[A case of chronically progressed peripheral neuropathy, spastic paraplegia, cerebellar ataxia and dementia associated with decreased alpha-galactosidase activity].
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Biomedical subjects
Publications and source records attributed to A Ueki.
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In order to elucidate the mechanism of hyperinsulinism following a treatment with glucocorticoid, insulin secretion induced with glucose or tolbutamide was investigated by a perifusion experiment on isolated islets of rats. The results are summarized as follows: 1. The fasting blood glucose level was significantly higher on the 2nd day (174.0 +/- 11.8 mg/dl) and 3rd day (179.6 +/- 9.5 mg/dl) in the glucocorticoid treated rats, than it was in the control rats (129.0 +/- 12.0 mg/dl). The serum insulin levels began to increase from the first day following the glucocorticoid treatment (17.2 +/- 1.3 microU/ml in the control rats, 27.6 +/- 2.1 microU/ml on the 1st day, 32.4 +/- 3.9 microU/ml on the 2nd day, and 34.5 +/- 1.4 microU/ml on the 3rd day). 2. The insulin content of the islets decreased with the glucocorticoid treatment (765.6 +/- 34.5 microU/islet in the control rat, 576.6 +/- 25.0 microU/islet on the 1st day, 629.2 +/- 36.9 microU/islet on the 2nd day, and 482.0 +/- 43.5 microU/islet on the 3rd day). 3. In the perifusion experiment, a biphasic pattern of insulin secretion was demonstrated with the stimulation of glucose in the control and glucocorticoid treated rats. A remarkable enhancement of insulin secretion was observed by the stimulation of 100 mg/dl glucose. The amount of insulin secretion at the first phase (up to 7 min. after the glucose stimulation) was 2.9 +/- 0.5 microU/islet on the 1st day, 2.7 +/- 0.3 microU/islet on the 2nd day and 3.8 +/- 0.1 microU/islet on the 3rd day; these amounts were high compared with that of 1.8 +/- 0.1 microU/islet in the control rat. The amount of insulin secretion at the second phase (8 to 60 min. after the glucose stimulation) was 28.5 +/- 2.5 microU/islet on the 1st day, 37.1 +/- 3.3 microU/islet on the 2nd day and 41.3 +/- 1.8 microU/islet on the 3rd day; these amounts were higher when compared with that of 24.7 +/- 0.7 microU/islet in the control rat. 4. The monophasic insulin secretion from isolated islets by the stimulation of tolbutamide was enhanced with the treatment of glucocorticoid. These results indicate that glucocorticoid directly enhances insulin secretion from the pancreatic islets at the physiological concentration of blood glucose, which seems to be an important factor in the occurrence of hyperinsulinemia associated with glucocorticoid therapy.
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The C3b and C3d receptor sites on one cell line of human diploid fibroblasts (WI-38) were reported in previous papers [3, 4]. In this paper we describe that C3b and C3d receptor sites can also be detected in fibroblast cell lines derived from other human tissues. We consider that C3b and C3d receptors are normally found on the cell surfaces of all human fibroblasts.
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Cell-to-cell interaction was investigated in various malignant tumor cells (human ovarial tumor, lung cancer, carcinoma of larynx and hamster melanoma cell) and in human lymphoblastoid cells (T-cell (MOLT-4 cell), thymoma cells and B-cells (Burkitt lymphoma cell)). Live lymphoblastoid cells did not adhere to the cell surfaces of tumor cells nor the lymphoblastoid cells were ingested by tumor cells without immunologic and specific treatment. Tumor cells as well as T-cells and B-cells had receptors to concanavalin A on their surfaces, and they showed marked cell binding of tumor cells and lymphoblastoid cells. Moreover, tumor cells that phagocytized lymphoblasts underwent marked cell destruction within 4 hours of cell binding. The cytolytic mechanism of the target tumor cell was probably related to contact with the lymphoblastoid cells and was increased by ingestive activity, and metabolic disturbance by lymphotoxin in tumor cells.
Electric stimulation to the substantia nigra (Pars reticulata) produced a monosynaptic inhibition of the neurons of the ventromedial nucleus of the thalamus in anesthetized cats.
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The presence of C3 receptor sites on the cell surfaces of WI-38 fibroblasts was reported in a previous paper. Here the effect of dexamethasone sodium sulfate of C3 receptor site function was studied. The incubation of WI-38 fibroblasts with dexamethasone sodium sulfate produces the biphasic mode of action, i.e., the growth-stimulating phase with low doses (90--230 mug/ml) and the growth-inhibiting phase with high doses (450--900 mug/ml). The function of C3 receptor sites on WI-38 fibroblasts seems to be very stable and cannot be suppressed by the pretreatment of WI-38 fibroblasts with dexamethasone in high concentrations, where the cell growth is inhibited.
The peripheral blood of an acute myelomonocytic leukemia patient has been cultured for 16 months. The culture is at present at the 140th population doupling level. The cultured cells have the characteristics of so-called lymphoblastoid cells and proliferate actively as individual cells in small clusters, or in large clumps consisting of large mononuclear cells. Some of these cells appeare to be lymphoid, but the majority are immature mononuclear cells with a tendency to lobulate. They gave a weakly positive peroxidase reaction at the beginning of cultivation, and have given a strongly positive esterase reaction persistently. The cytoplasm shows ciliary or tail-like projections as the cell matures. Complement (C3) receptor and IgG receptors are found on the cell surface, and active phagocytosis is mannifest. Colloidal iron particles or viable red blood cells attached to the cell membrane suggesting possible differentiation to reticulum cells or macrophages. The cultured cells are mostly diploid but some cells show chromosome abnormality. Herpes type virus was foun in the nucleus, cytoplasma and on the cell membrane. The transplanatation of cultured cells to the cheek pouch of hamsters produced small tumors with histological findings resembling reticulum cell sarcoma.
The presence of C3 receptor sites on WI-38 human diploid fibroblasts was reported in the previous paper. In this report we wish to describe that WI-38 fibroblasts carry C3b and C3d receptor sites on the cell surfaces.
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Sheep red cells, sensitized with 19S fraction of antiserum and subsequently treated with mouse serum as the source of complement (EAC), interact with human diploid fibroblasts (WI-38 cells) and form "Rosettes". Under a scanning electron microscope, EAC have not attached directly to the cell surface of fibroblasts, but to the fine processes or microvilli of the latter, as if there were fine bridges between EAC and the surface of fibroblasts. On the other hand, the attachment of sheep red cells washed in PBS (E) or sensitized with 19S fraction of antiserum (EA) to WI-38 cells was not observed. The pretreatment of WI-38 cells with mouse serum did not inhibit the interaction of WI-38 cells and EAC. No phagocytosis of EAC by WI-38 cells was observed in the 2 hrs incubation of both cells. From these results it is suspected that the interaction of WI-38 cells and EAC is immune adherence, and that WI-38 cells have the receptor site for complement, especially for C3, on the surface of cell membrane.
In our attempts at establishing a cancer cell line from various ascites of cancer bearing patients, a cell line was successfully established from the ascites of a 63-year-old female with primary ovarian tumor (embryonal carcinoma). Histological findings of the peritoneum, due to metastasis, appeared to be cystadenocarcinoma, revealing the differentiation to non-epithelial cells which formed coarse networks and fibers, and morphologic changes of tissue cultures also reflected such histologic findings. At present the subculture has reached the 95th population doubling level, and cultured cells have assumed the morphology of mesothelial cells or fibroblasts with about 50 chromosomes. As a human malignant cell line, it is useful for the study of human malignant tumor cell.
On the basis of the previous study, on the cell interaction between malignant tumor cells and other cells, especially with lymphocytes, the present study was carried out by investigating cell to cell interaction of human malignant tumor cells and human lymphoblastoid cells such as T-cell (MOLT-4 cell) and B-cell (Burkitt lymphoma cell). As a result it has been revealed that live lymphoblastoid cells were not adhered on the cell surface of the tumor cells, nor is it ingested by tumor cells, but in thepresence of HVJ (Sendai virus: 2,000 H.A. units) it adheres slightly on the cell surface of tumor cell but no cell fusion of tumor cells and lymphoblastoid cells is observable. On the other hand, the tumor cell as well as T-cell and B-cell all have receptors to concanavalin A (Con. A) on their cell surfaces, and they show a marked cell binding such as tumor cell and T-cell, tumor cell and B-cell, and there can be observed a marked phagocytosis of lymphoblastoid cells by tumor cells. Moreover, the tumor cells that have phagocytized lymphoblastoid cells undergo a marked cell destruction within 4 hours of cell-binding and phagocytosis, which is especially prominent in the case of phagocytosis of E.B cell by tumor cell.