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Biomedical subjects

G Kolde

Publications and source records attributed to G Kolde.

At least 37 records · Page 2Linked to original sources
PubMed1997

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. Only a few cells expressed the low-affinity IgE receptor (Fc epsilon RII) (Tü1 antibody) in some sections. These findings suggest that Langerhans' cells play an important role in the induction of transepithelial IgE-mediated allergy and in the mediation of inflammation of the nasal mucosa via their Fc epsilon RI.

Biopsy↗
PubMed1996

Skin involvement in amyotrophic lateral sclerosis.

BACKGROUND: Patients with sporadic amyotrophic lateral sclerosis (ALS) show disorganised collagen and elastin of the dermis. We looked for inflammatory alterations to cutaneous blood vessels. PATIENTS AND FINDINGS: Seven patients with sporadic ALS were investigated; five were confined to bed, but none had bedsores. Light and electron microscopy of skin showed an oedematous dermis with collagen fibrils of irregular diameter. Small blood vessels were characterised by duplicated basement membranes and deposition of beta-amyloid protein, the main component of the neuronal and non-neuronal amyloid deposits in Alzheimer's disease. These skin changes were seen in all degrees of disability, but none was found in age-matched and sex-matched controls. INTERPRETATION: The skin in ALS is characterised by a distinctive pattern of alterations of connective tissue and blood vessels. Examination of skin in an additional and easily accessible investigation which may help elucidate the pathogenesis of ALS.

Amyloid beta-Peptides↗
PubMed1996

Turnover and kinetics of epidermal Langerhans cells and their dendritic precursor cells in experimental contact dermatitis. A correlated ultrastructural-morphometric and immunohistochemical evaluation.

The numerical density of epidermal Langerhans cells (LCs) in contact sensitivity and toxic contact dermatitis is still a matter of controversy, mainly due to changes in the phenotypic markers of this antigen-presenting cell during the skin reactions. Since the electron microscopic detection of Birbeck granules is the most reliable marker for the identification of normal and pathologically altered LCs, we performed an ultrastructural-morphometric time-course analysis to evaluate their epidermal turnover in the earskin of BALB/c mice after painting the ears with the hapten 2,4-dinitrofluorobenzene and the irritant croton oil. The counts revealed degeneration and depletion of epidermal LCs in both allergic and toxic dermatitis. In contrast, a slightly increased number of activated epidermal LCs was found during contact sensitization. All experimental procedures resulted in an enhanced immigration of so-called indeterminate dendritic cells which also became ultrastructurally activated and often showed Birbeck granule-like formations at their cell membrane. Immunohistochemistry with the monoclonal antibody 4F7, a new marker for dendritic precursor cells of LCs, demonstrated a significant increase in these accessory cells in the epidermis. Our results indicate that contact sensitivity and toxic skin reactions are characterized by complex but distinct changes in the turnover, kinetics and cellular properties of epidermal LCs and their dendritic precursor cells.

Animals↗
PubMed1996

Induction of apoptosis in human HaCaT keratinocytes.

Although cell death by apoptosis has been recognized as an important control mechanism in the maintenance of tissue homeostasis and in the elimination of cells with damaged DNA, information on the induction and characteristics of apoptosis in keratinocytes is rather scarce. Apoptotic mechanisms may play an important role in normal and disturbed homeostasis of the skin. In the present study, we therefore investigated the effects of several potential inducers of apoptosis in the human keratinocyte cell line HaCaT. Apoptosis was assessed with respect to morphological changes by light and electron microscopic examinations and to DNA integrity by a specific ELISA. UVB irradiation induced the morphology and internucleosomal DNA fragmentation characteristic of apoptosis in a dose- and time-dependent manner. Interferon-gamma caused DNA cleavage at the linker regions without producing morphological features consistent with apoptotic cell death. In contrast, treatment with dithranol and NP-40 resulted in necrotic alterations in the keratinocytes. Treatment with the calcium ionophore A23187 caused morphological changes which were similar to the characteristics of 'nonapoptotic programmed cell death'. Dexamethasone, tumor necrosis factor-alpha, transforming growth factor-beta, TPA, retinoic acid, the podophyllin derivative etoposide, the thromboxane A2 analogue U46619, cycloheximide, and the nitric oxide donors sodium nitroprusside and S-nitroso-glutathione, which are all known to induce apoptosis in other cell types, did not affect HaCaT keratinocytes. These results demonstrate that apoptosis can be induced in keratinocytes in vitro but the apoptosis differs from that in other cell types, such as haematopoietic cells, with regard to the type of inducer and/or the sensitivity of the target cells. Since keratinocytes are affected by numerous external and internal stimuli, they might posses several protective mechanisms to prevent apoptosis and to ensure the structural integrity of the outermost barrier of the body.

Administration, Topical↗
PubMed1996

[Successful treatment of chronic discoid lupus erythematosus with argon laser].

We report on a patient with chronic discoid lupus erythematosus who was treated with argon-laser. The patient suffered from long-standing lesions and had been pretreated with various drugs; with no or slight improvement. After a few argon-laser applications, the treated skin lesions improved dramatically while the untreated lesional skin showed continuous disease activity. Histological and immunohistological investigations of biopsies from treated and untreated lesional skin suggest that endothelial mechanisms play a role in the generation and maintenance of discoid lesions in lupus erythematosus. This is the first reported case of successful treatment of chronic discoid skin lesions of a lupus erythematosus patient with argon-laser.

Adult↗
PubMed1996

Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo.

Human malignant melanoma is notoriously resistant to pharmacological modulation. We describe here for the first time that the synthetic retinoid CD437 has a strong dose-dependent antiproliferative effect on human melanoma cells (IC50: 5 x 10(-6) M) via the induction of programmed cell death, as judged by analysis of cell morphology, electron microscopical features, and DNA fragmentation. Programmed cell death was preceded by a strong activation of the AP-1 complex in CD437-treated cells as demonstrated by gel retardation and chloramphenicol transferase (CAT) assays. Northern blot analysis showed a time-dependent increase in the expression of c-fos and c-jun encoding components of AP-1, whereas bcl-2 and p53 mRNA levels remained constant. CD437 also exhibited a strong growth inhibitory effect on MeWo melanoma cells in a xenograft model. In tissue sections of CD437-treated MeWo tumors from these animals, apoptotic melanoma cells and c-fos overexpressing cells were colocalized by TdT-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) staining and in situ hybridization. Taken together, this report identifies CD437 as a retinoid that activates and upregulates the transcription factor AP-1, leading eventually to programmed cell death of exposed human melanoma cells in vitro and in vivo. Further studies are needed to evaluate whether synthetic retinoids such as CD437 represent a new class of retinoids, which may open up new ways to a more effective therapy of malignant melanoma.

Animals↗
PubMed1996

Production of interleukin-6 by human mast cells and basophilic cells.

Since mast cells and basophils are thought to play a central role in several types of cutaneous inflammatory and allergic reactions, and since interleukin-6 (IL-6) is an important mediator in these processes, we have studied the ability of the human mast cell line HMC-1, the human basophilic cell line KU812, and human skin mast cells to produce IL-6. All three cell types proved to be potent sources of this cytokine after appropriate stimulation. Transcription of IL-6 mRNA was first detectable 2 h after stimulation with the ester phorbol myristate acetate (PMA) and the calcium ionophore A23187 in both cell lines, as evidenced by semiquantitative reverse transcriptase polymerase chain reaction analysis. Whereas resting cells did not produce IL-6 protein, PMA/A23187-stimulated cells released immunoreactive and biologically active IL-6, as demonstrated and quantitated by enzyme-linked immunosorbent assay and by the use of TEPC 1033 cells, an IL-6-dependent murine plasmacytoma cell line. Stimulated KU812 cells secreted sevenfold more IL-6 (up to 15 ng/ml) than HMC-1 cells (up to 2.4 ng/ml). Immunoblotting of HMC-1- and KU812 cell-derived IL-6 revealed several IL-6 forms in the molecular weight range of 21 to 30 kDa. Immunoelectron microscopic studies of human skin biopsies provided evidence that unstimulated mast cells do not contain preformed IL-6 but accumulate IL-6 in cytoplasmic and extruded granules after IgE-dependent stimulation. These findings suggest that IL-6 secreted by human mast cells and basophils potentially contributes to allergic, other immunologically mediated and nonspecific inflammatory responses.

Basophils↗
PubMed1996

Induction of low zone tolerance to contact allergens in mice does not require functional Langerhans cells.

Epidermal Langerhans cells are known to be the major controlling element in the development of contact hypersensitivity. Haptenic molecules permeating the skin are taken up locally by Langerhans cells and then presented to T lymphocytes in the regional lymph nodes. Despite the presence of functional Langerhans cells, however, subsensitizing doses of hapten applied epicutaneously induce tolerance. We examined epidermal Langerhans cells at the site of contact with picryl chloride or oxazolone in BALB/c and C57B1/6 mice with regard to their responding to either subsensitizing or sensitizing doses of allergen. Subsensitizing doses did not interfere with the membranous adenosine triphosphatase system on Langerhans cells, known to relate to functional readiness of the cell. Accordingly, on electron microscopy the ultrastructure of Langerhans cells was found to be like that in untreated skin. In contrast, sensitizing doses caused a significant depletion of adenosine triphosphatase-positive Langerhans cells, and electron microscopy revealed marked cellular activation of Langerhans cells, with enlarged nuclei and increased numbers of mitochondria and Birbeck granules. Furthermore, subsensitizing doses induced tolerance regardless of whether Langerhans cells were functionally intact or had their function blocked arbitrarily. Blocking was achieved either by preceding ultraviolet B irradiation at the site of application or by painting of a sensitizer before painting another sensitizer on the same site. Moreover, not even surgical removal of the site within minutes after painting could prevent the induction of tolerance. The data suggest that subsensitizing doses of contact allergens painted on normal murine skin bypass involvement of epidermal Langerhans cells.

Adenosine Triphosphatases↗
PubMed1996

Successful treatment of cutaneous leishmaniasis using systemic interferon-gamma.

BACKGROUND: Interferon-gamma (IFN-gamma) is one decisive cytokine of T-helper type 1 (Th1) cells in experimental leishmaniasis. It activates macrophages to kill intracellular parasites and leads to a decline of less mature macrophages in the infiltrate. Application of IFN-gamma heals the disease in susceptible mice and has recently been shown to be of benefit in human disease when given locally or in combination with antileishmanial drugs. OBJECTIVE: We investigated the clinical and histological effects of systemic application of IFN-gamma in a case of human cutaneous leishmaniasis in which an ulcerating lesion endangered the left upper eyelid of a 4-year-old boy. RESULTS: IFN-gamma (100 mu g/m2 of body surface per day) was given subcutaneously for a period of 28 days. The well-tolerated treatment resulted in rapid and complete healing of the lesion without functional impairment. Histological examination disclosed the formation of dermal granulomas. Immunohistochemical characterization of the myelomonocytic cells in the lesion before and after treatment revealed a marked decrease of less-mature macrophages in the infiltrate. This phenomenon equals observations in healing lesions during naturally occurring resistance in murine leishmaniasis. CONCLUSION: Systemic monotherapy with IFN-gamma can be an effective treatment for complicated cases of human cutaneous leishmaniasis without the side effects sometimes observed with systemic pentavalent antimony. Its effects on the myelomonocytic infiltrate are similar to the ones observed during the physiological immune response in natural resistance.

Child, Preschool↗
PubMed1996

The scleroatrophic syndrome of Huriez: a cancer-prone genodermatosis.

We report a 24-year-old woman, her 6-year-old son and her 17-month-old daughter, who all suffer from a rare congenital genodermatosis first delineated by Huriez et al. in the 1960s. The clinical features of this autosomal dominant condition include scleroatrophy of the hands and feet, nail hypoplasia, mild palmoplantar keratoderma and hypohidrosis. Histological changes are non-specific, but immunohistological and ultrastructural examination in our index patient revealed an almost complete absence of epidermal Langerhans cells in the affected skin. This new finding may be linked to the cancer proneness of the scleroatrophic skin. In this family, the grandmother had died at the age of 37 years from metastatic squamous cell carcinoma which had arisen on the thenar eminence.

Adult↗
PubMed1995

In vitro analysis of the phenotypical and functional properties of the 4F7+ cutaneous accessory dendritic cell.

The monoclonal antibody 4F7 detects a molecule on dermal and epidermal Ia+ dendritic cells (DCs), and some of these cells are Birbeck granule-containing cells. Here we report on the phenotypical and functional characteristics of these cells which were highly enriched by 4F7-labelled immunomagnetic beads. The ultrastructural, immunocytochemical and cytochemical analyses of these preparations showed cells with the typical characteristics of DCs. The cells were found to express the DC marker NLDC145, but not 33D1. The C3bi receptor and marker F4/80 were only expressed by epidermal 4F7+ cells. The capacity of freshly isolated 4F7+ epidermal and dermal DCs to activate allogeneic T cells in a mixed leukocyte reaction was similar to the capacity of freshly isolated Langerhans cells. After culture, the epidermal cells showed a 4-5-fold increase in stimulation, whereas no difference was observed in the 4F7+ dermal DCs. We conclude that this new antibody recognizes a function-associated molecule on cutaneous DCs which are phenotypically and functionally related to Langerhans cells. The 4F7+ DCs may be precursors of epidermal Langerhans cells.

Animals↗
PubMed1995

Normolipemic papular xanthomatosis in erythrodermic atopic dermatitis.

We describe papular xanthomatosis that progressively developed in a patient with long-standing erythrodermic atopic dermatitis and normal lipid metabolism and without an associated systemic disease. Light microscopy showed a lobulated aggregate of sometimes foamy histiocytes. Ultrastructurally, these histiocytes contained lipid inclusions and lacked features of Langerhans or epithelioid cells. Other granulomatous skin diseases such as tuberculosis, sarcoidosis, or foreign body granuloma were excluded by histologic study, polarizing microscopic examination, electron microscopy, and microbiologic investigations. Nevertheless, these xanthomas showed an antigen expression pattern similar to that found in noninfectious granulomas (CD1a-, MS-1-, CD11c+, MRP-8/-14+, 25F9+, RM 3/1+/-, CD36(+), indicating that normolipemic papular xanthomatosis may be reactive process and should not be included among the true cutaneous non-Langerhans cell histiocytoses.

Adolescent↗
PubMed1995

Successful treatment of generalized lichen planus with recombinant interferon alfa-2b.

Three patients with generalized lichen planus were treated with interferon alfa-2b. The therapy was tolerated well by all patients with only minor side effects. A response was observed within 2 to 3 weeks. Itching and erythema decreased first, followed by gradual flattening and disappearance of papules and plaques after 8 to 10 weeks of treatment. After 12 weeks, therapy was discontinued after stepwise dosage reduction. In two patients, minor lesions recurred during dosage reduction. Both flares were controlled by readministration of interferon.

Adult↗
PubMed1995

Intact survival with transfusion-associated graft-versus-host disease proved by human leukocyte antigen typing of lymphocytes in skin biopsy specimens.

A transient transfusion-associated graft-versus-host disease occurred in a premature infant of 30 weeks of gestation. We demonstrated donor lymphocytes in a skin biopsy specimen with a two-step immunoperoxidase technique using monoclonal antibodies against human leukocyte antigen determinants specific for the donor. The girl survived and is immunocompetent.

Antibodies, Monoclonal↗
PubMed1995

Successful treatment of epidermolysis bullosa acquisita using intravenous immunoglobulins.

We report a 55-year-old man with severe inflammatory epidermolysis bullosa acquisita. The skin lesions did not respond to various immunosuppressive treatments. The combined administration of prednisone, azathioprine, dapsone and colchicine resulted only in a transient and incomplete resolution of the lesions. The bullae and increased skin fragility were successfully controlled by the addition of high-dose intravenous immunoglobulin therapy.

Azathioprine↗
PubMed1995

Treatment of urticaria pigmentosa using interferon alpha.

Long-term treatment with interferon alpha (IFN-alpha) has recently been shown to reduce the bone marrow infiltrate and cutaneous lesions in systemic mast cell disease. We therefore administered this cytokine to six patients with urticaria pigmentosa for up to 12 months, using subcutaneous injections of 5 x 10(6) U, initially five times, and subsequently three times a week. The generally well-tolerated therapy resulted in marked improvement of the cutaneous symptoms, especially in three of the patients who suffered from very severe pruritus. Two of the patients with bone marrow infiltration showed normal findings after treatment. However, in none of the patients was there any change in the skin lesions, or decrease in the degree of cutaneous mast cell infiltration, as evidenced by light and electron microscopic examination. These findings indicate that IFN-alpha is highly effective in the control of symptoms, but otherwise does not influence the cutaneous lesions of urticaria pigmentosa.

Adult↗