1,721,276 research outputs found
CYCLOSPORINE A INDUCES EPITHELIAL MESENCHYMAL TRANSITION IN MURINE TUBULAR EPITHELIAL CELL LINES MAINLY BUT NOT EXCLUSIVELY VIA INDUCTION OF TRANSFORMING GROWTH FACTOR (TGF-beta 1)
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Renal fibrosis: an update
No full textTubulointerstitial fibrosis invariably accompanies the course of chronic renal failure towards end-stage renal disease. Tubular epithelial cells. the predominant cell type in the tubulointerstitium, are increasingly being recognized for playing a dominant role as mediators of renal fibrogenesis, Tubular epithelial cells become activated either by the glomerular ultrafiltrate from their apical side or by mononuclear cells from their basolateral side. They initiate the scarring process by secreting chemokines, which in return attract mononuclear cells as well as growth factors that stimulate interstitial fibroblasts. In later phases of renal fibrogenesis, cellular changes of tubular epithelial cells contribute to the chronic impairment of renal function. Whereas tubular epithelial cells react by proliferation or hypertrophy to initial stimuli, they may undergo apoptosis or transdifferentiate into fibroblasts, and thus contribute to tubular atrophy in later stages of progressive renal disease. Resident interstitial fibroblasts are also important in renal fibrogenesis, and recent research has demonstrated that these cells are much more heterogeneous than expected. Cytokines such as fibroblast growth factor type 2 and epithelial growth factor have been shown to be pro-fibrogenic, whereas hepatocyte growth factor and bone morphogenic protein type 7 may inhibit fibrogenesis, Despite recent progress, further research is mandatory for a better understanding and the development of novel therapeutic approaches. Curr Opin Nephrol Hypertens 10:315-320 (C) 2001 Lippincott Williams & Wilkins
Role of fibroblast activation in inducing interstitial fibrosis
No full textTubulointerstitial fibrosis is an obligate finding in endstage diseased kidneys. Renal fibrosis is defined as excessive matrix deposition that leads to tissue destruction and impairment of renal function. This process is often independent of the initial underlying disease and is not self-limited, in contrast to normal wound healing. Fibroblasts are the main effector cells in fibrogenesis, and mainly contribute to increased synthesis of matrix components. Increased matrix production is preceeded by massive proliferation of fibroblasts. The transformation from quiescent interstitial cells to proliferating and excessively matrix-producing cells has been termed fibroblast activation, which includes functional implications as well as phenotypic changes such as the expression of ct-smooth muscle actin ("myofibroblasts"). Activation of fibroblasts typically occurs through four distinct mechanisms: stimulation by growth factors ("auto- and paracrine"), by direct cell-cell contacts, by extracellular matrix via integrins, and by environmental conditions such as hyperglycemia or hypoxia in renal disease. The crucial step though, that distinguishes wound healing from fibrosis, is the perpetuation of the activated state. The clarification of cellular events connected with fibrogenesis has led to new approaches for therapy. Direct targeting of fibroblasts, inhibition of matrix deposition and specific inhibition of fibroblast activation have proved successful in experimental models and thus may lead to new approaches in the treatment of progressive renal disease
Tuberculous meningitis in a renal transplant recipient
No full textTuberculous meningitis is a very rare, but serious extrapulmonary complication of mycobacterial infections in immunocompromised patients, such as organ transplant recipients. We describe here a 66-year-old Turkish woman without any history of tuberculosis, who received a renal allograft transplant in 1994. After a pilgrimage to an endemic area for tuberculosis, she presented with fever and headache in August 1998. Clinical examination revealed positive meningism and hyperreflexia. Lymphocytosis was noted in her cerebrospinal fluid (CSF) and Mycobacterium tuberculosis infection was detected by PCR within the CSF. Despite immediate triple antituberculosis therapy, the patient's clinical condition deteriorated rapidly, with the development of septic shock syndrome, and she died three weeks after admission due to cardiovascular and respiratory failure. Mycobacterial infections, including extrapulmonary manifestations, should thus be considered in all renal transplant recipients presenting with unexplained fever. Preventive therapy, i.e. isoniazid prophylaxis, may also be recommended for patients risking exposure in areas endemic for tuberculosis
Lysine 3 acetylation regulates the phosphorylation of yeast 6-phosphofructo-2-kinase under hypo-osmotic stress
No full textN-terminal acetylation in the yeast Saccharomyces cerevisiae is catalysed by any of three N-terminal acetyltransferases (NAT), NatA, NatB, and NatC, which contain the catalytic subunits Ard1p, Nat3p and Mak3p, respectively. Yeast 6-phosphofructo-2-kinase (PFK2) was found to be acetylated at the amino acid lysine 3. The Lys3-Arg mutant was not acetylated and the mutation causes a slight decrease in enzyme activity. PFK2 from yeast cells exposed to hypo-osmotic stress is known to be phosphorylated at Ser8 and Ser652 (Dihazi et al., 2001 a). We have taken a mass spectrometric approach to investigate the influence of PFK2 acetylation on its phosphorylation. Wild-type PFK2 and the Lys3-Arg mutant were purified from hypo-osmotically stressed cells and analysed with MALDI-TOF MS for phosphorylation. Wild-type PFK2 without any tag sequence was found to be acetylated and two times phosphorylated at the N-terminal peptide T1-40 carrying the acetylation. The same results were observed with C-terminally His-tagged PFK2. When the His-tag was added to the N-terminus of the protein PFK2, acetylation was found to be incomplete and only one phosphate was incorporated in the peptide T1-41. The Lys3-Arg mutant of PFK2 was not at all post-translationally modified at the N-terminal peptide. Our data indicate that Lys3 acetylation affects the N-terminal phosphorylation of PFK2 under hypo-osmotic stress
Influence of Stiffness and Damping Parameters of Passive Seismic Control Devices in One-Sided Rocking of Masonry Walls
No full textThis paper analyzes the influence of horizontal damped and undamped restraints in terms of the amplification of the response of rocking masonry walls subjected to seismic excitations. It also makes a practical contribution to the design of antiseismic devices conceived to control rocking motion, avoiding or at least limiting undesirable response amplifications that would lead to local or global failure. A horizontal restraint, simulating an elastoplastic steel tie-rod, was coupled with a damper, whose action is included in a proposed equation of motion. Parametric analyses were performed for three typical façades of masonry buildings, showing that, if the stiffness of tie-rod increases, the seismic vulnerability of a rocking façade is not necessarily reduced. Therefore, the calculation of rocking spectra is recommended in order to identify stiffness ranges in which amplification could occur. A simple method for calculating the design damping coefficient of a shock absorber is proposed and the consequent mitigation of vulnerability is demonstrated in various analysis configurations. Graphs plotting time-dependent ratios between the energy dissipated by the shock absorber and the seismic input energy are shown to be a useful tool for quantifying the effectiveness of the shock absorber itself in dissipating energy. The reduction of these time-dependent ratios occasionally observed for specific earthquake time ranges reveals that adverse frequencies are occasionally present in seismic excitation and allows for the identification of the optimal damping coefficient
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