Demonstration of anaphylatoxins C3a, C4a and C5a in the scales of psoriasis and inflammatory pustular dermatoses

Complement components C3a, C4a and C5a were assayed in corneal scale extracts from psoriasis and other dermatoses characterized by sterile subcorneal pustules, using radioimmunoassay. Larger amounts were detected in psoriasis and related pustular dermatoses than in extracts of non-inflammatory stratum corneum. It is concluded that complement is activated via the classical pathway and releases the neutrophil chemotactic fragment C5a.     

Inhibition of endocytosis activates alternative degradation pathway of βAPP in cultured cells

Background: Alzheimer’s disease associated βAPP is sequentially endoproteolyzed by α/β‐secretase and γ‐cleavage. In the process, extracellular shedding by α‐secretase (ADAM 9/10/17) or β‐secretase (BACE 1/2) at position L¹⁷ or D¹ (Aβ numbering) are prerequisites for the generation of P3 or Aβ, respectively. In addition, several alternative extracellular cleavage sites in βAPP have been reported at position I^?6, V^?3, R⁵, E¹¹, F²⁰, and A²¹. Among these sites, position R⁵ is considered to be cleaved by α‐secretase‐like activity, whereas position E¹¹, F²⁰ and A²¹ are cleaved by β‐secretase. Therefore, extracellular shedding of βAPP is thought to be mediated exclusively by α/β‐secretase activities. However, so far the characteristics of cleavages at position V^?3 and I^?6 are not well understood. The aim of this study is to characterize these two cleavages of βAPP. Methods: We analyzed the conditioned media of βAPP wt or sw expressing cells with or without pharmacological agents. Results: Here, we show that the cleavage at position I^?6 of βAPP has characteristics distinct from that of α/β‐secretase, while the cleavage at V^?3 seems to be mediated by β‐secretase. Although inhibition of endocytosis enhances the cleavages at both V^?3 and I^?6, PMA, an α‐secretase stimulator, treatment enhances neither of these cleavages. Interestingly, a β‐secretase inhibitor, z‐VLL‐CHO, suppressed V^?3 but not I^?6 cleavage. The pathological βAPP Swedish mutant adjacent to the cleavage sites shows similar effects. Conclusions: Our data demonstrate that neither α nor β‐secretase undergoes extracellular shedding at I^?6 of βAPP. Therefore, our data may indicate a novel alternative βAPP degradation pathway which is up‐regulated upon low level of endocytosis.     

Determination of released CD4 and CD8 antigens in the suction-blister fluid and horny-tissue extract in patients with psoriasis

The amounts of soluble CD4 and CD8 antigens were measured in suction-blister fluid and extracts of horny tissue in patients with psoriasis. The levels of soluble CD4 and CD8 in the suction-blister fluid of lesional skin in psoriasis was significantly higher than from normal skin and the uninvolved skin in psoriasis. Levels of soluble CD4 and CD8 in the extracts of horny tissue in psoriasis were significantly higher than those from non-psoriatic skin.     

Regression of plane warts following spontaneous inflammation

This paper describes the clinical and histopathological features in ten cases of spontaneously involuting plane warts. In all, rapid regression occurred after the sudden development of an inflammatory reaction. At an early stage a degenerative change appears in the upper epidermis and the typic features of the warts are masked. At the height of the reaction an intense mononuclear cell infiltrate in the dermis associated with epidermal spongiosis, exocytosis cell necrosis and focal parakeratosis is found. It is suggested that the development of cell mediated immunity may be responsible for spontaneous involution of warts.     

Functional assessment of the stratum corneum under the influence of oral aromatic retinoid (etretinate) in guinea-pigs and humans. Comparison with topical retinoic acid treatment

Clinically we have noted that the skin of patients treated with long-term oral etretinate becomes uniformly soft and smooth to touch, like facial skin that becomes smoother and less wrinkled following treatment with topical tretinoin. This suggests that retinoids, whether used systemically or topically, alter the physical properties of the skin, particularly of the stratum corneum (SC). To study the influence of retinoids on the SC, we serially assessed the functional properties of the SC non-invasively in retinoid-treated humans and experimental animals. SC hydration and barrier function were assessed by measurement of high-frequency conductance and transepidermal water loss (TEWL), respectively. Daily application of topical retinoic acid creams was found to rapidly induce a time- and dose-dependent, linear increase in SC hydration of the forearm skin of healthy adults over a 2-week period and to compromise its water barrier function in a similar fashion. Systemic administration of high-dosage etretinate, 4 or 8 mg/kg/day, to guinea-pigs also induced dose-dependent increases in both SC hydration and TEWL measured on the plantar skin after 1 month. Moreover, in the animals given etretinate 4 mg/kg/day we confirmed a slight but significant decrease in the number of cell layers of the plantar SC. Likewise, patients with various dermatoses began to show similar functional changes of the SC in the uninvolved skin of the flexor surface of the forearms 3 weeks after the start of oral etretinate treatment, consisting of 50 mg daily for 2 weeks, followed by gradual dose tapering.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autologous mixed lymphocyte reaction is reduced in patients with psoriasis

The autologous mixed lymphocyte reaction (auto-MLR) was studied to test the interactions between immunocompetent cells in patients with psoriasis. The auto-MLR in 20 patients with psoriasis was significantly lower than in 16 normal controls. Lower values were found in untreated psoriatic patients than in those in remission following treatment. The values in the latter group were significantly lower than in controls and in six patients with atopic dermatitis in remission. The tendency for an increase in the auto-MLR with a decrease in disease activity was further confirmed in five patients studied before and after treatment. In contrast, the allogeneic lymphocyte reaction (allo-MLR) in psoriatics was similar to that in normal controls.