Comparison of the suppressive effects of soluble CR1 and C5a receptor antagonist in acute arthritis induced in rats by blocking of CD59

We investigated the effects of suppression of complement activation at C3 level and inhibition of C5a on acute synovitis in rats. Acute synovitis was induced in Wistar rats by intra-articular (i.a.) injection into one knee of 0.3 mg of MoAb 6D1 (anti-rat CD59 antibody). In the treatment groups, soluble CR1 (sCR1) or C5a receptor (C5aR) antagonist was administered intra-articularly or intravenously and effects on the course of the acute synovitis were monitored. Synovitis induced by 6D1 was characterized by joint swelling, thickening of synovial tissue, cellular infiltration and deposition of membrane attack complex (MAC) on the synovial surface. Neither inflammatory change nor MAC deposition was found in rats which received an i.a. injection of sCR1 to suppress complement activity in the joint. Intra-articular injection of sCR1 did not reduce plasma complement activity. Intravenous administration of sCR1 suppressed plasma complement activity but had no effect on the course of the arthritis and synovitis with MAC deposition was observed. Neither i.a. nor i.v. injection of C5aR antagonist had any suppressive effects on inflammatory change or MAC deposition in synovium. The data show that inflammatory change induced by 6D1 was mediated by local complement activation and was not accompanied by systemic complement activation. C5a generation was not responsible for the observed inflammation, suggesting that other complement activation products, possibly MAC, mediate the inflammatory change observed in this model of acute synovitis in rats.     

Cardiovascular risk factors in people with different genotypes in the insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme (ACE)

The deletion (D) allele of an insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme (ACE) has been reported to be an independent risk factor for myocardial infarction (MI), particularly in people lacking traditional risk factors. Furthermore, a borderline association between Lp(a) lipoprotein level and the I/D polymorphism at the ACE locus was reported in one study. We have searched for possible "level gene" or "variability gene" effects of ACE genes on Lp(a) lipoprotein, total cholesterol (TC), high density lipoprotein (HDL) cholesterol (HDLC), low density lipoprotein (LDL) cholesterol (LDLC), triglycerides (TG), apolipoprotein B (apoB), apolipoprotein A-I (apoA-I), and body mass index (BMI). None of these variables differed significantly between genotypes in the I/D polymorphism in any of three population samples. A single population sample created by combining the three series, exhibited an insignificant trend towards individuals carrying the D-allele having a higher level of Lp(a) lipoprotein than those lacking it, and DD homozygotes had a significantly higher Lp(a) lipoprotein level than the combined group of ID/II individuals (p = 0.03). These results may indicate that the D-allele of the I/D polymorphism at the ACE locus could influence the level of Lp(a) lipoprotein.     

Analysis of the mechanism of lipoprotein(a) assembly

We have assessed the ability of a battery of purified recombinant apolipoprotein(a) (r-apo(a)) derivatives to bind to immobilized low-density lipoprotein (LDL) by ELISA. Removal of the apo(a) kringle IV type 8 and type 9 sequences dramatically reduced apo(a) binding to LDL. The binding of apo(a) to LDL was effectively inhibited by arginine, lysine, the lysine analogue ε-aminocaproic acid and proline; comparable inhibition was observed using the 17K and KIV_5–8 r-apo(a) derivatives, suggesting a direct role for sequences contained in the latter species in mediating the initial non-covalent interactions which precede specific disulfide bond formation. We also determined that r-apo(a) binds directly to a synthetic apoB peptide spanning amino acid residues 3732–3745; this interaction appeared to be mediated by sequences present in apo(a) kringle IV types 8 and 9, and could be inhibited by arginine, lysine and proline. The results of this study indicate that the efficiency of Lp(a) assembly is a direct function of the initial non-covalent interactions between apo(a) and LDL; in addition, these studies suggest that Cys3734 in apoB mediates covalent linkage with apo(a) by virtue of the ability of the apoB sequences surrounding this residue to directly interact with apo(a) KIV type 9.     

High levels of Lp(a) lipoprotein in a family ith cases of severe pre-eclampsia

We report a family with two cases of severe pre-eclampsia/eclampsia in which very high levels of Lp(a) lipoprotein were found. The serum level of Lp(a) lipoprotein is genetically determined and the Lp(a) apolipoprotein has a close homology to plasminogen. Very high levels of Lp(a) lipoprotein might interfere with the fibrinolytic/thrombolytic process in man. A previous report suggested that a high maternal serum Lp(a) lipoprotein level can cause fetal growth retardation, and it is proposed that very high levels might lead to increased deposition of fibrin in the uterine spiral arteries in pregnancy, which is central in the pathogenesis of pre-eclampsia. If confirmed, a very high Lp(a) lipoprotein level could be one risk factor for pre-eclampsia that is genetically determined.     

Restriction site polymorphism at the LPA (Lp(a) apoliprotein; apoliprotein(a)) locus

A restriction site polymorphism in the Lp(a) apolipoprotein gene (the LPA gene) is reported. The basis for the polymorphism is presence or absence of an MspI restriction site that appears to be 3' to the last kringle IV structure of the gene. The "1" gene (presence of the restriction site) has a frequency of 0.316 and the "2" gene (absence of the restriction site) has a frequency of 0.684. Both members of each of 67 monozygotic (MZ) twin pairs had the same genotype and there was Mendelian segregation of the DNA variants in 40 families with a total of 75 children. There was a lower proportion of people with genotype 1-1 in the top quartile than in the 3 bottom quartiles of the population distribution of Lp(a) lipoprotein levels but the difference did not reach statistical significance.     

腺苷A2a受体在炎症反应中的作用

腺苷广泛分布于全身各组织器官,可通过与细胞表面相应G-蛋白偶联受体结合发挥抑制炎症反应,对抗缺血/缺氧和免疫调节等生物学作用.目前发现腺苷受体有4种亚型,即A1R、A2aR、A2bR和A3R.其中A2a腺苷受体(A2aR)广泛分布于神经胶质细胞,巨噬细胞,树突状细胞,肥大细胞,自然杀伤细胞等免疫细胞及内皮细胞和上皮细胞中,在相应的腺苷配体作用下,可通过腺苷-腺苷受体系统介导炎症反应和发挥免疫调节作用.     

甲型副伤寒杆菌鞭毛蛋白H1a基因原核表达系统构建及其表达产物的免疫原性和保护作用

目的 构建甲型副伤寒杆菌（Salmonella paratyphi A）H1a基因原核表达系统，确定表达产物rH1a免疫原性和保护作用，检测甲型副伤寒杆菌临床菌株H1a基因携带和表达情况。方法 采用高保真PCR从甲型副伤寒杆菌临床株JH01中扩增H1a基因，T-A克隆后测序，构建H1a基因原核表达系统pET32a-H1a-E．coli B121DE3。采用SDS-PAGE和BioRad凝胶图象分析系统检查rH1a表达情况，Ni-NTA亲和层析法收集rH1a。采用Western blot鉴定其免疫反应性和免疫原性。建立PCR和ELISA检测98株甲型副伤寒杆菌临床菌株H1a基因携带和表达频率。观察rH1a对甲型副伤寒杆菌50001株感染小鼠的免疫保护作用。结果 与报道的相关序列比较，所克隆的H1a基因核苷酸和氨基酸序列相似性均为99．59％。rH1a表达量为细菌总蛋白的60％左右。甲型副伤寒杆菌全菌抗血清能识别rH1a并与之结合。rH1a免疫家兔可产生抗体。100％（98／98）甲型副伤寒杆菌临床菌株均含有H1a基因并表达H1a。500μg rH1a灌喂或皮下注射免疫小鼠受甲型副伤寒杆菌50001株攻击后的存活率均为50．0％，若加入5μg rLTB，存活率分别上升至75．0％和66．7％。结论 本研究成功地从甲型副伤寒杆菌临床菌株中构建了H1a基因高效原核表达系统。rH1a有良好的免疫原性和一定的免疫保护作用。甲型副伤寒杆菌临床菌株广泛存在H1a基因并高频率表达。     

细胞衰老与p16INK4a的转录调控

抑癌基因p16~(INK4a)可特异地抑制CDK4及CDK6,在抑制细胞生长、促进细胞衰老等方面发挥重要的生物学作用。由于p16~(INK4a)功能的重要性,近年来,针对p16~(INK4a)转录调控方面的研究取得了一系列进展,发现了一系列正性和负性调控元件和转录调控因子,如:E47、Id1、Jun B、Bmi-1、RREB等,为进一步认识细胞增殖规律以及衰老进程具有重要的理论意义。     

Producción científica en educación médica en Latinoamérica en Scopus, 2011-2015

Objective

To describe the scientific production in medical education in Latin America in Scopus, in the period 2011-2015.

氧化修饰引起脂蛋白（a）结构和生化特性变化

本文观察了体外丙二醛（ＭＤＡ），铜离子（Ｃｕ２＋氧化修饰的脂蛋白（ａ）［Ｌｐ（ａ）］结构和生物学性质的变化。氧化修饰Ｌｐ（ａ）过氧化程度增高，负电荷增加，易被巨噬细胞—清道夫受体识别和摄取。ＭＤＡ修饰Ｌｐ（ａ）出现新的ＭＤＡ－ＬＤＬ位点；同纤维蛋白溶酶原（Ｐｇ）竞争抑制试验显示氧化、修饰Ｌｐ（ａ）同Ｐｇ同源性增加。提示载脂蛋白（ａ）状态同动脉粥样硬化的病理过程有关。