TNF血清水平和体外细胞毒性与急性白血病分疗效果的关系

本文用双夹心ＥＬＩＳＡ法检测急性白血病患者血清ＴＮＦα，同时用体外细胞毒试验检测重组人肿瘤坏死因子对白血病原代细胞活性，并与带路临床化疗效果比较。结果显示：急性白血病患者血清ＴＮＦ水平显著高于正常对照组，但不预示白血病的化疗效果；ｒｈＴＮＦα对白血病细胞活性缓解组高于未缓解组，与患者临床化疗效果密切相关。     

TNF血清水平和体外细胞毒性与急性白血病化疗效果的关系

本文用双夹心ＥＬＩＳＡ法检测急性白血病患者血清ＴＮＦａ，同时用体外细胞毒试验（ＭＴＴ法）检测重组人肿瘤坏死因子（ｒｈＴＮＦａ）对白血病原代细胞毒活性，并与患者临床化疗效果比较。结果显示：急性白血病患者血清ＴＮＦ水平显著高于正常对照组，但不预示白血病的化疗效果；ｒｈＴＮＦａ对白血病细胞毒活性缓解组高于未缓解组，与患者临床化疗效果密切相关。提示这种试验可能有临床价值。     

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、...     

急性白血病患者血浆肿瘤坏死因子及抑制物

利用ＴＮＦ细胞毒生物学活性检测法和ＴＮＦ抑制物生物活性检测法，检测２２例初治急性白血病体内ＴＮＦ和ＴＮＦＩＮＨ水平。急性白血病患血浆ＴＮＦ水平明显增高。达１１．４２±６．０２ｕ／ｍｌ。抗人ＴＮＦａ单抗能完全中和Ｍ４，Ｍ５，Ｍ６型急性非淋巴细胞白血病患血浆ＴＮＦ活性。部分患血浆中同时存在ＴＮＦ和ＴＮＦＩＮＨ。ＴＮＦ阴性的患血浆中亦单独存在ＴＮＦＩＮＨ活性，和正常人相比明显增高，其对ｔｈＴＮＦ     

胸腺因子D对白血病IL-6和TNF的调控作用

探讨胸腺因子Ｄ（ＴＦＤ）对白血病患者白介素６（ＩＬ－６）和肿瘤坏死因子（ＴＮＦ）的调控作用,以便在白血病治疗中正确使用ＴＦＤ。在白血病化疗同时,加用ＴＦＤ５０ｍｇ＋１０％葡萄糖注射液５００ｍｌ,ＶＤ,ｑｄ×３ｍｏｎ,检测治疗前后ＩＬ－６活性和ＴＮＦ水平。结果：急性淋巴细胞性白血病（ＡＬＬ）和急性非淋巴细胞白血病（ＡＮＬＬ）的ＩＬ－６和ＴＮＦ均比正常对照组高（Ｐ＜０．０１）。化疗加用ＴＦＤ治疗后,ＡＬＬ的ＩＬ－６和ＴＮＦ及ＡＮＬＬ的ＴＮＦ均比治疗前和化疗组显著降低。ＴＦＤ加化疗药物联合应用,可能是白血病的有效治疗方法。     

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。     

急性肾小球肾炎不同病中TNF和sTNFR的变化

大量文献[1] 已经证明ＴＮＦ α在肾脏疾病中是一种重要的炎性因子 ,而ｓＴＮＦＲ通过竟争性结合ＴＮＦ可阻断ＴＮＦ与膜受体的结合 ,从而限制其生物学活性 ,对疾病的良性转归具有一定意义 ,本文探讨了儿童急性肾小球肾炎 (ＡＧＮ )中ＴＮＦ α及ｓＴＮＦＲ水平的变化。1　对象和方法1 1　临床观察对象　临床确诊的ＡＧＮ患儿 2 6例 ,急性发作期均在住院 2ｄ内静脉取血 ,恢复期 15例 ,于出院前取血 ,分离血清冻存待测。正常对照组 2 0例 ,年龄、性别与患者有可比性。1 2　测定方法　ＴＮＦ α采用ＲＩＡ法 ,单位ｎｇ/Ｌ ,试剂盒为北京北方所…     

TNF抗瘤特性

肿瘤坏死因子是一种重要的免疫调节因子，具有较强的抗肿瘤效应、非种属特异性与时相特异性，对不同谱系肿瘤细胞的细胞毒作用存在敏感性差异。ＴＮＦ抗肿瘤效应是通过多途径的综合机制发挥作用的。其中，转ＴＮＦ基因在体内的表达呈现旁分泌效应的局部抗瘤特性而发挥强效抗癌作用。免疫效应细胞及大多数细胞因子与ＴＮＦ具有协同抗肿瘤效应，而效应细胞产生的内源性ＴＮＦ能增强其自身的抗肿瘤效应     

Autologous Is Superior to Allogeneic Hematopoietic Cell Transplantation for Acute Promyelocytic Leukemia in Second Complete Remission

To identify favored choice of transplantation in patients with acute promyelocytic leukemia (APL) in second complete remission, we studied 294 patients with APL in second complete remission (CR2) receiving allogeneic (n = 232) or autologous (n = 62) hematopoietic cell transplantation (HCT) reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR) from 1995 to 2006, including 155 with pre-HCT PML/RAR∝ status (49% of allogeneic and 66% of autologous). Patient characteristics and transplantation characteristics, including treatment-related mortality, overall survival (OS), and disease-free survival, were collected and analyzed for both univariate and multivariate outcomes. With median follow-up of 115 (allogeneic) and 72 months (autologous), 5-year disease-free survival (DFS) favored autologous with 63% (49% to 75%), compared with allogeneic at 50% (44% to 57%) (P = .10). OS was 75% (63% to 85%) versus 54% (48% to 61%) (P = .002), for autologous and allogeneic transplantation, respectively. Multivariate analysis showed significantly worse DFS after allogeneic HCT (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.16 to 3.06; P = .011) and age > 40 years (HR, 2.30; 95% CI, 1.44 to 3.67; P = .0005). OS was significantly worse after allogeneic HCT (HR, 2.66; 95% CI, 1.52 to 4.65; P = .0006); age > 40 (HR, 3.29; 95% CI, 1.95 to 5.54; P < .001), and first complete remission < 12 months (HR, 1.56; 95% CI, 1.07 to 2.26; P = .021). Positive pre-HCT PML-RAR∝ status in 17 of 114 allogeneic and 6 of 41 receiving autologous transplantation did not influence relapse, treatment failure, or survival in either group. The survival advantage for autografting was attributable to increased treatment-related mortality (TRM) in the allogeneic group of 30% compared to 2% in the autologous group, in addition to the added mortality associated with GVHD. We conclude that autologous HCT yields superior OS for APL in CR2. Long-term DFS in autologous recipients, even with minimal residual disease–positive grafts, remains an important subject for further study.     

一种高活性人新型TNF的研制

肿瘤坏死因子（ＴＮＦ）除抗肿瘤活性外，还具有其它广泛的生物学活性，但因其严重的毒副作用极大地限制了它的临床应用。在ＴＮＰ结构与功能关系研究的基础上，该文作者利用ＰＣＲ技术构建了一种新型人ＴＮＦ的编码基因，并使其在大肠杆菌中进行了高效表达。活性测定结果表明，新型ＴＮＦ对Ｌ９２９细胞的细胞毒活性较天然型人ＴＮＰ增高了约７１４倍。     

In vivo evidence for a functional role of both tumor necrosis factor (TNF) receptors and transmembrane TNF in experimental hepatitis

The significance of tumor necrosis factor receptor 1 (TNFR1) for TNF function in vivo is well documented, whereas the role of TNFR2 so far remains obscure. In a model of concanavalin A (Con A)-induced, CD4⁺ T cell-dependent experimental hepatitis in mice, in which TNF is a central mediator of apoptotic and necrotic liver damage, we now provide evidence for an essential in vivo function of TNFR2 in this pathophysiological process. We demonstrate that a cooperation of TNFR1 and TNFR2 is required for hepatotoxicity as mice deficient of either receptor were resistant against Con A. A significant role of TNFR2 for Con A-induced hepatitis is also shown by the enhanced sensitivity of transgenic mice overexpressing the human TNFR2. The ligand for cytotoxic signaling via both TNF receptors is the precursor of soluble TNF, i.e. transmembrane TNF. Indeed, transmembrane TNF is sufficient to mediate hepatic damage, as transgenic mice deficient in wild-type soluble TNF but expressing a mutated nonsecretable form of TNF developed inflammatory liver disease.     

Origin and evolution of TNF and TNF receptor superfamilies

The tumor necrosis factor superfamily (TNFSF) and the TNF receptor superfamily (TNFRSF) have an ancient evolutionary origin that can be traced back to single copy genes within Arthropods. In humans, 18 TNFSF and 29 TNFRSF genes have been identified. Evolutionary models account for the increase in gene number primarily through multiple whole genome duplication events as well as by lineage and/or species-specific tandem duplication and translocation. The identification and functional analyses of teleost ligands and receptors provide insight into the critical transition between invertebrates and higher vertebrates. Bioinformatic analyses of fish genomes and EST datasets identify 14 distinct ligand groups, some of which are novel to teleosts, while to date, only limited numbers of receptors have been characterized in fish. The most studied ligand is TNF of which teleost species possess between 1 and 3 copies as well as a receptor similar to TNFR1. Functional studies using zebrafish indicate a conserved role of this ligand-receptor system in the regulation of cell survival and resistance to infectious disease. The increasing interest and use of TNFSF and TNFRSF modulators in human and animal medicine underscores the need to understand the evolutionary origins as well as conserved and novel functions of these biologically important molecules.     

Crucial role of tumor necrosis factor (TNF) receptor 2 and membrane-bound TNF in experimental cerebral malaria

Tumor necrosis factor (TNF) has been implicated in the pathogenesis of experimental cerebral malaria (CM), but the respective role of its two types of receptors has not been established. A significant increase in the expression of TNF-receptor 2 (TNFR2, p75), but not of TNFR1 (p55), was found on brain microvessels at the time of CM in susceptible animals. Moreover, mice genetically deficient for TNFR2 (Tnfr2°) were significantly protected from experimental CM, in contrast to TNFR1-deficient (Tnfr1°) mice, which were as susceptible as wild-type mice. To identify the factors involved in the protection from CM conferred by the lack of TNFR2, we assessed in both knockout and control mice the serum concentrations of mediators that are critical for the development of CM, as well as the up-regulation of intercellular adhesion molecule-1 (ICAM-1) in the brain microvessels. No significant difference in serum levels of TNF and interferon-γ was found between infected wild-type and Tnfr1° or Tnfr2° mice. Interestingly, the pronounced ICAM-1 up-regulation and leukocyte sequestration, typically occurring in brain microvessels of CM-susceptible animals, was detected in infected control and Tnfr1° mice – both of which developed CM – whereas no such ICAM-1 up-regulation or leukocyte sequestration was observed in Tnfr2° mice, which were protected from CM. Making use of microvascular endothelium cells (MVEC) isolated from wild-type, Tnfr1° or Tnfr2° mice, we show that soluble TNF requires the presence of both TNF receptors, whereas membrane-bound TNF only needs TNFR2 for TNF-mediated ICAM-1 up-regulation in brain MVEC. Thus, only in MVEC lacking TNFR2, neither membrane-bound nor soluble TNF cause the up-regulation of ICAM-1 in vitro. In conclusion, these results indicate that the interaction between membrane TNF and TNFR2 is crucial in the development of this neurological syndrome.     

不同剂量内毒素刺激枯否细胞分泌肿瘤坏死因子-α及内皮素-1的体外观察

目的:探讨体外脂多糖(LPS)刺激枯否细胞(KC)分泌肿瘤坏死因子-α(TNF-α)及内皮素-1(ET-1)的作用。方法:采用大鼠肝KC分离与培养技术,动态观察LPS刺激KC分泌TNF-α和ET-1的作用。结果:LPS具有明显活化KC作用,在一定LPS浓度范围内对KC分泌的TNF-α及ET-1有促进作用。结论:LPS可促进体外培养的KC分泌TNF-α及ET-1,这可能与内毒素血症导致的肝损伤有关。     

Control of established experimental allergic encephalomyelitis by inhibition of tumor necrosis factor (TNF) activity within the central nervous system using monoclonal antibodies and TNF receptor-immunoglobulin fusion proteins

Tumor necrosis factor (TNF) activity was inhibited during the development of actively-induced, chronic relapsing experimental allergic encephalomyelitis (CREAE) in Biozzi AB/H mice, using a mouse TNF-specific (TN3.19.12) antibody and bivalent human p55 and p75 TNF receptor-immunoglobulin (TNFR-Ig) fusion proteins. The development of disease could be inhibited when repeated doses of antibody were administered prior to the anticipated onset. It has now also been shown that a therapeutic effect is evident even when antibody is administered after the onset of clinical signs, further indicating an important role for TNF in pathogenic effector mechanisms in CREAE. Although biologically-active TNF was not detected in the circulation, TNF-α was detected in lesions within the central nervous system (CNS). This suggested that the CNS may be the main site for TNF-specific immunomodulation and was supported by the observation that intracranial injection was significantly more potent than that administered systemically, for both antibody and TNFR-Ig fusion proteins. The fusion proteins were as effective as antibody at doses 10—100-fold lower than that used for antibody, reflecting their higher neutralizing capacity in vitro. Although treatment was not curative and relapse inevitably occurred in this model if treatment was not sustained, the data indicate that anti-TNF immunotherapy, especially within the CNS, can inhibit CREAE and may, therefore, be useful in the control of human neuroimmunological diseases.     

D-二聚体测定与急性早幼粒细胞白血病

目的探讨D -二聚体含量与急性早幼粒细胞白血病(APL)经全反式维甲酸(ATRA)治疗前后弥漫性血管内凝血(DIC)发生率的关系及意义。方法应用ELISA法检测21例APL患者(包括7例合并DIC患者)发病时及应用ATRA治疗后D -二聚体水平的变化 ,并与正常对照组比较。结果21例APL患者治疗前血浆D -二聚体水平(2.38±0.98)mg/L较正常对照组(0.25±0.09)mg/L明显升高(P<0.01) ,其中7/21例并发DIC者(2.52±0.12)mg/L明显高于14/21例不并发DIC者 ,(2.18±0.96)mg/L。结论APL患者D -二聚体检测值随维甲酸治疗逐渐降低 ,并可预测ATRA治疗过程中DIC变化及预后     

2型糖尿病患者血清肿瘤坏死因子和唾液酸检测的临床意义

分别应用放射免疫分析法和分光光度计法检测了 35名正常人和 82例 2型糖尿病患者血清中肿瘤坏死因子 (TNF)和唾液酸 (SA)含量。结果表明 :2型糖尿病患者无肾病组和伴有肾病组血清中TNF和SA含量均非常显著地高于正常人 ,尤以伴有肾病组为甚 (P <0 .0 0 1)。这说明 2型糖尿病患者血清中TNF和SA含量与疾病的发生和发展密切相关