Accumulation of mitochondrial DNA deletions in myotubes cultured from muscles of patients with mitochondrial myopathies

 Myoblast cultures were established from muscle biopsies of two patients harboring heteroplasmic mitochondrial (mt) DNA deletions. The accumulation kinetics of the deleted mtDNA was followed during myoblast to myotube differentiation. The percent- age of deleted mtDNA was determined by quantitative PCR in myoblasts, myotubes, and muscle biopsies. The deleted form accounted for 65% of the mtDNA present in a muscle biopsy from a patient harboring a 5.6-kb deletion. The percentage of deleted mtDNA was 1.2% in myoblasts and increased progressively after differentiation, up to 12% at 21 days after the commitment time. In a second patient harboring a 2.8-kb deletion, the percentage of deleted mtDNA increased much more slowly: from 0.07% in myoblasts to 0.21% after 22 days of differentiation, as compared with 45% in the muscle biopsy. Thus, a three- and ten-fold increase, respectively, in the fraction of deleted mtDNA occurred during the differentiation of myoblasts to myotubes from the two patients. The faster accumulation of deleted mtDNA in the first patient’s cells was linked to an earlier myoblast to myotube differentiation, suggesting that the level of deleted mtDNA is inversely related to the rate of cell proliferation. Received: 16 April 1996/Accepted: 29 July 1996     

Plasma and erythrocyte manganese concentrations

This study was carried out to assess manganese (Mn) status after an acute episode of myocardial infarction. Plasma and erythrocyte Mn concentrations were measured from admission to hospital to day 15 postadmission in 21 patients suffering from acute myocardial infarction and in three control groups. The determination of Mn in these biological fluids was performed by electrothermal atomic absorption spectrometry. Plasma Mn was higher (p<0.01) and erythrocyte Mn was similar in the acute myocardial infarction group compared to healthy age-matched control group. Plasma and erythrocyte Mn remained unchanged during the 2 wk after acute myocardial infarction and were not correlated to enzyme activities. A decrease of erythrocyte Mn with age, expressed in nmol/L, was noted (p<0.02). These results suggest that plasma and erythrocyte Mn do not provide an indication of myocardial damage. Nonetheless, Mn status in elderly merits further attention.     

Neutrophil extracellular traps activate lung fibroblast to induce polymyositis‐related interstitial lung diseases via TLR9‐miR‐7‐Smad2 pathway

Excessive neutrophil extracellular trap (NET) formation may contribute to polymyositis (PM)‐associated interstitial lung diseases (ILD), but the underlying mechanism is not fully revealed. In this study, we found that NET accelerated the progression of ILD and promoted pulmonary fibrosis (PF) in vivo. miR‐7 expression was down‐regulated in lung tissue of PM group than control group, and NETs further decreased miR‐7 expression. TLR9 and Smad2 were up‐regulated in lung tissue of PM group than control group, and NETs further increased TLR9 and Smad2 expressions. In vitro experiments showed that PMA‐treated NETs accelerated the proliferation of LF and their differentiation into myofibroblast (MF), whereas DNase I decreased the promotion effect of NETs. Neutrophil extracellular trap components myeloperoxidase (MPO) and histone 3 also promoted the proliferation and differentiation of LF. In addition, we demonstrated that TLR9 involved in the regulation of NETs on LF proliferation and differentiation, and confirmed the interaction between miR‐7 and Smad2 in LF. Finally, miR‐7‐Smad2 pathway was confirmed to be involved in the regulation of TLR9 on LF proliferation and differentiation. Therefore, NETs promote PM‐related ILD, and TLR9‐miR‐7‐Smad2 signalling pathway is involved in the proliferation of LFs and their differentiation into MFs.     

Rituximab in immunologic glomerular diseases

Experimental data suggest that the B-cell antigen CD20 may play a significant role in the pathogenesis of many diseases including glomerular diseases. These and other findings underpin the central concept of B-cell-depleting therapies that target CD20 antigen as treatments for lupus nephritis, idiopathic membranous nephropathy, focal segmental glomerulosclerosis, cryglobulinemic glomerulonephritis, antibody mediated renal allograft rejection and recurrent glomerulonephritis in renal allograft. Use of rituximab as a B-cell depleting therapy has been associated with clinical improvement and has emerged as a possible adjunct or alternative treatment option in this field of nephrology.     

APE/Ref-1在中枢神经系统氧化应激反应中的保护作用

化学性质活泼的自由基（free radicals）在保持产生和清除平衡的稳衡性动态下能履行正常的生理功能,但超过生物体的清除能力则可导致多种疾病.无嘌呤/无嘧啶核酸内切酶/氧化还原因子1（apurinic/apyrimidinic endonuclease/redox-factor 1, APE/Ref-1）是一种体内分布广泛的多功能蛋白质,通过修复DNA的无嘌呤/无嘧啶（apurinic/apyrimidinic, AP）部位参与DNA的碱基切除修复(base excision repair, BER).APE/Ref-1还可通过还原许多转录因子的半胱氨酸残基使之易于与DNA结合而调控真核细胞的基因表达.APE/Ref-1的抗细胞凋亡作用使其在自由基所致中枢神经系统病变如脑缺血-再灌注损伤、神经退行性病变、脑动脉粥样硬化中发挥了重要作用.     

水稻主要病虫综合防治专家系统—系统外壳的研制

按照国家八五项目要求,以水稻病虫害管理知识为背景,笔者构建了水稻主要病虫综防专家系统外壳（ESRIPM）．并初步建立了珠江三角洲稻区主要害虫综合防治专家系统,系统中提出一种知识的组织方法,成功地把模型引入专家系统中．本系统具有知识编辑、咨询、专家系统;系统维护、4个一级子系统,系统中已装入三化螟,稻飞虱,稻纵卷叶螟等害虫综防管理的知识,并通过调试．本系统采用下拉式菜单,人机界面友好,操作简单．此专家系统外壳也适用建立其它各种害虫管理的专家系统．     

硫氧还蛋白与心血管疾病

硫氧还蛋白是细胞内最重要的二硫键还原酶,对维持细胞内蛋白质的还原状态并正常发挥功能着重要的作用,此外。硫氧还蛋白、硫氧还蛋白还原酶和硫氧还蛋白过氧化物酶组成了细胞内最重要的抗氧化系统之一,在对抗细胞的氧化应激上起着重要作用。心血管疾病是威胁人类健康的主要疾病,它与炎症反应和氧化应激有着密切的联系。文章将从硫氧还蛋白的抗氧化、抗炎、抗细胞凋亡,调控与炎症基因表达有关的核转录因子的转录活性,以及调节细胞内蛋白质的亚硝基化等诸多方面阐述硫氧还蛋白在防御心血管疾病方面可能具有的生物学功能。     

Acylgalactosylceramides in Developing Dysmyelinating Mutant Mice

Acylgalactosylceramides (AGC) from forebrains of normal and dysmyelinating (quaking and shiverer) mice were purified by Florisil column chromatography and preparative TLC. These procedures resolved the AGC on the basis of their R_f values into two main fractions which co-nigrate with their homologs from rat forebrains. In control animals, AGC were detectable in mouse forebrains from the eighth postnatal day and reached maximal values within 20 days. The same developmental pattern was obtained in dysmyelinating shiverer mice but the AGC content was reduced to approximately 30% of control values. In quaking mutants, the AGC were hardly detected. They were also present in sciatic nerve of normal mice and to a lesser extent in trembler mice. Gas chromatography-mass spectrometry analysis of both ester- and amide-linked fatty acids isolated from AGC of normal and shiverer mice shows that the shiverer mutant AGC display a chemical structure similar to that of normal AGC. AGC constituents of control myelin are reduced by approximately 70% in shiverer myelin, indicating that these molecules can be considered as early markers of oligodendrocyte differentiation. The early arrest of myelinogenesis in the quaking animals and the near absence of AGC are in good agreement with this proposal. Moreover, the reduced amount of AGC in the trembler PNS indicates that AGC could also be early markers for differentiation of the Schwann cell.     

Incidence of Fungal Necrotrophic and Biotrophic Pathogens in Pioneer and Shade‐tolerant Tropical Rain Forest Trees

This study assessed the hypothesis that plant life history traits determine the incidence of fungal biotrophic and necrotrophic pathogens in pioneer vs. shade‐tolerant tropical plant species. Considering that pioneer species mainly invest in induced defenses, we expected a negative relationship between the incidence of biotrophic and necrotrophic pathogens; in contrast, as shade‐tolerant species invest heavily in constitutive defenses, we expected to find no correlation between the incidence of biotrophic and necrotrophic pathogens. These ideas were evaluated by assessing standing levels of fungal damage in a set of pioneer and shade‐tolerant species from the Lacandona tropical rain forest (Mexico). The results showed that among pioneer plant species, leaves with biotrophic lesions were between 34 and 44 percent more abundant than those with necrotic lesions. In contrast, among shade‐tolerant species, the proportions of leaves with necrotic lesions were 17–23 percent higher than those of leaves with injuries caused by biotrophic pathogens. Our study suggests that tropical tree species might present different defense strategies depending on the life‐style of the pathogens that attack them, and the life history strategy of the attacked host plant species. Thus, the host constitutive and induced defenses, as well as the mechanisms used by different types of pathogens to circumvent those defenses maybe responsible for the patterns of attack observed in perennial tropical plants. Abstract in Spanish is available at http://www.blackwell‐synergy.com/loi/btp .     

Babesia bigemina,Babesia argentina, and Anaplasma marginale: Coinfectious immunity in bovines

Forty-eight intact and eight splenectomized cattle were used to evaluate different systems of coinfectious immunization against Babesia bigemina, Babesia argentina, and Anaplasma marginale. Coinfectious immunity was induced by two methods: (1) blood of cattle acutely infected with B. bigemina, B. argentina and A. marginale was used as the source of inoculum and the post vaccination reactions were chemotherapeutically controlled with Imidocarb, Ganaseg, Gloxazone, and Liquamycin, and (2) by artificially inducing babesiosis with the blood of carrier cattle with chronic infections of B. bigemina and B. argentina without chemotherapy. The degree of resistance was determined by bloodborne and tick-borne challenges. Ticks were collected from cattle and identified as Boophilus microplus and Dermacentor nitens. Vaccinated cattle demonstrated a high degree of resistance to babesiosis and anaplasmosis; however, cattle without coinfectious immunity were treated chemotherapeutically to prevent death losses.