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Biomedical subjects

R Makidono

Publications and source records attributed to R Makidono.

At least 19 recordsLinked to original sources
PubMed1997

[Radioresistant CD4+ T cells in normal, unprimed mice: with verification of the Bergonie-Tribondeau law].

This is the first report on radioresistant CD4+ T cells found in normal, unprimed mice. After sublethal whole body irradiation, regular CD4+ as well as primitive NK1.1 + CD4+ T cells were enriched in the spleen. Since it has been well established that virgin T and B cells are highly radiosensitive, these cells were once assumed to be a unique lymphocyte population for which radiosensitivity does not follow the general law of radiation sensitivity for mammalian cells (Bergonie-Tribondeau law). These cells exhibited higher proliferative response to accessory cells than the non-irradiated control cells in the syngeneic mixed leukocyte reaction (SMLR). This indicated that virgin CD4+ T cells sensitized to, and readily respond to self-MHC class II molecules are radioresistant, and that their radioresistance, as activated cells, is consistent with the Bergonie-Tribondeau law.

Animals↗
PubMed1996

[A mechanism involved in augmentation of anti-tumor immunity by irradiation to the tumor: tumor irradiation promoted generation of CD4+helper T cells against a murine immunogenic tumor].

It has long been suggested but not generally accepted that anti-tumor immunity is enhanced by irradiation of the tumor. In this study, the mechanism involved in enhancing the effect of irradiation on tumor immunity was analyzed. 20 Gy of irradiation to a murine hepatoma, MH134, in the thigh muscle of syngeneic C3H/He mice, augmented the generation of cytotoxic T cells (CTL) in the spleen. It was assumed that radiation-damaged apoptotic tumor cells are readily phagocytosed by macrophages and that tumor specific transplantation antigen (TSTA) is presented as a complex with MHC class II antigen on macrophages to CD4+ T cells. To examine the hypothesis, that irradiated tumor cells induce CD4+ helper T cells required for the generation of CD8+ CTL, C3H/He mice were immunized with 2 x 10(7) MH134 cells which contained irradiated tumor cells (100 Gy, in vitro) at varying ratios. When irradiated tumor cells are contained at levels of 60-80%, the generation of helper T cells as well as CTL against the tumor was significantly enhanced. The findings obtained suggest that tumor irradiation enhances anti-tumor immunity by promoting the induction of antigen-specific helper T cells, which play a key role in anti-tumor immunity, i.e., either generating CTL or antibody-forming B cells depending on the activity of TH1 or TH2 subset cells.

Animals↗
PubMed1994

[Hematopoietic and lymphoid cell recovery from radiation damage by cytokines].

Radiation therapy causes various degrees of damage to hematopoietic cells. Cepharanthine (CE), a plant alkaloid, showed the most prominent restorative effect on hematopoiesis among the antileukopenia drugs examined in a previous study. Its mechanism of action was further analyzed in this study, and the following results were obtained: Intravenous administration of CE every other day for 10 days after irradiation increased CFU-S two-fold. CE-conditioned medium from bone marrow stroma cells increased CFU-C. Higher concentrations of CE in the culture non-specifically suppressed the growth of various types of cells, including T cells. However, this suppression disappeared in the presence of peritoneal exudate macrophages (PEC). When Con A blasts were co-cultivated on PEC, concentrations between 10(-6) to 10(-12) M promoted growth of both PEC and T cells. 10 pg/ml and 8 pg/ml of IL-1 were produced from 10(6)/ml of PEC and bone marrow stroma cells, respectively, in 24 hrs with CE. A lesser amount was also produced from thymus stroma cells. A detectable amount of IL-6 was produced from CE-stimulated bone marrow stroma cells. These findings suggested that CE acted as a cytokine-inducer on various epithelial cells in the body and the cytokines thus produced stimulated multipotential hematopoietic progenitors and their progeny as growth and/or differentiation factors.

Alkaloids↗
PubMed1992

[Severe damage of CD4-2H4+ T subpopulation cells (naive T cells and suppressor/inducer) by radiation therapy, their recovery being promoted by a plant alkaloid].

Radiation therapy eventually causes severe damage of lymphocytes. We examined numbers of CD4+ (helper/inducer) and CD8+ (cytotoxic/suppressor) T cells, as well as CD4-2H4+ and CD8-2H4+ subpopulation cells in the peripheral blood of patients during the radiation therapy, when lymphocytes decreased to the lowest level (500-1000/mm3). The highest molecular isoforms of the CD45 antigen family, recognized by monoclonal antibody (2H4), are designated CD45RA. Mature but antigen non-primed, naive T cells expressing CD45RA were assumed to be most radiosensitive among T cells, from the view point of radiation biology. Analysis of their damage was, therefore, the focus of this study. The mean values for all cell populations were significantly reduced as compared to those of normal individuals, the CD4-2H4+ cells having been affected most severely. Recovery was first detected in CD8-2H4+ cells after one month. Intravenous injections of a plant alkaloid, Cepharanthin, was effective in promoting recovery of CD4-2H4+ subpopulation.

Alkaloids↗
PubMed1991

[The predictive value of the anti-cardiolipin antibody test for malignant tumors].

To determine the predictive value of the IgG anti-cardiolipin antibody test for malignant tumor, two groups of the patients of Kurume and Kyushu University Hospitals were examined by quantitative enzyme linked immunoadsorbent assay (ELISA) for their serum anti-cardiolipin antibodies. With the first group of the patients consisting of a mixture of benign diseases and malignant tumors, the antibody was positive at 57% (39/72). With the second, malignant tumor group, 38% (19/50) was positive for the antibody. When examined for the specificity of the antibodies by a binding inhibition assay, it was shown that the antibodies in the tumor patients were less specific to cardiolipin: antibodies to cardiolipin in tumor patients were blocked by the specific antigen, cardiolipin, in a lesser degree than those in the control syphilis patients, and highly cross-reacted with 2 related phospholipids, i.e., phosphatidyl glycerol and phosphatidic acid. These findings obtained in this study suggest that ELISA for cardiolipin has the value for the tumor diagnosis, supplementing already established assays.

Antibodies↗
PubMed1990

Effect of cross-reactivity of alpha-fetoprotein monoclonal antibody on quantitation of serum AFP and radioimmunodetection of hepatocellular carcinoma.

Murine hybridomas were generated by immunizing mice with purified alpha-fetoprotein (AFP) to determine the cross-reactivity of AFP antibodies with human serum albumin (HSA). Eighteen out of 23 hybridoma products were cross-reactive with HSA. All 23 monoclonal antibodies (MAbs) could be subgrouped into 3 groups by their binding affinity to AFP and HSA, and one MAb from each group, IIB3, IIIB1 and IIIC6, were chosen for this study. The affinity to AFP was highest for IIB3 followed by IIIC6 and IIIB1, and that to HSA was in the order IIIB1 greater than IIB3. Immunohistochemical staining revealed no cross-reactions of these antibodies with HSA at the tissue level. IIB3 was the most efficient in the quantitative assays, indicating high affinity and specificity (non-cross-reactivity) of the antibodies, both of which are prerequisites for in vitro assays. Scans with good tumor localization were obtained from mice which received 131I-labeled IIB3 or IIIC6 after xenografting of the human hepatocellular carcinoma. The images obtained with IIB3 were inhibited in the presence of either AFP or HSA in the circulation. These findings indicated that the use of cross-reactive and/or high-affinity antibodies against AFP provides an inhibitory factor for tumor localization. MAb IIIC6, because of its high specificity and moderate affinity to AFP, seems to be the best candidate for immunoscintigraphy of the tumors in future studies.

Animals↗
PubMed1987

[Decrease in radio-sensitivity of the tumor by radiation-induced damage to immuno-related cells].

Immunological competence plays an important role in response of patients to radiation therapy and dose of radiation required for tumor control depends also on the immunocompetence of the individual patient. Radiation therapy (even localized irradiation) can, however, cause lymphopenia and induce an immunodeficient state. This may facilitate growth of residual tumor cells or metastatic foci, this negating benefits of the therapy. A brief overview of damage to T and B lymphocytes as well as macrophages and natural killer (NK) cells by radiation therapy was presented. The restoration and potentiation of the immunological competence of the patients by biological response modifiers (BRM) such as OK432 (a bacterial preparation), recombinant interferon (rIFN-gamma) and recombinant interleukin-2 (rIL-2) with or without lymphokine activated killer (LAK) cells, were discussed.

B-Lymphocytes↗
PubMed1979

Antigenicity of erythrocytes as analyzed in terms of their cross-reactivity.

The antigenicity of human erythrocytes of four different ABO blood groups and sheep erythrocytes of unknown blood type from different individual sheep were analyzed in terms of their cross-reactivity with antibody-producing cells (plaque-forming cells, PFC) and serum antibody in immunized C57BL/6 and C3H/He mice. The antigenicity of human erythrocytes of different ABO blood groups in the C57BL/6 mice, as determined by the number of specific PFC, was, in decreasing order, AB = A greater than B = O (p less than 0.005). The efficiency of immunogenicity of the human erythrocytes in terms of their cross-reactivity with PFC was, in order, AB = A = B greater than O, and the degree of reactinogenicity was, in order, AB greater than A greater than B greater than O. The order of antigenicity of sheep erythrocytes from different animals, SRBC No. 1 - No. 6, was No. 1 (= No. 2) greater than No. 3 = No. 4 = No. 5 greater than No. 6 in C57BL/6 mice and No. 1 = No. 2 = No. 3 = No. 4 = No. 6 greater than No. 5 in C3H/He mice, determined by the number of specific PFC (p less than 0.01). The cross-reactivity of SRBC No. 1 - No. 6 with PFC demonstrates that the order of immunogenicity of SRBC was No. 1 = No. 2 = No. 3 = No. 4 = No. 5 greater than No. 6 in C57BL/6 mice and No. 1 = No. 2 = No. 3 = No. 4 = No. 6 greater than No. 5 in C3H/He mice, and that of their reactinogenicity was No. 1 greater than No. 2 =No. 3 = No. 4 = No. 5 greater than No. 6 in C57BL/6 mice and No. 1 greater than No. 4 = No. 6 greater than No. 2 = No. 3 greater than No. 5 in C3H/He mice. The cross-reactivity at the antibody level was indicative of the immunologic characteristics of blood cells of low antigenicity (human group O erythrocytes and SRBC No. 5 and No. 6). SRBC No. 5 and No. 6 were somewhat opposed to each other regarding antigenicity in C57BL/6 and C3H/He mice. This signifies the presence of different immunogenic components on SRBC No. 5 and No. 6. The production of anti-SRBC No. 1 antibody reached its peak on the third day after secondary immunization. That of anti- SRBC No. 1, cross-reactive with SRBC No. 6, occurred after a longer latent period, reaching its peak on day 6. This indicates that SRBC No. 1 possesses more than one kind of immunogenic component or immunogenic determinant group on its surface.

ABO Blood-Group System↗