中枢神经系统感染患儿血脑屏障与脑脊液白蛋白指数的变化

目的探讨中枢神经系统感染患儿血脑屏障（blood-brain barrier,BBB）与脑脊液（cerebrospinal-fluid,CSF）白蛋白指数的变化。方法采用溴甲酚绿法和免疫比浊法检测18例化脓性脑膜炎患儿急性期、恢复期及22例病毒性脑炎患儿急性期血清和CSF中白蛋白水平,并计算出CSF白蛋白指数。与正常对照组比较。结果化脓性脑膜炎、病毒性脑炎患儿急性期CSF白蛋白、CSF白蛋白指数显著高于正常对照组（P〈0.001）,且化脑组显著高于病脑组（P〈0.001）。化脑组恢复期患儿CSF白蛋白、CSF白蛋白指数与对照组无明显差异（P〉0.05）。结论监测CSF白蛋白和CSF白蛋白指数的水平可作为化脓性脑膜炎和病毒性脑炎早期诊断、鉴别诊断,以及判断BBB损伤程度的参考指标。     

急慢性乙型肝炎患者血浆uPA和uPAR的检测及意义

目的研究急慢性乙型肝炎uPA和uPAR的表达，探讨肝炎发病时血液纤溶的变化及意义。方法应用酶联免疫吸附试验（ELISA）测定血浆uPA和uPAR的水平。结果急慢性乙型肝炎血浆uPA和uPAR水平与对照组比较均有意义地高于对照组（P〈0．01）；慢性乙型肝炎重度组血浆uPA和uPAR水平显著高于急性乙型肝炎组（P〈0．05），亦显著高于慢性乙型肝炎中轻度组（P〈0．05和P〈0．01）；急性乙型肝炎血浆中uPAR水平显著高于慢性乙型肝炎中轻度组（P〈0．01）；乙型肝炎急性期血浆中uPA和uPAR水平显著升高，恢复期明显回落（P〈0．05和P〈0．01），但仍明显高于正常对照组（P〈0．01）；急慢性乙型肝炎血浆中uPAR水平与凝血酶原时间（PT）（r=0．605，P〈0．01）和国际标准化比率INR（r=0．603，P〈0．01）、胆红素（TB）（r=0．649P〈0．01）呈正相关。结论急慢性乙型肝炎uPA和uPAR水平的升高，与炎症的严重程度有关，与肝细胞损伤程度有关，是肝炎发病时血液凝血和纤溶系统失衡的重要原因之一。     

脑脊液C反应蛋白、前白蛋白、腺苷脱氨酶和β2-微球蛋白水平在儿童脑膜炎诊断中的临床价值

目的 探讨脑脊液C反应蛋白、前白蛋白、腺苷脱氨酶和β2-微球蛋白水平变化在儿童脑膜炎诊断中的临床价值.方法 检测儿童脑膜炎患者脑脊液C反应蛋白、前白蛋白、腺苷脱氨酶和β2-微球蛋白四者水平,与对照组进行比较并进行统计学分析.结果 与对照组比较,脑膜炎组的C反应蛋白、腺苷脱氨酶和β2-微球蛋白水平显著升高,前白蛋白水平明显降低.与结核性脑膜炎组比较,病毒性脑膜炎组的前白蛋白水平,细菌化脓性脑膜炎组的C反应蛋白和前白蛋白水平均明显升高;与病毒性脑膜炎组比较,细菌化脓性脑膜炎组、结核性脑膜炎组的腺苷脱氨酶和β2-微球蛋白水平显著升高.与对照组比较,脑膜炎组C反应蛋白、前白蛋白和腺苷脱氨酶三者单独检测,及上述四者联合检测的阳性率均明显升高,差异均有统计学意义(P<0.01或P<0.05).结论 联合检测脑脊液C反应蛋白、前白蛋白、腺苷脱氨酶和β2-微球蛋白水平对儿童脑膜炎诊断具有重要临床价值.     

肝癌患者组织中凝血及纤溶因子的基因表达检测与分析

目的:检测组织因子（TF）、尿激酶型纤溶酶原激活物（uPA）及其受体（uPAR ）mRNA在肝细胞癌组织中的表达并探讨其临床意义。 方法:利用RT-PCR法分别检测27例肝细胞癌、癌旁及27例正常肝组织中TF、uPA、uPA mRNA表达阳性率及相对表达强度，并结合临床病理资料进行分析。 结果:TF、uPA、uPAR在肝细胞癌组织中阳性率及相对表达强度分别为62.96%（17/27）、70.37%（19/27）、77.78%（21/27）；0.567±0.268、0.964±0.458、0.784±0.322,均显著高于癌旁组织及正常组织，差异显著(P<0.05)。3者在肝癌组织中相对表达强度与肿瘤大小及部分侵袭转移指标有关，其中TF mRNA表达强度在肝内及肝外转移及门脉癌栓组高于无肝内及肝外转移及无门脉癌栓组(P<0.05) ，uPA mRNA在有包膜侵润、肝内转移及门脉癌栓组高于无包膜侵润、无肝内转移及门脉癌栓组(P<0.05)；uPAR mRNA在有肝内转移及门脉癌栓组高于无肝内转移及门脉癌栓组(P<0.05)。经Pearson检验肝细胞癌患者TF、uPA和uPAR mRNA表达呈正相关［TF-uPA：r=0.373(P<0.01)，TF-uPAR：r=0.534(P<0.01)，uPA-uPAR：r=0.365 (P<0.01)］。 结论:肝细胞癌组织中TF、uPA及uPAR的mRNA显著升高并与部分侵袭转移指标有关，提示3者可能在肝细胞癌的发生及侵袭转移起协同作用。     

Mx1蛋白在颅内感染患者外周血中的表达及其作用初探

通过检测颅内感染患者外周血单个核细胞(peripheral blood mononuclear cell,PBMC)中Mx1蛋白表达,探讨Mx1蛋白对颅内感染患者可能的免疫学作用及临床价值。应用流式细胞术、ELISA分别检测58例颅内感染患者(病毒性脑膜炎35例、化脓性脑膜炎23例)及16例健康对照组人群PBMC中Mx1蛋白表达及外周血中IFN-α、IFN-β分泌水平。结果显示病毒性脑膜炎组Mx1蛋白表达及IFN-α、IFN-β分泌均高于化脓性脑膜炎组患者及健康对照组人群(P0.01);而化脓性脑膜炎组与健康对照组人群之间无统计学差异(P0.05)。病毒性脑膜炎患者PBMC中Mx1蛋白表达上调,其可能参与了中枢神经系统抗病毒免疫过程,同时会为鉴别病毒性脑膜炎与化脓性脑膜炎提供一定临床帮助。     

基质金属蛋白酶3和尿激酶型纤溶酶原激活物受体在2型糖尿病大血管病变中的变化

目的： 探讨基质金属蛋白酶3（MMP-3）和尿激酶型纤溶酶原激活物受体（uPAR）在2型糖尿病大血管病变中的变化。方法: 用ELISA双抗体夹心法测定26例正常对照和39例2型糖尿病患者（其中单纯2型糖尿病15例、合并大血管病变24例）的血浆MMP-3和uPAR水平。结果: 单纯糖尿病组uPAR高于正常对照（P<0.05）而MMP-3无显著差异；合并大血管病变组MMP-3显著高于正常对照和单纯糖尿病组（P<0.01，P<0.01），而uPAR亦高于正常对照及单纯病变组（P<0.01，P<0.05）。2型糖尿病血浆MMP-3水平和uPAR水平呈正相关， LDL-C与uPAR呈正相关且是uPAR主要影响因素。 结论: MMP-3和uPAR与2型糖尿病大血管病变发生密切相关，MMP-3可作为2型糖尿病血管病变的循环标志物。     

闽东地区小儿颅内感染52例临床分析

目的 探讨小儿各型颅内感染的临床表现、脑脊液及CT影像学检查在鉴别诊断中的价值。方法 本文回顾性分析了52例1996年3月-2003年5月闵东医院住院的颅内感染患儿的临床表现、脑脊液常规检查及CT影像学表现。结果 脑脊液白细胞数在各型颅内感染中无显著性差异,各组间P>0.05;蛋白含量细菌性感染组(包括化脓性脑膜炎及结核性脑膜炎)显著高于无菌性感染组(包括病毒性脑炎及流行性乙型脑炎),P<0.001;糖含量则前组显著低于后组,P<0.01;组内无显著性差异,P>0.05。氯化物含量结脑显著低于其余各组,P<0.01。结论 脑脊液生化常规对各型颅内感染具有鉴别诊断意义。白细胞计数不能作为鉴别的金标准。CT检查对结脑患儿诊断意义较大。     

血浆脑钠素水平在病毒性心肌炎患者中的临床意义

目的 探讨血浆脑钠素(BNP)水平在病毒性心肌炎(VMC)患者中的临床意义及预后.方法 测定48例病毒性心肌炎患者及40例非心肌炎患者BNP浓度及射血分数(EF),随访2年,观察两组患者,分析血浆BNP与心肌炎的相关性以及BNP对病毒性心肌炎患者预后的影响.结果 VMC组血浆BNP、EF值与对照组比较显著高于对照组(P＜0.01,P＜0.05).VMC组BNP显著升高患者死亡率高.结论 VMC患者中血浆BNP水平升高,BNP显著升高患者预后差.     

脑病患者脑脊液β_2-m RIA的临床价值

我们对74例脑病住院患者进行了脑脊液β_2-m放射免疫分析(RIA),同时进行脑脊液常规检查现将结果报告如下。 对象和方法 一、对象:对照组32例,脑脊液常规检查正常,最后诊断排除神经系统疾患者,74例病人均进行脑脊液常规检查并经临床确诊,其中结核性脑膜炎(结脑)组21例,化脓性脑膜炎(化脑)组26例,病毒性脑膜炎(病毒脑)组18例,胶质瘤组9例。每份脑脊     

脑脉通联合溶栓对血栓栓塞性脑缺血大鼠纤溶酶原激活物及其受体的影响

脑缺血损伤可引起血脑屏障破坏,溶栓治疗可以再通血流,保护脑组织免受损伤,但可使颅内出血增加。脑脉通已被证实对脑缺血损伤有保护作用。本实验拟对脑脉通联合溶栓对脑缺血大鼠血脑屏障的保护作用及其可能的作用机制进行探讨。将实验大鼠随机分组;运用自体血栓结合线栓阻塞大鼠大脑中动脉制备血栓栓塞性脑缺血动物模型;大鼠缺血后3h、6h、9h经导管由区域动脉进行溶栓;动脉给药后24h观察大鼠脑组织颅内出血率变化,用免疫组织化学法测定脑组织IgG、IV型胶原蛋白(CoLIV)、尿激酶型纤维蛋白酶原激活物(uPA)和uPA受体(uPAR)表达的变化。结果显示,模型组大鼠脑内出血率增高,其9h、6h组IgG水平增高、CoLIV降低,各组uPA和uPAR表达明显;溶栓组颅内出血率较模型组增高,各用药组9h的IgG降低、Co-LIV增强,uPA和uPAR表达减弱;各组9h较3h和6h的IgG表达增强,CoLIV减弱,uPA和uPAR表达显著;联合组的颅内出血率较溶栓组降低,其9h组的IgG分别较脑脉通组降低、CoLIV增强,uPA和uPAR表达减弱。上述结果提示,脑缺血可引起血脑屏障破坏,溶栓可增加颅内出血率,脑脉通联合溶栓可保护血脑屏障受损,降低颅内出血的发生,其作用可能与降低脑组织uPA和uPAR表达以增加CoLIV水平有关。     

Cerebrospinal fluid plasminogen activator inhibitor-1 in patients with neurological disease.

AIM: To study cerebrospinal fluid (CSF) concentrations of plasminogen activator inhibitor type-1 (PAI-1) in patients with neurological disease. METHODS: CSF PAI-1 concentrations were measured in 51 patients with neurological disease and 20 reference subjects using an ELISA. The patient group comprised three patients with viral meningitis, 20 with encephalitis, nine with acute lymphoblastic (n = 7) and myeloid (n = 2) leukaemia (with central nervous system involvement), and 19 with multiple sclerosis. RESULTS: Raised PAI-1 concentrations were observed in patients with leukaemia, encephalitis and multiple sclerosis. There was no difference in the mean concentrations of PAI-1 in patients with meningitis when compared with the reference subjects. The highest mean (SEM) PAI-1 concentration was found in patients with leukaemia (1.28 (0.36) ng/ml), and the next highest in those with encephalitis (1.19 (0.20) ng/ml). these values were much higher than those in patients with viral meningitis. In a previous report, raised CSF tissue-type plasminogen activator (tPA) activities were detected in patients with multiple sclerosis, leukaemia and encephalitis, with mean activities in decreasing order. PAI-1 concentrations in the same patients were the reverse of their corresponding tPA activities, being higher in those with leukaemia and encephalitis, than in patients with multiple sclerosis. There was no association between CSF PAI-1 concentrations and age in either patients or controls. Similarly, there was no association between CSF PAI-1 concentrations and urokinase-type plasminogen activator (uPA). CONCLUSIONS: Raised CSF PAI-1 concentrations may be used as a non-specific marker of neurological disease. Moreover, PAI-1 may play an important role in regulating the functions tPA, and probably uPA, in CSF.     

Expression of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 and -2 in hepatocellular carcinoma

It has become more and more clear in recent decades that the plasminogen activation system, which includes urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), plasminogen activator inhibitor (PAI)-1 and PAI-2, plays a very important role in the aggressiveness of cancer. Using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), the expression of these four components of the uPA system was analyzed in 19 cases of hepatocellular carcinoma (HCC) and 18 cases of the adjacent non-cancer tissues which all had chronic active hepatitis with liver fibrosis or liver cirrhosis. Four cases of normal liver tissues, as controls for immunohistochemical stains, were obtained from the hepatectomized liver of patients with metastatic cancer in the liver. The positive rates of uPA, uPAR, PAI-1 and PAI-2 for immunohistochemical stains in cancer tissues were 78.9, 68.4, 57.9 and 31.6%, respectively. Positive signals were mainly distributed in the cytoplasm of the cancer and in stromal cells. Moreover, the strong stains were chiefly located in the invasive front of the cancer cells. No specific stain was detected in four cases of normal liver tissues. In ELISA, there were significant differences between cancer and non-cancer tissues in concentration of uPA, uPAR and PAI-1 (P < 0.0003, 0.0024 and 0.01, respectively), but there was no significant difference in that of PAI-2 (P = 0.37). These results suggest that uPA, uPAR and PAI-1 are related to invasion of HCC.     

检测DM2患者血浆tPA、PAI-1、uPA及uPAR水平的价值

目的:检测2型糖尿病(DM2)血浆tPA、PAI-1、uPA及uPAR水平,探讨其临床价值.方法:分别以ELISA检测尿蛋白正常组、尿蛋白阳性组、严重尿蛋白组和对照组的tPA、PAI-1、uPA及uPAR水平.结果:与对照组相比,尿蛋白正常组的tPA和PAI-1变化不明显(P＞0.05);尿蛋白阳性组tPA活性明显下降...     

Immunohistochemical expression of uPA, uPAR, and PAI-1 in breast carcinoma. Fibroblastic expression has strong associations with tumor pathology

The urokinase-type plasminogen activator (uPA) system has been implicated in tumor spread. We have used immunohistochemistry to examine three components of this system, ie, uPA, uPA receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1), in a pilot study on 142 cases of breast carcinoma. We wished to determine whether there were any relationships between expression of the proteins in either tumor cells or fibroblasts and clinical and pathological features. Strong uPA expression in each cell type was significantly related to high tumor grade (P = 0.013 and 0.008, respectively), and was more common in invasive than in in situ carcinomas (P < 0.0001). Fibroblastic expression of uPAR was only related to the presence of invasion (P < 0.0001). Strong PAI-1 expression in both cell types was seen in high-grade tumors (tumor cells, P = 0.012; fibroblasts, P < 0.001), but only fibroblastic expression was related to the presence of invasion (P = 0.042). Fibroblastic expression of both uPA and uPAR were positively correlated with tumor size. Although patients with strong fibroblastic expression of uPA showed a tendency toward a shorter time to relapse, none of the plasminogen activator proteins were significantly associated with relapse-free survival. These results suggest that strong expression of uPA, uPAR, and PAI-1 in fibroblasts rather than in tumor cells have the most impact on the clinical behavior of breast cancer. Larger prospective studies are needed to confirm these findings.     

尿激酶型纤溶酶原激活物受体及可溶性尿激酶型纤溶酶原激活物受体与炎症相关的研究进展

尿激酶型纤溶酶原激活物受体（urokinase plasminogen activator receptor,uPAR）与尿激酶型纤溶酶原激活物（urokinase plasminogen activator,uPA）同为纤溶酶原激活系统的主要成员,是一种协调多种信号转导途径的多功能分子,可溶性尿激酶型纤溶酶原激活物受体（soluble urokinase plasminogen activator receptor,suPAR）是其可溶形式。除凝血-纤溶以外,uPAR参与了肿瘤侵袭及炎症等多种疾病过程,而suPAR可能是一种良好的炎性标志物。本文就uPAR及suPAR在炎症中的作用进行简要综述。     

Cerebrospinal fluid activity of tissue plasminogen activator in patients with neurological diseases.

AIM: To study cerebrospinal fluid (CSF) activity of tissue plasminogen activator (tPA) in patients with neurological diseases. METHODS: CSF tPA and urokinase (uPA) activities were studied using an immunocapture assay and zymography in 44 patients with neurological disease and 20 reference subjects. The patient group comprised three patients with meningitis, 21 with encephalitis, nine with acute lymphoblastic (n = 7) and myeloid (n = 2) leukaemia, seven with multiple sclerosis, three with facial paresis, and one with polyradiculitis. RESULTS: Raised tPA activities were observed in patients with multiple sclerosis, leukaemia and encephalitis. In contrast, there were no differences in the mean activities of tPA in patients with meningitis or other diseases compared with the reference subjects. The highest tPA activities were found in patients with multiple sclerosis. The mean activity in patients with leukaemia was higher than in those with meningitis and polyradiculitis, but not encephalitis and facial paresis. Although the CSF tPA activity correlated positively with age in reference subjects, no correlation was observed in patients. Samples were qualitatively screened for both tPA and uPA activity by zymography and positive samples were quantitated. Some of the samples had quantifiable levels of uPA activity: three of seven multiple sclerosis samples, 10 of 21 samples from patients with encephalitis and five of nine leukaemic samples. The highest activities were recorded in patients with leukaemia. uPA was not detected in the CSF of the patients with meningitis, facial paresis or polyradiculitis. CONCLUSIONS: Plasminogen activator activity can be measured reliably in CSF and the assessment of tPA activity may be useful for studying the pathogenesis of neurological diseases.     

Decreased urokinase receptor expression on granulocytes in HIV-infected patients

Pericellular proteolysis initiated by receptor-bound urokinase-type plasminogen activator (uPA) is considered important for directed migration of granulocytes to inflammatory sites. Using flow cytometry and whole-cell binding of radiolabelled-uPA, we found a high level of uPA-receptor (uPAR) expression in granulocytes (3.9 x 104 +/- 0.9 x 104 sites/cell). Modulation of uPAR expression was assessed in the presence of chemoattractant gradients. Our findings demonstrate that interleukin (IL)-8, leukotriene B4(LTB4) and formyl-methionyl-leucyl-phenylalanine (f MLP) caused a dose-dependent upregulation of uPAR on granulocytes in healthy controls. Modulation of uPAR expression is known to regulate chemotactic response. As determined by flow cytometry, uPAR expression by granulocytes from human immunodeficiency virus (HIV)-infected patients was distinctly lower than that of healthy control cells (P < 0.001). However, upregulation of uPAR in response to chemoattractants was similar to that observed in healthy controls. In HIV-infected patients, the uPAR expression on granulocytes correlated (P < 0.001, n = 10) with the number of CD4+ blood cells. In contrast, the expression of IL-8 receptor, CD11b, CD18 and CD62 was not significantly altered in HIV-patients compared with healthy controls.