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Biomedical subjects

D Müller

Publications and source records attributed to D Müller.

At least 235 records · Page 13Linked to original sources
PubMed1993

Stimulation of bile flow and inhibition of biliary secretion of taurocholate and leukotriene C4 in thioacetamide-induced liver fibrosis.

In order to study the relation of hepatic fibrogenesis to biliary elimination, female Uje:WIST rats were treated with thioacetamide (TAA). This treatment results in single cell necrosis, fibrosis, nodular parenchyma und proliferation of bile ducts. In isolated perfused livers from pretreated rats, liver hemodynamics, bile flow, and secretion of taurocholate and leukotriene C4 were determined. After TAA-pretreatment, sinusoidal efflux of glucose and pyruvate was reduced increasing lactate/pyruvate ratio threefold. Biliary secretion of [14C]taurocholate and [3H]leukotriene C4 was lowered by 47% and 35%, respectively, compared to controls. In contrast, basal bile flow was increased after TAA-treatment. The beta-adrenergic agonist isoproterenol stimulated bile flow threefold over controls. The increased stimulation was correlated with increased liver weight after TAA-treatment. We postulate that both increased bile flow and stimulation by isoproterenol are due to proliferation of bile ducts and increased ductular bile secretion partially compensating for disturbed hepatocellular secretion.

Animals↗
PubMed1993

Cerebral amyloid angiopathy. Frequency, significance and immunohistochemistry.

For the assessment of the anatomical distribution of cerebral amyloid angiopathy (CAA) as well as that of amyloid plaques (AP), 955 post-mortem brain specimens from 653 patients (aged 14 to 95 years) were made available from a general hospital. Using histological and immunohistochemical techniques, we demonstrated amyloid angiopathy chiefly in the occipital, parietal and temporal regions. Senile plaques were mostly found in parietal, temporal and occipital areas. In our cases, neurofibrillary tangles were rarely prominent in the regions examined. There was often a significant difference in the frequency of amyloid angiopathy and of plaques in distinct areas between men and women. Congophilic angiopathy was associated with senile plaques in 82.3%, and neurofibrillary tangles with plaques in 76.9%. In comparison, the correlation of amyloid plaques with CAA (32.5%) and of plaques with neurofibrillary tangles (11.5%) was less pronounced. There was a strong association of cerebral vascular amyloid with age in both sexes, it was more pronounced in women than in men. Unexpectedly, CAA showed a decrease in frequency in men in the 7th and 8th decade of life. In addition, there was a positive correlation between the amount of CAA and spontaneous hemorrhages, but no correlation with ischemic encephalopathy. Immunohistochemistry showed that cerebral amyloid was neither amyloid of the AA- nor of the ATTR-(Antitransthyretin-, formerly anti-AF)-type. An antibody to the beta-protein (anti-A beta) showed cerebral vascular deposits to be congruent with the Congo red method, whereas senile plaques stained weakly and neurofibrillary tangles could not be stained at all with these antibodies.

Adolescent↗
PubMed1993

Reduced, positive nitrogen balance and elevated plasma free fatty acid concentration in growing, glutamate-induced obese rats.

Glutamate-induced obesity of Wistar-rats is known to develop under normophagic and normoinsulinemic conditions, although hyperphagia and hyperinsulinemia are common to obese individuals. Rats of this obesity model show retarded growth, reduced mass of some organs, carcass and whole body as well as an extraordinary high fat content, whereas protein content is reduced. In this study, nitrogen (N) balance, urinary excretion of urea-N, ammonia-N, creatine-N and alpha-amino acid-N and plasma free fatty acid concentration of growing, glutamate-induced obese rats were determined. The main results were independent of frame of reference (mmol N/kg body mass; mmol N/kg0.75 metabolic body mass; N in % of nitrogen intake): Nitrogen intake, urinary excretion of alpha-amino acids and nitrogen excretion in faeces were equal between lean and obese rats. Nitrogen excretion in urine was elevated in obese rats, mainly resulting from increased amounts of urea and ammonia. Nitrogen balance was positive in both groups, but reduced in obese rats. These data point to normal digestion of food proteins, but an unusual high oxidative desamination rate of the absorbed amino acids in obese rats. Taking into account the various hormonal and nerval alterations in glutamate-induced obese rats, resulting e.g. in increased hepatic insulin concentration, the retained amino acid carbon should be channelled into hepatic fatty acid synthesis. Really, unfasted and overnight fasted obese rats showed elevated plasma free fatty acid concentrations. Channeling of amino acids into lipogenesis may explain the low muscle mass and striking fat accumulation--despite normophagia and peripheral normoinsulinemia--of growing, glutamate-induced obese Wistar-rats.

Amino Acids↗
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↗