白细胞介素－1受体拮抗剂对肺间质纤维化的影响

白细胞介素－１（ＩＬ－１）是一种具有多种生物活性的细胞因子，它参与了肺间质纤维化形成的过程。白细胞介素－１受体拮抗剂（ＩＬ－１ｒａ）能和ＩＬ－１竞争靶细胞表面受体，阻断ＩＬ－１的效应。为了探索治疗肺间质纤维化的新途径，我们在博莱霉素所致大鼠肺间质纤维化模型上，气管灌注重组人ＩＬ－１ｒａ，观察病理变化、胶原蛋白量以及转化牛长因子－βｍＲＮＡ在肺内表达的变化，评价ＩＬ－１ｒａ对肺间质纤维化形成的影响，结果发现这些指标在ＩＬ－１ｒａ治疗组和对照组间并无明显差异。     

心房颤动消融术后二尖瓣峡部房性心动过速的发生机制及消融治疗

目的探讨心房颤动(简称房颤)患者环肺静脉左房线性消融术后二尖瓣峡部房性心动过速(简称房速)的发生机制及其消融策略。方法122例房颤患者采用EnSite-NavX和环状电极行环肺静脉左房线性消融,术后32例复发房颤或房速,8例经EnSite-NavX激动标测及拖带标测证实存在二尖瓣峡部房速,在三维导航下于左下肺静脉口部下缘至二尖瓣环之间行线性消融,对不能成功阻断二尖瓣峡部传导者予以冠状静脉窦内消融。术中同时探查双侧肺静脉电位,如传导恢复予以再次隔离。结果8例中2例呈无休止性发作,6例为阵发性,可被程序刺激诱发。房速的周长217.5±20.6ms,其中顺钟向折返5例,逆钟向折返3例。二尖瓣峡部线性消融至完全性双向传导阻滞5例,3例心内膜途径失败者经冠状静脉窦内消融,其中1例获得成功。术后随访5.5±4.3个月,6例无房颤及房速发作,1例仍有阵发性房速发作。另1例术后房速呈无休止发作,予以胺碘酮及美托洛尔控制心室率治疗。结论环肺静脉线性消融术后发生的二尖瓣峡部房速与左房线性消融治疗房颤的致心律失常作用有关,其主要的机制是消融线相关的大折返性心动过速,阻断峡部传导可以治疗此类房速。     

IL-1ra对Fn LPS诱导人牙髓细胞合成IL-1β的拮抗作用

目的观察人重组白细胞介素1受体拮抗剂(IL-1ra)对内毒素脂多糖（LPS）刺激的人牙髓细胞分泌IL-1β的拮抗作用。方法用ELISA夹心法检测IL-1β含量。结果人牙髓细胞经LPS刺激后,IL-1β含量明显增加。当加入高浓度的IL-1ra后,IL-1β含量与对照组相比有显著性降低,在LPS刺激牙髓细胞60分钟以前加入一定浓度的IL-1ra,牙髓细胞培养上清液中IL-1β的含量显著降低,但在90分钟以后再加入IL-1ra,则IL-1β的含量无明显变化。结论高剂量的IL-1ra能够抑制LPS刺激的牙髓细胞分泌IL-1β,从而拮抗IL-1的生物学活性。     

用包涵体复性的方法制备重组人白细胞介素-1受体拮抗剂

通过大肠杆菌将IL-1ra表达成包涵体,将包涵体用8M尿素溶解后,稀释4倍后直接用离子交换柱层析进行复性和纯化,复性后得到的IL-1ra纯度大于95%,生物活性大于1×105IU/mg,内毒素含量也比较低。Western-Blotting印迹也表明重组蛋白具有IL-1ra的抗原活性。     

脊髓损伤中枢性疼痛大鼠损伤节段上WDR神经元的电生理变化

为研究脊髓损伤后慢性中枢性疼痛 (CCP)的发生机制 ,将大鼠以重物坠落法造成脊髓损伤CCP模型 ,记录损伤平面上广动力范围 (WDR)神经元诱发放电的变化 ,并以正常大鼠为对照进行比较。发现 :具有CCP大鼠的WDR神经元的诱发电位晚成分的放电阈值、潜伏期、放电频率、放电数与对照相比有非常显著性差异 (P <0 .0 1) ;早成分除放电数有非常显著性差异 (P <0 .0 1)外 ,其他指标与对照组相比无显著差异。提示 :脊髓损伤后上位中枢WDR神经元的高兴奋性可能是CCP的原因     

Jakob Lenz ou la folie à l’opéra

Scenes of madness were common in XIXth century operas. Most of the time they were involving love hindered women, who become mad victims of family or social conflicts. A contemporary opera, “Jakob Lenz” has a different approach of the problem as it is based upon a real case of schizophrenia. The German poet, Jakob Lenz (1751-1792), who had been a prominent figure of the so called Sturm und Drang movement and a close friend of Goethe, happened to be slowly engulfed by insanity. The opera, whose composer is Wolfgang Rihm, depicts Lenz’s attempt to overcome his madness in a small village of the Vosges mountains, helped bya then famous protestant minister, Jean-Frederic Oberlin. The cure proved to be a failure and the remaining years of his life were spent in aimless drifting and poverty. Rihm’s opera is based upon a short story written by Georg Büchner, a romantic writer, of early XIXth century.     

À propos de la folie à l’opéra

The author evokes the importance of the themes of insanity in opera works, since the l6th century up to the present time. Among those problems: what about the “lyrical delight” provoked by such madness scenes? What is the importance of those operatic arias, in particular since the romantic era? Is there a peculiar, specific, function of the women’s voices in relation to such symptoms?     

Polymorphonuclear leucocytes selectively produce anti-inflammatory interleukin-1 receptor antagonist and chemokines, but fail to produce pro-inflammatory mediators

The role of neutrophils in the immune response has long been regarded as mainly phagocytic, but recent publications have indicated the production of several cytokines by polymorphonuclear leucocytes (PMN). The results of the individual reports, however, vary considerably. In this study, we established a cytokine profile of pure human neutrophils and demonstrated that minor contamination of peripheral blood mononuclear cells (PBMCs) in PMN preparations can lead to false-positive results. In our hands, peripheral blood PMN fail to produce the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha). Instead, they secrete large amounts of the chemokine IL-8 and the anti-inflammatory IL-1 receptor antagonist (IL-1ra). Additionally, PMN preparations of a high purity show production of the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and growth-related oncogene-alpha (GRO-alpha), as well as macrophage colony-stimulating factor (M-CSF). The neutrophil therefore represents a novelty by producing the antagonist of IL-1beta (i.e. IL-1ra) in the absence of IL-1beta itself. To support our results, we differentiated stem cells from human cord blood into PMN and monocytes, respectively. These in vitro-differentiated PMN showed the same cytokine profile as peripheral blood PMN lacking IL-1beta, while differentiated monocytes produced the expected IL-1beta in addition to IL-1ra. The clear anti-inflammatory nature of their cytokine profile enables PMN to antagonize pro-inflammatory signals in experimental conditions. It is therefore possible that PMN play a key role in immune regulation by counteracting a dysregulation of the inflammatory process. Clinical studies, in which administration of recombinant G-CSF had a favourable effect on the outcome of severe infections and even sepsis without worsening inflammation, could thus be explained by our results.     

Adhesion dependent release of hepatocyte growth factor and interleukin-1 receptor antagonist from human blood granulocytes and monocytes: Evidence for the involvement of plasma IgG,complement C3 and β2 integrin

Objective:Evolving evidence of anti-inflammatory effects is observed in patients with rheumatoid arthritis or ulcerative colitis following periodic adsorptive granulocyte and monocyte (GM) apheresis with a column containing cellulose acetate (CA) beads as apheresis carriers. This study was undertaken to obtain insights into mechanisms of anti-inflammatory actions of adsorptive GM apheresis with CA beads. Methods:In a series of in-vitro experiments, we investigated the effects of plasma proteins and the leucocytes 2 integrin (CD18) on granulocyte adsorption to CA beads. Results:Granulocyte adsorption to CA beads required plasma IgG, the complement C3 and was inhibited by an antibody to leucocytes CD18. Further, hepatocyte growth factor (HGF) and interleukin-1 receptor antagonist (IL-1ra) which have strong anti-inflammatory actions were released by granulocytes that adhered to CA beads. Conclusions:Plasma IgG, C3 derived complement activation fragments and leucocytes CD18 are involved in granulocyte adhesion to CA beads and hence the release of HGF and IL-1ra.Received 27 October 2003; returned for revision 16 December 2003; accepted by M. J. Parnham 8 January 2004