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Biomedical subjects

M Tokuda

Publications and source records attributed to M Tokuda.

212 records · Page 12Linked to original sources
PubMed1978

Experimental Coxsackie virus B-3 and B-4 myocarditis in mice.

Mice were inoculated with recently isolated Coxsackie virus B-3 and B-4 intraperitoneally. Severest lesions in the hearts were observed in mice between the age of 7 and 14 days. Grossly yellow-white patches were seen on the hearts of mice from the 7th day to the 6th month after virus inoculation. Microscopically, the heart showed extensive myocardial necrosis, inflammation with small mononuclear cells and calcification on the day of 7. There were myocardial fibrosis and calcification at the 6th month after inoculation with Coxsackie virus B-3, and at the 3rd month after inoculation with Coxsackie virus B-4, but generally pathologic changes were less severe in the latter. Myocardial fibrosis in the present experiment was most prominent among the experiments we have studied. It was confirmed that chronic myocardial fibrosis follows acute Coxsackie virus myocarditis in mice. Possible role of Coxsackie virus myocarditis in the development of cardiomyopathy was briefly discussed.

Animals↗
PubMed1976

Effects of rubidium on behavioral responses to methamphetamine and tetrabenazine.

Different groups of mice were injected subcutaneously every other day with rubidium chloride at three doses (0.41(50), 1.23(150) and 3.69(450) meq/kg (mg/kg)) or with saline as a control for a period of 2-3 weeks. Rubidium administered acutely did not affect spontaneous locomotor activities, while it tended to increase the activities when administered repeatedly though the increase was not statistically significant. The methamphetamine-induced hyperlocomotor activities were potentiated in the rubidium groups as compared with those in the saline group, this effect of ribidium being increased with prolongation of repeated administrations. Monotonic decreases in ambulation after tetrabenazine were not significantly affected in the rubidium-treated animals though the decreases were sometimes preceded by slight increases and recovery from the decrement tended to be more rapid. After tetrabenazine in the rubidium-treated groups, incidences of catalepsy were increased and jumping behavior and Straub tail responses occurred in a few cases. The results suggest that rubidium potentiates the excitatory action of methamphetamine on spontaneous locomotor activities, as contrasted with inhibitory influence of lithium.

Animals↗
PubMedDate not supplied

Rapid analysis of guanidino compounds in serum from nephritic patients using column-switching with isocratic elution.

The rapid method for baseline separation of ten guanidino compounds in serum from nephritic patients was designed using a single eluent with a column switching system. A porous graphitic carbon column and an octadecyl-bonded silica gel columns were used, (50 mm x 4.6 mm i.d.). Separation was completed within 15 min. The stable baseline permitted highly sensitive detection with excellent reproducibility. The system was applied to analyze guanidino compounds in sera from 175 nephritic patients. The hemodialysis process could not completely eliminate guanidino compounds, and the degree of removal varied between patients. The correlation among metabolites indicated the differences in disease.

Chromatography, Gel↗
PubMedDate not supplied

Lymphocyte subsets in lung tissues of non-specific interstitial pneumonia and pulmonary fibrosis associated with collagen vascular disorders: correlation with CD4/CD8 ratio in bronchoalveolar lavage.

This study was designed to evaluate the distribution of lymphocyte subsets in lung specimens that were obtained by open-lung biopsy from 8 patients with idiopathic nonspecific interstitial pneumonia/fibrosis (NSIP) and 10 patients with pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). Distributions of B lymphocytes, CD4-positive T lymphocytes, and CD8-positive T lymphocytes were evaluated immunohistochemically and compared with the cell composition in BALF. Correlation between CD4/CD8 ratios in bronchoalveolar lavage fluids (BALF) and CD4/CD8 ratios in lung tissues was also examined. B lymphocytes were mostly restricted in lymphoid follicles. CD4-positive T lymphocytes were observed inside and around lymphoid follicles and in the thick fibrotic wall of reconstructed alveoli with fibrosis. In contrast, CD8-positive T lymphocytes were diffusely distributed, especially in relatively thin alveoli. Correlation was weak between CD4/CD8 ratios in lung tissue and CD4/CD8 ratios in BALF. However, even in patients with very low CD4/CD8 ratios in BALF, many CD4 lymphocytes were observed in lung tissues, suggesting that CD8-positive lymphocytes diffusely distributed in thin alveolar architecture were more easily recovered in BALF than CD4-positive lymphocytes. Therefore, a low CD4/CD8 ratio in BALF may indicate that the alveolar structure was not severely reconstructed by fibrosis. This is the first report that compared lymphocyte subsets in lung tissues and in BALF.

Aged↗
PubMedDate not supplied

Cellular signaling mechanisms for stimulation of growth hormone secretion and growth hormone primary transcripts by immunosuppressant agents, FK506 and cyclosporin A, in cultured rat pituitary cells.

Although an immunosuppressant, FK506, has been known to stimulate growth hormone (GH) release from rat somatotropes, the cellular signaling mechanism is unknown. In the present study, intracellular signaling pathways were investigated for FK506- and cyclosporin A (CsA)-induced GH release in cultured rat anterior pituitary cells. Northern and Western blot analysis revealed that the FK506-binding protein (FKBP12) and the CsA-binding protein (cyclophilin A) exist at the mRNA and protein level in the rat anterior pituitary tissue. FK506 and CsA increased GH release in a dose-dependent manner and inhibited calcineurin (CaN) activity in the cultured pituitary cells. The third immunosuppressant, rapamycin (RP), inhibited the FK506-induced GH release, although RP alone had no effect. Protein kinase A (PKA) inhibitors, H-89 and HA-1004 and EGTA blocked FK506- and CsA-induced GH release. TGF-beta did not alter basal GH release, but inhibited FK506-induced GH release. GH primary transcripts were increased by FK506, and the effects were blocked by H-89 and HA-1004. These results suggest that the immunosuppressants, FK506 and CsA, stimulate GH release by inhibiting CaN activity which results in the activation of the PKA system in the rat somatotropes. TGF-beta receptors might be involved in FK506-induced GH release as a separate pathway. FK506 also stimulates GH primary transcripts via a PKA-dependent mechanism in a manner similar to its effects on GH release.

Animals↗
PubMedDate not supplied

Effects of luteinizing hormone, follicle-stimulating hormone, and epidermal growth factor on expression and kinase activity of cyclin-dependent kinase 5 in Leydig TM3 and Sertoli TM4 cell lines.

We examined the effects of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and epidermal growth factor (EGF) on the expression and kinase activity of cyclin-dependent kinase 5 (Cdk5) in Leydig TM3 and Sertoli TM4 cell lines. Hormonal regulation of the expression and activity of Cdk5 by using normal and hypophysectomized rat testes was also investigated to elucidate its role. Cdk5 levels and kinase activity were significantly elevated in TM3 cells that were grown in the presence of 7.5% serum, EGF, or LH and were associated with an increase in testosterone production compared with controls. These increases were accompanied by an increase in proliferation of TM3 cells after treatment with serum or EGF but not with LH suggest that Cdk5 may be involved in cellular differentiation that is induced with LH treatment. In contrast, the presence of neither serum, EGF, nor FSH had a significant effect on Cdk5 activity levels in the Sertoli TM4 cell line, and there was no correlation with proliferative activity or transferrin levels. A significant decrease in Cdk5 expression and activity were noted in rat testis after hypophysectomy compared with normal rat testis and is associated with a simultaneous decrease in testosterone and transferrin levels. Immunohistochemical analysis revealed that Cdk5 was strongly expressed in the nuclei and cytoplasm of Leydig cells, Sertoli cells, spermatogonia, and peritubular cells of normal adult rat testis. After hypophysectomy, the pattern of Cdk5 staining differed markedly from that in normal rat testis and a profound reduction in staining of Cdk5 was observed in each tubule. Our results suggest that LH and EGF influence and modulate Cdk5 expression and activity in Leydig TM3 cells and may, conceivably, be involved in signal transduction cascades that are initiated by hormones or growth factors. Cdk5 in Sertoli TM4 cells is likely to possess some constitutive functions that are not affected by the cells' proliferation state. Moreover, Cdk5 is probably involved in the constitutive and hormonally stimulated activities of the rat testis, in addition to its involvement in cell proliferation.

Animals↗
PubMedDate not supplied

The overexpression of cyclin-dependent kinase (CDK) 2 in laryngeal squamous cell carcinomas.

We examined the expression of CDK2 using immunohistochemistry in 102 cases of laryngeal squamous cell carcinomas (LSCCs). The results showed that a total of 63.73% (65/102) patients revealed a CDK2 overexpression pattern and the CDK2 overexpression was correlated significantly with the tumor site, tumor size and advanced stage. A positive correlation between the CDK2 expression and proliferative activity of tumor cells measured by proliferating cell nuclear antigen was found (r = 0.894, p < 0.0001). The Kaplan-Meier's analysis showed that shorter disease-free survival was significantly associated with tumor grade, tumor size, lymph node metastasis and advanced stage. Overall survival was significantly associated with tumor grade, tumor size, lymph node metastasis, advanced stage and CDK2 overexpression. When CDK2 and PCNA were combined, the patients with both CDK2 overexpression and PCNA overexpression had a poorer overall survival. We concluded that the CDK2 overexpression may be associated with the malignant biological behavior of LSCCs.

Biomarkers, Tumor↗
PubMedDate not supplied

Expression of cyclin-dependent kinase 5 and associated cyclins in Leydig and Sertoli cells of the testis.

In this study, we examined the expression and subcellular localization of cyclin-dependent kinase 5 (Cdk5), cyclin D1, and cyclin E in Leydig and Sertoli cell lines that were cultured with 7.5, 1.0, 0.5, or 0% serum (mixture of a 2:1 ratio of horse serum and fetal bovine serum) and in the developing rat testis to verify the possible functions of Cdk5, cyclin D1, and cyclin E in the testis. The abundance of Cdk5 and cyclin E in the Leydig cell line, TM3, was significantly reduced at low serum concentrations. In contrast, serum concentration had no effect on Cdk5 and cyclin E levels in the Sertoli cell line, TM4. Cyclin D1 was detected by western blot analysis in TM4 cells only, and its abundance was serum dose dependent. The kinase activity of Cdk5 in TM3 and TM4 cells that were cultured at various serum concentrations coincided with the levels of Cdk5 expression. Immunohistochemical staining for Cdk5 and cyclin E revealed nuclear and cytoplasmic distribution, both in TM3 and TM4 cells. Moreover, cyclin D1 immunoreactivity was only detected in TM4 cells. In the developing rat testis, Cdk5 expression was most prominent at 2 and 3 weeks after birth. Cyclin D1 was strongly expressed at 1 and 2 weeks in premature rat testes. On the other hand, cyclin E was highly expressed in the adult testis. Immunohistochemical localization of Cdk5, cyclin D1, and cyclin E in 1-week-old and adult rat testes revealed expression in both Leydig and Sertoli cells. Our results suggest that Cdk5 in TM3 and Leydig cells of the testis might play a role in cell cycle regulation, whereas Cdk5 in TM4 and Sertoli cells of the adult testis might have some additional functions besides control of proliferation.

Animals↗