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Biomedical subjects

H Mimura

Publications and source records attributed to H Mimura.

At least 127 records · Page 7Linked to original sources
PubMed1984

Ontogenesis of iodothyronine-5'-deiodinase. Induction of 5'-deiodinating activity by insulin, glucocorticoid, and thyroxine in cultured fetal mouse liver.

To elucidate the regulatory mechanism of ontogenetic development of iodothyronine-5'-deiodinase in the fetal and neonatal period, fetal mouse liver of the 19th day of gestation, in which no iodothyronine-5'-deiodinating activity was detectable, was cultured in Dulbecco-Vogt medium supplemented with 10% thyroid hormone-depleted fetal calf serum, insulin, hydrocortisone, and thyroid hormones. Iodothyronine-5'-deiodinating activity of the homogenate was assessed by the amount of iodide released from outer-ring-labeled reverse T3 and expressed as picomoles of 127I- per milligram of protein per minute. The enzyme activity was induced in a dose-dependent manner; optimal concentrations for insulin, hydrocortisone, and thyroxine were 1 microgram/ml, 0.4 microgram/ml, and 10(-6) M, respectively. Without supplementation of either hydrocortisone or thyroxine, no 5'-deiodination was detected. The enzyme activity was observed after 3 d of culture, peaked at days 14-20, and then gradually decreased. Lineweaver-Burk analysis revealed that the increase in activity was primarily due to an increase in Vmax (day 3, 0.2 pmol/mg protein per min; day 20, 2.5 pmol/mg protein per min). Half maximal thyroxine (T4) and triiodothyronine (T3) concentrations were 1 X 10(-7) M (free T4: 4 X 10(-10) M), and 2 X 10(-9) M (free T3: 5.0 X 10(-11) M), respectively, whereas reverse T3 did not elicit any activity at 10(-8)-10(-6) M. These results suggest that ontogenetic development of iodothyronine-5'-deiodinase in the liver of the fetal and neonatal mouse is induced by physiological concentrations of glucocorticoid and thyroid hormones, and that insulin plays a permissive role in enhancing T3 formation from T4 in the liver.

Animals↗
PubMed1983

Modulating effect of glutathione disulfide on thyroxine-5'-deiodination by rat hepatocytes in primary culture: effect of glucose.

To investigate whether an increase in the intracellular glutathione disulfide (GSSG) concentration actually regulates T4-5'-deiodination in intact cells, rat hepatocytes in primary culture were exposed to glutathione-oxidizing agents (diamide and tertiary butylhydroperoxide) or vinblastine, and their effects on 5'-deiodination of T4 were studied. Deiodinating activity was determined from the 125I- fraction released from [3',5'-125I]T4 added to the serum-free culture medium. Total glutathione (T-GSH) and GSSG levels were determined enzymatically. Diamide (1 mM) and tertiary butylhydroperoxide (0.5 mM) increased the GSSG fraction to approximately 40% of the T-GSH at 5 min, followed by a rapid decrease in GSSG. Glucose deprivation of the medium caused a greater GSSG level at 5 min, followed by a delayed normalization of the increased GSSG level. T4-5'-deiodinating activity was minimally decreased in hepatocytes exposed to 1 mM diamide in the presence of glucose in the medium, but was significantly inhibited in the absence of glucose. Vinblastine, in contrast, gradually and steadily increased the GSSG fraction, and by 3 h, GSSG exceeded 20% of T-GSH (at 10(-4) M vinblastine). This was accompanied by a significant inhibition of 5'-deiodinating activity. When the enzyme activity was inhibited, the T-GSH level was decreased to 40-80% of the control level, which per se cannot account for the decreased T4-5'-deiodinating activity, as reported previously. These data suggest that the increased GSSG level, but not the T-GSH concentration, modulates T4-5'-deiodination in intact cells, and that glucose stimulates the enzyme activity by maintaining glutathione in the reduced form, probably through supplying NADPH, a cofactor for GSSG reductase.

Animals↗
PubMed1983

Serum propylthiouracil concentration in patients with Graves' disease with various clinical course.

The serum levels of propylthiouracil (PTU) were determined by radioimmunoassay in 10 normal subjects and in 11 patients with Graves' disease after a single 100 or 200 mg oral dose of PTU. The serum half-life of PTU in the normal subjects and in hyperthyroid patients with uneventful clinical course was 75 +/- 19 min (mean +/- SD, n = 6) and 73 +/- 13 min (n = 7), respectively. Maximum serum PTU concentrations were usually attained within 1 h after a single 200 mg oral dose and at 1 h were 5.3 +/- 1.4 micrograms/ml (3.1 +/- 0.82 X 10(-5) M) in normal subjects (n = 6) and 4.8 +/- 2.4 micrograms/ml (2.8 +/- 1.4 X 10(-5) M) in hyperthyroid patients (n = 7). These between-group differences were not significant. Serum PTU concentrations were low in a pregnant hyperthyroid patient with a weak response to PTU treatment. In another patient, who appeared resistant to PTU therapy, the serum PTU level increased as expected at testing, and it was later confirmed that, during treatment, he had not taken the drug as prescribed. In a patient who developed agranulocytosis due to methimazole and subsequently fever due to PTU, the half-life of PTU was prolonged to about 130 min. These findings suggest that monitoring the serum PTU levels in patients with Graves' disease can be of clinical value in patients who do not respond to treatment. Furthermore, it may provide some clues as to the mechanism by which toxic reaction develops.

Administration, Oral↗
PubMed1983

[Influence of the surgical stress on graft-versus-host reaction in mice--the suppressor activity to GVH reaction induced by the surgical operation].

The influences of surgical stress on the local graft-versus-host reaction (GvHR) in F1 mice were studied. Skin incision to the F1 mice inflicted to 1 day prior to injection of parental spleen cells produced impairment of popliteal lymph node enlargement, however, this effect was not observed when GvHR was induced on the day 3 and 5 after operation. Spleen cells from hind limb amputated F1 mice exhibited suppressor activity on local GvH reaction when injected into naive syngenic F1 mice together. This suppressor activity was markedly detected 3 and 24 hrs after operation, then gradually reduced and completely disappeared on the day 7. These suppressor activity completely disappeared by the treatment with anti-Thy 1.2. antibody and complement. These results showed that GvH reaction was suppressed by the surgical stress, and this suppression was due to suppressor T lymphocytes in the spleen.

Amputation, Surgical↗
PubMed1983

[Post-operative suppression of natural killer activity].

The effects of anesthesia and surgical procedures on natural killer (NK) cell activity were studied. The data indicated that splenic lymphocytes taken from mice 1 to 5 days after surgery showed significantly diminished activity of natural killing. When splenic lymphocytes were treated by anti-Thy 1 antibody and complement, NK activity to Lewis lung carcinoma cells was remarkably depressed in normal mice, but was not depressed in laparotomized mice. Peripheral lymphocytes from cancer patients following major surgery also showed depressed NK activity. The suppression was first detected during the operation. In patients undergoing major gastrointestinal surgery, the suppression was at its maximum during first three days and decreased to control levels by the day 7 to 14. Following major thoracic surgery, the suppression continued more longer.

Animals↗
PubMed1979

Studies on pancreatic duct system. II Comparative study of histological features, and three-dimensional reconstruction of pancreatic ducts.

Three-dimensional reconstruction of pancreatic ducts were made from specimens of pancreases from chronic pancreatic injury dogs following adjuvant injection, one patient with chronic non-alcoholic pancreatitis, and 2 patients with chronic alcoholic pancreatitis. The ductal alterations of alcoholic pancreatitis showed more apparent changes than those of non-alcoholic pancreatitis. The lesions in experiment such as uneven surface, irregular dilatation, tortuosity, and anastomosis, resembled to those of alocholic calcifying pancreatitis. Although gross appearance of the reconstructed ducts in advanced cases of experimental pancreatic injury revealed some resemblance to that of alcoholic calcifying pancreatitis, histologically, the epithelial changes of the former were different from those of the latter. Thus we concluded that more complicated factors than those considered in experiment play a role in combination in the pathogenesis of bead-like dilatation of the pancreatic ducts of chronic pancreatitis.

Alcoholism↗