抄録
(1) Treatment and prognosis of polycythemia vera among Japanese.
With the purpose of knowing the present states of therapy and prognosis of polycythemia vera in Japan, we asked to the doctors in about 600 hospitals concerning the details of the polycythemia vera patients they had treated since 1950. Analysis of the data of 153 cases (male 87, female 66) we have thus collected, revealed that the survival rate of the patients was apparently reduced as compared to normal Japnese, and that this reduction was mainly caused by the low survival rate among the patients who have been treated by chemotherapy. The patients treated with radioactive phosphorus showed a similar survival rate to the normal people. In 22 cases, death was confirmed. Main cause of death was cerebral vascular lesion (6 cases) and gastrointestinal bleeding (6 cases). Acute leukemia was observed in a case who had received 32P therapy 8 years prior to his death.
(2) Clinical effect of vercyte.
A derivative of the piperazine (vercyte), which has been tried in the treatment of polycythemia vera in the United State, has been administered to 4 patients with polycythemia vera. The drug was effective in all patients, and no side effect was observed.
(3) Mechanism of action of vercyte.
To study the mechanism of action of vercyte, spleen cells from phenylhydrazine-injected mouse was incubated in vitro with vercyte to observe the effect of the drug on RNA, DNA and protein synthesis. It was found that the DNA synthesis was most strongly affected by the drug. Incorporation of the thymidine, deoxyuridine, and orotic acid into DNA were similarly inhibited. Activities of thymidine-kinase and DNA-polymerase of cell-sup from phenylhydrazine mouse spleen was not inhibited by the vercyte. When the calf-thymus DNA was preincubated with the vercyte, however, its template activity with DNA-polymerase was markedly decreased by the drug. Template activity with DNA-dependent RNA polymerase of the calf-thymus DNA or chromatin from the mouse spleen cells was also significantly reduced by the vercyte. It was suggested, therefore, that the vercyte inhibited the template activity by binding with DNA. Changes in the karyotype of the bone marrow cells obtained from vercyte injected mouse also support the above suggestions on the binding of the vercyte with DNA.
(4) Sensitivity to vercyte of various hematopoietic cells.
When the sensitivity to the vercyte was compared among colony-forming cells (Till & McCulloch), erythropoietin-responsive cells, and erythroblasts, the undifferentiated colony forming cells, which have been considered as the multipotential stem cells, were most resistant to the vercyte. There was no difference among erythroblasts, granulocytes, and lymphocytes in their sensitivities to the vercyte which were measured by the reduction in DNA-synthesis.
(5) Effect of vercyte on human hematopoietic cells.
DNA synthesis in the normal human bone marrow cells in vitro was inhibited by adding vercyte. The degree of the inhibition was identical to the one observed in mouse bone marrow cells. The leukemic leukocytes from a patient with chronic myelogenus leukemia who became resistant to vercyte treatment were less sensitive to the vercyte than normal bone marrow cells.
