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Biomedical subjects

K Orita

Publications and source records attributed to K Orita.

At least 343 records · Page 19Linked to original sources

Role of MLC serum inhibitory factors in high MLC-reactive kidney transplant recipients pretreated with donor-specific blood transfusion (DST).

In order to clarify the beneficial effect of donor-specific blood transfusions (DST) on kidney allograft survival, sera from 16 patients treated with DST were studied using the mixed lymphocyte culture (MLC) serum inhibition test. The results demonstrate that MLC inhibitory factors could be induced in the serum of the recipients after the completion of DST, and that these factors are directed against cells of the recipient but not against cell from the donor. Regarding the correlation with rejection episodes and clinical outcome, a significant improvement in renal transplant survival and reduction in rejection episodes was observed when MLC inhibitory factors were present in post-DST sera. These data suggest that such factors may contain antibodies directed against recognition sites on T lymphocytes, e.g., anti-idiotypic antibodies, and be associated with prolonged graft survival of living-related, high MLC-reactive one-haplotype-mismatched kidney.

Adult↗

Primary cultures of human livers and their albumin-producing capacity.

Primary cultures of surgically obtained noncancerous portions of human liver tissues were made. Liver tissues were poorly dissociated with collagenase, but well dissociated with dispase. The yield and viability of cells were improved somewhat when dissociated with collagenase followed by dispase. The mean cell yield was 1.1 X 10(6) cells/g liver. The epithelial-like morphology of the dissociated liver cells was maintained for about one week, but thereafter degenerative alteration of cells was observed. In liver explant culture, an active outgrowth of cells was observed for more than one month. Albumin production in culture fluids from dissociated livers was detectable for about 2 weeks, but later became undetectable, while that from explant culture was detectable for at least one month. These data demonstrate that adult human hepatocytes can be isolated from noncancerous portions of livers with relatively high yield, and that albumin production of the dissociated cells is detectable for several days.

Adult↗

Suppression of natural killer cell activity by surgical stress in cancer patients and the underlying mechanisms.

The influence of surgical stress on the natural killer (NK) activity of peripheral blood lymphocytes in patients with carcinoma of the lung or gastrointestinal system was studied. The peripheral blood lymphocytes of the patients showed a marked decrease in NK activity against K-562 cells as target cells 1-2 days after surgery. The activity remained lowered for 2 weeks after thoractomy and for 1 week after laparotomy. No appreciable suppression of NK activity was observed with normal human peripheral blood lymphocytes preincubated with postoperative patient sera. Peripheral blood mononuclear cells obtained postoperatively from patients lost NK activity after ultraviolet irradiation, without any detectable loss of viability. Such irradiated mononuclear cells showed inhibition of NK activity after a 24-hour preincubation with peripheral blood lymphocytes from normal subjects. Similar suppressive activity was demonstrable in a fraction of mononuclear cells with adhesiveness to plastic petri dishes, while non-adherent cells had no such activity. When added immediately to the cytotoxicity assay system without the 24-hour preincubation, patient mononuclear cells caused no inhibition of NK activity, whereas adherent cells from normal subjects enhanced NK activity. The findings seems to indicate that, following surgical stress, plastic dish-adherent peripheral blood mononuclear cells become deprived of NK helper activity and exert suppression, thus causing postoperative depression of NK activity.

Gastrointestinal Neoplasms↗

Artificial liver support for postoperative hepatic failure with anion exchange resin (BR-601).

An artificial liver support system for plasma exchange and plasma perfusion through BR-601 resin using a membrane separator was applied to 5 patients with postoperative liver failure. Percent absorption of total and direct bilirubin, and of bile acids were 77.1 +/- 6.4, 78.4 +/- 6.1, and 93.4 +/- 3.6%, respectively, when 250 ml of plasma was treated. Percent reductions in total and direct bilirubin, and in bile acids were 24.5 +/- 5.8, 25.5 +/- 5.8 and 30.9 +/- 8.5%, respectively. In contrast, percent reductions in total and direct bilirubin, and in bile acids by plasma exchange were 30.9 +/- 13.3, 34.5 +/- 12.5 and 24.2 +/- 8.5%, respectively. The coma grade was improved in 4 out of 5 cases, but unfortunately the patients did not recover. In conclusion, plasma perfusion through BR-601 resin is expected to play a promising role in artificial liver support systems because of its capacity to absorb bilirubin and bile acids.

Adult↗

Beneficial effect of donor-specific blood transfusions (DST) on living-related kidney allograft survival.

The survival rate of 19 patients who underwent living-related kidney transplantation after donor-specific blood transfusions (DST) was compared with that of 32 historical controls receiving transplants without DST. The graft survival rate of the DST group was 82% after two and three years. The graft survival rate of the DST group was significantly better than the 53% rate after two years obtained with the 32 historical controls (p less than 0.05). We tested sera from 16 DST-treated recipients to study the beneficial effect of DST on kidney allograft survival using the mixed lymphocyte culture (MLC) serum inhibition test. The results demonstrated that MLC inhibitory factors were induced in the serum of the recipient after completion of DST. This inhibition of MLC was observed by treatment of responder lymphocytes with serum obtained three weeks after DST plus rabbit complement. The inhibitory effect was also specific for responder cells in anti-donor MLC. Regarding the correlation with rejection episodes, these MLC inhibitory factors were often observed in the non-rejection group (p less than 0.05). The data suggest that such factors may be anti-idiotypic antibodies and be associated with prolonged graft survival.

Adult↗

[Effect of human recombinant-gamma interferon on the immune function of peripheral blood lymphocytes in cancer patients].

We administered recombinant gamma-interferon (ReIFN-gamma) daily to 7 cancer patients, and the effect on the immune function of peripheral blood lymphocytes was studied. Following the administration of ReIFN-gamma, no characteristic changes were observed in leukocyte count, lymphocyte count, OKT4/OKT8 or Leu 7. Natural killer cell cytotoxicity was augmented in all cases from the first week of administration and retained a high level of activity during the period of treatment. In contrast, the blastogenesis of PBL with PHA decreased from the first week. Suppressor cell activity was augmented from the first week and maintained throughout this period. As to clinical effect, two patients who had metastatic liver tumors showed a response to the administration of ReIFN-gamma.

Aged↗

[Synergistic effect of recombinant human interferon-beta and -gamma on human colon cancer transplanted into nude mice].

The antitumor effect of recombinant human interferon-beta (r IFN-beta) and recombinant interferon-gamma (r IFN-gamma) was studied in vivo using a pulmonary metastatic model involving nude mouse human colon cancer xenografts. The results indicated that both r IFN-beta and r IFN-gamma had an inhibitory effect on pulmonary metastases. Furthermore, a combination of r IFN-beta and r IFN-gamma acted synergistically in the inhibition of pulmonary metastases. These results suggested that a combination of r IFN-beta and -gamma could be a most effective form of interferon therapy for cancer.

Animals↗

Complete regression of mouse hepatoma transplanted after partial hepatectomy and the immunological mechanism of such regression.

We have investigated the effect of partial hepatectomy (HEP) on tumor growth. MH-134 hepatoma cells, which were inoculated in syngeneic C3H/He mice from 3 to 10 days after HEP, grew with a linear increase in size until 7 days, began to regress, and disappeared 14 days after the inoculation. The survival rate was 100%, and the recurrence of tumor was not observed during the following 4 mo. On the other hand, the growth of another syngeneic tumor, X-5563, and of an allogeneic Ehrlich tumor was not affected by HEP. When MH-134 tumor cells were inoculated 7 days before or 15 days after HEP, tumor regression was not observed. The Winn assay showed the presence of tumor-neutralizing activity in spleen cells of MH-134 tumor-regressed mice. Cytotoxic activity against MH-134 tumor cells was also detected in the spleen cells. Analysis by using monoclonal antibodies showed that the effector cells were Thy-1+ and Lyt-2+ cells. Thus, HEP and the following liver cell regeneration may play a role in augmentation of specific immune response to the transplanted hepatoma cells.

Animals↗

Augmentation of anti-tumor activity by immunization with Mycobacterium tuberculosis (Tbc) and tuberculin-coupled tumor cells.

The anti-tumor effect of immunization with heat-killed Mycobacterium tuberculosis (Tbc) and Tuberculin (PPD)-coupled syngeneic tumor cells was examined in vivo. Three tumor cell lines were employed. Immunization of Tbc-primed BALB/c mice with PPD-coupled syngeneic Meth-A tumor cells displayed a potent anti-tumor effect on viable Meth-A cells inoculated subcutaneously. Neither PPD-coupled LLC (Lewis Lung Carcinoma) cells nor sonicated PPD-coupled Meth-A cells were capable of immunizing these mice. PPD-coupled syngeneic whole tumor cells were indispensable for induction of this tumor-specific resistance. Immunization of Tbc-primed C3H/He mice with PPD-coupled syngeneic MH134 tumor cells did not elicit anti-tumor activity against MH134, but additional pretreatment of mice with cyclophosphamide brought on an anti-tumor effect. Antimetastatic reactivity was investigated in C57BL/6 mice bearing LLC, with a reduction in metastases noted. This antimetastatic effect was observed even when the mice were immunized with PPD-coupled LLC cells three days after removal of the initial tumor. Immunization with Tbc and PPD-coupled Meth-A cells together with intraperitoneal administration of murine or rat interleukin 2 (IL 2) further augmented anti-Meth-A resistance. Murine IL 2 further inhibited tumor growth during the early stage, while rat IL 2 showed an anti-tumor effect throughout the course of tumor growth.

Animals↗

Effect of lymphotoxin-like substance (OH-1) on metastatic tumor proliferation.

The effect of a lymphotoxin-like substance, OH-1, released by human acute lymphatic leukemia BALL-1 cells, on metastatic tumor proliferation was investigated in BDF1 mice with transplanted Lewis lung carcinoma cells. Mitomycin-C, cyclophosphamide and adriamycin were used as control agents. The effect of OH-1 on metastases, as determined by comparison of the numbers of pulmonary nodules and by 3H-thymidine labeling indices, was significant. Also, investigation of the effect of OH-1 on host immunity showed that, while the control preparations had considerable side effects, immunodepression and emaciation were not noted with OH-1. As to direct cytotoxicity, OH-1 is principally cytostatic in activity and effects cell progression delay in both the G1 and G2 phases.

Animals↗

[Clinical evaluation of schizophyllan (SPG) in advanced gastric cancer (the second report)--a randomized controlled study].

We reported previously that Schizophyllan (SPG) combined with MMC + 5-FU (MF regimen) or Tegafur (F regimen) had a significant life-prolonging effect over chemotherapeutic regimens in patients with inoperable and recurrent gastric cancer in a randomized controlled study. In the present paper, we have further investigated the effect of SPG on life-span followed-up for more than 2 years. A significant life-prolonging effect of SPG was reconfirmed in patients given either the MF regimen (154 patients) or the F regimen (213 patients). Thus, SPG combined with chemotherapeutics has proved to be useful for treating patients with inoperable and recurrent gastric cancer, resulting in a significant prolongation of life-span without serious side effects despite having no influence on tumor size.

Antineoplastic Combined Chemotherapy Protocols↗