[Determination of the UV erythema threshold value using UV gradient exposure].
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Biomedical subjects
Publications and source records attributed to H Meffert.
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Results of previous investigations have indicated that photochemotherapy (PUVA) attacks membranes of target cells. Using the combination of a stopped-flow technique and laser irradiation we were able to prove that the fast PUVA effect is explainable solely by the membrane damage. Lymphoid cells of healthy persons or psoriatics were taken, within 1 ms mixed with 8-methoxy-psoralen (8-MOP) at concentrations of 1.0, 0.1, and 0.5 microgram/ml, and then irradiated by a 337-nm laser pulse (0.5 mJ/cm2) lasting some picoseconds. Approximately 1 ms after administration of 8-MOP to the cell surface at least 10% of the cells were damaged, as could be judged using the standard trypan blue exclusion test. This happened at 8-MOP concentrations of 1.0 or 0.1 microgram/ml plus laser irradiation, but a concentration of 0.05 microgram/ml 8-MOP plus laser exposure did not cause any effect within 8 ms after mixing. There was no difference between using lymphoid cells from healthy persons or from psoriatics. The fact that only a very short time is necessary before cell damage occurs means that, as far as the fast PUVA effect is concerned, a photochemical reaction involving nuclear DNA can be discounted.
Treatment of human peripheral blood mononuclear cells with UVB light, the photosensitizing system 8-methoxypsoralen plus UVA light (PUVA), or hematoporphyrin derivative plus visible light leads to an inhibition of their stimulatory capacity in an allogeneic mixed leukocyte reaction despite unaltered expression of HLA-DR antigens when tested immediately after irradiation. However, HLA-DR positive cells disappear among mononuclear cells in the interval between 4 and 8 h after treatment with either UVB, PUVA, hematoporphyrin derivative and light, or heating to 45 degrees C. The expression of HLA-DQ, but not HLA-A,B,C, antigens, was similarly affected by these treatments. The significance of these results is discussed.
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The combined treatment of murine skin grafts with 8-methoxypsoralen and longwave ultraviolet radiation (PUVA) leads to a prolonged survival after transplantation on allogeneic recipients. This may be due to inactivation of intragraft antigen presenting cells like epidermal Langerhans cells. In this study the effects of PUVA or middle range ultraviolet radiation (UVB) on ATPase positive Langerhans cells and immunogenicity of murine skin grafts were compared. Graft immunogenicity is reduced immediately after PUVA treatment, whereas the number of ATPase positive Langerhans cells decreases later, reaching its minimum three days after irradiation. UVB light reduces the number of ATPase positive Langerhans cells to a similar degree but skin graft survival is prolonged only marginally. Obviously, the effects of photochemotherapy on the ATPase activity of Langerhans cells reflect only partially the alterations of skin graft immunogenicity. Other antigen presenting cells like dendritic cells in the dermis may be of importance. Because these cells are located deeper in the graft they are better reached by stronger penetrating longwave ultraviolet radiation (PUVA) than by UVB.
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Using a 0.075% 8-methoxypsoralen solution, minimal phototoxic doses and improvement of psoriasis lesions were investigated in 15 patients suffering from chronic stationary psoriasis. The time interval between topical 8-methoxypsoralen application and long-wave ultraviolet light irradiation was increased stepwise. The mean minimal phototoxic dose declined with increasing time interval and reached its minimum 2 h after 8-methoxypsoralen application. In spite of that, antipsoriatic efficiency was maximal 15 min after application. In order to obtain a favorable relationship between antipsoriatic efficiency and unwanted side effects when using topical PUVA treatment, irradiation should be started 15 min after 8-methoxypsoralen application.
The influence of combined photochemical treatment with a haematoporphyrin derivative and visible light on antigen-presenting cells was evaluated. Treatment of murine skin grafts with this procedure prolonged their subsequent survival on allogeneic recipients. The haematoporphyrin derivative and light decreased the ATPase activity of epidermal Langerhans cells in murine skin. When stimulator cells in a human allogeneic mixed leucocyte reaction were treated with the haematoporphyrin derivative and light, they lost their stimulatory capacity. It is proposed that the haematoporphyrin derivative and visible light interfere, on analogy with ultraviolet radiation, with the function of antigen-presenting cells.
Disodium cromoglycate was applied before patch testing in patients with contact allergy to propipocaine hydrochloride, nickel and formaldehyde. The responses obtained were mitigated to a high degree when compared with similar effects due to corticoids.
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