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Biomedical subjects

K Kuma

Publications and source records attributed to K Kuma.

At least 217 records · Page 12Linked to original sources
PubMed1986

Identification of parathyroid hormone messenger ribonucleic acid in an apparently nonfunctioning parathyroid carcinoma transformed from a parathyroid carcinoma with hyperparathyroidism.

mRNA coding for pre-pro-PTH, a precursor of PTH, was sought in an apparently nonfunctioning parathyroid carcinoma that had transformed from one that was previously functioning. Total poly(A+) RNA was prepared by phenol-chloroform-isoamyl alcohol extraction and oligo-dT-cellulose affinity chromatography from the tumor tissue and bovine parathyroid glands. In the rabbit reticulocyte lysate cell-free translation system, total poly(A+) RNA from the tumor as well as that from bovine parathyroid glands directed the translation of a product which was specifically precipitated by an anti-PTH serum and which migrated at the same position as pre-pro-PTH on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results indicated the presence of mRNA coding for pre-pro-PTH (PTH mRNA) in an apparently nonfunctioning parathyroid carcinoma, suggesting that PTH synthesis is not always absent in parathyroid carcinomas which are not accompanied by hyperparathyroidism.

Animals↗
PubMed1986

Serum triiodothyronine to thyroxine ratio: a newly recognized predictor of the outcome of hyperthyroidism due to Graves' disease.

Patients with untreated hyperthyroidism due to Graves' disease have a proportionally greater increase in the serum T3 than in the T4 concentration and, therefore, have an elevation of the serum T3 to T4 ratio. The aim of this study was to investigate the alterations of the serum T3 to T4 ratio in relation to the outcome of antithyroid drug therapy. Of 47 patients with hyperthyroid Graves' disease, 37 patients had a serum T3 to T4 ratio greater than 20 ng/micrograms before therapy (normal range, 12-20; mean, 16.0). In 7 of 37 patients, serum T3 to T4 ratios remained high during a 2-yr course of antithyroid drug therapy, and in 6 of them (86%), hyperthyroidism recurred after cessation of drug therapy. In the remaining 30 patients, the initial high serum T3 to T4 ratios decreased to normal (less than 20) during treatment, and 15 of them (50%) had a remission of the disease after cessation of the drug. Of the 10 patients with initial serum T3 to T4 ratios within the normal range, this ratio remained normal during treatment, and 8 (80%) had a remission. Goiter size was larger in patients with high serum T3 to T4 ratios, and a reduction of goiter size occurred in some patients (57%) with decreasing serum T3 to T4 ratios. The serum T3 to T4 ratio is a simple and useful predictor of the outcome of antithyroid drug therapy in patients with Graves' disease. A ratio greater than 20 throughout therapy indicates that the likelihood of relapse is high, and a ratio below 20 either initially or during therapy is an indicator of prolonged remission.

Adult↗
PubMed1986

Monoclonal gammopathy in Hashimoto's thyroiditis and malignant lymphoma of the thyroid.

Serum protein electrophoresis was performed in 681 patients (43 men and 638 women) with an initial diagnosis of Hashimoto's thyroiditis between April and November 1983. All patients whose thyroid size was estimated to be greater than 50 g underwent biopsy; 1 man was found to have thyroid prelymphoma, and 13 patients (4 men and 9 women) were found to have malignant lymphoma of the thyroid. Monoclonal gammopathy (M-component) was demonstrated in 5 of 667 patients (0.7%) with Hashimoto's thyroiditis (1 man and 4 women), 1 man with thyroid prelymphoma, and 3 of the 13 patients (23.1%) with malignant lymphoma of the thyroid (2 men and 1 woman). Intracytoplasmic monoclonal immunoglobulin was found in the 1 thyroid prelymphoma and in all 3 malignant lymphoma of the thyroid in patients who had M-component in their serum, but not in thyroid tissue from any of the 5 patients with Hashimoto's thyroiditis who had M-component in their serum. Thus, the finding of monoclonal intracytoplasmic immunoglobulin in tissue sections permitted the diagnosis of malignant lymphoma of the thyroid or thyroid prelymphoma.

Adult↗
PubMed1986

Binding of immunoglobulin G from patients with autoimmune thyroid diseases to solubilized guinea pig fat cell membranes crosslinked with 125I-TSH.

Binding of immunoglobulin G (IgG) to Triton-solubilized fat cell membranes crosslinked with 125I-TSH was studied by an indirect immunoprecipitation method. Guinea pig fat cell membranes (FCM) containing TSH receptors with an association constant of 1.92 X 10(9) M-1 were first reacted with 125I-TSH, then treated with a crosslinker, dissuccinimidyl suberate. The dissociation of 125I-TSH from the crosslinked 125I-TSH-FCM complexes due to the addition of 100 mU/ml unlabeled TSH was 9.0%, while it was 33% without the treatment. To the Triton-solubilized FCM crosslinked with 125I-TSH, 50 micrograms each of IgG from 20 normal controls, 20 patients with Graves' disease and 20 with Hashimoto's disease was added and precipitation was effected by adding anti-human IgG. In patients with Graves' disease, 125I-TSH-FCM complexes immunoprecipitated ranged from 1.10 to 4.18% with an average of 2.4 +/- 0.99 (S. D.) % which was significantly higher than those in normal controls (1.6 +/- 0.29%). The values in the patients with Hashimoto's disease averaged 1.7 +/- 0.53 (S. D.) which did not differ significantly from those of controls. The value did not correlate with either TSH-binding inhibiting activities or titers of anti-microsomal antibodies. These data suggest the presence of TSH-receptor antibodies which react with antigens other than TSH-binding sites in the patients with Graves' disease.

Adipose Tissue↗
PubMed1986

Immunoglobulin G subclasses of anti-thyroid peroxidase autoantibodies in human autoimmune thyroid diseases.

A distribution of immunoglobulin G (IgG) subclass of anti-thyroid peroxidase (TPO) autoantibodies was studied to know whether anti-TPO autoantibodies are closely implicated in the pathogenesis of human autoimmune thyroid diseases. As a result of analyzing 14 patients' sera, 7 with Graves' disease and 7 with Hashimoto's thyroiditis, anti-TPO autoantibodies were found to consist of mainly IgG1 subclass. Percentages of both IgG1 and IgG2 subclasses in IgG class of autoantibodies corresponded to those in the normal serum composition, whereas IgG3 subclass was scarcely contained in anti-TPO autoantibodies and IgG4 subclass markedly increased. It was thought that anti-TPO autoantibodies had a capability to lyse thyroid follicular cells by the mechanism of antibody-dependent complement-mediated cytolysis, because IgG1 and IgG2 subclasses of antibodies can fix complement and TPO locates in apical membrane surface of thyroid follicular cells. Comparing Graves' disease with Hashimoto's thyroiditis, mean percentages of both IgG1 and IgG2 subclasses of 2 groups were statistically different. Namely, sera of patients with Graves' disease had higher and lower mean percentages of IgG1 and IgG2 subclasses of autoantibodies, respectively, than those with Hashimoto's thyroiditis, though no plausible explanation for these differences can be offered at the present time.

Adult↗
PubMed1986

Paired determination of thyroid-stimulating and TSH-binding inhibitory activities in patients with Graves' disease during antithyroid drug treatment.

Sequential changes in thyroid-stimulating antibodies (TSAb) and TSH-binding inhibitor immunoglobulins (TBII) during antithyroid drug treatment were studied in 17 patients with Graves' disease. Before treatment, TSAb and TBII were detected in 17 (100%) and 13 (76.5%) patients, respectively, with a significant correlation between the two activities (r = 0.600, n = 17, P less than 0.02). In 9 patients who became euthyroid as early as after 1-4 months of treatment, the TSAb and TBII activities both gradually decreased, and there was a good correlation between the changes of these activities during treatment. Among the 7 patients in whom small changes in TSAb and TBII activities were observed, 4 showed poor control of the thyrotoxicosis during the whole observation period (7 months-2 years). One patient who showed a marked dissociation between the changes in TSAb and TBII activities developed hypothyroidism, when his TBII became remarkably high. These potent TBII inhibited cAMP production induced by bTSH. These findings indicate that 1) changes in TSAb and TBII activities reflect the clinical course of hyperthyroidism in most patients with Graves' disease, and 2) development of a blocking-type of TBII may induce hypothyroidism in some patients after the treatment.

Adolescent↗
PubMed1986

[Prognostic values of the doubling time of serum carcinoembryonic antigen and calcitonin levels in medullary thyroid carcinoma].

Fifteen patients operated on for medullary thyroid carcinoma with elevated postoperative serum calcitonin (CT) levels underwent serial measurements of serum CT and carcinoembryonic antigen (CEA) levels. Both CT and CEA levels showed an exponential increase in 12 patients and a slight decrease in three. CEA levels manifested less fluctuation than CT levels. The doubling time of these tumor marker levels calculated from the regression line in each patient showed a strong correlation with three-year survival, recurrence within five years, and the time interval between surgery and recurrence of the tumor, allowing quantitative prediction of the prognosis. However, the doubling time of CEA was longer than that of CT in most patients.

Adult↗
PubMed1985

Improved method of thyroid peroxidase extraction from the human thyroid gland.

This study describes a new method of solubilizing thyroid peroxidase (TPO) and partial purification of TPO from a small surgical specimen of human thyroid tissue. Graves' thyroid tissue was homogenized and centrifuged to obtain the 100 000 X g pellet. To solubilize TPO from the 100 000 X g pellet protein, the following four detergents were used: Triton X-100, digitonin, sodium deoxycholate, and 3-[(3-choramidpropyl)-dimethylammonio] 1-propanesulfate (CHAPS). For some samples, two detergents were combined and trypsin was also used. The best solubilization of TPO activity was obtained from the combination of digitonin-CHAPS-trypsin treatment or deoxycholate-CHAPS-trypsin treatment. The solubilized crude TPO was then chromatographed on a Sephacryl S 300 column. The results of chromatography indicated that detergent treatment alone did not separate TPO from other membrane proteins and the addition of trypsin was required for separation of TPO. Sephacryl chromatography of detergent-trypsin solubilized TPO was suitable as an initial step for purification of TPO from a small human thyroid tissue.

Cholic Acids↗
PubMed1985

[Studies on the pathogenesis of subacute thyroiditis].

UNLABELLED: Despite the fact that subacute thyroiditis (SAT) is a common disease, its pathogenesis is still uncertain. At present, viral infection is simply thought to be a possible pathogenic factor. In Caucasians and Chinese, however, a strong association has recently been found between HLA-Bw35 and SAT. Therefore, genetic factors are also thought to participate in the onset of SAT. In this study we have further attempted to clarify the pathogenesis of this disease in this regard. PROTOCOL: HLA typing for A, B and C loci (class I antigens) was performed on 89 patients with SAT (males: 7, females: 82) aged from 23 to 66 years, and DR and MT loci (class II antigens) were investigated in 55 patients. In 12 patients, viral antibody titers were measured as soon as possible after onset and two weeks later. The viral antibodies evaluated were those of Influenza A and B, Coxsackie A9, B1, B2, B3, B4, B5 and B6, Echo 3, 7, 11 and 12, Parainfluenza 1, 2, 3 and 4, and Adeno 8 virus. The following results were obtained: In class I HLA typing, the frequency of HLA-Bw35 in SAT was 67.4%, which was significantly (p less than 0.0001) higher than that in the control (14.1%). On the other hand, the frequency of Cw1 in SAT (14.6%) was significantly (p less than 0.01) lower than that of the control (32.1%), and that of Cw3 (65.2%) was significantly (p less than 0.01) higher than that of the control (46.5%). In class II HLA typing, the frequency of DRw8 in SAT was 38.2%, which was significantly (p less than 0.05) higher than that of the control (21.9%). Other antigens showed no significant changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Alterations in circulating thyroid hormones and thyrotropin in euthyroid patients with Graves' disease after total thyroidectomy: comparison between responders and nonresponders to TSH-releasing hormone.

Eleven euthyroid patients with severe exophthalmos of Graves' disease who had been treated with antithyroidal drugs for one to three years prior to total thyroidectomy were studied. All patients were clinically and biochemically euthyroid at the time of operation. According to their responses of TSH to TRH prior to operation, the patients were divided into two groups: (1) five responders and (2) six nonresponders. In group 1, serum TSH levels increased significantly on the third day after thyroidectomy (from 1.5 +/- 0.3 to 8.6 +/- 1.4 microU/mL: P less than 0.05); serum T4 concentrations decreased significantly and were in the hypothyroid range by the third day. In group 2, serum TSH levels rose from 0.5 +/- 0.01 to 3.2 +/- 0.5 microU/ml (P less than 0.05) on the ninth postoperative day; serum T4 concentrations decreased on the third day after operation but did not attain hypothyroid levels until the 12th day. Thus after total thyroidectomy the following are concluded: (1) serum TSH levels even in treated euthyroid patients with Graves' disease, rose more gradually in TRH-nonresponders in comparison with TRH responders; (2) the time when serum TSH elevation occurs is dependent upon serum concentrations of thyroid hormones (serum T3 and T4).

Adult↗
PubMed1985

Genetic analysis of subacute (de Quervain's) thyroiditis.

A weak association between subacute (de Quervain's) thyroiditis and HLA-DRw8 (relative risk = 2.19, X2 = 3.86) was observed. However, the association was not statistically significant if p value was corrected. Since it was confirmed that the association of subacute thyroiditis with HLA-B35 was primary, and since this association was extremely strong, the two models (dominant and recessive) for the effect of an HLA-linked gene which has a major effect on the pathogenesis of subacute thyroiditis were tested by the method described by Thomson & Bodmer using the frequency of HLA-B35 in the patients. The data most fit to the recessive model for the HLA-linked major gene involved in subacute thyroiditis.

Genetic Linkage↗
PubMed1985

Immunogenetics of Hashimoto's and Graves' diseases.

Haplotypes of the human major histocompatibility complex (HLA) and the immunoglobulin allotype (Gm) were analyzed in all 243 members of 37 families in which 2 or more first degree relatives had Graves' disease. In 10 families with 70 members where 1 or more first degree relatives had Hashimoto's disease, 26 (37%) had Graves' disease, and 14 (20%) had Hashimoto's disease. In the other 27 families, consisting of 173 members, 70 (40%) had Graves' disease, and none had Hashimoto's disease. The disease-associated haplotypes of HLA and Gm for each family were identified by determining the haplotypes concordant in 2 members with Graves' disease. In 10 families with Graves' and Hashimoto's diseases, all 14 members with Hashimoto's disease had the same disease-associated haplotypes of both HLA and Gm as had members with Graves' disease in each family. Among 96 members with Graves' disease in 37 families, 74 were used for the determination of the disease-associated haplotypes. In the remaining 22 members with Graves' disease, 21 had both disease-associated haplotypes in their families. Our findings in these families suggest that 1) in Hashimoto's disease as in Graves' disease, two genes linked to HLA and Gm, respectively, control the susceptibility of the disease; 2) common immunogenetic factors are involved in the pathogenesis of both Hashimoto's and Graves' disease, and 3) those who do not have immunogenetic factors are very unlikely to develop Hashimoto's or Graves' disease.

Female↗
PubMed1985

Increased cyclic nucleotide phosphodiesterase (PDE) and calmodulin activities in soluble fraction of Graves' thyroid: analysis of increase in Ca+2 dependence of PDE activities.

Phosphodiesterase (PDE) and calmodulin (CaM) activities were studied in soluble fractions of normal and Graves' thyroid tissue. Normal and Graves' thyroid tissues were obtained at thyroid surgery. PDE activities were assayed with cAMP and cGMP as substrates. CaM activity was measured as the ability to activate bovine thyroid CaM-dependent PDE. cAMP and cGMP PDE activities were increased 1.5- and 2.2-fold above normal in Graves' thyroid, respectively. The major cause of the increase in enzyme activities was their higher Ca+2 dependence. CaM activity also was 1.6-fold increased in Graves' thyroid, although it probably does not contribute to the increase in the Ca+2 dependence of PDE activities because of its relative sufficiency vs. PDE in normal thyroid. Three forms of cAMP and cGMP PDE activities were eluted from Sephadex G-200 columns, with mol wt of 280,000, 140,000, and 80,000-100,000, respectively. The first peak had little or no CaM dependence, the second peak had moderate or dominant CaM dependence, and the third peak revealed weak or dominant CaM dependence. The increase in the CaM-dependent form of the third peak of PDE activity in Graves' thyroid tissue may explain the increase in Ca+2 dependence of PDE activities.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1985

Serum ferritin as a marker of thyroid hormone action on peripheral tissues.

Serum ferritin measurements were evaluated as a marker of thyroid hormone action on peripheral tissues. Mean serum ferritin concentrations were not significantly different in euthyroid, thyrotoxic, and hypothyroid subjects due to a wide spread in ferritin levels among individuals. Intraindividual changes in serum ferritin, however, occurred with changing thyroid function. All 18 patients with thyrotoxic Graves' disease had a decrease in serum ferritin levels when they became euthyroid during antithyroid drug therapy. Furthermore, a significant intraindividual correlation between serum levels of ferritin and T4 or T3 was found in 2 patients with thyrotoxic Graves' disease in whom levels were measured serially throughout the course of therapy. Similarly, serum ferritin levels increased in all 12 hypothyroid patients with Hashimoto's disease when euthyroidism was achieved with L-T4 therapy. Administration of 75 micrograms T3 daily for 1 week to 11 euthyroid subjects resulted in a 23-243% (mean +/- SD, 117 +/- 70%) increase in serum ferritin above basal values. In contrast, in 3 patients with thyroid hormone resistance, the same treatment produced rises in serum ferritin concentrations of only 2%, 5%, and 15%. Our data suggest that alterations in thyroid status in a given individual produce changes in serum ferritin levels. Measurement of this protein before and after T3 therapy may prove useful in the diagnosis of thyroid hormone resistance.

Adult↗
PubMed1985

A long term clinical, immunological, and histological follow-up study of patients with goitrous chronic lymphocytic thyroiditis.

Goiter size, thyroid function, antimicrosomal and antithyroglobulin antibodies, and thyroid histology were compared in 43 patients with goitrous chronic lymphocytic thyroiditis (Hashimoto's disease) confirmed by biopsy before and after an interval of 10-20 yr. Although all were given thyroid hormone therapy, 13 patients took it infrequently, and are considered untreated. Among these 13 patients, 5 (38%) became hypothyroid, and 1 became thyrotoxic. Goiter size decreased in 17 (57%) of 30 patients during therapy and in 3 (23%) of 13 untreated patients, and the incidence of reduction was greater in treated than in untreated patients (P less than 0.05). However, in 13 (43%) of the patients, goiter size did not decrease even during treatment. Titers of antithyroid antibodies decreased in only 8 (21%) of 38 patients. There was no significant correlation between changes in antibodies and the size of goiter, and treatment with thyroid hormone did not decrease the titers of antibodies. In patients whose goiters were initially diffusely enlarged and regressed significantly in size during the follow-up period, the initial biopsies showed histological changes in diffuse lymphocytic infiltration and diffuse epithelial changes. Comparative studies of histological differences between patients who were treated with thyroid hormone and those who were not were made in the patients who had no change in goiter size during the observation period, which was greater than 10 yr. The histological changes were similar in both groups at the beginning of the study, and no significant histological changes during the period of greater than 10 yr were found in either group. In one patient who developed thyrotoxicosis after 20 yr and was rebiopsied, the histological picture was that of thyroid hyperplasia and lymphocytic thyroiditis. These data indicate that goitrous chronic lymphocytic thyroiditis changes little as a function of time in many patients regardless of whether thyroid hormone is administered.

Autoantibodies↗
PubMed1985

Extramedullary plasmacytoma of the thyroid gland producing gamma heavy chain.

We encountered a 65-year-old man with gamma heavy chain disease associated with extramedullary plasmacytoma of the thyroid gland. Serum electrophoresis revealed an abnormal fast gamma band that cross-reacted with anti-IgG (Fc gamma) sera immunoelectrophoretically. Intracytoplasmic monoclonal immunoglobulin, IgG (Fc gamma), was demonstrated in thyroid tissue sections using an indirect immunofluorescence method. After surgery, the serum abnormal fast gamma band disappeared. At the time of writing, the patient has survived 18 months post-surgery.

Aged↗
PubMed1985

Immunohistological phenotyping of thyroid infiltrating lymphocytes in Graves' disease and Hashimoto's thyroiditis.

Subsets of lymphocytes in the thyroid were immunophenotyped by their surface antigens in frozen tissues of Hashimoto's thyroiditis and Graves' disease. Using triple layer immunoperoxidase staining (IP), monoclonal antibodies (T3, Leu 3, T8, anti-Tac and Leu 7) were employed to detect markers of T cell subsets, activated T cells, and a natural killer associated antigen. B cells were identified by 2 step IP with anti-IgD antisera. Excluding those cells forming lymphoid follicles, the density of lymphocytes infiltrating between thyroid epithelial cells was much higher in Hashimoto's thyroiditis than in Graves' disease. However, relative proportions of subsets were similar in both diseases. Most of the infiltrating cells were T3 positive T cells (T3+), with more T8+ (suppressor/cytotoxic T) than Leu 3+ (inducer/helper T). Some Leu 7+ were occasionally seen, but surface IgD positive mature B cells (IgD+) were almost absent. In contrast, IgD+ cells were densely aggregated in primary lymphoid follicles and mantle zones of secondary follicles. In these regions, Leu 3+ cells were about twice as frequent as T8+ cells. Some Leu 7+ and scarce Tac+ cells were also found. The present study indicates a major involvement of immunoregulatory T cells in autoimmune thyroid disease, and also suggested intrathyroidal maturation of B cells.

Adult↗