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31.
HM Chaung CH Hong CP Chiang SK Lin YS Kuo WH Lan CC Hsieh 《Canadian Metallurgical Quarterly》1996,95(7):545-550
This review reports the different genetic factors that have been identified either as risk factor for Alzheimer's disease (AD) or directly causing the disease. First are reviewed epidemiological data and biological mechanisms about the apoplipoprotein E gene allele epsilon 4 that is a major risk factor for Alzheimer's disease. The second part describes the mutations responsible for early-onset autosomal dominant AD found in three different genes. The gene located on chromosome 21 encodes the amyloid precusor protein (APP). The presenilin 1 and presenilin 2 genes, located on chromosome 14 and 1 respectively, encode not yet known membrane proteins. 相似文献
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T De Brito CR Carneiro MC Nakhle DM Lima CP Abrantes-Lemos M Sandoval AM Silva 《Canadian Metallurgical Quarterly》1998,6(4):368-376
Gene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of loco-regional recurrence in diseases such as non-small cell lung cancer (NSCLC), as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can in certain circumstances provide an effective means of delivering therapeutic genes to tumour cells. Although multiple genes are involved in the process of carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumours. Pre-clinical studies both in vitro and in vivo have shown that restoration of p53 function can induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy is feasible and safe using both retroviral and adenoviral vectors, and that it induces tumour regression in patients with advanced NSCLC and recurrent head and neck cancer. Other pre-clinical studies indicate that gene therapy may have useful synergy with cytotoxic and radiation therapy. This paper describes the different gene therapy strategies under investigation and the pre-clinical data that provides a rationale for the gene replacement approach, reviews clinical trial data and presents novel ideas for improving current vectors and gene delivery to tumours. 相似文献
34.
The aims of this study were to establish a working rabbit heart model of regional myocardial ischaemia in which electrophysiologic parameters and arrhythmogenesis could be correlated and to explore the mechanisms underlying the antiarrhythmic activity of lignocaine. Monophasic action-potential duration (MAPD90), effective refractory period (ERP), and conduction delay were measured at three ventricular sites in isolated hearts paced at 3.3 Hz. The hearts were treated before and throughout 30 min of ischaemia and 15 min of reperfusion with a vehicle or 20 microM lignocaine. In both groups, ischaemia produced a similar shortening in MAPD90. Lignocaine decreased ERP shortening during ischaemia from -56+/-4 to -32+/-6 ms. An ischaemia-induced increase in conduction delay was greater in the lignocaine than the control group (49+/-7 vs. 11+/-2 ms). Ischaemia-induced dispersion of repolarisation was reduced by lignocaine from 66+/-4 to 32+/-7 ms, and dispersion of refractoriness was decreased from 57+/-6 to 16+/-3 ms. Lignocaine decreased inducibility of ventricular fibrillation (VF) during ischaemia from 86 to 25%. We conclude that, in this model, the antiarrhythmic activity of lignocaine during regional ischaemia is associated with an increase in ischaemia-induced conduction delay and reduced dispersion of repolarisation and refractoriness. 相似文献
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SB Dennis VG Allen KE Saker JP Fontenot JY Ayad CP Brown 《Canadian Metallurgical Quarterly》1998,76(10):2687-2693
Poor performance of livestock that graze tall fescue (Festuca arundinacea Schreb.) has been associated with the endophyte fungus Neotyphodium coenophialum [Morgan-Jones and Gams] Glenn, Bacon, and Hanlin). Recent evidence suggests lowered Cu status and a depression of Cu-related immune function in steers that graze endophyte-infected (E+) tall fescue. Greenhouse and field studies investigated relationships between the endophyte and Cu concentrations in tall fescue. Seventeen infected 'Kenhy' clones were divided, and one plant of each pair was treated three times with Benomyl to remove the endophyte (E-). Plants were watered with nutrient solution in a greenhouse for 6 mo before sampling. Copper concentrations were greater (P < .001) in E- than in E+ clones (3.4 vs 2.8 microg/g; SE, .06). In the second greenhouse experiment, genetically similar E+ and E- 'Kentucky'-31 (KY-31) and 'Georgia Jessup' were grown from seed and fertilized with nutrient solution to produce mature plants. Copper concentrations were higher (P < .05) in E- than in E+ tall fescue (8.6 vs 7.6 microg/g; SE, .3). In a field plot experiment in Texas, E+ and E- KY-31 were grown with 0, 50, and 100% replacement of potential evapotranspiration. By September, Cu concentrations were higher (P < .05) in E- than in E+ tall fescue (7.3 vs 6.6 microg/g; SE, .2). In pasture experiments, KY-31 E+ (> 70% infection level) and E- (< 5% infection level) tall fescue were grown in Virginia at two locations with three rates of N fertilizer. Copper concentrations were higher (P < .05) in E- than in E+ tall fescue (4.8 vs 4.5 microg/g; SE, .1) and increased (P < .01) linearly in response to N. Our data demonstrate that the presence of the endophyte is associated with lower Cu concentrations in tall fescue, which may contribute to lowered Cu status in animals and thus contribute to the etiology of fescue toxicity. 相似文献
37.
MD Dake DC Miller RS Mitchell CP Semba KA Moore T Sakai 《Canadian Metallurgical Quarterly》1998,116(5):689-703; discussion 703-4
OBJECTIVE: Our goal was to determine whether endovascular stent-grafting is feasible and effective for patients with aneurysms of the descending thoracic aorta. METHODS: Starting in July 1992, we conducted a prospective, uncontrolled clinical trial in 103 patients (mean age 69 years [range 34-89 years]) who underwent endovascular treatment of aneurysms of the descending thoracic aorta using a custom-fabricated, self-expanding stent-graft device. Follow-up was 100% complete and averaged 22 months. Sixty-two patients (60%) were judged not to be reasonable candidates for a conventional "open" surgical procedure. RESULTS: Complete thrombosis of the aneurysm was ultimately achieved in 86 (83%) patients. The early mortality rate was 9% +/- 3% (+/- 70% CL). Multivariable analysis revealed that myocardial infarction or stroke was linked with a higher likelihood of early death (P = .001). Early serious complications included paraplegia in 3% +/- 2% and stroke in 7% +/- 3%. Actuarial survival estimates at 1 year and 2 years were 81% +/- 4% and 73% +/- 5% (+/- 1 SE), respectively; being judged not to be a surgical candidate portended a higher probability of death (P = .003). According to the intent-to-treat principle, "treatment failure" (including all late sudden unexplained deaths) occurred in 38 patients; 53% +/- 10% of patients were free from treatment failure at 3.7 years. Stent-graft related complications occurred commonly and were linked with several anatomic, technical, and patient-related risk factors. CONCLUSIONS: This 5-year clinical trial involving use of a "first generation" device indicates that endovascular stent-grafting of descending thoracic aortic aneurysms is feasible with acceptable medium-term results. More refined, commercially developed devices available today offer less traumatic and more precise stent-graft deployment; these major technical advantages, coupled with important lessons we have learned over time and better patient selection, should be associated with more salutary clinical results in the future. 相似文献
38.
The use of combined sensors and advanced algorithms using different principles can improve rate performance over a single sensor system. Combinations of sensors and more sophisticated algorithms, however, invariably increase the complexity of pacemaker programming. An automatically optimized combined minute ventilation and activity DDDR pacemaker was developed to minimize repeated sensor adjustment. The device used subthreshold (below cardiac stimulation threshold) lead impedance to detect lead configuration at implantation automatically, followed by "implant management," including setting of lead polarity and initiation of DDDR pacing. Automatic sensor adaptation was achieved by programming a "target rate histogram" based on the patient's activity level and frequency of exertion, and the rate profile optimization process matched the recorded integrated sensor response to the target rate histogram profile. In nine patients implanted with the DX2 pacemakers, the implant management gave 100% accuracy in the detection of lead polarity. Rate profile optimization automatically increased the pacing rate during exercise between discharge and 3-month follow-up (hall walk: 78 +/- 3 vs 98 +/- 3 beats/min, and maximal treadmill exercise: 89 +/- 6 vs 115 +/- 5 beats/min, P < 0.001) with a significant increase in exercise duration during maximal exercise (7.18 +/- 1 min vs 9.56 +/- 2 min, P = 0.05). The accuracy of rate profile optimization versus manual programming was assessed at 1 month, and there was no significant difference between pacing rate kinetics and maximal pacing rate between the two methods of programming. In conclusion, pacemaker automaticity can be initiated at implantation and the self-optimized rate adaptive response appeared to be comparable to that derived from a manual programming procedure, which may reduce the need to perform time consuming sensor programming. 相似文献
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BV Worgul Y Kundiev I Likhtarev N Sergienko A Wegener CP Medvedovsky 《Canadian Metallurgical Quarterly》1996,35(3):137-144
The general epidemiological acceptability of prevalence, or incidence, for assessing risk of radiation cataract development has dictated an almost exclusive dependence on cataract onset as a measure of cataractogenicity for given doses of radiation. The advent of instrumentation capable of acquiring images amenable to quantitative analyses offers the possibility of exploiting "relative opacification" as an added, if not exclusive, parameter. This development is particularly important in efforts to assess populations such as that in the Altai, which are temporally far removed from their exposure and among whom there exists a large subset with extant cataracts. The new technologies, Scheimpflug and retroillumination imaging, combined with the application of the appropriate analytical algorithms can not only provide quantitative and nonsubjective assessment of lens transparency, but also serve as a means to immortalize the state of the pathology at the time of acquisition. Highly relevant to the assessment of an aging exposed population is the use of lens epithelial fragments as potential dosimeters. The material is routinely available as a result of cataract extraction procedures and is amenable to the application of a modified micronucleus (MN) assay. The MN assay in the lens has tremendous advantages over its use in other tissues for a number of reasons, not least of which is that lens MNs are extremely long-lived. Given the relative ease of application and its potential as a radiation bioindicator, the lens MN assay should be considered in any follow-up of populations exposed to ionizing radiation. 相似文献