|Budget Amount *help
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1990: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
To evaluate the role of biliary proteins and biliary lipid particles in the pathogenesis of cholesterol gallstone formation, we performed an ultrastructural studies using transmission electron microscopy. Conclusions were as follow ;
1. There are three different types of lipid particle in human gallbladder bile and supersaturated model bile solutions, lecithin-cholesterol vesicle, bile salt micelle, and discoidal particle.
2. Apolipoprotein A-1, an anti-nucleating factor, stabilizes nonmicellar lipid particles by binding to discoidal particles, followed by inhibition of transformation to multilamellar liposome.
3. On the other hand, a high hepatic output of cholesterol into bile correlates a high incorporaion of linoleate and arachidonate into biliarylecithin, resulting in the induced synthesis and secretion of mucin, a pronucleating factor, by the gallbladder. This is mediated by an arachidonate-prostanoid pathway. Mucin promotes vesicular aggregation and fusion, resulting in fastnucleation.
Thus, cholesterol crystal nucleation is regulated by the balance between anti-nucleating factors and pronucleating factors. In addition, nucleation occurs from the non micellar lipid particles, i. e. vesicles, discoidal particles.