急性白血病患者IL—6,TNF—α和sIL—6R含量及其与白血病负荷的？…

应用生物学检测法，ＥＬＩＳＡ法和间接免疫荧光分析了２４例急性白血病患者外周血ＩＬ－６，ｓＩＬ－６Ｒ和ＴＮＦ－α的含量及其与白血病细胞负荷的相关性。结果显示：（１）急性白血病患者外周血ＩＬ－６，ｓＩＬ－６Ｒ及ＴＮＦ－α水平明显升高，其中急性Ｂ淋巴性白血病的ＩＬ－６，ｓＩＬ－６Ｒ急性Ｔ淋巴性白血病的ＴＮＦ－升高尤为明显；（２）Ｂ－ＡＬＬ的ＩＬ－６，ＴＮＦ－α及Ｔ－ＡＬＬ的ＴＮＦ－α水平与白血病细胞负     

IL－6和TNF对白血病细胞的调控作用及意义

通过诱导急性白血病肿瘤细胞自分泌白细胞介素６和肿瘤坏死因子，利用急性白血病原代肿瘤细胞和肿瘤细胞系ＨＬ－６０和Ｋ５６２，分别观察了ＩＬ－６和ＴＮＦα对急性白血病细胞的调控作用。结果发现，急性白血病细胞存在着ＩＬ－６和ＴＮＦα的自分泌作用，而ＴＮＦα和ＩＬ－６对白血病细胞则有诱导分化作用；进一步研究发现，ＴＮＦα对急性白血病细胞株还可呈现生长抑制作用；而ＩＬ－６则可表现为生长促进作用。ＩＬ－６和ＴＮＦα对急性白血病细胞的这种凋控在白血病的发病和免疫调控治疗中将有意义。     

IL－6和TNF对白血病细胞的调控作用及意义

通过诱导急性白血病肿瘤细胞自分泌白细胞介素６和肿瘤坏死因子，利用急性白血病原代肿瘤细胞和肿瘤细胞系ＨＬ－６０和Ｋ５６２，分别观察了ＩＬ－６和ＴＮＦα对急性白血病细胞的调控作用。结果发现，急性白血病细胞存在着ＩＬ－６和ＴＮＦα的自分泌作用，而ＴＮＦα和ＩＬ－６对白血病细胞则有诱导分化作用；进一步研究发现，ＴＮＦα对急性白血病细胞株还可呈现生长抑制作用；而ＩＬ－６则可表现为生长促进作用。ＩＬ－６和ＴＮＦα对急性白血病细胞的这种凋控在白血病的发病和免疫调控治疗中将有意义。     

急性髓细胞白血病血清IL—6,TNF—α水平的变化及意义

急性髓细胞白血病血清ＩＬ－６、ＴＮＦ－α水平的变化及意义马晓星徐军王鲁群杨道理迟翠芳（济南军区总医院免疫科，济南２５００３１）肿瘤坏死因子（ＴＮＦ）和白细胞介素６（ＩＬ－６）具有多种生物学活性。除发挥正常的生理功能外，还参与了某些肿瘤和白血病的发生、...     

1995年第2卷索引（主题词、关键词）

１９９５年第２卷索引（主题词、关键词）Ａ奥曲肽高血压，门脉胰高血糖素ＢＢ超肝病卵巢恶性肿瘤ＢＡ－ＥＬＩＳＡＴ３、Ｔ４白内障，ＳＯＤ、ＬＰＯ白血病，ＴＮＦ白血病，急性ＩＬ－６．ｓＩＬ－６Ｒ白血病，淋巴细胞性，急性糖皮质激素受体膀胱癌，ＣＥＡ（尿）表皮生...     

多发性骨髓瘤和白血病细胞中白细胞介素—6激活的核因子 …

用阻滞电泳方法检测ＩＬ－６激活的核因子,以比较在多发性骨髓瘤细胞系ＳＫＯ－００７和转染ＩＬ－６受体基因的Ｔ淋巴母细胞白血病细胞系Ｍｏｌｔ－４中ＩＬ－６信号转导的差异。结果表明,在ＳＫＯ－００７细胞中,核因子可与双链探针ＡＰＲＥ,ＳＩＥ（ｍ６７）和ＮＦ－ＩＬ－６ＲＦ结合,被激活的核因子的量与ＩＬ－６受体的水平正相关;而在转染ＩＬ－６受体基因的Ｍｏｌｔ－４细胞中,核因子只与ＡＰＲＥ和ＮＦ－ＩＬ－６ＲＥ     

烧伤病人TNF,IL—6的变化与氧自由基关系的研究

研究烧伤后ＴＮＦ、ＩＬ－６的变化与氧自由基的关系。采用酶标法检测血清ＴＮＦ和ＩＬ－６，改良八木国夫法检测血清ＭＤＡ，动态观察了烧伤病人伤后１０ｄ内血清ＴＮＦ、ＩＬ－６和ＭＤＡ的变化以及抗氧化剂对血清ＴＮＦ和ＩＬ－６的影响。结果显示烧伤病人血清ＴＮＦ、ＩＬ－６和ＭＤＡＦ均显著增高（Ｐ〈０．０１）；ＴＮＦ与ＭＤＡ的变化呈正相关（ｒ＝０．４５，Ｐ〈０．０５）；抗氧化剂可降低血清ＴＮＦ（Ｐ〈０．０５）和Ｉ     

急性T淋巴细胞白血病中Tal~d重排的结合部顺序研究

应用多聚酶链反应和ＤＮＡ测序技术，对２８例急性Ｔ急性淋巴细胞白血病（Ｔ－ＡＬＬ）患者进行ＳＩＬ－ＴＡＬ－１重排的检测和重排结合部的顺序分析。结果发现，５例有ＳＩＬ－ＴＡＬ－１融合基因，对其中４例的ＤＮＡ重排结合部分析表明均为Ｔａｌｄ１信号所介导、且存在着Ｎ顺序，证实Ｔａｌｄ１的重排是由免疫球蛋白／Ｔ细胞受体基因Ｖ－（Ｄ）－Ｊ重组酶系的错误所致，在Ｔ－ＡＬＬ的发病中具有重要的意义。     

Graves病患者治疗前后血清TNF-α和IL-6的动态变化

目的：检测Ｇｒａｖｅｓ病（ＣＤ）患者治疗前后血清白细胞介素－６（ＩＬ－６）和肿瘤坏死因子（ＴＮＦ－α）的动态变化，探讨甸子与ＣＤ发生发展之间的内在联系。方法：于治疗前和治疗后８周与２４周采集患者静脉血，分别采用放免法和超敏酶免法检测血清ＩＬ－６和ＴＮＦ－α含量。结果：ＣＤ患者血清ＩＬ－６和ＴＮＦ－α水平明显升高；应用抗 状腺药物８周和２４周甲状腺激素恢复正常后，ＩＬ－６和ＴＮＦ－α水平明显升高；应     

再生障碍性贫血患者免疫调节剂治疗前后TNF和IL—2水平变化及意义

为了探讨再生障碍性贫血（ＡＡ）的免疫发病机理及抗Ｔ淋巴细胞单克隆抗体（ＭｃＡｂ－Ｔ）的免疫调节治疗作用，采用放射免疫法检测３０例ＡＡ患者ＭｃＡｂ－Ｔ治疗前后血清肿瘤坏死因子（ＴＮＦ）和白细胞介素－２（ＩＬ－２）水平及其中１０例ＡＡ外周血核细胞（ＰＢＭＮＣ）体外诱生ＴＮＦ和ＩＬ－２水平的变化。结果表明，治疗前ＡＡ患者血清ＴＮＦ水平显著曾高（Ｐ〈０．０１），ＰＢＭＮＣ诱生的ＴＮＦ和ＩＬ－２水平均明显高     

TRAF6在抗β2GPI/β2GPI复合物诱导THP-1细胞表达组织因子时的活化

目的:探讨肿瘤坏死因子受体相关因子6(TRAF6)在抗β2 GPI/β2 GPI复合物诱导单核细胞株THP-1表达组织因子(TF)中的作用.方法:采用一定剂量抗β2 GPI/β2 GPI复合物刺激THP-1细胞一定时间,收集细胞总RNA及总蛋白,实时定量PCR检测细胞TF mRNA水平,发色底物法检测细胞TF活性;RT-qPCR及Western blot分别检测细胞TRAF6mRNA和蛋白表达情况;进一步采用蛋白酶体抑制剂MG-132,观察是否能够干预抗β2 GPI/β2 GPI复合物对细胞的刺激效应.结果:抗β2 GPI/β2 GPI复合物(100 mg/L)能够刺激THP-1细胞表达TF mRNA及活性,与对照相比差异显著(P<0.05);使细胞TRAF6 mRNA和蛋白表达均增加,并显示时间相关性,分别在刺激15 min和30 min时表达至高峰;MG-132(5μmol/L)明显抑制抗β2 GPI/β2 GPI复合物(100 mg/L)对THP-1细胞TRAF6 mRNA和蛋白的刺激效应及TF的诱导表达.结论:抗β2 GPI/β2 GPI复合物诱导THP-1细胞表达TF过程中,TRAF6被激活并发挥重要作用.     

Intraglomerular expressions of IL-1 alpha and platelet-derived growth factor (PDGF-B) mRNA in experimental immune complex-mediated glomerulonephritis.

Acute lung injury frequently develops following haemorrhage, and is characterized by increased proinflammatory cytokine levels and massive neutrophil accumulation in the lung. Blood loss produces rapid increases in tumour necrosis factor-alpha (TNF-alpha) mRNA expression among pulmonary cell populations which precede the development of lung injury. In order to examine the role of TNF-alpha in producing acute inflammatory lung injury, we treated mice following haemorrhage and resuscitation with a TNF antagonist, composed of soluble dimeric human p80 TNF receptor linked to the Fc region of human IgG1 (sTNFR:Fc). Therapy with sTNFR:Fc prevented the post-haemorrhage increases in circulating and pulmonary TNF-alpha levels normally found following blood loss. Administration of sTNFR:Fc also diminished the increase in IL-1 beta, IL-6, TNF-alpha and interferon-gamma (IFN-gamma) mRNA normally found in the lungs following haemorrhage. However, therapy with sTNFR:Fc was not associated with improvement in the histologic parameters of post-haemorrhage lung injury, such as neutrophil infiltration and interstitial oedema. In contrast to the effects of sTNFR:Fc on cytokine mRNA levels among intraparenchymal pulmonary mononuclear cells, such therapy following haemorrhage was associated with increased amounts of mRNA for TNF-alpha among peripheral blood mononuclear cells, as well as increased IFN-gamma titres in serum and bronchoalveolar lavage (BAL) specimens. These results indicate that therapy with sTNFR:Fc in the post-haemorrhage period, although capable of decreasing proinflammatory cytokine expression in the lungs, does not prevent the development of acute lung injury in this setting.     

肿瘤患者血清IL-6、TNF-α、CRP水平与凝血功能的相关性分析

目的通过探讨血清IL-6、TNF-α、CRP水平与凝血因子PT、APTT、D-D、FIB、PLT水平的变化,分析血清炎症因子与凝血指标的关系。方法选取我院2016年4月至2018年4月的肿瘤患者70例,检测血清炎症因子IL-6、TNF-α、CRP水平及凝血因子PT、APTT、D-D、FIB、PLT水平,分析肿瘤患者血清炎症因子与凝血指标的相关性。结果0期肿瘤患者血清症因子IL-6、TNF-α、CRP水平均低于Ⅰ、Ⅱ、Ⅲ期的肿瘤患者,Ⅰ期肿瘤患者血清症因子IL-6、TNF-α、CRP水平均低于Ⅱ、Ⅲ期的肿瘤患者,Ⅱ期瘤患者血清症因子IL-6、TNF-α、CRP水平均低于Ⅲ期的肿瘤患者,差异均有统计学意义(P<0.05)。0期肿瘤患者凝血因子PT、D-D、FIB水平均低于Ⅱ、Ⅲ期的肿瘤患者,0期肿瘤患者凝血因子APTT、PLT均高于Ⅰ、Ⅱ、Ⅲ期的肿瘤患者,Ⅰ期肿瘤患者凝血因子PT、D-D、FIB水平均低于Ⅲ期的肿瘤患者,Ⅰ期肿瘤患者凝血因子PT、D-D、FIB水平均高于Ⅲ期的肿瘤患者,差异均有统计学意义(P<0.05)。血清IL-6水平与凝血因子D-D、FIB水平呈正相关(P<0.05),与凝血因子APTT、PLT水平呈负相关(P<0.05);血清IL-6水平与凝血因子PT无相关(P>0.05)。血清TNF-α、CRP水平与凝血因子PT、D-D、FIB水平均呈正相关(P<0.05),与凝血因子APTT、PLT水平均呈负相关(P<0.05)。结论肿瘤患者成分输血后,凝血功能随着临床分期增加,凝血功能紊反应加剧,且血清IL-6、TNF-α、CRP与凝血功能紊乱有关。     

巨噬细胞细胞毒因子分泌调节的研究

小鼠腹腔巨噬细胞(Mφ)产生细胞毒因子(Mφ—CF),需激活和刺激两个信号。激活信号(A23187)单独不能诱导Mφ—CF,但能促进刺激信号(LPS)的诱导作用。活化的Mφ经LPS作用2小时内开始分泌Mφ—CF,8小时达(?),后逐降。对酵母多糖的吞噬伴有一定程度的Mφ—CF分泌,但吞噬乳胶颗粒则否。数株肿瘤细胞有明显的刺激Mφ—CF分泌的作用。PKc激活剂不能刺激Mφ—CF的产生。     

Purification and characterization of lipopolysaccharide induced TNF-like factor from rabbit serum

A TNF-like factor was purified from lipopolysaccharide (LPS) induced New Zealand white rabbit serum. The TNF-like factor was purified by DEAE-Sephacel, Sephacryl S-200, Mono-Q, CM-affi gel Blue, Superose 12 H/R preparative columns to the specific activity of 4×10⁶ U/mg protein. The purified protein was 45 kDa in its oligomeric form and 22 kDa in its monomeric form. Rabbit TNF-like factor had a pI value of 5.0 and was resistant to trypsin digestion. The TNF-like factor reacted with polyclonal-Ab against human TNF on immunoblot and immunoprecipitation analysis and interacted with human TNF receptors. Taken together, rabbit TNF-like factor might be a high molecular weight form of rabbit TNF.     

Factor V Leiden (R506Q) and risk of venous thromboembolism: a case-control study based on the Spanish population

Resistance to activated protein C (APC) is a frequent cause of thrombophilia. Most patients showing APC-resistance have a G to A mutation at codon 506 of the factor V that converts arginine to glutamine. This mutation is present in populations worldwide with frequencies ranging from 0.01 to 0.05. Genotyping of 150 control individuals from the Spanish population showed that 3.33% of them carried the mutation. Several studies have measured resistance to APC (following a classical functional assay) and have determined the factor V genotype in a number of thrombophilic patients, in an attempt to compare the predictive vaiue of both laboratory methods. To assess the incidence of the factor V mutation among Spanish thrombophilic patients, we genotyped 51 of these. The frequency of mutation carriers rose from 3.33% in the controls to 53% in the patients. We found significant differences for the thrombosis-free survival curves and for the age at the first thrombotic event between patients who carried or did not carry the mutation. Analysis of relatives of 16 patients who carried the factor V mutation suggests the existence of additional genes that modulate the effect of the factor V gene in the development of venous thrombosis among carriers of the G to A mutation.     

血小板第4因子(PF4)抗血管新生的机理初探

研究血小板第４因子抑制血管新生的机制。方法通过研究ＰＦ４与纤维母细胞生长因子－２及其受体间的相互作用来探讨ＰＦ４抑制血管新生的机制。结果：ＦＧＦ２与低亲和力和高亲和力位点的结合受ＰＦ４抑制，这种抑制呈浓度依赖性。５－１０μｇ／ｍｌ的ＰＦ４能量大限度地抑制ＦＧＦ２与低亲和力或高亲和力位点结合。     

中国人动脉血栓性疾病与活化蛋白C裂解FV和FVIII基因位点突变的相关性研究

目的 :检测脑血栓 (CT)和急性心肌梗死 (AMI)患者活化蛋白C(APC)抵抗 (APCR)及APC裂解凝血因子V (FV )和凝血因子VIII(FVIII)肽链的基因位点突变。方法 :用单链构象多态性分析 (SSCP)方法 ,检测 10 2例CT、46例AMI和 10 5例健康人的APC裂解FV肽链 (Arg3 0 6、Arg 5 0 6、Arg 679和结合部位 1865～ 1875 )、裂解FVIII肽链 (Arg3 3 6、Arg 5 62和结合部位 2 0 0 5～ 2 0 18)的基因位点。结果 :对照组和患者组均未检出FV的突变基因。结论 :中国人动脉血栓性疾病患者无APC裂解FV和FVIII肽链的基因突变 ,患者的APC敏感性的降低可能由其他因素所致     

血小板活化因子受体拮抗剂对实验性肾病综合征的疗效观察及机制探讨

目的:探讨血小板活化因子受体拮抗剂对实验性肾病综合征的疗效及机制。方法: 实验大鼠均复制成阿霉素(ADR)肾病模型,分为2组:ADR肾病组和ADR肾病+血小板活化因子(PAF)受体拮抗剂(BN52021)组。结果: ADR肾病+BN52021组大鼠各期尿蛋白量、血清总蛋白下降幅度、血清胆固醇上升幅度均显著低于ADR肾病组(P＜0.05),第21 d时血清肌酐含量显著低于ADR肾病组(P＜0.05);电镜下肾组织病理改变显著轻于ADR肾病组。ADR肾病组中,肾皮质PAF最大产量在14 d(先于最大蛋白尿量),而肿瘤坏死因子(TNFα)最大含量在21 d,而且, ADR肾病+BN52021组肾皮质内PAF、TNFα含量显著低于ADR肾病组。结论: PAF可能直接或间接通过刺激肾小球固有细胞(肾小球系膜细胞、上皮细胞等)产生TNF导致肾小球损伤,PAF拮抗剂可能通过抑制肾皮质内PAF、TNFα合成,而减轻肾小球损伤。     

Efficacy,Safety, and Pharmacokinetics of Beroctocog Alfa in Patients Previously Treated for Hemophilia A

Purpose

Beroctocog alfa is a second generation recombinant factor VIII manufactured by removing the B-domain from factor VIII. This prospective clinical trial was conducted to evaluate the efficacy, safety, and pharmacokinetics of beroctocog alfa in patients of ages ≥12 years previously treated for severe hemophilia A.

Materials and Methods

Seventy subjects received beroctocog alfa as an on-demand treatment for acute hemorrhage.

Results

The final hemostatic effect was excellent in 35 subjects (50%) and good in 26 subjects (37.1%). The drug showed an overall efficacy rate of 87.1%. The majority of acute hemorrhages was treated by administering the study drug once (86.2%) or twice (10.0%), and the mean dose administered per single infusion was 28.55±6.53 IU/kg. Ten subjects underwent 12 surgical procedures, and hemostatic efficacy was excellent in seven cases (58.3%) and good in five cases (41.7%), showing a 100% efficacy rate. A total of 52 of 88 subjects (59.0%) experienced 168 adverse events. There were 18 serious adverse events (10.7%) in 11 subjects, and two (mild dyspnea and facial edema) in one subject were related to the study drug. Only one subject formed a de novo factor VIII inhibitor, for an occurrence rate of 1.4% (one-sided 95% upper confidence limit: 3.85%). The final elimination half-life was 13.3 h and 12.6 h at baseline and 6 months after administration, respectively.

Conclusion

Our results suggest that beroctocog alfa is safe and efficacious as either an on-demand treatment for acute hemorrhage or a surgical prophylaxis in patients with hemophilia A.