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Biomedical subjects

E Bailey

Publications and source records attributed to E Bailey.

At least 91 records · Page 5Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Joint Report of the Fifth International Workshop on Lymphocyte Alloantigens of the Horse, Baton Rouge, Louisiana, 31 October-1 November 1987.

Six laboratories participated in the Fifth International Workshop on Lymphocyte Alloantigens of the Horse, testing 132 alloantisera against lymphocytes of 880 horses chosen to represent different families and breeds. Most of the alloantisera were produced by lymphocyte immunization between horses matched at the ELA-A locus. All horses were also tested with antisera contributed to the workshop by participating laboratories which identified ELA specificities A1-A10 and W12-W21. Previously identified workshop specificities ELA-W14, W15 and W19 were accepted as products of the ELA-A locus based on family and population studies by the workshop. Their designations were changed to ELA-A14, ELA-A15 and ELA-A19, respectively. Two new specificities were identified, namely ELA-W22 (W22) and ELA-W23 (W23). Population and family studies indicated that W22 and W23 as well as W13 are products of an ELA locus other than ELA-A. The presence of these specificities was correlated with the presence of certain ELA-A locus specificities, e.g. W13 with A3, W22 with A2 and W23 with A5. However, the association was not complete and W13, W22 and W23 also segregated with other ELA-A specificities in some families. Evidence for recombination was found between the ELA-A locus and the locus or loci encoding these specificities resulting in seven recombinant haplotypes found among the data presented in this workshop. Further studies are required for definitive assignment of the specificities to a class I or class II locus.

Animals↗

Equine neonatal isoerythrolysis: evidence for prevention by maternal antibodies to the Ca blood group antigen.

Foals with the Ca blood group antigen on their RBC were given colostrum with anti-Ca antibodies (6 foals) or colostrum without anti-Ca antibodies (6 foals). The PCV were determined at birth and 2, 4, and 6 days after birth for the foals in each group. Significant differences were not observed for the PCV between the 2 groups, indicating that foals were not adversely affected by ingesting colostrum with the anti-Ca antibody. Standardbred mares without the Aa blood group antigen were evaluated to determine whether production of anti-Ca antibodies influenced production of anti-Aa antibodies. Of 266 mares without the Aa antigen, 3 of 61 (5%) mares without the Ca blood group antigen produced anti-Aa antibodies and 43 of 205 (21%) with the Ca blood group antigen produced anti-Aa antibodies. These 2 groups of mares were significantly (P = 0.006) different; Ca-negative mares were less likely to produce antibodies to Aa than were mares with the Ca blood group antigen. This observation was consistent with a hypothesis of antibody-mediated immunosuppression of immune response to the Aa blood group antigen by antibodies to the Ca blood group antigen, ie, when a mare is exposed to her foal's RBC and already has antibodies to the Ca blood group antigen on the foal's RBC, then she is less likely to initiate an immune response to the Aa blood group antigen also on the foal's RBC.

Animals↗