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.     

Trends in low-cost, high-performance substrate technology

The trends in high density interconnection (HDI) multichip module (MCM) techniques that have the potential to reduce interconnection cost and production time are described. The implementation in laminated dielectric (MCM-L) technology of a workstation processor core illustrates current substrate technology capabilities. The design, routing, layout and thermal management of the processor core are described. Thin-film deposited dielectric (MCM-D) technology is discussed as a cost-effective method for future interconnection applications     

The virtual reality modeling language explained

VRML stands for Virtual Reality Modeling Language. Technically, VRML is neither virtual reality nor a modeling language. Virtual reality generally implies an immersive 3D experience, which typically requires a head mounted display (HMD) and 3D input devices, such as digital gloves. VRML neither requires nor imposes immersion. Furthermore, a true modeling language would contain richer geometric modeling primitives and mechanisms. VRML provides a bare minimum of geometric modeling features but contains numerous features unavailable in a modeling language. If VRML is not virtual reality or a modeling language, what is it? This question has several answers. At its core, VRML serves as a 3D interchange format. It defines most of the commonly used semantics found in today's 3D applications such as hierarchical transformations, light sources, viewpoints, geometry, animation, fog, material properties, and texture mapping. Here's a second answer to: what is VRML? It's a 3D analog to HTML. This means that VRML serves as a simple, multiplatform language for publishing 3D Web pages. The fact that some information, including games, engineering models, scientific visualizations, educational experiences, and architecture, can best be experienced in 3D has motivated this language. Typically, these types of projects require intensive interaction, animation, and user participation and exploration beyond what a page, text, or image based format can handle. Another answer is that VRML provides the technology to integrate 3D, 2D, text, and multimedia into a coherent model     

Seeking the truth about ad hoc join costs

In this paper, we re-examine the results of prior work on methods for computing ad hoc joins. We develop a detailed cost model for predicting join algorithm performance, and we use the model to develop cost formulas for the major ad hoc join methods found in the relational database literature. We show that various pieces of “common wisdom” about join algorithm performance fail to hold up when analyzed carefully, and we use our detailed cost model to derive op timal buffer allocation schemes for each of the join methods examined here. We show that optimizing their buffer allocations can lead to large performance improvements, e.g., as much as a 400% improvement in some cases. We also validate our cost model's predictions by measuring an actual implementation of each join algorithm considered. The results of this work should be directly useful to implementors of relational query optimizers and query processing systems. Edited by M. Adiba. Received May 1993 / Accepted April 1996     

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.