Search PubMed⌕ Search

Biomedical subjects

W Gerok

Publications and source records attributed to W Gerok.

At least 253 records · Page 14Linked to original sources
PubMed1985

Relapsing pancreatitis associated with duodenal wall cysts. Diagnostic approach and treatment.

A case of enterogenous cysts of the duodenum in a 44-yr-old man complicated by duodenal obstruction and relapsing pancreatitis is presented. The cystic duodenal lesions were visualized by endoscopic retrograde cholangiopancreatography and for the first time by computed tomography and abdominal sonography. Thus, the diagnosis was made preoperatively. The cysts were excised successfully during a Whipple procedure. Awareness of this rare condition combined with modern x-ray, sonographic, and endoscopic techniques permit accurate preoperative diagnosis.

Adult↗
PubMed1985

The glutamine analog acivicin as antipyrimidine. Studies on the interrelationship between pyrimidine and urea synthesis in liver.

The inhibition of cytosolic carbamoyl-phosphate synthetase II by acivicin was used to study the role of the cytosolic carbamoyl phosphate pool as the exclusive substrate source for de novo pyrimidine synthesis in rat hepatocytes. De novo pyrimidine synthesis was stimulated: 1. by uridine triphosphate deficiency (incubation with D-galactosamine) leading to a stimulation of cytosolic carbamoyl phosphate synthesis, and 2. by accumulation and efflux of mitochondrial carbamoyl phosphate (incubation with ammonium ions and L-norvaline). The stimulated orotate formation from cytosolic carbamoyl phosphate in UTP depleted cells was completely blocked by acivicin. It was not influenced by an inhibition of mitochondrial carbamoyl phosphate synthesis mediated by 4-pentenoate, since mitochondrial carbamoyl phosphate did not participate in cytosolic pyrimidine synthesis even in the presence of ammonium ion concentrations maintaining physiological rates of urea synthesis. An excess of ammonium ions led to an artificial accumulation and efflux of mitochondrial carbamoyl phosphate, which could be avoided by 4-pentenoate. The non-regulated stimulation of pyrimidine synthesis from surplus mitochondrial carbamoyl phosphate was not inhibited by acivicin. Utilization of mitochondrial carbamoyl phosphate for de novo pyrimidine synthesis presumably does not occur under physiological conditions because mitochondrial CP efflux depends on the accumulation of this metabolite in the mitochondria under experimental or pathological circumstances. Acivicin inhibition of CPS II thus cannot be bypassed by mitochondrial CP. It is suitable as inhibitor of the physiological de novo pyrimidine synthesis.

Animals↗
PubMed1985

First clinical experiences with a selective chemotherapy of hepatocellular carcinoma with 5-fluorouridine in combination with other antipyrimidines.

Sixteen unselected patients with non-resectable hepatocellular carcinoma were treated in a phase I study with 261 cycles of D-galactosamine and 6-azauridine prior to 5-fluorouridine. Thirty % of the patients survived for more than one year without signs of tumor progression and with an unchanged performance status. The compatibility of this chemotherapeutical method was quite satisfactory. The only extrahepatic side effect was a leucopenia and/or thrombocytopenia which was reversible upon reduction of the 5-fluorouridine dose. The heterogeneity of the 16 patients treated to date does not allow a definite statistical evaluation of the reported clinical observations and results. A final decision about the clinical applicability of this concept of a selective chemotherapy of hepatocellular carcinoma requires further experience.

Adult↗
PubMed1985

Functional hepatocyte heterogeneity in ammonia metabolism. The intercellular glutamine cycle.

In the rat liver acinus area synthesis and glutaminase activity are predominantly localized in the periportal area, whereas glutamine synthetase activity and the transport system for glutamate in the plasma membrane are perivenous. Detoxification of ammonium ions at low concentrations occurs exclusively by glutamine synthesis, but not by urea formation. Therefore, the two pathways of ammonia detoxification in the liver acinus represent the sequence of a low-affinity, but high-capacity system (urea synthesis) and a high-affinity system (glutamine synthesis). In agreement with this finding, obtained in experiments with the metabolically- and structurally-intact perfused rat liver, is also an almost complete inhibition of perivenous glutamine synthesis without impairment of periportal urea synthesis. This was shown after induction of a perivenous liver cell necrosis following CCl4 pretreatment with the consequence of a diminished hepatic ammonia extraction. Periportal glutaminase and perivenous glutamine synthetase are simultaneously active, resulting in an intercellular (as opposed to intracellular) glutamine cycle, being under the control of hormones, pH and portal ammonia and glutamine concentrations. The intercellular glutamine cycle provides an effective means for almost complete conversion of portal ammonium ions to urea by additional substrate supply of periportal urea synthesis, by periportal glutamine degradation and by the perivenous re-synthesis of glutamine from ammonia which escaped urea synthesis. Because urea synthesis, in contrast to glutamine synthesis, is a major pathway for the removal of bicarbonate, the switching of ammonia detoxification from urea synthesis to glutamine synthesis in acidosis or vice versa in alkalosis points to an important role of the liver in maintaining pH homeostasis. The acid-base-induced changes of the route of hepatic ammonia detoxification and therefore bicarbonate removal are performed by the regulatory properties of the enzymes of the intercellular glutamine cycle.

Acid-Base Equilibrium↗
PubMed1985

Glutamine metabolism in isolated perfused rat liver. The transamination pathway.

In isolated perfused rat liver, added 4-methyl-thio-2-oxobutyrate and phenylpyruvate are rapidly transaminated to the corresponding amino acids with glutamine, the latter being supplied via the portal vein or by endogenous synthesis. With portal glutamine concentrations below 5mM and in the presence of a oxo-acid acceptor, the flux through glutamine transaminases exceeded the ammonium ion-stimulated glutaminase flux. 4-Methylthio-2-oxobutyrate-induced extra glutamine uptake was not dependent on the perfusate pH in the range of pH 7 to 8. During glutamine/4-methylthio-2-oxobutyrate transamination, the amide nitrogen of glutamine is fully recovered as glutamate, ammonia, urea and alanine. Oxoglutarate formed by omega-amidase activity is released as glutamate or oxidized by oxoglutarate dehydrogenase. alpha-Cyanocinnamate, the inhibitor of the monocarboxylate translocator in the mitochondrial membrane inhibited 4-methylthio-2-oxobutyrate-induced glutamine uptake and methionine release by about 30%. This might indicate that about 2/3 of glutamine transaminase flux is cytosolic. alpha-Cyanocinnamate inhibited 4-methylthio-2-oxobutyrate-induced glutamate efflux by about 90%. Stimulation of flux through glutamine transaminases is accompanied by a 70-80% inhibition of glutaminase flux. This is not explained by a direct inhibition of glutaminase by 4-methylthio-2-oxobutyrate but by a substrate competition between glutaminase and glutamine transaminases. 4-Methylthio-2-oxobutyrate decreases glutamine release by the liver due to withdrawal by transamination. The oxo acid itself is without effect on glutamine synthetase flux. With respect to hepatocyte heterogeneity there is no evidence for a zonal distribution of glutamine transaminase activities, as it has been shown for glutamine synthetase and glutaminase activities.

Alanine↗
PubMed1985

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↗
PubMed1984

Amino acid, ammonia and neurotransmitter concentrations in hepatic encephalopathy: serial analysis in plasma and cerebrospinal fluid during treatment with an adapted amino acid solution.

We evaluated changes of advanced liver disease and hepatic encephalopathy on the concentrations of amino acids (AA) and ammonia in plasma and cerebrospinal fluid (CSF) and of the neurotransmitters norepinephrine, dopamine and 5-hydroxytryptamine (5-HT) as well as the 5-hydroxyindole acetic acid (5-HIAA) in CSF before and at the end of a 3-day period of treatment with infusions enriched with branched chain amino acids (BCAA). The subjects studied were 13 patients with alcoholic cirrhosis and hepatic encephalopathy stages 1-3 (n = 8) and stage 4 (n = 5). The patients in coma stages 1-3 recovered during the treatment (survivors), those in coma stage 4 died before the study period was finished (non-survivors). The data emerging from this study show: Alterations of AA concentrations are much more pronounced in the CSF than in the plasma. In the case of tryptophan the alterations in plasma and CSF were inverse. Before the treatment the CSF-plasma ratios of the concentrations of BCAA and aromatic amino acids (AAA) are increased reflecting an activated transport of both the BCAA and AAA through the blood-brain barrier. High dose BCAA nearly normalized CSF concentrations and CSF-plasma ratios of AAA assuming that the treatment brought about an effective competition of cerebral uptake between BCAA and AAA. The CSF concentrations of ammonia and glutamine decreased significantly during treatment while the plasma concentrations changed only moderately. As to the neurotransmitters, only the concentrations of 5-HT and its metabolite 5-HIAA correlated with the clinical picture and with the concentration of their precursor AA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Regulation of hepatic glutamate metabolism. Role of 2-oxoacids in glutamate release from isolated perfused rat liver.

In isolated perfused rat liver, addition of the oxoanalogues of leucine, isoleucine, methionine and phenylalanine is followed by a rapid and reversible stimulation of glutamate release. This is not observed with the corresponding amino acids or 2-oxoisovalerate, 2-oxoglutarate or oxaloacetate. The increased glutamate release by the liver is accompanied by a decrease in the tissue contents of 2-oxoglutarate and glutamate by about 25% and 50%, respectively. During the metabolism of glutamine, i.e. conditions with elevated tissue glutamate concentrations, 2-oxoacid-induced glutamate release is stimulated. In the presence of glutamine (5 mM), 2-oxoisocaproate, 2-oxo-4-methylvalerate and 2-oxo-4-methylthiobutyrate were found to be most effective and glutamate release by the liver increased linearly from about 80 nmol g-1 min-1 to 600 nmol g-1 min-1 at increasing 2-oxoacid concentrations up to 1 mM. When glutamate tissue levels were decreased by phenylephrine, stimulation of glutamate release by 2-oxoisocaproate was markedly diminished. 2-Oxoacid-stimulated glutamate release is independent of oxoacid metabolism, indicating that the effect is probably not explained by a 2-oxoacid/glutamate exchange across the liver plasma membrane. 2-Oxoacid-induced glutamate export predominantly occurs in a sodium-independent way. At low concentrations of 2-oxoisocaproate (below 0.2 mM), the increased glutamate release was accompanied by a slight inhibition of 14CO2 production from added [14C]glutamate, indicating a simultaneous glutamate uptake and release also under these conditions. Stimulation of glutamate release by 2-oxoisocaproate is followed by a decreased rate of urea and glutamine synthesis from portal ammonia, as a consequence of an increased glutamate release.

Animals↗
PubMed1984

The calcium pump in rat liver endoplasmic reticulum. Demonstration of the phosphorylated intermediate.

Rat liver microsomal fractions enriched with smooth-surfaced vesicles possess an ATP-supported Ca2+ transport activity, which is stimulated by oxalate and half-maximally activated at 3.5 X 10(-7) M free Ca2+. Catalysis of Ca2+ transport involves transient covalent binding of the terminal phosphate from ATP by the vesicles, resulting in the formation of a Mr 118,000 phosphopeptide, which is acid precipitable and unstable in the presence of hydroxylamine, which may be characteristic for an acylphosphate. Phosphorylation of the Mr 118,000 peptide requires the presence of Ca2+, while dephosphorylation is markedly accelerated by Mg2+. In the presence of Ca2+ and Mg2+ phosphorylation proceeds much faster than dephosphorylation, indicating that the latter may be rate limiting for the hydrolysis of ATP. The Mr 118,000 peptide is estimated to represent about 2% of total smooth-surfaced endoplasmic reticulum membrane protein. Comparative studies with sarcoplasmic reticulum from rat skeletal muscle suggest extensive homology of the Ca2+ transport ATPases.

Animals↗
PubMed1984

Effect of cimetidine on the hepatic extraction of indocyanine green, the portal pressure and the systemic circulation in patients with cirrhosis of the liver.

The effect of cimetidine on hepatic and systemic haemodynamic parameters was studied in seven patients with portal hypertension due to alcohol-induced cirrhosis of the liver and in one patient with peliosis hepatis following oral contraceptive steroids. The intravenous administration of cimetidine (350 mg as bolus, followed by 2 mg/min over 60 min) reduced the hepatic extraction of continuously infused indocyanine green (ICG) by 27%; this was statistically significant (P less than 0.01). Since the ICG clearance, calculated independently of hepatic perfusion, was lowered by 19%, this effect seems to be mainly due to a reduced capacity of the liver to remove the dye from the blood, rather than due to changes in perfusion. Cimetidine did not influence the elevated portal pressure in the patients with cirrhosis, or the normal pressure in the patient with peliosis hepatis. No significant effect was observed on heart rate, mean arterial pressure, pulmonary artery pressure, pulmonary capillary pressure and cardiac output. These studies indicate that the reduction of the hepatic ICG extraction following cimetidine is more the result of an inhibited capacity of the liver to remove the dye than of changes in the hepatic perfusion or in the systemic circulation.

Adult↗
PubMed1984

Depletion of blood plasma cytidine due to increased hepatocellular salvage in D-galactosamine-treated rats.

Pyrimidine nucleosides in blood plasma of rats were identified by different procedures, including chemical peak shift methods, before their quantification by reversed-phase high-performance liquid chromatography. The concentrations of uridine, cytidine, and deoxycytidine were 1.0 +/- 0.2, 10.6 +/- 1.9, and 33.4 +/- 5.4 mumol/l, respectively. Six hours after the administration of D-galactosamine, the level of circulating cytidine was severely depressed to 25% of control values; uridine decreased to 54% while deoxycytidine remained unchanged. 24 h after the dose of the amino sugar, the levels of cytidine and uridine returned to control values in blood plasma. Total acid-soluble uridine, cytidine, guanosine, and adenosine was determined by reversed-phase HPLC after treatment of the neutralized acid-soluble supernatant of freeze-clamped rat livers with phosphodiesterase and alkaline phosphatase. Six hours after its administration, D-galactosamine induced a 2.2-fold and a 1.6-fold rise in total acid-soluble uridine and cytidine, respectively. Co-administration of N-(phosphonoacetyl)-L-aspartate, an inhibitor of de novo pyrimidine synthesis, suppressed the increase in total acid-soluble uridine observed after D-galactosamine alone, but was without effect on the enhancement of total cytidine. Three hours after D-galactosamine and 15 min after [2-14C] cytidine, there was a rapid fall of the labeled nucleoside in blood plasma to 49% of control animals accompanied by a 2.8-fold rise in the total radioactivity of rat liver homogenates. From these results it can be concluded that the hepatocellular rise in total acid-soluble cytidine after D-galactosamine, in contrast to the increase in total acid-soluble uridine, originates from the phosphorylation of blood plasma cytidine via the salvage pathway. The depletion of circulating cytidine in the presence of hepatocellular UTP deficiency points to the importance of the liver and the hepatic UTP level for the clearance of blood plasma cytidine.

Animals↗
PubMed1984

[Diagnostic accuracy of sonography in liver metastases, with special reference to the primary tumor].

The accuracy of ultrasonography in the detection of liver metastases was studied in 245 patients. Sensitivity, specificity and positive and negative accuracy were defined and calculated. Taking into account only metastases more than 15 mm in diameter, sensitivity was 75.5%, positive accuracy was even higher at 83.0%. Specificity and negative accuracy were above 90%. The results are largely dependent on the type of primary tumour. Sensitivity for metastases of a bronchial or gastric carcinoma was about 50%. The results indicate that a positive ultrasound finding generally need not be checked by other methods, while a negative result, especially in certain types of tumour, is by no means sufficient to exclude metastases.

Breast Neoplasms↗
PubMed1984

Modification of the intramolecular turnover of terminal carbohydrates of dipeptidylaminopeptidase IV isolated from rat-liver plasma membrane during liver regeneration.

An intramolecular turnover of the terminal carbohydrates L-fucose, N-acetylneuraminic acid and D-galactose is a characteristic property of several liver plasma membrane glycoproteins, first demonstrated for dipeptidylaminopeptidase IV (EC 3.4.14.5., DPP IV). The core carbohydrates D-mannose and N-acetyl-D-glucosamine turn over like the polypeptide chain. The ratio of apparent half-lives of L-fucose and L-methionine of DPP IV is shifted from 0.17 in normal liver to 0.60 in regenerating liver. The ratio of half-lives of N-acetylneuraminic acid and L-methionine is only slightly changed from 0.43 in normal liver to 0.61 in regenerating liver. The ratio of apparent half-lives of D-mannose and L-methionine amounts to 0.80 in normal liver and 0.71 after partial hepatectomy. From this a drastic reduction of the intramolecular turnover of L-fucose on plasma membrane DPP IV in regenerating liver can be derived. The intramolecular N-acetylneuraminic acid turnover is affected to only a minor extent. D-Mannose turns over like the polypeptide in both normal and regenerating liver. The intramolecular L-fucose turnover may be involved in membrane glycoprotein recycling, which presumably is altered in regenerating liver. Additionally, L-fucose could regulate the rate of degradation of DPP IV, since core-fucosylated glycoproteins appear to be resistant to mammalian endo-N-acetylglucosaminidase.

Animals↗