Biomedical subjects

K Orita

Publications and source records attributed to K Orita.

At least 253 records · Page 14Linked to original sources

PubMed1989

The augmentation of lymphokine-activated killer cells induced by partial hepatectomy in mice.

Spleen cells that are cultured with interleukin 2 for as short a time as 4 days develop the ability to lyse syngeneic natural killer-resistant tumor cells but not to lyse syngeneic lymphoblasts. When mice were subjected to partial hepatectomy (HEP), the spleen cells exhibited not only an augmentation of natural killer activity, but also an augmentation of in vitro induction of lymphokine activated killer (LAK) cells. Furthermore, the LAK cells exhibited lytic activities against syngeneic lectin-induced lymphoblasts and regenerating liver cells. The sensitivity of regenerating liver cells to lysis by LAK cells was detected as early as one day after HEP, and continued until day 14. Analysis by cell depletion techniques using monoclonal antibodies and complement, as well as discontinuous gradient sedimentation, indicated that the LAK cells activated by HEP were Thy-1+, Lyt-2+, asialo GM1+ and Lyt-1-, lymphocytes with a low density. After the intravenous (i.v.) administration of anti-asialo GM1 before HEP, the in vitro induction of LAK cells was remarkably inhibited.

Animals↗

PubMed1989

Clinical values for an index predicting postoperative residual liver function by pre-operative liver-scintigraphy in patients with liver disease.

Hepatic resection is essential in treating hepatocellular carcinoma. However, before an operation, it is difficult to predict the functional reserve in the remnant following massive resection. We devised an original method by which effective liver volume was measured by liver scintigraphy. In order to predict the residual liver function before hepatic resection in a preoperative radiocolloid study, we obtained a predictive index by combining the K values with effective liver volumes which seemed to have the estimated residual liver function. Twenty-one patients with liver or biliary tract disease were selected at random for the present study. We divided them into 3 groups in accordance with prognosis after hepatic resection. There were statistically significant difference between the deceased group who died from hepatic failure and the group who died from causes other than hepatic failure; and between the deceased group who died from hepatic failure and the living group in the preictive index (p less than 0.01). Our data suggest that if the predictive index is above 0.45, the probability of hepatic failure after hepatic resection is low. We concluded that our predictive index is useful to use in preoperative prediction of post-hepatectomic residual liver function.

Aged↗

PubMed1989

The effect of anti-interleukin 2 monoclonal antibody treatment on the survival of rat cardiac allograft.

The effect of anti-interleukin 2 monoclonal antibody (anti-IL2 MoAb) and the accumulation of intravenously administered 125I-labeled anti-IL2 MoAb were examined in heterotopic rat cardiac allografts. Mouse anti-human recombinant IL2 MoAb was obtained by the hybridoma technique. The anti-IL2 MoAb, termed 8H-10, was an IgG2a which inhibited IL2-driven [3H]TdR incorporation in cytolytic T lymphocyte line cells at a dilution of 2(6). 8H-10 was injected iv at a dose of 200 micrograms/day for 8 consecutive days, beginning on the day of transplantation. Hearts from F344 rats (RT11v1) were transplanted into ACI recipient rats (RT1av1). The mean survival time was 7.6 +/- 0.8 days in untreated controls, 9.0 +/- 1.2 days in additional controls treated with mouse anti-sheep red blood cell monoclonal antibody, and 25.3 +/- 18.4 days in the anti-IL2 MoAb (8H-10)-treated group (P less than 0.05). Furthermore, the accumulation of intravenously administered 125I-labeled anti-IL2 MoAb (8H-10) was specifically seen in the grafted heart. In conclusion, these results suggest that IL2 may play an important role in allograft rejection and that anti-IL2 MoAb may serve as a useful immunosuppressive agent in clinical transplantation.

Animals↗

PubMed1989

Induction of antiidiotypic antibodies by donor-specific blood transfusions. Establishment of a human-mouse hybridoma secreting the MLR-inhibiting factor.

We describe a patient transfused with 200 ml of donor fresh whole blood three times at 2-week intervals. Three weeks after the last transfusion, transplantation and splenectomy were done at the same time. Splenic cells from this DST pretreated patient were fused with murine myeloma cells (X63-Ag8, 653). With DST pretreatment, various clones were developed in vivo, and finally 69 human immunoglobulin-secreting clones were obtained. Modulation of the alloantigen-specific MLR by supernatants from 69 clones showed various degrees of suppression or augmentation. The hybridoma clone 7 and clone 2, which had been secreting IgG antibody for more than 6 months, showed some degree of suppression in the alloantigen-specific MLR (mean suppression = 63%, 46% respectively). According to the result of MLR, clone 7 antibody was directed against recipient lymphocytes and clone 2 antibody was against donor lymphocytes. Immunoprecipitation was carried out by clone 7-IgG and clone 2-IgG. Clone 7-IgG specifically precipitated 1 molecule from the recipient lymphocyte with a molecular weight of 120 KD, similar to the molecular weight range reported for T cell receptors. Clone 2-IgG precipitated a 20 KD molecule from the donor lymphocyte. The data suggest that DST induces antibodies directed against the blood donor alloantigen-specific receptors on the recipient's T lymphocytes--and, at the same time, induces antibodies against donor lymphocyte antigens. These antibodies may be essential to prolongation of kidney allograft survival following DST.

Blood Transfusion↗

PubMed1989

Preventive and antiproliferative effects of tumor necrosis factor against experimental hepatic metastases of mouse colon-26 tumor.

This investigation was undertaken in order to assess both the preventive and antiproliferative effects of tumor necrosis factor (TNF) in a hepatic metastasis model, by means of inoculation of mouse colon-26 tumor cells into the portal vein via the superior mesenteric vein in male CDF1 mice, aged 5 weeks. Continuous 10-day administration of natural human TNF-alpha (nHuTNF-alpha) following the tumor cell inoculation caused no reduction but rather an increase in the number of hepatic metastases. However, pretreatment with this preparation daily for 10 days before the inoculation caused a remarkable decrease in the number of hepatic metastases. This prophylactic effect was reversed by the intravenous administration of anti-asialo GM1 antibody 24 h before the inoculation. The result of immunoperoxidase staining of liver specimens suggested that organ-associated natural killer cells might play a role in the metastatic inhibition. An apparent antiproliferative effect on metastatic liver tumors was also recognized following injection of nHuTNF-alpha from the 10th day after the inoculation. Thus, TNF appears to have important effects upon the host immune system, acting against liver metastases.

Animals↗

PubMed1989

Differences in intracellular calcium mobilization by interferon-beta and interferon-gamma in RPMI-4788 cells.

Human interferon (IFN) stimulates a 1.5- to 1.7-fold transient increase in the concentration of cytoplasmic-free calcium ion ([Ca2+]i) within 10-20 s upon exposure of RPMI-4788 cells to IFN. This early event of IFN-induced [Ca2+]i mobilization was measurable by loading the cells with Fura-2AM, a fluorescent Ca2+ indicator. The mobilization induced by IFN-beta or IFN-gamma was dependent on the concentration of each IFN. The increased [Ca2+]i gradually returned to its resting level within 60 s. The addition of EGTA (0.5-10 mM) to medium induced a marked decrease in the amount of [Ca2+]i mobilized by IFN-beta and a partial decrease by IFN-gamma. This finding suggests that the mechanisms of [Ca2+]i mobilization by IFN-beta and IFN-gamma might be different. While IFN-beta-induced mobilization may be mainly from an influx of the extracellular calcium ion ([Ca2+]o), IFN-gamma-induced mobilization may be a summation of an influx of [Ca2+]o and a release from intracellular Ca2+ stores.

Calcium↗

PubMed1989

Antitumor effect of natural human tumor necrosis factor-alpha and natural human interferon-alpha in combination against human cancer transplanted into nude mice.

We studied the in vivo antitumor effects of natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural human interferon-alpha (nHuIFN-alpha), both of which were produced by HVJ (hemagglutinating virus of Japan)-stimulated acute lymphatic B cell leukemia line, BALL-1 cells. To clarify the interaction between nHuTNF-alpha and nHuIFN-alpha, we used novel experimental models of lung metastasis and intraabdominal carcinomatosis which we developed in nude mice using a human tumor line, RPMI 4788. While the intravenous administration of nHuTNF-alpha or nHuIFN-alpha alone inhibited lung metastasis, the two cytokines given in combination synergistically inhibited lung metastasis. In a comparative study, nHuTNF-alpha and recombinant human interferon-gamma (rHuIFN-gamma) in combination also synergistically inhibited lung metastasis. Treatment with nHuTNF-alpha and nHuIFN-alpha combined significantly prolonged the survival of nude mice with intraabdominal carcinomatosis. Complete regression of five different human tumor xenografts was achieved by the simultaneous intratumoral injection of nHuTNF-alpha and nHuIFN-alpha. Histological examination revealed that tumor cell lysis occurred 24 h after the intratumoral administration of the cytokines. No significant signs of toxicity to nude mice were observed at any dose tested. The synergism of nHuTNF-alpha and nHuIFN-alpha may allow treatment at a relatively low dose range, thus minimizing side effects. The wide range of anticancer activity of these agents may provide better therapeutic efficacy. The in vivo assay systems which we have developed are useful for the analysis of the biological activities and interactions of cytokines and chemotherapeutic drugs.

Abdominal Neoplasms↗

PubMed1989

Effect of serum fractions obtained from cancer patients by double filtration plasmapheresis combined with natural tumor necrosis factors and cyclophosphamide on murine pulmonary metastases.

We investigated the effects of fractionated sera obtained from cancer patients by double filtration plasmapheresis (DFPP) plus antitumor agents on murine pulmonary metastasis. Fractions of the sera, in combination with natural human tumor necrosis factors (nTNF) and cyclophosphamide (Cy), were systemically administered to Lewis lung carcinoma-bearing mice. When the second filtrate (a plasma fraction containing substances composed of smaller molecular weight compounds) combined with low-dose nTNF (1,000 U/kg) and Cy (250 micrograms/kg) was administered to the mice, the degree of metastasis was significantly suppressed compared with the control group (p less than 0.01). In contrast, the discarded fluid (a plasma fraction containing larger molecular weight compounds) combined with the same doses of nTNF and Cy caused little inhibition of metastasis. Also, the discarded fluid significantly suppressed natural killer activity compared with normal sera (p less than 0.01). The results suggested that DFPP combined with nTNF and Cy is an efficient procedure to remove immunosuppressive factors from the sera of cancer-bearing hosts, to enhance the host antitumor immunity, and to suppress tumor proliferation.

Animals↗

PubMed1989

The effect and distribution of a protein-bound polysaccharide preparation, PSK (Krestin), intratumorally injected prior to surgery into gastric cancer patients.

In order to improve the postoperative prognosis of gastric cancer patients we have performed preoperative endoscopic intratumoral administration of various biological response modifiers. In the present study we have investigated the kinetics and the immune response augmenting effect of intratumorally injected PSK, a protein-bound polysaccharide preparation, by immunohistochemical methods using anti-PSK antibody and various other antibodies. PSK-containing cells were located in the tumor tissues and follicular marginal zones of regional lymph nodes. Intratumorally administered PSK appeared to be phagocytized by the histiocytes and to cause them to become antigen-presenting cells. These cells may play a major role in augmenting immune responses in gastric cancer patients.

Adult↗

PubMed1989

Antitumor effect of natural human tumor necrosis factor-beta against Lewis lung carcinoma in mice and its synergistic potentiation by interferon.

We investigated the antitumor effect of purified natural human tumor necrosis factor-beta (nHuTNF-beta) produced by human acute lymphoblastic leukemia BALL-1 cells stimulated with HVJ on pulmonary metastatic tumors of Lewis lung carcinoma (3LL) transplanted into BDF1 mice. nHuTNF-beta showed antiproliferative effects on metastatic tumors in a dose-dependent manner when administered daily for 10 days by the intravenous route. Histological examination of the tumors treated with nHuTNF-beta revealed that the tumor size and number of metastases were much reduced. Lytic cellular changes, including cytoplasmic vacuolation, loosening of the intercellular junction and both cytoplasmic and nuclear swelling, were found, but tumor necrosis was not. These findings indicate a therapeutic effect of Grade IIa according to the histological criteria of Shimosato and Ohboshi. In addition, synergistic augmentation of the antiproliferative effects of nHuTNF-beta by natural murine interferon-alpha/beta (nMu-IFN-alpha/beta) or recombinant murine interferon-gamma (rMuIFN-gamma) was recognized by median effect plot analysis. The results suggested that nHuTNF-beta may well deserve clinical trial as a new immunotherapeutical agent for human cancer.

Animals↗

PubMed1989

[Studies on AFP-producing capacity and some other properties of human hepatoma cells treated with various anticancer drugs].

The effect of various anticancer drugs on alpha-fetoprotein (AFP) secretion and some other properties of human hepatoma cells was investigated in vitro with the following results. (1) There was a high correlation between AFP secretion and cell number after treatment of human hepatoma cells with anticancer drugs and the amounts of AFP secreted per 10(4) cells per 72 hours (AFP-secreting capacity) were not affected within therapeutically achievable concentrations (TAC). (2) The AFP-secreting capacity was affected with some exceptions in the cells treated with higher concentration of drugs than TAC. Furthermore, chromosomal and morphological aberrations in the similarly treated cells, were also observed, suggesting the relationship between the change of AFP-producing capacity and that of some other properties.

Antineoplastic Agents↗

PubMed1989

Synergistic antitumor effects of natural human tumor necrosis factor-alpha and natural human interferon-alpha or -gamma on human cancer cell lines.

This study was conducted to assess the enhanced antitumor effects of natural human tumor necrosis factor alpha (nHuTNF-alpha) and natural human interferon alpha or gamma (nHuIFN-alpha or -gamma), in combination, on ten human cancer cell lines. The cell lines tested were colon cancer (RPMI4788), lung cancer (PC10), gastric cancer (MKN-1 and MKN-28), nasopharyngeal cancer (KB), leukemia (K562), lymphoma (Daudi), Liver cancer (H-7) and breast cancer (ZR-75-30 and ZR-75-1). A mixture of nHuTNF-alpha and nHuIFN-alpha (1:1, by unit) showed cytotoxic effects on nHuTNF-alpha resistant cell lines such as RPMI4788, KB and Daudi or nHuIFN-alpha resistant cell lines such as KB, and ZR-75-1, as well as on nHuTNF-alpha or nHuIFN-alpha sensitive cells. A synergistic antitumor effect occurred in four cell lines (RPMI4788, PC10, Daudi and ZR-75-1) treated with a combination of nHuTNF-alpha and nHuIFN-alpha. Also, a combined treatment with nHuTNF-alpha and nHuIFN-gamma (1:1/100, by unit) showed cytotoxic effects on nHuTNF-alpha or nHuIFN-gamma resistant cell lines such as MKN-1, MKN-28, Daudi, H-7 and ZR-75-1. A synergistic antitumor effect occurred in eight cell lines (RPMI4788, PC10, MKN-1, MKN-28, KB, Daudi, H-7 and ZR-75-1). Thus, the combined treatment with nHuTNF-alpha and nHuIFN-alpha or -gamma expanded the spectrum of sensitive cells. These results indicate that the combined use of nHuTNF and nHuIFN may provide a certain approach to cancer treatment.

Antineoplastic Agents↗

PubMed1989