Irritant resiniferonol derivatives from EgyptianThymelaea hirsuta L.

Summary Two new aromatic derivatives of 5, 12-dihydroxy-6, 7-epoxy-resiniferonol were isolated from the leaves and twigs ofThymelea hirsuta L. (fam. Thymelaeaceae). These compounds were assigned the structures 12-O-cinnamoyl-5-hydroxy-6, 7-epoxyresiniferonol-9, 13, 14-ortho benzoate 1 and 12-O-heptadecenoyl-5-hydroxy-6, 7,-epoxy-resiniferonol-9, 13, 14-ortho benzoate 2. Both compounds induced erythema of mouse ears in a dose of 0.1 g per ear.Acknowledgments. S. Ismail and M. El-Missiry are grateful to the Royal Society for a travel and support grant.     

Constituents of Egyptian Euphorbiaceae. IX. Irritant and cytotoxic ingenane esters fromEuphorbia paralias L.

Summary The irritant and cytotoxic constituents of the latex ofEuphorbia paralias L. were separated from the hydrocarbon fraction by means of solvent partition. 3 new ingenane esters were identified from the toxic ether fraction. The major compound was 3-angelyl-20-deoxyingenol and the 2 minor compounds were 3-hexanoyl-20-deoxyingenol and 3-angelylingenol. These compounds were of a similar potency to podophyllin in the inhibition of³H-thymidine uptake by TLX/5 mouse lymphoma cells. In addition the compounds produced a persistent erythema of the mouse ear in sub-microgram doses.Acknowledgments. F.J. Evans is grateful to the Royal Society for a travel grant.     

Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and a cardiomyopathy with conduction blocks which is life-threatening. Two modes of inheritance exist, X-linked (OMIM 310300) and autosomal dominant (EDMD-AD; OMIM 181350). EDMD-AD is clinically identical to the X-linked forms of the disease. Mutations in EMD, the gene encoding emerin, are responsible for the X-linked form. We have mapped the locus for EDMD-AD to an 8-cM interval on chromosome 1q11-q23 in a large French pedigree, and found that the EMD phenotype in four other small families was potentially linked to this locus. This region contains the lamin A/C gene (LMNA), a candidate gene encoding two proteins of the nuclear lamina, lamins A and C, produced by alternative splicing. We identified four mutations in LMNA that co-segregate with the disease phenotype in the five families: one nonsense mutation and three missense mutations. These results are the first identification of mutations in a component of the nuclear lamina as a cause of inherited muscle disorder. Together with mutations in EMD (refs 5,6), they underscore the potential importance of the nuclear envelope components in the pathogenesis of neuromuscular disorders.     

Identification of Alexandrin

Zusammenfassung Die als Alexandrin beschriebene Substanz, die als Bestandteil vonCentaurea alexandrina isoliert worden ist, wurde als -sitosterol--d-glukosid identifiziert.     

Perlecan, the major proteoglycan of basement membranes, is altered in patients with Schwartz-Jampel syndrome (chondrodystrophic myotonia)

Schwartz-Jampel syndrome (SJS1) is a rare autosomal recessive disorder characterized by permanent myotonia (prolonged failure of muscle relaxation) and skeletal dysplasia, resulting in reduced stature, kyphoscoliosis, bowing of the diaphyses and irregular epiphyses. Electromyographic investigations reveal repetitive muscle discharges, which may originate from both neurogenic and myogenic alterations. We previously localized the SJS1 locus to chromosome 1p34-p36.1 and found no evidence of genetic heterogeneity. Here we describe mutations, including missense and splicing mutations, of the gene encoding perlecan (HSPG2) in three SJS1 families. In so doing, we have identified the first human mutations in HSPG2, which underscore the importance of perlecan not only in maintaining cartilage integrity but also in regulating muscle excitability.