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.     

Long-wavelength 640×486 GaAs-AlGaAs quantum well infraredphotodetector snap-shot camera

A 9-μm cutoff 640×486 snap-shot quantum well infrared photodetector (QWIP) camera has been demonstrated. The performance of this QWIP camera is reported including indoor and outdoor imaging. The noise equivalent differential temperature (NEΔT) of 36 mK has been achieved at 300 K background with f/2 optics. This is in good agreement with expected focal plane array sensitivity due to the practical limitations on charge handling capacity of the multiplexer, read noise, bias voltage, and operating temperature     

Rapid infusion system for neurosurgical treatment of massive intraoperative hemorrhage

Using an illustrative case of severe closed head injury that resulted in a posterior fossa epidural hematoma (EDH) and supratentorial epidural/subdural hematomas (SDH), the massive blood losses associated with operative repair of the torn sigmoid sinus and the significant fluid losses associated with refractory diabetes insipidus were treated by the intraoperative use of the Rapid Infusion System (RIS, Haemonetics). The RIS can rapidly infuse warm blood, crystalloid, or colloid at rates up to 1.5 L/min, thereby limiting the commonly associated hypotension, hypothermia, and coagulopathies. During the suboccipital craniectomy for evacuation of the EDH and repair of the sigmoid sinus, the patient required 18 units of blood replacement secondary to a large tear in the sigmoid sinus. During a separate craniotomy for evacuation of the SDH, the patient also developed diabetes insipidus, which increased the operative fluid replacement to 39 L. Despite these massive blood and fluid losses, the RIS limited the hypotension to less than 2 min and prevented hypothermia and the frequently associated coagulopathies. When used in a neurosurgical setting associated with massive blood and/or fluid losses, the RIS accomplishes three important objectives: (1) rapid infusion of intravenous fluids for maintaining perfusion pressure, (2) rapid warming of fluids despite high intravenous infusion rates of cold crystalloids, thereby preventing intraoperative hypothermia, and (3) continuous monitoring of infusion rates and totals.     

Optimal control of auxiliary heating of passive-solar-heated buildings

Previous papers have demonstrated that low-cost off-peak electricity can be used to provide auxiliary heating for a passive-solar-heated residence. This paper describes the development of optimal control strategies for the operation of this auxiliary heating system. The temperature in the residence throughout the day as determined by computer simulation is presented for several optimal and conventional control strategies. The optimal control strategies improved the temperature control in the building compared to the conventional strategies. All strategies were shown to depend heavily on weather prediction. Computer simulations showed that errors in weather prediction had a small effect on heating cost and a large effect on being able to maintain the desired indoor temperature.     

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.