Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

The ground water behaviour pattern and foundation stabilisation practice at hartebeestfontein

Hartebeestfontein Gold Mining Company Limited, which produces 100 kg of gold per working day, has a mining lease area situated mainly over dolomite. A major river nearby governs the regional drainage. The formation of sinkholes and dolines, caused by fluctuations in the water table and the flow of water underground, often accelerated as the result of unavoidable or inadvertent surface activities, is common in such terranes. To maintain production, meticlous ground investigations under new installations plus periodic re-examination and stabilisation under existing ones, particularly key installations, is necessary. The local ground water behaviour pattern is controlled by three impervious major dykes and two major fissure zones, the latter draining surface water into the mine workings. Monthly water table measurements over 25 years show a steady rise to a limit over the area of one fissure zone and a drastic lowering over the other. The value of gravity techniques and thermal infra-red line scanning for cavity detection in the Hartebeestfontein context, is discussed. The procedures followed, for stabilising ground and foundations, are illustrated by means of case histories. The extension of the techniques, learnt from the stabilisation experience, to limiting water seepage into shafts sunk through dolomite, is also discussed.     

System Operational Evaluation of Mine Monitoring Systems

In the testing of mine monitoring systems, a software package was developed for the mine monitoring test facility designed at West Virginia University. The software establishes delay times of sensor input to annunciation for single alarms and multiple simultaneous alarms. The alarm measurement techniques for the test fixture are described, as is the software developed to analyze and graph monitoring system response data. Also included is the analysis capability of the facility, the criteria for evaluating mine monitoring systems, and typical test data from a sample system.     

COPD: using nutrition to prevent respiratory function decline

Close to three-fourths of patients with chronic obstructive pulmonary disease (COPD) suffer from weight loss. Identifying a single cause for this is difficult, as several factors-including chronic mouth breathing, dyspnea, aerophagia, certain medications, and depression-often act in concert. Malnutrition can exacerbate symptoms of COPD by decreasing ventilatory muscle strength, exercise tolerance, and immunocompetence, and by increasing the risk of depression and anxiety. Goals of nutrition intervention are to prevent or reverse malnutrition without worsening the disease process and to improve respiratory function, thereby reducing morbidity and delaying mortality. Recommendations for intake of fats, carbohydrates, protein, and water must be individualized.