Biomedical subjects

M Wildt

Publications and source records attributed to M Wildt.

9 recordsLinked to original sources

PubMed2006

BALF-derived fibroblasts differ from biopsy-derived fibroblasts in systemic sclerosis.

Growth of fibroblasts from bronchoalveolar lavage fluid (BALF) in patients with systemic sclerosis (SSc) has previously been described. The purpose of the present study was to characterise fibroblasts from BALF and bronchial biopsies from SSc patients with alveolitis and from controls, to analyse fibroblast proliferation, migration, stress fibres and proteoglycan production. BALF and bronchial biopsies were collected from 10 patients with SSc and alveolitis and from 15 controls. Outgrowth of fibroblasts was observed from the BALF of four patients, particularly in those with a markedly increased percentage of eosinophils in BALF, but not in any member of the control group. Increased levels of granulocyte-macrophage colony-stimulating factor, correlating with the percentage of eosinophils in BALF, were found in patients when compared with controls. Fibroblasts from BALF showed an elongated, mobile phenotype and increased proteoglycan production compared to the corresponding biopsy fibroblasts. In conclusion, outgrowth of fibroblasts with an altered phenotype is reported from bronchoalveolar lavage fluid in systemic sclerosis patients with alveolitis and an increased percentage of eosinophils in the bronchoalveolar lavage fluid. These findings indicate a possible role for eosinophil-fibroblast interaction in pulmonary fibrosis in systemic sclerosis.

Adult↗

PubMed2004

Longitudinal development of skin involvement and reliability of high frequency ultrasound in systemic sclerosis.

BACKGROUND: Measurement of skin involvement is essential for diagnosis and prognosis in systemic sclerosis. Assessment by palpation skin score is the current method. OBJECTIVE: To explore high frequency ultrasound as an objective method to improve skin characterisation by combining measurements of skin thickness and echogenicity. METHODS: Skin thickness and echogenicity were measured at the proximal phalanx of the second digit, the back of the hand, the forearm, and the lower leg and, in order to separate limited (lSSc) from diffuse SSc (dSSc), at the chest in 16 patients with early disease and in 16 controls. Measurements were repeated in each patient three or four times with an interval of 1-2 years. Ultrasound measurements of skin thickness were compared with the palpation skin score. RESULTS: Compared with controls, the skin was thickened on the phalanx, hand, forearm, and chest of patients with dSSc, but not patients with lSSc, at the 1 year examination. In dSSc the degree of thickening tended to diminish with time, and at 4 years, thickness was significantly decreased on the forearm and chest compared with the 1 year measurements. Low reflectancy was most pronounced at the 1 year evaluation on the forearm, hand, and phalanx in dSSc, and on the phalanx in lSSc. CONCLUSION: Separate measurements of skin thickness and echogenicity by high frequency ultrasound add a new dimension to the assessment of skin involvement in SSc, and this seems to be an objective non-invasive tool for use in the study of disease development and in clinical trials.

Adult↗

PubMed2004

Regulation of serotonin levels by multiple light-entrainable endogenous rhythms.

This study examined whether serotonin levels in the brain of the American lobster, Homarus americanus, are under circadian control. Using high-performance liquid chromatography and semi-quantitative immunocytochemical methods, we measured serotonin levels in the brains of lobsters at six time points during a 24-h period. Lobsters were maintained for 2 weeks on a 12 h:12 h light:dark cycle followed by 3 days of constant darkness. Under these conditions, brain serotonin levels varied rhythmically, with a peak before subjective dusk and a trough before subjective dawn. This persistent circadian rhythm in constant darkness indicates that serotonin levels are controlled by an endogenous clock. Animals exposed to a shifted light cycle for >10 days, followed by 3 days in constant darkness, demonstrate that this rhythm is light entrainable. Separate analyses of two pairs of large deutocerebral neuropils, the accessory and olfactory lobes, show that serotonin levels in these functionally distinct areas also exhibit circadian rhythms but that these rhythms are out of phase with one another. The olfactory and accessory lobe rhythms are also endogenous and light entrainable, suggesting the presence of multiple clock mechanisms regulating serotonin levels in different brain regions.

Animals↗

PubMed2001

Von Willebrand factor propeptide as a marker of disease activity in systemic sclerosis (scleroderma).

In 44 consecutive patients with systemic sclerosis (SSc), plasma concentrations of von Willebrand factor (vWf) were higher than those of the vWf propeptide, but the propeptide showed less variability within patient subgroups. Higher values of the propeptide were observed in patients with early pulmonary involvement. A closer correlation of the propeptide than of vWf to biochemical markers of activity was also evident. Our results suggest that the propeptide, despite a shorter circulating half-time and lower plasma concentrations than vWf, is more useful in the assessment of disease activity in SSc.

Adult↗

PubMed2000

Circulating collagen metabolites in systemic sclerosis. Differences between limited and diffuse form and relationship with pulmonary involvement.

OBJECTIVE: To study collagen metabolites in systemic sclerosis (SSc) and their relationship with clinical manifestations of the disease. METHODS: Forty-eight SSc patients, 13 with a diffuse form (dcSSc), 23 with a limited form (lcSSc) and 12 with suspected SSc not fulfilling the ACR criteria, and 31 healthy controls were examined. Serum concentrations of aminoterminal type III procollagen peptide (PIIINP), aminoterminal and carboxyterminal type I procollagen peptides (PINP and PICP) and cross-linked carboxyterminal telopeptide of collagen I (ICTP) were determined by radioimmunoassay. RESULTS: Increased serum concentrations of ICTP were found in SSc patients compared with controls. Distinctly higher levels of ICTP were observed in dcSSc than in lcSSc. High serum ICTP was correlated with skin score and acute phase reactants, and with reduced pulmonary function. Serum PIIINP concentration was elevated in both lcSSc and dcSSc. CONCLUSION: Augmented collagen catabolism accompanies the increased collagen synthesis in SSc. Serum ICTP concentration is a marker of this feature and also reflects clinical severity.

Adult↗

PubMed1999

Decreased capillary density in juvenile dermatomyositis and in mixed connective tissue disease.

OBJECTIVE: To assess whether quantitative capillary microscopy is a useful tool to evaluate capillary abnormalities in children with connective tissue diseases. METHODS: Eight children with juvenile dermatomyositis (JDM), 6 with mixed connective tissue disease (MCTD) and 23 healthy children were investigated with computer based quantitative capillary microscopy. Median disease duration was 1 year among JDM (1-4) and 3 years (1-7) among MCTD. RESULTS: Capillary density was decreased in JDM [median 2.5 (1.4-4.3) loops/mm (p < 0.001)] and in MCTD [median 5.0 (4.1-7.0) loops/mm (p < 0.05)] compared to healthy controls [median 6.8 (5.3-8.0) loops/mm]. Median capillary loop area was increased in JDM [median 8.5 (3.0-15.8) 10(-3) mm2 (p < 0.001)] and in MCTD [median 4.5 (3.0-6.0) 10(-3) mm2 (p < 0.02)] compared to controls [median 2.5 (1.0-4.0) 10(-3) mm2]. CONCLUSION: Quantitative nailfold capillary microscopy is a sensitive indicator of JDM. In MCTD this technique is less discriminative.

Adolescent↗

PubMed1996

Computer based quantitative analysis of capillary abnormalities in systemic sclerosis and its relation to plasma concentration of von Willebrand factor.

OBJECTIVES: To evaluate an objective and quantitative method for assessment of capillary abnormalities in systemic sclerosis (SSc). METHODS: Nailfold capillaries were investigated by capillary microscopy and photographed in 17 consecutive SSc patients (five with diffuse cutaneous systemic sclerosis (dSSc) and 12 with limited cutaneous systemic sclerosis (lSSc)) and in 17 healthy controls. Investigators having no access to clinical data made drawings from magnified projections of coded photographs and analysed them using a computer program. Capillary density (capillary loops/mm in the distal row) and median capillary loop area were calculated. Presence of functional or organic arterial changes was evaluated by measurement of finger pressure with finger cooling. Plasma concentration of von Willebrand factor (VWF) was analysed using an enzyme linked immunosorbent assay (ELISA). RESULTS: In 16 of 17 SSc patients and 13 of 17 controls the technical quality of the photographs was sufficient for computer analysis. Capillary density was decreased in dSSc (median 6.9 loops/mm) and in lSSc (median 3.8 loops/mm) compared with healthy controls (8.9 loops/mm) and median capillary loop area was increased in dSSc (7.3 x 10(-3) mm2) and in lSSc (8.5 x 10(-3) mm2) compared with healthy controls (5.0 x 10(-3) mm2). An inverse relation was found between capillary density and median capillary loop area in SSc patients. Plasma VWF was increased in patients (median 401 IE/l in dSSc and 409 IE/l in lSSc) compared with controls matched for age and sex (median 276 IE/l). Computer based analysis showed capillary density below the control range and median capillary loop area above the control range in 14 of 16 SSc patients. Measurement of finger pressure with finger cooling showed organic vascular changes in nine of 13 SSc patients. CONCLUSION: Computer based quantitative analysis has low interobserver variability and is a quantitative and sensitive method of assessing capillary abnormalities in SSc.

Adolescent↗

PubMedDate not supplied

Capillary density in patients with systemic sclerosis, as determined by microscopy counts and compared with computer-based analysis.

OBJECTIVE: To develop a method enabling capillary density to be determined rapidly and accurately in patients with systemic sclerosis. METHOD: Capillary density was determined in 11 controls and 22 patients: 5 with diffuse cutaneous systemic sclerosis (dSSc), 12 with limited cutaneous systemic sclerosis (lSSc), two with suspected systemic sclerosis (suspSSc), 2 with sclerodermatomyositis, and one with undifferentiated connective tissue disease. Using a microscope equipped with a graticule, nailfold capillaries were counted within a 3 mm length of the nailfold; these counts were made by 4 different observers. The results were compared with the corresponding values obtained by the computerbased analysis of photographs. RESULTS: The median capillary density according to the direct counts was 8.0 loops/mm (6.7-10.0) in the controls, 6.0 loops/mm (range 4.8-8.8) in the dSSc subgroup, 5.6 loops/mm (4.2-6.5) in the lSSc subgroup, and 7.2 loops/mm (6.2-8.2) in the suspSSc subgroup. In the series as a whole, there was no significant difference between the median values for the left hands and those for the right hands, nor between the median value for all digit IVs and the median value for all four digits analysed (II, III, IV, and V). Interobserver variation was small between the 4 different observers. Direct microscopy counts were slightly higher than the corresponding values obtained by computer-based analysis. CONCLUSION: Direct microscopy counting is a rapid, simple, and reliable means of determining capillary density for screening purposes.

Adult↗

PubMedDate not supplied

The association between changes in skin echogenicity and the fibroblast production of biglycan and versican in systemic sclerosis.

OBJECTIVE: To investigate a possible association between the longitudinal changes in skin involvement and the fibroblast production of proteoglycans in vitro, among patients with early and untreated systemic sclerosis (SSc). METHODS: In 11 patients, 6 with diffuse cutaneous systemic sclerosis (dSSc) and 5 with limited cutaneous systemic sclerosis (ISSc), and in 6 controls skin thickness and skin echogenicity of the forearm was measured by high frequency (20 MHz) ultrasound. A skin biopsy was taken from the area of the ultrasound measurements, and from cultivated fibroblasts the production of the proteoglycans versican, perlecan, biglycan and decorin were measured. To investigate longitudinal changes in skin involvement, the ultrasound examination was repeated after 1-3 years. RESULTS: Compared to controls, SSc patients had increased skin thickness at the first evaluation. Patients with dSSc had lower skin echogenicity than both patients with lSSc and the controls. Patients with greater changes in skin thickness and skin echogenicity produced more versican, whereas the production of biglycan and decorin was higher only in patients with greater changes in skin echogenicity. There was a negative correlation between fibroblast production of biglycan and disease duration. CONCLUSION: High fibroblast synthesis of the proteoglycans versican and biglycan is associated with changes in skin echogenicity and may predict more progressive skin sclerosis in SSc.

Adult↗