Biomedical subjects
Publications and source records attributed to A Eggert.
By selective investigation of human antral venous blood, concentrations of gastrin are sufficiently elevated for the quantitative differentiation of the various forms. The results of comparative determinations of gastrin from antral and peripheral venous blood are shown.
The methylmethacrylate-monomer deported into circulation from bone cement implantation during endoprothetic operation is subject to unaltered exhalation. Qualitative evidence of monomer excretion in the exhaled air is established in animal experiment. The quantitative determination of monomer in the exhaled air in man undergoing hip-joint replacement are stated and the method is demonstrated. Pharmacocinetically exhalation has priority over metabolisation.
Congenital, acquired, and traumatic defects of the diaphragm are reported. Special consideration is given to positional changes of the stomach due to the above lesions. Clinical examples are used to point out the diagnostics and surgical possibilities of reparation.
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Aetiology, pathogenesis, staging and the conservative and operative treatment of the lymphoedema are discussed. Only in 14 to 22% of all lymphoedema an operative treatment is required. Operative treatment is only indicated after the failure of conservative treatment. The latent (stage I) and the reversible (stage II) lymphoedema rarely demand an operation. Only the lymphovenous shunts or lymphadenovenous shunts may be indicated in stage II. In the irreversible lymphoedema (stage III) and in the elephantiasis (stage IV) the following operations have been developed: ligature of ectatic lymphtrunks, peripheral lymphovenous and lymphadenovenous shunts, skin-flap transplantations, free or pediculated transplantation of the greater omentum, lymphangioplastic operations (Thompson-operation) or excisional operations (Servelle-operation). The therapeutic principles of these operations are shown and late results are discussed.
The amount of methylmethacrylatemonomer that is released into the blood-stream, during the alloplastic replacement of the hip-joint, depends on the time taken to prepare the bone cement(so-called extracorporeal polymerization-time). In vitro experiments reveal that the release of monomers depends on the preparation time. Gas-chromatographic monomer determinations show, that by prolongation of the preparation time from 2 to 5 minutes, the amount of monomer released into the blood-stream is decreased by a factor of 7. With the increase in preparation time the number of hypotonic circulatory reactions caused by the monomers will decrease. Extension of the extracorporeal polymerization-time from 2 to 5 minutes decreases the incidence of intra-operative circulatory depressions from 95% to 26%. These results were obtained by intra-arterial measurements of the blood pressure in the radial artery.
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Explore the source record for details and available documents.
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Explore the source record for details and available documents.
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Expression of different neurotrophin receptors of the tyrosine kinase (Trk) family plays an important role in the biology and clinical behavior of neuroblastomas (NB). Observations from several independent studies suggest that high expression of TrkA is present in NB with favorable biological features and highly correlated with patient survival, whereas TrkB is mainly expressed on unfavorable, aggressive NB with MYCN-amplification. To determine expression of Trk receptors and ligands in primary NB, we developed a reliable semiquantitative duplex RT-PCR protocol, that requires only 1 microgram RNA per tumor sample. Activation of TrkA by its ligand nerve growth factor (NGF) initiates a cascade of signaling events and promotes neuronal differentiation in vitro. Activation of TrkB by its ligand brain derived neurotrophic factor (BDNF) has been associated with proliferation and survival of NB cells. To study Trk signal transduction pathways and their biological effects in NB, we stably expressed TrkA and TrkB cDNA in the human NB cell line SH-SY5Y. Introduction of TrkA and TrkB restored responsiveness of SH-SY5Y cells to the ligands NGF and BDNF, respectively, and resulted in morphological differentiation. Expression of TrkA resulted in growth inhibition of the transfectants compared to parental cells, whereas TrkB transfectants demonstrated an increased proliferation rate. Further insight into the differences of TrkA and TrkB signaling may suggest new options for the treatment of NB. As expression of TrkA is a strong prognostic factor especially in MYCN non-amplified NB, a prospective study of Trk receptor expression using RT-PCR should be performed for German neuroblastoma patients.
BACKGROUND: The neurotrophin-receptor TrkB plays an important role in pathogenesis, biology and prognosis of neuroblastoma. Expression of TrkB on aggressive neuroblastomas leads to proliferation and survival of the tumor cells and is associated with an unfavorable prognosis. It is now known that Trk receptors are also expressed in extraneural tissues including the kidney. PATIENTS AND METHODS: To study the role of the neurotrophin-receptor TrkB in nephroblastoma/Wilms' Tumor (WT), we determined TrkB mRNA expression by semiquantitative duplex RT-PCR in 39 primary WT. Comparison of mRNA expression levels with clinical variables was performed using Cox regression analysis. RESULTS: The 5-year overall survival was significantly worse for patients with tumors expressing high levels of a functional TrkB-receptor (TrkBfull) in comparison to patients with low levels of TrkBfull (70 % versus 100 %, p=0.005). Conversely, children with tumors expressing high mRNA levels of a functionally inactive truncated TrkB receptor (TrkBtrunc) had a significantly higher 5-year overall survival rate in comparison to patients with low levels of TrkBtrunc (100 % versus 68 %, p=0.003). The hazard ratios for TrkBfull and TrkBtrunc remained significant after adjusting for tumor stage. All WT with high levels of TrkB also expressed the ligand brain-derived neurotrophic factor (BDNF). CONCLUSIONS: Full-length and truncated TrkB appear to be important prognostic factors in WT. Their expression should be assessed prospectively in a larger panel of WT and may have a future role in patient assignment to risk-based treatment strategies. TrkB signaling may be reduced in WT with favorable outcome due to low numbers of TrkB receptors or a competitive effect of functionally inactive TrkBtrunc.
BACKGROUND: Experimental studies for the treatment of relapsed neuroblastoma include the use of hyperthermia in combination with chemotherapeutic drugs. Cytotoxic effects of alkylants and platinum compounds on tumor cells can be enhanced by hyperthermia in various in vitro models. However, the underlying molecular mechanisms are still largely unknown. METHOD: In this study, we used microarray-analysis as a new biological approach to gain insight into the pharmacogenomics and possible target genes of thermochemotherapy. As a model, LAN 1 neuroblastoma cells were treated for 1 h with low doses of cisplatin alone, with simultaneous heating to 42 degrees C or with hyperthermia alone. Gene expression was analyzed at five time points 0 to 24 h after treatment using U95Av2 oligonucleotide arrays (Affymetrix Inc). Significant changes of gene expression levels were calculated by similarity metrices and Pearson correlation. RESULTS: Only a few genes (n = 23) demonstrated altered expression following treatment of LAN 1 cells with cisplatin alone. Hyperthermia alone resulted in significant expression changes of 136 genes in comparison to untreated control cells. Combination therapy of cisplatin and hyperthermia resulted in expression changes of 251 genes, interestingly including 131 genes with unchanged expression under treatment with either cisplatin or hyperthermia alone. Significant changes of expression levels could be annotated to genes involved in heat shock response, protein degradation and apoptosis. These results are now being validated on mRNA- and protein levels by RT-PCR and Western Blot analysis. CONCLUSION: Microarray-Analysis is a suitable new approach for the identification of target genes, which might play an important role for the synergistic effect of hyperthermia and chemotherapy in tumor cells.
Proteomics can be defined as functional analysis of the full set of proteins by high-throughput technologies in a given system. The workflow of proteomics is a multi-step process comprising sample preparation, separation, quantification and identification of proteins. Due to the high complexity of different protein species and the wide dynamic range of protein amount within a cell system it is necessary to apply appropriate analysis methods. One approach is to separate proteins first by two-dimensional gel electrophoresis (2-DE) according to charge and molecular weight. Proteins are then fragmented and analyzed using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Identification of proteins can be achieved by comparing the mass/charge-ratios of these peptides to respective databases. Proteome analysis with respect to the identification of disease-associated patterns of molecules in different tissues is in the early stages, because standardisation of these techniques often remains to be established. However, proteome analyses is a promising tool to obtain holistic insights into the physiological status of a cell or cellular system. Compared to RNA-based studies some advantages are obvious: (1) post-translational modifications, e. g. phosphorylation, contributing to the activity status can be detected at the protein level only, (2) RNA-levels do not necessarily coincide with protein levels for a particular gene, (3) feedback-mechanisms within regulatory pathways can control protein activity without measurable changes in mRNA content.