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Biomedical subjects

S Matern

Publications and source records attributed to S Matern.

At least 109 records · Page 6Linked to original sources

Concordance of indirect methods for the detection of lactose malabsorption in diabetic and nondiabetic subjects.

In order to collect data on (1) the prevalence of lactose malabsorption and (2) the value of indirect diagnostic methods for hypolactasia in diabetics, we compared lactose tolerance tests using serum glucose, serum galactose (after oral ethanol intake) and breath hydrogen excretion as diagnostic cutoff in 144 nondiabetic and 46 diabetic subjects. A good rate of concordance was found for the hydrogen breath test and galactose-dependent lactose tolerance test. The glucose-dependent lactose tolerance test was found to be of satisfactory diagnostic value in nondiabetic subjects and was useless for diagnostic purposes in diabetics. Lactose malabsorption was no more frequent in diabetics than in controls and lactose intolerance was found to be less frequent in the diabetic group. A distinction between hypolactasia and other gastrointestinal disorders in diabetics is possible by ambulatory indirect tests.

Adult↗

[Coincidence of Gaucher disease with primary hepatocellular carcinoma].

Case report on a 48-year-old man with Gaucher's disease and a HBsAg-positive cirrhosis simultaneously. Postmortem examination revealed a hepatocellular carcinoma suggested by antecedent ultrasound examination. The coexistence of Gaucher's disease and hepatocellular carcinoma has not been described before. A possible relationship between Gaucher's disease and hepatocellular carcinoma is supposed due to Gaucher's disease and association to the hepatitis B infection.

Carcinoma, Hepatocellular↗

In vitro perfusion and incubation of rat pancreatic lobules in a kinetic system.

The use of pancreatic lobule preparations is one of the well-established approaches to study stimulus-secretion coupling in the exocrine pancreas in vitro. We have developed a kinetic system for the perfusion and intermittent incubation of rat pancreatic lobules. This model allows repeated hormone stimulation for up to 3 h while permitting rapid changes of the cellular environment with no accumulation of secretory or metabolic products. Tissue viability could be demonstrated over 6 h by in vivo toluidine blue exclusion, histology and electron microscopy. Lactate dehydrogenase leakage from cells over 6 h was only 2.4% of total content. No activated trypsin was detected in the perfusion medium. A biphasic dose response was established for cholecystokinin stimulation with a maximal response at 10(-8) M. We conclude that kinetic perfusion and incubation are technically feasible with rat pancreatic lobules. This in vitro model appears particularly suited for the investigation of pharmacologic and metabolic effects on the pancreatic acinar cell when rapid changes of the cellular environment are required and when the accumulation of secretory and metabolic products must be avoided. The technique described requires neither protease inhibition in the medium nor collagenase treatment of the cells.

Amylases↗

Urinary excretion of bile acid glucosides and glucuronides in extrahepatic cholestasis.

Recently the formation of bile acid glucosides has been described as a novel conjugation mechanism in vitro and in vivo. In 10 patients with extrahepatic cholestasis caused by carcinoma of the head of the pancreas we investigated excretion rates and profiles of urinary bile acid glucosides. Urinary bile acid glucosides and, for comparison, bile acid glucuronides were extracted and characterized according to established methods. In controls total urinary bile acid glucoside excretion was 0.22 +/- 0.03 mumol/24 hr (mean +/- S.E.M.)-in the range of bile acid glucuronide excretion (0.41 +/- 0.06 mumol/24 hr; mean +/- S.E.M.). A gas chromatography-mass spectrometry-characterized trihydroxy bile acid glucoside of still-unknown hydroxyl positions accounted for 65% of total urinary bile acid glucosides. In extrahepatic cholestasis total urinary bile acid glucoside excretion was 0.52 +/- 0.13 mumol/24 hr (mean +/- SEM), yet significantly lower than bile acid glucuronide excretion (1.53 +/- 0.13 mumol/24 hr; mean +/- SEM; p less than 0.001). In cholestasis the primary bile acid derivatives cholic and chenodeoxycholic acid glucosides amounted to 90%, whereas the trihydroxy bile acid glucoside had decreased to 5% of total bile acid glucoside excretion, indicating its alteration during enterohepatic circulation. The data establish the composition and quantity of urinary bile acid glucosides in healthy controls and cholestasis and constitute a quantitative comparison with another glycosidic conjugation reaction, bile acid glucuronidation.

Aged↗

Bile acid N-acetylglucosaminides. Formation by microsomal N-acetylglucosaminyltransferases in human liver and kidney.

Bile acid N-acetylglucosaminyltransferase activity has been identified in microsomes from human liver and kidney. In both organs the transferases required UDP-N-acetylglucosamine as sugar donor and were mainly active towards ursodeoxycholic acid. Minor activities were observed towards amidated ursodeoxycholic, hyodeoxycholic and beta-muricholic acids. No N-acetylglucosaminidation was detectable with the major primary and secondary bile acids suggesting a specific requirement of the enzymes for bile acids containing 7 beta-or 6 alpha-hydroxyl groups. Kinetic parameters and other catalytic properties of liver and kidney microsomal N-acetylglucosaminyltransferase activities towards ursodeoxycholic acid are described.

Acetylglucosamine↗

Isolation and characterization of UDP-glucose dolichyl-phosphate glucosyltransferase from human liver.

The enzyme UDP-glucose dolichyl-phosphate glucosyltransferase has been purified to near homogeneity from human liver microsomes. A 1100-fold enrichment over starting microsomal membranes was achieved by selective solubilization followed by anion- and cation-exchange chromatography, 5-HgUDP-thiopropyl-Sepharose affinity chromatography, butylagarose chromatography and hydroxyapatite chromatography. The glucosyltransferase was shown to be separated from other dolichyl-phosphate-dependent glycosyltransferases catalyzing the formation of dolichyl diphospho-N-acetylglucosamine and dolichyl phosphomannose. Sodium dodecyl sulfate/polyacrylamide gradient gel electrophoresis of the purified enzyme under reducing conditions revealed a protein band of Mr 36,000. Protection of the solubilized enzyme against rapid inactivation was achieved by its competitive inhibitor uridine. The purified glucosyltransferase activity exhibited a specific requirement for the presence of phospholipids. Phosphatidylethanolamine was the most effective activator of enzyme activity.

Chromatography, Affinity↗

[Liver calcifications in metastasizing vipoma].

A 53-year-old woman had suffered from watery diarrhoea and substitution-requiring hypokalaemia for 18 months. Ultrasonography and abdominal x-ray revealed multiple calcifications in the liver. Retrograde cholangiopancreaticography, performed because an endocrine-secreting pancreatic tumour was suspected, demonstrated occlusion of the major pancreatic duct and calcification in the body of the pancreas. Gastrointestinal hormone levels were elevated (vasoactive intestinal polypeptide 950 pg/ml, pancreatic polypeptide 1000 pmol/l and neurotensin 86 pmol/l) in the blood, and immunohistochemical results on cells of an adenocarcinoma obtained by needle biopsy confirmed a metastasizing VIPoma. Administration of the somatostatin analogue SMS 201-995 achieved marked improvement.

Adenoma, Islet Cell↗

N-acetylglucosaminides. A new type of bile acid conjugate in man.

Bile acids were extracted from human urine and were separated into groups of nonamidated and glycine- and taurine-conjugated compounds. Each group was subfractionated in a reversed-phase high performance liquid chromatography system, and the fractions were analyzed by negative ion fast atom bombardment mass spectrometry and also by gas chromatography-mass spectrometry after enzymatic removal of glycine and taurine moieties. The major glycosides of the non-amidated bile acids were more polar than reference bile acid glucosides and gave quasimolecular ions at m/z 592, 594, and 610 consistent with N-acetylglucosaminides of unsaturated dihydroxy and saturated di- and trihydroxy bile acids. Gas chromatography-mass spectrometry analyses of methyl ester trimethylsilyl ether derivatives showed fragments typical for N-acetylglucosaminides (m/z 173 and 186) in addition to those also given by glucosides (m/z 204 and 217). The N-acetylglucosaminides were inert toward alpha- and beta-glucosidase but were cleaved completely with N-acetylglucosaminidase. The released sugar moiety was identified as N-acetylglucosamine. One of the liberated bile acids was identified as ursodeoxycholic acid. The other acids were not identical to any known primary or secondary bile acid in humans. Fast atom bombardment mass spectrometry analyses of the glycine-and taurine-conjugated bile acid glycosides only showed ions consistent with the presence of glucosides (m/z 626 and 676). These compounds were sensitive only toward beta-glucosidase which liberated a trihydroxy bile acid as the major compound. Based on the recover of 13C- and 14C-labeled chenodeoxycholic acid glucoside added as internal standard, the daily excretion of nonamidated bile acid glycosides was estimated to be about 137 micrograms or 0.29 mumol, N-acetylglucosaminides constituting about 90%. The daily excretion of the glucosides of amidated bile acids was about 150 micrograms or 0.25 mumol, glycine conjugates constituting about 90%.

Acetylglucosamine↗

Control of dolichyl phosphoglucose formation in human liver microsomes. Kinetic and inhibition studies of nucleosides, nucleotides and analogues of UDPglucose.

A bisubstrate kinetic analysis of UDPglucose:dolichylphosphate glucosyltransferase from human liver microsomes has been carried out which indicated that the kinetics follow a sequential mechanism. Inhibition studies with nucleosides, nucleotides and analogues of the substrate UDPglucose revealed that the nucleoside moiety of UDPglucose, uridine, appears to be the smallest substrate analogue that is capable of specific interaction with the enzyme at the binding site for UDPglucose. The Ki values for uridine with respect to UDPglucose were 0.17 mM or 0.1 mM for enzyme reactions at pH 5.3 or pH 7.2, respectively. Modification of the uracil moiety especially at the 6 position or lack of the 2'-hydroxyl group in the ribose moiety lessened the inhibitory potency as compared to uridine. The phosphorylated derivatives of uridine, UMP and UTP, were similar in their inhibitory properties to uridine, whereas UDP was about 10-fold more potent as an inhibitor of glucosyltransferase as compared to uridine due to product inhibition. The inhibitory properties of sugar nucleotides as substrate analogues of UDPglucose were not only dependent on the presence of the uracil moiety but were also influenced by the nature of the sugar residue. Furthermore, enzyme activity was dependent on the presence of divalent metal ions and was maximally stimulated in the presence of Ca2+.

Glucosyltransferases↗

Effect of phenytoin, carbamazepine, and valproic acid on caffeine metabolism.

Three groups of non-smoking epileptic patients without liver disease receiving antiepileptic monotherapy have been compared with 10 healthy non-smoking volunteers. Group 1 received phenytoin (n = 10), Group 2 carbamazepine (n = 10) and Group 3 valproic acid (n = 6). Cytochrome P-450 activity was monitored by measuring urinary 6-beta-hydroxycortisol output and systemic antipyrine clearance. Both, 6-beta-hydroxycortisol output and antipyrine clearance were significantly enhanced in patients on phenytoin and carbamazepine, but not in those on valproic acid. On the other hand, phenytoin alone increased the clearance of caffeine from 1.5 (controls) to 3.6 ml.min-1.kg-1, and reduced its half life from 4.8 to 2.4 h. Carbamazepine and valproic acid had no effect on caffeine metabolism. The results are in keeping with the well known heterogeneity of the hepatic monooxygenase system, as phenytoin and carbamazepine induce different panels of cytochrome P-450 isoenzymes. Phenytoin treatment may impair the validity of the caffeine liver function test.

Adolescent↗

Sonographic changes of the pancreas in chronic renal failure.

Several abnormalities regarding pancreatic morphology and function have been reported in patients with chronic renal failure (CRF) with an incidence as high as 72%. In a prospective study we investigated 96 outpatients from our chronic ambulatory hemodialysis program by abdominal ultrasound. Of the patients with CRF, 20.6% were found to have morphologic alterations of the pancreas compared to 4.7% of controls. Although pathologic sonograms of the pancreas correlated with biliary disease, hyperparathyroidism and years of hemodialysis, the most obvious etiologic factor appeared to be the duration of CRF. Possible pathogenetic mechanisms are discussed and screening abdominal ultrasound examinations in patients with long-standing CRF are recommended.

Adult↗

Postoperative adaptation of the small intestine after total colectomy and J-pouch-anal anastomosis.

Twelve patients who underwent total colectomy and J-pouch-anal anastomosis were followed up to 3 years after surgery to evaluate the functional and morphologic changes of the small-bowel reservoir. Intestinal absorption was impaired for lactose in 18 percent, for D-xylose in 27 percent, and for 75SeHCAT in 83 percent. Morphologic changes in ileal-pouch specimens consisted of a marked flattening of the villi and augmentation in crypt number and length. The number of Paneth's cells was increased compared with normal ileum. Parameters, indicating neorectal function such as stool frequency, pouch volume, and intestinal transit, improved in time during the postoperative course. Because of impaired small-bowel function, which is not restricted to the pouch reservoir, the ileum acquires progressive colonic capacities in accordance with its morphologic transformation to a colonic type mucosa. None of our patients developed clinical malabsorption requiring regular therapeutic substitution beyond a well-balanced diet due to these morphologic and functional changes and postoperative acceptance was good or excellent in all but one case.

Adult↗

6 alpha-glucuronidation of hyodeoxycholic acid by human liver, kidney and small bowel microsomes.

Kinetic constants for the glucuronidation of hyodeoxycholic acid in man were determined using microsomal preparations of liver, kidney and small bowel. The affinity of hyodeoxycholic acid for the microsomal hepatic and extrahepatic enzymes was in the same range as previously observed for the monohydroxy bile acid lithocholic acid and about 3-14-times the affinity for the dihydroxy bile acids chenodeoxycholic, deoxycholic and ursodeoxycholic acids. The Vmax values for glucuronidation of hyodeoxycholic acid with hepatic microsomes were 10-30-times higher and with kidney microsomes 50-110-times higher than for the bile acids lacking a 6 alpha-hydroxy group. The site of glucuronidation was determined by gas chromatographic-mass spectrometric analysis of derivatives of products formed after periodate and chromic acid oxidation. Hyodeoxycholic acid glucuronides synthesized with microsomal preparations from the three organs were all found to be conjugated at the 6 alpha position. This has previously been shown to be the site of glucuronidation of endogenous hyodeoxycholic acid glucuronide excreted in urine.

Bile Acids and Salts↗

Formation of bile acid glucosides and dolichyl phosphoglucose by microsomal glucosyltransferases in liver, kidney and intestine of man.

Formation of glucosides of the bile acids chenodeoxycholic, ursodeoxycholic, deoxycholic and hyodeoxycholic acids has been detected in microsomes from human liver, kidney and intestinal mucosa. Hepatic and extrahepatic bile acid glucosyltransferase activities were characterized with respect to kinetic parameters and other catalytic properties. Whereas no marked organ-specific differences in the affinities of individual bile acids toward hepatic and extrahepatic glucosyltransferases were observed, microsomes from extrahepatic sources showed twice to 5-times the maximal rates of bile acid glucosidation estimated with microsomes from liver. In addition to bile acid glucoside formation, microsomes from human liver, kidney and intestinal mucosa catalyzed the synthesis of dolichyl phosphoglucose acting as natural glucosyl donor in bile acid glucosidation.

Bile Acids and Salts↗

Evidence for bile acid glucosides as normal constituents in human urine.

A glucosyltransferase catalysing formation of bile acid glucosides was recently isolated from human liver microsomes. In order to investigate the potential occurrence of such bile acid derivatives in vivo, a method was devised for their isolation and purification from urine. Conditions were established with the aid of glucosides of radiolabelled, unconjugated glycine and taurine conjugated bile acids prepared enzymatically using human liver microsomes. Analysis by gas chromatography and mass spectrometry of methyl ester trimethylsilyl ether derivatives indicated the excretion of glucosides of nonamidated hyodeoxycholic, chenodeoxycholic, deoxycholic, ursodeoxycholic and cholic acids and of glycine and taurine conjugated chenodeoxycholic and cholic acids. Additional compounds were present giving mass spectral fragmentation patterns typical of di- and trihydroxy bile acid glycosides. Semiquantitative estimates indicated a total daily excretion of about 1 mumol.

Bile Acids and Salts↗

A new technique for endoscopic implantation and explantation of large-bore biliary endoprostheses in patients with non-surgical common bile duct obstruction.

A new system for endoscopic implantation and explantation of large-bore biliary endoprostheses is presented. This technique permits corrective placement of prostheses dislodged during implantation, as well as explantation and replacement through the biopsy channel of the endoscope in a single sitting. The method has been successfully employed in 10 patients.

Aged↗