Factors associated with experiences of genetic discrimination among individuals at risk for huntington disease

The purpose of this study was to identify factors that are associated with experiencing genetic discrimination (GD) among individuals at risk for Huntington disease (HD). Multivariable logistic regression analysis was used to examine factors associated with experiencing GD in data from a cross‐sectional, self‐report survey of 293 individuals at risk for HD. The study sample comprised 167 genetically tested respondents, and 66 who were not tested (80% response rate). Overall, individuals who learn they are at risk for HD at a younger age (OR = 3.1; 95% CI: 1.5–6.2; P = 0.002), are mutation‐positive (OR = 2.8; 95% CI: 1.4–6.0; P = 0.006), or are highly educated (OR = 2.7; 95% CI: 1.4–5.1; P = 0.002) are more likely to experience GD, particularly in insurance, family, and social settings. Further, younger age was associated with discrimination in insurance (OR = 0.97; 95% CI: 0.94–1.00; P = 0.038). This study provides evidence that some people who are at risk for HD were more likely to experience GD than others. Individuals who learned they are at risk for HD at a younger age and those who are mutation‐positive were more likely to experience GD, particularly in insurance, family, and social settings. Younger individuals were more likely to experience discrimination in the insurance setting. Overall, highly educated individuals were also more likely to report discrimination. These results provide direction for clinical and family discussions, counseling practice, and policy aimed at mitigating experiences of GD. © 2010 Wiley‐Liss, Inc.     

Indexing disease progression at study entry with individuals at‐risk for Huntington disease

The identification of clinical and biological markers of disease in persons at risk for Huntington disease (HD) has increased in efforts to better quantify and characterize the epoch of prodrome prior to clinical diagnosis. Such efforts are critical in the design and implementation of clinical trials for HD so that interventions can occur at a time most likely to increase neuronal survival and maximize daily functioning. A prime consideration in the examination of prodromal individuals is their proximity to diagnosis. It is necessary to quantify proximity so that individual differences in key marker variables can be properly interpreted. We take a data‐driven approach to develop an index that can be viewed as a proxy for time to HD diagnosis known as the CAG‐Age Product Scaled or CAP_S. CAP_S is an observed utility variable computed for all genetically at‐risk individuals based on age at study entry and CAG repeat length. Results of a longitudinal receiver operating characteristic (ROC) analysis showed that CAP_S had a relatively strong ability to predict individuals who became diagnosed, especially in the first 2 years. Bootstrap validation provided evidence that CAP_S computed on a new sample from the same population could have similar discriminatory power. Cutoffs for the empirical CAP_S distribution can be used to create a classification for mutation‐positive individuals (Low–Med–High), which is, useful for comparison with the naturally occurring mutation‐negative Control group. The classification is an improvement over the one currently in use as it is based on observed data rather than model‐based estimated values. © 2011 Wiley‐Liss, Inc.     

野菊花水提液抗氧化作用的实验研究

目的：观察野菊花水提液的体内外抗氧化的作用。方法：分别用ＴＢＡ法、ＤＴＮＢ法及紫外分光光度测定脂质过氧化（ＬＰＯ）产物ＭＤＡ的含量、全血谷胱甘肽过氧化物酶（ＧＳＨ－Ｐx）及过氧化氢酶（ＣＡＴ）活力。结果：野菊花水提液体外可抑制大鼠心、脑、肝、肾组织自动ＬＰＯ及由Ｈ２Ｏ２引发的红细胞脂质过氧及溶血;小鼠ｉｇ给药２ｇ／（ｋｇ．ｄ）７ｄ,可显著升高全血ＧＳＨ－Ｐx、ＣＡＴ活力（Ｐ〈０．０５）。结论：野菊     

Astrocytic MLC1 involved in brain water homeostasis and myeline integrity

Tijdschrift voor Kindergeneeskunde -     

有机锡化合物抗肿瘤生物活性研究

有机锡(IV)化合物能明显地抑制大鼠脑组织中PKC活性和肿瘤细胞增殖，且两者之间存在着相关性。抗肿瘤活性的构效关系是：(1)有机基团R决定整个化合物的生物活性，Ph>Et>n-Bu；(2)卤素的电负性影响化合物活性的大小。抗肿瘤活性可能通过[snR₂]²⁺实现。并能部分地阻断HL-60细胞周期中的G_I期向S期的移行。[SnPh₂F₂]，[SnPh₂(CysOS)]H₂O和[SnPh₂Cl2·phen(CH₃)₂]对PKC的IC₅₀值分别为25，15和20 umol·L^-1，对HL-60细胞的IC₅₀值分别为0．5，4．0和0．3umol·L^-1。但它们无诱导分化HL-60和K562细胞的作用。     

Assessment of regional wall motion and perfusion by multigated myocardial scintigraphy after intracoronary Tl-201

Fourteen patients undergoing intracoronary thrombolysis for acute myocardial infarction had intracoronary injection of thallium-201 to assess myocardial salvage after reperfusion. Scintigrams of the perfused myocardium were gated and compared with both ungated scans and radionuclide ventriculograms (multigated blood pool scintigrams) to determine the value of gated perfusion images for studies of both perfusion and regional wall motion. Multigated and ungated thallium images provided comparable information about regional myocardial perfusion. Correlation between multigated thallium images of regional wall motion and radionuclide ventriculograms was poor (tau = 0.44). Assessment of wall motion was most accurate in well-perfused segments and least accurate in partially perfused segments.     

RNA干扰选择性下调血管平滑肌细胞结缔组织生长因子的表达

目的:从血管平滑肌细胞结缔组织生长因子的基础分泌及转化生长因子β1对其分泌的诱导作用入手,进一步观察并验证RNA干扰技术靶向抑制结缔组织生长因子对下游纤维化因子的影响。方法:实验于2006-03/2007-05在武汉协和医院心血管病研究所实验室完成。①实验材料:健康雄性成年SD大鼠,体质量150～180g。②实验方法及分组:分离培养成年大鼠血管平滑肌细胞,以5μg/L终浓度转化生长因子β1对培养的血管平滑肌细胞进行诱导,再通过脂质体法将靶向大鼠结缔组织生长因子的shRNA干扰质粒转染入血管平滑肌细胞,200mg/L终浓度的G418筛选出稳定转染细胞株后培养增殖进入后续实验。将实验分为5组,分别为对照组,不给与任何干预措施;转化生长因子β1刺激组,在培养的血管平滑肌细胞培养液中加入转化生长因子β1(5μg/L终浓度)刺激诱导24h;HK阴性质粒对照组,血管平滑肌细胞常规培养3～5代后转染HK阴性质粒继续培养48h;RNA干扰组,先以转化生长因子β1(5μg/L终浓度)诱导刺激血管平滑肌细胞24h后再转染干扰质粒继续培养48h;单纯转染试剂组,细胞常规培养3～5代后仅加入lipo2000转染试剂。③实验评估:通过逆转录-聚合酶链反应和(或)蛋白免疫印迹技术进一步检测各组心肌细胞结缔组织生长因子、纤维连接蛋白mRNA及蛋白的表达。结果:①组织块贴附法培养的原代血管平滑肌细胞,可见大量细胞紧密排列成长梭形。②倒置荧光显微镜下观察,脂质体lipo2000转染血管平滑肌细胞瞬时转染效率仅有大约30%左右;而通过加入G418进行稳定转染后,几乎所有细胞均可被激发出亮绿色荧光,转染效率可达95%以上。③对照组结缔组织生长因子、纤维连接蛋白均有低水平的基础分泌,在予以转化生长因子β1诱导后表达显著升高(P<0.01);而在靶向特异性RNA干扰后,与转化生长因子β1刺激组比较,结缔组织生长因子及纤维连接蛋白的表达均被显著抑制(P<0.01);并且纤维化因子纤维连接蛋白及胶原的表达与促纤维化因子结缔组织生长因子的表达有显著相关性。结论:血管平滑肌细胞可自主分泌结缔组织生长因子及细胞外基质成分;而通过RNA干扰靶向抑制结缔组织生长因子后可阻抑血管平滑肌细胞分泌下游纤维化因子。提示血管平滑肌细胞可主动参与心血管重塑及纤维化,而RNA干扰靶向沉默结缔组织生长因子基因的表达可以有效干预纤维化过程。     

Effect of granulocyte colony-stimulating factor treatment on ex vivo blood cytokine response in human volunteers

We explored the ex vivo alteration in the cytokine release of stimulated blood taken from healthy volunteers treated subcutaneously with 480 micrograms granulocyte colony-stimulating factor (G-CSF). In a double-blind, controlled, randomized study with 21 volunteers who received G-CSF once or twice 24 hours apart, we measured lipopolysaccharide (LPS)-inducible release of various cytokines and soluble receptors at different times after treatment. At day 1 after a single dose of G-CSF, mediator release was also initiated with muramyl dipeptide, Staphylococcus aureus enterotoxin A, lipoteichoic acid, streptolysin O, complement factor C5a, phytohemagglutinin, or phorbol myristate acetate. In blood from G-CSF-treated subjects, our major findings were (1) a maximal 12-fold increase in interleukin-1 receptor antagonist (IL-1ra) release and an increase of both the p55 and p75 soluble tumor necrosis factor (TNF) receptors; (2) a reduction in TNF release when using all the various stimuli described except LPS; (3) an increase in G-CSF and, to lesser extent, in IL-6, IL-8, and IL-10 release; and (4) an attenuation of interferon-gamma (IFN-gamma) and granulocyte-macrophage (GM)-CSF release. Our findings demonstrate that the major effect of G-CSF treatment is a change in the responsiveness of blood towards a variety of stimuli, which we interpret as a shift toward an antiinflammatory cytokine response.