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Biomedical subjects

C Shigemasa

Publications and source records attributed to C Shigemasa.

At least 91 records · Page 5Linked to original sources

Lower serum free thyroxine (T4) levels in painless thyroiditis compared with Graves' disease despite similar serum total T4 levels.

Serum total T4 (T4), total T3 (T3), free T4 (FT4), free T3 (FT3), and T4-binding globulin concentrations and T3 resin uptake values were measured in 17 women with thyrotoxicosis due to painless thyroiditis (PT) and compared with the same parameters in 17 women with thyrotoxicosis due to Graves' disease (GD) with similar serum T4 levels. The mean serum T3 resin uptake value and T3, FT4, and FT3 concentrations in the PT patients were significantly lower than those in the GD patients. The mean serum T4-binding globulin concentration [20.2 +/- 4.2 (+/- SD) microgram/mL] in patients with PT did not differ significantly from those in patients with GD (18.0 +/- 2.6 micrograms/mL) and normal euthyroid women (21.9 +/- 4.0 micrograms/mL). The serum T3 to T4 (nanogram per microgram) ratio was higher than 20 in 14 GD patients, but lower than 20 in all patients with PT, whereas the individual serum FT3 to FT4 ratio values considerably overlapped in the 2 groups. In patients with PT, FT4 correlated well with T4 at various times during the clinical course. These findings indicate that the elevation in serum FT4 in patients with PT is mostly due to the increase in circulating T4 levels, whereas GD patients also have some diminution in T4 binding. The serum T3 to T4 ratio, but not the FT3 to FT4 ratio, may be helpful for differentiation between the two diseases.

Adolescent↗

Examination of exchange assay for glucocorticoid receptor.

We examined a method for the measurement of total, activated and non-activated glucocorticoid receptors using sodium-p-hydroxymercuribenzoate (PHMB) and dithiothereitol (DTT) developed by Banerji and Kalimi (1981). Since the concentration of PHMB required for dissociation of the ligand from the receptors varied with the concentration of protein in the reaction mixture and the rate of reassociation of the ligand to the ligand-liberated receptors was sensitive to the concentration of PHMB used, it was necessary to find the minimum concentration of PHMB which was required for complete dissociation of the ligand. When the optimum concentration of PHMB was selected based on the concentration of protein in the cytosol, almost 100% exchange was attained in the non-heated dexamethasone (Dex)-receptor complexes by this method. However when Dex-receptor complexes were heated at 25 degrees C for 30 min, the amount of 3H-Dex reassociated with the glucocorticoid receptors dropped to 60% of that of the non-heated ones. DEAE-cellulose chromatography of the heated sample revealed that approx. 40% of the bound receptors were activated (eluted with 0.05 M KCl) during the heating period. After DEAE cellulose column chromatography of the exchanged 3H-Dex receptor, complexes reassociated with 3H-Dex were observed only in the fraction of unactivated receptor complexes (eluted with 0.2 M KCl). Furthermore, the fraction eluted with 0.05 M KCl in the DEAE cellulose chromatography of liver cytosol bound to unlabelled Dex did not exchange significantly with 3H-Dex with the method used in the present study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Serum free thyroxine and thyroxine-binding globulin concentrations in early phase of subacute thyroiditis.

Serum total thyroxine (T4), total triiodothyronine (T3), T4-binding globulin (TBG), free T4(FT4) and free T3(FT3) concentrations and the T3-uptake(T3-U) value were estimated in 11 patients with subacute thyroiditis, and compared with the same parameters in 11 patients with Graves' disease, whose serum T4 concentrations were similar to the former group. Seven patients with subacute thyroiditis, who were treated with dicrofenac sodium alone, were investigated as to the sequential changes in serum parameters during their clinical courses. The mean serum T3-U value and FT4, T3 and FT3 concentrations in patients with subacute thyroiditis were increased, but all were significantly lower than those in patients with Graves' disease (p less than 0.01, p less than 0.001, p less than 0.001 and p less than 0.001, respectively). Three patients with subacute thyroiditis, who showed shorter duration of symptoms than 10 days, had serum TBG excess. Thus the mean (+/- SD) serum TBG concentration (26.5 +/- 8.4 micrograms/ml) was significantly higher than that (18.3 +/- 2.9 micrograms/ml) in patients with Graves' disease (p less than 0.02). The ratios of serum T3 to T4 and FT3 to FT4 in patients with subacute thyroiditis were also significantly lower than those in patients with Graves' disease (p less than 0.001 and p less than 0.001, respectively). The serum FT4 in 7 patients treated with dicrofenac sodium alone decreased to the normal range after 3 to 8 weeks from the onset of the illness. In 3 patients with TBG excess and one patient (TBG; 29.0 micrograms/ml), serum TBG declined in consequence of the serum FT4 normalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pharmacokinetics of methimazole in normal subjects and hyperthyroid patients.

Serum and urinary concentrations of methimazole (MMI) were measured by high-performance liquid chromatography (HPLC) with an electrochemical detector (ECD) in 10 normal subjects and 43 hyperthyroid patients after intravenous and oral administration of the drug. The pharmacokinetic parameters of MMI were estimated in 5 normal subjects and 15 hyperthyroid patients according to a two-compartment model after intravenous injection of a 10 mg dose. The mean half-life of the distribution phase (T1/2 alpha) was 2.7 +/- 1.0 h (mean +/- SD) and 3.1 +/- 1.4 h and that of the slower-phase (T1/2 beta) was 20.7 +/- 9.6 h and 18.5 +/- 12.9 h in normal subjects and hyperthyroid patients, respectively. There were no significant differences between pharmacokinetic parameters of normal subjects and those of hyperthyroid patients. No correlations between free T4 index (FT4I) and pharmacokinetic parameters were observed. Maximum serum MMI concentrations (Cmax) (213 +/- 84 and 299 +/- 92 ng/ml) were attained 1.8 +/- 1.4 h and 2.3 +/- 0.8 h after a single dose of 10 mg in 5 normal subjects and in 15 hyperthyroid patients, respectively. In hyperthyroid patients the time taken to reach the peak concentration (Tmax) after a single dose of 10 mg was similar to that after a single 15 mg and 30 mg dose. The pharmacokinetic parameters, except Cmax and the area under the curve (AUC), were not affected by the administered dose and those, except Cmax, were not affected by the thyroid function. All urine was collected at intervals of 3 h for the first 12 h and then at 24 h and 48 h after intravenous and oral administration of MMI. In all subjects, MMI rapidly appeared in the urine and the rate of excretion was highest in the first 3 h. The cumulative urinary excretion of MMI was 5.5-8.5% of administered doses in normal subjects and hyperthyroid patients. These findings in the present study are compatible with the assumption that the extent of absorption of MMI is high, if not complete, and hyperthyroidism does not affect the kinetics of MMI, and that interindividual variation is observed in the time taken to reach the peak concentration after oral administration.

Administration, Oral↗

Receptor dynamics and tyrosine aminotransferase induction during the course of chronic treatment of rats with glucocorticoid.

The changes in the cytosol glucocorticoid receptor (GR) content during a long-term administration of a glucocorticoid were studied to examine the mechanism of the development of steroid hormone resistance. Dexamethasone (Dex) (0.2 microgram/ml and 2.0 micrograms/ml) was given to adrenalectomized rats, and the GR content was determined using the exchange assay 1, 10, 20 and 50 days after the start of administration. The activity of tyrosine aminotransferase (TAT) in the cytosol was also assayed as a measure of the biological responsiveness of these animals to the administered glucocorticoid. The dissociation constant (Kd) was elevated and the Bmaxs of the GR in the cytosol were decreased by the lower concentration of Dex. The Bmaxs decreased to 30% of the untreated controls within 24 h and this lower level was maintained as long as the hormone treatment continued. On the other hand, the cytosol obtained from animals treated with 2.0 micrograms/ml of Dex for 20-24 days did not show any measurable amount of binding to 3H-Dex. The activity of TAT was elevated 24 h after the administration of Dex but decreased gradually and steadily with time during the experimental period. To examine the biological potency of remaining GR in the liver cytosol, 2.0 micrograms/ml Dex was again administered after a long-term treatment. This treatment eliminated the remaining GR completely and induced TAT at almost the same rate as observed in the untreated control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Determination of thiamazole in serum by high-performance liquid chromatography with electrochemical detection.

A simple and sensitive method for the determination of thiamazole in serum by high-performance liquid chromatography with electrochemical detection is described. Thiamazole in serum was quantified without an extraction procedure at concentrations down to 10 ng/ml. This method was applied to determine the serum concentration of the drug in two healthy volunteers given a single oral dose of 10 mg of thiamazole. The concentration of the drug reached a maximum at 3-4 h after the oral dose and two elimination phases were observed.

Administration, Oral↗

Echographic findings and histological feature of the thyroid: a reverse relationship between the level of echo-amplitude and lymphocytic infiltration.

In 43 patients with Graves' disease, 5 patients with painless thyroiditis and 30 patients with Hashimoto-thyroiditis ultrasonographical observations and histological examinations by needle biopsy of the thyroid were carried out simultaneously. In all cases the level of echo-amplitude was well correlated with the rate of lymphocytic infiltrations and fibrosis. In cases which exhibited marked lymphocytic infiltrations in the thyroidal biopsy specimen, no apparent echoes or very low amplitude echoes were observed in the whole thyroid and in cases in which replacement with lymphocytic infiltration was observed in almost a half part of the thyroid, several sonolucent regions were observed in the thyroid and in cases in which lymphocytic infiltration or fibrosis was observed sporadically, low-amplitude and uniform echoes were observed in the whole or several regions of the thyroid. In cases with no lymphocytic infiltration in the histological specimen, diffuse high-amplitude and uniform echoes were observed throughout the whole lobe of the thyroid. In patients with painless thyroiditis, the amplitude of echo was low when the level of lymphocytic infiltration was high and the echo-amplitude showed a tendency to increase along with the decrease in the rate of lymphocytic infiltration. From these observations it is concluded that echo-amplitude is well correlated with lymphocytic infiltration and fibrosis in patients with Hashimoto-thyroiditis, Hashitoxicosis and painless thyroiditis.

Graves Disease↗

[Side effects of antithyroid drugs].

In order to investigate the incidence of side effects of antithyroid drugs and to study if there were any factors related to the onset of the side effects, clinical and laboratory findings were examined in 71 untreated Graves' patients. The overall incidence was 28.2% among 71 cases who were initially administered methimazole or propylthiouracil. The incidences were 23.2% (13 of 56 cases) for methimazole and 46.7% (7 of 15 cases) for propylthiouracil, respectively, which were significantly higher than those previously reported. Seventeen of 20 cases with side effects under the drug of first choice were administered the another antithyroid drug. Four of 17 (23.5%) cases successively had side effects. The side effects were observed within 1.5 months of administration of less than 150 tablets in total in most of the cases. The serum concentration of Ig-E and peripheral eosinophils(/mm3) at the onset of the side effects were significantly higher than those before treatment. These results suggest that allergic mechanism rather than accumulating may concern the onset of side effects. Since in cases without the side effects the peripheral eosinophils at 3 to 4 weeks after administration were significantly higher than those before treatment and 19 of 51 (38.0%) cases without side effects had a high concentration of Ig-E of more than 500 u/ml, it is suggested that allergic mechanism may be triggered in most of Graves' patients who were administered methimazole or propylthiouracil. Thus, immunological disturbances in Graves' disease seems to be the cause of the side effects of antithyroid drugs, although there was no correlation between antithyroid autoantibodies and development of the side effects.

Adolescent↗