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Biomedical subjects

B R Smith

Publications and source records attributed to B R Smith.

At least 343 records · Page 19Linked to original sources
PubMed1979

Metabolism and excretion of benzo(a)pyrene 4,5-oxide by the isolated perfused rat liver.

Benzo(a)pyrene 4,5-oxide was metabolized in the isolated perfused rat liver by epoxide hydrase and glutathione S-transferases to the corresponding dihydrodiol and to thioether conjugates (derivatives of glutathione), respectively. Epoxide hydrase was more important relative to the glutathione S-transferases in the biotransformation of this oxide by the intact organ than was indicated by the results from earlier studies with subcellular fractions. The dihydrodiol was rapidly released into the circulation or conjugated with glucuronic acid; sulfuric acid esters were not found. All conjugated metabolites were rapidly excreted in the bile but some were also released into the circulation. The enzymatic systems responsible for the metabolism and excretion of benzo(a)pyrene 4,5-oxide remained viable in the isolated perfused liver for at least 60 min. The toxicological significance of the release of polycyclic aromatic hydrocarbon metabolites from the liver into the vascular circulation and the possible significance of UDP:glucuronyltransferase activity in preventing chemically induced carcinogenesis are discussed.

Animals↗
PubMed1979

Benzo(a)pyrene oxidation, conjugation and disposition in the isolated perfused rabbit lung: role of the glutathione S-transferases.

The isolated perfused rabbit lung metabolised 7--11 % of 20 mumol of [14C]-benzo(a)pyrene added in the perfusion medium in 1 h. The major metabolite formed was 3-hydroxybenzo(a)pyrene, both free (30--40 % of the total metabolites) and conjugated (4 % of total metabolites). Quinones comprised 15 % of the total and metabolism at the 9, 10 position accounted for a further 10 %. Forty per cent of the water-soluble metabolites was chromatographically identical to the glutathione conjugate of benzo(a)pyrene 4,5-oxide. Sulphate and glucuronide conjugates were formed in small but detectable amounts, principally from phenols, but also from dihydrodiols. After 1 h the more water-soluble conjugates had diffused from the lung into the perfusion medium, but the majority (60--90 %) of the metabolic products were still concentrated within the lung. The lung's limited ability to conjugate its major metabolites of benzo(a)pyrene with sulphuric or glucuronic acid, coupled with slow elimination of the products formed, particularly dihydrodiols may contribute to the susceptibility of this organ to polycyclic aromatic hydrocarbon-induced carcinogenesis.

Animals↗
PubMed1979

Thyroglobulin and microsomal autoantibody production by cultures of Hashimoto peripheral blood lymphocytes.

Peripheral blood lymphocytes from patients with Hashimoto's thyroiditis have been cultured for 2--3 weeks in Marbrook flasks. During this period, readily detectable amounts of thyroglobulin and microsomal antibodies were synthesized by the cells and secreted into the culture medium. Gel filtration studies indicated that the autoantibodies produced in culture were of a similar molceular weight to the serum antibodies and this provided evidence that autoantibody synthesis in vitro was representative of autoantibody synthesis in vivo. Our data suggest that this culture technique may be used to make a detailed investigation of the human autoimmune disease process.

Adult↗
PubMed1978

Kinetics of immunoglobulin production by cultured human peripheral blood lymphocytes.

A study of immunoglobulin synthesis by human peripheral blood lymphocytes cultured in Marbrook flasks is described. Maximal amounts of immunoglobulin were produced by 3 weeks and most of this was synthesised between 6 and 21 days. In the region of 90% of the immunoglobulin was secreted into the medium. Pokeweed mitogen (PWM) stimulated cultures produced about 10 times as much immunoglobulin as cells cultured in medium only. After 21 days stimulated cultures produced about 150 microgram of IgG, 125 microgram of IgM and 50 microgram of IgA per 10(7) cells.

Cells, Cultured↗
PubMed1978

Thyrotropin receptors in adipose tissue, retro-orbital tissue and lymphocytes.

Thyrotropin (TSH) receptors on retro-orbital muscle and fat have been implicated in the pathogenesis of Graves' exophthalmos and it has been suggested that TSH has a direct effect on human fat metabolism. We have therefore investigated the interaction of biologically active 125I-labelled TSH with membranes prepared from human adipose, retro-orbital and thyroid tissue. Since lymphocytes contain receptors for several polypeptide hormones, TSH binding to lymphocyte membranes was also studied. We were unable to demonstrate TSH receptors in adult human adipose tissue, retro-orbital muscle and fat, or peripheral blood lymphocytes. In contrast, adult and neonatal guinea pig adipose tissue membranes showed similar TSH binding characteristics to guinea pig thyroid membranes.

Adipose Tissue↗
PubMed1978

Epithelioma cuniculatum pedis, a variant of squamous cell carcinoma.

The rare lesion of epithelioma cuniculatum pedis may be recognized by the gross appearance of a slow-growing, bulky, "squashy," non-healing, exophytic mass of long duration on the sole, exuding foul-smelling purulent keratin debris from numerous sinuses, and biopsies showing extensive infiltrating plaques of keratinizing, well-formed, squamous epithelium forming walls for numerous sinuses filled with purulent material. The rarity of the lesion, the slow growth, and biopsies showing relatively benign-appearing well-differentiated squamous epithelium caused considerable diagnostic difficulty to clinicians and pathologists. The tumor failed to heal, extensively penetrated the soft tissues, ultimately destroyed the metatarsal bones, and invaded the skin of the dorsum of the fott. The lesion should be treated as a slow-growing, well-differentiated squamous cell carcinoma by wide local excision or by amputation when extensive growth causes deformity of the foot or penetration of the metatarsal bones.

Adult↗
PubMed1978

Binding of thyroid stimulators to guinea pig testis and thyroid.

We have demonstrated TSH binding sites in membranes prepared from guinea pig testis. The binding of TSH to testicular homogenate was localized to the interstitial tissue and showed similar characteristics to the binding of TSH to thyroid membranes with high affinity (Ka = 2.5 X 10(10) M-1) but limited capacity (approximately 0.9-1.7 pg/mg equivalent testis homogenate). In addition, thyroid-stimulating antibodies inhibited the binding of TSH to both testicular and thyroid homogenate but failed to inhibit the binding of hCG to the testis preparation. These data suggested that the TSH-binding site was distinct from the hCG/LH binding site. Testicular and thyroid TSH-binding sites also appeared to demonstrate a similar degree of cross-reactivity with a crude preparation of hCG. In conclusion, our findings suggest that thyroid-stimulators may influence gonadal function. Furthermore, the ability of hCG to inhibit the binding of TSH to thyroid membranes provides a possible mechanism for the known thyroid-stimulating properties of hCG.

Animals↗
PubMed1978

Labelling of the thyroid cell surface with 125I.

The surface membrane proteins of cultured porcine thyroid cells have been labelled with 125I by the lactoperoxidase method. Evidence that the labelling was restricted to the cell surface was supported by the high viability of the cells in suspension, the high proportion of labelled material in the particulate fraction after homogenization and electron-microscopic autoradiographic studies. The labelled proteins were analysed by electrophoresis on polyacrylamide gels containing sodium dodecyl sulphate and this indicated the presence of ten major labelled protein bands with approximate molecular weights of 175 000, 155 000, 135 000, 88 000, 80 000, 52 300, 39 000, 30 000, 21 000 and 14 300. Comparison of the electrophoretic patterns obtained with cultured human and porcine thyroid cells suggested that there were species differences in the proportions of lower-molecular-weight proteins.

Animals↗
PubMed1978

Solubilization and partial characterization of human and porcine thyrotrophin receptors.

Thyrotrophin (TSH) receptors have been extracted from human and porcine thyroid membranes by treatment with Triton X-100. 125I-Labelled bovine TSH was used to monitor receptor activity. Analysis by gel filtration and electrophoresis on acrylamide gels containing sodium dodecyl sulphate suggested that Triton extracts of human thyroid membranes contained TSH receptors with a molecular weight in the region of 50 000 closely associated with Triton micelles of approximate molecular weight 300 000. Isoelectric focusing studies indicated that the Triton-solubilized TSH binding activity had an isoelectric point of pH 4--4.5. The soluble TSH receptors were heat-labile, showed optimum TSH binding at pH 7.4 and reduced hormone binding at high ionic strength. The TSH binding characteristics of membrane-bound and solubilized human TSH receptors were similar and both preparations gave curved Scatchard plots. Solublized porcine TSH receptors appeared to have a similar molecular weight to the human receptors and were also closely associated with Triton micelles of approximate molecular weight 300 000. Scatchard analysis of TSH binding to membrane-bound or solubilized porcine TSH receptors gave approximately linear plots with association constants of 2.8 +/- 0.95 (S.E.M.) X 10(9) and 1.7 +/- 0.27 x 10(9) l/mol respectively. Comparison of the binding capacities of the solubilized and membrane-bound porcine receptors indicated that the 0.5% Triton extracts contained 40% of the original TSH binding activity and that this was present at a concentration of 25 ng/ml.

Animals↗
PubMed1978

Cutaneous metastases from hepatomas.

Three cases of hepatomas metastasized to the skin in a series of 88 patients with hepatomas. The skin metastases differed from the usual dermal nodules, such as fibromas, inflammatory granulomas, and adnexal tumors, by their rather sudden appearance as solitary or multiple, nonulcerative, painless, firm, reddish-blue nodules on the scalp, chest, and shoulder. Biopsies of these nodules were necessary in order to confirm the diagnosis of the cutaneous metastases, which appeared before the primary tumors were recognized. Microscopically, the skin tumors were adenocarcinomas in two instances and hepatocellular carcinoma in one. The skin metastases were a late manifestation of the primary tumors; the patients died within three weeks to six months after the appearance of skin tumors. Necropsies showed widespread metastases.

Adenocarcinoma↗