Genetic and structural analyses of affinity maturation in the humoral response to HIV-1

Most broadly neutralizing antibodies (BNAbs) elicited in response to HIV-1 infection are extraordinarily mutated. One goal of HIV-1 vaccine development is to induce antibodies that are similar to the most potent and broad BNAbs isolated from infected subjects. The most effective BNAbs have very high mutation frequencies, indicative of the long periods of continual activation necessary to acquire the BNAb phenotype through affinity maturation. Understanding the mutational patterns that define the maturation pathways in BNAb development is critical to vaccine design efforts to recapitulate through vaccination the successful routes to neutralization breadth and potency that have occurred in natural infection. Studying the mutational changes that occur during affinity maturation, however, requires accurate partitioning of sequence data into B-cell clones and identification of the starting point of a B-cell clonal lineage, the initial V(D)J rearrangement. Here, we describe the statistical framework we have used to perform these tasks. Through the recent advancement of these and similar computational methods, many HIV-1 ancestral antibodies have been inferred, synthesized and their structures determined. This has allowed, for the first time, the investigation of the structural mechanisms underlying the affinity maturation process in HIV-1 antibody development. Here, we review what has been learned from this atomic-level structural characterization of affinity maturation in HIV-1 antibodies and the implications for vaccine design.     

Increased circulating apoptotic lymphocytes in children with Down syndrome

Down syndrome (DS) resembles immunodeficiency with increased infections, auto‐immune diseases, and hematological malignancies. Until now, immunological studies in DS mainly focused on T‐lymphocytes. We recently described a profound B‐lymphocytopenia in children with DS. This could be caused by increased apoptosis. Therefore, we determined expression of flowcytometric markers for apoptosis [Annexin‐V (AV) and propidium iodide (PI)] on peripheral lymphocytes in 72 children with DS and 32 age‐matched controls (AMC). Within the total lymphocyte compartment, apoptosis was more pronounced in DS; it increased with age. Moreover, apoptosis was highest within the B‐lymphocyte compartment which may be a contributing factor to the B‐lymphocytopenia found in DS. Pediatr Blood Cancer 2012; 59: 1310–1312. © 2012 Wiley Periodicals, Inc.     

早期肺癌立体定向放射治疗的临床研究进展

立体定向放射治疗(stereotactic body radiotherapy,SBRT)以及立体定向消融放射治疗(stereotactic ablative radiotherapy,SABR)为局部精确放射治疗方法,目前广泛运用于早期不能手术的非小细胞肺癌(non-small-cell lung cancer,NSCLC)。在部分临床试验中,其3年局部控制率及3年生存率已接近手术治疗的效果,并且对患者的肺功能影响小。本文对早期肺癌精准治疗的临床实践及研究进展作简要综述。     

腹泻小儿粪便中双歧杆菌含量变化和红细胞免疫功能关系

目的：研究腹泻小儿便中双歧杆菌含量变化与红细胞免疫的关系。方法：对42例腹泻小儿和38例正常小儿进行了粪便双歧杆菌含量、红细胞CR1(ECR1)数量及红细胞自然粘附肿瘤花环率(NTRR)的测定。结果：与正常小儿相比，腹泻小儿粪便中双歧杆菌含量明显下降，红细胞CR1数量无明显改变，NTRR明显下降。结论：小儿肠道内双歧杆菌含量与其红细胞CR1免疫活性有相关关系。     

CD4+CD25highT细胞在小细胞肺癌患者外周血中的表达及意义

目的探讨CD4+CD25high调节(抑制)性T细胞在小细胞肺癌患者外周血中的表达情况及其意义.方法应用流式细胞技术检测40例初诊小细胞肺癌患者,18例CE及CAP方案交替化疗后完全缓解的小细胞肺癌患者外周血中的CD4+CDhighT细胞,计算它们占CD4+T细胞的比率.结果初诊小细胞肺癌患者CD4+CD25highT细胞占CD4+T细胞的比率(6.69±2.32)%,高于健康对照组(4.13±1.25)%(P＜0.01);经化疗后完全缓解的小细胞肺癌患者外周血CD4+CD25highT细胞占CD4+T细胞的比率与初诊时相比无明显变化.结论小细胞肺癌患者外周血中CD4+CD25high调节T细胞占CD4+T细胞的比率增高,它们对小细胞肺癌患者具有免疫抑制作用.     

银苓Ⅰ号对铅中毒小鼠非特异免疫功能的影响

目的:探讨中药复方银苓Ⅰ号对铅中毒小鼠非特异免疫功能的影响。方法:小鼠自由饮用醋酸铅溶液造模,分别予银苓Ⅰ号或依地酸钠钙治疗3周;观察外周血弊细胞计数、碳粒廓清指数K及校正指数α、免疫脏器指数等非特异性免疫功能指标的变化。结果:银苓Ⅰ号对外周血白细胞计数、碳粒廓清指数K及校正指数α、免疫脏器指数有明显改善作用,而且碳粒廓清能力优于依地酸钠钙。结论:银苓号可在一定程度上对抗铅中毒所致的非特异免疫损害,效果优于依地酸钠钙。     

P-糖蛋白的免疫斑点定量分析

目的：建立改良的斑点酶联免疫吸附分析，用于膜表达抗原P—gP的血清学鉴定。方法：常规筛选mdr-1稳定表达的K562细胞系；免疫组化和阿霉索抗性鉴定。细胞固相化于圆形硝纤膜纸片，BSA和H2O2封闭。纸片置入ELISA测量井；按照ABC—ELISA程序测定mdr-1基因疫苗免疫小鼠血清抗P—gP的滴度。结果：免疫组化显示稳定表达mdr-1的K562细胞系膜P—gP阳性率近100％，阿霉素IC50较之对照细胞提高100％。斑点酶联免疫吸附分析中，全部对照血清OD450〈0．1（1：2000）；而mdr-1基因疫苗免疫的血清（1：2000）OD450均〉0．496；平行样的变异系数微小。结论：改良的免疫斑点方法可作为测量细胞表达抗原之快速、敏感的测量方法，用于特异性抗体的大样本筛选。     

Region-Specific Expression of Immunoregulatory Proteins on Microglia in the Healthy CNS

与中枢神经系统的空间结构高度一致,大部分的中枢神经系统疾病表现为区域性分布。虽然小胶质细胞已被公认在各种中枢神经系统疾病中发挥重要的作用,但是小胶质细胞是否表现为区域特异性目前还不清楚。因此,本研究目的是评估在健康成年小鼠的中枢神经系统的不同区域中小胶质细胞的不同表型。运用体外流式细胞仪分析CD11b,CD40,CD45,CD80,CD86,F4/80,TREM-2b,MHCII,CXCR3,CCR9以及CCR7的表面表达。这些免疫调节标记物大部分均存在于小胶质细胞上并且在表达水平上有明显的区域特异性差异。这些发现在很大程度上证实了在健康成年小鼠中枢神经系统的小胶质细胞中存在着免疫多样性。     

Factors influencing late allograft valve failure

Allograft valves are a valuable valve replacement substitute in the surgical management of heart valve disease. It remains the valve substitute of choice in the reconstruction of the right ventricular outflow tract in children with congenital heart disease and in the Ross procedure. However, its durability remains suboptimal, particularly in children. This article reviews the mechanisms and factors implicated in late allograft dysfunction, with a focus on the evidence for an immunological cause for allograft failure. Unravelling the mechanisms of allograft valve failure may allow modification of the allograft to improve its long‐term durability.     

Correlation of neuron specific enolase serum concentration and prognosis hi patients with severe head injury

AIM: To eluciate the role of neuron specific enolase(NSE) in predicting prognosis after severe head injury. METHODS: 30 patients with severe head injury were involved into this study, ranging from 26 to 64 years old. Concentration of NSE in serum was measured in all cases within 12 hours after head injury. And prognosis of all patients were evaluated by COS. RESULTS: The concentration of NSE in serum of both groups, with good or poor outcome, were higher than normal group. The concentrations within 12 hours after head injuries had a close relationship with the prognosis. As a serum marker to assess the prognosis, NSE had high positive prediction ratio. CONCLUSION: The finding suggested that NSE may be a promising predictor for assessing the prognosis after severe head injury.