Search PubMed⌕ Search

Biomedical subjects

W Gerok

Publications and source records attributed to W Gerok.

At least 37 records · Page 2Linked to original sources
PubMed1994

Modulation of phosphoenolpyruvate carboxykinase mRNA levels by the hepatocellular hydration state.

Exposure of isolated perfused rat livers to hypo-osmotic (225 mosmol/l) perfusion media for 3 h led to a decrease of about 60% in mRNA levels for phosphoenolpyruvate carboxy-kinase (PEPCK) compared with normo-osmotic (305 mosmol/l) perfusions. Conversely, PEPCK mRNA levels increased about 3-fold during hyperosmotic (385 mosmol/l) perfusions. The anisotonicity effects were not explained by changes in the intracellular cyclic AMP (cAMP) concentration or by changes of the extracellular Na+ or Cl- activity. Similar effects of aniso-osmolarity on PEPCK mRNA levels were found in cultured rat hepatoma H4IIE.C3 cells, the experimental system used for further characterization of the effect. Whereas during the first hour of anisotonic exposure no effects on PEPCK mRNA levels were detectable, near-maximal aniso-osmolarity effects were observed within the next 2-3 h. PEPCK mRNA levels increased sigmoidally with the osmolarity of the medium, and the anisotonicity effects were most pronounced upon modulation of osmolarity between 250 and 350 mosmol/l. The aniso-osmolarity effects on PEPCK mRNA were not affected in presence of Gö 6850, protein kinase C inhibitor. cAMP increased the PEPCK mRNA levels about 2.3-fold in normo-osmotic media, whereas insulin lowered the PEPCK mRNA levels to about 8%. The effects of cAMP and insulin were also observed during hypo-osmotic and hyperosmotic exposure, respectively, but the anisotonicity effects were not abolished in presence of the hormones. The data suggest that hepatocellular hydration affects hepatic carbohydrate metabolism also over a longer term by modulating PEPCK mRNA levels. This is apparently unrelated to protein kinase C or alterations of cAMP levels. The data strengthen the view that cellular hydration is an important determinant for cell metabolic function by extending its regulatory role in carbohydrate metabolism to the level of mRNA.

Animals↗
PubMed1994

[Differential diagnosis of diarrhea].

Diarrheal disease should be differentiated into acute and chronic forms. Acute diarrhea can most commonly be referred to infectious pathogens and is usually self-limiting. To establish a firm diagnosis is important for patients with special professions, e.g. food-handlers, cooks, etc. In patients with chronic diarrheal disease, the individual case history (e.g. abdominal operations, length and frequency of diarrhea, body weight, medications, etc.) is of paramount importance to differentiate between functional and organic illness. At least half of the patients in general practice suffer from functional, not from organic disease. Endoscopy of the gastrointestinal tract and tests of small bowel function are first-line procedures in patients with chronic diarrhea, followed by additional investigations (hormonal analysis, bacteriological tests, etc.), if indicated in a given patient.

Acute Disease↗
PubMed1994

Endotoxin-induced nitric oxide synthesis in the perfused rat liver: effects of L-arginine and ammonium chloride.

We used the single-pass-perfused rat liver model to study short-term regulation of endotoxin-inducible nitric oxide synthesis by following the release of nitrite and nitrate, the oxidation products of nitric oxide, into the effluent perfusate. In endotoxin-pretreated livers, the basal nitrite+nitrate release was 5.3 +/- 1.2 nmol.gm liver-1.min-1. Nitrite and nitrate release was stimulated by L-arginine in a dose-dependent and saturable fashion. Maximal nitrite+nitrate release with 1 mmol/L L-arginine infused to the influent perfusate was 10.2 +/- 1.1 nmol.gm liver-1.min-1, with a half-maximal effect at 53 mumol/L L-arginine. In the absence of molecular oxygen, nitric oxide synthesis was inhibited. Ammonium chloride infusion also stimulated nitrite and nitrate release to a maximal rate of 9.2 +/- 0.8 nmol.gm liver-1.min-1 with half-maximal effects at 60 mumol/L ammonium chloride. Ammonium chloride-stimulated nitrite and nitrate release was abolished when urea synthesis was inhibited by bicarbonate-free liver perfusion. Citrulline and ornithine (200 mumol/L each) were without effect on nitrite and nitrate release. L-Nitroarginine methyl ester inhibited both, L-arginine-and ammonium chloride-induced nitrite and nitrate release. Stimulation of nitric oxide synthesis by L-arginine and ammonium chloride addition (1 mmol/L each) was accompanied by a threefold-to-fourfold increase of cyclic GMP release into the effluent perfusate. In livers of endotoxin-pretreated rats the urea production from L-arginine was higher than that in untreated livers, suggesting induction of an L-arginine transport system in hepatocytes by endotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonium Chloride↗
PubMed1994

Antibodies and viremia in acute post-transfusion hepatitis C: a prospective study.

Fourteen patients who developed acute post-transfusion hepatitis C after open-heart surgery were studied for seroconversion, viremia, and aminotransferase. Anti-HCV antibodies were measured by first and second generation ELISA and became positive between one week and more than 6 months after infection. Seroconversion in four patients and passively transfused antibodies were only found by the second generation assay, indicating its significantly higher sensitivity. Viremia was detected by reverse transcription and the polymerase chain reaction within the first 4 weeks of infection in 13 patients and persisted for more than 2 years in all of them. One patient died of cardiac cause. Viral strains were heterogeneous between the different patients, but showed no significant variation within one patient during the course of hepatitis deduced from the results with different sets of oligonucleotides. Viremia preceded hepatitis by 4 weeks, seroconversion determined by ELISA II followed after an 8 week interval, and anti-C-100 antibodies appeared 26 weeks later. Aminotransferase activities returned to normal values in 10 patients.

Acute Disease↗
PubMed1994

Molecular therapeutic strategies in hepatitis B virus infection.

Chronic infection with the hepatitis B virus is a major health problem worldwide. The only established therapy is interferon-alpha, with an efficacy of only 30-40% in highly selected patients. Nucleoside analogues do not show a significant clinical benefit. Molecular therapeutic strategies aimed at blocking gene expression include antisense DNA/RNA and ribozymes acting at the posttranscriptional level and triple helix formation blocking at the transcriptional level. In vitro, antisense oligodeoxynucleotides inhibit viral replication and gene expression in human hepatoma cell lines. In vivo, an antisense oligodeoxynucleotide directed against the 5'-region of the pre-S gene of the duck hepatitis B virus inhibited viral replication and gene expression in ducks. In vitro, ribozymes accurately cleave HBV substrate RNA. Triple helix formation is another very promising molecular approach. Results in hepadnaviral infection are not yet available, however.

Base Sequence↗
PubMed1994

Excessive iron storage in a patient with Wilson's disease.

We report on an otherwise healthy female, mother of two children, with severe decompensated liver cirrhosis due to an iron overload and Wilson's disease. The patient was considered heterozygote for hemochromatosis on the basis of the autosomal recessive inheritance for hemochromatosis, the frequency of the hemochromatosis gene, and the laboratory parameters defining her iron overload. The case is interesting because of the coincidence of Wilson's disease and excessive iron storage.

Adult↗
PubMed1994

Proton magnetic resonance spectroscopy studies on human brain myo-inositol in hypo-osmolarity and hepatic encephalopathy.

BACKGROUND/AIMS: Recent in vivo studies using proton magnetic resonance (1H-MR) spectroscopy showed low levels of myo-inositol in the brain in hepatic encephalopathy; the pathogenetic relevance of this observation is unclear. METHODS: Myo-inositol and glutamine levels in the brain were studied in vivo by 1H-MR spectroscopy in patients with hypo-osmolarity and hepatic encephalopathy. RESULTS: A patient with severe plasma hypo-osmolarity (222 mOsm/L) had almost undetectable signals for myo-inositol and glutamine/glutamate in the brain. Both signals reappeared after normalization of plasma osmolarity, suggesting that both myo-inositol and glutamine were released as organic osmolytes from the brain. A decreased cerebral myo-inositol signal is also found in low-grade hepatic encephalopathy but is accompanied by an increased glutamine signal. Cirrhotics without hepatic encephalopathy have near-normal inositol signals, and patients with acquired immunodeficiency syndrome encephalopathy have increased inositol signals. CONCLUSIONS: The 1H-MR spectroscopic myo-inositol signal in the human brain predominantly reflects an osmosensitive inositol pool. It is hypothesized that its depletion in latent hepatic encephalopathy points to a disturbance of cell volume homeostasis in the brain as an early pathogenetic event. This may partly be caused by a hyperammonemia-induced glutamine accumulation in the brain.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Effects of anisotonic exposure on duck hepatitis B virus replication.

In cultured hepatocytes from in vivo duck hepatitis B virus-infected ducks the effect of medium osmolarity on viral replication was studied. A 10-day exposure to hypotonic media (277 mOsm/L due to removal of 26 mmol/L NaCl) lowered the duck hepatitis B virus DNA content of cells and of the medium by about 50%, whereas hyperosmotic exposure (421 mOsm/L by addition of 46 mmol/L NaCl) increased it about four-fold compared with normotonic standard incubation medium (329 mOsm/L). The tissue levels of viral RNA transcripts increased during the 10 days of hypertonic exposure but decreased only slightly after hypoosmotic treatment. Western-blot analysis for the production of viral pre-S/S proteins revealed a marked stimulation of viral protein synthesis in hypertonic media, whereas hypotonic exposure inhibited it. Conversely, total cellular protein synthesis as assessed from [3H]leucine incorporation into acid-precipitable material decreased during hyperosmotic exposure but increased during hypoosmotic exposure. We noted a comparable increase of duck hepatitis B virus DNA when raffinose (80 mmol/L) was added to hypotonic or normotonic media, without change in the NaCl concentrations. This suggests that the effects of anisotonicity on viral replication were not due to alterations of Na+ or Cl- activity in the incubation media, but might reflect changes of cellular volume. The effects of anisotonicity on viral replication were only seen after exposure of more than 8 hr of the cells to anisotonicity. The findings suggest that the cellular volume is an important determinant for duck hepatitis B virus replication, yet the underlying molecular mechanisms remain elusive.

Animals↗
PubMed1994

Origin and development of exocrine pancreatic insufficiency in experimental renal failure.

Chronic renal failure affects the physiological function of many organ systems. One of them is the exocrine pancreas. Although varying degrees of pancreatic insufficiency are the dominating clinical characteristic of uraemic pancreatic disease, it remains unclear whether this disease should be regarded as a manifestation of chronic pancreatitis, arising from recurring attacks of acute pancreatitis, or represents a distinct entity. The exocrine pancreas was studied in a model of experimental renal failure. The pancreas was removed from each rat at selected time points over eight weeks after subtotal nephrectomy and from a standard rat model of pancreatitis for comparison. The data show that the in vitro secretory response is considerably changed in renal failure (increased during early acute and decreased during chronic renal failure). While the pancreatic content of digestive enzymes progressively declines, DNA and protein synthesis increase over time. Acinar cell deletion is increased and accompanied by an increased rate of mitosis. This increased cellular turnover is not associated with tissue oedema, pancreatic fibrosis, inflammatory changes, autophagocytosis or subcellular redistribution of lysosomal hydrolases, all of which are characteristic for pancreatitis. The ultrastructural changes of uraemic pancreatic disease bear no resemblance to the changes seen in pancreatitis. It is concluded that the morphological and biochemical changes in early uraemic pancreatic disease are quite distinct, correspond with toxic damage of the pancreas, and are dominated by functional impairment and an increased cellular turnover.

Amylases↗
PubMed1994

Regulation of cell function by the cellular hydration state.

Cellular hydration can change within minutes under the influence of hormones, nutrients, and oxidative stress. Such short-term modulation of cell volume within a narrow range acts per se as a potent signal which modifies cellular metabolism and gene expression. It appears that cell swelling and cell shrinkage lead to certain opposite patterns of cellular metabolic function. Apparently, hormones and amino acids can trigger those patterns simply by altering cell volume. Thus alterations of cellular hydration may represent another important mechanism for metabolic control and act as another second or third messenger linking cell function to hormonal and environmental alterations.

Amino Acids↗
PubMed1994

[Hemodynamics, liver function and clinical follow-up after TIPS].

In 126 patients with liver cirrhosis treated electively with transjugular intrahepatic portosystemic stent shunt (TIPS) to prevent variceal rebleeding, the portosystemic pressure gradient decreased by 60%. In spite of this incomplete effect the risk for variceal rebleeding was still under 20% after 2 years. Only 1 patient died of variceal rebleeding. Shunt insufficiency occurred in 50%, mainly during the first year, but shunt function was restored in nearly all cases by radiologic intervention, i.e., redilatation or implantation of an additional stent. During the follow-up of 16 +/- 9 months, 21 patients (17%) died, one-third of them from progressive liver failure aggravated in 4 cases by severe drinking. De novo hepatic encephalopathy was observed in 10%, especially in older patients and patients with impaired liver function before TIPS. In such patients it is recommended that the shunt be dilated to 0.8 cm at most, and the TIPS procedure can be combined with transjugular embolization of the varices. The advantages of TIPS over both endoscopic sclerotherapy and drug treatment must be clarified in randomized studies, which have already been initiated in several centers.

Catheterization↗
PubMed1993

Endogenous hydroperoxide formation, cell volume and cellular K+ balance in perfused rat liver.

Addition of benzylamine (0.5 mM) to isolated perfused rat liver led to a net release of K+ of 10.5 +/- 0.3 mumol/g, which was accompanied by a decrease in liver mass by 9.3 +/- 0.4% and a decrease of the intracellular water space by 13.7 +/- 0.6%, suggestive of hepatocellular shrinkage. Benzylamine had no effect on the perfusion pressure, and there was a close relationship between benzylamine-induced net K+ release and the accompanying decrease in liver mass. Benzylamine-induced net K+ release was sensitive to inhibition of monoamine oxidase by pargyline and increased with benzylamine flux through monoamine oxidase, suggesting its dependence on intracellular H2O2 formation. In line with this, infusion of H2O2 (but not of benzaldehyde, the other product of benzylamine metabolism) stimulated net K+ release from the liver. However, at a given H2O2 load K+ release was about 2-3-fold higher when H2O2 was generated intracellularly during the oxidation of benzylamine, as compared with exogenously delivered H2O2. Inhibition of catalase by 3-amino-1,2,4-triazole (0.2 mM) significantly increased the benzylamine-induced net K+ release as well as the benzylamine-induced release of GSSG into bile, but had no effect on benzylamine oxidation at monoamine oxidase. In the presence of Ba2+ (1 mM) or in Ca(2+)-free perfusions, the benzylamine-induced net K+ efflux was diminished by 60-70% or about 30%, respectively. This was not explained by the 20-30% decrease in flux through monoamine oxidase observed under these conditions. The results suggest that metabolic generation of H2O2 inside the liver leads to a net K+ efflux and subsequent hepatocellular shrinkage. Net K+ efflux under these conditions is enhanced when catalase is inhibited, suggesting that the rate of both intracellular H2O2 generation and degradation can modulate cellular K+ balance and cellular volume. The data support the idea that oxidative stress may affect hepatocellular functions also by lowering the hepatocellular hydration state.

Animals↗
PubMed1993

Human liver calreticulin: characterization and Zn(2+)-dependent interaction with phenyl-sepharose.

A 60-kDa human calreticulin was isolated from liver homogenates. The protein was identified as calreticulin by its NH2-terminal amino acid sequence, by its mobility in SDS-PAGE, by its immunoreactivity with anti-calreticulin antibodies, by its Ca2+ binding, and by its localization to isolated ER membranes. In this study we show that Ca2+ binding to calreticulin results in Ca(2+)-dependent aggregation and precipitation of the protein. We also show that calreticulin and calsequestrin bind Zn2+ in 65Zn2+ overlay. In addition we have discovered that calreticulin exhibits a Zn(2+)-dependent interaction with hydrophobic matrix of phenyl-Sepharose that can be utilized in the purification of the protein.

Animals↗
PubMed1993

Cellular hydration state: an important determinant of protein catabolism in health and disease.

There is evidence that cellular hydration state is an important factor controlling cellular protein turnover; protein synthesis and protein degradation are affected in opposite directions by cell swelling and shrinking. An increase in cellular hydration (swelling) acts as an anabolic proliferative signal, whereas cell shrinkage is catabolic and antiproliferative. The cellular hydration state is mainly determined by the activity of ion and substrate transport systems in the plasma membrane. Hormones, substrates, and oxidative stress can change the cellular hydration state within minutes, thereby affecting protein turnover. We postulate that a decrease in cellular hydration in liver and skeletal muscle triggers the protein catabolic states that accompany various diseases.

Amino Acids↗
PubMed1993

Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver.

An increase of the hepatocellular hydratation state, induced by hypotonic exposure, amino acids or tauroursodeoxycholate, was shown to increase within minutes the Vmax of transcellular taurocholate transport and excretion into bile [Häussinger, Hallbrucker, Saha, Lang and Gerok (1992) Biochem. J. 288, 681-689]. This stimulatory effect of cell swelling on taurocholate excretion into bile is abolished in the presence of colchicine (5 microM). On the other hand, colchicine did not affect the stimulatory action of hypotonic cell swelling on 14CO2 production from [1-14C]glycine or [1-14C]glucose. Likewise, volume regulatory K+ fluxes following anisotonic exposure were not influenced in the presence of colchicine. Lumicolchicine (5 microM), a stereoisomer of colchicine without an inhibitory effect on microtubules, did not abolish the stimulation of taurocholate excretion into bile following hypo-osmotic exposure. Hypertonic cell shrinkage decreased taurocholate excretion into bile by about 35%; this effect was fully reversible upon normotonic re-exposure. With colchicine pretreatment, however, the hypertonicity-induced inhibition of taurocholate excretion was blunted and was no longer reversible upon normotonic re-exposure. The results suggest that stimulation of taurocholate excretion into bile in response to cell swelling involves a colchicine-sensitive, probably microtubule-dependent, mechanism, but not the stimulation of other cell-volume-sensitive pathways such as glycine oxidation or the pentose-phosphate shunt. It is hypothesized that the swelling-induced stimulation of taurocholate excretion into bile is due to a microtubule-dependent insertion of bile acid transporter molecules into the canalicular membrane.

Animals↗