Vasko, Radovan

[["dc.bibliographiccitation.firstpage","222"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Therapeutic Apheresis and Dialysis"],["dc.bibliographiccitation.lastpage","225"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Vasko, Radovan"],["dc.contributor.author","Koziolek, Michael"],["dc.contributor.author","Fuezesi, Laszlo"],["dc.contributor.author","Koenig, Fatima"],["dc.contributor.author","Strutz, Frank M."],["dc.contributor.author","Mueller, Gerhard Anton"],["dc.date.accessioned","2018-11-07T08:44:57Z"],["dc.date.available","2018-11-07T08:44:57Z"],["dc.date.issued","2010"],["dc.description.abstract","We report a case of a 27-year-old female with thrombotic microangiopathy as an initial presentation of an unexpected disseminated gastric carcinoma. Based on clinical features and laboratory findings, thrombotic thrombocytopenic purpura (TTP) was diagnosed and plasma exchange started. However, she had responded poorly to plasmapheresis, developed multiorgan failure and died 72 h after admission. Autopsy revealed a disseminated gastric adenocarcinoma with metastatic infiltration of dura mater and disseminated tumor cell emboli in the microcirculation of the liver and lungs. Genetic analysis revealed amplification of KRAS oncogene and aberrations in DCC tumor suppressor gene, which can explain the young age and advanced disease at presentation. The role of plasmapheresis in cancer-associated TTP is uncertain. Plasmapheresis delivers fresh coagulation factors and may theoretically promote microthrombi formation and lead to worsening of the disease. Thrombotic thrombocytopenic purpura seems to be a late and prognostically poor manifestation of an underlying malignancy, with majority of patients dying soon after diagnosis. It is important to be aware of this possibility in thrombotic microangiopathy, especially with atypical features and poor response to standard treatment."],["dc.identifier.doi","10.1111/j.1744-9987.2009.00710.x"],["dc.identifier.isi","000276036600014"],["dc.identifier.pmid","20438546"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20315"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell Publishing, Inc"],["dc.relation.issn","1744-9979"],["dc.title","Fulminant Plasmapheresis-refractory Thrombotic Microangiopathy Associated With Advanced Gastric Cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","96"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Kidney International"],["dc.bibliographiccitation.lastpage","109"],["dc.bibliographiccitation.volume","68"],["dc.contributor.author","Heeg, MHJ"],["dc.contributor.author","Koziolek, Michael Johann"],["dc.contributor.author","Vasko, Radovan"],["dc.contributor.author","Schaefer, L."],["dc.contributor.author","Sharma, K."],["dc.contributor.author","Mueller, Gerhard A."],["dc.contributor.author","Strutz, Frank M."],["dc.date.accessioned","2018-11-07T09:23:04Z"],["dc.date.available","2018-11-07T09:23:04Z"],["dc.date.issued","2005"],["dc.description.abstract","Background. The peptide hormone relaxin has been demonstrated to exert antifibrotic effects in renal and extrarenal tissues. The aims of this study were to identify potential anti-fibrotic effects of relaxin on human renal fibroblasts in vitro and to analyze their mechanisms. Methods. All experiments were performed in established renal fibroblast cell lines and in primary cortical fibroblasts. Effects of relaxin were analyzed on cell proliferation, apoptosis, activation of renal fibroblasts, synthesis and secretion of collagen type I and fibronectin, as well as on the secretion of matrix metalloproteinases (MMPs). Effects on transforming growth factor-beta 1 (TGF-beta 1) receptor binding were analyzed by flow cytometry and on TGF-beta 1 signal transduction by immunoblot analyses for Smad4 and 7, translocation from cytosol to nucleus for Smad2 and 3 as well as for phosphorylated and unphosphorylated forms of p38, c-Jun NH2 terminal kinase (JNK) and extracellular-regulated protein kinase (ERK). Finally, specific siRNAs for Smad2 and 3 were applied to assess the signal transduction pathway. Results. After stimulation with relaxin, tyrosine phosphorylation of a 220 kD protein was demonstrated, indicating interaction with the receptor. Relaxin had only modest inhibitory effects on cell proliferation, and no effects on apoptosis. Conversely, relaxin exerted robust effects on TGF-beta 1-induced fibroblast to myofibroblast transformation as well as on matrix synthesis and secretion even at the smallest dose tested. The secretion of MMP-2 and MMP-9 was induced noticeably by all investigated relaxin concentrations. TGF-beta 1 receptor binding was not influenced by relaxin; however, it prevented Smad2 phosphorylation, translocation to nucleus, and complex formation between Smad2 and 3 indicating a possible interaction with TGF-beta 1 signaling. These findings were corroborated by studies using siRNAs to Smad2 and 3 where siRNA to Smad2 but not to Smad3 inhibited the TGF-beta 1 induction of fibronectin synthesis. There was no influence of relaxin on intracellular Smad3, Smad4, and Smad7 translocation or phosphorylation of mitogen-activated protein (MAP) kinases. Conclusion. Relaxin is a potent inhibitor of TGF-beta 1-induced extracellular matrix (ECM) synthesis and secretion as well as fibroblast activation. Furthermore, it induces ECM degradation by induction of MMP-2 and MMP-9. These effects are mediated, at least in part, by inhibition of TGF-beta 1 signaling."],["dc.identifier.doi","10.1111/j.1523-1755.2005.00384.x"],["dc.identifier.isi","000229636800009"],["dc.identifier.pmid","15954899"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29491"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing Inc"],["dc.relation.issn","0085-2538"],["dc.title","The antifibrotic effects of relaxin in human renal fibroblasts are mediated in part by inhibition of the Smad2 pathway"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","51"],["dc.bibliographiccitation.journal","Nephrology Dialysis Transplantation"],["dc.bibliographiccitation.lastpage","52"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Vasko, Radovan"],["dc.contributor.author","Koziolek, Michael"],["dc.contributor.author","Kurz, Bernd"],["dc.contributor.author","Mueller, Gerhard Anton"],["dc.contributor.author","Strutz, Frank M."],["dc.date.accessioned","2018-11-07T09:38:39Z"],["dc.date.available","2018-11-07T09:38:39Z"],["dc.date.issued","2006"],["dc.identifier.isi","000239919000138"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33113"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.eventlocation","Glasgow, SCOTLAND"],["dc.relation.issn","0931-0509"],["dc.title","Hyperglycemia induces the expression of basic fibroblast growth factor (FGF-2) through activation of the protein kinase C beta-1 and p65 nf-kappa b in human renal fibroblasts"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1170"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Rheumatology"],["dc.bibliographiccitation.lastpage","1172"],["dc.bibliographiccitation.volume","48"],["dc.contributor.author","Buhl, Timo"],["dc.contributor.author","Bertsch, Hans-Peter"],["dc.contributor.author","Raab, Bjoern-Werner"],["dc.contributor.author","Kaune, Kjell Matthias"],["dc.contributor.author","Vasko, Radovan"],["dc.contributor.author","Strutz, Frank M."],["dc.contributor.author","Schoen, Michael Peter"],["dc.contributor.author","Lippert, Undine"],["dc.date.accessioned","2018-11-07T11:25:29Z"],["dc.date.available","2018-11-07T11:25:29Z"],["dc.date.issued","2009"],["dc.identifier.doi","10.1093/rheumatology/kep173"],["dc.identifier.isi","000270133800034"],["dc.identifier.pmid","19553374"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56632"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1462-0324"],["dc.title","Fulminant polyarteritis nodosa associated with acute myeloid leukaemia resulted in bilateral lower leg amputation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","684"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Nephrology Dialysis Transplantation"],["dc.bibliographiccitation.lastpage","698"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Koziolek, Michael Johann"],["dc.contributor.author","Mueller, Gerhard-Anton"],["dc.contributor.author","Zapf, Antonia"],["dc.contributor.author","Patschan, Daniel"],["dc.contributor.author","Schmid, Holger"],["dc.contributor.author","Cohen, Clemens D."],["dc.contributor.author","Koschnick, Stefan"],["dc.contributor.author","Vasko, Radovan"],["dc.contributor.author","Bramlage, Carsten"],["dc.contributor.author","Strutz, Frank M."],["dc.date.accessioned","2018-11-07T08:45:39Z"],["dc.date.available","2018-11-07T08:45:39Z"],["dc.date.issued","2010"],["dc.description.abstract","Methods. Functional data were analysed in folic acid nephropathy (FAN) at different time points (up to day 142 after induction). Immunostaining for CX3C-L, CD3, S100A4, collagen type I, fibronectin, alpha-smooth muscle actin, Tamm-horsfall protein, aquaporin 1 and 2 as well as quantitative real-time PCR (qRT-PCR) for CX3C-L, CX3C-R and fibroblast-specific protein 1 (FSP-1) were performed. Additionally, regulatory mechanisms and functional activity of CX3C-L in murine proximal and distal tubular epithelial cells as well as in fibroblasts were investigated. Results. CX3C-L/GAPDH ratio was upregulated in FAN 3.4-fold at day 7 further increasing up to 7.1-fold at day 106. The expression of mRNA CX3C-L correlated well with CX3C-R (R-2 = 0.96), the number of infiltrating CD3+ cells (R-2 = 0.60) and the degree of tubulointerstitial fibrosis (R-2 = 0.56) and moderately with FSP-1 (R-2 = 0.33). Interleukin-1 beta, tumour necrosis factor-alpha, transforming growth factor-beta as well as the reactive oxygen species (ROS) H2O2 were identified by qRT-PCR as inductors of CX3C-L/fractalkine (FKN) in tubular epithelial cells. Functionally, CX3C-L/FKN chemoattracts peripheral blood mononuclear cells, activates several aspects of fibrogenesis and induces the mitogen-activated protein kinases in renal fibroblasts. Conclusions. In FAN, there is a good correlation between the expression of CX3C-L with markers of interstitial inflammation and fibrosis which may result from upregulation by pro-inflammatory and pro-fibrotic cytokines as well as by ROS in tubular epithelial cells. The FKN system may promote renal inflammation and renal fibrogenesis."],["dc.description.sponsorship","Georg-August-University"],["dc.identifier.doi","10.1093/ndt/gfp602"],["dc.identifier.isi","000274987800011"],["dc.identifier.pmid","19934081"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20497"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0931-0509"],["dc.title","Role of CX3C-chemokine CX3C-L/fractalkine expression in a model of slowly progressive renal failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","F1452"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY"],["dc.bibliographiccitation.lastpage","F1463"],["dc.bibliographiccitation.volume","296"],["dc.contributor.author","Vasko, Radovan"],["dc.contributor.author","Koziolek, Michael"],["dc.contributor.author","Ikehata, Masami"],["dc.contributor.author","Rastaldi, Maria Pia"],["dc.contributor.author","Jung, Klaus"],["dc.contributor.author","Schmid, Holger"],["dc.contributor.author","Kretzler, Matthias"],["dc.contributor.author","Mueller, Gerhard Anton"],["dc.contributor.author","Strutz, Frank M."],["dc.date.accessioned","2018-11-07T08:28:53Z"],["dc.date.available","2018-11-07T08:28:53Z"],["dc.date.issued","2009"],["dc.description.abstract","Vasko R, Koziolek M, Ikehata M, Rastaldi MP, Jung K, Schmid H, Kretzler M, Muller GA, Strutz F. Role of basic fibroblast growth factor (FGF-2) in diabetic nephropathy and mechanisms of its induction by hyperglycemia in human renal fibroblasts. Am J Physiol Renal Physiol 296: F1452-F1463, 2009. First published March 11, 2009; doi: 10.1152/ajprenal.90352.2008.-Basic fibroblast growth factor (FGF-2) plays a role in renal fibrogenesis, although its potential implications for tubulointerstitial involvement in diabetic nephropathy are unknown. We evaluated the expression of FGF-2 in kidney biopsies from patients with diabetic nephropathy and studied the mechanisms of its induction in human renal fibroblasts under hyperglycemia. Tubulointerstitial expression of FGF-2 was significantly upregulated in diabetic nephropathy compared with control kidneys with a good correlation to the degree of the injury. Fibroblasts cultivated in high glucose displayed increased FGF-2 mRNA as well as protein synthesis and secretion compared with normal glucose. Proliferation rates under hyperglycemia were significantly higher and could be almost completely inhibited by addition of a neutralizing FGF-2 antibody. Alterations in proliferation were associated with changes in p27(kip1) expression. Hyperglycemia induced the expression of PKC-beta 1 and PKC-beta 2; however, only inhibition of PKC-beta 1 but not PKC-beta 2 led to a significant decrease of FGF-2 levels. Relevance of the culture findings and functional association was corroborated by colocalization of FGF-2 and PKC-beta in human diabetic kidneys in vivo. High glucose stimulated fibronectin synthesis and secretion, which could be substantially prevented by inhibition of PKC-beta 1 and to a lesser extent by inhibiting the FGF-2. Expression of active phosphorylated form of p38 mitogen-activated protein kinase was upregulated under hyperglycemia; however, its inhibition had no effects on FGF-2 synthesis. Our results implicate a role of FGF-2 in high glucose-altered molecular signaling in pathogenesis of diabetic renal disease."],["dc.description.sponsorship","EU [QLG1-2002-01215]; Georg-August-University"],["dc.identifier.doi","10.1152/ajprenal.90352.2008"],["dc.identifier.isi","000266342700024"],["dc.identifier.pmid","19279131"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16522"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Physiological Soc"],["dc.relation.issn","1931-857X"],["dc.title","Role of basic fibroblast growth factor (FGF-2) in diabetic nephropathy and mechanisms of its induction by hyperglycemia in human renal fibroblasts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","128A"],["dc.bibliographiccitation.journal","Journal of the American Society of Nephrology"],["dc.bibliographiccitation.lastpage","129A"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Vasko, Radovan"],["dc.contributor.author","Schmid, H."],["dc.contributor.author","Kretzler, M."],["dc.contributor.author","Mueller, Georg Anton"],["dc.contributor.author","Strutz, Frank M."],["dc.date.accessioned","2018-11-07T10:35:06Z"],["dc.date.available","2018-11-07T10:35:06Z"],["dc.date.issued","2003"],["dc.identifier.isi","000186219100605"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45018"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","36th Annual Meeting of the American-Society-of-Nephrology"],["dc.relation.eventlocation","SAN DIEGO, CALIFORNIA"],["dc.relation.issn","1046-6673"],["dc.title","Basic fibroblast growth factor (FGF-2) expression is strongly upregulated in human diabetic nephropathy and mediates hyperglycemia induced proliferation in cortical fibroblasts."],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]