Alternative pathway activation of complement by cultured human proximal tubular epithelial cells

Alternative pathway activation of complement by cultured human proximal tubular epithelial cells. Human proximal tubular epithelial cells (PTEC) incubated with normal human serum (NHS) were found to fix on their surface C3, properdin, terminal complement components and C5b-9 MAC neoantigen, but not C1q and C4, by immunofluorescence. Complement fixation was abrogated if PTEC were incubated with EDTA-treated NHS or C3-deficient human serum, but not with Mg EGTA-treated NHS or C1q-deficient human serum, showing the prevalent activation of the alternative pathway of complement. This event was followed by marked cytoskeleton alterations with disruption of the actin cortical network, redistribution of actin throughout the cytoplasm and formation of blebs, and by cell cytolysis. In addition, superoxide anion and hydrogen peroxide production and chemiluminescence response were detected in consequence of MAC insertion on PTEC plasma membrane. The dependency on MAC of the observed biological effects of complement fixation on PTEC surface was shown by using sera selectively deficient of terminal components of complement (C6 or C8), and therefore unable to form the C5b-9 MAC, and by restoring the ability to form MAC after addition of purified C6 or C8. The possible pathogenetic relevance of these observations in tubulointerstitial injury occurring in patients with complementuria due to non-selective proteinuria, is discussed

12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74645/1/j.1432-2277.2006.00414.x.pd

Everolimus with Optimized Cyclosporine Dosing in Renal Transplant Recipients: 6-Month Safety and Efficacy Results of Two Randomized Studies

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74668/1/j.1600-6143.2004.00389.x.pd

Interleukin-12 Is Synthesized by Mesangial Cells and Stimulates Platelet-Activating Factor Synthesis, Cytoskeletal Reorganization, and Cell Shape Change

Preliminary studies indicate the involvement of interleukin (IL)-12 in experimental renal pathology. In the present study, we evaluated whether cultured glomerular mesangial cells are able to produce IL-12 and whether IL-12 may regulate some of their functions, including the cytoskeletal reorganization, the change in cell shape, and the production of platelet-activating factor (PAF). The results obtained indicate that pro-inflammatory stimuli, such as tumor necrosis factor-α and bacterial polysaccharides, induce the expression of IL-12 mRNA and the synthesis of the protein by cultured mesangial cells. Moreover, cultured mesangial cells were shown to bind IL-12 and to express the human low-affinity IL-12 β1-chain receptor. When challenged with IL-12, mesangial cells produced PAF in a dose- and time-dependent manner and superoxide anions. No production of tumor necrosis factor-α and IL-8 was observed. Moreover, we demonstrate that IL-12 induced a delayed and sustained shape change of mesangial cells that reached its maximum between 90 and 120 minutes of incubation. The changes in cell shape occurred concomitantly with cytoskeletal rearrangements and may be consistent with cell contraction. As IL-12-dependent shape change of mesangial cells was concomitant with the synthesis of PAF, which is known to promote mesangial cell contraction, we investigated the role of PAF using two chemically different PAF receptor antagonists. Both antagonists inhibited almost completely the cell shape change induced by IL-12, whereas they were ineffective on angiotensin-II-induced cell shape change. In conclusion, our results suggest that mesangial cells can either produce IL-12 or be stimulated by this cytokine to synthesize PAF and to undergo shape changes compatible with cell contraction

Bileaflet mechanical heart valves thrombosis: in vitro detection by artificial neural networks.

Endothelial pannus and thrombus formation which usually deposit on bileaflet mechanical heart valves progressively lead to incomplete opening of the valve. At the final state, they block the hinge-leaflet mechanism and cause embolic events. As a consequence, hemodynamic performance of bileaflet valvular prostheses can be severely reduced. The early detection of thrombotic formations is then crucial for correct diagnosis. The present study analyzes the power spectra calculated from the phonocardiographic signals corresponding to prostheses\u2019 sounds as acquired in vitro, in order to check for the presence of differently shaped thrombotic deposits and to differentiate deposits in classes. Data were acquired during simulations in the aortic position with the Sheffield Pulse Duplicator. Different hydrodynamic working conditions were investigated, changing the pulse rate and the stroke volume. Thrombotic deposits of different weight and shape were placed on the valve leaflet and onto the annular housing, including the case of a thrombus completely blocking one leaflet. Power spectra were classified by an artificial neural network, specifically designed for this purpose. Thrombotic event classification was applied to five commercially available mechanical prostheses. The results obtained allow implementation of a diagnostic tool for the early detection of thrombotic deposit formation: it will result in an appropriate calibration of the anticoagulant therapy, preventing mechanical heart valve dysfunctions and thromboembolic complications