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Ulrich Costabel

Publications and source records attributed to Ulrich Costabel.

26 records · Page 2Linked to original sources

[Inhibition of cytokine release from alveolar macrophages in pulmonary sarcoidosis by pentoxifylline].

OBJECTIVE: Pentoxifylline (POF) has recently been shown to suppress the cytokine production from lipopolysaccharide (LPS) stimulated monocytes/alveolar macrophages (AM). Sarcoidosis is a granulomatous disease which is driven by the action of tumor necrosis factor (TNF-alpha) and other proinflammatory cytokines. It was investigated that the effects of POF on the production of TNF-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10 and the soluble TNF-alpha receptors (sTNFR-1 and sTNFR-2) from AM in sarcoidosis, as comparison to dexamethasone (DEX). METHODS: AM from 14 patients with active pulmonary sarcoidosis were cultured for 24 h with RPMI medium alone, or with LPS (100 micro g/L), and with POF at concentrations of 0.01 mmol/L, 0.1 mmol/L and 1 mmol/L, or with 0.1 mmol/L DEX. Cytokines in the culture supernatants were analysed by ELISA. RESULTS: POF induced a dose dependent suppression of the spontaneous TNF-alpha release from AM in sarcoidosis (P < 0.001), while the spontaneous release of other cytokines was unaffected by POF at all tested concentrations, but a trend for the inhibition of IL-10 production was found (P = 0.092). DEX 0.1 mmol/L inhibited the spontaneous release of TNF-alpha, sTNFR-2, IL-1beta and IL-10 (P < 0.001 or < 0.05 or <0.01). POF also suppressed the production of these LPS-stimulated cytokines except of sTNFR-1 (P < 0.05 or < 0.001). Similar to POF, DEX (0.1 mmol/L) inhibited the production of these LPS-stimulated cytokines (P < 0.05 or < 0.001), but not of sTNFR-1 and IL-1beta. CONCLUSIONS: Compared with DEX, POF may improve the therapy of sarcoidosis by either sparing or replacing corticosteroids. However, the precise clinical value of POF in the treatment of sarcoidosis and other lung diseases needs to be determined in further clinical trials.

Adult↗

Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis.

The cause(s) of sarcoidosis is unknown. Mycobacterium spp. are suspected in Europe and Propionibacterium spp. are suspected in Japan. The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species. Formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England. Genomes of Propionibacterium acnes, Propionibacterium granulosum, Mycobacterium tuberculosis, Mycobacterium avium subsp. paratuberculosis, and Escherichia coli (as the control) were counted by quantitative real-time PCR. Either P. acnes or P. granulosum was found in all but two of the sarcoid samples. M. avium subsp. paratuberculosis was found in no sarcoid sample. M. tuberculosis was found in 0 to 9% of the sarcoid samples but in 65 to 100% of the tuberculosis samples. In sarcoid lymph nodes, the total numbers of genomes of P. acnes or P. granulosum were far more than those of M. tuberculosis. P. acnes or P. granulosum was found in 0 to 60% of the tuberculosis and control samples, but the total numbers of genomes of P. acnes or P. granulosum in such samples were less than those in sarcoid samples. Propionibacterium spp. are more likely than Mycobacteria spp. to be involved in the etiology of sarcoidosis, not only in Japanese but also in European patients with sarcoidosis.

Actinomycetales Infections↗

Immune cells in bronchoalveolar lavage in peripheral lung cancer--analysis of 140 cases.

BACKGROUND: Changes in the bronchoalveolar lavage fluid (BALF) cell profile may reflect immunologic reactions of the lung in pulmonary malignancies. OBJECTIVE: Our aim was to analyse the BALF cell profile in peripheral lung cancer. METHODS: This study was a retrospective analysis of BALF samples containing tumor cells from patients with confirmed peripheral lung cancer (140 cases). Routine analysis and lymphocyte phenotyping by an immunoperoxidase technique with the monoclonal antibodies CD3, CD20, CD4, CD8, CD57, CD1, CD25, CD71 and HLA-DR were performed. The data were compared with those from healthy persons. RESULTS: We found a significantly lower proportion of macrophages (60%), and significantly elevated proportions of lymphocytes (24%) and neutrophils (13%) in cases with cancer when compared with controls. The proportion of eosinophils was higher in the cancer patients (2.4%), though not significantly. Regarding the lymphocyte phenotypes, we found a significantly elevated proportion of T cells (86%), a relatively low CD4/CD8 ratio (1.7 +/- 1.3), and a relatively higher percentage of HLA-DR+ lymphocytes (6.6%) in patients with cancer. There were no significant differences between smokers and nonsmokers in the cancer patients. In more than half of the cases, a positive staining for epithelial membrane antigen was found. CONCLUSION: Our observations confirm the possible participation of lymphocytes (activated and suppressor subtypes) and eosinophils in the response against tumor in peripheral airways.

Adenocarcinoma↗

Rare infiltrative lung diseases: a challenge for clinicians.

Rare diffuse infiltrative lung diseases are a challenge for clinicians, radiologists, and pathologists for at least three reasons: (a) their low incidence and prevalence hamper the acquisition of expertise and frequently the diagnosis is delayed; (b) therapeutic actions are mainly empirical and based on steroid use, and (c) pathogenetic events are difficult to explain and only recently new therapeutic measures taking advantage of innovative genetic and/or immunopathogenetic studies have been suggested. In this review rare diffuse lung disorders are briefly discussed (pulmonary alveolar proteinosis, inherited lipidoses, acute eosinophilic pneumonia, amyloidosis, pulmonary ossification, pulmonary alveolar microlithiasis). The list is obviously not exhaustive and arbitrarily chosen. The intent is, however, to emphasize that in this difficult field multidisciplinary expertise and the knowledge of the most recent pathogenetic mechanisms have the main role in diagnosis and treatment.

Acute Disease↗

Cockade-like structures in alveolar macrophages in extrinsic allergic alveolitis.

BACKGROUND AND OBJECTIVES: In immunocytochemical preparations of bronchoalveolar lavage (BAL) cells from patients with extrinsic allergic alveolitis (EAA), we observed the presence of alveolar macrophages with cockade-like structures in their cytoplasm (cockade+ alveolar macrophages). These cockade+ alveolar macrophages may reflect a subpopulation of alveolar macrophages which may show a different predominance in various interstitial lung diseases. In this study we aimed to compare the frequency of cockade+ alveolar macrophages in patients with EAA (n = 14) with the results obtained in patients with sarcoidosis (n = 11), idiopathic interstitial pneumonia (IIP; n = 10) and control subjects (n = 8). We also investigated the expression of the transferrin receptor CD71 on cockade+ alveolar macrophages. METHODS: In BAL fluid, the total number of cells and differential counts were determined, and immunocytologic examinations of macrophages and lymphocytes were done using monoclonal antibodies. The percentage of cockade+ alveolar macrophages was determined by counting 300 macrophages in the CD20 field of an immunocytochemical slide. RESULTS: The percentage of cockade+ alveolar macrophages was significantly higher in the EAA group (36 +/- 9%) compared to patients with sarcoidosis (12 +/- 5%) or IIP (11 +/- 10%) and control subjects (3 +/- 1%; p < 0.001). The proportion of CD71+ alveolar macrophages was significantly lower in EAA than in the other groups (p < 0.01), and the CD71 antigen was expressed on a significantly lower proportion of cockade+ alveolar macrophages compared to cockade- alveolar macrophages in EAA (p < 0.001). CONCLUSION: We conclude that cockade+ alveolar macrophages could play a role in the pathogenesis and differential diagnosis EAA.

Adult↗

Surfactant protein A detection in primary pulmonary adenocarcinoma without bronchioloalveolar pattern.

BACKGROUND: Immunohistochemical studies in human lung carcinoma reported positive staining of tumor cells for surfactant protein A (SP-A), especially in peripheral airway cell carcinoma, which include bronchioloalveolar carcinoma and in some reports also papillary subtypes. OBJECTIVE: The purpose of this study was to determine the SP-A expression in tumor cells of lung adenocarcinoma without a bronchioloalveolar pattern, classified according to the WHO. METHODS: In total, 169 primary adenocarcinomas of the lung (109 acinar, 32 solid with mucin, 24 papillary and 4 mucinous) were examined by immunohistochemistry for SP-A expression. RESULTS: Twenty-five percent of acinar, 38% of papillary and 3% of solid adenocarcinoma with mucin showed a positive intracytoplasmic SP-A reaction of the tumor cells. None of the mucinous adenocarcinomas stained for SP-A. This study included the largest number of acinar adenocarcinomas and solid adenocarcinomas with mucin studied for SP-A. We clearly demonstrated that also primary lung adenocarcinoma without a bronchioloalveolar pattern can express SP-A. A positive staining of hyperplastic type II cells surrounding the tumors or entrapped in the tumor could clearly be differentiated from the SP-A-positive stain of tumor cells. CONCLUSION: These results support the theory that SP-A-producing cells may generate not only bronchioloalveolar and papillary carcinoma, but also other subtypes of lung adenocarcinoma.

Adenocarcinoma↗

Reactive alveolar epithelium in chondroid hamartoma of the lung.

OBJECTIVE: To determine the morphologic characteristics of the nonciliated epithelium found in chondroid hamartoma of the lung. STUDY DESIGN: The morphologic characteristics and immunohistochemical reaction for surfactant protein A of the nonciliated epithelium in chondroid hamartoma of the lung was studied by immunohistochemistry. Alveolar epithelium in normal lung tissue and lung tissue surrounding primary lung cancer or metastatic lung lesions was used as a control. RESULTS: In all cases, the nonciliated epithelium in chondroid hamartoma showed the morphologic criteria of hyperplastic alveolar type II cells and a very strong positive surfactant protein A reaction in the cytoplasm when compared with alveolar epithelium of the normal lung. Similar hyperplastic type II cells were also found in the alveolar lung around metastatic or primary lung tumors. CONCLUSION: These findings may indicate that the nonciliated cells found in chondroid hamartoma of the lung are hyperplastic type II cells. This suggests that the alveolar epithelium found in chondroid hamartoma of the lung is a secondary reaction around the hamartoma and not a primary component of the lesion.

Adipose Tissue↗