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Biomedical subjects

T Mimura

Publications and source records attributed to T Mimura.

At least 127 records · Page 7Linked to original sources

Studies on pharmacological activation of human serum immunoglobulin G by chemical modification and active subfragments. III. Mechanism of anti-ulcerous action of alkylated light chain (Fr. I-L).

The effects of a new anti-ulcer agent Fr. I-L, a reduced and carboxamide-methylated light chain of human immunoglobulin G, on defensive factors in gastric mucosa were studied. Fr. I-L increased the mucopolysaccharide contents (hexosamine, uronic and sialic acids) in the gastric mucosa of intact rats and inhibited the decrease of mucopolysaccharide contents in the gastric mucosa of rats with phenylbutazone-induced gastric ulcers. The activation of the biosynthesis of mucopolysaccharides by Fr. I-L was suggested by tracing the incorporation of 35SO4(2-) into the gastric mucosa. The administration of aspirin or phenylbutazone caused an increase of mucopolysaccharase activity in the gastric mucosa and the concomitant administration of Fr. I-L blocked the elevation of the enzyme activities. Fr. I-L also showed inhibitory activities on the local fibrinolysis and lipid peroxidation in the gastric mucosa.

Animals

Mitogenic activity and in vitro fertilization inhibitory activity of Genypterus blacodes lectin.

A lectin which we purified from the mucous of Ophidiidae Genypterus blacodes showed a potent mitogenic activity which was comparable to that of concanavalin A (con A). On the other hand, the lectin treated with 2-mercaptoethanol showed an anti-mitogenic activity against con A and lipopolysaccharide (LPS). Lymphocytes were separated into a T cell rich fraction and B cell rich fraction by soybean agglutinin. The mitogenic activity of G. blacodes lectin was examined using these cells. It was suggested that the mitogenic activity of G. blacodes lectin was based on the stimulation of T cells. The lectin was also subjected to both the sperm agglutination and the in vitro fertilization tests in mouse. It was demonstrated that: a) the lectin receptors were ubiquitous on sperm; b) in vitro fertilization of mouse ova was completely blocked by the binding of the lectin to the zona pellucida of the ova.

Animals

Studies on pharmacological activation of human serum IgG by chemical modification and active subfragments. I. Induction of anti-ulcerogenic activity by chemical cleavage of interchain disulfide bonds in human IgG and properties of active subfragments.

Commercially available human IgG (native IgG) was passed through a DEAE cellulose column. Two fractions (Fr. I and Fr. II), responding equally against the anti-human IgG antibody were obtained. The carboxamide-methylated H and L chains from both fractions showed remarkable inhibitory activities on both the gastric ulceration and the gastric juice secretion in pylorus-ligated rats. The carboxamide-methylated L chain of rat IgG was also effective, while none of the human native IgG, Fr. I or Fr. II showed any effect. The reduction and the following alkylation of the interchain disulfide bonds were necessary for the induction of the biological activities of human IgG. Sulfonation of human IgG failed to induce the activities. Although the gastric acid secretion was clearly reduced by the administration of Fr. I-L (alkylated L chain of Fr. I), the gastric mucosal blood flow was not affected.

Alkylation

Studies on pharmacological activation of human serum IgG by chemical modification and active subfragments. II. Inhibitory effects of carboxamide-methylated L chain from human serum IgG on various ulcer models and its inhibition mechanism.

In view of the strong inhibitory effects of the carboxamide-methylated L chain (Fr. I-L) from human IgG on gastric ulceration and juice secretion, we carried out various experiments to clarify the mechanism of its action and obtained the following results. Fr. I-L inhibited the gastric ulceration induced by phenylbutazone or aspirin in rats, but no appreciable effect was observed on stress or acetic acid ulceration. The distribution of 14C-labelled Fr. I-L increased particularly in the stomach mucous membrane of rats after the intravenous or intraperitoneal administration. The hexosamine content in the gastric mucous membrane, reduced by the treatment with phenylbutazone, aspirin or pylorus-ligation, was recovered by the administration of Fr. I-L to an intact level. The high total of hexosamine levels found in the gastric juice after aspirin treatment or pylorus-ligation were decreased by the injection of Fr. I-L or cimetidine. The histochemical observation revealed that the concomitant administration of Fr. I-L with phenylbutazone or aspirin prevented the abolishment of Hematoxylin-Eosin, Periodic Acid Schiff and Alcian Blue staining polysaccharides from the stomach epithelial cells.

Animals

Inhibitory effects of unsaturated fatty acids of trans-2-C10:1 to trans-2-C16:1 several C18:n and C20:n on gastric secretion and experimental ulceration in rats.

Among various unsaturated fatty acids which were examined in this experiment, trans-2-tridecenoic acid was found to be a potent inhibitor on gastric secretion in rats (i.p. or i.d.). Therefore, the effects of trans-2-tridecenoic acid on several experimental ulcerations in rats were examined. At the dose of 10 mg/kg, trans-2-tridecenoic acid significantly decreased the ulcer index in pylorus-ligated rats; aspirin-, phenylbutazone-, histamine- and stress-induced ulcerations were also significantly inhibited at the dose of 25 mg/kg. Finally, effects of trans-2-tridecenoic acid on hexosamine and sialic acid contents in the gastric mucous were examined. In intact or phenylbutazone-induced ulcerated rats, trans-2-tridecenoic acid increased the sialic acid levels in the gastric mucous at the dose of 25 mg/kg. The decreased hexosamine content in the gastric mucous by phenylbutazone treatment was recovered by the administration of trans-2-tridecenoic acid.

Animals

Chronic effect of TSH on human thyroid tissue in organ culture.

The chronic effect of TSH on thyroidal cAMP concentrations and release of thyroid hormones was investigated using human thyroid tissue in organ culture. Normal human thyroid slices were placed in HAM's F-10 synthetic culture medium in Falcon organ tissue culture dishes, and incubated at 37 degrees in a humidified atmosphere of 5% CO2 in air. Medium was changed everyday and daily T3 or T4 release was determined using concentration of T3 or T4 in the medium. After incubation, slices were transferred to the medium containing 10 mM theophylline and incubated without TSH for an additional 30 min to determine thyroidal cAMP concentrations. Thyroidal cAMP concentrations in slices incubated with 10 mU/ml of TSH increased significantly at 2, 6, and 24 hr and even on the 6th day of incubation. Daily T3 release was significantly increased above control from the 3rd day and daily T4 release from the 4th day to the 11th day of incubation with 10 mU/ml of TSH. Histologically, almost all follicles were structurally maintained even on the 11th day of incubation. These results suggest that both thyroidal cAMP concentrations and release of thyroid hormones are stimulated chronically by TSH. This organ culture system is useful for investigating chronic effects of various materials on human thyroid tissue.

Cyclic AMP

[Divergent histology in the primary and metastatic lesions of thyroid carcinoma].

The metastatic lesions of malignant diseases tend to present similar histological findings as the primary tumor. However, thyroid carcinoma is one of the malignancies which may be an exception to this rule. We have reviewed 61 consecutive autopsies of thyroid cancer patients at the Ito Hospital and Kawasaki Medical School Hospital during a period between 1969-1982. Fifty-five of 61 cases of thyroid carcinoma were found to have metastatic spreads beyond the thyroid. The uniform pathological findings were present in 5 of 9 papillary adenocarcinomas, 14 of 15 anaplastic carcinomas, and 1 of two squamous cell carcinoma and one epidermoid carcinoma. The remaining 36 patients were found to have different histological findings in metastatic lesions from the primary tumor. The histological types in coexisting metastases varied from one lesion to the other; the primary tumor was adenocarcinoma, but one of the metastases was anaplastic and the others showed adenocarcinoma or its combination. Those histological divergence in the primary tumor and metastases can be considered as the results of anaplastic or squamous cell transformation from adenocarcinoma. Such alteration of the histological findings in thyroid carcinoma calls for the reassessment of the therapeutic strategy.

Adenocarcinoma

Anterior pituitary, thyroid, parathyroid and adrenal responses to subtotal thyroidectomy in patients with Graves' disease.

Changes in the serum levels of anterior pituitary, thyroid, parathyroid, and adrenal hormones following subtotal thyroidectomy in 31 patients with Graves' disease were investigated. In 14 patients, rapid ACTH tests were performed on the preoperative and the first, third, and seventh post-operative days. Remarkable differences were not seen with regard to the changes in anterior pituitary hormones or cortisol, compared to those seen during general surgery. As to the thyroid hormones, the serum level of triiodothyronine (T3) decreased markedly after surgery and fell to half that of the preoperative value on the first postoperative day. Thereafter, a low value of T3 was maintained during the early postoperative period. Unlike T3, the serum level of thyroxine (T4) decreased gradually until the 7th post-operative day. The levels of both epinephrine and norepinephrine increased transiently during surgery, but the serum level of norepinephrine increased again on the third postoperative day. In the postoperative period, almost half the number of patients showed an inadequate cortisol response to rapid ACTH tests. It is suggested that the unique responses, such as the rise in serum norepinephrine or an inadequate response of cortisol to ACTH, or hypocalcemia, after subtotal thyroidectomy in patients with Graves' disease is largely due to the rapid decrease of T3 in the hypothyroid state, as was noted during the postoperative period.

Adult

Resection of the trachea infiltrated by thyroid carcinoma.

Twenty-four thyroid carcinoma patients with infiltration of the trachea were treated surgically. The histological diagnosis in these cases included papillary adenocarcinoma in 22 different patients, medullary carcinoma in one patient, and undifferentiated carcinoma in one patient. In 19 of the patients hemoptysis was noted, and dyspnea was present in ten patients. In 14 of the 24 patients the carcinoma was diagnosed by radiographs of the neck, while in seven patients it was demonstrated bronchoscopically. In three patients tracheal infiltration by thyroid carcinoma was diagnosed by biopsy of the tracheal wall at operation. When the tracheal wall was infiltrated by thyroid carcinoma, treatment consisted of circumferential resection of the involved segment of the trachea followed by an end-to-end anastomosis. Of the 24 patients, 17 survived and six died. In the 17 patients who survived, 13 were disease free. Of this number, six survived more than five years after the initial tracheal resection.

Adenocarcinoma, Papillary

Inhibitory effects of alkylated Bence-Jones protein, k-type light chain, from urine of a patient with macroglobulinemia on gastric juice secretion and ulceration in rats.

Bence-Jones protein (BJP) was isolate from the urine of a patient with macroglobulinemia by salting out the ammonium sulfate, followed by chromatography on DEAE-cellulose column and gel filtration. This native BJP was identified as k-type light chain by immunoelectrophoresis and the native light chain showed almost no activity of inhibiting the gastric ulceration in pylorus-ligated rats. In contrast, reduction of the disulfide bond by 2-mercaptoethanol and alkylation of the thiol by iodoacetate in this native light chain resulted in significant inhibition of the gastric ulceration. The alkylated light chain also showed a significant inhibition of gastric juice secretion in pylorus-ligated rats.

Alkylation

Increase of anti-ulcerogenic activity by reduction and alkylation of disulfide bonds of a globulin fraction from bovine serum.

Bovine serum was subjected to ammonium sulfate fractionation, and subsequently chromatographed on DEAE-cellulose column to obtain a globulin protein having a weak anti-ulcerogenic activity, Fr.II-A. Agar immunoelectrophoresis and immunodiffusion using rabbit antiserum against bovine IgG revealed that Fr.II-A from bovine serum shared antigenic determinant with bovine IgG. Furthermore, Fr.II-A showed a single band on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. By reducing and alkylating the disulfide bonds by 2-mercaptoethanol and iodoacetic acid, Fr.II-A was separated into two subfragments in the same manner as in the case of immunoglobulin to produce Fr.L (molecular weight; 24000) and Fr.H (molecular weight; 50000). Fr.L showed anti-ulcerogenic activity up to about ten times greater than that of original Fr.II-A, but in the case of Fr.H, the activity increased approximately several times. Fr.L showed significant activity in preventing ulcer formation and gastric juice secretion in pylorus-ligated rats, and was also effective in reducing index of the phenylbutazone-induced ulcer.

Alkylation

A case report on disequilibrium hypercalcemia in hyperthyroidism. Comparison of calcium metabolism with other patients with hyperthyroidism.

The patient, a 30-year-old woman, was admitted to Itoh Hospital in February, 1979 for hyperthyroidism. She had a history of pyelonephritis and recurrent urinary tract infection. Laboratory data on admission revealed overt hyperthyroidism (T3: 405 ng/dl, T4: 22.5 micrograms/dl and T3U: 57.--%), severe hypercalcemia of 12.6 mg/dl and hypercalciuria. The PSP excretion and GFR were both decreased. Serum c-PTH was nondetectable. As the thyroid function improved, there was a gradual decrease and later normalization of plasma calcium, phosphate and urinary calcium excretion. When subtotal thyroidectomy was performed on October 19, 1979, hypertrophy of the parathyroid gland was not demonstrated. In comparison with 98 other hyperthyroid patients, the pathogenesis of hypercalcemia was discussed. In conclusion, hypercalcemia in the patient, T. Y., was regarded as a kind of disequilibrium hypercalcemia which resulted from a combination of increased bone turnover and decreased calcium excretion by the kidney.

Adult