Neuropathological findings in PINK1-associated Parkinson's disease

IntroductionBiallelic mutations in PTEN-induced putative kinase 1 (PINK1) is a relatively common cause of autosomal recessive early-onset Parkinson's disease (PD). However, only three PINK1 patients with brain autopsy have been reported in the literature.MethodsWe describe the clinical and pathological characteristics of a patient with early-onset PD. We screened for copy number variants SNCA, PRKN, PINK1, DJ-1, ATP13A2, LPA and TNFRSF9 by multiplex ligation-dependent probe amplification (MLPA), and subsequently we performed whole-exome sequencing.ResultsClinically the patient presented with typical parkinsonism that responded well to levodopa. After 23 years of disease she had a bilateral GPi deep brain stimulation (DBS) surgery. Genetic analyses revealed a heterozygous exon 4–5 deletion and a homozygous exon 1 [c. 230T > C (p.Leu77Pro)] mutation in PINK1. Post-mortem neuropathological examination after more than 30 years of disease revealed gliosis and a large loss of melanin-containing neurons in the substantia nigra. Lewy body pathology was evident in substantia nigra, temporal cortex, locus coeruleus and the parahippocampal region.ConclusionWe describe the first clinical and pathological characterization of a PINK1 patient with a typical disease presentation and long disease duration. Previous reports describe two patients with Lewy-related pathologies, albeit with differential distribution, and one patient with no Lewy-related pathology. Hence, it seems that only two patients with parkinsonism due to mutations in PINK1 are consistent with α-synucleinopathy distribution like that seen in the majority of cases with sporadic PD. Our data further extend the clinicopathological characterization of PINK1-associated PD.     

The role of exosomes in metastasis and progression of melanoma

The mechanisms of melanoma metastasis have been the subject of extensive research for decades. Improved diagnostic and therapeutic strategies are of increasing importance for the treatment of melanoma due to its high burden of mortality in the advanced stages of the disease. Intercellular communication is a critical event for the progression of cancer. Collective evidence suggests that exosomes, small extracellular membrane vesicles released by the cells, are important facilitators of intercellular communication between the cells and the surrounding environment. Although the emerging field of exosomes is rapidly gaining traction in the scientific community, there is limited knowledge regarding the role of exosomes in melanoma. This review discusses the multifaceted role of melanoma-derived exosomes in promoting the process of metastasis by modulating the invasive and angiogenic capacity of malignant cells. The future implications of exosome research and the therapeutic potential of exosomes are also discussed.     

2000-2004年浙江省温州市狂犬病流行病学分析

目的 了解浙江省温州市狂犬病的流行特征及其影响因素,以便采取更有针对性的防治对策和措施.方法 对报告的狂犬病病例做流行病学调查,在疫区对动物作尼氏小体检查.结果 2000-2004年共报告狂犬病病例26例,其中2004年发病最多.传染源为犬和猫.潜伏期为43 d.绝大部分患者未进行伤口处理或处理不规范.26例中20例在暴露后未接种疫苗,3例未全程接种.26例患者均未使用抗狂犬病血清.在疫区的犬中检出尼氏小体.结论 温州市是狂犬病新发疫源地.应提高群众的防范意识,一旦被动物抓伤、咬伤,应及时清洗创面,正确处理伤口,24 h内接种狂犬病疫苗和抗狂犬病血清.应进一步加强犬类等宿主动物的管理.     

血水混合物浓度及留存时间对模拟木质异物CT表现的影响:体外实验观察

目的 通过体外实验观察不同浓度血水混合物及留存时间对模拟木质异物CT表现的影响。方法 将20根杉木条置入含全血比例为0%、25%、50%、75%与生理盐水（血水）混合物及100%全血试管中,分别对应阴性对照（NC）组、T25组、T50组、T75组及T100组,每组4个样本。将试管置于恒温水浴锅中采集CT图像,每6 h重复一次,共采集300 h;比较相同时间点各组最低密度区CT值、最高密度区CT值和低密度区体积差异,评价时间及血水混合物浓度对木质异物CT参数的影响及其交互作用。结果 随时间延长,各组时间-最低密度区CT值曲线呈速升-缓升型,时间-最高密度区CT值曲线呈速升-平台型;NC组和T25组时间-低密度区体积曲线呈速降型,T50组、T75组及T100组时间-低密度区体积曲线呈缓降型。血水混合物浓度及时间均对木质异物最低密度区CT值、最高密度区CT值及低密度区体积存在影响（P均<0.05）,且二者对最低密度区CT值和低密度区体积存在交互作用（P均<0.05）。结论 血水混合物浓度及留存时间均影响木质异物CT表现。     

泛素阳性包涵体在运动神经元病的表达

目的：探讨泛素阳性包涵体在运动神经病（MND）中枢神经系统的分布、成分及与神经细胞变性的关系。方法：对5例MND和9例非神经系统变性病对照患者脑和脊髓进行苏木素－伊红、快蓝和Bodian常规染色,抗－泛素、抗－tau蛋白、抗－胶质纤维酸性蛋白和抗－神经丝蛋白抗体免疫组化染色。结果：5例MND抗泛素免疫组化染色在其中4例细胞 质内发现单线－线团样包涵体、透明包涵体、路易体样包涵体和不规则包涵体、相应前角细胞存在轻中度变性。3例海马颗粒细胞内出现泛素阳性包涵体。1例患者脊髓前角细胞内少数泛素阳性包涵体抗神经丝蛋白染色也阳性,各种泛不阳性包涵体抗tau蛋白及胶质纤维酸性蛋白染色为阴性,结论脊髓前角细胞质内的泛素阳性包涵体是MND较为特异的免疫病理改变,不同类型包涵体之间可能存在一定的演变规律,与相应神经细胞的变性相关。少数泛素阳性包涵体含有神经丝蛋白成分,海马颗粒细胞内出现泛素阳性包涵休提示此病同时累及非运动系统,并可能 与MND临床上智能或精神异常有关。     

日本血吸虫重组线粒体相关蛋白免疫学活性鉴定

分子筛进一步纯化并复性的融合蛋白均能刺激家兔产生特异性抗体 ,粗提包涵体蛋白免疫家兔 ,血清抗体滴度为 1∶2 5 6 0 0 ,复性蛋白及经分子筛纯化的蛋白免疫的家兔血清抗体滴度均为 1∶5 12 0 0 ,Westernblot结果显示 ,粗提包涵体蛋白、复性蛋白及经过分子筛进一步纯化并复性的蛋白均能被重感染兔血清和rSj338/2 6GST特异性免疫兔血清所识别。攻击实验中 ,粗提包涵体蛋白和经分子筛纯化的蛋白分别可诱导小鼠产生 2 7.8% (P <0 .0 1)和 30 .4 % (P <0 .0 1)的减虫率 ,4 0 .4 % (P <0 .0 1)和 4 3.5 % (P <0 .0 1)肝总减卵率。粗提包涵体蛋白中rSj338和经分子筛纯化的蛋白中rSj338分别可诱导小鼠产生 13.9% (P <0 .0 5 )和 2 0 .0 % (P <0 .0 5 )的减虫率 ,30 .0 % (P <0 .0 1)和 4 1.7% (P <0 .0 1)肝总减卵率。结论　获得的日本血吸虫线粒体相关的重组融合蛋白(rSj338/2 6GST)具有良好的免疫学活性 ,重组融合蛋白 (rSj338/2 6GST)及rSj338均可诱导宿主抗血吸虫感染的部分保护力。     

内镜头端透明帽辅助食管上段异物治疗的对照研究

目的通过比较非镇静状态下透明帽辅助治疗与常规内镜治疗前、治疗中2 min时血压、脉搏、血氧饱和度的动态变化,作呕反应程度,治疗完成时间,食管黏膜损伤情况和视野清晰度,以评价内镜头端透明帽辅助食管上段异物取出的可行性、安全性、有效性和耐受性。方法将144例患者随机分为透明帽辅助治疗组(72例)和常规内镜治疗组(72例);分别监测患者检查前、检查中2 min时的血压、脉搏、血氧饱和度,作呕反应程度,治疗完成时间,食管黏膜损伤情况和视野清晰度。结果透明帽辅助治疗组的血压、脉搏、血氧饱和度变化与常规内镜治疗组比较差异无统计学意义(P>0.05);透明帽辅助治疗组的视野清晰度明显高于常规内镜治疗组(P<0.01);透明帽辅助治疗组的治疗完成时间、作呕反应、黏膜损伤率均低于常规内镜治疗组(P<0.05)。结论内镜头端透明帽辅助食管上段异物治疗是一种可行、安全、有效的治疗方法,并具有较好的耐受性。     

婴幼儿上消化道异物内镜取出术的诊治体会

目的 总结内镜下婴幼儿上消化道异物取出的方法及技巧.方法 采用成人胃镜,静脉麻醉下对14例婴幼儿上消化道异物进行治疗.结果 内镜检查3例未见异物,11例异物成功取出.7例硬币中有5例使用鼠齿钳取出,2例使用鼠齿钳＋乳胶套的方法取出;1例磁铁片,使用网篮取出;1例大头针,使用橡胶头异物钳＋磁性异物钳取出;1例铁钉,使用圈套器取出;1例金属条,使用鼠齿钳＋外套管取出.14例患儿均无并发症.结论 内镜下婴幼儿上消化道异物取出术是安全的,创伤小、并发症少.针对不同的异物需采用不同的操作工具,可取得事半功倍的效果.