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Biomedical subjects

K Kuma

Publications and source records attributed to K Kuma.

At least 181 records · Page 10Linked to original sources
PubMed1989

Methimazole-induced agranulocytosis in Japanese patients with Graves' disease.

We reviewed the records of approximately 7000 Japanese patients whose hyperthyroidism was treated with methimazole (MMI) alone. Four patients (Group I) developed agranulocytosis during a second course of MMI therapy and eight patients (Group II) during an initial course. Six patients (three in each group) received less than 30 mg MMI daily. Agranulocytosis occurred after more than 2 months of therapy (12 weeks-1 year) in five patients. Seven patients were less than 40 years of age. One patient displayed a gradual protracted development of agranulocytosis. These results indicate that agranulocytosis after MMI may occur irrespective of dose, age, duration of treatment, and with a second exposure.

Adult↗
PubMed1989

The significance of antithyroglobulin and antithyroidal microsomal antibodies in patients with hyperthyroidism due to Graves' disease treated with antithyroidal drugs.

The presence of serum antithyroglobulin (TGHA) and antithyroidal microsomal (MCHA) antibodies in Graves' disease patients is associated with lymphocytic infiltration of the thyroid. The aim of this study was to determine the clinical significance of TGHA and MCHA during and after treatment of hyperthyroidism due to Graves' disease. One hundred and seventeen such patients were treated for 2 yr with methimazole and then followed for an additional year or more (mean, 30 months). The patients were classified into the following three groups: group I, patients negative for TGHA and MCHA before and during the 2 yr of treatment; group II, patients positive for MCHA but negative for TGHA before and during the 2 yr of treatment; and group III, patients who were positive for both TGHA and MCHA before and during treatment. The relapse rates after discontinuation of treatment in these groups were 39% (13 of 33), 27% (13 of 48), and 11% (4 of 36), respectively; the value in group I was significantly higher than that in group III (P less than 0.01). The results suggest that the presence of TGHA and MCHA may influence the prognosis of Graves' disease in patients treated with methimazole. Those patients who had neither antibody before and during treatment were most likely to have a relapse of hyperthyroidism, and those who had both antibodies were least likely to have a relapse.

Adolescent↗
PubMed1989

Role of thyrotropin receptor antibodies in the development of hyperthyroidism: follow-up studies on nine patients with Graves' disease.

TSH binding inhibitor immunoglobulin (TBII) and thyroid-stimulating antibody (TSAb) activities were measured serially for 4-32 months in nine patients before and during development of hyperthyroidism due to Graves' disease. Initially, all were euthyroid, seven had thyroid enlargement, one had proptosis, and seven had high serum titers of antithyroid microsomal antibodies. The occurrence of hyperthyroidism was preceded by detection of both TBII and TSAb in four patients and detection of TSAb alone in four patients. One patient had neither TBII nor TSAb when euthyroid. The mean initial TBII and TSAb activities were 10.2 +/- 15.2% (+/- SD) and 2677 +/- 4620%, respectively, when these patients were euthyroid. When they became hyperthyroid, both TBII and TSAb activities increased in all patients. At that time, TBII was detected in all but one (eight of nine subjects; 88.9%), with a mean activity of 58.8 +/- 23.4% (+/- SD), and TSAb was detected in all nine patients, with a mean value of 4508 +/- 4429%. These findings not only indicate the crucial role of TSH receptor antibodies in the development of hyperthyroidism due to Graves' disease, but also suggest that a certain period of subclinical Graves' disease exists before the onset of overt hyperthyroidism in most patients, in the sense that they have TSH receptor antibodies, especially TSAb, in their serum even though they are euthyroid.

Adult↗
PubMed1989

Development of spontaneous hypothyroidism in patients with Graves' disease treated with antithyroidal drugs: clinical, immunological, and histological findings in 26 patients.

Graves' disease may result eventually in hypothyroidism in approximately 5-20% of patients. In a few such patients hypothyroidism was associated with TSH-blocking antibodies, but whether the frequency of TSH-blocking antibodies in such patients is as high as it is (21%) in patients with primary myxedema is not known. This study was undertaken to determine the presence of various immunoglobulins [TSH binding inhibitor immunoglobulins, thyroid-stimulating antibodies (TSAb), and TSH-blocking antibodies] in 26 patients with Graves' disease who developed hypothyroidism from 0.5-10 yr or more after discontinuation of antithyroid drug therapy. Eight of the 26 patients (31%) had TSH-blocking antibodies, 16 (61%) had TSAb, and 14 (54%) had thyroid hormone binding inhibitor immunoglobulins. Thyroid needle biopsies were performed in 9 patients. Three of 5 patients who had subclinical hypothyroidism had chronic lymphocytic thyroiditis, and all had positive TSAb titers. Three patients had the fibrous variant of chronic lymphocytic thyroiditis; their TSAb values were 902%, 431%, and 1290%. One patient had follicular hyperplasia. We conclude that TSH-blocking antibodies may account for hypothyroidism in approximately one third of patients with Graves' disease who were previously treated with antithyroid drugs, and that autoimmune thyroiditis is comparable for the hypothyroidism in the remaining two thirds of Graves' disease patients.

Adolescent↗
PubMed1989

Changes in serum thyroid hormone, thyrotropin and thyroglobulin concentrations during thyroxine therapy in patients with solitary thyroid nodules.

We studied the effect of therapy with 0.1 mg/day T4 for 3 months on goiter size in 49 patients with solitary thyroid nodules. The nodule volume in 18 patients (responders) decreased by more than 50%. In this group the mean serum thyroglobulin (Tg) levels decreased significantly (from 425 to 61 micrograms/L; P less than 0.01). In the nonresponders the mean serum Tg levels did not change significantly (145 vs. 250 micrograms/L). The mean serum T4, free T4, free T3, and rT3 concentrations increased significantly in both groups during T4 therapy, serum T3 levels did not change, and serum TSH decreased. These findings demonstrate that serum Tg levels decrease when T4 therapy is effective. Thus, serum Tg measurements may prove a useful indicator of the efficacy of T4 therapy in patients with solitary nodules.

Adolescent↗
PubMed1989

Hashimoto's thyroiditis and HLA in Japanese.

To investigate genetic factors involved in the pathogenesis of Hashimoto's thyroiditis (HT; goitrous autoimmune thyroiditis), HLA class I and class II antigens were analyzed in both seropositive HT (99 patients) and seronegative HT (43 patients). The frequency of HLA-DRw53 antigen was increased significantly in both seropositive HT (antigen frequency, 0.83; relative risk, 33.3; P less than 0.0002; corrected P less than 0.001) and seronegative HT (antigen frequency, 0.81; relative risk, 3.02; P less than 0.01; corrected P less than 0.05). The etiological fraction values for HLA-DRw53 in seropositive HT and seronegative HT were 0.58 and 0.54, respectively. An increased frequency of HLA-DQw4 and a decreased frequency of HLA-DQw1 were observed in patients with seronegative HT. These data suggest that susceptibility to HT is primarily associated with HLA-DRw53 and that HLA-DQ alleles may control the production of autoantibodies to the thyroid gland. The mode of inheritance of disease susceptibility for HT (controlled by a major gene in linkage disequilibrium with HLA-DRw53) was investigated by the method of Thomson and Bodmer, and it was suggested that disease susceptibility was inherited in a dominant manner.

Female↗
PubMed1989

Malignant lymphoma of the thyroid and Epstein-Barr virus.

We have investigated the specific immune response to Epstein-Barr virus (EBV) of peripheral blood mononuclear cells (PBMC) from patients with malignant lymphoma of the thyroid. Coculture of PBMC and EBV resulted in EBV cell transformation and regression which was assayed by an EBV-induced B cell focus-regression assay technique. The EBV had been isolated from mouthwash samples. The specific immune response to EBV by outgrowth inhibition in PBMC from untreated EBV-seropositive patients with malignant lymphoma was significantly decreased when compared to PBMC from EBV-seropositive healthy subjects (p less than 0.05). This observation is at least consistent with the possibility that B-cell proliferation after continuous or recurrent EBV infection could be a causative factor or may potentiate malignant lymphoma of the thyroid.

Aged↗
PubMed1989

Marked increase of CD5 + B cells in hyperthyroid Graves' disease.

We examined the proportions of B lymphocytes bearing CD5 cell surface antigen (CD5+ B cells), which are capable of making autoantibodies, in peripheral blood from patients with various thyroid diseases. The level of CD5+ B cells was markedly increased (>9.0%) above the normal range (0.5-7.7%) in untreated, hyperthyroid patients with Graves' disease, although about 10% of the patients had no detectable serum thyroid-stimulating hormone (TSH) receptor antibody (TRAb). However, the levels of CD5+ B cells were normal in untreated patients with destructive thyrotoxicosis due to aggravation of Hashimoto's thyroiditis or subacute thyroiditis. In patients with stimulated hyperthyroid Graves' disease the levels of CD5+ B cells were correlated with those of thyroid hormones and TRAb, all significantly increased. However, once hyperthyroidism was controlled by anti-thyroid drugs, CD5+ B cells were decreased, followed in turn by reduction of TRAb. We conclude that the proportion of CD5+ B cells is useful as a therapeutic index and for diagnosis of Graves' disease and its differentiation from destruction-induced thyrotoxicosis.

Adult↗
PubMed1988

Epidermal growth factor receptors on cultured neoplastic human thyroid cells and effects of epidermal growth factor and thyroid-stimulating hormone on their growth.

Epidermal growth factor (EGF) receptors on primary-cultured human thyroid cells from 27 neoplasias (nine adenomas and 18 differentiated carcinomas) were analyzed and compared with those on the cultured nonneoplastic part of human thyroid cells. Total binding of 125I-EGF to the nonneoplastic part, adenoma, and carcinoma cells did not differ significantly. Scatchard analysis showed that the neoplastic human thyroid cells, like their adjacent nonneoplastic counterparts, consistently possessed EGF receptors with two components. In a paired study of five patients, the association constant of the carcinoma cells' high-affinity component (Ka1) was found to be significantly lower than that of adjacent nonneoplastic thyroid cells (P less than 0.05). Furthermore, a study of the cells from 18 carcinomas revealed that overall their Ka1s (4.15 +/- 0.82 x 10(9) M-1, mean +/- SEM) were significantly lower than those of adenoma cells (10.34 +/- 1.51 x 10(9) M-1, n = 9) and of nonneoplastic cells adjacent to them (8.32 +/- 0.84 x 10(9) M-1, n = 23). The difference in Ka1s for adenoma and nonneoplastic thyroid cells was not statistically significant. The number of receptor sites (Cmax) per cell was not significantly different in any of the three. Incorporation of [3H]thymidine (dThd) increased significantly in all kinds of thyroid cells examined following the addition of 10 nM EGF, and the paired study showed that the size of this increase was not significantly different in neoplastic and adjacent nonneoplastic cells. The addition of 300 microunits/ml of thyroid-stimulating hormone caused a significant increase in dThd incorporation by adenoma cells but not by carcinoma or nonneoplastic cells. Furthermore, combined treatment with EGF and thyroid-stimulating hormone additively promoted adenoma cell growth only. A close inverse relationship was observed between Ka1 and the stimulatory effect of EGF on the dThd uptake in both nonneoplastic thyroid cells and adenoma cells. Carcinoma cells also showed similar profiles, but Ka1 relative to dThd increases were much smaller than the other two.

Adenoma↗
PubMed1988

Thyroidal prelymphoma.

We treated a 32-year-old man with "thyroidal prelymphoma", morphologically resembling Hashimoto's thyroiditis and associated with monoclonal gammopathy (IgG, lambda). Immunohistochemistry revealed intracytoplasmatic monoclonal immunoglobulin (IgG, lambda) containing lymphoid cells in the interstitium of the thyroid tissue. After total thyroidectomy had been performed, the monoclonal immunoglobulin disappeared. Three years have passed since the surgery and this writing, there has been no recurrence. The existence of thyroidal prelymphoma suggests that chronic antigenic stimulation might produce lymphocytes which are more susceptible to neoplastic change (Hashimoto's thyroiditis----thyroidal prelymphoma----malignant lymphoma of the thyroid).

Adult↗
PubMed1988

Angiotensin-converting enzyme and anorexia nervosa.

Angiotensin-converting enzyme (ACE) activity was measured in 10 patients with anorexia nervosa, 6 with hyperthyroid Graves' disease, and 7 with primary hypothyroidism. Patients with anorexia nervosa had a low serum ACE activity (9.8 +/- 2.2 IU/l), as compared to findings in normal subjects (13.4 +/- 3.5 IU/l) (P less than 0.05). Patients with hyperthyroid Graves' disease had high serum ACE activity (23.7 +/- 5.8 IU/l), as compared to levels in normal subjects (P less than 0.01), and patients with primary hypothyroidism tended to have low serum ACE activity (10.1 +/- 1.8 IU/l), compared to the normal subjects (P less than 0.1). Following weight gain (before; 71.3 +/- 10.2% of ideal body weight, after; 88.7 +/- 5.6% of ideal body weight), serum ACE activity in patients with anorexia nervosa reverted to within the normal range (13.8 +/- 3.5 IU/l), and serum T3 concentration was restored to the normal range (before; 0.7 +/- 0.2 ng/ml, after; 1.1 +/- 0.3 ng/ml). In these patients, ACE activity correlated with the per cent of ideal body weight (P less than 0.05). These data suggest that, in underweight subjects with anorexia nervosa, decreased serum ACE activities may relate to emaciation.

Adolescent↗
PubMed1988

Enhanced thyroid iodine metabolism in patients with triiodothyronine-predominant Graves' disease.

Some patients with hyperthyroid Graves' disease have increased serum T3 and normal or even low serum T4 levels during treatment with antithyroid drugs. These patients with elevated serum T3 to T4 ratios rarely have a remission of their hyperthyroidism. The aim of this study was to investigate thyroid iodine metabolism in such patients, whom we termed T3-predominant Graves' disease. Mean thyroid radioactive iodine uptake was 51.0 +/- 18.1% ( +/- SD) at 3 h, and it decreased to 38.9 +/- 20.1% at 24 h in 31 patients with T3-predominant Graves' disease during treatment. It was 20.0 +/- 11.4% at 3 h and increased to 31.9 +/- 16.0% at 24 h in 17 other patients with hyperthyroid Graves' disease who had normal serum T3 and T4 levels and a normal serum T3 to T4 ratio during treatment (control Graves' disease). The activity of serum TSH receptor antibodies was significantly higher in the patients with T3-predominant Graves' disease than in control Graves' disease patients (60.5 +/- 19.2% vs. 20.4 +/- 18.2%; P less than 0.001). From in vitro studies of thyroid tissue obtained at surgery, both thyroglobulin content and iodine content in thyroglobulin were significantly lower in patients with T3-predominant Graves' disease than in the control Graves' disease patients. Thyroid peroxidase (TPO) activity determined by a guaiacol assay was 0.411 +/- 0.212 g.u./mg protein in the T3-predominant Graves' disease patients, significantly higher than that in the control Graves' disease patients (0.129 +/- 0.112 g.u./mg protein; P less than 0.01). Serum TPO autoantibody levels determined by immunoprecipitation also were greater in T3-predominant Graves' disease patients than in control Graves' disease patients (52.6 +/- 27.7% vs. 32.4 +/- 11.4%; P less than 0.05). Binding of this antibody to TPO slightly inhibited the enzyme activity of TPO, but this effect of the antibody was similar in the two groups of patients. The data suggest enhanced iodine metabolism in the thyroid gland of patients with T3-predominant Graves' disease, which may relate to the discordant T3 overproduction in patients with this type of Graves' disease.

Adolescent↗
PubMed1988

Deficiency of superoxide dismutase in endemic goiter tissue.

Superoxide dismutase (SOD) activity and its concentration were measured in thyroid tissues obtained from patients with Graves' disease, Hashimoto's thyroiditis, differentiated thyroid cancer, and endemic goiter (before and after iodine supplementation) as well as in normal thyroid tissue (paranodular tissue) from patients with follicular adenomas. SOD activity was measured by pyrogallol assay in ethanol-chloroform extracts of the thyroid homogenates. The SOD concentration in the thyroid extract was measured as immunoreactive SOD by electroimmunoassay. Endemic goiter tissues (n = 10) contained significantly lower SOD activity [mean, 1.9 +/- 1.9 (+/- SD) vs. 7.5 +/- 3.9 ng purified SOD/micrograms DNA; P less than 0.02] and concentration (mean, 0.2 +/- 0.1 vs. 0.8 +/- 0.5 ng SOD/microgram DNA; P less than 0.01) compared with those of normal tissues. No other pathological thyroid tissues had such consistently low SOD levels. Lactate dehydrogenase activity, a marker of cytosolic enzyme, was not lower in endemic goiter tissues than in normal tissues, suggesting that both tissues possessed functioning cells capable of producing cytosolic enzyme. Thyroid tissue from endemic goiter patients previously treated with iodized oil injection also had low SOD activity and concentration. Western blot analysis indicated that SOD protein in the endemic goiter tissue did not differ from that in normal thyroid tissue. We conclude that there is deficiency of cytosolic SOD in endemic goiter tissue. Since the deficiency of cytosolic SOD causes more prolonged exposure to oxygen free radicals, the decrease in SOD might contribute to the degenerative changes frequently found in these tissues.

Blotting, Western↗
PubMed1988

Recent gene conversion between genes encoding human red and green visual pigments.

Nucleotide sequences of the human X-linked red and green pigment genes were compared, and the number of silent substitutions per site (KSc) between these genes was analysed in comparison with the corresponding values of primate genes. Taking the retarded mutation rate of X-linked genes into consideration (Miyata et al., 1987), the red and green pigment genes were shown to have undergone gene conversion at around the time of separation of African apes and orangutan. Thus the recent gene conversion and retarded mutation rate in these X-linked genes are probably responsible for the strong sequence similarity between these genes, which is likely to facilitate the occurrence of red-green color blindness in the human population. It was also shown that the red pigment gene evolved about five times more rapidly than the green pigment gene since the latest gene conversion.

Animals↗
PubMed1987

Lipopolysaccharide-sensitive serine-protease zymogen (factor C) of horseshoe crab hemocytes. Identification and alignment of proteolytic fragments produced during the activation show that it is a novel type of serine protease.

The horseshoe crab clotting factor, factor C, present in the hemocytes is a serine-protease zymogen activated with lipopolysaccharide. It is a two-chain glycoprotein (Mr = 123,000) composed of a heavy chain (Mr = 80,000) and a light chain (Mr = 43,000) [T. Nakamura et al. (1986) Eur. J. Biochem. 154, 511-521]. In our continued study of this zymogen, we have now also found a single-chain form of factor C (Mr = 123,000) in the hemocyte lysate. The heavy chain had the NH2-terminal sequence of Ser-Gly-Val-Asp-, consistent with that of the single-chain factor C, indicating that the heavy chain is derived from the NH2-terminal part of the molecule. The light chain had an NH2-terminal sequence of Ser-Ser-Gln-Pro-. Incubation of the two-chain zymogen with lipopolysaccharide resulted in the cleavage of a Phe-Ile bond between residues 72 and 73 of the light chain. Concomitant with this cleavage, the A (72 amino acid residues) and B chains derived from the light chain were formed. The complete amino acid sequence of the A chain was determined by automated Edman degradation. The A chain contained a typical segment which is similar in sequence to a family of repeats in human beta 2-glycoprotein I, complement factors B, protein H, C4b-binding protein, and coagulation factor XIII b subunit. The NH2-terminal sequence of the B chain was Ile-Trp-Asn-Gly-. This chain contained the serine-active site sequence-Asp-Ala-Cys-Ser-Gly-Asp-Ser-Gly-Gly-Pro-. These results indicate that horseshoe crab factor C exists in the hemocytes in a single-chain zymogen form and is converted to an active serine protease by hydrolysis of a specific Phe-Ile peptide bond.

Amino Acid Sequence↗