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31.
Factor V and factor VIII are homologous cofactors in the blood coagulation cascade that have the domain structure A1-A2-B-A3-C1-C2, of which the B domain has extensively diverged. In transfected COS-1 monkey cells, expression of factor VIII is approximately 10-fold less efficient than that of factor V, primarily because of inefficient protein secretion and, to a lesser extent, reduced mRNA expression. To study the functional significance and effect of the B domain on expression and activity, chimeric cDNAs were constructed in which the B domains of factor V and factor VIII were exchanged. Expression of a factor VIII chimera harboring the B-domain of factor V yielded a fully functional factor VIII molecule that was expressed twofold more efficiently than wild-type factor VIII because of increased mRNA expression. Thus, sequences within the factor VIII B domain were not responsible for the inefficient secretion of factor VIII compared with factor V. Expression of a factor V chimera harboring the B domain of factor VIII was slightly reduced compared with wild-type factor V, although the secreted molecule had significantly reduced procoagulant activity correlating with dissociated heavy and light chains and resistance to thrombin activation. Interestingly, the factor V chimera containing the factor VIII B domain was efficiently activated by Russell's viper venum (RVV). A factor V B domain deletion (residues 710- 1545) molecule also exhibited significantly reduced procoagulant activity caused by resistance to thrombin cleavage and activation, although this molecule was activatable by RVV. These results show that, in contrast to factor VIII, thrombin activation of factor V requires sequences within the B domain. In addition, thrombin activation of factor V occurs through a different mechanism than activation by RVV. 相似文献
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Identification of the molecular defect in the erythrocyte membrane skeleton of some kindreds with hereditary spherocytosis 总被引:12,自引:0,他引:12
We have localized the molecular alteration in the membrane skeleton of two of four kindreds with hereditary spherocytosis (HS) to an alteration in the spectrin-protein-4.1 interaction due to a defective spectrin molecule. The defective spectrin-protein-4.1 interaction in these kindreds (referred to as type I HS) leads to a weakened spectrin- protein-4.1-actin ternary complex, which in turn may lead to the friable membrane skeleton and suggested membrane instability related to this disorder. Type I HS spectrin binds approximately 63% as much protein-4.1 as normal spectrin (with equal affinity). This defect does not correlate with splenic function or erythrocyte age in the circulation. However, the approximately 37% reduction in binding of protein-4.1 to HS spectrin approaches the theoretical value of 50% expected in this autosomal dominant disorder. All other type I membrane skeletal interactions (spectrin-syndein, spectrin heterodimer- heterodimer, syndein-band-3) were found to be normal. It would appear therefore that the defective HS spectrin-protein-4.1 interaction in type I hereditary spherocytosis may be the primary molecular defect rather than a secondary phenomena. 相似文献
33.
再发骨质疏松性椎体压缩骨折保守治疗患者出院后生存质量 总被引:1,自引:0,他引:1
目的:对比初次和再发骨质疏松性椎体压缩骨折(osteoporotic vertebral compression fractures,OVCFs)患者保
守治疗的生存质量,了解再次骨折对此类患者生存质量各方面的影响。方法:回顾性观察治疗OVCFs后出现再骨折
的患者30名(再骨折组)和同时期行保守治疗OVCFs后未发生再骨折的基本条件相似的患者30例(对照组),比较两组出
院后3个月时SF-36简明健康健康状况调查表的调查结果。结果:再骨折组治疗后的8个维度均不同程度较对照组变差
(均P<0.01)。结论:再骨折组患者的生存质量明显低于对照组,并且会进一步影响患者的心理预期、情绪和社会活动
的各个方面。 相似文献
34.
Aortic dissection--an update 总被引:7,自引:0,他引:7
Acute aortic dissection is a medical emergency with high morbidity and mortality requiring emergent diagnosis and therapy. Rapid advances in noninvasive imaging technology have facilitated the early diagnosis of this condition and should be considered in the differential diagnosis of any patient with chest, back, or abdominal pain. Emergent surgery is the treatment for patients with type A dissection while optimal medical therapy is appropriate in patients with uncomplicated type B dissection. Adequate beta-blockade is the cornerstone of medical therapy. Patients who survive acute aortic dissection need long-term medical therapy with beta-blockers and statins and appropriate serial imaging follow-up. Future advances in this field include biomarkers in the early diagnosis of acute aortic dissection and presymptomatic diagnosis with genetic screening. Overall patients with aortic dissection are at high risk for an adverse outcome and need to be managed aggressively in hospital and long term with frequent follow-up. 相似文献
35.
Re‐endothelialization of rat lung scaffolds through passive,gravity‐driven seeding of segment‐specific pulmonary endothelial cells 下载免费PDF全文
Michelle E. Scarritt Nicholas C. Pashos Jessica M. Motherwell Zachary R. Eagle Brian J. Burkett Ashley N. Gregory Ricardo Mostany Daniel J. Weiss Diego F. Alvarez Bruce A. Bunnell 《Journal of tissue engineering and regenerative medicine》2018,12(2):e786-e806
Effective re‐endothelialization is critical for the use of decellularized scaffolds for ex vivo lung engineering. Current approaches yield insufficiently re‐endothelialized scaffolds that haemorrhage and become thrombogenic upon implantation. Herein, gravity‐driven seeding coupled with bioreactor culture facilitated widespread distribution and engraftment of endothelial cells throughout rat lung scaffolds. Initially, human umbilical vein endothelial cells were seeded into the pulmonary artery by either gravity‐driven, variable flow perfusion seeding or pump‐driven, pulsatile flow perfusion seeding. Gravity seeding evenly distributed cells and supported cell survival and re‐lining of the vascular walls while perfusion pump‐driven seeding led to increased cell fragmentation and death. Using gravity seeding, rat pulmonary artery endothelial cells and rat pulmonary vein endothelial cells attached in intermediate and large vessels, while rat pulmonary microvascular endothelial cells deposited mostly in microvessels. Combination seeding of these cells led to positive vascular endothelial cadherin staining. In addition, combination seeding improved barrier function as assessed by serum albumin extravasation; however, leakage was observed in the distal portions of the re‐endothelialized tissue suggesting that recellularization of the alveoli is necessary to complete barrier function of the capillary–alveolar network. Overall, these data indicate that vascular recellularization of rat lung scaffolds is achieved through gravity seeding. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
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