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Greiber S.; Kramer-Guth A.; Pavenstadt H.; Gutenkunst M.; Schollmeyer P.; Wanner C. 《Nephrology, dialysis, transplantation》1996,11(5):778-785
BACKGROUND: Lipoprotein abnormalities are considered to accelerate glomerularinjury in various forms of renal disease, probably by affectingmesangial proliferation. Serum levels of the atherogenic Lipoprotein(a)(Lp(a)) are elevated in patients with nephrotic syndrome andLp(a) deposits have been identified in diseased glomeruli. Sofar, the influence of Lp(a) on mesangial cell function has notbeen defined. METHODS: The influence of Lp(a) on mesangial cell proliferation was assessedin a rat mesangial cell culture model by direct measurementof cell growth as well as analysis of DNA-synthesis and mRNAlevels of c-fos and c-myc, two growth-associated immediateearly response genes. RESULTS: Lp(a) triggered a biphasic response on DNA synthesis: 3H-thymidineuptake was increased when cells were incubated with Lp(a) (2.510µg/ml) for 24 h. The response was dose dependent, a maximaleffect was seen for Lp(a) 5 µg/ml. The stimulatory propertiesof Lp(a) were comparable to 10% fetal calf serum (FCS). No additiveeffect of 10% FCS and Lp(a) on DNA synthesis was observed. Cellproliferation was moderately stimulated (120±9% of control)by low levels of Lp(a) in the presence of small amounts of FCS.Messanger RNA levels for c-fos and c-myc were upregulated asearly as 15 min after incubation with Lp(a) 5 µg/ml, amaximum response was observed after 30 and 240 min respectively.Stimulation of DNA synthesis was partly blunted when cells wereincubated with Lp(a) in the presence of catalase 100 U/ml andsuperoxide dismutase 107M (SOD) but not in the presenceof SOD alone. Lp(a) in concentrations above 10 µg/ml depressedDNA-synthesis and elicted signs of cytotoxicity. The cytotoxiceffects of Lp(a) were not blunted by oxygen radical scavengers.The stimulatory and cytotoxic effects of Lp(a) were not restrictedto a specific isoform. CONCLUSION: Low concentrations of Lp(a) stimulated growth of mesangial cells,whereas higher concentrations had antiproliferative or toxiceffects. The stimulation of mesangial cell proliferation aswell as the cytotoxic effects causes by Lp(a) are both likelyto have a negative impact on the course of renal disease. 相似文献
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Zusammenfassung Das Guillain-Barré-Syndrom (GBS) ist eine akute, entzündliche, demyelinisierende Erkrankung des peripheren Nervensystems.
Die Erkrankung pr?sentiert sich klinisch mit symmetrischen L?hmungen, Areflexie und ausgepr?gten vegetativen St?rungen. Respiratorisches
Versagen und kardiovaskul?re Instabilit?t sind die Hauptgründe für die Verlegung eines Patienten mit GBS auf die Intensivstation.
Der vorliegende Bericht diskutiert am Beispiel eines 33j?hrigen Patienten mit Miller-Fisher-Syndrom (MFS), einer Sonderform
des Guillain-Barré-Syndroms, die Behandlung des ausgepr?gten GBS auf der Intensivstation.
Eingegangen: 9. Mai 1997 Akzeptiert: 23. Juni 1997 相似文献
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Bek MF Bayer M Müller B Greiber S Lang D Schwab A August C Springer E Rohrbach R Huber TB Benzing T Pavenstädt H 《The American journal of pathology》2006,168(1):20-32
Podocytes are crucial for the permeability of the glomerular filtration barrier. In glomerular disease, however, reactive oxygen species (ROS) may be involved in podocyte injury and subsequent proteinuria. Here, we describe ROS-dependent gene induction in differentiated podocytes stimulated with H(2)O(2) or xanthine/xanthine-oxidase. Superoxide anions and H(2)O(2) increased mRNA and protein expression of GAS5 (growth arrest-specific protein 5) and CHOP (C/EBP homology protein). Cultured podocytes overexpressing CHOP showed increased generation of superoxide anions compared to controls. In addition, the expression of alpha(3)/beta(1) integrins, crucial for cell-matrix interaction of podocytes, was down-regulated, leading to increased cell-matrix adhesion and cell displacement. The altered cell-matrix adhesion was antagonized by the ROS scavenger 1,3-dimethyl-2-thiourea, and the increase in cell displacement could be mimicked by stimulating untransfected podocytes with puromycin, an inductor of ROS. We next performed immunohistochemical staining of human kidney tissue (normal, membranous nephropathy, focal segmental glomerulosclerosis, and minimal change nephropathy) as well as sections from rats with puromycin nephrosis, a model of minimal change nephropathy. CHOP was weakly expressed in podocytes of control kidneys but up-regulated in most proteinuric human kidneys and in rat puromycin nephrosis. Our data suggest that CHOP-via increased ROS generation-regulates cell-matrix adhesion of podocytes in glomerular disease. 相似文献
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Lipoprotein(a) induces glomerular superoxide anion production 总被引:2,自引:0,他引:2
Greiber S; Kreusel M; Pavenstadt H; Schollmeyer P; Wanner C 《Nephrology, dialysis, transplantation》1997,12(7):1330-1335
BACKGROUND: Lipoprotein(a) (Lp(a)) is considered to accelerate glomerular
injury in various forms of renal disease. Several tissue culture studies
suggested that biological effects of Lp(a) are inhibitable by oxygen
radical scavengers. Since reactive oxygen metabolites (ROM) are important
mediators of renal disease, we studied the effects of native and oxidized
Lp(a) on generation of the ROM superoxide anion in isolated glomeruli and
compared them with the effects of native (nLDL) and oxidized LDL
cholesterol (oxLDL). METHODS: The effect of native and oxidized Lp(a) and
LDL on ROM production in isolated rat glomeruli was investigated with a
lucigenin chemiluminescence assay. RESULTS: Native Lp(a) caused a moderate,
dose dependent stimulation of glomerular ROM production: Maximum ROM
production to 159 +/- 9% of control glomeruli was induced by nLp(a) 20
micrograms/ml. Lp(a)-induced chemiluminescence was completely inhibited by
the cell permeable oxygen radical scavenger Tiron (10 Mm). Oxidized Lp(a)
(20 micrograms/ml) caused a more pronounced stimulation of ROM production
to 204 +/- 12% of control values. Interestingly, only oxLDL, but not nLDL
had a significant effect on glomerular ROM production (ox LDL 50
micrograms/ml: 192 +/- 19% of control). Lp(a) stimulated ROM production was
completely inhibited by the protein kinase C inhibitor bis- indolyl
malemide (BIM): BIM 10(-6) M inhibited 52 +/- 3%, BIM 10(- 5) M inhibited
94 +/- 5% of Lp(a)-induced ROM production. ROM production was also
inhibited, when intracellular CAMP levels were elevated by forskolin.
CONCLUSION: Lp(a) and oxLp(a) induce the activation of ROM in glomeruli by
a pathway that is sensitive to inhibition of protein kinase C and elevation
of intracellular CAMP levels.
相似文献
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Receptor-mediated lipoprotein uptake by human glomerular cells: comparison with skin fibroblasts and HepG2 cells 总被引:3,自引:1,他引:2
Quaschning T; Koniger M; Kramer-Guth A; Greiber S; Pavenstadt H; Nauck M; Schollmeyer P; Wanner C 《Nephrology, dialysis, transplantation》1997,12(12):2528-2536
Background: Currently the mechanisms of glomerular
lipid accumulation are not completely understood. The present study
characterizes the mechanisms of lipid uptake by glomerular cells. Since
renal diseases are frequently associated with an accumulation of
apoE-containing triglyceride-rich lipoproteins, we were interested to
investigate whether glomerular epithelial or mesangial cells possess VLDL
receptors besides the well established LDL receptors.
Methods: Uptake kinetics of
125I-labelled very-low-density lipoproteins (VLDL)
and low-density lipoproteins (LDL) in human glomerular epithelial and
mesangial cells were compared to lipid uptake in cells with established
receptor status, i.e. human skin fibroblasts and HepG2 cells.
Results: Glomerular epithelial cells, mesangial cells,
and skin fibroblasts as well as hepatocytes express VLDL receptor mRNA,
indicating that they exhibit VLDL receptors. LDL uptake in glomerular
epithelial cells, mesangial cells and skin fibroblasts occurred with a
lower specificity than in HepG2 cells (-25%). No differences were found for
the specificity of LDL uptake. VLDL uptake in HepG2 cells was inhibited
more effectively with VLDL than with LDL. In skin fibroblasts, glomerular
epithelial and mesangial cells, VLDL and LDL were equally effective
inhibitors of VLDL uptake. The degradation-uptake ratio of VLDL in
glomerular cells was elevated 50% compared to HepG2 cells, suggesting
highly efficient intracellular lipoprotein turnover in these cells.
Conclusion: We conclude that glomerular epithelial and
mesangial cells as well as skin fibroblasts and HepG2 exhibit VLDL
receptors additionally to their LDL receptors, even though the regulation
of VLDL receptor in HepG2 cells seems to differ from the regulation in
glomerular epithelial and mesangial cells. The high
degradation-uptake-ratio in these renal cells suggests the presence of an
effective clearance pathway which might serve as protection against
lipoprotein accumulation. 相似文献
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Uncomplicated hypospadias was found in eight members of a large, consanguineous Bedouin family. Virilization and fertility were normal in the only postpubertal individual. The inheritance is most likely autosomal recessive and we suggest that in some of the familial cases in which polygenic or multifactorial inheritance was previously proposed, homozygosity for recessive genes may be responsible for the increased risk to siblings. Dominantly transmitted hypertelorism with diastema was an independent and coincidental finding in this family. 相似文献
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M Bek K G Fischer S Greiber C Hupfer P Mundel H Pavenst?dt 《Nephrology, dialysis, transplantation》1999,14(3):581-587
BACKGROUND: Dopamine influences glomerular haemodynamics and dopamine receptors have been demonstrated in the glomerulus, but little is known about the cellular effects of dopamine in glomerular cells. The aim of this study was to investigate the influence of dopamine on the cellular functions of podocytes. METHODS: The effect of dopamine on membrane voltage was investigated in differentiated mouse podocytes. The membrane voltage was measured using the patch clamp technique. Reverse transcribed-polymerase chain reaction (RT-PCR) studies were performed to investigate the expression of dopamine receptor mRNA in mouse glomeruli and podocytes. RESULTS: The addition of dopamine (100 nM-1000 microM) caused a concentration-dependent depolarization of podocytes (EC50 is approximate to 10 microM). Like dopamine, the selective agonist of the D1-like receptor, SKF 82958, depolarized podocytes in a concentration-dependent manner. (EC50 is approximate to 50 microM). SKF 82958 stimulated a time-and concentration-dependent accumulation of cyclic adenosine 3',5'-monophosphate (cAMP) in podocytes (EC50 is approximate to microM). RT-PCR studies with primers derived from mouse sequences amplified mouse mRNA for the D1-like and the D2-like receptor in glomeruli, which were obtained by the sieve technique, whereas only mRNA for the D1-like receptor was detected in cultured mouse podocytes. CONCLUSION: The data indicate that dopamine induces a cAMP-dependent depolarization via a D1-like receptor in podocytes. 相似文献
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