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Biomedical subjects

S Matern

Publications and source records attributed to S Matern.

At least 127 records · Page 7Linked to original sources

Zinc and vitamin A deficiency in patients with Crohn's disease is correlated with activity but not with localization or extent of the disease.

A study of serum zinc and plasma vitamin A concentrations in 54 patients with Crohn's disease was performed. Compared with controls the patients had significantly lowered zinc and vitamin A concentrations. There was a marked correlation between zinc and vitamin A and the activity of the disease, as measured by the Crohn's disease activity index, and a weaker correlation with serum proteins considered to be indicators of disease activity. No correlation was found to vitamin B12 absorption, to the localization of the disease, or to previous ileal resection. The results suggest that zinc and vitamin A deficiency occurs in patients with active Crohn's disease and is not primarily caused by absorption abnormalities. Substitution might be helpful or even necessary in patients with highly active disease.

Adult↗

Formation of bile acid glucosides by a sugar nucleotide-independent glucosyltransferase isolated from human liver microsomes.

A heat-labile protein has been detected in microsomes from human liver which catalyzes the formation of glucosides of the bile acids chenodeoxycholic, deoxycholic, and ursodeoxycholic acids. This glucosyltransferase activity has been purified about 900-fold from human liver microsomes, resulting in homogeneity as determined by sodium dodecyl sulfate gel electrophoresis. The subunit molecular weight was calculated to be about 56,000. The enzyme was separated from bile acid UDP-glucuronosyltransferase [UDP-glucuronate beta-D-glucuronosyltransferase (acceptor-unspecific), EC 2.4.1.17] during purification and does not catalyze the formation of bile acid glucuronides. The purified glucosyltransferase utilizes lipophilic alkyl beta-D-glucopyranosides as artificial donor substrates and dolichyl phosphoglucose as natural donor for the transfer of glucose to bile acids and does not exhibit bile acid conjugating activity in the presence of sugar nucleotides such as UDP-glucose. The apparent Km values estimated for various alkyl beta-D-glucopyranosides decreased with increasing alkyl chain length from 680 X 10(-6) M for hexyl beta-D-glucopyranoside to 20 X 10(-6) M as estimated for decyl and dodecyl beta-D-glucopyranoside. The results suggest that a glucoside-conjugation pathway of bile acids exists in humans. This conjugation is catalyzed by a sugar nucleotide-independent glucosyltransferase and is therefore distinct from the known mechanisms of glycoside conjugation.

Bile Acids and Salts↗

Hepatic and extrahepatic glucuronidation of bile acids in man. Characterization of bile acid uridine 5'-diphosphate-glucuronosyltransferase in hepatic, renal, and intestinal microsomes.

Microsomal UDP-glucuronosyltransferase activity toward the bile acids (chenodeoxycholic, deoxycholic, ursodeoxycholic, lithocholic, and glycolithocholic) has been detected in human specimens of liver, kidney, and intestinal mucosa. The characteristics of hepatic and extrahepatic UDP-glucuronosyltransferase activities toward these bile acids were compared with respect to kinetic parameters and other catalytic properties. Whereas no organ-specific differences in the affinities of individual bile acids to hepatic and extrahepatic UDP-glucuronosyltransferases were observed, the individual bile acids showed reaction rates in liver that were about twice the rates estimated in kidney and about twice to three times the rates observed in duodenal mucosa. In intestinal mucosa the rate of chenodeoxycholic acid glucuronidation exhibited a progressive decrease from duodenum to colon, where it was 30% of the duodenal level. Comparison of the glucuronidation rates that were estimated with different bile acids in hepatic or extrahepatic tissues showed that for each organ a bile acid structure-activity relationship existed, with highest activity observed for lithocholic and ursodeoxycholic acids, which was about twofold higher compared with chenodeoxycholic or deoxycholic acids. Lowest activity was estimated for glycolithocholic acid. UDP-glucuronosyltransferase activity toward chenodeoxycholic acid was studied in biopsy specimens of liver that were obtained from a large group of patients with the following liver diseases: liver cirrhosis, liver fibrosis, granulomatous hepatitis, fatty liver hepatitis, and fatty liver. A significant decrease in enzyme activity was observed in patients with liver cirrhosis and in patients with granulomatous hepatitis compared with patients without liver disease.

Bile Acids and Salts↗

A rapid and sensitive method for the assay of UDP-glucuronosyltransferase activity toward bile acids.

A rapid and sensitive procedure is described for the assay of rat liver microsomal UDP-glucuronosyltransferase activity toward the bile acids chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, and lithocholic acid using the radioactively labeled bile acids as substrates. The unreacted bile acids were separated from the bile acid glucuronides formed as products of the enzymatic reactions by extraction with chloroform, leaving the bile acid glucuronides in the aqueous phases. The bile acid glucuronides were characterized by their mobilities in thin-layer chromatography and identified by their sensitivity to hydrolysis with beta-glucuronidase and inhibition of hydrolysis by the specific beta-glucuronidase inhibitor D-saccharic acid-1,4-lactone. Enzyme activities were optimal at pH 6.8 and were maximally stimulated about fourfold by the addition of the nonionic detergent Brij 58 at a concentration of 0.3 mg/mg microsomal protein. The kinetic parameters for the various bile acids as substrates were determined.

Animals↗

Isolation and characterization of rat liver microsomal UDP-glucuronosyltransferase activity toward chenodeoxycholic acid and testosterone as a single form of enzyme.

Microsomal UDP-glucuronosyltransferase activity toward chenodeoxycholic acid and testosterone has been isolated from rat liver and appears to be homogeneous in sodium dodecyl sulfate gel electrophoresis and polyacrylamide gradient gel electrophoresis. The conjugating activities toward chenodeoxycholic acid and testosterone co-purified and showed identical mobilities in disc gel electrophoresis, indicating that chenodeoxycholic acid and testosterone are glucuronidated by a single form of enzyme. UDP-glucuronosyltransferase activities toward estrone, bilirubin, 4-nitrophenol, and morphine did not co-purify with the activity toward chenodeoxycholic acid and testosterone and were not detectable in the pure enzyme in the presence or absence of phospholipids. In addition to glucuronic acid conjugation, the enzyme is able to catalyze galacturonic acid conjugation of chenodeoxycholic acid and testosterone. The enzyme has a subunit Mr approximately 54,000 and in the presence of the stabilizing detergent chenodeoxycholic acid, it appears to exist as an aggregate with an apparent Mr = 318,000 as estimated by gel filtration and 316,000 by polyacrylamide gradient gel electrophoresis.

Animals↗

[Extraintestinal complications of Crohn disease, demonstrated in a patient].

A patient with different extraintestinal complications of Crohn's disease is demonstrated. The case allows a discussion of frequency and importance of such complications in Crohn's disease. Vitamin-und trace element deficiency, protein loss and renal complications are the main complications. Determination of vitamin and trace elements may early detect beginning extraintestinal complications and may induce a corresponding therapy.

Crohn Disease↗

[Pathogenic significance of bile acids (author's transl)].

Because of their amphiphilic properties, bile acids have important physiological functions. However, they can also be pathogenetically active. Some recent findings on the biochemistry and enterohepatic circulation of bile acids are presented. In contrast to the adult liver where the only primary bile acids formed are cholic- and chenodeoxycholic acid, the foetal liver is able to synthesise a variety of "atypical" bile acids. Under certain circumstances, a retrograde differentiation is possible in the adult. The very effective transport systems in gut and in the sinusoidal and canalicular membrane of the liver cell limit the bile acids almost exclusively to the enterohepatic circulation. During transport in blood, through biomembranes and in the liver cytosol, bile acids are bound to carrier proteins. The carrier has been detected using photoaffinity labelling. Following biotransformation (sulphation and glucuronidation) pathogenetically active bile acids can be converted into derivatives which can be rapidly eliminated. Disturbances of these mechanisms result in functional defects and diseases. The pathological significance of bile acids in hepato-biliary diseases is represented with regard to the cholestatic and proliferative effect of individual bile acids. The significance of bile acids in chologenic diarrhea, steatorrhea and enteral hyperoxaluria are presented as examples of the pathogenetic effects of bile acids on the gut. In these diseases it is possible to recognise the specific effects of certain bile acids on the colon mucosa. Recent studies have demonstrated that bile acids are possibly of pathogenetic significance in the case of epidemiologically proven relationship between colon carcinoma and high fat, high cholesterol and low fibre diets.

Bile Acids and Salts↗

Spontaneous cholecystocolonic fistula: a model situation for bile acid diarrhea and fatty acid diarrhea as a consequence of a disturbed enterohepatic circulation of bile acids.

Fistulas between the biliary and gastrointestinal tract complicate 12% of cases with cholecystitis. Communications of the biliary tract occur with decreasing frequency into the duodenum, colon and stomach. Clinical symptoms of cholecysto-colonic fistulas are chills and temperature elevation indicating ascending cholangitis. As bile acids bypass the small intestine, diminished fat absorption results. The unusual amount of bile acids in the colon delays water absorption, causing bile acid diarrhea. A pneumocholangiogram is seen in only 50% of the cases. Barium enema will visualize the fistula most often.

Aged↗

[Determination of bile acids by radioimmunoassays (author's transl)].

The present paper, based on the current literature, considers the practical aspects of bile acid radioimmunoassays. The problems associated with the raising of specific antisera and their characterization are discussed. Features of assay design for bile acids are considered. Solid-phase radioimmunoassays are described for separate determination of unconjugated cholic acid and conjugated cholic acid in serum. The clinical application of specific bile acid radioimmunoassays is shown by an "oral cholate tolerance test" as a sensitive indicator of liver function and by an "oral cholylglycine tolerance test" for characterization of intestinal function in diarrheal states.

Bile Acids and Salts↗

Radioimmunoassay of serum-conjugated deoxycholic acid.

A specific, sensitive, and reliable radioimmunoassay for serum-conjugated deoxycholic acid has been developed with antiserum obtained after immunization of rabbits with deoxycholic acid--bovine serum albumin conjugate. The displacement curve of glyco [3H] deoxycholic acid was linear on a logit-log plot from 7.5 to 320 pmol of unlabeled glycodeoxycholic acid. At 50% displacement of bound label, the cross-reactivity of taurodeoxycholic acid was 100%, deoxycholic acid 30%, taurocholic acid 3%, and glycocholic acid 2%. No cross-reactivity was observed with free cholic acid, conjugated or free chenodeoxycholic acids and conjugated or free lithocholic acids. Fasting serum-conjugated deoxycholic acid concentrations in 10 healthy volunteers ranged from 0.18 to 0.92 mumol/1. Over a period of 5 hours following 0.5 g oral cholate administration the serum-conjugated deoxycholic acid concentration did not change in 5 fasting healthy persons, whereas an initial increase of serum cholic acid was observed.

Animals↗

Radioimmunoassay of serum conjugated cholic acid.

A radioimmunoassay for serum conjugated cholic acid is described using antiserum obtained five weeks after immunization of rabbits with cholic acid bovine serum albumin conjugate. Prior to the radioimmunoassay, extraction of bile acids was performed with Amberlite XAD-2. The displacement curve of glyco[3H]cholic acid was linear on a logit-log plot from 5 to 80 pmol of unlabelled glycocholic acid. Values for 8 normal fasting subjects ranged from 0.18 to 1.25 mumol/1. In 31 fasting subjects with or without liver disease serum values of conjugated cholic acid are related to serum bilirubin. Endoscopic retrograde cholangiopancreatography may influence serum levels of conjugated cholic acid.

Adult↗