Implication of Human Endogenous Retrovirus Envelope Proteins in Placental Functions

Human endogenous retroviruses (ERVs) represent 8% of the total human genome. Although the majority of these ancient proviral sequences have only retained non-coding long terminal repeats (LTRs), a number of “endogenized” retroviral genes encode functional proteins. Previous studies have underlined the implication of these ERV-derived proteins in the development and the function of the placenta. In this review, we summarize recent findings showing that two ERV genes, termed Syncytin-1 and Syncytin-2, which encode former envelope (Env) proteins, trigger fusion events between villous cytotrophoblasts and the peripheral multinucleated syncytiotrophoblast layer. Such fusion events maintain the stability of this latter cell structure, which plays an important role in fetal development by the active secretion of various soluble factors, gas exchange and regulation of fetomaternal immunotolerance. We also highlight new studies showing that these ERV proteins, in addition to their localization at the cell surface of cytotrophoblasts, are also incorporated on the surface of various extracellular microvesicles, including exosomes. Such exosome-associated proteins could be involved in the various functions attributed to these vesicles and could provide a form of tropism. Additionally, through their immunosuppressive domains, these ERV proteins could also contribute to fetomaternal immunotolerance in a local and more distal manner. These various aspects of the implication of Syncytin-1 and -2 in placental function are also addressed in the context of the placenta-related disorder, preeclampsia.     

Current status and perspectives in clinical islet transplantation

Beta-cell replacement, by either pancreas or islet transplantation, is the only treatment to achieve an insulin-independent, constantly normoglycemic state avoiding hypoglycemic episodes in patients with type-1 diabetes mellitus. This article reviews the current state of the worldwide experience based on data provided by the International Islet Transplant Registry; it also illustrates the perspectives of clinical islet transplantation.     

吲哚胺-2,3-双加氧酶在非小细胞肺癌中的表达

目的 探讨吲哚胺-2,3-双加氧酶(indoleamine-2,3-dioxygenase,IDO)在非小细胞肺癌中的表达及意义.方法 收集38例非小细胞肺癌组织和10例癌旁正常肺组织.用半定量免疫组织化学方法 检测肺组织中IDO蛋白阳性率,实时荧光定量PCR检测肺组织中IDO mRNA表达水平.结果肺癌组IDO蛋白阳性率和IDO mRNA表达水平均明显高于对照组,差异均具有统计学意义(均P＜0.05);而肺癌组按不同病理分型中,腺癌组和鳞癌组比较差异无统计学意义(P＞0.05).肺癌组按不同分化程度分为高、中、低3组,经统计学分析,3组中IDO阳性表达率和IDO mRNA表达水平差异均有统计学意义(均P＜0.05).肺癌组按有和无淋巴结转移分组比较,IDO蛋白阳性率和IDO mRNA表达水平差异也均有统计学意义(均P＜0.05).结论 IDO在非小细胞肺癌中呈高表达,与分化程度及有无淋巴结转移有关,但与肺癌病理分型无关.     

中西医治疗慢性乙型肝炎免疫耐受研究进展

慢性乙型肝炎在我国是一种常见病、多发病。感染乙肝病毒后,机体的免疫系统不能及时、有效、彻底地清除病毒导致乙型肝炎的免疫耐受,是慢性乙型肝炎迁延不愈、肝慢性损伤的一个主要机制。因而打破HBV感染后的免疫耐受状态,调整紊乱的免疫系统将是治疗慢性乙型肝炎的关键所在。文章主要对近年来中西医治疗慢性乙型肝炎免疫耐受方面的临床研究及实验研究进行综述,并对其研究现状简要分析。     

Haemophilia A: effects of inhibitory antibodies on factor VIII functional interactions and approaches to prevent their action

Factor VIII (FVIII) is an essential component of the intrinsic pathway of blood coagulation. Normal functioning of FVIII requires its interactions with other components of the coagulation cascade. In the circulation, it exists as a complex with von Willebrand factor (vWF). Upon activation by thrombin or activated factor X (FXa), activated FVIII (FVIIIa) functions as a cofactor for the serine protease factor IXa. Their complex assembled on the phospholipid surface activates FX to FXa, which consequently participates in formation of thrombin, the key protease of the coagulation cascade. Genetic deficiency in FVIII results in a coagulation disorder haemophilia A, which is treated by infusions of FVIII products. Approximately 25-30% of patients develop antibodies inhibiting FVIII activity (FVIII inhibitors). The major epitopes of inhibitors are located within the A2, C2 and A3 domains of the FVIII molecule. The inhibitory effects of antibodies are manifested at various stages of the FVIII functional pathway, including FVIII binding to vWF, activation of FVIII by thrombin, and FVIIIa incorporation into the Xase complex. We summarize the current knowledge of the FVIII sites involved in interaction with its physiological ligands and different classes of inhibitory antibodies and describe their inhibitory mechanisms. We outline the strategies aimed to overcome the effects of inhibitory antibodies such as development of human/porcine FVIII molecules, resistant to inhibitors. We also discuss approaches to modulate the antibody response, as well as efforts to develop a long-term immunotolerance to FVIII protein.     

A Cross‐Talk of Decidual Stromal Cells,Trophoblast, and Immune Cells: A Prerequisite for the Success of Pregnancy

Embryo implantation and formation of a functional placenta are complex processes that require a plethora of regulatory mechanisms involving both mother and embryo cells. Recently, an important role in this complicated cells and factors network was assigned to the decidual stromal cells (DSC) and trophoblast cells. Decidualization includes biochemical changes that trigger DSC to produce a number of factors required for the implantation and induction of immunotolerance in maternal immune system. Immunotolerance is achieved by a cascade of strictly controlled events starting with selective homing of immune cells to the feto‐maternal site, regulated proliferation, and predominant differentiation into a regulatory type of immune cells. Furthermore, cytotoxic effector functions are reduced owing to the influence of steroid hormones, factors, cytokines, and inhibitory receptors. Altogether the entire immune system of the mother is switched to tolerogenic functional state which is a prerequisite for the successful maintenance of pregnancy.     

DNA single strand conformation polymorphism identifies five defined strains of hepatitis B virus (HBV) during an outbreak of HBV infection in an oncology unit

An outbreak of hepatitis B virus (HBV) infection in a children's oncology unit was identified in which 61 children were shown to have been infected, 59 of them asyptomatically. In order to establish whether intra-unit cross infection had occurred, we used the single strand conformational polymorphism (SSCP) technique to analyse viral isolates from 57 of the infected children and 40 unrelated controls. HBV-specific primers were designed to amplify a 189 bp fragment of DNA encompassing part of the hypervariable pre-S1 region of the HBV genome. Denatured PCR products were compared after electrophoresis through polyacrylamide gels and staining with silver. By SSCP analysis, the unrelated infections each yielded a unique electrophoretic banding pattern, indicative of a variety of distinct virus strains. In contrast, most of the oncology patients had been infected with one of only five different strains. Three major groups comprising 19, 16, and 9 patients, respectively, and two minor groups of 5 and 3 patients were identified. Results indicate the occurrence of multiple episodes of cross infection, and demonstrate the sensitivity and value of SSCP as a technique to establish common sources of infection. © 1996 Wiley-Liss, Inc.     

Ultraviolette Strahlung – Immunantwort

Ultraviolet (UV) radiation can exert a variety of biological effects, including induction of skin cancer, premature skin ageing and inhibition of the immune system. The immunosuppressive properties of UV radiation are of major biological and clinical relevance since suppression of the immune system by UV radiation also contributes to the induction of skin cancer. Hence, understanding of the mechanisms by which UV radiation compromises the immune system is of primary importance. UV radiation suppresses the immune system in multiple ways. It inhibits antigen presentation, stimulates the release of immunosuppressive cytokines and induces the generation of lymphocytes of the regulatory subtype. The major molecular target for UV‐induced immunosuppression is UV‐induced DNA damage. Further elucidation of the mechanisms underlying UV‐induced immunosuppression will not only lead to a better understanding of the physiologic and pathologic effects of UV radiation but also contribute to the development of new protective strategies.