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D Müller

Publications and source records attributed to D Müller.

At least 19 recordsLinked to original sources
PubMed1992

Rat insulin-degrading enzyme: cleavage pattern of the natriuretic peptide hormones ANP, BNP, and CNP revealed by HPLC and mass spectrometry.

The degradation of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) by insulin-degrading enzyme (IDE) has been investigated. As revealed by high-performance liquid chromatography, all three peptides are sequentially cleaved at a limited number of sites, the latter of which were identified by mass spectrometric analyses. The studies revealed that ANP is preferred as substrate over BNP and CNP. ANP degradation is rapidly initiated by hydrolysis at the Ser25-Phe26 bond. Three additional cleavage sites were identified in ANP after prolonged incubation with IDE; in contrast, three and two bonds were hydrolyzed in BNP and CNP, respectively. Analysis of the nine cleavage sites shows a preference for basic or hydrophobic amino acid residues on the carboxyl side of a cleaved peptide bond. In contrast to most of the peptide fragments generated by IDE activity, the initial ANP cleavage product, F-R-Y, is rapidly degraded further by cleavage of the R-Y bond. Cross-linking studies with 125I-ANP in the presence of sulfhydryl-modifying agent indicate that IDE activity is inhibited at the level of initial substrate binding whereas metal-ion chelating agents only prevent hydrolysis. On the basis of its structural and enzymatic properties, IDE exhibits striking similarity to a number of recently-described endopeptidases.

Amino Acid Sequence↗
PubMed1992

Molecular characterization of a novel rat protein structurally related to poly(A) binding proteins and the 70K protein of the U1 small nuclear ribonucleoprotein particle (snRNP)

A cDNA has been isolated from a rat testis library which encodes a novel protein of 100 kDa that contains domains found in two different proteins involved in the processing of pre-mRNAs. Computer-assisted comparison reveals that one sequence motif of 30 amino-acid residues is very similar to a region conserved in the C-terminal part of eukaryotic poly(A) binding proteins (PABP). A second region of the rat 100 kDa protein, containing alternating basic, mostly arginine, and acidic amino-acid residues, is structurally related to sequence motifs found in the 70K protein of the U1 small nuclear ribonucleoprotein particle (snRNP), which is involved in RNA splicing. Northern blot analysis shows that a corresponding 9.5 kb transcript is highly expressed in rat testis; lower mRNA levels are found in other tissues such as liver, kidney, lung and brain. Ontogenic studies reveal that the expression of the 100 kDa protein-encoding gene and sexual maturation are correlated, being barely detectable during early post-natal life but reaching maximal levels around the first month after birth.

Amino Acid Sequence↗
PubMed1992

Exclusion mapping of the X-linked dominant chondrodysplasia punctata/ichthyosis/cataract/short stature (Happle) syndrome: possible involvement of an unstable pre-mutation.

Homology with the mouse bare patches mutant suggests that the gene for the X-linked dominant chondrodysplasia punctata/ichthyosis/cataract/short stature syndrome (Happle syndrome) is located in the human Xq28 region. To test this hypothesis, we performed a linkage study in three families comprising a total of 12 informative meioses. Multiple recombinations appear to exclude the Xq28 region as the site of the gene. Surprisingly, multiple crossovers were also found with 26 other markers spread along the rest of the X chromosome. Two-point linkage analysis and analysis of recombination chromosomes seem to exclude the gene from the entire X chromosome. Three different mechanisms are discussed that could explain the apparent exclusion of an X-linked gene from the X chromosome by linkage analysis: (a) different mutations on the X chromosome disturbing X inactivation, (b) metabolic interference, i.e. allele incompatibility of an X-linked gene, and (c) an unstable pre-mutation that can become silent in males. We favour the last explanation, as it would account for the unexpected sex ratio (M:F) of 1.2:1 among surviving siblings, and for the striking clinical variability of the phenotype, including stepwise increases in disease expression in successive generations.

Body Height↗
PubMed1992

Solvent damping of internal processes in myoglobin studied by specific heat spectroscopy and flash photolysis.

We address the question of dynamic coupling between protein and solvent by comparing the enthalpy relaxation of the solvent (75% v/v glycerol-water) to internal ligand binding in myoglobin. When the solvent relaxation is slow compared to intramolecular events we observe decoupling of protein motions from the solvent. In the opposite limit there is a significant contribution of the solvent to internal friction. The solvent enhances the apparent activation energy of transitions in myoglobin. This result is discussed in terms of a generalized Kramer's law involving a dynamic friction coefficient.

Animals↗
PubMed1992

Stimulation of testosterone production by atrial natriuretic peptide in isolated mouse Leydig cells results from a promiscuous activation of cyclic AMP-dependent protein kinase by cyclic GMP.

The aim of this study was to examine the possibility that atrial natriuretic peptide-stimulated testosterone production by mouse Leydig cells results from an activation of cAMP-dependent protein kinase (kinase A) by cGMP. In these cells, both 8Br-cGMP and 8Br-cAMP could stimulate testosterone production, though the latter was approximately 50-fold more potent. Following the stimulation of the cells with the atrial peptide, a dose-related decrease in the cellular protein-bound cAMP accompanied by a concomitant increase in the protein-bound cGMP was observed. The steroidogenesis stimulated by both human chorionic gonadotrophin (hCG) and atrial peptide was inhibited in a dose-dependent manner by a cAMP antagonist, adenosine 3',5'-cyclic monophosphothioate, Rp-isomer (RpcAMPS). In a cell-free [3H]cAMP binding assay, we have shown that unlabelled cGMP and RpcAMPS could competitively inhibit the [3H]cAMP binding, confirming that cAMP, RpcAMPS and cGMP could bind to the same binding protein. Finally, in a cell-free kinase A assay system, we have demonstrated that in lysates prepared from either atrial peptide or hCG-stimulated cells, the cellular kinase A was activated to an equal extent. We conclude from the data obtained that cGMP can bind to the cAMP-binding sites of kinase A and thereby brings about a promiscuous activation of this kinase. This appears to be an underlying mechanism by which atrial peptide hormone is able to stimulate the steroidogenesis in mouse Leydig cells.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Conserved outer membrane protein of Neisseria meningitidis involved in capsule expression.

In Neisseria meningitidis, translocation of capsular polysaccharides to the cell surface is mediated by a transport system that fits the characteristics of ABC (ATP-binding cassette) transporters. One protein of this transport system, termed CtrA, is located in the outer membrane. By use of a CtrA-specific monoclonal antibody, we could demonstrate that CtrA occurs exclusively in N. meningitidis and not in other pathogenic or nonpathogenic Neisseria species. Nucleotide sequence comparison of the ctrA gene from different meningococcal serogroups indicated that CtrA is strongly conserved in all meningococcal serogroups, independent of the chemical composition of the capsular polysaccharide. Secondary structure analysis revealed that CtrA is anchored in the outer membrane by eight membrane-spanning amphipathic beta strands, a structure of proteins that function as porins.

Amino Acid Sequence↗
PubMed1992

[Determination of exocrine pancreatic function in childhood with the pancreozymin-secretin test].

Pancreatic function can only be determined exactly via the pancreozymin-secretin test. We conducted this test in two versions: (1) under conditions of continuous perfusion with the possibility of volume correction and (2) as a simple tubing. We compared the results of 86 tubings with the results of 87 examinations under perfusion. For that purpose all patients were classified into four groups: group a) with 46 and 10 examinations, respectively, in patients suffering from cholestasis in early infancy, group b) with 7 and 12 examinations, respectively, in older patients with liver diseases, group c) with 8 and 17 examinations, respectively, in patients suffering from cystic fibrosis or Shwachman's syndrome and group d) with 25 and 48 examinations, respectively, in children with normal pancreatic function. Both examination methods nearly identical mean values of the enzyme activities in all four patient groups. However, mean variations were found to be higher in case of tubing. Therefore the lower limits (x - 2s) of this test were defined at a lower level than those of the tests under perfusion.

Amylases↗
PubMed1992

The therapy of benign myoclonic epilepsy in infants.

The authors report the results of treatment of 14 patients (10 male, 4 female, average age 20.3 years) with benign myoclonic epilepsy. Valproate monotherapy led to control of seizures in 10 cases, and to a distinct reduction of seizure frequency in 3 cases. Thrombocytopenia was the only side-effect encountered in this study.

Adolescent↗
PubMed1992

[Failure to thrive in young children--disorders of carbohydrate absorption?].

We examined 31 formerly hypotrophic newborn children (birth weight < 5th Kyank percentile) with failure to grow in infancy (weight < 3th Prader percentile). The rates of digestion and absorption of carbohydrates were determined by segmental perfusion of the small intestine and compared to the results of 21 patients with florid coeliac disease. Despite the normal structure of the mucous membrane of the small intestine, the rates of absorption of glucose in 14 formerly hypotrophic children and, additionally, in 12 and 10 of these children, respectively, the rates of hydrolysis of lactose and sucrose were nearly as low as in patients with florid coeliac disease. The reduced absorption and digestion of carbohydrates, respectively, could be a cause of subsequent failure to grow in some of the hypotrophic newborn children.

Celiac Disease↗
PubMed1992

[Left ventricular catheter ablation of the AV conduction system with radiofrequency electric current].

We report on a 32-year-old female patient with a history of recurrent atrial fibrillation and rapid ventricular response (up to 240 beats/min) resistant to multiple drug therapy. In this patient, we successfully performed a radiofrequency catheter ablation of the atrioventricular (AV) junction from the left ventricle, after radiofrequency energy application in His-position above the tricuspid valve was unsuccessful. This technique offers an-alternative treatment in patients in whom the conventional right-sided catheter ablation of the AV junction proves ineffective.

Adult↗
PubMed1991

Atrial natriuretic peptide (ANP) is a high-affinity substrate for rat insulin-degrading enzyme.

A cytosolic protein specifically binding to and degrading atrial natriuretic peptide (ANP) was purified from rat brain homogenate. Based on partial amino acid sequences and enzymatic properties, this protein with an apparent molecular mass of 112 kDa has been identified as the rat insulin-degrading enzyme (IDE). In addition to the known substrates, insulin and transforming-growth-factor alpha IDE binds also with high affinity (apparent Kd 60 nM) to ANP. Competition studies with structural variants of ANP demonstrate that both the C terminus and the disulfide loop of the molecule are essential for high-affinity binding. The data suggest that IDE might be involved in the cellular processing and/or metabolic clearance of ANP.

Affinity Labels↗
PubMed1991

[Thyroid abscess caused by Salmonella enteritidis].

A 70-year-old diabetic woman with a nodular goitre developed a swelling in the right neck, increasing over two weeks, as well as fever (38.2 degrees C), increased tendency towards sweating, finger tremors and pain on swallowing. Ultrasound examination of the thyroid raised the suspicion of an abscess, 3.5 x 1.5 cm, at the upper pole of the right thyroid lobe. Material obtained by fine-needle puncture grew Salmonella enteritidis. There have been no symptoms of gastroenteritis at any time. Stool and sputum cultures and nasopharyngeal swabs revealed the sites from which haematogenous spread had come. The abscess regressed (as monitored by ultrasound) within four weeks during intravenous treatment with 1,600 mg/d sulphamethoxazole and 320 mg/d trimethoprim (antibiotics determined by drug sensitivity tests) and after several ultrasound-directed needle punctures. Initially manifest hyperthyroidism (fT4: 3.4 ng/dl; basal TSH: 0.03 microU/l) regressed during the treatment without antithyroid treatment. The patient has been symptom-free for 6 months.

Abscess↗
PubMed1991

Lipid peroxidation in thioacetamide-induced macronodular rat liver cirrhosis.

Microsomes and isolated hepatocytes from thioacetamide (TAA)-induced macronodularly cirrhotic rat livers were analysed for their susceptibility to unstimulated and stimulated lipid peroxidation measured as malondialdehyde (MDA) formation. In microsomes from TAA-induced macronodularly cirrhotic livers the MDA production stimulated either by ascorbate-iron or by ADP-iron in a NADPH-regenerating system was decreased. Hepatic microsomes from TAA-treated rats exhibited a reduced cytochrome P450 content and lowered activities of ethylmorphine N-demethylase, ethoxycoumarin O-deethylase and epoxide hydrolase. Besides this, the microsomal fatty acid pattern of phosphatidylcholine and phosphatidylethanolamine was significantly changed after 6 months of TAA administration. The 18:2/20:4 ratio of phospholipid fatty acids was markedly increased. In contrast to the microsomes, in isolated hepatocytes from macronodularly cirrhotic livers the iron- and ascorbate-iron-stimulated MDA formation was increased. The hepatocellular GSH content was unaffected by TAA pretreatment, whereas the GSSG content exhibited a significant increase, thus leading to a pronounced reduction of the GSH/GSSG ratio. The calcium channel blocker verapamil (200 microM), known to be able to scavenge OH' radicals produced by the Fenton reaction, revealed an inhibitory effect on ascorbate-iron- and ADP-iron-stimulated lipid peroxidation in hepatocytes from normal as well as TAA-treated livers which is attributed to its antioxidative properties. In summary, lipid peroxidation is altered in TAA-induced macronodularly cirrhotic rat livers. Furthermore, the data clearly show that isolated microsomes and parenchymal cells prepared from cirrhotic livers react differently to prooxidant stimuli.

Animals↗