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1.
PE Sipila VJ Wiebe GB Hubbard SK Koester VD Emshoff JU Maenpaa GT Wurz RC Seymour MW DeGregorio 《Canadian Metallurgical Quarterly》1993,(15):2138-2144
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. 相似文献
2.
AE Speckens AM Van Hemert JH Bolk HG Rooijmans MW Hengeveld 《Canadian Metallurgical Quarterly》1996,26(4):745-752
BACKGROUND: Measurement of intracardiac hemodynamic parameters has been limited to brief periods in the acute care setting. We developed and evaluated an implantable hemodynamic monitor that is capable of measuring chronic right ventricular oxygen saturation and pulmonary artery pressure. METHODS AND RESULTS: The device consists of an electronic controller placed subcutaneously and two transvenous leads placed in the right ventricle (reflectance oximeter) and pulmonary artery (variable capacitance pressure sensor). Implantation was performed in 10 patients with severe left ventricular dysfunction. Average implant pulmonary artery pressures were systolic, 52 +/- 16 mm Hg; diastolic, 29 +/- 11 mm Hg; and mean, 40 +/- 12 mm Hg. The mean right ventricular oxygen saturation at implant was 51%. Provocative maneuvers, including postural changes, sublingual nitroglycerin, and bicycle exercise, demonstrated expected changes in measured oxygen saturation and pulmonary artery pressures over time. At follow-up of 0.5 to 15.5 months, there were no significant differences between pulmonary artery pressures or oxygen saturation values transmitted from the device and simultaneous measurement with balloon flotation catheters. Four of the pulmonary artery leads dislodged and three demonstrated sensor drift, whereas two of the oxygen saturation sensors failed. Four patients died and four received transplants. Pathological study did not demonstrate injury to the right ventricular outflow tract or pulmonic valve. CONCLUSIONS: Chronic measurement of hemodynamic parameters in the outpatient setting with implantable sensor technology appears to be feasible. The devices are well tolerated without significant untoward effects, and the sensors generally function well over time, providing reliable information. Clinical usefulness remains to be established. 相似文献
3.
We have used a variety of methods to characterize the genome of the archaeon Methanosarcina thermophila TM-1. Pulsed-field gel analysis indicates a genome size of 2.8 Mb. We have constructed a bacterial artificial chromosome (BAC) library of M. thermophila and have used it to generate physical maps for this organism. The library is made up of 384 clones with an average insert size of 58 kb representing 8.0 genome equivalents. The utility of the library for low-resolution physical mapping was shown by identifying NotI linking clones and using these to order the NotI macrorestriction fragments of M. thermophila into a 2.8 Mb map. Hybridization of nine single copy genes and a 16S rRNA sequence to these macrorestriction fragments forms the basis for the first genetic map in this organism. High-resolution physical maps, consisting of overlapping clones, have been created using HindIII fingerprints of BAC clones. In this way, we identified a minimal path of five clones that span a 270 kb NotI fragment. The ease of manipulating BAC clones makes the BAC system an excellent choice for the construction of low-resolution and high-resolution physical and genetic maps of archaeal genomes. It also provides a substrate for future genome-sequencing efforts. 相似文献
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The aim of this research was to determine if circadian rhythms have an effect on time trial cycling performance of 15 min duration. Seven males (Mean+/-SD): age, 22.3+/-4.9 yr; height 179.0+/-7.9 cm, body mass 74.5+/-15.5 kg; VO2max 68.0+/-5.7 ml x kg(-1) x min(-1) who were all competitive cyclists or triathletes with previous experience in laboratory testing procedures volunteered to participate in this study. Each of the seven subjects underwent a series of four tests; one VO2 max test, and three 15 min maximal performance tests, at varying times during a 24 hr period. Testing times were at 08.00-10.00; 14.00-16.00 and 20.00-22.00 hours. Heart rate was recorded during the last 10-15 seconds of each minute and blood lactate levels were taken at 5 and 10 min during exercise and again immediately post-exercise. O2 consumption was measured continuously using open circuit spirometry. RPE was measured using the Borg scale at 5 and 10 min during, and again immediately following the completion of testing. Resting oral temperature was the only variable to show a significant time of day effect (p<0.05). Oral temperature during the afternoon was higher than both morning and evening results by 0.76 degrees C and 0.09 degrees C respectively. Total work (kJ) and average power output (W) were recorded at their highest during the morning session and reached a trough during the afternoon session, but these differences were not significant (p = 0.9997 and 0.9972 respectively). The results obtained in this study indicate that while certain biological rhythms are present, they appear to have no effect on this type of cycling performance. Although athletic performance may be enhanced by training programs that are compatible with an individuals body clock, the ability to perform and train at various times has an adaptive response which appears to over-ride these naturally inherent rhythms. 相似文献
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MW Beatty ML Swartz BK Moore RW Phillips TA Roberts 《Canadian Metallurgical Quarterly》1993,27(3):403-413
Seven mechanical/physical properties were used to evaluate 10 unfilled resins: eight aromatic dimethacrylates and two urethane dimethacrylates. Physical property tests included compressive strength, Young's modulus in compression, uniaxial tensile strength, intrinsic yield point, toothbrush abrasion, Knoop hardness, and water sorption. Controlled changes were made in the following four material parameters: amount of crosslinking diluent present in the uncured monomer, functionality of the monomer, repeat unit chemistry of the monomer (urethane vs. aromatic structure) and mode of activation (chemical vs. visible light). Polymers containing a high concentration of crosslinking agent (50 wt%) were found to be tougher and to possess lower hardness than materials containing lesser amounts of crosslinking agent. This was attributed to the flexible nature of the triethylene glycol dimethacrylate crosslinking molecule. Exposure to water plasticized the highly crosslinked materials to the degree that the yield point and elastic modulus were effectively lowered. Most of the tested properties were unaffected by differences in functionality except resistance to toothbrush abrasion, which was enhanced for polymers derived from high functionality monomers. The urethane-based polymers sorbed substantially more water than the aromatic-based materials, which presumably resulted in lower values for surface hardness. However, the urethane resins were very tough, and excellent resistance to toothbrush abrasion was observed. Property differences caused by differences in activation mode were small, although the visible light materials did sorb more water. 相似文献
8.
All leaders in health care today are charged with the responsibility of transforming present practices into new and different ones that are needed for the future. The structural side of transforming is ultimately easier than the human side. However, the most frequent failures come from not concentrating sufficiently on the behavioral side of the change. Structural and psychological change must occur simultaneously and embrace each other for best results. 相似文献
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Traumatic aneurysms (TAs) are an unusual etiology for late neurological deterioration after traumatic brain injury (TBI) and represent less than 1% of all cerebral aneurysms. TAs most often are diagnosed acutely but may be delayed in presentation. To increase awareness of this serious but treatable condition when diagnosed early, we report a delayed TA after a motor vehicle accident. The patient experienced a seizure on day 46 postinjury while in rehabilitation and demonstrated persistent lethargy and hemiparesis. Neuroimaging revealed a large, ruptured left pericallosal artery TA, which was surgically clipped. The patient completed his rehabilitation course and was eventually discharged home with family. Among TBIs, TAs are associated with penetrating injuries and skull base or anterior cranial fossa fractures. Associated mortality is high, especially if rupture has occurred. Although TAs are rare, the clinician should be vigilant in the at-risk patient. 相似文献