Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).

The clinical efficacy and tolerability of the topical receptor-selective retinoid tazarotene in the treatment of congenital ichthyoses was investigated. Twelve consecutive patients with different forms of congenital ichthyosis were enrolled in an open, non-randomized, intraindividually controlled, half-side pilot study. Diagnoses were X-linked recessive ichthyosis, non-erythrodermic autosomal recessive lamellar ichthyosis, autosomal dominant ichthyosis vulgaris and ichthyosis bullosa of Siemens (IBS). Tazarotene 0.05% gel was applied unilaterally daily on a defined body area measuring 10% of the body surface area. The contralateral side was treated with an ointment containing 10% urea. After 14 days, application frequency was reduced to three times a week, and stopped after another 2 weeks. The follow-up period was 3 months. Reduction in scaling and roughness was used to assess the clinical response in the tazarotene-treated area compared with the control area. Clinical and laboratory assessments were performed every 14 days during the trial. Unilateral improvement in favour of the tazarotene-treated side was observed in nine of 12 patients (75%). Four patients (33%) achieved an excellent response and four (33%) achieved a good response. No therapeutic effect was seen in patients with IBS. The remission persisted during the reduction phase and after discontinuation for up to 2 months. Local irritation in three patients was the only side-effect detectable. Short-term topical application of tazarotene 0.05% gel is a very effective and well-tolerated treatment modality in different forms of congenital ichthyoses and may be an alternative to systemic retinoid therapy.

Gianotti-Crosti syndrome (GCS) is a distinct exanthematic, acrolocated eruption of childhood caused by a variety of infectious agents. Historically hepatitis B antigen positive (HBsAG+) papular acrodermatitis of childhood and HBsAg negative (HBsAg-) papulovesicular acrolocated syndrome have been distinguished. Here we characterize the spectrum of associated infectious agents in seven patients with confirmed GCS seen in our departments in the years 1994-1995. Where available, stored frozen serum samples were reanalyzed for antiviral antibodies. The mean age of the two girls and five boys was 22.5 months with a range of 8 to 53 months. None of the patients was HBsAG+. Four patients showed serologic evidence of an acute infection and one patient of a recent Epstein-Barr virus (EBV) infection. In two additional children vaccination preceded the appearance of GCS. In these two patients serologic investigations revealed no evidence of recent infection with most common viruses. Our results underline the role of viral infections other than hepatitis B in the etiology of GCS. EBV infection was the most commonly associated viral disease in our population. We agree with other authors that we should avoid using the terms papular acrodermatitis of childhood and papulovesicular acrolocated syndrome in describing HBsAg+ and HBsAg- forms of GCS.

Familial cylindromatosis is an autosomal dominant predisposition to multiple neoplasms of the skin appendages. The susceptibility gene has previously been mapped to chromosome 16q12-q13 and has features of a recessive oncogene/tumour suppressor gene. We have now evaluated 19 families with this disease by a combination of genetic linkage analysis and loss of heterozygosity in cylindromas from affected individuals. All 15 informative families show linkage to this locus, providing no evidence for genetic heterogeneity. Recombinant mapping has placed the gene in an interval of approximately 1 Mb. There is no evidence, between families, of haplotype sharing that might be indicative of common founder mutations.

Liposomes grafted with polymer have long been used in drug delivery applications, and block copolymersomes have emerged as attractive and more robust alternatives for both drug delivery and artificial organelle applications. Hybrid membranes that could combine the respective advantages of fluid lipid and robust polymer bilayers are an attractive and enticing alternative. The properties of membranes in amphiphile vesicles are challenging to study and many applications benefit from surface-based access to the membrane. We therefore explore the self-assembly and mechanical properties of supported hybrid bilayers (SHBs) composed of polybutadiene-block-poly(ethylene oxide) block copolymers and zwitterionic phosphatidylcholine lipids on SiO 2 supports. Quartz crystal microbalance with dissipation monitoring (QCM-D) measurements show that formation of SHB on SiO 2 by vesicle fusion depends on the mass fractions of lipids and block copolymers. Atomic force microscopy was used to study the microscopic mixing of lipids in the SHB to reveal that lipid-phase separation is not observed in SHBs. Force spectroscopy was performed to extract information about thickness and mechanical properties of the hybrid membranes. SHBs are shown to combine the properties of lipid membranes and polymer brushes, and the tip force required to rupture the membrane decreases and the bilayer thickness increases as the block copolymer fraction is increased.

No abstract

No abstract

No abstract