Effectiveness of lymphotropic therapy in patients with tuberculosis in relations to genetic markers

To study whether a combination of the carriage of genetic blood markers: haptoglobin phenotypes and red blood cell glucose-6-phosphate dehydrogenase, 60 patients with destructive tuberculosis were given a new drug treatment regimen by using regional lymphotropic therapy with 10% isoniazid. The efficiency of the treatment and residual changes were found to be directly related to what a patient has as genetic background. Defining the types of combinations of genetic markers may predict the course of disease, the efficiency of treatment, and outcomes.     

Association of HLA and other genetic markers in South Indian patients with pulmonary tuberculosis

Histocompatibility antigens (A, B & C loci) and 23 other single gene characters were studied in 204 pulmonary tuberculosis patients belonging to a single endogamous group in South India. None of the previously reported associations with HLA antigens was confirmed, nor any new one found. The blood O and Rh negative associations were also not confirmed, although a new association with the Jk blood group system appears possible. Of particular interest is the association with the phosphoglucomutase (PGM1) system, which parallels that found in a different population located some 1000 km away. Relative risks were calculated to measure the resistance of individuals with the PGM1*2+ allele.     

Relations of genetic markers with the development of infiltrative tuberculosis]

The examination included 84 patients with infiltrative pulmonary tuberculosis. A relationship of genetic markers to the development of the disease was studied. The incidence of antigens HLA of I (Cw4) and (DR2) classes is higher in patients with infiltrative pulmonary tuberculosis than that in healthy subjects. The incidence of certain alleles of protein loci is also increased: phenotype CB for locus ACR and phenotype 1-1 for locus ADA.     

Association of various genetic markers with tuberculosis and other lung diseases in Tuvinian children

Setting: Heredity factors influence susceptibility to tuberculosis and other lung diseases. Recent immunogenetic studies have confirmed the genetic predisposition to lung diseases in different populations. Precise knowledge of genetic aspects of disease susceptibility is important for improvement of public health.Objective: The aim of our research was to study the distribution of certain genetic markers in Tuvinian children suffering from tuberculosis and other lung diseases and to compare it with that in ethnically- and age-matched healthy donors. HLA-A, -B, -C and -DR antigens have been defined serologically by lymphocytotoxic assay, and variants of polymorphic protein loci Hp, Tf, Gc, ESD, ACP, PGM1, ADA, PGD have been defined by electrophoresis.Results: It was demonstrated that in Tuvinian children with tuberculosis the frequencies of HLA-DR2 and HLA-DRw53 antigens are increased in comparison with healthy donors. In children with non-tuberculous chronic lung diseases with allergic components the frequency of HLA-Al, -B5 and -B8 antigens and of genetic variants Hp2-2 and ESD1-1 was elevated.Conclusion: HLA complex genetic factors influence susceptibility to tuberculosis and other lung diseases in Tuvinian children.     

结核分枝杆菌北京基因型菌株新型分子遗传标志的鉴定

目的分析结核分枝杆菌北京基因型菌株与非北京基因型菌株间差异表达的蛋白质，寻找可用于快速区分北京基因型的分型标志。方法应用间隔寡核苷酸分型法对56株结核分枝杆菌进行基因分型，经双向电泳技术比较北京基因型菌株与非北京基因型菌株的全菌蛋白表达图谱差异，差异表达的蛋白质通过基质辅助激光解吸-电离飞行时间质谱仪进行质谱分析，蛋白质数据库进行检索。进而对差异表达的蛋白质相应基因及上游进行序列分析。结果56株结核分枝杆菌中有49株为北京型菌株，7株为非北京型菌株。两个基因型菌株中差异明显表达的蛋白质为Rv0927c，该蛋白质斑点在49株北京基因型菌株中均缺失，而在7株非北京菌株和H37Rv中均有出现。北京基冈型菌株Rv0927c基因有两个特征性突变：在421位核苷酸位点的AGC3个碱基缺失，以及该基因上游127位点G—A的突变；而非北京基因型菌株该基因及其上游序列与H37Rv完全相同。结论 Rv0927c基因在北京基因型菌株中的特征性突变，对开发新型区分北京基因型和非北京基因型结核分枝杆菌的方法奠定了基础。     

家族性致心律失常性右室心肌病与微卫星遗传标志的连锁分析

目的 研究探索致心律失常性右室心肌病(ARVC)家系与3个微卫星遗传标志的连锁关系，进行ARVC的基因定位。方法 选择微卫星遗传标志：D2S152、D14S252和D10S1664，对121例背景人群和5个中国人ARVC家系(家系编号1～5)，用每个微卫星引物扩增家系和背景人群DNA的微卫星片段，在DNA手工测序电泳仪槽上进行恒功率变性聚丙烯酰胺凝胶电泳、银染、读取等位基因片段，在常染色体显性和隐性两种遗传模式下进行连锁分析。结果 (1)根据D2S152的连锁资料，在常染色体显性遗传模式下，1～5号家系的连锁值(Logarithm of odd，LOD值)分别为2．17、-0．59、-∞(负无穷大)、-(表示此遗传模式下不支持连锁分析)、-∞，均为0=0。在常染色体隐性遗传模式下，1～5号家系的LOD值分别为-∞、-∞、-∞、-∞、0．18。(2)根据D14S252的连锁资料，在常染色体显性遗传模式下，1～5号家系的LOD值分别为-、-、-∞、-、0。在常染色体隐性遗传模式下，1～5号家系的LOD值分别为-∞、-0．81、-∞、-∞、0．09。(3)根据D10S1664的连锁资料，在常染色体显性遗传模式下，1～5号家系的LOD值分别为-、-、0．54、-、0．60。在常染色体隐性遗传模式下，1～5号家系的LOD值分别为-、-∞、-∞、-∞、-∞。结论 (1)1号家系与D2S152的连锁值已达2．17，连锁与不连锁的可能性之比为150：1，提示在D2S152附近存在ARVC的可能致病基因；排除3号家系与D2S152的连锁关系；需要收集更多资料才能决定2、4和5号家系是否与此位点连锁。(2)排除3号家系与D14S252的连锁，需要收集更多资料才能决定1、2、4和5号家系是否与此位点连锁。(3)5个家系与D10S1664的连锁关系都需收集更多资料。     

Investigation of genetic markers in patients with Crohn's disease and ulcerative colitis

Inflammatory bowel diseases (IBD) as Crohn's disease (CD) and ulcerative colitis (UC) are believed to have a genetic basis. Additional factors are supposed to promote the development of IBD. However, apart from a few reports of HLA associations which await confirmation by other groups strong associations to (a) particular genetic marker(s) are still lacking. We here report on previously unobserved associations of CD to MNSS and UC to the immunoglobulin heavy chain allotype Gm 1,-2,10. We suggest that these factors play a role in a wider spectrum of genetic markers for the development of IBD.     

结核病患者病耻感的研究进展

病耻感是患者因患病而产生的一种负性情绪体验。由于结核病患者缺乏疾病知识及公众对结核病患者的歧视态度,病耻感在结核病患者中广泛存在,并严重影响着患者的身心健康。结核病患者病耻感已受到国外学者的关注,并已编制出多个针对结核病患者病耻感的测评工具,其中使用范围最广的是由Van等编制的结核病相关病耻感量表。结核病患者病耻感水平与患者的性别、居住地、文化程度、婚姻状况、家庭收入等有关。降低病耻感水平对促进患者的康复有重要的意义,但目前干预性研究较少。建议以后的研究着重探索有效降低结核病患者病耻感水平的干预措施。     

Functional and genetic assessment of IFN-gamma receptor in patients with clinical tuberculosis.

OBJECTIVE: The molecular basis of the genetic vulnerability underlying the most common form of clinical tuberculosis (TB) remains largely unknown. We speculated that mild genetic defects in the interferon-gamma (IFN-gamma) signalling pathway caused a subtle functional impairment of IFN-gamma which would explain susceptibility to Mycobacterium tuberculosis in clinical TB. DESIGN: A case-control study. RESULTS: We evaluated functional responsiveness to IFN-gamma in monocytes from patients with clinical TB (n = 10), and analysed the genetic sequences of the IFN-gamma receptor 1 (IFN-gammaR1) and STAT1 genes in patients with disseminated TB (n = 18). IFN-gamma stimulated an increase in the expression of HLA-DR and CD64 on monocytes of both controls and patients; the rate of increase in expression was the same in both groups. Treatment with IFN-gamma before lipopolysaccharide (LPS) stimulation further increased tumour necrosis factor-alpha (TNF-alpha) production as compared to TNF-alpha production with LPS stimulation alone; the rate of increase in TNF-alpha production was the same in both groups. The known mutations in the coding sequences of the IFN-gammaR1 and STAT1 genes were not found in the patients with disseminated tuberculosis. CONCLUSION: These results suggest that impairment of the IFN-gamma signalling pathway did not account for cases of clinical TB in this study.     

结核病患者受歧视及产生病耻感的现状及研究进展

结核病是严重危害人类健康的慢性传染性疾病,病耻感在结核病患者中广泛存在,导致治疗延误,对个人和社会都造成严重后果。结核病患者遭受的歧视主要有家庭歧视、社会歧视、医疗机构歧视,以此产生的病耻感使患者进一步承受了心理上的痛苦,从而采取消极态度应对治疗和生活,造成不良的预后。结核病患者的病耻感在不同人口学特征的人群中程度不一。目前,中国乃至全球范围内缺乏有代表性的与结核病患者受歧视相关的调查报告,作者从结核病患者受歧视的现状、影响因素、产生原因及消除方法等多个方面梳理了目前国内外的相关研究工作,希望为改良对结核病患者的治疗和管理策略提供更多依据。     

Clinical and molecular genetic features of cerebrotendinous xanthomatosis patients in Chinese families

Metabolic Brain Disease - Cerebrotendinous xanthomatosis (CTX) is a lipid-storage disease caused by mutations in CYP27A1. Current publications of Chinese CTX were mainly based on case reports. Here...