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  • 1
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 124, No. 1-3 ( 2001), p. 183-186
    Kurzfassung: 〈 i 〉 Background: 〈 /i 〉 Regular use of inhaled β-adrenergic agonists may have adverse effects in some asthma patients. Polymorphisms of the β 〈 sub 〉 2 〈 /sub 〉 -adrenergic receptor (β 〈 sub 〉 2 〈 /sub 〉 -AR) can affect its regulation; however, results of smaller studies of the effects of such polymorphisms on response to β-agonist therapy have been inconsistent. 〈 i 〉 Methods: 〈 /i 〉 We examined the possible effects of polymorphisms at codons 16 (β 〈 sub 〉 2 〈 /sub 〉 -AR-16) and 27 (β 〈 sub 〉 2 〈 /sub 〉 -AR-27) on response to albuterol by genotyping 190 asthmatics who had participated in a trial of regular versus as-needed albuterol use. 〈 i 〉 Results: 〈 /i 〉 During the 16-week treatment period, patients homozygous for arginine (Arg/Arg) at β 〈 sub 〉 2 〈 /sub 〉 -AR-16 who used albuterol regularly had a small decline in morning peak expiratory flow (AM PEF). This effect was magnified during a 4-week run-out period, when all patients returned to as-needed albuterol only. By the end of the study, Arg/Arg subjects who had used albuterol regularly had an AM PEF 30.5 ± 12.1 liters/min lower (p = 0.012) than Arg/Arg patients who had used albuterol as needed only. Subjects homozygous for glycine at β 〈 sub 〉 2 〈 /sub 〉 -AR-16 showed no such decline. Evening PEF also declined in the Arg/Arg regular but not in as-need albuterol users. No significant differences between regular and as-needed treatment were associated with polymorphisms at β 〈 sub 〉 2 〈 /sub 〉 -AR-27. 〈 i 〉 Conclusions: 〈 /i 〉 Polymorphisms of the β 〈 sub 〉 2 〈 /sub 〉 -AR may influence airway responses to regular inhaled β-agonist treatment.
    Materialart: Online-Ressource
    ISSN: 1018-2438 , 1423-0097
    RVK:
    Sprache: Englisch
    Verlag: S. Karger AG
    Publikationsdatum: 2001
    ZDB Id: 1482722-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    S. Karger AG ; 1985
    In:  International Archives of Allergy and Immunology Vol. 77, No. 1-2 ( 1985), p. 241-243
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 77, No. 1-2 ( 1985), p. 241-243
    Kurzfassung: We have previously shown that 24-hour culture of human basophils with the antiinflammatory steroid dexamethasone produces an inhibition of the IgE-dependent release of histamine. In contrast, similar treatment of purified human lung mast cells does not inhibit the subsequent release of either histamine, prostaglandin D 〈 sub 〉 2 〈 /sub 〉 , or leukotriene (LT) C 〈 sub 〉 4 〈 /sub 〉 . We now show that incubation of mixed leukocytes for 24 h with 10 〈 sup 〉 ––7 〈 /sup 〉 〈 i 〉 M 〈 /i 〉 dexamethasone produces an inhibition of anti-IgE-induced basophil LTC 〈 sub 〉 4 〈 /sub 〉 release as detected by radioimmunoassay. In three experiments, control (CON) and dexamethasone (10 〈 sup 〉 ––7 〈 /sup 〉 〈 i 〉 M 〈 /i 〉 ; DEX)-treated cells were challenged with 0.01, 0.03 and 0.1 〈 i 〉 μ 〈 /i 〉 g/ml of anti-IgE, and histamine and LTC 〈 sub 〉 4 〈 /sub 〉 were monitored. LTC 〈 sub 〉 4 〈 /sub 〉 release (ng LTC 〈 sub 〉 4 〈 /sub 〉 / 〈 i 〉 μ 〈 /i 〉 g total cell histamine) from cells stimulated with anti-IgE was: 0.01 〈 i 〉 μ 〈 /i 〉 g/ml anti-IgE, 6.9 ± 4, 0.3 ± 0.1 (CON, DEX); 0.03 〈 i 〉 μ 〈 /i 〉 g/ml anti-IgE, 13.8 ± 4.7, 0.9 ± 0.5; 0.1 〈 i 〉 μ 〈 /i 〉 g/ml anti-IgE, 19.5 ± 2.3, 4.9 ± 1.2. Histamine release was inhibited by 50–75% by treatment with DEX in these experiments. Dose-response studies (n = 4) indicate that the inhibitory actions of DEX on LTC 〈 sub 〉 4 〈 /sub 〉 release occur in the range of 10 〈 sup 〉 ––10 〈 /sup 〉 to 10 〈 sup 〉 ––7 〈 /sup 〉 〈 i 〉 M 〈 /i 〉 . The concentration of DEX at which LTC 〈 sub 〉 4 〈 /sub 〉 release was inhibited by 50% (IC 〈 sub 〉 50 〈 /sub 〉 ) was approximately 2 × 10 〈 sup 〉 ––9 〈 /sup 〉 〈 i 〉 M 〈 /i 〉 . Another glucocorticoid (betamethasone) inhibited LTC 〈 sub 〉 4 〈 /sub 〉 release, while the nonglucocorticoids tetrahydrocortisone and 〈 i 〉 β 〈 /i 〉 -estradiol were inactive. High performance liquid chromatography (HPLC) analysis (coupled with RIA) indicated that the relative proportions of LTC 〈 sub 〉 4 〈 /sub 〉 , LTD 〈 sub 〉 4 〈 /sub 〉 , and LTE 〈 sub 〉 4 〈 /sub 〉 did not differ in supernatants from CON- and DEX-treated, anti-IgE-challenged cells. This suggests that DEX does not reduce immunoactive LTC 〈 sub 〉 4 〈 /sub 〉 by increasing its metabolism to LTD 〈 sub 〉 4 〈 /sub 〉 and LTE 〈 sub 〉 4 〈 /sub 〉 . Since basophil-derived sulfidopeptide leukotrienes may play an important role in inflammatory diseases, the inhibition of basophil leukotriene release by steroids may be a significant part of their antiinflammatory action.
    Materialart: Online-Ressource
    ISSN: 1018-2438 , 1423-0097
    RVK:
    Sprache: Englisch
    Verlag: S. Karger AG
    Publikationsdatum: 1985
    ZDB Id: 1482722-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Respiration, S. Karger AG, Vol. 50, No. 2 ( 1986), p. 116-122
    Materialart: Online-Ressource
    ISSN: 0025-7931 , 1423-0356
    Sprache: Englisch
    Verlag: S. Karger AG
    Publikationsdatum: 1986
    ZDB Id: 1464419-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 89, No. 2-3 ( 1989), p. 301-305
    Kurzfassung: The role played by neutrophils (PMNs) in the genesis of lung injury in diverse clinical situations, such as bronchial asthma, idiopathic pulmonary fibrosis, and the adult respiratory distress syndrome, is an area of intensive investigation. Functional studies of PMNs, particularly those obtained from the alveoli by bronchoalveolar lavage, should shed light on their contribution to lung injury. However, it has not been demonstrated whether procedures used to harvest cells from the lung (bronchoalveolar lavage), particularly the potentially prolonged exposure to saline, commonly used to perform lavage, and other components of lavage fluid, can alter the functional characteristics of PMNs. In this report we demonstrate that a 2- to 3-hour exposure of neutrophils to saline from both humans and sheep in vitro does not alter the functional characteristics of PMNs as determined by superoxide anion generation after activation with phorbol myristate acetate (PMA; 6.96 ± 0.44 vs. 7.60 ± 0.32 nmol O 〈 sub 〉 2 〈 /sub 〉 /250,000 PMNs for control and saline-treated human cells, respectively, after a 45-min incubation with 10 〈 sup 〉 –– 〈 /sup 〉 〈 sup 〉 7 〈 /sup 〉 〈 i 〉 M 〈 /i 〉 PMA, and 4.73 ± 0.30 vs. 4.50 ± 0.42 nmol O 〈 sub 〉 2 〈 /sub 〉 /250,000 PMNs for control and saline-treated sheep cells). In a second series of experiments, we studied the effect of exposure of human PMNs to bronchoalveolar lavage fluid supernatants obtained from normal volunteers on superoxide anion generation by neutrophils. Again, spontaneous (1.27 ± 0.49 vs. 1.65 ± 0.71 nmol O 〈 sub 〉 2 〈 /sub 〉 /200,000 PMNs for control and lavage fluid-treated cells, after a 45-min incubation), PMA-triggered (10 〈 sup 〉 ––6 〈 /sup 〉 〈 i 〉 M 〈 /i 〉 ; 5.67 ± 0.27 vs. 5.18 ± 0.55 nmol O 〈 sub 〉 2 〈 /sub 〉 /200,000 PMNs), and f-met peptide-triggered (10 〈 sup 〉 ––6 〈 /sup 〉 〈 i 〉 M 〈 /i 〉 ; 3.34 ± 0.41 vs. 3.04 ± 0.64 nmol O 〈 sub 〉 2 〈 /sub 〉 /200,000 PMNs) generation of superoxide anion was not affected. Therefore, we conclude that prolonged exposure of neutrophils to either saline or bronchoalveolar lavage fluid supernatants does not alter their capacity to generate superoxide anion and that biochemical studies of neutrophils obtained from the air spaces by bronchoalveolar lavage with saline should provide useful information about the functional characteristics of these cells.
    Materialart: Online-Ressource
    ISSN: 1018-2438 , 1423-0097
    RVK:
    Sprache: Englisch
    Verlag: S. Karger AG
    Publikationsdatum: 1989
    ZDB Id: 1482722-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Intervirology, S. Karger AG, Vol. 32, No. 1 ( 1991), p. 10-18
    Materialart: Online-Ressource
    ISSN: 0300-5526 , 1423-0100
    RVK:
    Sprache: Englisch
    Verlag: S. Karger AG
    Publikationsdatum: 1991
    ZDB Id: 1482863-7
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: Cardiology, S. Karger AG, Vol. 65, No. 2 ( 1980), p. 85-100
    Materialart: Online-Ressource
    ISSN: 1421-9751 , 0008-6312
    RVK:
    Sprache: Englisch
    Verlag: S. Karger AG
    Publikationsdatum: 1980
    ZDB Id: 1482041-9
    Standort Signatur Einschränkungen Verfügbarkeit
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