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    Effect of Cobalt-60 Irradiation on Bradykinin B2 Receptor Expression on Human HF-15 Cells
    (2003-11-06) Blaukat, Andree; Micke, Oliver; Micke, Patrick
    Bradykinin is a key mediator of pain and inflammation. Although radiotherapy has proven to be beneficial in the treatment of inflammatory disorders, the effect of irradiation on the bradykinin pathway in human cells has not been evaluated yet. Therefore, the aim of the study was to establish a human cell culture system and to analyze bradykinin B2 receptor expression in response to different doses of gamma-ray exposure. Cultured human foreskin fibroblasts (HF15) were irradiated with 0.5 Gy, 2.0 Gy, 5.0 Gy and 10.0 Gy single doses using a Cobalt 60 radiation source. Before treatment (0h) as well as 6, 24, and 48 hours after radiation the bradykinin receptor surface density was quantified by a ligand binding assay using radioactive [3H]bradykinin. A dose and time dependant expression of the bradykinin B2 receptor was observed. Initially, higher doses (2 and 10 Gy) induced a fast upregulation of the receptor, followed by long lasting downregulation compared to baseline levels. In contrast the lowest dose (0.5 Gy) induced a fast down regulation of the receptor. After 24 h and 48 h the levels increased again but remained below baseline levels. A dose- and time-dependant change in bradykinin B2 receptor expression on HF-15-cells in response to irradiation was demonstrated. The results may imply radio-biological explanations for the beneficial effect of radiotherapy in benign inflammatory diseases.
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    Gender specific expression of tumor suppressor PKCd versus oncogenic PKCn in renal cell carcinoma
    (2003-09-30) Brenner, Walburgis; Färber, Gloria; Hengstler, Jan G.; Herget, Thomas; Thüroff, Joachim W.; Wiesner, Christoph
    Tumor incidence for renal cell carcinoma is two-fold higher in males than in females. Members of the protein kinase C (PKC) gene family have been shown to be relevant for carcinogenesis. However, little is known about a possible gender specific role of PKC in renal cell carcinoma (RCC). In this study, we quantified expression of eleven PKC-isoforms in clear cell RCCs (ccRCC) and in the corresponding normal renal tissue. A possible association of PKC-isoforms with gender of the patients was examined. Tissue specimens of 27 patients, 14 males and 13 females, with ccRCC and of the corresponding normal renal tissue were examined. Expression of PKC-isoforms were detected by Western blot analysis and quantified by computer-aided integration. In ccRCCs, as well as in the corresponding normal renal tissue, all PKC-isoforms except PKCy and 0 were detectable. Clear associations with gender of the patients were observed: (i) PKCd was reduced in tumor tissue of female patients (p = 0.023), but not of male patients (p = 0.198). (ii) A 3.6-fold enhanced expression of the oncogene PKC? was found in tumor tissue of female compared to male patients (p = 0.049). Gender specific differences in PKCd as well as PKCn expression suggest that different molecular mechanisms are relevant for carcinogenesis of ccRCC in male and female patients. This may become important for classification and treatment of ccRCC.
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    Immunotoxicity of co-exposures to heavy metals
    (2003-05-07) Attia, Dalia Ismail; Bienfait, Heinz-G.; Bolm-Audorff, Ulrich; Faldum, Andreas; Hengstler, Jan G.; Janssen, Kai; Jung, Detlev; Konietzko, Johannes; Mayer-Popken, Otfried; Reifenrath, Michael
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    Detoxification Strategy of Epoxide Hydrolase
    (2003-03-13) Arand, Michael; Cronin, Annette; Hengstler, Jan G.; Herrero Plana, Maria Elena; Lohmann, Matthias; Oesch, Franz
    The human microsomal epoxide hydrolase, a single enzyme, has to detoxify a broad range of structurally diverse, potentially genotoxic epoxides that are formed in the course of xenobiotic metabolism. The enzyme has developed a unique strategy to combine a broad substrate specificity with a high detoxification efficacy, by immediately trapping the reactive compounds as covalent intermediates and by being expressed at high levels for high trapping capacity. Computer simulation and experimental data as well as existing epidemiologic studies reveal this detoxification strategy as the mechanistic basis for a threshold in the tumorigenesis of mutagenic carcinogens.
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    Cryopreservation of islets of Langerhans
    (2003-02-10) Beyer, Jürgen; Feilen, Peter J.; Hengstler, Jan G.; Kann, Peter; Mach, Marc-Alexander von; Ringel, Michael; Schlosser, Josef; Schneider, Stephan; Weber, M. M.; Weiland, Marcus; Weilemann, L. Sacha