Biomedical subjects

Marie Wildt

Publications and source records attributed to Marie Wildt.

3 recordsLinked to original sources

PubMed2006

Functional and phenotypical comparison of myofibroblasts derived from biopsies and bronchoalveolar lavage in mild asthma and scleroderma.

BACKGROUND: Activated fibroblasts, which have previously been obtained from bronchoalveolar lavage fluid (BALF), are proposed to be important cells in the fibrotic processes of asthma and scleroderma (SSc). We have studied the motility for BALF derived fibroblasts in patients with SSc that may explain the presence of these cells in the airway lumen. Furthermore, we have compared phenotypic alterations in activated fibroblasts from BALF and bronchial biopsies from patients with mild asthma and SSc that may account for the distinct fibrotic responses. METHODS: Fibroblasts were cultured from BALF and bronchial biopsies from patients with mild asthma and SSc. The motility was studied using a cell migration assay. Western Blotting was used to study the expression of alpha-smooth muscle actin (alpha-SMA), ED-A fibronectin, and serine arginine splicing factor 20 (SRp20). The protein expression pattern was analyzed to reveal potential biomarkers using two-dimensional electrophoresis (2-DE) and sequencing dual matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-TOF). The Mann-Whitney method was used to calculate statistical significance. RESULTS: Increased migration and levels of ED-A fibronectin were observed in BALF fibroblasts from both groups of patients, supported by increased expression of RhoA, Rac1, and the splicing factor SRp20. However, these observations were exclusively accompanied by increased expression of alpha-SMA in patients with mild asthma. Compared to BALF fibroblasts in mild asthma, fibroblasts in SSc displayed a differential protein expression pattern of cytoskeletal- and scavenger proteins. These identified proteins facilitate cell migration, oxidative stress, and the excessive deposition of extracellular matrix observed in patients with SSc. CONCLUSION: This study demonstrates a possible origin for fibroblasts in the airway lumen in patients with SSc and important differences between fibroblast phenotypes in mild asthma and SSc. The findings may explain the distinct fibrotic processes and highlight the motile BALF fibroblast as a potential target cell in these disorders.

Adult↗

PubMed2005

Small intestinal manometry in patients with systemic sclerosis.

OBJECTIVES: The study explores, by the use of manometry, the frequency and severity of small intestinal involvement in patients with systemic sclerosis, and relates the manometric findings to clinical symptoms, radiology, and some intestinal regulatory peptides. METHODS: Stationary antroduodeno-jejunal manometry was used to study small bowel involvement in 10 patients with systemic sclerosis and dysmotility of the oesophagus or signs of malabsorption. Measurements were made during fasting, after a meal, and after octreotide administration and were then compared with a sex-matched control group of healthy individuals. Plasma samples were taken in order to analyse levels of motilin, peptide YY, cholecystokinin, and somatostatin. RESULTS: Manometry was abnormal, with signs of intestinal pseudo-obstruction in eight out of 10 patients. In the control group, one individual had an abnormal manometry, as a result of burst activity. The mean contractile amplitudes during fasting and periods after food, spontaneous phase III periods, and octreotide-induced activity complexes were significantly reduced in the systemic sclerosis group when compared with controls. None of the patients, including two with advanced manometric intestinal disturbances, had small intestinal dilatation when examined by radiography. The plasma peptide levels did not differ significantly between the two groups. CONCLUSIONS: In eight out of 10 patients the manometric criteria for intestinal pseudo-obstruction were fulfilled, with a motility pattern consistent with both neuropathy and myopathy. The release of motility-regulating peptides was unaffected.

Adult↗

PubMed2004

Presence of activated mobile fibroblasts in bronchoalveolar lavage from patients with mild asthma.

Activated fibroblasts are suggested to be involved in the deposition of extracellular matrix in the formation of peribronchial fibrosis in asthma. We report the novel finding of activated elongated fibroblasts accompanied by elevated numbers of eosinophils in bronchoalveolar lavage fluid from 5 out of 12 patients with mild asthma (= 42%), whereas no fibroblasts were observed in the control subjects without asthma (n = 17). The elongated fibroblasts migrated twice as far when compared with fibroblasts from corresponding bronchial biopsies from the same patients, accompanied by an induced expression of RhoA and Rac1, indicating that the increased expression of these proteins are linked to increased migratory capabilities. Moreover, the elongated fibroblasts had an elevated production of the proteoglycans biglycan, versican, perlecan, and decorin, which correlated to an active cytoplasm in these cells. Differential expression patterns between the two fibroblast groups in motility-regulating proteins, such as cofilin, nuclear chloride ion channel protein, and heat-shock protein 20, were identified by two-dimensional electrophoresis and mass spectrometry. These findings indicate the presence of activated and mobile fibroblasts accompanied by an induced inflammatory response outside the airway epithelium in patients with mild asthma, results that may play a role in formation of airway fibrosis.

Adolescent↗