自制苏芪合剂联合治疗Ⅲ～Ⅳ级IgA肾病的临床疗效观察

目的 探讨自制苏芪合剂对Ⅲ～Ⅳ级IgA肾病患者的疗效及患者T细胞功能的改善.方法 28例Ⅲ～Ⅳ级IgA肾病患者随机分为两组,对照组:醋酸泼尼松-日1mg,kg,隔日晨起顿服,盐酸苯那普利-日10mg;治疗组:在上述用药的基础上加用自制苏芪合剂.8周后,观察患者缓解率、T细胞功能及不良反应.结果 治疗组患者在缓解率、T细胞功能改善等方面优于对照组,且因糖皮质激素的使用而出现的不良反应少于对照组.结论 苏芪合剂联合治疗Ⅲ～Ⅳ级IgA肾病疗效显著并能有效改善T细胞功能.     

In Vivo Anergized T Cells Form Altered Immunological Synapses In Vitro

T cells contact allogeneic antigen presenting cells (APCs) and assemble, at their contact interface, a molecular platform called the immunological synapse. Synapse-based molecules provide directional signals for the T cell--either positive signals, resulting in T-cell activation, or negative signals causing T-cell inactivation or anergy. To better understand the molecular basis of in vivo T-cell anergy we analyzed the contacts made between in vivo anergized T cells and APCs, and determined which signaling molecules were included or excluded from their immunological synapses. Anergy was induced in TCR transgenic mice by the intravenous injection of semiallogeneic donor spleen cells. T cells from anergized mice were mixed with APCs, the T-cell/APC synapses imaged using deconvolution microscopy, and their molecular compositions were determined. T cells from anergic mice formed unstable immunological synapses in vitro with allogeneic APCs and failed to recruit the signaling proteins necessary to initiate T-cell activation. These findings suggest that T-cell anergy induced by exposure to semiallogeneic donor cells is associated with defects in the earliest events of T-cell activation, immunological synapse formation and recruitment of TCR-mediated signaling proteins.     

造血干细胞移植后慢性移植物抗宿主病相关的膜性肾病一例

目的 总结造血干细胞移植后慢性移植物抗宿主病（cGVHD）相关的膜性肾病的诊疗体会。方法 为1例急性淋巴细胞白血病患者施行HLA全相合的无关供者外周血造血干细胞移植，术后应用甲氨喋呤和他克莫司（FK506）预防GVHD。术后第19d发生急性GVHD，经甲泼尼龙治疗逆转。分别于术后182d、235d停用FK506和泼尼松，5d后患者出现cGVHD表现，肝功能异常，并伴肾病综合征的相关表现，病理诊断为膜性肾病Ⅱ期，遂给予FK506和泼尼松治疗，同时辅以利尿、降脂等措施。结果发生膜性肾病时，患者的尿蛋白＋＋＋＋，白细胞75个／μl，上皮细胞359．5个／pl，病理性管型＋，管型计数为167个／μl，24h尿蛋白定量为4．28g；肾组织活检，无肾小球硬化，肾小球体积稍大，部分血管袢受压，开放欠佳，肾小球基底膜轻微增厚，外观呈僵硬感，系膜基质轻、中度增殖；间质区部分肾小管扩张，肿胀、变性，未见明显间质纤维化和炎症细胞浸润；Masson染色可见基底膜上皮侧嗜复红物沉积；免疫荧光检查，IgG＋＋＋，C3＋＋＋，IgA＋＋，沿毛细血管袢呈颗粒状节段性分布，系膜区呈团块状分布；IgM、Clq、CA均阴性。电镜下可见肾小球基底膜上皮下沉积物，并有基膜增厚，毛细血管系膜基质轻度增生。经泼尼松和FK506治疗，2个月后尿蛋白转阴。结论 造血干细胞移植后出现肾病综合征或蛋白尿，应考虑GVHD相关膜性肾病的可能，肾穿刺活检有助于诊断，糖皮质激素和FK506治疗有效。     

兔视网膜方向选择性神经节细胞树突的独特分枝模式及其生理意义

本实验研究了兔视网膜中的方向选择性神经节细胞 (direction selective retinal ganglion cells,DS cells)树突野的分枝模式。测量了视网膜中方向选择性神经节细胞和作为经典分枝模式神经元代表的α神经节细胞的树突直径。发现 ,方向选择性神经节细胞的树突在分枝后直径达到 0 .5 μm,进一步分枝树突直径仍保持在 0 .5 μm左右 ,这样 ,在方向选择性神经节细胞树突野中大多数树突直径在 0 .5μm左右。而作为经典分枝模式神经元代表的α神经元的树突每次分枝后都逐级变细 ,最终直径达到 0 .5μm左右 ,这样 ,α神经节细胞的树突直径大部分都大于 0 .5μm。我们应用程序“NEU RON”对在两种神经元模型中 ,抑制点落于兴奋点与胞体之间 (proximal)和抑制点不落于兴奋点与胞体之间 (distal)这两种情况进行模拟。我们发现 ,当抑制点不落于兴奋点与胞体之间时 ,在方向选择性神经节细胞的树突分枝模型中 ,抑制效果更强。那么 ,将使得方向选择性神经节细胞对抑制点落于兴奋点和胞体之间的要求变得不是那么迫切。所以 ,方向选择性神经节细胞的这种独特分枝模式 ,也许可以避免或至少减轻其在发育中可能会产生的连线的复杂性。并且 ,我们对得出的结论进行了电路分析 ,对方向选择性神经节细胞这种独特的分枝模式具有的?     

In vivo detection of single cells by MRI.

The use of high-relaxivity, intracellular contrast agents has enabled MRI monitoring of cell migration through and homing to various tissues, such as brain, spinal cord, heart, and muscle. Here it is shown that MRI can detect single cells in vivo, homing to tissue, following cell labeling and transplantation. Primary mouse hepatocytes were double-labeled with green fluorescent 1.63-microm iron oxide particles and red fluorescent endosomal labeling dye, and injected into the spleens of recipient mice. This is a common hepatocyte transplantation paradigm in rodents whereby hepatocytes migrate from the spleen to the liver as single cells. One month later the animals underwent in vivo MRI and punctuated, dark contrast regions were detected scattered through the livers. MRI of perfused, fixed samples and labeled hepatocyte phantoms in combination with histological evaluation confirmed the presence of dispersed single hepatocytes grafted into the livers. Appropriate controls were used to determine whether the observed contrast could have been due to dead cells or free particles, and the results confirmed that the contrast was due to disperse, single cells. Detecting single cells in vivo opens the door to a number of experiments, such as monitoring rare cellular events, assessing the kinetics of stem cell homing, and achieving early detection of metastases.     

供者表达活化性杀伤细胞免疫球蛋白样受体对造血干细胞移植预后的影响

目的 观察供者表达活化性杀伤细胞免疫球蛋白样受体（aKIR）对受者造血干细胞移植（HSCT）预后的影响。方法 1996年至2001年共行亲缘性人类白细胞抗原（HLA）全相合骨髓移植59例，以序列特异性引物多聚酶链反应法（SSP-PCR）检测供者aKIR的表型。分析供者表达aKIR对受者移植后病毒、细菌和真菌感染及出血、复发、存活情况的影响。结果 供者表达aKIR与受者移植后出血、病毒及细菌感染发生的概率无明显相关性；当供者表达KIR3DS1表型时，发生真菌感染概率增高（X^4．804，P=0．028）。供者表达aKIR对受者HSCT后存活率和白血病复发率均无明显影响。结论 亲缘性HLA全相合HSCT中，供者表达aKIR并不能改善受者的移植效果。     

肝病患者血清诱导间充质干细胞表达肝细胞特异性标志物的实验研究

目的：观察重型肝病患者血清对人骨髓间充质干细胞（MSCs）的诱导分化作用，探讨人MSCs分离培养、体外扩增的条件和方法。方法：从肋骨分离、培养人骨髓MSCs、体外扩增培养、鉴定，并采用重型肝病患者血清诱导培养，分别在诱导培养0、7、14、21、28天时留取细胞，并采用免疫细胞化学方法检测肝特异性标志物（AFP、Alb、CK-18）、用PAS进行糖原染色实验。结果：诱导后5天、MSCs表现为肝细胞样细胞，随着诱导培养时间的延长，肝特异性标志物逐渐出现和成熟。AFP在7天时表达水平最高，培养14、21、28天时表达逐渐减弱；Alb、CK- 18和糖原随着诱导时间的延长，表达逐渐增强。结论：密度梯度离心，贴壁培养和消化时间控制相结合，是一种较为有效的分离纯化方法。重型肝病患者血清能诱导骨髓MSCs表达肝细胞的特异性标志物。     

Role of Integrin CD103 in Promoting Destruction of Renal Allografts by CD8+ T Cells

Infiltration of CD8(+)TCRalphabeta(+) T-effector populations (CD8 effectors) into graft epithelial compartments has long been recognized as a key lesion in progression of clinical renal allograft rejection. While the afferent phase of allograft immunity is increasingly well-defined, the efferent pathways by which donor-reactive CD8-effector populations access and ultimately destroy the graft renal tubules (rejection per se) have received remarkably little attention. This is an important gap in our knowledge of transplantation immunology, because epithelial compartments comprise the functional elements of most commonly transplanted organs including not only kidney, but also liver, lung, pancreas, and intestine. Furthermore, there is increasing evidence that attack of graft epithelial elements by CD8-effector populations not only causes short-term graft dysfunction but is also a major contributor to development of chronic allograft nephropathy and late graft loss, which now represent the salient clinical problems. Recent studies of the T-cell integrin, alpha(E)beta(7) (CD103), have provided insight into the mechanisms that promote interaction of CD8 effectors with graft epithelial compartments. The purpose of this communication is to review the known properties of the CD103 molecule and its postulated role in the efferent phase of renal allograft rejection.     

Isochronic transplantation of neonatal grafts in the visual cortex of cats: responsiveness,ocular dominance and specificity of cortical cells to visual stimulation

Summary The visual cortex of adult cats was studied physiologically following neonatal isochronic transplantation of grafts from areas 17,18, which were placed homotopically, in order to reveal their functional integration and thus possible repairing of damaged cortical neuronal circuits. Three homograft cats, in which transplantation was carried out between siblings (228 cortical cells) were compared to 4 animals receiving reimplanted autografts of the equivalent size (131 cells) as well as 3 animals with analogous sectioning of the visual cortex (162 cells) (pseudograft controls). The location of the boundaries between the transplant region and the host were determined using the Nissl's method for staining histological cross sections. Extracellular unit recording revealed typical waveform of the action potentials in the transplanted region and in the surrounding host tissue of all groups of cats. Visual responsiveness in the homograft cats was 17.5% in the transplanted region and 80.4% in the unoperated hemisphere; the corresponding results were 40.3% for the transplanted region and 82.2% for the unoperated hemisphere in the autografts and 23.1% and 73.4% in the pseudografts. The specificity of the cells to visual stimulation as expressed by their orientation and direction specificity, indicated preservation of these properties in the transplanted cats. While all responsive cells in the transplanted region of the homografts were orientation specific, their proportion was 60% in the autografts and 55.5% in the analogous region in the pseudograft controls. As to the direction specific cells, their performance in the grafted region of the grafted cats was even much higher than that of the pseudograft controls. The ocular dominance distribution of the cells showed preservation of binocularity in the transplanted region (90.0% binocular cells) of the homografts; it was however smaller in the equivalent region of the autografts (65.0%) and remarkably reduced (20.0%) in the pseudografts. It was concluded that despite the deafferentation induced during the transplantation procedure, a remarkable visual responsiveness was found in the transplanted region, indicating postoperative recovery. However, the cells there were mainly affected in their activity and less in their specificity to visual stimulation.