Biomedical subjects
Publications and source records attributed to T Mimura.
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The results of treatment were analyzed in relation to serum microsomal antibody (MCAb) titre before treatment in 1185 patients with Graves' disease. The percentage of patients who had ablative therapy because of poor response to antithyroid drug treatment was significantly greater in those with MCAb haemagglutination test (MCHA) titres greater than 1:25,000. With 131I treatment, the patients with MCHA titres greater than 1:6400 responded significantly less to therapy, although the analysis was done in 146 selected patients with certain defined radiation doses and small goitres. With surgical treatment, the percentage of the patients entering into remission was significantly smaller for patients with MCHA titres greater than 1:25,000, because of an increase in both hypothyroidism and relapses. The incidence of hypothyroidism was significantly higher in patients with marked lymphocyte infiltration and/or lymphoid follicles. The degree of these histological findings in Graves' disease was not marked in spite of high MCAb titre and it was significantly different from that in Hashimoto's disease when analyzed in relation to the MCHA titre. These data indicate that in Graves' patients with high MCAb titre, remission is difficult to obtain by treatment, and suggest that the significance of MCAb is different in Graves' disease and Hashimoto's disease. The titre in Graves' disease may be one expression of the activity of this disease.
The course of the cAMP response to thyrotropin (TSH) in 23 specimens of differentiated thyroid carcinoma and the adjacent normal tissue was studied. In the carcinomatous tissue, the cAMP concentration in slices incubated with TSH was significantly greater after 2 h than after 15 min of incubation; the level was almost the same at both times in normal tissue. The effects of an initial exposure of thyroid slices to TSH (50 U/l) on the subsequent cAMP responsiveness to the hormone were investigated in seven more differentiated thyroid carcinomas. In normal tissue, the cAMP level in slices exposed to TSH, washed, and exposed again was lower after the third incubation than in slices exposed to TSH only in the third. In contrast, the cAMP level tended to be greater after the second of 2 TSH incubations in 5 out of the 7 specimens of carcinomatous tissue. The data suggest that differentiated thyroid carcinoma lacks desensitization of the cAMP response to TSH.
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The inhibitory effects of several polysaccharides, dextran, xylofuranan, and ribofuranan, and their sulfated counterparts on the infectivity and replication of human immunodeficiency virus (HIV) were examined by using an HTLV-I-carrying cell line, MT-4, in vitro. Dextran sulfate (Mw 34 X 10(3], xylofuranan sulfate, and ribofuranan sulfate completely prevented HIV-induced cytopathic effects (CPE) at concentrations greater than 10 micrograms/ml and dextran sulfate (Mw 7 X 10(3] at concentrations greater than 100 micrograms/ml. However, the non-sulfated compounds did not prevent them at any concentration tested. The anti-HIV effect of these polysaccharides was confirmed by measuring HIV-specific antigen expression in infected MT-4 cells. In cocultures with MOLT-4 and MOLT-4/HIVHTLV-IIIB cells, formation of multinucleated cells was completely inhibited in the presence of 100 micrograms/ml of these sulfated compounds. Dextran sulfate showed 20-30% growth inhibition of uninfected MT-4 cells at 1000 micrograms/ml but dextran sulfate, xylofuranan sulfate, and ribofuranan sulfate showed no effect on sulfated polysaccharides efficiently inhibited the reverse transcriptase activity of avian myeloblastosis virus and HIV.
Multiple endocrine neoplasia, type IIb (MEN IIb) is a rare syndrome characterized by the occurrence of medullary thyroid carcinoma (MTC), pheochromocytoma and mucosal neuroma. A 35-year-old male patient with MEM IIb having megacolon, marfanoid habitus and no family history of the disease underwent surgery. Because MTC was present in both lobes, total thyroidectomy and modified neck dissection were performed. Pheochromocytoma was found bilaterally and bilateral adrenalectomy with adrenal autotransplantation in the rectus abdominis muscle was carried out. Postoperative course was satisfactory except for transient hypocalcemia and mild ileus. After the slow corticosteroid weaning process, his adrenocortical function was at the lower level within a normal range. In August 1986 (24 postoperative months), he was maintained by the administration of 10mg of hydrocortisone every three days, and calcitonin and CEA levels in sera were normal. We collected 15 cases reported in Japanese literatures. MTC and mucosal neuroma were found in all cases, whereas pheochromocytoma was present in 9 cases. Bilateral and multicentric occurrences were usual, and total thyroidectomy and bilateral adrenalectomy were, warranted. We believe that autotransplantation following bilateral adrenalectomy is a worthy alternative.
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The fertilization ratio of mouse ova in vitro decreased when glucose concentration in the medium was lowered. However, the addition of phloretin-2'-beta-D-glucose (phloridzin), known as a glucose uptake inhibitor, restored the fertilization ratio back to the control level. The glucose moiety of the phloridzin seemed to be responsible for this effect.
A 65-year-old woman presented with an episode of hematemesis and a recurrent cervical goiter due to Graves' disease. The angiogram revealed bleeding esophageal varices which had developed through a drainage vein of the vascular goiter. Total thyroidectomy resulted in eradication of the esophageal varices.
Aspartame (APM; L-aspartyl-L-phenylalanine methyl ester) was investigated for its ability to alter brain amino acids and monoamines in overnight fasted rats allowed to consume commercial diets for 60 minutes. In addition, the effects of mealing on the changes in plasma and brain amino acids and brain monoamines induced by glucose and/or insulin, and known pharmacologically active compounds, were studied. The consumption of the commercial chow largely prevented changes in blood glucose and amino acids, and brain amino acids and the monoamines dopamine, norepinephrine and serotonin that might be expected to occur following glucose with or without insulin. Feeding failed to prevent changes in the above parameters when 5-hydroxy-tryptophan, p-chlorophenylalanine and reserpine were administered. The oral administration of up to 250 mg/kg BW APM with water or glucose followed by free feeding failed to alter brain monoamines. These studies demonstrate the potent ability of food to normalize biochemical parameters in blood and brain that otherwise might occur, and clearly show the lack of effect on brain monoamine levels of abuse doses of APM when administered with food.
Aspartame (APM; L-aspartyl-L-phenylalanine methyl ester), was investigated for its ability to alter levels of the large neutral amino acids and monoamines in overnight fasted rats allowed to consume meals with or without protein for two hours. Additionally, the possible long term behavioral consequences of APM in 25% casein diets with or without 10% sucrose were determined. Acute APM ingestion increased both plasma and brain phenylalanine and tyrosine levels, but brain tryptophan levels were not altered regardless of dietary protein. Brain norepinephrine and dopamine levels were unaltered by any of the diet while serotonin levels were slightly increased when a protein-free diet was consumed. But APM and/or protein ingestion minimized this increase of brain serotonin levels as much as controls. Chronic APM ingestion failed to influence diurnal feeding patterns, meal size distributions, or diurnal patterns of spontaneous motor activity. The chronic ingestion of abuse doses of APM produced no significant chemical changes in brain capable of altering behavioral parameters believed to be controlled by monoamines in rats.
An anti-sperm monoclonal antibody was developed from female C57BL/6 mice immunized with epididymal sperm from a syngeneic male mouse. Immunofluorescence staining revealed that the antibody did not react to fresh epididymal sperm but attached to the capacitated sperm found in the peri-vitelline spaces of the ova. When the antibody was applied to sperm incubated in vitro, variously stained sperm were observed. It was presumed that the antigenic site detected by the antibody was hidden in the fresh epididymal sperm and was spread from the acrosomal cap region to the entire head during the capacitation process.
The relationship between changes in glucose tolerance with treatment of hyperthyroidism and various factors that might be relevant to carbohydrate metabolism were investigated in 64 hyperthyroid patients with abnormal glucose tolerance, including 35 cases with fasting plasma glucose (FPG) levels of 140 mg/dl or more. All patients had diffuse toxic goiter. After correction of the hyperthyroidism, glucose intolerance improved in almost all cases, even in cases with fasting hyperglycemia, but diabetes mellitus in patients with FPG above 140 mg/dl and/or delta IRI/delta PG X 30' during a 50-g oral glucose tolerance test below 0.10, persisted. Patients who showed diabetic glucose tolerance even after remission from thyroid dysfunction had significantly lower delta IRI/delta PG X 30' values and a higher incidence of family histories of diabetes mellitus than those not showing diabetic glucose tolerance. There were no significant differences in serum T3 and T4 levels between these two groups of patients. The findings suggest that predisposition to diabetes may be an important factor in persistent glucose intolerance in the hyperthyroidism of Graves' disease. The FPG and delta IRI/delta PG X 30' values may be useful in predicting which patients with hyperthyroidism will have permanent diabetes.
A potent platelet antiaggregant action of an antiarrhythmic peptide (AAP) was demonstrated to be a cause of the antithrombotic effect. AAP (10, 20 or 40 mg/kg, i.v.) inhibited ex vivo platelet aggregation induced by collagen in a dose-dependent manner. AAP also inhibited the platelet aggregation of platelet-rich plasma (PRP) induced by collagen, Ca-ionophore A-23187, adenosine diphosphate (ADP), thrombin or arachidonic acid in vitro. The IC50 was 2.5 mM for collagen, 1.7 mM for A-23187, 5 mM for ADP, 0.4 mM for thrombin and 0.15 mM for arachidonic acid. The aggregation inhibitory activity of the peptide on washed platelet (WP), in a Ca2+-free medium, was stronger than on PRP. The IC50 was 1 mM for collagen and 20 microM for A-23187. No significant difference was found between antiaggregant activities of platelet-free plasma (PFP) from AAP-treated rats and PFP from normal rats supplemented with AAP. The direct action of AAP on platelets was also supported by the incorporation of AAP into platelet cytoplasma which caused a decrease of Ca2+-dependent 3':5'-cyclic nucleotide phosphodiesterase (Ca-PDE) activity. It was considered that AAP showed its platelet aggregation inhibitory activity by decreasing intracellular Ca2+ concentration through the inhibition of Ca-PDE activity.