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Biomedical subjects

B Maisch

Publications and source records attributed to B Maisch.

At least 307 records · Page 17Linked to original sources

Immune reactions in infective endocarditis. I. Clinical data and diagnostic relevance of antimyocardial antibodies.

Clinical data from 72 patients with infective endocarditis (41 with defined pathogen, 31 with no pathogen isolated) were analyzed with respect to the diagnostic relevance of immunologic parameters. In our patients from a rural area, no significant changes in the epidemiology and pathogenesis of infective endocarditis were observed. Antiendocardial and antisarcolemmal (ASA) antibodies were demonstrated in 60% to 100% of cases. Their frequency depended on the endocarditic pathogen and on the clinical course: in subacute or chronic endocarditis these antibodies were found regularly, in acute lethal cases their occurrence was diminished. Whereas antiendocardial antibodies are diagnostic markers of endocarditis, ASA and antimyolemmal antibodies in particular most likely indicate myocardial involvement in endocarditis. Only complement fixing antimyolemmal antibodies induced cytolysis of vital, adult, heterologous cardiac cells. Our data suggest that antibody-mediated cytolysis in vitro may also play a pathogenetic role in vivo.

Adult↗

Immune reactions in infective endocarditis. II. Relevance of circulating immune complexes, serum inhibition factors, lymphocytotoxic reactions, and antibody-dependent cellular cytotoxicity against cardiac target cells.

Circulating immune complexes (IC) were detected in 35 out of 41 patients (85%) with infective endocarditis of known bacterial origin in contrast to only 9 out of 20 patients (45%) with endocarditis but negative blood cultures (p less than 0.05). Peak IC levels of 33.25 +/- 24.33 micrograms/ml in the early period fell significantly to 8.38 +/- 13.37 micrograms/ml after antibiotic treatment (p less than 0.001). High levels of IC coincided with relative hypocomplementemia. Erythrocyturia was observed in 51 of 58 IC-positive patients demonstrating peripheral sequelae of circulating IC. Incidence and concentrations of IC correlated neither with the mere presence of the rheumatoid factor nor with the titers of antimyolemmal antibodies, nor with antibody mediated cytolysis in the presence of complement. Serum inhibition factors (SIF) and E-rosette inhibitory factors (RIF) were not demonstrated, indicating that IC in endocarditis do not suppress phytohemagglutinin-induced lymphocyte proliferation or the E-rosetting of T cells. Significant lymphocytotoxicity against heterologous cardiac target cells without serum (LC) could be demonstrated in 11 out of 23 patients (48%) with endocarditis as compared to its absence in controls (n = 33, p less than 0.01). In assays of antibody-dependent cellular cytotoxicity (ADCC), either enhancement or blocking of lymphocytotoxicity by autologous serum or both was observed. The modulation of lymphocytotoxicity was most likely due to antimyolemmal antibodies, to IC, or to both, although effects of other serum factors cannot be ruled out completely.

Antibody-Dependent Cell Cytotoxicity↗

[Significance of immunologic effector mechanisms in infectious endocarditis].

Whereas a number of investigations deals with extracardiac manifestations of immune reactions in infective endocarditis (e.g. circulating immune complexes), immunological effector mechanisms directed against the heart itself have not yet been analyzed. In 72 patients with infective endocarditis (41 patients with defined pathogen, 31 no pathogen isolated) humoral und cellular immunological effector mechanisms were investigated. Antibodies directed against the cytoskeleton of myocardial cells and against the endocardium were demonstrated in 60% to 100% depending on the infective pathogen and the clinical course. Whereas the antibodies were found in subacute and chronic courses regularly, they were found less frequently in acute lethal cases. Antibodies directed against connective tissue, endocardium and sarcolemma were indicative of, but not specific for the endocardial affection. Those antibodies which were directed against the inner parts of the sarcolemma, the myolemma, appear to be indicators of an additional myocardial affection, if they are cytolytic against vital cardiocytes in vitro. Circulating immune complexes are non-specific markers of an increased immunoreactivity. They were detected in 35 out of 41 patients with defined bacterial pathogen in the early phase of the disease. Both, their incidence and serum concentrations decreased significantly after antibiotic treatment. Cellular immune reactions directed against vital heart cells (e.g. cytotoxic reactions) can most likely be attributed to K- or NK-lymphocytes and were found in 48% of patients. Serum factors such as circulating immune complexes and/or antimyolemmal antibodies may enhance or block this cytotoxic reaction.

Adult↗

Immune reactions in tuberculous and chronic constrictive pericarditis. Clinical data and diagnostic significance of antimyocardial antibodies.

Humoral immune reactions were analyzed in 12 patients with exudative tuberculous pericarditis, 10 patients with constrictive pericarditis due to former tuberculosis, 10 patients with viral pericarditis, 20 patients with pulmonary tuberculosis, and 98 healthy donors. Pericarditis occurred in 12.5% of the patients with tuberculosis, whereas the incidence of tuberculosis in the 149 patients with pericarditis was 8%. Repeated pericardial puncture and pericardial effusions of greater than 500 ml with impending cardiac tamponade had to be performed in 4 patients. Clinical data indicated probable myocardial involvement in 4 of 12 patients. Antimyolemmal antibodies, which are a muscle-specific subtype of antisarcolemmal antibodies, were found in all patients with exudative tuberculous pericarditis and viral perimyocarditis, in only 1 of 12 patients with constrictive pericarditis, and in no patients with pulmonary tuberculosis. Antifibrillary antibodies--primarily of the antimyosin type--were missed in patients with viral heart disease but were demonstrated in 75% of patients with tuberculous pericarditis. Only sera with complement-fixing antimyolemmal antibodies of the IgG type in titers greater than 1:40 induced cytolysis of vital adult heterologous cardiocytes isolated and enriched by silica sol gradient centrifugation. These findings suggest not only that antimyolemmal antibodies are diagnostic indicators of perimyocardial involvement in tuberculous pericarditis, but also that they may play a significant role in its pathogenesis.

Antibody Specificity↗

Diagnostic relevance of humoral and cell-mediated immune reactions in patients with acute viral myocarditis.

Sera of 177 patients with acute myocarditis (10 coxsackie B 3/4, four influenza, four mumps, 15 cytomegalovirus, 144 undefined) were tested by indirect immunofluorescence for autoantibodies against heart and skeletal muscle and vital or air-dried adult cardiocytes. Antibody-dependent cytolysis, lymphocytotoxicity and antibody-dependent cellular lymphocytotoxicity were assessed using viral adult rat cardiocytes as target cells. Muscle-specific anti-sarcolemmal antibodies of the anti-myolemmal type--often associated with non-organ-specific anti-endothelial antibodies--were demonstrated in nine out of 10 patients with coxsackie B, in all patients with influenza and mumps and in 65 out of 144 patients with undefined myocarditis. In contrast, 13 out of 15 patients with cytomegalovirus myocarditis lacked anti-sarcolemmal antibodies but had low titre anti-inter fibrillary antibodies instead. In the presence of complement, anti-myolemmal antibodies induced cytolysis of vital cardiocytes, whereas hepatocytes remained unaffected. Titres of anti-myolemmal antibodies correlated with the degree of cardiocytolysis. The anti-myolemmal immunofluorescent pattern and the cytolytic serum activity could be absorbed with the respective viral antigens suggesting that these antibodies cross-react with moieties of the virus itself and may be both diagnostic and aetiological markers in acute viral myocarditis. Lymphocyte-mediated cytotoxicity against heterologous cardiac target cells could not be observed in our patients with myocarditis of proven viral aetiology. However, lymphocyte-mediated cytotoxicity was demonstrated in 10 ASA-positive and one ASA-negative patient with myocarditis of unknown origin. ASA-positive sera blocked lymphocytotoxicity in three of these patients.

Autoantibodies↗

Assessment of antibody mediated cytolysis of adult cardiocytes isolated by centrifugation in a continuous gradient of Percoll in patients with acute myocarditis.

Principal objections to conventional cytotoxicity assays in cardiac disease with myocytes as target cells are the use of fetal or neonatal myocardium, the cell-membrane of which does not express all antigenic determinants, and the use of trypsin as enzyme for isolation of the cells, since this alters the myolemmal membrane considerably. An improved and rapid procedure for the isolation of intact adult cardiocytes with collaggenase was developed. by means of a performed continuous self-generating silica sol and gradient centrifugation average enrichment of 81% vital myocytes was achieved by a single isopycnic procedure. The yield was improved to 94 +/- 3% vital cells by identical second centrifugation. Cardiocytes isolated by this method were used as target cells in an assay measuring the cytolytic activity of antibodies in the presence of complement: sera of patients suffering from acute viral myocarditis (Coxsackie B- and influenza-virus) with complement fixing antisacrolemmal antibodies (ASA) of the IgG- and IgM-type showed significant cardiocytolysis. ASA are postulated to play a role in the pathogenesis of acute Coxsackie B- and influenza-virus myocarditis.

Acute Disease↗

[Etiology of pericardial effusion following radiation therapy of Hodgkin's disease].

Radiation doses delivered to the anterior pericardium between 1969 and 1979 were ascertained in 16 patients with Hodgkin's disease, in whom pericardial effusions had developed after multiple-field therapy using 5 ventral fixed fields to the mediastinum as a supra-diaphragmatic primary treatment. The appearance of effusions was directly dependent on the dosage, if doses between 53 and 128 Gy had been delivered; in such patients, seriousness of the clinical symptoms was related to the importance of the dose delivered to the anterior pericardium. Control groups consisted of two collectives comprising 9 patients with primary pericardial affection due to Hodgkin's disease, and 11 comparable further patients without complications after mantle treatment; in these collectives, one case in the second group excepted, antisarcolemmal antibodies were not observed. On the other hand, these antibodies could be detected in 5 out of 11 patients with Hodgkin's disease who suffered from pericardial complications following radiation therapy. Possible diagnostic and pathogenetic significance of the present findings is discussed.

Adolescent↗

Clinical significance of immunopathological findings in patients with post-pericardiotomy syndrome. II. The significance of serum inhibition and rosette inhibitory factors.

Serum inhibition factors (SIF) that suppress phytohaemagglutinin-induced blast transformation of normal lymphocytes, and lymphocyte E-rosette inhibitory factors (RIF) that inhibit the T cell-specific property of E-rosette formation were determined in sixty-five patients before and after cardiac surgery. SIF was found in the first post-operative week in almost all patients; patients with complete post-pericardiotomy syndrome (PPS) still had these factors in the fourth postoperative week. The appearance of SIF correlated well with the intensity of the PPS. Persistence of SIF in eleven out of eighteen patients with clinically incomplete PPS reaffirms the probability that they had an 'immunologically' positive PPS. RIF was to be found in one third of the patients with complete or incomplete PPS and may be of prognostic value. The two factors were not identical.

Alpha-Globulins↗

[Alterations in the passive and active performance of cat papillary muscle induced by variation of preload (author's transl)].

In the isolated cat papillary muscle a rapid change in length induces a viscoelastic process of relaxation, during which the diastolic tension attains its new equilibrium after a delay. Its time course may be approximated both after stretching and releasing by a total of four exponential functions being marked by highly diverse time constants. During the stretch-induced relaxation phase the isometrically active papillary muscle shows a marked increase in mechanogram amplitudes, which is preceded in the first seconds by a short-term decrease. An opposite behavior is to be recorded after abrupt releases. The mechanograms of the stationary state prove to be exclusively a function of the degree of stretch, while the contractions in the early relaxation phases are dependent on the speed, direction and scale of the preceding change in length. The higher the stretching step chosen, the more clearly reduced are the mechanogram amplitudes of the early relaxation phase in comparison to the stationary state. This applies especially right of the optimum of force-development and contradicts a viscoelastic interpretation of the systolic phenomena in the poststretch phase. The findings after abrupt stretching point to either an initial decrease of amplitude or to a delayed approach of the contractions to their stationary state. Stretch-induced changes in the time course of the action potentials would constitute an adequate basis for the interpretation of these phenomena.

Animals↗

Acute effect of calcium channel blockers on adriamycin exposed isolated adult cardiocytes.

When tested with isolated, calcium-resistant resting rat cardiocytes in an in vitro assay system, adriamycin exerted a dose-dependent cytotoxic effect which could easily be assessed by the ATP depletion of the heart cells and the loss of vitality as monitored by morphological changes (blebbing, spherical contraction). Apart from extremely high non pharmacological concentrations of verapamil and diltiazem, both calcium antagonists left the cardiocytes intact and without loss of internal ATP when given alone to the medium. Coincubation of adriamycin and verapamil or diltiazem did not increase adriamycin toxicity to the cardiocytes; instead a remarkable ATP preservation by verapamil could be demonstrated when both drugs (adriamycin and verapamil) were incubated simultaneously with the heart cells. This acute protective effect was limited in time and could no longer be detected after 9 hours. Diltiazem in coincubation experiments exerted neither a toxic nor an acute protective effect on adriamycin-exposed heart cells.

Adenosine Triphosphate↗

Enrichment of vital adult cardiac muscle cells by continuous silica sol gradient centrifugation.

A major improvement in the isolation of vital adult cardiocytes was achieved by isopycnic preformed continuous silica sol gradient centrifugation after perfusion of the heart with collagenase. Vital rat cardiocytes were enriched to 90-95% vital cells reproducibly and constantly by one- or two-step gradient centrifugations. The isolated cardiocytes were tolerant to calcium concentrations up to 0.03 mmol/l, to diluted human serum, and to human complement. Gentamycin (50 microgram/ml) exerted a cytotoxic effect on myocytes, whereas Penicillium and Streptomycin in concentrations of 50 IU/ml did not induce cytolysis of vital cells. Digoxin 15 ng/ml) decreased the natural decay of myocytes of 20% in 25 hours to 8%. Enriched of vital cardiocytes by silica sol gradient centrifugation following their isolation by perfusion with collagenase may be helpful for investigations depending on a high yield of vital myocardial cells.

Animals↗