Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pigment gallstones are defined as any dark brown-to-black stone, consisting of calcium salts of bilirubin, phosphate, carbonate and other anions, and can be separated into carbonate- and noncarbonate-containing groups. Pigment stones predominate in the rural Orient, in cirrhosis, and in elderly United States patients undergoing cholecystectomy. Clinical associations include bile duct obstruction, stasis, and possibly hemolysis. Of pigment stones, 50% are radioopaque and account for two-thirds of all opaque stones. The concentrations of bile salts, phospholipids,, cholesterol, and total bilirubin in bile are similar to normal levels, but the concentration of unconjugated bilirubin is increased in the bile of some patients. Increased unconjugated bilirubin in bile may be caused by increased hydrolysis of excreted conjugated bilirubin. Unconjugated bilirubin is solubilized by bile salts, but the interaction is primarily nonmicellar. Ionized calcium and pH are important determinants of solubility. Sulfated glycoproteins, excreted in increased amounts in patients with cholelithiasis, may be the site of pigment stone precipitation because these compounds bind calcium salts tightly. E coli is frequently cultured from pigment stones in Japan but not in the United States; thus, bacterial beta-glucuronidase may be important in stone formation in Japan but probably not in the West. Stasis leads to increased calcium secretion and to increases in the concentration of sparingly soluble compounds that may then precipitate. Incomplete emptying of the gallbladder may result in the same concentration process. Unsaturated fats and chronic vagal stimulation cause pigment stone formation in animals. At present, surgery is the only treatment for pigment lithiasis.
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PMID:Pigment gallstones. 31 81

The results of this study suggest that infection with beta-glucuronidase active bacteria is the initial event in the nucleation of primary bile duct stones (PBDS). PBDS from five patients were morphologically fragile and "earthy" with alternating light and dark brown pigment layers with no evidence of a distinct central nucleus that may have been reminiscent of a different structure. Chemically, calcium bilirubinate and calcium palmitate were prominent throughout their structure. All bile duct biles had a positive culture and were always associated with at least one bacterial species which was beta-glucuronidase active. Moreover, fragments of PBDS nuclear areas had positive cultures that were comparable with those present in their individual bile duct bile. Microscopic examination of bile showed abundant precipitation of calcium bilirubinate granules in all samples. Thus, bile duct bile infection with beta-glucuronidase active bacteria (e.g. E. coli, C. perfringens) appears to be a key factor in PBDS pathogenesis, having a precursor role, rather than being a consequence. Bile stasis is likely to be a co-factor which must have a supportive role in subsequent stone growth.
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PMID:Primary bile duct stones and bacterial activity. 146 14

Neutrophils (PMNs) may be exposed to high concentrations of biliary products during cholestasis and other hepatic disorders. We have previously reported that bile and certain bile salts enhance superoxide (O2-) release from neutrophils activated with phorbol myristate acetate (PMA) (Dahm et al.: Toxicol. Appl. Pharmacol. 95, 82, 1988), suggesting that PMN oxidative metabolism might be altered in toxicoses or disease states characterized by elevations in serum bile salts and other biliary products. In the present study, we characterized the priming effect of lithocholate for O2- release and also examined the effects of lithocholate on enzyme release from PMNs. PMNs preincubated with lithocholate at concentrations which did not directly stimulate O2- release (3-100 microM) and activated with PMA released greater amounts of O2- than controls exposed to PMA alone, illustrating a priming effect. O2- release from lithocholate-primed PMNs rose sharply between 5 and 10 min after PMA addition and then ceased between 10 and 30 min. The priming effect of lithocholate toward PMA-activated PMNs was reduced approximately 50% by washing PMNs after lithocholate addition and was not dependent on extracellular Ca2+, although removal of Ca2+ from the incubation buffer enhanced the cytotoxicity of lithocholate toward PMNs. In Ca2(+)-supplemented medium, lithocholate primed PMNs for O2- release when formyl-methionyl-leucyl-phenylalanine (FMLP, 10(-8)-10(-6) M) or calcium ionophore, A23187 (10(-7) or 10(-6)M), was used to activate PMNs. Lithocholate (100 microM) by itself had only marginal effects on release of lysozyme or beta-glucuronidase from PMNs. However, lithocholate (100 microM) inhibited beta-glucuronidase release from FMLP-stimulated PMNs to near-baseline levels. When FMLP was added to PMNs prior to lithocholate, beta-glucuronidase release was not reduced as it was when the order of addition was the reverse. Lithocholate had no effect on PMA-stimulated lysozyme release. These results indicate that lithocholate has different actions on PMN O2- release and enzyme release and suggest that lithocholate might exert its action on the PMN plasma membrane.
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PMID:Differential effects of lithocholate on rat neutrophil activation. 211 79

Studies in rats indicate that neutrophils (polymorphonuclear leukocytes (PMNs] are associated with areas of tissue damage after treatment with the hepatotoxicant, alpha-naphthylisothiocyanate (ANIT). Several synthetic and naturally occurring substances stimulate PMNs to release cytotoxic mediators, such as superoxide (O2-). The purpose of the present study was to test the hypothesis that ANIT stimulates the release of O2- from isolated rat PMNs. PMNs derived from rat peritoneum were treated with ANIT in vitro and tested for release of O2-. ANIT caused the release of O2- from PMNs in a concentration-dependent manner. Maximal O2- release (10 +/- 1 nmoles/30 minutes/2 x 10(6) cells) was achieved by an ANIT concentration of 110 microM. This ANIT-induced O2- release was significantly reduced or blocked completely by preincubation of PMNs for 10 minutes with 10 microM or 100 microM SKF 525A, respectively. The beta-isomer of ANIT, which does not cause cholestasis in vivo, did not stimulate O2- release. ANIT-stimulated O2- production decreased sharply after 5 minutes of incubation with ANIT and ceased entirely between 10 to 15 minutes. Shortly after this decrease in O2- production was an increase in the extracellular activity of lactate dehydrogenase. PMNs exposed to ANIT also failed to exclude trypan blue dye, either in the presence or in the absence of superoxide dismutase and catalase, suggesting a direct, oxygen radical-independent, cytotoxic effect of ANIT on PMNs. Release of the lysosomal enzyme, beta-glucuronidase, occurred within 5 minutes of incubation of isolated PMNs with ANIT (110 microM). These results indicate that exposure of rat PMNs to the hepatotoxicant, ANIT, causes the release of cytotoxic agents, whereas its less hepatotoxic beta-isomer does not.
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PMID:The cholestatic agent, alpha-naphthylisothiocyanate, stimulates superoxide release by rat neutrophils in vitro. 216 98

Levels of the lysosomal enzymes beta-glucuronidase and beta-hexosaminidase were determined in tissues from rats at 1-7 weeks after permanent bile duct occlusion (28 animals) and sham operation (16 animals). With increasing duration of bile duct occlusion, increasing levels were found in the liver and spleen, whereas levels were unaffected in the pancreas, kidneys, brain, muscle, and skin. Histochemical investigation showed that the lysosomal enzymes accumulated in the hepatocytes and in the increasing numbers of reticuloendothelial cells of the liver and spleen during cholestasis. No significant accumulation of lysosomal enzymes was seen in the pancreas. In preparations of isolated hepatocytes and non-parenchymal cells increased specific activity of lysosomal enzymes in cholestasis appeared in both cellular fractions. It is assumed that the serum increase of lysosomal enzymes in late cholestasis is partly due to a release from activated macrophages in the liver and spleen.
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PMID:Tissue content and localization of lysosomal enzymes in cholestatic rats. 294 Jun 72

Eighteen patients with total extrahepatic cholestasis undergoing PTCD were classified into three groups, depending on the bilirubin decrease rate at two weeks after PTCD. Serum and biliary esterified bile acids in each group were measured before PTCD and at 24 hours, 48 hours, 1 week, and 2 weeks after PTCD. Bile acids were measured by Okuyama's methods (HPLC), and esterified bile acids were calculated from the difference between samples treated with sulfatase or beta-glucuronidase for enzymatic hydrolysis and untreated samples measured at the same time. The following results were obtained. The percentages of biliary esterified bile acids in total bile acids were as follows: before PTCD, in the fair improvement group, sulfate (S) = 6.4 +/- 4.6% (mean +/- S.D.), glucuronide (G) = 11.7 +/- 9.0%; in the poor improvement group, S = 2.8 +/- 1.6%, G = 1.0 +/- 0.9% and at 24 hours after PTCD, in the fair group, S = 9.1 +/- 7.5%, G = 7.5 +/- 4.3%; in the poor group, S = 2.9 +/- 2.4%, G = 1.7 +/- 1.1%. The percentages of esterified bile acids in the fair group were higher than in the poor group, and significant differences were noted in G (p less than 0.05). Thus PTCD is expected to reduce jaundice in cases with high percentages of biliary esterified bile acids before and shortly after PTCD.
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PMID:Change in serum and biliary esterified bile acids in patients with extrahepatic cholestasis during percutaneous transhepatic cholangiodrainage. 338 78

Serum 3 beta-hydroxy-5-cholenoic acid (3 beta-OH-delta 5) was analyzed in 100 cases (90 patients with hepatobiliary diseases, 10 normal subjects) and its clinical significance investigated. The measurement of 3 beta-OH-delta 5 was performed by high performance liquid chromatography (HPLC) with immobilized 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) as the enzyme column. Esterified 3 beta-OH-delta 5 was measured after enzymatic hydrolysis with sulfatase and beta-glucuronidase. 3 beta-OH-delta 5 was hardly detected in normal cases. On the other hand, serum 3 beta-OH-delta 5 levels were remarkably high in cholestatic cases and also high in other cases with high bilirubin levels. The ratio of glycine- to taurine-conjugates (G/T ratio) was effective in discriminating cholestasis from hepatocellular damage such as in cases of acute hepatitis or fulminant hepatitis. More than 90% of the 3 beta-OH-delta 5, which is toxic, was sulfated or glucuronidated, suggesting detoxification by esterified bile acids. Significant increases of taurine-conjugated 3 beta-OH-delta 5 were observed in cases with pruritus, and a relationship between taurine-conjugated and pruritus was presumed. Therefore, analysis of 3 beta-OH-delta 5 is considered to be effective in clarifying the pathogenesis of hepatobiliary diseases.
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PMID:Clinical evaluation of serum 3 beta-hydroxy-5-cholenoic acid in hepatobiliary diseases. 347 20

Studies of the activity uptake of radiolabelled 99mTc2S7 colloid in different tissues showed a moderately increased uptake in the lung 1 week and a greatly increased uptake 3 weeks after permanent bile duct occlusion. Three weeks after bile duct occlusion the activity uptake was also slightly increased in the spleen and moderately reduced in the liver. In pulmonary tissue of cholestatic rats, the levels of alkaline and acid phosphatase, beta-glucuronidase, and beta-hexosaminidase were determined after 6 weeks. The pulmonary contents of beta-glucuronidase was increased tenfold, and that of beta-hexosaminidase was increased fourfold in cholestasis. Histochemical investigation showed that the lysosomal enzymes were located in the macrophages, which in cholestasis were abundant in alveolar walls and inside alveoli. Macrophages were also frequently seen to engorge pulmonary veins.
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PMID:Radiolabelled colloid uptake distribution and pulmonary contents and localization of lysosomal enzymes in cholestatic rats. 371 95

Plasma levels of the lysosomal enzymes beta-glucuronidase and beta-hexosaminidase were studied for 6 weeks after permanent bile duct occlusion (19 animals) or sham operation (5 animals). The bile duct-occluded animals had a stable bilirubinemia throughout the observation period. The median level of beta-glucuronidase in controls was 0.45 U/l. In jaundiced animals the median level was 1.09 at 0.5 weeks, 1.28 at 2 weeks, and 1.58 at 6 weeks after bile duct occlusion. The median level of beta-hexosaminidase in controls was 18.5 U/l. In jaundiced animals the median level was 18.0 at 0.5 weeks, 20.8 at 2 weeks, and 53.3 at 6 weeks after operation. Compared with beta-glucuronidase, prominent elevation of the beta-hexosaminidase level appeared much later after bile duct obstruction, which might suggest a closer association with reticuloendothelial system function for the latter enzyme.
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PMID:Lysosomal enzymes, alkaline phosphatase, and bilirubin in plasma after bile duct transection in the rat. 404 38

A histochemical study of conjugated and total bilirubin was made on liver biopsies of 150 patients. Three types of cholestasis were defined: type I, characterized by the presence of intracellular pigment granules in the hepatocytes; type II, showing intracellular granules and extracellular thrombi (this group may be subdivided according to the eventual presence of coarse pigment deposits in the parenchymal cells); and type III, showing intracellular granules, extracellular thrombi, and also bile pigment in the Kupffer cells. The fine liver cell granules correspond mainly to conjugated bilirubin, whereas the coarse deposits usually contain unconjugated pigment. The extracellular thrombi mostly contain conjugated bilirubin; the Kupffer cell pigment is predominantly of the unconjugated type. In cholestasis types II and III a diffuse directly reacting pigment is also observed. The finding of unconjugated pigment in different locations and the eventual deconjugation by beta-glucuronidase is discussed. A correlation was found between the different types of cholestasis, the level of bilirubinaemia, and its dynamic evolution. This suggests that the proposed types of cholestasis may represent successive stages of increasing cholestasis. The type of cholestasis and the nature of the pigment are largely independent of the aetiology. It is shown that a large percentage of minor degrees of cholestasis is missed when only conventional histological methods are used. The mechanisms by which morphological cholestasis is brought about are discussed in the light of the present findings.
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PMID:A clinical and histochemical study of cholestasis. 543 Mar 80


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