Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0008325 (cholecystitis)
 3,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The positional specificity of the phospholipase A (EC 3.1.1.4) in human gallbladder epithelium has been studied using 14C-phosphatidylethanolamine radiolabeled either in the 1-acyl or in the 2-acyl position. After heating of homogenized epithelial cells at 70 degrees C for 2 min, their lysophospholipase activity was lost. In contrast, the ability to hydrolyze 14C-phosphatidylethanolamine in biosynthetically radiolabeled Escherichia coli was largely retained. The amounts of radioactivity found in the products of hydrolysis under different conditions suggest that there are two different phospholipase A activities in the gallbladder epithelium: one, with optimal activity at pH 7, that requires Ca2+ and is specific for the 2-acyl position, and another, with optimal activity at pH 4, that does not require Ca2+ and that, apart from the 2-acyl position, attacks the 1-acyl position as well. It is possible, therefore, that a complete deacylation of diacylphosphoglycerides in the gallbladder wall is brought about in two different ways: at neutral pH through a combined action of phospholipase A2 and lysophospholipase, the latter being able to hydrolyze the 1-acyl-lysophosphoglyceride, and, at acid pH, through the action of phospholipase A1 and A2 activity, presuming 1-acyl- and 2-acyl-lysophosphoglycerides are also attacked. Both these processes have to be considered in order to explain a turnover of diacylphosphoglycerides that physiologically would prevent the accumulation of lytic lysophosphoglycerides. The possible relevance of these findings to the pathogenesis of aseptic cholecystitis is inferred.
 ...
PMID:The prerequisites for local lysolecithin formation in the human gallbladder. III. Demonstration of two different phospholipase A activities. 3 26

The positional specificity of the phospholipase A in human gallbladder epithelium was studied by using biosynthetically radioabeled diacylphosphoglycerides as substrates. Diacylphosphoglyceride in 14C-palmitic acid-labeled, autoclaved E.coli was hydrolyzed under the formation of monoacylphosphoglyceride and fatty acid that were both radiolabled. In contrast, diacylphosphoglyceride in 14C-oleate-labeled bacteria was hydrolyzed so as to give radiolabel in the fatty acid only. Since 14C-palmitate occupies predominantly the 1-acyl position and 14C oleate the 2-acyl position of the major E. coli diacylphosphoglycerides, these findings suggest that: 1) the phospholipase attacks and 2-position of diacylphosphoglycerides, and 2) a complete deacylation of diacylphosphoglycerides in the gallbladder wall is brought about by the combined action of phospholipase A2 and lysophospholipase, the latter being able to hydrolyze the 1-acyllysophosphoglyceride. It appears, therefore, that the biochemical preequisites for a local formation and degreadation of lysolecithin in the gallbladder itself are met by the positional specificity of theenzymes present. This finding further substantiates the hypothesis that lysolecithin is an adjustable mediator of aseptic cholecystitis.
 ...
PMID:The prerequisites for local lysolecithin formation in the human gallbladder. II. Studies on the positional specificity of the phospholipase A activity. 67 50

An experimental model of anomalous arrangement of the pancreaticobiliary ducts (APBD) was produced by pancreaticocholecystostomy performed in 29 mongrel dogs. Our purpose was to study carcinogenesis of the extrahepatic biliary tract by DNA ploidy analysis with cytofluorometry. The amylase level in the bile was elevated in all 25 dogs tested except the controls. The phospholipase A2 level in the bile was elevated in all selected dogs except the controls. Common bile duct (CBD) dilatation was found in 23/29 (79%) of the dogs, and biliary stones were found in 3/29 (10%) dogs. Inflammatory changes were observed microscopically in all specimens except those from the controls. Intramural glandular structures were found in 17/25 (68%) of gallbladder (GB) specimens and 10/25 (40%) of CBD specimens; goblet cells were found in 7/25 (28%) of GB specimens and 2/25 (8%) of CBD specimens. In the controls neither glandular structures nor goblet cells were observed except for two GB specimens showing mild cholecystitis. Cytofluorometry showed 21% GB and 7% CBD diploidy, 69% GB and 65% CBD low ploidy, 10% GB and 28% CBD high ploidy patterns of histograms. These results show that, APBD may be central to high risk condition or play a key role to develop atypical biliary tract epithelium and DNA ploidy abnormality with or without biliary duct dilatation.
 ...
PMID:Experimental studies on carcinogenesis in anomalous arrangement of the pancreaticobiliary ducts. 141 51

In the experiment on 30 mongrel dogs, acute enzymatic cholecystitis (AEC) was modelled by means of intraduodenal connection with a fluoroplastic catheter of the common bile duct and pancreatic duct. The animals died at day 3-5 from transudative biliary peritonitis. A correlation between the severity of the clinical course, pronouncement of enzymologic shifts (increase in activity of amylase and phospholipase A2, content of biliary malonic dialdehyde) and morphological changes in the gallbladder and common bile duct in the form of necrosis and round-cell infiltration of the mucosa was revealed. Only decompression of the bile duct within the first 6 h from the moment of AEC development contributes to regression of clinical and enzymologic disorders and recovery of the animals.
 ...
PMID:[Acute experimental enzymatic cholecystitis (clinico-morphological comparisons)]. 171 18

To elucidate the pathogenesis of acute acalculous cholecystitis, the gallbladder was subjected to ischemia-reperfusion by simultaneously occluding the middle hepatic artery and the superior mesenteric vein in dogs, and the degree of inflammation and biochemical changes in the gallbladder mucosa were studied by varying the duration of ischemia or reperfusion. Ischemia alone did not induce cholecystitis either macroscopically and histologically, although it increased phospholipase A2 (PLA2) activity, content of lipid peroxide, and superoxide dismutase (SOD) activity in the mucosa with prolongation of the ischemic time. Cholecystitis was produced in all animals by 45-min ischemia followed by 90-min reperfusion as the shortest ischemia and reperfusion times. In this model, prolongation of the ischemic time increased the area of mucosal inflammation horizontally with increases of the PLA2 activity, content of lipid peroxide, and SOD activity, whereas by prolonging the reperfusion time the inflammation area spread deeper vertically toward the serosal side with significant increase in the mucosal PLA2 activity, content of lipid peroxide, and SOD activity. These results revealed that ischemia-reperfusion plays an important role in the pathogenesis of acute acalculous cholecystitis, causing the generation of free radicals and the activation of membrane-bound PLA2.
 ...
PMID:Experimental study on the pathogenesis of acute acalculous cholecystitis, with special reference to the roles of microcirculatory disturbances, free radicals and membrane-bound phospholipase A2. 175 95

It has been demonstrated in experimental cholecystitis in cats produced by lysophosphatidylcholine that the development of inflammation is associated with the exsorption of a large amount of protein into the gallbladder lumen. It was subsequently demonstrated that in feline experimental cholecystitis the protein produced was albumin and that its production was decreased by vesicular transport inhibitors, suggesting an active secretory process. In the present study, the effect of lysophosphatidylcholine on protein production by fresh, isolated human gallbladder mucosal cells was evaluated. Isolated gallbladder mucosal cells were incubated with [14C]leucine for 24 hr in tissue culture medium. The cells readily incorporated the radioactive label into cellular protein, a process inhibited by cycloheximide. Exposure of the cells to lysophosphatidylcholine for 1 hr in buffer solution resulted in loss of intracellular protein into the buffer solution. Exposure of the cells for 1 hr prior to lysophosphatidylcholine administration to vesicular transport inhibitors, colchicine, and cytochalasin B and to 4 degrees C culture conditions failed to alter the lysophosphatidylcholine-produced passage of the 14C label extracellularly. SDS-PAGE evaluation of the protein produced demonstrated that human gallbladder mucosal cells continuously produced a 66-kDa protein that was not increased by increasing concentration of lysophosphatidylcholine and a 14-kDa protein that increased with increasing concentrations of lysophosphatidylcholine. Employing Western blotting with specific antibodies, the 66-kDa protein was demonstrated to not be albumin but a 66-kDa glycoprotein, and the 14-kDa protein was demonstrated to contain phospholipase A2. Human gallbladder mucosal cells produced a protein and glycoprotein in response to lysophosphatidylcholine by a mechanism not related to vesicular transport.
 ...
PMID:Lysophosphatidylcholine-stimulated protein and glycoprotein production by human gallbladder mucosal cells. 755 54

Lysolecithin has been implicated as a contributing factor in the pathogenesis of cholecystitis and cholesterol cholelithiasis. The phospholipases are key enzymes in the generation of a number of metabolites including lysolecithin, but conflicting reports exist concerning the presence of these enzymes in the biliary tract. In this study, measurement of phosphatidylcholine-specific phospholipase activity by means of the hydrolysis of radiolabeled phosphatidylcholine (100 nmol) by 90 micrograms of homogenate protein during a 60-min incubation demonstrated substantial enzyme activities in gastric fundus and distal ileum (90% and 70% hydrolysis, respectively), whereas activity was virtually undetectable in gallbladder mucosa (0.7% hydrolysis). Additional studies were conducted in prairie dogs fed diets high in cholesterol or with trace amounts of cholesterol using homogenates of gallbladder mucosa, seromuscularis and full-thickness tissue, as well as samples of hepatic and gallbladder bile. The only hydrolytic activity in excess of blank values that was detected was a highly variable phospholipase A2 activity in several gallbladder biles from animals given diets with both low levels and high levels of cholesterol, with the enzyme activities of the two dietary groups being similar. These results demonstrate that prairie dog gallbladder contains extremely low levels of phospholipase activity, in marked contrast to other gastrointestinal tissues. However, there was evidence of a phospholipase A2 activity in gallbladder bile. In light of the low activity in gallbladder tissue, the source of this enzyme appears to be the liver and not the gallbladder.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Biliary phospholipases in the prairie dog model for cholesterol cholelithiasis. 811 2