胃癌临床特征与TβRⅡ、COX-2表达的关系

目的 :研究在胃癌与非癌组中转化生长因子 β受体Ⅱ (TβRⅡ )、环氧合酶 2 (COX 2 )的表达 ,以探求胃癌临床特征与TβRⅡ、COX 2表达的关系。方法 :对 1 997～ 2 0 0 2年底经手术病理诊断为胃癌早期 2 9例 ,中期 1 3例及晚期 2 0例进行随访调查。存档蜡块重新制片、读片 ,免疫组织化学S P法染色。检测TβRⅡ、COX 2和与微血管密度 (MVD)在胃癌和非癌组织中的表达情况 ,分析它们与胃癌临床特征的关系。结果 :TβRⅡ表达在不典型增生组与早期胃癌组间 (P <0 .0 5) ,早中期与晚期胃癌组间 (P <0 .0 1 ) ,肿瘤组织不同浸润深度 (P <0 .0 5) ,分化程度 (P <0 .0 5)及有无淋巴结转移 (P <0 .0 1 ) ,各组间差异有显著性。COX 2表达在早期胃癌组与非癌组织相比(P <0 .0 1 ) ,有无淋巴结转移组间 (P <0 .0 5) ,早中期与晚期胃癌组间 (P <0 .0 1 )表达的差异有显著性。TβRⅡ不同表达 (P <0 .0 5)和COX 2不同表达 (P <0 .0 1 )的MVD差异有显著性。COX回归分析显示 ,TβRⅡ是胃癌患者有价值的预后因素。结论 :TβRⅡ、COX 2的表达与MVD有明显的关系 ,与浸润深度、淋巴结转移和预后等胃癌的临床特征有关。TβRⅡ与术后生存率有密切关系 ,可作为胃癌预后的参考指标     

Functional Analysis of Mature Hematopoietic Cells From Mice Lacking the beta c Chain of the Granulocyte-Macrophage Colony-Stimulating Factor Receptor

Mice with a null mutation of the c chain of thegranulocyte-macrophage colony-stimulating factor (GM-CSF),interleukin-3 (IL-3), and IL-5 receptors (c-null mice) develop analveolar proteinosis-like lung disease. The pathogenesis of thisdisease is uncertain and, although a defect in alveolar macrophagefunction has been postulated, no previous analysis of maturehematopoietic cells in mice with alveolar proteinosis has beenreported. Therefore, we undertook a functional analysis of the maturehematopoietic cell compartment in c-null mice. In addition, wereexamined the roles of the GM-CSF receptor chain and the cchain in signaling by GM-CSF. Neutrophils and macrophages fromc-null mice were capable of normal survival and phagocytosis in theabsence of stimulus and of similar levels of nitric oxide production inresponse to interferon- and lipopolysaccharide. GM-CSF-mediatedaugmentation of survival, phagocytosis, and hydrogen-ion productionwere absent in neutrophils from c-null mice. Interestingly, we wereunable to show any ability of the GM-CSF receptor -chain alone tomediate glucose transport in these cells. In keeping with the c-null mice lung pathology, examination of lavage fluid from the lungs ofc-null mice showed increased cellularity. This was caused by anincrease in the number of lymphocytes, neutrophils, and macrophages.Large foamy cells in the lavage fluid from c-null mice wereidentified as macrophages using immunohistochemistry. Functionalanalysis showed that these c-null alveolar macrophages were capableof phagocytosis but uptake of colloidal carbon and cellular adhesionwere reduced. In summary, mature hematopoietic cells with a nullmutation of the c receptor were unable to perform GM-CSF-mediatedhematopoietic cell functions including glucose transport, but respondednormally to a range of other ligands.     

DPP-4 Inhibitors Repress NLRP3 Inflammasome and Interleukin-1beta via GLP-1 Receptor in Macrophages Through Protein Kinase C Pathway

Background

Anti-atherosclerotic effects of dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown in many studies. Since inflammation and immune response play a key role in atherogenesis, we examined the effect of DPP-4 inhibitors on the expression of nod-like receptor family, pyrin domain containing 3 (NLRP3) Inflammasome and Interleukin-1beta (IL-1β) in human macrophages.

Methods and Results

THP-1 macrophages were incubated with oxidized low density lipoprotein (ox-LDL) with or without DPP-4 inhibitors (sitagliptin and NVPDPP728). The effects of DPP-4 inhibitors on the expression of NLRP3, toll-like receptor 4 (TLR4) and pro-inflammatory cytokine IL-1β were studied. Both DPP-4 inhibitors induced a significant reduction in NLRP3, TLR4 and IL-1β expression; concurrently, there was an increase in glucagon like peptide 1 receptor (GLP-1R) expression. Simultaneously, DPP-4 inhibitors reduced phosphorylated-PKC, but not PKA, levels. To determine the role of PKC activation in the effects of DPP-4 inhibitors, cells were treated with PMA- which blocked the effect of DPP-4 inhibitors on NLRP3 and IL-1β as well as TLR4 and GLP-1R. Over-expression of GLP-1R in macrophages with its agonist liraglutide also blocked the effects of PMA.

Conclusion

DPP-4 inhibitors suppress NLRP3, TLR4 and IL-1β in human macrophages through inhibition of PKC activity. This study provides novel insights into the mechanism of inhibition of inflammatory state and immune response in atherosclerosis by DPP-4 inhibitors.     

胃癌雌激素受体和孕激素受体的检测及临床意义

目的：为了研究雌激素受体（Ｅｓｔｒｏｇｅｎ ｒｅｃｅｐｔｏｒ,ＥＲ）的孕激素受体（Ｐｒｏｇｅｓｔｅｒｏｎｅ ｒｅｃｅｐｔｏｒ,ＰｇＲ）在胃癌中的表达以及与临床病理学之间的关系。方法：我们采用免疫组织化学法对９１例胃癌作了测定。结果：９１例胃癌的ＥＲ,ＰｇＲ阳性率分别为３９．６％,４１．８％。在９１例胃癌中,分化好的腺癌细胞ＥＲ,ＰｇＲ阳性率均为４７．９％,高于分化差的癌细胞的ＥＲ,ＰｇＲ阳性率（３     

血管紧张素1型受体和2型受体的交互作用

血管紧张素Ⅱ (AngⅡ )主要作用于血管紧张素 1型受体和 2型受体 (AT1、AT2 )而发挥作用 ,AngⅡ与受体间的复杂相互作用在其生理效应的发挥中担当重要角色。本文重点讨论AT1与AT2 间的交互作用及与缓激肽 /NO/cGMP之间的关系 ,有助于对肾素 血管紧张素系统 (RSA)病理生理机制的理解及拮抗RAS疗法新策略的发展。     

Effect of beta blockade and beta stimulation on stage fright

Stage fright, physiologically the "fight or flight" reaction, is a disabling condition to the professional musician. Because it is mediated by the sympathetic nervous system, we have investigated the effects of beta blockade on musical performance with propranolol in a double blind fashion and the effects of beta stimulation using terbutaline. Stage fright symptoms were evaluated in two trials, which included a total of 29 subjects, by questionnaire and by the State Trai Anxiety Inventory. Quality of musical performance was evaluated by experienced music critics. Beta blockade eliminates the physical impediments to performance caused by stage fright and even eliminates the dry mouth so frequently encountered. The quality of musical performance as judged by experienced music critics is significantly improved. This effect is achieved without tranquilization. Beta stimulating drugs increase stage fright problems, and should be used in performing musicians only after consideration of the detrimental effects which they may have on musical performance.     

Platelet Biology and Receptor Pathways

The main function of platelets is to participate in primary hemostasis through four distinct steps: adhesion, activation, secretion, and aggregation. Unraveling the molecular mechanisms underlying these steps has led to a better understanding of the pathophysiology of bleeding disorders, on one hand, and of thrombotic diseases, such as acute coronary syndromes, on the other. Platelets are cytoplasmic fragments of megakaryocytes formed in the bone marrow. They lack nuclei but contain organelles and structures, such as mitochondria, microtubules, and granules. Platelet granules contain different bioactive chemical mediators, many of which have a fundamental role in hemostasis and/or tissue healing. The platelet cytoplasm contains an open canalicular system that increases the effective surface area for the intake of stimulatory agonists and the release of effector substances. The submembrane region contains microfilaments of actin and myosin that mediate morphologic alterations characteristic of shape change. Resting platelets remain in the circulation for an average of approximately 10 days before being removed by macrophages of the reticuloendothelial system. A wide variety of transmembrane receptors cover the platelet membrane, including many integrins, leucine-rich repeat receptors, G protein-coupled receptors, proteins belonging to the immunoglobulin superfamily, C-type lectin receptors, tyrosine kinase receptors, and a variety of other types. In this article, we will review platelet biology under physiological and pathological conditions, with particular emphasis on the function of their membrane receptors.     

Alcohol and the Opiate Receptor

A number of in vivo studies have suggested that alcohol and the opiates may be integrally related in the brain. In this study we report that 0.1, 0.2, and 0.4% ethanol significantly increases the density of binding sites for [³H]naloxone in isolated brain membranes.     

柯萨奇-腺病毒受体与病毒性心肌炎

柯萨奇 腺病毒受体是一种普通的存在于心肌细胞表面的病毒受体 ,作为柯萨奇病毒和腺病毒的共同受体 ,在它们感染心肌细胞的过程中起着关键性的作用。     

Toll样受体4与动脉粥样硬化

动脉粥样硬化是一种慢性炎症疾病。Toll样受体家族(TLRs)识别抗原相关的分子模式(PAMPs)后激发先天性免疫反应。TLR4不仅识别外源性配体脂多糖(LPS),也识别动脉损伤过程中表达的内源性配体。越来越多的研究表明TLR4可能在动脉粥样硬化病变的发生和发展过程中发挥主要作用。现对近年有关TLR4在动脉粥样硬化中的作用的研究进展作一综述。此外,还将讨论对TLR4信号的可能干预措施。