Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Black and brown pigment gallstones are morphologically, compositionally, and clinically distinct. Black stones form primarily in the gallbladder in sterile bile and are associated with advanced age, chronic hemolysis, alcoholism, cirrhosis, pancreatitis, and total parenteral nutrition. Brown stones form not only within the gallbladder but also within the intrahepatic and extrahepatic ducts; they are uniformly infected with enteric bacteria and are usually associated with ascending cholangitis. Brown stones are related to juxtapapillary duodenal diverticula and are the predominant type of de novo common bile duct stones. Cholecystectomy is usually curative in black pigment stone disease, whereas stones often recur after cholecystectomy for brown stone disease. The pathogenesis of black stones is probably related to nonbacterial, nonenzymatic hydrolysis of bilirubin conjugates. At the pH of bile, this results in two monohydrogenated bilirubin anions that precipitate with calcium ions. Bilirubin monoconjugates that are increased in several conditions, such as Gilbert's syndrome and chronic hemolysis, may play a pivotal role in black stone formation as a source of unconjugated monohydrogenated bilirubin and as a possible co-precipitant with calcium. The precipitation of calcium carbonate and phosphate is influenced by local gallbladder factors. Brown pigment stones are formed in bile infected with enteric bacteria that elaborate hydrolytic enzymes: beta-glucuronidase, phospholipase A, and conjugated bile acid hydrolase. The resulting anions of bilirubin and fatty acids form insoluble calcium salts. We used nb/nb mice with a chronic hemolytic anemia as a model of hemolysis-induced black stone disease. The presence of 40% bilirubin monoconjugates in mouse gallstones indicated the importance of this moiety in the pathogenesis of black stones. Other data obtained by marrow transplantation experiments in mice revealed the relative importance of genotype versus the hemolytic anemia on determinants such as biliary bile acid composition and mucin secretory glands in the mouse gallbladder neck. Additional physical chemical studies of the interaction of unconjugated bilirubin in model bile solutions will be helpful in further delineating the pathogenesis of both black and brown pigment gallstones.
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PMID:Pigment gallstone disease. 202 17

A series of human multinucleate giant cells (MGCs) of the endocytotic type were studied using enzyme histochemical methods for dehydrogenases, glycosidases, phosphatases, and peptidases. Several enzyme patterns were found. The subgroup of MGCs associated with inflammatory granulomatous processes (sarcoidosis, granulomatous myositis, familial granulomatosis, lymphogranuloma, granulomatous cholangitis) was characterized by high activities of nonspecific esterase (NE) and tartrate-sensitive acid phosphatase (AcPase-Ts). There was no detectable activity of peptidases or tartrate-resistant isoenzyme of acid phosphatase (AcPase-Tr). This enzyme equipment was indistinguishable from that in mononuclear precursors in the granulomas. The other MGCs of the series displayed enzyme patterns substantially different from their monocytic precursors (blood monocytes and Langerhans cells). The subgroup of foreign body associated MGCs (resorption of fat, keratin, and suture material) was characterized by high activities of NE, AcPase-Tr, and greatly variable activities of both peptidases studied. The latter lacked predilection for certain subcellular regions. The subgroup of osteoclasts and so-called giant cell tumours (osteoclastoma, giant cell tumour of soft parts, giant cell epulis of peripheral, and central types) displayed very low activity of NE, high activity of AcPase-Tr, and strong activities of peptidases. The latter were localized near the surface membrane of the polykarya. MGCs in histiocytosis X (HX) differed from the previous group by higher values of NE in average. All MGC types had common denominator in the absence of alkaline phosphatase activity, on average intense dehydrogenase activities, mostly low beta-glucuronidase and highly variable alpha-mannosidase activities. The enzyme pattern heterogeneity is discussed with regard to the phenomenon of enzyme induction and depression occurring in course of polykaryon production. The variability of phenomenon may reflect reactive adaptation to varying functional demands imposed on MGCs under different conditions.
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PMID:Enzyme patterns in human endocytotic multinucleate giant cells--a histochemical study. 287 82

To investigate the role of cholangitis in hydrolysis of bilirubin in bile with brown pigment gallstones, bilirubin composition and bacterial growth in hepatic bile with and without cholangitis were studied. The study included 38 brown pigment gallstone cases (28 without cholangitis and 10 with cholangitis). The proportion of unconjugated bilirubin in hepatic bile with cholangitis (16.9 +/- 8.5%, mean +/- SD) was significantly higher than that without cholangitis (3.7 +/- 1.8%, P less than 0.001). A positive correlation was found between bacterial population with beta-glucuronidase activity and the proportion of unconjugated bilirubin in bile in cases of brown pigment stones with cholangitis (P less than 0.05) but not in those without cholangitis despite the fact that bacterial species and population are similar regardless of the presence of cholangitis. In cholangitis, pH of bile becomes lower toward the optimal pH of bacterial beta-glucuronidase. Together the lower concentration of bile acid and the lower pH in bile result in lower solubility of unconjugated bilirubin, promoting its precipitation. Thus occasional bouts of cholangitis may result in periodic deposition of bilirubinate on brown pigment stones with layered structures by inducing cyclic changes of bile composition in situ.
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PMID:Unconjugated bilirubin in hepatic bile with brown pigment gallstones and cholangitis. 304 14

Hepatolithiasis is associated with bile stasis and bacterial infection. Gallstones found in the intrahepatic bile duct are mostly calcium bilirubinate stones, the presence of which is closely related to the presence of bacteria. In the present study, a high incidence of bile infection was found in hepatolithiasis: 52 of 54 cases (96.3%). This is in concordance with the other reports from Japan as well as from East Asia. E coli was the most frequent isolate followed by Klebsiella, Streptococcus (D), and Pseudomonas. Because of the frequent isolation of E coli in calcium bilirubinate stone cases, beta-glucuronidase from E coli has been thought to be responsible for the formation of calcium bilirubinate stones by effecting hydrolysis of bilirubin glucuronide to free bilirubin, which is insoluble in water. The recent introduction of improved anaerobic culture techniques has led to an increasing number of reports on the presence of anaerobes in the biliary tract. Anaerobes were isolated in 6 of 29 cases of hepatolithiasis (20.7%) in our series but more frequently in Kaohsiung, Taiwan (25 of 57 cases, or 44.4%). Bacteroides and Clostridium were the most frequent isolates from the biliary tract and were shown to have beta-glucuronidase activity. Anaerobes were often found together with aerobes, suggesting the possibility of a synergistic effect that may influence the occurrence and development of cholangitis, which is often associated with hepatolithiasis. Though the biliary tract and liver are usually sterile, when an infection of the biliary tract occurs the route by which bacteria reach the region is thought to be hematogenous, lymphatic, or direct intraluminal ascending infection, the last being the most likely. Treatment of cholangitis associated with hepatolithiasis should be directed toward the removal of stones and termination of bile stasis. When cholangitis ensues, control of bacterial infection by antibiotics should be started without delay. The choice of antibiotics in controlling cholangitis is presented.
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PMID:Bacteriology of hepatolithiasis. 638 75