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N Takane

Publications and source records attributed to N Takane.

9 recordsLinked to original sources
PubMed2000

Single-fiber analysis of mitochondrial A3243G mutation in four different phenotypes.

Five unrelated patients harboring the A3243G mutation in the mitochondrial DNA (mtDNA) but presenting with different clinical phenotype were studied for their percentage of mutation at the single muscle fiber levels. One patient had a clinically and pathologically defined Leigh syndrome (LS), two showed mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), another showed progressive external ophthalmoplegia (PEO), and the other showed mitochondrial diabetes mellitus (MDM). The mutation load was greater in the muscle from the patient with LS (92%), who showed more than 80% even in the non-ragged red fibers (RRF) and also presented the highest proportion of RRF. The patients with MELAS had lower mutation levels as well as a lower proportion of RRF, and these two parameters were even lower in the PEO and MDM patients. These results were consistent with the concept that differences in the mutation load and in the somatic distribution of the mutation among different cells and tissues are responsible for the differences in phenotypical expression of the disease.

Adenine↗
PubMed2000

Heterogeneous presentation in A3243G mutation in the mitochondrial tRNA(Leu(UUR)) gene.

AIMS: To clarify the phenotype-genotype relation associated with the A3243G mitochondrial DNA mutation. METHODS: Five unrelated probands harbouring the A3243G mutation but presenting different clinical phenotype were analysed. Probands include Leigh syndrome (LS(3243)), mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS(3243)), progressive external ophthalmoplegia (PEO(3243)), and mitochondrial diabetes mellitus (MDM(3243)). Extensive clinical, histological, biochemical, and molecular genetic studies were performed on five families. RESULTS: All patients showed ragged red fibres (RRF), and focal cytochrome c oxidase (COX) deficiency except for the patient with MDM(3243). The mutation load was highest in the proband with LS(3243) (>90%), who also presented the highest proportion of RRF (68%) and COX negative fibres (10%), and severe complex I plus IV deficiency. These proportions were lower in the probands with PEO(3243) and with MDM(3243). CONCLUSION: The most severe clinical phenotype, LS(3243), was associated with the highest proportion of the A3243G mutation as well as the most prominent histological and biochemical abnormalities.

Adolescent↗
PubMed1995

Poly(ADP-ribose) synthesis induced by nitric oxide in a mouse beta-cell line.

Nitric oxide (NO) has been implicated as an immunological effector molecule that mediates beta-cell dysfunction associated with Type 1 diabetes. To assess whether NO induces poly(ADP-ribose) synthesis in islet cells, we examined the effect of nitroprusside on islet cells. The exposure of mouse islet cells and a beta-cell line (beta TC1) to 0.05-0.2 mM nitroprusside resulted in the reduction of intracellular nicotinamide adenine dinucleotide (NAD) levels. Nitroprusside stimulated poly(ADP-ribose) synthetase activity in beta TC1 cells. An inhibitor of poly(ADP-ribose) synthetase, 3-aminobenzamide, prevented both NAD decrease and poly ADP-ribosylation. These observations suggest that NO-induced pancreatic beta-cell damage may be ascribable to the activation of poly(ADP-ribose) synthetase that results in the decrease of NAD content.

Animals↗
PubMed1993

Nitric oxide and nitric oxide synthase mRNA induction in mouse islet cells by interferon-gamma plus tumor necrosis factor-alpha.

It has been shown that nitric oxide (NO) is involved in islet cell damage induced by interleukin-1 (IL-1). Here we show that interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) synergistically induced NO production and inducible NO synthase (iNOS) mRNA expression in mouse islet cells. Cycloheximide (CXH) did not prevent the iNOS mRNA expressions. The combination of IFN-gamma and TNF-alpha, which is highly cytotoxic to mouse islet cells, failed to destruct islet cells in the absence of L-arginine or in the presence of NG-monomethyl-L-arginine (NMMA). These observations suggest that NO is a primary effector in islet cell damage caused by IFN-gamma plus TNF-alpha.

Amino Acid Oxidoreductases↗
PubMed1993

Interleukin-1 induction of tumor necrosis factor-alpha mRNA and bioactive tumor necrosis factor-alpha in a pancreatic beta-cell line by a mechanism requiring no de novo protein synthesis.

Interleukin-1 (IL-1) has been implicated as an effector in insulitis of Type 1 (insulin-dependent) diabetes. Exposure of a beta-cell line (beta TC1) to IL-1 beta resulted in an increase of preproinsulin mRNA at 0.5 h followed by a gradual decrease. Tumor necrosis factor-alpha (TNF-alpha) mRNA expression by beta TC1 cells was demonstrated 1-3 h after the addition of IL-1 beta. TNF bioactivity was detected in homogenates of beta TC1 cells exposed to IL-1. The supplementation of cycloheximide (CHX) together with IL-1 beta resulted in the superinduction of TNF-alpha mRNA, suggesting that de novo protein synthesis is not required in IL-1-induced TNF-alpha mRNA expression. Endogenous TNF-alpha of beta-cells may be involved in the islet lesion of type 1 diabetes.

Actins↗
PubMed1993

Effects of free radical scavengers on cytokine actions on islet cells.

We investigated the effect of free radical scavengers on the actions of cytokines on islet cells. Interferon-gamma and tumor necrosis factor-alpha reduced the nicotinamide adenine dinucleotide content of mouse islet cells; the combination of interferon-gamma (4 x 10(5) U/l) and tumor necrosis factor-alpha (4 x 10(5) U/l) caused nicotinamide adenine dinucleotide reduction by approximately 40%. Dimethyl urea and dimethyl sulfoxide prevented the decrease, whereas superoxide dismutase, catalase, and mannitol were not effective. Dimethyl urea and dimethyl sulfoxide protected islet cells from the synergistic cytotoxic action of interferon-gamma and tumor necrosis factor-alpha. Major histocompatibility complex class II antigen induction by interferon-gamma and tumor necrosis factor-alpha was also inhibited by dimethyl urea and dimethyl sulfoxide, but not by superoxide dismutase, catalase and mannitol. Since superoxide dismutase of a membrane-penetrable form attenuated the class II antigen induction, the inefficiency of superoxide dismutase, catalase and mannitol may be attributable to their inability to penetrate islet cells. These results suggest that the intracellular generation of free oxygen radicals is involved in islet cell cytotoxicity and class II molecule expression by interferon-gamma and tumor necrosis factor-alpha, and that nicotinamide adenine dinucleotide reduction may be associated with islet cell dysfunction caused by the cytokines.

Animals↗
PubMed1993

Effects of the carbohydrate composition of a low-protein meal on the postprandial responses of plasma glucose and insulin in diabetic patients.

We determined whether, in 15 diabetic patients, a conventional low-protein diet containing a high proportion of mono- and disaccharides would lead to a deterioration of postprandial glucose metabolism. Three different test meals were given on 3 different days. We found that a high proportion of simple carbohydrates, when consumed as a low-protein meal, aggravated the postprandial hyperglycemia in diabetic patients. The substitution of complex carbohydrates for simple sugars in the meal suppressed postprandial hyperglycemia in diabetic patients.

Adult↗
PubMed1993

Pancreatic beta-cell-selective production of tumor necrosis factor-alpha induced by interleukin-1.

Cytokines have been regarded as effector molecules responsible for beta-cell death and major histocompatibility complex hyperexpression in endocrine pancreas of type I diabetes. However, the mechanism that results in beta-cell-selective destruction has not been elucidated. We demonstrated in this study, using cell lines of transformed mouse beta-cells and alpha-cells, that only pancreatic beta-cells but not alpha-cells produced tumor necrosis factor-alpha when exposed to interleukin-1 beta. Northern blot analysis confirmed the beta-cell-selective expression of tumor necrosis factor-alpha mRNA. Interleukin-1 beta also provoked tumor necrosis factor-alpha mRNA expression in vitro by normal mouse islet cells. Because tumor necrosis factor-alpha has been shown to potentiate beta-cell cytotoxicity of interleukin-1 and interferon-gamma, tumor necrosis factor-alpha produced in situ by beta-cells might be self-destructive. In fact, a low dose of interleukin-1 beta in combination with a low dose of interferon-gamma preferentially injured beta-cells. Hence endogenous tumor necrosis factor-alpha production by beta-cells may be involved in beta-cell-selective destruction in type 1 diabetes.

Animals↗