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Biomedical subjects

S Nakada

Publications and source records attributed to S Nakada.

At least 109 records · Page 6Linked to original sources

Susceptibility of lipids to mercurials.

Affinity of mercury compounds to various phospholipids and fatty acids were examined. Inorganic mercury showed a higher affinity to lipids containing unsaturated fatty acids than to those composed of saturated fatty acids. This suggests that inorganic mercury may easily act on the double bonds of fatty acid residues in phospholipids which are major components of the biomembrane. On the other hand, methylmercury was almost inert to these lipids regardless of the presence or absence of unsaturated bonds.

Chemical Phenomena↗

Uptake of methylmercury and inorganic mercury by mouse glioma and mouse neuroblastoma cells.

Methylmercury was taken up preferentially by mouse glioma and mouse neuroblastoma cells relative to inorganic mercury. Methylmercury uptake was depressed by lowering the cellular ATP level or the incubation temperature, while the uptake of inorganic mercury was not affected by these treatments. When the cells were treated with reagents such as cytochalasin B, colchicine and vinblastine which are known to affect membrane permeability, changes in permeability to methylmercury caused by these reagents were markedly different from those to inorganic mercury. Inorganic mercury above 2 x 10(-5)M caused the release of 2-deoxyglucose trapped in the cells and the amount of inorganic mercury taken up by the cells increased markedly at higher concentrations. Inorganic mercury thus appeared to move into the cells after disrupting the membrane barrier, while methylmercury can penetrate the cells without any noticeable damage to the barrier.

Animals↗

Mechanism of methylmercury cytotoxicity: by biochemical and morphological experiments using cultured cells.

Effects of methylmercury on the cell growth of mouse glioma in vitro were studied in relation to the microtubules as a possible target. The electron microscopic observation revealed that methylmercury added in culture medium specifically attacked microtubules in the cells at growth inhibitory concentration, while mercuric mercury injured microtubules to the same extent as other cell organelles. However the latter showed a little stronger depressing effect on tubulin polymerization in vitro than the former. Further, 3 other inorganic metal ions (Cd2+, Cu2+ and Cr3+), which were reported to suppress tubulin polymerization in vitro, did not disturb the microtubule networks even at their cell growth inhibitory concentrations. Therefore, of these metal compounds tested, when they were added in the culture medium, methylmercury seemed to specifically interact with microtubules and cause inhibition of cell growth.

Animals↗

Change in permeability of liposomes caused by methylmercury and inorganic mercury.

The effects of two mercurial compounds, methylmercury and inorganic mercury, on lipids were examined by measuring permeability change of lipid bilayer, liposome. Both decrease in the cholesterol content and increase in the content of unsaturated fatty acid moieties in the lipid bilayers, augmented to susceptibility of the liposomes to the mercurial compounds. Inorganic mercury and methylmercury disrupted the lipid membrane to essentially the same extent. The influence on the permeability seems to be specific for mercury compounds. The significant increase in the permeability of some liposomal preparation noted even at the mercurial concentration of 10(-7) M strongly suggests that lipid in biomembrane could be one of the primary targets of these toxic substances.

Animals↗

Chemosensitivity testing of ovarian cancer using the histoculture drug response assay: sensitivity to cisplatin and clinical response.

Despite cytoreductive surgery and chemotherapy, the prognosis of advanced ovarian cancer is still poor. Predicting the chemosensitivity of tumors might improve the outcome. Therefore, we investigated the clinical value of the histoculture drug response assay for ovarian cancer. Tumor specimens were cultured for 7 days on collagen gel sponge in medium containing cisplatin, and the 50% inhibitory concentration was determined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay. Then the in vitro sensitivity to cisplatin was compared with the clinical response and survival. Apoptosis of tumor cells was also investigated. Among 173 ovarian cancer patients, 164 were evaluable by the assay, and 29 patients had measurable lesions for which the clinical response could be determined. The 5-year survival rate was significantly higher in patients with chemosensitive tumors than in those with chemoresistant tumors when the cutoff value was set at a 50% inhibitory concentration of 25 microg/mL and the accuracy of the assay was 82.8% (24/29). As chemosensitivity to cisplatin became greater, the number of apoptotic cells also increased. This chemosensitivity assay may help predict the clinical response to cisplatin-based chemotherapy, thus improving the survival of ovarian cancer patients.

Adult↗