Fifteen patients with Darier's disease (five patients), epidermolytic hyperkeratosis (five patients), and pityriasis rubra pilaris (five patients) were treated with doses ranging from 1.0 to 3.0 mg per kg body weight of 13 ‐cis retinoic acid. There was marked clinical improvement in the patients with Darier's disease which was sustained in two out of five on stopping treatment after 6 months. Three patients with pityriasis rubra pilaris went into remission, and required no further treatment on stopping 13‐cis retinoic acid after 6 months; however two patients did not respond at all. All five patients with epidermolytic hyperkeratosis responded, but relapsed rapidly on discontinuation of therapy. The major histological change noted was the reduction in stratum corneum organisation and cohesion, with reduction in stratum corneum layers. Serum cholesterol and triglycerides became raised after 1 month's therapy, but tended to fall during the following 5 months of therapy. High density lipoproteins remained depressed during treatment. In selected cases, 13‐cis retinoic acid is a useful therapy for Darier's disease, pityriasis rubra pilaris and epidermolytic hyperkeratosis.

We have investigated the factors governing the plasminogen-dependent fibrinolysis catalyzed by the serine proteinase, plasminogen activator (EC 3.4.21.-), under physiologic conditions. We found that live rabbit fibroblasts digested much less fibrin than predicted by cell-free assay of the secreted plasminogen activator. The reduced catalytic activity of plasminogen activator expressed by cells growing on fibrin was regulated by the salt concentration of culture medium. The plasminogen activators of cells from several mammalian species were inhibited by physiologic salt concentrations (0.15 M NaCl) in cell-free assays. CaCl2 and KCl, but not D-glucose, were also effective inhibitors. The catalytic activity of purified human urokinase and of plasmin was unaffected by increased ionic strength. Plasminogen activators secreted both spontaneously and in response to stimulation by the tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate, were inhibited by 0.15 M NaCl. Physiologic salt concentration appeared to function by interacting with plasminogen activator, or plasminogen, and a third component, possibly a reversible inhibitor. One consequence of this regulation of plasminogen activator under physiologic conditions is the limitation of plasminogen-dependent fibrin degradation by living cells.