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S Müller

Publications and source records attributed to S Müller.

At least 55 records · Page 3Linked to original sources
PubMed2004

Affinity of single S. cerevisiae cells to 2-NBDglucose under changing substrate concentrations.

BACKGROUND: Saccharomyces cerevisiae is a widely employed microorganism in biotechnological processes. Since proliferation and product formation depend on the capacity of the cell to access and metabolize a carbon source, a technique was developed to enable for analyzing the S. cerevisiae H155 cells' affinity to extracellular glucose concentrations. METHODS: The fluorescent glucose analogue 2-NBDglucose was employed as a functional parameter to analyze the cells' affinity to glucose. Structural parameters (proliferation, neutral lipid content, granularity, and cell size) were also investigated. Cells were grown both in batches and in chemostat regimes. RESULTS: The 2-NBDglucose uptake in individual cells proceeds in a time- and concentration-dependent manner and is affected by respiratory and respirofermentative modes of growth. The process is inhibited by D-glucose, D-fructose, D-mannose, and sucrose, but not L-glucose, D-galactose or lactose; maltose is a weak inhibitor. The affinity of the individual cells to 2-NBDglucose was found to be high at low extracellular glucose concentrations, and weak at high concentrations. An additional, underlying pattern in the cells' affinity to glucose was detected, illustrated by the recurrent appearance of two subpopulations showing distinctly differing quantities of this substrate. CONCLUSIONS: A multiparameter flow cytometry approach is presented that enables, for the first time, for analysis of the affinity of individual S. cerevisiae cells to glucose. Besides the adjustment of the yeast cell metabolism to extracellular glucose concentrations by altering their affinity to glucose, at least one further mechanism is clearly involved. Two subpopulations of cells were resolved, with different affinities not correlated with other cellular parameters measured.

4-Chloro-7-nitrobenzofurazan↗
PubMed2004

[Principles of PET/CT and clinical application].

Medicine today imposes high demands on diagnosing disease. Techniques should be preferably noninvasive, identify the disease at an early stage, and be quick and accurate. Frequently, these demands can only be met by employing various diagnostic modalities. Consequently, the integration of two imaging modalities, such as the combination of PET and CT, increases the quality of coregistration and facilitates a timely diagnosis. However, complex imaging procedures require a judicious choice of the areas of application. If, for example, both PET and CT are indicated then a combined PET/CT exam results in improved diagnosis, whereby the actual benefit will depend upon the clinical problem. Typically we expect an advantage of 10% with PET/CT compared to separate examinations with CT and PET. In addition, PET/CT allows for new indications and applications, which cannot be performed satisfactorily with independent examinations and retrospective image alignment. One example is the application of PET/CT in radiation therapy planning.

Artifacts↗
PubMed2004

Mechanical and optical characteristics of a new fiber optical system used for cardiac contraction measurement.

In order to obtain a better physiological performance and a closer restoration of the regular rhythm of failing hearts, a new fiber optical sensor system for the measurement of cardiac contraction has been developed. It consists of an opto-electrical unit and a sensing fiber which has to be positioned in the heart. The objective of this new fiber optic sensor system is to use the inotropic information to adjust a stimulation algorithm in single or multichamber pacing or to detect arrhythmia in insufficient heart function. In this study, the mechanical and optical characteristics of different fibers are investigated. The relationship between the attenuation (with an achieved numerical maximum of 0.3 dB), the bending diameter and the angle of bending is determined in a range of 20-160 mm. The most suitable fiber for the application in cardiological problems is determined (WT8 fiber), for which the sensitivity is analyzed. Additionally, power spectra are calculated from WT8 fiber signals obtained from pig hearts, working under physiological conditions. The maximal frequency response was 23 Hz. It is concluded that the fiber optical measurement of cardiac contraction is not only feasible and reproducible, but the WT8 fiber also shows optimal behavior in the range of parameters occurring in the heart chambers. Nevertheless, in order to restrict the measured signal reliably to bending processes within the chambers only, it is concluded that a special combined fiber has to be constructed with a high sensitivity only at its terminal section within the heart.

Algorithms↗
PubMed2004

Natural variation in the response of Caenorhabditis elegans towards Bacillus thuringiensis.

Almost nothing is known about the natural ecology of the nematode Caenorhabditis elegans, including its interactions with parasites. To help rectify this discrepancy, we assessed natural variation in the response of C. elegans towards a potential parasite, the soil bacterium Bacillus thuringiensis. Our results show that 10 isolates from across the world differ significantly in survival rate and infection level when confronted with a parasitic strain of B. thuringiensis. Furthermore, behavioural responses are identified as an important component of C. elegans defence, including evasion and possibly reduced ingestion of parasites. Again, the natural isolates show significant differences in these traits. In conclusion, worm defence is indicated to be complex and variable across space, implying that parasites play an important role in the ecology of this species. Based on these results, we expect C. elegans to be a promising model host for future analysis of the evolutionary dynamics of parasite-host interactions.

Animals↗
PubMed2004

Gene expression patterns of epithelial cells modulated by pathogenicity factors of Yersinia enterocolitica.

Epithelial cells express genes whose products signal the presence of pathogenic microorganisms to the immune system. Pathogenicity factors of enteric bacteria modulate host cell gene expression. Using microarray technology we have profiled epithelial cell gene expression upon interaction with Yersinia enterocolitica. Yersinia enterocolitica wild-type and isogenic mutant strains were used to identify host genes modulated by invasin protein (Inv), which is involved in enteroinvasion, and Yersinia outer protein P (YopP) which inhibits innate immune responses. Among 22 283 probesets (14,239 unique genes), we found 193 probesets (165 genes) to be regulated by Yersinia infection. The majority of these genes were induced by Inv, whose recognition leads to expression of NF-kappa B-regulated factors such as cytokines and adhesion molecules. Yersinia virulence plasmid (pYV)-encoded factors counter regulated Inv-induced gene expression. Thus, YopP repressed Inv-induced NF-kappa B regulated genes at 2 h post infection whereas other pYV-encoded factors repressed host cell genes at 4 and 8 h post infection. Chromosomally encoded factors of Yersinia, other than Inv, induced expression of genes known to be induced by TGF-beta receptor signalling. These genes were also repressed by pYV-encoded factors. Only a few host genes were exclusively induced by pYV-encoded factors. We hypothesize that some of these genes may contribute to pYV-mediated silencing of host cells. In conclusion, the data demonstrates that epithelial cells express a limited number of genes upon interaction with enteric Yersinia. Both Inv and YopP appear to modulate gene expression in order to subvert epithelial cell functions involved in innate immunity.

Adhesins, Bacterial↗
PubMed2004

Regulated expression and subcellular localization of HMGB1, a chromatin protein with a cytokine function.

High mobility group box protein 1 (HMGB1) has been considered as a ubiquitous nuclear protein with an architectural function, but even early reports have described its presence outside of the nucleus. Today, we have only started to understand the extranuclear and extracellular functions of HMGB1: we know that it participates in developmental and differentiation processes, triggers and modulates many of the inflammatory cascades in the body, and may even be involved in the metastatic invasion programme of cancer cells. Given such diverse roles, it is important to know which cells express HMGB1, where, and how much. The present review deals with the expression pattern of HMGB1 and provides evidence that, far from being housekeeping, the HMGB1 gene is tightly regulated. This can have implications for therapeutic intervention on inflammatory diseases as well as cancer.

Apoptosis↗
PubMed2004

A fiberoptic sensor system for cardiac monitoring and electrotherapy.

Commercially available cardiac pacemakers and implantable cardioverters/defibrillators (ICD) predominantly use the intracardiac derived electrocardiogram (ECG) for detection of arrhythmias. To achieve an automatic control of the heart frequency in accordance with cardiovascular strain and an improved detection of life-threatening arrhythmias, it is desirable to monitor the heart by an input signal correlated with the hemodynamic state. One possible approach to derive such a signal, is to measure the inotropy (mechanical contraction strength of the heart muscle). For this purpose an optoelectronic measurement system has been designed. The fundamental function of the system has been shown in earlier investigations using an isolated beating pig heart. In this paper further results showing the correlation of the fiberoptic sensor signal with the left ventricular stroke volume are presented. To make the system useful for implantable devices, further improvements with regard to power consumption and signal quality were achieved.

Animals↗
PubMed2003

[Histopathological diagnosis of Barrett's mucosa and associated neoplasias. Results of a consensus conference of the Working Group for "Gastroenterological Pathology of the German Society for Pathology" on 22 September 2001].

There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was therefore the aim of a consensus conference of the "Working Group for Gastroenterological Pathology within the German Society of Pathology" to achieve standardization regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular biological methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.

Barrett Esophagus↗
PubMed2003

PIAS/SUMO: new partners in transcriptional regulation.

Protein inhibitor of activated STATs (PIAS) proteins were initially identified as negative regulators of cytokine signalling that inhibit the activity of STAT-transcription factors. Evidence is accumulating that PIAS proteins function as transcriptional coregulators in various other important cellular pathways, including Wnt signalling, the p53 pathway and steroid hormone signalling. Most interestingly, recent work from several laboratories revealed that PIAS proteins act as E3-like ligases that stimulate the attachment of the ubiquitin-like SUMO modifier to target proteins acting in these pathways. Since in most cases the SUMO ligase activity and the transcriptional coregulator activity are functionally correlated, the PIAS/SUMO pathway appears to be an important mechanism of transcriptional regulation. In this review we will discuss some key findings that exemplify the role of PIAS proteins in the regulation of transcriptional processes and propose a model how the PIAS/ SUMO system may modulate transcriptional activities by mediating the assembly of coactivator or corepressor complexes within distinct subnuclear structures.

Animals↗
PubMed2003

Analysis of bacterial DNA patterns--an approach for controlling biotechnological processes.

Optimisation of biotechnological processes catalysed by microbial cells requires detailed information about operational limits of the single cells. Their performance is correlated with distinct physiological states. We related these states to cell cycle events, which were found to proceed extremely diversely in different bacterial strains. Characteristic DNA patterns were found flow cytometrically, depending on the type of strain, substrates and growth conditions involved; this information can be used for the development of control strategies of bioprocesses, although some skill is required. Four bacterial strains (the Gram-negative strains Acinetobacter calcoaceticus 69-V, Ralstonia eutropha JMP 134, Ochrobactrum anthropi K2-14 and the Gram-positive strain Rhodococcus erythropolis K2-3) were grown in mono- and mixed cultures on different substrates, and analysed regarding their proliferation behaviour. The resulting DNA distribution patterns provided three types of valuable information. First, correlation of proliferation activity with the appearance of a major part of cells within the C(2) stage of the cell cycle is a strain-specific feature. Second, bacteria usually maintain more than one chromosome under limiting growth conditions: DNA replication is completed in such cases, but cell division fails. Third, high growth rates are associated with uncoupled DNA synthesis. Its general initiation might be genetically determined in the first place, but it is promoted by optimal growth conditions and the presence of substrates that can be metabolised at high rates, thereby allowing substantial amounts of carbon, other nutrients and energy to be used exclusively for DNA synthesis.

Biotechnology↗
PubMed2003

MTS-conjugated-antiactive caspase 3 antibodies inhibit actinomycin D-induced apoptosis.

Caspase 3 is critically involved in the pathway of apoptosis. We have conjugated a MTS-transport-peptide to monoclonal and polyclonal anti-caspase-3 antibodies to suppress Actinomycin D-induced apoptosis in human lymphoma T cells. The advantage of using trans-membrane antibodies compared to conventional apoptosis inhibitors is their specific target recognition in the living cell and their lower toxicity compared to conventional apoptosis inhibitors. We could show that a MTS-transport-peptide modified monoclonal anti-caspase-3 antibody reduces Actinomycin D induced apoptosis, as shown by DNA ladder electrophoresis and cell death ELISA. These results indicate that antibodies have a therapeutic potential to inhibit apoptosis in a variety of diseases.

Antibodies↗
PubMed2002

Segregation in strongly ordering compounds: a key role of constitutional defects.

For the example of the B2 CoAl(100) surface, we demonstrate that even slight deviations from an ordered alloy's ideal stoichiometry in a subsurface region or in the bulk can drastically affect its surface composition. By experimental surface analysis and first-principles calculations, we show that Co antisite atoms segregate to the very surface, driven by the same strong interactions which enforce order in the bulk. Our findings are consistent with the lack of antisite segregation we found earlier for the much weaker ordering FeAl(100), and resolve contradictory reports for NiAl(100).

Journal Article↗
PubMed2002

Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors.

AIMS/HYPOTHESIS: A population-based sample was studied to define immune abnormalities in individuals at risk of Type II (non-insulin-dependent) diabetes mellitus because of impaired glucose tolerance. METHODS: A total of 1653 individuals aged 55 to 74 years participated in a population based survey in Southern Germany (KORA Survey 2000). Those without a history of diabetes were subjected to an OGTT. Randomly selected subjects with IGT ( n=80) were compared with non-diabetic control subjects ( n=77) and patients with Type II diabetes ( n=152) of the same population-based sample after matching for age and sex. Immune parameters were analysed in serum with rigidly evaluated ELISA. RESULTS: Serum pro-inflammatory cytokine interleukin 6 (IL-6) concentrations were higher in subjects with IGT and Type II diabetes than in the control subjects (median 1.8 and 2.5 vs 0.8 pg/ml, p<0.0001). Soluble IL-6 receptors potentiate IL-6 bioactivity and their concentrations were mildly increased in Type II diabetes ( p<0.05). These immune changes seem relevant because IL-6 dependent acute-phase proteins C-reactive protein, serum amyloid A protein and fibrinogen were also increased in IGT and Type II diabetes. Circulating concentrations of TNF-alpha and its two receptors sTNF-R60 and sTNF-R80 were not increased in IGT subjects compared with the control subjects. CONCLUSION/INTERPRETATION: Our study shows systemic up-regulation of selected inflammatory mediators in patients with Type II diabetes and IGT. The pattern observed is non-random and fits with an IL-6 associated rather than TNF-alpha associated response.

Acute-Phase Proteins↗
PubMed2002

Iron content in musculus longissimus lumborum et thoracis (m.l.l.t.) of fattening pigs.

Pork is among the most essential dietary sources of iron in Germany, considering its beneficial absorption rate. During 1997 and 1998 meat samples from 52 pigs per year were collected at the Thuringian performance testing station in order to examine the total iron content of pork. Musculus longissismus lumborum et thoracis (13./14. thoracic vertebra) from the right side of the carcasses were prepared for analyses. The total iron content was measured by atomic emission spectroscopy with inductively coupled plasma. The iron content of the meat was 4.18 +/- 0.97 mg/kg fresh material. This result was significantly lower than corresponding data from literature. An influence of the genetic composition of the pigs examined on the total iron content could be observed. The daily gain (R = -0.26) and intramuscular fat content (R = -0.28) were inversely correlated to the iron content. However, the lean meat proportion (R = 0.26) as well as haem pigment content (R = 0.27) were directly correlated to the total iron content of the meat.

Animals↗
PubMed2002

Initial results in the assessment of multiple myeloma using 18F-FDG PET.

This prospective study was undertaken to investigate the appearance of multiple myeloma on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET). Furthermore, the accuracy of FDG-PET in detecting myeloma lesions and its influence on patient management were evaluated. Forty-three patients with known multiple myeloma (n=28) or solitary plasmacytoma (n=15) underwent FDG-PET. The results of routinely performed radiographs and of scans obtained using all available imaging modalities (MRI, CT), as well as the clinical course, were used for verification of detected lesions. Focally increased tracer uptake was observed in 38 of 41 known osteolytic bone lesions (sensitivity 92.7%) in 23 patients. In addition, 71 further bone lesions which were negative on radiographs were detected in 14 patients. Twenty-six (36.6%) of these lesions could be confirmed in ten patients. As a result of FDG-PET imaging, clinical management was influenced in five (14.0%) patients. The positive predictive value for active disease was 100% in patients with focal or mixed focal/diffuse skeletal FDG uptake and 75% in patients with diffuse bone marrow uptake. Depending on the interpretation of the PET scans in patients with diffuse bone marrow uptake, the sensitivity ranged from 83.8% to 91.9% and the specificity from 83.3% to 100%. FDG-PET thus proved highly accurate in detecting multiple myeloma, and revealed a greater extent of disease than routine radiographs in 14 of 23 (60.9%) patients who had osteolytic bone lesions. FDG-PET might contribute to the initial staging of solitary plasmacytoma.

Adult↗
PubMed2002

Recent advances in the search for new anti-coccidial drugs.

Coccidia provide a rich hunting ground for drug-designers, as there are significant biochemical differences between the parasites and their hosts. Recent years have brought the discovery of the plastid and its possible metabolic machinery, characterisation of acidocalcisomes, reports on the apparent absence from some coccidia of a typical mitochondrion, and the discovery of the mannitol cycle and shikimate pathway in the parasites. Moreover, modern technologies such as genomics and proteomics are bringing new insights into the biochemistry of coccidia and highlighting possible drug targets in abundance. A major issue for would-be drug discoverers is to decide upon the targets to prioritise. This review provides an update on recent findings on how coccidia differ biochemically from vertebrates. It includes discoveries within coccidian parasites themselves but also uses findings in Plasmodium to provide an overview of biochemical features that may be characteristics of many apicomplexan parasites and so potential targets for broad-spectrum drugs.

Animals↗
PubMed2002

Side differences of knee joint cartilage volume, thickness, and surface area, and correlation with lower limb dominance--an MRI-based study.

OBJECTIVE: To test the hypotheses that absolute side differences in knee joint cartilage morphology are substantially smaller than intersubject variability, and that systematic side differences are determined by (force) dominance of the lower limbs. METHODS: Fifteen healthy volunteers with definite dominance of one lower limb were studied. Knees were imaged sagittally with a validated, high-resolution MR sequence. Transverse MR images of the thigh and calf were acquired with a spin echo sequence. Knee joint cartilage volume, thickness and joint surface areas, as well as muscle cross sectional areas were determined with in house post-processing software. RESULTS: Absolute side differences amounted to 5.0+/-3.7% for the knee cartilage volume, 3.8+/-3.1% for cartilage thickness, and 3.4+/-1.7% for joint surface areas. The intersubject variability was 24.8%, 14.4%, and 14.1%, respectively. Volunteers with dominance of one of both lower limbs did not display significant side differences in cartilage morphology, but the side differences of the thigh musculature correlated positively with side differences of knee joint cartilage volume (r=+0.68; P< 0.01). CONCLUSIONS: The results advocate the use of cartilage parameters from the contra-lateral limb for retrospectively estimating cartilage loss in patients with unilateral osteoarthritis (OA), and for determining local risk factors of OA in cross-sectional epidemiological studies, which are specific to pre-morbid cartilage morphology. Functional (force) dominance of one of both lower limbs does not explain side differences of articular cartilage morphology, but side differences are positively associated with side differences in muscle cross sectional areas.

Adult↗