Biomedical subjects
Publications and source records attributed to J Strausz.
In the report on 35 CT-guided fine needle transthoracic biopsies the authors show the relevance of invasive radiological methods in tumor diagnostics. The results are compared with those published in the literature. CT-guided transthoracic biopsy is of crucial importance in final diagnosis of certain thoracic diseases.
Six patients with obstruction of the trachea were treated with silicone rubber endothracheal stents implanted with flexible bronchoscope. In every case the stent caused significant clinical improvement of the ventilation. At the postintubation stenosis the stent can result a final recovery, at the malignant processes the implantation seems to be a new palliative method.
Bronchoalveolar lavage is a relative simple bronchological method just slightly loading the patient. The data about recovered cellular fraction--except the detection of tumour cells and certain pathogens--rarely forms a basis for diagnosis. The determination of the activity of inflammatory processes on the basis of cellular data or immunocytological characteristics can not be considered reliable parameter to be used in the clinical practice. Bronchoalveolar lavage proved to be an optimal experimental method to study the pathomechanism of different lung diseases. Due to the high costs, examinations are worth performing only in well equipped centres.
An activation of T-cells that is restricted to the lung has been demonstrated in pulmonary sarcoidosis. The role of blood monocytes (MO) and alveolar macrophages (AM) in this concept of compartmentalized inflammation has not yet been evaluated. In order to elucidate this question, we measured the release of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) by peripheral blood mononuclear cells (PBMNC) and AM in 43 patients with sarcoidosis (32 with active, 11 with inactive disease) without therapy and correlated the spontaneous monokine release to parameters of the T-cell alveolitis and the course of the disease. TNF alpha as well as IL-1 were spontaneously released by AM of the active group, i.e., 2,385 +/- 735 pg/ml/10(8) cells/24 h and 7/12 (IL-1+/total), respectively. Autologous PBMNC were quiescent, releasing only baseline levels of any monokine. AM were not activated in the inactive group, releasing 500 +/- 212 pg/ml/10(6) cells/24 h TNF alpha, whereas 1/5 were IL-1-positive (p less than 0.05 in both comparisons), which is within the range of the control group. Kinetic experiments revealed that the TNF alpha gene of AM is activated in vivo, resulting in TNF alpha mRNA-positive, TNF alpha-releasing cells that, cultured in vitro, regulate the TNF alpha gene transcription down and cease to release TNF alpha. Interestingly, there is no stringent correlation between the spontaneous release of TNF alpha by AM and signs of T-cell activation as soluble interleukin-2 (IL-2) receptor serum concentration, release of IL-2, and expression of IL-2 receptor by alveolar T-cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Current concepts of the immunopathology of sarcoidosis claim a central role for activated pulmonary T-lymphocytes in the maintenance of inflammatory processes. We hypothesized that the pulmonary sarcoidosis disease activity could be monitored by the measurement of serum levels of sIL-2R. We evaluated the sIL-2R in 28 sarcoidosis patients at multiple time points before, during and after therapy and compared the results with the clinical activity of the disease. Before therapy out of 24 episodes with active disease 20 exhibited elevated levels of sIL-2R. Six out of 21 episodes with inactive disease after tappering off corticoid therapy had sIL-2R levels above the upper limit of the normal range. Disease activity under therapy as well segregated with the sIL-2R serum level. Our results demonstrate that the activity of pulmonary sarcoidosis is reflected accurately by the serum level of sIL-2R suggesting that phenomenons of T-cell activation determining the course of the disease are monitored by this approach.
In pulmonary sarcoidosis an activation of alveolar T lymphocytes and alveolar macrophages (AM) has been demonstrated. There is evidence that in contrast to acute disease a heightened T-cell response cannot be observed in the chronic phase of sarcoidosis. The role of AM in the inflammatory process of chronic sarcoidosis is not yet intensively evaluated. To address this question we measured the release of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) by AM of 39 patients with chronic sarcoidosis (duration greater than 4 years; 30 active, 9 inactive diseases) without therapy and correlated the monokine release with parameters of T-cell alveolitis and the course of the disease. The T4/T8 ratio was higher in the active than in the inactive group without reaching statistical significance. TNF alpha as well as IL-1 is spontaneously released by AM of the active group 2,099 +/- 518 pg/ml TNF alpha/10(6) cells/24 h and 8/13 (IL-1+/total) respectively. In the inactive group the AM release 375 +/- 246 pg/ml TNF alpha/10(6) cells/24 h which is in the range of the control and 1 out of 5 patients was IL-1-positive. There was no correlation between the monokine release and any parameter of T-cell alveolitis. These data support the hypothesis that the inflammatory process in chronic sarcoidosis is dominated by the activity of AM and that this activity determines the course of the disease.
The evaluation of activation markers such as T4/T8 ratio and HLA-DR expression of lymphocytes of bronchoalveolar lavage (L-BAL) is an important clinical approach for the staging of sarcoidosis. However, it is not known to what extent this is paralleled by an exaggerated lymphocyte function. We investigated the dependence of L-BAL activation markers on the production of interleukin-2 (IL-2) by L-BAL and on the soluble IL-2 receptor serum level (sIL-2R) in 116 patients with sarcoidosis. In none of the combinations tested was a correlation between the two groups of parameters found; r less than 0.5, upper 90% confidence limit of r less than 0.8. Interestingly, IL-2 production is independent of HLA-DR+ T4 L-BAL, and sIL-2R production is independent of the percentage of IL-2+ L-BAL. Our data indicate that the L-BAL activation markers and the functional activity of T-cells represent independent phenomena.
Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory interstitial lung disease characterized by the accumulation of alveolar macrophages (AMs) and neutrophils in the lower respiratory tract, parenchymal cell injury, and fibrosis of the alveolar structure. Reactive oxygen intermediates (ROI) are claimed to be a major cause of tissue damage in IPF; however, the source of ROI has not been unequivocally identified. AMs, as well as neutrophils, are capable of releasing these agents. The contributions of these possible sources are not known. To address this question, we evaluated the spontaneous and stimulated (PMA or zymosan) ROI release of total bronchoalveolar cells and isolated AMs in 14 patients with IPF by means of luminol-enhanced chemiluminescence. Bronchoalveolar lavage (BAL) cells from 17 individuals without any signs of inflammation served as controls. In comparison with the controls, the spontaneous as well as the stimulated ROI release of total BAL cells in IPF are markedly increased (20,763.9 +/- 5,079.3 versus 2,509.5 +/- 300.6 counts/10 s/2.10(5) cells, spontaneously, IPF versus control; 106,819.3 +/- 33,802.8 versus 8,919 +/- 1,357.9 PMA induced; 41,597.1 +/- 8,442.6 versus 6,223.8 +/- 1,025.1 zymosan induced, p less than 0.001). Measurement of the ROI release of purified AMs revealed that these cells produce the bulk part of ROI released by BAL cells (84%). In spite of the fact that, on a per cell basis, the ROI release of neutrophils is 1.7-fold of that of AMs, there is no correlation between the ROI production of total BAL cells and the percentage of neutrophils in BAL, demonstrating a minor role of these cells in the generation of the total ROI burden in IPF.(ABSTRACT TRUNCATED AT 250 WORDS)
Currently there are no animal models available for interstitial lung diseases with unknown origin, such as sarcoidosis. Inflammatory cells obtained from patients have several disadvantages for the in-vitro verification of pathogenetical concepts. Thus, in-vitro models are desirable. Employing cell lines we present models that are suited to study the angiotensin-converting enzyme release and the production of oxygen radicals by activated macrophages and their fusion to giant cells.
Current concepts of the immunopathology of sarcoidosis indicate that activated pulmonary T-lymphocytes play a central role in the maintenance of inflammatory processes. For the clinical management of the disease parameters which reflect the compartmentalized T-cell activation in the lung and which can be obtained from the peripheral blood are desired. Activated T-cells are known to release sIL-2R. Thus, we hypothesized that in pulmonary sarcoidosis disease activity could be monitored by the measurement of serum levels of sIL-2R. Our results demonstrate that disease activity is reflected more accurately by the serum level of sIL-2R than that of ACE, suggesting that phenomena of T-cell activation determining the course of the disease are monitored by this approach.
Mediators of lymphocytic alveolitis in sarcoidosis are able to activate alveolar macrophages. In sarcoidosis, there is a pre-activation of the alveolar macrophages, which is reflected in an elevated production of O2 by the alveolar macrophages. There is a positive correlation between this radical load in the distal respiration tract and parameters of lymphocytic alveolitis.
The results of the present investigation show that, in IPF, alveolar macrophages are preactivated, and are capable, both spontaneously and also after cellular stimulation with a variety of stimulants, of producing appreciably more cytotoxic oxygen metabolites as compared with alveolar macrophages from healthy control subjects. A striking finding is the fact that the production of oxidants following stimulation with the complement factors C3a-C5a and aggregated IgG is appreciably lower than following stimulation with PMA or zymosan. This might be evidence in support of the theory that the alveolar macrophages in IPF are activated by immune complexes.
Serum sIL-2-R levels were measured in 28 sarcoidosis patients at multiple time points before, during, and after therapy, with a mean follow-up time of 10.2 +/- 5.2 months, and the results compared with the clinical activity of the disease. Before therapy, 20 out of 24 episodes with active disease exhibited elevated levels of sIL-2-R (918 +/- 362 U/ml). In inactive disease after tapering off corticoid therapy the sIL-2-R levels were 453 +/- 274 U/ml. Disease activity under therapy also correlated with sIL-2-R serum levels. 23 out of 29 episodes with signs of activity under therapy had elevated sIL-2-R levels (808 +/- 409 U/ml). Only three of 28 patients in whom disease activity ceased after therapy had been initiated had raised sIL-2-R levels (mean: 401 +/- 140 U/ml). These results demonstrate that the activity of pulmonary sarcoidosis is reflected accurately by the serum levels of sIL-2-R, suggesting that the course of the disease can be monitored by this approach.
Current concepts of the immunopathogenesis of sarcoidosis favor a central role of activated, interleukin-2 (IL-2) producing helper T-cells at sites of inflammation. Normally, activated T-cells release IL-2 and express IL-2 receptors (IL-2R). IL-2R+ cells, however, are not uniformly found in patients with clinically active disease. To determine whether the lack of IL-2R+ cells is caused by a dysregulation of the IL-2R gene or by the mode of T-cell activation in pulmonary sarcoidosis, we quantified IL-2 and IL-2R m-RNA transcripts, IL-2 release, and IL-2R surface protein in peripheral blood lymphocytes of patients with sarcoidosis and normal control subjects before and after in vitro stimulation as a function of time. Additionally, we determined the percentage of IL-2R+ bronchoalveolar lavage (BAL) and peripheral blood lymphocytes in our study population and evaluated the in vivo transcriptional activity of the IL-2R gene. In peripheral blood lymphocytes, maximal IL-2R mRNA accumulation is found between 6 and 24 h, and maximal accumulation of IL-2 mRNA is found between 24 and 48 h. No differences emerged between normal subjects and patients with sarcoidosis. In six of 19 patients, we observed elevated numbers of IL-2R+ BAL lymphocytes and found IL-2R mRNA in those cells. These results are in accordance with the concept of a compartmentalized T-cell activation in sarcoidosis, resulting in IL-2 and IL-2R positive BAL cells and quiescent peripheral blood lymphocytes.
Interstitial lung diseases are characterised by chronic inflammatory processes in the lower respiratory tract, parenchymal cell injury and progressive fibrosis of the alveolar structure. Oxygen radicals are claimed to be a major cause of the tissue damage in the lung. We evaluated the spontaneous and stimulated oxygen radical release of bronchoalveolar lavage (BAL) cells in 35 patients with sarcoidosis and 17 patients with IPF. In comparison with the control in both diseases the spontaneous as well as the stimulated oxygen radical release of the BAL cells is markedly increased. In IPF alveolar macrophages produce the buk part of radicals (84%). Due to their low percentage and in spite of a higher activity on a per cell basis the contribution of neutrophils to the total radical burden is only marginal. In sarcoidosis there is a positive correlation between the oxygen radical release of AM and the CD4/CD8 ratio of BAL lymphocytes. Our results demonstrate that the clinical activity of sarcoidosis and IPF is reflected by the oxygen radical release of BAL cells.
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