3,378 research outputs found
Independent regulation of P53 stabilisation and activation after Rb deletion in primary epithelial cells
No full textWe have previously reported that deletion of the retinoblastoma gene Rb leads to rapid but transient p53 stabilisation. We investigated here the pathways involved. We show that upon Rb-deletion dysregulated E2F activates p19ARF expression that localises in the nucleoli. There it interacts with MDM2, leading to P53 stabilisation. At the same time, ATR is activated, activating CHK1 that may phosphorylate P53 but also contribute to inhibition of MnSOD expression leading to accumulation of ROS (reactive oxygen species) and subsequent DNA injury, which in turn maintains ATR/CHK1 activated. However, from 72 h after Rb deletion, NPM interacts with P19ARF and concomitantly the interaction between p19ARF and MDM2 decreases leading to a return to P53 degradation. This occurs despite the persistence of the DNA damage response pathways. We therefore observe in primary cells not subjected to exogenous gene expression or exogenous DNA damaging treatment, activation of 2 concomitant pathways of activation of P53 that are dealt with in independent manner: an oncogenic pathway with rapid activation of ARF which is 'switched off' downstream of p19ARF activation after 72 h of induction and a DNA damage response pathway keeping a low level of transcriptionally active P53 sufficient to deal with a physiological elevation of oxidative DNA injury. A possible connection between the two pathways is discussed
Improving the outcome of paediatric orthopaedic trauma: an audit of inpatient management in Southampton
No full textFamilial congenital pseudarthrosis of the ulna
No full textA mother and daughter, both presented with congenital pseudarthrosis of the ulna due to neuro-fibromatosis. The daughter is one of identical twins, the second twin not having a pseudarthrosis. The mother's uncle also had pseudarthrosis of the tibia. This suggests a complex variable genetic inheritance pattern for pseudarthrosis in neurofibromatosis. Despite having had no treatment, the mother had minimal symptoms, minimal deformity, and no radial head dislocation.<br/
Monitoring the treatment of developmental dysplasia of the hip with the Pavlik harness – The role of ultrasound
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Oculoauriculovertebral spectrum: New manifestations
No full textWe present a case of oculoauriculovertebral spectrum (hemifacial microsomia, Goldenhar's syndrome) found shortly after birth with right iliac hypoplasia, absent right public and ischial ossification centres and posterior urethral valves, which have not previously been described in this spectrum.<br/
Observations on the removal of metal implants
No full textA total of 86 adult patients who underwent routine surgery to remove metal internal fixation devices were studied prospectively. At the time of surgery, 46 patients were symptomatic, but only 27 requested surgery; 59 were admitted for routine surgery on medical advice. There was no correlation between symptoms, the length of time the implant had been in situ or the location of the implant. Good results were achieved in 91 per cent of symptomatic patients and no problems occurred in 95 per cent of asymptomatic cases. Overall there was a 3 per cent complication rate including one refracture, one radial nerve injury and one haematoma. No wound infections occurred.Potential difficulties in the removal of implants and possible risks of retained implants are discussed, relating to refracture, osteopenia, metal toxicity and neoplasia. In conclusion, it may be appropriate to leave asymptomatic implants in situ, except for femoral and tibial diaphyseal plates.<br/
Ultrasound screening of hips at risk for CDH. Failure to reduce the incidence of late cases
No full textOf 4,617 babies born in Coventry in 1986, a total of 448 (9.7%) had either clinical abnormality of the hip or at risk factors for CDH. All were examined by ultrasound, but only 17 required treatment (3.7 per 1,000); in five of these no clinical abnormality had been detected. An additional 81 babies had ultrasound abnormalities but did not require treatment, despite the fact that ultrasound at first showed major hip displacement in 17 of them. Three late cases of CDH have presented among the babies born in 1986, but not examined by ultrasound. This incidence of late CDH is unchanged compared with the previous nine years, although ultrasound had detected covert displacement in a number of hips. <br/
Pathological fracture of tibia in patient with corticosteroid-dependent psoriasis treated by functional bracing
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