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Biomedical subjects

M Sawamura

Publications and source records attributed to M Sawamura.

158 records · Page 9Linked to original sources
PubMed1980

Inhibition of experimental blood-borne lung metastasis by protease inhibitors.

The inhibitory effects of protease inhibitors on blood-borne metastasis in male Donryu rat lung were studied. Injection i.v. of 10(6) Yoshida ascites hepatoma AH7974 cells induced about 118 +/- 92 (S.D.) metastatic foci in rat lung after 3 weeks. Leupeptin (50 mg/kg body weight twice a day), injected i.p. from 2 days before to 4 days after the inoculation of tumor cells, reduced the number of metastatic foci to about 49 +/- 45 (p less than 0.005). Leupeptin also suppressed the formation of metastatic foci of Yoshida ascites hepatoma AH100B cells (p less than 0.001). Elastatinal (100 mg/kg body weight twice a day) and chymostatin (100 mg/kg body weight once a day) did not inhibit formation of metastatic foci of AH7974 cells. Injection i.v. of 10(6) AH7974 cells induced pulmonary thrombi within 1 hr. Leupeptin (50 mg/kg body weight twice a day) reduced the number of thrombi from 1298 +/- 395 to 646 +/- 218, when injected i.p. for 2 days before the inoculation of the cells (p less than 0.005). Chymostatin and elastatinal did not significantly change the number of pulmonary thrombi. These results indicate that leupeptin inhibited metastasis formation and suggest that this effect may be due to the inhibition of thrombus formation after the arrest of circulating tumor cells.

Animals↗
PubMed1979

Mutagenicity of the naturally occurring carcinogen cycasin and synthetic methylazoxymethanol conjugates in Salmonella typhimurium.

The aglycone methylazoxymethanol of the naturally occurring carcinogenic glucoside, cycasin, has previously been shown to be mutagenic, but cycasin per se has not. In this work, cycasin was demonstrated to be mutagenic using a modification of the Ames Salmonella test in which it was preincubated with beta-glucosidase and the tester strain in liquid medium. The mutagenicity of cycasin to six histine-depedent Salmonella strains varied considerably with strain HisG46 being the most susceptible. Methylazoxymethyl-beta-D-glucosiduronic acid, which also is nonmutagenic per se, similarly became mutagenic when preincubated with beta-glucuronidase. Methylazoxymethyl acetate, which is slightly mutagenic by the Ames standard pour plate method, became highly mutagenic on preincubation. The mutagenicity of free methylazoxymethanol was confirmed, and a linear dose-response relationship was observed. The common conditions required for activation of nonmutagenic methylazoxymethanol conjugates, the glucoside cycasin and methylazoxymethyl-beta-D-glucosiduronic acid, are 90-min preincubation at 30 degrees, pH 6.5, with an appropriate hydrolase and Salmonella typhimurium HisG46.

Azo Compounds↗
PubMed1978

Mutagenicity of aclacinomycin A and daunomycin derivatives.

An antitumor antibiotic aclacinomycin A, was nonmutagenic in a Salmonella test, but its derivative, N-demethylaclacinomycin A, was mutagenic. Similarly, 1-deoxypyrromycin, a hydrolysis product of aclacinomycin A, was nonmutagenic, but N-demethyl-1-deoxypyrromycin was mutagenic. Daunomycin was highly mutagenic, but N-methyldaunomycin showed only weak mutagenicity, and N-dimethyldaunomycin was nonmutagenic. The aglycones of aclacinomycin A and daunomycin were not mutagenic. Thus, the amino moiety of anthracycline glycosides is concluded to be essential for mutagenesis.

Aclarubicin↗
PubMedDate not supplied

Increased oxidative DNA damage in stroke-prone spontaneously hypertensive rats.

1. The amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of the total systemic oxidative stress in vivo, in stroke-prone spontaneously hypertensive rats (SHRSP) was not different from that in control normotensive Wistar-Kyoto (WKY) rats at 6 weeks of age, but became higher than control values after the development of severe hypertension at 14-17 weeks of age. 2. The amount of urinary 8-OHdG was not significantly different between SHRSP treated with anti-hypertensive agents and those not treated at 14 weeks of age. 3. Stroke-prone spontaneously hypertensive rats were exposed to DNA damage by oxidative stress at the early stage when they developed severe hypertension, but this increase in DNA damage was not the secondary effect of hypertension.

8-Hydroxy-2'-Deoxyguanosine↗
PubMedDate not supplied

Soluble dietary fibre improves insulin sensitivity by increasing muscle GLUT-4 content in stroke-prone spontaneously hypertensive rats.

1. The effects of soluble dietary fibre (psyllium) on peripheral insulin sensitivity and skeletal muscle GLUT-4 protein expression were studied in 12 male stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-caloric diet from 5 to 9 weeks of age. 2. In the psyllium-supplemented group, fasting plasma glucose was significantly reduced and glucose levels following an oral glucose tolerance test were significantly lower than in the cellulose-supplemented group at 30 (P < 0.05) and 60 min (P < 0.01). However, there was no difference in insulin secretion. 3. In the psyllium-supplemented group, skeletal muscle GLUT-4 content was significantly increased in the plasma membrane (P < 0.001), but not in the intracellular membrane. 4. No significant difference was found in phosphatidylinositol 3 (PI3)-kinase activity between cellulose and psyllium diet not only in the basal state but also when stimulated by insulin. 5. These results demonstrate that psyllium increases blood glucose disposal by increasing skeletal muscle plasma membrane GLUT-4 content without PI3-kinase activation.

Animals↗
PubMedDate not supplied

Beneficial effects of fish oil on glucose metabolism in spontaneously hypertensive rats.

1. Increased interest in fish oil led us to examine their metabolic effects in spontaneously hypertensive rats, which have been reported to have glucose intolerance. 2. Rats were divided into three groups: (i) a control group fed standard rat laboratory chow; (ii) a lard group fed a high-fat diet containing 20% lard; and (iii) a fish oil group fed a high-fat diet containing 20% fish oil for 14 weeks. 3. Systolic blood pressure and fasting blood glucose were markedly increased in the lard group, whereas in the fish oil group they were only transiently increased at the beginning and decreased to levels seen in the control group. 4. Intraperitoneal glucose tolerance test demonstrated that fish oil reversed the impairment of glucose disposal found in the lard group. However, plasma insulin levels were raised transiently at 30 min in the fish oil group compared with the control group. 5. Insulin secretion from pancreatic islets stimulated with glucose in vitro was also enhanced by fish oil. 6. These results lead us to conclude that fish oil improves glucose tolerance by enhancing insulin secretion from pancreatic beta-cells.

Animals↗
PubMedDate not supplied

Proliferative effect of mevalonate metabolites other than isoprenoids on cultured vascular smooth muscle cells.

1. Recent investigations revealed that isoprenoid compounds serve as key substances for cellular proliferation through post-translational modification. Previously we reported that tissues of spontaneously hypertensive rats (SHR) had a lower activity of isoprenoid biosynthesis when compared with the normotensive control rat (WKY). However, cultured vascular smooth muscle cells (VSMC) of SHR showed an enhanced growth rate. These findings led us to investigate further the effect of isoprenoid compounds on VSMC proliferation. 2. When the cells of WKY were stimulated with 5% fetal calf serum (FCS) in the presence of lovastatin, [3H]-thymidine incorporation decreased in a dose-dependent manner and was completely inhibited at 30 mumol/L. Exogenously added mevalonate showed a protective effect against lovastatin (81% protection at 0.1 mumol/L). 3. Fluoromevalonate (Fmev), an inhibitor of mevalonate-PP decarboxylase which converts mevalonate-PP into isoprenoids, showed a dual inhibitory effect. DNA synthesis was partially inhibited at 0.01-1 mumol/L, however at 10 mumol/L there was no detectable inhibition. The inhibitory effect was again observed at concentrations over 10 mumol/L. 4. In the presence of lovastatin and Fmev to block both HMG CoA reductase and mevalonate-PP decarboxylase, exogenous mevalonate dose dependently stimulated [3H]-thymidine incorporation induced by FCS. 5. These data suggest the positive effect of the initial mevalonate derivatives other than isoprenoid compounds on the proliferation of VSMC.

Animals↗
PubMedDate not supplied

[Successful treatment with vincristine for an elderly patient with idiopathic thrombocytopenic purpura].

A 77-year-old female was referred to our hospital in March 1991 because of a severe bleeding tendency. Her blood count on admission was as follows: Hb 7.5 g/dl, WBC 4.6 x 10(9)/l with normal differentiation and platelet 2 x 10(9)/l. One month prior to admission, her blood count was normal. Initially, acute idiopathic thrombocytopenic purpura (ITP) was suspected, because of the acute onset of the bleeding tendency and thrombocytopenia. High dose intravenous immunoglobulin (400 mg/kg/day for 5 days) and bolus methylprednisolone (1 g/day for 3 days then tapered) were administered, starting March 13. Her platelet count had increased immediately on March 20 to 40 x 10(9)/l. However, platelet count decreased to 4 x 10(9)/l in the following two weeks. Her clinical course differed from that of typical acute ITP. Because the treatment with prednisolone was not effective, it was changed to intravenous infusion of vincristine (VCR) at a weekly dose of 1 mg for 6 weeks. The treatment was extremely effective, and her platelet count reached over 200 x 10(9)/l. The treatment was discontinued. Three weeks later, her platelet count decreased to 15 x 10(9)/l, the administration of VCR was resumed, and her platelet count recovered again. Throughout her clinical course, no side effect of VCR was noticed except for mild hypesthesia of the fingertips. VCR therapy was considered to be an useful treatment in elderly patients with ITP.

Aged↗