食管癌患者血缘亲属及不同性别食管癌患病风险比较研究

目的 对比分析食管癌病例组与对照组血缘亲属食管癌患病风险,并了解食管癌家族中危险亲属人群患病的新线索.方法 采用病例对照研究方法 ,对食管癌病例组及对照组各720例进行逐层分析,以比较两组各血缘亲属父系、母系食管癌患病危险度(OR)的大小及差异.结果 (1)病例组Ⅰ级亲属食管癌患病危险度(1.34%～2.24%)显著高于对照组(0.78%～1.21%)(P＜0.01);Ⅰ级亲属中病例组父母亲食管癌患病危险度为6.11%,显著高于对照组父母亲食管癌患病危险度2.97%(P＜0O01).(2)以血缘亲属中父系和母系亲属逐层分析可见,病例组父系食管癌患病危险度(0.87%～1.01%)与母系患病危险度(0.50%～0.79%)均显著高于对照组父系食管癌患病危险度(0.53%～0.65%)与母系患病危险度(0.38%～0.47%)(P＜0.05).进一步分析显示,病例组父系中男性亲属与母系中女性亲属,即父系中祖父、父亲、叔伯食管癌患病危险度为2.68%与母系中外祖母、母亲、姨的食管癌患病危险度1.91%均显著高于对照组父系中男性亲属食管癌患病危险度1.50%与母系中女性亲属食管癌患病危险度0.92%(P＜0.01).结论 山西省食管癌患者血缘亲属发病危险主要是父亲及其兄弟、母亲及其姐妹,其下代患食管癌风险要大.     

近年火车创伤中关节损伤变化的特点

目的 探讨与分析快速列车所致火车创伤中关节损伤的变化特点。方法 集1997～2000年火车提速后10214例火车创伤中1279例关节损伤病例，分析在特定条件下的致伤因素、损伤严重程度、损伤类型特点，经AIS-ISS评分证实与预后的关系。结果 提速后关节损伤发生率由提速前33.54％上升到34.12％，死亡率由28.88％上升到30.33％，多关节离断伤由19.84％上升到34.13％，开放性关节损伤由31.71％上升到63.65％，关节离断伤的死亡率由21.19％上升到49.07％。结论 火车创伤无疑是十分严重的损伤，多发伤率远高于其他损伤，治疗棘手，多器官功能不全综合征(MODS)是致死的主要因素。     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Selection of cytotoxic T lymphocytes against autologous human melanoma from lymph nodes with metastatic melanoma using repeatedin vitro sensitization

Our goal was to determine the cytotoxic activity of effector cells in lymph nodes with metastatic melanoma. Lymphocytes contained within tumor cells from metastatic lymph nodes of two patients were allowed to proliferate in recombinant IL-2 (rIL-2, 100-1,000 units/ml) after 14–21 days of culture. Each set of lymphocytes showed cytotoxicity against autologous melanoma (AM, mean 72%) at effector to target ratio of 201 and K562 cells (mean 60%) using 4-h chromium-51 release assay. Using unlabeled AM and K562, each AM could partially block the activity against K562, but K562 could not block the activity against AM. These activated lymphocytes underwentin vitro sensitization (IVS) with irradiated AM cells and rIL-2 at 2-week intervals. After repeated IVS over about 50 days, each patient's lymphocytes showed cytotoxicity against AM (mean 54%) but not K562 (mean 5%,P < 0.001). These results indicate that different cytotoxic effector cells were present in the early and late phase of lymphocyte tumor culture. Repeated IVS resulted in the selection of specific cytotoxic T lymphocytes. Cold target inhibition assay demonstrated that melanoma cells contained common and individual AM-associated antigen in addition to K562-associated antigens.This work was supported by Biomedical Research Support Grant of the University of Arizona (no. 2S07 RR05675-20), the Elsa U. Pardee Foundation Grant, partly by the Arizona Chronic Disease Research Commission and partly by CA23074 from the National Institutes of Health, Bethesda, 20892, U.S.A.Recipient of the American Cancer Society Clinical Oncology Career Award, 1987–90.