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Biomedical subjects

T Okayasu

Publications and source records attributed to T Okayasu.

At least 37 records · Page 2Linked to original sources

Cytotoxicity of galactose, tyrosine and methionine in cultured suckling rat hepatocytes: relation to liver immaturity.

Monolayers of suckling rat hepatocytes cultured for 24 hours were treated with galactose, I-tyrosine and I-methionine. The purpose was to study the reasons for the clinical improvement of patients with neonatal hepatitis after dietary restriction of these nutrients. Galactose, tyrosine, and methionine was cytotoxic on suckling rat hepatocytes, yet had no effect on adult rat hepatocytes. Furthermore, the pretreatment of suckling rat hepatocytes with dexamethasone ameliorated the cytotoxicity and induced a differentiation of the cells. These results suggested that the cytotoxicity resulted from the immaturity of suckling rat hepatocytes and therefore dietary restriction of galactose, tyrosine and methionine might be a useful treatment for patients with neonatal hepatitis.

Animals

[A case of benign fibrous histiocytoma of the lung in a child].

A case of benign fibrous histiocytoma of the lung in a 8 years old boy was presented. He was first admitted in May, 1983, with recurrent pneumonia. Chest X-ray showed a ill-defined mass in the right lower lobe. Bronchoscopy revealed a round tumor, 1 cm. in maximum diameter, with complete obstruction of the Truncus Intermedius. Endoscopic resection was performed and partial obstruction of the Truncus Intermedius remained. He was re-admitted with pneumonia of the right middle lobe in March, 1986. Bronchoscopy showed severe stenosis of the Truncus Intermedius. Right middle and lower lobectomy was performed. The 4 X 4 X 3 cm tumor was located in the median of the Truncus Intermedius. Microscopically, the lesion composed of fibroblast-like cells and histiocyte-like cells. The patient's post-operative course was uneventful. He has no signs of local recurrence or metastasis. We believe, this is the first reported primary benign fibrous histiocytoma of the lung in a child in Japan.

Bronchial Neoplasms

[MR imaging of gynecological neoplasms using a low-magnetic-field machine].

Magnetic resonance (MR) images were obtained from 171 patients with benign and malignant neoplasms in the uterus and ovary, by using a low magnetic-field machine with 0.22 T, and its usefulness is discussed. Small uterine neoplasms (a few mm of its diameter) can be detected as an abnormal intensity. Therefore, the detectability is helpful for determination of their staging. In addition, some adenomyosis can also detected as distinctive findings, although it is difficult to point out those diseases by other imaging modalities. From MR images of ovarian cystic tumor, the biochemical information of its fluid content can be obtained. However, it is difficult to get distinctive features from MR images of solid neoplasms. Even though the magnetic field is low such as 0.22 T, MR images are useful for diagnosis of gynecological neoplasms because of the high contrast image quality and the capability of providing tomograms with arbitrary planes.

Adult

[A case of mediastinal schwannoma originating from the intrathoracic vagal nerve].

A 46-years-old man was admitted because of an abnormal shadow on X-ray. The operation underwent under the diagnosis of benign tumor in the antero-superior mediastinum. At the operation, the tumor arise from the right intrathoracic vagal nerve and it was resected with the transection of vagal nerve. The histological diagnosis was schwannoma. Postoperative course was uneventful except the slight hoarseness. Intrathoracic vagal tumor is rare and we have found 19 reported cases among Japanese literatures. This case is considered to be the 20th case originated from the intrathoracic vagal nerve in Japan.

Cranial Nerve Neoplasms

[A case of primary pulmonary cryptococcosis].

A 53-year-old male was admitted because of an abnormal chest roentgenogram showing a solitary tumor shadow in the right upper lung field. Laboratory data was normal. Although examination with the bronchoscope and sputum cytology showed no abnormal findings, a partial resection of the right upper lobe was performed. Microscopic examination of the lesion was cryptococcosis. As another focus was not found by systemic examination, the lesion was disclosed primary pulmonary cryptococcosis. Cryptococcosis is rare but we must think of it when we meet a solitary tumor shadow on the chest roentgenogram.

Cryptococcosis

[Inhibitory effect of UFT on postoperative lung metastasis of mammary adenocarcinoma in SHR rats].

It is well known that UFT has significant therapeutic effects against experimental and clinical cancers at the primary sites. In this experiment, we studied the inhibitory effect of UFT on the lung metastasis of spontaneously developed rat mammary carcinoma (SST-2) after surgical excision of the primary site. In comparison of UFT-treated (15 or 30 mg/kg/day) with 5-FU-treated (9.7 or 19.5 mg/kg/day) groups, UFT was more effective than 5-FU in the antitumor activity and the inhibitory effect of lung metastasis with/without surgical excision of the primary sites. Rats (5-10 rats per group) were inoculated s.c. with 1 x 10(6) SST-2 cells and administered with UFT orally (15, 30 or 60 mg/kg/day) starting the day after tumor inoculation for 30 days. The therapeutic effect of UFT was studied by the growth rate of primary tumor and the numbers of metastatic colonies in the lung 35 days after tumor inoculation, comparing the UFT-treated with control groups. UFT administration at the doses of 30 or 60 mg/kg/day markedly inhibited the growth of the primary tumors and the number of metastatic lung colonies decreased, compared with that of the control group. However, in the group of rats treated at the dose of 60 mg/kg/day, 60% of rats died from the side effects of UFT such as weight loss, hemorrhage etc. In all groups in which the primary tumors were surgically excised 20 days after tumor inoculation and then treated with UFT (15, 20 or 30 mg/kg/day), we observed marked prolongation of survival period and inhibition of lung metastasis as well. Furthermore, we studied the effect of combination therapy of UFT and lentinan (1 mg/kg/day i.p.) on the metastasis of SST-2 cells after surgical excision of the primary sites. It was more effective than UFT alone. Thus, it is clear that UFT is an effective anticancer drug to inhibit metastasis of tumors in the lung after surgical excision of primary tumor.

Adenocarcinoma

[Functions of large granular lymphocytes--a case of large granular lymphocytosis with characteristic cell surface antigens].

A 58-year-old male visited the hematological clinic of Surugadai Nihon University Hospital, Tokyo, complaining of numbness around both elbows. The peripheral leukocyte count was 12,400/microliters, and large granular lymphocytes (LGL) occupied 79% of the leukocytes. The cell surface antigen studied by flow cytometry were the positive CD 2, 3, 5, 8, 11, and Leu-7, and the negative CD1, 4, 10, 16 (Leu-11), 19, 20, and OKTIa1. IgG-FCR checked by mean of the EA-rosette formation was positive. The LGL showed the negative NK cell activity and the positive ADCC and LAK cell activities. It was interesting that LGL was negative for CD16 (Leu-11) while they had ADCC activity. Since the rearrangement of the receptor gene in T-cells was demonstrated by the southern blot analysis, the proliferation of LGL was considered to be a clonal one. LGL did not inhibit the colony formation of granulocyte and erythrocyte precursors in the plasma clot culture. It was thus considered that this might partially explain the fact that the patient's neutrophil, Hb and platelet levels remained normal.

Antibody-Dependent Cell Cytotoxicity

Increase in insulin binding affinity by chloroquine in cultured rat hepatoma cells.

Chloroquine increased the binding of 125I-labeled insulin to rat hepatoma cells (R-Y121B) at 4 degrees C. The effect of chloroquine on insulin binding was amplified at 23 degrees C, and a large increase in cell-associated radioactivity was observed. Scatchard analysis showed that chloroquine increased the affinity of insulin for cells at both 4 degrees C and 23 degrees C, and that this increase eventually caused the accumulation of insulin internalized by cells at 23 degrees C.

Animals

Concanavalin A changes not only the number of insulin binding sites but also the binding affinity in rat hepatoma cells in culture.

When rat hepatoma cells (R-Y121B) were first incubated with labeled insulin, followed by concanavalin A, at 500 micrograms/ml at 23 degrees C, the total cell-associated radioactivity increased. At 4 degrees C, however, this increase was not observed. Scatchard analysis revealed that concanavalin A increased insulin binding affinity. The bound insulin was internalized together with concanavalin A. When the cells were incubated with concanavalin A prior to insulin addition, however, the total cell-associated radioactivity decreased at both temperatures. This was caused by the masking of insulin binding sites by the lectin.

Animals

Platelet-activating factor stimulates metabolism of phosphoinositides via phospholipase A2 in primary cultured rat hepatocytes.

Addition of platelet-activating factor (PAF) to cells doubly labeled with [14C]glycerol plus [3H]arachidonic acid resulted in a transient decrease of [14C]glycerol-labeled phosphatidylinositol (PI) and a transient increase of [14C]glycerol-labeled lysophosphatidylinositol (LPI). [3H]Arachidonate-labeled PI, on the other hand, decreased in a time-dependent manner. The radioactivity in phosphatidylethanolamine, phosphatidylcholine, sphingomyelin, and phosphatidylserine did not change significantly. The 3H/14C ratio decreased in PI in a time-dependent manner, suggesting the involvement of a phospholipase A2 activity. Although PAF also induced a gradual increase of diacylglycerol (DG), the increase of [14C]glycerol-labeled DG paralleled the loss of triacyl [14C]glycerol and the 3H/14C ratio of DG was 16 times smaller than that of PI. Thus, DG seemed not to be derived from PI. In myo- [3H]inositol-prelabeled cells, PAF induced a transient decrease of [3H]phosphatidylinositol-4,5-bis-phosphate (TPI) and [3H]phosphatidylinositol-4-phosphate (DPI) at 1 min. PAF stimulation of cultured hepatocytes prelabeled with 32Pi induced a transient decrease of [32P]polyphosphoinositides at 20 sec to 1 min. [32P]LPI appeared within 10 sec after stimulation and paralleled the loss of [32P]PI. [3H]Inositol triphosphate, [3H]inositol diphosphate, and [3H]inositol phosphate, which increased in a time-dependent manner upon stimulation with adrenaline, did not accumulate with the stimulation due to PAF. These observations indicate that PAF causes degradation of inositol phospholipids via phospholipase A2 and induces a subsequent resynthesis of these phospholipids.

Animals

[A case of breast carcinoma with lung metastasis].

A 37-year-old female, who had undergone a left standard mastectomy in May, 1983 for breast cancer, was treated with Tamoxifen and FT-207 postoperatively. The patient had no further evidence of disease until two and one-half years later, when a routine chest film showed a single, half-rounded density 6.5 cm in diameter in the hilus of her left lung. Bestrabucil, the benzoate of an estradiol-chlorambucil conjugate, was administered p.o. at a daily dose of 200 mg for four weeks. Thereafter, the tumor greatly decreased in size to 3.0 cm in diameter. When a left upper lobectomy was performed, the tumor was found to be necrotic tissue. Microscopically, a small cancer nest similar to the primary breast carcinoma was observed in the center of the necrosis. The necrotic tissue was surrounded with cellular infiltrate, markedly consisting of histiocytes.

Adenocarcinoma

[Clinical study of a synthetic calcitonin derivative (elcatonin) in patients with metastatic bone tumors].

Forty-three cases of metastatic bone tumor were treated with Elcatonin. The agent was injected intramuscularly to each patient at a dose of 40 units twice daily. Twelve patients (28%) experienced pain relief within 4 days after treatment and after 4 weeks, twenty-eight patients (65%) had palliation of pain. In patients with hypercalcemia (4 cases), a decrease of serum Ca was observed one week after administration of Elcatonin. Improved bone scintigram was observed in 37.5% of cases, and radiographic improvement in 20% of cases. These data indicate that Elcatonin is effective for achieving pain relief and in improving the state of invaded bones when administered in combination with conventional treatment modalities for patients with metastatic bone tumors.

Adult

Immune regulation of the L5178Y murine tumor-dormant state. I. In vivo and in vitro effects of prostaglandin E2 and indomethacin on tumor cell growth.

Immunization and intraperitoneal challenge of DBA/2 mice with L5178Y lymphoma cells results in the suppression and maintenance of the L5178Y cells in a tumor-dormant state in the peritoneal cavity for many months. Cell-mediated immune responses involving lymphocytes and macrophages are involved in maintenance of the tumor-dormant state. Macrophages that have increased immunosuppressive activity and that produce increased amounts of PGE2 appear in the peritoneal cavity of tumor-dormant mice before the breakdown of the tumor-dormant state and formation of ascitic tumors. We report here that the tumor-dormant state can be terminated with formation of ascitic tumors by treatment of tumor-dormant mice with PGE2. Treatment with indomethacin results in inhibition of tumor cell growth and elimination of all recoverable tumor cells. Cultures of peritoneal cells (PC) from mice harboring L5178Y cells in a tumor-dormant state were used to analyze the PGE2 and indomethacin effects. Tumor cells did not grow out in the high-cell density PC cultures prepared from many tumor-dormant mice, but addition of PGE2 to these cultures resulted in tumor cell growth. The tumor cell growth that did occur in the PC cultures from some tumor-dormant mice was associated with PGE2 production by the associated host cells, and the addition of indomethacin to these cultures inhibited both PGE2 synthesis and tumor cell growth. Removal of plastic-adherent cells from the PC cultures eliminated the restraint on tumor cell growth. These experiments suggest that L5178Y tumor cells are maintained in a tumor-dormant state by host peritoneal cells, which are under PGE2 regulation.

Animals

Metabolism of platelet-activating factor in primary cultured adult rat hepatocytes by a new pathway involving phospholipase C and alkyl monooxygenase.

The metabolic fate of 1-O-[3H]alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF-acether) upon interaction with primary cultured adult rat hepatocytes was investigated. [3H]PAF-acether was transformed time-dependently into [3H]lyso-PAF-acether, 1-O-[3H]alkylglycerol and finally converted to 3H-labeled fatty aldehyde. 1-O-[3H]Alkyl-2-acyl-sn-glycero-3-phosphocholine (alkylacyl-GPC) was formed after a long incubation time and with a smaller amount compared with that formed in platelets and neutrophils. When lipids from cells, cell surfaces and incubation medium were analyzed separately, most of the transformed products of [3H]PAF-acether remained in the cells. When 1-O-[3H]alkyl-2-lyso-sn-glycero-3-phosphocholine was incubated with hepatocytes, it was mainly converted into 1-O-[3H]alkylglycerol. 3H-labeled fatty aldehyde and [3H]alkylacyl-GPC were also found. Hepatocytes metabolized slowly from 1-O-[1-14C]hexadecylglycerol to 3H-labeled fatty aldehyde and 3H-labeled phospholipid. These findings suggest that cultured hepatocytes mainly catabolize exogeneous PAF-acether by removing the acetyl residue and the polar head group and, finally, by cleaving an ether bond. The deacetylation-reacylation step, which is important in platelets and neutrophils, was not shown to be a main metabolic pathway of PAF-acether in cultured hepatocytes.

Animals

The active immunotherapy of a 3-methylcholanthrene-induced rat tumor with Friend virus-infected (xenogenized) tumor cells.

We investigated the various conditions necessary for potentiating the immunogenicity of viable Friend virus (FV)-infected rat fibrosarcoma KMT-17 cells. The immunogenicity was most potent among cells passaged through three generations of FV-tolerant rats; a single subcutaneous immunization induced an increase in the transplantation resistance (LTD50) of 10,000 or more. It was also found that intradermal immunization of the tumor cells induced stable and potent resistance to the transplantation of non-xenogenized tumor cells soon after immunization, and that irradiated non-xenogenized tumor cells were effective in supplying booster immunization. Active immunotherapy against KMT-17 cells pre-transplanted subcutaneously was carried out on the basis of the above findings with the results that the active anti-tumor immunization alone caused a complete regression in 30% of the tumor-burdened rats. These findings indicate the possibility of achieving active immunotherapy with xenogenized tumor cells.

Animals