Protein expression of double-stranded RNA-activated protein kinase (PKR) in intrahepatic bile ducts in normal adult livers, fetal livers, primary biliary cirrhosis, hepatolithiasis and intrahepatic cholangiocarcinoma.

BACKGROUND/AIM: The protein expression of double-stranded RNA-activated protein kinase (PKR) in intrahepatic bile ducts has not been investigated. METHODS: Immunohistochemistry and a semiquantitative scoring method in normal liver and biliary diseases were used for the investigation. RESULTS: In "normal" adult livers (n=10), intrahepatic bile ducts were negative for PKR. In normal fetal livers (n=25), primitive biliary epithelia were almost negative for PKR. In primary biliary cirrhosis (PBC) (n=30), damaged bile ducts were frequently positive for PKR, while uninvolved bile ducts were negative. In hepatolithiasis (n=27), proliferated bile ducts were positive for PKR, and the PKR score correlated with the degree of proliferation. In cholangiocarcinoma (CC) (n=44), PKR expression was frequently noted, and the PKR score correlated with good differentiation of CC, being highest in well-differentiated CC and lowest in poorly-differentiated CC. The PKR score decreased in the following order: CC (mean PKR score=3.96), hepatolithiasis (2.56), PBC (1.60), normal fetal liver (0.40), and normal adult livers (0.00). The PKR expression in hepatocytes was "baseline" in normal adult livers, while moderately increased in fetal livers, PBC, hepatolithiasis and CC. CONCLUSIONS: Although the significance of these data is unclear, they suggest (i) that PKR is absent in bile ducts in normal adult and fetal livers, (ii) that PKR in bile duct cells newly emerges or increases in PBC, hepatolithiasis, and CC, (iii) that PKR accumulates in damaged bile ducts in PBC, (iv) that PKR increases in parallel with biliary cell proliferation in hepatolithiasis, and (v) that PKR expression correlates with differentiation in CC. PKR expression in intrahepatic bile ducts seems to be associated with inflammation or cell proliferation of the bile duct cells.

Trypsin(ogen) content of pancreatic calculi in chronic calcified pancreatitis in man.

Protein analysis of intraductal precipitates and calculi is important to elucidate the mechanism of stone formation in chronic pancreatitis. We revealed human cationic trypsin immunoreactivity in protein extracts of pancreatic stones from 11 of 13 patients with chronic calcified pancreatitis, ranging from 0 to 42.3 ng/micrograms protein. On gel filtration the immunoreactivity eluted as one peak, which is identical to that of human cationic trypsinogen. On immunostaining of pancreatic stone, using an immunogold technic and scanning electron microscopy, the immunoreactivity was observed more densely in the amorphous portion of the center of the stones than in the concentric laminar layer of the periphery. Only negligible activity was detected for elastase 1 or amylase in the stone extracts. These results suggest that the presence of trypsinogen in pancreatic stone is not due to coprecipitation or adsorption of pancreatic enzymes but that trypsinogen is more likely involved in an initial step of intraductal precipitate formation than in a subsequent step of stone formation. However, the absence of trypsinogen in the stones from two of the 13 patients also suggests that trypsinogen is not the sole protein initiating precipitate formation.

Role of urease in the formation of infection stones: comparison of ureases from different sources.

Bacterial and vegetable ureases were found to differ in certain important respects. For maximal clinical relevance, in vitro studies on the pathogenic role of urease should use whole bacterial cells of Proteus spp., and urease inhibitors should be assessed without preincubation of enzyme with inhibitor. Urease from Proteus morganii was very different from ureases of other species of Proteus; this factor should be taken into account when infections with P. morganii are being treated.

Evaluation of biliary and pancreatic function in pancreolithiasis. Value of the determination of gamma-glutamyl transpeptidase.

Ten patients with pancreolithiasis and ten controls underwent a 110-minute pancreozymin-secretion test in which post-pancreozymin collection periods were prolonged to 30 minutes. Gamma-Glutamyl transpeptidase concentrations and outputs of duodenal aspirate in response to pancreozymin and to secretin were greatly increased in patients with pancreolithiasis. No correlation was noted between gamma-glutamyl transpeptidase and bile pigment concentrations. The mean concentrations and outputs of amylase in disease were much less than those in control subjects throughout the test. Two categories of pancreolithiasis were distinguished with respect to the distribution and size of the calculi and amylase secretion. We suggest that, in pancreolithiasis, there is an increase in ductal or centroacinar cell mass.