[Amyloidosis of the respiratory tract].
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Biomedical subjects
Publications and source records attributed to W Petermann.
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In this study various precipitation methods have been used to concentrate the proteins from broncho-alveolar-lavages. The highest percentage of proteins was recovered from the broncho-alveolar-lavages using the method of Wessel & Flügge (Anal. Biochem. 138 (1984) 141-143). The recovered proteins were further analysed by SDS-polyacrylamide gel electrophoresis. Except for low molecular mass proteins, the method of Wessel & Flügge proved to be the most effective for the recovery of individual proteins. In general, the method of Wessel & Flügge seems to be the superior method for concentrating proteins of broncho-alveolar-lavages for further analysis.
Sarcoidosis is a granulomatous disorder which can be characterized by various immunologic abnormalities including lymphocyte dysfunctions. The purpose of this study was to investigate the B-lymphocyte reactivity in the peripheral blood of 29 various patients with pulmonary sarcoidosis. A significant decrease in the production of IgG, IgM and IgA in supernatants of cultivated sarcoidosis B-cells both after stimulation with a T-cell dependent polyclonal B-cell activator (pokeweed mitogen) and with a T-cell independent polyclonal B-lymphocyte activator (Klebsiella pneumoniae) was seen, which suggested a disturbance in the B-cell differentiation of sarcoidosis patients. Those patients which were known to have a clinically active disease or a high intensity alveolitis in the bronchoalveolar lavage fluid showed a greater reduction in the B-cell differentiation response. Further evaluation of Ig-G subclasses displayed a significant decrease in the secretion of IgG1, IgG3 and IgG4. In contrast to the differentiation, the proliferation response of sarcoidotic peripheral blood lymphocytes to different mitogens did not differ from healthy controls.
In order to determine the efficacy and safety of the new quinolone ofloxacin in the treatment of chronic lower respiratory disease, 674 patients (353 with chronic bronchitis, 212 with community-acquired pneumonia and 109 with hospital-acquired pneumonia) were treated with ofloxacin 200 mg twice a day. In total, 627 patients (93%) showed a satisfactory clinical response, and 47 patients (7%) had no change or deterioration. Neither severe side effects nor interactions between ofloxacin and coadministered theophylline were seen. This is important in patients suffering from chronic obstructive airways disease. The antibiotic spectrum of ofloxacin covers nearly all bacterial pathogens causing infectious respiratory disease; furthermore, ofloxacin reaches high concentrations in pulmonary secretions and tissue. Ofloxacin is a proven antibiotic substance useful in the treatment of lower respiratory tract infections.
Pulmonary histiocytosis X is the local manifestation of a systemic disorder of unknown cause characterised by infiltration of Langerhans cell like histiocytes and parenchymal fibrosis. In a male smoker with histologically proved histiocytosis X and functional impairment bronchoalveolar lavage showed an increase in CD-1/OKT-6 antigen positive histiocytes to 8%. Northern blot analysis of RNA from bronchoalveolar lavage cells showed an exaggerated expression of the M-CSF gene and of the c-fms gene encoding for the corresponding receptor. An increased level of c-sis RNA, which encodes the B chain of platelet derived growth factor, was also found. Diffuse reticulonodular infiltrates on the chest radiograph resolved with glucocorticoid treatment and CD-1/OKT-6 antigen positive histiocytes fell to 3%. Macrophage colony stimulating factor, c-fms and c-sis gene expression were reduced almost to normal after treatment. The results suggest that macrophage colony stimulating factor and platelet derived growth factor may have a role in the initiation or maintenance of pathological reactions in pulmonary histiocytosis X.
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Bronchoalveolar lavage was performed in 14 patients suffering from histologically confirmed Wegener's granulomatosis who also showed x-ray signs of lung involvement. Cell distribution and immunophenotypical characterisation of lymphocytes and alveolar macrophages of patients suffering from Wegener's granulomatosis were compared with the findings obtained from 10 controls. The bronchoalveolar lavage of the granulomatosis patients showed a significant increase of the total cell count, signalling inflammatory involvement of the lung. Differential cytgological analysis showed a significant increase in the total number of granulocytes in the lavage fluid of the Wegener's granulomatosis patients (in one case up to 40%). The median granulocyte count was increased fivefold compared with the control. The increase of the granulocyte count was mainly conditioned by an increase in the number of neutrophilic granulocytes but there was also a significant increase in eosinophilic granulocytes. There was also a slight but significant increase in the lymphocyte count in the bronchoalveolar lavage fluid of patients with Wegener's granulomatosis. The number of CD-3-positive lymphocytes was significantly higher than with the controls. No significant differences were noted for the CD-4-positive, CD-8-positive and CD-19-positive lymphocytes. Immunophenotyping of the alveolar macrophages with monoclonal differentiation markers of the Ki-M-Series showed that the alveolar macrophages of patients with Wegener's granulomatosis resembled an immunophenotype that was close to that of monocytes. The number of proliferating macrophages was also higher than with the controls.
Alveolar macrophages (AM) in sarcoidosis display an enhanced mitotic activity. Immunocytochemical detection of the proliferation-associated Ki-67 antigen revealed significant increase in the number of proliferating AM in active sarcoidosis as compared with inactive stages of disease. Macrophage proliferation may provide an additional marker of disease activity. Since growth of macrophages is regulated by hematopoietic growth factors, we examined the expression of macrophage colony-stimulating factor (M-CSF), granulocyte M-CSF, and interleukin-3 by bronchoalveolar lavage cells in active sarcoidosis. Expression of granulocyte M-CSF or interleukin-3 genes could not be detected. AM in active sarcoidosis displayed M-CSF RNA to a comparable level like normal AM. They differed, however, in about 50% of cases analyzed, from normal AM by an enhanced level of c-fms proto-oncogene (M-CSF-receptor) expression. The enlarged proportion of proliferating AM in active sarcoidosis may be the result of an increased influx of strongly fms expressing macrophage precursors into the alveoli and autostimulation of macrophages by M-CSF.
The proliferation of alveolar macrophages in 47 patients with pulmonary sarcoidosis was investigated using immune peroxidase stains with the monoclonal antibody Ki-67. In patients suffering from sarcoidosis, a significantly elevated number of Ki-67-positive alveolar macrophages was observed. The number of proliferating alveolar macrophages showed a significant positive correlation both with the number of lymphocytes in the BAL fluid and with the T4/T8 quotient in the BAL fluid of sarcoidosis patients.
Bronchoalveolar lavage was performed in 28 patients with pulmonary sarcoidosis. Enzyme cytochemical staining with the tartrate-resistant acid phosphatase revealed a significantly increased portion of sarcoidosis macrophages showing a monocyte-like phenotype. Immunocytochemical staining with the proliferation-associated monoclonal antibody Ki-67 showed an increase of proliferating monocyte/macrophages related to disease activity in sarcoidosis. A functional activation of alveolar macrophages in sarcoidosis is indicated by spontaneous interleukin-1 secretion and increased release of oxygen free radical in sarcoidosis alveolar macrophages.
Alveolar macrophages obtained from 28 patients with pulmonary sarcoidosis were investigated to determine their ability spontaneously to release interleukin 1. In 14 of these patients, a significant spontaneous liberation of interleukin 1 was observed; the BAL parameters of these patients pointed to an elevated activity of the disease.
In fibrosing alveolitides that are associated with rheumatoid arthritides, the BAL fluid reveals a characteristic cell pattern. These cellular changes occur at an earlier date than do the radiological signs of pulmonary fibrosis. Together with a measurement of the CO diffusion capacity, BAL is a suitable monitoring parameter for fibrosing alveolitides in rheumatoid arthritis.
Fibrosing alveolitides are associated with a characteristic cellular pattern in the BAL fluid. In contrast, acute interstitial fibrosing pulmonary changes in patients receiving cytostatic drug treatment cannot be detected in the BAL fluid, since the direct influence of cytostatic agents on the cellular constitution of the BAL fluid predominates.
Reports on the development of tolerance have modified the use of nitrates in the treatment of coronary heart disease. Dosage limitations and nitrate-free intervals are frequently recommended to solve this problem (4, 5). In the clinical setting of acute myocardial infarction continuous application of glyceryl trinitrate (GTN) is still a widely used therapy (1). In this study we investigated whether a low-dose intravenous GTN administration leads to a rapid development of tolerance. During the observation period of 60 h, no attenuation of drug effects on the pulmonary pressures could be detected. Subsequent oral medication also showed an undiminished nitrate response.
Alveolar macrophages from 28 patients with pulmonary sarcoidosis, from 6 patients with idiopathic pulmonary fibrosis and from 8 control subjects were tested for their spontaneous interleukin-1 release. Whereas alveolar macrophages from the controls and from the patients with idiopathic pulmonary fibrosis did not show a significant release of interleukin 1, 14 of the sarcoidosis patients displayed a considerable spontaneous interleukin-1 secretion. Besides radiographic signs of an increased disease activity these patients revealed a significantly elevated number of lymphocytes and a significantly increased T4/T8-ratio in the bronchoalveolar lavage indicating an enhanced inflammatory activity of sarcoidosis. The spontaneous interleukin-1 release is possibly due to a raised number of immature alveolar macrophages in the lung of patients with sarcoidosis.
Oxidative metabolism in phagocytes such as granulocytes, monocytes, and alveolar macrophages is becoming of increasing interest in efforts to determine the pathogenetic mechanisms in diseases related to tissue damage, e.g., sarcoidosis. The release of free oxygen radicals is dependent on the activation of the oxidative metabolism and can be measured by means of chemiluminescence. Basic luminol-dependent chemiluminescence released by monocytes and alveolar macrophages from 12 patients with untreated pulmonary sarcoidosis stage II was increased (p less than 0.01) compared with 12 control subjects. A less distinct difference could be observed in the chemiluminescence response of granulocytes (P less than 0.05). After stimulation with zymosan, alveolar macrophages and monocytes (P less than 0.01) as well as granulocytes (P less than 0.05) had an enhanced luminol-dependent chemiluminescence compared with the control group. Emission of chemiluminescence by alveolar macrophages was considerably lower than that of granulocytes and monocytes. No significant correlation could be demonstrated between chemiluminescence response of granulocytes and monocytes and cellular markers of sarcoidotic activity such as lymphocytosis in bronchoalveolar lavage and T-helper/T-suppressor ratio in the lavage fluid. In contrast to that, a significant correlation (P less than 0.01) could be observed both between nonstimulated chemiluminescence and stimulated chemiluminescence and lymphocytosis and T-helper/T-suppressor ratio in bronchoalveolar lavage. Enhanced chemiluminescence may indicate inflammatory activation in pulmonary sarcoidosis.
Alveolar macrophages differ from their percursors in blood, monocytes, by expressing strong activity of the tartrate resistant variant of acid phosphatase (TAcP). A study was carried out to analyse the expression of this enzyme cytochemical marker by alveolar macrophages from bronchoalveolar lavage cells from 34 patients with sarcoidosis and 12 control subjects. Alveolar macrophages from control subjects displayed a strong and homogeneous staining pattern and only 0.1% of cells were negative after staining. Macrophages from patients with sarcoidosis showed reduced TAcP activity and up to 7% of the cells were negative. The percentage of TAcP negative macrophages was correlated with the percentage of lymphocytes and with the ratio of CD4 to CD8 lymphocytes among cells recovered by bronchoalveolar lavage. The reduced TAcP activity in alveolar macrophages from patients with sarcoidosis may be due to an increased recruitment of immature precursors from blood.
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