肿瘤病人红细胞免疫功能与自然杀伤细胞活性的关系

①目的　探讨恶性肿瘤病人红细胞免疫功能与自然杀伤 (NK)细胞活性的关系。②方法　选择原发性肺癌、卵巢癌及白血病病人各 2 0例为研究对象 ,以 2 0名健康人为正常对照 ,采用免疫黏附法测定红细胞黏附肿瘤细胞的能力 ,采用MTT法测定NK细胞活性。③结果　恶性肿瘤病人红细胞黏附肿瘤细胞的能力和NK细胞活性明显低于正常对照组 (F =9.2 9、12 .85 ,q =5 .15～ 7.86 ,P <0 .0 1) ;正常人红细胞胞质液可以显著提高自身及病人NK细胞活性 (F =4 .32～ 5 .89,q =3.96～ 4 .4 9,P <0 .0 5、0 .0 1)。④结论　红细胞免疫功能与NK细胞活性密切相关。     

Cyclin D1在胶质瘤细胞系中表达分布模式的初步研究

目的：探讨cyclin D1在胶质瘤细胞系中的细胞周期表达模式，将为从生物学功能上阐明cyclin D1在胶质瘤细胞周期演进中的作用．方法：利用流式细胞仪双参数法和细胞同步化，确定cyclin D1在胶质瘤细胞系SHG-44和BT-325中的细胞周期表达分布模式．结果：在胶质瘤细胞系SHG-44和BT-325中，Cyclin Dl的表达呈细胞周期依赖性：在SHG-44中，cyclin D1在G1期表达最高，4h左右达到峰值，S期及G2／M期下降，但仍可检测到；在BT-325中，cyclin D1在G1期表达最高，6h左右达到峰值，S期及G2／M期下降，但仍可检测到．结论：cyclin D1蛋白质的表达呈细胞周期依赖性，且与细胞周期行进有关；cyclin D1在SHG-44和BT-325胶质瘤细胞进入G1期的早期发挥着重要的生物学作用。     

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目的 对供者肝脏等器官的联合获取、修整和保存方法进行研究。方法 采用原位腹主动脉和门静脉插管、低温灌注，快速多器官联合获取、低温保存技术及体外修整获得可供移植的肝移植物。结果 获取122例供者的移植物，平均热缺血时间为4min30s，平均获取时间为20min，平均冷缺血时间为10h。均采用4℃的HCA液(高渗枸橼酸盐腺嘌呤溶液)和UW液灌注和保存。118例修整成适用于临床用的肝的移植物，76例供肝在移植前留取了病理活检标本，病理检查提示供肝结构正常。移植术后，无原发性肝无功能发生。结论 该方法适合于供者肝脏等器官的快速联合获取、修整和保存。     

P-glycoprotein (P-gp) function in T cells: implications for organ transplantation

P-glycoprotein (P-gp), a member of the adenosine triphosphate (ATP)-binding cassette (ABC) family of transporter molecules, is responsible for maintaining low intracellular concentrations of a variety of extracellular compounds and xenobiotics, and for transport of various intracellular molecules. Many drugs are P-gp substrates and intracellular concentrations of these agents may be critical for drug action. Experience in oncology indicates that repeated exposure to P-gp substrate cytotoxic drugs leads to the selection of drug-resistant tumor cells that overexpress P-gp. Since immunosuppressive agents such as cyclosporine, tacrolimus, sirolimus and corticosteroids are substrates for P-gp and since T-cells also express P-gp, it is conceivable that an analogous mechanism exits for therapy-resistant graft rejection. As will be discussed in this article, P-gp may interfere with the response to immunosuppressive therapy through several distinct mechanisms, and as such may represent an attractive therapeutic target.     

Role of Natural Killer Cell Subsets in Cardiac Allograft Rejection

To achieve donor-specific immune tolerance to allogeneic organ transplants, it is imperative to understand the cell types involved in acute allograft rejection. In wild-type mice, CD4(+) T cells are necessary and sufficient for acute rejection of cardiac allografts. However, when T-cell responses are suboptimal, such as in mice treated with costimulation-targeting agents or in CD28-deficient mice, and perhaps in transplanted patients taking immunosuppressive drugs, the participation of other lymphocytes such as CD8(+) T cells and NK1.1(+) cells becomes apparent. We found that host NK but not NKT cells were required for cardiac rejection. Ly49G2(+) NK cells suppressed rejection, whereas a subset of NK cells lacking inhibitory Ly49 receptors for donor MHC class I molecules was sufficient to promote rejection. Notably, rejection was independent of the activating receptors Ly49D and NKG2D. Finally, our experiments supported a mechanism by which NK cells promote expansion and effector function of alloreactive T cells. Thus, therapies aimed at specific subsets of NK cells may facilitate transplantation tolerance in settings of impaired T-cell function.     

Transplant Tolerance in Non-Human Primates: Progress, Current Challenges and Unmet Needs

Given the significant morbidity associated with current post-transplant immunosuppressive regimens, induction of immune tolerance continues to be an important goal of clinical organ transplantation. While many strategies for inducing tolerance have been successfully applied in murine models, significant barriers are faced when translating these approaches to the clinic. This has necessitated pre-clinical studies in the more closely related model system, the non-human primates (NHP). In this review, we will discuss the four most prominent strategies for inducing transplantation tolerance and highlight their relative success and shortcomings in NHP. These strategies are: (1) T-cell costimulation blockade (2) mixed chimerism induction (3) T-cell depletion and (4) tolerance induction through regulatory T-cells. After discussing the progress that has been made with each of these strategies, we will identify this field's most pressing unmet needs and discuss how we may best overcome the resulting barriers to tolerance induction.     

不同免疫抑制剂对肾移植患者精子参数的影响

目的:研究不同免疫抑制剂对肾移植患者精子运动功能的影响。方法:20例肾移植患者应用以普乐可复(FK506+霉酚酸酯+泼尼松)、17例应用环孢素(CsA+硫唑嘌呤+泼尼松)为主的免疫抑制治疗方案,15例正常男性为对照组。采用计算机辅助的精子分析系统分别检测精子活率、运动参数(前向运动百分率、直线速度VSL、曲线速度VCL、平均路径速度VAP)和精子形态。结果:3组精子活率[(81.7±5.7)%、(79.4±6.8)%、(83.8±6.0)%]、VCL[(24.1±8.6)%、(23.9±4.4)%、(24.8±4.2)%]和VAP[(19.7±6.6)%、(18.6±2.9)%、(21.0±4.0)%]差异均无显著性(P>0.05);FK506组的精子前向性运动百分率[(46.4±8.1)%]和VSL[(15.4±4.6)%]均显著高于CsA组[(33.3±6.4)%、(10.2±2.4)%],畸形率[(67.8±5.7)%]显著低于CsA组[(80.1±5.6%](P<0.05)。结论:FK506和霉酚酸酯的联合应用,有助于肾移植患者精子运动功能及形态的恢复。     

A Synergistic Effect Between PG490-88 and Tacrolimus Prolongs Renal Allograft Survival in Monkeys

This study was undertaken to determine if PG490-88 and tacrolimus (Tac) act synergistically to prevent renal allograft rejection in monkeys and to explore possible mechanisms of synergy between these agents. MHC-mismatched renal allografts were transplanted into cynomolgus monkeys after bilateral nephrectomy. Recipients were divided into the following groups: (i) no treatment; (ii) PG490-88 (0.03 mg/kg); (iii) Tac (1 mg/kg); (iv) PG490-88 (0.01 mg/kg) + Tac (1 mg/kg) and (v) PG490-88 (0.03 mg/kg) + Tac (1 mg/kg). Through synergy PG490-88 and Tac inhibited anti-CD3/PMA-induced T-cell proliferation and IFN-gamma expression in vitro. Tac monotherapy only marginally prolonged survival (27 +/- 3.2 days), while the combination of PG490-88 and Tac significantly prolonged graft survival to a median of 99 days (PG490-88 at 0.03 mg) and 38.5 days (PG490-88 at 0.01 mg/kg). Prolonged survival correlated with inhibited IgM production as well as reduced T-cell infiltration, IL-2 protein expression and NF-AT/NF-kappaB activity. We conclude that PG490-88 and a subtherapeutic dose of Tac significantly prolong renal allograft survival in monkeys through the synergistic inhibition of T-cell activation and a decrease in IFN-gamma production and NF-AT/NF-kappaB activity.     

Kidney Transplantation Substantially Improves Endothelial Progenitor Cell Dysfunction in Patients with End-Stage Renal Disease

Endothelial progenitor cells (EPC) are involved in endothelial repair and maintenance. Dysfunction of EPC may contribute to accelerated arteriosclerosis in chronic kidney disease. Kidney transplantation (KTx) improves both survival and endothelial function of dialysis patients. In a prospective study, we tested to which extent KTx changes EPC biology. We studied number and function (migratory activity, adhesion to extracellular matrix proteins and to mature endothelial cells [EC]) of EPC in 20 patients during dialysis and 3, 6, 9 and 12 months after KTx. Twenty-two healthy volunteers served as matched controls. Circulating precursor populations were measured by flow cytometric analysis. Cytokines relevant for EPC mobilization were monitored. Compared to the dialysis state, KTx increased the migration of EPC to approximately 2-fold. Adhesion to fibronectin and to collagen type IV was significantly increased after KTx. An improved adhesion rate of EPC to mature EC was observed. The number of EPC decreased. The amount of precursor populations showed no difference compared to the pretransplant state. Our study shows an improved function of EPC after KTx. This finding indicates an improved potential for endothelial repair which in turn may contribute to enhanced endothelial function and reduced cardiovascular morbidity after KTx.     

Monitoring motor function during resection of tumours in the lower brain stem and fourth ventricle

Objectives Even in the days of modern microsurgery, the removal of a brain stem lesion remains a surgical challenge. Especially when operating on children, the prognosis is directly related to the radicality of the resection; however, a radical resection is often associated with surgical morbidity. Intraoperative neuromonitoring could help to minimise the surgical morbidity, but few studies have been performed to clarify the value of this monitoring. We investigated a prospective series of 21 patients with lesions involving the brain stem for the prognostic value and benefits of neuromonitoring.Methods We performed intraoperative neuromonitoring of cranial nerve function by electromyography (EMG) and motor evoked potential (MEP). The results were correlated with postoperative neurological deficits.Conclusions There is a good correlation between intraoperative neurophysiological events and postoperative neurological deficits in patients with lesions of the brain stem. In general, transient, prolonged, spontaneous activity in EMG is associated with a transient paresis of the respective muscle, whereas a permanent spontaneous activity is associated with a permanent deficit. Intraoperative neuromonitoring reliably predicts postoperative neurological function in patients with tumours of the lower brain stem and fourth ventricle. This neuromonitoring guides the neurosurgeon in the operation and may decrease surgical morbidity. We recommend using monitoring of MEP and EMG of the lower cranial nerves in surgery on all patients with lesions involving the lower brain stem and fourth ventricle.