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Biomedical subjects

M Beyer

Publications and source records attributed to M Beyer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Dual effect of glucocorticoids on apoptosis of human autoreactive and foreign antigen-specific T cells.

The efficacy of glucocorticoids in the treatment of multiple sclerosis may involve the induction of T cell apoptosis. Here, we report that glucocorticoids have two different effects on the vulnerability of human antigen-specific T cells: (i) steroids induce T cell apoptosis in a CD95-independent, but caspase-dependent manner; (ii) steroids protect T cells from CD95-mediated apoptosis which, however, is also caspase-dependent. An increase in BCL-2 expression is observed upon incubation with steroids. Thus, inhibition of CD95-mediated T cell apoptosis may be an undesirable side-effect resulting in survival of activated T cells and the maintenance of pathogenic immune responses might explain the lack of long-term glucocorticoid therapy.

Apoptosis↗
PubMed2000

No induction of apoptosis by IFN-beta in human antigen-specific T cells.

Interferon (IFN)-beta, the most effective immunomodulatory treatment for MS, inhibits the proliferation of myelin-specific T cells. We report that IFN-beta moderately enhances the expression of the death receptor, CD95, at the surface of human antigen-specific T cells. However, T-cell apoptosis was not induced by IFNbeta-1a or IFNbeta-1b as assessed by caspase activity or DNA fragmentation. Immunomodulation mediated by IFN-beta does not directly involve apoptotic pathways in human T cells.

Adjuvants, Immunologic↗
PubMed2000

Phagocytosis of neuronal or glial debris by microglial cells: upregulation of MHC class II expression and multinuclear giant cell formation in vitro.

Most CNS pathologies are accompanied by the occurrence of activated, phagocytic microglial cells. We intended to investigate whether (1) isolated microglial cells removed from the CNS cytokine network sustain their capacity to acquire an activated phenotype when challenged with cellular or noncellular debris; and (2) different substrates lead to different patterns of microglial activation. It was observed that although removed from their usual surroundings microglial cells preserve their ability to transform to an amoeboid morphology, form multinucleated giant cells, and enhance their expression of MHC class II when exposed to membranes of neuronal or glial origin. Furthermore, cellular substrates derived from primary hippocampal neuronal cultures, neuroblastic cells (B50), or glial cells were all able to induce similar morphological changes and enhanced expression of MHC class II. In contrast, phagocytosis of Latex beads induced an amoeboid morphology but no increase in the expression of immunologically relevant molecules. Interferon-beta (IFN-beta), a substance clinically used in the treatment of the relapsing-remitting form of multiple sclerosis, was shown to inhibit the phagocytosis-induced upregulation of MHC-class II. In summary, phagocytic microglial cells are independent from the CNS cytokine network in their transition from a resting to an activated phenotype; and different cellular substrates, regardless whether they are of neuronal, glial, or even malignant origin, result in similar morphological and functional changes.

Animals↗
PubMed2000

On-line and off-line monitoring of the production of cephalosporin C by Acremonium chrysogenum.

Process monitoring of cephalosporin C formation by Acremonium chrysogenum in laboratory investigations is considered. The goal of these investigations is the identification of bottlenecks in the biosynthesis and the improvement of the process performance. Based on reports of other research groups and own experience the key parameters were selected, which influence the process performance. They are: dissolved oxygen and pH values. In addition the concentrations of biomass, DNA, glucose and reducing sugars (glucose, maltose, maltotriose and oligosaccharides), methionine, other nitrogen sources (ammonium ion, other amino acids), organic acids, phosphate, sulfate, dissolved organic carbon, proteins, product and precursors in the cell free cultivation medium are monitored. In addition the intracellular concentrations of RNA, DNA, proteins, amino acids as well as the activities of the enzymes of the biosynthesis of cephalosporin C are determined. The influence of these parameters on the biosynthesis is discussed.

Acremonium↗
PubMed2000

Glucoamylase production in batch, chemostat and fed-batch cultivations by an industrial strain of Aspergillus niger.

The Aspergillus niger strain BO-1 was grown in batch, continuous (chemostat) and fed-batch cultivations in order to study the production of the extracellular enzyme glucoamylase under different growth conditions. In the pH range 2.5-6.0, the specific glucoamylase productivity and the specific growth rate of the fungus were independent of pH when grown in batch cultivations. The specific glucoamylase productivity increased linearly with the specific growth rate in the range 0-0.1 h(-1) and was constant in the range 0.1-0.2 h(-1). Maltose and maltodextrin were non-inducing carbon sources compared to glucose, and the maximum specific growth rate was 0.19 +/- 0.02 h(-1) irrespective of whether glucose or maltose was the carbon source. In fed-batch cultivations, glucoamylase titres of up to 6.5 g l(-1) were obtained even though the strain contained only one copy of the glaA gene.

Aspergillus niger↗
PubMed2000

Three-dimensional organization of vestibular related eye movements to rotational motion in pigeons.

During rotational motions, compensatory eye movement adjustments must continually occur in order to maintain objects of visual interest as stable images on the retina. In the present study, the three-dimensional organization of the vestibulo-ocular reflex in pigeons was quantitatively examined. Rotations about different head axes produced horizontal, vertical, and torsional eye movements, whose component magnitude was dependent upon the cosine of the stimulus axis relative to the animal's visual axis. Thus, the three-dimensional organization of the VOR in pigeons appears to be compensatory for any direction of head rotation. Frequency responses of the horizontal, vertical, and torsional slow phase components exhibited high pass filter properties with dominant time constants of approximately 3 s.

Animals↗
PubMed2000

Routine DNA cytometry of benign and malignant pleural effusions by means of the remote quantitation server Euroquant: a prospective study.

AIM: To analyse the practicability and potential assistance of static DNA cytometry performed by means of the remote quantitation server Euroquant and the internet in routine diagnostic analysis of pleural effusions, and to outline the role of DNA cytometry on pleural effusions in distinguishing between benign and malignant (and herein primary versus metastatic) effusions. MATERIALS AND METHODS: Cytological smears of 294 pleural effusions were stained with the Feulgen method. The DNA content of a minimum of 300 randomly chosen analysis nuclei and 30 reference nuclei (lymphocytes) was measured by internet connection to the remote quantitation server Euroquant. Cytometric features were derived from the histograms, and the time needed for case evaluation, the reliability of staining and measurement procedures, and the contribution to the final diagnosis were evaluated. RESULTS: Only 120 of 294 pleural effusions could be measured. The total measurement time for each specimen was 60 minutes. The guidelines of the consensus report on DNA measurements were fulfilled. Seventy eight malignant (18 mesotheliomas, 60 metastatic tumours) and 42 benign effusions were measured. Seven of 78 malignant effusions were euploid and none of 42 benign effusions were aneuploid. The sensitivity and specificity were 91% and 100%, respectively, for distinguishing benign from malignant effusions, and 95% and 100%, respectively, for discriminating between benign and malignant effusions caused by metastatic malignant tumours. CONCLUSIONS: Static DNA cytometry using the remote quantitation server Euroquant can be performed reliably in the routine diagnosis of pleural effusions; however, only 40% of effusions meet the technical requirements for static DNA cytometry. Within the measurable cases, static DNA cytometry made an important contribution to the confirmation/exclusion of malignancy.

Aged↗
PubMed2000

CT and arteriography in the evaluation of indirect myocardial revascularization with a free-muscle transplant: initial experience.

PURPOSE: To examine patients with advanced cardiovascular disease with radiology after indirect myocardial revascularization with a free-skeletal-muscle transplant and to determine whether the attached vessel remains patent over the middle and long terms. MATERIALS AND METHODS: In 10 patients with advanced, inoperable cardiovascular disease treated with indirect myocardial revascularization with a free-muscle transplant, radiologic follow-up was performed postoperatively and every 6 months. All 10 patients underwent selective arteriography of the anastomosed vessel and contrast material-enhanced helical computed tomography (CT) (transverse sections and reconstructions). RESULTS: All patients showed adequate vascular conditions postoperatively, as did nine of 10 patients after 1 year. In one patient, the anastomosed artery was occluded. CT showed time-dependent muscle degeneration in all patients. Postoperative, contrast-enhanced, superselective CT showed an area of high-attenuating uptake in the muscle transplant in all patients. After 1 year, CT depicted perfusion defects of the skeletal muscle in two patients. In eight patients, however, small vascular bridges from the skeletal muscle to the myocardium were detected. Radiologic results correlated well with clinical outcome and stress electrocardiograms. CONCLUSION: Helical intraarterial CT and arteriography were sensitive in depicting enhancement and remaining vital function in nine of 10 patients after indirect myocardial revascularization with a free-muscle transplant. This combination seems promising for postoperative examination in such patients.

Aged↗
PubMed2000

Recent developments and present status of telepathology.

Telepathology which is the diagnostic work of a pathologist at a distance has been developed to routine application within the last ten years. It can be classified in relation to application, technical solutions, or performance conditions. Diagnostic pathology performance distinguishes primary diagnosis (for example, frozen section statement) from secondary diagnosis (for example, expert consultation) and quality assurance (diagnostic accuracy, continuous education and training). Applications comprise (a) frozen section service; (b) expert consultations; (c) remote control measurements; and (d) education and training. The technical solutions distinguish active (remote control, live imaging) systems from passive (conventional microscope handling, static imaging), and the performance systems with interactive (on-line, live imaging) use from those with passive (offline, static imaging) practice. Intra-operative frozen section service is mainly performed with remote control systems; whereas expert consultations and education/training are commonly based upon Internet connections with static imaging in an off-line mode. The image quality, transfer rates, and screen resolution of active and passive telepathology systems are sufficient for an additional or primary judgment of histological slides and cytological smears. From the technical point of view, remote control telepathology requires a fast transfer and at least near on-line judgement of images, i.e., image acquisition, transfer and presentation can be considered one performance function. Thus, image size, line transfer rate and screen resolution define the practicability of the system. In expert consultation, the pixel resolution of images and natural color presentation are the main factors for diagnostic support, whereas the line transfer rate is of minor importance. These conditions define the technical compartments, especially size and resolution of camera and screen. The performance of commercially available systems has reached a high quality standard. Pathologists can be trained in a short time and use the systems in a routine manner. Several telepathology systems have been implemented in large Institutes of Pathology which serve for frozen section diagnosis in small hospitals located in the local area. In contrast, expert consultation is mainly performed with international connections. There is a remarkable increase of expert consultations by telepathology according to the experiences of the Armed Forces Institute of Pathology or the Department of Pathology, Thoraxklinik, Heidelberg. In expansion of these experiences, a "globalization" of telepathology can be expected. Telepathology can be used to shrink the period necessary for final diagnosis by request for diagnostic assistance to colleagues working in appropriate related time zones. Telepathology is, therefore, not a substitute of conventional diagnostic procedures but a real improvement in the world of pathology.

Europe↗
PubMed2000

Telecommunication--a new tool for quality assurance and control in diagnostic pathology.

Telepathology is the diagnostic work of a pathologist at a distance. It includes specific application fields which require specific system solutions. These comprise: a. frozen section service; b. expert consultations; c. remote control measurements, and d. education and training. Applications but, in addition, all aspects of diagnosis, especially those involved in the daily work flow of a pathologist. The image quality, transfer rates, and screen resolution of telepathology systems are sufficient for an additional or primary judgment of histological slides and cytological smears. It is, therefore, possible to include this technique into intralaboratory quality control of all steps of diagnostic procedures and to use this technique for quality assurance and control. Diagnostic quality is not a well defined term, and depends, in addition to external circumstances, on the diagnosis itself. The diagnostic quality can be maintained or even improved by use of telepathology systems. They can serve for control of image quality, access to various information sources, simultaneous transfer of images and diagnosis, and continuous education of the involved pathologists. For example, in continuous education and training, as a first step the pathologist should have access to an image data bank storing images related to the specific case, for example images taken from the same organ and from patients of similar age. The final stage would be an intra-diagnostic learning from the specific case; i.e. the time difference between questionnaires for a difficult diagnosis and the final diagnosis will become a minimum. Automated storing of the specific and diagnosis-associated images of the case will permit an open diagnostic system which will itself adjust to the micro-environment of the department of pathology. Although this future scenario has not been implemented to our knowledge, there is little doubt the development in telepathology will promote the technical procedures in the environment of a diagnostic pathologist. Telepathology is, therefore, not a substitute of conventional diagnostic procedures but a real improvement in the world of pathology.

Education, Medical, Continuing↗
PubMed1999

How strong is a covalent bond?

The rupture force of single covalent bonds under an external load was measured with an atomic force microscope (AFM). Single polysaccharide molecules were covalently anchored between a surface and an AFM tip and then stretched until they became detached. By using different surface chemistries for the attachment, it was found that the silicon-carbon bond ruptured at 2.0 +/- 0.3 nanonewtons, whereas the sulfur-gold anchor ruptured at 1.4 +/- 0.3 nanonewtons at force-loading rates of 10 nanonewtons per second. Bond rupture probability calculations that were based on density functional theory corroborate the measured values.

Journal Article↗
PubMed1999

Unimolecular reactions of dihydrated alkaline earth metal dications M2+(H2O)2, M = Be, Mg, Ca, Sr, and Ba: salt-bridge mechanism in the proton-transfer reaction M2+(H2O)2 --> MOH+ + H3O.

The unimolecular reactivity of M(2+)(H(2)O)(2), M = Be, Mg, Ca, Sr, and Ba, is investigated by density functional theory. Dissociation of the complex occurs either by proton transfer to form singly charged metal hydroxide, MOH(+), and protonated water, H(3)O(+), or by loss of water to form M(2+)(H(2)O) and H(2)O. Charge transfer from water to the metal forming H(2)O(+) and M(+)(H(2)O) is not favorable for any of the metal complexes. The relative energetics of these processes are dominated by the metal dication size. Formation of MOH(+) proceeds first by one water ligand moving to the second solvation shell followed by proton transfer to this second-shell water molecule and subsequent Coulomb explosion. These hydroxide formation reactions are exothermic with activation energies that are comparable to the water binding energy for the larger metals. This results in a competition between proton transfer and loss of a water molecule. The arrangement with one water ligand in the second solvation shell is a local minimum on the potential energy surface for all metals except Be. The two transition states separating this intermediate from the reactant and the products are identified. The second transition state determines the height of the activation barrier and corresponds to a M(2+)-OH(-)-H(3)O(+) "salt-bridge" structure. The computed B3LYP energy of this structure can be quantitatively reproduced by a simple ionic model in which Lewis charges are localized on individual atoms. This salt-bridge arrangement lowers the activation energy of the proton-transfer reaction by providing a loophole on the potential energy surface for the escape of H(3)O(+). Similar salt-bridge mechanisms may be involved in a number of proton-transfer reactions in small solvated metal ion complexes, as well as in other ionic reactions.

Journal Article↗
PubMed1999

Neovascularization in the human heart is associated with expression of VEGF-A and its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2). Results from cardiomyopexy in ischemic cardiomyopathy.

Cardiomyopexy is a novel means of revascularization in end-stage ischemic heart disease leading to neovascularization and increased perfusion of the damaged heart. So far, the mediators of this process have not yet been identified. However, among others, vascular endothelial growth factor-A (VEGF-A) is a strong candidate for inducing this process. We have performed cardiomyopexy in humans by transplanting a flap of the musculus latissimus dorsi onto the epicardium. One of the patients died 7 weeks after cardiomyopexy due to a septic process unrelated to the underlying cardiac disease. Tissue specimen from the transplanted muscle flap, from the myocardium and from the native musculus latissimus dorsi were analysed by histological and immunohistochemical methods. The transplanted muscle appeared severely degenerated and showed no immunoreactivity for von Willebrandt factor (vWF) and for VEGF-A nor for its receptors KDR and Flt-1. However, a granulation zone had developed next to the transplanted muscle enriched with monocytes and macrophages which is characterized by a network of capillaries reaching into the ischemic myocardium and providing evidence for strong induction of angiogenesis. This process is accompanied by the abundance of VEGF-A expression in the endothelial layer of vessels. In parallel, VEGF-receptor KDR is present in capillaries passing into the subepicardial region supporting the idea of VEGF-A-induced angiogenesis. The spatial expression pattern of VEGF-A and KDR suggests VEGF-A to be a promotor of angiogenesis leading to indirect myocardial revascularization.

Journal Article↗
PubMed1999

[The DEGAM-concept--development, dissemination, implementation and evaluation of guidelines for general practice].

The German Society for General Practice/Family Medicine (DEGAM) has launched a project to develop and implement national guidelines for general practice accordingly to international models. Guidelines are seen as statements to assist practitioners and patients in deciding about appropriate, effective and efficient health care. They should be evidence-based, feasible for primary care practices, and purposefully addressing to physicians as well as practice staff and patients. The development follows a comprehensive and well-structured programme (10 stages) which requires the appraisal of medical evidence, the involvement of experienced general practitioners on various stages (primary review, feasibility testing), and comments of concerned specialists, before a guideline is promulgated. Implementation of each guideline is promoted by at least five tools (full text, quick reference guide, telephone card for practice staff; patient leaflet, and information-prescription--"infozept"). Methodological quality is checked for the first time in Germany according to the standards of the German Agency for Quality Assurance. Different targets and criteria for evaluation of guidelines in primary care are mandatory part of the DEGAM-concept.

Evaluation Studies as Topic↗
PubMed1999

[Continuing medical education from the view of ambulatory care physicians--representative outcomes and needs in Bremen and Saxony-Anhalt].

RESEARCH QUESTION: To study the habits of ambulatory care physicians in CME, and to investigate the motivating and negative experiences with different types of CME in Germany. METHODS/SETTING: Survey with a five-page questionnaire posted to all ambulatory care physicians in the German states of Saxony-Anhalt (n = 3139) and Bremen (n = 1131). RESULTS: Response rates were 61.8% in Saxony-Anhalt and 41.7% in Bremen. 2412 questionnaires were available in this largest survey on that topic in Germany. Mean time devoted to CME was 4.6 hours per week, the respondents participated on the average at 14 CME-events per year. A content analysis was made to investigate positive and negative experiences. Practice orientation and personal exchange in small groups was appraised; criticism was mostly directed towards the efficiency and effectiveness of CME at large events (e.g. congresses). CONCLUSIONS AND SUGGESTIONS: Regionally performed surveys are able to guide the planning of CME about habits, wants and needs of the target group and may increase the attendance as well as the involvement. Motivating as well as critical experiences of the participants should be regarded more rigorously in the planning. Consideration can increase the quality and the impact of CME. This applies the more, when certification of the quality of CME and of individual CME-efforts are planned. This article will be followed in one of the next issues by a second from the same survey focusing on the attitudes of ambulatory care physicians towards quality improvement and their intentions to join quality circles (peer review groups).

Ambulatory Care Facilities↗
PubMed1999

[Promoting quality and quality circles from the viewpoint of established physicians--representative Bremen and Saxony-Anhalt results].

RESEARCH QUESTION: To study the attitudes of ambulatory care physicians towards quality improvement, the intentions to join quality circles (QCs, peer review groups) and the expectations directed towards them. METHODS/SETTING: Survey with a five-page questionnaire posted to all ambulatory care physicians in the German states of Saxony-Anhalt (n = 3139) and Bremen (n = 1131). RESULTS: Response rates were 61.8% in Saxony-Anhalt and 41.7% in Bremen. 2412 questionnaires were available in this largest survey on that topic in Germany. Necessity of quality improvement (QI) in ambulatory care was approved by the majority of the respondents (1.7 on a 5-point Lickert scale). Concerns existed about a rise in control and the risk of abuse of QI measures. 56.4% in Saxony-Anhalt and 52.3% in Bremen had the intention to join a QC. Motives and impediments of participation in QCs were investigated by content analysis. A causal dominance analysis was performed to identify the key elements for the decision to participate. The main benefits of QC-participation were expected as assistance in daily practice and exchange of experiences. The major obstacles were professional and private duties, fear of control and inefficiency. CONCLUSIONS: Policies that could be adequate to rise motivations and tackle on widespread fears should be purposely adapted to the needs and expectations of the physicians.

Attitude of Health Personnel↗
PubMed1998

Improved high-performance liquid chromatographic separation of peptidoglycan isolated from various Staphylococcus aureus strains for mass spectrometric characterization.

Reversed-phase high-performance liquid chromatography (RP-HPLC) of muropeptides, obtained by muramidase digestion of peptidoglycan in combination with amino acid analysis and plasma desorption time-of-flight mass spectrometry is today by far the best tool to analyze the fine structure of the peptidoglycans. Here we report further improvements of the RP-HPLC separation of muropeptides for analyzing the peptidoglycans of various methicillin-resistant strains of Staphylococcus aureus, with emphasis on a more detailed characterization of the interpeptide bridge of the peptidoglycans of this species.

Chromatography, High Pressure Liquid↗