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Biomedical subjects

G Kolde

Publications and source records attributed to G Kolde.

At least 55 records · Page 3Linked to original sources

Coexisting lichen planus and subacute cutaneous lupus erythematosus.

We report a patient who presented with annular erythematous skin lesions and generalized lichenoid papules. The clinical picture as well as histopathology, immunofluorescence and laboratory findings indicated coexistence of subacute cutaneous lupus erythematosus (SCLE) and extensive generalized lichen planus (LP). Clinically and histologically, SCLE-like lesions appeared to progress into LP-like lesions, supporting the concept of a common autoimmune pathophysiology in these disorders. Treatment with cyclosporin A (2.5 mg/kg body weight) resulted in a significant remission of the inflammatory skin lesions.

Aged↗

Mast cells in the cytokine network: the what, where from and what for.

The basic understanding of mast cell ontogeny and function has been fundamentally changed in recent years with observations that the cells produce and respond to a broad range of cytokines. These rapidly accruing data and their potential significance were discussed at the recent symposium "Mast Cells in the Cytokine Network", and the overview lectures of most speakers are summarized in this special journal issue. In the present introductory manuscript, the organizers of the meeting discuss data fundamental to an understanding of the topic and highlight aspects of special interest. They consider mast cells to be defined most reliably by their unique ultrastructure since the cells are highly heterogeneous in dependence of the species studied, their tissue location, their stage of development and probably also in relation to cytokines. Most other characteristics of mast cells are shared with diverse other cell types. Murine mast cell development is induced by several cytokines. These factors are mostly ineffective in human cells except for stem cell factor which causes mast cell development from CD34+/c-kit+ progenitors. There is however recent evidence that fibroblasts and keratinocytes produce additional growth factors for human mast cells. Regarding cytokine secretion, most molecules known so far are produced by both murine and human mast cells. The cells furthermore bear receptors for several cytokines, enabling them to respond in an autocrine and paracrine fashion. Mast cells may thus function within a complex cytokine network, affecting physiological as well as immunological and inflammatory processes.

Animals↗

Eosinophilic pustular folliculitis: successful treatment with interferon-alpha.

Eosinophilic pustular folliculitis (Ofuji's disease) is a rare skin disease of unknown etiology characterized by infiltrated circinate plaques with sterile follicular pustules in primarily seborrheic areas. Several therapeutic regimens have been reported to control the disease with inconsistent results. We here report on a patient with Ofuji's disease, who was successfully treated with interferon-alpha 2b.

Adolescent↗

An in vitro test for endocytotic activation of murine epidermal Langerhans cells under the influence of contact allergens.

Several in vivo and in vitro studies have shown that contact sensitizing agents induce enhanced internalization of cell membrane constituents by epidermal Langerhans cells (LC). However the intracellular distribution of the internalized material has not yet been clearly defined. For this reason we investigated the uptake of gold-labeled antibodies against MHC class II molecules by cultured murine LC under the influence of various contact sensitizing agents, non-sensitizing analogues, and irritants. Antigen-antibody complexes were visualized by light microscopy using the silver enhancement technique and by pre-embedding electron microscopy. Viability was monitored by staining dead cells with propidium iodide. For light-microscopic evaluation of the intracellular distribution pattern of gold particles, a stimulation index was defined and used for the assessment of endocytotic activation. Untreated and solvent treated (control) cells exhibited an accumulation of internalized gold complexes into large aggregates composed of few intracellular vesicles. Cytoplasmic staining was absent and few gold particles were detectable in the endocytotic organelles under these conditions. In contrast to the non-sensitizing compounds DCNB and DNBSO3, which had no effect at all, treatment with subtoxic concentrations of the contact sensitizing agents DNFB, DNCB, TNCB, K2Cr2O7, NISO4 and p-phenylenediamine resulted in diffuse intracellular staining which was most pronounced in the submembraneous region. This was due to the numerous endocytotic vesicles which were closely associated with the cell membrane. Consequently a significant increase in the stimulation index was noted for these compounds. An irritant such as sodium lauryl sulphate used in subtoxic concentrations did not influence the intracellular distribution of internalized gold particles whereas toxic amounts of this compound induced a diffuse intracellular staining pattern indicative of membrane destruction. This approach represents a practical and reliable test for endocytotic activation of murine LC and may be useful for in vitro tests of the activating and possibly sensitizing properties of new chemical compounds.

Allergens↗

[Essential cryofibrinogenemia with generalized livedo racemosa].

A 45-year-old male patient presented with cold-induced generalized livedo reticularis, repeated acral ulcerations and purpura, Raynaud's phenomenon, and peripheral polyneuropathy. The patient also experienced malaise, vertigo, and transient amaurosis whenever he was exposed to low temperatures. Skin biopsies of the livedo reticularis revealed marked dilatation of the small dermal blood vessels and circumscribed leukocytoclastic vasculitis. Essential cryofibrinogenaemia was diagnosed on the basis of detection of this cryoprotein in the chilled blood plasma with increased viscosity. Pulsed therapy with dexamethasone and cyclophosphamide resulted in marked relief of the symptoms, and cryofibrinogen was no longer detectable in the patient's plasma.

Biopsy↗

A unique non-Langerhans cell histiocytosis with some features of generalized eruptive histiocytoma.

A symmetric eruption of hundreds of coalescent small red macules and a few slightly elevated papules sparing the flexures was observed in a 73-year-old man. Light microscopic examination showed loose aggregates of small and large histiocytic cells. Electron microscopy showed an absence of Langerhans cell granules and lipid droplets. Features shared with generalized eruptive histiocytoma were the symmetry of the eruption sparing the flexures, the blue-red coloration, and the absence of lipid-containing foam cells and multinucleated giant cells. However, the primary occurrence of macules rather than papules or nodules, the tendency of the macules to coalesce, and the dimorphic histiocytoid infiltrate are not found in generalized eruptive histiocytoma. Nevertheless, immunohistochemistry confirmed that this unique condition is a form of MS-1+ cutaneous non-Langerhans cell histiocytosis.

Aged↗

Effects of immunological responsiveness on Langerhans cell behavior in contact sensitization.

The epicutaneous application of haptens results in a functional activation of the antigen-presenting Langerhans cells (LCs) which is necessary for the induction of contact sensitivity. In this ultrastructural study, we investigated the effects of the immune response on these cellular properties of the LCs by using 2 strains of guinea pigs with genetically determined high and non responsiveness, respectively, to the strong sensitizer 2,4-dinitrochlorobenzene (DNCB). After skin painting, both strains showed a similar cellular and endocytotic activation of the LCs and a similar intraepidermal localization of DNCB on immunoelectron microscopical visualization. There were however few LC-lymphoid cell interactions in the non responders, in contrast to numerous such appositions in the other strain. Intravenous tolerization with 2,4-dinitrobenzene-1-sulfonic acid, which is known to block the DNCB receptor of T cells, hampered the lymphoid cell interactions in the DNCB treated high responders, but it did not affect the LC activation. These in vivo observations demonstrate that the hapten-induced changes of the LC properties is the initial, T-cell independent event in contact sensitization.

Administration, Cutaneous↗

Human mast cells produce IL-8.

Recruitment of neutrophils is a common feature in diseases that are associated with mast cell activation. The mechanisms that mediate neutrophil activation are not well understood. IL-8 is a recently described potent chemotactic factor that might be pathogenetically involved in this process. We therefore studied the human mast cell line HMCI and human skin mast cells for their ability to produce IL-8 using various stimuli. IL-8-mRNA was expressed in a stimulus- and time-dependent fashion as detected by Northern blot analysis with an IL-8-specific cDNA probe. The molecular mass of HMCI-derived IL-8 was determined to be about 8 kDa by immunoblot analysis. Immunoreactive and biologically active IL-8 protein was measured in the cell culture supernatants of HMCI cells by an ELISA and a chemotaxis assay, respectively. On immunoelectron microscopy of stimulated skin mast cells, IL-8 was found along cytoplasmatic membranes and in intracellular granules. Our data indicate that mast cells may contribute to neutrophil recruitment by secretion of IL-8.

Calcimycin↗

Immunohistochemical comparison of cutaneous histiocytoses and related skin disorders: diagnostic and histogenetic relevance of MS-1 high molecular weight protein expression.

Twenty-nine cases of Langerhans cell histiocytosis (LCH), non-Langerhans cell histiocytoses (N-LCH), non-infectious granulomas, and fibroblast-related lesions were examined with a panel of monoclonal and polyclonal antibodies on freshly frozen tissue sections to characterize the macrophage phenotype of N-LCH syndromes. MS-1 high molecular weight extracellular protein, specific for sinusoidal endothelial cells and dendritic perivascular macrophages in normal human organs, was expressed by N-LCH cells but was not found in LCH cells, epithelioid cells in sarcoidosis, or palisading histiocytes in granuloma annulare. The subcellular location of MS-1 protein, i.e., cytoplasmic vs. peripheral/extracellular, allowed discrimination of small and large (foamy or multinucleated) N-LCH cells. MS-1-positive cells, which were found intermingled in cellular dermatofibromas but not in fibrous dermatofibromas, differed from MS-1-positive N-LCH cells by their dendritic morphology, and thus rather resembled their normal dermal counterparts. A preserved functional relationship of these two MS-1-positive cell types was indicated by the fact that N-LCH and cellular dermatofibromas were the only lesions found to be highly vascularized. As expected, CD1a showed high specificity for LCH, while CD34 was predominantly expressed by fibroblast-related lesions; in cellular dermatofibromas, CD34 and MS-1 expression partially overlapped. The other antigens tested showed non-specific or overlapping patterns of expression. In conclusion, assessment of MS-1 protein expression (in addition to assessment of CD1a and CD34) promises to be of diagnostic value in the discrimination of N-LCH from related skin disorders, and it may indicate a common differentiative pathway for most N-LCH disease entities.

Antibodies, Monoclonal↗

Functional and morphological characterization of 4F7+ spleen accessory dendritic cells.

Recently we have reported on the production of the mAb 4F7. This recognizes a molecule that is upregulated on dermal and epidermal dendritic cells after application of contact allergen. Furthermore, this antibody detects an antigen on spleen and lymph node dendritic cells. In this study, we characterize 4F7+ spleen dendritic cells and show that the mAb recognizes in situ few labeled cells in the white pulp of the spleen and approximately 1% of spleen single cell suspensions as evidenced by cell enrichment, immunoperoxidase staining and FACS analysis. Immunohistological characterization of the cells with mAbs revealed the expression of class II, class I MHC antigens, 33D1, CD11c, ICAM-1, and CD45 molecules. After enrichment and cultivation for approximately 3 days, these cells showed no adherent properties. The capacity of 4F7+ spleen dendritic cells to activate allogeneic T cells in the primary mixed lymphocyte reaction was similar to freshly isolated Ia+ Langerhans cells. With regard to the induction of a proliferative response of CD4+ naive T cells that were incubated with concanavalin A or anti-CD3 mAb, 4F7+ spleen dendritic cells were two to three times more potent than spleen microphages and B cells. Furthermore, 4F7+ cells efficiently stimulated the antigen dependent proliferation of a T helper cell line. The mAb 4F7 will be useful for the purification of dendritic cells and for functional and molecular biological studies.

Animals↗

Expression of an epitope as detected by the novel monoclonal antibody 4F7 on dermal and epidermal dendritic cells. I. Identification and characterization of the 4F7+ dendritic cell in situ.

Ears of Balb/c mice were treated epicutaneously with 0.5% 2,4-dinitrofluorobenzene (DNFB) to obtain monoclonal antibodies characterizing molecules on epidermal dendritic cells that are involved in the induction and elicitation of allergic contact dermatitis. Six hours after this treatment, epidermal cells were prepared from the ear skin, and Ia-positive cells were enriched by indirect panning and injected into rats. Hybridomas were generated and supernatants were screened for antibodies on ear skin from DNFB-treated and untreated animals. A clone (4F7) was isolated and characterized by immunohistochemistry and immunoelectron microscopy on murine skin and other organs. The monoclonal antibody 4F7 (IgG1) recognized distinct dendritic cells in the dermis and very few dendritic cells in the paracortical area of the lymph nodes, the white pulp of the spleen, and the mucosa of the large intestine in normal animals. By fluorescence activated cell sorter analysis, it stained about 1.64% of the dermal and no epidermal cells in the skin of untreated animals. Approximately 50% of the dermal 4F7+ cells expressed Ia molecules on their surface. Six hours after application of 0.5% DNFB, the expression of the 4F7 antigen was strongly enhanced in vivo on dendritic cells in both the dermis and epidermis. About 15% of the epidermal dendritic cells expressing 4F7 exhibited Birbeck granules, the other Birbeck granule-negative cells resembled indeterminate dendritic cells (IDCs). The dermal and epidermal 4F7+ cells could be highly (98%) enriched with 4F7-labeled immunomagnetic particles. Transmission electron microscopic analysis of such preparations showed typical characteristics of dendritic cells with 50% or 100%, respectively, of these cells expressing Ia molecules on their cell membrane. The results suggest that the 4F7 epitope is expressed on dendritic cells related to Langerhans cells and is upregulated by an inflammatory stimulus.

Animals↗

Demonstration of the high-affinity IgE receptor on human Langerhans cells in normal and diseased skin.

Epidermal dendritic cells of normal adult foreskin, and of lesional skin from patients with atopic eczema, stasis eczema and urticaria pigmentosa are shown to be highly reactive with two different monoclonal antibodies (29C6 and 6F7) specific for extracellular domains of the alpha-chain of the high-affinity IgE receptor. By their distribution pattern, the reactive cells are Langerhans cells. This is confirmed by immunoelectron microscopic demonstration of Birbeck granules in the labelled epidermal cells. Very weak staining is observed on the same cells with an antibody (Tü1) against the low-affinity IgE receptor. Pre-incubation of the sections with IgE partially blocks binding of 6F7 antibody. Langerhans cells, together with dermal mast cells, can therefore bind IgE with high efficiency, and may in this way participate in IgE-mediated cutaneous diseases.

Adult↗

[Dermatofibrosis lenticularis disseminata with osteopoikilosis. Buschke-Olldendorff syndrome].

Buschke-Ollendorff syndrome is characterized by the coincidence of dermato-fibrosis lenticularis disseminata and focal sclerotic bone dysplasia (osteopoikilosis). The case of a 39-year-old female is presented and the characteristic clinical, histopathological and radiological manifestations of this rare disease are reviewed. As focal bone lesions in Buschke-Ollendorff's syndrome are mostly asymptomatic, the rate of diagnosis could be increased if locations of predilection were subjected to X-ray examinations on clinical observation of the typical cutaneous manifestations.

Adult↗

[Lymphoplasmocytoid immunocytoma of the skin].

A 68-year-old male patient presented with numerous red-brown papules on the trunk and neck. Cutaneous lymphoplasmocytoid immunocytoma was diagnosed following histological and electron microscopical detection of atypical lymphoid cells in the dermis. Immunohistochemistry revealed a monoclonal proliferation of IgG-kappa-positive B-lymphocytes. There was no extracutaneous manifestation of the lymphoma. Complete remission was affected by total-body irradiation with an electron beam.

Biomarkers, Tumor↗

[Metastasizing eccrine porocarcinoma].

We report on an 84-year-old female patient who presented with abundant firm skin nodules and massive lymphoedema restricted to the left leg. Metastasizing eccrine porocarcinoma was diagnosed by the unusual circumscribed pattern of the cutaneous metastases and the histological detection of intraepidermal and intradermal PAS-positive tumour cells. This diagnosis was established by the histopathological reexamination of a small skin tumour on the left ankle, which had been misinterpreted as actinic keratosis 5 years before. The initiated local radiation therapy with fast neurons and cobalt-60 resulted in partial regression of the cutaneous metastases and lymphoedema, but was not able to hamper the fatal outcome directly resulting from tumour cachexia.

Aged↗

[Pseudoxanthoma elasticum. Clinically typical but frequently overlooked].

A 52-year-old man had small yellowish, striated or reticular papules since the age of 5 years. These appeared first on the large flexures, and later on the neck, abdomen, penis and the mucosa of the lips. He developed angina at the age of 47 years. A bypass operation, however, did not lead to complete regression of cardiac symptoms. Four years later, the vision in his right eye deteriorated because of arterial occlusion, and the patient was treated with laser coagulation; he was started on long-term treatment with acetylsalicylic acid (250 mg/d) and calcium dobesilate (1,500 mg/d). Despite this, the vision in his left eye also deteriorated progressively. Fundoscopy revealed bilateral pigmentary changes in the macular region, variations in the retinal arterial diameters and "angioid streaks". Pulses were absent in the right radial artery, the left posterior tibial artery and both dorsalis pedis arteries, but there were no trophic changes or symptoms. The serum total cholesterol (246 mg/dl), triglycerides (177 mg/dl) and LDL-cholesterol (193 mg/dl) were only slightly elevated. The diagnosis of pseudoxanthoma elasticum with typical changes in the elastic fibres was confirmed by elastin staining in a biopsy from one of the lesions.

Biopsy↗

Epidermal expression of the calcium binding surface antigen 27E10 in inflammatory skin diseases.

The expression of the heterodimeric complex of the calcium-binding proteins MRP-8 and MRP-14 was investigated in various inflammatory dermatoses using immunohistochemical staining with the monoclonal antibody 27E10. In addition to the inflammatory infiltrate, a positive staining was repeatedly found in the involved epidermis from patients with lichen planus, lupus erythematosus and psoriasis vulgaris, but not in normal skin epidermis and/or in epidermis from leucocytoclastic vasculitis patients. The keratinocytic expression of the 27E10 antigen was dissimilar to that of the MHC class-II molecules and the adhesion molecule ICAM-1. These data indicate that the 27E10 antigen is a distinct activation marker of inflammatory keratinocytes and may have proinflammatory properties.

Antigens, Surface↗