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J Müller-Quernheim

Publications and source records attributed to J Müller-Quernheim.

At least 109 records · Page 6Linked to original sources
PubMed1993

[Pulmonary toxicity caused by nitrofurantoin].

Nitrofurantoin is used in the treatment of, and to prevent, urinary tract infections. Since this chemotherapeutic agent was introduced in the fifties, quite a number of cases of acute and chronic pulmonary damage have been reported that were conditioned by nitrofurantoin. This is a report on three cases of pulmonary nitrofurantoin reactions, one of them acute and two chronic. All three patients were examined with the inclusion of bronchoalveolar lavage and transbronchial lung biopsy. In all three cases alveolitides of varying activity were confirmed. The radiological and CT findings are described.

Adult↗
PubMed1993

[Realistic in vitro study of oxygen radical liberation by alveolar macrophages and mononuclear cells of the peripheral blood after short-term exposure to SO2].

Alveolar macrophages (AM) located on the alveolar surface are directly exposed to air pollutants. We evaluated the effect of exposure to SO2 on the oxidative metabolism of AM and peripheral blood mononuclear cells (PBMNC) by measuring the spontaneous and stimulated reactive oxygen-intermediates (ROI) release. AM or PBMNC were placed on a polycarbonate membrane, which was in contact with the surface of a reservoir filled with RPMI 1640 allowing the cells to be supplied with nutrients by capillarity. For SO2 exposure times of 10, 20 and 30 minutes and concentrations of 2.5, 7.5 and 12.5 ppm were chosen. A 10-minute SO2-exposure up to 12.5 ppm induced a dose dependent maximal 3.6 fold increase of spontaneous ROI-production (r = 0.876; p < 0.005). A 30-minute exposure of 12.5 ppm SO2 exhibited a cytotoxic effect inducing the death of 62 +/- 9% of AM and caused a 63% decrease of ROI-release compared to 2.5 ppm SO2-exposure under identical conditions (r = -0.96; p < 0.005). These experiments demonstrate that AM and PBMNC are activated by SO2 and that concentrations in the range of 12.5 ppm SO2 are toxic and induce a decrease in ROI-release after 30 minutes exposure of these cells.

Aged↗
PubMed1993

[Alveolar macrophages and mononuclear cells of the peripheral blood in sulfur dioxide and chrysotile B exposure: a realistic in vitro test of oxygen free radical liberation].

Sulfur dioxide (SO2) and Asbest are frequently found at workplaces. They can induce airway and lung parenchymal injury. Alveolar macrophages (AM) play an important and decisive role in the damage of respiratory tissue. We evaluated the reactive oxygen intermediates (ROI) production of AM and peripheral blood mononuclear cells after exposure with SO2 and Chrysotile B. The cells were exposed in a special gas exposure chamber at 37 degrees C and 100% air humidity for 30 minutes to 1.5 or 2.5 ppm SO2. Afterwards they were incubated for one hour with 100 micrograms or 200 micrograms Chrysotile B. Control experiments were performed with cell exposure to synthetic air without SO2 and Chrysotile B. Spontaneous and phorbol myristate acetate (PMA) stimulated ROI-release were measured by chemiluminescence and the cell toxicity was evaluated with the trypan blue exclusion test. Our results show a dose-dependent increase of the spontaneous ROI-production of AM after SO2 and Chrysotile B exposure. Exposure to 100 micrograms Chrysotile B caused an 1.5 fold, exposure to 1.5 or 2.5 ppm SO2 plus 100 micrograms Chrysotile B resulted in an 2.4 respectively 3.3 fold increase in ROI-release compared to control experiments. Exposure of AM to 200 micrograms Chrysotile B yielded an 1.9 fold, exposure to 2.5 ppm SO2 plus 200 micrograms Chrysotile B a 3.9 fold elevation in the spontaneous ROI-production compared to control experiment with standard air. A similar reaction pattern was observed in PMA-stimulated AM and in peripheral blood mononuclear cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Evaluation of soluble CD 14 and neopterin as serum parameters of the inflammatory activity of pulmonary sarcoidosis.

CD14 represents the most specific marker for monocytes/macrophages. It has been demonstrated in vitro that monocytes/macrophages lose this antigen upon activation. Results of studies investigating the expression of membrane-bound CD14 on the surface of monocytes/macrophages in sarcoidosis patients are controversial. To investigate whether the soluble form of CD14 reflects monocyte/macrophage activation in sarcoidosis, serum levels of soluble CD14 were determined concurrently with other serum markers of monocyte/macrophage activation (neopterin, angiotensin-converting enzyme) in 50 consecutive patients with bioptically confirmed sarcoidosis. The patients were allocated to three groups according to disease activity and therapy. The soluble interleukin-2 receptor in serum and the CD4/CD8 ratio in lavage fluid were used to monitor T-lymphocyte activation. No significant differences in serum or bronchoalveolar lavage levels of soluble CD14 were observed in patients with active or inactive sarcoidosis. Despite the presence of normal soluble CD14 serum concentrations a correlation with serum neopterin and angiotensin-converting enzyme was found in active sarcoidosis (soluble CD14 versus neopterin, rs = 0.61 and 0.65, P < 0.05 and 0.01, respectively; soluble CD14 versus angiotensin-converting enzyme, rs = 0.6 and 0.72, P < 0.02 and 0.003, respectively). A correlation between soluble CD14 and parameters of T-cell activity was not demonstrated. We therefore conclude that soluble CD14 in serum is not a useful clinical parameter in establishing disease activity in sarcoidosis. Neopterin and angiotensin-converting enzyme serum concentrations are parameters with higher sensitivity, although specificity remains very low. The exact role of CD14 antigen in sarcoidosis requires further investigation.

Antigens, CD↗
PubMed1992

Measurement of lymphocyte proliferation: critical analysis of radioactive and photometric methods.

Different methods of lymphocyte proliferation are compared to identify a non-radioactive alternative to 3H-thymidine-test. The enzymatic assays evaluating the turnover of mitochondrial dehydrogenases (MTT-test) and lysosomal hexosaminidase (NAG-test) proved not sensitive enough to substitute for 3H-thymidine incorporation. The incorporation of the nucleotide analog 5-bromodeoxyuridine (BrdU) can be exploited using an ELISA-system (enzyme linked immunosorbent assay) employing a monoclonal anti-BrdU antibody to measure cell proliferation. An optimized test protocol of the BrdU-ELISA which fulfills the requirements for a sensitive and practicable non-radioactive alternative to 3H-thymidine-test is presented.

Autoradiography↗
PubMed1992

Lung-restricted activation of the alveolar macrophage/monocyte system in pulmonary sarcoidosis.

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)

Humans↗
PubMed1991

Spontaneous monokine release by alveolar macrophages in chronic sarcoidosis.

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.

Adult↗
PubMed1991

Correlation of clinical and immunologic parameters of the inflammatory activity of pulmonary sarcoidosis.

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.

Adult↗
PubMed1991

[Diabetes insipidus in sarcoidosis].

Sarcoidosis is a generalized disorder which involves the central nervous system in 5 per cent of patients presenting with the disease. We describe the case of a 22-year-old man who developed central diabetes insipidus with a daily urine production of 14,81 seven weeks after diagnosis of pulmonary sarcoidosis and parotid gland enlargement. Computed tomography showed a contrast enhancement of pituitary gland and stalk, no other intracranial manifestations were demonstrated. Intranasal administration of synthetic antidiuretic hormone (ADH) reduced urine volume to normal levels immediately. After discontinuation of 15 months therapy with corticosteroids and administration of ADH for 29 months spontaneous urine volume didn't exceed 31. The patient has been free of symptoms since discontinuation of therapy.

Administration, Intranasal↗
PubMed1990

[Immunopathogenesis of sarcoidosis: current practical knowledge].

Since the avenue of bronchoalveolar lavage detailed concepts of the immunopathogenesis of sarcoidosis have been developed. An alveolitis which parallels the inflammatory changes of the interstitium seems to be critical. Thus, the evaluation of the alveolitis yields information about the inflammatory processes in the interstitium. A compartmentalized activation of T-helper cells plays a central role in the maintenance and regulation of the alveolitis. Only the cells of the organs involved exhibit the features of activation, the cells of the peripheral blood are quiescent. By means of bronchoalveolar lavage the status of activation of the alveolar cells can be determined. Those parameters describe critical phenomenons of the disease. A detailed analysis of the activated alveolar cells disclosed mechanisms which generate serum parameters of clinical value.

Bronchoalveolar Lavage Fluid↗
PubMed1990

Assessment of local cellular immunity in lung cancer by bronchoalveolar lavage.

Small cell lung cancer (SCLC) is the most malignant of the pulmonary neoplasms and is associated with a poor local cellular immune response. 16 patients with non small cell lung cancer (NSCLC) and 11 patients with SCLC underwent bronchoalveolar lavage (BAL) in the lung which harbored the tumor in order to investigate the lymphocyte surface antigens utilizing the immunoperoxidase technique. Analysis of blood lymphocytes was performed in parallel. 8 patients with previous sarcoidosis in complete remission who underwent BAL and 10 normal blood donors served as controls. Among blood lymphocytes the CD3+, CD4+ and CD16+ cell populations were elevated significantly and the T4/T8 ratio was elevated in NSCLC patients, but only CD16+ were augmented in SCLC. Cell populations expressing the activation markers transferrin (TF) receptor, interleukin-2 (IL-2) receptor and the very late antigen VAL-1 were also increased in NSCLC, while SCLC was associated with antigen distributions similar to controls. No differences between the cohorts were seen in the expression of human leukocyte antigen (HLA)-DR. In BAL the population of CD3+ and CD4+ cells were reduced in SCLC and the T4/T8 ratio was diminished in contrast to controls and NSCLC patients, whereas these two latter groups did not differ from each other. The distribution pattern of CD16, TF receptor and IL-2 receptor in the study groups resembled that of cells of the blood stream, but CD16+ natural killer cells were additionally down regulated to control values in SCLC. No differences were seen in the distribution of VLA-1. HLA-DR+ cells were clearly elevated in both cancer groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1990

Oxygen radical production by alveolar inflammatory cells in idiopathic pulmonary fibrosis.

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)

Adult↗
PubMed1990

[In vitro models for the analysis of inflammatory processes in sarcoidosis].

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.

Cell Line↗
PubMed1990

[The serum level of the secreted interleukin 2 receptor (sIL-2R): a lymphocyte activity parameter in sarcoidosis].

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.

Humans↗
PubMed1990

[Oxygen radical production by alveolar macrophages in sarcoidosis in relation to activity status of bronchoalveolar lavage lymphocytes].

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.

Bronchoalveolar Lavage Fluid↗
PubMed1990

[Increased oxidative metabolism of alveolar macrophages in idiopathic fibrosing 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.

Bronchoalveolar Lavage Fluid↗
PubMed1990

[Reproducibility of differential bronchoalveolar lavage cytology in sarcoidosis in relation to elapsed time between bronchoalveolar lavage and sample processing].

The physiological saline solution that is usually employed for BAL is not suitable as a storage medium for BAL cells for any longer period of time: even when cooled to 4 degrees C, the lymphocyte component decreases significantly after a latency period of 24 hours. With respect to the differential cytology performed on BAL fluid, the tissue culture medium RPMI 1640 + 5% AB serum can be employed as a storage medium. But even with this medium, a very clear reduction in the total cell count in BAl is seen at 24 hours.

Bronchoalveolar Lavage Fluid↗