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Biomedical subjects

M Kitagawa

Publications and source records attributed to M Kitagawa.

At least 595 records · Page 33Linked to original sources

Inhibitory effect of tumor-bearing state on the generation of in vivo protective immune T cells in a syngeneic murine tumor system.

Tumor-specific immunity mediated by thymus-derived lymphocytes (T cells) was established in C3H/He mice against syngeneic X5563 plasmacytoma. Splenic T cells from mice, which exhibited resistance to tumor challenge, revealed a potent in vivo tumor-neutralizing activity as well as in vitro cytotoxicity. In contrast, spleen cells from mice 7 days after tumor cell inoculation (7-day tumor-bearing mice) exhibited no protective activity when assayed by in vivo tumor-neutralization test, whereas these cells exhibited almost comparable in vitro cytotoxic activity to that from the tumor-resistant mice. Any suppressor cell activity was not detected in 7-day tumor-bearing animals. While a slight in vivo protective activity was observed in the spleen cells from 14-day tumor-bearing mice, this activity was still significantly weaker than that of spleen cells from mice similarly inoculated with tumor 14 days before but whose tumor had been removed 7 days before the assay. The development of in vivo protective immunity in tumor-resected mice was suppressed by intravenous inoculation with 7000 R X-irradiated tumor cells. These results indicate that in vitro reactivity of immune T lymphocyte population is not always correlated with in vivo protective immunity, but there is a substantial decrease in in vivo immune capability of T cells from tumor-bearing animals, and that this suppression may be ascribed to the presence of a large amount of tumor-associated transplantation antigens rather than to suppressor cell activity.

Animals↗

Selective inhibition of T lymphocyte repopulation of lymphoid organs as a mechanism of immunosuppression in tumor-bearing mice.

The mechanism of selective suppression of T-cell activity in Ehrlich tumor-bearing mice was investigated in an adoptive cell transfer system of secondary antibody responses to haptens. The induction of secondary antidinitrophenyl (DNP) antibody response after stimulation with DNP-homologous carrier (TD) of thymus-dependent DNP-carrier (TD)-primed spleen cells was markedly inhibited in tumor-bearing recipient mice, whereas the response to thymus independent DNP-carrier (TID) was intact as compared to that seen in normal recipients. However, if tumors were induced in the DNP-TD-primed donor mice and the spleen cells were assayed for responsiveness to DNP-TD in normal recipients, they generated a normal anti-hapten antibody response. After the DNP-TD-primed cells had been transferred into normal recipients and tumors had been induced in the recipients before DNP-TD-stimulation, the cells in tumor-bearers responded normally. These results indicate that the tumor-bearing state neither directly suppresses the responsiveness of primed cells nor interferes with the mechanism for antigen stimulation of primed cells. Direct measurement of recovery of transferred primed T and B cells from the spleen of tumor-bearing recipients revealed that the net recovery of T-cell activity markedly decreased, whereas the recovery of B cells in the spleens of tumor-bearing hosts was not affected or was even higher than the normal. Prevention of repopulation by T lymphocytes of lymphoid organs due to a postulated change in the microenvironment is suggested as a mechanism for the selective suppression of T-cell activity in Ehrlich tumor-bearing animals.

Animals↗

Selective suppression of T-cell activity in tumor-bearing mice and its improvement by lentinan, a potent anti-tumor polysaccharide.

The cellular site of immunosuppression in Ehrlich tumor-bearing mice was analysed with particular reference to the T- and B-cell activities. The B-cell activity as measured by the anti-dinitrophenyl (DNP) antibody responses to DNP-thymus-independent carriers (TID) was not impaired in tumor-bearing mice as compared with normal mice, whereas the anti-DNP antibody response to DNP-thymus-dependent carriers (TD) and the development of helper T-cell activity to TD were markedly suppressed in tumor-bearing animals or mice pretreated with cell-free cancerous ascitic fluid. The selective suppression of T-cell response was not mediated by the generation of suppressor cell activity toward TD, which may depress the manifestation of developed helper T-cell activity. A marked suppression of T-cell response was observed when the animals were inoculated with tumor cells or injected with cancerous ascitic fluid prior to antigenic stimulation, but not when the animals were rendered tumor-bearing by such treatments after the immunization. The suppression of T-cell activity in both sarcoma 180 tumor-bearing mice and cell-free Ehrlich cancerous ascitic fluid-treated mice was prevented by treatment with lentinan, a potent anti-tumor polysaccharide. The applicability of this experimental system to the search for immunopotentiators relevant to tumor immunotherapy is discussed in the light of the preventive effect of lentinan on the suppression of T-cell response in tumor-bearing animals.

Animals↗

Enzyme immunoassay of testosterone using the testosterone-glucoamylase complex.

A highly sensitive, reproducible method was established for enzyme-coupled immunoassay of testosterone, involving coupling of testosterone to glucoamylase [EC 3.2.1.3] with a water-soluble coupling reagen carbodimide. No enzyme activity was lost during this coupling procedure. The sensitivity of the method was comparable to that of competitive protein binding assay.

Carbodiimides↗

Post-traumatic anterior pituitary insufficiency developed in a patient with partial lipodystrophy.

A case of partial lipodystrophy developing anterior pituitary insufficiency, chronic glomerulonephritis and pulmonary fibrosis was reported. The patient died of respiratory failure secondary to pituitary crisis during the hospital course. From the clinical course in recent several years and the postmortem examination the head injury following car accident in the past history was considered to be the most plausible cause of hypopituitarism. The etiology of pulmonary fibrosis remained unresolved.

Adrenal Glands↗

Histo-clinical classification and follow-up study of gastric polyp.

Gastric polyp was found in 1,616 cases or 0.23% of 711,455 persons through the gastric mass-survey. They were classified into 3 groups: hyperplastic polyp in 61%, gastric polyposa in 34%, and polyp composed of metaplastic epithelium with marked atypism (ATP) in 5%. Gastritis polyposa was subclassified into 5 groups according to its histo-clinical features. Malignant degeneration was suspected in 5 or 2.1% of 236 hyperplastic polyps operated, while no polyp which had changed into cancer was experienced among 974 polyps followed-up by biopsy during the time course of 6 months to 11 years at the longest. On the other hand, coexistence of gastric cancer was found in 13% of cases with ATP. In polyps composed of metaplastic epithelium, there are two kinds of polyp: metaplastic polyp in hyperplastic proliferation and neoplastic polyp. In the follow-up study of 1,104 polyps, the growth of polyp was seen in only 14, and 12 of which were hyperplastic polyp. No change from gastritis polyposa to hyperplastic polyp was observed. The increase in size in 14 polyps was seen mostly 3 to 4 years after they were found and was always transient. From these results, it is considered that most of gastric polyps clinically detected have already completed their growth.

Biopsy↗

Evaluation of mass screening program for stomach cancer.

Particular method and program of mass survey examination of gastric cancer were introduced into Miyagi Prefecture and the results accumulated during the past 14 years are presented. During this period, 1,427 cases of gastric cancer (0.18%), as well as many cases of other diseases of the stomach and duodenum, were found by the mass survey. 450 cases were those of early cancer in which invasion of carcinoma was limited to the mucosa and submucosa. The ratio of surgically confirmed early cancer cases to all the stomach cancer cases was 36.4%. Almost in all cases of early stomach cancer there were neither complaints nor clinical symptoms; that is, they were the cases of so-called preclinical cancer of the stomach. The prognosis after surgery of early stomach cancer was remarkably favorable with a five-year survival rate over 90% and the death rate due to stomach cancer was actually decreased in the surveyed population.

Adult↗

Isolation of soluble immunosuppressive substance(s) from Ehrlich ascites tumor cell nuclei.

A potent immunosuppressive principle was isolated in a soluble form from the nuclei of Ehrlich ascites tumor cells. DNA-free preparation, obtained from the purified nuclei by homogenizing in 2M NaCl-5M urea solution and removing the dissociated DNA with LaCl3-precipitation, revealed strong activity to suppress the development of helper thymus-derived lymphocyte activity in mice. Moreover, almost all of the immunosuppressive activity originally found in the nuclear residue fraction after extraction with sodium citrate solution was recovered in 0.25 N HCl extract which mainly contains proteins. The nuclear components of tumor cells were also detected in the body fluid of tumor-bearing animals, as examined by the reactivity with a rabbit antiserum specific for some nuclear component of Ehrlich tumor cells. These results suggest that the immunosuppressive principle in the nuclei of Ehrlich tumor cells is a histone-like substance, and liberated into the body fluid from tumor cell nuclei in the tumor-bearing state.

Animals↗

Preferential generation of killer or helper T-lymphocyte activity directed to the tumour-associated transplantation antigens.

Induction of killer and helper T-cell activities towards transplantation antigens of two tumour cell lines was analysed in the allogeneic and syngeneic host combinations. The lymphoid cells from C57BL/6 mice immunized with allogeneic viable or mitomycin C-treated X-5563 plasmacytoma cells derived from C3H/He mice revealed both killer and helper T-cell activities against alloantigens, whereas cells from mice immunized with tumour cells killed by a freezing and thawing procedure revealed predominantly helper T-cell activity. On the other hand, when C3H/He mice were immunized with viable syngeneic X-5563 plasmacytoma or MM102 mammary tumour cells, the former generated preferentially killer T-cell activity, whereas the latter induced predominantly helper T-cell activity against tumour-associated transplantation antigens. Thus, immunization with transplantation antigen(s) does not always induce both helper and killer T-cell activities in parallel, but a certain antigenic system induces predominantly one type of T-cell response, thus indicating that two distinct subsets of helper and killer T cells against the transplantation antigen(s) can be raised independently without an absolute requirement of collaboration between these different T-cells subsets.

Animals↗