Etiology of IgA nephropathy syndrome

Since Berger's original paper on mesangial IgA-IgG deposition with hematuria, there have been a number of clinical and pathological studies regarding IgA immune complexes, the mechanisms of glomerular IgA deposition leading to glomerular injury and animal models of IgA nephropathy. During the last quarter of this century, glomerular changes such as IgA nephropathy have also been observed in cases associated with other diseases, such as systemic lupus erythematosus, Schoenlein-Henoch purpura, liver cirrhosis and chronic inflammatory diseases of the lung. This evidence supports the idea of an IgA nephropathy syndrome. On the other hand, IgA is thought to be an important humoral factor at the mucosal immune system and appears to have an antibody function against various etiologic candidates of extrinsic or intrinsic substances at the mucosal and systemic immune system. Glomerular IgA deposition in IgA nephropathy syndrome is thought to result from elevated levels of circulating immune complexes or aggregated IgA due to an overproduction of polymeric IgA as antibodies in the serum and due to the clearance impairment of IgA immune complexes in the hepatic and splenic phagocytic system. The glomerular IgA subclass is not one-sided, but should be evaluated in comparison with the age of patients at renal biopsy; this indicates the approximate age of onset. Cirrhotic IgA glomerulonephritis is not related to Hepatitis B or C virus infection, but to the pathophysiologic condition of liver cirrhosis. Various etiologic candidates such as viral, microbial, dietary antigens or auto-antigens have been listed and experimental models of IgA nephropathy syndrome have provided some clues in understanding the etiology of primary IgA nephropathy. However much still remains to be clarified and some specific epitopes common among these etiologic candidates will have to be identified.     

Distribution of the largest neuron in mouse caudate-putamen nucleus: Its position in large-cell — Medium-cell clusters

Summary The position of the largest striatal neuron within territories delimited by medium-sized clustered neurons was charted in Nissl-stained sections through the mouse caudate-putamen nucleus. Medium-sized neuron somata occur in close proximity to this large cell at some point in the anteroposterior, mediolateral or dorsoventral extent of its soma. The size of the network of medium-sized neurons associated with the large cell may vary from two to 15 neurons. Even when this network is extensive, the large neuron is never completely surrounded. Most often, this cell also borders a fascicle of internal capsule fibers, and the entire cellular island may be aligned either parallel to or perpendicular to the orientation of these fibers. These findings suggest the hypothesis that cellular territories in the caudate-putamen nucleus have a very specific orientation in three dimensional space.     

上海人群中TAP与IgA肾炎相关性的研究

目的探讨上海人群中抗原处理相关转运蛋白（ＴＡＰ）与ＩｇＡ肾炎的相关性。方法用ＰＣＲ－ＳＳＯ方法对上海地区８８名正常人及４０名ＩｇＡ肾炎患者ＴＡＰ进行分型。结果在病人组及对照组中共发现３种ＴＡＰ１（ＴＡＰ１Ａ、１Ｂ、１Ｃ）及４种ＴＡＰ２（ＴＡＰ２＊０１０１、＊０１０２、＊０２０１、＊０２０２）等位基因。未发现病人组与对照组之间ＴＡＰ等位基因分布的差异。结论本文结果未能证明ＴＡＰ基因与ＩｇＡ肾炎相关，但不排除未检测的多态位点与ＩｇＡ肾炎关联的可能性。     

人和大鼠腰椎关节突关节的SP能神经纤维的分布

目的：证实支配腰椎关节突关节的神经支配和化学性质，方法：用逆行荧光素标记结合免疫组化法，研究７只大鼠腰部脊神经节细胞的周围突分支投射到腰椎关节突关节及其递质性质以及３例人腰椎关节突关节囊上神经末梢的化学性质，结果：发现大鼠一侧Ｌ５和Ｌ６之间的关节突关节受同侧Ｌ２－５节段的脊神经节的部分细胞周围突分支支配，其中有３３．３９９％的中型和小型细胞为中ＳＰ能免疫反应阳性，人的关节突关节囊含有ＳＰ阳性的神经     

Increase in tonsillar germinal centre B-1 cell numbers in IgA nephropathy (IgAN) patients and reduced susceptibility to Fas-mediated apoptosis

IgAN is a common form of primary glomerulonephritis and also a disease of tonsillar focal infection. The comprehensive mechanism underlying this disease remains to be defined. To better understand its pathogenesis, we investigated tonsillar CD5+ B cells (B-1 cells) with respect to IgA synthesis. Germinal centre (GC) B cells were isolated from the tonsils of IgAN patients and the number of B-1 cells in the GC determined by flow cytometry. GC B-1 and B-2 (CD5- B) cells were purified by cell sorter, the cells were incubated with agonist anti-CD40 MoAb and the ability for antibody production by B-1 and B-2 cells determined by ELISPOT assay. GC B-1 cells and B-2 cells were incubated with agonist anti-Fas MoAb, and apoptosis in GC B-1 cells and B-2 cells was analysed by flow cytometry. Although B-1 cells do not usually take part in the GC reaction, an increase in B-1 cell numbers was observed in the GC of tonsils from IgAN patients. These B-1 cells were likely IgA1 antibody-producing cells, since the prominent IgA subclass in IgAN is generally considered to be IgA1. Although Fas-dependent apoptosis is essential for the elimination of activated B cells, these B-1 cells showed a reduced susceptibility to Fas-mediated apoptosis. It is conceivable that activated B-1 cells may survive in the GC due to impaired apoptosis and thus produce abnormal antibodies. These findings suggest that the immune responses of B-1 cells in the tonsillar GC could thus have an impact on the pathogenesis of IgAN.     

IgA polyspecific autoantibodies in IgA nephropathy.

The specificity of circulating and kidney-bound IgA during IgA nephropathy is still a matter of discussion. In the present study, high levels of IgA antibodies directed against a panel of self and non-self antigens were found in the serum from patients with IgA nephropathy and were eluted from four out of the seven kidney biopsies studied. After immunoadsorption of pooled selected serum samples on TNP and actin-coated columns, polyspecific IgA antibodies were eluted. This supports the hypothesis that IgA-bearing B cells clones most probably producing polyspecific antibodies are a major feature of human IgA nephropathy. These findings also suggest that it may be hazardous to draw conclusions from the finding of apparently monospecific IgA antibodies in this condition.     

Immunopathological features of palatine tonsil characteristic of IgA nephropathy: IgA1 localization in follicular dendritic cells

IgA nephropathy (IgAN) is generally thought to be mediated by the glomerular deposition of circulating immune complexes containing IgA as the major antibody component. Upper respiratory infections and tonsillitis often precede IgAN. and in some cases tonsillectomy is affective for the (treatment of IgAN. Thus, the tonsil seems to be a unique organ causing initial and/or progressive events to generate nephritogenic immune complexes in IgAN. in this study we focused on the analysis of immunopathological features of the palatine tonsil characteristic of IgAN patients by using an immunohistochemical technique. The IgAl subclass was demonstrated in follicular dendritic cells (FDC) of the tonsil of IgAN patients, but not in FDC of non-IgAN controls. On the other hand, IgA2, IgG, IgM and C3 did not show any differences in distribution between the two groups. Moreover, the expression of decay-accelerating factor (DAF), an inhibitor of homologous complement activation, and transforming growth factor-beta I (TGF-/β1). an inducer of antibody-producing ceils to IgA class switching, in FDC and interdigitating dendritic cells of the tonsil, respectively, which was also clarified in this study for the first time, was found to be identically distributed in the two groups. These findings may support the idea that IgA1. possibly in an immune complex form, is trapped by FDC and plays an important role in the persistent activation of particular B cell repertoires responsible for ihe onset and/or progression of IgAN.     

Hemodynamic factors in the pathogenesis of diabetic nephropathy

Summary The pathogenesis of the diabetic glomerular lesion is unknown. However, cumulative indirect evidence favors hemodynamic factors associated with the abnormal endocrine environment as the cause of diabetic angiopathy. Experimental evidence suggests that the increased hydrostatic pressures in capillary beds, a hallmark of the early stages of insulin-dependent diabetes, are associated with macromolecular leakage leading to the typical thickening of glomerular capillary basement membrane and increased glomerular mesangial matrix even prior to the occurrence of systemic hypertension. Patients with renal or carotid artery stenosis seem to be protected against diabetic nephropathy and retinopathy on the stenosed side. The first signal of diabetic nephropathy even before deterioration of the renal function is microalbuminuria detected by sensitive methods such as radioimmunoassay. Not only in hypertensive, but even in normotensive diabetic patients with microalbuminuria antihypertensive therapy has been shown to reduce albumin excretion rate and to slow the progression of diabetic nephropathy. Once overt diabetic nephropathy has been established, hypertension is a constant accompaniment of the disease. Thus, hypertension may be a cause as well as a result of diabetic nephropathy. Tight control of blood sugar in close association with antihypertensive treatment reducing blood pressure to a lower normal limit, possibly with agents that specifically decrease glomerular capillary hydraulic pressure are the corner stone in protection against progression of the diabetic angiopathy.Abbreviations ECF extracellular fluid - ESRD end-stage renal disease     

基于永磁磁场的电子胶囊定位系统

为了确定可吞服式电子胶囊在人体内的位置,基于矩形永磁体空间磁场解析式,设计了定位系统,提出了相应的定位算法,并进行了实验。系统中两个三轴磁传感器封装在胶囊内,由胶囊和永磁体的空间位姿关系模型,建立了与传感器输出和胶囊位姿变量相关的一组非线性方程。对方程进行了数值求解,并和期望值进行了比较,结果发现该方法是切实可行的。