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Biomedical subjects

K Orita

Publications and source records attributed to K Orita.

At least 109 records · Page 6Linked to original sources
PubMed1994

Positive interactions between human interferon and cepharanthin against human cancer cells in vitro and in vivo.

A human tumor microcytotoxicity-viable cell-staining assay was used to test the antiproliferative effect of recombinant human interferon-beta or -gamma alone and in combination with bisbenzylisoquinoline alkaloid cepharanthin against four human tumor cell lines in vitro and in nude mice. Results obtained in the in vitro study indicate that combinations of interferon-beta/-gamma with cepharanthin show synergistic and, occasionally, additive antiproliferative effects in a dose-dependent manner on tumor viable cell-staining assay. Interferon-gamma combined with cepharanthin suppressed the growth of all four human tumor cell lines (RPMI 4788, PC 10, HeLa, ZR-75-1), and this enhanced antiproliferative effect was not dependent on the interferon species involved, including interferon-beta and -gamma. In an experimental model of pulmonary metastasis, in which human colon tumor cells were inoculated i.v. into nude mice, interferon-gamma alone exerted significant inhibitory activity against pulmonary metastasis in a dose-dependent manner, and cepharanthin alone also significantly inhibited metastasis. Furthermore, a combination of interferon-gamma with cepharanthin resulted in a considerable suppression of pulmonary metastasis. These studies indicate that due to their therapeutic potential, combinations of recombinant human interferon-beta or -gamma with cepharanthin might be a promising therapy for pulmonary metastasis of human cancers.

Alkaloids↗
PubMed1994

Endotoxin-induced liver injury after extended hepatectomy and the role of Kupffer cells in the rat.

Liver injury by endotoxin given during regeneration following a 70% hepatectomy was examined in Wistar rats. The intravenous administration of endotoxin caused an elevation of the serum GPT level, and severe damage of the remnant liver showing centrilobular necrosis with microthrombi. The highest mortality was induced by the administration of endotoxin to rats 24 h after hepatectomy. Kupffer cells in the regenerative phase of the liver showed an augmented in vitro production of both tumor necrosis factor (TNF) and interleukin-1 (IL-1). The simultaneous administration of heparin and prostagladin E1 (PGE1), which is known to suppress the production of TNF and IL-1, reduced the magnitude of liver injury and the mortality of these rats. The absence of any direct cytotoxic effect of TNF and IL-1 against liver cells suggested that the cytokines, produced by Kupffer cells, play an important but indirect role in the remnant liver injury induced by endotoxin after hepatectomy.

Animals↗
PubMed1994

Kupffer cell function in chronic liver injury and after partial hepatectomy.

The reticuloendothelial system (RES) plays an important role in the biological defense system. In the liver, Kupffer cells are the main constituent of the RES, and when their function is impaired postoperative complications may more often occur. By using 99mTc-labeled human serum albumin millimicrospheres (99mTc-HSA-MM) combined with assessment of single photon emission computed tomography (SPECT), we have attempted to determine the function of Kupffer cells independently of the hepatic blood flow. First, Kupffer cell function in rats with chronic liver injury caused by CCl4 was studied. The hepatic uptake rate in chronic liver injury was decreased, and a reduced phagocytic activity of the Kupffer cells was noted. The parameter concerning Kupffer cell degradation, the excretion rate (k), was markedly decreased in the early period of chronic liver injury. Changes in Kupffer cell function after 30% and 70% hepatectomy were also studied. After 30% hepatectomy, the excretion rate was decreased on the first postoperative day (POD), and it was increased beyond that found after sham operation on the 3rd POD. In contrast, slower recovery of uptake rate was demonstrated. After 70% hepatectomy, both uptake and excretion rates were markedly reduced, and recovery was prolonged beyond the 5th POD. The hepatic uptake was not parallel with the excretion rate in either experiment. These results suggest that the method that measures the hepatic excretion rate may provide a better assessment of Kupffer cell function than the current uptake measurement with radiolabeled colloid.

Animals↗
PubMed1994

Enhancement of antitumor cytotoxicity of hepatic lymphocytes by oral administration of PSK.

We have studied the effects of oral administration of a biological response modifier (BRM), PSK, on hepatic lymphocytes. Many PSK positive cells were observed in the liver by anti-PSK antibody staining. Flow cytometric analysis revealed an increase in the number of OX8 (CD8) positive cells in the non-parenchymal nonadherent liver cells (NPNALCs) which were isolated from the liver enzymatically digested by perfusion with collagenase. NPNALCs were fractionated by discontinuous density gradient centrifugation, and the number and cytotoxic activity of these cells were examined in each fraction. Although the yield of lymphocytes in each fraction was not significantly increased by the oral administration of PSK, the natural killer (NK) activity was markedly enhanced in low density fractions. The present findings suggest that oral administration of PSK is effective for prevention of liver metastasis through the augmentation of organ-associated NK activity.

Adjuvants, Immunologic↗
PubMed1994

Augmentation in cytotoxicity of lymphnode lymphocytes by OK-432.

It has been demonstrated that natural killer (NK) cell activity of lymphnode lymphocytes (LNL) is very low and hardly augmented by interferon. In this study, OK-432 was injected into the gastric cancer mass through endoscopy one week before the operation, through which NK activity of LNL was significantly increased. A single cell assay could divide the OK-432-injected patients into two groups; responder and non-responder. In responders, the increased activity induced by OK-432 was found also in the distal lymphnodes.

Adjuvants, Immunologic↗
PubMed1994

Lectin-activated killer cells rapidly induced by pokeweed mitogen conjugated beads and their in vivo antitumor effects.

Pokeweed mitogen (PWM) was found to induce rapidly killer cells in human peripheral blood mononuclear cells (PBMC). To avoid PWM contamination in infused lymphocytes, PBMC were stimulated with PWM-coated beads, CMC-1. One hour of stimulation with CMC-1 led to distinct cytotoxic activity in PBMC at 7 h, this reaching a peak at 23 h in the following in vitro culture. The cytotoxic activity and target cell spectrum of CMC-1-activated killer (PWM-AK) cells were similar to those of lymphokine-activated killer (LAK) cells, the precursor cells of PWM-AK cells, as are those of LAK cells which are also low-density lymphocytes. The in vivo antitumor effects of PWM-AK cells were examined in nude mice with peritoneal carcinomatosis generated by the human colon cancer cell line, RPMI 4788. The intraperitoneal (i.p.) injection of PWM-AK cells immediately after stimulation with CMC-1 significantly prolonged the survival of tumor-bearing mice, suggesting that these cells could be of value for clinical cancer therapy.

Animals↗
PubMed1994

The effect of deoxyspergualin (DSG) on rejection and graft-versus-host disease (GVHD) after small bowel transplantation.

Both rejection and graft-versus-host-disease may occur after fully allogeneic small bowel transplantation. In this study, we established unidirectional models of rejection and GVHD in rats and evaluated the efficacy of 15-deoxyspergualin (DSG). When F1 small bowel was transplanted into LEW rats (rejection model) the graft was acutely rejected. The administration of DSG (5 mg/kg per day for 10 days) significantly prolonged the survival, but was efficacious only when used prophylactically. When a unidirectional GVHD model (F1 --> LEW SBTx) was examined, the administration of DSG from day 0 after grafting greatly suppressed GVHD, resulting in more than 300 days survival. However, only cutaneous GVHD, but not fatal GVHD, was suppressed when the start of administration was postponed until day 4 after grafting. From in vitro studies, DSG inhibited natural killer cell activities to K-562 and skin epidermal cells. The response was well correlated with in vivo GVHD course. These results suggest that DSG is an effective immunosuppressant for both rejection and GVHD when used prophylactically. DSG exerted the effect more stongly against cutaneous GVHD than fatal GVHD by inhibiting natural killer systems.

Animals↗
PubMed1994

Effects of gastrectomy on motility, perfusion pressure, and caerulein-induced relaxation of sphincter of Oddi in dogs.

The effects of subtotal-gastrectomy (gastrectomy) on the spontaneous motility and caerulein-induced relaxation of the sphincter of Oddi (SO) were investigated in the dog. The spontaneous motility and the response to caerulein of the SO were recorded using perfusion method. The basal perfusion pressure (5.1 +/- 0.5 cmH2O) and the frequency of phasic contractions (6.1 +/- 0.5 cycles/min, c/min) of the SO increased to 8.2 +/- 0.6 cmH2O (p < 0.05) and 9.3 +/- 0.4c/min (p < 0.05) after gastrectomy, respectively. They were observed one month after operation (7.8 +/- 0.5 cmH2O and 9.1 +/- 0.9 c/min, p < 0.05), but did not change by vagotomy with sympathectomy (vagosympathectomy). In the spontaneous motility of the SO, the motility index increased to 143.7 +/- 18.7% (p < 0.05) at 4 hrs and 135.0 +/- 9.1% (p < 0.05) at one month after gastrectomy, but did not increase after vagosympathectomy. Caerulein had an inhibitory effect on the SO motility in the normal animal 48.0 +/- 4.2%). Gastrectomy reversed to the excitatory effect from the inhibitory effect to caerulein at 4 hrs (127.6 +/- 5.3%, p < 0.05) and at one month (126.6 +/- 5.3%, p < 0.05) after operation, but not reversed by vagosympathectomy and sham gastrectomy. The excitatory response to caerulein after gastrectomy was not effected by vagosympathectomy. It is concluded that gastrectomy induced the SO dysfunction, an increase of the perfusion pressure and the frequency of phasic contractions of the SO, and a change of the response to caerulein of the SO. These alterations suggests that one of the mechanisms of the regulation of the SO motility exist as the reflex from the stomach and/or uppermost duodenum through intrinsic nervous pathways.

Animals↗
PubMed1994

The importance of family study in the patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is a well-known autosomal dominant disorder characterized by the formation of multiple adenomatous polyps of the colon. Gardner's syndrome is a variant of familial polyposis coli, and both can be associated with colonic or extracolonic benign and/or malignant tumors. It has been widely recognized that an adenocarcinoma of the colon develops in virtually all cases, usually at an earlier age, if polyps are left untreated. Families of four individuals diagnosed of FAP were surveyed and 56 relatives of the families were examined. Of these 56, 21 had multiple colon polyps, 3 of whom had early-stage adenocarcinomas. We consider that familial survey of FAP individuals can be of considerable benefit for this high-risk population due to the autosomal nature of the disease, allowing diagnosis of an associated cancer at an earlier stage.

Adenomatous Polyposis Coli↗
PubMed1994

Clinical value of soluble interleukin-2 receptor in infectious complications.

In this study, we investigated serum-soluble interleukin-2 receptor (sIL-2r) and neopterin (NPT) levels in five patients with severe postoperative infections. A total of 25 synchronous determinations of sIL-2r and NPT were performed. A marked increase in sIL-2r and NPT levels was observed, and the increase in sIL-2r was significantly correlated to that of NPT which is a marker of macrophage activity. These results suggest that macrophages are involved in the stimulation of sIL-2r release, representing a potentially negative biological effect. The results indicate that sIL-2r may be a useful indicator of the efficacy of antibiotics and of prognosis.

Aged↗
PubMed1994

The enhancement of cell surface ICAM-I and HLA class I antigens in human gastric cancer cell lines by IFN-gamma.

Cytotoxic lymphocytes, including natural killer cells, lymphokine-activated killer cells, and cytotoxic T lymphocytes, adhere to and lyse cancer cells by recognizing cell surface antigens. Among the cell surface antigens, intercellular adhesion molecule-1 (ICAM-1) and HLA class I antigen are important for the cytotoxic activity of lymphocytes. The ICAM-1 and HLA class I antigen were examined in gastric cancer cell lines MKN-28 and MKN-45 by flow cytometry to determine whether their expression on the cell surface is enhanced by interferon gamma (IFN-gamma). The cell expression rate [stained cells/10(4) cells x 100(%)] was only 10% in ICAM-1 and about 20% in HLA class I antigen without IFN-gamma, but reached 70% in ICAM-1 and up to 60% in HLA class I antigen after incubation with IFN-gamma for 24-96 h. This enhanced expression of cell surface ICAM-1 and HLA class I antigen by IFN-gamma might increase sensitivity for cytotoxic lymphocytes.

Antigens, Neoplasm↗
PubMed1994

Suppression of hepatic natural killer activity by liver metastasis of cancer and restoration of killer activity by oral administration of a Basidomycetes-derived polysaccharide, PSK.

PSK (Krestin) is a protein-bound polysaccharide with antitumor and immunomodulatory activity. In this study, the effects of the oral administration of PSK were investigated on the natural killer (NK) activity of liver-associated lymphocytes and their subfractions separated by density gradient centrifugation, in WKAH rats with liver metastasis of KDA hepatoma. PSK was administered orally, at a dose of 500 mg/kg once a day for 3 weeks. The NK activity of nonparenchymal liver cells (NPLC) and their subfractions, including large granular lymphocytes (LGL), was markedly augmented by this treatment. The effects of oral PSK were also examined in CDF1 mice with liver metastases of Colon 26 adenocarcinoma; the survival of tumor-bearing mice was prolonged and both metastatic foci and liver weight were decreased. These results suggest that PSK may be effective for the suppression of liver metastasis through activation of liver-associated NK cells.

Adjuvants, Immunologic↗
PubMed1994

Unresponsiveness of antidonor cytotoxic T cells in a long-term stable renal transplant recipient.

The antidonor immune response was examined in a one haplotype-mismatched renal transplant recipient with an allograft that had been well-functioning for more than 10 years. Although the relative response of the mixed lymphocyte reaction (MLR) was (45.8)% and the MLR responder cells stimulated by donor cells produced measurable amounts of interleukin-2 (IL-2) (11.6 U/ml), the cytotoxic T lymphocytes (CTL) could not be generated against donor cells, even with exogenous IL-2. These results indicate that antidonor CTL precursors were either deleted or inactivated in this recipient.

Adult↗
PubMed1994

Synergistic effect of tumor necrosis factor-alpha and interferon-alpha on the induction of apoptosis detected by BM-1/JIMRO: a new marker of apoptosis.

The effects of the combination of natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural human interferon-alpha (nHuIFN-alpha) on the induction of apoptosis were investigated by immunohistochemical analysis with BM-1/JIMRO monoclonal antibody in RPMI 4788 tumor cells. Few tumor cells in the control culture could spontaneously undergo apoptosis. The number of positive cells increased at 2 and 4 h after treatment with nHuTNF-alpha (1 x 10(5) U/ml) and nHulFN-alpha (1 x 10(5) IU/ml). This effect was clearly maintained from 8 h up to 72 h of culture. The number of apoptotic cells also greatly increased with doses, suggesting that the apoptosis induced by nHuTNF-alpha and nHuIFN-alpha in combination was dose-dependent. nHuTNF-alpha or nHuIFN-alpha alone could induce apoptosis, but the induction increased significantly when the two cytokines were combined. These findings indicate that by combining nHuTNF-alpha and nHuIFN-alpha apoptosis can be synergistically induced in RPMI 4788 tumor cells, and may have specific therapeutic implications for clinical treatments using these two cytokines.

Antibodies, Monoclonal↗
PubMed1994

Regulatory effect of lymphokine-activated killer cells on epidermal proliferation induced by cholera toxin in mice.

We investigated the effects of lymphokine-activated killer (LAK) cells on epidermal hyperplasia induced by cholera toxin (CT). LAK cells showed cytotoxic activity against both tumor cell lines and proliferating normal cells including skin epidermal cells. When 1 x 10(7) LAK cells were injected intradermally together with 1.0 ng of CT, epidermal hyperplasia was markedly suppressed. The LAK effectors inhibiting epidermal hyperplasia showed surface phenotypes of asialo-GM1+, Thy-1+, Lyt-2- and L3T4-, that were different from those of LAK cells killing tumor cells in vitro. Epidermal hyperplasia induced by CT was not suppressed by topical administration of cytokines such as interleukin-2, interferon and tumor necrosis factor. Therefore, the antiproliferative effect of LAK cells might be attributed to their direct action on the epidermal cells.

Animals↗
PubMed1994

Ovarian metastasis in patients with colorectal carcinoma.

The records of 159 patients who underwent surgical resection of colorectal cancer were reviewed to assess the incidence of ovarian metastasis and to define the role of oophorectomy. Four of these patients presented with metachronous metastases, and one patient had synchronous ovarian involvement. The incidence of ovarian involvement was higher in younger patients. While most patients with ovarian involvement had the primary tumor located at the rectosigmoid region, a similar distribution of the primary tumor was observed in patients without ovarian metastasis. The histological type and degree of differentiation was similar regardless of whether or not ovarian metastasis was present. Of the patient without ovarian metastasis, 57% presented with nodal metastases and 3.2% with peritoneal dissemination, while all patients with ovarian metastasis had nodal and peritoneal involvement. Our results suggest that histological type and degree of differentiation of the primary tumor do not influence likelihood of ovarian metastasis. However, the exposure of the tumor to the serosal surface and the subsequent peritoneal dissemination may be an important route by which malignant tumor cells reach the ovaries. However, due to the wide lymphatic involvement in patients with ovarian metastasis, the lymphatic route may be important as well. Thus, we consider that oophorectomy should be performed in all postmenopausal women, when the ovaries are macroscopically affected, and in premenopausal patients with Astler-Coller B2 tumors or over.

Adult↗