Course and prognosis of chronic progressive multiple sclerosis: Results of an epidemiological study

In studies on the natural course of multiple sclerosis (MS), several forms of the disease are distinguished. The most important are the relapsing remitting and the chronic progressive forms. The relationship between these remains unclear. In a prospective epidemiological survey we studied the course of MS using the year in which the chronic-progressive phase started as a landmark. The reliability of this "year of progression" was examined in an observer agreement study. Data were acquired from 342 patients. Progression of the handicap was most rapid in case of a secondary progressive course, female sex, high relapse rate in the preceding remitting phase and "year of progression" at a higher age. Survival after the "year of progression" was lowest in the secondary progressive group. Determining the "year of progression" seems to be significant for the prognosis.     

Golgi study on macular mutant mouse after copper therapy

Summary This study was undertaken to elucidate the clinical and neuropathological effects of copper administration on the macular mutant mouse. Its hemizygote, which is considered to be a model of Menkes kinky hair disease (MKHD), was injected intraperitoneally four times with 10, 20, 20 and 30 g of cupric chloride on days 4, 6, 8 and 10, respectively. The hemizygote's curly whiskers gradually straightened and the frequent tonic seizures and ataxia disappeared after the injections. The body weight also gradually increased. In the cerebral cortex, the dendritic arborization of the pyramidal neurons in both the normal littermate and the treated hemizygote developed with time and reached the maximum around day 60. In the treated hemizygote, however, the arborization of the dendrites was significantly poor in comparison with that in the normal littermate from day 20 to 90. In the cerebellum of the treated hemizygote, the abnormal Purkinje cells with the few somal sprouts, thick stem dendrite and/or poor arborization, which were seen in the non-treated hemizygote, were improved by day 30, while their focal dendritic swellings remained even on day 60. These results indicate that the copper therapy improves not only the clinical manifestations but also the neuropathological changes, especially in the cerebellum.Supported in part by Grant no. 86-05-02 from the National Center of Neurology and Psychiatry of the Ministry of Health and Welfare, Japan     

Solubility of neurofibrillary tangles and ultrastructure of paired helical filaments in sodium dodecylsulphate

Summary Temporal cortex from 14 cases of Alzheimer-type dementia and 6 cases of Down's syndrome, all selected for severe Alzheimer pathology, was homogenised in distilled water, NaOH, or sodium dodecylsulphate (SDS) containing 0.1% -mercaptoethanol. The homogenates were stained with Congo red, and the neurofibrillary tangles and plaque cores were counted under crossed-polarisation microscopy. The number of tangles and plaque cores in the water-treated extracts was not related to age, sex, postmortem interval or duration of dementia. The number of tangles after extraction in SDS or NaOH, as a percentage of tangles in water-treated extracts, was 57±25 (mean±SD) for 1% SDS, 43±17 for 5% SDS and 37±22 for 0.2 M NaOH. Plaque cores were essentially insoluble in all three agents. The percentage of tangles insoluble in 1% SDS did not correlated with age or post-mortem interval but decreased with increasing duration of dementia. Enhanced tangle solubility with increasing duration of dementia suggests that the nature of tangles changes with time; one possibility is that this reflects transformation of intracellular to extracellular tangles. Paired helical filament (PHF) length and the number of repeats per PHF were measured in electron micrographs of PHF prepared with and without treatment by 1% SDS. There was no significant multimodality of PHF length to suggest that PHF broke at regular intervals. The mean repeat length (PHF length/number of repeats) was greater for PHF isolated in the presence of 1% SDS than in its absence, showing that SDS affects ultrastructure by untwisting PHF. An untwisting process may also occur in vivo producing the straight filaments found, together with PHF, in tangles and neurites.Supported by Miss E. Buchan (to the MRC Brain Metabolism Unit) and the British Foundation for Age Research and the Wellcome Trust (to P. A. M. Eagles). S. Hussey was in receipt of an MRC Partnership Award.     

Prospect for enzyme therapy in glycogenosis II variants: a study on cultured muscle cells

Summary Impairment of skeletal muscle function is the common feature of distinct clinical forms of glycogenosis type II. In the present study, muscle cultures from different patients were used to investigate the cause of clinical heterogeneity and the feasibility of enzyme replacement therapy. The activity of acid -glucosidase appears to be the primary factor in determining the extent of lysosomal glycogen storage in muscle, and thereby the clinical severity of the disease. Neutral -glucosidases do not seem influencial. Correction of the enzymatic defect was achieved in skeletal muscle cultures from patients by administration of a high-uptake form of acid -glucosidase, purified from human urine. The enzyme reaches the lysosomes, including the glycogen storage vacuoles, and the lysosomal glycogen content is reduced to control level. In normal muscle cells 20% of the total cellular glycogen pool is segregated in lysosomal compartments. This percentage is higher than in fibroblasts, which may partly explain why muscles are more prone to store glycogen. The relevance of this study for enzyme therapy is discussed.     

Adult-onset rod disease with abundant intranuclear rods

Summary The third case of adult-onset rod disease (nemaline myopathy) with abundant myofibrillar as well as intranuclear rods is described. The 61-year-old woman suffered from progressive weakness of proximal extremities and of the neck, mimicking polymyositis. Muscle biopsy revealed a striking myopathic pattern, with intranuclear rods occurring in 31% of the fibres. On light and electron microscopy and by immunohistochemical study, the rods differed from myofibrillar rods. The absence of -actinin in intranuclear rods suggests an enhanced readiness of actin filaments to bind to diverse proteins, instead of overproduction of -actinin as the pathogenetic basis of the rod formation.     

Ischemic stroke in infancy,childhood, and adolescence

The authors studied 34 patients with juvenile ischemic cerebrovascular disease over a 15-year period. Of the 34 patients, 23 had intracranial occlusions attributed to cerebral thrombosis or embolism and 11 had occlusions resulting from moyamoya disease. Clinicopathological features were evaluated in the 23 cases with ischemic stroke, but not those with moyamoya disease. The cause of the arterial occlusion remained undetermined in 11 patients and was found to be an embolism based on congenital heart disease in 8, on trauma in 3, and on infection in 1. Cerebral angiography was performed in 21 patients. Of these, 17 had stenoses or occlusions corresponding to their symptoms. CT scans were performed in 10 patients; the lesion in question showed no stenosis or occlusion with cerebral angiography. With regard to prognosis, patients with unknown etiology had good outcomes compared with those with congenital heart disease. With respect to acute infantile hemiplegia, 10 patients had convulsive seizures and 4 had a history of an earlier infection. Angiography and CT scans in patients with congenital heart disease demonstrated arterial occlusive sites in the middle cerebral artery region. Three patients had abscesses after their ischemic lesions.     

社区人群空腹血糖受损对估算肾小球滤过率的影响研究

背景 估算肾小球滤过率(eGFR)是反映慢性肾脏病严重程度的量化指标之一。研究表明糖尿病前期血糖升高可增加慢性肾脏病风险,但对eGFR直接影响报道较少。目的 探讨社区人群中空腹血糖(FPG)受损患者血糖水平对eGFR的影响。方法 选择2020年1—12月于南昌大学第二附属医院体检中心体检的人群,收集一般资料与临床资料(包括既往史、性别、年龄、体质指数、血压、尿酸、血脂、FPG、尿常规、血肌酐),经相应纳入标准与排除标准筛选,最终纳入28 601例受试者。根据FPG水平将受试者分为FPG升高组(5.6 mmol/L≤FPG<7.0mmol/L)、FPG正常组(3.9 mmol/L≤FPG<5.6 mmol/L),比较两组一般资料与临床资料。为明确FPG对e GFR影响,采用个案匹配控制对两组受试者进行多因素(性别、年龄、平均动脉压、尿酸、总胆固醇、体质指数)匹配,采用Mann-Whitney U秩和检验比较匹配后两组一般资料。采用Spearman秩相关检验分析FPG与eGFR在FPG升高组、FPG正常组及匹配后FPG升高组、FPG正常组间的相关性。结果 共获得FPG正常组患者...     

冠状动脉粥样硬化性心脏病患者心外膜脂肪组织的生物信息学研究

背景 心血管疾病（CVD）是常见病和多发病,患病率和死亡率呈快速上升趋势。动脉粥样硬化（AS是缺血性CVD的病理基础,研究表明心外膜脂肪组织（EAT）通过分泌外泌体（EXO）和生物活性物质促进AS进展,但其作用机制仍需进一步研究。目的 通过生物信息学方法挖掘冠状动脉粥样硬化性心脏病（CAD）患者EAT中的关键基因,探讨免疫细胞浸润情况,联合CAD患者EXO间差异表达基因（DEGs）推测EAT来源EXO间DEGs并进行验证,从细胞及分子水平上探讨EAT在CAD疾病过程中的作用机制。方法 从基因表达综合数据库（GEO）中下载关于EAT的数据集GSE64554、GSE120774,根据临床信息将EAT的测序数据分为CAD组和健康对照组,使用R语言及相关软件包进行生物信息学分析。首先使用R语言筛选CAD组与健康对照组EAT间DEGs,并进行GO富集分析和KEGG通路富集分析,构建蛋白质-蛋白质相互作用（PPI）网络,评估所选基因的生物学功能及可能参与其调控的转录因子。构建GSE64554数据集中EAT的加权基因共表达网络（WGCNA）,获取同CAD表型相关的基因模块,将所获EAT间DEGs与模...     

从脂肪组织的内分泌功能角度探讨其在慢性阻塞性肺疾病中的作用机制研究

脂肪组织除了通过其力学特征或机械功能对周边组织器官产生影响以外,还可以凭借非物理性的内分泌功能通过脂肪因子输出信号方式有效地建立起与呼吸系统等远程器官的互作信息网络,进而参与多种肥胖相关疾病的发生与发展。作为内分泌领域的突破性进展之一,脂肪组织的内分泌功能受到生命科学领域的关注。近年来,多项流行病调查研究揭示了肥胖是造成慢性阻塞性肺疾病（COPD）等呼吸系统疾病肺功能损害重要的危险因素。基于此,本文将分别梳理脂联素、瘦素、内脂素等脂肪因子在COPD中的作用机制,从脂肪组织内分泌功能角度为COPD的防治研究提供新思路。     

急性冠脉综合征患者强化抗栓治疗研究进展

急性冠脉综合征（ACS）是冠心病的严重类型,ACS患者不仅病死率较高,还存在缺血事件（如缺血性卒中、心肌梗死）复发风险。血小板聚集及血栓形成是导致ACS的重要原因。为降低缺血事件的发生风险,临床推荐ACS患者接受阿司匹林联合强效P2Y12抑制剂的双联抗血小板治疗12个月。然而在标准双联抗血小板治疗下,ACS患者残余缺血风险（经抗栓治疗后仍残留的缺血事件发生风险）仍旧较高。因此为进一步降低缺血事件发生风险,临床对强化抗栓方案的研究也逐渐增多。本文通过总结强化抗栓治疗方案的作用机制及其最新研究进展,发现延长双联抗血小板治疗时间、三联抗血小板治疗、双通道抑制（抗血小板联合抗凝治疗）等强化抗栓治疗方案可降低缺血事件发生风险,为进一步指导临床个体化抗栓治疗及明确最佳抗栓策略提供了参考。