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Biomedical subjects

M Kikuchi

Publications and source records attributed to M Kikuchi.

At least 1,063 records · Page 59Linked to original sources

Dual effects of veratridine on glucagon and insulin secretion: dependence upon extracellular and intracellular calcium.

The stimulatory effect of the sodium ionophore, veratridine (10, 25 and 50 microM), on glucagon and insulin secretion was investigated using monolayer cultures of newborn rat pancreas. The results suggest that intracellular accumulation of sodium modulates hormone secretion from both alpha- and beta-cells. The action of veratridine is dependent, at least in part, on the extracellular calcium as its effect was attenuated or lost when extracellular calcium was deleted. Its action was also dependent on intracellular calcium since preincubation of cells in low, normal, or high calcium to diminish, maintain, or increase intracellular calcium, followed by incubation with veratridine in the absence of calcium, altered the secretory responses of both glucagon and insulin. Ouabain (0.5 mM) stimulated glucagon and insulin secretion, although its effect was less than that of veratridine (50 microM). These results suggest that a common releasing mechanism, dependent on extra- and intracellular calcium, is involved in both endocrine cells.

Animals↗

Infantile digital fibromatosis. Ultrastructural, histochemical, and tissue culture observations.

Three cases of infantile digital fibromatosis were studied by electron microscopy, enzyme histochemistry, and tissue culture. The tumors were made up equally of myofibroblasts containing electron-dense inclusions which were composed chiefly of microfilaments measuring about 5 to 7 nm. Dense bodies usually observable in the smooth muscle cells were found in the bundles of these microfilaments and in the process of the inclusions, suggesting that these inclusions may represent an abnormal accumulation of contractile protein in the cytoplasm of tumor cells. Two cell lines were established from culture of the tumor cells, and the cultured cells also contained inclusion bodies showing the same morphologic characteristics as those of the original tumor cells. Lysosomal enzymes were abundant in the cultured cells, but they were scant in the cells of the fresh tissue specimens. Cocultivation of the cultured cells with human embryonic lung cells yielded no cytopathic effect.

Acid Phosphatase↗

Effect of tin on porphyrin biosynthesis.

Certain disturbances in porphyrin biosynthesis were examined in rabbits administered with either tin or lead. Stannous chloride treatment increased the concentrations of coproporphyrin in blood and urine, as did lead acetate treatment. No effect of tin on 5-aminolevulinic acid concentration was observed in blood and urine, whereas lead treatment increased it markedly in both. Tin profoundly inhibited the activity of 5-aminolevulinate dehydratase in blood, but did not alter it in liver although tin content in liver was considerably higher than that in blood. In contrast to a prolonged inhibition of erythrocyte 5-aminolevulinate dehydratase by lead, tin inhibition of erythrocyte 5-aminolevulinate dehydratase activity was rapidly reversed after the cessation of the metal treatment.

Aminolevulinic Acid↗

Cell culture of infantile digital fibromatosis.

Two cell cultures were obtained from excised tumors of two cases of infantile digital fibromatosis (IDF). The cells had eosinophilic cytoplasmic inclusion bodies characteristic of IDF. Although the rate of cells bearing the inclusion bodies was high at the earlier passage levels, it was reduced to zero by the 15th passage of one of the cultures, but the cells of the other culture continued to produce the inclusion bodies even at the 30th passage. Chromosome analysis revealed both cultures to have tetraploid cells in approximately 8 to 12% in late passage levels. No viruslike particles were found in electron microscopy. No tumors developed when the cells were inoculated into athymic, nude mice subcutaneously. These cell cultures will be valuable for characterizing the eosinophilic inclusion bodies and determining the origin of the tumors.

Animals↗

Dependency of cyclic AMP-induced insulin release on intra- and extracellular calcium in rat islets of Langerhans.

Calcium and cyclic AMP are important in the stimulation of insulin release. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) raises islet cAMP levels and causes insulin release at nonstimulatory glucose concentrations. In isolated rat pancreatic islets maintained for 2 d in tissue culture, the effects of IBMX on insulin release and 45Ca++ fluxes were compared with those of glucose. During perifusion at 1 mM Ca++, 16.7 mM glucose elicited a biphasic insulin release, whereas 1 mM IBMX in the presence of 2.8 mM glucose caused a monophasic release. Decreasing extracellular Ca++ a monophasic release. Decreasing extracellular Ca++ to 0.1 mM during stimulation reduced the glucose effect by 80% but did not alter IBMX-induced release. Both glucose and IBMX stimulated 45Ca++ uptake (5 min). 45Ca++ efflux from islets loaded to isotopic equilibrium (46 h) was increased by both substances. IBMX stimulation of insulin release, of 45Ca++ uptake, and of efflux were not inhibited by blockade of Ca++ uptake with verapamil, whereas glucose-induced changes are known to be inhibited. Because IBMX-induced insulin release remained unaltered at 0.1 mM calcium, it appears that cAMP-stimulated insulin release is controlled by intracellular calcium. This is supported by perifusion experiments at 0 Ca++ when IBMX stimulated net Ca++ efflux. In addition, glucose-stimulated insulin release was potentiated by IBMX. These results suggest that cAMP induced insulin release is mediated by increases in cytosolic Ca++ and that cAMP causes dislocation of Ca++ from intracellular stores.

1-Methyl-3-isobutylxanthine↗