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Biomedical subjects

H Ishitsuka

Publications and source records attributed to H Ishitsuka.

68 records · Page 4Linked to original sources
PubMed1982

Direct and specific inactivation of rhinovirus by chalcone Ro 09-0410.

Studies of various analogs related to the antipicornavirus agent, 4',5-dihydroxy-3,3',7-trimethoxyflavone (Ro 09-0179), led to the identification of 4'-ethoxy-2'-hydroxy-4,6'-dimethoxychalcone (Ro 09-0410), a new and different type of antiviral agent. Ro 09-0410 had a high activity against rhinoviruses but no activity against other picornaviruses. Of 53 rhinovirus serotypes so far tested, 46 were susceptible to Ro 09-0410 in HeLa cell cultures. The concentration of Ro 09-0410 inhibiting 50% of the types of rhinovirus was about 0.03 micrograms/ml, whereas the 50% cytotoxic concentration was 30 microgram/ml. Ro 09-0410 inactivated rhinoviruses in direct dose-, time-, and temperature-dependent fashion. Since infectivity, reduced by exposure to the agent, completely regained the original level by extraction of the agent with chloroform, the inactivation may be associated with the binding of the agent to some specific site of the rhinovirus capsid.

Antiviral Agents↗
PubMed1981

A simple and convenient assay method for phosphorolysis of 5'-deoxy-5-fluorouridine.

5'-Deoxy-5-fluorouridine (5'-DFUR) exhibits antitumor activity through its conversion to 5-fluorouracil by uridine phosphorylase (UPase) in mice. This mode of activation was confirmed by the fact that a mutant strain of Micrococcus flavus resistant to 5'-DFUR but sensitive to 5-fluorouracil was isolated and found to be deficient in UPase activity. Furthermore, since the enzyme level in tumor tissue should be useful as an indicator for therapy with 5'-DFUR, a simple assay method for the enzyme activity with use of the above bacterium was developed, in which the amount of 5-fluorouracil cleaved from 5'-DFUR by the enzyme was estimated through its antibacterial activity without separation from 5'-DFUR. This method is simple and efficient for handling a large number of samples.

Animals↗
PubMed1980

Role of uridine phosphorylase for antitumor activity of 5'-deoxy-5-fluorouridine.

5'-Deoxy-5-fluorouridine (5'-DFUR) was parenterally and orally effective on various transplantable tumors and its activity was better than that of other fluorinated pyrimidines. However, like 5-fluorouracil and 2'-deoxy-5-fluorouridine (FUdR), 5'-DFUR was ineffective on L1210 leukemia resistant to 5-fluorouracil, suggesting that it would exert its antitumor activity through converted 5-fluorouracil. In tissue culture, 5'-DFUR inhibited the growth of various tumor cells similarly to ther fluorinated pyrimidines. However, 5'-DFUR was unique in that uridine completely reversed its inhibitory effect. Enzymological study clarified that uridine inhibited the conversion of 5'-DFUR to 5-fluorouracil by a uridine phosphorylase, in parallel to its reverse effect on cell growth inhibition by 5'-DFUR. Furthermore, a subline of L1210 leukemia resistant to 5'-DFUR but not to 5-fluorouracil was found to lack the uridine phosphorylase. These results indicate that 5'-DFUR is a depot form of 5-fluorouracil which can be promptly activated by uridine phosphorylase. In addition, the uridine phosphorylase was found to be abundant in sarcoma-180 solid tumor, leading to a significantly higher concentration of converted 5-fluorouracil in this tumor than in other normal tissues. This provides a good explanation for the high chemotherapeutic index of 5'-DFUR against this tumor, which may be applicable also for other tumors.

Animals↗
PubMed1980

Comparative studies on the immunosuppressive effect among 5'-deoxy-5-fluorouridine, ftorafur, and 5-fluorouracil.

The immunosuppressive effect of 5'-deoxy-5-fluorouridine (5'-DFUR, Ro 21-9738) was examined for both humoral and cell-mediated immunity in mice in comparison with that of 5-fluorouracil and Ftorafur (FT-207). By both oral and intraperitoneal administration, 5'-DFUR was found to be much less suppressive than 5-fluorouracil and FT-207 in all immune responses tested; hemolysin plaque-forming cells, serum hemolysin titer, delayed-type hypersensitivity and allogeneic tumor rejection. Furthermore, 5'-DFUR did not induce any reduction in either the spleen weight, thymus weight, total spleen cell number, or peripheral leucocyte number.

Animals↗
PubMed1977

A simple and efficient microassay method for titration of interferon.

A simple and efficient microassay method for the titration of interferon was developed by the use of microtest plates for handling a large number of samples. L929 cells pretreated with interferon were infected with vesicular stomatitis virus (VSV) and cultured in the presence of 3H-uridine. The activity was expressed by the reduction of extracellular radioactive RNA released after destruction of the infected cells, which was measured in terms of the radioactivity incorporated into cold TCA-insoluble materials in the culture fluid. The interferon titer determined by this method was in the same order as that by the plaque reduction method. The activity by this method was parallel to, but lower than that expressed by the yield reduction of infectious viruses. This method requires only 0.025 ml of each test sample with higher than 1 NIH ref. unit/ml to detect its interferon activity and takes 2 to 3 days for assaying hundreds of samples.

Animals↗
PubMed1970

Release of tRNA from ribosomes by a factor other than G factor.

In addition to the G factor there exists another factor in the E. coli extracts which stimulates the release of tRNA from ribosomes. This factor is distinctly different from the G factor and may play a role in removing tRNA from the ribosome after the polypeptide chain termination factor has released the completed chain from the ribosome-bound tRNA.

Carbon Isotopes↗
PubMedDate not supplied

Restoration by recombinant interferon alpha A/D of host defense systems against tumor in immunosuppressed mice.

Recombinant human interferon alpha A/D (alpha A/D) restored or augmented host defense systems against tumors in immunosuppressed mice. In normal C57BL/6 mice, inoculation of B16 melanoma F1 cells caused few pulmonary metastasis, whereas in mice pretreated with cyclophosphamide (CY) it caused a high incidence of pulmonary metastasis, leading to earlier death than in the normal mice inoculated with the same dose of the tumor. alpha A/D given after the CY treatment counteracted the deleterious effects of the CY treatment. Since such restorative activity was seen even against the subline of B16 F1 which had been made resistant to its direct antiproliferative effect, alpha A/D seems to exert its effect indirectly through host defense systems. However, this activity of alpha A/D in the mice pretreated with CY was abrogated by inoculation of anti-asialo GM1 serum but not by i-carrageenan. The CY treatment reduced NK activity, while alpha A/D given after the CY treatment restored or augmented the NK cell activity in lung cells and peripheral blood mononuclear cells, but not in spleen cells. These findings suggest that the restoration or augmentation of NK activity in the lung and/or peripheral blood might be the major factor leading to the antimetastatic activity of alpha A/D in the mice treated with CY.

Animals↗
PubMedDate not supplied

Antitumor and antimetastatic activities of human recombinant interferon alpha A/D.

Human recombinant interferon alpha A/D (alpha A/D) was examined for its antitumor activity in several mouse tumor models using metastatic tumors, such as B16 melanoma F1, BL6 and F10, UV2237m fibrosarcoma, and K1735m melanoma. Therapeutic treatment with alpha A/D reduced the incidence of pulmonary metastasis and inhibited the tumor growth resulting in an increase of the mean survival time. Since alpha A/D also showed a prophylactic activity against the metastasis, its antitumor activity was suggested to be due to augmentation of the host defense systems. This was confirmed by the fact that alpha A/D inhibited the in vivo growth and incidence of pulmonary metastasis of B16 F1 sublines regardless of their sensitivity to the direct antiproliferative activity of the IFN in vitro.

Animals↗