Gene discovery for oral ulceration: a UK Biobank Study

Background

Oral ulceration is a common, painful condition of uncertain aetiology. Ulcers are characterised by immune-mediated mucosal destruction, inflammation, and a proliferative healing phase. Oral ulceration is heritable but the genetic basis remains poorly characterised. We aimed to identify genetic risk factors for oral ulcers, and find evidence for a common genetic basis or causal association between oral ulceration and autoimmune traits.

激光损伤后不同时间点鼠视网膜中水通道蛋白-1的表达

目的：采用免疫组化、荧光定量PCR法观察激光损伤后不同时间鼠视网膜中水通道蛋白?1（ aquaporin?1,AQP?1）的分布及其mRNA表达的变化。方法 Brown Norway（ BN）大鼠激光损伤视网膜后,脊椎脱臼法处死,摘除眼球,4％福尔马林固定,石蜡包埋。平行视神经矢状连续切片,HE染色、免疫组化染色和阴性对照。用已知有AQP?1表达的正常大鼠眼球眶周组织中的血管切片为阳性对照。另取出大鼠眼视网膜组织,行实时定量PCR检测。结果免疫组化切片显示,褐色粗颗粒出现在大鼠眼组织细胞中为阳性,无则为阴性。实时荧光定量PCR结果显示,正常组AQP?1 mRNA表达量为：（1．15±0．01）,激光损伤即刻：（1．10±0．01）;12 h：（1．10±0．03）;24 h：（1．16±0．01）;72 h：（1．13±0．01）。结论 AQP?1在眼内阳性表达于多个与水代谢有关的部位,视网膜上AQP?1 mRNA的表达在激光损伤后呈现动态变化,激光损伤初期呈上调,损伤后期呈下调表达。     

Non specific increased expression of class I major histocompatibility complex (MHC) antigens on rat liver grafts

Major histocompatibility complex (MHC) antigens play a major role in the rejection reaction and their increased expression may increase the host response to the foreign graft [1]. Several clinical [2–5] and experimental studies [6, 7] have demonstrated increased expression of MHC antigens on the different cell components of liver allografts during rejection. However modified expression of MHC antigens may also occur in certain liver diseases [8–10], after cholestasis [11] or on a regenerating liver [11]. In this experimental study in inbred rats, we compared the expression of MHC antigens on liver cells during rejection and non-immunological situations (cholestasis, cytolysis, regeneration).     

BN3C抗麻醉大鼠缺血性心律失常的作用

用结扎冠脉的方法造成大鼠缺血性心律失常，以观察ＢＮ３Ｃ对该模型的影响，结果表明，ＢＮ３Ｃｉｖ５μｇ／ｋｇ和１０μｇ／ｋｇ均可延心律失出现时间，降低室性期外收缩数目和室颤的发生率，并呈剂量依赖性，硝苯吡啶ｉｖ３０μｇ／ｋｇ与ＢＮ３Ｃｉｖ１０μｇ／ｋｇ的作用相似，提示ＢＮ３Ｃ对结扎冠脉所导致的大鼠缺血性心律失常有明显抑制作用，且强于硝苯吡啶。     

Single and combined effects of the vitamin D analogue KH1060 and cyclosporin A on mercuric-chloride-induced autoimmune disease in the BN rat.

Mercuric chloride induces in BN rats a self-limiting systemic autoimmune disease characterized by proliferation of autoreactive CD4+ T lymphocytes, polyclonal activation of B lymphocytes, and the development of an anti-glomerular basement membrane (GBM) nephritis with concomitant nephrotic range proteinuria. We have used this model of autoimmune disease to test the immunosuppressive ability of a novel vitamin D3 analogue KH1060. This compound prevents autoimmune manifestations including proteinuria, serum IgE, and serum anti-laminin antibodies in a dose-dependent manner, as does cyclosporin A (CyA). When dosages of KH1060 capable of partial reduction of proteinuria without causing significant hypercalcaemia are combined with small dosages of CyA also capable of partial prevention of proteinuria, an additive effect is seen, leading to complete prevention of proteinuria and substantial reductions in serum IgE and anti-laminin levels. Possible mechanisms of action are discussed and it is suggested that KH1060 could prove useful as an immunosuppressive agent in the treatment of autoimmune diseases.     

Study of plasma effects during hypoxia and hemorrhagic shock on polymorphonuclear neutrophil－vascular endothelial cellinterac

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PAF拮抗剂抑制环孢素A诱导的肾系膜细胞收缩作用的研究

本文采用SD大鼠肾脏系膜细胞培养及硅胶膜形态分析技术。研究环孢素A(CsA)诱导肾系膜细胞收缩作用及血小板活化因子拮抗剂BN52021对CsA诱导作用的抑制效应。结果示CsA引起系膜细胞收缩呈现时间和剂量依赖效应,其作用可逆。BN52021浓度为5×10~(-5)M时,可显著地抑制CsA的诱导作用。结果提示CsA通过可逆性诱导系膜细胞收缩引起肾小球毛细血管血流量和超滤系数(Kf)下降;血小板活化因子可能参与了这个过程,使用血小板活化因子拮抗剂可能有预防及治疗CsA肾毒性的作用。     

Resistance to BN myelogenous leukemia in rat radiation chimeras

Lewis → LBNF1 rat radiation chimeras showed marked resistance to transplanted BN myelogenous leukemia when compared to naive LBNF1, LBNF1 → LBNF1, or BN → LBNF1. This occurred in the absence of overt graft versus host disease or of anti-BN response in mixed lymphocyte culture. Bone marrow specific antigens may serve as the target of the resistance mechanism.     

Association of Endothelin with Lung Hemorrhage Induced by Immune Complexes in Rats

The participation of endothelins (ETs) in a model of neutrophil-dependent lung injury induced by intrabronchial instillation of rabbit antibodies to ovalbumin followed by i.v. injection of the antigens (Arthus reaction) was investigated. Hemorrhagic lesions were evaluated by measuring the extravasations of hemoglobin in lung parenchyma. From 5 min to 24 h after the Arthus reaction (AR), endothelin (ir-ET) levels in bronchoalveolar lavage fluid (BALF) and in plasma were measured by radioimmunoassay. BALF levels of ir-ET were not different between control and AR animals for the first 90 min after the antigen challenge but increased from 2 to 24 h after induction of AR. ET levels in the plasma did not change from the respective controls over the same 24 h period. Increased ir-ET in BALF was not affected by pretreatment with L-NAME (30 mg/kg, i.v.). A PAF antagonist (BN52021; 5 and 10 mg/kg, i.v.) increased ET content in BALF and decreased the intensity of the AR. Thiorphan (2 mg/kg, i.v.) inhibited the AR-induced hemorrhagic lesions in lungs. An ET_A receptor antagonist, BQ-123 (1 mg/kg, i.v.) potentiated, whereas the ET_B antagonist, BQ-788 (1 mg/kg, i.v.) inhibited the lung hemorrhage. It is concluded that ETs are released during and play a role in the lung AR.     

In vivo treatment with a monoclonal antibody to T helper cells in experimental autoimmune glomerulonephritis in the BN rat.

Experimental autoimmune glomerulonephritis (EAG) was induced in brown Norway (BN) rats by a single i.m. injection of homologous glomerular basement membrane (GBM) in Freund's complete adjuvant. This model of anti-GBM disease is characterized by the development, over several weeks, of circulating and deposited anti-GBM antibodies, accompanied by albuminuria. We examined the effects of treatment with MoAb W3/25 (anti-CD4) at different doses, starting at the time of immunization and continued for the duration of the study or for a limited period only. Continued treatment with W3/25, at a dose of 5 or 10 mg/kg intraperitoneally three times per week for 4 weeks, produced a marked reduction in circulating anti-GBM antibodies, absence of detectable deposited antibody and virtual absence of albuminuria. When W3/25 treatment, at 5 or 10 mg/kg, was stopped after 2 weeks, there was still a significant reduction in anti-GBM antibodies and albuminuria at 4 weeks. A similar effect on the disease was achieved when W3/25 was administered only three times during the first week at a dose of 30 mg/kg. Animals injected with W3/25 at a dose of 10 mg/kg through the course of disease showed < 10% W3/25+ cells by FACS analysis of splenic lymphocytes at week 4, while controls and animals treated for shorter periods showed > 30% W3/25+ cells. These results demonstrate that W3/25 can prevent the development of EAG, and that this effect is not dependent on persistent depletion of T cells. Further work is necessary to determine whether anti-T cell therapy is effective in established EAG, and may be worth investigating in human anti-GBM disease.