Stress proteins may provide a link between the immune response to infection and autoimmunity

Stress proteins are frequently the target of humoral and cell-mediatedimmune responses to infection. These proteins belong to highlyconserved gene families and there is substantial sequence homologybetween antigens produced by pathogenic organisms and the correspondingproteins from mammalian cells. Human T cells from sites of infectiousand autoimmune lesions proliferate in response to stress proteins,and mapping of antigenic determinants on a mycobacterial stressprotein shows that both species specific and highly conserved,‘self-like’, regions of the molecule can take partin immune recognition. It is proposed that the lymphocyte populationinduced in response to stress proteins of pathogens during infectionincludes cells capable of autolmmune recognition of the correspondingself protein. Local accumulation of self stress proteins—inresponse to viral infection, for example—may subsequentlyprovide a stimulus for proliferation of such autoreactive lymphocytes,thereby triggering a cycle of events which may contribute tothe pathological damage associated with autoimmune disease.     

TREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment

Variants in the microglial receptor TREM2 confer risk for multiple neurodegenerative diseases. However, it remains unknown how this receptor functions on microglia to modulate these diverse neuropathologies. To understand the role of TREM2 on microglia more generally, we investigated changes in microglial function in Trem2^−/− mice. We found that loss of TREM2 impairs normal neurodevelopment, resulting in reduced synapse number across the cortex and hippocampus in 1-month-old mice. This reduction in synapse number was not due directly to alterations in interactions between microglia and synapses. Rather, TREM2 was required for microglia to limit synaptic engulfment by astrocytes during development. While these changes were largely normalized later in adulthood, high fat diet administration was sufficient to reinitiate TREM2-dependent modulation of synapse loss. Together, this identifies a novel role for microglia in instructing synaptic pruning by astrocytes to broadly regulate appropriate synaptic refinement, and suggests novel candidate mechanisms for how TREM2 and microglia could influence synaptic loss in brain injury and disease.     

Platelet adhesion to damaged coronary arteries: Comparison in normal and von Willebrand disease swine.

The early response to coronary artery injury was investigated in normal swine and in swine with von Willebrand disease (vWD). Thirty minutes after coronary endothelial denudation, a monolayer of platelets was adherent to areas of simple injury in both bleeder and normal swine. The number of adherent platelets was not significantly different in the two phenotypes. Injury involving the media of the vessel produced platelet-fibrin thrombi. Platelet activation, as judged by pseudopod formation and platelet spreading over areas of simple injury, was significantly less in bleeder animals than in normal animals. These studies suggest that chemotaxis and initial contact adhesion of platelets to injured arterial wall is independent of the von Willebrand factor. On the other hand, the spreading and activation of platelets on the subendothelium appear to be dependent on the presence of plasma von Willebrand factor. Through this mechanism von Willebrand factor may contribute to arterial thrombosis and atherogenesis.     

蒿甲醚对大鼠肺泡Ⅱ型上皮细胞DNA的影响

目的:蒿甲醚除了具有良好的临床治疗作用外,对正常组织有极大的副作用。实验拟观察蒿甲醚对大鼠肺泡Ⅱ型上皮细胞的影响。方法:实验于2005-09-20/2007-03-10在山东省泰山医学院生命科学研究所、中心实验室和机能实验室完成。①实验材料:蒿甲醚购自昆明制药厂,分析纯,使用前先进行预处理,处理方法:研磨后用溶液配成1g/L的母液,超声助溶解后供实验用。Wistar大鼠70只,体质量(70±15)g,雌雄不拘,由山东大学医学院实验动物中心提供。实验过程中对动物处置符合动物伦理学标准。②实验方法:将大鼠随机分为普通饲料对照组(n=10)和实验组(n=60),实验组分6个亚组,分别在饲料中加入0.1,0.2,0.4,0.8,1.6,3.2mg/kg的蒿甲醚。采用单细胞凝胶电泳技术观察大鼠肺泡Ⅱ型上皮细胞DNA的改变。结果:70只大鼠,饲养过程中实验组死亡6只,死亡原因为饲料添加蒿甲醚造成。当饲料中的蒿甲醚浓度为0.1mg/kg时,大鼠肺泡Ⅱ型上皮细胞DNA损伤率与对照组相比,差异无统计学意义;饲料中的蒿甲醚浓度超过0.2mg/kg时,大鼠肺泡Ⅱ型上皮细胞DNA损伤率明显增加,与对照组相比,差异有统计学意义。且损伤程度与饲料中蒿甲醚含量呈正相关。结论:当饲料中的蒿甲醚浓度超过0.2mg/kg时,蒿甲醚可在一定程度上改变肺泡Ⅱ型上皮细胞的DNA生物学特性。且随着蒿甲醚浓度的升高,这种损害更为明显。     

The use of ratings of perceived exertion for regulating exercise levels in rowing ergometry

The purpose of this study was to examine the validity of the use of ratings of perceived exertion (RPE) to estimate and regulate exercise intensity during rowing ergometry. Nine competitive male rowers [mean age 28.6 years, (SD 6.3)] completed two rowing trials on an ergometer. The first trial (estimation) consisted of an incremental protocol designed to elicit a range of work outputs (WO) and heart rates (HR). The subjects indicated their perception of effort using a 15-point scale at each intensity level. In the second trial (production), 7–14 days later, the subjects were asked to produce exercise intensities corresponding to five levels of RPE: 15,11,17,13, and 19. Data analysis revealed high Pearson correlation coefficients between HR and RPE (r = 0.95,P < 0.01) and WO and RPE (r = 0.96,P < 0.01) during the estimation trial. In addition, significant correlations (P < 0.01) were obtained between the estimation and production trials for HR (r = 0.82) and WO (r = 0.84). Posthoc analysis of variance revealed that the observed differences in mean HR were not significant (P > 0.05) at three of the five intensity levels (RPE 15,17 and 19), but were at the two lowest RPE levels (11 and 13). Significant mean differences in WO were seen at all but RPE 17. These data support the validity of the RPE scale as a measure of physiological strain among competitive male rowers, and offer support for its use as a method of regulating the intensity of rowing ergometry, especially at higher levels.     

Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11

In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.      

Clinical profiling of recombinant follicle stimulating hormone (rFSH; Puregon): relationship between serum FSH and efficacy

Single-dose and multiple-rising dose studies of recombinantfollicle stimulating hormone (rFSH) in hypogonadotrophic maleand female volunteers demonstrated that the rate of FSH absorptionafter i.m. injection is higher in men than in women. In theabsence of endogenous FSH, a correlation between serum FSH andbody weight became apparent. The elimination half-life of rFSHwas not different between the sexes and was comparable withurinary FSH. However, the in-vitro bio:immuno ratio of serumFSH was significantly higher after the administration of rFSHthan after urinary FSH. When rFSH was administered daily witha fixed dose, steady state levels were reached within 3-5 days.Serum FSH concentrations increased in a dose-dependent mannerwhen the daily dose was increased weekly over 3 weeks from 75to 225 IU. In hypogonadotrophic women, rFSH induced normal folliculargrowth whereas oestrogen synthesis was impaired. In women pituitarysuppressed by a high-dose oral contraceptive, the daily administrationof 150 IU rFSH for 1 week induced more and larger antral folliclesthan the same regimen with urinary FSH, whereas the serum immunoactiveFSH concentrations measured 24 h after each dosing were similar.It is concluded that even though equal or lower serum immunoactiveFSH concentrations were obtained following the administrationof rFSH compared with urinary FSH, circulating bioactivity FSHconcentrations were higher. Therefore, the conventional ideathat serum immunoreactive FSH correlates positively with themagnitude of the ovarian response should be reconsidered.