一氧化氮对胎兔动脉导管胱硫醚-γ-裂解酶/硫化氢体系的影响

目的探讨H2S、NO对早产胎兔动脉导管的作用及其相互影响,进一步探索动脉导管开放与关闭的病理生理机制、意义及其影响因素,为临床上全面认识动脉导管的开放与关闭提供理论依据。方法将孕21d日本大耳白兔24只随机分成四组：空白对照组及三个处理组,处理组待孕龄23d和25d时分别腹腔注射以不同剂量的一氧化氮前体-硝普钠,待孕龄26d时解剖孕兔取胎兔,胎兔心脏取血1mL后立即解剖胎兔取动脉导管组织,进行实验。结果随着注射硝普钠浓度的增加,胎兔血浆中硫化氢含量、动脉导管组织CSEmRNA表达量均逐渐随注射剂量的增加而增加。各组间相比较,P<0.01,具有显著性差异。结论早产兔血浆中有H2S存在,早产兔动脉导管组织中存在CSEmRNA表达;给孕兔注射不同剂量硝普钠(在一定范围内)对早产兔动脉导管中H2S/CSE体系具有浓度依赖性促进作用。     

β-catenin and PPAR-γ levels in bone marrow of myeloproliferative neoplasm: an immunohistochemical and ultrastructural study

In accordance with increased proliferation in myeloproliferative neoplasm (MPN), the goal is to evaluate the immunoexpression of: β-catenin, PPAR-γ and Ki67 protein, to compare them with bone marrow ultrastructural characteristics in patients with MPN. Immunoexpression and electron microscopy of bone marrow was analyzed in 30 Ph-negative MPN patients, including per 10 patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The quantity of β-catenin immunoreactive cells was significantly higher in PV then in ET (p < 0.01) or PMF group of patients (p < 0.01) and also in ET versus PMF group of patients (p < 0.01). Erythroid lineage showed absent β-catenin staining without immunoreactivity in nucleus. In contrast, immunoreactivity for PPAR-γ was localized mostly in megakaryocytes and the highest number of PPAR-γ immunopositive cells was detected in PMF group of patients. In addition, the proliferative Ki67 index was significantly increased in the PMF and PV patients compared to patients with ET. Also, the megakaryocytes showed abnormal maturation in PMF group of patients as determined by ultrastructural analysis. These results indicated that PV dominantly expressed β-catenin and proliferation marker Ki67 in bone marrow, while PMF is linked preferentially to PPAR-γ immunopositive megakaryocytes characterized by abnormal maturation.     

BOOSTING T CELL COSTIMULATION IN CANCER: THE POSSIBILITIES SEEM ENDLESS

Effective immune strategies for eradication of human malignancies will require a thorough understanding of the interactions of cancer with the immune system. It will be crucial to understand how to optimize and sustain a T cell immune response. Recently, our understanding of the molecular interaction that occurs between an APC and a T cell during cognate interaction has increased dramatically. In this review, various costimulatory and inhibitory molecules of the B7 and TNF families will be discussed. The emphasis will be on how these costimulatory molecules impact T cell activation and on how they can be potentially used for the treatment of cancer. costimulation cancer T cell activation     

轻症和重症甲型 H1 N1流感患者免疫学特征比较分析

目的对比分析轻症和重症甲型H1 N1流感患者的细胞免疫学特征,为该病的病情监测和治疗提供科学依据。方法收集2009年7月1日至2009年12月31日于宁波市第二医院及宁海县第一医院就诊并确诊为甲型H1N1流感的204名患者作为病例组,其中轻症组52例,重症组152例,选取同时期的26名健康志愿者作为对照组;采用流式细胞仪检测各组外周血淋巴细胞亚群,采用ELISA方法检测各组血清干扰素-γ（IFN-γ）及白细胞介素-4（IL-4）水平。结果 H1N1流感患者重症组外周血淋巴细胞计数降低显著,与健康对照组及轻症组患者比较差异均有统计学意义（P＜0．01）;重症组T淋巴细胞、NK细胞、CD4＋T及CD8＋T淋巴细胞计数、百分比均较轻症组显著降低（ P＜0．01）,B淋巴细胞及CD4＋T/CD8＋T比值虽然较轻症组降低,但差异无统计学意义（P＝0．11,0．175）;轻症组和重症组血清IFN-γ水平均较健康对照组降低,但是重症组降低更为显著（与健康对照组和轻症组比较,P＜0．01）;同样,轻症组和重症组血清IL-4水平均较健康对照组降低,但各组间比较统计学差异均无显著性意义（P＞0．05）。结论甲型H1N1流感患者免疫功能的异常与病情轻重有一定关系,尤其是细胞免疫功能,监测患者的免疫功能变化,对于判断患者的病情有较好的参考价值。     

罗格列酮对急性肺损伤的保护作用

罗格列酮是过氧化物酶体增殖物激活受体-γ特异性配体之一,其调节糖、脂类代谢与稳态,促进细胞增殖、分化的作用已有详尽报道。近年来,罗格列酮在急性肺损伤中发挥的抗炎、抗氧化、保护内皮、减轻肺血管通透性、促进肺成熟以及抗纤维化的作用,日渐受到关注。     

T Cell Development in CD3-ζ Mutant Mice

Increasing evidence points to multiple pathways of T lymphocyte development. The well characterized thymus-dependent pathway gives rise to T cells bearing TCRαβ heterodimers and either CD4 or CD8αβ co-receptors. T cells of this lineage populate peripheral lymphoid compartments including lymph nodes, spleen, skin, and Peyer's patches. By comparison, factors which govern extrathymic T cell development are poorly understood. A variety of experiments have shown that intestinal intraepithelial lymphocytes (IELs) develop outside of the thymic environment, e.g., in the gut of nude, SCID, and β2m-/- mutant mice, and after transplanting bone marrow or fetal liver cells into irradiated thymectomized adult mice. This review focuses on the role of the CD3-ζ subunit in the development of both thymically and extrathymically derived T cells as determined by gene-targeting experiments in mice. Data from these and other T cell-related mutations continue to define crucial stages in thymocyte differentiation. Most interestingly, CD3-ζ mutant mice contain a unique population of intestinal IELs that develops independently of thymic selective processes and expresses a novel TCR/CD3 complex.     

IFN-γ is reciprocally involved in the concurrent development of organ-specific autoimmunity in the liver and stomach

Interferon (IFN)-γ acts as a critical proinflammatory mediator in autoimmune processes, whereas it exerts regulatory functions to limit tissue damage associated with inflammation. However, a detailed understanding of the complex roles of IFN-γ in the development of organ-specific autoimmunity is still lacking. Recently, we found that programmed cell death 1-deficient mice thymectomized 3 days after birth (NTx–PD-1^{? / ?} mice) concurrently developed autoimmune hepatitis (AIH) and autoimmune gastritis (AIG). In this study, we investigated the roles of IFN-γ in the development of AIH and AIG in this mouse model. In NTx–PD-1^{? / ?} mice, serum levels of IFN-γ were markedly elevated. Neutralization of IFN-γ prevented the development of AIG. However, the same treatment exacerbated hepatic T-cell infiltration in AIH. Because of the loss of anti-proliferative effects by IFN-γ, neutralization of IFN-γ increased T-cell proliferation in the spleen and liver, resulting in exacerbated T-cell infiltration in the liver. On the other hand, in the development of AIG, CD4⁺ T-cell migration into the gastric mucosa is essential for induction. CCL20 expression was up-regulated in the gastric mucosa, and anti-CCL20 suppressed CD4⁺ T-cell infiltration into the gastric mucosa. Importantly, anti-IFN-γ suppressed CCL20 expression and infiltration of CD4⁺ T cells in the gastric mucosa, whereas in vivo injection of recombinant IFN-γ up-regulated CCL20 expression in the stomach, suggesting that IFN-γ is critically involved in CD4⁺ T-cell accumulation in AIG by up-regulating local CCL20 expression. In conclusion, IFN-γ is involved differently in the development of AIH and of AIG. IFN-γ negatively regulates T-cell proliferation in fatal AIH, whereas it initiates development of AIG. These findings imply that increased production of IFN-γ induced by an organ-specific autoimmunity may trigger the concurrent development of another organ-specific autoimmune disease.     

Oral Administration of Type I Interferon Modulates the Course of Experimental Allergic Neuritis

We investigated the effect of oral administration of type I interferon (IFN) in experimental allergic neuritis (EAN) in Lewis rats immunized with bovine peripheral nerve myelin. Starting at 7 days preceding immunization, rats were fed daily until sacrifice either with 5000 U rat IFN-α/β or mock-IFN. The clinical severity of EAN was significantly reduced in IFN-α/β fed animals compared to mock-IFN fed controls. Demyelination, but not inflammation, was decreased in IFN-α/β fed compared to mock-IFN fed rats at day 20 after immunization. In situ IFN-γ production and inflammation were reduced when evaluated by immunocytochemistry at day 13 after immunization. Spleen cells from IFN-α/β fed compared to mock-IFN fed EAN rats showed significantly reduced proliferation to stimulation with Con A or peripheral nerve myelin. IFN-γ production in draining lymph node cells was significantly reduced after stimulation with bovine peripheral nerve myelin. Our data suggest that oral administration of IFN-α/β reduces the severity of EAN, possibly by a reduction in production.