Enhanced sensitivity to rapamycin following long-term oestrogen deprivation in MCF-7, T-47-D and ZR-75-1 human breast cancer cells

Human breast cancer cells (MCF-7, T-47-D and ZR-75-1) can adapt to circumvent any reduced growth rate during long-term oestrogen deprivation, and this provides three model systems to investigate mechanisms of endocrine resistance in breast cancer. In this paper we report consistent differences in the effects of three growth inhibitors following long-term oestrogen deprivation in all three cell models. Long-term oestrogen deprivation of MCF-7, T-47-D and ZR-75-1 cells resulted in reduced growth inhibition by PD98059 (2–10 µg/ml), implying a loss of dependence on mitogen-activated protein kinase pathways for growth. The growth inhibitor LY294002 (2–10 µM) inhibited growth of both oestrogen-maintained and oestrogen-deprived cells with similar dose–responses, implying continued similar dependence on phosphoinositide 3-kinase (PI3K) pathways with no alteration after adaptation to oestrogen independent growth. However, by contrast, long-term oestrogen deprivation resulted in an increased sensitivity to growth inhibition by rapamycin, which was not reduced by readdition of oestradiol. The enhanced inhibition of long-term oestrogen-deprived MCF-7-ED, T-47-D-ED and ZR-75-1-ED cell growth by combining rapamycin with LY294002 at concentrations where each alone had little effect, offers preclinical support to the development of therapeutic combinations of rapamycin analogues with other PI3K inhibitors in endocrine-resistant breast cancer.

RNA interference suppression of genes in glycosyl transferase families 43 and 47 in wheat starchy endosperm causes large decreases in arabinoxylan content

The cell walls of wheat (Triticum aestivum) starchy endosperm are dominated by arabinoxylan (AX), accounting for 65% to 70% of the polysaccharide content. Genes within two glycosyl transferase (GT) families, GT43 (IRREGULAR XYLEM9 [IRX9] and IRX14) and GT47 (IRX10), have previously been shown to be involved in the synthesis of the xylan backbone in Arabidopsis, and close homologs of these have been implicated in the synthesis of xylan in other species. Here, homologs of IRX10 TaGT47_2 and IRX9 TaGT43_2, which are highly expressed in wheat starchy endosperm cells, were suppressed by RNA interference (RNAi) constructs driven by a starchy endosperm-specific promoter. The total amount of AX was decreased by 40% to 50% and the degree of arabinosylation was increased by 25% to 30% in transgenic lines carrying either of the transgenes. The cell walls of starchy endosperm in sections of grain from TaGT43_2 and TaGT47_2 RNAi transgenics showed decreased immunolabeling for xylan and arabinoxylan epitopes and approximately 50% decreased cell wall thickness compared with controls. The proportion of AX that was water soluble was not significantly affected, but average AX polymer chain length was decreased in both TaGT43_2 and TaGT47_2 RNAi transgenics. However, the long AX chains seen in controls were absent in TaGT43_2 RNAi transgenics but still present in TaGT47_2 RNAi transgenics. The results support an emerging picture of IRX9-like and IRX10-like proteins acting as key components in the xylan synthesis machinery in both dicots and grasses. Since AX is the main component of dietary fiber in wheat foods, the TaGT43_2 and TaGT47_2 genes are of major importance to human nutrition.

Histopathology and laser autofluorescence of ischemic kidneys of rats

The purpose of this research was to evaluate the severity of renal ischemia/reperfusion injury as determined by histology and by laser-induced fluorescence (LIF) with excitation wavelengths of 442 nm and 532 nm. Wistar rats (four groups of six animals) were subjected to left renal warm ischemia for 20, 40, 60 and 80 min followed by 10 min of reperfusion. Autofluorescence was determined before ischemia (control) and then every 5-10 min thereafter. Tissue samples for histology were harvested from the right kidney (control) and from the left kidney after reperfusion. LIF and ischemia time showed a significant correlation (p < 0.0001 and r (2)=0.47, and p=0.006 and r (2)=0.25, respectively, for the excitation wavelengths of 442 nm and 532 nm). Histological scores showed a good correlation with ischemia time (p < 0.0001). The correlations between optical spectroscopy values and histological damage were: LIF at 442 nm p < 0.0001, LIF at 532 nm p=0.001; IFF (peak of back scattered light/LIF) at 442 nm p > 0.05, and IFF at 532 nm p > 0.05. After reperfusion LIF tended to return to preischemic basal levels which occurred in the presence of histological damage. This suggests that factors other than morphological alterations may have a more relevant effect on changes observed in LIF. In conclusion, renal ischemia/reperfusion changed tissue fluorescence induced by laser. The excitation light of 442 nm showed a better correlation with the ischemia time and with the severity of tissue injury.

Energy, protein, calcium, vitamin D and fibre intakes from meals in residential care establishments in Australia

Residents from high level (nursing homes) and low-level care facilities (hostel) being served the three common diet texture modifications (full diet, soft-minced diet and pureed diet) were assessed. Individual plate waste was estimated at three meals on one day. Fifty-six males and 156 females, mean age 82.9+/-9.5 (SD) years, of which 139 lived in nursing homes (NH) and 76 in hostels (H) were included. Mean total energy served from meals was 5.3 MJ/day, 5.1 to 5.6 MJ/day, 95% confidence intervals (CI), in NH which was less than in H, 5.9 MJ/day (CI 5.6 to 6.2 MJ/day) (P=0.007). Protein and calcium intakes were lower in NH, 44.5g (CI 41.5 to 47.5g), 359.0mg (CI 333.2 to 384.8mg), versus 50.5g (CI 46.6 to 54.3g), 480.5mg (CI 444.3 to 516.7mg) in H (P=0.017, P<0.001 respectively). There was no difference in nutrient/energy ratios, except for protein/energy, which was higher in NH 11.7 (CI 11.3 to 12.2) than in H 9.8 (CI 9.4 to 10.3) (P<0.001). Ability to self-feed had no significant effect on nutrient intakes in NH. The self fed group (N=63) had the following nutrient intakes: energy 4.0 MJ (CI 3.6 to 4.3 MJ), protein 44.6g (CI 40.3 to 48.9g), calcium 356.9mg (CI 316.3 to 397.4mg), fibre 14.9g (CI 13.2 to 16.5g). The assisted group (N=64) had the following nutrient intakes: energy 3.9MJ (CI 3.6 to 4.2MJ), protein 46.0g (CI 40.7 to 49.6), calcium 361.9mg (CI 327.8 to 396.1mg), fibre 14.9g (CI 13.2 to 16.1g). Of NH classified as eating impaired, 36% received no assistance with feeding and had lower intakes of protein 37.8g (CI 33.0 to 42.1g) compared to those receiving some assistance 46.1g (CI 41.3 to 50.9g) (P=0.026). Reduced energy intake accounted for the differences in nutrient intakes between nursing homes and hostels, except for protein. Strategies to effectively monitor nutrient intakes and to identify those with eating impairment are required in order to ensure adequate nutrition of residents in nursing homes and hostels.

The occupiers' burden: tackling food shortage and related health problems in post-war Germany 1945-47

The end of the Second World War brought much relief to its combatants, but a range of problems remained that would plague post-war Europe for years to come. Chief among them was food shortage. The breakdown of agricultural systems, essential services, and the state itself laid fertile ground for food shortage to develop in parts of post-war Germany occupied by the victorious powers. There is much to be gained from comparing the occupiers’ responses to this Horseman of the Apocalypse. The most fruitful comparison lies between the Soviets and British. Unlike the Americans whose economic might in the post-war period allowed them to better feed and supply Germans living in their occupation zone, domestic economic weaknesses hamstrung both Soviet and British responses to the more severe advent of food shortage which confronted them. Their responses were very different—some successful, others not—but all instructive for understanding the impacts of natural and policy factors on the development of food shortage and the consequences to the health of the population. The variety of these impacts have been obscured by the absence of this comparison in the literature, which is now made more feasible by the greater availability of the extensive resources that each occupier devoted to recording food and health data, particularly in the Soviet case. The data is not only relevant to the occupation period from 1945 to 1949, as it suggests long-term health impacts on those most exposed to the risk of food shortage then, and most at risk to the consequences of malnutrition decades later. In fact, as the available data defines regional differences in food rations and, accordingly, comparative food shortages in Soviet and British occupation zones, the situation in post-war Germany provides an excellent platform for future research linking differences in early nutrition to adult health outcomes.

Evidence for the monoclinic-tetragonal phase coexistence in Pb(Zr(0.53)Ti(0.47))O(3) thin films

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)