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Biomedical subjects

K Kuma

Publications and source records attributed to K Kuma.

At least 199 records · Page 11Linked to original sources

Immunologic and immunohistologic analysis of 27 cases with thyroid lymphomas.

Twenty-seven patients with stages I or II thyroid lymphomas were investigated immunologically. Approximately 60% of these patients had a goiter for longer than 1 year. Both the tests for serum antithyroid antibodies and histologic findings of the resected specimens showed that chronic lymphocytic (autoimmune) thyroiditis was usually present. The tumors were classified histologically as seven cases of follicular lymphomas and 20 cases of diffuse lymphomas. Immunocytologic study on suspended cells and immunohistologic study on frozen tissue sections showed that neoplastic cells in 22 of 27 cases expressed restricted immunoglobulin light chains. In remaining five cases, the neoplastic cells reacted with B-1, Leu-10, and/or Leu-14. These results indicate that thyroid lymphomas are exclusively B-cell-derived tumors.

Adult↗

[Studies on the half-life of C-terminal parathyroid hormone in chronic renal failure].

Subtotal parathyroidectomy (PTX) was performed for patients with hyperparathyroidism associated with chronic renal failure, and from sequential determination of PTH after PTX, the half-life of 2 different C-PTH was calculated. The half-life (T 1/2) of 46 approximately 84 PTH and 65 approximately 84 PTH was 18.1 +/- 3.9 and 14.0 +/- 2.2 hours (Mean +/- SD) respectively. Half-life of both C-PTH was markedly prolonged compared with that (30 approximately 60 minutes) of healthy subjects. It is considered that the longer half-life of 46 approximately 84 PTH than 65 approximately 84 PTH might be attributed to the difference of molecular weight, degrading enzymes and operative procedures. Determined value of C-PTH in chronic renal failure should be evaluated in consideration of prolonged metabolic clearance of C-PTH.

Adult↗

Thyroid carcinoma and hot nodule.

A 70-year-old woman presented with a nodule in the thyroid gland. 131I scintigraphy of the gland showed a hot nodule. Histology of the resected thyroid revealed a papillary adenocarcinoma. Although a thyroid carcinoma with a hot nodule seen on the radioiodine isotope scan is a very rare occurrence, it is clinically very important because it may indicate a thyroid malignancy.

Adenocarcinoma, Papillary↗

A new type of albumin with predominantly increased binding affinity for 3,3',5-triiodothyronine in a patient with Graves' disease.

A new type of serum albumin, that shows a markedly enhanced binding activity for 3,3', 5-triiodothyronine (T3), a somewhat increased activity for thyroxine (T4), and a normal activity for 3,3', 5-triiodothyronine (rT3) is described. This albumin was found in a patient with Graves' disease. After successful subtotal thyroidectomy, the existence of abnormal binding activity for T3 was suspected in this patient because of persistently increased total T3 concentrations in spite of elevated thyrotropin levels. Although free T3 and T4 concentrations measured by radioimmunoassay using commercial tracer analogue kits were markedly increased, those measured by equilibrium dialysis were within normal ranges. Electrophoretic studies revealed that these abnormalities were due to the markedly increased T3 binding activity by the serum albumin; that for T4 was also slightly increased. Scatchard plot analysis revealed that the association constant (Ka) for T3 of the patient's albumin was 5.1 X 10(6)/M (normal pooled albumin; 6.2 X 10(5)/M), and those for T4 and rT3 were 5.2 X 10(6)/M and 2.7 X 10(6)/M, respectively (normal pooled albumin; 2.1 X 10(6)/M for both T4 and rT3). The increased binding of albumin to T3 and T4 was markedly inhibited by barbitone, and 8-anilino-1-naphthalene-sulfonic acid. These characteristic features, and erroneously high values of free T3 and T4 concentrations measured by tracer analogue kits were similar to those seen in patients with familial dysalbuminemic hyperthyroxinemia, which have been previously reported. These findings strongly suggest that this albumin is a new variant in various dysalbuminemic syndromes, and the abnormal binding of iodothyronines moieties in these syndromes are not biochemically identical.

Adult↗

Separation and analysis of mononuclear cells infiltrating the thyroid of patients with Graves' disease.

A simple method was established for separating lymphocytes infiltrating the thyroid from thyroid epithelial cells. Namely, suspensions of minced thyroid from patients with Graves' disease were layered on a Percoll two-step density gradient (p = 1.050 and 1.077 g/ml) and centrifuged (400g, 30 min, 4 degrees C). In this way 0.1-18 X 10(5) lymphocytes/g of thyroid tissue with a purity of 65-95% were obtained. Thyroid lymphocytes were analyzed quantitatively with monoclonal antibodies by laser flow cytometry and compared with peripheral lymphocytes. The proportion of OKT3+ cells was decreased with increase in OKIa+ cells. The percentage of OKIa+ cells was significantly correlated with that of Leu12+ cells. The percentages of OKT4+ cells and OKIa+ cells were higher when analyzed with an extended gate window, which was arranged for detection of activated, large-sized lymphocytes. The percentages of OKT8+ and Leu7+ cells were not significantly different from those in peripheral blood. From these results it was concluded that the proportion of B lymphocytes is increased and that of T lymphocytes is decreased, the proportion of activated B lymphocytes is increased, some helper/inducer T cells are activated in the thyroid gland in Graves' disease, and these activated lymphocytes may be important in local production of antithyroid autoantibodies.

Adult↗

Isolation and characterization of the active cDNA of the human cell cycle gene (RCC1) involved in the regulation of onset of chromosome condensation.

The human RCC1 gene was cloned after DNA-mediated gene transfer into the tsBN2 cell line, which shows premature chromosome condensation at nonpermissive temperatures (39.5-40 degrees C). This gene codes for a 2.5-kb poly(A)+ RNA that is well conserved in hamsters and humans. We isolated 15 cDNA clones from the Okayama-Berg human cDNA library, and found two that can complement the tsBN2 mutation with an efficiency comparable to that of the genomic DNA clone. The base sequences of these two active cDNA clones differ at the 5' proximal end, yet both have a common open reading frame, encoding a protein of 421 amino acids with a calculated molecular weight of 44,847 and with seven homologous repeated domains of about 60 amino acids. This human RCC1 gene was located to human chromosome 1 using sorted chromosomal fractions.

Animals↗

The mechanism of spontaneous hypothyroidism in patients with Graves' disease after antithyroid drug treatment.

The natural course of Graves' disease results in hypothyroidism in up to 20% of patients previously treated with antithyroid drugs. The precise mechanisms are not known, although autoimmune destruction of thyroid tissue has been proposed. We studied sequentially obtained serum samples from three patients with hyperthyroid Graves' disease previously treated with an antithyroid drug who became hypothyroid to determine possible causes of their hypothyroidism. Antithyroglobulin and antithyroid microsomal autoantibodies, TSH binding inhibitory immunoglobulin (TBII), thyroid-stimulating antibody (TSAb), and thyroid stimulation-blocking activity were measured. Autoantibodies were markedly elevated throughout the clinical course in all three patients. Patient 1 had no TBII and blocking activity and extremely high TSAb when she was euthyroid as well as hypothyroid. Hypothyroidism was probably the result of autoimmune thyroid destruction. In patient 2, TSAb disappeared, and TBII and blocking activity increased markedly when she developed hypothyroidism, which thus appeared to result from blocking antibodies. Patient 3 had intermittent periods of hyper- and hypothyroidism before becoming and remaining euthyroid. While initially hypothyroid, TBII was weakly positive, and TSAb was strongly positive; subsequently, when hyperthyroidism recurred, TBII and TSAb were strongly positive. Hypothyroidism appeared to result from focal autoimmune thyroiditis. Patients with hyperthyroid Graves' disease may develop hypothyroidism later by different means. Autoimmune thyroiditis, diffuse or focal, with thyroid destruction is one mechanism. The appearance of antibodies that block TSH stimulation may be another.

Adult↗

HLA and thyrotoxic periodic paralysis in Japanese patients.

Periodic paralysis (PP) is a well recognized although rare and peculiar complication of thyrotoxicosis, especially among Chinese and Japanese patients. The susceptibility to autoimmune thyroid disease has recently been reported to be strongly linked to certain immunogenetic factors, and increased frequency of certain HLA antigens has been found in patients with Graves' disease. This study was, therefore, undertaken to determine HLA haplotypes in Japanese men with thyrotoxic periodic paralysis (TPP). HLA typing in 35 TPP patients and 263 normal men and women demonstrated highly significant increases (P less than 0.01) in HLA-A2, Cw3, and DRw8 in the TPP patients. In comparing TPP patients with thyrotoxic men who did not have PP, the frequency of DRw8 antigen was 2.5-fold greater in patients with PP than in those without it (62.8% vs. 28.6%). The data suggest that the HLA-DRw8 gene itself may play a significant role in the susceptibility to TPP among Japanese men.

Adult↗

HLA-DR antigen expression on intrathyroidal lymphocytes and thyrocytes in Hashimoto's thyroiditis and Graves' disease: an immunohistological study.

In frozen sections of thyroid glands with Hashimoto's thyroiditis (HT) and Graves' disease (GD), infiltrating lymphocytes were tested for their expression of HLA-DR antigens as a marker of in situ activation. In a combination of indirect immunoperoxidase and direct immunofluorescence staining, most of the immunoglobulin D positive mature B cells were found to be DR positive (DR+) in both diseases. In HT, sizable portions of both helper/inducer T (Leu3+) and suppressor/cytotoxic T (Leu2+) cells were DR+ in interfollicular regions as well as in lymphocyte clusters and lymphoid follicles. In GD, the proportion of DR+ cells in the interfollicular Leu2+ population was significantly lower than that of HT. DR+ thyrocytes were seen in all 14 cases of HT and in 14 out of 16 cases of GD, especially in the vicinity of lymphocyte aggregates. The extent of their DR expression was not correlated with the percentage of DR+ cells in either T subset. These results indicate that a significant portion of infiltrating T cells are activated in autoimmune thyroid diseases, and there may be bidirectional interaction between DR+ thyrocytes and DR+ T cells. The difference in frequency of Leu2+ DR+ cells may account for the difference between the immunopathological features of HT and GD.

Adolescent↗

[Diagnosis of adrenal medullary diseases in patients with sporadic or hereditary medullary thyroid carcinoma. A report of 37 cases with 8-year follow-up study].

Thirty-seven patients with medullary thyroid carcinoma were investigated to determine the status of adrenal medulla by computed tomography and 131I-metaiodobenzylguanidine (131I-MIBG) scintigraphy as well as measurements of urinary catecholamine excretion. Patients were followed up for 8 years in maximum. Fifteen patients belonged to multiple endocrine neoplasia type 2 including patients with incomplete phenotype. Computed tomography demonstrated adrenal tumors or enlargement in all 6 patients with urinary epinephrine (E) more than 30 micrograms/day, 4 of them were confirmed to have pheochromocytoma or adrenal medullary hyperplasia by surgery. In 2 patients with E less than 30 micrograms/day and epinephrine to norepinephrine (E/N) ratio more than 0.3 suggesting adrenal medullary hyperfunction, computed tomography revealed small adrenal tumors. Three of the remaining 7 patients with E less than 30 micrograms/day and E/N ratio less than 0.3 had equivocal enlargement of unilateral gland on computed tomography. 131I-MIBG scintigraphy demonstrated tracer uptake in adrenal glands with tumor more than 1cm in diameter. One of 2 adrenal glands with medullary hyperplasia showed a faint adrenal image on the scintiscan, but the other showed no tracer uptake. Pheochromocytoma became manifest in 4 patients during the follow-up period, 4, 13, 14 and 34 years after thyroid surgery. None of 22 patients with sporadic medullary thyroid carcinoma showed adrenal abnormalities on the examinations mentioned above.

Adrenal Gland Neoplasms↗

[Assessment of surgical treatments of medullary thyroid carcinoma by analysis of serum calcitonin levels].

In 67 patients with medullary thyroid carcinoma, serum calcitonin levels were measured before (S1) and after (S2) surgical therapy. Doubling time of serum calcitonin levels (T2) was calculated in each patient with elevated calcitonin levels after surgery. Residual tumor weight (W2) was estimated as W1S2/S1-S2) where W1 was resected tumor weight. Reduction index (alpha) is defined as S2/S1 = (1/2) alpha. alpha T2 indicates expected prolongation in survival (EPS) by surgical therapy. Expected duration of survival after surgery (EDS) is estimated as beta T2, where beta times of doubling of the residual tumor (W2) make 1000 g of tumor which would generally kill the host. Death within 3 years after surgery or recurrence within 5 years was best associated with short EPS followed by short T2 or small alpha. Postoperative calcitonin levels had a rather weak correlation with the prognosis, and preoperative calcitonin levels had almost no correlation with the prognosis during the present observation period. All 3 patients with EDS shorter than 3.9 years died within 2 years and 2 months after surgery. These parameters allow quantitative judgement of the surgical benefit and quantitative prediction of the prognosis in each individual patient.

Adult↗

[Studies on small thyroid carcinoma in dialysis patients with hyperparathyroidism].

For twenty long-term hemodialysis patients with medically uncontrolled hyperparathyroidism, subtotal parathyroidectomy (PTX) was performed and histological examination was done for 17 out of them, suspected of thyroid disease from operative findings. Thyroid carcinomas were found in 5 out of 17 patients by biopsied specimens of thyroids. Histological findings of carcinomas were follicular (2 cases) and papillary types (3 cases). In all cases, carcinomas were in occult state and the sizes of carcinomas of 4 cases were small being a diameter less than 10 mm. Among others, findings of follicular adenoma (2 cases) and chronic thyroiditis (1 case) were obtained. The incidence rate of thyroid carcinoma in this report seemed to be rather high as the incidence diagnosed from biopsied specimen at operation. Several factors such as immunological incompetence accompanied by renal failure, metabolic abnormalities of cells induced by parathyroid dysfunction and accelerated aging are considered to be involved as a cause of increased incidence of thyroid carcinoma in hemodialysis patients with hyperparathyroidism.

Adenocarcinoma↗

Malignant lymphomas of the thyroid gland. Analysis of 79 patients with emphasis on histologic prognostic factors.

Prognostic factors in 79 patients with malignant lymphomas involving the thyroid gland were analyzed. These patients suffered from progressively enlarging goiter with over 6 months duration in 60% of patients. The age at operation ranged from 16 to 80 years (median, 58 years). Male to female ratio was 1:1.8. Serum tests for antithyroid antibodies were positive in 83% of the patients, who also showed histologic evidence of chronic lymphocytic thyroiditis. Histologically, 52 cases (66%) were germinal center cell tumors with follicular or follicular and diffuse pattern in 9 cases. By the Working Formulation, 5-year survival rate of immunoblastic type (IBL) (13%) was much poorer than those of intermediate (79%) and low grade cases (92%) (P less than 0.001). The cases of IBL usually had a goiter of short duration, and frequently presented as advanced disease.

Actuarial Analysis↗

Plasmacytoma of the thyroid gland.

Primary plasmacytoma of the thyroid gland is a rare disease, and clinicopathologic features of this disease are not fully understood. Six cases of primary plasmacytoma of the thyroid, in which immunoperoxidase procedures confirmed a monoclonal nature of proliferating plasma cells are presented. All patients had antithyroid antibodies in their serum together with histologic evidence of chronic lymphocytic thyroiditis, suggesting an intimate relationship of these diseases. Review of the literature revealed that 18 cases, 14 cases from Western countries and 4 cases from Japan, described primary thyroid plasmacytoma. The authors summarized the clinicopathologic features in the current and previously reported cases.

Adult↗

Thyroid function and histology in forty-five patients with hyperthyroid Graves' disease in clinical remission more than ten years after thionamide drug treatment.

Thyroid function was determined in 45 patients with hyperthyroidism due to Graves' disease who had been diagnosed and treated with thionamide drugs between 1965 and 1971 and had remained clinically euthyroid for greater than 10 yr after discontinuation of therapy. Physical examination revealed that only 2 patients had signs of mild hyperthyroidism; all others were euthyroid. Measurements of serum concentrations of thyroid hormones and TSH revealed elevated free T4 index values and serum T3 in 3 (6.7%), T3 toxicosis in 4 (8.9%), and subclinical hypothyroidism in 2 patients (4.4%). The remaining 36 patients were biochemically euthyroid. TRH tests were performed in these 36 patients, and hyporesponsiveness was found in 3 and hyperresponsiveness in 5 patients. T3 suppression tests were performed in 15 of the 36 patients; 10 were suppressible and 5 were nonsuppressible. All suppressible patients responded to TRH. Large needle biopsies performed in 8 biochemically euthyroid patients and 1 patient with subclinical hypothyroidism revealed chronic lymphocytic thyroiditis in 7 and normal biopsies in 2 patients. Diffuse epithelial hyperplasia was not found in any of the specimens. Antithyroid antibody titers were significantly higher than in 1972 at the time of discontinuation of therapy using the same methods. These results suggest that Graves' disease may evolve into chronic thyroiditis in some patients who are in permanent remission, and some patients in apparent permanent remission have hyperthyroidism and concomitant chronic thyroiditis.

Amides↗