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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 152 (2005), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 132 (1995), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: There is evidence that T lymphocytes play a critical role in the pathogenesis of drug-induced bullous exanthems. Sulphonamides are known to be among the most frequent aetiological agents in these severe drug-induced cutaneous hypersensitivity reactions. Several studies indicate that cytochrome P450-dependent metabolites of sulphonamides act as the nominal allergens. A 70-year-old woman with a severe blistering exanthem caused by cotrimoxazole (sulphamethoxazole and trimethoprim) was studied. We employed an in vitro approach to determine whether cytochrome P450-dependent enzymes activated drug-specific T lymphocytes from this patient. Immunohistochemical analysis of involved skin revealed a majority of epidermal CD8+ T lymphocytes, whereas the dermal infiltrate was composed of both CD4+ and CD8+ T cells. Dermal T lymphocytes isolated from lesional skin proliferated in response to sulphamethoxazole, but not to trimethoprim, in the presence of autologous mononuclear cells used as antigen-presenting cells. The antigen-specific response of sulphamethoxazole-specific T cells was significantly augmented in the presence of murine liver microsomes with P450-dependent catalytic activities. Our observations suggest that some cutaneous hypersensitivity reactions to sulphamethoxazole are due to drug-specific T lymphocytes. Cytochrome P450-dependent enzymes may play a critical role in the formation of the nominal antigen, which is recognized by antigen-specific T cells.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 128 (1993), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The presence, phenotype, and functional characteristics of peripheral blood penicillin-specific T lymphocytes in individuals with cutaneous allergic reactions to penicillin were investigated using in vitro long-term culture techniques. Peripheral blood mononuclear cells from two penicillin-allergic patients were stimulated in vitro with penicillin, and T-cell blasts were clonally expanded by limiting dilution. Seven T-cell clones were derived, all of which were CD3+ CD4− CD8+ HLA-DR+, and produced IL-2 and IFN-γ upon stimulation. T-cell proliferation required the presence of antigen and autologous, but not allogeneic, antigen-presenting cells. In addition to the parent compound, the T-cell clones also developed a proliferative response to penicilloyl, the major metabolite of penicillin. The cloned T-cell lines were found to exhibit marked suppressor activity for Con A mitogenesis. The observed suppressor activity required cell-to-cell contact, as supernatants from these T-cell clones had no comparable inhibitory effect. These findings indicate that there is a predominance of penicillin-specific CD8+ T cells in the peripheral blood of individuals sensitized to beta-lactam antibiotics.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Amino-penicillins are a major cause of delayed-type reactions to penicillins.Objectives  The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy.Methods  We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach.Results  A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications.Conclusions  These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 133 (1995), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Background  Teenagers and young adults frequently develop maculopapular exanthema following amoxicillin intake within infectious mononucleosis. The underlying pathomechanisms are still largely unknown. Objectives  To investigate whether amoxicillin-induced exanthema in florid infectious mononucleosis is a disease-associated phenomenon or results from specific sensitization to the drug. Methods  Four patients with amoxicillin-induced exanthema within infectious mononucleosis were analysed in vivo by prick, intradermal and patch tests and in vitro by means of the lymphocyte transformation test (LTT) employing amoxicillin, ampicillin, benzylpenicillin and phenoxymethylpenicillin. Results  Drug-specific sensitization to amoxicillin in the LTT was observed in three patients, two of whom showed a side-chain-specific sensitization to amoxicillin and ampicillin. The in vitro results were confirmed in vivo by skin tests. Conclusions  These data suggest that real sensitization to amoxicillin and ampicillin may occur within infectious mononucleosis and may be detected in vivo and in vitro by means of skin tests and the LTT.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Chlorazepate is a benzodiazepine often used for pre-operative anxiolysis. The central metabolite responsible for the pharmacological and probably for the adverse effects of most benzodiazepines, including chlorazepate, is N-desmethyldiazepam. We report a woman who developed a generalized exanthem 1 day after receiving chlorazepate and four other drugs related to anaesthesia for surgery of the larynx. Patch tests pointed to chlorazepate as the culprit drug for the skin rash. Objectives The purpose of this study was to detect drug allergy to chlorazepate or a metabolite in vitro by means of the lymphocyte transformation test (LTT), and to determine the concentrations of the T-helper (Th) 2-type cytokine interleukin (IL) -5 and the Th1-type cytokine interferon (IFN) -γ in the culture supernatants. Methods We performed an LTT with peripheral blood mononuclear cells from the patient and a control, employing human liver microsomes containing cytochrome P450 enzymes as a metabolizing system, in parallel cultures. IL-5 and IFN-γ concentrations in the culture supernatants were assessed by enzyme-linked immunosorbent assay. Results In the LTT, no T-cell reactivity was observed to the parent compound chlorazepate, whereas coincubation of the drug with human liver microsomes yielded proliferative T-cell reactivity, which was associated with secretion of IL-5 but not of IFN-γ. Conclusions We conclude that addition of a metabolizing system may be advantageous for in vitro detection of T-cell reactivity to drug metabolites in the LTT.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Bullous pemphigoid (BP), linear IgA bullous dermatosis (LABD) and cicatricial pemphigoid (CP) are clinically distinct autoimmune bullous skin diseases characterized by autoantibodies against components of the epidermal basement membrane. Like most patients with BP, a significant subgroup of patients with CP has circulating IgG specific for BP180, a transmembraneous protein of hemidesmosomes. Moreover, sera of patients with LABD contain IgA autoantibodies reactive with a 97/120-kDa protein, LABD antigen 1, which is highly homologous to the extracellular portion of BP180. Objectives We aimed to determine whether, in these diseases, autoantibody reactivity to BP180 is restricted to distinct immunoglobulin subtypes. Methods Utilizing a baculovirus-encoded form of the ectodomain of BP180, sera from patients with BP (n = 10), CP (n = 9), LABD (n = 10) and normal human control sera (n = 10) were analysed by immunoblot for IgG, IgA and IgE reactivity against BP180.  Results All of 10 BP sera displayed IgG, IgA and IgE reactivity with BP180. Six and seven of nine CP sera, respectively, contained IgG and IgA autoantibodies reactive with BP180, but none of nine sera contained BP180-specific IgE. Nine of 10 LABD sera contained IgA, and six of 10 IgG, which was reactive with BP180, but none of 10 sera showed IgE reactivity to BP180.  Conclusions The presence of IgG and IgA autoantibody responses to BP180 in patients with three clinically distinct autoimmune bullous diseases indicates that an autoimmune response to the same distinct adhesion protein may lead to different clinical manifestations. It is therefore conceivable that variable epitopes of BP180 are targeted by the different autoantibody isotypes, resulting in the distinct clinical pictures.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 148 (1987), S. 755-761 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 199 (1994), S. 1400-1406 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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