Müller, Gerhard Anton

[["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","A100"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","MEDIZINISCHE KLINIK"],["dc.bibliographiccitation.lastpage","A101"],["dc.bibliographiccitation.volume","101"],["dc.contributor.author","Koziolek, Michael Johann"],["dc.contributor.author","Scheel, A."],["dc.contributor.author","Bramlage, Carsten Paul"],["dc.contributor.author","Grone, H. J."],["dc.contributor.author","Mueller, Gerhard A."],["dc.contributor.author","Strutz, Frank M."],["dc.date.accessioned","2018-11-07T09:59:01Z"],["dc.date.available","2018-11-07T09:59:01Z"],["dc.date.issued","2006"],["dc.identifier.isi","000237562000323"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37491"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Urban & Vogel"],["dc.publisher.place","Munich"],["dc.relation.issn","0723-5003"],["dc.title","Effective therapy of a hepatitis-C-associated immunocomplex nephritis by means of cryoprecipitate apheresis and interferon-alpha"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1668"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of the American Society of Nephrology"],["dc.bibliographiccitation.lastpage","1676"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Kondo, S."],["dc.contributor.author","Kagami, S."],["dc.contributor.author","Kido, H."],["dc.contributor.author","Strutz, Frank M."],["dc.contributor.author","Mueller, Gerhard A."],["dc.contributor.author","Kuroda, Y."],["dc.date.accessioned","2018-11-07T08:49:42Z"],["dc.date.available","2018-11-07T08:49:42Z"],["dc.date.issued","2001"],["dc.description.abstract","Renal interstitial fibrosis is characterized by increased proliferation of fibroblasts and excessive accumulation of extracellular matrix. Mast cell tryptase has been implicated in the development of tissue fibrosis in skin and lungs. However, the significance of mast cell tryptase in human renal diseases has not been investigated. The potential role of mast cell-derived tryptase in the development of renal fibrosis was studied using immunohistochemical techniques and cultured human renal fibroblast cell lines. Semiquantitative immunostaining analysis of samples from 70 patients with several renal diseases, including IgA glomerulonephritis (GN) (n = 30), non-IgA GN (n = 5), membranous GN (n = 5), focal segmental glomerulosclerosis (n = 4), minor glomerular abnormalities (n = 5), lupus nephritis (n = 3), and acute or chronic tubulointerstitial nephritis (n = 18), revealed that the degree of renal interstitial fibrosis was well correlated with the number of infiltrating tryptase-positive mast cells (P < 0.01). Mast cells could not be detected in damaged glomeruli in any form of renal disease. [H-3]Thymidine uptake experiments demonstrated that DNA synthesis by cultured renal fibroblasts was increased with the concentration of tryptase (0.5 to 5 nM) coincubated with heparin and was suppressed by coincubation with the protease inhibitors leupeptin and benzamidine hydrochloride. Tryptase alone also increased DNA synthesis by fibroblasts but exhibited less effectiveness, compared with the combination of tryptase and heparin. Conversely, heparin alone suppressed DNA synthesis by fibroblasts. Metabolic [S-35]methionine-labeling experiments with cultured renal fibroblasts indicated that tryptase increased the synthesis of fibronectin and collagen type I, in a dose-dependent manner. These findings suggest that mast cell tryptase plays a role in the proliferation and extracellular matrix protein production of renal interstitial fibroblasts and thus contributes to the development of renal interstitial fibrosis."],["dc.identifier.isi","000170019100010"],["dc.identifier.pmid","11461939"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21527"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1046-6673"],["dc.title","Role of mast cell tryptase in renal interstitial fibrosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Nephrology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Strutz, Frank M."],["dc.contributor.author","Niederkleine, Katrin"],["dc.contributor.author","Mueller, Gerhard Anton"],["dc.contributor.author","Ortiz, Alberto"],["dc.date.accessioned","2018-11-07T10:57:39Z"],["dc.date.available","2018-11-07T10:57:39Z"],["dc.date.issued","2005"],["dc.format.extent","A254"],["dc.identifier.isi","000208633501082"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50304"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.issn","1320-5358"],["dc.title","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)"],["dc.type","conference_abstract"],["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.issue","4"],["dc.bibliographiccitation.journal","MEDIZINISCHE KLINIK"],["dc.bibliographiccitation.volume","101"],["dc.contributor.author","Bramlage, Carsten Paul"],["dc.contributor.author","Schlumbohm, Christina"],["dc.contributor.author","Werner, C."],["dc.contributor.author","Mueller, Gerhard A."],["dc.contributor.author","Strutz, Frank M."],["dc.date.accessioned","2018-11-07T09:58:58Z"],["dc.date.available","2018-11-07T09:58:58Z"],["dc.date.issued","2006"],["dc.format.extent","A100"],["dc.identifier.isi","000237562000321"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37479"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Urban & Vogel"],["dc.publisher.place","Munich"],["dc.relation.issn","0723-5003"],["dc.title","Prenatal programming of arterial hypertonia in common marmosets (EUPEAH): Study design and first results"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1575"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Der Internist"],["dc.bibliographiccitation.lastpage","1578"],["dc.bibliographiccitation.volume","44"],["dc.contributor.author","Strutz, Frank M."],["dc.contributor.author","Scheel, A."],["dc.contributor.author","Koziolek, Michael Johann"],["dc.contributor.author","Kochsiek, T."],["dc.contributor.author","Eiffert, Helmut"],["dc.contributor.author","Mueller, Gerhard A."],["dc.date.accessioned","2018-11-07T10:34:23Z"],["dc.date.available","2018-11-07T10:34:23Z"],["dc.date.issued","2003"],["dc.description.abstract","When confronted by the combination of initial high fever associated with intense malaise, splenomegaly, elevated levels of transaminases, and acute renal failure, consideration must be given to the differential diagnosis of leptospirosis even in Germany. As a rule, the diagnosis is confirmed by serological testing based on the titer curve. Renal involvement is frequent, but usually has a good prognosis, especially if jaundice has not developed. Treatment with doxycycline or penicillin can shorten the disease course and exudation, possibly also the nephritis, or hinder it."],["dc.identifier.doi","10.1007/s00108-003-1090-6"],["dc.identifier.isi","000186903900012"],["dc.identifier.pmid","14689199"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44860"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0020-9554"],["dc.title","\"Idiosyncratic infection\" accompanied by fever, splenomegaly, and acute renal failure in a 24-year-old forestry student"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S202"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Arthritis & Rheumatism"],["dc.bibliographiccitation.lastpage","S203"],["dc.bibliographiccitation.volume","48"],["dc.contributor.author","Scheel, Alexander Konrad"],["dc.contributor.author","Meller, J."],["dc.contributor.author","Vosshenrich, R."],["dc.contributor.author","Kohlhoff, E."],["dc.contributor.author","Mueller, Gerhard A."],["dc.contributor.author","Strutz, Frank M."],["dc.date.accessioned","2018-11-07T10:36:17Z"],["dc.date.available","2018-11-07T10:36:17Z"],["dc.date.issued","2003"],["dc.identifier.isi","000185432800481"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45289"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.publisher.place","New york"],["dc.relation.conference","67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals"],["dc.relation.eventlocation","ORLANDO, FLORIDA"],["dc.relation.issn","0004-3591"],["dc.title","Early aortitis in the elderly: Diagnosis and follow-up"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","579"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Kidney International"],["dc.bibliographiccitation.lastpage","592"],["dc.bibliographiccitation.volume","59"],["dc.contributor.author","Strutz, Frank M."],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Renziehausen, A."],["dc.contributor.author","Raschke, B."],["dc.contributor.author","Becker, V."],["dc.contributor.author","van Kooten, C."],["dc.contributor.author","Mueller, Gerhard A."],["dc.date.accessioned","2018-11-07T09:25:10Z"],["dc.date.available","2018-11-07T09:25:10Z"],["dc.date.issued","2001"],["dc.description.abstract","Background. The prognosis of primary renal disease is often dependent on the degree of tubulointerstitial scarring. Scarring is caused by proliferation and excessive matrix production of renal fibroblasts and possibly other cellular elements. Transforming growth factor-beta (TGF-beta) is the most important cytokine for the induction of matrix synthesis in the kidney. How ever, its effects on renal fibroblast proliferation have not been determined. We have recently demonstrated that the expression of basic fibroblast growth factor (FGF-2) is robustly upregulated in human kidneys with tubulointerstitial fibrosis and that FGF-2 is a potent inducer of fibroblast proliferation. The present study examined the interaction between TGF-beta1 and FGF-2 in human renal fibroblasts. Methods. Experiments were performed on a transformed medullary fibroblast line and on primary cortical kidney and skin fibroblasts isolated from human biopsies. mRNA levels of FGF-2 and TGF-beta1 were analyzed by Northern blot analyses. Changes in protein expression were examined by immunoblots and enzyme-linked immunosorbent assay (ELISA). Bromodeoxyuridine incorporation assays and cell counts were used to analyze cell proliferation. The expression of cell cycle-regulatory proteins cyclin-dependent kinase (cdk) 2 and the cdk inhibitor p27(kipl) Were determined by immunoblots. Results. Stimulation of renal fibroblasts with FGF-2 resulted in no change of TGF-beta1 mRNA expression, whereas incubation of the cells with TGF-beta1 induced FGF-2 mRNA up to 3.51 +/- 0.21-fold after six hours. This increase could be blocked almost completely by the addition of cyclohexamide, indicating that the process is in large part dependent on protein synthesis. The up-regulation in FGF-2 mRNA expression was paralleled by de novo detection of FGF-2 protein in the supernatant. peaking after 12 to 24 hours, as determined by Western blot and ELISA, whereas cellular protein was only increased up to 2.1-fold. Interestingly, both methods detected re lease of FGF-2 protein to the supernatant already at three hours, indicating a role for TGF-beta1 in directly releasing preformed FGF-2. Since TGF-beta1 induced FGF-2, which results in fibroblast proliferation, we hypothesized that TGF-beta1 may cause fibroblast proliferation mediated by FGF-2. This hypothesis was verified by cell proliferation assays demonstrating that stimulation of renal fibroblasts with TGF-beta1 resulted in an up to 3.21 +/- 0.28-fold increase in bromodeoxyuridine incorporation and a 1.95 +/- 0.16-fold increase in cell number after 72 hours. This mitogenic effect of TGF-beta1 could he blocked completely by the addition of a neutralizing antibody to FGF-2 or the tyrosine kinase inhibitor tyrphostin AG1296, which blocks FGF receptor (FGFR) tyrosine kinase activity. Conversely, a neutralizing antibody to epidermal growth factor (EGF) or the tyrphostin B42. which inhibits EGF receptor signal transduction, had no effect. interestingly, a neutralizing antibody to PDGF had only minor effects in primary kidney fibroblasts but reduced TGF-beta1-induced proliferation considerably in primary skin fibroblasts. Finally. TGF-beta1-induced proliferation in kidney fibroblasts was paralleled by a robust increase in cdk 2 protein expression up to 72 hours, whereas p27(kipl), whose activity is maintained by TGF-beta in epithelial cells. was down-regulated up To 48 hours. Conclusions. Our studies demonstrate. to our knowledge for the first time. that TGF-beta1 induces proliferation in human renal fibroblasts and that this process is mediated largely by FGF-2. The induction of proliferation by TGF-beta1 via induction of FGF-2 may play an important role in the autonomy of renal fibroblast growth and thus in the pathogenesis of human fibrogenesis."],["dc.identifier.doi","10.1046/j.1523-1755.2001.059002579.x"],["dc.identifier.isi","000166979200018"],["dc.identifier.pmid","11168939"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29999"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Science Inc"],["dc.publisher.place","Malden"],["dc.relation.eventlocation","SAN ANTONIO, TEXAS"],["dc.relation.issn","0085-2538"],["dc.title","TGF-beta 1 induces proliferation in human renal fibroblasts via induction of basic fibroblast growth factor (FGF-2)"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]