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A Kapp

Publications and source records attributed to A Kapp.

At least 145 records · Page 8Linked to original sources
PubMed1997

Short-term immunotherapy: a prospective, randomized, double-blind, placebo-controlled multicenter study of molecular standardized grass and rye allergens in patients with grass pollen-induced allergic rhinitis.

BACKGROUND: Short-term immunotherapy (STI) can be beneficial for patients who are noncompliant with long-term specific immunotherapy. OBJECTIVE: The efficacy and tolerance of STI with seven preseasonal injections of molecular standardized allergens from grass and rye pollen has been investigated in a double-blind, placebo-controlled multicenter study with 87 patients at 12 German University hospitals. METHODS: Symptoms of the eyes, nose, and bronchi and use of symptomatic drugs were documented daily in diaries by patients with allergic rhinitis to grass and/or rye pollen and without bronchial asthma. Patients were monitored by skin prick test titration and measurement of levels of specific IgE and IgG4. RESULTS: The median nasal score for the 10 weeks with the strongest symptoms during the grass pollen season was significantly lower (p = 0.014) with 35.0 for STI (n = 41) versus 69.0 for placebo (n = 40); the overall symptom score was 54.0 for STI versus 97.5 for placebo (p = 0.020). Only STI-treated patients exposed to less than 40 pollen grains per cubic meter per week showed a significantly lower nasal symptom score of 39.0 versus 75.0 for placebo (p = 0.006); these patients also had fewer nasal symptoms and less use of topical nasal drugs (p < 0.001). The threshold dose in skin prick tests was significantly higher, being 9.06 histamine equivalent for skin prick test (HEP) for STI-treated patients who received the maximum dose (n = 22) versus 4.33 HEP for placebo (p = 0.005). Specific IgE levels were significantly higher, being 55.9 SU/ml for STI versus 39.2 SU/ml for placebo after seven injections (p = 0.006) and level of specific IgG4 was 5.36% for STI versus 1.28% for placebo (p < 0.001). No severe systemic reactions were observed. CONCLUSION: STI with seven preseasonal injections with molecular standardized allergens is effective and well tolerated.

Adolescent↗
PubMed1997

Milk-responsive atopic dermatitis is associated with a casein-specific lymphocyte response in adolescent and adult patients.

BACKGROUND: Specific T-cell responses to food antigens have been described in children with atopic dermatitis (AD). However, a subgroup of adolescent and adult patients still experiences food-responsive AD. OBJECTIVE: This study was designed to evaluate lymphocyte responses to bovine casein in adult patients with AD. METHODS: The stimulatory capacity of lipopolysaccharide-depleted bovine casein was tested in proliferation assays and in limiting dilution assays. Casein-specific T-cell clones (TCCs) were generated and characterized. RESULTS: Higher proliferative responses to casein and modulation of cytokine receptors were observed in patients with milk-responsive AD compared with individuals without clinical reactions on milk ingestion. The results did not correlate with the amount of casein-specific IgE in the serum. The frequencies of T cells that grew in the presence of casein or house dust mite antigens were similar. Only 27% of CD4+ casein-specific TCCs from these patients, but the majority of house dust mite-specific TCCs, produced IL-4 on mitogen stimulation. Interferon-gamma, on the other hand, was produced by the majority of TCCs with both specificities. CONCLUSION: A specific T-cell-mediated immune response to casein can be found in the blood of adolescent and adult patients with milk-related exacerbation of AD. In contrast to house dust mite-specific T cells, casein-specific T cells of adult patients who respond to cow's milk with worsening of AD produce little or no IL-4.

Adolescent↗
PubMed1997

Rapid expression of the CD69 antigen on T cells and natural killer cells upon antigenic stimulation of peripheral blood mononuclear cell suspensions.

The CD69 antigen has been identified as the earliest activation marker on the surface of cytokine- or mitogen-activated lymphocytes. The expression of this molecule may be a useful early marker of antigen- or allergen-specific activation of lymphocytes in vitro. We evaluated the expression of the CD69 and CD25 antigens on antigen- or allergen-stimulated lymphocytes and the proliferative responses as detected by thymidine incorporation. Peripheral blood mononuclear cells (PBMC) of allergic patients sensitized to Dermatophagoides pteronyssinus, bovine casein, or nickel sulfate were cultured in the absence or presence of clinically relevant allergens, tetanus toxoid, or recombinant interleukin (IL)-2. The respective binding of CD69 or CD25 antibodies to PBMC and thymidine incorporation were measured. An early expression of CD69, but not of CD25, antigen was detectable after 24-72 h of stimulation on up to 80% of natural killer (NK) cells and up to 10% of CD4+ T cells in PBMC cultures. Anti-IL-2 antibodies inhibited these increases of CD69 on NK cells and T cells by up to 60%. After 6 days of antigenic stimulation, the rates of both CD25+ and CD69+ lymphocytes were higher. Seventy-four percent of the CD25+ PBMC but only 55% of the CD69+ cells were CD3+ T lymphocytes at this time. No qualitative differences were detectable in allergen- or tetanus-toxoid-stimulated PBMC from allergic patients. The high expression of CD69 on NK cells in antigen-stimulated cultures suggests that these cells are easily activated by cytokines from antigen-stimulated T cells. CD69+ NK cells may serve as early-indicator cells in cultures with antigen- or allergen-stimulated mononuclear cells.

Adult↗
PubMed1997

Identification of aneuploidy in recurrent clear cell hidradenoma by DNA image cytometry (ICM-DNA).

Since malignant clear cell hidradenoma (CCH) is often characterized by only slight and sometimes by absent nuclear anaplasia, even in metastases, definitive differentiation from its benign counterpart by light microscopy may be very difficult. Herein, we report the case of a 72-year-old woman suffering from a CCH on the back, which showed local recurrence following incomplete excision. By light microscopy no unequivocal signs of malignancy were found either in the primary or the recurrent tumor. However, unusual deep extension to the subcutis with some architectural disorder was seen in the latter. Identification of prospective malignancy in such cases of borderline histopathological features is one of the main indications for diagnostic DNA image cytometry (ICM-DNA). Application of this method to enzymatic cell separation specimens of the recurrence detected marked DNA-aneuploidy with a stemline ploidy of 2.60 c and single events up to 6.7 c, whereas a nearly exact diploid DNA-stemline was found in the primary. We suppose from our results that a prospective malignant CCH with aneuploid DNA-stemline has developed out of its DNA-diploid counterpart. The need for total surgical removal of apparently benign clear cell hidradenomas is further stressed by this observation. Criteria for the diagnosis of malignancy in CCH are reviewed.

Adenoma, Sweat Gland↗
PubMed1997

Colonoscopic allergen provocation (COLAP): a new diagnostic approach for gastrointestinal food allergy.

BACKGROUND: The clinical relevance of gastrointestinal food allergy in adults is largely unknown because the mechanisms are poorly understood and the diagnosis is difficult to confirm. AIMS: To improve the diagnostic means for confirming intestinal food allergy on an objective basis, a new colonoscopic allergen provocation (COLAP) test was developed. PATIENTS: The COLAP test was performed in 70 adult patients with abdominal symptoms suspected to be related to food allergy, and in five healthy volunteers. METHODS: During the COLAP test, the caecal mucosa was challenged endoscopically with three food antigen extracts, a buffer control, and a positive control (histamine). The mucosal weal and flare reaction was registered semiquantitatively 20 minutes after challenge, and tissue biopsy specimens were examined for mast cell and eosinophil activation. RESULTS: No severe systemic anaphylactic reactions were found in response to intestinal challenge. The COLAP test was positive to at least one food antigen in 54 of 70 patients (77%), whereas no reaction in response to antigen was found in healthy volunteers. Antigen induced weal and flare reactions were correlated with intestinal mast cell and eosinophil activation, as well as with patients' history of adverse reactions to food, but not with serum concentrations of total or specific IgE or skin test results. CONCLUSION: The COLAP test may be a useful diagnostic measure in patients with suspected intestinal food allergy and may provide a new tool for the study of underlying mechanisms.

Adolescent↗
PubMed1997

Alkaptonuric ochronosis: report of two affected brothers.

Alkaptonuric ochronosis is a rare inborn metabolic disorder. Because of the deficient activity of the enzyme homogentisic acid oxidase, homogentisic acid accumulates in plasma, is deposited in various tissues and is excreted in large amounts in urine. Dark brown discoloration of urine on exposure to air or after addition of alkaline solution is characteristic. We describe two brothers with typical alkaptonuric ochronosis with dark urine, blue pigmentation of auricles and axillae, focal brown hyperpigmentation of sclerae, and anthropathy.

Ear Diseases↗
PubMed1996

Surface and mRNA expression of the CD52 antigen by human eosinophils but not by neutrophils.

Eosinophilic and neutrophilic granulocytes represent major effector cells in the inflammatory response. Whereas neutrophils are predominantly involved in bacterial infections, eosinophils are of essential importance in the allergic inflammation. Surface markers have been used to distinguish neutrophils (CD16+) from eosinophils (CD16-) and might indicate different functional properties of these cells. In this study, expression and functional activity of CD52 on human eosinophils and neutrophils was investigated in nonatopic healthy donors and from patients with hypereosinophilia. Flow cytometric analysis using different anti-CD52 monoclonal antibodies (MoAbs) (mouse IgG3, humanized IgG1, and rat IgM) showed significant and homogeneous expression of CD52 on human eosinophils, but not on neutrophils. In addition, reverse transcription-polymerase chain reaction and Northern blot analysis showed that CD52 mRNA was constitutively expressed in eosinophils but not in neutrophils. Furthermore, expression of CD52 could be diminished in a dose-dependent manner by preincubation of eosinophils with phosphatidylinositol-specific phospholipase C, suggesting that CD52 on eosinophils is anchored to the membrane through a glycosylphosphatidylinositol (GPI) molecule. Whereas the phorbolester phorbol myristate acetate was able to downregulate the expression of CD52 on eosinophils in a dose-dependent manner, different eosinophil activating cytokines and chemotaxins had no effect. Cross-linking of CD52 by mouse anti-CD52 MoAb (IgG3) and humanized anti-CD52 MoAb (IgG1) with goat antimouse antibody and mouse antihuman antibody, respectively, dose-dependently resulted in an inhibition of reactive oxygen species production of eosinophils after stimulation with C5a, platelet-activating factor, and granulocyte-macrophage colony-stimulating factor. In summary, this study shows that the GPI-anchored antigen CD52 is not only a useful marker to distinguish eosinophils from neutrophils. The data point out a novel role of the CD52 antigen on human eosinophils that might be of clinical relevance, because cross-linking of this molecule will stop the destructive power of human eosinophils in the inflammatory tissue.

Antibodies, Monoclonal↗
PubMed1996

CD88 antibodies specifically bind to C5aR on dermal CD117+ and CD14+ cells and react with a desmosomal antigen in human skin.

The expression of the C5aR (CD88) on human epidermal and dermal cells was studied with five anti-C5aR mAb directed to the N-terminal domain of the receptor. All mAb bound to suspended dermal CD117+ mast cells and to dermal CD14+ cells. The binding to CD14+ and CD117+ cells could be blocked by rC5a and by peptide EX-1 representing amino acid residues 1-31 of the C5aR. In acetone-fixed frozen or in paraformaldehyde-fixed, paraffin-embedded tissue, we detected a binding of the Abs to dermal perivascular cells and, additionally, to keratinocytes and dermal epithelial cells that could be blocked by EX-1. Immunoelectromicroscopy revealed a binding of anti-C5aR mAb to desmosomal regions in human epidermis. However, the following results indicate that CD88 mAb cross-react with epithelium in a specific way: 1) the binding to suspended epidermal cells and to the epidermal cell line HaCat could be blocked by EX-1 but not by rC5a; 2) FITC-labeled C5a bound to CD117+ and to CD14+ cells but not to epidermal cells; 3) C5a led to transient calcium fluxes in CD14+ and CD117+ dermal but not in epidermal cells; 4) C5aR mRNA was detectable by reverse transcription PCR in granulocytes but not in keratinocytes or in HaCat. Our results show that CD88 mAb are good tools for the investigation of the C5aR on hemopoietic cells. Results with epithelial cells should be considered with caution, as the binding of CD88 mAb that were raised to a synthetic peptide sequence may be due to a cross-reactivity.

Antibodies, Monoclonal↗
PubMed1996

Actin polymerization in human eosinophils, unlike human neutrophils, depends on intracellular calcium mobilization.

Eosinophils represent major effector cells in the allergic inflammation. In contrast to neutrophils, the mechanism of eosinophil activation during the inflammatory response is poorly understood. In this study, the relation between calcium fluxes, chemotaxis, and actin polymerization in eosinophils from healthy non-atopic donors was investigated. Pre-incubation of eosinophils with the intracellular calcium chelator BAPTA dose-dependently prevented an increase in the intracellular calcium concentration ([Ca2+]i), whereas the depletion of extracellular calcium in the test medium had no effect. The chemotactic response of eosinophils, which was measured by the modified boyden chamber technique upon stimulation with RANTES, C5a and PAF, was dose-dependently inhibited by the chelation of intracellular calcium as well as inactivation of the cells in Ca2+ -depleted medium. To evaluate whether other cell functions which are involved in the migratory response of eosinophils might be dependent on intracellular and extracellular calcium, actin polymerization was investigated. Flow-cytometric measurement of F-actin with NBD-phallacidin revealed that actin polymerization in human eosinophils in response to RANTES, C5a, and PAF was dose-dependently inhibited by the intracellular calcium chelator BAPTA. Since it is well known that actin polymerization in neutrophils is not affected by chelation of intracellular calcium, actin polymerization in these cells was investigated under the same conditions as for eosinophils. In contrast to eosinophils, BAPTA did not inhibit actin polymerization in neutrophils. In summary, these data demonstrate that intracellular calcium fluxes represent a prerequisite for eosinophil chemotaxis and actin polymerization in human eosinophils. Furthermore, regulation of actin polymerization in eosinophils differed from that of neutrophils on the level of intracellular calcium fluxes.

Actins↗
PubMed1996

Detection of C5a receptors on human eosinophils and inhibition of eosinophil effector functions by anti-C5a receptor (CD88) antibodies.

Eosinophils and complement activation are reported to play a crucial role in the pathogenesis of connective tissue diseases. Depositions of antigens and antigen-antibody complexes lead to complement activation with the generation of anaphylatoxins, particularly C5a, which is thought to be responsible for the infiltration and activation of eosinophils in the tissue. Previous studies suggested that the eosinophil C5a receptor differs structurally from the receptor expressed on neutrophils. In this study, we investigated the expression and functional properties of C5a receptors on human eosinophils using the C5a receptor monoclonal antibody S5/1 (anti-CD88 mAb). Flow cytometric analysis demonstrated that the anti-CD88 mAb bound homogeneously on the surface of human eosinophils from nonatopic healthy donors. In addition, no subpopulations with respect to C5a receptor expression were identified in normodense or hypodense eosinophils of patients with hypereosinophilia. Pre-incubation of eosinophils with anti-CD88 specifically inhibited C5a-induced intracellular calcium concentration transients. C5a-induced chemotactic activity of eosinophils was significantly inhibited after pre-incubation of cells with anti-CD88 mAb in a dose-dependent manner. Furthermore, anti-CD88 mAb inhibited dose-dependently the release of reactive oxygen species by eosinophils following stimulation with C5a. Thus, the human eosinophil C5a receptor is homogeneously expressed on normal eosinophils from healthy donors as well as on hypodense and normodense eosinophil subpopulations from patients with hypereosinophilia. Based on the inhibitory effect of the S5/1 mAb on C5a-stimulated eosinophil effector functions, we conclude that a single C5a receptor type exists on human eosinophils. In addition, the inhibitory effect of the S5/1 mAb on C5a functions may enable a new experimental approach to the treatment of diseases that have been associated with C5a-mediated activation.

Antibodies, Monoclonal↗
PubMed1996

Human eotaxin represents a potent activator of the respiratory burst of human eosinophils.

Increased numbers of eosinophils are found in parasitic infections, autoimmune diseases and allergic diseases such as allergic asthma. They are activated by distinct cytokines and chemokines leading to the immigration in the inflamed tissue and mediate tissue damage by releasing reactive oxygen species. Here, the effect of the recently cloned CC chemokine human eotaxin was investigated for its ability to affect different eosinophil effector functions and compared to the CC chemokines MCP-3 and RANTES. Human eotaxin induced chemotaxis of human eosinophils in a dose-dependent manner. The range of efficacy of the CC chemokines compared to the well-known chemotaxin C5a was eotaxin = RANTES > MCP-3 = C5a. In addition, eotaxin induced rapid and transient actin polymerization, a prerequisite for cell migration, in eosinophils in the same range of efficacy as observed for chemotaxis. To investigate whether eotaxin was able to activate the respiratory burst of eosinophils, release of reactive oxygen species was measured by lucigenin-dependent chemiluminescence. Eotaxin induced production of significantly high amounts of reactive oxygen species at a concentration between 10 ng/ml and 500 ng/ml. Surprisingly, the effect of eotaxin was comparable to the well-known eosinophil activator C5a. The range of efficacy of the CC chemokines compared to C5a in the activation of the respiratory burst was eotaxin = C5a > MCP-3 > RANTES. Production of reactive oxygen species was inhibited by pertussis toxin, staurosporin, genestein and wortmannin. Furthermore, eotaxin induced transient increases in intracellular calcium concentration ([Ca2+]i) in human eosinophils. Therefore, pertussis toxin-sensitive Gi-proteins, protein kinase C, tyrosine kinase, phosphatidylinositol-3-kinase and transient increases in [Ca2+]i are involved in the signal transduction of eosinophils following stimulation with eotaxin. In summary, this study reveals the importance of the CC chemokine eotaxin as a potent activator of the respiratory burst, actin polymerization and chemotaxis. Eotaxin, therefore, plays an important role not only by attracting eosinophils to the site of inflammation but also by damaging tissue by its capacity to induce the release of reactive oxygen species.

Actins↗
PubMed1996

[Erythema elevatum and diutinum in Crohn disease].

A 35-year-old woman suffering from Crohn's disease for 3 years developed painful erythematous nodular lesions predominantly on the dorsa of her hands and feet, as well as on her elbows and wrists. The clinical features and histopathological picture of leukocytoclastic vasculitis were both highly suggestive of erythema elevatum diutinum. No improvement of the skin lesions was observed during treatment with high doses of oral steroids. In contrast, treatment with dapsone resulted in a marked reduction of skin lesions. During a new attack of her Crohn's disease the erythema elevatum diutinum lesions flared again. The parallel clinical course of erythema elevatum diutinum and Crohn's disease, as well as the detection of immune complexes and neutrophilic granulocytes in lesions of both diseases, strongly suggest a common etiology. This hypothesis is discussed in context with this case and the recent literature.

Adult↗
PubMed1996

Human HMC-1 mast cells exclusively express the Fc gamma RII subtype of IgG receptor.

Because of their localization at the interface of the internal and external environment mast cells play a crucial role in the immune response and in inflammatory reactions. Effects may be mediated not only by the high-affinity IgE receptor, but also by IgG receptors. Since in rodent mast cells signal transduction via the Fc gamma receptor family has been shown, we analysed the expression of surface receptors for IgG on the human mast cell line HMC-1. It was shown by flow cytometric analysis that HMC-1 constitutively expressed the Fc gamma RII/CD32 subtype whereas Fc gamma RI/CD64 and Fc gamma RIII/CD16 were not expressed. This exclusive expression of the Fc gamma RII subtype of IgG receptor is similar to the expression pattern of basophils, although concerning cell surface molecules HMC-1 rather seem to resemble monocytes. In contrast to monocytes the expression profile on HMC-1 did not change upon stimulation with IL-4, TNF alpha, IFN gamma, PMA or salbutamol. Moreover, the mast cell-activating cytokine SCF and the calcium ionophore A23187 did not modulate the Fc gamma R profile in this study. To assess the importance of the exclusive Fc gamma RIII expression on HMC-1, we investigated whether the production of the cytokine TNF alpha is modulated via Fc gamma RII activation or if an increase in intracellular calcium could be observed. No significant modulation of TNF alpha release or of intracellular free calcium after crosslinking of Fc gamma RII by heat-aggregated IgG or by a second antibody was observed. It remains to be clarified whether this low-affinity subtype for the IgG receptor is involved in antigen-dependent sensitization of human tissue mast cells resulting in secretion of immunoregulatory cytokines. This mechanism may be important for disease states associated with circulating or tissue-bound immune complexes.

Albuterol↗
PubMed1996

The role of circulating food antigen-specific lymphocytes in food allergic children with atopic dermatitis.

In this study we evaluated antigen-specific in vitro responses of peripheral blood lymphocytes to lipopolysaccharide (LPS)-depleted food allergens in children who reacted to food challenge (cow's milk or hen's egg) with a deterioration of their atopic dermatitis (AD). Some of the children showed immediate symptoms (urticaria, bronchial asthma or gastrointestinal symptoms) as well. The proliferation of casein-stimulated lymphocytes from children reacting to cow's milk (age 0.7-5.9 years) was significantly higher (P < 0.01) than the proliferation of lymphocytes from 15 children with AD without milk allergy (age: 2.1-9.1 years). Twenty-eight T-cell clones (TCC) were established from the blood of three children sensitized to cow's milk and hen's egg who reacted to double-blind, placebo-controlled oral food challenge both with a deterioration of AD and with immediate symptoms. Surprisingly, 16 of 28 casein- or ovalbumin-specific TCC were CD8+. All TCC produced high amounts of IFN-gamma upon stimulation with concanavalin A. In addition, 75% of the CD4+ TCC and 44% of the CD8+ TCC secreted IL-4. Our results indicate that: (i) food-specific proliferation of blood lymphocytes can be detected in patients with clinically relevant food allergy with LPS-depleted allergens in vitro and (ii) circulating food-specific lymphocytes are CD4+ and CD8+ T cells with the capacity of producing both type 1 and type 2 cytokines.

Animals↗