| 1. |
- Bjärdahlen, Anette, et al.
(författare)
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Myofibroblast accumulation correlates with the formation of fibrotic tissue in a rat air pouch model.
- 2002
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 29:8, s. 1698-1707
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The pathogenesis of arthritic joints involves cartilage degradation and pannus formation. It is well known that pannus influences the cartilage; however, the mechanism behind how the degrading cartilage interacts with pannus is not well known. To investigate this interplay, the expression of extracellular matrix (ECM) components in pannus and the degrading cartilage was analyzed. METHODS: Studies were performed using a rat air pouch model where cotton with viable or killed cartilage was implanted into 7-day-old pouches for 1-28 days. The remodeling of cartilage and the formation of tissue in the cotton was characterized histologically by quantitation of infiltrated cells. The amounts of collagen, hyaluronan, and proteoglycan were estimated. RESULTS: Implantation of homologous femoral head cartilage in cotton resulted in extensive remodeling of cartilage and formation of ECM in the cotton. In cotton without cartilage, fibroblasts and myofibroblasts were the predominant cells in the early stage of analyses. The ECM formed in cotton was of a fibrotic type, with mainly collagen and smaller amounts of proteoglycans correlating to the presence of myofibroblasts. In the cotton with cartilage, however, inflammatory cells such as neutrophils, macrophages, and lymphocytes dominated. Delayed accumulation of collagen and increased synthesis of proteoglycans occurred early in cotton with viable as well as non-viable cartilage. In later stages, the cell pattern changed and the myofibroblasts emerged together with an increasing collagen formation. CONCLUSION: The interaction between cartilage and the newly formed granulation tissue results in a faster degradation of cartilage molecules, which in turn leak into the surrounding ECM and affect the recruitment of myofibroblasts. This indicates the importance of the micromatrix.
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| 2. |
- Olsson, Lars E, et al.
(författare)
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(1)H and hyperpolarized (3)He MR imaging of mouse with LPS-induced inflammation.
- 2009
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Ingår i: Journal of magnetic resonance imaging : JMRI. - : Wiley. - 1053-1807 .- 1522-2586. ; 29:4, s. 977-81
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the lipopolysaccharide (LPS) model of chronic obstructive pulmonary disease (COPD) in mouse with (1)H and hyperpolarized (HP) (3)He MR imaging. MATERIALS AND METHODS: Axial slices of the lung volume were acquired with HP (3)He and (1)H MRI at 4, 24, and 48 h after LPS exposure. A quantitative ventilation index was calculated from two HP (3)He acquisitions. A bronchoalveolar lavage (BAL) for a cell count was performed following magnetic resonance imaging (MRI). RESULTS: The LPS exposure resulted in a significant increase of cells in BAL, with maximum at 48 h. Lesions on (3)He images were characterized by ventilation defects, whereas lesions on (1)H images were hyperintense and were attributed to edema. The number of lesions was at maximum at 48 h. At this time point, and for both (3)He and (1)H MRI, the volume of the lesions was significantly higher for LPS-exposed mice compared to controls. At 4, 24, and 48 h the ventilation index from the (3)He data was significantly smaller for the LPS-exposed animals compared to controls. CONCLUSION: The time point 48 h after LPS exposure was advantageous for MRI evaluation. Functional read-out with (3)He MRI seems to be more sensitive than conventional (1)H MRI.
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| 3. |
- Olsson, Lars E, et al.
(författare)
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1H and hyperpolarized 3He magnetic resonance imaging clearly detect the preventative effect of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo.
- 2010
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; :Feb 3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proton ((1)H) magnetic resonance imaging (MRI) can be utilized to quantify pulmonary edema in endotoxin-induced pulmonary inflammation and hyperpolarized (HP) (3)He MRI can assess pulmonary ventilation. Neither of the methods has been applied to assess the impact of a drug on endotoxin-induced pulmonary inflammation in vivo. The aim of the current study was to evaluate the capability of (1)H and HP (3)He MRI to assess the effects of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo.Materials and Methods: Mice were exposed to an aerosol of either saline or endotoxin (5 mg/ml) for 10 min. Half of the endotoxin-exposed mice were pretreated with a glucocorticoid (budesonide 3 mg/kg; 2 times/day) and the other half with vehicle p.o. The first budesonide treatment was administered 1 h prior to the aerosol inhalation. Forty-eight hours after the aerosol exposure, the mice were anaesthetized for subsequent imaging. Hyperpolarized (3)He was administered and axial MR images of the lungs obtained. Matching (1)H MR images were then acquired. The mice were sacrificed and broncho-alveolar lavage (BAL) samples were harvested to determine total and cell differential counts.Results: The lesion volume on both (1)H and (3)He MRI, were markedly increased by endotoxin exposure (P < 0.001). Budesonide strongly reduced lesion volume (P < 0.001). The BAL cell count correlated strongly with both (3)He (P < 0.001; r = 0.96) and (1)H lesion volumes (P < 0.001; r = 0.97).Conclusions: Hyperpolarized (3)He MRI and (1)H MRI clearly visualized the preventative effect of budesonide on the impact of endotoxin on pulmonary ventilation and edema, respectively. The fact that ventilation defects on (3)He MRI corresponded to findings from conventional (1)H MRI, as well as to counts of BAL inflammatory cells suggests that these imaging techniques constitute promising tools for non-invasive monitoring of pulmonary inflammation in vivo.
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| 4. |
- Westergren-Thorsson, G, et al.
(författare)
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Proliferation of cultured fibroblasts is inhibited by L-iduronate-containing glycosaminoglycans
- 1991
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Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541. ; 147:3, s. 30-523
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Tidskriftsartikel (refereegranskat)abstract
- We have modified a method (Gilles et al: Anal. Biochem., 159:109-113, 1986) for measuring cell number, that is based on the binding of crystal violet to cell nuclei and used it to assay effects of various glycosaminoglycans on growth of human lung fibroblasts. The procedure was modified by growing cells in microcultures (96 well microplates) and by measuring the amount of adsorbed dye using a microplate photometer after solubilisation of the cells with detergent. There was a linear relationship between absorbance and cell number measured by a Coulter Counter. The method is rapid and sensitive and can be used for screening many samples as well as measuring growth rates at low initial cell densities. Even the low growth rates obtained in the absence of serum can be detected. Human lung fibroblasts were growth arrested by serum deprivation and then grown for periods of up to 4 days in the presence of serum and exogenously added glycosaminoglycans (range, 0.1-100 micrograms/ml). Hyaluronan, chondroitin sulfate, and dextran sulfate were without effects, whereas dermatan sulfate, certain heparan sulfates, and heparin suppressed growth (20%-50% inhibition). The antiproliferative activity of dermatan sulfate increased with increasing iduronate content. Certain heparan sulfates, with moderately high sulfate and L-iduronate contents were better inhibitors than heparin despite the fact that the latter glycan has even higher sulfate and L-iduronate contents. The antiproliferative effect of exogenous glycans appeared after a lag period of 3-4 days, suggesting that they interfered with factors produced by the cells. Furthermore, the degree of inhibition was greater when the initial cell density was low. Above a certain level of seeded cells (approx. 10,000 cells/well), there was no inhibition by any of the glycosaminoglycans. It is possible that exogenous glycans cannot overcome endogenous growth-promoting effects in densely seeded cultures.
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