Growth hormone signal transduction

Growth hormone (GH) promotes animal growth by stimulating bone and cartilage cell proliferation, and influences carbohydrate and lipid metabolism. Some of these effects are brought about indirectly via somatomedin induction in hepatocytes, others by acting directly on the target cells. In either case, GH first binds to specific receptors on cells to trigger a sequence of biochemical events culminating in a biological response. Recently much has been learnt about the molecular structure of GH receptor, its binding to ligand, and the ensuing signal transduction events.     

外源性生长激素对改善腹腔感染时生长激素不敏感状态中的作用

探索了外源性生长激素对改善腹腔感染时生长激素不敏感中的作用。应用盲肠结扎穿孔法（CLP）制备腹腔感染大鼠模型,同时给予外源性生长激素;应用放射免疫法测定血清生长激素（GH）水平;应用逆转录多聚酶链反应（RT-PCR）法测定肝组织胰岛素样生长因子I(IGF-I)、生长激素受体（GHR）和细胞因子信号传导抑制体3(SOCS-3)mRNA的表达;应用ELISA测定血清肿瘤坏死因子α(TNF-α)和白介素6(IL-6)水平。结果表明腹腔感染组大鼠血清生长激素水平与对照组无明显差异,但肝组织IGF-ImRNA表达明显下降;给予外源性生长激素后可明显降低血清TNF-α和IL-6水平,同时可更快地促使GHR和IGF-ImRNA表达的上调及下调SOCS-3mRNA的表达。腹腔感染时机体存在对生长激素的不敏感状态,给予外源性生长激素后可明显地改善感染状态下机体对生长激素的敏感性。     

CD1d and natural T cells: how their properties jump-start the immune system

Cellular and humoral immune mechanisms recruited to defend the host from infectious agents depend upon the early immune events triggered by antigen. The cytokine milieu within which the immune response matures is the most important of many factors that govern the nature of the immune response. Natural T cells, whose function is controlled by CD1d molecules, are an early source of cytokines that can bestow type 1 or type 2 differentiative potential upon helper T lymphocytes. This review attempts to illuminate the glycolipid antigen presentation properties of CD1d, how CD1d controls the function of natural T cells and how CD1d and natural T cells interact to jump start the immune system. CD1d is postulated to function as a sensor, sensing alterations in cellular lipid content by virtue of its affinity for such ligands. The presentation of a neo-self glycolipid, presumably by infectious assault of antigen-presenting cells, activates natural T cells, which promptly release pro-inflammatory and anti-inflammatory cytokines and jumpstart the immune system. Received 10 July 2000; received after revision 16 October 2000, accepted 16 November 2000     

Viewpoints on the proinflammation state of leukemia

Proinflammation represents a pathophysiological state on the early stage of a number of diseases, especially the infectious and immunological ones. In recent years, proinflammation has attracted much attention, and the term 損roinflammation factors?appears frequently in the literature. While investigating leukemia and leukemic cells from the angle of 損roinflammation state? we got some intriguing findings, e.g. we detected the significantly elevated expression of proinflammation factor IL-18 in patients with acute myeloid leukemia (AML), which could up-regulate matrix metalloproteinases (MMP) and specific tissue inhibitors (TIMPs). The increased MMP may play a role in the aggressiveness of myeloid leukemic cells, and be associated with a poor prognosis. This phenomenon reflects an ignored aspect of leukemia. Investigations from the angle of 損roinflammation state?have broaden the fields of tumor and leukemia study.     

The Janus kinase family of protein tyrosine kinases and their role in signaling

In the early 1990s, the search for protein kinases led to the discovery of a novel family of non-receptor tyrosine kinases, the Janus kinases or JAKs. These proteins were unusual because they contained two kinase homology domains and no other known signaling modules. It soon became clear that these were not ‘just another’ type of kinase. Their ability to complement mutant cells insensitive to interferons and to be activated by a variety of cytokines demonstrated their central signaling function. Now, as we approach the end of the decade, it is evident from biochemical studies to knockout mice that JAKs play non-redundant functions in development, differentiation, and host defense mechanisms. Here, recent progress is reviewed, with particular emphasis on structure-function studies aimed at revealing how this family of tyrosine kinases is regulated.     

猪SOSC5和SOCS6基因克隆及组织表达研究

本文以长白猪(Landrace)大脑cDNA为模板,克隆得到长白猪细胞因子抑制因子SOCS-5基因和长白猪SOCS-6基因.序列分析结果显示:长白猪SOCS-5基因cDNA全长1688 bp,编码一个含有536个氨基酸的前体蛋白,与人、牛、小鼠和大鼠的氨基酸序列一致性分别为97％、97％、94％和95％;SOCS-6基因cDNA全长1645 bp,编码一个含有535个氨基酸的前体蛋白,与人、牛、小鼠和大鼠的氨基酸序列同源性分别为:92％,97％,85％,82％.氨基酸结构分析显示,长白猪SOCS-5和SOCS-6基因都具有典型的中央SH2结构域和C末端有40个氨基酸的SOCS Box结构域;组织表达图谱分析结果显示:长白猪SOCS5基因在大脑、心脏、脾脏、肌肉组织大量表达,在下丘脑、肝脏、肾脏、小肠中也有表达;SOCS6基因在大脑、下丘脑、心脏、肝脏、脾脏、肾脏、肌肉及小肠均大量表达.此外,本研究还将SOCS-5和SOCS-6基因编码区序列克隆转入真核表达载体pcDNA3.1(+)中,为下一步功能验证做准备.     

铁筷子多糖抑制小鼠S180肉瘤生长的免疫调节作用

本文通过观察荷瘤小鼠体内细胞因子水平与荷瘤小鼠体内肿瘤大小的关系,探讨铁筷子多糖（Helleborus thibetanus Franch polysaccharose HFPS）抑制小鼠S180肉瘤生长的有关免疫学机制。得出结论：铁筷子多糖可能通过促进荷瘤小鼠免疫细胞及体内免疫分子的作用增强荷瘤小鼠免疫功能,从而达到抗肿瘤作用。     

一种趋化因子的筛选

趋化因子是—种细胞因子 ,它是由组织细胞和炎性细胞衍生的、具有白细胞趋化活性的肽分子。论文确定了筛选趋化因子的实验方法趋化小室实验及其最佳实验条件 :以含 0 .1% BSA(牛血清蛋白 )的 RPMI16 4 0培养基为阴性溶剂 ,以趋化因子 Fmlp为阳性对照 ,白细胞浓度为 1.6×10 3/ μL 等。在上述条件下 ,对从 10种蛇毒中分离的 32 7个样品进行筛选 ,得到有趋化活性的样品 5个 ,经体外细胞毒性实验验证 ,其中 4个对细胞无毒性。趋化因子在抗肿瘤和AIDS病的防治等方面具有药用价值。     

Regulation of insulin receptor function

Resistance to the biological actions of insulin contributes to the development of type 2 diabetes and risk of cardiovascular disease. A reduced biological response to insulin by tissues results from an impairment in the cascade of phosphorylation events within cells that regulate the activity of enzymes comprising the insulin signaling pathway. In most models of insulin resistance, there is evidence that this decrement in insulin signaling begins with either the activation or substrate kinase activity of the insulin receptor (IR), which is the only component of the pathway that is unique to insulin action. Activation of the IR can be impaired by post-translational modifications of the protein involving serine phosphorylation, or by binding to inhibiting proteins such as PC-1 or members of the SOCS or Grb protein families. The impact of these processes on the conformational changes and phosphorylation events required for full signaling activity, as well as the role of these mechanisms in human disease, is reviewed in this article. Received 3 August 2006; received after revision 1 December 2006; accepted 8 January 2007