[The clinical picture and therapy of progressive systemic scleroderma].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to N Sönnichsen.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The influence of the widely used topical dermatological treatment modalities anthralin, coal tar and pyrogallol on surface markers of epidermal Langerhans cells and contact sensitization was studied and compared with that of a PUVA treatment. A common effect of all dermatological therapies tested was inhibition of Langerhans cell ATPase, whereas an effect on MHC class II antigens was found only after PUVA or tar treatment. The induction of contact hypersensitivity was inhibited only by PUVA, and not by the other treatments. These results show that various forms of topical therapy influence surface markers and immunological function of epidermal Langerhans cells differently.
The influence of the ATPase inhibitors, lanthanum or cerium, on histamine release in basophils and mast cells was studied. Both compounds inhibited IgE- or A23187-induced histamine release. To exclude a general inhibition of calcium-dependent reactions in the cell, we tested the influence of these compounds on phagocytosis and superoxide production of neutrophil granulocytes. Phagocytosis of Candida albicans was inhibited partially, superoxide generation, measured by the INT test after stimulation with zymosan or aggregated gamma globulin, was not affected. Because of the inhibitory effect of lanthanum or cerium compounds on membrane ATPase and immunological function of epidermal Langerhans cells we propose that these compounds may be used in the treatment of atopic eczema, where both histamine-releasing mast cells and IgE-bearing Langerhans cell play a pathogenetically important role.
Treatment of an organism with UVB light or PUVA (8-methoxypsoralen + UVA light) not only leads to alterations in the irradiated skin but also to systemic immunomodulation, due to the release of several chemical mediators of immunosuppression like prostaglandins, acute-phase proteins, IL-1 inhibitor, alpha-melanocyte-stimulating hormone, propiomelanocorticotropin or other cytokines. A recently described mediator is urocanic acid, which is transformed by UV light in the skin from the trans- to the cis-isomer and that exerts a systemic immunomodulatory effect. In our experiments, treatment with PUVA or with cis-urocanic acid prevents the rejection of rat heart allografts in 50% and 40% of cases, respectively. Control grafts are rejected in fewer than 10 days. PUVA treatment of donor leukocytes before transfusion into the prospective recipient inhibits only their sensitizing, not their graft-protecting, effect on subsequent skin grafts in mice. PUVA treatment also prevents acute lethal GVH disease in mice after irradiation with a sublethal dose of x-rays and transfusion of semiallogeneic spleen cells. Treatment of recipient mice with cis-urocanic acid has the same effect. The humoral immune response to sheep erythrocytes is not influenced by cis-urocanic acid. These results demonstrate that PUVA treatment or its chemical mediator, cis-urocanic acid, may be used in transplantation and hematology as naturally occurring immunosuppressive agents, especially for the control and manipulation of GVH leukemia reaction.
Melkersson-Rosenthal syndrome (MRS) is characterized by the triad of facial paralysis, facial oedema, and lingua plicata in association with other symptoms, such as headache and mental changes. Because the origin of this syndrome is still unknown, only symptomatic treatment is possible. In 18 patients suffering from MRS, whether with a complete or with an incomplete picture, we used the antileprosy drug clofazimine for therapy. A decrease in the frequency and intensity of oedema was achieved by this therapy in 94% of patients. However, improvement persisting throughout a follow-up period of up to 3 years was seen in only 62% of patients. We demonstrate that clofazimine is an alternative to glucocorticosteroids for the treatment of MRS.
The regulation of IgE production in B lymphocytes of patients with atopic dermatitis by interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) was studied. IL-4 stimulated IgE production in vitro in B-cells of healthy donors and of children with atopic dermatitis, but had only a marginal effect on the high basal level of IgE production by lymphocytes from adult patients with atopic dermatitis. The addition of IFN-gamma prevented in all cases the stimulation of IgE synthesis induced by IL-4. The production of IgG and IgM was differently influenced. These results indicate that the in vitro production of IgE by mononuclear cells from adult patients is more resistant to the regulatory effects of IL-4 and IFN-gamma than is that in B cells of children with atopic dermatitis. We propose that a previous in vitro test of the responsiveness of IgE-producing B cells to IFN-gamma may be used to select patients with atopic dermatitis for treatment with IFN-gamma.
Explore the source record for details and available documents.
Splenopentin (SP-5: Arg-Lys-Glu-Val-Tyr), a pentapeptide corresponding to the residues 32-36 of the splenic hormone splenin, increases dose-dependently the number of bone marrow colonies (M and GM colonies). Therefore, we tested the stimulatory effect of SP-5 on the recruitment of epidermal Langerhans cells in skin deprived of these cells. A high dose of cyclophosphamide or dexamethasone led to a drastic decrease of LC density in murine skin with slow and incomplete restoration. SP-5 accelerated Langerhans cell recruitment and led to pretreatment levels of Langerhans cell density in the skin. These results indicate that SP-5 may possibly be used to treat disorders (e.g., HIV infection) where impaired Langerhans cell density and function can lead to secondary cutaneous infections.
It is supposed that anti-Ro(SS-A) antibodies play an important role in the development of photosensitive skin disease in subacute cutaneous lupus erythematosus and neonatal lupus erythematosus. The aim of the experiments was to demonstrate that anti-Ro(SS-A) antibodies and UVA-light cause a cytotoxic effect on human keratinocytes in vitro. Keratinocytes are irradiated with UVA-light in presence of serum containing anti-Ro(SS-A) antibodies (62 E, ELISA). After application of 20 J/cm2 UVA-light only 48.5% of the irradiated cells are still vital (standard trypan blue exclusions test). Examination by scanning electron microscopy shows plain depressions on the surface of the keratinocytes, which were irradiated in presence of anti-Ro(SS-A) antibodies.
Explore the source record for details and available documents.
Among the therapeutical modes of psoriasis, sea-water baths with salts from the Dead Sea in combination with ultraviolet light (Tomesa therapy) play an important part. In a previous paper, we showed that treatment of isolated murine skin with Tomesa salt solutions resulted in an irreversible decrease of ATPase-positive epidermal Langerhans' cells. Our present study is concerned with the treatment of healthy persons and psoriasis patients with baths containing Tomesa salts, which lead to reduced amounts of detectable Langerhans' cells in the epidermis, as well. Baths containing sodium chloride in comparable concentrations, however, were without effect at all. Our findings demonstrate that the antipsoriatic activity of Tomesa therapy is not only due to physical effects but may also be the result of definable pharmacological actions of the salts on skin cells.
Using surviving human skin, percutaneous absorption following topical application of hematoporphyrin derivative was investigated. Hematoporphyrin derivative gave strong red fluorescence, which was dependent from it's actual concentration, from the used kind of vehicle, from preparation time, and from time between preparation and application of hematoporphyrin derivative solution. Ultrastructural investigation verified cytoplasmatic membranes and mitochondria as the principal targets also after topical application followed by irradiation with visible light.
In the last years a new therapy of psoriasis was developed, which consists in a treatment with salt solutions, resembling the water of the Dead Sea, and ultraviolet light (Tomesa-therapy). We studied the influence of the used salt on ATPase positive epidermal Langerhans cells in murine ear skin. An irreversible partial reduction of the Langerhans cell ATPase was found after salt treatment of separated epidermis or of full skin preparations. These results may have implications for the optimization and broader application of this therapy.
Explore the source record for details and available documents.
The HIV-infection represents simultaneously a new and important problem. Multiple changes appear on skin and mucous membranes in all stages of the infection. These changes have an essential diagnostic significance especially in the early phase of the infection. The most important changes become represented systematically in relation to the progress of the disease.
There is in photosensitive lupus erythematosus a strong association of high titers of anti-Ro(SS-A) antibodies in the serum of the patient with the development of special skin reactions depending on UV-light. The aim of our experiments was to detect a cytotoxic effect of anti-Ro(SS-A) antibodies and UVA-light on human endothelial cells in vitro (standard trypan blue exclusion test, SEM). After UVA-doses of 1 to 100 J/cm2, which were tested, and influence of serum containing anti-Ro(SS-A) antibodies (62 E, ELISA) membrane destructions of endothelial cells depending on the UVA-dose can be seen, irrespective of the fact whether the antibodies are present throughout the irradiation or added afterwards. This cytotoxic reaction depends on complement. A UVA-dose of 100 J/cm2 causes lethal damage of 40% of the cells. These results were confirmed by scanning electron microscopy.
Explore the source record for details and available documents.