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| 3. |
- Zetterquist, W, et al.
(författare)
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Salivary contribution to exhaled nitric oxide
- 1999
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 13:2, s. 327-333
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Tidskriftsartikel (refereegranskat)
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| 4. |
- 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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- 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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| 6. |
- Andersson, Agneta, et al.
(författare)
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Domiciliary liquid oxygen versus concentrator treatment in chronic hypoxaemia: a cost-utility analysis
- 1998
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Ingår i: European Respiratory Journal. - 1399-3003. ; 12:6, s. 1284-1289
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Tidskriftsartikel (refereegranskat)abstract
- Whether long-term oxygen therapy (LTOT) improves quality of life in chronic hypoxaemia has been questioned. LTOT with an oxygen concentrator (C/C) and gas cylinders for ambulation is considered cumbersome compared to mobile liquid oxygen equipment (L). The hypothesis for this study was that LTOT with liquid oxygen treatment (L) improves patients' health-related quality of life, but that it is also more expensive compared to concentrator (C/C) treatment. A prospective, randomized multicentre trial comparing C/C with L for LTOT was conducted during a six-month period. Fifty-one patients (29 on L and 22 on C/C) with chronic hypoxaemia, regularly active outside the home, participated in the study initially. Costs for oxygen were obtained from the pharmacies. Patient diaries and telephone contacts with members of the healthcare sector were used to estimate costs. Health-related quality of life was measured by the Sickness Impact Profile (SIP) and the EuroQol, instruments at the start and after 6 months. The average total cost per patient for group C/C for the six-month period was US$1,310, and for group L it was US$4,950. Health-related quality of life measured by the SIP instrument showed significant differences in favour of group L in the categories/dimensions of physical function, body care, ambulation, social interaction and total SIP score. In conclusion, liquid-oxygen treatment was more expensive compared to concentrator treatment. However, treatment effects showed that liquid oxygen had a better impact on quality of life.
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| 7. |
- 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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| 8. |
- 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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| 9. |
- ERICSSON, CH, et al.
(författare)
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Repeatability of airway deposition and tracheobronchial clearance rate over three days in chronic bronchitis
- 1995
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 8:11, s. 1886-1893
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Tidskriftsartikel (refereegranskat)abstract
- Previous investigations on tracheobronchial clearance in chronic bronchitis or chronic obstructive pulmonary disease (COPD) have usually referred to measurements during a short time-period, i.e. a few hours. The purpose of this study, therefore, was to study regional particle deposition and tracheobronchial clearance during 72 h. In 14 patients with chronic bronchitis clearance of 111In-labelled 3.6 micrograms Teflon particles and lung function were measured on two occasions, with an interval of 2 weeks. Lung retention of test particles was measured at 0, 24, 48 and 72 h using a profile scanner. The weight of expectorated sputum samples was measured after the two clearance measurements. The particle retentions at all time-points were reproducible, as seen from the two measurements ( r > 0.90). The fast clearance phase was completed within 72 h. No correlation between sputum volume and clearance was seen. There was a significant negative correlation between airway resistance and the 72 h retention (r= -0.66), and an even better correlation between specific airway resistance and the 72 h retention (r = -0.82), indicating more central deposition in obstructed airways. There was no significant correlation between lung function tests reflecting smaller airways and the 72 h retentions. Deposition data agreed well with theoretical calculations and experimental data in healthy subjects. In spite of earlier findings that mucociliary transport is usually severely impaired in chronic bronchitis and COPD, the present results indicate that overall tracheobronchial mucus clearance in these patients is fairly effective, probably due to a productive cough. Alveolar deposition may be estimated by measurements of the 72 h retention in subjects with chronic obstructive pulmonary disease. The 72 h retention is dependent mainly on the calibre of larger airways. The present method of studying airway clearance during 3 days is highly reproducible.
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| 10. |
- FORNHEM, C, et al.
(författare)
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Allergen-induced late-phase airways obstruction in the pig: mediator release and eosinophil recruitment
- 1995
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 8:7, s. 1100-1109
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to develop a novel model for studies of mediator mechanisms involved in the late asthmatic reaction in the lower airways, by using the sensitized pig. The release of histamine and cysteinyl-containing leukotrienes (cys-LTs), as well as the levels of inflammatory cells in blood and bronchoalveolar lavage fluid, were determined and their relationship to plasma cortisol levels and pulmonary airways obstruction was noted. Specific-pathogen free pigs were actively sensitized with Ascaris suum allergen, and one group of animals was treated with a cortisol-synthesis inhibitor (metyrapone) by constant intravenous infusion. Ascaris suum allergen was nebulized into the lower airways and total lung resistance, blood leucocyte count and urinary levels of methylhistamine and leukotriene E4 (LTE4) were followed for 8 h, whereafter bronchoalveolar lavage was performed for analysis of leucocytes. An increase in urinary methylhistamine and LTE4 was seen during the acute allergic reaction in both groups of pigs. Metyrapone treatment prolonged the acute release of histamine, and this was seen together with a prolonged acute bronchoconstrictor response. In metyrapone-treated pigs, a continuous release over 8 h was seen for cys-LTs, but not for histamine. A late blood eosinophilia was also seen in metyrapone-treated animals, starting 4-6 h after allergen challenge. Late cys-LT release and eosinophilia were absent in non-metyrapone-treated animals. These results suggest that allergen-induced late release of cys-LTs as well as blood eosinophilia occur simultaneously with late-phase airways obstruction in the pig, and that all these reactions are prevented by high levels of endogenous cortisol.
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