Toll-Like Receptor (TLR2 and TLR4) Polymorphisms and Chronic Obstructive Pulmonary Disease

Toll-like receptors (TLRs) participate in the defence against bacterial infections that are common in patients with Chronic Obstructive Pulmonary Disease (COPD). We studied all tagging SNPs in TLR2 and TLR4 and their associations with the level and change over time of both FEV(1) and sputum inflammatory cells in moderate-to-severe COPD. Nine TLR2 SNPs and 17 TLR4 SNPs were genotyped in 110 COPD patients. Associations of SNPs with lung function and inflammatory cells in induced sputum were analyzed cross-sectionally with linear regression and longitudinally with linear mixed-effect models. Two SNPs in TLR2 (rs1898830 and rs11938228) were associated with a lower level of FEV(1) and accelerated decline of FEV(1) and higher numbers of sputum inflammatory cells. None of the TLR4 SNPs was associated with FEV(1) level. Eleven out of 17 SNPs were associated with FEV(1) decline, including rs12377632 and rs10759931, which were additionally associated with higher numbers of sputum inflammatory cells at baseline and with increase over time. This is the first longitudinal study showing that tagging SNPs in TLR2 and TLR4 are associated with the level and decline of lung function as well as with inflammatory cell numbers in induced sputum in COPD patients, suggesting a role in the severity and progression of COPD.     

Human Leukocyte Antigen Class I Supertypes and HIV-1 Control in African Americans

The role of human leukocyte antigen (HLA) class I supertypes in controlling human immunodeficiency virus type 1 (HIV-1) infection in African Americans has not been established. We examined the effects of the HLA-A and HLA-B alleles and supertypes on the outcomes of HIV-1 clade B infection among 338 African American women and adolescents. HLA-B58 and -B62 supertypes (B58s and B62s) were associated with favorable HIV-1 disease control (proportional odds ratio [POR] of 0.33 and 95% confidence interval [95% CI] of 0.21 to 0.52 for the former and POR of 0.26 and 95% CI of 0.09 to 0.73 for the latter); B7s and B44s were associated with unfavorable disease control (POR of 2.39 and 95% CI of 1.54 to 3.73 for the former and POR of 1.63 and 95% CI of 1.08 to 2.47 for the latter). In general, individual alleles within specific B supertypes exerted relatively homogeneous effects. A notable exception was B27s, whose protective influence (POR, 0.58; 95% CI, 0.35 to 0.94) was masked by the opposing effect of its member allele B*1510. The associations of most B supertypes (e.g., B58s and B7s) were largely explained either by well-known effects of constituent B alleles or by effects of previously unimplicated B alleles aggregated into a particular supertype (e.g., B44s and B62s). A higher frequency of HLA-B genotypic supertypes correlated with a higher mean viral load (VL) and lower mean CD4 count (Pearson''s r = 0.63 and 0.62, respectively; P = 0.03). Among the genotypic supertypes, B58s and its member allele B*57 contributed disproportionately to the explainable VL variation. The study demonstrated the dominant role of HLA-B supertypes in HIV-1 clade B-infected African Americans and further dissected the contributions of individual class I alleles and their population frequencies to the supertype effects.African Americans in the United States have been affected disproportionately by the human immunodeficiency virus type 1 (HIV-1) epidemic. They accounted for only 13% of the U.S. population but for 47% of AIDS cases diagnosed in the United States in 2006 (14, 17). An HIV-1 vaccine would be of enormous benefit to this subpopulation. One strategy for HIV-1 vaccine development seeks to capitalize on the recognition and destruction of HIV-1-infected cells by cytotoxic T lymphocytes (CTLs) (32, 33, 35).CTL recognition is critically dependent on binding, presentation, and cell surface display of a variety of antigenic peptides (epitopes) by extremely polymorphic human leukocyte antigen (HLA) molecules. As the relative importance of increasing numbers of HIV-1 epitopes for individual HLA class I molecules has been recognized (9, 16), the feasibility of developing a vaccine tailored to every epitope and HLA specificity has come to seem more remote. Conceptualization of epitope specificity in terms of broad groupings (supertypes) of HLA molecules may provide a rational but simpler approach to this challenge.Several efforts have succeeded at consolidating the huge spectrum of individual HLA class I alleles into four HLA-A and five HLA-B supertype categories (37-39), based on the ability of different HLA class I molecules to present similar epitopes. Unlike individual allele frequencies, which vary greatly across ethnic groups, all nine supertypes (comprising most, but not all, HLA-A and HLA-B alleles) are present in all human populations. This more uniform representation of allele groups may confer an advantage in the form of balancing selection (38).HLA alleles within one supertype that share epitope binding specificities might be expected to demonstrate similar associations with HIV-1 outcomes or vaccine response; conversely, alleles within a supertype that differ substantially in function might be expected to show differential responses to natural infection or vaccines designed on the basis of supertype (2). Functional heterogeneity of alleles within the supertypes could be due to differences in the class I alleles themselves (e.g., variable epitope avidity or tolerance to viral mutations), in host background (genetic epistasis), or in the virus (e.g., clade-related epitope specificities or viral escape).Previous work has detected associations between the HLA class I supertypes and HIV-1 outcomes for Caucasians with clade B infections (34, 44) and for native Africans with clade A or C infections (23, 28). We are unaware of studies among African Americans in the context of clade B HIV-1 infection or of any systematic attempt to tease apart the independent contributions of supertypes and their individual class I alleles to HIV-1 outcomes. Here we document the frequencies of the HLA class I alleles and supertypes in the Reaching for Excellence in Adolescent Care and Health (REACH) and HIV Epidemiologic Research Study (HERS) cohorts, and we report the relative effects of those alleles and supertypes on the degree of HIV-1 disease control.     

海洋生物制药现状及展望

现代生物技术在制药产业中发挥了重要作用,海洋生物技术的出现和发展推动了海洋生 物药物的研究,是今后生物技术药物的发展方向。综述了生物技术在海洋药物开发中的应用,并 展望了新世纪海洋生物制药的前景。     

10CM短柱快速分离3-MH的实验研究

本研究在改进后短程序基础上,对氨基酸分离柱进行了改进。改进后的分离柱长为10cm。比原来20cm长柱分离3—MH的时间缩短了近1/2。实验所得的(回收率为97.59%,分离度0.89±0.02。变异系数1.17)这些指标较国外用其它方法所得的结果有良好的相关性。多次测定结果说明长柱与短柱比较无明显差异。证明了短柱对3—MH含量无影响。这一改进所建立的方法大大地缩短了样品的分析时间,节约了大量进口试剂,开展这方面的工作将有利益提高严重烧伤、创伤后蛋白质代谢和营养学等方面的研究水平。