| 1. |
- Adner, Mikael, et al.
(författare)
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Contractile endothelin-B (ETB) receptors in human small bronchi
- 1996
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 9:2, s. 351-355
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Tidskriftsartikel (refereegranskat)abstract
- Endothelins (ETs) are a family of novel regulatory peptides and various lines of evidence suggest an important role for ETs in regulating pulmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA receptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of small bronchi in the pathogenesis of airway disease. In the present paper, improved methodology was used which enables in vitro studies of small human bronchi down to a diameter of 0.5-1.0 mm. Using the new methodology we have tried to further characterize this receptor. Small bronchi from the distal parts of the bronchial tree were obtained from pulmonary tissue removed from 15 patients with lung cancer. They were dissected and cut into ring segments, in which isometric tension was recorded. ET-1, ET-2 and ET-3 elicited strong concentration-dependent contractions of the human small bronchus. Basically, the three peptides were equipotent with about the same maximal response. Upon reapplication, they all showed the same tachyphylaxis pattern, reaching half the initial contraction. Comparative analysis of IRL 1620, a selective ETB receptor agonist, revealed that the effect of the ETB agonist was, in all respects, similar to the responses induced by the ETs. PD 145065, a combined ETA/ETB receptor antagonist competitively inhibited the contractions induced by IRL 1620, whereas FR139317, a selective ETA receptor antagonist, was without effect. In conclusion, the present study shows that accurate measurements can be made in vitro on small human bronchi and all present data are in favour of an ETB receptor mediating endothelin-induced contraction of human bronchi smaller than 1.0 mm.
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| 2. |
- Agace, W. W.
(författare)
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The role of the epithelial cell in Escherichia coil induced neutrophil migration into the urinary tract
- 1996
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 9:8, s. 1713-1728
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil influx to mucosal surfaces represents one of the earliest inflammatory responses to mucosal infection. We have been studying external interactions with urinary tract epithelial cells in an attempt to understand the molecular mechanisms behind this process. Uropathogenic Escherichia coli induced urinary tract epithelial cells to secrete the neutrophil chemoattractant interleukin-8 (IL-8). IL-8 secretion was higher in response to isogenic strains expressing type 1 or P fimbriae that adhered to the epithelial surface. Deliberate colonization of the human urinary tract with E. coli induced the local production of IL-8 and levels correlated with urinary neutrophil numbers suggesting a role for IL-8 in neutrophil migration. E. coli induced neutrophil migration across urinary tract epithelial layers in vitro, and this process was blocked with anti-IL-8 antibody. IL-8's activity was localized to the epithelial surface. Furthermore, these cells were shown to constitutively express IL-8 receptor A and B messenger ribonucleic acid (mRNA), suggesting a possible role for IL-8 on epithelial cell function. E. coli enhanced the expression of intercellular adhesion molecule-1 (ICAM-1) on urinary tract epithelial cells, and neutrophil migration across urinary tract epithelial layers in vitro was dependent on epithelial ICAM-1 and neutrophil Mac-1 (CD11b/CD18) expression. These results suggest that bacterial/epithelial cell interactions play a key role in the induction of neutrophil migration during mucosal infection, and show the necessity for host-derived chemotactic factors and cell adhesion events in E. coli induced transuroepithelial migration in vitro.
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| 3. |
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| 4. |
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| 5. |
- Beydon, L, et al.
(författare)
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Respiratory mechanics in patients ventilated for critical lung disease
- 1996
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Ingår i: European Respiratory Journal. - 0903-1936. ; 9:2, s. 73-262
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory mechanics, using flow interruption, was previously studied during the complete breath in healthy ventilated man, numerical techniques relieving constraints regarding flow pattern. The classical linear model of non-Newtonian behaviour was found to be valid. The present study was extended to subjects with critical lung disease. Subjects with acute lung injury (ALI; n = 2), acute respiratory distress syndrome (ARDS; n = 4), and chronic obstructive pulmonary disease (COPD; n = 3) were studied with and without positive end-expiratory pressure (PEEP). Functional residual capacity (FRC) was measured with sulphur hexafluoride (SF6) wash-out. The static pressure-volume (P-V) curve was linear at zero end-expiratory pressure (ZEEP), but nonlinear at PEEP. Its hysteresis was nonsignificant. In ALI/ARDS, PEEP increased lung volume by distension and recruitment, but only by distension in COPD. In ALI/ARDS, resistance was increased, at ZEEP. In COPD, resistance became extremely high during expiration at ZEEP. In ALI/ARDS at ZEEP, non-Newtonian behaviour, representing tissue stress relaxation and pendel-luft, complied with the classical linear model. At PEEP, the non-Newtonian compliance became volume-dependent to an extent correlated to the nonlinearity of the static P-V curve. In COPD, non-Newtonian behaviour was adequately explained only with a model with different inspiratory and expiratory behaviour. The classical model of the respiratory system is valid in ALI/ARDS at ZEEP. More advanced models are needed at PEEP and in COPD.
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| 6. |
- Bjorksten, B
(författare)
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Immunological outcome measures
- 1996
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Ingår i: EUROPEAN RESPIRATORY JOURNAL. - 0903-1936. ; 9, s. S22-S27
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
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| 8. |
- Bredin, CG, et al.
(författare)
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Integrin dependent migration of lung cancer cells to extracellular matrix components
- 1998
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 11:2, s. 400-407
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Tidskriftsartikel (refereegranskat)abstract
- Since tumour progression is dependent on the ability of malignant cells to interact with the extracellular matrix (ECM), we have investigated the significance of beta1 and beta3 integrins for migration of lung cancer cells to components of the ECM. In an in vitro hapto- and chemotactic assay system, five cell lines representing the major types of lung cancer were examined: adenocarcinoma (WART); squamous cell carcinoma (U-1752); small cell lung cancer (SCLC) (U-1906, 054 A) and large cell lung cancer (LCLC) (U-1810). Flow cytometric analyses were performed to characterize their integrin expression. U-1906, 054 A, WART and U-1752 all expressed beta1 integrins whereas U-1810 did not. However, U-1810 and U-1752 expressed beta3 integrins. All cell lines except U-1810 and U-1752 showed hapto- and chemotactic motility to fibronectin, laminin and type IV collagen and this motility was beta1 integrin-dependent except in the case of U-1810. However, the hapto- and chemotactic responses differed markedly between the separate cell lines and there was no distinct pattern to separate non-small cell lung cancer (NSCLC) from SCLC. No or very little migration was seen in control experiments with bovine serum albumin (BSA) or serum-free medium alone, indicating that the migration of the lung cancer cells require adhesion molecules, soluble or substratum bound. We have found the involvement of beta1 integrins in lung cancer cell migration in vitro towards fibronectin, laminin and type IV collagen except in the case of U-1810. The U-1810 cell line clearly differed from the rest of the cell lines by lacking expression of beta1 integrins.
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| 9. |
- Eichler, I., et al.
(författare)
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Human neutrophil lipocalin, a highly specific marker for acute exacerbation in cystic fibrosis
- 1999
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Ingår i: European Respiratory Journal. - 0903-1936 .- 1399-3003. ; 14:5, s. 1145-1149
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Tidskriftsartikel (refereegranskat)abstract
- Cystic fibrosis (CF) is characterized by the production of abnormally thick secretions in the airways, chronic bacterial endobronchial infections and a chronic, predominantly neutrophilic inflammatory response. Therefore, myeloperoxidase (MPO) and lactoferrin are frequently used as inflammatory markers. Recently, a new protein in the neutrophil granules, human neutrophil lipocalin (HNL) has been discovered. The aim of the present study was to investigate HNL in sera of patients with CF and its relation to MPO and lactoferrin as well as to acute pulmonary exacerbation. Serum concentrations of HNL, MPO and lactoferrin were determined in 42 patients with CF and in 25 healthy subjects. Patients with CF were divided into groups with and without acute pulmonary exacerbation (APE) and also with and without colonization with Pseudomonas aeruginosa (Pa). Median serum levels of HNL (200.5 microg x L(-1)), MPO (595 microg x L(-1)) and lactoferrin (1,356.5 microg x L(-1)) were significantly increased in patients with CF compared to control subjects (57.7, 178 and 478 microg x L(-1), respectively; p<0.0001). CF patients with APE had significantly increased serum concentrations of HNL (321 versus 97.7 microg x L(-1); p<0.0001), MPO (1,125 versus 300 microg x L(-1); p<0.005) and lactoferrin (4,936 versus 980 microg x L(-1); p<0.001) compared with patients in stable clinical condition. Similarly, patients colonized with Pa had significantly higher concentrations of HNL, MPO and lactoferrin than Pa negative patients. These results indicate that in patients with cystic fibrosis, serum concentrations of human neutrophil lipocalin are markedly increased with a strong relationship to myeloperoxidase and lactoferrin. Thus, determination of serum human neutrophil lipocalin concentrations may be another useful diagnostic tool to monitor neutrophil inflammation in cystic fibrosis. The more marked difference in human neutrophil lipocalin compared with myeloperoxidase concentrations with no overlap between patients with acute pulmonary exacerbation and those in stable condition even suggests that human neutrophil lipocalin may be a more sensitive and specific discriminator.
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| 10. |
- Engström, Carl-Peter, 1945, et al.
(författare)
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Reliability and validity of a Swedish version of the St George's Respiratory Questionnaire.
- 1998
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Ingår i: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - 0903-1936. ; 11:1, s. 61-6
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Tidskriftsartikel (refereegranskat)abstract
- The St George's Respiratory Questionnaire (SGRQ) was designed to measure quality of life (QoL) in obstructive pulmonary disease. Its reliability, validity and sensitivity have been demonstrated. The aim was to develop a Swedish version of the SGRQ and to confirm its scaling and clinical properties. The SGRQ was adapted for Swedish conditions following a translation-backtranslation procedure. The psychometric and clinical evaluation included 68 patients with chronic obstructive pulmonary disease (COPD). Supplementary QoL, clinical and physiological data were collected. A follow-up study was performed 1 yr later. Correlation analysis used a multitrait-multimethod model. Internal consistency reliability and discriminant validity were documented by performing a multitrait analysis. The results confirmed expected levels of associations. Correlation coefficients between the SGRQ total score and the Sickness Impact Profile Total score (a generic health measure), forced expiratory volume in one second (FEV1) and 6 min walking distance were 0.69, -0.42 and -0.61 respectively. The pattern of correlations in the Swedish data set was very similar to that of the original. The stability of the SGRQ scores was confirmed at follow-up after 1 yr. The reliability was satisfactory, with Cronbach's alpha coefficients >0.80 for the SGRQ and its subdimensions. In conclusion, the Swedish version of the St George's Respiratory Questionnaire is reliable, valid and compares well with the corresponding tests of the original version.
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