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Biomedical subjects

Christiane Fenske

Publications and source records attributed to Christiane Fenske.

4 recordsLinked to original sources

Comparison of different biological methods for the assessment of ecotoxicological risks.

To test the effects of heavy metals in river water, we compared the sensitivity of seven different biological test methods, using bacteria (Vibrio fischeri), human FL cells, protozoans (Paramecium spp.), nematodes (Rhabditis oxycerca), aquatic plants (Lemna minor), and fishes (Leuciscus idus melanotus). As test substance we used a representative mixture of 3.0 microg/l As, 2.5 microg/l Pb, 0.8 microg/l Cd, 1.7 microg/l Cr, 3.9 microg/l Cu, 6.7 microg/l Ni, 0.4 microg/l Hg, and 23.0 microg/l Zn, imitating the detectable heavy metal contamination of the Odra estuary (NE Germany/NW Poland). This mixture was defined as normal concentration (NC). Most sensitive was the test with L. minor (exposure time 10 d). The plants already showed phytotoxic effects at the heavy metal concentration found in the Odra estuary. Test systems with human cells, protozoans, and nematodes (exposure time 1-7 d) reacted at concentrations 85-100 times above the NC. Fish toxicity (exposure time 2 d) occurred from 130-fold concentration upwards. In contrast, the standard test carried out with luminescent bacteria (exposure time 30 min) was affected only at > 1000-fold concentrations. This test is therefore not suitable as an early warning system to detect ecological risks. Even the NC of heavy metals measured in the Odra estuary inhibits cells and the growth of aquatic plants. Of the single heavy metals tested, copper produced the strongest effects. Therefore, the reduction of heavy metal emissions, especially of copper-which can amplify the toxicity of other heavy metals-should be a task of highest priority.

Aliivibrio fischeri↗

Vascular endothelial growth factor naked DNA gene transfer enhances thrombus recanalization and resolution.

OBJECTIVES: Enhancing thrombus resolution may reduce the long-term complications of venous thrombosis. The aim of this study was to examine whether a sustained release of vascular endothelial growth factor (VEGF) would further improve thrombus recanalization. METHODS: Inferior caval vein thrombosis was induced in a cohort of 21 male Wistar rats. A plasmid encoding the human VEGF gene (phVEGF) was injected directly into thrombus (30 to 50 microg) and the muscle adjacent to the inferior vena cava (300 to 400 microg). A plasmid containing the gene encoding beta-galactosidase (pCMVbeta) was injected into the same sites of a separate cohort of rats to act as a control. Tissues were harvested after 1 and 2 weeks, and beta-galactosidase activity was measured to estimate transfection efficiency. Muscle and serum VEGF were measured by enzyme-inked immunosorbent assay. Thrombus size, recanalization, and organization were determined by computer-assisted image analysis. RESULTS: The efficiency of control plasmid transfection into muscle was about 1%. No serum hVEGF was detected in phVEGF- or pCMVbeta-treated animals. Significantly raised levels of hVEGF (P < .01) were detected in the muscle injected with phVEGF after 2 weeks compared with control muscle. There was a significant reduction in thrombus size of 23% (P < .05) and 48% (P < .001) in phVEGF-treated animals compared with pCMVbeta-treated controls after 1 and 2 weeks, respectively. Thrombus recanalization was a significantly greater in the phVEGF-treated group after 2 weeks (mean 19% +/- 2% [SEM]) compared with controls (mean 13% +/- 2%, P < .01). There were no differences in the thrombus organization score. CONCLUSION: VEGF gene therapy of venous thrombus resulted in smaller thrombi with greater recanalization. Angiogenic gene therapy may form the basis of a novel treatment that may improve the resolution of venous thrombi. CLINICAL RELEVANCE: Deep vein thrombosis may lead to residual venous obstruction or reflux and result in post-thrombotic complications that are debilitating and have a substantial socioeconomic impact. Enhancing the resolution of venous thrombi may reduce post thrombotic complications.

Animals↗

The adaptor disabled-2 binds to the third psi xNPxY sequence on the cytoplasmic tail of megalin.

The cytoplasmic tail (CT) of megalin possesses several functional motifs likely to participate in protein-protein interactions within the proximal tubular epithelial cell (PTEC) of the kidney. One such interaction is with the phosphotyrosine interaction domain (PID) of the adaptor protein disabled-2 (Dab2), a mitogen-responsive phosphoprotein, which interacts via its PID with Psi xNPxY (where Psi represents a hydrophobic residue) motifs on its binding partners. Megalin CT has three such motifs; it has been established that there is no interaction of Dab2 with the first (from N to C) (Biochem. J. 3 (2000) 613). Here, we analyse in real-time the binding of recombinant megalin CT, and of synthetic peptide sequences encompassing the second and third Psi xNPxY motifs, to Dab2PID in real-time using surface plasmon resonance (SPR). We report a binding affinity of DabPID for megalin CT of K(D) = 2.6 x 10(-7) +/- 5.3 x 10(-8). Direct binding and competition studies indicate that this interaction is with the third Psi xNPxY motif. The dissociation of Dab2 from the third Psi xNPxY peptide was significantly slower than that from the second (k(off) (mean +/- S.E.M.) (per s) = 0.002 +/- 0.002 vs. 0.007 +/- 0.002, P < 0.05). Synthetic peptide sequences encompassing the third Psi xNPxY but not the second inhibited Dab2PID binding both to intact megalin CT and to the third Psi xNPxY motif. Tyrosine phosphorylation of either motif did not exert a major effect upon competition efficacy. We further demonstrate for the first time the presence of Dab2 expression in primary human PTEC.

Adaptor Proteins, Signal Transducing↗