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.     

Characteristics of Milk Powders Produced by Spray Freeze Drying

Skim and whole milk powders were manufactured at lab scale by spray freeze drying (SFD), using liquid nitrogen as the cryogen. The polydispersity of droplet/particle sizes was limited using an encapsulator nozzle to atomize the feed. Particle morphology was examined using a scanning electron microscope. Samples were compared with equivalent spray-dried powders in tests of wettability and dissolution in water. The spray freeze-dried powders were found to be highly porous, with a uniform structure of pores throughout the entire particles. When tested in water, SFD skim milk powders wetted roughly three times as fast as industrially spray-dried agglomerated skim milk powders and were observed to dissolve rapidly by breaking down into smaller particles.     

Developing competency-based methods for near-real-time air combat problem solving assessment

Air combat scenarios present unique problems where the solution is not obvious. An advanced networked simulation environment can be used to train high-level cognitive air combat skills such as problem solving. A problem in the development of principled and construct oriented assessment is related to determining the level of specificity of the assessment. We present a detailed discussion of the definition of critical competencies associated with combat mission problem solving performance, and we describe our approach to develop and implement an embedded performance assessment system that maps outcomes to these competencies. Finally, we discuss the implications for our approach for comprehensive assessment and discuss our goals for an evaluation of the competency-based approach to assessment.     

Genetic definition of a new bovine papillomavirus type 1 open reading frame, E5B, that encodes a hydrophobic protein involved in altering host-cell protein processing

We have previously observed that bovine papillomavirus type 1 (BPV-1) induces the appearance of five cellular proteins in C127 mouse fibroblasts, four of which appear to arise by altered processing of resident endoplasmic reticulum proteins. Studies of various cell lines revealed that expression of the 3' end of the BPV early region was sufficient for induction of these changes. To identify the BPV gene responsible, we have utilized the simian virus 40 (SV40)/BPV-1 recombinant virus Pava-1, which expresses the 3' end of the BPV early region behind an SV40 early promoter. C127 cells infected with Pava-1 for 48 h show the expected BPV-associated alterations, as do cells infected with Pava constructs mutated in the E5 or E2 genes. However, a mutation in the start codon of a previously ignored open reading frame extending from nucleotides 4013 to 4170 (E5B) eliminated the BPV-associated changes. Similar results were obtained with COS cells infected with the Pava mutants and C127 cells transformed by full-length mutated BPV. Despite its influence on the processing of cellular endoplasmic reticulum proteins, this mutation in E5B did not alter BPV-transforming efficiency or the ability of transformants to form colonies in soft agar. The E5B open reading frame encodes a hydrophobic 52-amino-acid polypeptide that shares structural similarities with HPV6 E5A and HPV16 E5. Speculations on a role for E5B in the viral life cycle are discussed.     

Health education lessons learned: the H.A.P.I. Kids Program

Challenges exist for effective health communication and health education within diverse populations of the United States. This article addresses the development process for educational materials and lessons learned from the Healthy Asian and Pacific Islander (H.A.P.I.) Kids Program, a vaccination demonstration project funded by the Centers for Disease Control and Prevention to promote catch-up hepatitis B vaccination for older American Asian and Pacific Islander children. Simplicity and a common message were incorporated in multiple strategies to disseminate information to a diverse population. Community representatives from the Cambodian, Hmong, Filipino, Lao, and Vietnamese communities were instrumental in the material development process, which included needs assessment, design, and translation. By making the target community part of the development process, important health messages can be disseminated effectively, carrying great impact to an otherwise hard-to-reach community.     

Clinical and functional evaluation of health status of workers exposed to infrasound, noise and general vibration

The article covers complex evaluation of health state in building industry workers engaged into ferro-concrete production in St. Petersburg. The health state was considered under combined action of infrasound, noise and general vibration. Clinical and functional evaluation included medical examination by doctors, blood biochemistry and CBC, ECG, computer integral rheography, voice audiometry. Data for 62 moulders helped to assess acoustic environment at workplace and to reveal the morbidity structure.