Gold, Ralf

[["dc.bibliographiccitation.artnumber","e7624"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","PLoS One"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Linker, Ralf A."],["dc.contributor.author","Brechlin, Peter"],["dc.contributor.author","Jesse, Sarah"],["dc.contributor.author","Steinacker, Petra"],["dc.contributor.author","Lee, D. H."],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Tumani, Hayrettin"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Otto, Markus"],["dc.date.accessioned","2019-07-09T11:52:40Z"],["dc.date.available","2019-07-09T11:52:40Z"],["dc.date.issued","2009-10-28"],["dc.description.abstract","The identification of new biomarkers is of high interest for the prediction of the disease course and also for the identification of pathomechanisms in multiple sclerosis (MS). To specify markers of the chronic disease phase, we performed proteome profiling during the later phase of myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE, day 35 after immunization) as a model disease mimicking many aspects of secondary progressive MS. In comparison to healthy controls, high resolution 2 dimensional gel electrophoresis revealed a number of regulated proteins, among them glial fibrilary acidic protein (GFAP). Phase specific up-regulation of GFAP in chronic EAE was confirmed by western blotting and immunohistochemistry. Protein levels of GFAP were also increased in the cerebrospinal fluid of MS patients with specificity for the secondary progressive disease phase. In a next step, proteome profiling of an EAE model with enhanced degenerative mechanisms revealed regulation of alpha-internexin, syntaxin binding protein 1, annexin V and glutamate decarboxylase in the ciliary neurotrophic factor (CNTF) knockout mouse. The identification of these proteins implicate an increased apoptosis and enhanced axonal disintegration and correlate well the described pattern of tissue injury in CNTF -/- mice which involve oligodendrocyte (OL) apoptosis and axonal injury.In summary, our findings underscore the value of proteome analyses as screening method for stage specific biomarkers and for the identification of new culprits for tissue damage in chronic autoimmune demyelination."],["dc.format.extent","9"],["dc.identifier.doi","10.1371/journal.pone.0007624"],["dc.identifier.fs","544326"],["dc.identifier.pmid","19865482"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5819"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60250"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.subject.ddc","610"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Apoptosis"],["dc.subject.mesh","Axons"],["dc.subject.mesh","Disease Models, Animal"],["dc.subject.mesh","Encephalomyelitis, Autoimmune, Experimental"],["dc.subject.mesh","Gene Expression Profiling"],["dc.subject.mesh","Gene Expression Regulation"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Mice, Inbred C57BL"],["dc.subject.mesh","Mice, Transgenic"],["dc.subject.mesh","Multiple Sclerosis"],["dc.subject.mesh","Oligodendroglia"],["dc.subject.mesh","Proteome"],["dc.subject.mesh","Proteomics"],["dc.subject.mesh","Time Factors"],["dc.title","Proteome profiling in murine models of multiple sclerosis: identification of stage specific markers and culprits for tissue damage."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","14"],["dc.contributor.author","Hoepner, Robert"],["dc.contributor.author","Bagnoud, Maud"],["dc.contributor.author","Pistor, Maximilian"],["dc.contributor.author","Salmen, Anke"],["dc.contributor.author","Briner, Myriam"],["dc.contributor.author","Synn, Helen"],["dc.contributor.author","Schrewe, Lisa"],["dc.contributor.author","Guse, Kirsten"],["dc.contributor.author","Ahmadi, Farhad"],["dc.contributor.author","Demir, Seray"],["dc.contributor.author","Laverick, Louis"],["dc.contributor.author","Gresle, Melissa"],["dc.contributor.author","Worley, Paul"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Butzkueven, Helmut"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Lühder, Fred"],["dc.contributor.author","Chan, Andrew"],["dc.date.accessioned","2019-07-09T11:51:33Z"],["dc.date.available","2019-07-09T11:51:33Z"],["dc.date.issued","2019"],["dc.description.abstract","The limited efficacy of glucocorticoids (GCs) during therapy of acute relapses in multiple sclerosis (MS) leads to long-term disability. We investigated the potential of vitamin D (VD) to enhance GC efficacy and the mechanisms underlying this VD/GC interaction. In vitro, GC receptor (GR) expression levels were quantified by ELISA and induction of T cell apoptosis served as a functional readout to assess synergistic 1,25(OH)2D3 (1,25D)/GC effects. Experimental autoimmune encephalomyelitis (MOG35-55 EAE) was induced in mice with T cell-specific GR or mTORc1 deficiency. 25(OH)D (25D) levels were determined in two independent cohorts of MS patients with stable disease or relapses either responsive or resistant to GC treatment (initial cohort: n = 110; validation cohort: n = 85). Gene expression of human CD8+ T cells was analyzed by microarray (n = 112) and correlated with 25D serum levels. In vitro, 1,25D upregulated GR protein levels, leading to increased GC-induced T cell apoptosis. 1,25D/GC combination therapy ameliorated clinical EAE course more efficiently than respective monotherapies, which was dependent on GR expression in T cells. In MS patients from two independent cohorts, 25D deficiency was associated with GC-resistant relapses. Mechanistic studies revealed that synergistic 1,25D/GC effects on apoptosis induction were mediated by the mTOR but not JNK pathway. In line, 1,25D inhibited mTORc1 activity in murine T cells, and low 25D levels in humans were associated with a reduced expression of mTORc1 inhibiting tuberous sclerosis complex 1 in CD8+ T cells. GR upregulation by 1,25D and 1,25D/GC synergism in vitro and therapeutic efficacy in vivo were abolished in animals with a T cell-specific mTORc1 deficiency. Specific inhibition of mTORc1 by everolimus increased the efficacy of GC in EAE. 1,25D augments GC-mediated effects in vitro and in vivo in a T cell-specific, GR-dependent manner via mTORc1 inhibition. These data may have implications for improvement of anti-inflammatory GC therapy."],["dc.identifier.doi","10.1007/s00401-019-02018-8"],["dc.identifier.pmid","31030237"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16149"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59968"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1432-0533"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Vitamin D increases glucocorticoid efficacy via inhibition of mTORC1 in experimental models of multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","829"],["dc.bibliographiccitation.journal","Frontiers in Neurology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Ayzenberg, Ilya"],["dc.contributor.author","Ellrichmann, Gisa"],["dc.contributor.author","Schroeder, Christoph"],["dc.contributor.author","Tönges, Lars"],["dc.contributor.author","Klasing, Anja"],["dc.contributor.author","Pappa, Vaia"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Gold, Ralf"],["dc.date.accessioned","2019-11-27T10:45:37Z"],["dc.date.accessioned","2021-10-27T13:21:37Z"],["dc.date.available","2019-11-27T10:45:37Z"],["dc.date.available","2021-10-27T13:21:37Z"],["dc.date.issued","2019"],["dc.description.abstract","Objective: To report a rare case of brainstem encephalitis with low-titer acetylcholine receptor antibodies mimicking myasthenia gravis. Methods: The patient was investigated with repeated brain MRI, CSF examination, repetitive nerve stimulation, thoracic CT, and serologic screening. Our patient passed away and finally autopsy revealed a definitive diagnosis. Written informed consent was obtained from the relatives of the patient for access to clinical files for research purposes and publication. Results: We present a young woman with a subacute bulbar syndrome, who was initially diagnosed with myasthenia gravis based on clinical finding and elevated acetylcholine receptor antibodies. Episodes of numbness in the pharynx and tongue and moderate saccadic horizontal and vertical pursuits were atypical. Despite initial stabilization with intravenous immunoglobulins she developed acute asphyxia after regurgitation of food and had to be resuscitated with ultimately lethal outcome. Autopsy revealed an autoimmune T-cell mediated brainstem encephalitis. Serological screening revealed positive GAD and Ma2 autoantibodies, indicating its probable paraneoplastic nature. Conclusions: Brainstem encephalitis is an important differential diagnosis even in seropositive bulbar myasthenia gravis, as several autoimmune processes often co-occur. Sudden unexpected death must be taken into account in brainstem encephalitis, requiring prolonged monitoring of the patients."],["dc.identifier.doi","10.3389/fneur.2019.00829"],["dc.identifier.pmid","31428040"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16749"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92035"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","1664-2295"],["dc.relation.issn","1664-2295"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Brainstem Encephalitis With Low-Titer Acetylcholine Receptor Antibodies Mimicking Myasthenia Gravis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8434"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Journal of immunology (Baltimore, Md. : 1950)"],["dc.bibliographiccitation.lastpage","8443"],["dc.bibliographiccitation.volume","180"],["dc.contributor.author","Wüst, Simone"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","Kleiman, Anna"],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Lühder, Fred"],["dc.contributor.author","Reichardt, Holger M."],["dc.date.accessioned","2019-07-10T08:13:33Z"],["dc.date.available","2019-07-10T08:13:33Z"],["dc.date.issued","2008"],["dc.description.abstract","High-dose glucocorticoid (GC) therapy is widely used to treat multiple sclerosis (MS), but the underlying mechanisms remain debatable. In this study, we investigated the impact of GC administration on experimental autoimmune encephalomyelitis using different GC receptor (GR)-deficient mutants. Heterozygous GR knockout mice were less sensitive to dexamethasone therapy, indicating that the expression level of the receptor determines therapeutic efficacy. Mice reconstituted with homozygous GR knockout fetal liver cells showed an earlier onset of the disease and were largely refractory to GC treatment, indicating that the GR in hematopoietic cells is essential for the beneficial effects of endogenous GCs and dexamethasone. Using cell-type specific GR-deficient mice, we could demonstrate that GCs mainly act on T cells, while modulation of macrophage function was largely dispensable in this context. The therapeutic effects were achieved through induction of apoptosis and down-regulation of cell adhesion molecules in peripheral T(H)17 and bystander T cells, while similar effects were not observed within the spinal cord. In addition, dexamethasone inhibited T cell migration into the CNS, confirming that peripheral but not CNS-residing T lymphocytes are the essential targets of GCs. Collectively, our findings reveal a highly selective mechanism of GC action in experimental autoimmune encephalomyelitis and presumably multiple sclerosis."],["dc.identifier.pmid","18523311"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6206"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61275"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","0022-1767"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.subject.ddc","610"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Apoptosis"],["dc.subject.mesh","Blood-Brain Barrier"],["dc.subject.mesh","Cell Movement"],["dc.subject.mesh","Dexamethasone"],["dc.subject.mesh","Down-Regulation"],["dc.subject.mesh","Drug Delivery Systems"],["dc.subject.mesh","Encephalomyelitis, Autoimmune, Experimental"],["dc.subject.mesh","Female"],["dc.subject.mesh","Glycoproteins"],["dc.subject.mesh","Intercellular Signaling Peptides and Proteins"],["dc.subject.mesh","Leukocytes"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Mice, Inbred C57BL"],["dc.subject.mesh","Mice, Knockout"],["dc.subject.mesh","Mice, Transgenic"],["dc.subject.mesh","Peptide Fragments"],["dc.subject.mesh","Receptors, Glucocorticoid"],["dc.subject.mesh","T-Lymphocyte Subsets"],["dc.subject.mesh","T-Lymphocytes, Regulatory"],["dc.title","Peripheral T cells are the therapeutic targets of glucocorticoids in experimental autoimmune encephalomyelitis."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]