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R Schuster

Publications and source records attributed to R Schuster.

At least 55 records · Page 3Linked to original sources
PubMed1995

Use of mathematical models for predicting the metabolic effect of large-scale enzyme activity alterations. Application to enzyme deficiencies of red blood cells.

There are numerous examples showing that the metabolism of cells can be severely impaired if the activity of only one of the participating enzymes undergoes large-scale alterations, resulting, for example, from spontaneous mutations (inherited or acquired enzymopathies), the administration of toxic drugs or self-inactivation of enzymes during cell aging. However, a quantitative relationship between the degree of enzyme deficiency and the extent of metabolic dysfunction is very difficult to establish by experimental means. An alternative is to tackle this problem by mathematical modelling. Our approach is based on a comprehensive mathematical model of the energy and redox metabolism for human erythrocytes. We calculate stationary states of the cell metabolism, varying the activity of each of the participating enzymes by several orders of magnitude. The metabolic states are then evaluated in terms of a performance function which relates the metabolic variables to the overall functional fitness of the cell. The performance function for the erythrocyte takes into account the homeostasis of three essential metabolic variables: the energetic state (ATP), the reductive capacity (reduced glutathione), and the osmotic state. Based on the behaviour of the performance function at varying enzyme activities, we estimate those ranges of enzyme activities, in which the metabolic alterations should be either tolerable, associated with non-chronic or chronic diseases, or lethal. For most enzymopathies, the experimental and clinical observations can be satisfactorily rationalized by the computational results. Moreover, a surprisingly high correlation is found between the range of the activity range where disease is predicted by the model and the observed number of diseased probands. Another objective of our study was to contribute to the theory of metabolic control. The well-elaborated concept of the metabolic control theory is restricted to (infinitely) small activity alterations. In order to quantify the metabolic effect of finite (large-scale) changes in the activity of an enzyme, we propose, as a control measure, the effective activity E alpha, defined as the relative activity of an enzyme (with respect to the activity in a reference state) required to bring about a change in the stationary value of a metabolic variable by the (finite) factor alpha. We demonstrate that none of the existing extrapolation methods using the conventional control coefficient is capable to provide reliable predictions of the effective activities for all enzymes of erythrocyte metabolism.

Adenosine Triphosphate↗
PubMed1995

Evidence for lateral transfer and recombination in OspC variation in Lyme disease Borrelia.

The ospC gene was amplified by the polymerase chain reaction from each of 76 Lyme disease Borrelia strains. Restriction fragment length polymorphism (RFLP) analysis demonstrated 33 distinct RFLP types; two additional RFLP types were identified from published ospC sequences. For each RFLP type, at least one ospC gene was sequenced and the degree of sequence relatedness examined by construction of an ospC gene tree. The genes were extremely diverse, with sequence identity ranging from 74.4% to 99.0%; the majority of changes are localized within the central portion of the molecule. A comparison of ospC sequences suggests that recombination occurs frequently between ospC alleles; this genetic exchange is proposed to be mediated by lateral transfer of ospC sequences. Evidence indicates that recombination occurs between ospC genes from the same Borrelia species (i.e. B. afzelii and B. garinii) as well as between different Borrelia species (i.e. B. afzelii and B. garinii, B. burgdorferi and genogroup DN127).

Amino Acid Sequence↗
PubMed1994

Expression of the ligand-binding nicotinic acetylcholine receptor subunit D alpha 2 in the Drosophila central nervous system.

The D alpha 2 gene encodes a ligand-binding subunit of nicotinic acetylcholine receptors (nAChRs) from Drosophila melanogaster. We have studied the distribution of D alpha 2 transcripts and protein by in situ hybridization and immunohistochemistry, respectively, as well as the regulation of D alpha 2 gene expression in vivo using D alpha 2 promoter fragments fused to the Escherichia coli lacZ gene. Transcripts and protein from the D alpha 2 gene were detected exclusively in the central nervous system. Both in late embryos and adults D alpha 2-like immunoreactivity is widely but not uniformly distributed in the synaptic neuropil, suggesting that the D alpha 2 protein is a subunit of a synaptic nicotinic receptor. Its distribution resembles that of ALS and ARD proteins, two other nAChR subunits of the fly. Five different D alpha 2-lacZ fusion gene constructs were introduced into the Drosophila genome by P-element-mediated gene transfer to identity functional elements of the D alpha 2 promoter. All constructs produce a basic lacZ expression pattern that is compatible with the distribution of D alpha 2 transcripts and protein. A 880 bp upstream fragment harbors the cis elements for the expression of a weak but specific basic D alpha 2 pattern. The next 350 bp further upstream significantly enhance beta-galactosidase expression without influencing the pattern of expression. Between 1.7 and 7.3 kb upstream of the transcription start site one or more elements that are required for D alpha 2 expression in optic lobe tangential cells are located.

Animals↗
PubMed1993

Metabolic flux determination in C6 glioma cells using carbon-13 distribution upon [1-13C]glucose incubation.

A mathematical model of mammalian cell intermediary metabolism is presented. It describes the distribution of the carbon-13 isotope (13C) at the different carbon positions of metabolites in cells fed with 13C-enriched substrates. The model allows the determination of fluxes through different metabolic pathways from 13C- and 1H-NMR spectroscopy and mass spectrometry data. The considered metabolic network includes glycolysis, gluconeogenesis, the citric acid cycle and a number of reactions corresponding to protein or fatty acid metabolism. The model was used for calculating metabolic fluxes in a rat tumor cell line, the C6 glioma, incubated with [1-13C]glucose. After evolution to metabolic and isotopic steady states, the intracellular metabolites were extracted with perchloric acid. The specific enrichments of glutamate, aspartate and alanine carbons were determined from 13C-, 1H-NMR spectroscopy, or mass spectrometry data. Taking into account the rate of glucose consumption and of lactate formation, determined from the evolution of glucose and lactate contents in the cell medium, and knowing the activity of the hexose monophosphate shunt, it was possible to estimate the absolute values of all the considered fluxes. From the analysis the following results were obtained. (a) Glucose accounts for about 78% of the pyruvate and 57% of the CoASAc. (b) A metabolic channelling occurs at the citric acid cycle level; it favours the conversion of carbons 2, 3, 4, and 5 of 2-oxoglutarate into carbons 1, 2, 3, and 4 of oxaloacetate, respectively. The percentage of channelled metabolites amounts to 39%. (c) The pyruvate carboxylase activity and the efflux from the citric acid cycle are estimated to be very low, suggesting a lack of glutamine production in C6 cells. The results emphasize different metabolic characteristics of C6 cells when compared to astrocytes, their normal counterpart.

Alanine↗
PubMed1993

Immunohistochemical localization of a ligand-binding and a structural subunit of nicotinic acetylcholine receptors in the central nervous system of Drosophila melanogaster.

The distribution of two subunits of nicotinic acetylcholine receptors in the developing and the differentiated central nervous system of Drosophila melanogaster was studied. With subunit-specific antibodies raised against the ligand-binding alpha-like subunit ALS and the putative non-ligand-binding subunit ARD, we find both ALS-like and ARD-like immunoreactivity widely distributed in most neuropiles of the optic lobes, the protocerebrum, the deutocerebrum and the thoracic ganglion of the adult fly. With a single exception, namely in the lamina of the visual system, the antigens recognized by the two types of antibodies are colocalized. This observation is consistent with previous immunoprecipitation data indicating that the ALS and ARD proteins are integral components of the same hetero-oligomeric receptor that binds the nicotinic antagonist alpha-bungarotoxin with high affinity. During embryonic development ARD-like immunoreactivity is first detectable in approximately 10 hour old embryos. Both subunits are consistently detected in the central nervous system of the late embryo, the three larval stages, and all prepupal and pupal stages. During metamorphosis the optic stalk is transiently immunoreactive with anti-ARD, but not with anti-ALS antiserum. Although in larvae and adults, immunoreactivity with both types of antibodies is most abundant in synaptic regions, in embryos and pupae strong staining of cortical cell body layers is observed, in particular with anti-ARD antisera. As these developmental periods coincide with strong accumulation of ARD transcripts, the cell body staining may reflect newly synthesized and assembled receptors, while the functional ARD- and ALS-containing receptor may be destined for synapses.

Acetylcholine↗
PubMed1993

Infection patterns in the first intermediate host of Dicrocoelium dendriticum.

In order to establish the infection patterns in the first intermediate host of Dicrocoelium dendriticum, investigations were carried out on sheep pastures situated in the eastern part of Brandenburg, Germany, during the grazing periods in 1986, 1987, 1989 and 1990. It was found that the majority of specimens of the first intermediate host, Helicella obvia, become infected in the autumn of their second year of life, when their shell diameter is of medium size. The percentage of snails containing daughter sporocysts was highest in spring. Slimeball output could be provoked only in May and June.

Animals↗
PubMed1993

Refined algorithm and computer program for calculating all non-negative fluxes admissible in steady states of biochemical reaction systems with or without some flux rates fixed.

A refined algorithm together with a computer procedure for determining the complete set of non-negative, steady-state fluxes in biochemical reaction systems of any complexity, with or without some flux rates fixed, is given. It is shown that this set is a convex polyhedron, which may or may not be bounde. The algorithm is illustrated by several examples; one of them concerns intermediary metabolism. A computer code in standard C is presented.

Algorithms↗
PubMed1993

Giant lipomas of the hand and forearm.

Giant lipomas of the upper extremity are infrequently reported. They can alter function by restricting motion or producing compressive neuropathies. This report of four cases of giant lipoma in the hand and forearm illustrates these functional losses. The role of MRI and CT in preoperative evaluation of these lesions is discussed and a report of an anterior interosseous syndrome caused by a giant lipoma is presented.

Adult↗