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11.
D J Bowen 《Journal of clinical pathology》2002,55(1):1-18
This review focuses on selected areas that should interest both the scientist and the clinician alike: polymorphisms within the factor VIII and factor IX genes, their linkage, and their ethnic variation; a general assessment of mutations within both genes and a detailed inspection of the molecular pathology of certain mutations to illustrate the diverse cause–effect relations that exist; a summary of current knowledge on molecular aspects of inhibitor production; and an introduction to the new areas of factor VIII and factor IX catabolism. An appendix defining various terms encountered in the molecular genetics of the haemophilias is included, together with an appendix providing accession numbers and locus identification links for accessing gene and sequence information in the international nucleic acid databases. 相似文献
12.
石杉碱甲和乙促进小鼠的空间辨别学习和记忆 总被引:1,自引:0,他引:1
石杉碱甲和乙是从石杉科石杉属植物蛇足石杉[Huperzia scrrata(Thunb.)Trev.]中分得的二个新生物碱。“Y”迷宫实验表明,ip Hup-A 0.075~0.125 mg/kg或Hup-B 0.4~0.8mg/kg,均能明显促进小鼠的空间辨别学习,并能显著预防CO2产生的短时识别障碍,促进记忆保持和记忆再现。ig Hup-A 0.1~0.3 mg/kg或Hup-B 0.8 mg/kg也有促进学习的作用。促进作用Hup-A>Phys>Hup-B。剂量与效应曲线呈倒U型。 相似文献
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Kathleen Hawker 《Annals of Indian Academy of Neurology》2009,12(4):221-225
B cells have recently been identified as an integral component of the immune system; they play a part in autoimmunity through antigen presentation, antibody secretion, and complement activation. Animal models of multiple sclerosis (MS) suggest that myelin destruction is partly mediated through B cell activation (and plasmablasts). MS patients with evidence of B cell involvement, as compared to those without, tend to have a worse prognosis. Finally, the significant decrease in new gadolinium-enhancing lesions, new T2 lesions, and relapses in MS patients treated with rituximab (a monoclonal antibody against CD20 on B cells) leads us to the conclusion that B cells play an important role in MS and that immune modulation of these cells may ameliorate the disease. This article will explore the role of B cells in MS and the rationale for the development of B cell–targeted therapeutics. MS is an immune-mediated disease that affects over 2 million people worldwide and is the number one cause of disability in young patients. Most therapeutic targets have focused on T cells; however, recently, the focus has shifted to the role of B cells in the pathogenesis of MS and the potential of B cells as a therapeutic target. 相似文献
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E. Wieczerzak E. Jankowska S. Rodziewicz‐Motowido A. Giedo J. giewka Z. Grzonka M. Abrahamson A. Grubb D. Brmme 《Chemical biology & drug design》2005,66(Z1):1-11
Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, Ki, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K. 相似文献
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18.
目的探讨复方丹参注射液联合干扰素治疗慢性乙肝患者的疗效。方法110例慢性乙肝患者,按随机方法分成①对照组30例,应用普通保肝药物治疗,疗程6个月;②丹参组30例,应用复方丹参注射液(每ml含丹参、降香各1g)30ml加入10%葡萄糖溶液300ml中静脉注射1个月;③IFN组30例,应用IFN—α 3MU,隔日一次肌内注射,3个月;④联合组20例,应用复方丹参注射液30ml加10%葡萄糖溶液300ml静脉注射1个月,IFN-α 3MU,隔日一次肌内注射,3个月。丹参组,IFN组和联合组保肝药物治疗同对照组。四组病例在性别、年龄、病程,治疗前肝功能等方面均无统计学差异。治疗前检测肝功能,肝炎病毒标志,血清HA、IV—C、PCI—Ⅱ,部分病例进行肝穿病理检查。治疗开始后每月检测肝功能,3个月(治疗后)和6个月(随访时)时检测血清HA、IV—C、PCⅢ及乙肝病毒标志,治疗后1年行肝穿病理检查。结果治疗前四组患者血清HA、PCⅢ、IV—C水平无统计学差异;治疗后丹参组、IFN组、联合组血清HA、FCⅢ、IV—C水平较治疗前及对照组有不同程度的降低。结论复方丹参注射液联合IFN治疗可使血清HA、PCⅢ、IV—C有明显下降,肝组织病理改变明显改善,为目前有效的慢性乙肝治疗措施。 相似文献
19.
The aim was to determine whether the immunogenicity of an investigational hepatitis B vaccine (spHB) is at least as high as that of a licensed control vaccine, Engerix B®, and to evaluate its safety before inclusion in new pediatric combination vaccines. Two randomized, controlled, blind-observer, Phase 3 trials were performed: one in Argentina (344 participants aged 10–15 years, 10 μg HBsAg/dose) and one in Uruguay (344 participants aged 16–45 years, 20 μg HBsAg/dose). Both vaccines were given in a 0, 1, 6 month schedule to all participants with a baseline anti-Hep B antibody titer <0.6 mIU/mL. Antibody titers were measured pre-dose 1, 1 month after dose 2, pre-dose 3, and 1 month after dose 3. Statistical non-inferiority analyses were performed on seroprotection rates (SP) post-dose 3 (% with anti-Hep B titers ≥10 mIU/mL; delta non-inferiority limit of −10%). In both studies, SP for the spHB vaccine was 100% and the spHB vaccine was non-inferior in terms of SP to the licensed control vaccine. GMTs post-dose 3 were approximately 1.8- and 4.1-fold higher for spHB in the 10–15 year and 16–45 year age groups, respectively. Reactogenicity was low for each vaccine, after each dose. This highly immunogenic hepatitis B candidate vaccine was selected for further investigation as a component of new pediatric combination vaccines. 相似文献
20.
Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy. 相似文献