Summary. Myelodysplastic syndrome (MDS) is considered to be very rare in children. However, the only two published population-based studies reported widely divergent incidence ®gures. To further explore the epidemiology of childhood MDS and to evaluate the accuracy of cancer registry and treatment trial data, we conducted a population-based study of children aged 0±14 years in British Columbia (BC), Canada, between 1982 and 1996. MDS was diagnosed in 31 cases corresponding to an annual incidence of 3´2 per million children or 6% of all leukaemias, compared with an incidence of 6´0/million for acute myeloid leukaemia (AML), and of 0´5/million for chronic myeloid leukaemia. There was a non-signi®cant (P 0´19) trend toward an increase in MDS incidence with time, the increase was partly explained by an increasing number of patients with Down syndrome. Associated abnormalities were found in 48% of the MDS cases with Down syndrome as the most common (seven cases). Only one third of the MDS cases were correctly registered in the Cancer Registry and less than half of the eligible MDS patients were enrolled on a cooperative group study. Data on MDS from treatment-based studies and cancer registries were inaccurate and seemed to signi®cantly underestimate the incidence of MDS in children.
Complement receptor 3 (CR3) mediates both opsonic and nonopsonic phagocytosis of bacteria. Leukocyte adhesion deficiency (LAD) allows for the study of CR3-dependent phagocyte-bacterial ingestion, since LAD phagocytes do not express this receptor. Phagocytes from an infant with LAD were unable to ingest 50% of the Pseudomonas aeruginosa strains studied, which indicates a requirement for CR3. However, the remaining strains were phagocytosed in the absence of CR3, and ingestion was blocked by monoclonal antibodies directed at CD14. This CR3/CD14 receptor bias was further confirmed by using thioglycollate-elicited murine peritoneal macrophages, which have nonfunctional CR3 before activation. Results indicate that either CR3 or CD14 is involved independently in nonopsonic phagocytosis of different P. aeruginosa strains. Clearance of P. aeruginosa from the endobronchial space may be facilitated by nonopsonic phagocytosis, since low levels of opsonins are present. The impact of lung infection with P. aeruginosa may be determined, in part, by the phagocytic receptor that mediates ingestion.
Alloimmunization and platelet refractoriness occur in pediatric oncology and bone marrow transplant patients, but the incidence--particularly in children with acute myelogenous leukemia--appears to be low. The detection of LCTAbs predicts a poor response to random-donor platelet transfusion, but most such patients show improved CCIs with HLA-matched platelets. Routine use of white cell-reduction filters has thus far failed to eliminate alloimmunization in children requiring prolonged blood component support.
Inactivation of the tumor suppressor gene PTEN and overexpression of VEGF are two of the most common events observed in high‐grade malignant gliomas. The purpose of this study was to determine whether PTEN controls VEGF expression in gliomas under normoxic conditions. Transfer of PTEN to human glioma cells resulted in the transduction of a functional PTEN protein as evidenced by the upregulation of p27 and modification of the phosphorylation status of Akt. Under normoxic conditions, enzyme‐linked immunosorbent assay and Northern blot analyses showed downregulation of VEGF in PTEN‐treated cells. Moreover, conditioned media from PTEN‐treated glioma cells significantly diminished the ability of endothelial cells to grow and migrate. Western blot assays demonstrated that, in a normoxic environment, PTEN downregulates HIF‐1α. Finally, promoter activity assays showed that the VEGF promoter region containing the HIF‐1α binding site is necessary and sufficient for PTEN‐mediated downregulation of VEGF. Experiments with PI3‐K inhibitors and kinase assays suggested that PI3‐K is mediating the effect of PTEN on VEGF, and not the p42/p48 or p38 MAP kinases. These results indicate that restoration of PTEN function in gliomas may induce therapeutic effect by downregulating VEGF. Furthermore, this close functional relationship between PTEN and VEGF suggests that a better understanding of the transduction signal regulated by PTEN might enhance the knowledge of the cause and physiology of vascular and inflammatory diseases. Ann Neurol 2003
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