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Biomedical subjects

T Komaki

Publications and source records attributed to T Komaki.

At least 55 records · Page 3Linked to original sources

Dynamics of plasma lipoproteins and lipids during double filtration plasmapheresis (DEP).

Plasma lipids and lipoproteins obtained from different places of the circuit of double filtration plasmapheresis (DFP) were measured and effect of DFP therapy on removal of them was examined. When 2A was used as a second filter, 69.8%, 52.4%, 63.0%, 58.0%, 60.8%, 59.2% and 63.9%, respectively of beta-lipoprotein, cholesterol, triglyceride, high density lipoproteins (HDL), phospholipids, free cholesterol and lipoprotein (a) (Lp(a)) were removed from the patient's plasma. When 4A was used as a second filter, 69.0%, 56.8%, 53.2%, 45.4%, 56.0%, 50.9% and 51.7%, respectively of beta-lipoprotein, cholesterol, triglyceride, HDL, phospholipids, free cholesterol and Lp(a) were removed from the patient's plasma. In contrast, concentrations of free fatty acids (FFA) after DFP therapy using filter 4A and 2A increased to 222.8% and 256.4%, respectively. Thus, it was shown that except for FFA, DFP therapy using either 2A or 4A as a second filter is effective in reducing concentrations of plasma lipid and lipoproteins.

Adolescent↗

Two cases of systemic lupus erythematosus associated with hyperthyroidism.

We have experienced two cases (Case 1: 21-year-old female, Case 2: 26-year-old female) of systemic lupus erythematosus (SLE) associated with hyperthyroidism. Case 1 had been treated with methimazole (MMI) and betamethasone for approximately two years. Although thyroid function improved with the treatment, laboratory data of SLE deteriorated. She was successfully treated with betamethasone alone. Case 2, who had severe side effect (severe hemorrhage due to gastric ulcer) during prednisolone treatment for SLE, was found to have an additional hyperthyroidism. She was treated with intermittent prednisolone administration alone. Physical findings as well as laboratory data of both SLE and hyperthyroidism improved by the therapy.

Adult↗

Effect of anti-insulin antibodies on glycemic control in insulin treated diabetic patients.

In order to examine the effect of anti-insulin antibodies on serum insulin concentration and glycemic control, sera from 49 insulin-treated diabetic patients (20 males and 29 females) were examined for their titer of anti-insulin antibodies, and concentrations of total insulin (TIRI), free insulin (FIRI) and hemoglobin A1c. Titer of anti-insulin antibodies correlated only with TIRI (r = 0.72, p less than 0.001) and did not correlate with duration of insulin treatment, FIRI concentration, daily dose of insulin, or HbA1c concentration. These results indicate that elevated titer of anti-insulin antibodies in patients under insulin therapy, (1) increases total serum insulin concentration but does not affect serum free insulin level, and (2) has little effect, if any, on glycemic control and the required daily dose of insulin.

Adult↗

An improved and simplified method for the detection of thyroid hormone autoantibodies (THAA) in serum.

We have developed and evaluated a new and simplified method for the detection of thyroid hormone autoantibodies (THAA) in serum. The method includes acidification of serum followed by adsorption of liberated thyroid hormones onto dextran-coated charcoal and then alkalinisation of the serum in assay buffer prior to performing a binding study. Using our method, specific binding of 125I-T4 to serum THAA in two patients with Hashimoto's thyroiditis was almost the same regardless of whether or not the sera had been preincubated with a large amount of cold T4. On the other hand, without the acid treatment, preincubation with cold T4 considerably inhibited the binding of 125I-T4 to serum THAA in both cases. These results indicate that serum THAA can be easily detected under conditions in which circulating thyroid hormones hardly affect the binding study by using our new sensitive method.

Autoantibodies↗

Thyroid hormone autoantibodies (THAA) in two cases of Graves' disease: effects of antithyroid drugs, prednisolone, and subtotal thyroidectomy.

Changes in titers of serum thyroid hormone autoantibodies (THAA) and anti-thyroglobulin (Tg) antibodies during treatment with antithyroid drugs (methimazole and propylthiouracil) were examined in two cases of Graves' disease. Effects of prednisolone and subtotal thyroidectomy were also investigated in one case (case 1). Initially both cases had only anti-T4 autoantibodies in their serum. During methimazole therapy, the titer of anti-T4 autoantibodies increased in both cases, and anti-T3 autoantibodies became detectable and their titer increased in case 2. The influence of propylthiouracil on the titer of THAA was not clear. Both prednisolone plus methimazole therapy and subtotal thyroidectomy decreased the level of anti-T4 autoantibodies in case 1. There was a significant correlation between titers of THAA and anti-Tg antibodies in both cases, although titers of anti-Tg antibodies in case 1 stayed within the normal range throughout the investigation period. These results indicate that methimazole treatment could induce and/or enhance the production of THAA and THAA are antibodies against thyroid hormone-containing Tg molecule.

Autoantibodies↗

The effect of double filtration plasmapheresis on thyroid hormone economy and thyroid function.

Five cases of rheumatoid arthritis (RA), two cases of systemic lupus erythematosus (SLE), a case of mixed connective tissue disease (MCTD), and a case of cold urticaria were treated with double filtration plasmapheresis (DFP). Each aliquot of plasma was obtained at three different points of the DEP circuit during the treatment and concentrations of thyroid hormones as well as thyroxine binding globulin (TBG) were measured. Despite the removal of considerable amounts of triiodothyronine (T3), thyroxine (T4), and TBG from the plasma, levels of plasma free T3 (FT3) and free T4 (FT4) before and immediately after DFP treatment were not significantly different. These results indicate that DEP therapy rarely affects plasma concentration of active thyroid hormones in patients who undergo such therapy.

Adolescent↗

Concentrations of free thyroxine, total thyroxine, and total triiodothyronine in rabbits immunized with human thyroglobulin.

Levels of serum free thyroxine, total triiodothyronine and total thyroxine were measured in two rabbits (TG-1, TG-2) which had been immunized with human thyroglobulin and produced both anti-thyroglobulin and anti-thyroid hormone antibodies. Despite the presence of both anti-triiodothyronine and -thyroxine antibodies, levels of serum free thyroxine in serial sera obtained from a rabbit (TG-1) stayed within normal range up to 249 days after the first immunization, whereas in the other rabbit (TG-2), serum free thyroxine concentrations of serial sera declined after three immunizations and stayed at lower levels than normal range up to 249 days. Extraction of serial sera from both rabbits disclosed the presence of larger amounts of triiodothyronine and thyroxine in immune sera than preimmune sera. From these results, it is concluded that the presence of anti-thyroid hormone antibodies per se can reduce serum level of free thyroxine in rabbits.

Animals↗

Effect of anti-insulin antibodies on glycemic control in insulin treated diabetic patients.

In order to examine the effect of anti-insulin antibodies on serum insulin concentration and glycemic control, sera from 49 insulin-treated diabetic patients (20 males and 29 females) were examined for their titer of anti-insulin antibodies, and concentrations of total insulin (TIRI), free insulin (FIRI) and hemoglobin A1c. Titer of anti-insulin antibodies correlated only with TIRI (r = 0.72, p less than 0.001) and did not correlate with duration of insulin treatment, FIRI concentration, daily dose of insulin, or HbA1c concentration. These results indicate that elevated titer of anti-insulin antibodies in patients under insulin therapy, increases total serum insulin concentration but does not affect serum free insulin level, and has little effect, if any, on glycemic control and the required daily dose of insulin.

Adult↗

Genetic control of the production of anti-thyroid hormone antibodies in mice immunized with human thyroglobulin.

Various strains of mice with different H-2 and Igh-I allotypes were immunized with human thyroglobulin (HTg) and genetic control of the production of anti-thyroid hormone antibodies was examined. Anti-HTg antisera obtained from different strains of mice were examined for the presence of anti-thyroid hormone antibodies. At least one Ir-gene which controls the production of anti-T4 antibodies by immunization with HTg was identified in the I-A subregion. The presence of Ir-genes outside the H-2 was also suspected. Concerning the production of anti-T3 antibodies, only three strains (B10.A, C3H.SW, BALB/cJ) were high responders and therefore we were unable to identify the Ir-gene for them. These results indicate the presence of Ir-gene which controls the immune response in mice against thyroid hormone and suggest that the anti-thyroid hormone antibodies observed in various thyroidal and non-thyroidal disorders could be anti-HTg antibodies. The significance of genetic control of the production of anti-thyroid hormone antibodies in mice immunized with HTg is discussed.

Animals↗

[Investigations on the mechanism(s) of the production of anti-thyroid hormone antibodies 4: the effect of adjuvant on the immune response to human thyroglobulin].

Forty-five female DDYK mice were divided into three groups and immunized with different preparations of human thyroglobulin (HTg). Group 1 mice were immunized subcutaneously in the back with HTg emulsified with FCA. Group 2 mice were immunized subcutaneously in the back with HTg dissolved in PBS. Group 3 mice were immunized with HTg dissolved in PBS and FCA separately in the right (HTg) and left (FCA) of the back. After the fourth immunization (45 days after the first immunization), antisera as well as thyroid glands were obtained, and titers of anti-HTg, anti-T3, anti-T4 and the presence of lesions of autoimmune thyroiditis were examined. In group 1 mice, titers of anti-HTg and anti-T4 antibodies were significantly higher than those of the other two groups, whereas titers of anti-T3 antibodies were significantly lower than those of the other two groups. In group 1 mice, a significant correlation between titers of anti-T3 and anti-T4 antibodies was observed, whereas in group 2 and group 3 mice, no such correlation was observed. The incidence of lesions of autoimmune thyroiditis was significantly higher in group 2 and group 3 mice than in group 1 mice. Thus emulsification of HTg with FCA had inhibitory effects on the induction of experimental thyroiditis in mice immunized with HTg. These results indicate the possibility that FCA has a modulatory effect both quantitatively and qualitatively on the immune response against HTg in mice.

Animals↗

A case of Graves' disease with anti-triiodothyronine antibodies.

A case of Graves' disease with high serum thyroxine (T4) and low triiodothyronine (T3) levels which was therefore initially diagnosed as a T4-thyrotoxicosis is reported. Examination of the serum from the patient showed the presence of unusual protein which bound T3. It was later confirmed as IgG class anti-T3 antibodies. In addition to treatment with methylmercaptoimidazole (MMI), the patient was treated with prednisolone for 30 days (total amount 500 mg). Titers of anti-T3 antibodies in the sera were unchanged before and after prednisolone treatment. Our present case indicates that it is clinically important to bear the presence of autoantibodies in mind to account for a possible error in measuring T3 and T4 by radioimmunoassay (RIA). In the case that RIA determination gives an unexpectedly high or low T3 and/or T4 value, the presence of autoantibodies to them should be considered and a test for them is recommended.

Antibodies, Anti-Idiotypic↗

Production of anti-human thyroglobulin and anti-thyroid hormone antibodies in rabbits immunized with human thyroglobulin.

Two rabbits (TG-1, TG-2) were immunized with human thyroglobulin (HTg) and bled serially. Antisera were obtained at different times after the first immunization and kept separately and studied. In both rabbits production of anti-HTg, and anti-thyroid hormone antibodies such as anti-thyroxine (T4) and anti-triiodothyronine (T3) antibodies was observed. Binding parameters of anti-HTg antibodies with HTg, T4, and T3 were calculated in two selected antisera (70-day and 249-day). The Scatchard's plots of these antibodies were all curve-linear and were analyzed in two components: one, higher binding constant (Ka1) and smaller binding capacity (Cap1) and the other, lower binding constant (Ka2) and larger binding capacity (Cap2). Ka1 values of anti-HTg, anti-T4, and anti-T3 antibodies in sera from TG-1 obtained from 70-day and 249-day bleeding were 1.1 X 10(10) M-1, 6.0 X 10(9) M-1. 7.9 X 10(8) M-1 and 1.7 X 10(10) M-1, 6.5 X 10(9) M-1, 1.0 X 10(9) M-1, respectively. Those from TG-2 were 1.7 X 10(10) M-1, 1.8 X 10(9) M-1, 6.4 X 10(8) M-1 and 2.0 X 10(10) M-1, 3.1 X 10(9) M-1, 1.6 X 10(9) M-1, respectively. The significance of the production of anti-HTg and anti-thyroid hormone antibodies in rabbits immunized with HTg in relation to the antigenic structure of HTg molecule was discussed.

Animals↗

[Investigations on the mechanism(s) of the production of anti-thyroid hormone antibodies 3:Production of anti-rabbit thyroglobulin and anti-thyroid hormone antibodies in rabbits immunized with rabbit thyroglobulin].

Recently, the presence of anti-thyroid hormone antibodies has been reported in many cases of thyroidal and non-thyroidal disorders. In order to elucidate the immunological mechanism(s) in the production of anti-thyroid hormone antibodies, we immunized outbred rabbits and mice with different H-2 and Igh allotypes with human thyroglobulin (HTg) and showed that the production of both anti-HTg and anti-thyroid hormone antibodies is genetically controlled. In our present study, rabbit thyroglobulin (RTg) was purified from 4 rabbit thyroid glands and was immunized in two rabbits (RG-I, RG-2). The two rabbits were then serially bled and tested for the presence of anti-RTg and anti-thyroid hormone antibodies. In both rabbits, the production of anti-RTg and anti-thyroid hormone antibodies was observed. The binding constant of anti-RTg, anti-T4 and anti-T3 antibodies in RG-1 were 6 X 10(9)M-1, 9.5 X 10(8)M-1, 4.6 X 10(8)M-1, and those in RG-2 were 6.5 X 10(9)M-1, 5.6 X 10(8)M-1, 1.6 X 10(8)M-1, respectively. These results further strengthen the possibility that the antigen of the anti-thyroid hormone antibodies observed in various disorders so far reported is the HTg molecule. In addition, the fact that anti-RTg antibodies had a higher binding constant and capacity than anti-thyroid hormone antibodies suggests that the antigenic site(s) of RTg, which contains thyroid hormones, is not highly immunogenic.

Animals↗

Serum thyroglobulin concentration in normal pregnancy.

We measured the levels of serum thyroglobulin (Tg) in 52 pregnant females at various stages and compared them with those of 15 age-matched nonpregnant females. Serum Tg was measured by a solid-phase immunoradiometric assay. In pregnant females, mean serum Tg levels at the first, second, early third, and late third trimesters were 8.4 (range; 1.3-18.0), 9.2 (1.7-25.6), 10.1 (1.8-22.8), and 12.1 ng/ml (5.3-25.2), respectively. The statistical comparison was made after logarithmic transformation of the data. The mean value only at the late third trimester was significantly higher than that of controls (mean; 6.0 ng/ml, range; 1.5-23.6), but each value was within the normal range. Although serum Tg levels have been reported to be high at the end of pregnancy, our results indicate that the Tg levels in females could be clinically interpreted without regard to the coexistence of pregnancy.

Adult↗

Theoretical consideration of the effects of dilution on estimates of free thyroid hormones in serum.

When concentrations of free thyroid hormones in serum are measured by equilibrium dialysis, the serum sample is diluted by dialysis buffer, resulting in a new equilibrium for distribution of these hormones that differs from that in the original serum sample. We have derived a mathematical formulation, based on an equilibrium model for multiple ligands and multiple binding sites, to determine the effect of dilution on the concentrations of free hormones in serum. Computer simulations based on the formulation indicate that both free thyroxin (T4) and free triiodothyronine (T3) are decreased by dilution of serum, free T3 being affected more than free T4. This dilution-related decrease is more prominent in hyperthyroidism than in euthyroidism, and even more striking for sera in which binding capacities for thyroid hormones are decreased (e.g., in thyroxin-binding globulin deficiency or hypoalbuminemia). These simulations can provide a basis for minimizing experimental errors in the estimates of concentrations of free thyroid hormones by equilibrium dialysis.

Blood Proteins↗