四个E-选择素基因的多态性与哈尼族原发性高血压相关性研究

目的探讨E－选择素基因rs3917408G／T、rs5361A／C、rs5368C／T和rs3917429C／T等4个错义突变与哈尼族原发性高血压的关系。方法采用PCR测序技术，对云南哈尼族172例原发性高血压患者和133例正常对照的E－选择素基因的rs3917408G／T、rs5361A／C、rs5368C／T和rs3917429C／T突变进行检测。结果在哈尼族原发性高血压组，rs3917408T、rs5361C、rs5368T和rs39t7429T等位基因频率分别为2％、7％、28．8％和6．1％，正常对照组相应的等位基因频率分别为4％、4．9％、21．8％和1．1％，其中原发性高血压组rs3917429位点T等位基因频率显著高于正常对照组（P〈0．01），其余突变点两组之间的等位基因频率比较差异均无显著性（P〉0．05）。结论E－选择素基因rs3917429位点T等位基因与哈尼族原发性高血压相关。     

内毒素耐受对肺部E选择素和血管细胞间黏附分子1表达的影响

目的观察内毒素血症时内毒素耐受(ET)大鼠血清和肺部E选择素与血管细胞间黏附分子1(VCAM-1)的动态变化,及其与非内毒素耐受(non-ET)大鼠的异同。方法ET组SD大鼠腹腔注射脂多糖(LPS)0.6mg.kg-1.d-1,连续4d,建立ET模型。第5d两组大鼠均腹腔注射大剂量(6mg/kg)LPS诱导全身及肺部炎症反应。采用双抗体夹心酶联免疫吸附法测定注射大剂量LPS前(0h),以及注射后1,2,6和24h的血清、支气管肺泡灌洗液(BALF)及肺组织匀浆中E选择素与VCAM-1的蛋白水平。结果ET组和non-ET组在注射大剂量LPS后血清E选择素和VCAM-1的表达无显著差异(P>0.05)。ET组BALF中的E选择素的上升滞后于non-ET组:E选择素在non-ET组接受大剂量LPS后1h即出现明显升高,之后下降;ET组高峰则在6h;1h时ET组明显低于non-ET组[(36.66±10.24)pg/mL比(89.72±16.66)pg/mL,P<0.001]。肺组织E选择素表达与BALF中的变化趋势相似。BALF中的VCAM-1表达在ET组中0,1,2和6h四个时间点均低于non-ET组,其中1h时间点差异显著(P<0.01)。在2和6h时non-ET组肺组织的VCAM-1急剧升高,而ET组几乎无上升,non-ET组6h时较ET组明显升高(P<0.05)。结论在内毒素耐受状态下,大剂量LPS腹腔注射所致的肺部E选择素和VCAM-1早期表达被阻滞。     

Regulation of endothelial cell adhesion molecule expression in an experimental model of cerebral malaria

OBJECTIVE: Plasmodium falciparum malaria in humans and animal models of this disease have revealed changes in the infected host that are consistent with a systemic inflammatory response. Although it has been proposed that endothelial cell adhesion molecules (CAM) contribute to the adhesive interactions of Plasmodium-infected erythrocytes and immune cells with vascular endothelial cells, ECAM expression has not been systematically studied in Plasmodium-infected animals. METHODS: In this study, the dual radiolabeled monoclonal antibody method was used to quantify the expression of different ECAMs (ICAM-1, VCAM-1, P-selectin, E-selectin) in different regional vascular beds of Plasmodium berghei ANKA-inffected mice (PbA), a well-recognized model of human cerebral malaria. The roles of T lymphocytes and certain cytokines (TNF-alpha, IL-12, IFN-gamma) in mediating the infection-induced expression of ICAM-1 and P-selectin were assessed by using relevant mutant mice. RESULTS: Wild-type (WT) mice exhibited highly significant increases in the expression of ICAM-1, VCAM-1, and P-selectin (but not E-selectin) in all vascular beds on the 6th day of PbA infection. The PbA-induced upregulation of ICAM-1 was significantly blunted in mice that were either deficient in IFN-alpha, IL-12 (but not TNF1b) or T lymphocytes (Rag-1 deficiency); however, these responses were tissue specific. CONCLUSIONS: These findings indicate that vascular endothelial cells in most regional circulations assume an inflammatory phenotype and that cytokines and immune cells mediate this response in a tissue-specific manner.     

KAI1/CD82、E-选择素在乳腺癌中的表达及其临床意义

目的　探讨KAI1/CD82与E 选择素在人乳腺癌中的表达及其临床意义。方法　采用免疫组化方法对6 2例乳腺癌和15例乳腺良性病例中KAI1/CD82与E 选择素基因表达的水平进行研究。结果　乳腺癌中KAI1/CD82与E 选择素的表达与良性病变有显著差异(P <0 .0 5 )。KAI1/CD82在腋淋巴结转移组和远处转移组阳性表达率明显低于无腋淋巴结转移组和远处转移组(P <0 .0 5 ) ,生存期≥5年组KAI1/CD82阳性率明显高于生存期<5年组(P<0 .0 5 ) ,与生存期呈正相关。E- 选择素在腋淋巴结转移组和发生远处转移组阳性表达率明显高于无腋淋巴结转移组和远处转移组(P <0 .0 5 ) ,生存期≥5年组E 选择素阳性表达率明显低于生存期<5年组(P <0 .0 5 ) ,与生存期呈负相关。KAI1/CD82和E- 选择素均与临床病理类型、ER、PR、CerbB 2表达状态无关(P >0 .0 5 )。KAI1/CD82与E -选择素表达呈负相关(P <0 .0 5 )。结论　KAI1/CD82与E-选择素在乳腺癌的发生和发展及预后中起着重要作用。检测KAI1/CD82与E- 选择素的表达可能成为监测人乳腺癌进展及临床上判断预后的重要参考指标。     

E-选择素基因多态性与脑梗死的相关性研究

目的　探讨E -选择素 (E -selectin)基因多态性与广西地区壮族人脑梗死的关系。方法　采用聚合酶链反应 -限制性片段长度多态性 (PCR -RFLP)测定法检测 187例脑梗死及 2 10例对照者E -selectin基因第 2外显子G98T、第 4外显子A5 6 1C多态性 ,同时采用酶联免疫吸附试验 (ELISA)检测脑梗死和对照者血清E -selectin水平。结果　脑梗死组E -selectin血清水平显著高于对照组 (P <0 .0 1) ,E -selectin基因A5 6 1C基因型频率和等位基因频率在脑梗死组和对照组比较差异有显著性 (P <0 .0 5 ) ,对基因型频率的相对风险分析发现 ,AC基因型携带者患脑梗死的风险是AA基因型的 1.96 8倍 (OR =1.96 8,95 %CI:1.10 8～ 3.4 95 ) ,AC基因型携带者的E -selectin血清水平显著高于AA基因型 [(5 9.13± 15 .92 )ng mlvs (5 0 .4 6± 14 .38)ng ml,P <0 .0 1]。结论　E-selectin基因A5 6 1C多态性与脑梗死的发病具有相关性 ,C等位基因可能是广西地区壮族人脑梗死发病的遗传易感基因 ,携带AC基因型的个体可能通过促进E -selectin的高度表达进而增加脑梗死的发病风险。     

中枢神经系统感染与脑血管内皮细胞表面E选择素的表达

目的　研究中枢神经系统感染时血管内皮细胞E选择素的表达 ,以及地塞米松对其抑制作用。方法　将 5 4只小鼠随机分成侧脑室注射内毒素 (2 0 μg/2 0 μl)组、腹腔注射地塞米松 [1mg/(kg·12h) ]+侧脑室注射内毒素 (2 0 μg/2 0 μl)组、生理盐水组以及空白对照组。免疫组织化学法观察脑血管内皮细胞E选择素的表达 ,HE染色观察脑组织炎症反应。结果　空白对照组有少量E选择素表达 [(13 7± 2 7) %]。生理盐水组 [(13 5± 5 6 ) %]与空白对照组E选择素表达比较差异无显著性。内毒素组注射后E选择素表达在第 1天 [(31 8± 10 5 ) %]、第 2天 [(2 6 8± 9 6 ) %]明显增多 ,与生理盐水组比较差异有显著性 (P <0 0 1或 <0 0 5 ) ,注射后第 3天 [(15 7± 9 9) %]恢复正常 (P >0 0 5 ) ;注射后 3d内E选择素表达呈进行性下降 (F =4 0 8,P <0 0 5 )。地塞米松 +内毒素组于注射后第 1天和第 2天E选择素表达与内毒素组比较明显受到抑制 ,分别为 (13 0± 12 4 ) %、(8 8±6 0 ) %(P略 >0 0 5 ,P <0 0 5 ) ,与生理盐水组比较差异无显著性 ;同时脑组织炎症反应受到明显抑制。结论　中枢神经系统感染时脑血管内皮细胞E选择素的表达增加 ;地塞米松可通过抑制脑血管内皮细胞表面E选择素的表达来抑制炎症反应     

Plasma levels of D-dimer and circulating endothelial adhesion molecules in veno-occlusive disease of the liver following allogeneic bone marrow transplantation

Abstract: Veno-occlusive disease (VOD) of the liver is a frequent and life-threatening complication of BMT. Recently, successful treatment by t-PA has been reported but has been compromised by fatal bleeding events. Therefore, t-PA application should be restricted to patients with severe VOD. However, moderate and severe forms of VOD are difficult to distinguish in early stages. We analyzed plasma levels of cross-linked fibrin degradation products (D-dimer) and soluble endothelial adhesion molecules such as sE-selectin, sVCAM-1 and sICAM-1 in 10 consecutive patients undergoing allogeneic BMT to evaluate their use in identifying severe forms of VOD. During the observation period, 4 episodes of VOD occurred, 2 of which were fatal due to early onset of multiorgan failure. Concentrations of D-dimer generally increased after transplantation. However, there was an additional significant increase in D-dimer levels during severe VOD. Thus, D-dimer levels above 1000 μg/1 were only found in 2 cases with severe VOD and fatal outcome. When compared with bilirubin concentrations substantial increases of D-dimers appeared earlier during the course of severe VOD. In contrast, VOD episodes were not accompanied by significant increases in sE-selectin, sVCAM-1 and sICAM-1 levels. It is concluded that measurement of D-dimer concentrations may aid accuracy to the early diagnosis of severe VOD.     

Can E-selectin be a reliable marker of inflammation in lumbar disc disease?

The cause of sciatica and low back pain associating with lumbar disc herniation has not been clearly identified until now. Inflammation has been shown to occur via immunohistochemical and biochemical methods in herniated disc tissues. The important prognostic role of E-selectin has recently been substantiated by other studies in early rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). The important role of adhesion molecules in the initiation and progression of the inflammatory response is well known for infectious diseases and autoimmune disorders. In our study, we aimed to show the role of E-selectin as an inflammatory marker and the correlation of inflammation with straight-leg raise (SLR) test findings and subtype of disc herniation. We found that the cases with positive SLR test had higher rates of immunostaining with E-selectin. This led us to think that E-selectin might play an important role in the activity status of the disease, meaning patients with more limited movement capacity might benefit from E-selectin antagonist therapy. Among the many studies performed to identify the relationship between the inflammation markers and activity of lumbar disc herniation, this is the first investigation held with E-selectin.     

Effects of transdermal hormone replacement therapy on levels of soluble P- and E-selectin in postmenopausal healthy women

OBJECTIVE: To study the adhesion molecule pattern in postmenopausal women who were not receiving hormone replacement therapy (HRT), HRT users, and fertile women. DESIGN: Case-control study. SETTING: Second University of Naples, Naples, Italy. PATIENT(S): Fifty healthy naturally postmenopausal women and 20 fertile women. INTERVENTION(S): Twenty-six women received no HRT and 24 received continuous transdermal 17 beta-estradiol, 0.05 mg/d, plus oral acetate nomegestrol, 5 mg/d. MAIN OUTCOME MEASURE(S): Levels of the soluble forms of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin. RESULT(S): Women who did not received HRT showed a trend toward higher levels of soluble E-selectin and had significantly higher levels of soluble P-selectin than did fertile women. Levels of soluble E-selectin and soluble P-selectin were significantly lower in HRT users than in nonusers. Levels of VCAM-1 levels were significantly higher in HRT users than in fertile women, but no significant differences in CAM concentrations were found between the other groups. CONCLUSION(S): Menopause may lead to increased levels of soluble E- and soluble P-selectin, whereas long-term HRT is associated with lower selectin concentrations. This suggests that HRT may have a beneficial effect on endothelial function.     

Effect of route and type of nutrition on intestine-derived inflammatory responses

BACKGROUND: Immunological links between the gastrointestinal (GI) tract and respiratory tract has been postulated in the development and maintenance of mucosal immunity. Route and type of nutrition affects mucosal immunity by reducing cell populations within the Peyer's patches of the small intestine and lamina propria as well as altering cytokine profiles within these sites. In addition to the mucosal affects, these alternations in cytokines (decreases in interleukin-4 and interleukin-10) also appear to influence the vascular endothelium of the GI tract. DATA SOURCES: This review examines the laboratory data regarding cytokine profile within the gut, endothelial adhesion molecule expression within the intestinal and extraintestinal organs, and the effect of these alterations on neutrophil accumulation and organ responses to gut ischemia/reperfusion. It also describes the effect of a specific nutrient, glutamine, on the starved gut. CONCLUSIONS: Changes induced by failure to feed the GI tract affects GI vascularity increasing expression of proinflammatory adhesion molecules. These adhesion molecules attract neutrophils and prime them for subsequent ischemic events. Lack of feeding the gastrointestinal tract acts as a "first hit" and increases the inflammatory response to a secondary insult in the lungs, liver, and GI tract. The addition of the specific nutrient, glutamine, reverses many of these defects and favorably influences the proinflammatory effects of gut starvation.