MPO和NAT2基因多态性与成人急性白血病易感性

目的研究髓过氧化物酶（MPO）和N-乙酰基转移酶2（NAT2）基因多态性与成人急性白血病易感性的关系.方法用1∶1配对病例-对照研究方法,收集成人急性白血病患者和对照各139例,应用聚合酶链-内切酶片段（PCR-RFLP）方法分析病例组和对照组MPO和NAT2的基因多态性,比较不同基因型与成人急性白血病易感性.结果 MPO-463A等位基因分布频率病例组低于对照组,MPO（G-463A）各基因型在病例组与对照组中的分布差异有统计学意义（χ^2=7.026,P〈0.05,OR=0.505,95%CI=0.325～0.847）.NAT2乙酰化表型频率在病例组与对照组的分布差异无统计学意义（χ^2=2.260,P〉0.05）;但NAT2＊5 481T等位基因和NAT2＊6 590A等位基因分布频率病例组高于对照组（P〈0.05）.结论 MPO与成人急性白血病易感性相关,携带MPO（G-463A）突变基因型（GA/AA）个体可降低白血病的发病风险;NAT2乙酰化表型可能与白血病的易感性无关,但NAT2＊5（C481T）、NAT2＊6（G590A）单核苷酸突变频率病例组明显高于对照组.     

胶片剂量测量和验证方法的研究

目的设计和实现基于通用激光扫描仪的胶片剂量测量和验证系统。方法采用胶片饱和冲洗、非线性光学校正、多分辨率阈值滤波、离散傅里叶逆变换图像复原等方法,消除了普通扫描仪用于胶片剂量学定量处理中的各种伪影、噪声和畸变;采用过响应系数校正方法消除测量胶片对低能散射光子的过响应,改善了胶片剂量测量的准确性;采用γ结合NAT指标的方法对放疗计划进行二维定量验证,给出可视化图形表达和具有定量数据的验证结果。结果和三维水箱系统、VeriSoft胶片测量系统相比较,研制系统对放疗剂量的测量结果在±2%内符合一致,对IMRT放疗计划的定量验证结果在±3%内符合一致。结论该系统能够实现对放疗剂量的高精度测量和对适形调强放疗计划剂量的可靠验证。     

Inter-laboratory comparison of qualitative and quantitative detection of hepatitis C (HCV) virus RNA in diagnostic virology: a multicentre study (MS) in Italy

BACKGROUND: The importance of the standardisation of nucleic acid amplification technology (NAT) assays for the detection of hepatitis C virus RNA is well known today, as many studies carried out in different European countries attest. The results of a previous study performed in Italy (J. Clin. Virol. 1 (2003) 83) by the Italian Society of Clinical Microbiology (AMCLI) showed that the use of external reference standards and of multicentre collaborative studies significantly improves laboratory performance for the qualitative evaluation of HCV RNA. OBJECTIVES: the AMCLI organised a new study on the standardisation of both the qualitative and the quantitative evaluation of HCV RNA with NAT in order to improve the implementation of the diagnostic methods for HCV RNA detection. STUDY DESIGN: seventeen diagnostic centres of major Italian Hospitals participated in this quality control study. The study consisted of testing three panels, each made up of 10 coded samples including negative and positive samples. Positive samples contained four levels of HCV RNA (genotype 1). RESULTS AND CONCLUSION: Seven out of 510 qualitative results obtained were incorrect (1.4%), two false negative and five false positive. The results gave a sensitivity of 99.5% and a specificity of 95.8%. Regarding quantitative tests, the geometric mean (GM) and standard deviation (S.D.) could be calculated only for the three highest HCV RNA levels. The percentage of results within the range of GM +/- 0.5 log(10) varied from 91% to 100%. Some laboratories had some difficulty in the exact quantification of the lowest (3.00 log IU/ml) as well as of the highest viral levels (6.35 log IU/ml) values, very near to the limits of the dynamic range of the assays. The comparison of the results of this study with that previously carried out one confirms that a regular participation in external quality assessment (EQA) assures the achievement of a high proficiency level in the diagnosis of HCV infection.     

Metabolic polymorphisms and the micronucleus frequency in buccal epithelium of adolescents living in an urban environment

Micronuclei and other biomarkers were evaluated in oral cells from 11- to 16-year-old girls living in a foster home in the central area of México City. Variables analyzed for possible association with these biomarkers include smoking habits, body mass index, metabolic polymorphisms for NAT1 and GSTM1 and whether the cells were obtained from the cheek or pharynx. The results indicated that individuals having the NAT1*10 homozygous genotype showed a significant increase in chromatin buds and binucleated cells. When the damage in the cheek was compared with damage in the pharynx, a significant increase in micronuclei and binucleated cells was found for the latter tissue in all the individuals analyzed.     

Urothelial cell DNA adducts in rubber workers

Workers employed in the rubber industry appear to have a significant excess cancer risk in a variety of sites, including cancer of the urinary bladder. In this cross-sectional study, we investigated the occurrence of DNA adducts in exfoliated bladder cells of currently exposed, nonsmoking rubber workers (n = 52) and their relationship with occupational exposure estimates and acetylation phenotype (NAT2). Four DNA adducts were identified, with the proportion of positive samples (e.g., DNA samples with quantifiable levels of a specific DNA adduct) ranging from 3.8 to 79%. The highest proportion of positive samples and the highest relative adduct labeling levels were in workers involved in the production functions "mixing" and "curing," areas with potential for substantial exposure to a wide range of chemical compounds used in rubber manufacturing (P < 0.05 for adducts 2 and/or 3, compared to all other departments). No statistically significant relationships were found between identified DNA adducts and urinary mutagenicity or personal inhalable and dermal exposure estimates. Interestingly, subjects with a fast NAT2 acetylation phenotype tended to have higher levels of DNA adducts. This study suggests that rubber workers engaged in mixing and curing may be exposed to compounds that can form DNA adducts in urothelial cells. Larger studies among rubber workers should be conducted to study in more detail the potential carcinogenicity of exposures encountered in these work areas.     

Structure-Function Analyses of Single Nucleotide Polymorphisms in Human N-Acetyltransferase 1

Human N-acetyltransferase 1 (NAT1) alleles are characterized by one or more single nucleotide polymorphisms (SNPs) associated with rapid and slow acetylation phenotypes. NAT1 both activates and deactivates arylamine drugs and carcinogens, and NAT1 polymorphisms are associated with increased frequencies of many cancers and birth defects. The recently resolved human NAT1 crystal structure was used to evaluate SNPs resulting in the protein substitutions R64W, V149I, R187Q, M205V, S214A, D251V, E261K, and I263V. The analysis enhances knowledge of NAT1 structure-function relationships, important for understanding associations of NAT1 SNPs with genetic predisposition to cancer, birth defects, and other diseases.     

多线路接入医院网络实现多种应用的实践研究

选用思科ASA5550作为接入设备，对电信互联网、医保专用网、联通互联网实施接口配置，对这些外来线路进行统一规划后再与内部网络连接，以达到安全网络管理与规范管理的效果。同时解决了因多条线路接入导致网络拓扑复杂、设备成本高等问题。     

Evaluation of COBAS AmpliPrep nucleic acid extraction in conjunction with COBAS AmpliScreen HBV DNA, HCV RNA and HIV-1 RNA amplification and detection

BACKGROUND AND OBJECTIVES: This report describes the evaluation of the COBAS AmpliPrep instrument for fully automated generic nucleic acid extraction in conjunction with hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA, and human immunodeficiency virus (HIV)-1 RNA COBAS AmpliScreen amplification and detection using serial dilutions of the WHO international standards (IS) and the PeliCheck reference panels. MATERIALS AND METHODS: Serial diluted samples of the WHO IS and the PeliCheck reference panels were tested 24 times to determine the HBV DNA, HCV RNA and HIV-1 RNA detection limits by Probit analysis. The existence and extent of cross-contamination were assessed by testing alternating high titre HBV DNA-positive and -negative samples. The specificity of the AmpliPrep-AmpliScreen test for HBV was determined by testing 232 minipools consisting of six donations, all negative for HCV/HIV-1 nucleic acid testing (NAT) and HBsAg. In addition, a HBV genotypes A-G panel was tested. RESULTS: The respective 95% detection limits (and 95% CI) on the WHO IS and on the PeliCheck reference panels were 6.7 (4.3-13) IU/ml and 123 (68-301) gEq/ml for HBV DNA, 23 (11-106) IU/ml and 126 (84-233) gEq/ml for HCV RNA, and 187 (108-422) IU/ml and 183 (108-434) gEq/ml for HIV-1 RNA. Based on the WHO IS and the PeliCheck reference panels, no significant differences in sensitivity for HBV and HCV were found between AmpliPrep and the licensed MultiPrep extraction method. The sensitivity of AmpliPrep-AmpliScreen for HIV-1 was probably twofold lower as compared to the MultiPrep-AmpliScreen method. No cross contamination was observed. All 232 minipools were HBV NAT-negative. The AmpliPrep-AmpliScreen test for HBV detected HBV genotypes A-G with equal sensitivity. CONCLUSIONS: The AmpliPrep instrument combined with the AmpliScreen assays for HBV, HCV and HIV-1 is robust and suitable for NAT donor screening. The sensitivity criteria for HIV-1 and HCV as defined by the Paul Ehrlich Institute and the Food and Drug Administration for minipool NAT screening are met by this system. SINGLE SENTENCE SUMMARY: Generic COBAS AmpliPrep nucleic acid extraction in conjunction with COBAS AmpliScreen detection for HBV, HCV and HIV-1.