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Biomedical subjects

A Kapp

Publications and source records attributed to A Kapp.

At least 109 records · Page 6Linked to original sources
PubMed1999

Birch pollen-related foods trigger atopic dermatitis in patients with specific cutaneous T-cell responses to birch pollen antigens.

BACKGROUND: Patients with inhalant allergy caused by birch pollen frequently demonstrate immediate symptoms to cross-reactive fruits, vegetables, or both. The nature of late eczematous reactions to pollen related food antigens has not been investigated in detail. OBJECTIVE: The purpose of this study was to find out whether isolated late eczematous reactions to birch pollen-related food antigens can be observed in patients with atopic dermatitis (AD) who are highly sensitized to birch pollen antigens. A possible linkage of such reactions with specific T-cell responses to birch pollen antigens in the blood and lesional skin was examined as well. METHODS: We examined 37 adult patients with AD and hypersensitivity to birch pollen but without any history of immediate responses to food challenges. These patients underwent an elimination diet, including all birch pollen-related food antigens, followed by a double-blind, placebo-controlled, oral provocation. Blood and skin biopsy specimens were taken to examine a birch pollen-specific lymphocyte response. RESULTS: Seventeen patients reacted with a deterioration of AD symptoms. Food- or birch pollen-specific IgE did not differentiate these patients from nonreactive patients. A significantly higher increase in the proportion of blood lymphocytes expressing the cutaneous lymphocyte antigen on incubation with birch pollen antigens was found in cells from reactive compared with nonreactive patients. The proliferative response of skin-derived T-cell lines from reactive patients to birch pollen extract or Bet v 1 was significantly higher than that of nonreactive patients. An enrichment of more than 25% of T-lymphocyte subpopulations defined by T-cell receptor-Vbeta elements was detected in the majority of such antigen-stimulated T-cell lines from responsive patients. A higher frequency of birch pollen-reactive T cells was calculated from limiting-dilution assays, and a higher rate of birch pollen-specific T-cell clones was generated from cultures with skin-derived T cells from reactive patients. CONCLUSION: Our results show, for the first time, that a subpopulation of patients with hypersensitivity to birch pollen and AD reacts with worsening of eczema after oral challenge with birch pollen-related foods and that a birch pollen-specific T-cell response can be found in the lesional skin of these patients.

Administration, Oral↗
PubMed1999

Atopy patch test reactions are associated with T lymphocyte-mediated allergen-specific immune responses in atopic dermatitis.

BACKGROUND: Positive test reactions to epicutaneous application of aeroallergens served as a model of 'early' eczema in atopic dermatitis (AD) in a number of dermato-immunological studies. However, no quantitative evaluation has been performed so far comparing specific T-cell activation parameters in the peripheral blood of AD patients with positive or negative atopy patch tests (APT). OBJECTIVE: The purpose of this study was to investigate specific immunological parameters in patients with atopic dermatitis showing positive or negative atopy patch tests reactions. METHODS: APT results (n = 96) were compared with allergen-specific IgE, specific lymphocyte proliferation, and the expression of 'activation' markers on peripheral blood T-cells upon in vitro stimulation with house dust mite, cat or grass pollen allergens. RESULTS: Only a subpopulation (48%) of patients sensitized to aeroallergens (i.e. specific IgE > 0.7 kU/L) developed APT-reactions to the corresponding allergen. APT reactions were, however, significantly associated with allergen specific lymphocyte proliferation (p < 0.0001), and a higher number of CD54+ or CD30+ T-cells (p < 0.05) upon in vitro stimulation. CONCLUSION: The association of delayed skin reactions with allergen specific T-cell parameters in the blood points to an immunologically mediated mechanism leading to positive reactions in the APT.

Allergens↗
PubMed1999

Accuracy of frozen section measurements for the determination of Breslow tumour thickness in primary malignant melanoma.

AIMS: Microstaging of primary malignant melanoma (MM) and the width of surgical margins depend mainly on Breslow tumour thickness (BTT). The use of frozen section (FS) measurements of BTT has been doubted, and previous reports have shown conflicting results regarding the comparability to paraffin sections (PS). To look for significant differences of BTT due to freezing or paraffin embedding, we evaluated a larger series of melanocytic lesions as far as possible excluding other technical influences. METHODS AND RESULTS: Paired 'mirror sections' of 112 melanocytic lesions (33 MM and 79 melanocytic naevi) were measured according to Breslow on single corresponding PS and FS of the same tumour specimen. Comparing measurements on FS and PS, we found very small differences of BTT on average and an almost equal distribution of BTT in the two sets of values with no statistically significant difference by applying the Wilcoxon signed rank test. Concerning the clinically most important 1 mm-threshold of BTT, 110 (98.2%) of the lesions gave equal measurements in FS and PS. CONCLUSIONS: Frozen sections can be used for accurate measurements of Breslow tumour thickness. Consequently, intraoperative frozen section diagnosis of thick melanoma immediately followed by excision with wide surgical margins is possible in experienced centres.

Biopsy↗
PubMed1999

Evaluation of C3a receptor expression on human leucocytes by the use of novel monoclonal antibodies.

Varying results have been published in the past regarding the reactivity of different leucocyte subpopulations, including neutrophils, monocytes and B lymphocytes, to the anaphylatoxin C3a and its degradation product C3a(desArg). To better characterize the cellular distribution of C3a receptor (C3aR) expression, monoclonal antibodies against two different epitopes on the third extracellular domain of the human C3aR were generated. Quantification of C3aR as compared with C5aR densities was performed on peripheral blood leucocytes by quantitative indirect immunofluorescence. Eosinophils and basophils expressed similar numbers of C3aR and C5aR molecules/cell. On eosinophils 10 700+/-4500 (mean+/-SD) C3aR and 14 700+/-4100 C5aR were found, whereas basophils carried 8100+/-2100 C3aR and 13 500+/-3800 C5aR. Monocytes expressed approximately six times more C5aR than C3aR molecules on their surface (6000+/-2500 C3aR versus 34 100+/-9300 C5aR molecules) whereas on neutrophils, the expression of C5aR was more than 20 times higher than the expression of C3aR (3100+/-1000 C3aR versus 63 500+/-12 200 C5aR). No C3aR expression was detectable on peripheral blood-derived B lymphocytes and on tonsillar B cells before and after stimulation with interleukin-2/Staphylococcus aureus Cowan strain I. Our findings correspond well with the paucity of data on C3a-induced functional activities in monocytes and neutrophils and suggest that eosinophilic and basophilic granulocytes represent the primary effector cells in the peripheral blood which can be stimulated by C3a.

Animals↗
PubMed1999

Validity study for the stigmatization experience in atopic dermatitis and psoriatic patients.

A central experience of patients with atopic dermatitis and psoriasis is the feeling of stigmatization. This can be estimated by the "Questionnaire on Experience with Skin Complaints" (QES), based on the "Feelings of Stigmatization Questionnaire" by Ginsburg & Link. This study was designed to evaluate the psychometric properties of the QES, especially the validity of this questionnaire, and to supply more information about the stigmatization experiences of patients with atopic dermatitis and psoriasis. Three groups of patients were analysed: 76 with atopic dermatitis, 81 and 217 with psoriasis, respectively. The comparison of subgroups with different affected regions revealed that the genital region is especially relevant for the stigmatization experience in these patients. In addition, the feeling of stigmatization (estimated by the QES) is relatively independent of the different dimensions of the "Trier Scales of Coping with Diseases", except for the depressive coping style "Rumination" measuring a high amount of inner concern with the afflicting disease. It can be concluded that the QES is a valid and reliable instrument for examining the stigmatization experience of patients with atopic dermatitis and psoriasis.

Adaptation, Psychological↗
PubMed1999

Quantification of eosinophilic granule protein deposition in biopsies of inflammatory skin diseases by automated image analysis of highly sensitive immunostaining.

Eosinophilic granulocytes are major effector cells in inflammation. Extracellular deposition of toxic eosinophilic granule proteins (EGPs), but not the presence of intact eosinophils, is crucial for their functional effect in situ. As even recent morphometric approaches to quantify the involvement of eosinophils in inflammation have been only based on cell counting, we developed a new method for the cell-independent quantification of EGPs by image analysis of immunostaining. Highly sensitive, automated immunohistochemistry was done on paraffin sections of inflammatory skin diseases with 4 different primary antibodies against EGPs. Image analysis of immunostaining was performed by colour translation, linear combination and automated thresholding. Using strictly standardized protocols, the assay was proven to be specific and accurate concerning segmentation in 8916 fields of 520 sections, well reproducible in repeated measurements and reliable over 16 weeks observation time. The method may be valuable for the cell-independent segmentation of immunostaining in other applications as well.

Automation↗
PubMed1999

Helicobacter pylori infection and skin diseases.

There is increasing evidence for systemic effects of gastric H. pylori infection which may result in extragastrointestinal disorders. This review summarizes the available medical literature up to September 1999, identified through a MEDLINE research including own studies, regarding H. pylori and skin diseases. Due to current knowledge best evidence for a potential link of H. pylori infection exists for chronic urticaria although the data are still conflicting. Thus, the search for H. pylori should be included in the diagnostic management of chronic urticaria. With regard to other skin diseases such as rosacea, hereditary or acquired angioedema due to C1-esterase inhibitor deficiency, systemic sclerosis, Schönlein-Henoch purpura, Sjögren's syndrome, sweet's syndrome, and atopic dermatitis only single of few cases have been reported so far. Thus, we clearly need further randomized, double-blind and placebo-controlled studies including adequate diagnostic schedules, sufficient eradication treatment protocols, confirmation of eradication, and adequate control groups to establish a role of H. pylori in skin diseases. Caution must be taken not to accuse H. pylori as the infectious agent responsible for every disease, particularly since H. pylori infection is very common. Although from an epidemiological and morphological view the skin diseases to which H. pylori has been linked seem to be completely different it is striking that in most of them an autoimmune pathogenesis is suspected or considerable vascular impairment can be found.

Helicobacter Infections↗
PubMed1998

Human eosinophils produce biologically active IL-12: implications for control of T cell responses.

The present study assessed the capacity of eosinophils (EOS) to synthesize the cytokine IL-12. Blood-derived, highly purified human EOS from six atopic patients and two nonatopic individuals were treated in culture with IL-4, IL-5, granulocyte-macrophage CSF, IFN-gamma, TNF-alpha, IL-1alpha, RANTES, and complement 5a, respectively. The expression of both IL-12 protein and mRNAs for the p35 and p40 IL-12 subunits was strongly induced in all donors by the Th2-like cytokines IL-4 and granulocyte-macrophage CSF and was also moderately induced by TNF-alpha and IL-1alpha. IL-5 treatment resulted in IL-12 synthesis in four atopic donors and one nonatopic donor, whereas IFN-gamma induced IL-12 synthesis in only two atopic donors. In contrast, RANTES exclusively induced mRNA for the p40 subunit without detectable protein release, and complement 5a had no effect on IL-12 mRNA or protein expression. EOS-derived IL-12 was biologically active, because supernatants derived from IL-4-treated EOS superinduced the Con A-induced expression of IFN-gamma by a human Th1-like T cell line. This activity was neutralized by anti-IL-12 Abs. In conclusion, EOS secrete biologically active IL-12 after treatment with selected cytokines, which mainly represent the Th2-like type. Consequently, EOS may promote a switch from Th2-like to Th1-like immune responses in atopic and parasitic diseases.

Cell Line↗
PubMed1998

Detection of MCP-4 in dermal fibroblasts and its activation of the respiratory burst in human eosinophils.

CC-chemokines are an important family of proinflammatory mediators that promote the recruitment and activation of human eosinophils in chronic inflammatory diseases. Recently, a novel human CC-chemokine, monocyte chemotactic protein 4 (MCP-4), has been reported that shows amino acid sequence similarities with eotaxin and RANTES, induces chemotaxis of eosinophils, and signals through specific chemokine receptors. In this study, we investigated the effect of MCP-4 on different eosinophil effector functions leading to the activation of the respiratory burst. In human eosinophils, MCP-4 dose dependently induced the production of reactive oxygen species and actin polymerization as a related event. Pretreatment of eosinophils with different enzyme inhibitors interacting with the signal transduction cascade revealed that Gi protein, protein kinase C, tyrosine kinase, and phosphatidylinositol-3-kinase are involved in the signaling following stimulation with MCP-4. In addition, cytokine-stimulated human dermal fibroblasts expressed high levels of MCP-4 mRNA, suggesting that fibroblasts are a physiologic source of MCP-4. Therefore, this study demonstrates that there is an important role of MCP-4 in the activation of eosinophils and that the interaction between dermal fibroblasts and human eosinophils may play an important role within the cytokine network.

Actins↗
PubMed1998

Eotaxin-2 activates chemotaxis-related events and release of reactive oxygen species via pertussis toxin-sensitive G proteins in human eosinophils.

Eosinophils play an important role in allergic and autoimmune diseases. They are activated by distinct chemokines, leading to the immigration into the inflamed tissue, and mediate tissue damage by releasing reactive oxygen species. Recently, eotaxin was found to have the broadest spectrum of activities of all eosinophil-activating CC chemokines. In this study we investigated the effect of the novel CC chemokine, eotaxin-2, on eosinophil effector functions and compared its activity with eotaxin. Using nitrobenzoxadiazole-phallacidin staining and flow cytometry, we show that eotaxin-2 induced rapid and transient actin polymerization, a prerequisite for cell migration and modulation of the respiratory burst, in eosinophils in the same range of efficacy as observed for eotaxin. Eotaxin-2 induced the release of reactive oxygen species in a dose-dependent manner; half maximal and maximal release were found at 50 ng/ml and 500 ng/ml, respectively. Surprisingly, the efficacy of eotaxin-2 was comparable to that of eotaxin and C5a. Release of reactive oxygen species was inhibited by pertussis toxin, indicating the involvement of Gi proteins in the signaling of eotaxin-2. Moreover, the anti-CC chemokine receptor 3 (CCR3) monoclonal antibody, 7B11, was able to inhibit transient rise in the cytosolic Ca2+ concentration and the release of reactive oxygen species following stimulation with eotaxin-2. Therefore, eotaxin-2 represents a potent CC chemokine for human eosinophils activating chemotaxis-related events, such as actin polymerization, and the respiratory burst via the CCR3. Moreover, the efficacy of eotaxin-2 seems to be in the same range as that of eotaxin which might re-evaluate the recent profile of activity of CC chemokines in the activation of human eosinophils.

Actins↗
PubMed1998

[Tissue eosinophilia and local deposition of eosinophil-specific granule proteins. Regulation and significance for inflammatory response in atopic dermatitis and other inflammatory dermatoses].

Recent in vitro-studies have substantially increased our knowledge of eosinophil activation, the regulation of eosinophilia in the peripheral blood and the role of cytokines in that process. Accordingly, chemoattraction and activation of eosinophils by cytokines results in the local release of reactive oxygen species and toxic cationic granule proteins followed by local propagation of the inflammatory reaction and tissue damage. This extracellular tissue deposition of toxic granule proteins as an expression of complete activation of eosinophils, rather than only the presence of intact eosinophil granulocytes, is crucial for their functional effect in situ. Semi-quantitative studies of local eosinophil granula deposition so far have been done only in atopic dermatitis and a limited number of other inflammatory skin diseases as summarized in this review. Evaluation of the pathogenetic role of eosinophils may be of potential therapeutic importance.

Blood Proteins↗
PubMed1998

[Amicrobial intertriginous pustulosis in autoimmune diseases--a new entity?].

During the last decade an unusual amicrobial intertriginous pustulosis has been described in association with autoimmune disease in sixteen female patients. The clinical hallmark is a sterile pustular dermatosis preferentially located in intertriginous regions that responds to local or systemic corticosteroids. Histologic features are subcorneal sometimes spongiform neutrophilic pustules. We report an additional patient suffering from this unusual dermatosis. An overview of the patients described to date and a review of the literature are given in an attempt to delineate this amicrobial intertriginous pustulosis from the known pustular dermatoses.

Adrenal Cortex Hormones↗