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Biomedical subjects

E Bailey

Publications and source records attributed to E Bailey.

At least 19 recordsLinked to original sources
PubMed1992

Acetoxime is metabolized by human and rodent hepatic cytochrome P450 enzymes to the genotoxicant and carcinogen propane 2-nitronate.

The hepatocarcinogenicity of acetoxime has been tentatively linked with its metabolic oxidation to the potent genotoxicant and carcinogen propane 2-nitronate (P2-N). In order to test the hypothesis that acetoxime is metabolized to P2-N, the oxime (20 mM) was incubated with liver microsomes from mice, rats and two humans. Ion-pair HPLC analysis of the incubates afforded a peak that co-eluted with P2-N. P2-N exists in tautomeric equilibrium with 2-nitropropane (2-NP). Samples of the microsomal incubates, which had been adjusted to pH 5.5 and kept for 24 h in order to allow maximal tautomeric equilibration of P2-N to 2-NP to occur, were extracted with hexane. GLC analysis of the extracts yielded a peak that co-eluted with 2-NP, and gave a mass spectrum identical to that of authentic 2-NP. The metabolite peak obtained on HPLC was isolated and its hexane extract contained also 2-NP when investigated by GLC. P2-N was found by HPLC in the urine of rats that had received acetoxime (3.36 mmol/kg i.p.). Hexane extracts of urine samples, which had been adjusted to pH 5.5 and left for 24 h, contained 2-NP as demonstrated by GLC analysis. The results are consistent with the suggestion that the toxicity of acetoxime is associated with its biotransformation to P2-N.

Animals↗
PubMed1992

Office endoscopy.

Increasing numbers of physicians are considering office endoscopy. Planning for office endoscopy should include the nursing personnel who will be staffing the unit. This article introduces readers to office endoscopy and addresses issues involved in establishing an office-based endoscopy center.

Endoscopes↗
PubMed1992

Hormonal induction of malic enzyme in rat hepatocytes cultured on laminin-rich gels.

The levels of malic-enzyme mRNA and activity were determined in primary cultures of adult rat hepatocytes maintained on either rat-tail collagen or a laminin-rich substratum. Cells plated on laminin-rich gels exhibited substantially improved patterns of albumin and malic-enzyme expression when compared with cells maintained on rat-tail collagen. Moreover, hepatocytes plated on the laminin-rich matrix displayed marked malic-enzyme inducibility in response to tri-iodothyronine and dichloroacetate, especially in the presence of insulin. However, Northern blot analysis revealed that the ratio of the amounts of the two major malic-enzyme mRNA species (2.0 and 3.1 kb) was reversed when compared with that found in the liver in vivo, the altered levels of these two species being closer to those found in non-hepatic tissues. These findings indicate that, although the hormonal responsiveness of isolated hepatocytes maintained on laminin-rich gels is markedly improved, and approaches the degree of induction demonstrated in the liver in vivo, the mechanisms of control differ, indicating a loss of liver-specific expression.

Animals↗
PubMed1991

Pre-translational control of hepatic malic enzyme expression during the development of the rat.

The expression of hepatic cytosolic malic enzyme in the developing rat has been studied by molecular-biological techniques. Malic enzyme mRNA was barely detectable throughout the neonatal period, but increased to significant levels immediately before weaning. Northern-blot analysis demonstrated that the two major malic enzyme mRNA species displayed non-co-ordinate control during development, with the 2.0 kb form accumulating to a greater extent than the 3.1 kb form. A novel 1.6 kb mRNA species was found to predominate in foetal samples. Tri-iodothyronine treatment of neonatal rats caused premature induction of all three malic enzyme mRNA species. Dietary studies also showed precocious induction of the mRNA with diets high in carbohydrate, but not with those high in fat.

Aging↗
PubMed1991

Pathological changes of the mare endometrium and genotypes for transferrin and ELA.

Histological features of the endometrium, as assessed in biopsy samples, were related to Standardbred mare genotypes for transferrin, esterase (as a control) and equine leucocyte antigens (ELA). Pathological changes were found more frequently in each successively older age group of mares. Among mares aged 6-19 years, there were significant pathologic changes on first examination following an infertile breeding season for 46 of 90 (51%) of transferrin homozygotes and 50 of 146 (34%) of transferrin heterozygotes. The difference between the two groups was significant for the total data (chi 1(2) = 6.56, P = 0.010) and when the data were stratified for mare age at biopsy (chi 1(2) = 7.33, P = 0.0068). The effect of transferrin was similar in both trotters and pacers, especially for frequent genotypes commonly found in horses of both gaits. There was no effect of esterase and, in a smaller set of ELA-typed mares, no significant effect of ELA genotype on uterine biopsy category. Transferrin has a well-established microbiostatic and biocidal effect. Conceivably, heterozygotes for some combinations of transferrin variants could have a slower natural rate of endometrial deterioration than homozygotes.

Age Factors↗
PubMed1991

Biomonitoring of human exposure to alkylating agents by measurement of adducts to haemoglobin or DNA.

Recent analytical developments in the determination of adducts of DNA and protein with alkylating carcinogens are described which have considerably extended the number of carcinogens that can be examined. While sensitivity of detection equal to or better than one modified DNA base per 10(8) normal bases is now achievable for many specific alkylating carcinogens, further developments in the analytical methods are still needed for the identification and quantification of adducts derived from unknown and/or mixed exposures to carcinogens.

Alkylating Agents↗
PubMed1990

Monitoring exposure to 4,4'-methylenedianiline by the gas chromatography-mass spectrometry determination of adducts to hemoglobin.

The determination of the covalently bound reaction products of 4,4'-methylenedianiline (MDA) to hemoglobin was investigated as a possible method for biological dosimetry in humans. The extent of binding to rat hemoglobin of MDA was determined by dosing animals with the 14C-ring-labeled compound. Two adducts were released from the hemoglobin on hydrolysis under mildly basic conditions which were identified as MDA and N-acetyl-MDA and accounted for between 36 and 45% of the total radioactivity bound to the protein. A quantitative assay procedure was subsequently developed for measuring both of the base released adducts in rat hemoglobin. The method utilized solvent extraction followed by derivatization with pentafluoropropionic anhydride and subsequent separation and quantitation by capillary gas chromatography with selective ion monitoring mass spectrometry using deuterium-labeled analogues of MDA and N-acetyl-MDA as internal standards. A dose-response relationship was established in orally dosed rats between production of each of the hemoglobin released adducts and dose of MDA (1-12 mg/kg). The possible use of such adduct determinations as dosimeters for industrial workers exposed to MDA is discussed.

Aniline Compounds↗
PubMed1990

Influence of cigarette smoking on the levels of DNA adducts in human bronchial epithelium and white blood cells.

The presence of carcinogen-DNA adducts in human tissues is evidence of exposure to carcinogens and may be an indicator of cancer risk. DNA was isolated from non-tumorous bronchial tissue of 37 cigarette smokers, 8 former smokers and 8 non-smokers and analyzed for the presence of aromatic and/or hydrophobic DNA adducts in the 32P-post-labelling assay. Adducts were detected as bands of radioactive material when 5'-32P-labelled deoxyribonucleoside 3',5'-bisphosphates were chromatographed on polyethyleneimine-cellulose tlc plates, and the patterns indicated the formation of adducts by a large number of compounds. Adduct levels detected in DNA from non-smokers, former smokers and current smokers were 3.45 +/- 1.62, 3.93 +/- 1.92 and 5.53 +/- 2.13 adducts/10(8) nucleotides, respectively. The differences in adduct levels between smokers and former and non-smokers were statistically significant (p less than 0.01); and among the smokers, significant correlations were found between adduct levels and both daily cigarette consumption and total cigarette consumption (daily consumption X number of years smoked). DNA was also isolated from the peripheral-blood leukocytes of 31 heavy smokers (greater than 20 cigarettes/day) and 20 non-smokers and analyzed by 32P-post-labelling. Adduct levels in the smokers' samples were not significantly different from levels in the non-smokers' samples (2.53 +/- 1.31 and 2.12 +/- 1.44 adducts/10(8) nucleotides, respectively). Thus, evidence for carcinogen exposure was found in human bronchial epithelium, a target tissue for tobacco-induced tumour formation, but not in peripheral-blood cells, indicating possible limitations in the use of the latter as a surrogate, non-target tissue source of DNA for monitoring human exposure to inhaled carcinogens.

Adult↗
PubMed1990

Doctor-initiated consultations: a study of communication between general practitioners and patients about the need for reattendance.

It has been suggested that general practitioners have the potential to regulate a large percentage of their workload through their control of 'doctor-initiated' consultations. A survey was made of 300 consecutive consultations in a group practice. After their consultation patients completed a questionnaire asking what advice the doctor had given them on the need to reattend. At the same time the general practitioner completed a similar questionnaire about the need for reattendance and the advice given. The general practitioners judged that 74% of patients definitely or possibly needed to reattend, and only 26% definitely did not need to reattend. The coefficient of agreement between patients' and doctors' views on whether reattendance had been recommended was only 0.41. Thus the room for control of doctor-initiated consultations is limited by both clinical considerations and the apparent difficulty of accurately communicating the doctor's advice on reattendance to the patient.

Communication↗
PubMed1989

Reduction of nitromin to nitrogen mustard: unscheduled DNA synthesis in aerobic or anaerobic rat hepatocytes, JB1, BL8 and Walker carcinoma cell lines.

A novel route for the microsomal generation of nitrogen mustard from its N-oxide nitromin is demonstrated. The mustard was trapped as an adduct with diethyldithiocarbamate and estimated by capillary GLC. The enzyme responsible for this reduction could utilize either NADPH or NADH. Reduction occurred preferentially under anaerobic conditions. Purified cytochrome P450 reductase could carry out this reaction. Similar activities were seen using microsomal fractions from rat liver or liver derived BL8, JB1 or Walker 256 carcinoma cells, when these were expressed on a per mg of protein basis. Unscheduled DNA synthesis (UDS) was used as an index of activation of nitromin in these cell systems. In all instances, greater induction of UDS occurred in cells incubated with nitromin under anaerobic conditions.

Aerobiosis↗
PubMed1988

Hydroxyethylvaline adduct formation in haemoglobin as a biological monitor of cigarette smoke intake.

The ethylene oxide adduct formed on the N-terminal valine in haemoglobin was investigated as a biological monitor of tobacco smoke intake. The modified method developed for the determination of the hydroxyethylvaline adduct (HOEtVal) involved reaction of globin with pentafluorophenyl isothiocyanate, extraction of the HOEtVal thiohydantoin product, derivatization of this by trimethylsilylation and quantitation by capillary gas chromatography with selective ion monitoring mass spectrometry using a tetradeuterated internal standard. The method was applied to globin samples from 26 habitual cigarette smokers and 24 non-smokers. There was a significant correlation between cigarette smoke intake as measured by the average number of cigarettes smoked per day and HOEtVal levels (r = 0.537, p less than 0.01). Background levels were found in non-smokers (mean 49.9 pmol/g Hb, range 22-106 pmol/g Hb). Smoking increased these levels by 71 pmol/g Hb/10 cigarettes per day. Cotinine levels in plasma of the smokers were determined by GC-NPD using 2-methyl-4-nitroaniline as internal standard. For non-smokers cotinine was determined by GC-MS selective ion monitoring using d3-methylcotinine as internal standard. There was no correlation between number of cigarettes smoked per day and cotinine levels (r = 0.297, p greater than 0.05) although cotinine was correlated with HOEtVal (r = 0.43, p less than 0.01). The HOEtVal adduct levels thus appear to be a suitable biomonitor for exposure to hydroxyethylating agents in cigarette smoke, reflecting an integrated dose over the erythrocyte lifetime. This is in contrast to plasma cotinine determinations which reflect only the previous day's exposure to nicotine in smoke.

Biomarkers↗
PubMed1988

ELA and fertility in American Standardbred horses.

We have analysed the effects of ELA alleles and sire-dam ELA incompatibility on two measures of fertility, gestation length and foaling rate, in American Standardbred horses. Using multivariate statistical methods, we corrected for the effects of confounding factors such as dam and sire age, parity, inbreeding, and sire-dam kinship. These analyses revealed substantial differences between Standardbred trotters and pacers in the effects of several confounding factors. There appear to be no ELA effects on gestation length in either trotters or pacers. However our results suggest that there may be ELA effects on foaling rate associated with specific dam alleles, with sire-dam incompatibility, and possibly with specific sire alleles, and that these effects differ between trotters and pacers.

Age Factors↗