Demonstration of the high-affinity IgE receptor (Fc epsilon RI) on Langerhans' cells of diseased nasal mucosa.

Langerhans' cells in the skin have recently been shown to bind IgE molecules via the high-affinity IgE receptor (Fc epsilon RI). Using two highly specific antibodies against the antibody-binding alpha-chain of this receptor, 29C6 and 6F7, we demonstrate by immunohistochemistry and immunoelectron microscopy that Langerhans' cells of diseased nasal mucosa can express the Fc epsilon RI. Tissue sections from hyperplastic nasal conchae and nasal polyps of atopic and nonatopic patients have shown no basic differences in epithelial Fc epsilon RI-bearing cells.

Tacalcitol ointment in the treatment of psoriasis vulgaris: a multicentre, placebo-controlled, double-blind study on efficacy and safety.

Tacalcitol is a vitamin D analogue which ahs been developed for the therapy of psoriasis vulgaris. The treatment with a twice daily application of 2 micrograms/g ointment is efficacious and safe in Japanese patients. The objective of this randomized, placebo-controlled, intraindividual right-left comparison was to investigate the efficacy and safety of 8 weeks' therapy with a once daily application of a 4 micrograms/g tacalcitol ointment in Caucasian psoriatics.

Differential expression of CRABP II, psoriasin and cytokeratin 1 mRNA in human skin diseases.

In order to confirm and further explore the significance of the overexpression of the CRABP II (cellular retinoic acid binding protein type II) and psoriasin genes in psoriatic versus normal skin, we examined the mRNA expression levels of these two genes by in situ hybridization in skin samples from psoriatic plaques and in one case from the border between a psoriatic plaque and uninvolved skin. Both genes were markedly upregulated in lesional skin, with a shift from low to high expression in the transitional zone of the plaque. Expression of the cytokeratin 1 (K1) gene was, in contrast, high in normal skin and decreased in the transition from uninvolved skin to psoriatic plaque, Examination of mRNA levels of CRABP II and psoriasin in other hyperproliferative and inflammatory skin diseases showed high expression of psoriasin, and in some cases also of CRABP II, in atopic dermatitis, mycosis fungoides, Darier's disease and inflammatory lichen sclerosus et atrophicus.

Thrombin and melittin activate phospholipase C in human HaCaT keratinocytes.

Following the activation of specific receptors, phospholipase C has been shown to cleave the membrane phospholipid phosphatidylinositol bisphosphate into the 2nd messengers inositol 1,4,5-trisphosphate and diacylglycerol. Both 2nd messengers contribute to the regulation of cellular proliferation. The receptor for bradykinin is coupled to this pathway in keratinocytes, but knowledge about other activators of phospholipase C is limited.

[Value of dental treatment in interdisciplinary management of a child with epidermolysis bullosa dystrophica hereditaria (Hallopeau-Siemens)].

Severe dystrophic epidermolysis bullosa with oral involvement often leads to dental destruction and restricted food intake, resulting in malnutrition and maldevelopment. The patients become handicapped and have a poor prognosis. We report on a now 13-year-old Turkish child with normal secondary dentition who had severely damaged primary dentition.

MHC class II antigen expression is increased in different forms of urticaria.

Urticarial reactions encompass a variety of inflammatory and immunological reactions. In order to clarify specific aspects of these processes, we analyzed the distribution and sequential expression of major histocompatibility complex II (MHC class II) molecules in tissue sections from different types of whealing reactions. Using immunohistochemical techniques and monoclonal antibodies, expression of HLA-DR, HLA-DP, and HLA-DQ was examined on resident and infiltrating cells in different skin cell compartments, comparing early with longer-lasting wheals and lesional with uninvolved skin.

Glucocorticoid-induced modulation of cytokine secretion from normal and leukemic human myelomonocytic cells.

Since glucocorticoid effects on inflammatory processes may be mediated via modulation of cytokine release, different types of myelomonocytic cells were stimulated in vitro with lipopolysaccharide (50 ng/ml) or phorbol myristate acetate (25 ng/ml) plus the ionophore A23187, 2 x 10(-7) M, and release of interleukin (IL)-1 beta, IL-8 and tumor necrosis factor (TNF)-alpha was measured after 24 h by ELISA. Peripheral blood mononuclear cells from two allergic and two normal human donors released similarly large quantities of IL-8 and lower amounts of IL-1 beta and TNF-alpha. This also held for myelomonocytic cell lines, with THP-1 cells being most active, followed by U-937 and HL-60 cells.

Histamine releasability of basophils and skin mast cells in chronic urticaria.

In order to clarify the pathogenetic role of basophils and mast cells in chronic urticaria, histamine and leukotriene (LT)C4 release was examined in washed mixed leukocytes (n = 8) and skin mast cells (n = 5) from patients with chronic urticaria and compared with the same cells from normal controls (n = 9). Anti-IgE-stimulated basophil histamine release was significantly reduced in urticaria patients (median 2.9% vs 15.

The renin-angiotensin-system in the skin. Evidence for its presence and possible functional implications.

Among the several hormonal systems regulating body functions, the renin-angiotensin-system has long been considered a classical endocrine system with angiotensin II, its effector hormone, being synthesized in and subsequently distributed by the circulation to act on its numerous, mainly renal and cardiovascular target organs throughout the body. Angiotensin II has long been regarded to be primarily responsible for the regulation of blood-pressure and of volume- and electrolyte-homeostasis. Recent evidence suggests that it also affects cellular proliferation and differentiation via the so-called local or tissue-renin-angiotensin-systems.

Pseudoallergen-free diet in the treatment of chronic urticaria. A prospective study.

In chronic urticaria, the possible pathogenetic role of pseudoallergic reactions to food has been repeatedly discussed, but stringent prospective studies regarding their clinical significance are not available. All patients with chronic urticaria and/or angioedema hospitalized at the department of dermatology during a period of 2 years were therefore included in a prospective study. Patients (n = 64) were screened for common causes of urticaria and then evaluated for possible benefits of a stringently controlled pseudoallergen-free diet.

Pruritogenic effects of mitogen-stimulated peripheral blood mononuclear cells in atopic eczema.

The etiology of atopic pruritus is unclear and seems mostly histamine-independent. In order to investigate non-mast cells as possible sources of pruritogenic agents, peripheral blood mononuclear cells from 12 atopic eczema patients and 12 controls were incubated in vitro for 24 h with phytohemagglutinin or concanavalin A (both at 10 micrograms/ml) or with medium alone, and each subject was tested with his own cell supernatants and lysates by prick testing and by application on tape-stripped skin. Histamine (0.

Effect of CC chemokines on mediator release from human skin mast cells and basophils.

Chemokines are considered important mediators of various inflammatory processes. In human basophils, different CC chemokines are known to stimulate release of histamine and generation of leukotriene (LT)C4. In the present study, we have evaluated the effect of RANTES (regulated upon activation, normal T cell expressed and secreted), monocyte chemotactic protein (MCP)-1, MCP-2, MCP-3, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta on mast cell activation.

Dendritic cells generated from peripheral blood transfected with human tyrosinase induce specific T cell activation.

Peptides of melanosomal proteins have recently been shown to be recognized in an HLA-restricted mode by specific cytolytic T lymphocytes in melanoma patients. Dendritic antigen-presenting cells (DC) are considered to be the most effective stimulators of T cell responses, and the use of these cells has therefore been proposed to generate therapeutic responses to tumor antigens in cancer patients. We, therefore, generated DC from peripheral blood of normal donors in the presence of granulocyte/macrophage colony-stimulating factor and interleukin-4.

Gangliosides enhance IgE receptor-dependent histamine and LTC4 release from human mast cells.

Releasability of mast cells and basophils to an IgE-dependent stimulus is regulated by extra- and intracellular factors which are only partly understood. As gangliosides are known to modulate receptor-dependent processes in various cell types, we have evaluated the effect of these molecules on mast cell mediator release. Human skin mast cells and the human mast cell line HMC1 were pretreated with the gangliosides GM2, GM3 and GD1a as well as with asialo-GM3, heparin and buffer alone (controls).

Differential promoter activity in benign and malignant human cells of skin origin.

In order to develop systems to express mammalian proteins in human skin-derived cells, we tested 6 different viral and 1 eukaryotic promoter (pCMV, pRSV, pSV, pMMTV, pPoly E, pPoly L, pHMT) for their ability to drive the expression of the chloramphenicol acetyltransferase (CAT) enzyme in different human skin-derived cells. DNA was transfected in human keratinocytes derived from normal foreskin and cervix, in the HPV-negative cervical cancer line HT-3 and in malignant melanoma cell lines (SK-Mel 23, SK-Mel 37) using a liposome-based technique or calcium precipitation. Transfection efficacy was controlled by cotransfection of a beta-galactosidase gene construct.

Serum manganese superoxide dismutase is a new tumour marker for malignant melanoma.

Malignant melanoma in its disseminated stage is incurable. The most widely accepted criteria for the prognostic evaluation of melanoma are histopathological and clinical parameters, and the identification of additional simple, serological tumour markers is thus of paramount importance. Manganese-containing superoxide dismutase (MnSOD) belongs to a family of metalloproteins that catalyse the metabolization of oxygen radicals in order to protect these cells from radical damage.

Human c-myb is expressed in cervical carcinomas and transactivates the HPV-16 promoter.

Human c-myb is normally involved in the regulation of proliferation and differentiation of hematopoietic cells. Until now, only a few reports have described elevated c-myb gene expression in epithelial tissue, suggesting that under certain circumstances, c-Myb protein might play a role during the process of malignant transformation of epithelial cells. To investigate a possible role of c-myb during papillomavirus-associated carcinogenesis, we investigated the c-myb mRNA expression in human papillomavirus (HPV)-associated tumors and tumor cell lines.

Two novel mast cell phenotypic markers, monoclonal antibodies Ki-MC1 and Ki-M1P, identify distinct mast cell subtypes.

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 13 urticaria pigmentosa lesions, five mastocytomas and five 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.

[Interleukin 7 in dermatology. Molecular, immunologic and preclinical aspects].

The vast body of knowledge on interleukin-7 (IL-7) that has accumulated over the last few years, i.e. since its discovery in 1988, is of increasing relevance for dermatologists.

Characterization of gene regulatory elements for selective gene expression in human melanoma cells.

Since chemotherapy is not sufficiently effective, an alternative strategy for the treatment of advanced melanoma could be an in vivo gene therapy approach. For this purpose, a highly accurate delivery of the therapeutic gene and cell specific gene expression is essential. Since melanocytic cells are characterized by their pigmentation, and since tyrosinase is the key enzyme involved in melanogenesis, we studied the expression of a reporter gene which is under the control of the tyrosinase promoter or a combination of melanocyte-specific enhancer and tyrosinase promoter in ten human melanoma and four epithelial cell lines.

Comparison of adherent lymphokine-activated killer (a-lak) cells generated by IL-2 and IL-7 - cellular modifications induced by IL-7.

At present, the clinical application of plastic-adherent-lymphokine-activated killer (A-LAK) cells shows limited success in the immunotherapy of patients with advanced cancer because of a low responder rate, severe side effects and failures in yielding sufficient numbers of cells for adoptive transfers. Since interleukin-7 (IL-7) is able to induce LAK activity independently of IL-2, we investigated the ability of IL-7 to improve the yield and the properties of A-LAK cells. A-LAK cells from 7 healthy donors generated in the presence of IL-2, IL-7 or combinations of IL-2 plus IL-7 (each 1000 U/ml) were compared with regard to plastic adherence, expansion rate, immunophenotype, cytokine secretion and cytotoxicity against malignant melanoma cells and non-malignant target cells.

Pharmacological modulation of IL-6 and IL-8 secretion by the H1-antagonist decarboethoxy-loratadine and dexamethasone by human mast and basophilic cell lines.

Mast cells and basophils are central effector cells of allergic reactions and are involved in inflammatory diseases. These cell types produce an array of mediators including a broad spectrum of cytokines. In order to examine whether antiallergic drugs modulate the release of these mediators, we have investigated the influence of dexamethasone and decarboethoxy-loratadine (DEL), the active metabolite of the H1-blocking agent loratadine, on the release of IL-6 and IL-8 by the human mast cell line HMC-1 and the human basophilic cell line KU812 by ELISA.