In vivo analysis of functional domains from villin and gelsolin.

Transfected CV1 cells were used to compare the in vivo effects of various domains of villin and gelsolin. These two homologous actin modulating proteins both contain a duplicated severin-like sequence. Villin has in addition a carboxy-terminal domain, the headpiece, which accounts for its bundling activity. The effects of the villin-deleted mutants were compared with those of native villin. Our results show that essential domains of villin required to induce the growth of microvilli and F-actin redistribution are present in the first half of the core and in the headpiece. We also show that the second half of the villin core cannot be exchanged by its homolog in gelsolin. When expressed at high levels of CV1 cells, full length gelsolin completely disrupted stress fibers without change of the cell shape. Addition of the villin headpiece to gelsolin had no effect on the phenotype induced by gelsolin alone. Expression of the first half of gelsolin induced similar modifications as capping proteins and rapid cell mortality; this deleterious effect on the cell structure was also observed when the headpiece was linked to the first half of gelsolin. In cells expressing the second half of gelsolin, a dotted F-actin staining was often seen. Moreover elongated dorsal F-actin structures were observed when the headpiece was linked to the second gelsolin domain. These studies illustrate the patent in vivo severing activity of gelsolin as well as the distinct functional properties of villin core in contrast to gelsolin

Operative treatment of severe scoliosis in osteogenesis imperfecta: results of 20 patients after halo traction and posterior spondylodesis with instrumentation

Correction and stabilisation of the scoliotic spine in osteogenesis imperfecta is difficult. The optimal technique has yet to be determined, since no large series in which a single procedure has been carried out by a single surgeon using a single protocol has yet been described. The charts of 20 patients with osteogenesis imperfecta who had undergone halo gravity traction (HGT) and a posterior spondylodesis with Cotrel-Dubousset (n = 18) or Harrington (n = 2) instrumentation were reviewed. No correction was made at the time of the surgical spondylodesis. The average follow-up was 4.8 years (range 2-10.5 years). The preoperative traction improved the Cobb angle of the scoliosis by 32% (from a mean of 78.5 degrees to a mean of 53.3 degrees) and improved the kyphosis by 24% (from a mean of 56.0 degrees to mean of 42.5 degrees). This correction deteriorated slightly at final follow-up, for both the scoliosis and the kyphosis (mean 57.6 degrees and 44.4 degrees respectively). Few complications were encountered during the HGT period. In 16 cases no complications occurred during the follow-up period. Ambulation and functional ability were upgraded for 7 of 20 patient

An actin-binding site containing a conserved motif of charged amino acid residues is essential for the morphogenic effect of villin.

The actin-binding protein villin induces microvillus growth and reorganization of the cytoskeleton in cells that do not normally produce this protein. Transfection of mutagenized villin cDNAs into CV-1 cells was used to show that a conserved, COOH-terminally located cluster of charged amino acid residues (KKEK) is crucial for the morphogenic activity of villin in vivo. In vitro experiments with a 22 amino acid synthetic peptide corresponding to this region of villin provide evidence that this motif is part of an F-actin-binding site that induces G-actin to polymerize. Chemical cross-linking of actin to this peptide, the effects of amino acid substitutions in peptides, and the behavior of villin variants further corroborate the participation of the KKEK sequence in actin contacts

Le devenir des enfants opérés d'allongement pour hypoplasie congénitale des membres inférieurs. [The fate of children undergoing bone lengthening in congenital hypoplasia of the legs]

This retrospective study was conducted on 26 patients, 14 women and 12 men whose average inequality prognosis was 8.5 cm. They have been reviewed after they were more than 20 years old (mean 23.8 y). Between 1962 and 1979 these 26 patients have had 38 lengthening procedures with various methods. The results were evaluated after clinical examination and X-rays. The average radiological discrepancy was 1.5 cm at the follow-up. On the X-rays, the deterioration was rare for the hip point, more frequent for the knee and very frequent for the ankle and the foot. If the socio-professional integration was satisfactory, many problems remained unsolved at the review. The matter was the aspect of the lengthened limb considered as unesthetic and ugly by 22 patients. 20 of the 26 patients had problems to put on shoes. On the other hand two patients out of three had a relative intolerance to effort, cutaneous troubles probably in conjunction with vascular and trophic insufficiency with many concern for the future