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Biomedical subjects

R Fischer

Publications and source records attributed to R Fischer.

At least 109 records · Page 6Linked to original sources
PubMed2000

[Health and human rights--development of a questionnaire for measuring perceived human rights status].

Health and human rights as interlinked concepts are a promising new avenue in public health. The aim of this study was the development of a reliable and valid instrument for the measurement of the human right status. The reliability and validity of this new questionnaire for human rights (HRS = human right scale) was measured within a group of Public Health students (n = 42) and the participants of the KORA-fracture-study. Test-retest-reliability was 0.73 (ICC: 0.69) and Cronbach's alpha was 0.66-0.79. The evaluation of the validity with the help of a factor analysis and a reconstruction study pointed out, that the perceived human rights status has to be treated as an interlinked and not divisible concept. Both study groups showed deficits for items in the dimension justice and participation.

Adult↗
PubMed2000

Transient transformation of the rust fungus Puccinia graminis f. sp. tritici.

The biotrophic rust fungus Puccinia graminis f. sp. tritici (Pgt) was transformed by particle bombardment. The promoter from the Pgt translation elongation factor 1alpha (EF-1alpha) gene was fused to the bacterial marker genes hygromycin B phosphotransferase (hpt) and beta-glucuronidase (GUS). Transformation constructs were introduced into uredospores of Pgt, an obligate pathogen of wheat, by biolistic bombardment. Uredospores transformed with the construct containing the hpt gene germinated and initiated branching on selective medium, indicating that they had acquired resistance to hygromycin B. However, transformants stopped growing 5 days after bombardment. GUS activity in uredospores and germlings was histochemically detected 4-16 h after bombardment. GUS expression was also obtained using the INF24 promoter from the bean rust fungus Uromyces appendiculatus, demonstrating that heterologous genes can be expressed in P. graminis under the control of regulatory sequences from closely related organisms.

Artificial Gene Fusion↗
PubMed2000

First observation of different diffusion coefficients for two conformers in a neat liquid.

Self-diffusion coefficients were studied for the highly polar liquid N-methylformamide at pressures up to 200 MPa between the melting pressure curves and 420 K by the spin-echo method. N-Methylformamide exists as a mixture of two conformers in the neat liquid. These conformers have large differences at lower temperatures in their dynamic and structural properties. The self-diffusion coefficient of the cis-conformer being 17% lower than that of the trans-conformer at the same T and p. This is the first observation of such an effect. The experimental study is supported by Monte Carlo (MC) calculations which show that the first neighbors around a cis conformer are arranged differently than in an all trans liquid. The difference leads in the simulations to a much lower dielectric constant for the trans-cis mixture and might also explain the retardation of diffusion for the cis conformer.

Diffusion↗
PubMed2000

The basal ganglia in haemochromatosis.

Haemochromatosis is characterised by deposition of iron-containing pigment in various organs, but little is known about possible deposition in the brain and its clinical impact. We therefore investigated 14 patients with hereditary haemochromatosis with MRI, CT and transcranial ultrasound (TCS) and examined them neurologically. In six of the patients dense lesions were found within the lentiform nucleus on CT, all of whom displayed hyperechogenic lesions in the same area on TCS, as did one other patient. In these patients the relative signal intensities of the lentiform nucleus measured by MRI relaxometry were higher. No patient had clinical signs of basal ganglia disorders.

Adult↗
PubMed2000

[New developments in diagnosis of coronary heart disease--3D fusion image].

The interpretation of three-dimensional (3D) structures of the coronary tree and the myocardium by a clinician demands a subjective visual integration of two-dimensional (2D) images of cardiac diagnostic procedures like coronary angiography and myocardial scintigraphy. Although in the conventional analysis of 2D display scintigraphic myocardial perfusion segments are arbitrarily assigned to three major coronary artery systems, the standard myocardial perfusion distribution territories correspond with the individual pathologic-anatomic coronary tree in only 50-60% of the patients. Hence, the mental integration of both 2D images of coronary angiography and myocardial scintigraphy does not necessarily allow an accurate assignment of particular myocardial perfusion regions to the corresponding vessels. For an objective assignment of each vessel segment of the coronary tree to the corresponding myocardial regions, we have developed a 3D "fusion image" technique and applied it to patients with coronary artery disease. Cause-and-effect relationships may be more obvious with 3D data fusion and may enable an easier comparison of anatomy and physiology. Preliminary results demonstrate that our newly developed 3D fusion image is useful for accurate assignment of coronary vessel segments to the corresponding myocardial perfusion regions and suggest that it may allow the clinician a comprehensive and accurate assessment of the patient's myocardial status.

Coronary Angiography↗
PubMed2000

[A rare cause of muscle pain and elevated creatine kinase level--the paroxysmal non-hereditary angioedema].

Systemic capillary leak syndrome is a rare idiopathic disorder characterized by recurrent episodes of hypotension and hemoconcentration due to sudden transient extravasation of up to 70% of plasma. Less than 40 cases have appeared in the literature. Mortality rates 5 years after diagnosis have been reported to be up to 75%. Clinical findings are generalized edema and intravasal fluid deficiency. Laboratory features include hypoalbuminemia and extreme hemoconcentration. A common finding is a monoclonal gammopathy. Rare manifestation of this syndrome is rhabdomyolysis due to increased compartment pressure and ischemic myonecrosis. Early diagnosis and exclusion of other clinical disorders like rheumatic myopathies and myositis are critical concerning prognosis and therapy. We describe a 46-year-old woman with rhabdomyolysis and systemic capillary leak syndrome whose condition is stable for a total of 30 months under a prophylactic regimen with oral terbutaline plus theophylline. A brief survey of the literature is given.

Adrenergic beta-Agonists↗
PubMed2000

Selectins (CD62L, CD62P) and megakaryocytic glycoproteins (CD41a, CD42b) mediate megakaryocyte-fibroblast interactions in human bone marrow.

Previous in vitro studies are in keeping with the finding that isolated and enriched megakaryocytes attach to bone marrow fibroblasts and generate an increased growth of these cells. This process was assumed to depend on a close spatial relationship between both cell types which supports the paracrine effect of platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta1. Moreover, adhesion molecules including beta1 integrin receptors and fucosylated structures were determined to play an important role in these complex interactions. However, up to now the influence of megakaryocyte expressed glycoproteins CD41a and CD42b in these processes was not investigated. In addition, the role of megakaryocytic CD62P and also of CD62L, both adhesion molecules of the selectin group, could also be of interest. Following isolation and enrichment of bone marrow megakaryocytes and fibroblasts, both cell populations were characterized regarding their expression of these factors by applying immunocytochemical techniques. Additionally, their influence on adhesion of megakaryocytes to fibroblasts as well as fibroblast growth was evaluated by comparative megakaryocyte-fibroblast co-cultures and inhibition studies using specific monoclonal antibodies (mabs). Fibroblast monocultures served as controls. In these experiments, selectin-specific antibodies significantly reduced megakaryocyte attachment to fibroblast feeder layers and fibroblast growth in the co-cultures. The effect of CD41a and CD42b specific antibodies was limited to megakaryocyte-dependent fibroblast growth. These results elucidate the involvement of the selectins CD62P and CD62L in the basal activation of megakaryocytes inducing their attachment to bone marrow fibroblasts. In contrast, the megakaryocyte glycoproteins CD41a and CD42b exert their effect on the megakaryocyte dependent fibroblast growth. Altogether, it is tempting to speculate that the various interactions of these mediators reflect certain steps in the complex pathomechanisms causing the evolution of (reactive) myelofibrosis in hematopoietic neoplasias accompanied by megakaryocytic proliferation.

Bone Marrow↗
PubMed2000

Nuclear migration in fungi--different motors at work.

Lower fungi such as Saccharomyces cerevisiae and Aspergillus nidulans are ideal organisms for studying the molecular biology underlying nuclear migration in eukaryotic cells. In this review, the role of different motor proteins such as dynein, kinesin and myosin will be discussed.

Aspergillus↗
PubMed2000

Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies.

This report describes the stable expression of a medically important antibody in the staple cereal crops rice and wheat. We successfully expressed a single-chain Fv antibody (ScFvT84.66) against carcinoembryonic antigen (CEA), a well characterized tumor-associated marker antigen. scFv constructs were engineered for recombinant antibody targeting to the plant cell apoplast and ER. Up to 30 microg/g of functional recombinant antibody was detected in the leaves and seeds of wheat and rice. We confirmed that transgenic dry seeds could be stored for at least five months at room temperature, without significant loss of the amount or activity of scFvT84.66. Our results represent the first transition from model plant expression systems, such as tobacco and Arabidopsis, to widely cultivated cereal crops, such as rice and wheat, for expression of an antibody molecule that has already shown efficacy in clinical applications. Thus, we have established that molecular pharming in cereals can be a viable production system for such high-value pharmaceutical macromolecules. Our findings provide a strong foundation for exploiting alternative uses of cereal crops both in industrialized and developing countries.

Animals↗
PubMed2000

Molecular farming of pharmaceutical proteins.

Molecular farming is the production of pharmaceutically important and commercially valuable proteins in plants. Its purpose is to provide a safe and inexpensive means for the mass production of recombinant pharmaceutical proteins. Complex mammalian proteins can be produced in transformed plants or transformed plant suspension cells. Plants are suitable for the production of pharmaceutical proteins on a field scale because the expressed proteins are functional and almost indistinguishable from their mammalian counterparts. The breadth of therapeutic proteins produced by plants range from interleukins to recombinant antibodies. Molecular farming in plants has the potential to provide virtually unlimited quantities of recombinant proteins for use as diagnostic and therapeutic tools in health care and the life sciences. Plants produce a large amount of biomass and protein production can be increased using plant suspension cell culture in fermenters, or by the propagation of stably transformed plant lines in the field. Transgenic plants can also produce organs rich in a recombinant protein for its long-term storage. This demonstrates the promise of using transgenic plants as bioreactors for the molecular farming of recombinant therapeutics, including vaccines, diagnostics, such as recombinant antibodies, plasma proteins, cytokines and growth factors.

Animals↗
PubMed2000

Methylcitrate synthase from Aspergillus nidulans: implications for propionate as an antifungal agent.

Aspergillus nidulans was used as a model organism to investigate the fungal propionate metabolism and the mechanism of growth inhibition by propionate. The fungus is able to grow slowly on propionate as sole carbon and energy source. Propionate is oxidized to pyruvate via the methylcitrate cycle. The key enzyme methylcitrate synthase was purified and the corresponding gene mcsA, which contains two introns, was cloned, sequenced and overexpressed in A. nidulans. The derived amino acid sequence of the enzyme shows more than 50% identity to those of most eukaryotic citrate synthases, but only 14% identity to the sequence of the recently detected bacterial methylcitrate synthase from Escherichia coli. A mcsA deletion strain was unable to grow on propionate. The inhibitory growth effect of propionate on glucose medium was enhanced in this strain, which led to the assumption that trapping of the available CoA as propionyl-CoA and/or the accumulating propionyl-CoA itself interferes with other biosynthetic pathways such as fatty acid and polyketide syntheses. In the wild-type strain, however, the predominant inhibitor may be methylcitrate. Propionate (100 mM) not only impaired hyphal growth of A. nidulans but also synthesis of the green polyketide-derived pigment of the conidia, whereas in the mutant pigmentation was abolished with 20 mM propionate.

Amino Acid Sequence↗
PubMed2000

Serum ferritin iron in iron overload and liver damage: correlation to body iron stores and diagnostic relevance.

The iron content of serum ferritin has been determined in groups of patients with normal or increased iron stores by using a technique of ferritin immunoprecipitation followed by iron quantitation with atomic absorption spectroscopy. The results were correlated to individual liver iron concentrations, measured non-invasively by superconducting quantum interference device (SQUID) biomagnetometry. A close correlation between serum concentrations of ferritin protein and ferritin iron was found (r = 0.92) in all groups of patients. However, the correlation between ferritin iron concentration and individual liver iron concentration was poor in patients with hemochromatosis (r = 0.63) and patients with beta-thalassemia major (r = 0.57). The degree of ferritin iron saturation was about 5% in iron-loaded patients, which contrasts with results in two recent studies but confirms older observations. In patients with liver cell damage, the ferritin iron saturation in serum was significantly higher than that found in groups with iron overload disease, probably indicating the release of intracellular iron-rich ferritin into the blood. The monitoring of patients undergoing bone marrow transplantation indicated that the release of iron-rich and iron-poor ferritin occurred during phases of hepatocellular damage and inflammation, respectively. We find the benefits of serum ferritin iron measurement to be marginal in patients with iron overload disease.

Adult↗
PubMed2000

Clinical manifestations of AB-amyloidosis: effects of biocompatibility and flux.

BACKGROUND: Highly permeable biocompatible dialysis membranes may postpone the development of AB-amyloidosis, but the relative contribution of enhanced flux or reduced inflammation by highly biocompatible membranes and sterile dialysis fluid remains unknown. METHODS: In this retrospective investigation, 89 patients with end-stage renal disease maintained on regular haemodialysis for at least 10 years and treated with one type of dialysis membrane exclusively were selected for analysis. They were divided into three groups: low-flux, bioincompatible cellulose (I), low-flux, intermediately biocompatible polysulphone or PMMA (II), or high-flux, highly biocompatible polysulphone or AN69 (III). In addition, the patients were analysed according to the microbiological quality of the dialysis fluid, which had been tested regularly and was classified either as standard or as intermittently contaminated. The clinical manifestations indicative of AB-amyloidosis, namely, carpal tunnel syndrome, arthropathy and bone cysts, were diagnosed after recruitment. RESULTS: Clinical symptoms were most pronounced in group I, intermediate in group II, and lowest in group III. Patients treated with intermittently contaminated dialysis fluid showed a higher prevalence of AB-amyloidosis than patients with less contaminated dialysis fluid. Logistic regression analysis demonstrated that the flux characteristics of the dialyser and the microbiological quality of the dialysis fluid as well as the biocompatibility of the dialyser were independent determinants of AB-amyloidosis. CONCLUSION: It would be prudent clinical practice to employ high-flux biocompatible membranes in conjunction with ultrapure dialysis fluid for the treatment of end-stage renal disease patients who need to remain on long-term haemodialysis.

Acrylic Resins↗
PubMed2000

Efficacy and tolerability of 20 mg pantoprazole versus 300 mg ranitidine in patients with mild reflux-oesophagitis: a randomized, double-blind, parallel, and multicentre study.

BACKGROUND AND AIM: The aim of this study was to compare the efficacy and tolerability of low dose pantoprazole (20 mg) (a gastric proton pump inhibitor) with standard dose ranitidine (300 mg) (a histamine-receptor antagonist), in their ability to relieve symptoms and heal oesophageal lesions associated with gastrooesophageal reflux disease (GORD). METHODS: Patients with endoscopically established mild GORD (stage I, modified Savary-Miller classification) were enrolled into a multicentre, randomized, double-blind, parallel-group comparison study (intention-to-treat population, n = 201; age range, 18-82 years). Patients took either oral pantoprazole 20 mg in the morning (n = 101) or ranitidine 300 mg in the evening (n = 100) once daily for 4 weeks or, if the healing was not complete, 8 weeks. Relief from key symptoms (heartburn, acid regurgitation, pain on swallowing) was assessed after 2, 4, and if applicable, 8 weeks. Healing of lesions was confirmed endoscopically after 4 and, if applicable, 8 weeks. RESULTS: Complete relief from key symptoms was noted after 2 weeks in 70/88 (80%) patients treated with pantoprazole vs 45/89 (51%) patients treated with ranitidine ('per-protocol and key-point available' populations, P < 0.001); the corresponding results after 4 weeks were 77/88 (88%) vs 51/88 (58%) (P < 0.001). Complete healing of lesions after 4 weeks of treatment was seen in 74/88 (84%) vs 49/89 (55%) in the pantoprazole and ranitidine group, respectively (P < 0.001, per-protocol); by week 8 the cumulative healing rates were 84/88 (95%) vs 69/89 (78%) in the pantoprazole and ranitidine group, respectively (P < 0.001). For the intention-to-treat populations, the corresponding values for healing after 4 and 8 weeks were 73% vs 49% (P < 0.001) and 83% vs 69% (P < 0.05), respectively. Both study medications were well tolerated. CONCLUSION: Compared to ranitidine 300 mg, the regimen with pantoprazole 20 mg provides faster relief from symptoms and is significantly more effective in healing of oesophageal lesions in patients with mild reflux-oesophagitis. Thus, the low dose of pantoprazole offers a treatment approach which minimizes drug exposure and costs while retaining high efficacy.

2-Pyridinylmethylsulfinylbenzimidazoles↗