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Biomedical subjects

B R Smith

Publications and source records attributed to B R Smith.

At least 307 records · Page 17Linked to original sources
PubMed1981

Family history, cigarette smoking and other risk factors in patients with myocardial infarction.

All patients entering a coronary care unit had data collected and stored prospectively on a computer file. Family history and risk factor data have been abstracted for those with confirmed myocardial infarction. These data are compared between those aged less than 50 years and those aged between 50 and 70 years. Cigarette smoking habits are compared with age matched data from the 1976 census population study of cigarette smoking habits. The risk factors of hypercholesteolaemia, obesity, diabetes, hypertension and cigarette smoking greater than 20 per day, do not separate the two age groups although cigarette smoking is more prevalent in the patient groups compared with the census population. Age of fathers' death is not different between the two age groups but death from myocardial infarction, presence of ischaemic heart disease during life in fathers and fewer nonsmokers in the younger age group clearly separate them from older age group patients. This study serves to emphasise that in order to prevent the development of myocardial infarction special attempts sould be made to prevent cigarette smoking in those whose fathers have died of a myocardial infarction or have symptoms of ischaemic heart disease.

Age Factors↗
PubMed1981

Metabolism of benzo(a)pyrene and benzo(a)pyrene 4,5-oxide in rabbit lung.

For several years our laboratory has been investigating the biotransformation of various environmental pollutants by lung. Studies have been performed with pulmonary subcellular fractions, purified monooxygenase and glutathione transferase enzymes, and preparations having intact cellular structure including the isolated perfused lung and cell fractions enriched in alveolar macrophages, Clara cells and alveolar type II cells. Collectively, these investigations have identified several metabolic factors which may contribute to the pulmonary toxicity mediated by certain polycyclic aromatic hydrocarbons (PAH). First, although lung has low overall cytochrome P-450-dependent monooxygenase activity for many substrates, relative to liver, this activity is localized in only a few cell types and specific activity in certain cell types, such as the non-ciliated bronchiolar epithelial (Clara) cell, can be high. Second, oxidative metabolites of benzo(a)pyrene tend to accumulate in pulmonary tissue due, at least in part, to the low ability of lung (relative to liver) to conjugate and detoxify phenolic, dihydrodiol and epoxide metabolites. Thus, products such as benzo(a)pyrene 7,8-dihydrodiol are available for further cytochrome P-450-dependent oxidation to ultimate carcinogens and cytotoxins. Moreover, the lung is efficient in removing benzo(a)pyrene 4,5-oxide and presumably other oxidized PAH metabolites, from the bloodstream. Consequently, the uptake of relatively stable electrophilic metabolites released by the liver may also contribute to pulmonary toxicity.

Animals↗
PubMed1981

Sex hormones enhance immunoglobulin synthesis by human peripheral blood lymphocytes.

Using a protein A haemolytic plaque assay to detect immunoglobulin synthesis by human peripheral blood lymphocytes cultured with pokeweed mitogen, we have shown a significant increase in IgG plaque-forming cells in the presence of physiological concentrations of testosterone and oestradiol. Higher concentrations of these steroids inhibit plaque-forming cells. There was no difference in the response to testosterone and oestradiol of lymphocytes derived from male subjects or menstruating or post-menopausal females.

Adult↗
PubMed1981

Acetylcholine receptor antibody synthesis in lymphocyte cultures.

The synthesis of immunoglobulin and acetylcholine receptor antibody by lymphocytes extracted from the peripheral blood and thymus of patients with myasthenia gravis was investigated using the Marbrook culture system. Small amounts of immunoglobulin were synthesised by thymic lymphocytes cultured in medium without mitogen for 14 days and acetylcholine receptor antibody activity was detectable in cultures from 3 out of 5 patients with thymic hyperplasia. Addition of Pokeweed mitogen to the cultures increased both IgG and acetylcholine receptor antibody synthesis and under these conditions receptor antibody activity was detectable in all 5 thymic lymphocyte cultures studied. Peripheral blood lymphocytes also produced small amounts of IgG when cultured in the absence of mitogen but acetylcholine receptor antibody levels were undetectable. In the presence of Pokeweed mitogen, however, peripheral blood lymphocytes synthesised increased amounts of IgG and acetylcholine receptor antibody activity was detectable in cultures of lymphocytes from 3 out of 4 patients. The amount of acetylcholine receptor antibody per microgram IgG, the specific activity, was greater in cultures of thymic lymphocytes than the specific activity of IgG in serum, suggesting that the hyperplastic thymus may be a major site of acetylcholine receptor antibody synthesis. Therefore it should be possible to use the culture system described to investigate the processes involved in the breakdown of self-tolerance in myasthenia gravis.

Adolescent↗
PubMed1981

The metabolism and excretion of styrene oxide-glutathione conjugates in the rat and by isolated perfused liver, lung and kidney preparations.

The metabolism and excretion of styrene oxide-glutathione conjugates were studied in the intact rat and by isolated perfusion techniques in rat lung, liver and kidney. The intact animals converted the styrene oxide-glutathione conjugates almost entirely to styrene oxide-n-acetylcysteine derivatives mercapturic acids), with much smaller amounts of cysteine, cysteinylglycine and (unchanged) glutathione conjugates. Only small amounts of biliary excretion (approximately 5%) and less than 1% of fecal excretion of radioactivity were found. The isolated perfused kidney retains the capacity to transform virtually all of the glutathione conjugates at the dose level studied (25-30 mumol/kidney) and the principal component in urine from the isolated kidney was the cysteine conjugate. Isolated perfused lung experiments demonstrated that this organ has a minor role in styrene oxide-thioether conjugate. Isolated perfused lung experiments demonstrated that this organ has a minor role in styrene oxide-thioether conjugate metabolism. The isolated perfused liver experiments showed that phenobarbital pretreatment has little effect on biliary excretion but barbital pretreatment has little effect on biliary excretion but that it causes profound qualitative and quantitative effects on metabolism of styrene oxide-glutathione conjugates in the perfusion medium. The high level of styrene oxide-cysteine conjugates in the perfusion medium of an isolated perfused liver, especially after phenobarbital treatment, is consistent with the theory that gamma-glutamyltransferase activity is extracellular. The high-pressure liquid chromatography system of analysis described offers the ability to simultaneously separate and quantitate the major thioether conjugates of styrene oxide and other electrophilic epoxides.

Animals↗
PubMed1980

Carbimazole and autoantibody synthesis in Hashimoto's thyroiditis.

Serum thyroxine, thyrotrophin, and thyroid microsomal antibody levels were measured in 20 patients with Hashimoto's thyroiditis and hypothyroidism before, during, and after treatment with carbimazole or placebo. Thyroid microsomal antibody levels fell during treatment in the 10 patients who received carbimazole, while serum thyroxine and thyrotrophin levels did not change. There were no changes in the placebo group. The study proves support for the concept that carbimazole may act directly on autoantibody synthesising lymphocytes localised in the thyroid. Such an effect might be valuable in influencing the autoimmune process in autoimmune thyroid disease.

Autoantibodies↗
PubMed1980

Carbimazole and the autoimmune response in Graves' disease.

Microsomal antibodies and antibodies directed toward the receptor for thyroid-stimulating hormone (TSH) decreased in parallel while patients with Graves' disease were taking carbimazole, whereas no significant changes were observed during treatment with placebo or propranolol. The changes in autoantibody levels during carbimazole treatment were independent of changes in serum thyroxine and could have been due to a direct effect of the drug on autoantibody synthesis. Evidence for this suggestion was provided when low doses of methimazole (the active metabolite of carbimazole) were found to inhibit thyroid-autoantibody production in cultured lymphocytes. Since thyroid lymphocytes are probably a major site of thyroid-antibody synthesis in Graves' disease and methimazole is concentrated in the thyroid during treatment, a local action of the drug on antibody production seems likely. This possibility could be important in the use of carbimazole to control hyperthyroidism.

Antibody Formation↗
PubMed1980

Prediction of relapse in hyperthyroid Graves' disease.

Within a year of stopping a 6-month course of carbimazole treatment 41 of 65 patients (63%) with hyperthyroid Graves' disease had a recurrence of their hyperthyroidism. By combined analysis of the HLA-DRw3 status and the level of thyrotrophin-receptor antibody at the time of drug withdrawal relapse or remission could be predicted in 62 of the 65 patients.

Adult↗