The Experts below are selected from a list of 1911 Experts worldwide ranked by ideXlab platform
M Fujiwara - One of the best experts on this subject based on the ideXlab platform.
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in vivo lymphocyte mediated myocardial injuries demonstrated by adoptive transfer of Experimental autoimmune Myocarditis
Circulation, 1992Co-Authors: Makoto Kodama, Y Matsumoto, M FujiwaraAbstract:BACKGROUNDTo elucidate the mechanisms of immune-related myocardial injuries, we examined whether autoimmune Myocarditis was passively transferable by use of humoral or cellular factors.METHODS AND RESULTSActive Myocarditis was elicited in Lewis rats by immunization with human cardiac myosin fraction in complete Freund's adjuvant. This Experimental Myocarditis was characterized by macroscopic features such as pericardial effusion, enlargement of the heart, and gray discoloration of the cardiac surface. Histologically, extensive myocardial necrosis and numerous inflammatory cell infiltrations were observed. Interestingly, multinucleated giant cells were frequently observed in the lesions. Transfer of the disease by the humoral factor was examined by use of fresh sera and immunoglobulin fraction of pooled sera from rats with severe Myocarditis, and transfer by the cellular factor was tested by use of spleen cells and lymph node cells from the diseased rats. When naive Lewis rats were given 15.75 mg of immuno...
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in vivo lymphocyte mediated myocardial injuries demonstrated by adoptive transfer of Experimental autoimmune Myocarditis
Circulation, 1992Co-Authors: Makoto Kodama, Y Matsumoto, M FujiwaraAbstract:BACKGROUNDTo elucidate the mechanisms of immune-related myocardial injuries, we examined whether autoimmune Myocarditis was passively transferable by use of humoral or cellular factors.METHODS AND RESULTSActive Myocarditis was elicited in Lewis rats by immunization with human cardiac myosin fraction in complete Freund's adjuvant. This Experimental Myocarditis was characterized by macroscopic features such as pericardial effusion, enlargement of the heart, and gray discoloration of the cardiac surface. Histologically, extensive myocardial necrosis and numerous inflammatory cell infiltrations were observed. Interestingly, multinucleated giant cells were frequently observed in the lesions. Transfer of the disease by the humoral factor was examined by use of fresh sera and immunoglobulin fraction of pooled sera from rats with severe Myocarditis, and transfer by the cellular factor was tested by use of spleen cells and lymph node cells from the diseased rats. When naive Lewis rats were given 15.75 mg of immuno...
Makoto Kodama - One of the best experts on this subject based on the ideXlab platform.
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transplantation of mesenchymal stem cells attenuates myocardial injury and dysfunction in a rat model of acute Myocarditis
Journal of Molecular and Cellular Cardiology, 2007Co-Authors: Shunsuke Ohnishi, Makoto Kodama, Bobby Yanagawa, Koichi Tanaka, Yoshinori Miyahara, Hiroaki Obata, Masaharu Kataoka, Hatsue Ishibashiueda, Kenji Kangawa, Soichiro KitamuraAbstract:Abstract Acute Myocarditis is a non-ischemic inflammatory disease of the myocardium for which there is currently no specific treatment. We have previously shown that mesenchymal stem cells (MSC) can ameliorate heart injury during acute ischemia and in dilated cardiomyopathy; however, the therapeutic potential in acute Myocarditis is unclear. In this study, we investigated the ability of MSC to attenuate myocardial injury and dysfunction during the acute phase of Experimental Myocarditis. Ten-week-old male Lewis rats were injected with porcine myosin to induce Myocarditis. Cultured MSC (3 × 10 6 cells/rat) were injected intravenously 7 days after myosin injection. At 3 weeks, myosin injection resulted in severe inflammation and significant deterioration of cardiac function. MSC transplantation attenuated increases in CD68-positive inflammatory cells and monocyte chemoattractant protein-1 (MCP-1) expression in myocardium, and improved cardiac function in this model. Furthermore, myocardial capillary density was higher in Myocarditis tissue, and was further increased by MSC transplantation. In vitro , cultured adult rat cardiomyocytes were injured in response to MCP-1, whereas this effect was attenuated by MSC-derived conditioned medium, suggesting cardioprotective effects of MSC acting in a paracrine manner. MSC transplantation attenuated myocardial injury and dysfunction in a rat model of acute Myocarditis, at least in part through paracrine effects of MSC.
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in vivo lymphocyte mediated myocardial injuries demonstrated by adoptive transfer of Experimental autoimmune Myocarditis
Circulation, 1992Co-Authors: Makoto Kodama, Y Matsumoto, M FujiwaraAbstract:BACKGROUNDTo elucidate the mechanisms of immune-related myocardial injuries, we examined whether autoimmune Myocarditis was passively transferable by use of humoral or cellular factors.METHODS AND RESULTSActive Myocarditis was elicited in Lewis rats by immunization with human cardiac myosin fraction in complete Freund's adjuvant. This Experimental Myocarditis was characterized by macroscopic features such as pericardial effusion, enlargement of the heart, and gray discoloration of the cardiac surface. Histologically, extensive myocardial necrosis and numerous inflammatory cell infiltrations were observed. Interestingly, multinucleated giant cells were frequently observed in the lesions. Transfer of the disease by the humoral factor was examined by use of fresh sera and immunoglobulin fraction of pooled sera from rats with severe Myocarditis, and transfer by the cellular factor was tested by use of spleen cells and lymph node cells from the diseased rats. When naive Lewis rats were given 15.75 mg of immuno...
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in vivo lymphocyte mediated myocardial injuries demonstrated by adoptive transfer of Experimental autoimmune Myocarditis
Circulation, 1992Co-Authors: Makoto Kodama, Y Matsumoto, M FujiwaraAbstract:BACKGROUNDTo elucidate the mechanisms of immune-related myocardial injuries, we examined whether autoimmune Myocarditis was passively transferable by use of humoral or cellular factors.METHODS AND RESULTSActive Myocarditis was elicited in Lewis rats by immunization with human cardiac myosin fraction in complete Freund's adjuvant. This Experimental Myocarditis was characterized by macroscopic features such as pericardial effusion, enlargement of the heart, and gray discoloration of the cardiac surface. Histologically, extensive myocardial necrosis and numerous inflammatory cell infiltrations were observed. Interestingly, multinucleated giant cells were frequently observed in the lesions. Transfer of the disease by the humoral factor was examined by use of fresh sera and immunoglobulin fraction of pooled sera from rats with severe Myocarditis, and transfer by the cellular factor was tested by use of spleen cells and lymph node cells from the diseased rats. When naive Lewis rats were given 15.75 mg of immuno...
Konstantinos Savvatis - One of the best experts on this subject based on the ideXlab platform.
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Interleukin-6 receptor inhibition modulates the immune reaction and restores titin phosphorylation in Experimental Myocarditis
Basic Research in Cardiology, 2014Co-Authors: Konstantinos Savvatis, Bernhard Schieffer, Irene Müller, Matthias Fröhlich, Kathleen Pappritz, Christin Zietsch, Nazha Hamdani, Karin Klingel, Karsten Grote, S Van LinthoutAbstract:Increased levels of interleukin-6 (IL-6) have been observed in patients with acute Myocarditis and are associated with poor prognosis. This study was designed to examine whether treatment with anti-IL-6 receptor antibody improves cardiac dysfunction and left ventricular (LV) remodeling in Experimental Coxsackie virus B3 (CVB3)-induced Myocarditis. C57BL6/J mice were subjected to acute CVB3 infection. One day after viral infection mice were treated with a single injection of an anti-IL-6 receptor antibody (MR16-1, tocilizumab) or control IgG. Seven days after viral infection, LV function was examined by conductance catheter technique, cardiac remodeling assessed by estimation of titin phosphorylation, cardiac fibrosis, and inflammatory and antiviral response by immunohistochemistry, RT-PCR and cell culture experiments. Compared to controls, infected mice displayed an impaired systolic and diastolic LV function associated with an increase in cardiac inflammation, fibrosis and impaired titin phosphorylation. IL-6 receptor blockade led to a shift of the immune response to a Th1 direction and significant reduction of viral load. In addition, cardiac immune response, extracellular matrix regulation and titin function improved, resulting in a preserved LV function. IL-6 receptor blockade exerts cardiac beneficial effects by antiviral and immunomodulatory actions after induction of an acute murine CVB3 virus Myocarditis.
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mesenchymal stromal cells but not cardiac fibroblasts exert beneficial systemic immunomodulatory effects in Experimental Myocarditis
PLOS ONE, 2012Co-Authors: Konstantinos Savvatis, Kathleen Pappritz, Sophie Van Linthout, Kapka Miteva, Dirk Westermann, Joerg C Schefold, Gerhard Fusch, Alice Weithauser, Ursula Rauch, P M BecherAbstract:Systemic application of mesenchymal stromal cells (MSCs) in inflammatory cardiomyopathy exerts cardiobeneficial effects. The mode of action is unclear since a sufficient and long-acting cardiac homing of MSCs is unlikely. We therefore investigated the regulation of the immune response in coxsackievirus B3 (CVB3)-induced acute Myocarditis after intravenous application of MSCs. Wildtype mice were infected with CVB3 and treated with either PBS, human MSCs or human cardiac fibroblasts intravenously 1 day after infection. Seven days after infection, MSCs could be detected in the spleen, heart, pancreas, liver, lung and kidney, whereby the highest presence was observed in the lung. MSCs increased significantly the myocardial expression of HGF and decreased the expression of the proinflammatory cytokines TNFα, IL1β and IL6 as well as the severity of Myocarditis and ameliorated the left ventricular dysfunction measured by conductance catheter. MSCs upregulated the production of IFNγ in CD4+ and CD8+ cells, the number of IL10-producing regulatory T cells and the apoptosis rate of T cells in the spleen. An increased number of CD4+CD25+FoxP3 could be found in the spleen as well as in the circulation. In contrast, application of human cardiac fibroblasts had no effect on the severity of Myocarditis and the systemic immune response observed after MSCs-administration. In conclusion, modulation of the immune response in extracardiac organs is associated with cardiobeneficial effects in Experimental inflammatory cardiomyopathy after systemic application of MSCs.
Atsushi Anzai - One of the best experts on this subject based on the ideXlab platform.
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self reactive cd4 il 3 t cells amplify autoimmune inflammation in Myocarditis by inciting monocyte chemotaxis
Journal of Experimental Medicine, 2019Co-Authors: Atsushi Anzai, John E Mindur, Lennard Halle, Soichi Sano, Jennifer L Choi, Shun He, Cameron S Mcalpine, Christopher T Chan, Florian KahlesAbstract:: Acquisition of self-reactive effector CD4+ T cells is a major component of the autoimmune response that can occur during Myocarditis, an inflammatory form of cardiomyopathy. Although the processes by which self-reactive T cells gain effector function have received considerable attention, how these T cells contribute to effector organ inflammation and damage is less clear. Here, we identified an IL-3-dependent amplification loop that exacerbates autoimmune inflammation. In Experimental Myocarditis, we show that effector organ-accumulating autoreactive IL-3+ CD4+ T cells stimulate IL-3R+ tissue macrophages to produce monocyte-attracting chemokines. The newly recruited monocytes differentiate into antigen-presenting cells that stimulate local IL-3+ CD4+ T cell proliferation, thereby amplifying organ inflammation. Consequently, Il3-/- mice resist developing robust autoimmune inflammation and myocardial dysfunction, whereas therapeutic IL-3 targeting ameliorates disease. This study defines a mechanism that orchestrates inflammation in Myocarditis, describes a previously unknown function for IL-3, and identifies IL-3 as a potential therapeutic target in patients with Myocarditis.
Jacob George - One of the best experts on this subject based on the ideXlab platform.
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transfer of endothelial progenitor cells improves myocardial performance in rats with dilated cardiomyopathy induced following Experimental Myocarditis
Journal of Molecular and Cellular Cardiology, 2005Co-Authors: Lael Werner, Varda Deutsch, Iris Barshack, Hylton Miller, Gad Keren, Jacob GeorgeAbstract:Endothelial progenitor cells (EPCs) home to sites of tissue injury and differentiate into mature endothelial cells. Their transfer feasibility has been proven in models of hindlimb ischemia and myocardial infarction.We investigated, the effect of delivery of spleen-derived EPC in a rat model of inflammatory-mediated myocardial damage. Male Lewis rats (N = 25) were immunized against myosin. Healthy donor Lewis rats were sacrificed, their spleens harvested, separated on Ficoll gradient centrifugation, and grown on fibronectin coated plates with endothelial cell medium for 5 days. Ten days after myosin immunization, spleen cell derived EPC were collected, and labeled 2 ◊ 10 7 cells per rat were injected into the femoral vein of diseased rats. Cell transplantation was repeated twice, 2 and 4 weeks after initial cell transfer. Rats with inflammatory-mediated cardiomyopathy exhibited a significant mobilization of EPC from the bone marrow to the periphery and their ability to adhere to fibronectin, mature endothelial cells and cultured cardiomyocytes was significantly reduced when compared to healthy rats. Transfer of EPC resulted in a functional improvement in cardiac performance evident by higher fractional shortening by echocardiography (a 15% increase). Histological studies exhibited reduced scar tissue and thickened ventricular walls in rats receiving EPC as compared with untreated animals. EPC transfer is effective in attenuating myocardial damage in a model of non-ischemic dilated cardiomyopathy. © 2005 Elsevier Ltd. All rights reserved.
