Rabies virus binding at neuromuscular junctions

Morphological, immunocytochemical, biochemical, and immunological techniques have been used to describe rabies virus binding to a sub-cellular unit and molecular complex at the neuromuscular junction (NMJ). Early after infection in vivo, virus antigen and virus particles were found by immunofluorescence, electron microscopy and immunoelectron microscopy in regions of high density acetylcholine receptors (AChR) at NMJs. One monoclonal antibody (alpha-Mab) to the alpha subunit of the AChR blocked attachment of radio-labeled rabies virus to cultured muscle cells bearing high density patches of AChR. A sub-cellular structure, resembling an array of AChR monomers, bound both rabies virus antigens and alpha-Mab. By immunoblotting with electrophoretically transferred motor endplate proteins, rabies virus proteins and alpha-Mab bound to two proteins of 43 000 and 110 000 daltons. A rabies virus glycoprotein antibody detected virus antigen bound to the 110 000 dalton protein. An auto-immune (anti-idiotypic) response followed immunization of mice with rabies virus glycoprotein antigen; the antibody was directed to the 110 000 dalton protein. This auto-antibody altered the kinetics of neutralization by rabies virus antibody and induced the formation of rabies virus antibody after inoculation of mice. These results define, at the neuromuscular junction, a rabies virus receptor which may be part of the acetylcholine receptor complex.     

通络胶囊治疗偏头痛的临床与实验研究

认为正气不足、病理体质为偏头痛的发病基础 ,以气血失调为主 ,寒热虚实错杂是本病的基本病机。据此确立扶正固本、祛风活络、化瘀止痛的治疗原则 ,拟通络胶囊治疗偏头痛 30例 ,与太极通天液治疗 30例对照 ,结果表明 ,治疗组愈显率 83.33% ,总有效率 93.33% ,与对照组相比有显著性差别 (P<0 .0 1) ,在改善兼症方面亦优于对照组 (P<0 .0 5或 P<0 .0 1) ,并能改善患者颅内血管功能状态。动物实验表明 ,通络胶囊能提高实验动物痛阈 ,同时提高大鼠下丘脑 5 - HT及 β-内啡呔水平 ,并能改善大鼠软脑膜微循环。     

Animal models of Parkinson's disease: An empirical comparison with the phenomenology of the disease in man

Summary Animal models are an important aid in experimental medical science because they enable one to study the pathogenetic mechanisms and the therapeutic principles of treating the functional disturbances (symptoms) of human diseases. Once the causative mechanism is understood, animal models are also helpful in the development of therapeutic approaches exploiting this understanding. On the basis of experimental and clinical findings. Parkinson's disease (PD) became the first neurological disease to be treated palliatively by neurotransmitter replacement therapy.The pathological hallmark of PD is a specific degeneration of nigral and other pigmented brainstem nuclei, with a characteristic inclusion, the Lewy body, in remaining nerve cells. There is now a lot of evidence that degeneration of the dopaminergic nigral neurones and the resulting striatal dopamine-deficiency syndrome are responsible for its classic motor symptoms akinesia and bradykinesia. PD is one of many human diseases which do not appear to have spontaneously arisen in animals. The characteristic features of the disease can however be more or less faithfully imitated in animals through the administration of various neurotoxic agents and drugs disturbing the dopaminergic neurotransmission.The cause of chronic nigral cell death in PD and the underlying mechanisms remain elusive. The partial elucidation of the processes underlie the selective action of neurotoxic substances such as 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has however revealed possible molecular mechanisms that give rise to neuronal death. Accordingly, hypotheses concerning the mechanisms of these neurotoxines have been related to the pathogenesis of nigral cell death in PD.The present contribution starts out by describing some of the clinical, pathological and neurochemical phenomena of PD. The currently most important animal models (e.g. the reserpine model, neuroleptic-induced catalepsy, tremor models, experimentally-induced degeneration of nigro-striatal dopaminergic neurons with 6-OHDA, methamphetamine, MPTP, MPP⁺, tetrahydroisoquinolines, -carbolines, and iron) critically reviewed next, and are compared with the characteristic features of the disease in man.     

Editor's note for debate Sporadic dementia of Alzheimer type: Role of amyloid in etiology is challenged

Summary Alzheimer's disease is a heterogenous neurodegenerative disorder. Whereas only a minority is due to genetic abnormalities and mostly with early onset, the majority of all Alzheimer cases is sporadic and with late onset. Therefore, in the latter, age-related disturbances in cellular metabolism may come into focus with respect to the etiopathogenesis rather than the primary formation of amyloid. In this Editor's note for debate, the role of amyloid as a causative factor of sporadic Alzheimer's disease is challenged. Instead, as a possible primary abnormal event in sporadic Alzheimer's disease, the perturbations in neuronal glucose metabolism and the subsequent ATP deficit with its impacts on the secondary amyloid formation are discussed to open a new field of research and another aspect for debate.     

Zur Bedeutung von sekretorischen und stukturassoziierten Proteasen von Aspergillus fumigatus für die Pathogenese der invasiven Aspergillose

Zusammenfassung. Ein Charakteristikum der invasiven Aspergillose ist, daß Aspergillus fumigatus in der Lage ist, proteinreiche Gewebsschichten des Wirtes zu penetrieren. Verantwortlich hierfür könnten sekretorische Proteasen des Pilzes sein, die fibrilläre Proteine wie Kollagen oder Elastin aufweichen und so der Hyphe das Eindringen ermöglichen. Allerdings sprechen Infektionsversuche mit Gendeletions-Mutanten von allen bekannten sekretorischen Aspergillus-Proteasen gegen eine entscheidende Beteiligung dieser Enzyme an der Pathogenese der invasiven Aspergillose. Ebenso deuten mikroskopische Untersuchungen an Gefäßwand-pene-trierenden Aspergillen nicht auf eine stärkere Auflösung des Bindegewebes, so daß auch eine rein mechanische Verdrängung der Struktur-Proteine durch das Wachstum der Hyphe möglich wäre. Weiter vorstellbar ist auch eine streng lokalisierte Proteolyse an dén Wachstumszonen der Hyphen durch Zellwand-assoziierte Proteasen. Kandidaten für einen solchen Mechanismus sind Aspartat- und Serinproteasen, deren Aktivitäten in der Zellwandfraktion von A. fumigatus gefunden wurden. Summary. In the course of invasive aspergillosis, Aspergillus fumigatus is capable of penetrating any tissue of the host. Secretory proteinases of the fungus might facilitate the hyphae to grow through fibrillar proteins like elastin and collagen. However, using systemic infection models, no significantly reduced virulence could be shown with fungal mutants deficient for all known secretory proteinases. Thus, secretory proteinases might be of minor relevance for the pathogenesis of invasive aspergillosis. In addition, microscopic examination of aspergilli penetrating vessel walls did not reveal obvious lysis of wall proteins, thus emphasizing a mechanical disruption of fibrillar proteins by the growing hyphae. However, a strictly localized proteolysis at the tips of growing hyphae caused by wall associated proteinases might be involved. Candidates for such a mechanism art the activities of aspartic and serine proteinases which we have discovered in the cell wall fraction of A. fumigatus.     

儿童特发性再生障碍性贫血的诊断与治疗

再生障碍性贫血(再障)以全血细胞减少和骨髓增生降低为显著特点。绝大多数病例为特发性,部分为继发性,与辐射、化学物和药物暴露、病毒感染有关。特发性再障发病机制不清,但免疫机制介导的造血干细胞损伤发挥着极为重要的作用。诊断主要依靠典型的临床表现和骨髓形态学检查,注意与其他可导致全血细胞减少的疾病鉴别,尤其是低增生性骨髓增生异常综合征。应综合患者年龄、临床严重程度、有无造血干细胞来源及其种类等因素,制定个体化治疗方案,合理选择联合免疫抑制治疗和造血干细胞移植的类型和时机。重视对症支持治疗措施。     

儿童呼吸道病毒感染与免疫应答

急性呼吸道感染(ARTI)是儿科最为常见的疾病,其中病毒所致的ARTI占半数以上。呼吸道病毒与机体免疫系统之间的相互作用是发病的关键环节。文章介绍了我国常见的呼吸道病毒病原的流行病学、病毒免疫逃逸与进化、机体保护性/病理性抗病毒免疫应答的研究进展,以提高儿科医师对呼吸道病毒感染的认识。     

Bluetongue Virus Infection of Goats: Re-Emerged European Serotype 8 vs. Two Atypical Serotypes

In recent years, numerous atypical Bluetongue virus (BTV) strains have been discovered all around the world. Atypical BTV strains are phylogenetically distinct from the classical BTV serotypes 1–24 and differ in terms of several biological features. For the first time, the atypical strains BTV-25-GER2018 and BTV-33-MNG3/2016 as well as the re-emerged classical strain BTV-8-GER2018 were evaluated comparatively in a pathogenesis study in goats—the natural host of atypical BTV. A substantial number of in-contact animals were included in this study to detect potential contact transmissions of the virus. After infection, EDTA blood, ocular, nasal and oral swab samples as well as serum were collected regularly and were used for virological and serological analyses, respectively. Our study showed differences in the immunological reaction between the two atypical BTV strains (no group-specific antibody detection) and the classical BTV strain BTV-8-GER2018 (group-specific antibody detection). Furthermore, we observed an increase in the total WBC count (neutrophils and lymphocytes) in goats infected with the atypical BTV strains. No horizontal transmission was seen for all three strains. Our study suggests that the atypical BTVs used in the trial differ from classical BTVs in their immunopathogenesis. However, no evidence of direct contact transmission was found.     

糖尿病性心肌病的发病机理探析

目的：探讨糖尿病性心肌病（DC）的发病机制。方法：查阅研读近年的大量文献，将所获信息整理分类，得出结论。结果：糖尿病性心肌病（DC）是以持续高血糖、RAS的作用、Ca^2＋转运异常等因素共同作用，使存心肌细胞代谢障碍，导致心脏结构和功能障碍，心肌细胞凋亡，心肌间质纤雏化，引起左心室舒张收缩功能不全，心室肥厚重构，功能渐丧而致心力衰竭。结论：从以上各方面探讨了DC的发病机制，希望能为DC早期防治提供理论依据。