Glass Abuse and Urban Licensed Premises

Burge in her recent review (November 1989 JRSM, p 673) postulates that abnormal protease activity may contribute to altered cell proliferation, differentiation and keratinization in Darier's disease. This seems highly plausible, especially if one looks at the abnormalities of cell proliferation and differentiation that exist in a disease where abnormal protease activity has definitely been identified. For example, in recessive dystrophic epidermolysis bullosa (RDEB), where we know that production of collagenase, serine protease and cysteine protease is abnormal', there is a recognized tendency to neoplasiawith squamous cell carcinoma found in affected areas. Also, evidence that controlling protease activity can greatly modify the extent of skin disease in RDEB adds further weight to her argument. For example, RDEB collagenase is much more thermolabile at low calcium concentrations than in normals", and levels of this protease are greatly increased. Reducing calcium levels controls collagenase activity! and, in RDEB, calcium chelators appear to halve blistering", and calcium channel agents have dramatically improved dysphagia", Keratinocyte proliferation can also be inhibited by attenuating calcium activity, this time by antagonizing the intracellular calcium receptor calmodulin (CaMf. It is hard to assess whether proteases are involved here because CaM has a direct cell cycle effect", CaM is also linked to DNA repair and DNA polymerase-o" and dysfunction here could explain the increased risk of dermal malignancy in RDEB. Cysteine protease, also calcium dependent, is also crucial to the dynamic organization of cell structure''; processing proteins in cell membranes, cytoskeleton and microtubules. Thus, protease abnormalities could well explain the altered cell dynamics in Darier's disease and this merits further clinical investigation. D P MACLEOD 94 Woodwarde Road,