Effects of a Th1- versus a Th2-biased immune response in protection against Helicobacter pylori challenge in mice

The roles that T helper type 1 (Th1) and T helper type 2 (Th2) Helicobacter pylori-specific immune responses play in protection from H. pylori challenge are poorly understood. It is expected that Th2 immune responses are required for protection against extracellular bacteria, such as H. pylori. However, recent studies have suggested that Th1 immunity is required for protection. The mechanisms by which this might occur are unknown. Our goal in this study was to more clearly define the effects of a Th1- versus a Th2-promoting H. pylori vaccine on immunity and protection. Therefore, we tested a Th1 vaccine consisting of an H. pylori sonicate and CpG oligonucleotides (CpG) and a Th2 vaccine consisting of a lipopolysaccharide (LPS)-depleted H. pylori sonicate combined with cholera toxin (CT). We demonstrate that although the Th2-promoting vaccine induced stronger systemic and local immune responses, only the Th1-promoting vaccine was protective.     

A coupled electromechanical model for the excitation-dependent contraction of skeletal muscle

This work deals with the development and implementation of an electromechanical skeletal muscle model. To this end, a recently published hyperelastic constitutive muscle model with transversely isotropic characteristics, see Ehret et al. (2011), has been weakly coupled with Ohm’s law describing the electric current. In contrast to the traditional way of active muscle modelling, this model is rooted on a non-additive decomposition of the active and passive components. The performance of the proposed modelling approach is demonstrated by the use of three-dimensional illustrative boundary-value problems that include electromechanical analysis on tissue strips. Further, simulations on the biceps brachii muscle document the applicability of the model to realistic muscle geometries.     

Complementary surface epitopes, myotropic adhesion and active grip in Trypanosoma cruzi-host cell recognition

Plasma membranes with complementary surface epitopes and with essentially the same orientation as tissue infective metacyclic trypomastigotes and epimastigotes of Trypanosoma cruzi adhere to L6 myoblast host cells preferentially to smooth muscle and epithelial cells as a function of time, surface area and concentration in saturation phenomena at 4 and 37°C. The initial adhesion rates are partially calcium ion dependent and, at saturation, they are also dependent on high energy phosphorylated intermediates, exerting an active grip on adherent parasite membranes. These phenomena are consistent with the existence of parasite attachment molecules on the external surface of the plasma membrane and complementary host cell receptor structures with the capacity to bind them.     

CDMNP-PEG-CD磁纳米颗粒诱导的骨骼肌反应性分析

目的　探讨SOMNP、CDMNP及CDMNP-PEG-CD磁性纳米颗粒置入小鼠骨骼肌所诱发的免疫反应性。 方法　以磁性Fe3O4与SiO2复合制备SOMNP, 将聚乙二醇（PEG）、环糊精（β-CD）分子链接SOMNP合成CDMNP,进一步添加聚假单胞烷（polypseudorotaxanes）合成CDMNP-PEG-CD磁性纳米颗粒。分别将3种纳米颗粒置入B6小鼠腓肠肌。组化染色、免疫荧光及FACS分析,分别评估不同置入时段SOMNP、CDMNP和CDMNP-PEG-CD纳米颗粒所诱发的肌毒性及肌内炎性渗出特征。 结果　SOMNP链接β-CD、PEG/β-CD及polypseudorotaxanes将限制纳米颗粒的肌内扩散,导致CDMNP和CDMNP-PEG-CD在肌内的滞留时间延长、材料邻近区肌细胞坏死、肌内单核/巨噬细胞聚集。较之CDMNP-PEG-CD, CDMNP纳米颗粒吸引更多T细胞进入肌组织。 结论　SOMNP、CDMNP及CDMNP-PEG-CD纳米颗粒均为潜在的体内免疫诱导物。polypseudorotaxanes修饰赋予CDMNP-PEG-CD纳米颗粒较好的体内相容性。     

微小RNA调节骨骼肌发育与损伤修复的作用及其机制

microRNAs是一类非编码小RNAs分子,新近发现其具有重要的调节基因表达的功能,它能通过抑制翻译和降解靶mRNA来负性调控转录后水平的基因表达,miRNAs已经被证实在肌肉发育和肌细胞增殖和分化的调节中具有重要作用。最近研究发现,肌肉特异性转录因子控制一些microRNAs的表达,通过多种机制调节肌肉发育和功能。结合信息学、生物化学和遗传基因学方法,不仅将阐明骨骼肌microRNAs调控网络,更好地理解肌肉组织的调节,还将通过鉴定候选microRNAs的潜在临床应用靶点,增加肌肉营养不良的治疗干预的新机会。     

Haemodynamic considerations in the design of a skeletal muscle ventricle

Skeletal muscle ventricles (SMVs) configured to operate as diastolic counterpulsators show promise as cardiac assist devices. In four pigs, SMVs were connected to the aorta by a single-limbed conduit and activated during every third cardiac diastole. During the assisted beats, mean, diastolic aortic pressure increased by 30.3±2.2%, peak diastolic aortic pressure increased by 38.5±2.7%, the endocardial viability ratio increased by 42.3±3.4%, and mean left anterior descending coronary artery flow increased by 61.6±4.5%. Although there are major advantages to making the connection to the aorta by a single-limb conduit, the lack of separation between inlet and outlet means that such devices must be designed carefully to avoid thrombogenesis under chronic conditions. Design rules were developed for this configuration, based on earlier in vitro studies. They addressed the problem of statis by promoting the development of a propagating vortex that travels the length of the ventricle and ensured proper exchange of blood with the circulation by limiting the volume of the connecting conduit. An SMV compatible with these rules, was connected in a pig. At elective termination 1 week later, activation of the SMV increased peak diastolic pressure by 20.1% and reduced left-ventricular stroke work in the post-assisted beat by 10.1%. The SMV was free from thrombus.     

针刺对运动性骨骼肌损伤大鼠骨骼肌线粒体自噬的影响

目的:通过观察针刺对大负荷运动大鼠骨骼肌线粒体自噬相关蛋白表达的影响,探讨针刺在运动性骨骼肌损伤修复中的作用及其机制。方法:将128只成年雄性Sprague-Dawley大鼠随机分为4组:空白对照(control,C;n=8)组、单纯运动(exercise,E;n=40)组、单纯针刺(acupuncture,A;n=40)组和运动针刺(exercise and acupuncture,EA;n=40)组。其中,E和EA组进行1次下坡跑运动,A组和EA组(运动后即刻)施加针刺处理。后3组根据干预后不同时相又分为0 h、12 h、24 h、48 h和72 h亚组(n=8),分别于对应时点分离比目鱼肌进行检测,使用透射电子显微镜观察骨骼肌线粒体超微结构变化;采用ELISA法检测比目鱼肌线粒体定量酶柠檬酸合成酶(CS)的含量变化;应用Western blot法检测骨骼肌PTEN诱导假定激酶1(PINK1)、parkin和微管相关蛋白1轻链3(LC3)的蛋白表达变化。结果:1次大负荷运动后大鼠比目鱼肌线粒体出现明显肿胀和肌膜下积聚等超微结构异常变化,伴有大量自噬体形成;同时CS的含量明显减少(P0.05);线粒体自噬蛋白PINK1、parkin和LC3均出现一过性的表达升高(P0.05)。运动后针刺明显改善了线粒体超微结构的异常变化,减少自噬溶酶体的出现,同时抑制CS的含量减少,下调PINK1、parkin和LC3在线粒体上的表达(P0.05)。结论:1次大负荷运动后骨骼肌线粒体结构和数量受损,通过激活PINK1/parkin途径诱发线粒体自噬的过度发生。大负荷运动后针刺可以缓解骨骼肌线粒体的损伤,其作用机制可能是通过下调线粒体外膜蛋白PINK1表达,抑制其对下游胞浆蛋白parkin的招募,进而影响LC3与线粒体的结合以抑制线粒体自噬过度激活。     

Pathomorphological signs of damage to capillary endothelium in skeletal muscle after traumatic injury to or replantation of a limb

Several months after an extensive crush injury to or replantation of a limb in rats, capillary endotheliocytes of its skeletal muscle are seen to undergo ultrastructural changes of both “dark” and “light” types. Destructive/degenerative changes of the “light” type are accompanied by intracellular edema and cytoplasmic homogenization and can eventually result in monocellular colliquative necrosis. Changes of the “dark” type are characterized by signs of functional overstrain in the endotheliocytes, succeeded by destructive/degenerative cytoplasmic changes, increased electron density of intracellular organelles, loss of distinct boundaries by the nucleus and intracellular structures, rupture of cell membranes, endothelial desquamation, and some other changes, which eventually lead to coagulation necrosis, followed by breakdown of the cell into small fragments. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N^no 10, pp. 378–383, October, 1994     

Interstrain peculiarities of the secondary immune response in mice

CBA, CC57BR, C57B1/6, BALB/c, and outbred white mice were intraperitoneally or subcutaneously (C57B1/6 strain) immunized with sheep red cells in a dose optimal for the development of delayed-type hypersensitivity but subthreshold for antibody production. Seven days later the mice were reimmunized with sheep red cells in various doses subcutaneously (CBA, C57B1/6, BALB/c, outbred mice) or intraperitoneally (CBA, CC57BR, outbred mice), and 5 days after reimmunization the intensity of antibody production and delayed-type hypersensitivity was assessed. Intact mice were controls. The immunization was found to selectively enhance delayed-type hypersensitivity in C57B1/6, CC57BR, and BALB/c mice and to intensify antibody production in CBA mice; both phenomena were observed in outbred mice. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 11, pp. 499–501, November, 1994 Presented by K. P. Kashkin, Member of the Russian Academy of Medical Sciences     

rIL-18对肺炎链球菌肺炎小鼠Th1/Th2免疫应答的影响

目的 研究重组白细胞介素18(rIL-18)对肺炎链球菌肺炎小鼠Th1/ Th2免疫应答的影响.方法 鼻腔接种肺炎链球菌建立小鼠肺炎链球菌肺炎模型,将Balb/c小鼠24只随机分为3组,分别为对照组,肺炎组和肺炎rIL-18干预组(n=8 ),RT-PCR法检测各组小鼠肺组织中IFN-γ、IL-4 mRNA 的表达,同时支气管肺泡灌洗液(BALB)进行活菌计数,有核细胞分类计数.结果 ①肺炎rIL-18干预组BA LF中性粒细胞和巨噬细胞计数显著高于肺炎组和对照组(P＜0.001);②肺炎rIL-18 干预组BALF活菌计数显著低于肺炎组(P＜0.001);③肺炎rIL-18干预组肺组织IFN- γ mRNA表达上调而IL-4 mRNA表达下调(P＜0.001).结论 在小鼠肺炎链球菌肺炎早期给予rIL-18可诱导IFN-γ的合成,促进Th1免疫应答,使Th1/ Th2免疫平衡向Th1免疫偏移、促进宿主对肺炎链球菌的防御.     

Mechanisms of pathogenesis in Chagas disease

Chagas disease, caused by the obligate unicellular parasite Trypanosoma cruzi, presents itself in a diverse collection of clinical manifestations, ranging from severe, fatal heart and digestive tract pathologies to unapparent or minor alterations that do not compromise survival. Over the years, a number of mechanisms have been proposed to explain the pathogenesis of chagasic tissue lesions, all of which have faced some criticism or been received with skepticism. This article excludes the autoimmunity hypothesis for Chagas disease because it has been extensively reviewed elsewhere, and summarizes the various alternative hypotheses that have been advanced over the years. For each of these hypotheses, an outline of its main tenets and key findings that support them is presented. This is followed by the results and comments that have challenged them and the caveats that stand on their way to wider acceptance. It is hoped that this writing will draw attention to our shortcomings in understanding the pathogenesis of Chagas disease, which, unfortunately, continues to figure among the most serious health problems of the American continent.     

pBudCE4.1/PPE68DNA疫苗诱导Balb/c小鼠产生Th1免疫应答

目的构建结核分枝杆菌PPE68 DNA疫苗,并探讨其在小鼠体内诱导的Th1免疫应答。方法将结核分枝杆菌PPE68基因和复制子OriM基因亚克隆入真核表达质粒pBudCE4.1中构建穿梭质粒,并用其免疫Balb/c小鼠,于第3次免疫后2周处死小鼠,分别检测免疫小鼠血清IgG2a水平、IFN-γ和IL-12水平;特异性蛋白刺激后淋巴细胞增殖状态;小鼠肺、脾组织病理改变情况。结果 PPE68 DNA疫苗免疫小鼠后血清中的IgG2a水平、IFN-γ和IL-12均有意义的提高,脾淋巴细胞增殖显著。脾肺未见明显病理改变。结论 PPE68DNA疫苗可有效诱导小鼠Th1免疫应答,为进一步研究其抗MTB的免疫保护作用奠定了基础。     

Contractile properties of skeletal muscle fibre bundles from mice deficient in carbonic anhydrase II

The function of cytosolic carbonic anhydrase (CA) isozyme II is largely unknown in skeletal muscle. Because of this, we compared the in vitro contractile properties of extensor digitorum longus (EDL) and soleus (SOL) fibre bundles from mice deficient in CA II (CAD) to litter mate controls (LM). Twitch rise, 1/2 relaxation time and peak twitch force at 22°C of fibre bundles from CAD EDL [28.4±1.4 ms, 31.2±2.3 ms, 6.2±1.0 Newton/cm² (N/cm²), respectively] and CAD SOL (54.2±7.5 ms, 75.7±13.8 ms, 2.9±0.5 N/cm², respectively) were significantly higher compared to LM EDL (20.5±2.2 ms, 21.9±3.7 ms, 4.5±0.2 N/cm²) and LM SOL (42.8±3.5 ms, 51.4±2.4 ms, 2.1±0.4 N/cm²). However, in acidic Krebs–Henseleit solution, mimicking the pH, PCO₂, and HCO₃ ^– of arterial blood from CAD mice, twitch rise, 1/2 relaxation time, and peak twitch force of fibre bundles from CAD EDL (19.3±0.7 ms, 19.7±2.3 ms, 4.8±0.8 N/cm²) and CAD SOL (41.4±3.6 ms, 51.9±5.5 ms, 2.2±0.7 N/cm²) were not significantly different from LM fibre bundles in normal Krebs–Henseleit solution (EDL: 19.7±1.1 ms, 21.6±0.6 ms, 4.7±0.2 N/cm²; SOL: 42.5±3.1 ms, 51.8±2.6 ms, 1.8±0.3 N/cm²). A higher pH_i during exposure to acidic bathing solution was maintained by CAD EDL (7.37±0.02) and CAD SOL (7.33±0.05) compared to LM EDL (7.28±0.04) and LM SOL (7.22±0.02). This suggests that the skeletal muscle of CAD mice possesses an improved defense of pH_i against elevated pCO₂. In support of this, apparent non-bicarbonate buffer capacity (in mequiv H⁺ (pH unit)^–1 (kg cell H₂O)^–1) as determined by pH microelectrode was markedly increased in CAD EDL (75.7±4.1) and CAD SOL (85.9±3.3) compared to LM EDL (39.3±4.7) and LM SOL (37.5±3.8). Both latter phenomena may be related to the slowed rate of intracellular acidification seen in CAD SOL in comparison with LM SOL upon an increase in PCO₂ of the bath. In conclusion, skeletal muscle from mice deficient in CA II exhibits altered handling of acid–base challenges and shows normal contractile behavior at normal intracellular pH.     

Peculiarities of primary humoral immune response in mice with cytostatic disease

Single intraperitoneal injection of cyclophosphamide in a maximum permissible dose (250 mg/kg) followed by immunization with thymus-dependent antigen (sheep erythrocytes) markedly suppressed the formation of antibody-producing cells in the spleen, especially at early stages of cytostatic disease, and delayed the synthesis of specific antibodies in male CBA/CaLac mice. Platidiam (cisplatin) injected in comparable doses 4 days before immunization practically did not suppress the formation of antibody-producing cells and their functional activity, but being injected 30 days before immunization reduced the number of antibody-producing cells. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 4, pp. 440–443, April, 2000     

Carbon dioxide,extracellular pH and fibre water in frog skeletal muscle

The fibre water of frog skeletal muscle was increased by exposure of the muscle to CO₂. Exposure to acid at constant PCO₂ caused no change in fibre water although muscle weight decreased, whereas exposure to alkali increased fibre water.Supported by the Schweizerische Stiftung für Midizinisch-Biologische Stipendien     

Individual variations of the immune response in BALB/c mice

The nature and the causes of variations of the immune response to thyroid hormones are analyzed in BALB/c mice. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 1, pp. 80–82, January, 1995 (Presented by Yu. A. Romanov, Member of the Russian Academy of Medical Sciences)     

Electron-microscopic investigation of satellite cell formation in skeletal muscle during physical exertion

The content of condensed chromatin is increased in nuclei of skeletal muscle fibers of rats after repeated physical exertion continued until exhaustion. Some muscle fiber nuclei, together with part of the sarcoplasm, were separated from the muscle fibers. Satellite cells formed from the separated parts of the muscle fibers.Laboratory of Functional Morphology, All-Union Scientific-Research Institute of Physical Culture, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Kupriyanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 11, pp. 1385–1388, November, 1976.     

Increased association of Trypanosoma cruzi with sialoadhesin positive mice macrophages

Trypanosoma cruzi is a parasite with large amounts of sialic acid (SA) residues exposed at its surface that seems to be involved in macrophages infection. Some macrophages, present in T. cruzi infected tissues, expresses sialoadhesin (Sn), a receptor that recognizes SA. Thus, the involvement of Sn in the association of T. cruzi to macrophages was investigated. Sn was induced in mice peritoneal macrophages by homologous serum (HS) cultivation. Epimastigotes and trypomastigotes associated more to HS cultured macrophages than to fetal bovine serum (FBS). Blocking of Sn with antibodies reduced the association of trypomastigotes to similar level as for FBS cultured macrophages. Desialylation reduced the association of parasites to HS cultured macrophages indicating the Sn importance. Furthermore, the entrance mechanism of trypomastigotes to Sn positive macrophages has a phagocytic nature as demonstrated by scanning electron microscopy and cytochalasin D treatment. Sn positive macrophages may important in the initial trypomastigote infection, thus in the establishment of Chagas disease.