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  • 1
    Electronic Resource
    Electronic Resource
    IgE-mediated basophil releasability is influenced by intrinsic factors and by IgE on the cell surface (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 50 (1995), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Experiments were done to clarify the mechanisms associated with releasability of histamine. First, washed leukocytes from 23 asthmatic patients sensitive to mite allergen were challenged with Der p 1, a major allergen isolated from Dermatophagoides pteronyssinus, or anti-IgE. A significant correlation was observed between the ratio of Der p 1-specific IgE liter to total IgE level (S/T) in the patient's plasma and either the reactivity (maximal percentage of histamine release; rs= 0.514, P= 0.016, n= 23) or the sensitivity (the minimum allergen concentration required to achieve 25% histamine release; rs= -0.790, P= 0.0002) to Der p 1. Additionally, the reactivity to Der p 1 was significantly correlated with that to anti-IgE (rs= 0.690, P= 0.0012), indicating that an intrinsic cellular property may be one of the contributing factors in immunologic histamine release. In a second series of experiments, sinus mast cells were passively sensitized with immunoglobulins prepared from the patient's plasma. A statistically significant correlation was found between either the reactivity or the sensitivity to Der p 1 and S/T, thus indicating that S/T is an indicator of the releasability of histamine. When basophils or mast cells were passively sensitized with mouse IgE and subsequently stimulated with antimouse IgE, the reactivity to antihuman IgE was significantly correlated with that to antimouse IgE (rs= 0.966, P= 0.0023, n= 11). These observations suggest that an intrinsic cellular property regulates reactivity in immunologic histamine release. Taken together, our results suggest that an intrinsic cellular property, as well as specific IgE antibody levels on the cell surface, is an important factor in determining histamine release in response to IgE-dependent activation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1995.tb02506.x
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  • 2
    Electronic Resource
    Electronic Resource
    Atopic asthma caused by Candida albicans acid protease: case reports (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 49 (1994), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Two cases of atopic asthma caused by acid protease produced by Candida albicans are reported. Both patients had high levels of serum IgE antibodies against the acid protease and showed positive conjunctival and immediate bronchial responses when challenged with the protease. Significant histamine release was detected in both patients when their peripheral leukocytes were challenged with the protease antigen. These findings clearly showed that C. albicans acid protease is the causative allergen of atopic asthma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1994.tb02102.x
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  • 3
    Electronic Resource
    Electronic Resource
    Urinary leukotriene E4 and 11-dehydrothromboxane B2 in patients with aspirin-sensitive asthma (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 52 (1997), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The objective of this study was to define the participation of cysteinyl leukotrienes (LTs) or thromboxane A2 in the pathogenesis of aspirin-sensitive asthma (ASA). Leukotriene E4 (LTE4) and 11-dehydrothromboxane B2 (11DTXB2) values in spot urine were measured in 22 asthmatics with a history of aspirin sensitivity and in 17 without such a history of aspirin-sensitive asthma [NASA]) in the outpatient clinic. The urinary LTE4 value was significantly higher in ASA patients than in NASA (340±47 vs 65±15 pg/mg·cr, P〈0.001), but there was no significant difference in urinary 11DTXB2 between the two groups (891±77 vs 657±90 pg/mg·cr). A high value of LTE4 was not associated with type of asthma, severity of disease, oral prednisolone treatment, sex, or age. A higher value of 11DTXB2 was observed in the atopic type than the nonatopic type in ASA (1086±111 vs 697±147 pg/mg·cr, P〈0.05). No correlation was observed between urinary LTE4 and 11DTXB2 in either ASA or NASA. In conclusion, LTs may play an important role in the pathogenesis of ASA, and TXA2 in the pathogenesis of the atopic type in ASA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1997.tb01032.x
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  • 4
    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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  • 5
    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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  • 6
    Electronic Resource
    Electronic Resource
    Allergens from Dermatophagoides mites with chymotryptic activity (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 23 (1993), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A new set of allergens from Dermatophagoides pteronyssinus and D. farinae (provisionally named DPS and DF5, respectively) was isolated from the whole culture of mites. The apparent molecular weights of both allergens were shown to be 25000 on SDS-PAGE under a reducing condition and 27000 on Sephadex G-75 gel nitration chromatography. Both DP5 and DF5, as well as Der f III, possessed proteolytic activity. The results of substrate specificity and susceptibility to various protease inhibitors of DP5 and DF5 strongly suggested that they belonged to the chymotrypsin-like serine protease family. In sera from 88 mite-allergic patients, specific IgE antibodies to DP5 and/or DF5 were detected in only 41% of the sera by radio-allergosorbent test, while 90% and 93% had specific IgE antibodies to Der p I and/or Der f I and Der p II and/or Der f II, respecti vely.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1993.tb00343.x
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  • 7
    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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  • 8
    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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  • 9
    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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  • 10
    Electronic Resource
    Electronic Resource
    Increased Generation of Leukotriene C4 from Eosinophils in Asthmatic Patients (1985)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 40 (1985), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Human eosinophils with a density of over 1.095 were isolated from peripheral blood by dextran sedimentation, centrifugation with Lymphoprep and density gradients with Percoll. After the cells (1 × l05ml) were incubated with 1 μg/ml calcium ionophore A23187 for 20 min, leukotriene C4 (LTC4) content in the supernatant was measured by radioimmunoassay. The generation of LTC4 was significantly higher in the cells from extrinsic asthmatics (23.5 ± 14.8 ng/l06 cells, mean ± SD, n= 26, P 〈 0.01) and intrinsic asthmatics (24.6 ± 20.6 ng/106 cells, n= 27, P 〈 0.01) as compared with normal healthy subjects (8.3 ± 7.7 ng/106 cells, n= 10). There was no significant difference in the generation of LTC4 between intrinsic and extrinsic asthmatics. These observations indicate that eosinophils from asthmatic patients have increased ability to release LTC4.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1985.tb00884.x
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