血清NO、IL-6及IL-8与急性高原病的关系研究

目的 :了解血清一氧化氮 (Nitricoxide ,NO)、白介素 - 6 (Interleuk - 6 ,IL - 6 )及白介素 - 8(Interleuk - 8,IL - 8)与急性高原病 (Acutehighaltitudediseaes ,AHAD)及NO与IL -6、IL - 8之间的关系。方法 :将 4 7例AHAD患者随机分为两组 ,一组为常规药物治疗组 (2 3例 ) ,另一组为NO治疗组 (2 4例 )。常规药物治疗组给予吸氧、氨茶碱、地塞米松、速尿等药物常规治疗 ,NO治疗组仅给予吸入由海拔 36 5 8m高度的空气平衡的 1 0 ppm的NO气体 ,每天2次 ,上午、下午各 1h ,并对两组AHAD患者治疗前后的血清NO(NO以其代谢终产物NO3-和NO2 - 表示 )、IL - 6及IL - 8含量进行观察比较。结果 :两组治疗后的血清IL - 6及IL - 8含量均显著低于治疗前 ,NO含量则均显著高于治疗前 (NO治疗组P <0 .0 0 1 ,常规药物治疗组P <0 .0 5～ 0 .0 1 )。且两组治疗后的血清NO、IL - 6及IL - 8含量亦具有显著性差异 (P <0 .0 5 )。结论 :血清NO、IL - 6及IL - 8与AHAD有着密切关系 ,NO能抑制AHAD患者IL -6及IL - 8的分泌 ,对患者的康复有着积极的作用     

急性高原病患者治疗前后NO、CGRP和ET的变化及相互关系

目的 :了解血清一氧化氮 (NitricOxide ,NO)、血浆降钙素基因相关肽 (CGRP)和内皮素 (ET)与急性高原病的关系和NO对急性高原病的治疗作用。方法 :将 4 7例急性高原病患者随机分为常规药物治疗组 (2 3例 )和NO治疗组 (2 4例 )。并对两组患者治疗前后的血清NO和血浆CGRP、ET的变化情况进行了对照比较 (NO以其代谢终产物NO3-和NO2-表示 )。结果 :两组治疗后的血清NO和CGRP均显著高于该组治疗前 ,ET则显著低于治疗前 ,NO治疗组P <0 .0 1,常规药物治疗组P <0 .0 5。两组治疗后的NO和ET相差亦具有显著性(P <0 .0 5 )。治疗前血清NO含量与血浆CGRP、ET呈显著的相关性 (r =0 .38,P <0 .0 1和r =- 0 .6 3,P <0 .0 0 1)。结论 :急性高原病患者血清NO、血浆CGRP和ET水平的高低与急性高原病的发病有着密切的关系 ,三者有着协调和对抗作用 ,吸入NO治疗急性高原病显著优于常规药物治疗。     

硝苯吡啶对急进高原现场幼猪氧动力学的影响

目的 :了解硝苯吡啶 (Nifedipine ,NF)对急性缺氧幼猪氧动力学的影响。方法 :利用右心漂浮导管法对快速进入高原急性缺氧幼猪应用NF后氧动力学的变化进行观察。结果 :应用NF后 ,急性缺氧幼猪的肺动脉平均压 (mPAP)、肺血管阻力 (PVR)显著降低 (其中mPAP :P <0 .0 1,PVR :P <0 .0 0 1) ;心输出量 (CO)、SaO2 、PaO2 、氧输送 (DO2 )、氧消耗 (VO2 )、氧摄取率 (O2Ext)显著提高 (CO :P <0 .0 1,SaO2 、PaO2 、DO2 、VO2 、O2Ext:P <0 .0 0 1)。结论 :NF能降低急性缺氧幼猪的PVR ,通过改变CO而提高组织的DO2 、VO2 ,改善组织因缺氧引起的氧代谢障碍。     

Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2

Background:

Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2.

Methods:

Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers.

Results:

An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3–34, P<0.001). This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2.

Conclusions and inte

No evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers.     

Evidence for a link between TNFRSF11A and risk of breast cancer

Intracellular signaling mediated by the receptor activator of nuclear factor-κB [Rank, encoded by the tumor necrosis factor receptor superfamily, member 11a (Tnfrsf11a) gene] is fundamental for mammary gland development in mice, regulating the expansion of stem and progenitor cell compartments. Conversely, Rank overexpression in mice promotes abnormal proliferation and impairs differentiation, leading to an increased incidence of tumorigenesis. Here, we show that a common genetic variant near the 5'-end of TNFRSF11A, rs7226991, is associated with breast cancer risk in the general population and among carriers of mutations in the breast cancer 2, early onset (BRCA2) gene. Akin to the results of the Cancer and Genetics Markers of Susceptibility initiative, combined analysis of rs7226991 in two Spanish case-control studies (1,365 controls and 1,323 cases in total) revealed a significant association with risk: odds ratio (OR) = 0.88, 95% confidence interval (CI) 0.78-0.98, P (trend) = 0.025. Subsequent examination of BRCA1 (n = 1,017) and BRCA2 (n = 885) mutation carriers revealed a consistent association in the latter group: weighted hazard ratio ((w)HR) = 0.70; 95% CI 0.55-0.88; and P (trend) = 0.003; compared to BRCA1 mutation carriers, (w)HR = 0.91; 95% CI 0.76-1.10; and P (trend) = 0.33. The results of this study need to be replicated in other populations and with larger numbers of BRCA1/2 mutation carriers.     

Epigenetic-based treatments emphasize the biologic differences of core-binding factor acute myeloid leukemias

Acute myeloid leukemia (AML) is a heterogeneous group of disorders characterized by an abnormal proliferation of the myeloid precursors and a maturation block. The most common chromosomal lesions in AML are the t(8;21) and inv(16). To better understand the leukemogenic mechanism of these fusion proteins, we performed gene expression studies in samples from (8;21), AML1 mutated and inv(16) patients, as well as from the Kasumi-1 cell line and a U937 cell line expressing the AML1-ETO fusion gene. To assess the influence of associated epigenetic lesions, we performed gene expression studies in Kasumi-1 cells and cells extracted from an Inv(16) patient, both treated with demethylating and HDAC inhibitor agents. Shared deregulated genes in the different types of core-binding factor leukemias were identified. We found a tight link between Inv(16) and mutant AML1 samples. Furthermore, some of the genes deregulated by the leukemogenic process reverted to their normal expression with demethylating and HDAC inhibitor treatment, highlighting the role of chromatin remodeling processes in AML.     

Simulated ABO and Rh blood typing

BACKGROUND: Blood typing historically has been used to introduce students to the concepts of immunohematology. Risk of disease transmission has compelled school districts to prohibit the use of human blood in student laboratories. A method is needed that will safely simulate ABO and Rh typing. STUDY DESIGN AND METHODS: A method that uses inorganic salt solutions to simulate ABO and Rh antigens and antibodies was studied. Additional salt solutions and diluents were tested to investigate the feasibility of simulating both ABO and Rh typing in a more realistic medium. RESULTS: Cobalt nitrate and sodium hydroxide were found to successfully simulate D and anti-D, respectively. The addition of these solutions did not produce cross- reactions in ABO tests. Use of simulated blood as a diluent improved the appearance of the samples. CONCLUSION: This method can safely and inexpensively simulate ABO and Rh blood typing procedures and provide students with hands-on blood-typing experience.