Background: The apolipoprotein E (APOE, gene;apoE, protein) ε4 allele is the most commonly identified genetic risk factor for typical late-onset sporadic Alzheimer’s disease (AD). Each APOE ε4 allele roughly triple...Background: The apolipoprotein E (APOE, gene;apoE, protein) ε4 allele is the most commonly identified genetic risk factor for typical late-onset sporadic Alzheimer’s disease (AD). Each APOE ε4 allele roughly triples the relative risk for AD compared to that of the reference allele, APOE ε3. Methods: We have employed hyperspectral fluorescence imaging with an amyloid-specific, conformation-sensing probe, p-FTAA, to elucidate protein aggregate structure and morphology in fresh frozen prefrontal cortex samples from human postmortem AD brain tissue samples from patients homozygous for either APOE ε3 or APOE ε4. Results: As expected APOE ε4/ε4 tissues had a significantly larger load of CAA than APOE ε3/ε3. APOE isoform-dependent morphological differences in amyloid plaques were also observed. Amyloid plaques in APOE ε3/ε3 tissue had small spherical cores and large coronas while amyloid plaques in APOE ε4/ε4 tissues had large irregular and multi-lobulated plaques with relatively smaller coronas. Despite the different morphologies of their cores, the p-FTAA stained APOE ε3/ε3 amyloid plaque cores had spectral properties identical to those of APOE ε4/ε4 plaque cores. Conclusions: These data support the hypothesis that one mechanism by which the APOE ε4 allele affects AD is by modulating the macrostructure of pathological protein deposits in the brain. APOE ε4 is associated with a higher density of amyloid plaques (as compared to APOE ε3). We speculate that multilobulated APOE ε4-associated plaques arise from multiple initiation foci that coalesce as the plaques grow.展开更多
Inflammatory bowel diseases are the consequence of a dysregulated mucosal immune system. The mucosal immune system consists of two arms, innate and adaptive immunity, that have been studied separately for a long time....Inflammatory bowel diseases are the consequence of a dysregulated mucosal immune system. The mucosal immune system consists of two arms, innate and adaptive immunity, that have been studied separately for a long time. Functional studies from in vivo models of intestinal inflammation as well as results from genome-wide association studies strongly suggest a crossregulation of both arms. The present review will illustrate this interaction by selecting examples from innate immunity and adaptive immunity, and their direct impact on each other. Broadening our view by focusing on the cross-regulated areas of the mucosal immune system will not only facilitate our understanding of disease, but furthermore will allow identification of future therapeutic targets.展开更多
Many identified and yet unknown factors contribute to the pathogenesis of inflammatory bowel disease(IBD).The genome-wide association studies clearly support the earlier developed concept that IBD occurs in geneticall...Many identified and yet unknown factors contribute to the pathogenesis of inflammatory bowel disease(IBD).The genome-wide association studies clearly support the earlier developed concept that IBD occurs in genetically predisposed individuals who are exposed to distinct environmental factors,which together result in dysregulation of the mucosal immune system.Thus,the majority of previous studies have focused on the immune response within the intestinal wall.The present review aims to emphasize the contribution of three extraluminal structures to this inflammatory process,namely the mesenteric fat tissue,the lymphatics and the microvasculature.Broadening our view across the intestinal wall will not only facilitate our understanding of the disease,but will also us to identify future therapeutic targets.展开更多
目的分析多杀巴斯德菌致假体周围感染的特点。方法计算机检索Pubmed、Cochrane Library、Web of Science数据库自1998年1月至2018年1月多杀巴斯德菌引起假体周围感染的相关文献,根据纳入标准与排除标准进一步筛选。结果共收集9篇文献。...目的分析多杀巴斯德菌致假体周围感染的特点。方法计算机检索Pubmed、Cochrane Library、Web of Science数据库自1998年1月至2018年1月多杀巴斯德菌引起假体周围感染的相关文献,根据纳入标准与排除标准进一步筛选。结果共收集9篇文献。其中6篇来自欧洲国家,3篇来自美国。入选文献中共10例患者。平均年龄70(57~84)岁,女性患者6例。膝关节感染7例,髋关节感染2例,肩关节感染1例。8例与猫接触相关,1例与马接触相关,1例与狗接触相关。5例合并既往病史,其中4例与多杀巴斯德菌假体周围感染危险因素相关。5例X线报告中2例X线发现有假体松动。白细胞计数、C反应蛋白、血浆沉降率均高于正常值,6例关节穿刺液培养结果均为阳性。在抗生素治疗加手术干预的所有病例中,≥1年随访结果显示治愈。结论多杀巴斯德菌假体周围感染患者多数存在明确的动物接触史。早期诊断并通过手术加抗生素治疗可以获得良好的预后。展开更多
文摘Background: The apolipoprotein E (APOE, gene;apoE, protein) ε4 allele is the most commonly identified genetic risk factor for typical late-onset sporadic Alzheimer’s disease (AD). Each APOE ε4 allele roughly triples the relative risk for AD compared to that of the reference allele, APOE ε3. Methods: We have employed hyperspectral fluorescence imaging with an amyloid-specific, conformation-sensing probe, p-FTAA, to elucidate protein aggregate structure and morphology in fresh frozen prefrontal cortex samples from human postmortem AD brain tissue samples from patients homozygous for either APOE ε3 or APOE ε4. Results: As expected APOE ε4/ε4 tissues had a significantly larger load of CAA than APOE ε3/ε3. APOE isoform-dependent morphological differences in amyloid plaques were also observed. Amyloid plaques in APOE ε3/ε3 tissue had small spherical cores and large coronas while amyloid plaques in APOE ε4/ε4 tissues had large irregular and multi-lobulated plaques with relatively smaller coronas. Despite the different morphologies of their cores, the p-FTAA stained APOE ε3/ε3 amyloid plaque cores had spectral properties identical to those of APOE ε4/ε4 plaque cores. Conclusions: These data support the hypothesis that one mechanism by which the APOE ε4 allele affects AD is by modulating the macrostructure of pathological protein deposits in the brain. APOE ε4 is associated with a higher density of amyloid plaques (as compared to APOE ε3). We speculate that multilobulated APOE ε4-associated plaques arise from multiple initiation foci that coalesce as the plaques grow.
基金Supported by SFB 633 of the Deutsche Forschungsgemeinschaft
文摘Inflammatory bowel diseases are the consequence of a dysregulated mucosal immune system. The mucosal immune system consists of two arms, innate and adaptive immunity, that have been studied separately for a long time. Functional studies from in vivo models of intestinal inflammation as well as results from genome-wide association studies strongly suggest a crossregulation of both arms. The present review will illustrate this interaction by selecting examples from innate immunity and adaptive immunity, and their direct impact on each other. Broadening our view by focusing on the cross-regulated areas of the mucosal immune system will not only facilitate our understanding of disease, but furthermore will allow identification of future therapeutic targets.
基金Supported by SFB 633 of the Deutsche Forschungsgemeinschaft
文摘Many identified and yet unknown factors contribute to the pathogenesis of inflammatory bowel disease(IBD).The genome-wide association studies clearly support the earlier developed concept that IBD occurs in genetically predisposed individuals who are exposed to distinct environmental factors,which together result in dysregulation of the mucosal immune system.Thus,the majority of previous studies have focused on the immune response within the intestinal wall.The present review aims to emphasize the contribution of three extraluminal structures to this inflammatory process,namely the mesenteric fat tissue,the lymphatics and the microvasculature.Broadening our view across the intestinal wall will not only facilitate our understanding of the disease,but will also us to identify future therapeutic targets.
文摘目的分析多杀巴斯德菌致假体周围感染的特点。方法计算机检索Pubmed、Cochrane Library、Web of Science数据库自1998年1月至2018年1月多杀巴斯德菌引起假体周围感染的相关文献,根据纳入标准与排除标准进一步筛选。结果共收集9篇文献。其中6篇来自欧洲国家,3篇来自美国。入选文献中共10例患者。平均年龄70(57~84)岁,女性患者6例。膝关节感染7例,髋关节感染2例,肩关节感染1例。8例与猫接触相关,1例与马接触相关,1例与狗接触相关。5例合并既往病史,其中4例与多杀巴斯德菌假体周围感染危险因素相关。5例X线报告中2例X线发现有假体松动。白细胞计数、C反应蛋白、血浆沉降率均高于正常值,6例关节穿刺液培养结果均为阳性。在抗生素治疗加手术干预的所有病例中,≥1年随访结果显示治愈。结论多杀巴斯德菌假体周围感染患者多数存在明确的动物接触史。早期诊断并通过手术加抗生素治疗可以获得良好的预后。