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Biomedical subjects

Y Masaki

Publications and source records attributed to Y Masaki.

At least 163 records · Page 9Linked to original sources
PubMed1987

Serum C3 and C4 levels and complement-dependent antibody-mediated cytotoxic activity of islet cell surface antibody in type 1 (insulin-dependent) diabetic children.

The role of complement in the pathogenesis of diabetes was studied in 31 Type 1 (insulin-dependent) diabetic children by assaying serum islet cell surface antibody, C3, C4 and serum complement-dependent antibody-mediated cytotoxicity. Nine of 21 islet cell surface antibody-positive children were within 5 months of disease onset and showed significantly lower serum C3 and C4 levels than either 1 year later or the remainder of the islet cell surface antibody-positive children at 6-12 months after disease onset. The overall trend of all islet cell surface antibody-positive diabetic children within 1 year of disease onset was toward increased serum C3 and C4 levels as the disease progressed. Serum C4 concentration and complement-dependent antibody-mediated cytotoxicity which showed an initial negative correlation were uncorrelated 1 year later. Four children who were initially strongly islet cell surface antibody-positive but negative 1 year later also exhibited significantly higher (p less than 0.05) mean serum C4 levels after 1 year. There was a significant decrease in complement-dependent antibody-mediated cytotoxicity when sera from the diabetic children were treated with either ethylene glycol tetra-acetic acid or ethylene diamine tetra-acetic acid. These data strongly suggest that complement-dependent antibody-mediated cytotoxicity induced by the classical complement pathway involving an islet cell surface antibody may play an important role in the pathogenesis of Type 1 diabetes.

Adolescent↗
PubMed1987

Rat fetal islets as a useful model for the study of insulin release failure.

To study the mechanism of imparied insulin secretion from rat fetal islets, the insulin responsiveness of islets from fetuses (day 21.5 of gestation) to a variety of secretagogues was compared with that of adult rat islets. Forskolin (30 microM)-induced insulin release from fetal and adult islets was 2.7-and 2.5-fold higher, respectively, than that from islets treated with 5.6 mM glucose alone. The effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA) (200 nM) were also similar in fetal and adult islets. Thus, the responsiveness to forskolin and TPA showed no significant difference in adult and fetal islets. A synergistic effect of combinations of various insulin secretagogues was observed in adult islets; however, a weak synergistic effect was present with gliclazide plus TPA only in fetal islets. After islets were cultured in RPMI 1640 (containing 11.1 mM glucose), gliclazide-, forskolin-, and TPA-induced insulin release reached the levels obtained in adult islets. However, the synergistic effect of gliclazide and TPA disappeared after culture of the islets. These results suggest that the poor insulin secretion from fetal islets is not due to a defect in the activating system of either cAMP or C-kinase, but to the immaturity of the interaction of those messenger systems.

Animals↗
PubMed1986

Suppressive effect of mizoribine on humoral antibody production in DBA/2 mice.

The mode of action of mizoribine (MZR) as a B cell inhibitor was studied using DBA/2 mice. Its in vitro administration significantly delayed the primary response in hemagglutinin production against sheep erythrocytes by suppressing the IgM antibody formation. In vitro plaque-forming cell (PFC) response against both T-dependent and T-independent antigens, such as TNP-SRBC and TNP-Brucella abortus, was dose-dependently suppressed by MZR. Since PFC formation by the T-depleted fraction of splenocytes was likewise suppressed, MZR may inhibit humoral antibody response by directly affecting the B cells (and/or macrophages) as well as by modulating the regulatory T cells. MZR may only act on a certain stage of the cell cycle of B lymphocytes following antigenic stimulation. It may not interfere with the initial antigen recognition or with mature B cells.

Animals↗
PubMed1986

Effect of clonidine on insulin secretion: a case report.

We have recently seen a case of non-insulin-dependent diabetes mellitus with hypertension in which chronic treatment with oral clonidine gave rise to elevation of blood glucose and decreased insulin secretion. When the response of insulin secretion to glucose administration during clonidine therapy was compared with that after 12 days of wash-out for clonidine in this patient (who was then receiving phentolamine mesylate), there was a marked suppression of insulin secretion to stimulation by intravenous glucose during oral clonidine therapy. This result indicates that the decreased insulin secretion associated with oral clonidine therapy is very unlikely to be due to any direct action of clonidine on beta cells of the pancreatic islets and may be due to suppression of catecholamine release via central alpha-adrenergic receptor stimulation.

Blood Glucose↗
PubMed1986

[Sensitivity of esophageal cancer to anticancer agents and supplementary chemotherapy combined with surgical treatment].

The authors examined the sensitivities of esophageal cancer to Bleomycin (BLM), Peplomycin (PEP), Cisplatin (CDDP) and 5-FU by the INAS method using 3H-thymidine or 14C-formate as labeled precursors, and determined the concentrations of anticancer agents in cancer lesions by the Band Culture method. On the other hand, the authors investigated the superiority or inferiority of various methods of BLM administration by observing the prevention effect of BLM on the development of experimental esophageal cancer in rats. Forty-three cases out of 76, 57%, showed a sensitivity to BLM, 60% to PEP, 38% to CDDP and 56% to 5-FU. As to the types of roentgenological findings, the superficial and tumorous types showed a high sensitivity rate. As to the types of macroscopical findings, the protruded and superficial types showed a high sensitivity rate. As to the types of histological findings, well differentiated squamous cell carcinoma showed a high sensitivity rate. Sensitivity was higher in metastatic lymph nodes than in main cancer lesions. Tumor tissues which had undergone previous hyperthermic management (at 42 degrees C) showed a higher sensitivity than those which had not. PEP at a half dose brought about the same grade of anticancer effect as BLM. The sensitivities of esophageal cancer to various anticancer agents showed individual differences among clinical cases. Therefore, combination chemotherapy for esophageal cancer was thought to be an effective administration method. The divided administration of small doses of BLM was thought to be more superior than the one-shot administration of a large dose for esophageal cancer. The results of the INAS sensitivity test were perfectly coincident with the effects of chemotherapy in clinical cases of esophageal cancer.

Animals↗
PubMed1986

Relation of hydrolytic enzymes in spleen to immunological dysregulation in mice.

In order to know the role of hydrolytic enzymes in various immunological disturbances, we compared the enzymatic changes in the spleens of nude mice and NZB/W mice relative to their respective controls. In spite of the different immunological features of these models, multivariate analysis demonstrated that there is some commonness in enzymatic changes between the two models. The enzymes related to such commonness included glycosidases, alkaline phosphatase, fMet-AP, and esterase. These enzymes may play some important roles in immunologic dysregulation , especially in relation to B-cell dominance in these disease models.

Animals↗
PubMed1985

[Long-term toxicological studies with mizoribine (Bredinin) in beagle dogs (the first report). Blood chemistries, pharmacokinetics of mizoribine and fertility studies of the male dogs].

For long-term toxicological studies, mizoribine at the dose of 2.5 mg/kg body weight was administered orally to two male and two female Beagle dogs for 36 consecutive months, once a day, 6 days a week, with a day-off on the 7th of each week. As a control group, 2 male and 2 female dogs were kept under the same conditions as the treated group. The above experiment resulted in no abnormal general symptoms being found in either group. In addition, body weight gain instead of weight loss was observed in both groups. Moreover, hematological and biological parameters were in the normal range, and no statistical difference was obtained between the two groups. An additional 10 mg/kg of mizoribine was administered once to both groups at the months of 6, 12, 18, 24, or 36 after the onset of this toxicological study so as to determine the pharmacokinetic behavior of serum mizoribine. This resulted in no significant difference being observed between the two groups. Therefore, it can be inferred that accumulation of mizoribine is not induced by its long-term repeated administration. In fertility study, the analysis of the sperm and the mating ability of a male dog with an appropriate healthy female dog revealed that mizoribine at this dose did not provoke any abnormalities in male gonadal functions.

Animals↗
PubMed1984

Effect of mizoribine on lupus nephropathy of New Zealand black/white F1 hybrid mice.

Therapeutic trials with mizoribine (MZR), an imidazole nucleoside immunosuppressant, on experimental lupus nephropathy of NZB/W F1 mice resulted in the following. The MZR treatment, 20 mg per kilogram of body weight every other day, starting at 14 weeks of age, caused a significantly prolonged survival time of mice with a mean life span of 54.3 +/- 4.2 weeks, compared with the untreated controls, who had a mean survival time of 38.1 +/- 2.9 weeks (P less than 0.01). In addition, MZR suppressed the elevation of serum anti-DNA antibody titers, the spontaneous development of splenomegaly, and the histological development and progression of glomerulonephritis observed in untreated animals. Although no definite explanation is available at present to explain how MZR caused decreased anti-DNA antibody production and delay in the development of glomerulonephritis in these animals, it is suggested that it acts by directly suppressing the hyperfunctioning B cells of lupus mice. MZR may prove to be a promising immunosuppressant for the treatment of human lupus, in view of its lesser side effects such as bone marrow suppression or hepatotoxicity.

Animals↗
PubMed1983

Modification of crescentic Masugi nephritis in the rabbit by Bredinin, a new immunosuppressant.

Experiments were undertaken to ascertain whether progression of crescentic Masugi nephritis in rabbits could be prevented by the administration of Bredinin (BR). Crescentic glomerulonephritis can be induced with high reproducibility by intramuscular preimmunization on day 1, followed by intravenous injections on days 3 and 5 of nephrotoxic duck gamma-globulin (NTD gamma-gl). 30 rabbits were divided into 3 groups including controls (group 1). Two groups of 10 nephritic rabbits were each treated with 10 mg/kg of BR either after or before the development of proteinuria (groups 2 and 3). In group 3, the onset of proteinuria showed a significant delay and duration of survival was significantly prolonged, compared with controls. Serum antibody titers after day 8 and creatinine levels after day 10, as well as the initial amounts of proteinuria, were also significantly lower during treatment in group 3 than in controls. Histologically, the prominent diffuse intra- and extra-capillary proliferation with monocyte accumulations observed in the control group were markedly diminished in group 3. These results suggest that early treatment in crescentic glomerulonephritis with BR will suppress the production of humoral antibody and prevent progression of the glomerular lesions.

Animals↗
PubMed1983

Immunosuppressive effect of bredinin on cell-mediated and humoral immune reactions in experimental animals.

Bredinin (BR), an imidazole nucleoside isolated from Eupenicillium brefeldianum was previously reported to prolong kidney allograft survival in dogs. The immunosuppressive effect of BR was studied in experimental animals. In beagles, in vitro responses of lymphocytes stimulated by mitogens or allogeneic cells were suppressed by in vitro BR treatment. BR, given in vivo, also showed an inhibitory action against development of delayed hypersensitivity reaction to tubercle bacilli in guinea pigs or against hemagglutinin production following booster SRBC injection in rabbits. Of note may be the fact that BR was found to have an immunosuppressive potency comparable to that of azathioprine and, in addition, to show a decreased hepatotoxicity compared with the latter.

Animals↗