Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

BACKGROUND. The identification and treatment of individuals with tuberculosis (TB) is a global public health priority. Accurate diagnosis of pulmonary active TB (ATB) disease remains challenging and relies on extensive medical evaluation and detection of Mycobacterium tuberculosis (Mtb) in the patient’s sputum. Further, the response to treatment is monitored by sputum culture conversion, which takes several weeks for results. Here, we sought to identify blood-based host biomarkers associated with ATB and hypothesized that immune activation markers on Mtb-specific CD4⁺ T cells would be associated with Mtb load in vivo and could thus provide a gauge of Mtb infection.METHODS. Using polychromatic flow cytometry, we evaluated the expression of immune activation markers on Mtb-specific CD4⁺ T cells from individuals with asymptomatic latent Mtb infection (LTBI) and ATB as well as from ATB patients undergoing anti-TB treatment.RESULTS. Frequencies of Mtb-specific IFN-γ⁺CD4⁺ T cells that expressed immune activation markers CD38 and HLA-DR as well as intracellular proliferation marker Ki-67 were substantially higher in subjects with ATB compared with those with LTBI. These markers accurately classified ATB and LTBI status, with cutoff values of 18%, 60%, and 5% for CD38⁺IFN-γ⁺, HLA-DR⁺IFN-γ⁺, and Ki-67⁺IFN-γ⁺, respectively, with 100% specificity and greater than 96% sensitivity. These markers also distinguished individuals with untreated ATB from those who had successfully completed anti-TB treatment and correlated with decreasing mycobacterial loads during treatment.CONCLUSION. We have identified host blood-based biomarkers on Mtb-specific CD4⁺ T cells that discriminate between ATB and LTBI and provide a set of tools for monitoring treatment response and cure.TRIAL REGISTRATION. Registration is not required for observational studies.FUNDING. This study was funded by Emory University, the NIH, and the Yerkes National Primate Center.     

异丙酚和异氟醚对非体外循环搭桥术患者围术期细胞因子的影响

目的:研究异丙酚和异氟醚对非体外循环搭桥术患者围术期炎性与抗炎性细胞因子平衡的影响。方法:择期非体外循环搭桥患者50例,随机分为2组。异丙酚组微量泵输入剂量为4～6mg·kg-·1h-1,异氟醚组吸入浓度为1%～1.5%。检测诱导前、打开心包、旁路血管开放30min,术后2h、24h血清白细胞介素6(IL-6)、白细胞介素10(IL-10)和肿瘤坏死因子α(TNF-α)的浓度。结果:2组患者旁路血管开放后IL-6浓度较术前升高(P<0.01),术后2h达高峰;术后2h异氟醚组高于异丙酚组(P<0.05)。IL-10浓度变化趋势与IL-6相似,旁路血管开放后、术后2h和24h异丙酚组高于异氟醚组(P<0.05)。2组患者TNF-α水平均无显著变化。结论:异丙酚麻醉促进IL-10的产生,抑制IL-6的产生,控制术中应激反应异丙酚优于异氟醚。     

同种异体骨支撑架微创治疗股骨头坏死的临床研究

目的应用改良髓芯减压术结合同种异体骨支撑架加自体骨和脱钙骨基质（decalcified bone matrix，DBM）治疗早期股骨头坏死，探索早期股骨头坏死的微创治疗方法。方法2004年1月～2005年4月，23例24个髋关节采用经大转子下通过股骨颈钻隧道至股骨头骨坏死区，将装有自体松质骨和DBM的同种异体骨支撑架经隧道拧入骨坏死区直至软骨下骨约5mm处，隧道远端用自体髂骨填塞。观察手术前后Harris评分变化、x线影像学表现及是否需进一步治疗。结果本组所有患者均获得随访，平均随访19（12—27）个月，以最后一次随访资料作为最终评价依据。Harris评分，术前优良率为43．5％（10／23）。术后优良率为91．3％（21／23）。22侧髋关节影像学表现保持稳定，无明显并发症发生。结论同种异体骨支撑架植入结合自体松质骨和DBM治疗成人股骨头坏死，增加了股骨头负重区软骨下骨的机械支撑，成骨作用强，有利于股骨头坏死的修复与重建，同时，不破坏患者股骨头本身的血液供应，创伤小，操作简单，值得临床推广使用。     

Association between cord blood IgE and genetic polymorphisms of interleukin-4, the β-subunit of the high-affinity receptor for IgE, lymphotoxin-α, and tumor Necrosis factor-α

High cord blood immunoglobulin E (cbIgE) is known to be associated with increased risks of atopic diseases in childhood. The relationship between genetic polymorphisms and high cbIgE has not been well documented. A cross-sectional study was conducted to assess the association between cbIgE and genetic polymorphisms of interleukin (IL)-4 -590C/T, the beta-subunit of the high-affinity receptor for IgE (FcepsilonRI-beta) E237G, lymphotoxin (LT)-alphaNcoI alleles, and tumor necrosis factor (TNF)-alpha -308G/A. A total of 320 mother-neonate pairs were recruited from four maternity hospitals from different locations of Taiwan. Cord blood was obtained and assayed for cbIgE. Polymerase chain reaction followed by restriction fragment length polymorphism was used to assess the genotypes. Three hundred pairs of mothers and neonates were included in the final analysis. Infants with IL-4 -590 C allele were found to have higher risk of elevated cbIgE (> or =0.35 IU/ml, 24.3%) (p = 0.004). After adjusting for gender, birth order, maternal age, and history of allergic disease in maternal and paternal families, odds ratios for CC and CT genotypes were 4.41 and 3.16 (95% confidence interval 0.78-22.67, and 1.66-6.13), respectively, using TT genotype as reference. The genotypes of FcepsilonRI-beta, LT-alpha, and TNF-alpha were not associated with cbIgE before or after the adjustment. Our finding suggested a significant association of cbIgE with genetic polymorphism of IL-4 -590C/T, but not with the genotypes of FcepsilonRI-beta, LT-alpha, and TNF-alpha.     

TNF-α和低氧对胰腺癌细胞表达VEGF-A、C的调节

目的:探讨细胞活素肿瘤坏死因子-α(TNF-α)、SNAP(S-Nitroso-Nacetyl-penicillamine)对胰腺癌细胞产生血管内皮生长因子A、C(VEGF-A、C)的调节.方法:用Northern杂交和Western杂交法分析6种人胰腺癌细胞株中VEGF-A、C基因和蛋白的表达;以TNF-α或SNAP刺激其中两个细胞株后用逆转录-聚合酶链式反应技术(RT-PCR)分析其VEGF-A、C基因的表达.结果:Northern杂交法显示这6种胰腺癌细胞株均有4.1kb VEGF-A基因和2.4kb VEGF-C基因的表达;Western杂交法显示它们均有分子量为43kD的VEGF-A蛋白质和分子量为55kD的VEGF-C蛋白质的表达.RT-PCR分析法显示:TNF-α使细胞株COLO-357产生VEGF-A、VEGF-C mRNA分别减少约1～2.5倍、1～2倍,使细胞株CAPAN-1产生VEGF-A、VEGF-C mRNA分别减少约1倍、1.6～2.5倍;而SNAP刺激细胞株COLO-357产生VEGF-A mRNA增加约5倍,刺激细胞株CAPAN-1产生VEGF-A mRNA增加约4倍,但对这两种细胞株产生VEGF-C mRNA均无明显刺激作用.结论:细胞活素TNF-α和低氧通过调节血管内皮生长因子A、C的表达而影响胰腺癌细胞的生物学特性,抑制癌细胞的增殖,促进其凋亡、死亡或进展、恶化.     

多次发病的传染性单核细胞增多症

传染性单核细胞增多症为EB(Epstein-Barr)病毒引起的一种急性或亚急性全身性免疫异常疾病。一次患病后,可获得持久免疫力,多次发病罕见。本文报告了一例传染性单核细胞增多症,9年内3次发病,结合文献资料复习,就本病的诊断、治疗、临床分型、复发问题以及与肿瘤的关系进行了讨论。     

Arsenical necrosis of the jaws

After a brief historical review of the use of arsenic in dental practice two cases of arsenical necrosis of the jaws, affecting the maxilla and mandible respectively, are reported. Both patients were treated conservatively over an extended period with excellent results. It is concluded that there is no justification, whatsoever, for the use of arsenic in modern dental practice and that, although prolonged, conservative treatment of chemical necrosis of the jaws is preferable to more radical treatment.     

PLASMA FOLLISTATIN CONCENTRATIONS INCREASE FOLLOWING LIPOPOLYSACCHARIDE ADMINISTRATION IN SHEEP

1. The effect of inflammation induced by lipopolysaccharide (LPS) injection on plasma follistatin (FS) concentrations was investigated. 2. Plasma FS and tumour necrosis factor-α concentrations increase following LPS administration in ewes. 3. The rise in FS is similar, but more sustained, to that previously observed after surgery. 4. These results indicate a possible functional link between FS, inflammation and the acute-phase response.     

大鼠腹腔肥大细胞肿瘤坏死因子合成与释放的研究

应用免疫细胞化学技术及酶联免疫吸附试验（ELISA）对大鼠腹腔肥大细胞合成和释放肿瘤坏死因子（TNF）的状况进行了观测。结果:新鲜分离纯化的大鼠腹腔肥大细胞胞浆呈TNF蛋白阳性。单纯肥大细胞培养早期（2～4 h）,上清液中未能检测到TNF,随着培养时间延长,上清液中TNF含量增多;盐酸吗啡与肥大细胞共同培养2h时,上清液中出现可测TNF。四甲基偶氮唑盐（MTT）比色分析试验表明,肥大细胞培养上清液具体有TNF的抗肿瘤活性中。提示:大鼠腹腔肥大细胞能合成和释放TNF,盐酸吗啡能促进肥大细胞释放TNF。