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Biomedical subjects

H Yamaue

Publications and source records attributed to H Yamaue.

At least 73 records · Page 4Linked to original sources
PubMed1990

[Clinical application of adoptive immunotherapy by cytotoxic T lymphocytes induced from tumor-infiltrating lymphocytes].

The tumor-infiltrating lymphocytes (TIL) were cultured with interleukin 2 (IL-2) to induce the cytotoxic T lymphocytes possessing autologous tumor-killing activity from 21 cancer patients (11 with solid tumor and 10 with malignant peritoneal or pleural effusions), and transferred into 7 patients as IL-2-activated TIL adoptively. The clinical application of activated TIL by adoptive transfer could result the complete regression of malignant pleural effusions in a patient with pancreatic cancer, and the nearly complete regression of malignant ascites in a patient with gastric cancer. The autologous tumor cells were isolated at the purity of more than 90% by Ficoll-Hypaque and Percoll discontinuous gradients, and then the TIL were cultured with IL-2 until 4 weeks. The optimal concentration of IL-2 was 1,500 IU/ml to obtain maximum proliferation and autologous tumor killing activity. The cytotoxic activities of activated TIL at 3 weeks-incubation was 72 +/- 15, 42 +/- 26, 27 +/- 21 and 22 +/- 15% against K562, Daudi, KATO-III and autologous tumor, respectively. By negative selection method, it was clarified that the killer cells recognizing autologous tumor consisted of CD4 or CD8 positive T lymphocyte in 43% of patients. The CD8 positive cells and CD56 positive cells increased, the CD4 positive cells and CD16 positive cells decreased by flow cytometry. The activated TIL could lyse not only cultured tumor cell lines, also other autologous tumor cells. The CD56+ cells were isolated by the Panning method, these cells could not lyse autologous tumor cells. Thus, it was indicated that the cytotoxic T lymphocytes recognizing autologous tumor could be generated from TIL and the adoptive immunotherapy of activated TIL was effective in cancer therapy.

Adult↗
PubMed1990

[Defective autologous mixed lymphocyte reaction (AMLR) in gastric cancer patients].

Autologous mixed lymphocyte reaction (AMLR) is an important reaction regulating the immune system in the various diseases. This is the first report investigating AMLR not only in peripheral blood but also in the spleen of gastric cancer patients. AMLR in the spleen of gastric cancer patients was significantly suppressed compared with that of peripheral blood of gastric cancer patients and patients without cancer. In investigation of AMLR composed of peripheral blood cells and spleen cells of gastric cancer patient, AMLR on splenic non-T cells as a stimulator was significantly suppressed compared with peripheral blood non-T cells as a stimulator. It suggests that abnormalities of non-T cells caused suppression of AMLR in the spleen of gastric cancer patients.

Female↗
PubMed1990

Successful adoptive immunotherapy with OK432-inducible activated natural killer cells in tumor-bearing mice.

We had demonstrated that the NK cell mediated cytotoxicity of murine spleen cells could be augmented by in vivo priming and subsequent in vitro challenge with a streptococcal preparation OK432, and the cell surface phenotype of induced killer cells was Thy-1+, asialo GM1+, suggesting that the activated cells were of NK lineage (OK-NK cell). We had also clarified that IL-2 played a major role in inducing the OK-NK cells via the production of IFN-gamma. In this study, we examined the effect of adoptive transfer of OK-NK cells on syngeneic tumors in mice. Mice were implanted with SP2 myeloma cells intraperitoneally (i.p.), or C26 colon adenocarcinoma cells subcutaneously to make the models of peritonitis carcinomatosa or solid tumor, and the OK-NK cells were transferred i.p. or intratumorally, adoptively. By the adoptive transfer of OK-NK cells, 92% of mice bearing SP2-tumor had be cured. The tumor growth of C26-solid tumor was inhibited, and the survival rate of mice bearing C26-tumor was significantly increased. The intratumoral remnants of 125I-labelled OK-NK cells were 61, 27 and 8% at 4, 12 and 36h after intratumoral transfer, respectively. By multiple transfer of OK-NK cells, the antitumor effect was more effectively augmented than that of a single transfer. Results in this study suggested that OK-NK cells could be useful for the therapy of cancer patients.

Adenocarcinoma↗
PubMed1990

Functional and phenotypic analyses of interleukin 2-activated tumor-infiltrating lymphocytes.

The tumor-infiltrating lymphocytes (TILs) were cultured with interleukin 2 (IL-2) to induce the activated killer cells possessing autologous tumor-killing activity, and analysed their cell surface phenotypes and assessed anti-tumor killing activity. Furthermore, the activated TILs were transferred into 7 patients adoptively resulting in complete remission in a patient with pancreatic cancer and partial remission in another patient with gastric cancer. The cytotoxic activities of activated TILs at 3 weeks-incubation was 72 +/- 15, 42 +/- 26, 27 +/- 21 and 25 +/- 15% against K562, Daudi, KATO-III and autologous tumor, respectively. The negative selection method, indicated that the killer cells recognizing autologous tumor cells consisted of CD4- or CD8-positive T lymphocytes and CD16- or CD56-positive natural killer cells. The activated TILs could not only lyse cultured tumor cell lines, but also autologous tumor cells.

Adult↗
PubMed1990

Impairment of autologous mixed lymphocyte reaction in the spleen and peripheral blood lymphocytes of patients with idiopathic portal hypertension.

The etiology of idiopathic portal hypertension (IPH) is unknown, although many studies have suggested that it might be an autoimmune disease. The autologous mixed lymphocyte reaction (AMLR) involves the proliferation of T lymphocytes when co-cultured with autologous non-T cells and may reflect immune control mechanisms in vivo. The AMLRs in the spleen and peripheral blood of three patients with IPH were measured and it was shown that the AMLRs both in the spleen and peripheral blood were significantly suppressed compared to those of normal healthy subjects. By allogeneic MLR, there was a tendency that the disturbance of non-T cells was more intensive than that of T cells. The AMLR of peripheral blood did not improve by splenectomy. Thus, the depressed cause of AMLR in patients with IPH was suggested mainly to disturbance of the antigen-presenting ability of non-T cells, and it was suggested that not only the spleen cells, but systemic immune disturbance caused the impairment of AMLR in IPH.

Aged↗
PubMed1989

[Role of interleukin 2 and interferon gamma in induction of activated natural killer cells by the streptococcal preparation OK432].

The natural killer (NK) cell mediated cytotoxicity to syngeneic tumor cells can be augmented by in vivo priming and subsequent in vitro challenge with the streptococcal preparation OK432. Supernatants of coculture of spleen cells with OK432 contained Interleukin 2 (IL-2) and Interferon (IFN), mainly IFN-gamma. As the anti-mouse IFN-gamma monoclonal antibody but not anti-mouse IFN-alpha antibody inhibited the induction of activated NK cells with OK432, the IFN-gamma participated in this response. The incubated spleen cells with IL-2 receptors increased with OK432 treatment by flow cytometry, and the NK cell and IFN activities of supernatants were also abrogated by the treatment with anti-mouse IL-2 receptor monoclonal antibody to block the interaction between IL-2 and these receptors of effector cells. By panning method, it was clarified that the incubated spleen cells with IL-2 receptors were responsible for the production of IFN-r. These results suggest that IL-2 plays a major role to induce the activated NK cells from murine spleen cells primed in vivo and subsequently challenged in vitro with OK432, by the production of IFN-gamma.

Animals↗
PubMed1989

[Successful adoptive immunotherapy with OK432-inducible activated natural killer cells on tumor-bearing mice].

We had demonstrated that the NK cell mediated cytotoxicity of murine spleen cells could be augmented by in vivo prime and subsequent in vitro challenge with the streptococcal preparation OK432, and the cell surface phenotype of induced killer cells was Thy 1+, asialo GM1+, suggesting the activated NK cells (OK-NK cell). The culture supernatants of spleen cells with OK432 possessed the activity of IL-2 and IFN-gamma, and the IL-2 played a major role to induce the OK-NK cells via the production of IFN-gamma. In this study, we examined the effect of adoptive transfer of OK-NK cells on tumor-bearing mice. The mice were implanted SP2 myeloma cells intraperitoneally (i.p.), or C26 colon adenocarcinoma cells subcutaneously (s.c.) to make the models of peritonitis carcinomatosa or solid tumor, and the OK-NK cells were transferred i.p. or i.t., adoptively. By the adoptive transfer of OK-NK cells, the 92% of mice bearing SP2-tumor had be cured. The tumor growth of C26-solid tumor was inhibited, and the survival rate of mice bearing C26-tumor was increased, significantly. The intratumoral remnants of 125I-labelled OK-NK cells were 61.27 and 8% after intratumoral transfer, respectively. By multiple transfer of OK-NK cells the anti-tumor effect was more augmented than that of a single transfer. Thus we recognized the anti-tumor effect of adoptive transfer of OK-NK cells on tumor-bearing mice, and suggested that OK-NK cells could be useful for the therapy of cancer patients.

Adenocarcinoma↗
PubMed1989

[Induction of activated natural killer cells by the streptococcal preparation OK432 (I). Induction from spleen cells of normal or tumor-bearing mouse primed in vivo and subsequently challenged in vitro with OK432].

The present study shows that natural killer cell-mediated cytotoxicity of BALB/c mouse spleen cells to syngeneic tumor cells was augmented by in vivo priming or in vitro stimulation with the streptococcal preparation OK432. The augmentation of spleen cell cytotoxicity to syngeneic tumor cells by in vivo priming alone with OK432 was lower than that obtained by in vitro stimulation alone with OK432. When the murine spleen cells primed in vivo with OK432 were rechallenged in vitro with OK432 at various intervals, the natural cytotoxicity was more strongly enhanced than that seen with in vitro stimulation alone. The cell surface phenotype of killer cells activated with OK432 was Thy1+ and asialo GM1+, suggesting the activated natural killer cell. Mice were transplanted with syngeneic colon adenocarcinoma cells, and primed in vivo with OK432, and then their spleen cells were subsequently challenged in vitro with OK432. These cells displayed a strong cytotoxic activity not only to the transplanted adenocarcinoma cells but also to other syngeneic tumor cells.

Animals↗
PubMed1989

Role of interleukin-2 and interferon-gamma in induction of activated natural killer cells from mice primed in vivo and subsequently challenged in vitro with the streptococcal preparation OK432.

The natural-killer(NK)-cell-mediated cytotoxicity to syngeneic tumor cells can be augmented by in vivo priming and subsequent in vitro challenge with the streptococcal preparation OK432. Supernatants of cocultures of spleen cells with OK432 contained interleukin-2 (IL-2) and interferon (IFN), mainly IFN-gamma. As the anti-(mouse IFN-gamma) monoclonal antibody but not anti-(mouse IFN-alpha) antibody inhibited the induction of activated NK cells with OK432, the IFN-gamma participated in this response. The enhancement of NK cell activity and production of IL-2 were partially inhibited by the pretreatment of spleen cells with mitomycin C or irradiation, and were completely abolished by pretreatment with actinomycin D. The IL-2 activity after treatment with various metabolic inhibitors ran parallel to the NK activity in a system augmented with OK432. The activity of incubated spleen cells with IL-2 receptors was increased by OK432 treatment, and the NK cell and IFN activities of supernatants were also abrogated by the treatment with anti-(mouse IL-2 receptor) monoclonal antibody, to block the interaction between IL-2 and these receptors of effector cells. The panning method clarified that the incubated spleen cells with IL-2 receptors are responsible for the production of IFN-gamma. These results suggest that IL-2 plays a major role in inducing the activated NK cells from murine spleen cells primed in vivo and subsequently challenged in vitro with OK432, by the production of IFN-gamma.

Adjuvants, Immunologic↗
PubMed1987

Induction of activated natural killer cells from murine spleen cells primed in vivo and subsequently challenged in vitro with the streptococcal preparation OK432.

The present study shows that natural killer cell-mediated cytotoxicity of BALB/c mouse spleen cells to syngeneic tumor cells was augmented by in vivo priming or in vitro stimulation with the streptococcal preparation OK432. The augmentation of spleen cell cytotoxicity to syngeneic tumor cells by in vivo priming alone with OK432 was lower than that obtained by in vitro stimulation alone with OK432. When the murine spleen cells primed in vivo with OK432 were rechallenged in vitro with OK432 at various intervals, the natural cytotoxicity was more strongly enhanced than that seen with in vitro stimulation alone. The cell surface phenotype of killer cells activated with OK432 was Thy 1+ and asialo GM1+, suggesting the activated natural killer cell. Next, mice were transplanted with syngeneic colon adenocarcinoma cells, and primed in vivo with OK432. These spleen cells were subsequently challenged in vitro with OK432. These spleen cells displayed a strong cytotoxic activity not only to the transplanted adenocarcinoma cells but also to other syngeneic tumor cells.

Adenocarcinoma↗
PubMed1985

Microwave tissue coagulation applied clinically in endoscopic surgery.

On the basis of the ample basic knowledge acquired by repeated experiments, we applied our microwave tissue coagulator in endoscopic surgery, in a total of 59 patients with benign and malignant lesions encountered during a period of two years beginning in July, 1981. Hemostasis was achieved in 96.5% of all the cases with bleeding lesions in the digestive tract. Stenosis was alleviated in 86% of the cases with esophageal or rectal stenosis. Furthermore, the technique was successfully used for hemostasis and tumor reduction in inoperable early cancer cases. Our device is unique in that the electrode is thrust into tissue, which assures us of a satisfactory result. In this point, it must be clearly distinguished from an electrocoagulator or a laser coagulator, which is associated with a risk of injuring intact tissue. The range of coagulation is adjustable by changing the length of the monopolar antenna and electric output, and by employing a coaxial cable of appropriate thickness. In conclusion, our microwave tissue coagulator can be used easily and safely in clinical endoscopic surgery.

Adult↗