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E Grau

Publications and source records attributed to E Grau.

At least 55 records · Page 3Linked to original sources
PubMed1993

Hyperammonemia decreases protein-kinase-C-dependent phosphorylation of microtubule-associated protein 2 and increases its binding to tubulin.

Hyperammonemia increases the polymerization of brain microtubules, which is controlled by the binding of microtubule-associated protein (MAP) 2; binding of MAP-2 is, in turn, regulated by phosphorylation. We have found that the binding of MAP-2 to tubulin is greatly increased by hyperammonemia, however, the brain content of MAP-2 is not affected. Microtubules isolated from hyperammonemic rats contained approximately twice the MAP-2/mg microtubular protein that of microtubules isolated from control animals. MAP isolated from brain microtubules of hyperammonemic rats stimulated the polymerization of tubulin more than MAP isolated from control animals. This appears to be due to the increased content of MAP-2. In vitro phosphorylation, using brain homogenates, showed that protein-kinase-C-dependent phosphorylation of MAP-2 was markedly decreased in hyperammonemic rats. Hyperammonemia also affected the intracellular distribution of brain protein kinase C; its content in the cytosol increased about 23%, while in membranes it decreased by 46%. The possible role of decreased protein-kinase-C-dependent phosphorylation on the increased binding of MAP-2 to tubulin and in the increased polymerization of microtubules in the brain of hyperammonemic rats is discussed.

Ammonia↗
PubMed1993

The joint distribution of patterns in random sequences with application to the RC-measure for expressivity.

A method was previously developed for computation of pattern probabilities in random sequences under Markov chain models. We extend this method to the calculation of the joint distribution for two patterns. An application yields the distribution of the right choice measure for expressivity and how significance bounds depend on sequence length. These bounds are used to show that the choice of pyrimidine in codon position 3 of Escherichia coli genes deviates considerably from a general Markov process model for coding regions. We also derive some statistical evidence that this significant deviation is limited to codon position 3.

Algorithms↗
PubMed1993

Ammonium injection induces an N-methyl-D-aspartate receptor-mediated proteolysis of the microtubule-associated protein MAP-2.

We have shown previously that chronic hyperammonemia increases, in brain, the polymerization of microtubules that is regulated mainly by the level and state of phosphorylation of microtubule-associated protein 2 (MAP-2). Activation of the N-methyl-D-aspartate (NMDA) receptor dephosphorylates MAP-2. Because we have found that acute ammonia toxicity is mediated by the NMDA receptor, we have tested the effect of high ammonia levels on MAP-2 in brain. Microtubules isolated from rats injected intraperitoneally with 6 mmol/kg ammonium acetate showed a marked decrease of MAP-2. Also, the amount of MAP-2 in brain homogenates, determined by immunoblotting, was markedly reduced, presumably by proteolysis. The content of MAP-2 was decreased by approximately 75% 1-2 h after ammonium injection and returned to normal values after 4 h. Proteolysis of MAP-2 was prevented completely by injection of 2 mg/kg MK-801, a specific antagonist of the NMDA receptor, suggesting that proteolysis is mediated by activation of this receptor. L-Carnitine, which protects rats against ammonia toxicity, also prevented MAP-2 degradation. Because activation of the NMDA receptor increases [Ca2+]i, we determined whether rat brain contains a Ca(2+)-dependent protease that selectively degrades MAP-2. We show that there is a cytosolic Ca(2+)-dependent protease that degrades MAP-2, but not other brain proteins. The protease has been identified tentatively as calpain I, for it is inhibited by a specific inhibitor of this protease. Our results suggest that ammonium injection activates the NMDA receptor, leading to an increase in [Ca2+]i, which activates calpain I. This, in turn, selectively degrades MAP-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗
PubMed1993

Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 alpha, beta and gamma genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm.

The HNF-3 alpha, beta and gamma genes constitute a family of transcription factors that are required for hepatocyte-specific gene expression of a number of genes, e.g. transthyretin, alpha-1 antitrypsin and tyrosine aminotransferase. These genes share a highly conserved DNA-binding domain first found in the Drosophila gene, forkhead, which is required for the normal patterning of the developing gut and central nervous system in Drosophila. In adult mouse tissues, transcripts from HNF-3 alpha and beta have been localised to the liver, intestine and lung, whereas HNF-3 gamma is found in the liver, intestine and testis. In light of the early developmental significance of forkhead in Drosophila, we have compared the patterns of expression of HNF-3 alpha, beta and gamma mRNAs during murine embryogenesis. We find that these genes are sequentially activated during development in the definitive endoderm. HNF-3 beta mRNA is expressed in the node at the anterior end of the primitive streak in all three germ layers and is the first gene of this family to be activated. Subsequently, HNF-3 alpha is transcribed in the primitive endoderm in the region of the invaginating foregut and HNF-3 gamma appears upon hindgut differentiation. These genes have different anterior boundaries of mRNA expression in the developing endoderm and transcripts are found in all endoderm-derived structures that differentiate posterior to this boundary. Therefore, we propose that these genes define regionalization within the definitive endoderm. Furthermore, differential mRNA expression of HNF-3 alpha and beta is detected in cells of the ventral neural epithelium, chordamesoderm and notochord. In the neural epithelium, expression of HNF-3 alpha and beta mRNA becomes localised to cells of the floor plate. We propose that, in addition to their characterised requirement for liver-specific gene expression, HNF-3 alpha and beta are required for mesoderm and neural axis formation. We also conclude that HNF-3 beta is the true orthologue of the Drosophila forkhead gene.

Animals↗
PubMed1992

Treatment of hyperammonemia with carbamylglutamate in rats.

A protein-free diet causes a paradoxical increase of blood ammonia levels that seems to be due to decreased liver content of acetylglutamate, the physiological activator of carbamylphosphate synthetase. The purpose of this study was to assess whether oral administration to rats of carbamylglutamate, a metabolically stable activator of carbamylphosphate synthetase, could decrease the blood ammonia levels increased by the protein-free diet. We show that ingestion of moderate doses of carbamylglutamate increased about sixfold the liver content of carbamylphosphate synthetase activators and restores to normal values the blood ammonia levels. Excess ammonia is eliminated in urine as urea. These results indicate that carbamylglutamate, which is not toxic, could be useful in the treatment of hyperammonemia, especially in cirrhosis.

Administration, Oral↗
PubMed1992

The susceptibility of MAP-2 to proteolytic degradation increases when bound to tubulin.

During experiments studying dietary effects on phosphorylation/dephosphorylation of MAP-2 we found that incubation of microtubules with alkaline phosphatase resulted in extensive proteolysis of MAP-2 but not of tubulin or Tau proteins. In the absence of tubulin, when microtubule-associated proteins (MAPs) were incubated with alkaline phosphatase, MAP-2 was not proteolyzed. This suggests that binding to tubulin induces a conformational change in MAP-2 which makes it more susceptible to proteolysis. The proteolysis of MAP-2 by alkaline phosphatase was prevented by inhibitors of serine proteases, suggesting that the commercial preparation of the enzyme is contaminated by a serine protease and/or that the enzyme also has a weaker proteolytic activity. In addition, selective proteolysis of MAP-2 can be obtained with the metalloprotease collagenase. Brain homogenates are shown to contain a Ca(2+)-dependent protease which selectively degrades MAP-2 bound to tubulin. These results suggest that selective proteolysis of tubulin-bound MAP-2 could play a role in the regulation of microtubule dynamics in response to extracellular signals.

Alkaline Phosphatase↗
PubMed1992

Low molecular weight heparin (CY-216) versus unfractionated heparin in chronic hemodialysis.

In 14 patients undergoing chronic hemodialysis, we investigated the safety and efficacy of the low molecular fragment (CY-216) in comparison to unfractionated heparin (UFH) in the prevention of clotting in the extracorporeal circuit (ECC). In this study, 168 hemodialysis sessions were undertaken with UFH in 2 bolus doses (5,437 +/- 1,477 SD IU) and 231 with CY-216 in a single bolus dose [initial dose 150 anti-Xa U Institut Choay (IC)/kg]. There were no clots in the bubble trap in any UFH sessions, and 14.8% had coagulated fibers in the dialyzer. Clotting in the bubble trap was observed in 2 CY-216 sessions (0.8%) and coagulated fibers in 22.6% of the sessions. At the end of the study, the mean dose of CY-216 was 250 anti-Xa UIC/kg but a dose of 350 anti-Xa UIC/kg was needed in the 2 patients treated by recombinant human erythropoietin. Anti-Xa levels at the end of the runs were higher (0.47 +/- 0.1 U/ml) in the CY-216 group than in the UFH group (0.28 +/- 0.1 U/ml). There was a correlation between anti-Xa levels and efficacy in the CY-216 group. An anti-Xa activity above 0.4 U/ml was needed in order to minimize thrombus formation. Antithrombin III-protease complexes (ATM) and D dimer fibrin derivatives (D dimer) were used as thrombotic markers but they were of little value for the detection of fibrin formation in the ECC. Our findings suggest that CY-216 administered as a single bolus dose seems to be of similar effectiveness to UFH.

Aged↗
PubMed1991

Ammonium ingestion prevents depletion of hepatic energy metabolites induced by acute ammonium intoxication.

Ingestion of an ammonium containing diet produces hyperammonemia and protects rats against acute ammonium intoxication. Acute ammonium toxicity has been attributed to the depletion of energy metabolite intermediates. We show here that hyperammonemia affords considerable protection against depletion of hepatic energy metabolites evoked by ammonium acetate injection. In control rats there were marked decreases in the content of acetoacetate, beta-hydroxybutyrate, ATP, 2-oxoglutarate, lactate, and pyruvate while phosphoenolpyruvate increased markedly. In hyperammonemic rats beta-hydroxybutyrate, ATP, 2-oxoglutarate, and lactate were not significantly affected while pyruvate increased markedly and phosphoenolpyruvate slightly. These results suggest that in controls the activity of pyruvate kinase is inhibited after ammonium injection while in hyperammonemic rats it is not inhibited. The content of alanine (an inhibitor of pyruvate kinase) reached 2.8 mumol/g in controls and 1.6 mumol/g in hyperammonemic rats, 15 min after ammonium injection. This could explain the different effects of ammonium injection on control and hyperammonemic rats.

Acetates↗
PubMed1991

Hepatocellular carcinoma and squamous cell carcinoma in a patient with Fanconi's anemia.

Acute leukemia, hepatocellular carcinoma, and squamous cell carcinoma have been reported in patients with Fanconi's anemia. We report on a 31-year-old woman who developed squamous cell carcinoma of the esophagus and hepatocellular carcinoma. Jaundice and hepatic tumor developed in 1981, after she had received oxymetholone for 10 years. Liver biopsy revealed peliosis hepatis. Androgenic therapy was stopped and the jaundice resolved. However, the hepatic tumor was observed to be unchanged. The patient died of disseminated squamous cell carcinoma, but no metastatic lesions from hepatocellular carcinoma were detected in the autopsy. The association of Fanconi's anemia and squamous cell carcinoma is reviewed, and the malignant potential of androgen-related hepatic tumors is discussed.

Adult↗
PubMed1991

[Oculographic findings in the Arnold-Chiari malformation type I].

The paper deals with 5 adults carriers of this syndrome diagnosed by means of nuclear magnetic resonance (NMR). Neither the conventional radiography nor the plain computerized tomography showed indicative clues of the deformity. However electronystagmography prove in all cases a vertical down beating nystagmus. In one instance the nystagmus become rotatory at lateral glance. In all cases appeared an altered smooth pursuit and a lack of suppression fixation of the vestibular nystagmus. The AA. emphasize the diagnostic value of the electronystagmography (which tracings could spare several other, sometimes expensive, examinations) and suggest a prompt MRI.

Adult↗