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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coxsackie B viruses (types 1 to 5) are the most frequent reported cause of acute viral myocarditis. To study the pathogenesis of the disease at the cellular level, we simulated an infectious situation by infecting cultured human foetal heart cells with Coxsackie B3 (CB3) virus. Successful replication of this virus could be demonstrated by the presence of virus particles inside cultivated foetal myocytes together with high titres of progeny virus of 10(8) plaque-forming units (PFU) per millilitre culture medium. Within 9 h of infection networks of myocytes lost their ability to contract spontaneously followed by disintegration and replacement by overgrowing fibroblasts which survived the infection. These cells produced CB3 virus continuously over several months, indicating carrier state infection of human myocardial fibroblasts. Human fibroblasts interferon (IFN-beta) was found to act as a potent inhibitor of the replication of this virus. Virus yields could be reduced from 1.2 x 1.8 x 10(5) PFU/ml culture medium when human heart cells were incubated with IFN-beta 20 h prior to challenge with a high input multiplicity of 50 PFU of CB3 virus per cell, demonstrating the major protective role of IFN-beta in CB3 viral infection. It thus appear that IFN-beta might become useful as an antiviral agent in the treatment of Coxsackie myocarditis.
J Mol Cell Cardiol 1985 Feb
PMID:Coxsackie B3 virus can replicate in cultured human foetal heart cells and is inhibited by interferon. 388 51

Oxygen free radicals and their metabolites generated from activated neutrophils have been implicated in mediating the cardiovascular dysfunction of such diverse etiologies as myocardial ischemia and reperfusion injury, Gram negative sepsis, myocarditis and acute cardiac allograft rejection, but a direct demonstration of neutrophil derived oxygen free radical mediation of cardiovascular dysfunction has not been accomplished. In this study, we have demonstrated that activation of the canine neutrophil system, in vivo, results in the generation of oxygen free radicals that are capable of disrupting cardiovascular function producing a significant decrease in mean arterial pressure and cardiac index without any significant effect on the conduction system of the myocardium. Neutrophil depletion or pretreatment with superoxide dismutase and catalase inhibited the effects of activated neutrophils. This study provides evidence that neutrophil-derived reduced oxygen intermediates are able to induce severe cardiovascular dysfunction.
J Mol Cell Cardiol 1984 Nov
PMID:Neutrophil-derived, oxygen free radical-mediated cardiovascular dysfunction. 652 Aug 76

A detailed description is presented of immunohistochemical methods for identification of various types of immune effector cells in rat heart, involving the use of antibodies conjugated with different fluorochromes for the simultaneous demonstration of 2 or 3 different antigens by means of fluorescence microscopy. The initial results of the application of these techniques to the study of the myocarditis induced by interleukin-2 (IL-2) are also presented. Antibodies used included: OX6 antibody (for MHC class II molecules, mainly expressed by dendritic cells): W3/25 and OX8 antibody, for the demonstration of the rat equivalents of CD5 and CD8, respectively: asialo-GM1 ganglioside antibody for the identification of natural killer (NK) cells and lymphokine activated killer (LAK) cells, and ED2 antibody for labeling of macrophages. Fluorochromes used were: fluorescein isothiocyanate (green), tetramethylrhodamine isothiocyanate (red), Texas red sulfonyl chloride (red), and 7-amino-4-methylcoumarin-3-acetic acid (blue). IL-2-induced myocarditis was characterized histologically by infiltration of the myocardium by mononuclear inflammatory cells, microvascular alteration, interstitial edema, and myocyte damage and necrosis. In the initial stages, NK/LAK cells were the predominant type of infiltrating lymphocytes; however, the numbers of these cells decreased sharply in subsequent stages. Macrophages also were initially abundant, and continued to be prevalent throughout the late stages. CD8+ lymphocytes were more numerous than CD4+ lymphocytes. Dendritic-cells showed a diffuse increase in number and also accumulated around foci of myocyte necrosis. Three phenotypes of dendritic cells were recognized, and the possible implications of these findings are discussed. It is hoped that these techniques will prove useful for the immunohistochemical evaluation of various inflammatory diseases of the heart.
J Mol Cell Cardiol 1995 Jan
PMID:Immunofluorescence techniques for the identification of immune effector cells in rat heart: applications to the study of the myocarditis induced by interleukin-2. 753 83

In a preceding communication (Wallukat et al., 1992, Z Kardiol 81 [Suppl. 4]: 79-83), it was reported that synthetic peptides, corresponding in amino acid sequence to either the first or the second extracellular loop of the human beta 1-adrenoceptor, selectively suppressed the metoprolol- and bisoprolol-sensitive positive chronotropic action exerted in cultures of beating neonatal rat cardiomyocytes by the serum immunoglobulin fraction of patients with myocarditis and idiopathic dilated cardiomyopathy (DCM) and by affinity-purified autoantibodies from that fraction. These observations added to existing evidence that these antibodies were directed against the beta 1-adrenoceptor and might thus contribute to the harmful chronic cardiac adrenergic drive to which patients with DCM are believed to be exposed. Specifically, they pointed to the putative first and second extracellular loops of this receptor (these loops are each identical in man and the rat) as the sites of epitopes recognized by the chronotropically active, beta 1-agonistic autoantibodies. Now we report on the mapping of these epitopes with the help of two series of short synthetic overlap peptides, one series forming part of the first and the other of the second extracellular loop of the beta 1-adrenoceptor. Inhibition of the positive chronotropic response of cultured rat cardiomyocytes to the anti-beta 1-receptor autoantibodies (EC50 = 0.14 +/- 0.01 nM) from the serum immunoglobulin fraction of patients with DCM was taken as reflecting the neutralization of these antibodies by a particular overlap peptide. In this way the sequences S-F-F-C-E-L (residues 129-134) and A-R-R-C-Y-N-D (residues 206-212) emerged as the dominant epitopes in the first and second extracellular loops, respectively, followed with respect to neutralizing ability by the first loop sequence E-Y-G-S-F-F (residues 126-131) and the second loop sequences H-W-W-R-A-E (residues 197-202) and P-K-C-C-D-F (residues 213-218). Synthetic peptides corresponding to the sequences of the third extracellular loop of the beta 1-receptor (residues 346-356) and of the second extracellular loop of the human beta 2-receptor (residues 172-197) failed to neutralize the beta 1-agonistic autoantibodies. Using dithiothreitol as a reducing agent a disulfide bridge between cysteine 132 in the first and cysteine 209 in the second extracellular loop was considered to be essential for the chronotropic action of these autoantibodies.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Cardiol 1995 Jan
PMID:Anti-beta 1-adrenoceptor autoantibodies with chronotropic activity from the serum of patients with dilated cardiomyopathy: mapping of epitopes in the first and second extracellular loops. 753 84

The mitochondrial respiration rate and morphometric indices in endomyocardial biopsy samples were measured in 43 patients with dilated cardiomyopathy selected in accordance to WHO criteria by endomyocardial biopsy studies after excluding of various forms of myocarditis, alcoholic cardiomyopathy and other specific diseases of the heart. A group of 13 patients with unusually high mean myocyte diameter, 30 +/- 4 microns, and nuclear size, 57 +/- 5 microns, was selected. The remainder of patients (n = 30) had significantly lower mean myocyte diameter and nuclear size, 23 +/- 3 and 42 +/- 6 microns, respectively, (p < 0.01). Creatine-stimulated elevation in mitochondrial respiration rate as measured in saponin-skinned fibers was found in the former group to be much lower (36 +/- 4%) as compared with the remainder (90 +/- 12%). Also, the former group of patients had higher left ventricular enddiastolic pressure and volume index with concomitantly decreased ejection fraction. The results indicate that marked nuclear and cellular hypertrophy is associated with lower creatine-stimulated mitochondrial respiration rate and more severe cardiac failure. They suggest that disorders in energy supply to myofibrils may be related to disturbances in cellular genetic apparatus.
Mol Cell Biochem 1995 Feb 09
PMID:Cellular hypertrophy in cardiomyopathic patients is associated with lower creatine-stimulated mitochondrial respiration. 777 53

In order to address the question whether the virus or immune reactions to the heart induce cardiac damage in the murine model of coxsackievirus B3 induced myocarditis, calcium-resistant cardiac myocytes of a myocarditis susceptible strain of mice were isolated and exposed to myocarditic coxsackievirus B3. The tetrazolium salt MTT was used to visualize the effect of the virus upon cell viability by inverse light microscopy and by an EA test. Coxsackievirus B3 infected isolated adult cardiac myocytes as well as infected cultured cardiac fibroblasts were examined. In vitro the virus killed the myocytes within 16 h of infection whereas the fibroblasts survived the infection. Since coxsackievirus B3 is able to kill cardiac myocytes by itself, immunosuppressive treatment of acute coxsackievirus B3 induced myocarditis may be harmful by eliminating host immune defence mechanisms and, therefore, may lead to an enhanced viral spread and virus induced myocyte necrosis in the heart.
J Mol Cell Cardiol 1994 Jul
PMID:Coxsackievirus B3 infection leads to cell death of cardiac myocytes. 796 59

Inflammation of heart tissue is a pathological feature of infections and autoimmune diseases, and sometimes also occurs after heart transplantation. In these situations, the invasive infiltration of lymphocytes, most probably cytotoxic (CD8-positive) T cells, is likely to be the cause of cardiac damage, as shown by the results of studies on experimental animal models of myocarditis. However, the cellular and molecular events underlying the interactions between lymphocytes and cardiomyocytes have hitherto not been investigated. In the present study we describe a new procedure for obtaining ventricular heart cells from neonatal mice and for maintaining them in serum-free medium in culture dishes coated with certain matrix components. Such cells adhered, spread, and were functionally active since they started a beating rhythm after 2 days. T and B cells which had been surface-labelled with biotin were added to these cells and lymphocyte adhesion was measured. The number of lymphocytes which became bound to the cardiomyocytes was calculated from the amount of biotin which remained associated with the monolayer after extensive washing to remove non-adherent cells. Colourimetric detection, using a streptavidin-peroxidase reagent, showed that an average of approximately 10 activated lymphocytes bound per heart cell, four times greater than the attachment of resting T cells. The results of this study provide a reproducible basis for using monoclonal antibodies which react against lymphocyte surface receptors and their cognate ligands to identify the specific adhesion molecules involved in heart cell recognition and interaction.
J Mol Cell Cardiol 1994 May
PMID:Interactions between cardiomyocytes and lymphocytes in tissue culture: an in vitro model of inflammatory heart disease. 807 17

Concerning cardiac contractile proteins, antigenicity and myocardiotogenicity were discussed. In normal states, these proteins are immunologically tolerant, and can not provoke any heart-specific disease. Why the proteins can provoke such lethal autoimmune myocarditis has not been completely elucidated. Shortly after cardiac infection or myocardial ischemia, these proteins may work as the antigen for the autoimmune myocarditis. First of all, the role of cardiac myosin has been strongly emphasized. But, the antigen determinants: epitope proteins remain unclear. Either cross-activity to the streptococcal M protein and/or the alpha-helical coiled-coil protein may be an important factor to determine antigenicity. In this autoimmune myocarditis, the roles of T-lymphocyte and cardiac dendritic cell are noticeable. Through further study on the relation between antigen epitope and the infectious agents in the heart; on cardio-cytotoxicity of the T-lymphocyte and on the precise contribution of cardiac dendritic cells, this autoimmune myocarditis will be more clarified.
Mol Cell Biochem 1993 Feb 17
PMID:Cardiac contractile proteins and autoimmune myocarditis. 845 88

In susceptible DBA/2 mice coxsackievirus B 3-induced myocarditis leads to inflammatory and necrotic lesions in the myocardium 7-10 days after virus inoculation. The purpose of this study was to determine whether hemodynamic changes occur in murine coxsackievirus B 3 myocarditis and whether they are correlated to histological cardiac lesions throughout the infection. Left ventricular function was determined by open chest puncture of the left ventricle in the course of acute coxsackievirus B 3 infection. Histological cross sections of the heart were stained with hematoxylin/eosin and scored blindly for myocarditic lesions. Left ventricular function was preserved until day 7 post-virus inoculation Left ventricular systolic pressure, +dP/dtmax and -dP/dtmax and heart rate declined significantly from day 7 to day 10. The decrease in these parameters did not correlate with viral concentrations in the heart on the day of hemodynamic measurements. The decrease was related to histological changes on day 10, but not on day 7 of the infection. The data suggest (a) that a cumulative loss of cardiac myofibers, induced either by the virus and/or by immune reactions to the heart, is likely to lead to a late depression of cardiac function, and (b) that there is a weak and only temporary structure-function relationship in the heart in coxsackievirus B 3 myocarditis. Therefore, in addition to an analysis of histological changes, the measurement of cardiac function appears to be very important in order to completely evaluate the severity of myocarditis and the usefulness of any therapy.
J Mol Cell Cardiol 1995 Aug
PMID:Left ventricular hemodynamic parameters in the course of acute experimental coxsackievirus B 3 myocarditis. 852 20

Accumulation and adhesion of leukocytes to cardiac myocytes play important roles in the pathogenesis of inflammation-mediated myocardial injury such as ischaemia/reperfusion and myocarditis. The involvement of leukocyte chemotactic factors has been speculated in these processes. We investigated the expression of cytokine-induced neutrophil chemoattractant (CINC) in rat cardiac myocytes. CINC is a rat equivalent of human interleukin-8. On exposure to interleukin-1 alpha (IL-1 alpha), cultured neonatal rat cardiac myocytes released appreciable levels of CINC both dose- and time-dependently. Tumor necrosis factor-alpha and lipopolysaccharide also significantly increased CINC accumulation in the culture supernatant. CINC mRNA expression was not observed in unstimulated myocytes, however, the expression was markedly induced by exposure to IL-1 alpha with a peak elevation at 3 h. Potent chemotactic activity for neutrophils was detected in the supernatant of cultured rat cardiac myocytes by stimulation with IL-1 alpha. This IL-1 alpha-induced chemotactic activity was significantly inhibited by polyclonal anti-CINC antiserum. Addition of dexamethasone, genistein, actinomycin D or cycloheximide significantly suppressed the IL-1 alpha-induced CINC accumulation. Under hypoxia (95%N2 + 5%CO2), CINC accumulation was increased in a time-dependent manner, and reoxygenation after hypoxia further intensified CINC accumulation. This hypoxia reoxygenation-induced CINC expression was significantly inhibited by pretreatment with dexamethasone. In conclusion, inflammatory stimuli induce the expression of CINC in rat cardiac myocytes, which may lead to myocardial injury via accumulation and activation of neutrophils.
J Mol Cell Cardiol 1995 Sep
PMID:Expression of cytokine-induced neutrophil chemoattractant in rat cardiac myocytes. 852 63


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