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  • 1
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims:  To study the expression of mucins in peripheral airways in patients with chronic obstructive pulmonary disease (COPD).Methods and results:  Peripheral lung sections from smokers with COPD (n = 9) and age-matched controls including smokers (n = 11) and lifelong non-smokers with normal lung function (n = 6) were stained with alcian blue, periodic acid–Schiff (PAS) and by immunohistochemistry of mucins (MUC): MUC2, MUC4, MUC5AC, MUC5B and MUC6. Histochemical staining and immunoreactivity of bronchiolar epithelium were graded and the presence or absence of stained mucus in the bronchiolar lumen was evaluated. There were no differences in alcian blue and PAS epithelial staining between the three groups. Intraluminal PAS staining was significantly more frequent among COPD subjects (P 〈 0.05). The expression of MUC5AC was significantly higher in the bronchiolar epithelium of patients with COPD (P 〈 0.05). Within the bronchiolar lumen, the predominant mucin was MUC5B. Intraluminal MUC5B was significantly more frequent among COPD patients (P 〈 0.05).Conclusions:  COPD is specifically associated with increased expression of MUC5B in the bronchiolar lumen and of the mucin MUC5AC in the bronchiolar epithelium. These changes in mucin production in the peripheral airways may contribute to the pathophysiology of COPD.
    Type of Medium: Electronic Resource
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  • 2
    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
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have developed a guinea pig model of trimellitic anhydride-induced airway hypersensitivity responses. In one group of guinea pigs, injected intradermally with 0.1 ml 30% trimellitic anhydride (TMA), we examined the specificity of the bronchopulmonary response to TMA comparing the effect of intravenous TMA conjugated to guinea pig serum albumin (GPSA) with a control hapten (procion dye) protein conjugate (PD-GPSA). A significant increase in pulmonary inflation pressure (PIP) was provoked in sensitized animals following intravenous injection with TMA-GPSA (20%; 0–400, median; range) as compared to intravenous injection of PD-GPSA. In the second group we compared three different methods of sensitization: single injection of 0.1 ml of 0.3% TMA; four injections of 0.1 ml of 0.1% TMA; and a single high dose injection of 30% TMA. Following intravenous TMA-GPSA guinea pigs sensitized with a single injection 0.3% TMA had an increase in PIP of 395%; 220–600, while those given four repeat injections of 0.1% TMA had an increase in PIP of 343%; 315–490. These results were significantly higher than the increase in PIP (160%; 0–220) which occurred in guinea pigs sensitized with a single dose of 30% TMA. Four of 11 guinea pigs given low dose injections of TMA had bronchopulmonary responses to inhaled TMA-GPSA. All sensitized guinea pigs had specific IgG1 antibodies demonstrated by enzyme linked immunosorbent assay (ELISA) and confirmed by ELISA inhibition. Four guinea pigs sensitized by low dose injections of TMA had IgE antibodies demonstrated by passive cutaneous anaphylaxis.We conclude that intradermal sensitization to free TMA induces a specific immune and airway hypersensitivity response to TMA-GPSA. Single low dose injection of TMA is the most effective method of sensitization. Intradermal sensitization to free TMA may be a valuable method of sensitization for the developing of an animal model of occupational asthma caused by low molecular weight chemicals.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 20 (1990), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    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
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 25 (1995), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    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
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Patients with severe asthma are often inadequately controlled on existing anti-asthma therapy, constituting an unmet clinical need.Objective This randomized, double-blind, placebo-controlled trial evaluated the ability of omalizumab, a humanized monoclonal anti-IgE antibody, to improve disease control sufficiently to enable inhaled corticosteroid reduction in patients with severe allergic asthma.Methods After a run-in period when an optimized fluticasone dose (〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:09547894:CEA1916:ges" location="ges.gif"/〉1000 μg/day) was received for 4 weeks, patients were randomized to receive subcutaneous omalizumab [minimum 0.016 mg/kg/IgE (IU/mL) per 4 weeks; n=126] or matching placebo (n=120) at intervals of 2 or 4 weeks. The study comprised a 16-week add-on phase of treatment followed by a 16-week fluticasone-reduction phase. Short-/long-acting β2-agonists were allowed as needed.Results Median reductions in fluticasone dose were significantly greater with omalizumab than placebo: 60% vs. 50% (P=0.003). Some 73.8% and 50.8% of patients, respectively, achieved a 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:09547894:CEA1916:ges" location="ges.gif"/〉50% dose reduction (P=0.001). Fluticasone dose reduction to 〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:09547894:CEA1916:les" location="les.gif"/〉500 μg/day occurred in 60.3% of omalizumab recipients vs. 45.8% of placebo-treated patients (P=0.026). Through both phases, omalizumab reduced rescue medication requirements, improved asthma symptoms and asthma-related quality of life compared to placebo.Conclusion Omalizumab treatment improves asthma control in severely allergic asthmatics, reducing inhaled corticosteroid requirements without worsening of symptom control or increase in rescue medication use.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Studies on the inflammatory process in the large airways of patients with mild/moderate COPD have shown a prevalent T lymphocyte and macrophage infiltration of the bronchial mucosa. However, bronchial inflammation in more severe disease has not been extensively studied.Objective The aim of the present study was to characterize the lymphocyte infiltration in the bronchial mucosa of subjects with severe, compared to mild, COPD, and to examine the relationship between airflow limitation and T lymphocyte numbers in the bronchial mucosa.Methods We examined bronchial biopsies obtained from nine smokers with severe airflow limitation, nine smokers with mild/moderate airflow limitation and 14 smokers with normal lung function. Immunohistochemical methods on cryostat sections were used to assess the number of CD3+, CD4+, CD8+ cells and the number of CD3+ cells coexpressing the chemokine receptor CCR5 (CCR5+CD3+) in the subepithelium.Results Subjects with severe COPD had lower numbers of CD3+, CD8+ and CCR5+CD3+ cells than mild/moderate COPD (P 〈 0.012, P 〈 0.02 and P 〈 0.02, respectively) and control smokers (P 〈 0.015, P 〈 0.005 and P 〈 0.015, respectively). In subjects with airflow limitation the number of CD3+ and CD8+ cells was inversely correlated with the degree of airway obstruction (r = 0.59, P 〈 0.015 and r = 0.52, P 〈 0.032, respectively).Conclusions Bronchial inflammation in severe COPD is characterized by lower numbers of CD3+ and CD8+ cells and decreased numbers of CD3+ cells coexpressing the chemokine receptor CCR5. T lymphocyte infiltration is inversely correlated with the degree of airflow limitation.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have studied the effects of tachykinin-depletion on airway microvascular leakage induced by allergen challenge in ovalbumin-sensitised guinea pigs, Tachykinin-depletion was obtained by capsacin pretreatment 1 week before inhaled allergen challenge. Capsaicin pretreatment did not change airway microvascular permeability induced by allergen challenge. Capsaicin pretreatment did not change airway microvascular permeability induced by allergen challenge. Thus, sensory neuropeptides may not be important in allergen induced acute airway microvascular leakage in guinea pig in vivo.
    Type of Medium: Electronic Resource
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