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Biomedical subjects

T Hosoya

Publications and source records attributed to T Hosoya.

At least 235 records · Page 13Linked to original sources

Effect of the administration of cycloheximide to thioacetamide-primed rats or partial-hepatectomized rats on the RNA polymerase I activity in isolated nuclei of liver.

1. Twenty-four hours after administration of thioacetamide to normal rats, the activity and amount of RNA polymerase I in isolated liver nuclei were almost doubled. 2. When cycloheximide was administered to the drug-treated rats and normal rats 1 or 2 hr before death, the reduction in the activity was of the same degree, that is, about half of the activity of liver nuclei from normal rats. 3. Partial hepatectomy also caused about 2-fold increase in the RNA polymerase I activity in isolated liver nuclei after 16 hr, but the increased activity was almost completely abolished by injection of cycloheximide 1-3 hr before killing.

Acetamides↗

Regulation of thyroid peroxidase activity by thyrotropin, epidermal growth factor and phorbol ester in porcine thyroid follicles cultured in suspension.

The activity of thyroid peroxidase (TPO) in porcine follicles cultured for 96 h in suspension with five hormones (5H) still attained over 50% of that in the freshly isolated follicles. On the other hand, the activity in those cultured with 5H + TSH (6H) was several times higher than that cultured with 5H after 96 h, although an initial decrease of TPO activity during the first 24 h of culture was observed in both conditions. The ability of follicles to metabolize iodide (uptake and organification) when cultured with 6H for 96 h was also several times higher than that of those cultured with 5H. The half-maximal dose of TSH for stimulation of TPO activity and iodide metabolism was 0.03-0.04 mU/ml and the effect was mediated by cAMP. These results indicate that in porcine thyroid follicles in primary suspension culture, TPO activity as well as the ability of iodide metabolism is induced by chronic TSH stimulation. In addition, epidermal growth factor (EGF, 10(-9)M) and phorbol 12-myristate 13-acetate (PMA, 10(-8) M) completely inhibited TSH stimulation on both activities and also basal (5H) activity of iodide metabolism.

Animals↗

Peroxidase activities in autonomously functioning nodules and adjacent non-tumorous portions of thyroids.

Peroxidase activities of autonomously functioning thyroid tumors (T) and surrounding non-tumorous tissue (N) in 5 patients were determined by employing guaiacol or iodide as the second substrates. The mean values for specific activities of T were 30 times (in iodide oxidation assay) or 4 times (in guaiacol oxidation assay) as high as those in N, being significantly higher than those of non-functioning tumors. The thyroglobulin-iodination activity of thyroid peroxidase in T was also found to correlate well to the iodide oxidation activity. These results suggest that the enhanced peroxidase activity in the nodules plays an essential role in the function of autonomously functioning thyroid nodules.

Adenoma↗

[Intra-arterial chemotherapy of malignant glioma after osmotic blood-brain barrier disruption].

Reversible transient osmotic blood-brain barrier disruption was used to increase drug delivery to the brain. The authors treated 10 cases of malignant gliomas with intra-arterial chemotherapy after osmotic blood-brain barrier disruption. Ten patients received intra-arterial anticancer drugs (5-FU, ACNU, IFN-beta) after intra-arterial infusion of 20% mannitol to open the blood-brain barrier at the tumor site. Clinical responses in 9 evaluable cases were 1 Complete Response, 3 Partial Responses, 5 No Change and no Progressive Disease in CT examination. Response rate was 44.4% (4/9). The most untoward effect of this method was myelosuppression. Platelet and leukocyte count diminished below 20,000 and 2,000, respectively in 3 cases, and 2 out of these 3 cases died of severe infection. The other complications were eye pain during mannitol infusion in all cases, when the selective catheterization of the internal carotid artery failed to pass the origin of the ophthalmic artery. Decreased activity was seen in 70%, nausea and vomiting in 50%, swelling of external decompression area in 33%, increased neurological deficit in 20%, but all these side effects were transient. This method was considered an effective treatment for malignant gliomas.

Aged↗

[Uric acid metabolism in patients with chronic glomerulonephritis].

Serum uric acid (SUA), creatinine clearance (Ccr), urinary excretion of uric acid (UUAV) and uric acid clearance (CUA) were determined in 357 patients with IgA nephritis (IgAN) and 81 patients with membranous nephropathy (MGN) in an attempt to clarify uric acid metabolism in patients with chronic glomerulonephritis, and UUAV/Ccr and CUA/Ccr levels were measured to investigate their correlations. As a result, hyperuricemia that could hardly be explained with a decline of Ccr alone was recognized in many cases, since the patients with hyperuricemia exceeding 7.0 mg/100 ml of SUA registered even as high as 25.5% in IgAN and 33.3% in MGN, whereas those with the Ccr levels higher than 80 ml/min registered 22.3% in IgAN and 38.0% in MGN. Although the SUA level increased and the UUAV and CUA levels decreased along with a decline of Ccr in IgAN, no similar trends were recognized in MGN. When the distribution of UUAV was studied in the patients with the Ccr levels higher than 80 ml/min, the patients whose UUAV levels higher than 800 mg/24 hrs that suggested excessive uric acid production were markedly as low as 3.9% in IgAN and 3.7% in MGN. Thus, the cause of hyperuricemia could not be attributed to an amount in the uric acid production. On the other hand, the patients whose CUA levels lower than 6.0 ml/min in the distribution of CUA that suggested a decrease of uric acid excretion registered 47.4% in IgAN and 63.0% in MGN, respectively, which equally appeared to be a type of lowered excretion in a majority of patients whose hyperuricemia was recognized in IgAN and MGN. The mechanism of the lowered excretion of uric acids from the kidney despite the normal level of Ccr has yet to be clarified.

Adult↗

Anti-thyroid peroxidase antibody activity in sera of patients with systemic lupus erythematosus.

Although patients with SLE have autoantibodies to thyroid peroxidase (TPO), IgG from sera of SLE patients does not inhibit TPO activities, in contrast with IgG from sera of patients with thyroid disorders. This finding suggests that the specificities of anti-TPO autoantibodies in SLE are different from those in cases of thyroid disorders. These autoantibodies to TPO should be considered when searching for associations between SLE and autoimmune thyroid disorders.

Adolescent↗

[Characterization of thyroglobulin and thyroid peroxidase activity in patients with functioning thyroid benign tumors].

The content and chemical and immunological properties of thyroglobulin (Tg) and the activity of thyroid peroxidase (TPO) were studied in nodular and extranodular (periphery) thyroid tissue from patients with functioning thyroid tumors (hot nodules). From the present observations, the tumor extracts contained fairly large amounts of Tg, similar to that in the periphery tissue, while the content of Tg was markedly decreased in non-functioning thyroid tumors (cold nodules). The iodine content of Tg was significantly higher in nodular tissue compared with periphery tissue. These observations were in contrast to the results seen in the cold nodules in which hormone synthesis was defective. On the nature of carbohydrate moiety as compared with normal tissue, oligosaccharides of Tg from the periphery tissues changed in a manner similar to that of tumor oligosaccharides. That is, high-mannose type oligosaccharides were markedly decreased whereas multiantennary and unidentified oligosaccharides were increased. These observations were similar to those of non-functioning tumors. The content of sialic acid decreased markedly both in the tumor and periphery tissues. Immunologically, Tg preparations of the tumor and periphery tissue did not show the same affinity to the antibodies, depending on the content of iodine. Therefore, it seems that the contribution of the iodine content and iodo-amino acid has little or no significance in the heterogeneous nature of Tg-immunogenecity. Benign tumors and the periphery tissue were subjected to assay for thyroid peroxidase activity by the method employing guaiacol as the second substrate. The specific activities of the tumors were generally higher than those of periphery tissues, both in functioning and non-functioning benign tumors. In non-functioning carcinoma, on the other hand, TPO activities were lower in tumor portions than in periphery portions. This indicates that non-functioning thyroid carcinomas have a different characteristic.

Adenoma↗

Enhanced thyroid iodine metabolism in patients with triiodothyronine-predominant Graves' disease.

Some patients with hyperthyroid Graves' disease have increased serum T3 and normal or even low serum T4 levels during treatment with antithyroid drugs. These patients with elevated serum T3 to T4 ratios rarely have a remission of their hyperthyroidism. The aim of this study was to investigate thyroid iodine metabolism in such patients, whom we termed T3-predominant Graves' disease. Mean thyroid radioactive iodine uptake was 51.0 +/- 18.1% ( +/- SD) at 3 h, and it decreased to 38.9 +/- 20.1% at 24 h in 31 patients with T3-predominant Graves' disease during treatment. It was 20.0 +/- 11.4% at 3 h and increased to 31.9 +/- 16.0% at 24 h in 17 other patients with hyperthyroid Graves' disease who had normal serum T3 and T4 levels and a normal serum T3 to T4 ratio during treatment (control Graves' disease). The activity of serum TSH receptor antibodies was significantly higher in the patients with T3-predominant Graves' disease than in control Graves' disease patients (60.5 +/- 19.2% vs. 20.4 +/- 18.2%; P less than 0.001). From in vitro studies of thyroid tissue obtained at surgery, both thyroglobulin content and iodine content in thyroglobulin were significantly lower in patients with T3-predominant Graves' disease than in the control Graves' disease patients. Thyroid peroxidase (TPO) activity determined by a guaiacol assay was 0.411 +/- 0.212 g.u./mg protein in the T3-predominant Graves' disease patients, significantly higher than that in the control Graves' disease patients (0.129 +/- 0.112 g.u./mg protein; P less than 0.01). Serum TPO autoantibody levels determined by immunoprecipitation also were greater in T3-predominant Graves' disease patients than in control Graves' disease patients (52.6 +/- 27.7% vs. 32.4 +/- 11.4%; P less than 0.05). Binding of this antibody to TPO slightly inhibited the enzyme activity of TPO, but this effect of the antibody was similar in the two groups of patients. The data suggest enhanced iodine metabolism in the thyroid gland of patients with T3-predominant Graves' disease, which may relate to the discordant T3 overproduction in patients with this type of Graves' disease.

Adolescent↗

Thyroglobulin and thyroid peroxidase share common epitopes recognized by autoantibodies in patients with chronic autoimmune thyroiditis.

Monoclonal antibodies specific for human thyroid peroxidase (TPO) were prepared by the hybridoma technique using hyperimmune spleen cells from mice immunized with TPO purified from thyroid glands from patients with Graves' disease. Use of the microenzyme-linked immunosorbent assay method revealed that some of the monoclonal antibodies cross-reacted strongly with human thyroglobulin (Tg). Conversely, monoclonal anti-Tg antibodies cross-reacted with TPO, albeit to a lesser degree. Some anti-Tg autoantibodies in serum from patients with chronic autoimmune thyroiditis purified by Tg affinity chromatography bound TPO, and such binding was completely inhibited by Tg. Western blotting experiments revealed that thyroid microsomal 103K proteins recognized by mouse monoclonal and polyclonal anti-TPO antibodies were recognized by some monoclonal anti-Tg antibodies and anti-Tg autoantibodies, and conversely, that 19S Tg was recognized by some monoclonal anti-TPO antibodies. TPO was immunoprecipitated by anti-Tg autoantibodies isolated by Tg affinity chromatography. On the other hand, the specificity for TPO of the anti-Tg autoantibodies was not identical with that of anti-TPO autoantibodies. These cross-reactivities were not due to contamination of TPO with Tg or vice versa, or to contamination of the anti-Tg autoantibody preparations with anti-TPO autoantibodies. Taken together, these data indicate that Tg and TPO share common antigenic determinants and that some of those determinants are recognized by autoantibodies in the serum of patients with chronic autoimmune thyroiditis.

Adolescent↗

In vivo effects of thyroid hormone, glucocorticoid, androgen, and somatotropin on RNA polymerase I activities in isolated liver nuclei.

In the 'template-engaged' form activity of RNA polymerase I in nuclei of normal rat livers, about 40% of the activity was found to be influenced by thyroid hormones and glucocorticoids and can be eliminated by 1 h treatment with cycloheximide. On the other hand, the 'free' form activity of the enzyme in rat liver nuclei and the total amount of the enzyme in nucleoli were scarcely affected by these hormones. These results suggest that a considerable portion of rRNA synthesis in rat liver nucleoli is regulated by the initiation of rDNA transcription, probably with the participation of glucocorticoid- and thyroid hormone-dependent short-lived protein(s). When somatotropin, in addition to glucocorticoids and thyroid hormones, was depleted by hypophysectomy, the 'template-engaged' form activity of RNA polymerase I was reduced to 30% of the normal level. The activity was restored completely by a single injection of triiodothyronine plus somatotropin, but not by injections of the individual hormones. From these results, it is likely that the stimulating effects of glucocorticoids and thyroid hormones on rRNA synthesis are maintained by the action of somatotropin which seems to occur in a different mechanism from those of the former two hormones. In contrast to these hormones, androgen showed no acute effect on 'template-engaged' form activity of RNA polymerase I in liver nuclei.

Adrenalectomy↗

Peroxidase activity and thyroglobulin iodination activity of thyroid peroxidase in non-functioning thyroid tumours.

Both lesion (L) and adjacent normal (N) thyroid tissue from 48 patients with non-functioning adenomas and adenomatous goitres were assayed for peroxidase activity by the 'mini' assay method employing guaiacol or iodide as the second substrate. A considerable proportion of thyroids (46% of adenomas and 22% of adenomatous goitres) demonstrated no iodide oxidation activity in L although they had guaiacol oxidation activity, and these were grouped as subgroups A. The rest of these non-functioning tumours, termed subgroups B, had both guaiacol and iodide oxidation activity which was higher (3.0-4.6 times in guaiacol assay and 7.3-14.1 times in iodide assay) in L than in N. These data indicate that the non-functioning in subgroups A may be due to a lack of iodide oxidation activity and that some other defects such as an iodide transport defect may be involved in subgroups B. Furthermore, a precise and rapid assay method for thyroglobulin iodination activity of thyroid peroxidase was developed, with modifications of previous methods. On the basis of this method, we found that there is a good correlation (r = 0.94) between iodide oxidation assay and thyroglobulin iodination assay, leading to the conclusion that thyroglobulin iodination assay can be replaced by iodide oxidation assay.

Adenoma↗

Effect of thyroid hormone on the phosphorylation of 110k proteins and the activity of protein kinase NII of rat liver nucleoli.

When rat liver nucleoli were incubated with [gamma-32P] ATP, it was found that 110k proteins were predominantly phosphorylated. The phosphorylation of 110k proteins was decreased by thyroidectomy to about 80% of the normal level and restored 12 h after the injection of triiodothyronine. The activity of nucleolar protein kinase NII which is responsible for phosphorylation of 110k proteins was also increased by about 20-50% after injecting triiodothyronine into thyroidectomized rats. The hormone-stimulated enhancement in the phosphorylation of 110k proteins and protein kinase NII in nucleoli were abolished within 1 h after an injection of cycloheximide, without any change in the amount of the proteins.

Adenosine Triphosphate↗