Alaska Native Cancer epidemiology in the Arctic

Cancer incidence and its possible relation to environmental contaminants, including radiation, continues to be a perceived health threat for the arctic-dwelling Alaska Native (Inupiat Eskimo) people despite the lack of a direct link to high-dose exposure. To better understand this concern, all known malignancies diagnosed in this population (n = 177) in three consecutive eight-year periods (1971–1994) were evaluated.The most recent average incidence rate (age-adjusted to world standard population) of 315 per 100 000 (95% confidence interval, CI = 248–382) represents a 33% surge (albeit non-significant) in Alaska Native cancer incidence over the initial period studied. The male rate 366 (95% CI = 266–466) for the same period exceeds the female rate 258 (95% CI = 169–347) by 42%. Two patterns of cancer incidence are seen at the village level. One, a 24 y upward trend found in the villages of Barrow, Point Hope and Kaktovik (combined rate of increase significant [P = 0.047]) associated with lung cancer; and the other, a stable trend over the past 16 y, associated with colon and rectal cancer. Lung cancer is the predominant cancer by site and is primarily a male disease. The recent male lung cancer incidence rate of 137 (95% CI = 73–201) exceeds the female rate by greater than five times. Total lung cancer cases are primarily confined to four villages where the incidence significantly (P = 0.0043) exceeds the remaining population. The major female cancers are colon/rectal and breast with cancer of the cervix virtually eliminated. Breast cancer is found primarily in two villages where its excess is significant (P = 0.025).Inupiat Eskimo cancer epidemiology is unique, differing from both the Alaska Native and other Circumpolar populations. At present, this uniqueness cannot be explained by an overt environmental contaminant exposure. Although tobacco very likely plays a central role, it by itself cannot fully explain the extremely high male lung cancer rate and why only specific villages are affected. Genetic predisposition and environmental factors may play a synergistic role as cofactors. A cooperative investigative effort with the Inupiat population is indicated and may go a long way in reducing cancer concern in the region.     

荧光原位杂交技术分析人结肠菌群方法研究

建立荧光原位杂交技术分析人体内结肠菌群的方法。取受试者新鲜粪便 ,选用 5种特异性的 16SrRNA寡核苷酸探针 ,检测粪便样本收集后的保存时间、温度 ,离心条件及样本固定液存放时间对杂交计数结果的影响。结果建立最佳实验条件为 :粪便样本收集后应尽快在 4℃下保存 ,放置时间不要超过 12小时即作处理 ;样本的适宜离心条件为 70 0g 2分钟 ;样本用多聚甲醛固定后在 - 80℃下存放时间不要超过 5个月。该方法具有较好的稳定性 ,可以有效地检出个体之间结肠菌群的差异。     

CYP1B1基因敲除对成年小鼠肝脏脂肪代谢的影响及可能机制

目的探讨CYP1B1对高脂膳食诱导的成年小鼠脂肪代谢的作用。方法 CYP1B1基因敲除(KO)和野生型(WT)雄性成年C57/BL小鼠(6 w龄)各16只,给予低脂(LFD,30%)、高脂肪(HFD,60%)饲料共6 w。小鼠处死后取血清、附睾脂肪和肝脏组织检测相应的生化和分子生物学指标。结果 6 w高脂膳食后,KO小鼠能量摄入总量稍高于WT小鼠,但其体重增量和附睾脂肪组织重量均显著低于WT小鼠;WT小鼠脂肪细胞直径明显大于KO小鼠,且血糖、血清及肝脏组织中甘油三酯(TG)水平亦明显高于KO小鼠;肝脏组织RT-PCR结果显示,CYP1B1基因敲除后,启动脂肪形成的核因子及脂肪合成相关基因如CD36、SREBP1c、SCD1等表达下降,而调控脂肪氧化分解的基因如CPT-1α,UCP-2表达显著上升;蛋白印迹结果显示,CYP1B1基因敲除增强腺苷-磷酸激酶(AMPK)的磷酸化。结论 CYP1B1基因敲除对成年小鼠营养性肥胖的保护作用可能与AMPK磷酸化增强并调控肝脏中脂肪代谢相关基因的表达有关。     

Immunoblotting characterization of neutrophil antigenic targets in autoimmune neutropenia

We characterized neutrophil autoantigens using an immunoblotting technique with antibodies obtained from patients with autoimmune neutropenia. These results were correlated with serologic characterization of the antibodies, using indirect immunofluorescence and leukoagglutination. Of the 17 sera immunoblotted, 16 showed discrete bands in the molecular weight range of 30 to 112. Three patients with Felty's syndrome reacted with an antigenic target of 80 to 84 Kd molecular mass, a finding not seen in any of the other patients studied. By serologic testing, none of the autoimmune sera showed serologic specificity for any known neutrophil-specific alloantigen. Using an anti-NA-1 serum, we identified antigenic targets at 40, 50, and 101 Kd in both NA-1-positive and NA-1-negative neutrophils. Ten of 17 autoimmune sera showed reactivity in this corresponding range. These studies demonstrate that immunoblotting may be used to identify antigenic targets in autoimmune neutropenia and may suggest a specificity of these antibodies not definable by serologic techniques. Correlation of immunoblot reactivity with disease states associated with immune neutropenia may be useful in the study of the pathogenesis of the different forms of autoimmune neutropenia.