On the association between glioma,wireless phones,heredity and ionising radiation

We performed two case–control studies on brain tumours diagnosed during 1 January 1997 to 30 June 2000 and 1 July 2000 to 31 December 2003, respectively. Living cases and controls aged 20–80 years were included. An additional study was performed on deceased cases with a malignant brain tumour using deceased controls. Pooled results for glioma yielded for ipsilateral use of mobile phone odds ratio (OR) = 2.9, 95% confidence interval (CI) = 1.8–4.7 in the >10 years latency group. The corresponding result for cordless phone was OR = 3.8, 95% CI = 1.8–8.1. OR increased statistically significant for cumulative use of wireless phones per 100 h and per year of latency. For high-grade glioma ipsilateral use of mobile phone gave OR = 3.9, 95% CI = 2.3–6.6 and cordless phone OR = 5.5, 95% CI = 2.3–13 in the >10 years latency group. Heredity for brain tumour gave OR = 3.4, 95% CI = 2.1–5.5 for glioma. There was no interaction with use of wireless phones. X-ray investigation of the head gave overall OR = 1.3, 95% CI = 1.1–1.7 for glioma without interaction with use of wireless phones or heredity. In conclusion use of mobile and cordless phone increased the risk for glioma with highest OR for ipsilateral use, latency >10 years and third tertile of cumulative use in hours. In total, the risk was highest in the age group <20 years for first use of a wireless phone.     

Evidence for a functional association between phosphatidylinositol 3-kinase and c-src in the spreading response of osteoclasts to colony-stimulating factor-1

Osteoclasts are bone-resorbing cells whose normal function depends in part upon their ability to migrate over the bone surface to initiate new sites of bone resorption. The growth factor/cytokine, colony-stimulating factor-1 (CSF-1), potently stimulates osteoclast motility, in a c-src-dependent fashion. The intracellular signaling molecules that participate with c-src in CSF-1-induced remodeling of the osteoclast cytoskeleton have not been identified. Here we demonstrate, using the inhibitors wortmannin and LY294002, that activation of phosphatidylinositol 3-kinase (PI3-K) is required for CSF-1-induced spreading in osteoclasts. After CSF-1 treatment of osteoclast-like cells, PI3-K activity associated with the CSF-1 receptor c-fms, is increased, and the 85-kDa regulatory subunit of PI3-K and c-src coimmunoprecipitate. CSF-1 induces redistribution of PI3-K to the periphery of the cell. The association between p85 and c-src is due in part to a direct interaction between the proline-rich sequences of p85 and the SH3 domain of c-src. In vitro, the c-src SH3 domain stimulates PI3-K activity. Taken together, the current data suggest that c-src, via its SH3 domain, may participate in CSF-1-induced activation of PI3-K and that PI3-K and c-src are in the signaling pathway that subserves CSF-1-induced cytoskeletal changes in osteoclasts.     

Modulation of mouse and human phenobarbital-responsive enhancer module by nuclear receptors

The constitutive androstane receptor (CAR) regulates mouse and human CYP2B genes through binding to the direct repeat-4 (DR4) motifs present in the phenobarbital-responsive enhancer module (PBREM). The preference of PBREM elements for nuclear receptors and the extent of cross-talk between CAR and other nuclear receptors are currently unknown. Our transient transfection and DNA binding experiments indicate that binding to DR4 motifs does not correlate with the activation response and that mouse and human PBREM are efficiently 'insulated' from the effects of other nuclear receptors despite their substantial affinity for DR4 motifs. Certain nuclear receptors that do not bind to DR4 motifs, such as peroxisome proliferator-activated receptor-alpha and farnesoid X receptor, can suppress PBREM function via a coactivator-dependent process that may have relevance in vivo. In competition experiments, mouse PBREM is clearly more selective for CAR than human PBREM. Pregnane X, vitamin D, and thyroid hormone receptors can potentially compete with human CAR on human PBREM. In contrast to the selective nature of PBREM, CYP3A enhancers are highly and comparably responsive to CAR, pregnane X receptor, and vitamin D receptor. In addition, the ligand specificities of human and mouse CAR were defined by mammalian cotransfection and yeast two-hybrid techniques. Our results provide new mechanistic explanations to several previously unresolved aspects of CYP2B and CYP3A gene regulation.     

Everyday functioning in young children with cerebral palsy: functional skills,caregiver assistance,and modifications of the environment

Everyday functioning is described in 95 children with cerebral palsy (CP; 55 males and 40 females; mean age 58 months, SD 18 months, range 25 to 87 months) using the three scales of the Pediatric Evaluation of Disability Inventory (PEDI): Functional Skills, Caregiver Assistance, and Modifications of the Environment. Types of CP in the children were hemiplegia, (n=19), spastic/ataxic diplegia, (n=44), spastic quadriplegia, (n=16), dyskinetic, (n=9), and mixed (n=7). Symptoms were grouped by severity according to the Gross Motor Function Classification System (GMFCS): 23% were classified at level I, 21% at level II, 10% at level III, 23% at level IV, and 23% level V. A large variability in functioning in mobility, self-care, and social function was seen because of the heterogeneity of children with CP. Limitations in achievement of activities, need for assistance, and use of assistive devices increased progressively with GMFCS level. Furthermore, these children differed to a great extent from the normative sample of the PEDI. Stepwise regression analysis showed that the GMFCS was a good predictor of everyday functioning with age and learning problems as significantly contributing factors, particularly in self-care and social function. In conclusion, the three scales of the PEDI represent different but strongly related aspects of everyday functioning in young children with CP.