EBV+ B Lymphoma Cell Lines from Patients with Post-Transplant Lymphoproliferative Disease Are Resistant to TRAIL-Induced Apoptosis

Lymphomas associated with post-transplant lymphoproliferative disease (PTLD) represent a significant complication of immunosuppression in transplant recipients. In immunocompetent individuals, EBV-specific cytotoxic T lymphocytes (CTL) prevent the outgrowth of activated B lymphoblasts through apoptosis induction. Soluble versions of TNF-related apoptosis-inducing ligand/Apo2 ligand (TRAIL) can induce apoptosis in numerous tumor cell types. Given the therapeutic potential of TRAIL, we examined the sensitivity of EBV⁺ spontaneous lymphoblastoid cell lines (SLCL) derived from patients with PTLD to treatment with soluble TRAIL. Despite abundant expression of TRAIL receptors (TRAIL-R), resistance to TRAIL-induced apoptosis was observed in all SLCL examined. This resistance could not be overcome by concomitant treatment with several pharmacological agents. Unlike BJAB positive control cells, for each SLCL tested, cleavage and activation of caspase 8 was inhibited due to failed recruitment of FADD and caspase 8 to TRAIL receptors upon stimulation. Further indicative of a proximal defect, TRAIL receptor aggregation could not be detected on the cell surface of SLCL following ligand engagement. These results suggest that the use of TRAIL for eliminating PTLD-associated tumors may be of limited clinical utility, and illustrate another mechanism by which EBV⁺ B lymphoma cells can evade tumor surveillance at the level of death receptor signaling.     

大孔树脂富集三裂叶蟛蜞菊倍半萜内酯A和B的研究

目的 大量富集三裂叶蟛蜞菊倍半萜内酯A，B(WTA，WTB)。方法 采用气相色谱法测定WTA和WTB，并以WTA和WTB的含量、洗脱率、精制度为考察指标，研究D101大孔树脂吸附WTA和WTB的工艺条件及参数。结果 通过大孔树脂吸附后，WTA和WTB的洗脱率达90％，50％乙醇洗脱部分中WTA和WTB的含量为总固物的4．01％～4．09％。结论 可以采用大孔树脂富集WTA和WTB。     

江门市区实施乙型肝炎免疫策略16年的效果评价

目的：对江门市区1986年1月1日起全面实施的乙型肝炎(乙肝)免疫策略进行效果评价。方法：运用血清流行病学调查和疫情资料对比分析，比较实施“免疫策略”前后江门市区0～15岁人群乙肝发病率和感染率变化情况和乙肝表面抗体(抗-HBs)增长情况。结果：实施“免疫策略”后16年，0～15人群的乙肝发病率由1985年的367．39／10万，降至2001年的21．10／10万，下降94．26％；HBsAg阳性率由1985年的9．17％降至2002年的0．6％，下降93．46％；乙肝病毒总感染率由1985年的35．82％降至2002年的1．20％，下降96．65％；抗-HBs阳性率由1985年的24．64％上升到2002年的93．00％，上升2．77倍。结论：江门市区现行乙肝免疫策略效果显，能有效预防和控制地区性大面积的乙肝流行与传播。经过一代人的努力，能彻底改变人口乙肝高发病率和HBV高感染率及高携带率的状况。     

Ethyl-EPA in Huntington disease—Potentially relevant mechanism of action

The pathomechanisms involved in the neuronal dysfunction in Huntington disease (HD) are still unresolved and may be heterogeneous. One potential mechanism might be related to the induction of mitochondrial dysfunction in the CNS. This might lead firstly to neuronal dysfunction and finally to the activation of apoptotic pathways. Several compounds, which should alleviate mitochondrial dysfunction, have been tested in preclinical models as well as in clinical trials of different scale. Recently we reported the efficacy of Ethyl-eicosapentaenoic acid (Ethyl-EPA) in patients with HD. Ethyl-EPA is a polyunsaturated fatty acid from the n − 3 group, which is in clinical development for HD and melancholic depression. In our trial with Ethyl-EPA in HD responding patients could be characterized by either a lower CAG repeat number or a chorea-predominant clinical expression of the disease. Here we would like to describe some evidence on the potential mechanism of action of Ethyl-EPA in HD. We specifically focus on pathways, which are known to be influenced in HD and are modified by Ethyl-EPA and which points to an involvement of mitochondrial function as a common target. Some attention is given to the NF-kappa B pathway and the c-Jun amino-terminal kinases (JNK) pathway, which both may lead to an activation of the antiproliferative factor p53 and consequently mitochondrial dysfunction. Further the effects of EPA or Ethyl-EPA in preclinical models of HD are described. The evidence from these studies led to the design of phase III clinical trials, which are ongoing.     

IL-2和IL-4联合诱导B细胞死亡受体CCR3的表达及其功能研究

目的　研究在IL 2和IL 4作用下 ,趋化性细胞因子受体CCR3在人生发中心 (germinalcenter,GC)B细胞上的表达及其功能特性。方法　采用流式细胞术检测人GCB细胞上CCR3表达和在CCR3配体eotaxin作用下B细胞的凋亡 ,实时定量RT PCR和Northernblot法检测GCB细胞内CCR3mRNA的表达 ,淋巴细胞趋化和黏附试验检测B细胞的趋化和黏附能力。结果　人GCB细胞极低表达趋化性细胞因子受体CCR3,经IL 2和IL 4作用后 ,GCB细胞高表达CCR3,但此时CCR3不能在其配体作用下诱导GCB细胞的趋化和黏附功能 ,而是诱导GCB细胞凋亡。结论　IL 2和IL 4联合诱导人GCB细胞CCR3表达 ,CCR3可能具有死亡受体的功能。     

核转录因子κB与前列腺癌

核转录因子κB(nuclearfactorofkappaB ,NF κB)是一种多极性核转录因子 ,参与调控多种与免疫反应、凋亡、炎症、肿瘤形成和转移有关的基因表达。近年来 ,NF κB在肿瘤发生、耐药、转移中的作用及其机制逐渐成为医学研究的热点。本文主要综述了NF κB的结构、生物学功能及其抗凋亡诱发肿瘤的机制 ,NF κB调控的前列腺癌相关基因的表达和调控 ,NF κB参与前列腺癌浸润与转移的机制及其在前列腺癌基因治疗中的可能策略等。     

Parallel image reconstruction using B-spline approximation (PROBER).

A new reconstruction method for parallel MRI called PROBER is proposed. The method PROBER works in an image domain similar to methods based on Sensitivity Encoding (SENSE). However, unlike SENSE, which first estimates the spatial sensitivity maps, PROBER approximates the reconstruction coefficients directly by B-splines. Also, B-spline coefficients are estimated at once in order to minimize the reconstruction error instead of estimating the reconstruction in each pixel independently (as in SENSE). This makes the method robust to noise in reference images. No presmoothing of reference images is necessary. The number of estimated parameters is reduced, which speeds up the estimation process. PROBER was tested on simulated, phantom, and in vivo data. The results are compared with commercial implementations of the algorithms SENSE and GRAPPA (Generalized Autocalibrating Partially Parallel Acquisitions) in terms of elapsed time and reconstruction quality. The experiments showed that PROBER is faster than GRAPPA and SENSE for images wider than 150x150 pixels for comparable reconstruction quality. With more basis functions, PROBER outperforms both SENSE and GRAPPA in reconstruction quality at the cost of slightly increased computational time.     

Chronic delta hepatitis in haemophiliacs

The seroepidemiological profile of HBV and HDV was investigated in 640 male haemophiliacs. Twenty-seven of forty-four HBsAg carriers were anti-HDV-IgG positive, 22 were also anti-HDV-IgM positive. A markedly lower prevalence of HDV infection was found in patients with anti-HBc in the absence of HBsAg and anti-HBs (6/41). Repeated detection of anti-HDV-IgM in 5/41 individuals of this group indicates that circulating HBsAg is not an absolute prerequisite for chronic HDV infection. Overall, chronically active HDV infection was detected more frequently in quiescent than in active chronic HBV infections. Anti-HDV-IgM was not detected in the absence of anti-HDV-IgG antibodies. Anti-HDV-IgG may disappear after resolution of HDV infection, as indicated by the low prevalence (1/42) in such individuals with past HBV infection as well as by loss of anti-HDV-IgG observed in two patients.     

Treatment of hepatitis B and C after liver transplantation. Part 1, hepatitis B

Abstract The outcome of OLT for HBV-related liver disease is dependent on the prevention of allograft re-infection. Over the past decade, major advances have been made in the management of HBV transplant candidates. The advent of long-term hepatitis B immune globulin (HBIG) administration as a prophylaxis against HBV recurrence, and the introduction of new antiviral agents against HBV infection, such as lamivudine (LAM), were a major breakthrough in the management of these patients. Results of OLT for HBV infection are similar to those achieved with other indications. Pre-OLT antiviral treatment such as LAM can suppress HBV replication before OLT and thus decrease the risk of re-infection of the graft. Combination prophylaxis with LAM and HBIG after transplantation highly effectively reduces the rate of HBV re-infection, even in HBV replicative cirrhotic, patients. The optimal HBIG protocol in the LAM era is yet to be defined: dosing of HBIG, routes of administration, and possibility of stopping HBIG. Several antiviral drugs have been developed for the management of HBV infection on the graft, so outcome is currently good.     

血清乙型肝炎病毒标志物不同表现模式及肝功能异常对肾移植受者存活率的影响

目的　探讨血清乙型肝炎病毒标志物不同表现模式对肾移植受者长期存活的影响。方法　对 62例血清乙型肝炎病毒标志物阳性者及 1 96例血清乙型肝炎病毒标志物全阴性者肾移植术后的肝功能、人肾均存活的存活率等指标进行随访和回顾性分析。结果　术后早期血清乙型肝炎病毒标志物阳性组与血清乙型肝炎病毒标志物阴性组比较 ,肝功能异常发生率的差异无显著性 (P >0 .0 5) ;术后中远期 ,HBsAg、HBeAg及抗 HBc阳性者的肝功能受损率明显高于血清乙型肝炎病毒标志物阴性组及HBsAg、抗 HBe、抗 HBc阳性者 (P <0 .0 5) ,其人肾均存活的存活率也最低 (P <0 .0 5)。结论　对HBsAg、抗 HBe及抗 HBc阳性者进行肾移植应慎重 ,而HBsAg、HBeAg及抗 HBc阳性者则不适宜接受肾移植