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排序方式: 共有1406条查询结果,搜索用时 15 毫秒
41.
JH Noseworthy P O'Brien BJ Erickson D Lee D Sneve GC Ebers GP Rice A Auty WJ Hader A Kirk P Duquette J Carter G Francis L Metz E Shuster 《Canadian Metallurgical Quarterly》1998,51(5):1342-1352
OBJECTIVE: To determine whether sulfasalazine is better than placebo in slowing disability progression in MS. METHODS: In this randomized, double-blind, placebo-controlled phase III trial, 199 patients with active relapsing-remitting (n = 151) or progressive (n = 48) MS were evaluated at 3-month intervals for a minimum of 3 years (94% completed 3 years of follow-up; mean follow-up, 3.7 years). MRI studies were performed at 6-month intervals on a subset of 89 patients. RESULTS: Sulfasalazine failed to slow or prevent disability progression as measured by the primary outcome (confirmed worsening of the Expanded Disability Status Scale [EDSS] score by at least 1.0 point on two consecutive 3-month visits). Sulfasalazine influenced favorably a number of secondary outcomes during the first 18 months of the trial (e.g., annualized relapse rate, proportion of relapse-free patients; progressive subgroup only: rate of EDSS progression at 1 and 2 years, median time to EDSS progression) but these positive findings were not sustained into the second half of the trial. CONCLUSIONS: Sulfasalazine does not prevent EDSS score progression in the subset of MS patients studied by this protocol. Treatments may improve relapse-related outcomes in MS, at least temporarily, without providing sustained slowing of EDSS progression. Phase III MS trials should be of sufficient length to determine a meaningful impact on disease course. 相似文献
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We examined the effect of meprin A, the major matrix degrading metalloproteinase in rat kidney, on the laminin-nidogen complex. N-terminal sequence information from the most abundant 55 kDa fragment revealed that it was a breakdown product of nidogen rather than laminin. In comparison with over 50 nidogen cleavage sites produced by other proteases, the meprin A-induced nidogen cleavage site at amino acid position 899-900, a glutamine-glycine site in the G3 domain, is unique. In addition, these data demonstrate that meprin A degrades the G3 domain of nidogen even in the presence of laminin binding, which usually accords protection from proteolytic degradation. Meprin A also degraded purified nidogen into similar breakdown products. Given that the tubular basement membrane is located on the basilar side of the cell, the location of meprin A on the apical brush border makes it difficult to envision a role for meprin A in injury-induced basement membrane component breakdown. Thus, we examined the possibility that following renal tubular epithelial cell injury, meprin A undergoes a translocation to reach the underlying basement membrane. After renal ischemia-reperfusion there was a marked alteration in meprin A staining with meprin A now distributed throughout the renal tubular cell cytoplasm and directly adherent to the tubular basement membrane. This was in contrast to the usual linear staining of the brush border of tubules in the corticomedullary junction. These data provide unequivocal evidence that following injury, meprin A undergoes redistribution and/or adherence to the tubular basement membrane. Since in our in vitro studies, we identified a distinct meprin-induced 55 kDa nidogen breakdown product, the urine was also examined for the presence of nidogen degradation products after rat renal ischemia-reperfusion injury. Western blots showed a marked increase in the urinary 55 kDa nidogen fragment as early as the first day following ischemia-reperfusion injury and continuing for six days. Taken together, these in vivo data strongly support the notion that the nidogen breakdown products are the result of partial degradation of tubular basement membrane by meprin A following renal tubular ischemia-reperfusion injury. 相似文献
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45.
HA Langendijk RJ Lamers GP ten Velde DG Sanders JM de Jong F Kessels EF Wouters 《Canadian Metallurgical Quarterly》1998,41(5):1037-1045
BACKGROUND: The purpose of this study was to evaluate whether the chest radiograph is a reliable tool to assess response to radiotherapy. MATERIALS AND METHODS: Pre- and post-treatment chest radiographs and computed tomographs (CT) of 63 patients with nonsmall cell lung cancer (NSCLC) treated by radiotherapy were reviewed by four observers with regard to suitability for tumor measurement, and response. Suitability for tumor measurement was expressed as the number of measurable diameters. In addition, the consequences to clinical outcome were studied by survival analysis. RESULTS: The CT turned out to be more suited for tumor measurement before as well as after radiotherapy, resulting in an increase of the number of measurable cases. The number of measurable cases with CT was 52 (83%) as compared to 28 (44%) with chest radiography. Especially in case of centrally localized tumors, the presence of an atelectasis, or squamous cell carcinoma, CT contributed to a higher rate of measurable cases. The interobserver agreement with regard to response using chest radiograph was good (mean kappa = 0.74). In 25 of 28 cases (89%) measurable with CT as well as with chest radiograph, response was equally classified. When CT was used, the median survival of the responders was 14.2 months as compared to 6.8 months of the nonresponders. When chest radiograph was used, the median survival of these groups was 12.0 and 6.6 months respectively, which was not significantly different when response was assessed by CT. CONCLUSION: We conclude that CT is more suited for tumor measurement because more measurable lesions can be found and more evaluable lesions on chest radiograph become measurable on CT. The chest radiograph does have a valuable role to play in those lesions that are measurable because of the good interobserver agreement with regard to the response classification, the high overall agreement between CT and chest radiograph in case of measurable cases, and the lack of important differences with regard to survival. 相似文献
46.
TE Cawston VA Curry CA Summers IM Clark GP Riley PF Life JR Spaull MB Goldring PJ Koshy AD Rowan WD Shingleton 《Canadian Metallurgical Quarterly》1998,41(10):1760-1771
OBJECTIVE: To study the interaction of interleukin-1alpha (IL-1alpha) and oncostatin M (OSM) in promoting cartilage collagen destruction. METHODS: Bovine, porcine, and human cartilage and human chondrocytes were studied in culture. The levels of collagenase (matrix metalloproteinase 1 [MMP-1]) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by bioassay and enzyme-linked immunosorbent assay (ELISA). The levels of OSM in rheumatoid synovial fluid were measured by ELISA. RESULTS: When combined with OSM, IL-1alpha, IL-1beta, and tumor necrosis factor alpha released proteoglycan and collagen from cartilage. OSM was the only member of the IL-6 family to have this effect. Human tendon also responded to IL-1alpha and OSM. OSM increased the production of MMP-1 and TIMP-1 but when combined with IL-1alpha, synergistically promoted MMP-1 production in human chondrocytes and synovial fibroblasts. High levels of OSM were found in human rheumatoid synovial fluids, and confocal microscopy showed that OSM was produced by macrophages in rheumatoid synovial tissue. CONCLUSION: These results highlight an important new mechanism by which there is irreversible loss of collagen from cartilage. 相似文献
47.
A part of a larger study of the health behaviors of adolescent women, this investigation examined health-promoting behaviors and the influence of cognitive, social, and environmental factors on these health-promoting behaviors of rural adolescent women. The sample consisted of 128 rural African-American and white adolescent women. Forty-four percent of the variance in health-promoting behavior of this sample was explained by five variables: self-image, problem solving, mother's education, employment status, and family structure. Self-image was the most salient predictor of health-promoting behavior, explaining 33% of the variance. 相似文献
48.
GP Xue JS Johnson DJ Smyth LM Dierens X Wang GD Simpson KS Gobius JH Aylward 《Canadian Metallurgical Quarterly》1996,45(1-2):120-126
Temperature-regulated expression of recombinant proteins in the tac promoter (Ptac) system was investigated. Expression levels of fungal xylanase and cellulase from N. patriciarum in E. coli strains containing the natural lacI gene under the control of the Ptac markedly increased with increasing cultivation temperature in the absence of a chemical inducer. The specific activities (units per milligram protein of crude enzyme) of the fungal xylanase and cellulase produced from recombinant E. coli strain pop2136 grown at 42 degrees C were about 4.5 times higher than those of the cells grown at 23 degrees C and were even slightly higher when compared with cells grown in the presence of the inducer isopropyl beta-D-thiogalactopyranoside. The xylanase expression level in the temperature-regulated Ptac system was about 35% of total cellular protein. However, this system can not be applied to E. coli strains containing lacIq, which confers over production of the lac repressor, for high-level expression of recombinant proteins. In comparison with the lambda PL system, the Ptac-based xylanase plasmid in E. coli pop2136 gave a considerably higher specific activity of the xylanase than did the best lambda PL-based construct using the same thermal induction procedure. The high-level expression of the xylanase using the temperature-regulated Ptac system was also obtained in 10-litre fermentation studies using a fed-batch process. These results unambiguously demonstrated that the temperature-modulated Ptac system can be used for overproduction of some non-toxic recombinant proteins. 相似文献
49.
J.J. Sharples R.H.D. McRae R.O. Weber A.M. Gill 《Environmental Modelling & Software》2009,24(5):637-646
Assessing fuel moisture content to within a reasonable degree of accuracy is an important part of wildland fire management. In this paper we introduce a fuel moisture index that provides a simple and intuitive method for assessing fuel moisture content. The method can be quickly and easily applied in a field setting to provide a dimensionless measure of fuel moisture content. We compare the index with predictions from several models for fuel moisture content and conclude that it provides an equivalent measure of fuel moisture content for a number of fuel types. We go on to briefly discuss how the index could be used to construct a simple and intuitive fire danger index. 相似文献
50.
J.J. Sharples R.H.D. McRae R.O. Weber A.M. Gill 《Environmental Modelling & Software》2009,24(6):764-774
Fire danger rating systems are used to assess the potential for bushfire occurrence, fire spread and difficulty of fire suppression. Typically, fire danger rating systems combine meteorological information with estimates of the moisture content of the fuel to produce a fire danger index. Fire danger indices are used to declare fire bans and to schedule prescribed burns, among other applications. In this paper a simple fire danger index F that is intuitive and easy to calculate is introduced and compared to a number of fire danger indices pertaining to different fuel types that are used in an operational setting in Australia and the United States. The comparisons suggest that F provides a plausible measure of fire danger rating and that it may be a useful pedagogical tool in the context of fire danger and fire weather. 相似文献