各型乙型肝炎患者血清sIL-2R、IFN-γ和IL-l变化的研究

目的:探讨各型乙型肝炎患者血清sIL-2R、IFN-γ和IL-l变化及其临床意义。方法:收集急性肝炎、慢性肝炎、慢性重型肝炙和活动性肝硬变患者血清标本各16份,16例健康人血清标本作为正常对照组,采用酶联免疫吸附试验(ELISA)检测各型乙型肝炎患者血清中sIL-2R和IFN-γ水平,采用MTT法检测各型乙型肝炎患者血清中IL-1水平,并与正常对照组进行比较。结果:急性肝炎患者血清sIL-2R、IFN-γ和IL-1水平均明显升高(P<0.01);慢性肝炎患者血清sIL-2R水平升高(P<0.05),IFN-γ水平无明显变化,IL-1水平稍降低;慢性重型肝炎患者血清sIL-2R和IFN-γ水平升高(P<0.05 and P<0.01 respectiveIy).但IL-1水平降低;活动性肝硬变患者血清sIL-2R和IFN-γ水平明显升高(P<0.01),但IL-1水平无明显变化。结论:血清sIL-2R、IFN-γ和IL-1参与各型乙型肝炎的发病机制,调整血清中细胞因子含量可能有助于乙型肝炎的治疗。     

血清可溶性IL-2受体测定在急慢性肝脏疾病中的意义

目的 探讨急慢性肝病可溶性白介素2受体的改变,为诊断病情演变和预后判定寻找可靠的依据。 方法 健康对照(n=30)研究,采用夹心酶联免疫吸附法测定173例各型肝病患者血清IL-2受体(sIL-2R)水平,包括急性病毒性肝炎80例,慢性乙型肝炎21例,肝炎后肝硬化35例和原发性肝癌37例,并对测定结果进行分析。 结果 各组患者血清sIL-2R均明显高于对照组(P<0.01),其中急性病毒性肝炎黄疸期血清sIL-2R明显高于恢复期(P<0.01),各型急性肝炎之间血清sIL-2R无显著差异(P>0.05);急性肝炎组明显高于慢性肝炎组(P<0.01);慢性乙型肝炎ALT异常组血清sIL-2R明显高于ALT正常组(P<0.01);Child's C级肝炎后肝硬化者明显高于CHild'B,A级者(P<0.01);原发性肝癌者血清sIL-2R水平与肿瘤体积大小有关(P<0.05)。 结论 急慢性肝病患者血清sIL-2R水平均明显增高,其水平的高低在一定程度上反映了机体免疫功能状态和肝细胞损伤的程度。     

细胞因子与乙型肝炎慢性化的关系

探讨乙型肝炎慢性化过程中细胞因子所起的作用。对 10 0例慢乙肝患者及 15例正常人群检测了血清TNF、IL - 2R、IL - 6、IL - 8、及HBVDNA定量等项指标。与对照组比较 ,各型慢乙肝患者血清TNF、IL - 2R、IL - 6、IL- 8含量均有不同程度升高 ,重度 >中度 >轻度。HBVDNA复制水平与血清TNF、IL - 2R、IL - 6水平及病程与血清TNF、IL - 2R、IL - 6、IL - 8水平均呈正相关。慢乙肝患者血清TNF、IL - 2R、IL - 6和IL - 8水平能够反映肝细胞损害的程度 ,在乙肝慢性化过程中 ,均不同程度发挥了作用     

慢性乙型肝炎患者血清IL-18水平与HBV DNA含量的关系

目的检测慢性乙型肝炎（CHB）患者血清IL-18与HBV DNA含量,探讨乙型肝炎慢性化的机理,为慢性乙型肝炎的治疗提供依据。方法分离97例CHB临床血清标本,用双抗体夹心ELISA法检测血清IL-18水平;用核酸荧光定量聚合酶链反应测HBV DNA含量;以30位健康献血者的血清为对照。结果结果与正常对照相比,CHB患者IL-18水平明显升高（P〈0.05）,lL-18水平在HBV DNA阳性各组间无显著差异。结论血清lL-18与CHB的疾病过程相关,与HBV DNA含量无关。     

大肠癌患者血清中sIL-2R、IL-8水平变化及其意义

目的:探讨sIL-2R、IL-8在大肠癌患者术前术后血清中表达及临床意义.方法:双抗体夹心ELISA法检测28例大肠癌患者的sIL-2R、IL-8血清水平;并同时检测大肠息肉患者17例和健康人25例作为对照组.结果:大肠癌患者血清中sIL-2R、IL-8含量明显高于对照组以及大肠息肉组(180.1±83.22VS 61.3±12.12,52.3±11.21;3.09±0.21 VS 2.49±0.19,2-33±0.18,均P＜0.001),手术后显著下降,其中根治组下降显著(80.2±40.31VS 114.1±72.3,2.53±0.15 VS 2.81±0.17,均P＜0.01),姑息组亦有所下降(242.1±60.3 V5 319.84±67.3,2.77±0.20 VS 3.67±0.19;均P＜0.05).大肠癌患者血清slL-2R、IL-8变化与分化程度呈正相关.结论:动态监测sIL-2R、IL-8的血清表达量有助于临床进行疗效评价,判断大肠癌患者的预后.     

外周血T细胞亚群及sIL-2R水平与HBV前C区变异相关性研究

目的:探讨慢性乙型肝炎患者HBV前C区变异与宿主免疫之间的关系.方法:采用msPCR法检测102例慢性乙型肝炎患者血清HBV Pre-C变异,并用APAAP法检测T细胞亚群改变,用双抗体夹心ELISA法检测血清sIL-2R水平.结果:在102例HBV DNA阳性CHB患者中HBV Pre-C1 896变异检出率达64%(65/102).变异株组及野生株组外周血CD4、CD4/CD8比值明显下降;CD8明显增高,与正常对照组比较差异均具显著性意义(P＜0.01).变异株组CD4、CD4/CD8比值显著低于野生株组(P＜0.05);而CD8显著高于野生株组(P＜0.01).变异株组sIL-2R水平均显著高于野生株组(P＜0.01),两组水平均显著高于正常对照组(P＜0.01).结论:变异株组较野生株组存在更为严重的免疫紊乱,并通过多种途径激活宿主免疫,导致肝损伤.     

膦甲酸钠抗乙肝病毒疗效与血清IL—2、TNF—α变化的关系

目的探讨慢性乙型肝炎(CHB)患者采用膦甲酸钠(PFA)抗病毒治疗前、中、后血清白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)水平的变化与HBeAg、HBV DNA定量变化的关系及PFA对机体的免疫调节作用.方法选择慢性乙型肝炎患者30例,给予膦甲酸钠注射液2.4g/次静滴,Bid,疗程28d,收集治疗前、中、后血清标本,采用FQ-PCR法(荧光定量PCR)检测HBV DNA含量、双抗体放射免疫法测定血清IL-2水平及顺序饱和法测定TNF-α水平.结果14/30(46.7%)例患者治疗结束后HBV DNA、HBeAg阴转,ALT复常,为应答组;16/30(53.3%)例患者上述指标无变化.为无应答组.应答组(14例)治疗前、中、后HBV DNA定量分别为4.52士1.14、3.40±1.20和0 QTY/μl(对数值);而无应答组(16例)分别为4.43士1.29、4.12士1.02和3.83±1.06 QTY/μl.治疗中期有8例HBV DNA阴转,阴转率为26.7%(8/30),其中4例HBeAg阴转,阴转率为13.3%(4/30),治疗结束后14例HBVDNA阴转的病例中10例HBeAg阴转,占33.3%(10/30).无论是应答组还是无应答组,治疗前血清IL-2及TNF-α水平均较正常组为高(P＜0.05).在治疗过程中,应答组IL-2及TNF-α有所上升,无应答组IL-2及TNF-α有所下降,但经统计分析P＞0.05,均无明显临床意义.结论膦甲酸钠具有明显抑制乙肝病毒复制的作用,但短期内无明显的免疫调节作用.     

慢性乙型肝炎患者白细胞介素-18、转化生长因子-β1、HBV DNA与肝脏损伤的关系

目的 探讨慢性乙型肝炎(CHB)患者外周血IL-18、转化生长因子(TGF)-β1、HBVDNA与肝功能损伤及肝纤维化发生发展的关系.方法 67例慢性乙型肝炎患者作为实验组,20例健康体检者作为健康对照组.双抗体夹心ELISA法及荧光定量PCR法检测外周血IL-18、TGF-β1和HBV DNA.48例患者行肝穿刺组织学检查.统计学处理采用方差分析,对方差不齐者采用秩和检验;各指标相关性采用偏相关分析.结果 乙型肝炎轻、中、重度及肝炎肝硬化组血清TGF-β1、IL-18及ALT、Tbil水平均不同程度高于健康对照组(P<0.01),IL-18、TGF-β1水平随CHB程度加重逐渐升高,TGF-β1各组间差异均有统计学意义(P<0.01),尤以肝硬化组升高显著.高病毒量组与低病毒量组ALT、Tbil比较差异无统计学意义.但与对照组比较差异均有统计学意义(F=10.970,F=7.528;F=14.698,F=13.395;均P<0.05);TGF-β1水平随纤维化分期SO～4逐步升高,除S3与S4比较无差异外,其余两两比较差异有统计学意义(P<0.01或P<0.05).IL-18仅S1期与其他各期有差异,HBV DNA在各期间均差异无统计学意义;偏相关性分析显示IL-18与ALT、Tbil呈正相关(r=0.480 6,r=0.5047,P<0.01),HBV DNA与lL-18、TGF-β1、ALT、Tbil无相关性.结论 血清IL-18、TGF-β1水平可作为判断肝脏损伤严重程度的指标.血清TGF-β1与肝炎肝硬化的程度密切相关.HBV DNA与肝脏损伤及纤维化关系不大.     

继发型肺结核患者多项血清检测的临床意义

目的研究血清白介素1(IL-1)、可溶性白介素2受体(sIL-2R)和白介素10(IL-10)的检测在继发型肺结核患者的临床意义。方法采用酶联免疫方法(ELISA)检测71例继发型肺结核患者和21例对照组血清中IL-1、sIL-2R、IL-10的水平变化。结果与对照组相比较,继发型肺结核组血清中sIL-2R的含量明显升高(P0.01),而IL-1和IL-10的含量无明显变化(P0.05)。进一步分析结果显示,继发型肺结核组血清中sIL-2R的含量与抗酸杆菌的数量有关(P0.05),IL-10的含量在有空洞的继发型肺结核患者血清中明显升高(P0.05)。结论血清sIL-2R和IL-10可作为继发型肺结核感染、恶性程度诊断的主要指标,具有重要的研究价值。     

定量PCR对乙型肝炎患者血清HBVDNA的测定与分析

目的:观察各类型乙型肝炎患者血清HBV DNA复制水平及其与临床病情、乙肝血清学诊断标志变化的关系。方法:应用美国Brotronics公司的一种新型定量PCR HBV DNA检测法测定85例乙肝患者血清HBV DNA。利用荧光素标记引物在扩增过程中能量转换的原理对模板DNA进行定量检测,由计算机自动控制和分析。结果:85例乙型肝炎患者HBV DNA检出率94.1％。63例CHB与LC患者中,HBeAg阳性与抗HBe阳性病例均表现较高的HBV DNA复制水平。7例AH与3例SH乙肝血清学诊断标志不典型,但也表现一定HBV DNA水平。血清ALT的异常变化与HBV DNA复制水平无显著相关性。结论:定量HBV DNA PCR法具有很高灵敏度和特异性,定量PCR测定HBV DNA优于斑点杂交法。     

Classification and characterization of hereditary types 2A, 2B, 2C, 2D, 2E, 2M, 2N, and 2U (unclassifiable) von Willebrand disease.

All variants of type 2 von Willebrand disease (VWD) patients, except 2N, show a defective von Willebrand factor (VWF) protein (on cross immunoelectrophoresis or multimeric analysis), decreased ratios for VWF:RCo/Ag and VWF:CB/Ag and prolonged bleeding time. The bleeding time is normal and FVIII:C levels are clearly lower than VWF:Ag in type 2N VWD. High resolution multimeric analysis of VWF in plasma demonstrates that proteolysis of VWF is increased in type 2A and 2B VWD with increased triplet structure of each visuable band (not present in types 2M and 2U), and that proteolysis of VWF is minimal in type 2C, 2D, and 2E variants that show aberrant multimeric structure of individual oligomers. VWD 2B differs from 2A by normal VWF in platelets, and increased ristocetine-induced platelet aggregation (RIPA). RIPA, which very likely reflects the VWF content of platelets, is normal in mild, decreased in moderate, and absent in severe type 2A VWD. RIPA is decreased or absent in 2M, 2U, 2C, and 2D, variable in 2E, and normal in 2N. VWD 2M is usually mild and characterized by decreased VWF:RCo and RIPA, a normal or near normal VWF multimeric pattern in a low resolution agarose gel. VWD 2A-like or unclassifiable (2U) is distinct from 2A and 2B and typically featured by low VWF:RCo and RIPA with the relative lack of high large VWF multimers. VWD type 2C is recessive and shows a characteristic multimeric pattern with a lack of high molecular weight multimers, the presence of one single-banded multimers instead of triplets caused by homozygosity or double hereozygosity for a mutation in the multimerization part of VWF gene. Autosomal dominant type 2D is rare and characterized by the lack of high molecular weight multimers and the presence of a characteristic intervening subband between individual oligimers due to mutation in the dimerization part of the VWF gene. In VWD type 2E, the large VWF multimers are missing and the pattern of the individual multimers shows only one clearly identifiable band, and there is no intervening band and no marked increase in the smallest oligomer. 2E appears to be less well defined, is usually autosomal dominant, and accounts for about one third of patients with 2A in a large cohort of VWD patients.     

SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer

AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients. METHODS: One hundred and fifty-six CRC patientswere followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was performed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics anal...     

Hemodynamic, renal, and steroidogenic actions of prostaglandins E1, E2, A2, and F2 alpha in European eels

Seawater-adapted eels were implanted with both venous and arterial cannulae and catheterised. Prostaglandin in 0.9% glucose saline was given either by 10 microliters injection or by infusion (40 ng/min) while blood pressure recordings and blood samples were taken from the dorsal aorta. Glomerular filtration rates were calculated from the clearance of [3H]inulin, renal plasma flow from the clearance of PAH, and functional tubular mass from measurements of glucose reabsorption maxima (TmG). Cortisol levels were measured by radioimmunoassay. Injections of prostaglandin E1, E2, and A2 (0.01-10 ng/kg body wt) induced transient reductions in dorsal aortic blood pressure whilst concentrations of between 10 and 100 ng/kg body wt caused both prolonged vasodepression and glomerular antidiuresis, with decreased TmG and CPAH. Fractional excretion of electrolytes remained unchanged. Doses of 10-50 micrograms/kg body wt caused an initial glomerular diuresis, increased TmG and CPAH but were without effect on the fractional excretion of the filtered load. This diuretic action was followed by a longer period of antidiuresis. The vasodepression during 24 hr prostaglandin infusion became less severe after an initial 2-hr period, indicating a degree of tachyphylaxis. Prostaglandin F2 alpha in doses of 10-50 micrograms/kg body wt was slightly vasopressor but with no obvious effect on kidney function. All prostaglandins so far used, given either by infusion or injection caused a significant increase in cortisol production. These results suggest that prostaglandins may play similar roles throughout a range of vertebrates.     

TET2, ASXL1, IDH1, IDH2, and c-CBL genes in JAK2- and MPL-negative myeloproliferative neoplasms

Mutations in the TET2 and ASXL1 genes have been described in approximately 14% and 8% of patients, respectively, with classic myeloproliferative neoplasms (MPN), but their role as possible new diagnostic molecular markers is still inconclusive. In addition, other genes such as IDH1, IDH2, and c-CBL have also been reported in several myeloid neoplasms. We have studied the mutational status of TET2 (complete coding region), ASXL1 (exon12), IDH1 (R132), IDH2 (R140 and R172), and c-CBL (exons 8 and 9) in 62 MPN patients (52 essential thrombocythemia (ET), five polycythemia vera (PV), and five primary myelofibrosis (PMF)) negative for both JAK2 (V617F and exon 12) and MPL (exon 10) mutations. Pathogenic alterations in the TET2 gene were detected in three out 52 ET cases (4.8%). ASXL1 gene pathogenic mutations were also detected in three cases (two ET and one PMF). One ET patient harbored, simultaneously, one TET2 and one ASXL1 mutations. Mutations in the TET2 and ASXL1 genes showed no association with the JAK2 46/1 haplotype. Analysis of a JAK2V617F-positive cohort of 50 ET patients showed no mutations in either the TET2 or ASXL1 genes. Regarding IDH1, IDH2, and c-CBL genes, no mutations were found in any patient. In conclusion, TET2 and ASXL1 pathogenic mutations are found in 8% of MPN lacking JAK2 and MPL mutations, whereas IDH1, IDH2, and c-CBL mutations are not detected in this subset of patients.     

CO2, not HCO3-, facilitates oxidations by Cu,Zn superoxide dismutase plus H2O2

The Cu,Zn superoxide dismutase catalyzes HCO(3)(-) -dependent oxidations by H(2)O(2). This activity has been shown to depend on the creation of a bound oxidant at the Cu(II) by interactions with H(2)O(2). The bound oxidant was then thought to oxidize HCO(3)(-) to CO(3)(.-), which diffuses into the bulk solution and there oxidizes diverse substrates. We now find that CO(2) rather than HCO(3)(-) facilitates the peroxidations catalyzed by Cu,Zn superoxide dismutase. This fact was shown by a lag in the rate of peroxidation of NADPH when NaHCO(3)(-) was added last and by a burst in the rate when aqueous CO(2) was added last. Both the lag and the burst were eliminated by carbonic anhydrase.     

Vaccine news,March 2, 2000

Much is happening to accelerate development of vaccines, especially for AIDS, tuberculosis and malaria. Major initiatives were announced at a meeting of the President's Millennium Vaccine Initiative, March 2 at the White House.