Van de Graaff neutrons for superficial tumor therapy.
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Biomedical subjects
Publications and source records attributed to T Inada.
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Cell-mediated immunity (CMI) to mouse adenovirus (M-Ad) infection was studied by macrophage migration inhibition test (MMI) as one of in vitro correlates of CMI. Both direct and indirect tests showed clearly that migration of packed peritoneal exudate cells (PEC) (immune mouse or nonimmune guinea pig) was remarkably inhibited; MIF was produced by interactions between immune PEC and infected cell extracts and between immune spleen cells and infected cells or their extracts. The antigen(s) responsible for the above MMI was demonstrated in 6- to 12-hour infected ME cells, and FUdR-treated infected ME cells. Since under these conditions there is S antigen(s) synthesis but not capsid antigen synthesis, the antigen(s) concerned must be an S antigen(s). T cells sensitized to infected cells were shown to be required to induce MMI. The MMI is specific for M-Ad, since no cross MMI was observed between M-Ad and SV40 systems. Time course study of the development of CMI to M-Ad by MMI tests showed that CMI became detectable 4 days post-infection (pi), reached its peak level about 10 days pi, and faded away rapidly in about 10 days thereafter.
Immune spleen cells (ISC) from mice immunized with a sublethal dose of mouse adenovirus (M-Ad) were shown by the 51Cr release test to be cytotoxic to target mouse embryonic cells or lymphoid cells infected with M-Ad. The number of ISC required for release of statistically significant amounts of 51Cr from target cells varied from one sample to another, ranging from 5 to greater than or equal to 30 ISC per target cell. When 24-h-infected mouse embryonic cells were used as targets, the release of 51Cr became evident in 6 h after the addition of ISC to the cells, gradually increased with time, and then leveled off. Cytolytic activity of M-Ad ISC is specific for M-Ad, since ISC do not lyse mouse embryonic cells infected with human adenovirus type 12 and vice versa. Kinetic study of the development of cell-mediated immunity to M-Ad assayed by 51Cr release showed that cytolytic activity of ISC in infected mice became detectable 4 days postinfection, reached its peak level about 7 to 10 days postinfection, and fell to undetectable levels about 10 days thereafter. This is consistent with the data obtained by inhibition of intracellular viral antigen synthesis or by the macrophage migration inhibition test in our prevous reports.
The type of effector cells in immune spleen cells (ISC) responsible for cell-mediated cytolysis of mouse adenovirus-infected cells was characterized. When ISC were pretreated with anti-mouse thymocyte or anti-Thy1.2 serum and complement, their cytolytic activity assayed by the (51)Cr release test was completely abolished, whereas it was not significantly reduced either when ISC were pretreated with anti-mouse immunoglobulin serum and complement or after ISC were kept standing at 37 degrees C for 2 h in a plastic dish to remove adherent cells. These data indicate that the effector cells in ISC are T cells. The release of nonspecific or specific soluble cytotoxic factor(s) from ISC upon contact with mouse adenovirus-infected cells was not demonstrated, but about 30 U of interferon activity per ml was detected. However, 10 times as many units of exogenous interferon or more showed no effect on (51)Cr release from target infected cells or on the inhibition of viral antigen synthesis in infected cells. Experiments with mouse cells of different major histocompatibility antigens indicated that the cytotoxicity of ISC is effective when sensitizer and target cells share all or part of the same H-2 gene complex but not effective when they are of a different H-2 gene complex.
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A virus-specific cell surface antigen(s) was detected on mouse adenovirus-infected cells by the immunofluorescent antibody technique. It was demonstrated in infected cells regardless of the mouse strain or animal species used. It became detectable on the cell surface about 6 h postinfection and was demonstrated in 90% of infected cells at 24 to 36 h postinfection. On the other hand, intracellular capsid antigens became detectable by the immunofluorescent antibody technique at about 24 h postinfection. Since it was also detected on virus-infected cells treated with 5'-fluorodeoxyuridine to block viral deoxyribonucleic acid synthesis, it was synthesized at the early stage of infection and may not be a virus structural component. The relationship between this serologically detectable cell surface antigen(s) and cell-mediated immune response to virus infections is discussed.
Three human cell lines, Burkitt lymphoma cells (P3HR-1), epidermoid carcinoma cells (HeLa S3-1), and melanoma cells (HMV) were irradiated with 200 kV X-rays under three different oxygen conditions. The values of D0 and D10(-2) were estimated for survival curves, and then the dose-modifying factors (DMF) were calculated, for the oxygenated and hypoxic irradiations. These DMF values for oxygenation were not different for each cell line, but those for hypoxia revealed considerable difference for cell lines. From the comparison of modifications due to variable oxygen concentrations on the survival curves of Burkitt lymphoma cells with those of other resistant cells, it is concluded that the shoulder of the survival curves becomes larger primarily with lowering of the oxygen tension, and then D0 value increases followed by a decrease in n value, while in oxygenation, the decrease in D0 value takes place after n value becomes close to 1.
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The radiation response of cultured Burkitt lymphoma cell, known as a particular cell line of high radiosensitivity, was studied by the colony formation method. The values of n, Dq, and Do derived from the survival curve after a single dose X-irradiation resulted in small values as 1.1, 10 rad, and 125 rad. The maximum recovery of about 5% was observed 3 hr after the irradiation by a split-dose experiment. In the survival curve derived from a split-dose irradiation, n and Dq increased while Do remained unchanged. The reason for these increases in n and Dq may be attributed to the nonhomogeneous or mixed population response.
The effects of 2 MeV neutrons were compared with those of 200 kV X-rays for the criterion of lethality in mastocytoma cells of ascites type. The cells prepared as suspension were exposed to the radiations in vitro under aerobic condition and transplanted in the abdominal cavity of mice. Their viability was estimated according to the growing speed of the excreted amount of urinary 5-HIAA in the host animal. The RBE varied between a value of 3.1 at the 10 per cent level of cell survival to 1.8 for the mean lethal dose (Do).
Dependence of the survival curves of Burkitt lymphoma cells, which were featured by their small n or Dq values, on linear energy transfer (LET) obtained for different quality of radiation was revealed markedly in the change of D0 value, together with a small change in n value. Relative biological effectiveness (RBE) compared with Dq, n and D37 values of Burkitt lymphoma cells for high LET radiation was smaller than that of other cell lines. This finding supports the hypothesis that in Burkitt lymphoma cells the recovery capacity from sublethal damage (Dq) is so small even after low LET irradiation that LET does not modify the suppression of recovery. Similar survival curves with n value closely equal to 1 were obtained for four different mammalian cell lines (Burkitt lymphoma p3HR- 1, human melanoma HMV, HeLa-S3, and L5178Y) after 2 MeV neutron irradiation. This fact may suggest that the radiation which has an LET value at which n value of the survival curve is to be 1 will be optimum for therapeutic purpose to the radioresistant tumors.
In this paper the results of the clinicopathological study on a total of 79 bladder tumor cases are presented. They are principally related to the stromal proliferation or branching of the tumors. The tumor cases consist of those with a good prognosis as well as those with a poor prognosis. In the former category there are 61 cases with a long survival history (with or without recurrence); the remainder (18 cases) had a history of a short survival (dying within 2 years). Histologically there was a marked difference in the regularity of the stromal branching of the tumor between those cases with a long survival history and those cases with a short survival history. In the former group the regular type of stromal branching was predominant; in the latter group the irregular type was predominant.
The role(s) of helper T lymphocytes in preventing or altering tolerance induction in DNP-specific B lymphocytes was studied. As DNP-reactive helper T cells were reactive against the DNP-portion of the DNP-D-GL molecule, we could probe definitively the physiological role of helper T cells in preventing tolerance induction in B lymphocytes by DNP-D-GL. The results demonstrated that the induction of DNP-specific B cell tolerance by DNP-D-GL can be completely prevented by the presence of DNP-reactive helper T cells, and provide evidence that one critical role of helper T cell participation in humoral responses to antigens is to circumvent the development of a tolerogenic signal that, in the absence of such T cell function, might otherwise ensue after binding of the antigenic determinants by specific B lymphocytes.
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