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  • 1
    Electronic Resource
    Electronic Resource
    Levels of cysteinyl leukotriene receptor mRNA in human peripheral leucocytes: significantly higher expression of cysteinyl leukotriene receptor 2 mRNA in eosinophils (2001)
    Oxford, UK : Blackwell Science, Ltd
    Clinical & experimental allergy 31 (2001), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Cysteinyl leukotrienes (CysLTs) have been implicated as important contributors in the pathophysiology of asthma and their biological effects are mediated by at least two distinct G-protein-coupled receptors. cDNA sequences of cysteinyl leukotriene receptor 1 (CysLTR1) and cysteinyl leukotriene receptor 2 (CysLTR2) have recently been elucidated.Objectives Our aim is to explore gene expression and the comparative expression of CysLTR1 mRNA and CysLTR2 mRNA in human peripheral blood leucocytes.Methods Gene expression of CysLTR1 and CysLTR2 mRNAs in human peripheral blood eosinophils, neutrophils, monocytes and T lymphocytes has been measured by competitive reverse transcription-polymerase chain reactions using RNA or DNA competitors.Results (a) When cellular levels of CysLTR1 mRNA were normalized to those of G3PDH mRNA, the relative concentration of CysLTR1 mRNA in eosinophils (43.8 ± 37.2, n = 29) was significantly higher than that in neutrophils (18.7 ± 23.3, n = 11), monocytes (0.93 ± 1.1, n = 10) and T lymphocytes (3.4 ± 2.4, n = 11). (b) When measured using each DNA competitor, mRNAs for both types of CysLTR coexisted in each type of leucocyte. The ratio of CysLTR1 mRNA to CysLTR2 mRNA was significantly lower in eosinophils (0.65 ± 0.42, n = 12) than in neutrophils (6.9 ± 4.9, n = 12), monocytes (1.8 ± 0.9, n = 10) and T lymphocytes (4.5 ± 5.7, n = 10). (c) Human umbilical vein endothelial cells expressed CysLTR2 mRNA, but not CysLTR1 mRNA.Conclusion These studies reveal that CysLTR1 mRNA and, in particular, CysLTR2 mRNA are abundantly expressed at high levels in eosinophils, raising the possibility that CysLTR2 may have an important physiological role in eosinophils and a CysLTR2 antagonist may be a good target for preventing signal transduction by CysLTs in eosinophils.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2001.01184.x
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  • 2
    Electronic Resource
    Electronic Resource
    Affinity of IgE antibody to antigen influences allergen-induced histamine release (2000)
    Oxford BSL : Blackwell Science Ltd
    Clinical & experimental allergy 30 (2000), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Although affinity of an antibody for an antigen is recognized to be an important factor in determining its biological effects, little is known about the relevance of such affinity of IgE antibodies to the functional response.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectivesTo investigate the effect of IgE antibody affinity to Der p 2 on Der p 2-induced histamine release from human basophils.〈section xml:id="abs1-3"〉〈title type="main"〉MethodsThe most probable value of the dissociation constant (Kd) of IgE antibody to Der p 2 was calculated and histamine release by Der p 2-challenged leucocytes was used to evaluate the biological efficacy of the IgE antibody.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsThe most probable Kd value of IgE antibody to Der p 2 ranged from 5.6 to 177.8 pM in 14 asthmatic patients sensitive to Der p 2. A significant correlation was observed in Der p 2-induced histamine release between the sensitivity and the Kd value for Der p 2-specific IgE antibody (rs = 0.797, P = 0.0040), suggesting that the higher the affinity, the lower the amount of allergen required for the release of a specific level of histamine.〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionApart from the changes associated with the reactivity, the sensitivity of histamine release is closely related to the affinity of IgE antibody for its antigen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2000.00921.x
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  • 3
    Electronic Resource
    Electronic Resource
    Transient contribution of mast cells to pulmonary eosinophilia but not to hyper-responsiveness (2002)
    Oxford, UK : Blackwell Science, Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background We have recently demonstrated that the transfer of interleukin (IL)-5-producing CD4+ T cell clones into unprimed mice is sufficient for the development of eosinophilic inflammation in the bronchial mucosa upon antigen inhalation.Objective The aim of this study was to elucidate the possible contribution of mast cells in eosinophilic inflammation and bronchial hyper-responsiveness (BHR), and to discriminate between the roles of CD4+ T cells and mast cells.Methods Mast cell-deficient mice (WBB6F1-W/Wv) and their congenic normal littermates (WBB6F1−+/+) were immunized with ovalbumin and challenged by inhalation with the relevant antigen.Results Airway eosinophilia was induced with equivalent intensity in +/+ and W/Wv mice 6, 24, 96 and 216 h after antigen inhalation. In contrast, 48 h after antigen challenge, eosinophilic infiltration into the bronchial mucosa was significantly less pronounced in W/Wv mice than in +/+ mice. Anti-CD4 monoclonal antibody (mAb), anti-IL-5 mAb, and cyclosporin A were administered next, demonstrating that the airway eosinophilia of W/Wv mice induced 48 h after antigen challenge was almost completely inhibited by each of these three treatments, but that of +/+ mice was significantly less susceptible. Bronchial responsiveness to acetylcholine was increased 48 h after antigen challenge and was not significantly different between +/+ and W/Wv mice. Administration of anti-IL-5 mAb completely inhibited the development of BHR in both +/+ and W/Wv mice.Conclusion These results indicate that, in mice, mast cells do have a supplemental role in the development of pulmonary eosinophilia but not BHR. CD4+ T cells totally regulate these responses by producing IL-5.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0022-0477.2001.01248.x
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  • 4
    Electronic Resource
    Electronic Resource
    Urinary 3-bromotyrosine and 3-chlorotyrosine concentrations in asthmatic patients: lack of increase in 3-bromotyrosine concentration in urine and plasma proteins in aspirin-induced asthma after intravenous aspirin challenge (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 34 (2004), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Eosinophil peroxidase and myeloperoxidase halogenate tyrosine residues in plasma proteins and generate 3-bromotyrosine (BY) and 3-chlorotyrosine (CY), respectively.Objectives (1) To estimate urinary concentrations of BY and CY in asthmatic patients. (2) To investigate BY concentration in relation to urinary leukotriene E4 (LTE4) concentration in order to evaluate the activation of eosinophils in patients with aspirin-induced asthma (AIA).Methods BY and CY were quantified with a gas chromatograph-mass spectrometer using 13C-labelled compounds as internal standards.Results (1) Activation of eosinophils and neutrophils by immobilized IgG1 induced preferential formation of BY and CY, respectively. (2) A significantly higher concentration of BY was observed in the urine from asthmatic patients than in that from healthy control subjects (45±21.7 vs. 22.6±10.8 ng/mg-creatinine, P〈0.01). CY concentration was also elevated in the urine from asthmatic patients (4.4±3.2 vs. 1.5±1.0 ng/mg-creatinine, P〈0.01). (3) After intravenous aspirin challenge of aspirin-induced asthmatic patients, the concentration of BY in urine did not significantly change. No significant change was also observed in the ratio of BY concentration to total tyrosine concentration in plasma proteins. In contrast, the concentration of urinary LTE4 significantly increased after the intravenous aspirin challenge.Conclusion Determination of BY and CY concentrations may be useful for monitoring the activation of eosinophils and neutrophils in asthmatic patients, respectively. After aspirin challenge of AIA patients, the increased concentration of urinary LTE4 did not accompany changes in BY concentration in both urine and plasma proteins. These results may preclude the activation of eosinophils after aspirin challenge in patients with AIA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.01968.x
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  • 5
    Electronic Resource
    Electronic Resource
    Increase in urinary leukotriene B4 glucuronide concentration in patients with aspirin-intolerant asthma after intravenous aspirin challenge (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 34 (2004), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Aspirin challenge of aspirin-intolerant asthma (AIA) patients causes a significant increase in leukotriene E4 (LTE4) concentration in urine. However, knowledge on leukotriene B4 (LTB4) generation in patients with AIA is insufficient. Recent research has demonstrated that exogenously administered LTB4 is excreted as glucuronide into the urine in human healthy subjects.Objective The purpose of this study is to estimate urinary LTB4 glucuronide (LTBG) concentration in the clinically stable condition in healthy subjects and asthmatic patients and to investigate changes in urinary LTBG concentration in patients with AIA after aspirin challenge.Methods A provocation test was performed by intravenous aspirin challenge. After urine was hydrolysed by β-glucuronidase, the fraction containing LTB4 was purified by high-performance liquid chromatography and LTB4 concentration was quantified by enzyme immunoassay. Urinary LTBG concentration was calculated as the difference between the concentration obtained with hydrolysis and that without hydrolysis.Results (1) After hydrolysis, the presence of urinary LTB4 was verified by gas chromatography-mass spectrometry-selected ion monitoring. (2) The urinary LTBG concentration was significantly higher in the asthmatic patients than in the healthy subjects (median, 5.37 pg/mg creatinine [range 1.2–13] vs. 3.32 pg/mg creatinine [range, 0.14–10.5], P=0.0159). (3) The patients with AIA (n=7), but not those with aspirin-tolerant asthma (n=6), showed significant increases in LTBG and LTE4 excretions after aspirin challenge. (4) When the concentrations after aspirin challenge were analysed simultaneously, a significant linear correlation was observed between urinary LTBG concentration and urinary LTE4 concentration in patients with AIA (Spearman's rank correlation test, r=0.817, P=0.0003).Conclusion LTBG is present in human urine, albeit at a concentration lower than urinary LTE4. In addition to a marked increase in cysteinyl-leukotriene production, aspirin challenge induced LTB4 production in AIA patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.02034.x
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  • 6
    Electronic Resource
    Electronic Resource
    A comparative study of eicosanoid concentrations in sputum and urine in patients with aspirin-intolerant asthma (2002)
    Oxford, UK : Blackwell Science, Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Although many studies have assumed that the overproduction of cysteinyl- leukotrienes (cys-LTs) and an imbalance of arachidonic acid metabolism may be plausible causes for the pathogenesis of aspirin-intolerant asthma (AIA), there has been little experimental evidence to substantiate this notion in lower airways of patients with AIA.Objectives The purpose of this study was to compare the eicosanoid concentrations in sputum and urine from patients with AIA.Methods The concentrations of sputum cys-LTs, prostaglandin E2 (PGE2), PGF2α, PGD2 and thromboxane B2 were measured to assess local concentrations of eicosanoids in patients with AIA and in those with aspirin-tolerant asthma (ATA). The concentrations of two urinary metabolites, leukotriene E4 (LTE4) and 9α11βPGF2, were also measured to corroborate the relationship between the eicosanoid biosynthesis in the whole body and that in lower airways.Results The concentration of PGD2 in sputum was significantly higher in patients with AIA than in those with ATA (median, 5.3 pg/mL vs. 3.1 pg/mL, P 〈 0.05), but there was no significant difference in the concentration of the corresponding metabolite, 9α11βPGF2, between the two groups. No differences were noted in the concentrations of other prostanoids in sputum between the two groups. The sputum cys-LT concentrations showed no differences between the two groups, in spite of the observation that the concentration of urinary LTE4 was significantly higher in patients with AIA than in those with ATA (median, 195.2 pg/mg-cre vs. 122.1 pg/mg-cre, P 〈 0.05). There was a significant correlation among the concentration of cys-LTs, the number of eosinophils and the concentration of eosinophil-derived neurotoxin (EDN) in sputum.Conclusion The urinary concentration of LTE4 does not necessary reflect cys-LT biosynthesis in lower airways. A significantly higher concentration of PGD2 in sputum from patients with AIA suggests the possible ongoing mast cell activation in lower airways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2745.2002.01507.x
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  • 7
    Electronic Resource
    Electronic Resource
    Measurement of Dermatophagoides mite allergens on bedding and human skin surfaces (2003)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 33 (2003), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The level of the Dermatophagoides mite group 1 (Der 1) allergens in reservoir dust has been used as an index of exposure in most studies. However, the mite allergen level in reservoir dust cannot directly reflect the personal exposure level.Objective We sought to develop a new method for quantifying the Der 1 allergens on bedding and human skin surfaces as an index of exposure to mite allergens.Methods Samples were obtained with a small adhesive tape from the forearm skin of 30 healthy volunteers and from their regularly used mattresses. The level of Der 1 allergens collected onto the adhesive tape was measured by a newly developed sensitive fluorometric ELISA for Der p 1 and Der f 1.Results The Der 1 allergens could be detected in all the samples from bedding surfaces and in 28 of the 30 samples from skin surfaces. The Der 1 levels by adhesive tape sampling from the mattresses correlated with those by reservoir dust sampling. The sampling of the skin and bedding surface with adhesive tape correlated, but skin sampling did not correlate with reservoir sampling.Conclusion The Der 1 allergens on bedding surfaces and on human skin surfaces could be quantified with a very simple sampling technique. The system developed in this study will provide a new tool for the assessment of mite allergen exposure in daily life.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2003.01820.x
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  • 8
    Electronic Resource
    Electronic Resource
    Possible involvement of mast-cell activation in aspirin provocation of aspirin-induced asthma (2001)
    Copenhagen : Munksgaard International Publishers
    Allergy 56 (2001), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Although there is increasing evidence of the importance of cysteinyl leukotrienes (LT) as mediators of aspirin-induced bronchoconstriction in aspirin-sensitive asthma, the cellular origin of the LT is not yet clear. Methods: Urinary concentrations of leukotriene E4 (LTE4), 11-dehydrothromboxane B2, 9α,11β-prostaglandin F2, and Nτ-methylhistamine were measured during the 24 h following cumulative intravenous administration of increasing doses of lysine aspirin to asthmatic patients. In addition, the urinary concentrations of these metabolites were measured on 5 consecutive days in a patient who suffered an asthma attack after percutaneous administration of nonsteroidal anti-inflammatory drugs. Results: In aspirin-induced asthma patients (AIA, n=10), the basal concentration of urinary LTE4, but not the other metabolites, was significantly higher than that in aspirin-tolerant asthma patients (ATA, n=10). After intravenous aspirin provocation, the AIA group showed a 13.1-fold (geometric mean) increase in excretion of LTE4 during the first 3 h, and 9α,11β-prostaglandin F2 also increased in the AIA group during the first 0–3 h and the 3–6 h collection period. Nτ-methylhistamine excretion was also increased, but to a lesser degree. Adminis-tration of aspirin caused significant suppression of 11-dehydrothromboxane B2 excretion in both the AIA and ATA groups. When the percentage of maximum increase of each metabolite from the baseline concentrations was compared between the AIA group and the ATA group, a significantly higher increase in excretion of LTE4, 9α,11β-prostaglandin F2, and Nτ-methylhistamine was observed in the AIA group than the ATA group. An increased excretion of LTE4 and 9α,11β-prostaglandin F2 has been detected in a patient who suffered an asthma attack after percutaneous administration of nonsteroidal anti-inflammatory drugs. Conclusions: Considering that human lung mast cells are capable of producing LTC4, prostaglandin D2, and histamine, our present results support the concept that mast cells, at least, may participate in the development of aspirin-induced asthma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.2001.00913.x
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  • 9
    Electronic Resource
    Electronic Resource
    Nasal blockage and urinary leukotriene E4 concentration in patients with seasonal allergic rhinitis (2003)
    Oxford, UK : Munksgaard International Publishers
    Allergy 58 (2003), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Cysteinyl-leukotrienes have been reported to have a primary role in the induction of nasal blockage of allergic rhinitis. However, there has been little experimental evidence that substantiates the relationship between nasal blockage severity and urinary leukotriene E4 (U-LTE4) concentration in patients with seasonal allergic rhinitis (SAR).Methods: The concentrations of urinary mediators in 20 SAR patients were measured using an enzyme immunoassay to determine the relationship between nasal blockage severity and U-LTE4 concentration in patients with SAR.Results: The basal U-LTE4 concentration was significantly higher in SAR patients with severe nasal blockage than in those with mild nasal blockage and in healthy control subjects. Although U-LTE4 concentrationwas significantly higher in patients with both asthma and SAR than in SAR patients with mild nasal blockage, no significant difference in the U-LTE4 concentration between patients with both asthma and SAR and SAR patients with severe nasal blockage was found. There was a significant correlation between U-LTE4 and urinary 9α11β-prostoglandin F2 (9α11βPGF2) concentrations (rs = 0.51, P = 0.02) in SAR patients.Conclusions: Although specific sites and cells of cysteinyl-leukotriene biosynthesis could not be determined in this study, severe nasal blockage is associated with the increased excretion level of U-LTE4.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1398-9995.2003.00159.x
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  • 10
    Electronic Resource
    Electronic Resource
    Effects of a nitro compound patch on neuropathy in Churg-Strauss syndrome (2003)
    Oxford, UK : Munksgaard International Publishers
    Allergy 58 (2003), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1398-9995.2003.00157.x
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