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Biomedical subjects

T Kashimoto

Publications and source records attributed to T Kashimoto.

At least 55 records · Page 3Linked to original sources
PubMed1986

Mechanism of the inhibitory effect of thiopentone on stimulus-secretion coupling in chromaffin cells.

This study was undertaken to clarify the mechanism of action of thiopentone on stimulus-secretion coupling in cholinergic postsynaptic cells using cultured bovine adrenal chromaffin cells. Thiopentone (20-100 microns) inhibited carbachol-induced Ca2+ uptake into, and catecholamine release from the cells in a concentration-dependent manner. The inhibition of catecholamine release was almost parallel to the inhibition of Ca2+ uptake. The inhibitory effect of thiopentone was not overcome by an increase in the concentration of carbachol, whereas that of alcuronium was. Contrary to the inhibition by diltiazem, which was reversed by increasing the Ca2+ concentration, the inhibition by thiopentone was not overcome by a high Ca2+ concentration. Compared with the inhibition of carbachol-induced catecholamine release, a higher concentration of thiopentone was required to inhibit high K+ (56 mM KCl)-induced catecholamine release (200 microns thiopentone exhibited 32% inhibition). The results suggest that thiopentone blocks the stimulus-secretion coupling in the chromaffin cells as a result of inhibiting Ca2+ uptake through nicotinic receptor-linked channels. The linkage between receptor stimulation and Ca2+ channel activation seems to be the process most susceptible to inhibition by the barbiturate.

Animals↗
PubMed1985

Polychlorinated biphenyl poisoning: correlation of sensory and motor nerve conduction, neurologic symptoms, and blood levels of polychlorinated biphenyls, quaterphenyls, and dibenzofurans.

In 1979 in Taiwan, more than 2000 people were poisoned with rice cooking oil contaminated with polychlorinated biphenyls (PCB). One hundred ten patients were studied within one year of the exposure. The blood PCB levels were 39.3 +/- 16.6 ppb. The blood levels of the PCB derivatives, polychlorinated quaterphenyls (PCQ) and polychlorinated dibenzofurans (PCDF), were 8.6 +/- 4.8 and 0.076 +/- 0.038 ppb, respectively. Both the sensory and motor nerve conduction velocities (NCV) of the patients were significantly lower than the control. Abnormal slowing of sensory NCV was found in 43.6% and abnormal slowing of motor NCV was seen in 21.8%. Patients who had higher PCQ blood levels had significantly slower median nerve sensory NCV than those with lower PCQ levels. Patients with higher PCB blood levels had significantly slower peroneal nerve motor NCV than those with lower PCB levels.

Adolescent↗
PubMed1985

Mechanism of the effect of droperidol to induce catecholamine efflux from the adrenal medulla.

The study was undertaken to determine whether droperidol had an effect to induce catecholamine efflux from the adrenal medulla as a mechanism for the possible pressor effect of droperidol in patients with pheochromocytoma and, if so, to ascertain the site of action of this compound. The efflux of catecholamines from perfused dog adrenals was increased from control level, 0.15 micrograms/min, to 0.66 micrograms/min by the administration of droperidol 6.6 microM. This effect of droperidol was not dependent on extracellular Ca++, in contrast to acetylcholine. The concomitant secretion of catecholamines and dopamine-beta-hydroxylase was observed in response to acetylcholine and caffeine. However, droperidol-, histamine-, and reserpine-induced catecholamine efflux was not accompanied by dopamine-beta-hydroxylase release. In additional studies, chromaffin granules were isolated with a Millipore filter technique from the bovine adrenal medulla and were incubated for 10 min in an isotonic medium to examine the direct effects of droperidol. Droperidol did not enhance the efflux of catecholamines from the granules in contrast to histamine. The uptake of 14C-norepinephrine into the granules was inhibited by droperidol in a manner comparable to reserpine. The results suggest that droperidol induces catecholamine efflux from adrenal medullary cells and the efflux probably is caused by a nonexocytotic mechanism. A contributing mechanism was an inhibition of catecholamine uptake into chromaffin granules, resulting in an increased diffusion of catecholamines out of the cell.

Acetylcholine↗
PubMed1985

Biological effect of PCBs, PCQs and PCDFs present in the oil causing yusho and yu-cheng.

Male Sprague-Dawley rats were daily given orally for 22 days a regimen consisting of polychlorinated biphenyls (PCBs), 1 mg/day; polychlorinated quaterphenyls (PCQs), 1 mg/day; polychlorinated dibenzofurans (PCDFs), 10 micrograms/day; or a mixture of PCBs, PCQs and PCDFs (Mix-1, 1 mg + 1 mg + 10 micrograms/day). Female Cynomolgus monkeys were daily administered PCBs (5 mg), PCQs (5 mg) or a mixture (Mix-2) containing 5 mg PCBs + 20 micrograms PCDFs for 20 weeks. The PCBs, and PCDFs had the components of PCBs, PCQs and PCDFs similar to those contained in Japanese yusho oils, respectively. The PCB-treated rats and monkeys showed hepatic hypertrophy, immunosuppression and increased drug-metabolizing enzyme activities in hepatic microsomes, but were devoid of the dermal symptoms characteristic of yusho. PCQs caused an increase in drug-metabolizing enzyme activities in hepatic microsomes and immunosuppression in monkeys, but these effects were much smaller than those found with PCBs treatment. On the other hand, treatment with PCDF or Mix-1 or Mix-2 caused hypertrophy of the liver, immunosuppression, increase in drug-metabolizing enzyme activities of hepatic microsome to much greater extent than observed with PCBs, being more than 100 times as effective as PCBs. In addition PCDFs and the mixtures containing PCDFs caused weight loss and thymic atrophy. PCDFs and Mix-2-treated monkeys showed the dermal symptoms that are characteristic of yusho patients but were not observed in monkeys treated with PCBs and PCQs alone. These results suggest that PCDFs are the primary causative agent of yusho.

Animals↗
PubMed1985

PCBs, PCQs and PCDFs in blood of yusho and yu-cheng patients.

Individual blood samples obtained from yusho and yu-cheng patients who had been poisoned by ingesting contaminated cooking oils, from workers occupationally exposed to polychlorinated biphenyls (PCBs) and from unexposed individuals were analyzed for PCBs, polychlorinated quaterphenyls (PCQs) and polychlorinated dibenzofurans (PCDFs) by gas chromatography and mass spectrometry. PCBs were found in the blood of all samples. PCQs were detected in the blood of 54 of 56 living yusho patients 11 years after the outbreak, and in all yu-cheng patients 6 months following poisoning. These facts indicate that the presence of PCQs in the blood was a good mark of past ingestion of the toxic oil. In the yu-cheng cases, PCDFs as well as PCBs and PCQs were detected in all blood samples. These identified isomers have been reported to be remarkably highly toxic compounds, i.e., both the 2,3,7,8-tetrachlorinated and 2,3,4,7,8-pentachlorinated compounds are toxicologically hundreds to thousands of times more toxic than PCB. In view of the high toxicity of PCDFs found in the yu-cheng patients' blood, we must deduce that they are the primary causal agents of yusho as well as of the yu-cheng incident.

Benzofurans↗
PubMed1985

PCBs, PCQs and PCDFs in tissues of yusho and yu-cheng patients.

All five samples of oil involved in the recent yu-cheng outbreak were heavily contaminated with PCBs, PCQs and PCDFs at levels, on the average, of 62, 20 and 0.14 ppm, respectively. The samples not only had roughly one-tenth of the contamination by PCBs, PCQs and PCDFs but also three to four times lower ratios of PCQs and PCDFs to PCBs than samples of oil involved in yusho in Japan. PCBs, PCQs and PCDFs present were all composed of similar congeners to the ones found in the yusho specimens, though some variation of the component ratios of PCBs and PCDFs were observed. On the other hand, five patients with yusho who died 1 to 10 years following poisoning had markedly higher tissue levels of PCDFs and PCQs than did a worker occupationally exposed to PCBs. Taking great differences in the process of the healing and the tissue levels of PCBs, PCQs and PCDFs between the two poisoning cases into consideration, PCDFs and PCQs--especially the former--and not PCBs are deduced to be strongly associated with the development of yusho.

Benzofurans↗