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Biomedical subjects

H Eckhardt

Publications and source records attributed to H Eckhardt.

At least 19 recordsLinked to original sources
PubMed2000

Prevalence of viral genome in endomyocardial biopsies from patients with inflammatory heart muscle disease.

In the report of the 1995 World Health Federation/International Society and Federation of Cardiology (WHF/ISFC) Task Force on the Definition and Classification of Cardiomyopathies, the definition of heart muscle diseases was updated. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy are now recognized in this definition. Enteroviruses, adenoviruses and cytomegaloviruses are considered as main etiopathological factors in the pathogenesis of inflammatory heart disease. A wide range of different assays have been and are currently being used, either alone or in combination, to assay for the presence of enteroviral RNA and/or DNA of cytomegalo- and adenoviruses in endomyocardial biopsy and explanted heart samples. The prevalence of cardiotropic viruses in endomyocardial biopsies of patients with clinically suspected inflammatory cardiomyopathy varies widely: enteroviral genome was detected in endomyocardial biopsies of 3 to 53% of patients, cytomegaloviral DNA was detected in 3 to 40% of patients with inflammatory heart disease and adenoviruses in 3 to 23% of the patients. This report summarizes the methods that have been used and the results of molecular biological investigation with polymerase chain reaction, which were reported by several groups over the last years. Taking this together it seems to be clear that the improvement of molecular biological techniques and the experience of people working with these methods will lead to more reliable results on prevalence, persistence and the diagnostic value of these investigations. These findings have to be taken into account in future diagnostic and therapeutic studies in the field of cardiomyopathies.

Adenovirus Infections, Human↗
PubMed2000

Detection of viral and bacterial protein in endomyocardial biopsies of patients with inflammatory heart muscle disease?

The development of highly sensitive molecular biological methods such as in-situ hybridization and polymerase chain reaction (PCR) made it possible to detect viral/bacterial nucleic acid in human endomyocardial biopsies. However, only a few investigations addressed the problem of latent persistence of viral and bacterial genome and the detection of the corresponding proteins, which could have important consequences for the clinical course of the disease. The purpose of this study was to determine whether protein of various viruses (adenovirus, enterovirus, cytomegalovirus, influenza A and B virus, herpes simplex virus 1 and 2) and bacteria (chlamydia pneumonia) can be detected in endomyocardial biopsies of patients with myocarditis and dilated cardiomyopathy with and without inflammation by use of an immunofluorescence assay and to compare the frequency of its detection with the results of PCR, immunohistology and serology. Thirty-nine patients with myocarditis and dilated cardiomyopathy with and without inflammation were examined by a direct immunofluorescence assay using the endomyocardial biopsy as antigen. Each of the samples was additionally studied by immunohistological methods and PCR for the detection of infiltrating cells and the genome of cardiotropic viruses or bacteria. Fourteen of patients were considered to have myocarditis (group 1), 9 dilated cardiomyopathy with inflammation (group 2), 10 dilated cardiomyopathy (group 3), 6 to have no myocarditis or dilated cardiomyopathy (group 4). Using a direct immunofluorescence assay we could show only that 1 patient without histological myocarditis or dilated cardiomyopathy (group 4) was positive for influenza B and chlamydia pneumonia antigens in the endomyocardial biopsy. In addition we have determined influenza B-specific antibodies, such as IgG (marginal titer) and IgA (high titer) and chlamydia pneumonia-specific antibodies, such as IgG (marginal titer) in serum of this patient. A second patient with dilated cardiomyopathy was found to be positive for protein of chlamydia pneumonia, who was shown to have chlamydia pneumonia-specific antibodies, such as IgG (high titer) in serum. There was no correlation with PCR results, but good correlation with influenza B and chlamydia pneumonia-specific antibodies in sera of these patients. In this investigation we have determined viral/bacterial-specific antibodies using serological methods and proteins of these agents using immunoflourescence. Despite the detection of virus or bacteria-specific antibodies in the sera and detection of viral and/or bacterial protein in the biopsies of some of the patients viral and/or bacterial genome was not found in the biopsy. This may be explained by the focal character of myocarditis and sampling error, because for technical reasons we use different biopsies for immunohistochemical and molecular biological investigations.

Adult↗
PubMed1998

[Cardiotropic DNA viruses and bacteria in the pathogenesis of dilated cardiomyopathy with or without inflammation].

In the report of the 1995 WHO/ISFC task force on the definition and classification of cardiomyopathies a new entity within the dilated cardiomyopathies was introduced as "inflammatory cardiomyopathy". It is defined as myocarditis associated with cardiac dysfunction. Idiopathic, autoimmune and infectious forms of inflammatory cardiomyopathy are now recognized through this definition. Dilated cardiomyopathy with inflammation (DCMi, chronic myocarditis) was also defined by a recent ISFC task force as > 14 lymphocytes/macrophages/mm3. Enteroviruses, adenoviruses and cytomegaloviruses are considered as main etiopathogenetic factors in the pathogenesis of inflammatory heart disease and have been demonstrated as important trigger for inflammatory cardiac disease. They may also cause dilated cardiomyopathy by viral persistence or secondary immunopathogenesis due to antigenic or molecular mimicry. For the detection of viral persistence the investigation of endomyocardial biopsies in patients with cardiomyopathy by the use of polymerase chain reaction and southern blot analysis is an important step for the standardization of diagnostic criteria on virally induced inflammatory cardiomyopathy. Present studies indicate an incidence of cytomegalovirus-DNA in patients with inflammatory cardiomyopathy in 10%, adenoviral-DNA in 17% and borreliosis only in rare cases (< 1%). In dilated cardiomyopathy without inflammation the respective incidences were for cytomegalovirus 12%, 15% for adenovirus and only 0.5% of cases for borreliosis. In addition the results of immunohistochemical analysis and molecular biological investigations of endomyocardial biopsies may have implications for future therapeutic studies. Depending on the etiology of the disease, immunosuppression may have benefit for patients with virus-negative cardiomyopathy with inflammation in contrast to patients with cytomegalo-, adenovirus-DNA or enteroviral persistence, in whom immunomodulation with hyperimmunoglobulins or immunoglobulins may be a feasible therapeutic option. Patients with a positive PCR for Borrelia burgdorferi should be treated with 3rd generation cephalosporines and/or sublactam.

Biopsy↗
PubMed1985

The influence of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on the levels of dopamine, serotonin and their metabolites in the caudate nucleus of the rat.

Until now it has been generally believed that N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) could induce a Parkinson-like syndrome only in man and in the rhesus monkey, a syndrome which begins with degeneration of the nigrostriatal system and is accompanied by a marked reduction in dopamine levels in the caudate nucleus. Rats, guinea pigs and cats subjected to comparable doses of NMPTP showed neither motor nor biochemical disturbances. In the present study it could be demonstrated, however, that long-term treatment of rats with a total dose of 116.9 mg NMPTP/kg brings about changes in the metabolism of the biogenic amines dopamine and serotonin in the caudate nucleus. The treatment reduced the dopamine and homovanillic acid levels to about 50% of their normal values, 3.4-dihydroxyphenylacetic acid also to 60% of the control levels. These experiments demonstrate that NMPTP, given in appropriate doses for a sufficient time, is capable of producing neurodegenerative changes in rats as well. This implies that the rat is a suitable experimental animal for studies with NMPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1979

Blocking of the initiation of protein biosynthesis by a pentanucleotide complementary to the 3' end of Escherichia coli 16 S rRNA.

Hydrogen bonding between the 3' terminus of 16 S rRNA (... C-A-C-C-U-C-C-U-U-A-OH3) and complementary sequences within the initiator region of mRNA may be a crucial event in the specific initiation of protein biosynthesis (Shine, J., and Dalgarno, L. (1974) Proc. Natl. Acad. Sci. U. S. A. 71, 1342-1346; Steitz, J. A., and Jakes, K. (1975) Proc. Natl. Acad. Sci. U. S. A. 72, 4734-4738). Using equilibrium dialysis, we have studied the binding of G-A-dG-dG-U (which is complementary to the 3' end of 16 S rRNA and which has been synthesized enzymatically) to initiation factor-free Escherichia coli ribosomes. We have also investigated the effects of the pentanucleotide on initiation reactions in E. coli ribosomes. G-A-dG-dG-U has a specific binding site on the 30 S ribosome with an association constant of 2 x 10(6) M-1 at 0 degrees C. G-A-dG-dG-U inhibits the R17 mRNA-dependent binding of fMet-tRNA by about 70%, both with 70 S ribosomes and 30 S subunits. In contrast, the A-U-G-dependent initiation reaction and the poly(U)-dependent Phe-tRNA binding was not affected by the pentanucleotide with both ribosomal species.

Escherichia coli↗