Kidney transplantation is the preferred treatment of patients with end stage renal disease, as it provides longer patient survival and better quality of life compared to dialysis. Prediction of... Show moreKidney transplantation is the preferred treatment of patients with end stage renal disease, as it provides longer patient survival and better quality of life compared to dialysis. Prediction of DGF, response to steroid resistant rejection and long-term graft outcome remain difficult when using merely clinical parameters. Numerous studies have reported on the predictive value of molecular markers for AR and worse graft outcome. However, the heterogeneity of AR and the variation among transplant centers leads to controversial results and preclude a more general clinical application. In the first part of this thesis, we aimed to investigate the molecular markers of steroid resistance and long-term graft survival on the basis of acute rejection biopsies. In the second part, we focused on genetic variants associated with acute rejection in kidney transplantation. In the final part we described the possible immune regulatory effect of S100 calcium binding proteins. Show less
This thesis presents another approach for direct cytosolic delivery via membrane fusion. This approach is based on a complementary pair of coiled-coil forming peptides, K (KIAALKE)4 and E (EIAALEK... Show moreThis thesis presents another approach for direct cytosolic delivery via membrane fusion. This approach is based on a complementary pair of coiled-coil forming peptides, K (KIAALKE)4 and E (EIAALEK)4 and is mimicking the action of the SNARE-complex. The SNARE-complex is responsible for fusion between vesicles and membranes of cells in the synapse and is also composed of coiled-coil forming peptides. In our system, the peptides are conjugated to a cholesterol anchor via a polyethylene glycol (PEG) spacer, yielding lipopeptides CP4K4 and CP4E4. Membrane fusion between liposomes and the plasma membrane of the cells is triggered by these two lipopeptides when each embedded within the lipid bilayer of the liposomes or the plasma membrane of the cell. Show less
