We investigated whether atrophy and hypertrophy signalling were altered in the diaphragm of chronic obstructive pulmonary disease (COPD) patients.We studied diaphragm fibre dimensions and proportion, expression of markers of the ubiquitinproteasome pathway, nuclear factor (NF)-kB pathways, muscle regulatory factors and myostatin in diaphragm biopsies from 19 patients with severe COPD and 13 patients without COPD.Type I proportion was significantly increased in the diaphragm of COPD patients while type II proportion was decreased. The cross-sectional area of all fibre types was reduced in the COPD patients. In addition, MAFbx mRNA was higher in the diaphragm of COPD patients while Nedd4 mRNA decreased. Cytoplasmatic levels of inhibitor protein IkBa and IkBb were decreased in the COPD patients as was NF-kB p50 DNA-binding activity. MyoD mRNA and its nuclear protein content were decreased in the diaphragm of COPD patients and myogenin mRNA and protein levels remained unchanged. Myostatin mRNA was decreased but its protein levels in the nuclear and cytoplasmic fraction were significantly increased in the COPD patients.These data show that the ubiquitin-proteasome pathway, the NF-kB pathway and myostatin protein were up-regulated in the diaphragm of COPD patients while MyoD expression was reduced. These alterations may contribute to diaphragm remodeling in COPD.

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.

Three hundred and forty-one drugs, commonly used in intensive care units (ICU), were chosen for an investigation of possible activation or inhibition of the histamine metabolizing enzyme diamine oxidase (DAO). After examination of 164 substances, using both canine and human DAO in an in vitro screening test, 61 agents inhibited DAO activity to various degrees. Of these, 44 inhibited the enzyme from both species, 4 inhibited the canine enzyme only and 13 the human DAO only. No compound tested was able to enhance the enzyme activity. The inhibiting agents included representatives of all major therapeutic groups. A particularly strong inhibition was observed with the neuromuscular blocking drugs d-tubocurarine, pancuronium and alcuronium, however, the other commonly used neuromuscular blocking drug, suxamethonium, was without effect. Similarly with the cephalosporines, cefotiame and cefuroxime caused a marked inhibition of the human DAO activity, whereas another regularly-used substance of this class, cefotaxime, inhibited neither the human nor the canine enzyme in concentrations up to 10(-3) M. The observation that within a given therapeutic group some members inhibit and others do not, could be useful in choosing a therapy concept which minimizes the risk of a more severe 'histamine' reaction in seriously ill patients.

To understand the role of histamine in the aetiology and pathogenesis of human diseases reliable data are urgently needed for the histamine content and for the activities of histamine-forming and -inactivating enzymes in human tissues. In order to make a substantial progress toward this aim a tissue-sampling programme during surgical interventions was carefully conceived and conducted. From March 1982 until January 1983 106 tissue specimens were taken from 56 patients who underwent surgery. Only healthy tissues, not injured or oedematous, and without adherent structures were taken by only one surgeon who was interested in this research and experienced in tissue preparation procedures in biochemistry. The times of 'warm' ischaemia during the operative procedures were visually estimated, the times between resection of the organs or specimens and deep-freezing of the tissues were precisely recorded. Compared to previous work in the literature and especially to our own work using the same assays for determination higher histamine contents were found in this study in most of the tissues, in particular in the gastrointestinal tract. Also the diamine oxidase activities were considerably higher in many organs, e.g. 3-4 times higher in the gastrointestinal tract when compared with those in publications of our group who used always the same analytical test. However, the histamine methyltransferase activities in this study were not at variance to those determined in previous investigations. Many of them were reported in this communication for the first time. Since the methods for histamine determination and those for measuring enzymic activities were not different in this study and in previous communications of our group we are convinced that the optimized tissue-sampling and -preparation techniques were responsible for the higher values in this communication. But the problem of the 'warm' ischaemia period could not be solved by sample-taking procedures of this type during operations. There are good reasons to prefer biopsy specimens for the analysis of histamine storage and metabolism in human tissues in health and disease, but - unfortunately - they are not always available.

Human cytomegalovirus (CMV) can persist in many organs after primary infection. Not only is it suspected to cause morbidity during reactivation in patients under immunosuppression, but it may also induce long-term latency by chronic disease, e.g. in the myocardium. Endomyocardial biopsies of 27 patients with active myocarditis, 35 patients with healing, 41 patients with healed and 25 patients with ongoing myocarditis according to the Dallas Criteria and 52 patients with dilated cardiomyopathy (DCM) and the biopsies of 25 healthy heart donors were studied for persisting CMV-DNA by polymerase chain reaction (PCR) and in-situ hybridization (ISH). CMV-DNA could be assessed in 5-14% of patients in the different stages of myocarditis and in 22% of patients with DCM. Although two biopsies of the control group showed a positive result, studies by in-situ hybridization demonstrated that in patients with heart muscle disease CMV persists in all cell types including myocytes, whereas in the controls it is only found in interstitial cells. CMV antigens could not be detected in the myocardium with our methods. It must be assumed that infection by CMV is more a persistent or latent than an active infection.