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Biomedical subjects

N Tokuda

Publications and source records attributed to N Tokuda.

At least 73 records · Page 4Linked to original sources
PubMed1987

Analysis of tissue lymphocytes by double fluorescent staining--gastric cancer tissue and regional lymph nodes.

An immunohistochemical study was performed on human lymphocytes in the tissue of gastric cancer, and also in the regional lymph nodes, by double fluorescent staining, using monoclonal antibodies. Leu3a+8+ cells (inducer T cells) which consist about 30 per cent of Leu 3a+ cells were seen in the tissue surrounding the gastric cancer. The other 70 per cent of Leu 3a+ cells were Leu3a+8- cells (helper T cells). In the lymph nodes they were noted in T cell areas in almost the same proportions, while in germinal centers, only Leu3a+8- cells were found. On the other hand, OKT8+Leu15- cells (cytotoxic T cells) were noted in a large number, while OKT8+Leu15+ cells (suppressor T cells) were few. Further, an increase of OKT8+Leu15- cells was seen around gastric cancer or metastatic cancer in lymph nodes. These immunohistochemical findings suggest that cytotoxic T cells are the main component in the tissue of gastric cancers and the regional lymph nodes. Increases in inducer T cells and helper T cells are probably required to induce cytotoxic T cells around the cancer tissue.

Antibodies, Monoclonal↗
PubMed1987

Drug-induced tolerance to allografts in mice. X. Augmentation of split tolerance in murine combinations disparate at both H-2 and non-H-2 antigens by the use of spleen cells from donors preimmunized with recipient antigens.

In a fully allogeneic murine combination of C3H/HeSlc (C3H) (H-2k) and C57BL/6CrSlc (B6) (H-2b), C3H mice were primed i.v. with 1 X 10(8) spleen cells from B6 mice preimmunized i.v. with 5 X 10(7) C3H spleen cells and then were given i.p. 200 mg/kg cyclophosphamide (CP) 2 days later (Im-B6-Sc plus CP group). The tolerant state in those recipient mice was compared with that in mice made tolerant conventionally with 1 X 10(8) naive B6 spleen cells plus 200 mg/kg CP (naive-B6-Sc plus CP group). B6 skin was rejected in an almost normal fashion in both the naive-B6-Sc plus CP group and the Im-B6-Sc plus CP group. However, EL4 tumor allografts (B6 origin) inoculated after complete rejection of B6 skin grafts were specifically accepted in both groups. Moreover, the tumor growth in the Im-B6-Sc plus CP group was faster than that in the naive-B6-Sc plus CP group. Mixed lymphocyte reaction, cytotoxic T lymphocyte activity, and antibody production against the tolerogen were depressed more profoundly in the Im-B6-Sc plus CP group than in the naive-B6-Sc plus CP group. These observations were consistent with the results from tumor allografting. The other immunological parameters examined in the present study, including helper T cell activity and delayed foot-pad reaction, were retained in the Im-B6-Sc plus CP group at the same levels as in the naive-B6-Sc plus CP group. These observations were consistent with the results from skin allografting. In conclusion, tumor allograft tolerance was made more profound by the use of spleen cells from donors preimmunized with recipient antigens as the tolerogen than by the use of naive spleen cells. However, skin allograft tolerance was not achieved at all by these same treatments. The contribution of graft-versus-host disease to this phenomenon was excluded by the chimeric analysis in AKR/JSea (H-2k) mice given the preimmunized (with AKR antigens) B6 spleen cells plus CP. These results strongly support the existence of a less proliferative lymphocyte population which does not evoke cell divisions to mature even after the strong stimulation with the preimmunized spleen cells and is resistant to tolerance induction.

Animals↗
PubMed1987

Drug-induced tolerance to allografts in mice. XII. The relationships between tolerance, chimerism, and graft-versus-host disease.

When AKR/J Sea (AKR, H-2k) mice were primed i.v. with 1 X 10(8) viable spleen cells from naive C3H/He Slc (C3H, H-2k) mice and treated i.p. with 200 mg/kg cyclophosphamide (CP) 2 days later, a minimal degree of mixed chimerism associated with tolerance to C3H skin was established without graft-versus-host disease (GVHD) and maintained for at least one month. When AKR mice were primed i.v. with 1 X 10(8) viable spleen cells from C3H mice preimmunized i.v. 7 days earlier with 5 X 10(7) viable AKR spleen cells, and treated with 200 mg/kg CP, chimerism became exclusive, but lethal GVHD occurred in the AKR mice. Moreover, most of normal AKR mice primed with the preimmunized C3H spleen cells without CP died of GVHD. In contrast, in a major histocompatibility complex (MHC)-incompatible combination of AKR (H-2k)-C57BL/6 Cr Slc (B6, H-2b), mixed chimerism, tolerance to skin allografts, and GVHD were not observed, whether or not the mice had been treated with naive or preimmunized B6 spleen cells with or without CP.

Animals↗
PubMed1987

[An immunohistochemical study using a double staining method for regional lymph nodes in gastric cancer].

We have performed a double immunofluorescent staining of two monoclonal antibodies, obtained from gastric cancer patients, that were directed against lymphocyte surface antigens on the regional lymph nodes. Through this method we were able to identify the lymphoid cell subset in detail. As a result of our double staining, most OKT8+ lymphocytes were also found to be Leu 15- lymphocytes and these OKT8+ Leu 15- lymphocytes were regarded as being cytotoxic effector cells or precursors. A few OKT8+ Leu 15+ lymphocytes (suppressor T lymphocytes) were obtained. More Leu 3a+ Leu 8- lymphocytes (helper T lymphocytes) were observed than Leu 3a+ Leu 8- lymphocytes (suppressor inducer T lymphocytes). To investigate whether these T lymphocytes were activated, we used an OKT 9 monoclonal antibody directed against the transferrin receptor and an OKIa1 monoclonal antibody directed against the HLA-DR framework. Such double stained lymphocytes (activated T lymphocytes) were few.

Antibodies, Monoclonal↗
PubMed1986

Different characteristics of allogeneic and trinitrophenyl-modified H-2-restricted cell-mediated lympholysis: analysis of differences in interleukin-2 dependency using an ontogenical approach.

Ontogenical development of in vitro allogeneic cell-mediated lympholysis (CML) and in vitro trinitrophenyl (TNP)-modified CML was studied mainly in correlation with helper cell activity, using C3H/HeN and C57BL/6 mice. Allogeneic and TNP-modified CML were not detected in the spleen of these mice at 1 week after birth. Allogeneic CML was detectable, in parallel with increases in age. This activity in 5-week-old mice was much the same as in the 8-week-old mice but the TNP-modified CML did not appear until 8 weeks after birth. Exogenous interleukin-2 (IL-2) induced sufficient activity of TNP-modified CML, even in spleen cells from 1-week-old mice, while the same treatment had a weak but significant effect on the induction of allogeneic CML in these same cells. Experiments on the mixed lymphocyte reaction (MLR) in the presence of exogenous IL-2 showed that lymphocyte proliferation in response to TNP-modified cells was higher than that in response to allogeneic cells. These results suggest different dependencies on IL-2 between allogeneic and TNP-modified killer precursor cells. Endogenous IL-2 production and proliferative response in MLR showed that helper cells contributing to the TNP-modified CML matured later, compared to allogeneic CML. Different sensitivities to IL-2 in two types of CML, in addition to different ontogenical developments, suggest that cytotoxic T lymphocytes to allogeneic cells differ quantitatively and qualitatively from TNP-modified H-2-restricted killer cells.

Aging↗
PubMed1986

Allograft rejection and immune responses against allogeneic antigens in neonatally thymectomized mice.

Skin allograft survival and immune responses against allogeneic antigens homologous to skin grafts were observed in BALB/c Cr Slc (BALB) mice (H-2d) thymectomized at 1 day after birth and grafted with skin from major histocompatibility complex (MHC)-incompatible, fully allogeneic C3H/HeN (C3H) (H-2k) or MHC-compatible allogeneic DBA/2 Cr Slc (DBA) mice (H-2d), at 14 weeks of age. In neonatally thymectomized (NTx) BALB mice, survival of C3H skin grafts was not prolonged at all, but survival of DBA skin grafts was prolonged significantly, although the survival periods of DBA skin grafts were very different among individual recipients. In NTx recipients grafted with C3H skin, delayed foot-pad reaction (DFR) was not reduced, but cytotoxic lymphocyte (CTL) activity and cytotoxic antibody (CTAb) production were appreciably depressed. CTL and CTAb were reduced profoundly and consistently in all NTx mice grafted with DBA skin, while DFR was reduced to various degrees in each. The degrees of depression of DFR in these NTx mice correlated well with the prolongation of DBA skin survival, although the sample number was small. The rejection of skin allografts appears to be attributable largely to a T cell subset, the function of which can be expressed as DFR. Thymus dependency in the ontogenic development is low as compared with other T cell subsets.

Animals↗
PubMed1986

Drug-induced in vitro tolerance to allogeneic antigens. I. Establishment of a tolerance induction system in a fully allogeneic murine combination.

C3H/HeSlc (H-2k) spleen cells were cultured with mitomycin C (MMC)-treated C57BL/6CrSlc (H-2b) spleen cells for 2 days and incubated with 5-fluorouracil (5-FU) for a further 9 hr. Thereafter, those C3H/He spleen cells were recultured with the same allogeneic cells for 5 days. Cell-mediated cytotoxicity (CMC) and mixed lymphocyte reaction (MLR) were profoundly suppressed, antigen-specifically, in such C3H/He spleen cells. In contrast, interleukin 2(IL-2) production was not impaired in the restimulating mixed lymphocyte culture (MLC) with C57BL/6. Moreover, an adequate amount of exogenous IL-2 added to the restimulating MLC did not lead to a restoration of the depressed CMC. Suppressor cell activity in the CMC assay was not detected in the C3H/He spleen cells exposed to such a tolerance induction. These results suggest that the unresponsiveness to alloantigens in CMC and MLR was induced through a clonal deletion mechanism, and there may exist a 5-FU-resistant--thus less-proliferative--cell population that can produce IL-2 even after the tolerance induction.

Animals↗
PubMed1986

[Malignant paraganglioma of the peri-iliac artery].

A malignant nonfunctioning paraganglioma of the pelvic retroperitoneum (left external iliac artery) with metastases to the femoral lymph nodes was found in a 68-year-old woman at exploratory laparotomy. Light microscopy showed a typical alveolar pattern with fine vascular stroma. The tumor cells had finely granular eosinophilic cytoplasm and oval to round nuclei with pleomorphism and mitotic figures, Grimelius stain showed no argyrophilic granules, but S 100 protein was demonstrated in the cytoplasm by the PAP method of Sternberger. Formaling fixed tissues were examination by electron microscopy, and dense core granules consistent with neurosecretory granules were found in the cytoplasm of some tumor cells.

Aged↗
PubMed1986

Drug-induced tolerance to allografts in mice. IX. Establishment of complete chimerism by allogeneic spleen cell transplantation from donors made tolerant to H-2-identical recipients.

Graft-versus-host reaction (GVH) after allogeneic spleen cell transplantation was completely suppressed in an H-2-matched murine combination (AKR/J Sea [H-2k]----lethally irradiated C3H/He Slc [H-2k]) by pretreatment of the donors with recipient spleen cell antigen plus cyclophosphamide (CP). Irradiated recipients receiving cells became chimeric. In contrast to the H-2 matched combination, lethal GVH reaction could not be prevented in an H-2-mismatched fully allogeneic combination (C57BL/6 Cr Slc [H-2b]----lethally irradiated C3H/He Slc [H-2k]) by pretreatment of the donors. The results suggest that the effectors responsible for the GVH reaction were abrogated by pretreatment of the donors with allogeneic recipient spleen cells plus CP in the H-2-matched combination, but donor pretreatment failed to abrogate GVH reaction in the H-2-mismatched combination.

Animals↗
PubMed1985

Cell-mediated lympholysis (CML) to allogeneic and trinitrophenyl (TNP)-modified cells: re-evaluation of the role of the thymus in CML.

The role of the thymus in cell-mediated lympholysis (CML) to allogeneic and trinitrophenyl (TNP)-modified cells was re-evaluated using adult thymectomized (ATx) and neonatal thymectomized (NTx) mice. CML to TNP-modified cells was used as the model of the major histocompatibility complex (MHC)-restricted CML. CML to TNP-modified cells, but not to allogeneic cells was reduced at late stages after ATx and remained low even in NTx-11 (thymectomy at 11 days of age) mice. Interleukin-2 (IL-2) producing activity in such mice was lower than that in the normal controls, while allogeneic CML was maintained at the same level as seen in the controls. The addition of exogenous IL-2 to in vitro culture led to a restoration of the generation of CML to TNP-modified cells, in neonatal thymectomized mice. These results suggested that thymus-dependency differs in the 2 forms of CML and that the CML to TNP-modified cells showed a higher thymus-dependency than did the allogeneic CML. Moreover, the activity of helper T cells may exert a direct influence on CML to TNP-modified cells, as compared to allogeneic cells.

Animals↗