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Biomedical subjects

W Gerok

Publications and source records attributed to W Gerok.

At least 271 records · Page 15Linked to original sources
PubMed1984

Hepatocyte heterogeneity in ammonia metabolism: impairment of glutamine synthesis in CCl4 induced liver cell necrosis with no effect on urea synthesis.

After induction of a perivenous liver cell necrosis by CCl4 pretreatment of the rat, ammonia uptake by perfused liver is decreased. This was due to an inhibition of glutamine synthesis from added ammonia, whereas urea synthesis was not affected by CCl4 pretreatment. The data confirm recent findings on hepatocyte heterogeneity in ammonia metabolism and are explained by an impairment of perivenous glutamine synthetase, but not of periportal urea synthesis, by the perivenous liver cell necrosis induced by CCl4. Regarding the pathogenesis of hyperammonemia in acute severe liver disease like CCl4 poisoning, the data point to a role of an impaired glutamine synthesis, but not to an impairment of urea synthesis.

Ammonia↗
PubMed1984

[Vascular diseases of the liver: cavernous transformation of the portal vein, Osler disease and Budd-Chiari syndrome].

Vascular disorders of the liver except portal hypertension are rare. They can be visualised via ultrasound, as demonstrated by two cases of cavernous transformation of the portal vein, one case of Osler's disease of the liver, and one case of Budd-Chiari's syndrome. The cavernous transformation and the occlusion of the hepatic veins can be diagnosed by ultrasound, while Osler's disease cannot be differentiated with certainty from other disorders.

Budd-Chiari Syndrome↗
PubMed1984

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↗
PubMed1984

Determination of short-circuit current in the in vivo perfused rat colon.

Current pulses (I) were injected into the lumen of proximal colonic segments in vivo, and the corresponding voltage deflections (delta PD) superimposed on the transcolonic PD were recorded. From the exponential decay of delta PD along the colon axis, the electrical length constant (lambda) was determined. Based on cable analysis the input resistance (= delta PD x = 0/I) and lambda made it possible to calculate the specific resistance (Rm) of the colonic epithelium as 128 +/- 16 omega X cm2. As Rm proved to be an ohmic resistor, the extrapolation from open-circuit PD (8-12 mV, lumen negative) to zero PD was feasible and made the calculation of short-circuit current (= PD/Rm) equal to 70 +/- 16 microA/cm2. In the presence of amiloride short-circuit current decreased to about 50%, whereas with theophylline it increased by about 30%. Substitution of luminal Na+ with choline or Cl- with cyclamate was associated with a marked increase of Rm. The rheogenic component of net Na+ transport was estimated to be only 8%. Electroneutral Na+ absorption functionally coupled with Cl- absorption displayed the characteristic feature of ion transport in the rat proximal colon.

Animals↗
PubMed1984

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↗
PubMed1984

[Immunogenetic findings in Crohn disease, ulcerative colitis and gluten sensitive enteropathy].

Immunogenetics explain the influence of genetic dispositions and regulation mechanisms on the defence mechanisms of organisms. In this paper the interrelationship between immunogenetic findings and Crohn's disease, ulcerative colitis and glutensensitive enteropathy are presented. The association with HLA-antigens and the complement factors Bf and C 4 are described. An increased association of HLA-antigens with Crohn's disease and ulcerative colitis have not been observed, with one exception, the association between HLA-Bw 35 (53%) and ulcerative colitis in a particular ethnic group in Israel. In contrast, there is a distinct association between the complement allotype Bf-F and Crohn's disease (68%) and ulcerative colitis (50%), compared with controls (29%). Glutensensitive enteropathy shows no increased occurrence of complement factors however there is an association with HLA-B8 (83%) DR 3 (94%) and DR 7 (61%). The phenotype description of the genes of the main histocompatibility complexes allows, amongst others, a conclusion concerning the pathogenesis and diagnosis of certain diseases. A new approach to these diseases has been introduced.

Celiac Disease↗
PubMed1984

Fibronectin concentration in ascites differentiates between malignant and nonmalignant ascites.

Differentiation between malignant and nonmalignant ascites by means of laboratory parameters has so far not been completely achieved. One hundred and four patients with ascites (34 malignant, 51 cirrhotic, and 19 other) were studied for fibronectin concentration in ascites. The first 47 patients (13 malignant and 34 cirrhotic) were used to determine mean values and standard deviation (178 +/- 96 vs. 8.3 +/- 15.3 micrograms/ml) and to define a cutoff concentration between both groups (75 micrograms/ml). Several other parameters were analyzed simultaneously in these patients (total protein: 3.93 +/- 1.46 vs. 1.50 +/- 1.02 g/dl; white cell count: 2022 +/- 1153 vs. 569 +/- 405/mm3; lactic acid: 3.86 +/- 2.57 vs. 1.83 +/- 0.72 mmol/L; lactic acid dehydrogenase: 357 +/- 329 vs. 61 +/- 35 U/L; serum/ascites ratio of lactic acid dehydrogenase: 1.11 +/- 1.13 vs. 4.06 +/- 2.00; pH: 7.275 +/- 0.229 vs. 7.513 +/- 0.042). Their accuracy (mean of sensitivity and specificity) was always less than 87% due to a considerable overlap between both groups. Five patients with other causes of ascites could not be classified at all. Application of fibronectin determination on the subsequent 57 patients (21 malignant, 17 cirrhotic, and 19 other) revealed a sensitivity, specificity, and negative and positive accuracy for malignant ascites of 100%. Calculation of these parameters for all 104 patients gave identical values. The inclusion of 3 patients without final diagnosis in the group of nonmalignant ascites reduced specificity to 97.1 and positive accuracy to 94.4%. However, these values were superior to all other methods used so far. Fibronectin determination in ascites in combination with other parameters suitable for exclusion of infectious or pancreatic origin of ascites may prove useful in the differential diagnosis of ascites.

Abdominal Neoplasms↗
PubMed1984

[Functional liver cell heterogeneity].

Hepatocytes from different subacinar localizations differ not only in their enzyme equipment, but have also different functions in intermediary metabolism. Gluconeogenesis, amino acid breakdown, urea synthesis and oxidative metabolism occur predominantly periportal, whereas glycolysis, glutamine synthesis and drug metabolism are predominantly perivenous. This metabolic zonation is rather dynamic and is influenced by hormones, oxygen-tension, substrate concentrations, circadian rhythms and development. There are metabolic interactions between differently localized hepatocyte populations: the product of one population may serve as the substrate for another. Hepatocyte heterogeneity in ammonia and glutamine metabolism provides new aspects on the pathogenesis of hyperammonemia in severe liver disease. Glutamine is degraded in the periportal area of the acinus, whereas there is a simultaneous resynthesis of glutamine in the perivenous area, resulting in an intercellular glutamine cycle. This provides an effective means for almost complete detoxication of ammonia by urea synthesis. The rate of hepatic bicarbonate elimination is regulated by the intercellular glutamine cycle pointing to the important role of the liver in maintaining pH homeostasis. Such a device also explains the development of an alkalosis in severe liver disease as a consequence of a diminished bicarbonate removal by the liver.

Acid-Base Equilibrium↗
PubMed1984

[Zinc and vitamin A deficiency in gastrointestinal diseases].

It has been established rather surely that patients with chronic liver disease, Crohn's disease, chronic pancreatis and celiac disease are deficient in zinc and vitamin A. A large number of clinical symptoms can be caused by these deficiencies, due to the fact that these compounds have numerous functions. Zinc deficiency in liver cirrhosis is probably caused by portosystemic shunting, whereas in Crohn's disease abnormalities of protein metabolism are suggested as etiologic factor. Vitamin A deficiency can be considered as a consequence of disturbed zinc metabolism. Some studies in appropriate patients receiving substitution therapy with zinc and/or vitamin A had positive results. However, the necessity of substitution in the diseases mentioned has not yet been conclusively demonstrated.

Celiac Disease↗
PubMed1983

Hepatocyte heterogeneity in glutamate uptake by isolated perfused rat liver.

Glutamate is simultaneously taken up and released by perfused rat liver, as shown by 14CO2 production from [1-14C]glutamate in the presence of a net glutamate release by the liver, turning to a net glutamate uptake at portal glutamate concentrations above 0.3 mM. 14CO2 production from portal [1-14C]glutamate is decreased by about 60% in the presence of ammonium ions. This effect is not observed during inhibition of glutamine synthetase by methionine sulfoximine. 14CO2 production from [1-14C]glutamate is not influenced by glutamine. Also, when glutamate accumulates intracellularly during the metabolism of glutamine (added at high concentrations, 5 mM), 14CO2 production from [1-14C]glutamate is not affected. If labeled glutamate is generated intracellularly from added [U-14C]proline, stimulation of glutamine synthesis by ammonium ions did not affect 14CO2 production from [U-14C]proline. After induction of a perivenous liver cell necrosis by CCL4, i.e. conditions associated with an almost complete loss of perivenous glutamine synthesis but no effect on periportal urea synthesis, 14CO2 production from [1-14C]glutamate is decreased by about 70%. The results are explained by hepatocyte heterogeneity in glutamate metabolism and indicate a predominant uptake of glutamate (that reaches the liver by the vena portae) by the small perivenous population of glutamine-synthesizing hepatocytes, whereas glutamate production from glutamine or proline is predominantly periportal. In view of the size of the glutamine synthetase-containing hepatocyte pool [Gebhardt, R. and Mecke, D. (1983) EMBO J. 2, 567-570], glutamate transport capacity of these hepatocytes would be about 20-fold higher as compared to other hepatocytes.

Animals↗
PubMed1983

Heterogeneous turnover of terminal and core sugars within the carbohydrate chain of dipeptidylaminopeptidase IV isolated from rat liver plasma membrane.

Dipeptidylaminopeptidase IV, a plasma membrane-bound glycoprotein, is characterized by an intramolecular heterogeneous turnover of the protein backbone and carbohydrate chain. The faster turnover of the latter is restricted only to the outer sugars. The inner core sugars D-mannose and N-acetyl-D-glucosamine turn over at the same rate as the protein backbone.

Animals↗
PubMed1983

The phosphoprotein intermediate of a Ca2+ transport ATPase in rat liver endoplasmic reticulum.

Smooth endoplasmic reticulum vesicles from rat liver display an ATP-supported Ca2+ transport which is mediated by a (Ca2+ + Mg2+)-ATPase. During the catalytic cycle the terminal phosphate from ATP is incorporated to form an acid-precipitable reaction product(118 000-Mr in SDS-gel electrophoresis) with stability characteristics of an acylphosphate. Comparative studies with sarcoplasmic reticulum vesicles from fast-twitch skeletal muscle suggest that the 118 000-Mr phosphopeptide may be identified with the phosphorylated reaction intermediate of a Ca2+ transport ATPase in endoplasmic reticulum, similar to that in sarcoplasmic reticulum of muscle.

Adenosine Triphosphatases↗
PubMed1983

[Gluten-sensitive enteropathy--in the light of new clinical and pathogenetic aspects].

The corn protein gluten causes the gluten-sensitive enteropathy in susceptible persons (HLA-antigens). The diagnosis is made on the basis of the morphological criteria of villous atrophy of the jejunal mucosa and the clinical observation that the malabsorption can be healed by a gluten-free diet. The disease, which occurs in children and adults, is a distinct entity. Life-long adherence to a gluten-free diet is difficult. Intentional or unintentional reintroduction of gluten often causes masked disease states. These are best classified on the basis of electron-microscopy study of the jejunal biopsy. We propose a new classification of the phases of remission. A group of diseases exist which are closely related to gluten-sensitive enteropathy. Frequently villous atrophy is detectable. However, the disease does not respond to a gluten-free diet. The pathophysiology of these diseases is at present unclear. Diseases involving autoimmune processes also appear to be associated with gluten-sensitive enteropathy. The common factor is probably an immuno-genetic defect. This is supported by the existence of common HLA-antigen constellations. Gluten has been characterised in vitro as a lectin with oligomannose specificity. This provides a new pathomechanism for the gluten induced enterocytic destruction.

Celiac Disease↗
PubMed1983

[Tryptophan loading test as a function parameter in liver diseases].

Because of its specific hepatic degradation tryptophan was orally administered (50 mg/kg) to patients with various chronic liver diseases (n = 30) and to healthy volunteers (n = 8) as a test for hepatic function. The plasma half life of tryptophan was determined between 4 and 8 h after the amino acid load. It was found that in patients with cirrhosis (n = 25) the half life of tryptophan was prolonged to 4.7 +/- 0.4 h (means +/- SD), compared to 2.0 +/- 0.1 h in the controls. The tryptophan half life also correlated with the plasma concentration of albumin, bilirubin, cholinesterase and prothrombin time in these patients. In addition a significant correlation was observed with the galactose elimination capacity and the 45 min retention of BSP. Thus, the oral tryptophan loading test may be suitable for a more specific determination of functional impairment of the liver in chronic liver disease. In decompensated cirrhotic patients alterations of the tryptophan metabolism seen to be related to indicators of hepatic encephalopathy. The test may therefore be used to assess the degree and risk of hepatic encephalopathy in such patients.

Adult↗
PubMed1983

Regulation of flux through glutaminase and glutamine synthetase in isolated perfused rat liver.

1. Glutaminase and glutamine synthetase are simultaneously active in the intact liver, resulting in an energy consuming cycling of glutamine at a rate up to 0.2 mumol per g per min. 2. An increase in portal glutamine concentration was followed by an increased flux through glutaminase, but flux through glutamine synthetase remained unchanged. Glutaminase flux was also increased by ammonium ions or glucagon; these effects were additive. 3. Glutamine synthetase flux was increased by ammonium ions, but this activation was partly overcome by increasing portal glutamine concentrations. Glutamine synthetase flux was slightly increased by glucagon at portal glutamine concentrations of about 0.2-0.3 mM, but was strongly inhibited above 0.6 mMs. 4. During experimental metabolic acidosis there was an increased net release of glutamine by the liver, being due to opposing changes of flux through glutaminase and glutamine synthetase. Conversely, an increased glutamine uptake by the liver during metabolic alkalosis was observed due to an inhibition of glutamine synthetase and an activation of glutaminase. However, the two enzyme activities respond differently depending on whether glucagon or ammonium ions are present.

Ammonium Chloride↗
PubMed1983

The lectin properties of gluten as the basis of the pathomechanism of gluten-sensitive enteropathy.

The pathogenesis of gluten-sensitive enteropathy is as yet unknown. According to one theory gluten may act as a lectin with toxic properties for the intestinal cells. We can now confirm this theory by laser nephelometric measurements and demonstrate the oligomannosyl specificity of this lectin-like protein gluten. Furthermore, we demonstrate the highly more intensive binding capacity of gluten for the glycoproteins of the immature crypt cells of the intestinal brush border compared to those from the mature villous zone. It is discussed that gluten-sensitive enteropathy is caused by a genetically determined defect-glycosylation of intestinal glycoproteins with the synthesis of more mannosylated glycoproteins.

Celiac Disease↗
PubMed1983

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↗