High level expression of differentially localized BAG-1 isoforms in some oestrogen receptor-positive human breast cancers

Sensitivity to oestrogens and apoptosis are critical determinants of the development and progression of breast cancer and reflect closely linked pathways in breast epithelial cells. For example, induction of BCL-2 oncoprotein expression by oestrogen contributes to suppression of apoptosis and BCL-2 and oestrogen receptor (ER) are frequently co-expressed in tumours. BAG-1/HAP is a multifunctional protein which complexes with BCL-2 and steroid hormone receptors (including the ER), and can suppress apoptosis and influence steroid hormone-dependent transcription. Therefore, analysis of expression of BAG-1 in human breast cancer is of considerable interest. BAG-1 was readily detected by immunostaining in normal breast epithelial cells and most ER-positive tumours, but was undetectable or weakly expressed in ER-negative tumours. BAG-1 positive cells showed a predominantly cytoplasmic or cytoplasmic plus nuclear distribution of staining. A correlation between ER and BAG-1 was also evident in breast cancer derived cell lines, as all lines examined with functional ER expression also expressed high levels of BAG-1. In addition to the prototypical 36 kDa BAG-1 isoform, breast cancer cells expressed higher molecular weight isoforms and, in contrast to BCL-2, BAG-1 expression was independent of oestrogens. BAG-1 isoforms were differentially localized to the nucleus or cytoplasm and this was also independent of oestrogens. These results demonstrate a close association between BAG-1 and functional ER expression and suggest BAG-1 may be useful as a therapeutic target or prognostic marker in breast cancer. © 1999 Cancer Research Campaig

HLA B27 allele types in homogeneous groups of juvenile idiopathic arthritis patients in Latvia

Juvenile idiopathic arthritis (JIA) is a heterogeneous condition and therapeutic strategies vary in different JIA types. The routinely accepted practice to start with Sulphasalazine (SS) as the first line treatment in patients with HLA B27 positive JIA proves to be ineffective in a large proportion of children

Chemical drinking water quality in Ghana : water costs and scope for advanced treatment

To reduce child mortality and improve health in Ghana boreholes and wells are being installed across the country by the private sector, NGO's and the Ghanaian government. Water quality is not generally monitored once a water source has been improved. Water supplies were sampled across Ghana from mostly boreholes, wells and rivers as well as some piped water from the different regions and analysed for the chemical quality. Chemical water quality was found to exceed the WHO guidelines in 38% of samples, while pH varied from 3.7 to 8.9. Excess levels of nitrate (NO3−) were found in 21% of the samples, manganese (Mn) and fluoride (F−) in 11% and 6.7%, respectively. Heavy metals such as lead (Pb), arsenic (As) and uranium (U) were localised to mining areas. Elements without health based guideline values such as aluminium (Al, 95%) and chloride (Cl, 5.7%) were found above the provisional guideline value. Economic information was gathered to identify water costs and ability to pay. Capital costs of wells and boreholes are about £1200 and £3800 respectively. The majority of installation costs are generally paid by the government or NGO's, while the maintenance is expected to be covered by the community. At least 58% of the communities had a water payment system in place, either an annual fee/one-off fee or “pay-as-you-fetch”. The annual fee was between £0.3–21, while the boreholes had a water collection fee of £0.07–0.7/m3, many wells were free. Interestingly, the most expensive water (£2.9–3.5/m3) was brought by truck. Many groundwater sources were not used due to poor chemical water quality. Considering the cost of unsuccessful borehole development, the potential for integrating suitable water treatment into the capital and maintenance costs of water sources is discussed. Additionally, many sources were not in use due to lack of water capacity, equipment malfunction or lack of economic resources to repair and maintain equipment. Those issues need to be addressed in combination with water quality, coordinated water supply provision and possible treatment to ensure sustainability of improved water resources

BAG-1 expression and function in human cancer

BAG-1 is a multifunctional protein that interacts with a wide range of target molecules to regulate apoptosis, proliferation, transcription, metastasis and motility. Interaction with chaperone molecules may mediate many of the effects of BAG-1. The pathways regulated by BAG-1 play key roles in the development and progression of cancer and determining response to therapy, and there has been considerable interest in determining the clinical significance of BAG-1 expression in malignant cells. There is an emerging picture that BAG-1 expression is frequently altered in a range of human cancers relative to normal cells and a recent report suggests the exciting possibility that BAG-1 expression may have clinical utility as a prognostic marker in early breast cancer. However, other studies of BAG-1 expression in breast cancer and other cancer types have yielded differing results. It is important to view these findings in the context of current knowledge of BAG-1 expression and function. This review summarises recent progress in understanding the clinical significance of BAG-1 expression in cancer in light of our understanding of BAG-1 function