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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 26 (1996), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and IL-5 are important in tissue eosinophil accumulation and high IgE production in allergic inflammatory reaction.Objective We examine lung GM-CSF, IL-4 and IL-5 expression in a murine model of allergic bronchopulmonary aspergillosis (ABPA) characterized by eosinophil and lymphocyte lung infiltration and elevated serum IgE level.Methods C57BL/6 mice were intranasally treated three times a week for 1, 2 or 3 week(s) with Aspergillus fumigatus (Af) antigen or saline and were sacrificed on days 7, 14 and 21. Immunohistochemical analyses for GM-CSF, IL-4 and IL-5 were performed on lung sections.Results Af treatment induced a remarkable pulmonary eosinophil influx. Increased numbers of lung T lymphocytes and GM-CSF positive cells were observed on days 14 and 21. IL-4 and IL-5 positive cells were increased significantly only on day 14. Immunostained serial sections showed that most (≥98%) cytokine positive cells were CD3 positive. Few eosinophils (〈2% of cytokine positive cells) were immunoreactive for GM-CSF and IL-5. Significant correlations were found between the number of GM-CSF and IL-5 positive cells, and the number of eosinophils in Af-treated lung (r = 0.62, P 〈 0.05 and r = 0.52, P 〈 0.05, respectively), and between the number of IL-4 positive cells and the serum total IgE level (r = 0.64, P〈0.01).Conclusions Our data suggest a role for T lymphocyte GM-CSF, IL-4 and IL-5 in Af-induced mouse pulmonary eosinophilia and increased serum IgE production and further support the importance of T helper (TH) cells in the pathogenesis of ABPA.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 35 (2005), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background IL-4 is a key factor for T helper type 2 (Th2) differentiation and Ig class switching to IgE and IgG4 during the development of immune responses. IL-4 is produced by T cells, mast cells, basophils, and eosinophils. However, there is also evidence suggesting that rat alveolar macrophages (AMs) produce IL-4.Objective Given the importance of AMs and Th2-related diseases in the lung, we investigated the production of IL-4 by human AMs.Methods Human AMs were isolated from bronchoalveolar lavage, purified, and IL-4 production was investigated at mRNA and protein levels using real-time PCR, flow cytometry, immunocytochemistry, and ELISA. The presence of IL-4 was investigated in subjects with asthma or asymptomatic airway hyper-responsiveness, and in normal non-smokers.Results IL-4 and IL-4δ2 (a splice variant found in other IL-4 producing cells) mRNAs were found in all these subjects, but IL-4 expression could not be correlated with a particular disease. Protein production was verified by immunocytochemistry and flow cytometry analysis demonstrating, respectively, up to 69% and 59% positive AMs, regardless of the subject condition. Furthermore, phorbol-12-myristate-13-acetate and calcium ionophore stimulated the release of IL-4 after 48 h treatment in the presence of anti-IL-4 receptor antibody.Conclusion Our results show for the first time that IL-4 and IL-4δ2 mRNA are expressed and IL-4 protein produced and released by human AMs, suggesting a contribution of these cells in the modulation of Th2 immune response.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Pathophysiology of corticosteroid (CS)-resistant asthma remains incompletely understood.Objective To determine if failure of asthma to clinically improve with CS is due to a defective response of airway bronchial inflammation to these drugs.Methods Twenty-one asthmatics having a decreased baseline FEV1 that improved ≥ 30% with inhaled β2 agonist got bronchial biopsies before and at the end of an oral CS treatment (methylprednisolone 40 mg daily for 14 days). They were arbitrarily divided into two groups according to baseline FEV1 improvement following this treatment: ≥ 23% designated as CS-sensitive (CSS) (n = 10) and 〈 15% as CS-resistant (CSR) (n = 11).Results Before oral CS, counts of bronchial mucosa inflammatory cells identified by immunohistochemistry (CD3, MBP, tryptase, CD68, neutrophil elastase and CD25 for lymphocytes, eosinophils, mast cells, macrophages, neutrophils and IL-2 receptors, respectively) were similar in CSS and CSR subjects. Oral CS decreased CD3+ cell counts (medians: 60–20 cells/mm2; P = 0.014) and MBP+ cell counts (medians: 19–4 cells/mm2; P = 0.03) in CSS asthmatics, but only tryptase+ cell counts in CSR asthmatics (medians: 30–18 cells/mm2; P = 0.05). Few bronchial neutrophil elastase+ cells were observed and their counts were similar in the two groups of asthmatics before and when on oral CS (all medians: = 2 cells/mm2).Conclusions These data show that, in these subjects with moderate to severe asthma, lymphocytes and eosinophils constitute most of the inflammatory cells infiltrating the bronchial mucosa. They also demonstrated that clinical impaired response to CS is associated with a persistent bronchial mucosa cellular infiltrate despite oral CS treatment. Additional studies are required to determine the role of this CS-resistant bronchial inflammation in the impaired asthma clinical response to these drugs.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Tissue eosinophils express more membrane receptors and release more mediators than blood eosinophils, suggesting that migration from blood to tissue modulates eosinophil phenotype and functions.Objective We postulated that eosinophil passage through endothelial basement membrane, an important step of eosinophil migration into tissue, may be responsible for some of these changes.Method We previously showed that 5-oxo-6, 8, 11, 14-eicosatetraenoic acid (5-oxo-ETE) in combination with IL-5 promotes eosinophil migration through Matrigel®, a mouse tumour cell-derived basement membrane. Using this model, we evaluated the effect of trans-Matrigel migration on purified human blood eosinophil expressions of CD44, CD69 and HLA-DR that either increase or appear on activated eosinophils, and releases of peroxidase (EPO), leukotriene (LT) C4 and granulocyte-monocyte colony stimulating factor (GM-CSF).Results IL-5, but not 5-oxo-ETE, increased eosinophil expression of CD44 and CD69. Migration of eosinophils through Matrigel significantly increased CD44 expression level over the one induced by IL-5 (P = 0.0001). Migration through Matrigel did not modify CD69 expression compared with the one obtained in the presence of IL-5 alone; however, incubation of eosinophils on Matrigel decreased IL-5-induced CD69 (P = 0.0001). Trans-Matrigel migration did not modify HLA-DR expression, nor EPO, LTC4 and GM-CSF releases.Conclusion These data show that in vitro trans-Matrigel migration and Matrigel contact modulate eosinophil membrane receptor expression. Consequently, they suggest that migration through basement membrane mediates changes in cell-surface phenotype observed on activated eosinophils and probably prepares them for interactions with tissue components and cells.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    Clinical & experimental allergy 31 (2001), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A previous study suggested that the long-acting β2-adrenergic agonist salmeterol (SM) had inhibitory effects on bronchial mucosal inflammation 6 hours after allergen exposure.To further evaluate the influence of SM on allergen-induced airway inflammation.We studied, in a randomized, double-blind, cross-over trial, 16 mild asthmatic patients who had a dual asthmatic response to allergen inhalation. Subjects received 50 µg of SM or placebo (P), twice daily for 1 week each, separated by a 2-week wash-out period. At the end of each treatment period, after withholding SM for 24 h, they had a methacholine inhalation test (medication was resumed after the test), followed 24 h later by an AC with the concentration of allergen that had induced a LAR at baseline. Airway inflammation was assessed 24 h after the AC by bronchoalveolar lavage (BAL) (n = 16) and bronchial biopsies (n = 13).As expected, SM improved baseline FEV1 and PC20 (P ≤ 0.009) and decreased the allergen-induced early bronchoconstrictive response. There were no significant differences in BAL cell counts after the two treatments. On bronchial biopsies, numbers (median, mm2) of submucosal CD45 (P: 43 ± 23; SM: 161 ± 43, P = 0.031), CD45Ro (P: 37 ± 19; SM: 126 ± 41, P = 0.047) and AA1 positive cells (P: 38 ± 6, SM: 65 ± 17, P = 0.006) were significantly higher after SM than P treatment. The numbers of CD4 (P: 11 ± 10; SM: 32 ± 7, P = 0.085), HLA-DR (P: 65 ± 30; SM: 116 ± 36, P = 0.079) and EG2 positive cells (P: 25 ± 15; SM: 38 ± 26, P = 0.09) tended to increase with SM treatment.In summary, compared to placebo, 1 week of regular use of SM is associated with an increase in bronchial inflammatory cells 24 h after AC. This is in keeping with the recommendation that salmeterol should only be used with an anti-inflammatory agent, particularly in the context of significant allergen exposure.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 465 (1986), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Respiration Physiology 83 (1991), S. 179-187 
    ISSN: 0034-5687
    Keywords: Animal, man ; Collateral ventilation ; Fibroscope ; Lung volume, and collateral resistance
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Respiration Physiology 41 (1980), S. 267-277 
    ISSN: 0034-5687
    Keywords: Cardiogenic oscillations ; Nitrogen washout
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 39 (1994), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: C57BL/6 mice treated with intranasal instillation of 100 μg of Aspergillus antigen three times a week developed a pulmonary eosinophilia, observed in the bronchoalveolar lavage (BAL) and on hislopatholo-gical examination. At week 3, the instillation of Aspergillus antigen provoked a 10-fold increase in the BAL cell number and eosinophils were the predominant inflammatory cells (66.4′%,). Histopathological findings showed focal alveolar lesions with pcribronchial and perivascular infiltration of lymphoid cells, numerous eosinophils, epithelioid cells, and granulomus with giant cells. Increases in total IgF. and IgG1 levels in BAL fluid (33-fold and 14-fold) and serum (67-fold and 8-fold) were observed also (P〈0.05). IgGl specific to Aspergillus fumigatus (Af) was detected only in the antigen-treated mice.At 12 weeks, there was a persistent but less intense eosinophilia both in BAL and on histopathological examination accompanied by steadily elevated total IgE and total FgGl and a higher level of specific IgGl-Af in BAL fluids and sera. No bronchocentric granulomatosis, mucoid impaction nor bronchiecta-sis could be observed.Data from the study described here showed that in mice repeated exposure to Aspergillus antigen leads to a strong inflammatory pulmonary response, characterized by remarkable pulmonary eosinophilia and elevations of total IgE, total IgG 1 and specific TgG1-Af in both BAL and serum, which are the hallmarks of human allergic bronchopulmonary aspergillosis also. However, this inflammation did not induce the chronic histological features of the human disease.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 35 (1997), S. 2991-2998 
    ISSN: 0887-624X
    Keywords: NMR spectroscopy ; polyurethane ; isophorone diisocyanate ; IPDI ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Chemical structure investigations of polyurethane binders based on difunctional linear glycidyl azide polymer (GAP) cured with isophorone diisocyanate (IPDI) were performed using 13C-NMR spectroscopy in solution. Chemical functions such as urethane, urea, allophanate, and biuret were all expected to be detected in these polymeric binders. 13C-NMR assignment of the C—O urethane and urea functions were found in these polymers as determined by using model compounds of IPDI. The 13C-NMR data gathered in this article can be considered as basic parameters for further characterization of polyurethane structure based on IPDI. Also, 13C CP MAS NMR spectra of GAP-IPDI-based polymers were carried out to identify the various chemical functions present in solid polyurethane elastomer. In addition, the curing evolution of a GAP-IPDI-based polymer at 50 and 80°C in bulk was monitored, and the reaction path of the binder was readily determined. Some conclusions on the effects of the cure catalyst and the curing temperature were also drawn. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 2991-2998, 1997
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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