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Biomedical subjects

I Sato

Publications and source records attributed to I Sato.

At least 361 records · Page 20Linked to original sources

Studies on antineoplastic activity of naphthomycin, a naphthalenic ansamycin, and its mode of action.

An antibiotic, identical with naphthomycin, was isolated from a soil Streptomyces. The antibiotic displayed significant therapeutic activity by ip administration against murine tumors: Ehrlich carcinoma and IMC carcinoma implanted ip. The maximum increase of life-span was more than 169% in Ehrlich carcinoma, and 128% in IMC carcinoma. The antibiotic exhibited a potent cytotoxicity against murine leukemic cells: P388, L1210, and L5178Y. IC50 was 0.4-1.3 microgram/ml in culture. The activity of naphthomycin was reversed by SH compounds: 2-mercaptoethanol, dithiothreitol, and glutathione. DNA and RNA syntheses were more markedly inhibited by naphthomycin than protein synthesis in L5178Y cells. Approximately 50% inhibition of nucleic acid syntheses was observed at an antibiotic concentration of 2 micrograms/ml. Naphthomycin blocked alkaline phosphodiesterase obtained from L5178Y cells: IC50 was ca. 7.6 micrograms/ml. The antibiotic neither caused metaphase arrest nor prevented tubulin polymerization. The results suggest that the mechanism of cytotoxicity of naphthomycin is the inhibition of various SH enzymes, particularly those involved in nucleic acid biosynthesis. The mode of action is unique in the ansamycin group of antibiotics.

Animals↗

Biological activity of cadeguomycin. Inhibition of tumor growth and metastasis, immunostimulation, and potentiation of 1-beta-D-arabinofuranosylcytosine.

Cadeguomycin retarded growth of sc solid IMC carcinoma in CDF1 mice, and pulmonary metastasis of Lewis lung carcinoma in C57BL/6 mice. The antibiotic enhanced phagocytic activity of murine peritoneal macrophages and IL-1 production by P388D1 cells. Delayed type hypersensitivity was stimulated and interferon was induced by the drug. The results suggest that cadeguomycin inhibits tumor growth and metastasis in association with modification of the immune system. The cytotoxicity of arabinosylcytosine to K562 and YAC-1 cells was markedly enhanced by cadeguomycin in culture. The combined administration of arabinosylcytosine and cadeguomycin displayed potentiation in the inhibition of growth of ip-implanted P388 leukemia and metastasis of sc-implanted P388 leukemia to the regional lymph nodes. Cadeguomycin showed low toxicity for mice.

Adjuvants, Immunologic↗

Inhibition of tumor growth and metastasis in association with modification of immune response by novel organic germanium compounds.

The effects of two novel organic germanium compounds, 1-phenyl-2-carbamoylethylgermanium sesquisulfide (PCAGeS) and 1-phenyl-2-carbamoylethylgermanium sequioxide (PCAGeO), on transplantable murine tumors and immune responses were studied. Both drugs showed low toxicity for mice. In culture, neither substance displayed significant cytotoxicity against murine tumor cells L1210 leukemia, L5178Y lymphoma, or IMC carcinoma. Growth of subcutaneously transplanted IMC carcinoma or Meth-A fibrosarcoma was markedly reduced by oral administration of PCAGeS. PCAGeO exhibited a similar but smaller effect on the tumor growth. Pulmonary metastasis of Lewis lung carcinoma was inhibited by oral or intraperitoneal treatment with PCAGeS. The activity of cyclophosphamide or Adriamycin against L1210 leukemia was significantly potentiated by oral administration of PCAGeS. PCAGeS enhanced the delayed-type hypersensitivity response to sheep red blood cells (SRBC) of mice or restored the response suppressed by ascitic IMC carcinoma, but did not significantly affect the formation of antibody to SRBC. PCAGeO similarly stimulated the DTH reaction. Phagocytic activity of peritoneal macrophages was enhanced by oral treatment of mice with PCAGeS. The results suggest that PCAGeS and PCAGeO display tumor-inhibitory activity by modification of the immune mechanism.

Animals↗

Significance of a gastric mass screening survey.

We analyzed the rate of occurrence of gastric cancer in a population of 39,250 by mass screening survey. In 0.123% of the total subjects gastric cancer was detected, 0.064% was at early stage and 0.059% at an advanced stage. The incidence of gastric cancer in the newly examined persons was 0.17%, 0.08% was at early stage and 0.09% at advanced stage. Of the frequently examined persons 0.07% was found to have gastric cancer, 0.043% at early stage and 0.027% at an advanced stage. The rate of occurrence of early gastric cancer was significantly higher than that of advanced gastric cancer within a 1 1/2 year interval of screening. From these results, gastric mass screening survey is considered to be effective in detecting asymptomatic gastric cancer in the "newly examined persons," and also to be beneficial in detecting "early" gastric cancer at intervals of 1 1/2 years of screening.

Adult↗

Abnormal heart rate response to exercise in vasospastic angina: pathophysiologic mechanism in the provocation of coronary spasm.

To examine the alteration in control function of the heart, which may account for the pathophysiologic condition precipitating coronary arterial spasm, the dynamic property of heart rate response to exercise in vasospastic angina was evaluated by using our previously developed frequency analytic procedure. We studied 21 patients with vasospastic angina, divided into two groups (active angina and inactive angina) and 12 normal control subjects. When compared with the transfer function of the heart rate control system in normal control subjects, the transfer function in patients with active vasospastic angina showed moderately lower gain, especially in the middle frequency range, and significantly delayed phase angle over the whole frequency range, especially in the middle and high frequency ranges. These abnormalities were not observed in inactive vasospastic angina. The present exercise test to detect abnormal heart rate control can feasibly be used in the detection and management of vasospastic angina.

Adult↗

Relationship between lipids and angiographically defined coronary artery disease in Japanese patients.

The relationship between the severity and extent of coronary artery disease (CAD) and the lipid profiles was evaluated in 120 Japanese male patients, who underwent coronary angiography. Analysis of the lipid quartile distribution showed that the percentage of patients with significant CAD increased as the total cholesterol (TC) increased and high-density lipoprotein cholesterol (HDL-C) decreased. In addition, as the number of vessels with marked coronary artery stenosis increased, TC and TC/HDL-C increased while HDL-C decreased. However, within this population, triglyceride level, high blood pressure, and smoking were not significantly associated with coronary angiographic findings.

Adult↗

Electron microscopic studies on IgA nephropathy.

We carried out electron microscopic studies on renal tissues from 9 patients with IgA nephropathy. Electron dense deposits were present in the mesangial area in all cases, subendothelial deposits in 4, and subepithelial deposits in only one. In basement membrane, segmental swelling and rarefaction of basement membrane substance were observed. In some cases the degenerated basement membrane substance protruded through the dilated endothelial fenestration into capillary lumina. Focal splitting, attenuation, mouse eaten appearance, and herniation of basement membrane were seen in a high incidence. Mesangial cells possessed well developed rough endoplasmic reticulums and polysomes. In the peripheral areas of mesangial cell cytoplasm, there was accumulation of electron dense substance and this was occasionally continuously present in the mesangial matrix. There was segmental swelling of endothelial cell cytoplasm, resulting in loss of fenestration. Epithelial cells had well developed rough endoplasmic reticulums and polysomes. Segmental foot process fusion was seen, and these processes, regardless of fusion, became electron denser in the area close to the basement membrane. Multivesiculated bodies were present in all cases in the epithelial cells and in 7 cases in the endothelial cells. Spherical microparticles were present in 3 cases in the urinary space or between the basement membrane and the epithelial cells.

Basement Membrane↗