Tumani, Hayrettin

[["dc.bibliographiccitation.firstpage","822"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","European Journal of Neurology"],["dc.bibliographiccitation.lastpage","826"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Millonig, A."],["dc.contributor.author","Dressel, Alexander"],["dc.contributor.author","Bahner, D."],["dc.contributor.author","Bitsch, Annette"],["dc.contributor.author","Bogumil, T."],["dc.contributor.author","Elitok, E."],["dc.contributor.author","Kitze, Bernd"],["dc.contributor.author","Tumani, Hayrettin"],["dc.contributor.author","Weber, F."],["dc.contributor.author","Gneiss, C."],["dc.contributor.author","Deisenhammer, Florian"],["dc.date.accessioned","2018-11-07T11:12:24Z"],["dc.date.available","2018-11-07T11:12:24Z"],["dc.date.issued","2008"],["dc.description.abstract","Background and purpose: Interferon beta (IFN beta) preparations have some effect on the progressive phase of multiple sclerosis ( MS). This limited effect might be partially because of a certain number of IFN beta non-responders. Myxovirus resistance protein A (MxA)-a marker of IFN beta bioactivity - was correlated with the clinical response during an uncontrolled trial, investigating the safety of IFN beta-1 beta in primary progressive (PPMS) patients. Methods: Twenty PPMS were treated with IFN beta-1 beta (s.c.) for 1 year. Blood samples were taken before and 1, 2, 3, 6, 9, 12, and 15 months after treatment initiation and MxA protein levels were measured. Patients were clinically evaluated by EDSS and the more sensitive Incapacity Status Scale (ISS) and stratified in a stable and a progressing group. Results: Using ISS criteria, 11 patients remained stable and nine patients progressed during treatment. The mean area under the curve of log MxA levels during treatment were significantly higher in stable than in progressing patients (10.87 vs. 5.99; P = 0.002). Conclusion: A good biological response to IFNb might be associated with a better clinical effect of this drug and could be helpful in future clinical studies for early identification of treatment responders."],["dc.identifier.doi","10.1111/j.1468-1331.2008.02190.x"],["dc.identifier.isi","000257715400022"],["dc.identifier.pmid","18549400"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53656"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1351-5101"],["dc.title","MxA protein - an interferon beta biomarker in primary progressive multiple sclerosis patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1498"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Journal of Neurology"],["dc.bibliographiccitation.lastpage","1501"],["dc.bibliographiccitation.volume","251"],["dc.contributor.author","Bitsch, Annette"],["dc.contributor.author","Dressel, Alexander"],["dc.contributor.author","Meier, K."],["dc.contributor.author","Bogumil, T."],["dc.contributor.author","Deisenhammer, Florian"],["dc.contributor.author","Tumani, Hayrettin"],["dc.contributor.author","Kitze, Bernd"],["dc.contributor.author","Poser, Sigrid"],["dc.contributor.author","Weber, F."],["dc.date.accessioned","2018-11-07T10:43:31Z"],["dc.date.available","2018-11-07T10:43:31Z"],["dc.date.issued","2004"],["dc.description.abstract","We conducted an open-labeled clinical trial of interferon beta-1b (IFNB) treatment in 20 patients with primary progressive multiple sclerosis (PPMS) and longitudinally monitored autoantibodies against double-stranded DNA (dsDNA), thyroid peroxidase (TPO),myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), synapsin and S-100B. Before treatment, one patient had elevated TPO antibodies, four patients had elevated antibodies against S-100B, two patients against MOG or synapsin and one patient against MBP. In two patients we observed a continuous increase of dsDNA or TPO antibodies above the normal range. This rise paralleled IFNB treatment. In addition, 11 of 20 patients developed neutralizing antibodies against IFNB. There was no increase of autoantibodies directed against central nervous system antigens. Like patients with relapsing remitting or secondary progressive multiple sclerosis, PPMS patients may be at risk of an autoimmune response during IFNB treatment."],["dc.identifier.doi","10.1007/s00415-004-0580-3"],["dc.identifier.isi","000226302000010"],["dc.identifier.pmid","15645350"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47070"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","0340-5354"],["dc.title","Autoantibody synthesis in primary progressive multiple sclerosis patients treated with interferon beta-1b"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","205"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Neuroscience Letters"],["dc.bibliographiccitation.lastpage","208"],["dc.bibliographiccitation.volume","289"],["dc.contributor.author","Dabbert, D."],["dc.contributor.author","Rosner, S."],["dc.contributor.author","Kramer, M."],["dc.contributor.author","Scholl, U."],["dc.contributor.author","Tumani, Hayrettin"],["dc.contributor.author","Mader, M."],["dc.contributor.author","Weber, F."],["dc.date.accessioned","2018-11-07T10:33:43Z"],["dc.date.available","2018-11-07T10:33:43Z"],["dc.date.issued","2000"],["dc.description.abstract","Glatiramer acetate (GA), represents an established treatment of relapsing/remitting multiple sclerosis (MS). The mechanisms responsible for the effect of GA are not fully understood. We generated GA-, myelin basic protein (MBP)- and purified protein derivative (PPD)-specific T cell lines from three MS patients and one healthy donor. The GA-specific lines were CD3(+), CD4(+), CD8(-) and produced tumor-necrosis-factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-10 (IL-10) after stimulation with GA in the presence of irradiated peripheral blood mononuclear cells. MBP-specific T cell lines showed an identical phenotype and secreted TNF-alpha, IFN-gamma, IL-4, IL-10, but not IL-6. Co-culture experiments demonstrated, that GA-specific T cell lines have the capability to suppress the proliferation of MBP-specific T cell lines. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved."],["dc.identifier.doi","10.1016/S0304-3940(00)01289-1"],["dc.identifier.isi","000088629600013"],["dc.identifier.pmid","10961665"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44680"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Sci Ireland Ltd"],["dc.relation.issn","0304-3940"],["dc.title","Glatiramer acetate (copolymer-1)-specific, human T cell lines: cytokine profile and suppression of T cell lines reactive against myelin basic protein"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1224"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Journal of Neurology"],["dc.bibliographiccitation.lastpage","1228"],["dc.bibliographiccitation.volume","250"],["dc.contributor.author","Yushchenko, M."],["dc.contributor.author","Mader, M."],["dc.contributor.author","Elitok, E."],["dc.contributor.author","Bitsch, Annette"],["dc.contributor.author","Dressel, Alexander"],["dc.contributor.author","Tumani, Hayrettin"],["dc.contributor.author","Bogumil, T."],["dc.contributor.author","Kitze, Bernd"],["dc.contributor.author","Poser, Sigrid"],["dc.contributor.author","Weber, F."],["dc.date.accessioned","2018-11-07T10:35:52Z"],["dc.date.available","2018-11-07T10:35:52Z"],["dc.date.issued","2003"],["dc.description.abstract","Recent reports have shown that matrix-metalloproteinases (MMPs) facilitate T-cell migration into the CNS and play a role in disruption of the blood-brain-barrier and myelin breakdown. An increase of MMP-9 serum levels predicts disease activity in relapsing remitting multiple sclerosis (RRMS). Interferon-beta (IFN-beta), which is an established treatment for RRMS, inhibits T-cell migration in vitro in parallel with the downregulation of MMP expression. Only limited data are available for primary progressive multiple sclerosis (PPMS) which differs in demographic and immunological aspects as well as in MRI criteria from RRMS. In this study, 19 patients with laboratory-supported definite PPMS were treated with 8 x 10(6) IU IFN-beta1b (Betaferon(R)) subcutaneously every other day. Serum was collected before treatment and on months 1, 2, 3,6 and 9 during treatment. Levels of MMP-9 and of its natural inhibitor known as tissue-inhibitor of matrix-metalloproteinase-1 (TIMP-1) were quantified by ELISA. In addition MMP-2 serum levels were determined by zymography. 19 healthy volunteers served as controls. Before treatment serum levels of MMP-9 were elevated in patients with PPMS compared with controls, whereas there was no difference in TIMP-1 serum levels. During treatment with IFN-beta1b the concentration of MMP-9 in the serum of 18 out of 19 PPMS patients decreased, whereas serum levels of MMP-2 and TIMP-1 remained nearly unaffected. Our results demonstrate that the MMP-9 to TIMP-1 ratio in patients with PPMS is elevated in comparison with healthy controls. The suppression of MMP-9 by IFN-beta1b indicates that this drug is immunomodulatory active in PPMS patients. Further studies are necessary to test if IFN-beta exerts a beneficial effect in PPMS."],["dc.identifier.doi","10.1007/s00415-003-0191-4"],["dc.identifier.isi","000186231900015"],["dc.identifier.pmid","14586607"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45190"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Dr Dietrich Steinkopff Verlag"],["dc.relation.issn","0340-5354"],["dc.title","Interferon-beta-1b decreased matrix metalloproteinase-9 serum levels in primary progressive multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","PII S0304-3940(02)00311-7"],["dc.bibliographiccitation.firstpage","125"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neuroscience Letters"],["dc.bibliographiccitation.lastpage","128"],["dc.bibliographiccitation.volume","326"],["dc.contributor.author","Bahner, D."],["dc.contributor.author","Klucke, C."],["dc.contributor.author","Kitze, Bernd"],["dc.contributor.author","Elitok, E."],["dc.contributor.author","Bogumil, T."],["dc.contributor.author","Dressel, Alexander"],["dc.contributor.author","Tumani, Hayrettin"],["dc.contributor.author","Weber, F."],["dc.contributor.author","Poser, Sigrid"],["dc.contributor.author","Bitsch, Annette"],["dc.date.accessioned","2018-11-07T10:24:34Z"],["dc.date.available","2018-11-07T10:24:34Z"],["dc.date.issued","2002"],["dc.description.abstract","Serum levels of interleukin-12 heterodimer (IL-12p70) and its homodimeric subunit (IL-12p40) were analyzed by enzyme-linked immunosorbent assay in 18 patients with primary progressive multiple sclerosis (MS) during 3 months before and 3 months under treatment with interferon-beta-1b (IFNbeta-1b, Betaferon(TM), eight million units (MIU) every other day subcutaneously). Median IL-12p40 levels in MS patients before treatment (66.5 and 63.9 pg/ml) were not elevated compared to 18 healthy controls. IL-12p40 significantly increased during treatment (P < 0.0001, median 105.3 pg/ml after 1 month and 95.3 pg/ml after 3 months). Detectable serum levels of IL-12p70 before therapy were only found in one patient. IL-12p70 did not increase during treatment. These data show that immunological processes may also play a role in primary progressive MS and that IFNbeta-1b has an immunomodulating effect in this particular MS subtype. (C) 2002 Published by Elsevier Science Ireland Ltd."],["dc.identifier.doi","10.1016/S0304-3940(02)00311-7"],["dc.identifier.isi","000176623000014"],["dc.identifier.pmid","12057844"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42687"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Ireland Ltd"],["dc.relation.issn","0304-3940"],["dc.title","Interferon-beta-1b increases serum interleukin-12 p40 levels in primary progressive multiple sclerosis patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","PII S0165-5728(02)00353-3"],["dc.bibliographiccitation.firstpage","193"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","197"],["dc.bibliographiccitation.volume","133"],["dc.contributor.author","Brettschneider, Johannes"],["dc.contributor.author","Ecker, D."],["dc.contributor.author","Bitsch, Annette"],["dc.contributor.author","Bahner, D."],["dc.contributor.author","Bogumil, T."],["dc.contributor.author","Dressel, Alexander"],["dc.contributor.author","Elitok, E."],["dc.contributor.author","Kitze, Bernd"],["dc.contributor.author","Poser, Sigrid"],["dc.contributor.author","Weber, F."],["dc.contributor.author","Tumani, Hayrettin"],["dc.date.accessioned","2018-11-07T09:46:11Z"],["dc.date.available","2018-11-07T09:46:11Z"],["dc.date.issued","2002"],["dc.description.abstract","The soluble form of the CD14 molecule (sCD14), a macrophage activity marker, was measured in the plasma of 17 patients with primary progressive multiple sclerosis (PPMS) and 20 patients with relapsing remitting MS (RRMS). In patients with PPMS, sCD14 levels were determined before and after treatment with interferon beta (IFNB). In both PPMS and in RRMS, sCD14 levels were significantly elevated compared to healthy controls. In patients with PPMS, sCD14 levels increased significantly during the first 3 months of IFNB therapy, then slightly decreased, but still remained elevated compared with levels before therapy. Therefore, the elevated sCD14 levels may be a marker in evaluating biological response to IFNB therapy. (C) 2002 Elsevier Science B.V. All rights reserved."],["dc.identifier.doi","10.1016/S0165-5728(02)00353-3"],["dc.identifier.isi","000179874700020"],["dc.identifier.pmid","12446022"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34811"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0165-5728"],["dc.title","The macrophage activity marker sCD14 is increased in patients with multiple sclerosis and upregulated by interferon beta-1b"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","244"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","251"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Yushchenko, M."],["dc.contributor.author","Weber, F."],["dc.contributor.author","Mader, M."],["dc.contributor.author","Scholl, U."],["dc.contributor.author","Maliszewska, M."],["dc.contributor.author","Tumani, Hayrettin"],["dc.contributor.author","Felgenhauer, K."],["dc.contributor.author","Beuche, W."],["dc.date.accessioned","2018-11-07T09:14:24Z"],["dc.date.available","2018-11-07T09:14:24Z"],["dc.date.issued","2000"],["dc.description.abstract","Matrix metalloproteinase-9 (MMP-9) was investigated by enzyme-linked immunosorbent assay (ELISA) and zymography in III paired CSF and serum samples from patients with various neurological disorders. In 20 patients with blood-brain barrier (BBB) impairment but normal CSF cell count, elevated levels of MMP-9 were not observed by ELISA measurement. Another 11 patients characterized in the same way, exhibited only slightly increased MMP-9 levels. In contrast, in 12 patients with intact BBB but elevated CSF cell count, MMP-9 was increased too. It was shown by the more sensitive zymography that MMP-9 increased if CSF cell count exceeded five cells per mul. Spearman rank statistics revealed that MMP-9 concentration in CSF correlated with CSF cell count (r=0.755; P<0.0001), but not with CSF/serum albumin ratio (Q(AIb)) (r=0.212; P=0.057), a measure for BBB impairment, Moreover, the CSF/serum MMP-9 ratio (Q(MMP-9)) did not correlate with Q(AIb)(r=0.192; P=0.100). By use of a Boyden chamber, in which granulocytes migrated through a reconstituted basement membrane, it was demonstrated that the MMP-9 concentration in the lower chamber correlated very significantly with the number of accumulated cells (r(2)=0.7692; P<0.0001). The meaning of the increase of MMP-9 in CSF is critically discussed. (C) 2000 Elsevier Science B.V. All rights reserved."],["dc.identifier.doi","10.1016/S0165-5728(00)00339-8"],["dc.identifier.isi","000090030800028"],["dc.identifier.pmid","11024556"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27400"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0165-5728"],["dc.title","Matrix metalloproteinase-9 (MMP-9) in human cerebrospinal fluid (CSF): elevated levels are primarily related to CSF cell count"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","368"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Acta Neurologica Scandinavica"],["dc.bibliographiccitation.lastpage","373"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Dressel, Alexander"],["dc.contributor.author","Kolb, A. K."],["dc.contributor.author","Elitok, E."],["dc.contributor.author","Bitsch, Annette"],["dc.contributor.author","Bogumil, T."],["dc.contributor.author","Kitze, Bernd"],["dc.contributor.author","Tumani, Hayrettin"],["dc.contributor.author","Weber, F."],["dc.date.accessioned","2018-11-07T08:51:21Z"],["dc.date.available","2018-11-07T08:51:21Z"],["dc.date.issued","2006"],["dc.description.abstract","Objectives - It is unknown whether the immunological effects of binterferon (IFN-beta) differ in primary progressive multiple sclerosis (PPMS) when compared with relapsing - remitting multiple sclerosis (RRMS). Therefore, we investigated the effects of IFN-beta 1b treatment in PPMS on proliferation and cytokine pattern of peripheral blood mononuclear cells (PBMC) and interleukin-10 (IL-10) serum level. Methods - Eighteen patients were treated with IFN-b1b for 12 months in an open-label trial. Serum and PBMC were collected longitudinally. Results - Interleukin-10 serum levels increased ( P 0.02) during treatment. Tumor necrosis factor-alpha was increased in anti CD3 (OKT3) antibody stimulated PBMC during treatment (P = 0.04), whereas secretion of IL-10 was decreased in OKT3 ( P 0.04), but increased in concavalin A stimulated PBMC ( P 0.02). Conclusions - Interleukin-10 serum levels rose in IFN-b1 beta-treated patients as has been observed in RRMS. The changes in cytokine patterns secreted by T-lymphocytes of PPMS patients, however, differ from effects observed in RRMS supporting the hypothesis that PPMS differs in some immunological aspects from RRMS."],["dc.identifier.doi","10.1111/j.1600-0404.2006.00700.x"],["dc.identifier.isi","000241733500002"],["dc.identifier.pmid","17083335"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21913"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0001-6314"],["dc.title","Interferon-beta 1b treatment modulates cytokines in patients with primary progressive multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","386"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Acta Neurologica Scandinavica"],["dc.bibliographiccitation.lastpage","392"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Bitsch, Annette"],["dc.contributor.author","Bahner, D."],["dc.contributor.author","Wachter, C."],["dc.contributor.author","Elitok, E."],["dc.contributor.author","Bogumil, T."],["dc.contributor.author","Dressel, Alexander"],["dc.contributor.author","Polak, T."],["dc.contributor.author","Tumani, Hayrettin"],["dc.contributor.author","Weber, F."],["dc.contributor.author","Poser, Sigrid"],["dc.contributor.author","Kitze, Bernd"],["dc.date.accessioned","2018-11-07T10:43:14Z"],["dc.date.available","2018-11-07T10:43:14Z"],["dc.date.issued","2004"],["dc.description.abstract","Endothelial activation is a key feature of multiple sclerosis (MS) pathogenesis. It is modulated by interferon beta-1b (IFNB-1b) treatment in relapsing-remitting MS (RRMS) patients. This particular pharmacodynamic effect still has to be proven in primary progressive MS (PPMS). In the current study, serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and sE-selectin were analyzed longitudinally in 18 PPMS patients before, during and after 12 months of treatment with IFNB-1b. During drug therapy there was a significant early and sustained increase of sVCAM-1 (overall P < 0.0001). Flu-like symptoms induced by IFNB-1b and also concomitant infections were associated with higher sVCAM-1 levels. Neutralizing antibodies to IFNB-1b were associated with lower sVCAM-1 levels. In conclusion, IFNB-1b modulates the adhesion cascade in patients with PPMS in a similar way it does in RRMS. Nevertheless, a clinical effect of IFNB in PPMS still has to be proven in a randomized controlled clinical trial."],["dc.identifier.doi","10.1111/j.1600-0404.2004.00347.x"],["dc.identifier.isi","000224904300007"],["dc.identifier.pmid","15527451"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/46999"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Munksgaard"],["dc.relation.issn","0001-6314"],["dc.title","Interferon beta-1b modulates serum sVCAM-1 levels in primary progressive multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]