- 著者
- Emiko Kurisaki Masao Sato Sigeyuki Asano Hirobumi Gunji Mamoru Mochizuki Hajime Odajima Haruki Wakasa Hiroshi Satoh Chiho Watanabe Kouichi Hiraiwa
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Journal of Health Science (ISSN:13449702)
- 巻号頁・発行日
- vol.45, no.6, pp.309-317, 1999-12-31 (Released:2008-04-14)
- 参考文献数
- 20
- 被引用文献数
- 2 1
It has been assumed that "smelter disease" is caused by sulfuric dioxide. A typical episode resulting in "smelter disease" occurred in Fukushima, Japan. Twenty-seven workers became ill and eventually three of them died. The concentration of mercury (Hg) was found to be higher in all tissues and blood of the three victims than in those of normal Japanese, although the concentrations of zinc, cadmium, copper and lead in all tissues examined were within the normal range. The clinical course after the incident and autopsy findings clarified the cause of death to be acute Hg fume poisoning. To determine the histological localization of Hg and metallothionein (MT), Hg staining by the photo-emulsion method and immunostaining using anti-MT antibody were carried out. Numerous Hg granules were observed in the epithelia of the proximal tubules of the renal cortex using the photo-emulsion histochemical method. The liver of victims contained a few Hg granules in the hepatic cellular cytoplasm and sinusoid. Immunostaining of the kidney showed a strong positive reaction with anti-MT in the proximal tubules outside the medulla. The presence of Hg-bound MT in the kidneys of the victims was confirmed by gel chromatography. This is the first evidence of Hg-MT in the tissues of humans with acute Hg fume poisoning. Mercury might induce the synthesis of MT in human tissues. In addition, fractionation of the supernatants on gel chromatography revealed that most of the Hg in the kidney and lung of the patient who had the most severe renal and lung damage and who was the first of the three victims to die was distributed in high molecular weight protein fractions (HMW) and a small portion of Hg was bound to MT. These findings suggest that the amount of synthesized MT in tissues was not sufficient for MT to bind to Hg. The amount of Hg absorbed into tissues may be too large for MT to protect tissues, and thereby Hg may be bound to HMW.
- 著者
- Takahiro Tokuhisa Masafumi Yano Masakazu Obayashi Toshiyuki Noma Mamoru Mochizuki Tetsuro Oda Shinichi Okuda Masahiro Doi Jinyao Liu Yasuhiro Ikeda Takeshi Yamamoto Tomoko Ohkusa Masunori Matsuzaki
- 出版者
- The Japanese Circulation Society
- 雑誌
- Circulation Journal (ISSN:13469843)
- 巻号頁・発行日
- vol.70, no.6, pp.777-786, 2006 (Released:2006-05-25)
- 参考文献数
- 42
- 被引用文献数
- 18 20
Background The Ca2+ regulatory proteins in the sarcoplasmic reticulum (SR) play a key role in the pathogenesis of heart failure. In the present study the effect of chronic β-receptor-stimulation on cardiac and SR functions was assessed, with or without angiotensin-II receptor antagonist treatment recently reported to have anti-β-adrenergic activity. Methods and Results Rats were treated with isoproterenol with (+) or without (-) candesartan (CAN) and then SR vesicles were isolated from the left ventricular muscle. Both Ca2+-uptake and the amount of SR Ca2+-ATPase were significantly lower in the CAN (-) group than in the shams, but those were almost normally restored in the CAN (+). Although the level of the protein kinase A (PKA)-phosphorylation of the SR Ca2+ release channel, known as the ryanodine receptor (RyR2), was elevated in the CAN (-), no Ca2+-leak was detected. However, SIN-1 (O2 - donor) induced Ca2+-leak in the CAN (-) at a 10-fold lower dose than in the sham and CAN (+). In cardiomyocytes, SIN-1 decreased cell shortening and the peak Ca2+ transient and prolonged time from peak to 70% decline in CAN (-), again at 10-fold lower dose than in the sham and CAN (+). Conclusion Chronic β-receptor-stimulation did not induce any Ca2+-leak from the SR, whereas Ca2+-leak was easily induced when oxidative stress was applied to the PKA-phosphorylated RyR2. Candesartan not only improved Ca2+-uptake, but also prevented PKA-phosphorylation, rendering the SR less susceptible to Ca2+-leak. (Circ J 2006; 70: 777 - 786)