growth rather than fruiting body formation. Thus, the RNA synthesis pattern observed appeared to be related to development per se rather than to nutritional depletion or growth on a solid surface alone. The radioactivity incorporated into the unstable 5S to 16S RNA fraction accumulated as the pulse length was increased from 10 to 30 min; in contrast, an analogous unstable fraction from vegetative cells decreased as pulse length was increased. This suggested that developmental 5S to 16S RNA was more stable than vegetative cell 5S to 16S RNA (presumptive messenger RNA). However, during a 45-min chase period, radioactivity in 30-min-pulse-labeled developmental 5S to 16S RNA decayed to an extent twice that of developmental RNA located in 16S and 23S regions of sucrose density gradients and was considerably less stable than the 5S, 16S, and 23S RNA species labeled during a 30-min pulse of vegetative cells.

Micropore Filters↗