胸腺五肽显著增强干扰素在抗病毒治程中的特异性CTL效应

目的:探究在e抗原(HBe Ag)阳性的慢性乙型肝炎患者采用聚乙二醇干扰素-2a(peg-2a)联合核苷类药物治疗过程中,加用胸腺五肽对细胞免疫应答的影响。方法:选择采用聚乙二醇干扰素α-2a联合核苷类药物(拉米夫定+阿德福韦酯)治疗48周,HBe Ag仍为阳性,且HLA-A2阳性的慢性乙型肝炎患者18例,分为两组。一组原方案延长联合治疗作为对照,另一组在原方案基础上再加用胸腺五肽治疗(10 mg/次,2次/周,共24周)治疗,所有病人均治疗至96周。并做体外HBV特异性细胞毒T淋巴细胞(HBV specific CTL)培养增殖,通过Elispot技术分析其分泌细胞因子(肿瘤坏死因子-α,干扰素-γ,白介素-10)的功能。结果:HBe Ag转阴率,治疗96周时联合胸腺五肽组为44.4%(4/9),原方案对照组为22.2%(2/9)。HBs Ag滴度,48周时,HBs Ag为4571±3772 IU/m:;96周时,联合胸腺五肽组为1962±2869 IU/m L,转阴1人,原方案对照组为3490±3124 IU/m L,P=0.093。HBV特异性CTL培养增殖,96周时联合胸腺五肽组高于原方案对照组,且联合胸腺五肽组TNF-的分泌也高于原方案对照组,P0.05。结论:胸腺五肽显著增强干扰素抗病毒治疗过程中的特异性CTL效应。     

CO2 激光联合胸腺五肽治疗尖锐湿疣的临床效果分析

目的:探讨CO2激光联合胸腺五肽治疗尖锐湿疣的临床疗效。方法:将我院2010年2月-2011年8月期间收治的82例尖锐湿疣患者随机分为两组,治疗组50例采用CO2激光器治疗联合胸腺五肽肌注;对照组32例单纯采用CO2激光器治疗;两组治疗疗程结束后观察临床疗效。结果:治疗组50例,一次治愈者46例,占92%;二次治愈者4例,占8%。对照组32例,一次治愈者19例,占59.4%;二次治愈者13例,占40.6%。两组一次治愈率比较差异明显,具有统计学意义(P<0.05)。两组术后局部轻度水肿和疼痛,无需处理1~3天缓解或痊愈。结论:CO2激光联合胸腺五肽治疗尖锐湿疣临床疗效好,并具有治疗简便,术后不良反应少,治愈率高等特点。     

Effects of thymic polypeptides on the thymopoiesis of mouse embryonic stem cells

The thymus provides a unique cellular and hormonic microenvironment for the development of immunocompetent T cells. Thymic polypeptides have been widely used clinically for the treatment of tumors, infectious diseases and immune deficiency diseases. They have already shown the ability to stimulate the maturation of hematopoietic stem cells towards the CD3+CD4+ T cell lineage. However, their effects on the thymopoiesis of embryonic stem cells are still unexplored. In this paper, we compared the effects of three thymic polypeptides, thymopentin (TP5), thymosin alpha-1 (Talpha-1) and thymopeptides on the in vitro thymopoiesis of mouse embryonic stem (ES) cells. Using the embryoid body induction system, we found that both Talpha-1 and thymopeptides effectively induced ES cells to differentiate sequentially into the CD3+ and CD4+/CD8+ T cells. These T cells had T cell receptor (TCR) Vbeta gene rearrangement and most were TCRalphabeta T cells. We also found that the expression of the Notch receptor and its ligands Delta-like-1 and Delta-like-4 gradually increased during the induction. However, TP5 failed to induce the T cell differentiation of the ES cells. In summary, this is the first report to demonstrate that Talpha-1 can stimulate the T cell early stage differentiation from ES cells using the embryoid body protocol. These findings provide a powerful model for studying T cell development and may open new venues for the clinical application of Talpha-1.     

New conformationally restricted analog of the immunosuppressory mini-domain of HLA-DQ and its biological properties

Our previous studies revealed that the nonapeptide fragment of HLA-DQ located in the beta 164-172 loop of the Thr-Pro-Gln-Arg-Gly-Asp-Val-Tyr-Thr sequence suppresses the immune humoral and cellular responses [30]. Based on the crystal structure of HLA-class II molecules we designed and synthesized a cyclic analog with restricted conformation, cyclo(Suc-Thr-Pro-Gln-Arg-Gly-Asp-Val-Lys)-Thr-OH (Suc = succinyl) by reacting a Lys side chain with a succinylated N-terminus. The cyclization product more potently suppresses the cellular immune response than its linear counterparts and is efficiently cleaved by trypsin. The results indicate that the beta 164-172 loop may serve as a functional epitope on the HLA class II surface for intermolecular binding.     

Protease-Catalyzed Synthesis of a Precursor Dipeptide,Z-Asp-Val-NH2 of Thymopentin,in Organic Solvents

Abstract

The protease-catalyzed, kinetically controlled synthesis of a precursor dipeptide, Z-Asp-Val-NH₂ of thymopentin (TP-5), in organic solvents was studied. Z-Asp-OMe and Val-NH₂ were used as the acyl donor and the nucleophile, respectively. An industrial alkaline protease alcalase was used to catalyze the synthesis of the target dipeptide in water-organic cosolvent systems. The conditions of the synthesis reaction were optimized by examining the effects of several factors, including organic solvents, water content, temperature, pH, and reaction time on the yield of Z-Asp-Val-NH₂. The optimum conditions using alcalase as the catalyst are pH 10.0, 35°C, in acetonitrile/Na₂CO₃-NaHCO₃ buffer system (9:1, V/V), reaction time 5 h, with a yield of 63%. The dipeptde product was confirmed by LC- MS.     

Synthesis of a Precursor Dipeptide of Thymopentin in Organic Solvents by an Enzymatic Method

Abstract

The protease‐catalyzed, kinetically controlled synthesis of a precursor dipeptide of thymopentin(TP‐5), Z‐Arg‐Lys‐NH₂ in organic solvents was studied. Z‐Arg‐OMe was used as the acyl donor and Lys‐NH₂ was used as the nucleophile. An industrial alkaline protease alcalase and trypsin were used to catalyze the synthesis of the target dipeptide in water‐organic cosolvent systems. The conditions of the synthesis reaction were optimized by examining the effects of several factors, including organic solvents, water content, temperature, pH, and reaction time on the yield of Z‐Arg‐Lys‐NH₂. The optimum conditions using alcalase as the catalyst are pH 10.0, 35°C, in acetonitrile/DMF/Na₂CO₃‐NaHCO₃ buffer system (80∶10∶10, V/V), 6 h, with the dipeptide yield of 71.1%. Compared with alcalase, the optimum conditions for trypsin are pH 8.0, 35°C, in ethanol/Tris‐HCl buffer system (80∶20, V/V), 4 h, with the dipeptide yield of 76.1%.     

CO_2激光联合胸腺五肽治疗尖锐湿疣的临床效果分析

目的：探讨CO2激光联合胸腺五肽治疗尖锐湿疣的临床疗效。方法：将我院2010年2月-2011年8月期间收治的82例尖锐湿疣患者随机分为两组,治疗组50例采用CO2激光器治疗联合胸腺五肽肌注;对照组32例单纯采用CO2激光器治疗;两组治疗疗程结束后观察临床疗效。结果：治疗组50例,一次治愈者46例,占92%;二次治愈者4例,占8%。对照组32例,一次治愈者19例,占59.4%;二次治愈者13例,占40.6%。两组一次治愈率比较差异明显,具有统计学意义（P〈0.05）。两组术后局部轻度水肿和疼痛,无需处理1~3天缓解或痊愈。结论：CO2激光联合胸腺五肽治疗尖锐湿疣临床疗效好,并具有治疗简便,术后不良反应少,治愈率高等特点。     

Isolation and Characterization of Collagen - Synthesizing Polysomes from Chick Embryos

Collagen - synthesizing polysomes were isolated by low-speed oentrifugation of the post-mitochomirial supernatant of chick homogenates. Electron microscopy of the fraction thus isolated shows it to be exclusively composed of ribosomes. Amino acid incorporation in vitro showed that these particles were efficient in the incorporation of proline, but not tryptophan, as opposed to ribosomes obtained from the supernatant of the low-speed oentrifugation. The incorporation process was highly dependent on GTP, and exibited an optimal Mg²⁺ concentration of 5.6 mN. The reaction was inhibited by RNase, elongation inhibitors as anysomycin, sparsomycin, fusidic acid and GDPCP. It was also moderately inhibited by initiation inhibitors such as aurintricarboxilic acid and pyrocatechol violet. The product of the incorporation was characterized as collagen by its sensitivity towards purified collagenase, lack of tryptophan, chromatography in CN-cellulose and molecular sieve chromatography in Sephadex G-200.