Epitope Context and Reshaping of Activated T Helper Cell Repertoire

In recent years, a growing interest in the study of peptide antigenicity in relation to the role of flanking sequences and protein topology in processing, presentation, and recognition has been observed. However, the information available on the antigenicity of recombinant fusion proteins and their effect on the selection of antigen receptor repertoires is limited. To analyze the role of molecular topology of T epitopes in a system relevant to human pathology, we have used the bacterially expressed Schistosoma japonicum glutathione S transferase (GST) to construct recombinant antigens containing HIV-1 derived T cell determinants, and human T cell clones specific for these determinants. We found that antigenicity of a given GST—peptide combination was not the same when T cells and antigen presenting cells from different individuals were tested. Our results show that differences in processing and presentation of chimeric proteins are not dictated by the use of diverse restriction elements. We also found that the context in which an antigenic peptide is delivered affects the recruited repertoire as defined according to T cell receptor Vβ usage and fine specificities of selected T cells.     

地尔硫对冠心病的抗氧化作用

目的：观察地尔硫对冠心病病人的抗脂质过氧化及抗氧自由基作用。方法：冠心病病人３０例为治疗组（男性２１例，女性９例，年龄５８±ｓ６ａ），给予地尔硫３０ｍｇ，ｐｏ，ｔｉｄ，共４ｗｋ。健康人组３０例（男性１８例，女性１２例，年龄５８±９ａ）。结果：治疗组在给药前较健康人组的血清ｏｘＬＤＬ，ＬＰＯ，ＳＣＬ，ＬＣＬ值显著升高，Ｐ＜０．０１，ＧＳＨ－Ｐｘ显著降低，Ｐ＜０．０１，ＳＯＤ活力两者无明显差异，Ｐ＞０．０５。治疗组用药后与用药前相比ｏｘＬＤＬ，ＬＰＯ，ＳＣＬ，ＬＣＬ值显著下降，Ｐ＜０．０１或＜０．０５，ＧＳＨ－Ｐｘ显著升高，Ｐ＜０．０１，治疗组治疗后与健康人组相比，除ＬＣＬ外，其他指标皆无明显差异，Ｐ＞０．０５。结论：地尔硫是一良好的抗氧化剂。     

Intrahepatic Delivery of Glutathione by Conjugation to Dextran

Glutathione was covalently attached to dextran (T-40) by the CNBr activation method. The compound obtained was a water-soluble powder containing 10 (w/w%) glutathione, which was gradually released from the conjugate in aqueous media. Mice depleted of glutathione by treatment with buthionine sulfoximine, a potent inhibitor of -glutamylcysteine synthetase, exhibited a significant increase in hepatic glutathione level after intravenous injection of the conjugate. In mice given a lethal dose of acetaminophen, the survival rate increased progressively with coadministration of the conjugate, whereas little improvement was found when free glutathione was given. The conjugate maintained the serum transaminase activities at lower level after acetaminophen administration. These findings suggest that the dextran conjugate of glutathione is transported into hepatic cells and is intracellulary hydrolyzed to free form, which protects mice from hepatotoxicity due to acetaminophen.     

Alterations of plasma antioxidants and mitochondrial DNA mutation in hair follicles of smokers

The effects of long-term smoking on mitochondrial DNA (mtDNA) deletions in hair follicles were investigated in subjects with different antioxidant capacity. Twenty-two male smokers with a smoking index of greater than 5 pack-years and without any known systemic diseases were recruited for this study. Forty healthy nonsmoking males were included as controls. We found that the concentrations of ascorbate and alpha-tocopherol and the activities of glutathione S-transferase (GST) and glutathione peroxidase in blood plasma were significantly decreased in smokers. The levels of glutathione and protein thiols in whole blood and the incidence of a 4,977 bp deletion of mtDNA (dmtDNA) in hair follicles were significantly increased in smokers. A significantly higher incidence of the 4,977 bp dmtDNA was found in smokers with plasma GST activity less than 5.66 U/l (OR = 7.2, P = 0.020). Using multiple covariate ANOVA and logistic regression, we found that age and low plasma GST activity were the only two risk factors for the 4,977 bp dmtDNA. These results suggest that smoking depletes antioxidants and causes mtDNA deletions and that plasma GST may play an important role in the preservation of the mitochondrial genome in tissue cells of smokers.     

Use of glutathione inhibitors and glutathione transferases to overcome tumor resistance to cytostaticsin vivo

Preincubation of cells of BDF1 hybrid mice with P388 leukemia with doxorubicin and buthionine sulfoximine leads to the manifestation of a therapeutic effect of the antibiotic. Injection of buthionine sulfoximine and ethacrinic acid to mice with leukemia does not alter the therapeutic effect of the antibiotic. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 2, pp. 212–214, February, 1995 Presented by N. N. Trapeznikov, Member of the Russian Academy of Medical Sciences     

P糖蛋白和谷胱甘肽—S—转移酶在肾细胞癌中的表达

探讨肾细胞癌与多药耐药的关系，方法：应用免疫组化方法，检测４例术前未进行化疗的肾细胞癌和１６例正常肾组织中的Ｐ糖蛋白和谷胱甘肽－２转移－π表达。结果：Ｐ－ａｇ和ＧＳＴ－π外地１６例正常肾组织中的表达率均匀１００％，在４４例肾细胞癌组织中分别为６３．６５和５４．５％Ｐｇ，Ｐ－ｇｐ和／或ＧＳＴ－π阳性表达率为７９．５％。     

Physical training and fasting erythrocyte activities of free radical scavenging enzyme systems in sedentary men

Summary Effects of 10 weeks of physical training on free radical scavenging enzyme systems in erythrocytes were investigated in 7 sedentary healthy male students. The training consisted of running over 5 km, 6 times/week. Their maximum oxygen uptake and 12 min walk-run performance increased significantly after training. Of the antioxidant enzyme systems examined in the erythrocytes, both catalase activity and concentration and total glutathione reductase (GR) activity also showed significant increases following the training. The erythrocyte GR activity coefficient also increased significantly. These results suggest that chronic aerobic exercise increases riboflavin requirements and has some positive effects on antioxidative processes.     

Effects of sex hormones and antihormones on the activity of redox system enzymes of human erythrocyte glutathione

Effects of estradiol and testosterone and of the antiandrogens cyproterone acetate, niftolide, and antiestrogen tamoxifen on the activities of human erythrocyte glutathione peroxidase and glutathione reductase were studiedin vitro. In contrast to hormone preperations, antihormones in high concentrations (10⁻⁴−5×10⁻⁴ M) modified the enzyme activities. Cyproterone acetate and tamoxifen increased the activity of glutathione reductase, while tamoxifen stimulated glutathione reductase and inhibited glutathione peroxidase. Niftolide inhibited both enzymes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 8, pp. 185–187, August, 1997