Search PubMed⌕ Search

Biomedical subjects

M Toyoda

Publications and source records attributed to M Toyoda.

At least 199 records · Page 11Linked to original sources

Tumorigenic conversion of xeroderma pigmentosum lymphoblastoid cells without karyotypic alteration.

In order to examine the process of malignant transformation of human somatic cells, we studied the tumorigenic conversion of an Epstein-Barr-virus-immortalized lymphoblastoid cell line (LCL) derived from a patient with xeroderma pigmentosum (XP) complementation group A. Repeated irradiation of the XP cells, XP7NI, with UV-light and subsequent treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in the acquisition of tumorigenicity in athymic nude mice. The tumorigenicity of XP7NI cells was also induced by TPA treatment alone. The tumors formed in athymic mice were of B-cell lymphoma with characteristic histology, cell surface immunoglobulins and an antigen as detected by a B-cell-specific monoclonal antibody (MAb), CD20. The surface immunoglobulins and the HLA type of these tumor cells were identical with those of the parental cells. These malignantly transformed cells retained the same UV sensitivity, serum requirement, colony-forming ability in soft agar, and normal human karyotype as the parental cells. Unlike other tumorigenic lymphoblastoid cell lines, this XP lymphoblastoid cell line provides a unique case in that process(es) leading to tumorigenicity may be induced by UV and TPA without apparent karyotypic changes.

Animals↗

Positron emission tomography using pyruvate-1-11C in two cases of mitochondrial encephalomyopathy.

Positron emission tomography (PET) using pyruvate-1-11C was carried out to investigate the in vivo metabolism of pyruvate in the brains of patients with mitochondrial encephalomyopathy and Leigh's disease. Two epileptic patients were studied as control subjects. Radioactivity was eliminated from the brain tissue of the epileptic patients soon after injection of pyruvate-1-11C. PET images of mitochondrial encephalomyopathy patients showed an increase in radioactivity in the cerebral cortex, basal ganglia and thalamus, with elimination of radioactivity being slower than that of epileptic patients. One patient with Leigh's disease showed similar PET images. PET using pyruvate-1-11C is useful for the evaluation of mitochondrial energy metabolism in the brain.

Brain Diseases↗

1,25-Dihydroxyvitamin-D3 regulation of interleukin-2 and interleukin-2 receptor levels and gene expression in human T cells.

1,25-Dihydroxyvitamin-D3 (1,25-D3) is known to inhibit DNA synthesis, immunoglobulin and lymphokine production [interleukin-2 (IL-2), gamma interferon (G-IFN), and granulocyte-monocyte colony-stimulating factor (GM-CSF)] by mitogen-stimulated human peripheral blood mononuclear cells (PBMCs). Recent data suggest these inhibitory effects are mediated at the gene level through inhibition of mRNA accumulation of specific lymphokines in the activated cells. In previous studies, we have demonstrated the CD8+ T cell population was less sensitive to the anti-proliferative actions of 1,25-D3 than CD4+ T cells. The purpose of this investigation was to further assess ability of 1,25-D3 to regulate CD4+ and CD8+ T cell functions. Initial experiments showed that 1,25-D3 inhibited both IL-2 production and mRNA accumulation in mitogen-stimulated PBMC. However, IL-2 receptor (IL-2R) expression and mRNA accumulation in stimulated PBMC was not affected by 1,25-D3. Both FACS sorted CD4+ and CD8+ T cells expressed IL-2R equally upon stimulation and neither showed an inhibitory effect on this expression by 1,25-D3. Human CD4+ and CD8+ T cells showed a stimulus-specific production of IL-2. CD4+ cells stimulated with mitogen and HLA-DR positive accessory cells produced measurable levels of IL-2 that were completely inhibited by 1,25-D3. CD8+ T cells did not generate measurable amounts of IL-2 in this system. However, CD4+ and CD8+ T cells produced large amounts of IL-2 when stimulated with mitogen and a protein kinase C activator, phorbol myristate acetate (PMA). Under these circumstances, both CD4+ and CD8+ T cell IL-2 production was inhibited completely by 1,25-D3. These data suggest that IL-2R expression in PBMCs and T cell subsets is equal and unaffected by 1,25-D3 while IL-2 production in T cell subsets is stimulus-specific and completely inhibited by 1,25-D3.

Adult↗

1,25 dihydroxyvitamin-D3 regulation of immunoglobulin production in peripheral blood mononuclear cells of patients with systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) is a multisystem disease characterized by an increase in the secretion of autoantibodies. The mechanisms of autoantibody-induced disease have not been clarified. 1,25-Dihydroxy-vitamin D3 (1,25-D3) is known to be important in the regulation of normal human lymphocyte functions. Among its regulatory functions is the ability to inhibit mitogen-stimulated production of immunoglobulin. The experiments reported here explored the regulation of IgG production by peripheral blood mononuclear cells (PBMCs) of patients with inactive and active SLE. 1,25-Dihydroxyvitamin D3 inhibited mitogen-stimulated IgG production in cells from normal individuals and inactive SLE patients, but not spontaneous IgG production by PBMCs from active SLE patients. Addition of exogenous IL-2 (5-50 U/ml) to 1,25-D3-treated cells from all patient groups did not affect IgG production significantly under any conditions tested. The addition of IL-2 to PMBCs had no effect on IgG production in normal individuals or inactive SLE patients, but stimulated IgG production in PBMCs of active SLE patients. We conclude that the regulation of mitogen-stimulated IgG production in inactive SLE patients by 1,25-D3 and IL-2 is similar to normal individuals, but IgG production by active SLE PBMCs is unresponsive to 1,25-D3 regulation and is increased with the addition of IL-2.

Adult↗

Cardiomyopathy characterized by abnormal accumulation of desmin-type intermediate filaments in cardiac muscle fibers. A case report and review of the literature.

A 42-year-old Japanese male, who had been suffering from congestive heart failure and electrocardiographic abnormalities (A-V block, intraventricular conduction disturbance, ventricular tachycardia), died after a clinical course of 2 years and 1 month. Macroscopic investigation revealed dilation of the left ventricle and thickening of the right ventricular wall. The unique finding in this case was a circumferential fibrous scar in the median circular layer and outer oblique layer of the left ventricular wall. Biopsy and autopsy materials revealed diffuse loss of myofibrils in the central zone of cardiac muscle fibers, and replacement with aniline blue-positive homogeneous material (17-35% of the area of one muscle fiber). Electron microscopy revealed abnormal accumulation of fine filamentous material (7.5-25 nm in diameter), which was immunohistochemically proved to be desmin-type intermediate filament. Moreover, sarcoplasmic reticulum-like material was detected in the degenerated area. At autopsy, degeneration was detected all over the heart. The ventricular muscle fibers were more severely affected than the atrial muscle fibers. The conduction system was also affected, in some parts more severely than the surrounding ordinary muscle fibers. The pathogenesis of this disorder remains to be clarified.

Adult↗

[Observation with SEM on the displacement of mucosal surface in process of denture fabrication].

The process of denture fabrication entails a series of steps that begin with impression-taking. Dimensional accuracy and displacement of surface repeatability affect results in these individual steps. Although changes in individual materials have already been measured in the past, there has been almost no measurement up to now of denture fabrication up to the denture base, using the mucous membrane as the standard and then measuring changes in the displacement of surface repeatability for each step. Noticing this lack, the authors used a Scanning Electron Microscope (SEM), presently the only non-contact measuring instrument that can be used, and measured changes at the different stages including the mucous membrane, the impression materials, the plaster and the resin. A drying process is required for the mucous membrane, and such a process can cause changes in the mucous membrane which is the basis of measurement. For this reason, the authors used Araldite, a product from Ciba-Geigy AG, as a replica material and made replicas for all the test materials, using the replicas for measurement. Results were as follows: 1. Araldite was used as the replica material, thus making it possible with the SEM to observe changes in the displacement of surface repeatability at the individual stages. 2. Major changes in the accuracy of surface were observed during impression-taking and in the period of moving from the impression material to the plaster. 3. During high-power observation with the SEM, the fine bumps on the surface of the plaster and resin disappeared and the surfaces became smooth. This is believed to be the result of the separating agent and heat.

Dental Impression Materials↗

[A case of advanced gastric cancer with Virchow's node metastasis, responding to concomitant plasma exchange and immunochemotherapy].

We report a case of advanced gastric cancer with Virchow's node metastasis which responded to concomitant plasma exchange and immunochemotherapy. Plasma exchange was conducted three times in total (once a week) using a membrane type plasma separator, with fresh frozen plasma as exchange fluid. Immunochemotherapy was performed simultaneously using MMC, FT and OK-432. By the end of the third plasma exchange, Virchow's node was confirmed by palpation and ultrasonic examination to have vanished. Diminution of the gastric cancer, and improvement of stenosis of the stomach were confirmed under endoscopy. We surmised that plasma exchange eliminated the immunosuppressive substances in serum, and intensified the anticancer effects of MMC and FT, resulting in the disappearance of the Virchow's node and diminution of the gastric cancer itself.

Adenocarcinoma↗

[Specific cytoplasmic crystalline inclusions in multiple myeloma with amyloidosis].

It is widely known that multiple myeloma is sometimes followed by amyloidosis. It is also not particularly rare that inclusions exist in myeloma cells. However, there has been no previous report of a case of myeloma with both inclusions and amyloidosis. A 60-year-old female initially complained of a tendency to bleed, which was caused by fibrinolysis. Amyloid deposition in bone marrow stroma and the gastric submucosa was recognized, in addition to crystalline inclusion in the cytoplasm of myeloma cells. An immunoelectron microscopic study demonstrated the amyloid fibrils and the crystals to react positively to anti-lambda serum. No crystals were found in macrophages, and no relationship was recognized between lysosomes and crystalline inclusions in the cytoplasm of myeloma cells. This case had disturbed transportation or secretion of the lambda type L chain and it was considered that crystals derived from the lambda type L chain were formed in the cytoplasm of myeloma cells.

Amyloidosis↗

[Studies on chemical analysis of mycotoxin (XX). Chemical analysis of aflatoxins in corn and corn-products].

The investigation was carried out to analyze aflatoxins contaminated corn. 1) Methanol, chloroform and acetonitrile were used as the extraction solvents for aflatoxins added to corn. As the result, the method using acetonitrile was found to be effective to extract and detect aflatoxins. 2) The Rapid detection of aflatoxins was made possible by using the affinity column (containing monoclonal antibodies against aflatoxins bound onto agarose) and the mini-column. The detection-limit was 20 ppb of aflatoxins in samples.

Aflatoxins↗

Instability of Mex- phenotype in human lymphoblastoid cell lines.

Three lymphoblastoid cell lines (LCLs) had extremely low activities of O6-alkylguanine-DNA alkyltransferase (O6-AGT), and were classified as Mex-. They were highly sensitive to cell killing by 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosoure a hydrochloride (ACNU), whereas NMO2, a Mex+ LCL with a high O6-AGT activity, was resistant to the agent. Small fractions of these Mex- LCLs survived the treatment with 10 micrograms/ml of ACNU for 24 h, and the surviving cells were found to be resistant to subsequent treatments with the agent. In addition, they contained O6-AGT activities comparable to that of NMO2 and were therefore regarded as Mex+. These results suggest that the Mex- phenotype in LCLs is unstable.

Cell Division↗

An autopsy case of diffuse myelomatosis associated with systemic kappa light chain deposition disease (LCDD). A patho-anatomical, immunohistochemical and immunobiochemical study.

A case of systemic light chain deposition disease in a 48-year-old man is presented. Clinically, the patient showed the signs of multiple organ (liver, heart and kidney) failure, but multiple myeloma was not diagnosed. Autopsy revealed generalized deposition of hyaline, a Congo red-negative substance, especially in the arterial walls of various organs. In the bone marrow, myelomatous proliferations of plasma cells positive for kappa light chain were recognized. The deposited substance was ultrastructurally different from amyloid fibrils, and was identified as kappa light chain by immunohistochemistry. A liver tissue extract was immunobiochemically examined and the deposited substance was confirmed to consist of kappa light chain, its molecular weight being approximately 14,000 to 17,000 Da.

Autopsy↗

[Positron emission tomography using pyruvate-1-11C on mitochondrial encephalomyopathy].

In order to investigate in vivo metabolism of pyruvate in the brain, positron emission tomography (PET) using pyruvate-1-11C were performed on two patients with mitochondrial encephalomyopathy, one patient with Leigh disease and one patient with epilepsy. PET images of epilepsy showed less RI uptakes in brain tissues than in skull muscles. And RI was cleared rapidly from the brain tissues. But PET images of mitochondrial encephalomyopathies showed increased RI uptakes and slow RI clearance in cerebral cortices, basal ganglia and thalamus. Also RI was cleared slowly or accumulated in ventricles. This suggested that pyruvate metabolism may be impaired with metabolical trapping of 11C by lactic acids, since it is said that 11C of pyruvate-1-11C is cleared rapidly from the normal brain tissues by decarboxylation of pyruvate. The usefulness of PET studies with pyruvate-1-11C are suggested for investigating pyruvate metabolism in brain tissues, and for diagnosing mitochondrial encephalomyopathy.

Brain↗