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  • 1
    Keywords: analysis, ANTAGONISM, ARRAY, CELL, cell proliferation, cell signaling, CELL-GROWTH, CELL-PROLIFERATI
    Abstract: CCN proteins affect cell proliferation, migration, attachment, and differentiation. We identified CCN3 as a suppressed gene following platelet-derived growth factor ( PDGF)-BB or -DD stimulation in a cDNA-array analysis of mesangial cells. In vitro growth-arrested mesangial cells overexpressed and secreted CCN3, whereas the addition of the recombinant protein inhibited cell growth. Induction of mesangial cell proliferation by PDGF-BB or the specific PDGF beta-receptor ligand PDGF- DD led to downregulation of CCN3 mRNA, confirming the array study. Specific PDGF alpha-receptor ligands had no effect. CCN3 protein was found in arterial smooth muscle cells, the medullary interstitium, and occasional podocytes in the healthy rat kidney. Glomerular CCN3 was low prior to mesangial proliferation but increased as glomerular cell proliferation subsided during mesangioproliferative glomerulonephritis (GN). Inhibition of PDGF- B in mesangioproliferative disease led to overexpression of glomerular CCN3 mRNA. CCN3 localized mostly to podocytes in human glomeruli, but this expression varied widely in different human glomerulonephritides. Glomerular cell proliferation negatively correlated with CCN3 expression in necrotizing GN. Our study identifies CCN3 as an endogenous inhibitor of mesangial cell growth and a modulator of PDGF- induced mitogenesis
    Type of Publication: Journal article published
    PubMed ID: 17914348
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  • 2
    Keywords: APOPTOSIS ; CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; proliferation ; PROTECTION ; SURVIVAL ; COMBINATION ; human ; INHIBITION ; MODEL ; MODELS ; GENE ; GENES ; TISSUE ; TIME ; NF-KAPPA-B ; ACTIVATION ; RESPONSES ; kidney ; GRAFT ; TRANSPLANTATION ; RAT ; RAT-KIDNEY ; IMMUNE-RESPONSES ; TARGET ; prevention ; UP-REGULATION ; DAMAGE ; MUSCLE ; SMOOTH-MUSCLE CELLS ; IMMUNE-RESPONSE ; REJECTION ; RENAL-ALLOGRAFT ; CHRONIC REJECTION ; ENDOTHELIAL- CELLS ; HEME OXYGENASE-1 ; TRANSPLANTS
    Abstract: Background. Chronic rejection with development of transplant arteriosclerosis is the major culprit involved in loss of kidney allografts. The allografts fate was thought to depend on the intensity of the host immune responses and the potency of immunosuppressive regimens. Recent data suggests that grafts contribute to their own survival by way of up-regulation of "cytoprotective" genes. Methods. We analyzed the expression of four cytoprotective genes. A20. Bcl-2, Bcl-x(L), and heme oxygenase (HO)-1, in three rat renal allograft models of chronic rejection: Fisher 344-Lewis (F344/Lew), Dark Agouti- Brown Norway (DA/BN), and DA-Wistar-Furth (TF). We chose these genes for their known anti-inflammatory and anti-apoptotic function in endothelial cells (EC) and the atheroprotective function of A20 in smooth muscle cells (SMC). Results. Twenty- eight and 9 weeks following transplantation, F344/Lew and DA/BN transplants had stable graft function. Histopathologic analysis showed moderate tissue damage, minimal cellular infiltrates, and preserved vascular integrity correlating with high expression of A20 in SMC. Conversely, impaired allograft function in the DA/WF combination with substantial transplant arteriosclerosis was noted in 60% of the grafts correlating with absent or decreased A20 expression in EC and SMC. In all combinations, expression of HO-1, 136-2, and Bcl-x(L) colocalized with infiltrating cells and was not informative on the graft,status. Conclusions. We demonstrate for the first time a strict correlation between A20 expression in the vessel and the absence of transplant arteriosclerosis in rat kidney- allograft models. This data is similar to data obtained in human kidney allografts and suggests that A20 may represent a novel therapeutic target for the prevention of chronic allograft rejection
    Type of Publication: Journal article published
    PubMed ID: 12544863
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  • 3
    ISSN: 1432-1041
    Keywords: Dihydrotachysterol ; bioavailability ; pharmacokinetics ; human ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The bioavailability of four preparations containing dihydrotachysterol (DHT2) was tested in two separate trials with administration of single, oral doses of 1 mg per individual. The relative bioavailability of corresponding preparations (capsules vs capsules and oral solution vs oral solution) was tested in a randomised, crossover pattern within the same group of volunteers. Two different groups of 24 healthy volunteers took part in each trial. Solution and capsule bioavailability was also compared inter-individually. A new sensitive HPLC-method (quantification limit 0.5 ng · ml-1) was used for the measurement of DHT2 concentration in serum. Three of the preparations tested had a similar bioavailability (mean AUC values of 195.5–223 ng · h · ml-1); the bioavailability of the fourth preparation (A.T.10 oral solution) was considerably lower (mean AUC value 111.5 ng · h · ml-1). The present dosage recommendations of all four preparations are identical. A new dosage recommendation is thus required for the oral solution with low bioavailability (A.T.10).
    Type of Medium: Electronic Resource
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