ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response.

Nijmegen breakage syndrome (NBS) is characterized by extreme radiation sensitivity, chromosomal instability and cancer. The phenotypes are similar to those of ataxia telangiectasia mutated (ATM) disease, where there is a deficiency in a protein kinase that is activated by DNA damage, indicating that the Nbs and Atm proteins may participate in common pathways. Here we report that Nbs is specifically phosphorylated in response to gamma-radiation, ultraviolet light and exposure to hydroxyurea. Phosphorylation of Nbs mediated by gamma-radiation, but not that induced by hydroxyurea or ultraviolet light, was markedly reduced in ATM cells. In vivo, Nbs was phosphorylated on many serine residues, of which S343, S397 and S615 were phosphorylated by Atm in vitro. At least two of these sites were underphosphorylated in ATM cells. Inactivation of these serines by mutation partially abrogated Atm-dependent phosphorylation. Reconstituting NBS cells with a mutant form of Nbs that cannot be phosphorylated at selected, ATM-dependent serine residues led to a specific reduction in clonogenic survival after gamma-radiation. Thus, phosphorylation of Nbs by Atm is critical for certain responses of human cells to DNA damage.

Tardy displacement of traumatic radial head dislocation in childhood.

The diagnosis of traumatic dislocation of the radial head, either isolated or as part of a Monteggia fracture-dislocation, was delayed in 10 of the 110 children treated with these injuries during the study period. In eight children, the dislocation was overlooked on the initial radiographs. In two children, the radial head was reduced on the initial elbow radiographs, but it was dislocated 10 days later in one child and 21 days later in the other. The most likely explanation is that the radial head dislocated at the time of impact, spontaneously reduced by the time the first radiographs were obtained, and redislocated while the arm was in a cast. We conclude that radiographic assessments of the radiocapitellar joint, by using the radiocapitellar line, are required in children with elbow and forearm injuries at presentation and when the cast is removed.

Investigation of a hydroxyapatite and calcium sulfate composite supplemented with an osteoinductive factor.

In the search for a suitable bone graft substitute, a study was conducted using a material that combined a proven osteoconductive composite, hydroxyapatite-calcium sulfate (HA/CS), with an osteoinductive factor, bovine osteogenic factor (OF). The initial study demonstrated the osteoinductive potential of OF in the rabbit muscle model. Once satisfied that the OF was active, it was added to the HA/CS composite and placed in 8-mm trephine defects in the rabbit cranium. This HA/CS/OF was directly compared to HA/CS augmented with a control protein, rabbit serum albumin (RSA). Animals were sacrificed at 4 and 8 weeks. Results demonstrated increased bone formation with the addition of the OF to the composite with bridging of the defects, in most cases, by 4 weeks. No bridging was seen, at this time period, in the other defects left unfilled or filled with HA/CS/RSA. Osteogenic factor, with the appropriate delivery system, can induce bone formation in the rabbit muscle. It may also increase the rate of bone formation at early time periods in a bony defect site when the delivery system is the osteoconductive composite HA/CS.