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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 143 (2000), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Erythema elevatum diutinum (EED) is a type of leucocytoclastic vasculitis of unknown aetiology. We report a patient with unusually widespread and disabling EED that had been unresponsive to corticosteroids and antibiotics, but resolved on dapsone. Biopsies of fresh lesions showed typical features of leucocytoclastic vasculitis, with prominent neutrophil infiltration, marked expression of the β2-integrins CR3 and LFA-1, and increased mast cell numbers. Older lesions exhibited granulation tissue and fibrosis, macrophages were more dominant, β2-integrins were expressed less markedly, and mast cell numbers were lower. In vitro chemotaxis of the patient’s peripheral blood neutrophils prior to treatment showed increased random migration and directed migration towards interleukin-8 (by 424%), but a profoundly decreased responsiveness towards the bacterial peptide analogue N-formyl-methionyl-leucyl-phenylalanine (fMLP) (by 98%). These values returned to normal after dapsone treatment and clinical improvement 5 months later. These findings support the concept that in EED, activation via cytokines such as interleukin-8 allows a selective recruitment of leucocytes to tissue sites, while immune complexes and bacterial peptides sustain the persistent local inflammatory infiltrate and the leucocytoclastic vasculitis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We investigated whether patients with contact allergy differed from non-contact-allergic, non-atopic controls with regard to genotype and phenotype of the polymorphic enzyme N-acetyltransferase 2 (NAT2). 55 contact-allergic patients recruited from the Information Network of Departments of Dermatology (IVDK) were compared to 85 controls from among local health care personnel. NAT2 activity was calculated from HPLC analysis of the ratio of the caffeine metabolites 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine (1MX) in the urine. NAT2 genotype was determined by polymerase chain reaction (PCR). A statistically significantly increased proportion of rapid acetylators was found in contact-allergic patients. This may have 2 possible implications: acetylation may enhance contact sensitization; or NAT2 status may be a genetic marker for contact sensitizability.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Objectives:  The strip patch test (SPT), proposed by Spier and Sixt (Hautarzt 1955;6:152–9), is a modification of the patch test (PT). This technique is used to enhance penetration through the stratum corneum for poorly penetrating substances such as medicaments. So far, a standardised procedure is lacking. This multicentre study aims at standardising the SPT procedure.Methods:  A total of 83 healthy volunteers participated. In each subject, we determined the number of strips (A) until the surface became glistening and then calculated the median number of strips in the sample (Ā = 26). We ascertained the median number of strips in the sample (ā = 11) that was necessary to achieve a first statistically significant and medically relevant increase of the TEWL revealing a critical stratum corneum strip depth. For the finally calculated number of strips for each subject (a/A = (ā/Ā)⇔a = A × (ā/Ā)), the actual increase in test sensitivity was substantiated employing SLS 0.125% aqueous.Standardisation results:  Perform stripping at one upper part of the back until the surface becomes glistening: gently press a 25 mm diameter adhesive tape downward vertically for about 2 seconds and then remove it in one quick movement at the angle in direction of adherence; continue stripping with a new tape cut on exactly the same skin area. Multiply number of strips by the correction factor (cf = ā/Ā = 11/26 = 0.4). Perform calculated number of strips likewise on the contralateral site and then apply there the test preparation for 24 hours.Conclusions:  If clinically an allergic contact dermatitis is expected but PT is negative, the SPT might reveal the potential allergen.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Basophils participate in allergic diseases by invading affected tissues and secreting histamine, leukotriene (LT)C4, IL-4 and IL-13 following FcεRI cross-linking. A reduction of basophil mediator production is therefore of considerable therapeutical interest. Macrolactam derivatives, which inhibit calcineurin activation, may be candidates for antiallergic therapy as they reduce both symptoms of inflammatory skin disease in animal models and mast cell degranulation.Objective To investigate the effects of the calcineurin antagonists ascomycin and cyclosporin A on IgE-dependent mediator release from human basophils.Methods Basophils were purified by Ficoll density centrifugation, elutriation and negative selection. Histamine release was measured spectrofluorometrically; LTC4, IL-4 and IL-13 secretions were assayed by enzyme-linked immunosorbent assay (ELISA). Lysed cells were subjected to Western blotting using specific antibodies to phospho-p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK)-1 and -2.Results Ascomycin (0.01 nm to 1 µm) and cyclosporin A (0.1 nm to 10 µm) strikingly inhibited (maximally 100%) anti-IgE-induced histamine and cytokine release from basophils, and these actions were unaffected by IL-3 priming. Ascomycin, however, was less potent at blocking LTC4 secretion, whereas cyclosporin A was unable to block production of this mediator. In immunoblotting studies, ascomycin and cyclosporin A reduced IgE-dependent p38 MAPK activation but were less potent at reducing ERK phosphorylation in basophils.Conclusion Calcineurin antagonists like ascomycin and cyclosporin A block IgE-dependent basophil degranulation and cytokine synthesis. Calcineurin may target p38 MAPK activation, but seems to have less activity on ERK phosphorylation. This is paralleled by a reduced or even absent effect of calcineurin antagonists on eicosanoid production.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Experimental dermatology 5 (1996), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract Since the presence of major histocompatibility complex (MHC) antigens has recently been reported on murine and human mast cells under various conditions, we have investigated their expression on mast cells in different types of cutaneous inflammation. Cryostat sections from lesional biopsies of patients with psoriasis, atopic eczema, chronic urticaria, lichen planus, bullous pemphigoid and urticaria pigmentosa were immunohistochemically stained with monoclonal antibodies against MHC class I and class II antigens using a double staining APAAP/toluidine blue methodology. While strongly positive staining with the antibody directed against MHC class I antigens was found on nearly all mast cells in normal skin and in inflammatory dermatoses, reactivity for HLA-DR and HLA-DQ antigens on mast cells could not be detected, except for less than 2% of cells with doubtful staining. Human mast cells therefore probably play no significant rôle as antigen-presenting cells in the conditions studied.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Several groups have previously reported that rodent or human leukemic mast cells produce inflammatory cytokines such as TNF-α and IL-8 as well as the pro-allergic cytokines IL-4, IL-5 and IL-13. Comparatively little is known, however, regarding the ability of normal human skin mast cells to secrete these factors following either IgE-dependent or IgE-independent modes of activation. We therefore investigated whether normal human skin mast cells produce these cytokines following stimulation by a variety of secretagogues. Enriched isolated skin mast cells released both TNF-α and IL-8 following activation with either anti-IgE, SCF, substance P, compound 48/80 or A23187. This release was dose- and time-dependent, with maximal levels being reached within 4 h of stimulation involving, in part, the secretion of preformed stores of both cytokines. In accordance with this, using lysates of highly purified (〉90%) skin mast cells, we could demonstrate that both TNF-α and IL-8 mRNA and protein were present in both unstimulated as well as stimulated mast cells. In stark contrast to these results, no significant levels of either IL-4, IL-5 or IL-13 were detected, regardless of the secretagogue used or the period of stimulation. These results show that human skin mast cells are capable of rapidly secreting pro-inflammatory cytokines like TNF-α and IL-8 following IgE-dependent activation and stimulation by the neuropeptide substance P, SCF and the basic polypeptide analogue compound 48/80. In contrast to other types of human mast cells however, human skin mast cells were incapable of secreting IL-4, IL-5 or IL-13 in these settings.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Experimental dermatology 2 (1993), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract Langerhans cells in the skin have recently been shown to bind IgE molecules via a high-affinity IgE receptor. Using two specific antibodies, 29C6 and 6F7, against the α-chain of the high-affinity IgE receptor we here demonstrate that Langerhans cells express this receptor in oral mucosa. A specific antibody. Tül, against the low-affinity IgE receptor showed only low expression of this receptor. High-affinity binding for IgE may be important for induction and support of Langerhans cell-dependent transepithelial IgE-mediated allergic reactions and inflammation.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Experimental dermatology 8 (1999), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Gangliosides are physiological components of the outer cell membrane. In the present study, the role of ganglioside expression during differentiation of human mast cells was evaluated. After 11 days of culture in medium known to induce mast cell differentiation, 70% of peripheral blood mononuclear cells (PBMC) showed positive staining for the high affinity IgE receptor and tryptase on immunocytochemistry and an associated 20-fold increase of ganglioside GM3 expression. Furthermore, exogenous addition of GM3 during cultivation of PBMC in medium containing low levels of growth factors induced an increase of mast cell specific tryptase. The association of ganglioside expression with mast cell differentiation was confirmed by experiments with the human mast cell line HMC-1. FcɛRI-positive cultured cells enriched with immunobeads exhibited a 3-fold higher expression of GM3, compared to FcɛRI negative HMC-1 cells. Furthermore, measurable amounts of the gangliosides GM2, GM1 and GD1a were found only in the FcɛRI positive cells. A corresponding transient increase of mRNA for GalNAcT, the key enzyme in the production of these latter gangliosides, could be detected preceding the expression of these gangliosides and the FcɛRI by RT-PCR. Taken together, these data point to a functional role of gangliosides in the differentiation of human mast cells.
    Type of Medium: Electronic Resource
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  • 10
    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
    Notes: Summary In order to identify more specific or selective mast cell markers, the reactivity of two monoclonal antibodies, Ki-MC1 and Ki-M1P, was studied by immunohistochemistry in two human cell lines (mast cell line HMC-1, basophilic cell line KU812), in mast cells cultured from blood precursors, in adherent mononuclear cells from peripheral blood, and in mast cells of tissue sections from 1 3 urticaria pigmentosa lesions, live mastocytomas and live normal skin specimens. Toluidine blue staining, fluorescence staining with FITC-conjugated avidin, and immunohistochemical staining (APAAP) with other mast cell reactive monoclonal antibodies, was performed for comparison. Double staining with the APAAP method, using the Ki-antibodies and toluidine blue, was also carried out. Both Ki-antibodies showed reactivity for skin mast cells, but with a different staining pattern. In addition, the Ki-MC1 antibody did not react with the cell lines, and reacted only with a few peripheral blood mononuclear cells and cultured mast cells. In contrast, the Ki-M1P antibody reacted with almost all cultured mast cells and blood mononuclear cells, but stained only about one-half of lesional and one-fifth of normal skin mast cells. Ki-M1P also reacted with many toluidine blue-negative dermal cells, particularly in urticaria pigmentosa. Ki-MC1 antibody can thus be considered as a useful additional marker for normal skin mast cells. In contrast, the Ki-M1 P antibody primarily identifies immature mast cells and monocytes/macrophages, suggesting that these cell types probably originate from the same bone marrow precursor.
    Type of Medium: Electronic Resource
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