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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 Rapid clinical tolerance can be induced over several hours by very fast bee venom immunotherupy (VIT) protocols.Objective To investigate the mechanisms underlying VIT we examined the changes of blood basophil responsivetiess during VIT.Methods Seven bee venom allergic patients with a history of severe systemic reactions after a bee sting were investigated. A cumulative dose of 111.1 μg bee venom (BV) was administered sc over 3.5 h under intensive care conditions according to an ultra-rush protocol. The release of histamine and the formation of leukotrienes in response to BV, major BV allergen Phospholipase A2 (PLA), IgE receptor cross-linking with the use of monoclonal antibodies against IgE and IgE receptor, as well as IgE independent activation in response to C5a were determined in vitro before and after ultra-rush VIT.Results We demonstrated a decrease of total histamine in peripheral blood leucocytes just after VIT. Histamine release in response to all the stimuli used is not affected by ultra-rush VIT, if expressed as per cent release of total histamine. However, the absolute amount of product released in response to stimulation was decreased, particularly with allergen (BV, PLA). We also found a significant reduction of LTC4 formation after VIT in samples stimulated with specific allergen (BV, PLA).Conclusion Blood basophils are a target for VIT, which induces impaired release of both preformed and newly generated mediators. However, we believe the basic mechanisms of rapid clinical tolerance induced by ultra-rush VIT remain to be investigated.
    Type of Medium: Electronic Resource
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  • 2
    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  Fungal components can cause allergic symptoms either through inhalation, ingestion or contact. Whereas respiratory allergy is thought to be induced by spores, allergic reactions following ingestion are attributed to other parts of the mushroom. Reports of food-related allergic reactions due to the edible mushroom Boletus edulis have occasionally been reported.Objective  The aim of the study was to investigate whether separate allergens may be detected in alimentary allergy to Boletus edulis.Methods  Sera of two subjects, one with recurrent anaphylaxis and the other with a predominantly oral allergy syndrome following ingestion of Boletus edulis, have been analysed by a time-course digestion assay using simulated gastric fluid and by SDS-PAGE immunoblotting. Sera of four Boletus edulis skin prick test-negative subjects and all without clinical symptoms to ingested Boletus edulis served as controls.Results  In lyophilized Boletus edulis extract, at least four water-soluble proteins were detected, the most reactive at 55 kDa and at 80 kDa. Following the time-course digestion assay, IgE binding was found to a 75-kDa protein, but only if the sera of the subject with recurrent anaphylaxis was used.Conclusion  The data indicate that Boletus edulis can cause an IgE-mediated food allergy due to a digestion-stabile protein at 75 kDa. No IgE immune response to this protein was detected in the serum of a subject with respiratory allergy and oral allergy syndrome to Boletus edulis nor in control sera.
    Type of Medium: Electronic Resource
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  • 3
    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
    Notes: Background rapid administration of bee venom in cumulative doses exceeding the quantity contained in one bee sting is well tolerated by most of the patients during 3.5 h of ultra-rush bee venom immunotherapy (VIT). The mechanism of this tolerance is unknown. Objective The aim of the study was to verify the hypothesis that either slow mediator depletion of mast cells or blockade of their surface receptor mechanisms by increasing doses of allergen might be the major mechanisms of tolerance induced by ultra-rush VIT. Methods Nine bee venom allergic patients with a history of severe systemic reactions after a bee sting, positive skin tests and bee venom specific serum IgE antibodies were treated as follows: on the first day a cumulative dose of 111 μg was administered over 3.5 h under intensive care conditions. Further injections were given on day 7, day 21 and thereafter at 4 week intervals, Intradermal tests with codeine phosphate (nonspecific mast cell degranulation) and bee venom were performed before the initiation of VIT and 30 min after the last injection on the same day as well as before the subsequent bee venom injections. Results No significant changes of skin reactivity to both codeine phosphate and bee venom were observed on day I (before initiation of VIT and after the last injection on the same day). Conclusions Ultra-rush VIT does not induce mediator depletion or surface receptor blockade in skin mast cells.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The synthesis of IgE is regulated by cytokines secreted from T-helper cells. The studies on cytokine secretion by peripheral blood mononuclear cells (PBMC) upon stimulation with antigen or allergen are ditficult due to low levels of cytokines, especially of inlerieukin-4 (IL-4).Objective ln this study we tried lo establish a culture system, which could enable the measurement of the cytokine profiles in specifically activated cultures.Methods Three methods to potentiate cytokine secretion were evaluated: PBMC from bee venom or house dust mite (Dermatophagoides pteronyssinus) allergic patients as well as normal subjects were stimulated either with the major bee venom allergen phosphoiipase A2 (PLA) or with the major D. pteronyssinus allergen (Der p 1) or with the control antigens tetanus toxoid (TT) and purified protein derivate (PPD). After 7 days of culture the cells were restimulated either wilh pkistie bound 0KT3 F(ab)2 monoclonal antibodies (MoAbs), with the appropriate antigen + antigen presenting cells or with IL-2. The secretion of cylokines (IL-4, IFNγ) was measured after restimulation of the cultures (day 8).Results While OKT3 F(ab)2 was unable lo activate resting T cells, it could restimulate preactivaled cells. Restimulalion with OKT3 F(ab)2 induced higher IL-4 and IFN7 secretion than restimulation with IL-2 or antigen. TT and PLA stimulated a similar cytokine secretion prolile in normal and PLA allergic subjects with substantial levels of both lL-4 and IFNγ. In contrast, PPD induced virtually only IFNγ secretion. Der p 1 stimulated mainly IL-4 seerclion but also IFNγ production in some mite allergic palienis.Conclusion We have established a cell culture system, which combines antigen specificity with a strong cytokine inducing signial provided by anti-CD3 MoAbs. TH-1 and TH-2 characteristic cytokine patterns can be observed in short-term PBMC cultures already after 8 days of culture.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background It has been shown that drugs comprise a group of non-peptide antigens that can be recognized by human T cells in the context of HLA class II and that this recognition is involved in allergic reactions. Recent studies have demonstrated a MHC-restricted but processing- and metabolism-independent pathway for the presentation of allergenic drugs such as lidocaine and sulfamethoxazole (SMX) to drug-specific T cells. However, there is little information so far on the precise molecular mechanisms of this non-covalent drug presentation.Objective The aim of this study was to evaluate the requirements for a specific peptide occupying the groove of the MHC class II molecule for the efficient presentation of non-covalently bound drugs to CD4+ T cells.Methods We analysed the effect of coincubation or prepulse of antigen presenting cells (APC) with different peptides on the proliferative responses of SMX-specific CD4+ T cell clones. In a second series of experiments, we eluted HLA-bound peptides from the surface of antigen presenting cells by mild acid treatment. Successful removal of peptides was tested directly using labelled peptides and functionally by monitoring activation and proliferation of peptide-specific T cell clones. Finally, the presentation of SMX to SMX-specific T cell clones before and after elution of MHC class II bound peptides was tested.Results We found that neither peptide coincubation nor peptide prepulse of APC altered the proliferative response of SMX-specific T cells. APC treated with the acid for a short time retained cell viability, MHC class II expression and antigen presenting cell function. However, defined peptides could be eluted from surface MHC class II molecules nearly quantitatively. Nevertheless, the chemically non-reactive drug SMX could still be presented to specific T cells independent of the presence of distinct self-peptides.Conclusion Our data suggest that small molecules like drugs can bind to a multitude of HLA-bound peptides or that, similar to superantigens, they might bind directly to HLA.
    Type of Medium: Electronic Resource
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  • 6
    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: Background The most frequent side-effects of drug therapy are skin eruptions. Their pathomechanism is rather unclear.Objective In this prospective study we investigated the T cell activation and drug specificity in different forms of drug-induced exanthemas from 22 patients.Methods During acute drug allergy, liver parameters and T cell subset activation in the circulation (up-regulation of CD25 and HLA-DR) were evaluated and skin biopsies of the acute lesion performed. After recovery, the causative drug was identified by lymphocyte transformation (LTT) and scratch-patch tests.Results Seventeen of 22 (17/22) patients had maculo-papular exanthema, 4/22 bullous exanthema and 1/22 urticaria. The causative drugs were mainly antibiotics, anti-epileptics and anti-hypertensives. Up-regulation of HLA-DR on circulating CD4+ and/or CD8+ T cells was detected in 17 patients, being most marked in patients with bullous reactions or hepatic involvement. The LTT was positive in 14/21 analysed and the patch test in 7/15. All patients showed lymphocytic infiltration in the skin biopsy of the acute lesion. Generally CD4+ T cells dominated; a higher percentage of circulating CD8+ T cells was found in patients with bullous skin reactions or hepatic involvement.Conclusion Our data demonstrate activation and drug specificity of T cells in drug-induced skin eruptions. A predominant CD8+ T cell activation leads to more severe (bullous) skin symptoms or liver involvement, while predominant activation of CD4+ cells elicits mainly maculo-papular reactions.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Diagnosis of anaphylaxis is clinically based and usually straightforward. However, data on the epidemiology of anaphylaxis, particularly the most profound and life-threatening form such as anaphylactic shock are limited and thought to be under-reported.Objective The primary aim of this study was to investigate the incidence and the causes of severe anaphylaxis with circulatory signs in the Canton Bern, which comprises about 940 000 inhabitants or approximately one-seventh of the population of Switzerland.Methods During a 3-year period, 1 January 1996 to 31 December 1998, all medical records (7739 documents) from the two allergy clinics of the Canton Bern have been reviewed. In addition, all seven board-certified specialists of the Foederatio Medicorum Helveticorum (FMH) in Allergology and Clinical Immunology of this Canton as well as all 17 hospitals with emergency units of this area have been contacted for cases with an anaphylactic event not referred to the allergy clinics.Results Overall, 226 individuals, 106 females (47%) with a mean age of 41 years (range, 5–74 years) and 120 males (53%) with a mean age of 38 years (8 months–83 years) were diagnosed as having presented generalized, life-threatening anaphylaxis with circulatory symptoms. Altogether, these patients experienced 246 episodes of severe systemic reactions. In addition, death due to anaphylaxis occurred in three subjects. The annual incidence of anaphylaxis per 100 000 inhabitants per year ranged between 7.9 and 9.6 cases. Hymenoptera stings (58.8%), drugs (18.1%), and foods (10.1%) were the most commonly identified culprits for anaphylaxis. In 5.3% of all anaphylactic events, the cause could not be identified.Conclusion The incidence rate of severe life-threatening anaphylaxis with circulatory signs in the Canton Bern, Switzerland, with 7.9–9.6 per 100 000 inhabitants per year is comparable to the findings of other epidemiological investigations. In most events, a causal agent or allergen could be identified by a careful allergological examination.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 7 (1978), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Using a rosette technique with IgM coated bovine red blood cells (EA-IgM) receptors for IgM can be demonstrated on human B-lymphocytes. While in the peripheral blood B cells with IgM receptors are found only occasionally, between 7 and 33%, mean 16%, of tonsil B-lymphocytes exhibit receptors for IgM. This was shown in double marker studies using EA-IgM for the demonstration of IgM receptors and fluorochrome labelled conjugates for the demonstration of S-IgD, S-IgM and B cell antigens. These receptors are specific for IgM, they can be completely blocked by IgM-anti OVA complexes and partially by free IgM, but not at all by aggregated human IgG. They are sensitive to trypsin and pronase but reconstitute after further incubation at 37°C. These data show that not only T and CLL cells but also some normal B-lymphocytes have receptors for IgM. We favour the view that CLL lymphocytes may derive from these B-lymphocytes, which may represent a certain maturation step in B cell development.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: All iodinated contrast media (CM) are known to cause both immediate (≤1 h) and nonimmediate (〉1 h) hypersensitivity reactions. Although for most immediate reactions an allergic hypersensitivity cannot be demonstrated, recent studies indicate that the severe immediate reactions may be IgE-mediated, while most of the nonimmediate exanthematous skin reactions, appear to be T-cell mediated. Patients who experience such hypersensitivity reactions are therefore advised to undergo an allergologic evaluation. Several investigators have found skin testing to be useful in confirming a CM allergy, especially in patients with nonimmediate skin eruptions. If a patient with confirmed allergy to a CM needs a new CM exposure, a skin test negative CM should be chosen and premedication may be tried. However, none of these precautional measures is a guarantee against a repeat reaction. More research focusing on pathomechanisms, diagnostic testing and premedication is therefore clearly needed in order to prevent CM-induced hypersensitivity reactions in the future.
    Type of Medium: Electronic Resource
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