Aspergillus myositis in a patient with a myelodysplastic syndrome

We present the case of an elderly man who, while being treated with corticosteroids for a myelodysplastic syndrome, developed myositis of the calf due to Aspergillus fumigatus. Despite therapy with amphotericin B the myositis failed to resolve and he died. At autopsy, a localized necrotizing myositis of the right calf was found with no evidence of disseminated Aspergillus infection. Myositis in the setting of disseminated candidiasis or cryptococcosis has been previously reported. This case is unique in that it is the first reported case of localized fungal myositis and of myositis caused by Aspergillus.     

Bovine sarcocystosis: Sarcocystis species,diagnosis, prevalence,economic and public health considerations,and association of Sarcocystis species with eosinophilic myositis in cattle

Infections by Sarcocystis in cattle are ubiquitous worldwide. There is considerable debate concerning the identity of Sarcocystis spp. in cattle. Proper diagnosis of Sarcocystis spp. is important to assess their economic and public health importance. Currently there are seven named species: Sarcocystis hirsuta, Sarcocystis cruzi, Sarcocystis hominis, Sarcocystis bovifelis, arcocystis heydorni, Sarcocystis bovini and Sarcocystis rommeli. Additionally, there are unnamed Sarcocystis spp. Two species, S. hominis and S. heydorni, are zoonotic. One out of seven species (S. hirsuta, contracted from cats) forms macroscopic cysts which can be visible during carcass inspection. Current molecular characterization is based on DNA extracted from sarcocysts from naturally infected cattle because DNA was not characterized from tissues of experimentally infected cattle or feces of experimentally infected definitive hosts. Sarcocystis cruzi (transmitted via canids) is recognized as the most pathogenic species and it causes abortion, low milk yield, poor body growth, and outbreaks of clinical sarcocystosis and death. Additionally, Sarcocystis infections have been linked to an inflammatory condition of striated muscles termed bovine eosinophilic myositis (BEM). Cattle affected by BEM appear clinically normal. Diagnosis of BEM at slaughter occurs when inspecting the carcass surface, or once the carcass has been divided into prime cuts or quarters. Sex and breed have no apparent influence on prevalence of BEM. The condition evidently occurs with equal frequency in steers, cows, and heifers. Virtually all striated muscles can be affected including skeletal muscles, the muscles of the eye, larynx, and the heart. In the USA, regulations require condemnation of BEM-affected parts, or (in severe cases) the entire carcass. These aesthetic considerations result in economic losses. Cattle experimentally infected with Sarcocystis did not have BEM at slaughter. Here, we review the status of Sarcocystis spp. and BEM in cattle including prevalence, lesions, epidemiology, and association of BEM with different species of Sarcocystis.     

我国首例肌曲霉病及其试验研究

目的报道国内首例肌曲霉病,对所分离的黄曲霉进行形态、药敏、rDNA序列分析研究。方法对患者病变肌组织行B超和病理检查;将分离菌株接种于察氏培养基观察形态学特征;微量法测定MIC值;酚氯仿法提取DNA,扩增ITS间区序列并进行多序列分析。结果B超示左腓肠肌不规则回声,病理示肌细胞变性、坏死,肌组织内见分枝分隔菌丝。表型及基因型特征为黄曲霉;分离菌株对多种抗真菌药物耐药;多基因序列分析显示所分离菌株与标准株及自然和临床分离株具有100%的相似性。给予特比萘芬治疗3个月后痊愈。结论黄曲霉可致肌肉感染;药敏试验对临床治疗具有指导意义;环境中普遍存在的真菌可引起免疫低下患者致死性感染。     

Ultrastructure and development of Pleistophora ronneafiei n. sp., a microsporidium (Protista) in the skeletal muscle of an immune-compromised individual

This report provides a detailed ultrastructural study of the life cycle, including proliferative and sporogonic developmental stages, of the first Pleistophora species (microsporidium) obtained from an immune-incompetent patient. In 1985, the organism obtained from a muscle biopsy was initially identified as belonging to the genus Pleistophora, based on spore morphology and its location in a sporophorous vesicle. Since that initial report, at least two new microsporidial genera, Trachipleistophora and Brachiola, have been reported to infect the muscle tissue of immunologically compromised patients. Because Trachipleistophora development is similar to Pleistophora, and as Pleistophora was only known to occur in cold-blooded hosts, the question of the proper classification of this microsporidium arose. The information acquired in this study makes it possible to compare Pleistophora sp. (Ledford et al. 1985) to the known human infections and properly determine its correct taxonomic position. Our ultrastructural data have revealed the formation of multinucleate sporogonial plasmodia, a developmental characteristic of the genus Pleistophora and not Trachipleistophora. A comparison with other species of the genus supports the establishment of a new species. This parasite is given the name Pleistophora ronneafiei n. sp.     

C4亚型人肠道病毒71型的小鼠肌肉适应株对小鼠具有致死毒力

目的人肠道病毒71型（EV71）感染婴幼儿可导致手足口病,偶尔伴随有严重的并发症。建立EV71的小鼠模型是深入研究病毒感染的致病机制、进行疫苗和药物评价的基础。方法将EV71的临床分离株在小鼠骨骼肌中进行系列传代,得到了小鼠的肌肉适应株MP10。使用MP10经腹腔注射感染10日龄ICR小鼠,对感染小鼠的症状、病毒复制和病理进行了监测。结果与临床分离株相比,MP10对人横纹肌瘤细胞（rhabdomyosarcoma cell,RD细胞）的感染力提高,并且对小鼠的毒力增强,MP10感染10日龄小鼠可导致其瘫痪和死亡。病毒主要在骨骼肌中复制,并引发大面积的坏死性肌炎,同时神经组织未观察到病变。病理分析发现：感染小鼠体内与呼吸运动相关的肌肉均发生严重的坏死性肌炎,推测此类肌肉的坏死会影响小鼠的呼吸功能,从而成为导致小鼠死亡的因素之一。结论建立了C4亚型EV71毒株感染10日龄ICR小鼠的模型,该模型可作为研究EV71感染的致病机制、以及疫苗和药物评价的工具。     

Genetic aberrations in macroautophagy genes leading to diseases

The catabolic process of macroautophagy, through the rapid degradation of unwanted cellular components, is involved in a multitude of cellular and organismal functions that are essential to maintain homeostasis. Those functions include adaptation to starvation, cell development and differentiation, innate and adaptive immunity, tumor suppression, autophagic cell death, and maintenance of stem cell stemness. Not surprisingly, an impairment or block of macroautophagy can lead to severe pathologies. A still increasing number of reports, in particular, have revealed that mutations in the autophagy-related (ATG) genes, encoding the key players of macroautophagy, are either the cause or represent a risk factor for the development of several illnesses. The aim of this review is to provide a comprehensive overview of the diseases and disorders currently known that are or could be caused by mutations in core ATG proteins but also in the so-called autophagy receptors, which provide specificity to the process of macroautophagy. Our compendium underlines the medical relevance of this pathway and underscores the importance of the eventual development of therapeutic approaches aimed at modulating macroautophagy.     

Calcium dysregulation,and lithium treatment to forestall Alzheimer's disease – a merging of hypotheses

Intracellular Ca²⁺ concentrations are tightly regulated, and elevated levels sustained over periods of time can cause cellular deterioration. The putative role of dysregulated intracellular Ca²⁺ in Alzheimer's disease had led to the hypothesis that controlling intracellular Ca²⁺ may forestall cognitive decline. Lithium has been shown to reduce intracellular Ca²⁺ concentrations. Two well-characterized neuronal targets of lithium that may affect intracellular Ca²⁺ levels are N-methyl-d-aspartate (NMDA) receptors and inositol monophosphatase (IMP). Results from a recent single-center placebo-controlled randomized trial suggest that long-term lithium treatment at subtherapeutic doses may have the potential to delay the progression of disease, and observational studies have shown that lithium reduces the prevalence of dementia in subjects with bipolar disorder on long-term lithium therapy. I am advancing the hypothesis that lithium may protect against cognitive decline by stabilizing intracellular Ca²⁺ through a dual, synergistic mechanism of targeting both extracellular and intracellular sites, via antagonizing NMDA-receptors and inhibiting IMP. Insights derived from this hypothesis could lead to an improved understanding of the molecular pathology of Alzheimer's disease, and have implications on the evaluation and use of therapeutics that alter intracellular Ca²⁺ levels.     

双歧杆菌对新生大鼠坏死性小肠结肠炎肠损伤及肠道菌群影响

目的建立新生SD大鼠坏死性小肠结肠炎（NEC）模型,探讨添加双歧杆菌对新生大鼠NEC模型肠损伤的保护作用及肠道菌群的影响,为应用双歧杆菌防治NEC提供依据：方法SD新生大鼠出生48h开始给予鼠配方奶人工喂养,100％氮气缺氧90s,4℃冷刺激10min,每天2次,连续3d,建立新生SD大鼠NEC模型。按析因设计,32只新生SD大鼠随机分成4组,每组动物各8只。A组为NEC模型组并在出生48h起每日给予长双歧杆菌灌胃（1×10^8CFU／d）;B组为NEC模型组,C组为对照组,都未添加双歧杆菌;D组为对照组并给予长双歧杆菌灌胃（1×10^8CFU／d）。在最后一次缺氧、冷刺激后24h空腹断头处死大鼠,留取回盲部近端肠管组织进行肠组织损伤评分,组织学评分≥2确定为NEC;实验前后留取各组新生鼠粪便,按照张秀荣方法进行肠道菌群检测。应用Kruskal-Wallis H检验等方法进行统计学分析,α=0．05为显著性检验标准。结果开始造模后,A、B组新生SD大鼠相继出现腹泻、腹胀、萎靡、活动减少,A组程度较轻。A、B、C和D组肠组织损伤评分（^-x±s）分别为1．88±0.84、3．13±0．84、0．63±0．52、0．50±0.54,各组间肠组织损伤评分差异有显著性,与B组相比,A组肠组织损伤评分明显降低,但仍高于C、D两组,差异均有显著性。各组实验前肠道细菌总数,杆菌、球菌数,G^＋杆菌、G^＋球菌数差异均无显著性,肠道菌群中杆球菌比值在正常范围中。实验结束时,各组间新生鼠肠道细菌总数,杆菌、球菌数,杆球菌比值,G^＋杆菌、G^＋球菌数及其占肠道总菌群数的比率差异均有显著性;除B组杆菌数外,与实验前相比,各组新生大鼠实验结束后肠道细菌总数、球菌数、杆菌数、G^＋杆菌数、G^＋球菌数均有显著增加,差异均有显著性;A、B组肠道杆球菌比值和G^＋杆菌数占肠道总菌群数比     

Development of Anncaliia algerae (Microsporidia) in Drosophila melanogaster

Representatives of the genus Anncaliia are known as natural parasites of dipteran and coleopteran insects, amphipod crustaceans, but also humans, primarily with immunodeficiency. Anncaliia algerae‐caused fatal myositis is considered as an emergent infectious disease in humans. A. (=Nosema, Brachiola) algerae, the best studied species of the genus, demonstrates the broadest among microsporidia range of natural and experimental hosts, but it has never been propagated in Drosophila. We present ultrastructural analysis of development of A. algerae in visceral muscles and adipocytes of Drosophila melanogaster 2 wk after per oral experimental infection. We observed typical to Anncaliia spp. features of ultrastructure and cell pathology including spore morphology, characteristic extensions of the plasma membrane, and presence of “ridges” and appendages of tubular material at proliferative stages. Anncaliia algerae development in D. melanogaster was particularly similar to one of A. algerae and A.(Brachiola) vesicularum in humans with acute myositis. Given D. melanogaster is currently the most established genetic model, with a fully sequenced genome and easily available transgenic forms and genomic markers, a novel host–parasite system might provide new genetic tools to investigate host–pathogen interactions of A. algerae, as well to test antimicrosporidia drugs.     

Higher eukaryotic aminoacyl-tRNA synthetases in physiologic and pathologic states

Summary The aminoacyl-tRNA synthetases play a dual role in cell metabolism by synthesizing aminoacyl-tRNAs and an odd dinucleotide diadenosine-5, 5-P¹, P⁴-tetraphosphate which appears to be involved in DNA replication and the control of cell proliferation. This review is a synthesis of recent results on the structure, genetics, cell biology, physiology, role in neoplasia, and role in autoimmune myositis of the higher eukaryotic aminoacyl-tRNA synthetases.