Polyisoprenyl phosphates: natural antiinflammatory lipid signals

Lipoxins (LX) and aspirin-triggered 15-epimer LX are leukocyte-derived eicosanoids generated during host defense that serve as down-regulatory signals. The specific intracellular events that govern cellular responses to inhibitory extracellular signals are of wide interest in order to understand pivotal intracellular events in diseases characterized by enhanced inflammatory responses, such as asthma, rheumatoid arthritis and atherosclerosis. We recently uncovered a novel role for polyisoprenyl phosphates, in particular presqualene diphosphate (PSDP), as natural down-regulatory signals in human neutrophils that directly inhibit phospholipase D and superoxide anion generation. Activation of LXA₄ receptors (ALXR) reverses proinflammatory receptor-initiated decrements in PSDP and inhibits cellular responses. These findings represent evidence for a novel paradigm for lipid-protein interactions in the control of cellular responses, namely receptor-initiated degradation of repressor lipids that is subject to regulation by aspirin treatment via the actions of aspirin-triggered 15-epimer LX at the ALXR, and identify new templates for antiinflammatory drugs by design.     

Integrins and cardiovascular disease

Cardiovascular diseases involve abnormal cell-cell interactions leading to the development of atherosclerotic plaque, which when ruptured causes massive platelet activation and thrombus formation. Parts of a loose thrombus may detach to form an embolus, blocking circulation at a more distant point. The integrins are a family of adhesive cell receptors interacting with adhesive proteins or with counterreceptors on other cells. There is now solid evidence that the major integrin on platelets, the fibrinogen receptor α _IIb  β ₃ , has an important role in several aspects of cardiovascular diseases and that its regulated inhibition leads to a reduction in incidence and mortality due to these disorders. The development of α _IIb  β ₃ inhibitors is an important strategy of many pharmaceutical companies which foresee a large market for the treatment of acute conditions in surgery, the symptoms of chronic conditions and, it is hoped, maybe even the successful prophylaxis of these conditions. Although all the associated problems have not been solved, the undoubted improvements in patient care resulting from the first of these treatments in the clinic have stimulated further research on the role of integrins on other vascular cells in these processes and in the search for new inhibitors. Both the development of specific inhibitors and of mice with specific integrin subunit genes ablated have contributed to a better understanding of the function of integrins in development of the cardiovascular system.     

Amoeboid movement: A review and proposal of a ‘membrane ratchet’ model

Summary Diverse cell types, including Amoebae, leukocytes, embryonic cells and tumour cells move about on solid surfaces to accomplish such activities as feeding, bacterial destruction, embryological development and metastasis. Theories of the mechanism of this movement are reviewed and a model is proposed which invokes the existence of specific, laterally mobile, transmembranous structures in the cell membrane, which are reversibly adhesive for both the contractile apparatus of the cell internally, and the substratum externally. By this model, the movement of all these cell types can be explained.     

Organoselenides as potential immunostimulants and inducers of interferon gamma and other cytokines in human peripheral blood leukocytes

Summary A number of organoselenium compounds have been described as anti-inflammatory, antioxidant, glutathione peroxidase-like agents and inhibitors of prostaglandin synthesis. Here we report that bis [2-(N-phenyl-carboxamido)]phenyl diselenide, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (Ebselen) and related compounds are inducers of interferon gamma (IFN-) and tumor necrosis factor (TNF) in human peripheral blood leukocytes. The IFN and TNF response was rapid, occurring within 20 h, and high-up to 1000 and 2000 units ml^–1-and was clearly related to the dosage and the structure of the compounds. The action of the compounds and phytohemagglutinin was synergistic. The IFN gamma and TNF production was reduced after removing adherent cells. Although the mode of action of the compounds is not known, they appear to interact directly or indirectly with both adherent and non-adherent leukocytes, and stimulate the synthesis of a set of different cytokines including factors controlling the cell proliferation. Therefore, organoselenides may be regarded as the biological response modifiers.     

2-乙基-3-羟基-6-苯硫基-4(1H)-吡啶酮对自由基的清除和抑制作用

研究2-乙基-3-羟基-6-苯硫基-4(1n)-吡啶酮(HPP)对羟自由基和超氧阴离子自由基的影响．用荧光分光光度计测定Fenton反应产生的羟自由基的清除率和生成抑制率，用比色法测定黄嘌呤-黄嘌呤氧化酶体系和大鼠腹腔多型核白细胞呼吸爆发产生的超氧阴离子自由基的清除率．HPP对Fenton反应产生的自由基有显的清除和抑制作用，且活性比羟自由基的特异性清除剂甘露醇强，对化学反应和大鼠腹腔多型核白细胞呼吸爆发产生的超氧阴离子自由基也有明显的清除作用，且活性较维生素E稍强．可见HPP是一种良好的氧自由基清除剂。     

Mitogenic activity of selenoorganic compounds in human peripheral blood leukocytes

Summary A variety of organoselenium compounds were originally described as antiinflammatory, antioxidant or glutathione-peroxidase-like agents, and as inhibitors of prostaglandin and leukotriene synthesis. Recently, the compounds have also been found to be inducers of interferon gamma and tumor necrosis factor in human peripheral blood leukocytes (PBL). We evaluated the effects of bis [2-(N-phenylcarboxamido)phenyl] diselenide and Ebselen^®; 2-phenyl-1,2-benzisoselenazol-3(2H)one, on the incorporation of tritiated thymidine into the DNA of PBL cultured in vitro. Both compounds were mitogenic and this effect was correlated with the expression of interleukin 2 receptor in T-lymphocytes. Therefore, we suggest that the selenoorganic compounds may induce mitogenic cytokines.     

一种在微机上实现白细胞自动分类的方法

阐述一种用微机实现白细胞自动分类的方法。系统采用二分树分类器实现对６种 白细胞分类。对确定二分树分类器的结构、细胞特征选择和结点分类器等问题作了详 细讨论；提出两种适用于微机系统的特征选择方法——相关分析法和二步选择法；给 出不同情况下系统的分类准确率。结果表明．本文提出的方法在训练集上获得的分类 准确确率达９３％，考试集上的分类准确率为８６％．     

血液白细胞的计算机自动分类研究

用计算机实现血液中白细胞的自动分类,要求:(1)分类精度尽可能地高;(2)识别速度要快.(3)分类系统性能要稳定.价格低廉,且便于操作.前两个要求很容易被人理解,而第三个要求却往往被人忽视,然而这却很重要。它直接关系到这种系统能否推广使用而不至于永远停留在实验阶段.目前,困外出售的自动分类系统都是以大型或中型计算机为主机,依赖于专用硬件的支持,使得系统的价格昂贵而在国内医院难以施用.至今尚无理想的系统可供临床普及