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Vascular access for renal dialysis is a lifeline for about 120 000 individuals in the United States. Stethoscope auscultation of vascular sounds has some utility in the assessment of access patency, yet can be highly skill-dependent. The objective of the study was to identify acoustic parameters that are related to changes in vascular access patency. The underlying hypothesis is that stenoses of haemodialysis access vessels or grafts cause vascular sound changes that are detectable using computerised data acquisition and analysis. Eleven patients participated in the study. Their vascular sounds were recorded before and after angiography, which was accompanied by angioplasty in most patients. The sounds were acquired using two electronic stethoscopes and then digitised and analysed on a personal computer. Vessel stenosis changes were found to be associated with changes in acoustic amplitude and/or spectral energy distribution. Certain acoustic parameters correlated well (correlation coefficient = 0.98, p < 0.0001) with the change in the degree of stenosis, suggesting that stenosis severity may be predictable from these parameters. Parameters also appeared to be sensitive to modest diameter changes (> 20%), (p < 0.005, Wilcoxon rank sum test). These results suggest that computerised analysis of vascular sounds may be useful in vessel patency surveillance. Further testing using longitudinal studies may be warranted. [ABSTRACT FROM AUTHOR]

Oestrogen receptor alpha (ERalpha) is an oestrogen-activated transcription factor, which regulates proliferation and differentiation of mammary epithelial cells by activating or repressing gene expression. ERalpha is a critical prognostic indicator and a therapeutic target for breast cancer. Patients with tumours that express higher level of ERalpha have better prognosis than patients with tumours that are ERalpha negative or express lower level of ERalpha. Better prognosis in ERalpha-positive patients is believed to be due to repression of proinvasive gene expression by ERalpha. Oestrogen receptor alpha represses gene expression by transrepressing the activity of the transcription factors such as nuclear factor-kappaB or by inducing the expression of transcriptional suppressors such as MTA3. In this report, we show that ERalpha transrepresses the expression of the proinvasive gene interleukin 6 (IL-6) in ERalpha-negative MDA-MB-231 breast cancer cells stably overexpressing ERalpha. Using these cells as well as ERalpha-positive MCF-7 and ZR-75-1 cells, we show that tumour necrosis factor alpha (TNFalpha) and the phosphatidylinositol-3-kinase (PI3-kinase) modulate transrepression function of ERalpha by reducing its stability. From these results, we propose that TNFalpha expression or PI3-kinase activation lead to reduced levels of ERalpha protein in cancer cells and corresponding loss of transrepression function and acquisition of an invasive phenotype. [ABSTRACT FROM AUTHOR]

The t(10;11)(p13;q14-21) is a non-random translocation described in acute lymphoblastic and myeloid leukaemias. It results in the fusion of the gene CALM, which encodes a clathrin assembly protein, on 11q14 to the gene AF10, a putative transcription factor on 10p13. Here we describe for the first time, the occurrence of a CALM-AF10 fusion in a case of acute megakaryoblastic leukaemia. Fluorescence in situ hybridisation and reverse transcriptase polymerase chain reaction were used to confirm the presence of a CALM-AF10 fusion. A novel splice variant of CALM missing nt 1927-2091 was also detected. Though CALM is a cytoplasmic protein, the chimaeric fusion product is able to localise to both the nucleus and cytoplasm. Analysis of the fusion variants suggests, however, that the critical fusion product is likely to be cytoplasmic and contain the interactive leucine zipper of AF10. [ABSTRACT FROM AUTHOR]

Chimaeric fusion genes created by nonrandom chromosomal translocations are characteristic of childhood acute lymphoblastic (ALL) and myeloid (AML) leukaemias. Although the mechanisms leading to these chromosomal rearrangements are unclear, careful analysis of the primary genomic fusion sequence has suggested a number of possible mechanisms. These include, aberrant VDJ recombinase activity, topoisomerase II-mediated breakage followed by erroneous end joining, illegitimate recombination mediated by repetitive DNA sequences, proteins that bind to specific DNA binding sites and errors in nonhomologous end joining following double-stranded DNA breaks. Fusions detected to date include the MLL-AF4 fusion in infantile ALL, the TEL-AML1 in childhood ALL and the AML1-ETO and MLL-CALM in childhood AML. While events leading to the formation of chimaeric fusion genes occur in utero, only a few develop clinically overt leukaemia at a later date in early childhood. This suggests that additional postnatal genetic hits are required in preleukaemic cells. Murine models of TEL-AML1 and AML1-ETO support this hypothesis, as the transgenes are insufficient themselves to induce leukaemia.