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.     

Moral value transfer from regulatory fit: What feels right is right and what feels wrong is wrong.

People experience regulatory fit (E. T. Higgins, 2000) when the strategic manner of their goal pursuit suits their regulatory orientation, and this regulatory fit feels right. Fit violation feels wrong. Four studies tested the proposal that experiences of fit can transfer to moral evaluations. The authors examined transfer of feeling wrong from fit violation by having participants in a promotion or prevention focus recall transgressions of commission or omission (Studies 1 and 2). Both studies found that when the type of transgression was a fit violation, participants expressed more guilt. Studies 3 and 4 examined transfer of feeling right from regulatory fit. Participants evaluated conflict resolutions (Study 3) and public policies (Study 4) as more right when the means pursued had fit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

MRI of primary malignant cardiovascular tumors

In 1895 Trendelenburg described his sign to determine the integrity of hip function. We found the sign to be positive in a patient whose hip was clinically and radiologically normal, and therefore investigated this in other patients. We confirmed that a medial shift of the mechanical axis of the leg below the hip may cause a positive Trendelenburg sign. This has not been previously described.     

Orthotropic Plate Model for Estimating Deflections in Filled Grid Decks

Concrete filled grid bridge decks exhibit orthogonal elastic properties and significant two-way bending action enabling orthotropic plate theory to determine structural response for these elements. Current American Association of State Highway and Transportation Officials load and resistance factor design (LRFD) specifications employ an orthotropic plate model to predict live load moment in concrete filled grid bridge decks but provide no guidance for computing displacement, a potentially important serviceability consideration. This paper presents equations to approximate the maximum deflection in concrete filled grid bridge decks based on orthotropic plate theory, multiple patch loads, LRFD design truck and tandem load cases, the influence of multiple spans, and the two most common deck orientations.     

Percutaneous transhepatic drainage of the nondilated biliary system

Although reticulocyte counts can be reliably performed for up to 48 h after storage in EDTA, it is unclear whether this is applicable to the pediatric age group. In order to evaluate this, manual reticulocyte counts were performed on 20 specimens from pediatric patients stored at 4 degrees C for up to 24 h post collection. Samples were evaluated at 1-3, 6, 12, 18, and 24 h after storage in EDTA vacutainer tubes at 4 degrees C. The age of the subjects ranged from 1 day to 9 years with a median age of 3 years. Patients' reticulocyte counts ranged from 0 to 27% (5.89 +/- 7.21). No clinically significant changes were evident in the reticulocyte count over 24 h after specimen collection. The mean of the 20 specimens at 1-3 h was 5.50 and at 24 h was 5.40 (P > .05). The standard deviation of the mean values ranged from 7.03 to 7.26 (P > .05). The results indicate that reticulocyte counts may be performed on previously drawn blood held at 4 degrees C for up to 24 h post collection in a pediatric population without significant difference from baseline values.     

Structure and gene expression of avian cyclin D2

Avian cyclin D2 (Cyl D2)-encoding cDNA clones were isolated from a chicken UG9 T-cell lambda gt10 library. Sequence analysis revealed a high degree of sequence conservation with both the mouse and human Cyl D2, and somewhat lower similarity with the mouse and human Cyl D1 and D3. The homology is highest between species in the Cyl-box domain which is well conserved among human, mouse and chicken. A single 6.0-kb CYL2 mRNA is produced in both avian B- and T-cells, as expected.     

A 44-GHz monolithic waveguide plane-wave amplifier with improvedunit cell design [using pHEMTs]

A 44-GHz monolithic waveguide plane-wave amplifier (PWA) with improved unit cell design is presented in this paper. The unit cell is a two-stage direct-coupled design and satisfies size, bistability, and stability requirements of the waveguide PWA. The ultra-compact unit cell had a cell size of 0.8 mm², and showed a small-signal gain of 8 dB and an output power of 15 dBm at 44 GHz with a corresponding dc-to-RF efficiency of 10%. A monolithic waveguide PWA using these unit cells showed a “flange-to-flange” gain of 5 dB, an output power of 0.3 W, and an efficiency of 2% at 44 GHz     

Healthy Aims: Developing New Medical Implants and Diagnostic Equipment

Healthy Aims is a 23- million, four-year project, funded under the EU's information society technology sixth framework program to develop intelligent medical implants and diagnostic systems (www.healthyaims.org). The project has 25 partners from 10 countries, including commercial, clinical, and research groups. This consortium represents a combination of disciplines to design and fabricate new medical devices and components as well as to test them in laboratories and subsequent clinical trials. The project focuses on medical implants for nerve stimulation and diagnostic equipment based on strain-gauge technology.     

Biochemical properties and cellular localization of the Drosophila DG1 cGMP-dependent protein kinase

The protein encoded by the Drosophila cGMP-dependent protein kinase gene, DG1, was expressed in Sf9 cells. cGMP (10 microM) stimulated histone H2B phosphorylation by the DG1 protein kinase 20-fold. Maximal activity was observed at 40-50 mM Mg2+. The concentrations of cGMP, cAMP, cIMP, 8-bromo-cGMP, and 8-bromo-cAMP that gave 50% activation were 0.19 +/- 0.06, 11.7 +/- 2.8, 5.3 +/- 1.5, 0.04 +/- 0. 01, and 0.62 +/- 0.06 microM, respectively. cGMP activation was cooperative with a Hill coefficient (nH) of 1.28 +/- 0.10, whereas activation by cAMP was not cooperative. DG1 kinase expressed in Sf9 cells was found to be a dimer with an amino-terminal dimerization domain. It also autophosphorylated in a reaction stimulated by cGMP and cAMP. Immunoadsorbed DG1 protein from fly extracts was also capable of autophosphorylation, and this assay was used to quantitate the DG1 kinase in extracts from heads and bodies of adults and whole embryos. Activity was highest in heads of either sex and male bodies, intermediate in female bodies, and lowest in embryos. These results were in accord with DG1 mRNA abundance. Tissue distribution of the DG1 kinase was investigated by immunohistochemistry. In embryos, specific immunoreactivity was observed in large cells scattered along the anterior-posterior axis at stage 13. Prominent staining of adult heads was restricted to the proximal level of the lamina cortex.     

The diastolic debate: is it time to discard Korotkoff phase IV in favour of phase V for blood pressure measurements in pregnancy?

The IgE-mediated allergic response involves a series of physiological pathways that result in the array of symptoms commonly associated with allergy. This article describes the mediators that prompt specific clinical responses and identifies those at risk for latex hypersensitivity.