Immunohistochemical localization of tissue factor pathway inhibitor-1 (TFPI-1), a Kunitz proteinase inhibitor, in Alzheimer''s disease

Senile plaques in Alzheimer's disease (AD) are composed principally of Aβ, a 4 kDa fragment of the amyloid precursor protein (APP). Longer forms of APP which contain a Kunitz proteinase inhibitor (KPI) domain are elevated in aged and in AD brains. Tissue factor pathway inhibitor-1 (TFPI) contains three tandem KPI domains and has been well characterized for its role as a natural anticoagulant in the extrinsic coagulation pathway. Functionally, the first two KPI domains of TFPI bind and inhibit the activity of factor Xa and VIIa respectively. In addition, TFPI and APP-KPI share a common clearance mechanism through the low density lipoprotein receptor-related protein (LRP). As part of an ongoing study of the role of KPI-containing proteins in AD, the current study examines TFPI localization in the brain. We report here that TFPI is immunohistochemically localized to microglia in both AD and non-AD individuals and is localized to some senile plaques in AD. Western blot analyses indicate that the amount of TFPI is elevated in frontal cortex samples from AD brains. We propose that TFPI may play a cell specific role in proteinase regulation in the brain.     

健康人携带的白喉棒状杆菌生物学性状分析

目的：探讨健康人携带的白喉棒状杆菌的生物学特性及其与标准的产毒菌株的生物学性状的差异。方法：采用鸡蛋斜面培养基，亚碲酸钾血琼脂平板和肉汤培养基观察其生长特性，测定多种系列化反应性，毒力和药物敏感性。结果：健康人携带的白喉杆菌的培养特性典型均无毒力；发酵麦芽糖和发酵蔗糖的菌株较多，有较多的耐麦迪霉素，苯唑青霉素和洁霉素的菌株。结论：健康人所携带的白喉杆菌的生物学特性不同于标准的有毒力的菌株。     

50岁以上正常人左室舒张期彩色多普勒血流频谱参数变化的研究

目的探讨５０岁以上正常人左室舒张期脉冲多普勒频谱的参数变化情况。方法选择一年半时间内受检的所有５０岁以上正常人４７５例，按每１０岁为一组分４组进行分析。受检者取左侧卧位，常规显示心尖四腔心切面，取样容积置于二尖瓣尖，使声束与二尖瓣血流方向夹角＜１５°，以连续三个心动周期的平均值分别测量Ｅ峰、Ａ峰、Ｅ／Ａ及Ｅ峰减速时间并统计。结果发现Ｅ峰高于正常值低限的例数、平均Ｅ峰血流速度以及Ｅ／Ａ均随着年龄的增加而下降，Ｅ峰减速时间则随着增龄而增加。结论左室舒张期血流频谱的所有参数与年龄有显著的相关性，明显随着增龄而变化，并且有其规律性。     

Comparison of silver stainings and immunohistology for the detection of neurofibrillary tangles and extracellular cerebral amyloid in paraffin sections

Summary The sensitivities of six silver-staining methods and immunohistology for beta and tau protein were compared for their ability to demonstrate neurofibrillary tangles (NFT) and senile plaques (SP) in paraffin sections. Serial sections of the hippocampal area of 35 brains showing these neuropathological findings were cut and stained by the methods of Cross, Campbell, Bielschowsky, Gallyas, Yamaguchi, our variant (method of Reusche) and immunohistology. In the detection of NFT, the techniques of Gallyas, Bielschowsky, our method and tau protein immunostaining were the most sensitive methods. The procedure of Campbell and again our method were proven to be superior to the other stainings in demonstrating SP as well as diffuse and subpial amyloid. Moreover, our method reliably stained vascular and perivascular amyloid which can be identified in brains with congophilic angiopathy. Due to a lack of control in certain steps of the procedures most of the silver-staining methods are complicated and to not present reliable results. Our variant is easy to perform and, thus, may be used as a sensitive, simple and reliable alternative for the impregnation of the main lesions (NFT and SP) occurring in senile dementia of Alzheimer type and brains with normal aging for screening, retrospective and quantitative studies and for routine purposes.Parts of this paper were presented at the IV. European Meeting of Neuropathology, Berlin Germany, 1992     

Diffuse type of senile plaques in the cerebellum of Alzheimer-type dementia demonstrated byβ protein immunostain

Summary We studied senile plaques (SP) in the cerebella of six autopsied subjects with Alzheimer-type dementia (ATD) and ten non-ATD autopsied subjects between the ages of 78 and 90. Neither SP nor amyloid angiopathy (AA) was observed in any of the non-ATD subjects. In the four of the six ATD subjects, diffuse plaques in the molecular layer were seen as ill-defined areas of fine fibrillar materials by protein immunostaining with formic acid pretreatment, the modified Bielschowsky stain, and periodic acid-methenamine silver (PAM) stain. The plaques were not visible with Bodian, Congo red, or periodic acid-Schiff stains. Compact plaques in the Purkinje cell or in the granular cell layers were found in three of the six subjects. Their amyloid core was often surrounded by areolar amyloid deposits. AA was observed in three of the six subjects. The argyrophilia of the diffuse and compact plaques, demonstrated by the modified Bielschowsky and PAM stains, became undetectable when the sections were first treated with formic acid. Such treatment made the plaques immunoreactive with protein antiserum. The findings suggested that cerebellar diffuse plaques and compact plaques consist mainly of an amyloid component, and are characteristic of ATD.     

Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain

Summary A monoclonal antibody, termed AD11/8, reactive to microglial cells, was produced by immunization of mice with partially purified amyloid fibrils of senile (neuritic) plaques. With immunoperoxidase staining on human tissues, AD11/8 also recognized macrophages in the red pulp of the spleen, Kupffer cells in the liver, and macrophages in the bone marrow. The results show that AD11/8 recognizes the antigens associated with mononuclear phagocytes lineage. In normal brains a few resting microglial cells were stained in gray matter, and less frequently in white matter. In senile dementia of the Alzheimer type numerous microglial cells were stained intensively and they often formed clusters in gray matter. By double immunostaining with AD11/8 and a polyclonal antibody against synthetic amyloid -protein, clustered microglial cells were observed in and around senile plaques with amyloid deposits. Some amyloid plaque cores were surrounded by microglial cell processes. These results indicate that microglial cells may play an important role in senile plaque formation.Supported in part by the Grant-in Aid for Scientific Research from the Ministry of Education, Science and Culture, the grants for Research of Dementia and for Primary Amyloidosis from the Ministry of Health and Welfare, Japan     

The effect of design of residential homes in creating dependency among confused elderly residents: A study of elderly demented residents and their ability to find their way around homes for the elderly

A study of 13 homes for elderly people examining the effect of the environment on demented residents looked into the complexity of the design from the residents' point of view. Two principal tools were used in this investigation: ‘route diagrams’, which describe a resident's use of the home, and a measure devised to indicate each resident's ability to find her way around the home. These are described and the relationship between them explored. From this the following tentative conclusions are drawn:

• (i) The variables that influence a resident's ability to find her way around differ between group and communally designed homes.
• (ii) It would appear that group homes provide a more favourable design, especially in the case of physically frail demented elderly people.
• (iii) In group homes, the level of lighting is an important aid to a demented person in finding her way around.
• (iv) In communal homes, residents seem most able to find their way around homes that have been adapted from older premises.
• (v) In both types of home, ‘meaningful decision points’ can be seen as aids to a resident finding her way around.

     

社区老年期痴呆患者的随访研究

痴呆是一类高死亡率疾病 ,和心脏病、癌症及中风一起已成为威胁老年健康和生命的主要因素。本研究随访调查原有社区老年期痴呆患者 12 9例十年后的生存状况 ,现将资料报告如下。1　对象和方法1.1　对象1991年长沙市社区流调发现的 12 9例老年期痴呆患者[1] ,其中AD 116例 ,VD 13例。1.2　方法自编调查表 ,包括人口学资料 ,躯体疾病情况等。采用简易智力状态检查 (MMSE)、日常生活能力量表 (ADL)及功能活动调查表 (POD) [2 ] 对存活者进行功能评定。对于死者进一步了解死亡原因。2　结　　果2 .1　AD组和VD组生存时间频度分布病程≤ …     

米氮平与氟西丁治疗老年抑郁症患者的对照研究

目的探讨米氮平治疗老年抑郁症患者的疗效和副反应。方法46例符合CCMD-3抑郁症诊断标准的年龄〉60岁老年抑郁症患者，应用米氮平和氟西丁各23例进行随机对照研究，观察6周，采用汉密顿抑郁量表（HAMD）和副反应量表（TESS）观察患者对治疗的疗效和副反应的变化。结果两种药物疗效相仿，米氮平起效快，副反应少。结论米氮平治疗老年抑郁症患者安全有效，副反应小。     

帕罗西汀合用心理行为干预治疗老年期抑郁症的疗效

目的探讨帕罗西汀合用心理行为治疗对老年期抑郁症的疗效。方法将60例老年期抑郁症随机分成两组，进行为期6周的对照研究，出院后随访1年，分别用心理行为合并帕罗汀治疗（研究组）和帕罗西汀治疗（对照组）；采用汉密尔顿抑郁量表（HAMD）和临床疗效总评量表（CGI—SI）进行评定。结果研究组在治疗6周后HAMD评分（9．32±2．28）较对照组（13.17±3．39）有显著性差异（P〈0．01），研究组CGI—SI较对照组有显著性差异（P〈0．01），1年末随访时HAMD评分研究组（9.19±2．33）较对照组（13．98±4．96）有显著性差异（P〈0.01）。且研究组复发率低于对照组（P〈0.05）。结论帕罗西汀合用心理行为治疗对老年期抑郁症的疗效优于帕罗西汀，且复发率低。