Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease

Summary Immunocytochemical staining with monoclonal antibodies to the -protein on tissue sections which have been pretreated with formic acid is not only a very specific but also a highly sensitive method for the detection of amyloid deposits in the brains of Alzheimer's disease victims. We report here a spectrum of morphological appearance of the brain amyloid deposits which are one of the main histopathological correlates of this disorder. Deposits of the -protein are not only found in the well-known lesions [congophilic angiopathy and senile (neuritic) plaques] but are also seen under various morphological forms for which the word plaques does not appear an appropriate term: amyloid fibrils are found as large areas of diffuse infiltration of the neuropil, as ribbon-like infiltration in the subpial layer of the cerebral cortex, as granular deposits in the white matter, as diffuse deposits in the molecular layer of the cerebellum and the basal ganglia and as star-shaped deposits in the cerebellar Purkinje cell layer. The morphology of these deposits seems to depend on the cyto-and fibroarchitectonics of the brain region in which they are found, on the amount of amyloid deposited, and also on the type of staining technique used. It is only under specific circumstances that the deposition of amyloid in the neuropil is accompanied by the formation of paired helical filaments in nerve cell processes and their parent perikarya. In conclusion, our studies suggest that the extent of brain amyloidosis in Alzheimer's disease is much wider than so far appreciated.Supported in part by grants 5-AGO-4220-05 and 5-HD-22634-02 from the National Institutes of Heath     

A unique exonic splice enhancer mutation in a family with X-linked mental retardation and epilepsy points to a novel role of the renin receptor

The renin-angiotensin system (RAS) is essential for blood pressure control and water-electrolyte balance. Until the discovery of the renin receptor, renin was believed to be mainly a circulating enzyme with a unique function, the cleavage of angiotensinogen. We report a unique mutation in the renin receptor gene (ATP6AP2) present in patients with X-linked mental retardation and epilepsy (OMIM no. 300423), but absent in 1200 control X-chromosomes. A silent mutation (c.321C>T, p.D107D) residing in a putative exonic splicing enhancer site resulted in inefficient inclusion of exon 4 in 50% of renin receptor mRNA, as demonstrated by quantitative RT-PCR. Analysis of membrane associated-receptor molecular forms showed the presence of full-length and truncated proteins in the patient. Functional analysis demonstrated that the mutated receptor could bind renin and increase renin catalytic activity, similar to the wild-type receptor, but resulted in a modest and reproducible impairment of ERK1/2 activation. Thus, our findings confirm the importance of the RAS in cognitive processes and indicate a novel specific role for the renin receptor in cognitive functions and brain development.     

一种可生物降解温度敏感型聚乙二醇-聚己内酯-聚乙二醇水凝胶的合成和表征

合成了一系列分子量较低的聚乙二醇．聚己内酯-聚乙二醇（Poly（ethylene glycol）-Polycaprolactone-Poly（ethylene glycol），PEG-PCL—PEG）三嵌段共聚物。分别采用FTIR和1H—NMR对其结构进行了表征。所合成的PEG-PCL-PEG共聚物具有良好的水溶性，当水溶液浓度高于临界凝胶浓度（Critical gel concentration，CGC）时，随着温度的变化聚合物水溶液会呈现特有的凝胶-溶胶转变。研究了共聚物亲水疏水链段的比例和长度，以及热历史等对凝胶-溶胶转变行为的影响。通过调节上述条件，可以在一定程度上拓宽凝胶-溶胶转变温度范围，有助于PEG—PCL-PEG水凝胶在可注射药物控制释放系统等方面的应用。     

抗体包被对红细胞变形性影响的研究

作者对抗体包被的红为性进行研究，发现抗体包被改变了红细胞的变形性，在我们研究的抗体量范围内，抗体量越多，红细胞的变形性越小，作者从血液流变学的角度对上述结果作了讨论，并提出了通过测定其对红细胞变形性的影响来比较准确地标定抗体效价的可能性。     

人胚胎大脑海马发育过程中凋亡神经元超微结构观察

本文借助电子显微镜技术对 4月胎龄组及 6月胎龄组水囊引产胎儿海马中段部位的凋亡神经元超微结构进行观察、拍照 ,并对结果进行了分析讨论。结果显示 :两组对象中均可见凋亡神经元 ,所见的凋亡神经元的超微结构变化基本相同 ,即细胞核内有明显的染色质边集和凝结成块的现象 ,并可见核膜皱缩和扭曲。另外 ,6月组凋亡细胞的结构变化较 4月组更为明显。在 6月组细胞质内和核内均有小体出现 ,其他细胞器无显著变化。从而更进一步说明在胚胎海马发育中存在着神经元不同性质的死亡现象 -即正常死亡和凋亡。而且提出 6月组显现出更为明显的凋亡神经元形态变化     

Proximal tubular epithelial cell integrins respond to high glucose by altered cell-matrix interactions and differentially regulate matrixin expression

Thickening of the tubular basement membrane (TBM) occurs in diabetic nephropathy, but the effects of high glucose on the functional aspects of proximal tubular epithelial cells are not clearly understood. In the present study, we examined the effects of elevated glucose concentrations on (a) integrin expression by human proximal tubular epithelial cells (HK-2) and integrin-mediated interactions with type IV collagen (colIV) and laminin, major components of TBM; (b) the expression of matrixins/matrix metalloproteinases (MMPs), which is regulated by integrins; and (c) the expression of tissue inhibitors of metalloproteinases (TIMPs). HK-2 cells cultured in 25 mM glucose underwent a reduction of the expression of alpha3, beta1, alpha(v)beta3, and alpha5 integrin subunits, with a concomitant increase of the alpha2 subunit, compared with cells grown in 5 mM glucose. Adhesion experiments demonstrated that high glucose led to increased cell adhesion on either colIV or laminin. Experiments of competition of adhesion using anti-integrin antibodies indicated that HK-2 cells in 5 mM glucose used mainly alpha(v)beta3 and alpha5beta1 integrins to adhere to colIV, whereas in 25 mM glucose they additionally used alpha2beta1. In the case of laminin, a beta1-mediated adhesion was observed when HK-2 cells were in 5 mM glucose, whereas in 25 mM glucose, alpha2beta1 and alpha(v)beta3 were also involved. Elevated glucose concentrations resulted in decreased expression of MMP-9 and MMP-2, whereas an increase in TIMP-1 and a decrease in TIMP-2 expression were observed. We also examined which integrins mediated the expression and secretion of matrixins MMP-2 and MMP-9. Ligation of alpha3beta1 with mAbs resulted in induction of MMP-2 expression and secretion, whereas antibody ligation of alpha(v)beta3 led to down-regulation of MMP-9. The above data implicate integrins of proximal tubular epithelial cells in the regulation of MMPs and in the development of TBM thickening in diabetic nephropathy.     

耳穴静态电测量中的瞬变响应

耳穴电参数时变关系实验表明，在测量起始ｔ＜２τ时，因瞬变作用，电位Ｅ（ｔ）和压降Ｕ（ｔ）为瞬态响应，响应函数呈指数关系，特征参数为弛豫时间τ，τ≈ＲＣ；ｔ＞２τ时，为时变间期。电路分析给出数学描述，并与耳穴和模拟实验结果较相符。提示，时变特征应以ｔ＞２τ后提取，静态电测量时，采样应避开瞬变期，可提高准确性。该工作对正确鉴别时变性和特征提取，全面认识耳穴电特性具有重要意义。