宫颈癌患者核糖核酸酶抑制因子基因突变分析和常见食源性致病菌快速检测技术体系的建立
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:核糖核酸酶(RNase)是降解RNA的酶类,核糖核酸酶抑制因子(ribonuclease inhibitor,RI)能和碱性RNase(AKR)结合而抑制其活性,从而减少RNA的降解。核糖核酸酶抑制因子(RI)是一种存在于细胞浆中的50KD的酸性蛋白质,广泛分布与哺乳动物的各种组织器官中,其中在人的胎盘中含量最为丰富。血管生成因子(angiogenin,Ang)是一种单链的碱性蛋白质,分子量为14KD,属于核糖核酸酶(RNase)超家族的一员,其氨基酸序列与核糖核酸酶A有35%的一致性。血管生成因子主要催化18S和28S rRNA的有限水解,但它重要的生物学功能是具有诱导新血管网形成的作用。肿瘤生长依赖于其周围新血管的生成,以便给其提供生长所需的必要物质。RI是由7个亮氨酸重复序列排列折叠而成,每个重复单位含有一个短的β片层和一个长的α螺旋,β片层排列在马蹄形的内表面形成平行的β片层,而α螺旋装饰外表面,7个亮氨酸重复单位有规律的环状排列是N末端C末端在空间上较为接近。RI可与RNase A以1:1化学计量比紧密结合,对其产生竞争性抑制作用,以极低的Ki值(4×10~(-14) mol/L)控制胞内RNA水平。血管生成因子的氨基酸残基组成与核糖核酸酶A(RNase A)具有35%的同源性,它们有着极其相似的空间结构都可以作为配体与RI结合。而RI-Ang复合体的解离常数要比RI-RNase A复合体低约60倍。RI抑制肿瘤的机制目前认为包括两个方面:①RI能强烈抑制血管生成因子的血管生成活性。②RI能阻断肿瘤细胞对于血管生成因子的黏附,防止瘤细胞又黏附到血管生成因子上被带到新生成的血管上。
     方法:核糖核酸酶抑制因子基因(RNH)位于11号染色体短臂,即11P~(15)。此部位分布着许多重要的基因,如ras基因。RNH基因包括11个外显子,10个内含子,为了进一步研究RNH基因与肿瘤发生的关系,RI基因是否是抑癌基因,本实验设计21对引物,利用PCR-SSCP方法,研究核糖核酸酶抑制因子全基因在肿瘤细胞中有无突变,采用正常人的全血标本与宫颈癌患者全血标本。为了增强PCR的检测效果,阳性内参采用β-actin。对于宫颈癌患者的核糖核酸酶抑制因子全基因的突变研究尚没有成型SSCP分析方法的条件,所以在实验中对于各种条件进行了初步的摸索和优化。
     结果:PCR实验结果表明,从普通琼脂糖凝胶电泳可以看出正常人和宫颈癌患者都扩增出了相应的21个片段,电泳图谱未显示有差别。SSCP技术在不含变性剂的中性聚丙烯酰胺凝胶中电泳时,DNA单链的迁移率除与DNA链的长短有关外,更主要的是取决于DNA单链所形成的构象。此次聚丙烯酰胺凝胶电泳尽量避免其影响因素,采用4%的聚丙烯酰胺凝胶以提高检出率。实验中扩增的片段最小231bp,最大970bp。
     结论:SSCP分析的结果显示正常人与宫颈癌患者的核糖核酸酶抑制因子基因未发现其在遗传学上的差异,但尚不能肯定其他肿瘤没有发生突变。
     创新点:
     1.首次对宫颈癌患者核糖核酸酶抑制因子基因突变进行了分析;
     2.设计了全基因序列引物,共21对引物;
     3.建立了SSCP分析核糖核酸酶抑制因子基因突变的最适条件。
     目的:据WHO估计,全世界每年发生食源性疾病数十亿人,每年几乎有二百万儿童死于腹泻,而大部分腹泻是由被微生物污染的食品和水引起,其中66%以上是由细菌性致病菌所致。常见的食源性致病菌主要有沙门氏菌、空肠弯曲菌、单核细胞增生李斯特氏菌、大肠杆菌O_(157):H_7、志贺氏菌、金黄色葡萄球菌、副溶血弧菌、霍乱弧菌等。对上述食源性致病菌的检测在一定程度上可以有助于其得到有效的控制;传统的检测程序复杂,所用试剂繁多,费时费力,灵敏度低,假阴性比较严重,已经不能适应现代检食品安全的要求。PCR方法、实时荧光PCR方法、全自动免疫荧光方法等快速检测方法是近年了发展起来的全新检测技术,具有快速、简便、灵敏度高、特异性强、自动化程度高等优点。本研究着重于常见致病菌快速检测方法体系的建立,并应用于样品的检测;同时对于检出的沙门氏菌进行流行病学调查,针对传统的检测方法鉴定到血清型后,依赖详细评价阳性案例和一批适当的对照,确定调查与特殊疾病的关联因素,不能区分同一血清型不同菌株同源性的特点,本研究用脉冲凝胶电泳方法对其进行分子分型,为研究其流行病学特征和同源性提供分子生物学技术依据。
     方法:①本研究采用PCR和实时荧光PCR技术,根据尽量避免假阴性(漏检)的基本原则进行靶基因的选择。再依据尽量从理论上避免检测的假阳性及假阴性并提高检测灵敏度的原则来设计引物和探针。从基因序列库中下载所有已经公开发表的靶基因序列,运用DNAStar软件中的SeqMan和MegAlign模块进行排序比较。利用ABI Primer Express 2.0,DNAStar PrimerSelect等寡核甘酸设计软件在保守区段设计多套引物和探针,确保引物之间、引物与探针之间不会形成稳定的二聚体,然后在GenBank上做BLAST分析,确认所设计的引物和探针与其它生物物种的基因序列不存在互补配对现象,然后进行引物、探针筛选,针对8种食源性致病菌分别建立普通PCR和实时荧光PCR检测体系并进行优化。②采用平板菌落记数的做为对照试验,以确定各个检测方法的灵敏度。在独立进行的灵敏度的验证实验中,每个稀释梯度均与国标法和行标法进行了对照。③同时采用了对照菌株进行了检测方法的特异性实验。④运用以上建立的方法,对鸡胴体淋洗液样品进行沙门氏菌检测;即样品经过前增菌和选择性增菌后,分别采用4种不同的方法进行检测,即普通PCR方法、实时荧光PCR方法、免疫学方法(VIDAS)和传统的微生物检验方法。⑤PFGE方法对分离到的7株鼠伤寒沙门氏菌进行增菌,制成一定浓度的菌悬液后,制备琼脂糖菌体包埋胶块,用溶菌酶、蛋白酶K和TE缓冲液依次处理提取菌体DNA后,用限制性内切酶XbaI消化胶块,再用脉冲凝胶电泳仪进行DNA分子分型;同时使用全球统一参考菌株沙门菌Braenderup血清型H9812,XbaI酶切,作为分子量标准(Marker);对电泳后的图谱,采用BioNumerics软件对其同源性进行聚类分析比较,菌株的同源性用相似性系数(矩阵)和百分数表示。
     结果:
     ①建立了沙门氏菌、空肠弯曲菌、单核细胞增生李斯特氏菌、大肠杆菌O_(157):H_7、志贺氏菌、金黄色葡萄球菌、副溶血弧菌以及霍乱弧菌8种常见食源性致病菌的普通PCR和实时荧光PCR快速检测的标准操作程序。其核心内容包括靶基因的确定、特异性扩增引物和探针的设计和筛选以及扩增反应体系的优化。
     ②对所研制的8种常见食源性致病菌的普通PCR和实时荧光PCR快速检测方法最优反应体系的灵敏度进行了测试,结果显示:单核细胞增生李斯特氏菌核酸提取法优于直接煮沸法,其他的细菌没有显著性差异;实时荧光定量PCR检出限数小于普通PCR,前者检测体系的灵敏度可达到了10~2cfu/mL左右:8种常见食源性致病菌中单核细胞增生李斯特氏菌、大肠杆菌O_(157):H_7和志贺氏菌的检出限比较低;上述8种常见致病菌的检测方法的灵敏度均优于国标法。
     ③采用对照菌株测试了各个检测体系的特异性,结果表明各个检测体系对所有对照菌株都没有阳性检测信号产生,显示其特异性极高,没有出现一例非特异性的检测结果。
     ④应用上述建立的方法,共检测了56份鸡胴体淋洗液样品中的沙门氏菌,普通PCR检出阳性样品34份,实时荧光PCR阳性样品36份,VIDAS阳性样品28份;PCR和实时荧光定量PCR均无假阳性和假阴性结果。结果显示该3种检测方法均可以用于鸡胴体中沙门氏菌的快速检测。
     ⑤针对以上检出的鼠伤寒沙门氏菌,进行菌体DNA经酶切、脉冲凝胶电泳后,沙门氏菌参考菌株和每个待测菌株均出现了15条以上的条带,图谱经软件分析后结果显示:FJ003号和FJ004号两个菌株的相似度约为96.2%,FJ001号和FJ002号相似度为95.8%,FJ007号和FJ001、FJ002号的相似度为83.8%,7个菌株彼此的相似度范围为61.0%~96.2%。按照85%相似度的评定标准,同一血清型的7株鼠伤寒沙门氏菌可以分成5个型。PFGE具有分辨力高,是研究鼠伤寒沙门菌分子流行病学较好的基因分型方法。
     结论:
     本课题成功建立了8种常见食源性致病菌一整套普通PCR和实时荧光PCR检测方法,并且把实时荧光PCR反应条件一致化,使之更具有可操作性;在靶基因选择方面的有创新,设计了有自主知识产权的引物和探针,具有灵敏度高、特异性强等特点;建立的快速检测方法适用于多种国外食物微生物权威方法的前增菌液,同时即可用于筛选,又可用于确认;特别适用于检验检疫、疾病控制、临床诊断、产品质量检验等对上述致病菌的检测。
     本次试验采用Xba I酶作为鼠伤寒沙门菌染色体DNA的限制性内切酶,产生的电泳条带较理想,每株约产生16~25条电泳带,说明本次试验所选用的限制性内切酶和电泳条件适合鼠伤寒沙门菌的分型;按照85%相似度的评定标准,将7株菌株分成5个型。本实验方法可以帮助确定同一血清型菌株之间的亲缘关系。
     创新点:
     1.成功建立了常见食源性致病菌的普通PCR和实时荧光PCR检测方法,方法具有技术先进、特异性好、灵敏度高、快速准确等特点,检出限可达10~2cfu/mL,与传统检测方法相比,灵敏度提高了3个数量级;
     2.新建立的方法已经通过了行业标准的审定;
     3.方法中有自主知识产权的引物和探针序列;
     4.方法中含8种常见的致病菌的检测,致病菌的数目比较多;
     5.成功应用PFGE对检出的鼠伤寒沙门氏菌进行了分子分型,分型精确,确定了同一血清型菌株之间的亲缘关系。
Objective: Ribonuclease Inhibitor (RI) is a 50KD acidic protein existing in cytoplasm, which lies in all tissues and organs of the mammals extensively, especially affluent in the placenta of humans. RI can decrease the RNA degradation by RNase A, because RI can inhibit the activity of RNase A for the combination with alkaline RNase. Angiogenin (Ang) is a single strand 14 KD alkaline protein, belonging to RNase A superfamily, and which can induce the formation of newly formed vascular net. The growth of tumor depends on the formation of the newly formed circumambient vascular, they can supply the necessary nourishment for the growth of tumor. There is 35% homology between the amino acid residues of the Ang and RNase A and their similar spatial structure can both combine with RI as ligand. The dissociation constant of the RI-RNase complex was higher than the RI-Ang complex by 60 times, and RI can inhibit the formation of the newly formed vascular effectively. The objective of the paper was to establish an effective method for analysis of gene mutation of Ribonuclease Inhibitor (RNH) in the blood cells of patients with cervical carcinoma, what's more, the RNH of 30 normal persons and 18 patients with cervical carcinoma were detected by means of the method established in the experiment.
    Method: The RNH lies in the galianconism of the No. 11 chromosomes (11P~(15.5)), the whole length of the gene is 12310bp, including in 11 extron and 10 intron. The target gene fragments must contain the whole sequence of extron when primers were designed, and several target gene fragments contained two adjacent extron and parts of the adjoining introns, and there
    were 11 pairs of such primers. But the longer intron were divided into several fragments eligibly for amplification, and all the target gene fragments were less than 1000 bp, and there were 10 pairs of such primers, so there were 21 pairs of primers in the experiment, and most of the target gene fragments were between 300-700bp. The conditions of Polymerase Chain Reaction (PCR) were optimized by using the genome DNA extracted from the normal persons' blood cells, then the target gene fragments were amplified using the DNA extracted from the normal persons and the patients with cervical carcinoma as mould respectively, the 21 primers were designed as above. β-actin were adopted as the internal standard to verify the results of PCR. Single strand conformation polymorphism (SSCP) was used to the mutation analysis. The amplification products of the normal persons' DNA were used for the optimization of the experiment. The gene mutations were judged by the difference of the electrophorestic mobility shift of the degenerative single strand DNA on the polyacrylamide gel. All the target gene fragments were amplified used the 21 designed primers after optimization.
    Results: The PCR products were undertaken the electrophoresis on the agarose gel, then the electrophorestic mobility shift of each product(s) of the 21 primers were compared, but there is no significant differences. The most optimized conditions of the SSCP in the experiments were as follows: The ratio of the acrylamide and Methylene-bis-Acrylamide was 49:1, the concentration was 4%, and glycerin was not contained, the thickness of the gel was 1 mm, the voltage was 220v, the temperature was 4℃, buffer solution was 0.5×TBE, the volume of the sample was 5 μ l. The groups of SSCP analysis were same as the agarose gel electrophoresis, the electrophorestic mobility shifts were obtained according to equation of M=Ld/Vt, the fine repeatabilities were checked by the General Linear Model. There were not significant differences in the results of the single strand DNA electrophorestic mobility shift in polyacrylamide gel electrophoresis. The results showed that there was not significant genetic difference between the gene of RI of the normal persons and patients with cervical carcinoma.
    Objective The aim of our study was to establish the techniques protocols for the rapid detecton of 8 species foodborn pathogen, and we compare the efficiency of different methods for rapid Salmonella detection in whole chicken rinses samples and to optimize the most appropriated method of detection. For the Salmonella typhimurium from the above samples, we also study the relationship among different strains, a molecular epidemiological analysis method — pulsed-field gel electrophoresis (PFGE) for the analysis of DNA restriction fragment length polymorphism (RFLP) in S. tyhpimurium was used.
    Methods Accroding to the pathogen's high reserve sequence, designing the prime and probe, and the specificity and sensitivity of the rapid protococls were done to evaluate the new methods suitabiltiy. The microbiological culture, the broth culture-PCR, the real-time PCR and VIDAS methods were used for the detection of Salmonella spp. in Whole Chicken Rinses. Each Salmonella typhimurium strain isolated from Whole Chicken Rinses was enriched, the Bacteria Cell Suspension Buffer (CSB) were mixed with melted 1% SeaKem Gold:1% SDS agarose, then dispense part of mixture into appropriate well(s) of reusable plug mold. The total genome DNA in agarose plugs was extracted in turn with lysozyme solution, proteinase K solution and TE buffer. The agarose pulgs were digested with restriction enzyme Xba I, followed by pulsed-field gel electrophoresis (PFGE). Salmonella ser. Braenderup H9812 standards was used. The bands were analyzed with statistics software.use BioNumerics software for database maintenance, tiff image normalization, and analysis and pattern
    comparisons.
    Results The rapid detection methods are more sensitive , specific and efficient, the detecting limite for PCR was about 10~4cfu/mL, 10~2cfu/mL for real-time PCR, suitable for Salmonella, Staphylococcus aureus, Shigella, Campylobacter jejuni, O_(157).H_7, Listeria monocytogenes, Vibrio paraheamolyticus and Vibrio cholera. The processing is rapid and simple, will be a routine and practical protocols for detecting and identifying pathogenic microorganisms. Using the above methods for Salmonella, total 56 Whole Chicken Rinses samples were detected, Salmonella were founded in 34 samples by the PCR, 36 positive by Real-time PCR, and 28 by VIDAS. Conclusion The above three detecting method were suitable for the rapid detection of Salmonella in Whole Chicken Rinses. 7 S. tyhpimurium isolated from Whole Chicken Rinses were subtyed using PFGE, the lanes with the Salmonella ser. Braenderup H9812 and 7 S. tyhpimurium had above 15 bands, the similarity between of FJ001 and FJ002 is 95.2%, 96.2% similarity is found between FJ003 and FJ004, the similarity range among total 7 S. tyhpimurium is from 61.0% to 96.2%. Taking 85% similitude as criterion, 7 strains of S. tyhpimurium were divided into 5 PFGE types. The typeability, the high discriminatory power and the stability of PFGE-RFLP make this a valuable method to be used in conjunction with serotyping.
引文
1.吴毓,赵宝昌等。N端缺失突变对核糖核酸酶抑制因子活性懂得影响,中国生物化学与分子生物学报2004年12月20(6):773-777。
    2. Lee F S, Fox E A, et al. Primary structure of human placental ribonuclease inhibitor. Biochemistry, 1988, 27: 8545-8553.
    3. Hofsteenge J, Kieffer B, Matthies R et al. Amino acid sequence of the ribonuclease inhibitor from porcine liver reveals the presence of leucinerich repeats. Biochemistry, 1988, 27: 8537-8544.
    4. Yee Chao, MD, PhD, et al Prognostic Significance of Vascular Endothelial Growth Factor, Basic Fibroblast Growth Factor, and Angiogenin in Patients With Resectable Hepatocellular Carcinoma After Surgery Annals of Surgical Oncology, 10(4): 355-362 2003.
    5. Tsuyoshi Etoh, Kenji Shibuta et al. Angiogenin Expression in Human Colorectal Cancer: The Role of Focal Macrophage Infiltration Clinical Cancer Research Vol. 6, 3545-3551, September 2000.
    6. Terrence M. Katona, Blake Lee Neubauer et al. Elevated Expression of Angiogenin in Prostate Cancer and Its Precursors. Clinical Cancer Research Vol. 11, 8358-8363, December 1, 2005.
    7. Hiroyuki Hisai, Junji Kato et al. Increased Expression of Angiogenin in Hepatocellular Carcinoma in Correlation with Tumor Vascularity Clinical Cancer Research Vol. 9, 4852-4859, October 15, 2003.
    8. S Montero, C Guzman et al. Angiogenin expression and prognosis in primary breast carcin-oma Clinical Cancer Research, Vol 4, Issue 9 2161-2168, 1998.
    9. Tsuyoshi Etoh, Kenji Shibuta et al. Angiogenin Expression in Human Colorectal Cancer: The Role of Focal Macrophage Infiltration Clinical Cancer Research Vol. 6, 3545-3551, 9 2000.
    10. S Shimoyama, F Gansauge et al. Increased angiogenin expression in pancreatic cancer is related to cancer aggressiveness Cancer Research, Vol 56, Issue 12 2703-2706, 1996.
    11. Sagrario Montero, Belen Lloveras et al. Increased Serum Angiogenin Concentration in Colorectal Cancer Is Correlated with Cancer Progression. Clinical Cancer Research Vol. 5, 3722-3723, November 1999.
    12. DP Barton, A Cai et al. Angiogenic protein expression in advanced epithelial ovarian cancer Clinical Cancer Research, Vol 3, Issue 9 1579-1586, 1997.
    13. Lee F S, Shapiro R, Vallee B L. Tight-binding inhibition of angiogenin and ribonuclease inhibitor. Biochemistry, 1989, 28: 225-230.
    14. Shapiro R, Vallee B L. Human placental ribonuclease inhibitor abolishes both angiogenic and ribonucleolytic activity of angiogenin. Proc Natl Acad Sci USA, 1984, 84(8): 2238-2241.
    15. Folkman J. Tumor angiogenesis [J]. Adv Cancer Res, 1985, 43 (1):175-203.
    16. Maeda BK, Chung YS, et al. Tumor angiogenesis as a predictor of recurrence in gastric carcinoma [J]. J Clin Oncol, 1995,13(2): 477-481.
    17. Parkin DM, Pisani P, Ferlay J. Global cancer stastiatics, CA Cancer J clin, 1999, 49: 31.
    18. Zysman M, Saka A, Millar A, etal. Methylation of adenomatous polyposis coli in endometrial cancer occurs more frequently in tumors with microsatellite instability phenotype[J]. Cancer Research, 2002, 62(13):3663-3666.
    19.崔秀云 田余祥 人胎盘核糖核酸酶抑制因子研究。生命的化学 1995年15卷5期24-25。
    20.丁晓华 基因表达的调控。医学分子生物学原理和方法 第一版 上海科学出版社 2000 9。
    21. Nisreen El-Hashemite, Dagan Wells and Joy D. A. Delhanty Single cell detection of b-thalassaemia mutations using silver stained SSCP analysis: an application for preimplantation diagnosis Molecular Human Reproduction vol. 3 no. 8: 693-698, 1997.
    22. Moira Behn and Marcus Schuermann Sensitive detection of p53 gene mutations by a 'mutant enriched' PCR-SSCP technique Nucleic Acids Research, 1998, Vol. 26, No. 5 1356-1358.
    23. C. A. Skinner, G. Rumsby, and J. W. Honour. Single Strand Conformation Poly-morphism (SSCP)Analysis for the Detection of Mutations in the CYZWBI Gene Journal of Clinical Endocrinology and Metabolism 1996 by The Endocrine Society.
    24. Orita M. lwhana H, Kanazawa H, et al. Detection of Polymorphisms of human DNA by gel electrophoresis as single strand conformation polymorphisms. Procedings of the National Academy of Sciences, 1989, 86: 2766-70.
    25. Orita M. Suzuki Y, Sekiya T, Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Cenomics. 1989 5: 874-879.
    26. A Gupta, S Agarwal Efficiency and cost effectiveness: PAGE-SSCP versus MDE and Phast gels for the identification of unknown β thalassaemia mutations J Clin Pathol: Mol Pathol 2003;56:237-239.
    
    27. E Braggio, C R Bonvicino, F R Vargas, S Ferman, A L A Eisenberg and H N Seuanez Identification of three novel RB1 mutations in Brazilian patients with retinoblastoma by "exon by exon" PCR mediated SSCP analysis Downloaded from jcp.bmjjournals.com on 7 February 2006.
    
    
    28. Hans Peter Hinrikson, Fabrizio Dutly, Satheesh Nair and Martin Altwegg Detection of three different types of Tropheryma whippelii' directly from clinicalspecimens by sequencing, single-strandconformation polymorphism (SSCP) analysis and type- specific PCR of their 16S-23S ribosomal intergenic spacer region International Journal of Systematic Bacteriology (1999), 49, 1701-1706.
    
    29. R. B. Gasser, Y. G. Abs EL-Osta and R. M. Chalmers Electrophoretic Analysis of Genetic Variability within Cryptosporidium parvum from Imported and Autochthonous Cases of Human Cryptosporidiosis in the United Kingdom APPLIED AND ENVIRONMENTAL MICROBIOLOGY, May 2003, p. 2719-2730.
    
    30. LIANG MA AND JOSEPH A. KOVACS Rapid Detection of Mutations in the Human-Derived Pneumocystis carinii Dihydropteroate Synthase Gene Associated with Sulfa Resistance ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,2001 Mar. 2001, p. 776-780.
    
    31. MARIE-HE'LE'NE MAYRAND, et al. Detection of Human Papillomavirus Type 16 DNA in Consecutive Genital Samples Does Not Always Represent Persistent Infection as Determined by Molecular Variant Analysis JOURNAL OF CLINICAL MICRO- BIOLOGY, Sept. 2000, p. 3388-3393.
    
    32. R.M.Myers,S.G.Fischer,T.Maniatis,L.S.Lerman,Modification of the melting properties of duplex DNA by denaturing gradient gel electrophoresis [J]Nucleic Acids Res, 1985, 13: 3111 -3129.
    
    33. NAKAMURA H.KANEKO S.YAMAOKA Y,et al.PCR-SSCP analysis of the ribosomal DNA ITS regions of the willow rust fungi in Japan[J].Ann Phytopathol Soc Jpn,1998.64:102-109.
    
    34. 陈卫等 PCR-SSCP法检测宫颈癌P~(53)基因突变。肿瘤防治研究1999年第26卷第1期16-17。
    35.Hayashi K.PCR.SSCP.一种检测突变的方法。国外医学卫生学分册 1994年21卷4期204-205。
    36.朱敏等PCR-SSCP分析线粒体DNA突变的方法学改进。中国运动医学杂志2000年19卷第3期291-292。
    37. Sheffield V C,Beck J S,Kwitek A E,et al.The sensitivity of single strand conformation polymorphism andlysis for the detection of single base substitu tions.Genomics, 1993, 16:325-332.
    38. Orita M, Suzuki Y, Sekiya J,et al.Sensitive detection of point mutations and DNA polym-orphism susing the polymerase chain reaction. Genomics, 1989,5:874-879.
    39. Hayashi K, Yandell DW. How sensitive is PCR-SSCP Hum Mutat, 1993, 2: 338-346.
    40.梅平 刘双信等PCR-SSCP灵敏度的影响因素。皖南医学院学报2000年19卷第4期271-272。
    41.于景崔等一种简单迅速筛选肿瘤基因组中基因突变的方法。中国地方病学杂志2000年5月19卷第3期221-223。
    42.田余祥等 核糖核酸酶抑制因子基因在人乳腺癌中的表达及突变分析。肿瘤2002年9月22卷第5期402-404。
    43.赵蔚明等应用PCR-SSCP银染法检测宫颈癌中p~(53)基因突变。中国医学科学院学报1995年6月17卷第3期219-221。
    1. KuoML, Den BestenW, Bertwistle D, et al. N-terminal polyubiquitination and degradation of the Arf tumor suppressor[J]. Genes Dev, 2004; 18 (15): 1862-1874.
    2. Lindastrom Mikael S, Wiman Kias G. Myc and E2F1 induce p53 through p14ARF-independent mechanisms in human fibroblasts[J]. Oncogene, 2003; 22 (32): 4993-5005.
    3. Md Kamrul Hasan, Tomoko Yaguchi, Takashi Sugihara, et al. CARF is a novel- protion that cooperates with mouse p19ARF ( human p14 ARF) in activating p53 [ J ]. J Biol Chem, 2002; 277 (40) : 37765-37770.
    
    4. Weber JD, Mei - L ing Kuo, DiGiammarino EL, et al.Cooperative signals governing ARF - Mdm2 interaction and nucleolar localization of the complex [J]. M ol Cel B iol, 2000; 20 (7) : 2517-2528.
    
    5. Suzuki H, KuritaM, Mizumoto K, et al. p19ARF - induced p53 - independent apop- tosis largely occurs through BAX[J]. B iochem B iophys Res Commun, 2003; 312 (4) : 1273-1277.
    
    6. Suzuki H, KuritaM, Mizumoto K, et al. The ARF tumor suppressor inhibits BCL6 - mediated transcriptional repression[J]. B iochem B iophys Res Comm un, 2005; 326 (1): 242-248.
    
    7. KishiM, NakamuraM, NishimineM, et al. Genetic and epigenetic alteration profiles formultiple genes in salivary gland carcinomas[J]. OralOncol, 2005; 41 (2) : 161-169.
    
    8. ZemaitisM, RiegerN, Fischer JR, et al. Aberrant promoter methylation of tumor suppressor genes in serum from lung cancer patients: frequency and correlation with clinicopathological characteristics[J]. Medicina, 2005;41 (2) : 123-131.
    
    9. L ind GE, Thorstensen L, Lovig T, et al. A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines [J]. Mol Cancer, 2004; 3 (1) : 28.
    
    10. Anacleto C, Rossi B, Lopes A, et al. Development and application of a multiplex PCR procedure for the detection of DNA methylation in colorectal cancer[ J ]. Oncol Rep, 2005; 13 (2) : 325-328.
    
    11. Tang Shaohui, Luo Hesheng, Yu Jieping, et al. Relationship between alterations of p16 ( INK4a ) and pl4(ARF) genes of CDKN2A locus and gastric carcinogenesis[ J ]. ChineseM ed J, 2003; 116 (7) : 1083-1087.
    
    12. Chang L in - L i, YehWen - Ting, Yang Shu - Yuan, et al. Genetic alterations of p16 INK4a and p14ARF genes in human bladder cancer [J]. J U rol, 2003; 170 ( 2 Pt 1) : 595-600.
    
    13. Raschke S, BalzV, Efferth T, et al. Homozygous deletions of CDKN2A caused by alternative mechanisms invarious human cancer cell lines[J]. Genes Chromosomes Cancer, 2005; 42 (1) : 58-67.
    
    14. Huang HY, Illei PB, Zhao Z, et al. Ewing sarcomas with p53 mutation or p16 /p14ARF homozygous dele2tion: a highly lethal subset associated with poor chemo- response[J]. J Clin Oncol, 2005; 23 (3) : 548-558.
    
    15. Hsu HS, Wang YC, Tseng RC, et al. 5 ' cytosine-phospho - guanine island methylation is responsible for p14ARF inactivation and inversely correlates with p53 overexpression in resected non - small cell lung cancer[J]J. Clin Cancer Res, 2004; 10 (14) : 4734-4741.
    
    16. Sekine L ,Takami S ,Guang SG, et al . Role of epidermal growth factor receptor over expression ,K2ras point mutation and c2myc amplification in the carcinogenesis of non2small cell lung cancer [J] . Oncol Rep ,1998 ,5 (2) :351-354.
    
    17. Rodenhuis S ,Slebos RJC. Clinical significance of ras oncogene activation in human lung cancer[J] . Cancer Res ,1992 ,52(3) :2665-2669.
    
    18. Jonesbolin SE ,Johansson E , Palmisano WA , et al . Effect of promoter and intron- polymorhisms on murine lung K2ras gene expression [J] Carcinogenesis,1998,19 (8) : 1503-1508.
    
    19. Algarra I ,Perez M,Serrano MJ , et al . C2K2ras overexpression is characteristic for metastases derived from a methylcholanthrene2induced fibro sarcoma[J] . Invasion Metastasis , 1999 ,18(6) :261-270.
    
    
    20. Nelson HH ,Christiani DC ,Mark EJ , et al . Implications and prognostic value of K2ras mutation for early stage lung cancer in women [J] . J Natl CancerInst, 1999 , 91 (23) :2032-2038.
    
    21. Takahashi T ,Munakata M,Ohtsuka Y. Expression and alteration of ras and p53 proteins in patients with lung carcinoma accompanied by idiopathic pulmonary fibrosis [J ] . Cancer ,2002 ,95(3) :624-633.
    
    22. Kobayshi Y, Kawaoi A , Katon R. Mutation of ras oncongene in disoproanol nitrosamine induced rat thyroid carcinogenesis [J] Virchows Archiv ,2002 ,441 (3) :289-295
    
    23. HarkinghamJE ,Kotasek D ,Sage RE , et al . Detection of circulating tumor cells in colorectal cancer by immunobead2PCR is a sensitive prognostic marker for relapse of disease [J ] . Mol Med ,1995 ,1 (7) : 789-794.
    
    24. Kopreski MS ,Benko FA , Kwee C , et al . Detection of mutant K-rasDNA in plasmor serumof patients with colorectal cancer[J] .Br J Cancer ,1997 ,76 (10) : 1293 -1299.
    
    25. Van Rossum A, Schuuring2Scholtes E, Seggelen V, et al. Comparative genome analysis of cortactin and HS1: the significance of the Factin binding repeat domain[J]. BMC Genomic, 2005, 6 (1) : 15.
    
    26. Schuuring E, Verhoeyen E, Litvinov S, et al. The product of the EMS1 gene, amp- lified and overexp ressed in human carcinomas, is homologous to a vsrc substrate and is located in cell-substratum contact sites[J]. M ol Cell Biol, 1993, 13 (5) : 2891-2898.
    
    27. Wu H, Parsons JT. Coractin, an 80 /85-kilodalton pp60src substrate, is a filamentous actin-binding protein enriched in the cell cortex[J]. J Cell B iol, 1993, 120 (6) : 1417-1426.
    
    28. Van Rossum A, De Graaf JH, Schuuring2Scholtes E, et al. Alternative splicing of the actin binding domain of human cortactin affects cellmigration[J]. J Biol Chem, 2003, 278 (46) : 45672-45679.
    
    29. Organdy CJ, Musgrove EA, Hui R, et al. Cyclin D1, EMS1 and 11 q 13 amplification in breast cancer[ J ]. B reast Cancer Res Treat,2003, 78 (3) : 323-335.
    
    30. Li Y, TondraviM, Lin J, et al. Cortactin potentiates bone metastasis of breast cancer cells [ J ]. Cancer Res, 2001, 61 ( 18 ) : 6906-6911.
    
    31. Alavi S, Namazie A, Calcaterra TC, et al. Clinical app lication of fluorescence in situ hybridization for chromosome 11 q 13 analysis in head and neck cancer[ J ]. Laryngoscope, 1999, 109 (6) : 874-879.
    
    32. Rodrigo JP, Suarez C, GonzalezMV, et al. Variability of genetic alterations in different sites of head and neck cancer [ J ]. Laryngoscope, 2001, 111 (7) : 1297-1301.
    
    33. Rodrigo JP, Garcia LA, Ramos S, et al. EMS1 gene amp lification correlates with poor prognosis in squamous cell carcinomas of the head and neck[ J ]. Clinical Cancer Research, 2000, 6(8): 3177-3182.
    
    34. Yuan BZ, Zhou XL, Zimonjic DB, et al. Amp lification and overex-pression of the EMS1 oncogene, a possible p rognosticmarker, in human hepatocellular carcinoma[ J ]. J M ol D iagnostics, 2003, 5 ( 1) :49-53.
    
    35. Zaharieva BM, Simon R, Diener PA, et al. High2throughput tissue microarray analysis of 11q13 gene amp lification ( CCND1, FGF3,FGF4, EMS1) in urinary bladder cancer[ J ]. J Pathol, 2003, 201(4) : 603-608.
    
    
    36. Ohta M,lnoue H .Cotticelli WG, et al . The FHIT gene , spanning the chromosome 3p14. 2 fragile site and renal carcinoma-associated t (3 ;8) breakpoint , is abnormal in digestive tract cancers. Cell , 1996 ,84 (4) :587-596.
    
    37. Sard L , Accomero P , Tomielli S ,et al . The tumor- suppressor gene FHIT is invo- lved in the regulation of apoptosis and in cell cycle control . Proc Natl Acad Sci USA , 1999 ,96 (15) :8489-8492.
    
    38. Ishii H , Dumon KR , Vecchione A ,et al . Effect of adenoviral transduction of the fragile histidine triad gene into esophageal cancer cells. Cancer Res ,2001 ,61 (4) :1578-1584.
    
    39. Brenner C ,Bieganowski P , Pace HC , et al . The histidine triad superfamily of nucleotide-binding proteins ,Cellular Phys , 1999 ,181 (2) : 179-185.
    
    40. jChaudhuri AR , Khan IA , Prasad V ,et al . The tumor suppressor protein Fhit. A novel interaction with tubulin. J Biol Chem, 1999 , 274 ( 34) :24378-24382.
    
    41. Yang Q ,Nakamura M,Nakamura Y, et al . Two-hit inactivation of FHIT by loss of heterozygosity and hypermethylation in breast cancer. Clin Cancer Res ,2002 ,8 (9) : 2890-2893.
    
    42. Tsujiuchi T , Sasaki Y, Oka Y, et al . Alterations of the fragile histidine triad gene in hepatitis C virus-associated hepatocellular carcinoma. J Gastroenterol Hepatol , 2005 , 20 (1) :87-94.
    
    43. Yuan BZ , Keck-Waggoner C , Zimonjic DB , et al . Alterations of the FHITgene in human hepatocellular carcinoma. Cancer Res ,2000 ,60 (4) : 1049-1053.
    
    44. Gramantieri L , Chieco P , Di Tomasc M ,et al . Aberrant fragile histidine triad gene transcripts in primary hepatocellular carcinoma and liver cirrhosis.Clin Cancer Res , 1999 ,5(11) :3468-3475.
    
    45. Schlott T , Ahrens K, Ruschenburg I ,et al . Different gene expression of MDM2 , GAGE-1 , - 2 and FHIT in hepatocellular carcinoma and focal nodular hyperplasia. Br J Cancer , 1999 ,80(1-2) :73-78.
    
    46. Wang F , Denison S , Lai JP , et al . Parkin gene alterations in hepatocellular carcinoma. Genes Chromosomes Cancer ,2004 ,40(2) :85-96.
    
    47. Chen YJ , Chen PH , Chang JG, et al . Aberrant FHIT transcripts in hepatocellular carcinomas. BrJ Cancer , 1998 ,77 (3) :417-420.
    
    48. Shimada Y.Satio A ,Suzuki M, et al . Cloning of a novel gene ( INGlL)homolo- gous to ING1 ,a candidate tumor suppressor [J] . Cytogenet Cell Genet ,1998 ,83 (324) :232-235.
    
    49. Cheung KJ ,Li G. The tumor suppressor ING1 : structure and function[J ] . Exp Cell Res ,2001 ,268(1) :126.
    50. Boland D .Olineck V ,Bonnefin P , et al . A panel of Cab antibodies recognize endogenous and ectopically expressed ING1 protein[J ] . Hybridoma , 2000 ,19 (2) : 161- 165.
    
    51. Garkavtsev I ,Riabowol K. Extension of the replicative life span of human diploid fibroblasis by inhibition of the p33( ING1) candidate tumorsuppressor [J ] .Mol Cell Biol ,1997 ,17 (4) :2014-2019.
    
    52. Garkavtsev I .Grigorian IA ,Ossovskaya VS , et al . The candidate tumor suppressor p33ING1 cooperate with p53 in cell growth control [J] . Nature ,1998 ,391 (6664) :295-298.
    
    53. Helbing CC ,Veillette C .Riabowol K, et al . A novel candidate tumor suppressor ,ING1 ,is involved in the regulation of apoptosis[J ] . Cancer Res , 1997 , 57 (7) :1255-1258.
    
    54. Leung KM, Po LS ,Tsang FC , et al . The candidate tumour suppressor ING1b can stabilize p53 by disrupting the regulation of p53 by MDM2[J ] . Cancer Res , 2002 , 62(17) :4890-4893.
    
    55. Cheung KJ Jr .Mitchell D ,Lin P , et al . The tumor suppressor candidate p33I-NG1 mediates repair of UV2damaged DNA[J] . Cancer Res ,2001 ,61(13) :4974-4977.
    
    56. Scott M,Bonnefin P ,Vieyra D , et al . UV2induced binding of ING1 to PCNA regulates the induction of apoptosis [J ] . J Cell Sci ,2001 ,114(19) :3455-3462.
    
    57. Zhu JJ ,Liao WM,Li FB , et al . p33( INGlb) enhances chemosensitivity of osteosarcoma cell U20S to etoposide [J ] . Ai Zheng ,2004 ,23 (6) :640-644.
    
    58. Cheung K.JJ ,Bush JA ,Jia W, et al . Expression of the novel tumour suppressor P33ING1 is independent of p53 [ J ] . Br J Cancer , 2000 , 83(11) :1468-1472.
    
    59. Kameyama K,Huang CL ,Nakashima T , et al . Reduced ING1b gene expression plays an important role in carcinogenesis of non2small cell lung cancer patients[J ] . Clin Cancer Res ,2003 ,15 (9) :4926-4934.
    
    60. Takahashi M,Seki N ,Ozaki T , et al . Identification of the p33ING1-regulated genes that include cyclin B1 and proto2oncogene DEK by using cDNA micrarray in a mouse mammory epithelial cell line NMuMG[J ] .Cancer Res , 2002 ,62(8): 2203- 2209.
    
    61. Gunduz M,Ouchida M,Fukushima K, et al . Genomic structure of the human ING1 gene and tumor2specific mutations detected in head and neck squamous cell carcinomas[J ] . Cancer Res ,2000 ,60 (12) :3143-3146.
    62. Gunduz M,Ouchida M,Fukushima K, et al. Allelic loss and reduced expression of the ING3, a candidate tumor suppressor gene at 7q31, in human head and neck cancers[J]. Oncogene, 2002, 21 (28): 4462-4470.
    63. Shinoura N, Muramatsu Y, Nishimnra M, et al. Adenvirus-mediated transfer of p33 (ING1) with p53 drastically augments apoptosis in gliomas[J]. Cancer Res, 1999, 59(21): 5521-5528.
    64. Nouman GS, Anderson JJ, Wood KW, et al . Loss of nuclear expression of the inhibitor of growth p33ING1b in childhood acute lymphoblastie leukaemia[J]. J Clin Pathol, 2002, 55(1): 126.
    65. Dickman S. First P53 relative may be new tumorsu ppressor[J]. Science, 1997, 277: 1 605-1 606.
    66. Kaghad M, Bonnet H, Yang A, et al. Monoalle lically expressed gene related to P53 at 1 p36 a region frequently deleted in neuroblastoma and ot her human cancers[J]. Cell, 1997, 90(4): 809-819.
    67. Kaelin WG J r. The P53 gene family [J]. Oncogene, 1999, 18: 7 701-7 705.
    68. Pozniak CD, Radinovic S, Yang A, et al. Ananti-apoptotic role for the P53 family member, P73, during developmental neuron deat h[J] Science, 2000, 289: 304-306.
    69. Dickman S. First P53 relative may be a new tum or suppressor [J]. Science. 1997. 277: 1605-1606.
    70. Jost C, Marin M, Kaelin WG,et al. P73 is a human P53-related protein that can induce apoptosis[J]. Natutre, 1997, 389: 191-194.
    71. Kaghak M,Monocallelically expressioned in neuroblastoma and other human cancer [J]. Cell, 1997, 90: 809.
    72. Jost CA, Marin MC, Kaelin WG J R. P73 is a human P53-related proten that can induce apoptosis[J]. nature, 1999, 389: 191-194.
    73. Mai M, Yokomizo A, Qian C, et al. Activation of P73 silent allele in lung cancer[J]. Cancer Res, 1998. 58 (11): 2 347-2 349.
    74.何勇,范世志,蒋耀光,等.人非小细胞肺癌组织P73基因转录表达研究[J].中国肺癌杂志,2000,3(1):17-19。
    75. Tokuchi Y, Hashimoto T, Kobayashi Y, et al. The expression of P73 is increased in lung cancer. independent of P53 gene alteration[J]. Br J Cancer, 1999, 80 (10): 1 623-1 629.
    76.黄立军,王云杰,崔大祥,等.P73基因在肺癌组织中的表达[J].癌症,2001,20 (1):49-52。
    77.梁兵,张贺山,范伟,等.P73基因在肺鳞癌组织中的表达[J].中华结核和呼吸杂志,2002,25(9):557-558。
    78. Nomoto S, Haruki N, Kondo M, et al. Search for mutatiion and examination of allelie expression imbalance of P73 gene at Ip36. 33in human lung cancer [J], Cancer Res, 1998, 58: 1 380 -1 383.
    79. Holl steon M, Sidransky D, Nogel stein B, et al. P53 mutations in human cancers[J]. Science, 1991, 253: 49-53.
    80.陈洪雷,陈福春,王敏,等.人非小细胞肺癌组织P63和P73的表达及意义[J].肿瘤防治杂志,2003,10(10):1 015-1 018.
    81. Latres E, Chiarle R, Schulman BA, et al. Role of the Fbox protein Skp2 in lymphomagenesis[J]. Proc Natl Acad Sci USA, 2001, 98(5): 2515-2520.
    82. GstaigerM, Jordan R, Lim M, et al. Skp2 is oncogenic and overexpressed in human cancers[J]. Proc Natl Acad Sci USA, 2001, 98(9): 5043-5048.
    83. Erickson LA, PapottiM, VolanteM, et al. Merkel cell carcinomas: expression of Sphase kinase-associated protein 2(Skp2), p27, and proliferation markers[J]. Endocr Pathol, 2003, 14(3): 221-229.
    84. Schiffer D, Cavalla P, Fiano V, et al. Inverse relationship between p27/Kip. 1 and the Fbox protein Skp2 in human astrocytic gliomas by immunohistochemistry and Western blot[J]. NeurosciLett, 2002, 328(2): 125-128.
    85. Hershko D, Bornstein G, Ben-lzhak O, et al. Inverse relation between levels of p27 (kip1) and of its ubiquitin ligase subunit Skp2 in colorectai carcinomas[J]. Cancer, 2001, 91(9): 1745-1751.
    86. Ishii T, Matsuse T, MasudaM, et al. The effects of S2phase kinaseassociated protein 2 (SKP2) on cell cycle status, viability, and chemoresistance in A549 lung adenocarcinoma cells[J]. Exp Lung Res, 2004, 30 (8): 687-703.
    87. Masuda TA, Inoue H, Sonoda H, et al. Clinical and biological significance of Sphase kinase-associated protein 2 (Skp2) gene expression in gastric carcinoma modulation ofmalignant phenotype by Skp2 overexp ression, possibly via p27 proteolysis[J]. Cancer Res, 2002, 62(13): 3819-3825.
    88. Shigemasa K, Gu L, O 'Brien T J, et al. Skp2 overexp ression is a prognostic factor in patients with ovarian adenocarcinoma[J]. Clin Cancer Res, 2003, 9 (5): 1756-1763.
    89. Takanami I. The prognostic value of overexp ression of Skp2 mRNA in non-small cell lung cancer [ J ]. Oncol Rep, 2005, 13(4): 727-731.
    
    90. Kamata Y, Watanabe J, Nishimura Y, et al. High exp ression of Skp2 correlat- eswith poor p rognosis in endometrial endometrioid adenocarcinoma[ J ]. J Cancer Res Clin Oncol, 2005, 131(9): 591-596.
    
    91. ]Seki R, Okamura T, Koga H, et al. Prognostic significance of the Fbox proteinSkp2 exp ression in diffuse large B-cell lymphoma [ J ].Am J Hem atol, 2003, 73 (4) : 230-235.
    
    
    92. Lin R, Wang TT, MillerWH J r, et al. Inhibition of FBox p rotein p45 ( SKP2) exp ression and stabilization of cyclin-dependent kinase inhibitor p27 (KIPl) in vitamin D analog-treated cancer cells [ J ]. Endocrinology, 2003, 144 (3) : 749-753.
    
    93. NakamuraM,Matsuo T, Stanffer J, et al. Retinoic acid decreases targeting of p27 for degradation via an N2myc-dependent decrease in p27 phosphorylation and an N2myc independent decrease in Skp2[ J ]. Cell Death D iffer, 2003, 10 (2) : 230-239.
    
    94. Shintani S, Li C, Mihara M, et al. Gefitinib ('Iressa', ZD1839) ,an epidermal growth factor recep tor tyrosine kinase inhibitor, up-regulates p27KIPl and induces G1 arrest in oral squamous cell carcinoma cell lines[ J ]. O ral Oncol, 2004, 40 (1) : 43-51.
    
    95. Pene F, Claessens YE, Muller O, et al. Role of the phosphatidylinositol3-kinase /Akt and mTOR /P70S62kinase pathways in the proliferation and apoptosis in multiple- myeloma [ J ]. Oncogene, 2002,21 (43) : 6587-6597.
    
    96. Sumimoto H, Yamagata S, Shimizu A, et al. Gene therapy for human small-cell lung carcinoma by inactivation of Skp22 with virallymediated RNA interference[ J ]. Gene Ther, 2005, 12 (1) : 95-100.
    
    97. ]Kodo Y, Kitajima S, Shimizu A, et al. Small interfering RNA targeting of Sphase kinase- interacting protein-inhibits cell growth of oral cancer cells by inhibiting p27 degradation[J]. M ol Cancer Ther,2005, 4 (3) : 471-476.
    
    98. Feng J,Nancy PC, Ruiyun L, et al. RNA Silencing of S2phase kinase interacting protein- inhibits proliferation and centrosome amp lification in lung cancer cells[J]. Oncogene, 2005, 24 (21) : 3409-3418.
    
    99. Lee SH,McCormick F. Downregulation of Skp2 and p27 /Kipl synergistically induces apop tosis in T98G glioblastoma cells [ J ]. J M ol M ed, 2005, 83 (4): 296-307.
    [1] Burkhard Malorny, Jeffrey Hoorfar, Cornelia Bunge. Multicenter Validation of the Analytical Accuracy of Salmonella PCR: towards an International Standard. Appl Environ Microbiol. 2003 January; 69(1): 290-6.
    
    [2] Burkhard Malorny, Reiner Helmuth. European ring trial Detection of Salmonella by the Polymerase Chain Reaction.http://www.pcr.dk/
    
    [3] Rahn K, De Grandis SA, Clarke RC, et al. Amplification of an invA gene sequence of Salmonella typhimurium by polymerase chain reaction as a specific method of detection of Salmonella. Mol Cell Probes. Aug. 1992, 6(4):271-9.
    
    [4] Bacteriological Analytical Manual Online Chapter 9 2004 Vibrio http://www.cfsan.fda.gov/-ebam/bam-toc.htmL
    
    [5] Bej, A. K., D. P. Patterson, C. W. Brasher, et al. Detection of total and hemolysin-producing Vibrio parahaemolyticus in shellfish using multiplex PCR amplification of tlh, tdh and trh. J. Microbiol. Meth. 1999, 36:215-225.
    
    [6] M. D'Agostino et al. European ring trial Detection of Listeria Monocytogene by the Polymerase Chain Reaction.http://www.pcr.dk/
    
    [7] KRZYSZTOF KWIATEK, ELZBIETA WOJDAT, ARTUR RZEZUTKA et al. Comparison of PCR and other methods in the detection of Listeria Monocytogenes in milk inoculated experimentally with the bacteria. Bull. Vet. Inst. Pulawy 47, 357-362, 2003.
    
    [8] Cesar Bin Kingombe, Maria-Lucia Cerqueira-Campos, Yvon-Louis Trottier et al. Detection of Shigella spp. in foods by the polymerase chain reaction. http://www.hc-sc.gc.ca/food-aliment
    
    [9] Bisweswar Nandi, Ranjan K. Nandy, Sarmishtha Mukhopadhyay et al. Rapid Method for Species-Specific Identification of Vibrio cholerae Using Primers Targeted to the Gene of Outer Membrane Protein OmpW. Journal of Clinical Microbiology, 2000 November, 38(11):4145-51.
    
    [10] Amir Abdulmawjood, Michael Bulte. Detection of E. coli O157 in cattle carcass swabs by using Polymerase Chain Reaction, http://www.pcr.dk/
    
    [11] Patricia M. Desmarchelier, Sima S. Bilge, Narelle Fegan et al. A PCR Specific for Escherichia coli O157 Based on the rfb Locus Encoding 0157 Lipopolysaccharide. Journal of Clinical Microbiology, 1998 June, 36(6): 1801-4.
    [12] WALTER E. HILL, STACYE P. KEASLER, MARY W. TRUCKSESS. Polymerase Chain Reaction Identification of Vibrio vulnificus in Artificially Contaminated Oysterst. Applied and Environmental Microbiology, Mar. 1991, 57(3): 707-11.
    [13] Stonnet V, Guesdon JL. Campylobacter jejuni: specific oligonucleotides and DNA probes for use in polymerase chain reaction-based diagnosis. FEMS Immunol Med Microbiol. Dec. 1993, 7(4): 337-44.
    [14] 阳成波 蒋原 黄克和等.PCR法和培养法调查食品和水中空肠弯曲杆菌的比较研究.中国人兽共患病杂志,2003,19(1):91-4.
    [15] J. HOORFAR, P. AHRENS, P. RADSTROM. Automated 59 Nuclease PCR Assay for Identification of Salmonella enterica. Journal of Clinical Microbiology, Sept. 2000, 38(9): 3429-35.
    [16] George Blackstone. Typing Vibrio parahaemolyticus Without a Culture. FDA/Gulf Coast Seafood Laboratory.
    [17] David Rodriguez-La'zaro, 1 Marta Herna'ndez,2 Mariela Scortti et al. Quantitative Detection of Listeria monocytogenes and Listeria innocua by Real-Time PCR: Assessment of hly, iap, and 1in02483 Targets and AmpliFluor Technology. Applied and Environmental Microbiology, Mar. 2004, 70(3): 1366-77.
    [18] Johnson JL, Brooke CI., Fritschel SJ, Comparison of the BAX for screening E.coli O157: H7 methods with conventional methods for detection of extremely low levels of Escherichia coli O157:H7 in ground beef [J], Appl Environ Microbiol, 1998, 64(11): 4390.
    1. Oskoui, R., W. A. Davis, and M. N. Gomes. 1993. Salmonella aortitis. A report of a successfully treated case with a comprehensive review of the literature. Archives of Internal Medicine 153:517-525.
    
    2. Darwin, K. H., and V. L. Miller. 1999. Molecular basis of the interaction of Salmonella with the intestinal mucosa. Journal of Clinical Microbiology Review 12:405-428.
    
    3. Ezaki, T., Y. Kawamura, and E. Yabuuchi. 2000. Recognition of nomenclatural standing of Salmonella typhi (Approved Lists 1980), Salmonella enteritidis (Approved Lists 1980) and Salmonella typhimurium (Approved Lists 1980), and conservation of the specific epithets enteritidis and typhimurium. Request for an opinion. International Journal of Systematic and Evolutionary Microbiology 50:945-947.
    
    4. Miller, M. E., G. R. Fogel, and W. K. Dunham. 1988. Salmonella spondylitis. A review and report of two immunologically normal patients. Journal of Bone and Joint Surgery-American 70:463-466.
    
    5. Barthel, M., S. Hapfelmeier, L. Quintanilla-Martinez, M. Kremer, M. Rohde, M. Hogardt, K. Pfeffer, H. Russmann, and W. D. Hardt. 2003. Pretreatment of mice with streptomycin provides a Salmonella enterica Serovar typhimurium colitis model that allows analysis of both pathogen and host. Infection and Immunity 71:2839-2858.
    
    6. Hossain, A., M. D. Reisbig, and N. D. Hanson. 2004. Plasmid-encoded functions compensate for the biological cost of AmpC overexpression in a clinical isolate of Salmonella typhimurium. Journal Antimicrobial Chemotherapy 53:964-970.
    
    7. Drevets, D. A., P. J. M. Leenen, and R. A. Greenfield. 2004. Invasion of the central nervous system by intracellular bacteria. Clinical Microbiololy Review. 17:323-347.
    
    8. R. Capita, C. Alonso-Calleja, M.C. Garcia-Fernandez, and B Moreno. 2002. Review: Trisodium phosphate (TSP) treatment for decontamination of poultry. Food Science and Technology International 8: 11-24.
    
    9. Nicholson, T. L., and A. J. Baumler. 2001. Salmonella enterica Serotype Typhimurium elicits cross-immunity against a Salmonella enterica serotype enteritidis strain expressing LP fimbriae from the lac promoter. Infection and Immunity 69: 204-212.
    
    10. Gonzalez, J. M., M. Jimenez, M. Velez, J. Mingorance, J. M. Andreu, M. Vicente, and G. Rivas. 2003. Essential cell division protein FtsZ assembles into one monomer-thick ribbons under conditions resembling the crowded intracellular environment. Journal of Biological Chemistry 278:37664-37671.
    
    11. Alexander O. Gill and Richard A. Holley. 2004. Mechanisms of Bactericidal Action of Cinnamaldehyde against Listeria monocytogenes and of Eugenol against L. monocytogenes and Lactobacillus sakei. Applied and Environmental Microbiology 70: 5750-5755.
    
    12. Yang, H., M. E. Berrang, T. Liu, C. L. Hofacre, S. Sanchez, L. H. Wang, and J. J. Maurer. 2003. Rapid detection of Campylobacter coli, C.jejuni, and Salmonella enterica on poultry carcasses by using PCR-enzyme-linked immunosorbent assay. Applied and Environmental Microbiology 69:3492-3499.
    
    13. Taitt, C. R., Y. S. Shubin, R. Angel, and F. S. Ligler. 2004. Detection of Salmonella enterica Serovar typhimurium by using a rapid, array-based immunosensor. Applied and Environmental Microbiology 70: 152-158.
    
    14. Thorns, C. J., M. M. Bell, M. G. Sojka, and R. A. Nicholas. 1996. Development and application of enzyme-linked immunosorbent assay for specific detection of Salmonella enteritidis infections in chickens based on ntibodies to SEF14 fimbrial antigen. Journal of Clinical Microbiology. 34:792-797.
    
    15. McClelland, M., L. Florea, K. Sanderson, S. W. Clifton, J. Parkhill, C. Churcher, G. Dougan, R.K. Wilson, and W. Miller. 2000. Comparison of the Escherichia coli K.-12 genome with sampled genomes of a Klebsiella pneumoniae and three Salmonella enterica serovars, Typhimurium, Typhi and Paratyphi. Nucleic Acids Research 28:4974-4986.
    
    16. Baumler, A.J., Heffron, F. 1997. Reissbrodt, RL. Rapid detection of Salmonella enterica primers specific for iroB. Journal of Clinical Microbiology 35:1224-1230.
    
    17. Cano, R.J., Rasmussen, S.R., Fraga, G.S., Palomares, J.C. 1993. Fluorescent detection-polymerase chain reaction (FD-PCR) assay on microwell plates as a screening test for Salmonellas in foods. Journal of Applied Bacteriology 75:247-253.
    
    18. Cohen, H.J., Mechanda, S.M., Lin,W. 1996. PCR amplification of the fimA gene sequence of Salmonella typhimurium, a specific method for detection of Salmonella spp.Appl.Environ.Microbiol 12:4303-4308.
    
    19. Doran,J.L.,Collinson, S.K.,Burian,J.,Sarlos,G.,Todd,E.C.D.,Munro, C.K. 1993. DNA-based diagnostic tests for Salmonella species targeting agfA,the structural gene for thin, aggregative fimbriae. Journal of Clinical Microbiology 31:2263-2273.
    
    20. Hashimoto,Y.,Itho,Y.Fujinaga,Y.,Khan,A.Q.,Sultana,F. 1995. Development of nested PCR based on the viaB sequence to detect Salmonella typhi.J.Clin.Microbiol 33,775-777.
    
    21. Rexach,L.,Dilassier,F.,Fach,P. 1994. Polymerase chain reactin for Salmonella virulence-associated plasmid genes:a new tool in Salmonella epidemiolygy. Epidemiological Infection 112,33-43.
    
    22. K.-S.Yeh,T.-H.Chen,C.-W.Liao,C.-S.Chang,H.-C.Lo. 2002. PCR amplification of the Salmonella typhimurium fimY gene sequence to detect the Salmonella species. International Journal of Food Microbiology 78:227-234.
    
    23. Palacios, G., I. Casas, A. Tenorio, and C. Freire. 2002. Molecular identification of enterovirus by analyzing a partial VP1 genomic region with different methods. Journal of Clinical Microbiology 40:182-192.
    
    24. Overbergh, L., A. Giulietti, D. Valckx, B. Decallonne, R. Bouillon, and C.Mathieu. 2003. The use of real-time reverse transcriptase PCR for the quantification of cytokine gene expression. Journal of Biomolecular Techniques 14:33-43.
    
    25. Donnelly, C. W. 1994. Listeria monocytogenes, p. 215-252. In Y. H. Hui, J. R. Gorham, K. D. Murrell, and D. O. Cliver (ed.), Foodborne disease handbook: diseases caused by bacteria, vol. 1. Marcel Dekker, New York, N.Y.
    
    26. Lammerding, A. M., and M. P. Doyle. 1990. Stability of Listeria monocytogenes to non-thermal processing conditions, p. 195-202. In A. J. Miller, J. L. Smith, and G. A. Somkuti (ed.), Foodborne listeriosis. Elsevier, New York, N.Y.
    
    27. Lou, Y., and A. E. Yousef. 1999. Characteristics of Listeria monocytogenes important to food processors, p. 131-224. In E. T. Ryser and E. H. Marth (eds.) Listeria, listeriosis, and food safety, 2nd ed. Marcel Dekker Inc., New York, N.Y.
    
    28. McLauchlin, J., M. H. Greenwood, and P. N. Pini. 1990. The occurrence of Listeria monocytogenes in cheese from a manufacturer associated with a case of listeriosis. International Journal of Food Microbiology 10:255-262.
    
    29. Vazquez-Boland, J. A., M. Kuhn, P. Berche, T. Chakraborty, G. Dominguez-Bernal, W. Goebel, B. Gonzalez-Zorn, J. Wehland, and J. Kreft. 2001. Listeria Pathogenesis and Molecular Virulence Determinants. Clinical Microbiology Reviews 14: 584 - 640.
    
    30. Murray, E. G. D., R. A. Webb, and M. B. R. Swann. 1926. A disease of rabbits characterised by a large mononuclear leukocytosis, caused by a hitherto undescribed bacillus Bacterium monocytogenes (n. sp.). Journal of Pathological Bacteriology 29:407-439.
    
    31. Seeliger, H. P. R. 1988. Listeriosis—history and actual developments. Infection 16:S80-S84.
    
    32. Stevens, R., K. E. Howard, S. Nordone, M. Burkhard, and G. A. Dean. 2004. Oral immunization with recombinant Listeria monocytogenes controls virus load after vaginal challenge with feline immunodeficiency virus. Journal of Virology 78: 8210-8218.
    
    33. Jose, A., V. Boland, M. Kuhn, P. Berche, T. Chakraborty, G. Dominguez-Bernal, W. Goebel, B. Gonzalez-Zorn, J. Wehland, and J. Kreft. 2001. Listeria Pathogenesis and Molecular Virulence Determinants. Clinical Microbiology Reviews 14: 584-640.
    
    34. Czajka, J., and C. A. Batt. 1994. Verification of causal relationships between Listeria monocytogenes isolates implicated in food-borne outbreaks of listeriosis by randomly amplified polymorphic DNA patterns. Journal of Clinical Microbiology 32:1280-1287.
    
    35. Schmidt, H., and M. Hensel. 2004. Pathogenicity islands in bacterial pathogenesis. Clinical Microbiology Reviews 17:14-56.
    
    36. Rocourt, J., and C. Jacquet. 1994. Epide'miologie des infections humaines a' Listeria monocytogenes en 1994: certitudes et interrogations. Annals of Institute Pasteur 5:168-174.
    
    37. Borezee, E., E. Pellegrini, J. L. Beretti, and P. Berche. 2001. SvpA, a novel surface virulence-associated protein required for intracellular survival of Listeria monocytogenes. Microbiology 147: 2913-2923.
    
    38. Emond, E., I. Fliss, and S. Pandian. 1993. A ribosomal DNA fragment of Listeria monocytogenes and its use as a genus-specific probe in an aqueous-phase hybridization assay. Applied and Environmental Microbiology 59:2690-2697.
    
    39. Dawn, M.,N. and Carl, A., B. 1999. Detection of viable Listeria monocytogenes with a 5'Nuclease PCR Assay. Applied and Environmental Microbiology 65(5): 2122-2127.
    
    40. Ingeborg,H., Dieter, K.,Angelika,L.and Martin,W. 2001 Detection and quantification of the iap gene of Listeria monocytogenes and Listeria innocua by a new real-time quantitative PCR assay. Research Microbiology 152:37-46.
    
    41. Palacios, G., I. Casas, A. Tenorio, and C. Freire. 2002. Molecular identification of enterovirus by analyzing a partial VPl genomic region with different methods. Journal of Clinical Microbiology 40:182-192.
    
    42. Paton, J. C, and A. W. Paton. 1998. Pathogenesis and Diagnosis of Shiga Toxin-Producing Escherichia coli Infections. Journal of Clinical Microbiology Review 11:450 - 479.
    
    43. Nataro, J. P., and J. B. Kaper. 1998. Diarrheagenic Escherichia coli. Journal of Clinical Microbiology Review 11:142-201.
    
    44. Izumiya, H., J. Terajima, A. Wada, Y. Inagaki, K. I. Itoh, K. Tamura, and H. Watanabe. 1997. Molecular typing of enterohemorrhagic Escherichia coli O157:H7 isolates in Japan by using pulsed-field gel electrophoresis. Journal of Clinical Microbiology 35:1675-1680.
    
    45. Bettelheim, K. A., M. A. Hornitzky, S. P. Djordjevic, and A. Kuzevski. 2003. Antibiotic resistance among verocytotoxigenic Escherichia coli (VTEC) and non-VTEC isolated from domestic animals and humans. Journal of Medical Microbiology 52:155-162
    
    46. Friedrich, A. W., K. V. Nierhoff, M. Bielaszewska, A. Mellmann, and H. Karch. 2004. Phylogeny, Clinical Associations, and Diagnostic Utility of the Pilin Subunit Gene (sfpA) of Sorbitol-Fermenting, Enterohemorrhagic Escherichia coli O157:H7. Journal of Clinical Microbiology 42: 4697-4701.
    
    47. Gannon, V. P., S. D'Souza, T. Graham, R. K. King, K. Rahn, and S. Read. 1997. Use of the flagellar H7 gene as a target in multiplex PCR assays and improved specificity in identification of enterohemorrhagic Escherichia coli strains. Journal of Clinical Microbiology 35:656-662.
    
    48. Paton, J. C, and A. W. Paton. 1998. Pathogenesis and diagnosis of shiga oxin-producing Escherichia coli infections. Journal of Clinical Microbiology Review 11: 450-479.
    
    49.丁建强.肠出血性大肠杆菌O157H7研究进展.国外医学流行病学传染病学分册,1996,23:204-208.
    
    50. Elliott, S. J., V. Sperandio, J. A. Giron, S. Shin, J. L. Mellies, L. Wainwright, S. W. Hutcheson, T. K. McDaniel, and J. B. Kaper. 2000. The locus of enterocyte effacement (LEE)-encoded regulator controls expression of both LEE- and non-LEE-encoded virulence factors in enteropathogenic and enterohemorrhagic Escherichia coli. Infection and Immunity 68:6115-6126.
    
    51. Nielsen, E. M., and M. T. Andersen. 2003. Detection and characterization of verocytotoxin-producing Escherichia coli by automated 5' nuclease PCR assay. Journal of Clinical Microbiology 41:2884-2893.
    
    52. Novicki, T. J., J. A. Daly, S. L. Mottice, and K. C. Carroll. 2000. Comparison of Sorbitol MacConkey agar and a two-step method which utilizes enzyme-linked immunosorbent assay toxin testing and a chromogenic agar to detect and isolate enterohemorrhagic Escherichia coli. Journal of Clinical Microbiology 38:547-551.
    
    53. Pyle, B. H., S. C. Broadaway, and G. A. McFeters. 1999. Sensitive detection of Escherichia coli O157:H7 in food and water by immunomagnetic separation and solid-phase laser cytometry. Applied and Environmental Microbiology 65:1966-1972.
    
    54. Jothikumar, N., and M. W. Griffiths. 2002. Rapid detection of Escherichia coli O157:H7 with multiplex real-time PCR assays. Applied and Environmental Microbiology 68:3169-3171.
    
    55. Vora, G. J., C. E. Meador, D. A. Stenger, and J. D. Andreadis. 2004. Nucleic acid amplification strategies for DNA microarray-based pathogen detection. Applied and Environmental Microbiology 70:3047-3054.
    
    56. Newland,J.W.& Neill,R.J. 1988. DNA probes for shiga-like toxins I AND II and for toxin-converting bacteriophages. Journal of clinical Microbiology 26:1297-7.
    
    57. Smith,H.W.,Green,P.&Parsell,Z. 1983. Vero cell toxins I Escherichia coli and related bacteria:transfer by phage and conjugation and toxin action in laboratory animals,chickens and pigs. Journal of General Microbiology 129:3121-37.
    
    58. Boyce,T.G.,Swerdlow,D.L.&Griffin,P.M. 1995. Escherichia coli O157:H7 and the hemolytic-uremic syndrome. New England Journal of Medicine 333:364-368.
    
    59. Nathalie Y.Fortin,Ashok Mulchandani,and Wilfred Chen. 2001. Use of real-time polymerase chain reaction and molecular beacons for the detection of Escherichia coli O157:H7. Analytical Biochemistry 289:281-288.
    
    60. Palacios, G., I. Casas, A. Tenorio, and C. Freire. 2002. Molecular identification of enterovirus by analyzing a partial VP1 genomic region with different methods. Journal of Clinical Micrabiology 40:182-192.
    
    61. Overbergh, L., A. Giulietti, D. Valckx, B. Decallonne, R. Bouillon, and C. Mathieu. 2003. The use of real-time reverse transcriptase PCR for the quantification of cytokine gene expression. Journal of Biomolecular Techniques 14:33-43.
    
    62. World Health Organization. 2002. The increasing incidence of human campylo- bacteriosis. Report and proceedings of a W.H.O. consultation of experts, Copenhagen, Denmark, 21-25 November 2000. W.H.O./CDS/CSR/APH publication 2001.7. World Health Organization, Geneva, Switzerland.
    
    63. Manfredi, R., A. Nanetti, M. Ferri, and F. Chiodo. 1999. Fatal Campylobacter jejuni bacteraemia in patients with AIDS. Journal of Medical Microbiology 48: 601-603.
    
    64. McCarthy, N., and J. Giesecke. 2001. Incidence of Guillain-Barre Syndrome following Infection with Campylobacter jejuni. American Journal of Epidemiology 153: 610-614.
    
    65. Smith, T., and M. S. Taylor. 1919. Some morphological and biological characters of the Spirilla (Vibrio fetus, n. sp.) associated with the disease of the fetal membranes in cattle. Journal of Experimental Medicine 30: 299-311.
    
    66. Vandamme, P., and J. De. Ley. 1991. Proposal for a new family, Campylo- bacteraceae. International Journal of Systematic Bacteriology 41: 451-455.
    
    67. Barros-Velazquezl, J., A. Jimenezl, and T. G. Villa. 1999. Isolation and typing methods for the epidemiologic investigation of thermotolerant campylobacters. International Microbiology 2: 217-226.
    68. Crushell, E., S. Harty, F. Sharif, and B. Bourke. 2004.Enteric Campylobacter: purging its secrets? Pediatric Research. 55: 3-12.
    
    69. Butzle, J. P. 2004. Campylobacter, from obscurity to celebrity. Clinical Microbiology & Infection 10:868-876.
    
    70. Stanley, K., and K. Jones. 2003. Cattle and sheep farms as reservoirs of Campylobacter. Journal of Applied Microbiology 94:104-113.
    
    71. Connerton, P. L., C. M. Loc Carrillo, C. Swift, E. Dillon, A. Scott, C. E. D. Rees, C. E. R. Dodd, J. Frost, and I. F. 2004. Connerton. longitudinal study of Campylobacter jejuni bacteriophages and their hosts from broiler chickens. Applied Environmental Microbiology 70: 3877-3883.
    
    72. Mills, S. D., B. Kuzniar, B. Shames, L. A. Kurjanczyk, and J. L. Penner. 1992.Variation of the O antigen of Campylobacter jejuni in vivo. Journal Medical Microbiology 36: 215-219.
    
    73.潘蔚绮.李广兴.空肠弯曲菌病的研究进展.黑龙江兽牧兽医.2002.448-490.
    
    74. Nachamkin, I., B. M. Allos, and T. Ho. 1998. Campylobacter species and Guillain-Barre syndrome. Clinical Microbiology 11: 555-567.
    
    75. S. L. W., and P. J. 2003. Jordan. Evaluation of 11 PCR Assays for species-level identification of Campylobacter jejuni and Campylobacter coli. Journal of Clinical Microbiology 41: 330-336.
    
    
    76. Payne, R. E., M. D. Lee, David W. Dreesen, and Harold M. Barnhart. 1999. Molecular epidemiology of Campylobacter jejuni in broiler flocks using randomly amplified polymorphic DNA-PCR and 23S rRNA-PCR and role of litter in its transmission. Applied Environmental Microbiology 65: 260-263.
    
    77. Ng, L. K., C. I. Kingombe, W. Yan, D. E. Taylor, K. Hiratsuka, N. Malik, and M. M. Garcia. 1997. Specific detection and confirmation of Campylobacter jejuni by DNA hybridization and PCR. Applied Environmental Microbiology 63: 4558-4563.
    
    78. Waage, A. S., T. Vardund, V. Lund, and G. Kapperud. 1999. Detection of small numbers of Campylobacter jejuni and Campylobacter coli cells in environmental water, sewage, and food samples by a seminested PCR assay. Applied Environmental Microbiology 65: 1636-1643.
    
    79. Mette, A. S., J. Engberg, L. B. Larsen, K. Begtrup , and K. A. Krogfelt. 2001. Antibody responses to Campylobacter infections determined by an enzyme-linked immunosorbent assay: 2-year follow-up study of 210 patients. Clinical and Diagnostic Laboratory Immunology 8: 314-319.
    
    80. Frank St, M., C. M. Szymanski, J.J. Li, K. H. Chan, N. H. Khieu, S. Larocque, W. W. Wakarchuk, J. R. Brisson, and M. A. Monteiro. 2002. The structures of the lipooligosaccharide and capsule polysaccharide of Campylobacter jejunigenome sequenced strain NCTC 11168. European Journal of Biochemistry 269:5119-5136.
    
    81. Grennan, B., N. A. O'Sullivan, R. Fallon, C. Carroll, T. Smith, M. Glennon,and M. Maher. 2001. PCR-ELISA for the detection of CampylobcCter jejuniand Campylobacter coli in poultry samples. BioTechniques 30: 602-606, 608-610.
    
    82. Gaynor, E. C, S. Cawthraw, G. Manning, J. K. MacKichan, S. Falkow, and D. G. Newell. 2004. The genome-sequenced variant of Campylobacter jejuni NCTC 11168 and the original clonal clinical isolate differ markedly in colonization, gene expression, and virulence-associated phenotypes. Journal of Bacteriology 186: 503-517.
    
    83. Overbergh, L., A. Giulietti, D. Valckx, B. Decallonne, R. Bouillon, and C. Mathieu. 2003. The use of real-time reverse transcriptase PCR for the quantification of cytokine gene expression. Journal of Biomolecular Technology 14:33-43.
    
    
    84. Palacios, G., I. Casas, A. Tenorio, and C. Freire. 2002. Molecular identification of enterovirus by analyzing a partial VP1 genomic region with different methods. Journal of Clinical Microbiology 40: 182-192.
    
    85. Ashkenazi S. 2004. Shigella infections in children: New insights. Seminars in Pediatric Infectious Diseases 15(4):246-252.
    
    86. Herold S, Karch H, Schmidt H. 2004. Shiga toxin-encoding bacteriophages -genomes in motion. International Journal of Medical Microbiology 294(2-3): 115-121.
    
    
    87. Fontaine A, Arondel J, Sansonetti PJ. 1988. Role of Shiga toxin in thepathogenesis of bacillary dysentery, studied by using a Tox-mutant of Shigella dysenteriae 1. Infection and Immunity 56(12): 3099-3109.
    
    88. Davis H, Taylor JP, Perdue JN, Stelma GN Jr, Humphreys JM Jr, Rowntree R 3rd, Greene KD. 1988. A shigellosis outbreak traced to commercially distributed shredded lettuce. American Journal of Epidemiology 128(6):1312-1321.
    89. Jegathesan M. 1984. Serotype prevalence and antibiotic susceptibility of Shigella strains isolated in Malaysia during 1980 and 1981. Journal of Diarrhoeal Diseases Research 2(2): 102-104.
    
    90. Vu Dinh Thiem, Orntipa Sethabutr, Lorenz von Seidlein, Tran Van Tung, Do Gia Canh, Bui Trong Chien, Le Huu Tho, Hyejon Lee, Huo-Shu Houng, Thomas L. Hale, John D. Clemens, Carl Mason, and Dang Duc Trach. 2004. Detection of Shigella by a PCR assay targeting the ipaH gene suggests increased prevalence of Shigellosis in Nha Trang, Vietnam. Journal of Clinical Microbiology 42(5): 2031-2035.
    
    
    91. Loh Jin Phang, Yap Peng Huat Eric. 2001. Development of a rapid homogenous real-time PCR assay for detection of Shigella species. Singapore Microbiologist. Microbiology and Biotechnology News, January - March.
    
    92. Richardson JF, Reith S. 1993. Characterization of a strain of methiciUin-resistant Staphylococcus aureus (EMRSA-15) by conventional and molecular methods. The Journal of Hospital Infection 25(1): 45-52.
    
    93. Lyon HB Jr, Rantz LA. 1950. Staphylococcus aureus in an outbreak of infantile diarrhea. Pediatrics 5(4): 617-620.
    
    94. Drysdale A. 1950. Staphylococcus aureus food poisoning; an account of an outbreak in Khartoum. The Journal of Tropical Medicine and Hygiene 53(1): 12-14.
    
    95. Welsch M, Salmon J. 1950. Certain aspects of staphylolysis. Annales de l'lnstitut Pasteur (Paris) 79(5): 802-813.
    
    96. Hunter ME, Mudd S, Wooburn MA. 1950. The morphological characteristics of paired sulfonamide- susceptible and sulfonamide-resistant strains of Staphylococcus aureus. Journal of Bacteriology 60(3): 315-320.
    
    97. Gershenfeld L, Micklin E. 1951.The effect of pH on the liquefaction of gelatin medium by Staphylococcus aureus. American Journal of Pharmacy and the Sciences Supporting Public Health 123(9): 295-305.
    
    98. Gamova-Kaiukova NI. 1951. Differential culture medium for isolation of staphyloccoci from food products. Mikrobiologiia 20(4): 337-339.
    
    99. Aaron RS. 1951. Staphylococcus aureus meningitis and bacteremia. New York State Journal of Medicine 51(8): 1059-1060.
    
    100. Oker-Blom N. 1952. Serological studies in rheumatoid arthritis. II. Absorption of the streptococcal agglutinating factor from sera of patients with rheumatoid arthritis by Streptococcus haemolyticus and Staphylococcus aureus. Annales Medicinae Experimentalis et Biologiae Fenniae. 30(2): 139-143.
    
    101. Oker-Blom N., Widholm O. 1952. Serological studies in rheumatoid arthritis. III. Comparison between the agglutination of Streptococcus haemolyticus and Staphylococcus aureus and antistreptolysin and antistaphylolysin titers in sera of patients with rheumatoid arthritis. Annales Medicinae Experimentalis et Biologiae Fenniae 30(2): 144-148.
    
    102. Ribner BS, Landry MN, Kidd K, Peninger M, Riddick J. 1989. Outbreak of multiply resistant Staphylococcus aureus in a pediatric intensive care unit after consolidation with a surgical intensive care unit. American Journal of Infection Control 17(5): 244-249.
    
    103.何国坚,邹焕荣,池海波,廖长征.复合PCR鉴别葡萄球菌及其多重耐药基因.临床检验杂志,2004.4.
    104. Nabin K. Shrestha, Marion J. Tuohy, Gerri S. Hall, Carlos M. Isada, and Gary W. Procop. 2002. Rapid identification of Staphylococcus aureus and the mecA gene from BacT/ALERT blood culture bottles by using the LightCycler system. Journal of Clinical Microbiology 40(7): 2659-2661.
    
    105. Park KS, Ono T, Rokuda M, Jang MH, Okada K, Iida T, Honda T. 2004. Functional characterization of two type III secretion systems of Vibrio parahaemolyticus. Infection and immunity 72(11): 6659-6665.
    
    106. Iida T. 2004. Pathogenicity and genome of Vibrio parahaemolyticus. Nippon Saikingaku Zasshi. 59(3): 457-464.
    
    107. Martinez-Urtaza J, Lozano-Leon A, DePaola A, Ishibashi M, Shimada K, Nishibuchi M, Liebana E. 2004. Characterization of pathogenic Vibrio parahaemolyticus isolates from clinical sources in Spain and comparison with Asian and North American pandemic isolates. Journal of Clinical Microbiology 42(10): 4672-4678.
    
    108. Yeung PS, Boor KJ. 2004. Effects of acid stress on Vibrio parahaemolyticus survival and cytotoxicity. Journal of Food Protection 67(7): 1328-1334.
    
    109. Alam MJ, Miyoshi S, Shinoda S. 2003. Studies on pathogenic Vibrio parahaemolyticus during a warm weather season in the Seto Inland Sea, Japan. Environmental Microbiology 5(8): 706-710.
    110. DePaola A, Ulaszek J, Kaysner CA, Tenge BJ, Nordstrom JL, Wells J, Puhr N, Gendel SM. 2003. Molecular, serological, and virulence characteristics of Vibrio parahaemolyticus isolated from environmental, food, and clinical sources in North America and Asia. Applied and Environmental Microbiology 69(7): 3999-4005.
    
    111. Wong HC, Chang CN, Chen MY. 2004. Effects of heat, acid, and freeze-thaw challenges on survival of starved Vibrio parahaemolyticus in minimal salt medium, tryptic soy broth, and filtered oyster homogenate medium. Journal of Food Protection 67(6): 1243-1246.
    
    112.Nishino T, Nayak BB, Kogure K. 2003. Density-dependent sorting of physiologically different cells of Vibrio parahaemolyticus. Applied and Environmental Microbiology 69(6): 3569 -3572.
    
    113. Lang PA, Kaiser S, Myssina S, Birka C, Weinstock C, Northoff H, Wieder T, Lang F, Huber SM. 2004. Effect of Vibrio parahaemolyticus haemolysin on human erythrocytes. Cellular microbiology 6(4):391-400.
    
    114. Yamazaki M, Inuzuka K, Matsumoto M, Miwa Y, Hiramatsu R, Matsui H, Sakae K, Suzuki Y, Miyazaki Y. 2003. Epidemiological study of outbreaks and sporadic cases due to Vibrio parahaemolyticus—serotype O3:K6 in Aichi Prefecture, Japan, during 1988 and 2001. Kansenshogaku Zasshi 77(12):1015-1023.
    
    115. Hara-Kudo Y, Sugiyama K, Nishibuchi M, Chowdhury A, Yatsuyanagi J, Ohtomo Y, Saito A, Nagano H, Nishina T, Nakagawa H, Konuma H, Miyahara M, Kumagai S. 2003. Prevalence of pandemic thermostable direct hemolysin-producing Vibrio parahaemolyticus O3:K6 in seafood and the coastal environment in Japan. Applied and Environmental Microbiology 69(7):3883-3891.
    
    116. Laohaprertthisan V, Chowdhury A, Kongmuang U, Kalnauwakul S, Ishibashi M, Matsumoto C, Nishibuchi M. 2003. Prevalence and serodiversity of the pandemic clone among the clinical strains of Vibrio parahaemolyticus isolated in southern Thailand. Epidemiology and Infection 130(3):395-406.
    
    117. Abbott SL, Powers C, Kaysner CA, Takeda Y, Ishibashi M, Joseph SW, Janda JM. 1989. Emergence of a restricted bioserovar of Vibrio parahaemolyticus as the predominant cause of Vibrio-associated gastroenteritis on the West coast of the United States and Mexico. Journal of Clinical Microbiology 27: 2891-2893.
    
    118. Andrews LS, Park DL, Chen Y-P. 2000. Low temperature pasteurization to reduce the risk of vibrio infections from raw shell-stock oysters. Food Additives and Contaminants 19: 787-791.
    
    119. Venkateswaran, K., N. Dohmoto, and S. Harayama. 1998. Cloning and nucleotide sequence of the gyrB gene of Vibrio parahaemolyticus and its application in detection of this pathogen in shrimp. Applied and Environmental Microbiology 64: 681-687.
    
    120. Yung Bu Kim, Jun Okuda, Chiho Matsumoto, Naoki Takahashi, Satoru Hashimoto, and Mitsuaki Nishibuchi. 1999. Identification of Vibrio parahaemolyticus strains at the species level by PCR targeted to the toxR gene. Journal of Clinical Microbiology 37(4): 1173-1177.
    
    121. Karagozova AV, Sal'nikova OI. 1995. The expression of the pathogenic properties of the Vibrio cholerae 0139 serogroup in vitro. Zh Mikrobiol Epidemiol Immunobiol. (3): 7-10.
    
    122. Datta A, Sasmal D, Datta GC, Pal SC. 1977. Isolation and characterisation of a non-toxinogenic mutant of V. cholerae and possibility of a live oral cholera vaccine. Indian Jounal of medical research 65(6):770-776.
    
    123. Raziuddin S. 1977. Variations in whole cell extractable lipids of two antigenically different strains of Vibrio cholerae under different growth conditions. Indian Jounal of Biochemistry & Biophysics. 14(2): 163-166.
    
    124.Sanyal SC, Prescott LM, Sakazaki R, Sinha R. 1972. Variations of Heiberg's classification in Vibrio cholerae strains. Indian Jounal of medical research 60(7): 1007-1009.
    
    125. Oashi M, Shimada T, Fukumi H. 1972. In vitro production of enterotoxin and hemorrhagic principle by Vibrio cholerae, NAG. Japanese Journal of Medical Science & Biology 25:179-194.
    
    126. Kamzolkina NB, Karaeva LT, Dzhaparidze MN, Kokorina TA. 1977. Trial of the toxins of the Sonne microbe and cholera vibrio in an isolated loop of mouse small intestine. Zh Mikrobiol Epidemiol Immunobiology 6: 84-88.
    
    127. Epstein MH, Feldman AM, Brusilow SW. 1977. Cerebrospinal fluid production: stimulation by cholera toxin. Science 196:1012-1013.
    
    128. Lifson N, Hakim AA, Lender EJ. 1972. Effects of cholera toxin on intestinal permeability and transport interactions. American Journal of Physiology 222: 1479-1487.
    
    129. Mishan'kin BN, Romanova LV, Lomov IuM, Shimaniuk NIa, Vodop'ianov SO, Cherepakhina IIa, Suchkov IIu, Duvanova OV. 2000. Vibrio cholerae 0139 isolated from humans and the water from open reservoirs: a comparative genotyping. Zh Mikrobiol Epidemiol Immunobiol 3:3-7
    
    130. McArthur, J. 1977. The rapid diagnosis of cholera. Journal of Tropical Medicine and Hygiene 80:99-101.
    
    
    131. Lipp, E. K., I. N. G. Rivera, A. I. Gil, E. M. Espeland, N. Choopun, V. R. Louis, E. Russek-Cohen, A. Huq, and R. R. Colwell. 2003. Direct Detection of Vibrio cholerae and ctxA in Peruvian Coastal Water and Plankton by PCR. Applied and Environmental Microbiology 69:3676-3680.
    
    132. Qadri, F., G. Jonson, Y. A. Begum, C. Wenneras, M. J. Albert, M. A. Salam, and A. M. Svennerholm. 1997. Immune response to the mannose-sensitive hemagglutinin in patients with cholera due to Vibrio cholerae 01 and 0139. Clinical and Diagnostic Laboratory Immunology 4:429-434.
    
    133. Hyun, C. S., and G. A. Kimmich. 1984. Interaction of cholera toxin and Escherichia coli enterotoxin with isolated intestinal epithelial cells. American Journal of Gastrointestinal and Liver Physiology 247:623-631.
    
    134. Zhang, X. b., and F. L. Kiechle. 2004. Glycosphingolipids in Health and Disease. Annals of Clinical &Laboratory Science 34:3-13.
    
    135. Lee, V. T., and O. Schneewind. 2001. Protein secretion and the pathogenesis of bacterial infections. Genes & Development 15:1725-1752.
    
    136.Jobling, M. G., and R. K. Holmes. 2001. Biological and biochemical characterization of variant a subunits of Cholera toxin constructed by site-directed mutagenesis. Journal of Bacteriology 183:4024-4032.
    
    137. Lavelle, E. C, A. Jarnicki, E. McNeela, M. E. Armstrong, S. C. Higgins, O. Leavy, and K. H. G. Mills. 2004. Effects of Cholera toxin on innate and adaptive immunity and its application as an immunomodulatory agent. Journal of Leukocyte Biology 75:756-763.
    [1] Rambabu Naravaneni and Kaiser Jamil Rapid detection of food-borne pathogens by using molecular techniques Journal of Medical Microbiology (2005), 54, 51-54
    [2] Cohen, H.J., Mechanda, S.M., Lin,W. 1996. PCR amplification of the fimA gene sequence of Salmonella typhimurium, a specific method for detection of Salmonella spp.Appl.Environ.Microbiol 12:4303-4308.
    [3] Doran,J.L.,Collinson, S.K.,Burian,J.,Sarlos,G.,Todd,E.C.D.,Munro, C.K. 1993. DNA-based diagnostic tests for Salmonella species targeting agfA,the structural gene for thin, aggregative fimbriae. Journal of Clinical Microbiology 31:2263-2273.
    [4] Hashimoto,Y.,Itho,Y.Fujinaga,Y.,Khan,A.Q.,Sultana,F. 1995. Development of nested PCR based on the viaB sequence to detect Salmonella typhi.J.Clin.Microbiol 33,775-777.
    [5] Rexach,L.,Dilassier,F.,Fach,P. 1994. Polymerase chain reactin for Salmonella virulence-associated plasmid genes:a new tool in Salmonella epidemiolygy. Epidemiological Infection 112,33-43.
    [6] K.-S.Yeh,T.-H.Chen,C.-W.Liao,C.-S.Chang,H.-C.Lo. 2002. PCR amplification of the Salmonella typhimurium fimY gene sequence to detect the Salmonella species. International Journal of Food Microbiology 78:227-234.
    [7] HUGUETTE J. COHEN,* SUBBAIAH M. MECHANDA, AND WEI LIN PCR Amplification of the fimA Gene Sequence of Salmonella typhimurium, a Specific Method for Detection of Salmonella spp. APPLIED AND ENVIRONMENTAL MICROBIOLOGY, Dec. 1996, p. 4303-4308
    [8] Yang, H., M. E. Berrang, T. Liu, C. L. Hofacre, S. Sanchez, L. H. Wang, and J. J. Maurer. 2003. Rapid detection of Campylobacter coli, C. jejuni, and Salmonella enterica on poultry carcasses by using PCR-enzyme-linked immunosorbent assay. Applied and Environmental Microbiology 69:3492-3499.
    [9] USDA/FSIS Laboratory Guidebook MLG 4.03 Isolation and Identification of Salmonella from Meat, Poultry, and Egg Products 10/1/2004
    1. Hunter Susan B, Vauterin Paul, Lambert—Fair Mary Ann, et al. Establishment of a universal size standard strain for use with the PulseNet standardized pulsed-field gel electrophoresis protocols: converting the national databases to the new sizestandard.[J]. JClinMicrobiol. 2005, 43: 1045—1050.
    2. Talon D, cailleaux V, Thouverez M, et al. Discriminatory power and usefulness of pulsed-field gel electrophoresis in epidemiological studies ofpseudomonas aernginosa[J]. J Hop Infection, 1996, 32: 135—145.
    3.金春光,徐景野,章丹阳,等。伤寒沙门菌的脉冲场凝胶电泳分型方法研究。中国卫生检验杂志,2005,15(10):1 172-1 173。
    4. PulseNet USA CDC. Section 5.1,5.2, 5.4 Standardized protocol for molecular subtyping of Escherichia coil O157: H7, non-typhoidal Salmonella serotypes, and Shigella sonnei by Pulsed-Field Gel Electropthoresis(PFGE) 2004.6.
    5. Kim A, Lee YJ, Kang MS, Kwag SI, Cho JK Dissemination and tracking of Salmonella spp. in integrated broiler operation. J Vet Sci, 8(2): 155-61 2007.
    6. Lindqvist N, Pelkonen S Genetic surveillance of endemic bovine Salmonella Infantis infection. Acta Vet Scand, 49(1): 15 2007.
    1. Xiao w, Oefner PJ, Denaturing High-Performance Liquid Chromatography: A Review. Human Mutation, 2001, 17: 439—474.
    2. Oefner PJ, Undethill PA. Comparative DNA sequencing by denaturing high—performance liquid chromatography(DnPLC). Am J Hum Genet, 1995, 57: 266.
    3.杨金萍.食品安全与食源性疾病.国外医学卫生学分册.2003.30(2):124-126.
    4. Spiro A,Lowe M,Brov, ql D. A bead-based method for multiplexed identification and quantitation of DNA sequences using flow cytometry. Appl Envir Mier6biol, 2000, 66: 4258-4265.
    5. Bortolin SM, BlackH, Modil, etal. Analytical validation of the tag—it high throughput microsphere-based universal array genotyping platform: application to the multiplex detection of a panel of thrombophilia associated single—nucleotide polymorphisms, a Chem, 2004, 50: 2028—2036.
    6.金大智,谢明杰,曹际娟.食品中单增李氏菌实时荧光PCR检测鉴定方法的建立.辽宁师范大学学报(自然科学版).2003.26(1):73-76.
    7. Giovanna franciosa et al. Characterization of Listeria monocytogenes Strains Involved in Invasive and Noninvasive Listeriosis Outbreaks by PCR-Based Fingerprinting Techniques Applied and environmental microbiology. 2001 67 (4): 1793-1799
    8.陈炳卿,孙长颢.食品污染与健康.化学工业出版社.2002.7第一版.:3-4.
    9.李业鹏.美国食品安全系统.中国食品卫生杂志.2001.13(4):44-49.
    10.寇运同,马洪明,刘晨光.用PCR技术快速检测食品中的单核细胞增生性李斯特菌.食品科学.2001.22(5):52-55.
    11. Yang S. Augulo FC. Alterkruse SF. Evaluation of safe food-handling instructions on raw meat and poultry products. J Food Prot. 2000. 63(10): 1321.
    12.韩伟,顾明.聚合酶链反应与自动荧光免疫酶标检测弯曲菌属的试验.2003.13(3):32-34.
    13.曹泽虹,李勇.用PCR法快速测定食物中毒病原菌.微生物学通报.2001.28(4):73-76.
    14. William P. C., Kelly M. P., Morelli L et al. Selective Enumeration and Identification of Potentially Probiotic Lactobacillus and Bifidobacterium Species in Mixed Bacterial Populations. International J. of Food Microbiology. 1997. 35(1): 1-27.
    15.翁文川,覃文.联用VIDAS法和API Listeria法对食品中李斯特氏菌检验及分类.2000.21(4):59-62.
    16. Rudolf A, Gloeckner F. O., Neef A. Modern Methods in Subsurface Microbiology. In situ Identification of Microorganisms with Nucleic Acid Probes. FEMS Microbiology Reviews. 1997. 20(3-4): 191-200.
    17. Tortora G. J., Funke B. R. Microbiology: An introduction. 4th ed. Redwood City Calif., the Beniamin/Gummings Publishing Company Inc. 1992: 262-269.
    18. Dawn M. Norton, Meghan A. Mccamey et al. Molecular Studies on the Ecology of Listeria monocytogenes in the Smoked Fish Processing Industry. Applied and Environmental Microbiology. 2001. 67(1): 198-205.
    19. Hazel D. M., Kell D. B. Flow Cytometry and Sensitive Immunomagnetic Separation-PCR Method for the Detection of Escherichial Coli 0157: H7 in Raw Milk and Ice Cream. J of Diary Research. 1997. 64(1): 87-93.
    20.周帼萍,刘瑞祥.分子生物学技术在食品微生物快速鉴定中的应用.武汉食品工业学院学报.1999.1:36-38.
    21. Giovanna Franciosa, Stefania Tartaro, Christina Wedell-Neergaard, Paolo Aureli. Characterization of listeria monocytogenes Strains Involved in Invasive and Noninvasive Listeriosis Outbreaks by PCR-Based Fringerprinting Techniques. Applied and Environmental Microbiology. 2001. 67(4): 1793-1799.
    22. L.O' Connor, J. Joy, M. Kane, T. Smith, M. Maher. Rapid Polymerase Chain Reaction/DNA Probe Membrance-Based Assay for the Detection of Listeria and listeria monocoytogenes in food. Journal of Food Protection. 2000. 63(3): 337-342.
    23. A. M. Sewell, D. W. Warburton, A. Boville, E. F. Daley, K. Mullen. The development of an efficient and rapid enzyme linked fluorescent assay method for the detection of listeria spp. From foods. International Journal of Food Microbiology. 2003. 81: 123-129.
    24. K. S. Yeh, T. H. Chen, C. W. Liao, C. S. Chang, H. C. Lo. International Journal of Food Microbiology. 2002. 78: 227-234.
    25. M. Manzano, L. Cocolin, C.Cantoni, G.Comi. Detection and identification of listeria monocytogenes in food by PCR and oligonucleotide-specific capture plate hybridization. Food Microbiology. 1998. 15: 651-657.
    
    26. Marija Trkov, Gorazd Avgustin. An improved 16S rRNA based PCR method for the specific detection of Salmonella enterica .International Journal of Food Microbiology. 2002.80: 67-75.
    
    27. G. R. Campbell, J. Prosser, A. Glover, K. Killham. Detection of Escherichia coli 0157: H7 in soil and water using multiplex PCR. Journal of Applied Microbiology. 2001.91: 1004-1010.
    
    28. Pina M. Fratamico, Lori K. Bagi, Tiziana Pepe. A Multiplex Polymerase Chain Reaction Assay for Rapid Detection and Identification of Escherichia coli 0157:H7 in foods and Bovine Feces. Journal of Food Protection. 2000.63(8): 1032-1037.
    
    29. K. H. Chow, T. K. Ng, K.Y.Yuen, W. C. Yam. Detection of RTX Toxin Gene in vibrio cholerae by PCR. Journal of Clinical Microbiology. 2001. 39(7): 2594-2597.
    
    30. Kenji Hirose, Ken-Ichiro Itoh, Hiroshi Nakajima et al. Selective Amplification of tyv (rfbE), prt (rfbS) ,viaB,fliC Genes by Multiplex PCR for Identification of Salmonella enterica Serovars Typhi and Paratyphi A. Journal of Clinical Microbiology. 2002. 40(2): 633-636.
    
    31. Wim J. B. Wannet, Michiel Reessink, Henk A.Brunings, Henny M.E. Maas. Detection of Pathogenic Yersinia enterocolitica by a Rapid and Sensitive Duplex PCR Assay. Journal of Clinical Microbiology. 2001.39(12): 4483-4486.
    
    32. AOAC. Official Methods of Analysis. 15th ed. Arrlington VA. 1990.Mark Ibekwe, Pamela M. Watt, Catherine M. Grieve et al. Multiplex Fluorogenic Real-Time PCR for Detection and Quantification of Escherichia coli 0157:H7 in Dairy Wastewater Wetlands. Applied and Environmental Microbiology. 2002.68(10): 4853-4862.
    
    33. C.H.Kim, M. Khan, D. E. Morin et al. Optimization of the PCR for Detection of Staphylococcus aureus nuc Gene in Bovine Milk. J. Dairy Sci. 2001. 84: 74-83.
    
    34. Danbing Ke, Christian Menard, Francois J. Picard. Development of Conventional and Real-Time PCR Assay for the Rapid Detection of Group B Streptococci. Clinical Chemistry. 2000. 46(3): 324-331.
    
    35. Hege Karin Nogva, Knut Rudi, Kristine Naterstad et al. Application of 5' -Nuclease PCR for Quantitative Detection of listeria monocytogenes in Pure Cultures, Water, Skim Milk, and Unpasteurized Whole Milk. 2000. 66(10): 4266-4271.
    
    36. Thean Yen Tan, Sally Corden, Rosemary Barnes et al. Rapid Identification of Methicillin-Resistant Staphylococcus aureus from Positive Blood Cultures by Real-Time Fluorescence PCR. Journal of Clinical Microbiology. 2001. 39(12): 4529-4531.
    
    37. Ken Takai, Koki Horikoshi. Rapid Detection and Quantification of Members of the Archaeal Community by Quantitative PCR Using Fluorogenic Probes. Applied and Environmental Microbiology.2000. 66(11) : 5066-5072.
    
    38. James C.Mcavin, Patricia A. A Reilly, Robert M. Roudabush et al. Sensitive and Specific Method for Rapid Identification of Streptococcus pneumoniae Using Real-Time Fluorescence PCR. Journal of Clinical Microbiology. 2001. 39(10): 3446-3451.
    
    39. David F. Waller, Steven A.Ogata. Quantitative Immunocapture PCR Assay for Detection of Campylobacter jejuni in Foods. Applied and Environmental Microbiology. 2000. 66(9): 4115-4118.
    
    40. Ye, R., Wang, T., Bedzyk, L, Croker, K. , 2001. Applications of DNA microarrays in microbial systems. J. Microbiol. Methods 47, 257 - 272.
    
    41. Dawn-Marie Norton, Carl A. Batt. Detection of Viable listeria monocytogenes with a 5' Nuclease PCR Assay. Applied and Environment Microbiology. 1999. 65(5): 2122-2127.
    
    42. Lockhart, D. J. , Dong, H. , Byrne, M. C. , Follettie, M. T. , Gallo, M. V. , Chee, M.S., Mittmann, M. , Wang, C. , Kobayashi, M. , Horton, H. , et al. , 1996. Expression monitoring by hybridization to high-density oligonucleotide arrays. Nat. Biotechnol. 14, 1675- 1680.
    
    43. Schena, M., 2000. Microarray Biochip Technology. Eaton Publishing, Natick, MA.
    
    44. Belosludtsev, Y. , Iverson, B. , Lemeshko, S. , Eggers, R. , Wiese, R. , Lee, S. , Powdrill, T. , Hogan, M. , 2001. DNA microarrays based on noncovalent oligonucleotide attachment and hybridization in two dimensions. Anal. Biochem. 292, 250-256.
    
    45. Alexandre, I., Hamels, S. , Dufour, S. , Collet, J. , Zammatteo, N. , De_Longueville, F. , Gala, J. L. , Remade, J. , 2001. Colorimetric silver detection of DNA microarrays. Anal. Biochem. 295, 1-8.
    
    46. Call, D. R. , Brockman, F. J. , Chandler, D. P. , 2001b. Detecting and genotyping Escherichia coli 0157:H7 using multiplexed PCR and nucleic acid microarrays. Int. J. Food Microbiol. 67, 71 - 80.
    
    47. Chrisey, L.A., Lee, G.U., O' Ferrall, C.E. , 1996. Covalent attachment of synthetic DNA to self-assembled monolayer films. Nucleic Acids Res. 24, 3031-3039.
    
    48. Call, D. , Chandler, D. , Brockman, F. , 2001a. Fabrication of DNA microarrays using unmodified oligonucleotide probes. Biotechniques 30, 368- 379.
    
    49. Karsten, S., van Deerlin, V., Sabatti, C. , Gill, L., Geschwind, D., 2002. An evaluation of tyramide signal amplification and archived fixed and frozen tissue in microarray gene expression analysis. Nucleic Acids Res. 30, e4.
    
    50. Chizhikov, V., Rasooly, A., Chumakov, K. , Levy, D. , 2001. Microarray analysis of microbial virulence factors. Appl. Environ. Microbiol. 67, 3258- 3263.
    
    51. Small, J. , Call, D. R. , Brockman, F. J. , Straub, T. M. , Chandler, D. P. , 2001. Direct detection of 16S rRNA in soil extracts by using oligonucleotide microarrays. Appl. Environ. Microbiol. 67, 4708- 4716.
    
    52. Rudi, K., Skulberg, O.M., Skulberg, R. , Jakobsen, K.S., 2000. Application of sequence-specific labeled 16S rRNA gene oligonucleotide probes for genetic profiling of cyanobacterial abundance and diversity by array hybridization. Appl. Environ. Microbiol. 66, 4004- 4011.
    
    53. Guo, Z. , Guilfoyle, R. A. , Thiel, A. J. , Wang, R. , Smith, L. M. , 1994. Direct fluorescence analysis of genetic polymorphisms by hybridization with oligonucleotide arrays on glass supports. Nucleic Acids Res. 22, 5456 - 5465.
    
    
    54. Georgios Keramas, Dang Duong Bang, Marianne Lund,et al. , 2003. Development of a sensitive DNA microarray suitable for rapid detection of Campylobacter spp. Molecular and Cellular Probes 17. 187-196.
    
    55. Woo-Sung Jung, Serka Kim, Suk-In Hong, Nam-Ki Min, Chi-Woo Lee, Se-Hwan Paek. 2004. DNA probe chip system for multiple detection of food poisoning microorganisms. Material science and Engineering. 24, 47-51.
    
    56. C. van Ijperen, P. Kuhnert, J. Frey and J. P. Clewley. 2002. Virulence typing of Escherichia coli using microarrays. Molecular and Cellular Probes. 16, 371-378.
    
    57. Nikolay Sergeev, Margaret Distler, Shannon Courtney et al., 2004. Multipathogen oligonucleotide microarrray for environmental and biodefense applications. Biosensors and Nioelectronics. 20, 684-698.
    
    58. Sufian F. Al-Khaldi, Doralis Villanueva, Vladimir Chizhikov. 2004. Identification and characterization of Clostridium perfringens using single target DNA microarray chip. International Journal of Food Microbiology. 91, 289-296.
    
    59. Adelaide. E. warsen, Melissa. J. Krug, Call, D. R. et al., 2004. Simultaneous discrimination between 15 fish pathogens by using 16S ribosomal DNA PCR and DNA microarrays. Applied and environmental microbiology. 7, 4216-4221.
    
    60. Smith, J. G. , Kong, L. , Abruzzo, G. K. , Gill, C. J. , Flattery, A.M., Scott, P.M., Bramhill, D. , Cioffe, C. , Thompson, C. M., Bartizal, K. , 1996. PCR detection of colonization by Helicobacter pylori in conventional, euthymic mice based on the 16S ribosomal gene sequence. Clin. Diagn. Lab. Immunol. 3, 66- 72.
    
    61. Greisen, K. , M. Loeffelholz, A. Purohit, and D. Leong. 1994. PCR primers and probes for the 16S rRNA gene of most species of pathogenic bacteria, including bacteria found in cerebrospinal fluid. J. Clin. Microbiol. 32:335 - 351.
    
    62. Helps, C. R., Harbour, D.A., Corry, J.E., 1999. PCR-based 16S ribosomal DNA detection technique for Clostridium estertheticum causing spoilage in vacuum-packed chill-stored beef. Int. J. Food Microbiol. 52, 57- 65.
    
    63. Matar, G.M., Koehler, J. E., Malcolm, G. , Lambert-Fair, M.A., Tappero, J., Hunter, S. B., Swaminathan, B., 1999. Identification of Bartonella species directly in clinical specimens by PCR-restriction fragment length polymorphism analysis of a 16S rRNA gene fragment. J. Clin. Microbiol. 37, 4045-4047.
    
    64. Siqueira, J. F. , Rocas, I. N. , Favieri, A., Santos, K. R. , 2000. Detection of Treponema denticola in endodontic infections by 16S rRNA gene-directed polymerase chain reaction. Oral Microbiol. Immunol. 15, 335- 337.
    
    65. Tesfaye, M. , Holl, F.B., 1998. Group-specific differentiation of Rhizobium from clover species by PCR amplification of 23S rDNA sequences. Can. J. Microbiol. 44, 1102- 1105.
    
    66. Straub, J. A., Hertel, C. , Hammes, W.P., 1999. A 23S rDNA-targeted polymerase chain reaction-based system for detection of Staphylococcus aureus in meat starter cultures and dairy products. J. Food Prot. 62, 1150- 1156.
    
    67. Rong-Fu Wang, Mar jorie L. Beggs, Latriana H. Robertson, Carl E. Ceriglia. Design and evaluation of oligonucleotide-microarray method for the detection of human intentinal bacteria in fecal samples. FEMS Microbiology Letters 213(2002)175-182.
    
    68. Frahm, E. , Heiber, I. , Hoffmann, S. , Koob, C. , Meier, H. , Ludwig, W. , Amann, R. , Schleifer, K.H., Obst, U., 1998. Application of 23S rDNA-targeted oligonucleotide probes specific for enterococci to water hygiene control. Syst. Appl. Microbiol. 21, 450 - 453.
    
    69. R. M Anthony, T. J. Brown, G. L. French, Rapid diagnosis of bacteremia by universal amplification of 23S ribosomal DNA followed by hybridization to an oligonucleotide array. Journal of clinical microbiology, Feb 2000,38(2) :781-788.
    
    70. Bang-Xing Hong, Li-Fang Jiang, Yu-Shan Hu, Dan-Yun Fang, Hui-Yu Guo. 2004. Application of oligonucleotide array technology for the rapid detection of pathogenic bacteria of foodborne infections. Journal of Microbiological Methods. 58: 403-411.
    
    71. Madico, G. , Quinn, T. C. , Boman, J. , Gaydos, C. A. , 2000. Touchdown enzyme time release-PCR for detection and identification of Chlamydia trachomatis, C. pneumoniae, and C. psittaci using the 16S and 16S - 23S spacer rRNA genes. J. Clin. Microbiol. 38, 1085- 1093.
    
    72. Sasaki, Y. , Yamamoto, K. , Amimoto, K. , Kojima, A., Ogikubo, Y. , Norimatsu, M. , Ogata, H. , Tamura, Y. , 2001. Amplification of the 16S - 23S rDNA spacer region for rapid detection of Clostridium chauvoei and Clostridium septicum. Res. Vet. Sci. 71, 227 - 229.
    
    73. Wu, L. , Thompson, D. , Li, G. , Hurt, R. A. , Tiedje, J.M. , Zhou, J. , 2001. Development and evaluation of functional gene arrays for detection of selected genes in the environment. Appl. Environ. Microbiol. 67, 5780 - 5790.
    
    74. Borucki, M., Krug, M., Muraoka, W. , Call, D.R., 2003. Discrimination among listeria monocytogenes isolates using a mixed genome DNA microarray. Vet. Microbiology. 92, 351-362.
    
    75. Hakenbeck, R. , Balmelle, N. , Weber, B. , Gardes, C. , Keck, W. , de_Saizieu, A., 2001. Mosaic genes and mosaic chromosomes: intra- and interspecies genomic variation of Streptococcus pneumoniae. Infect. Immun. 69, 2477 - 2486.
    
    76. Guschin, D.Y., Mobarry, B.K., Proudnikov, D. , Stahl, D.A., Rittmann, B. E. , Mirzabekov, A.D., 1997. Oligonucleotide microchips as genosensors for determinative and environmental studies in microbiology. Appl. Environ. Microbiol. 63, 2397 - 2402.
    
    77. Dorrell, N. , Mangan, J. A. , Laing, K. G. , Hinds, J. , Linton, D. , Al_Ghusein, H., Barrell, B.G., Parkhill, J., Stoker, N.G., Karlyshev, A. V. , et al., 2001. Whole genome comparison of Campylobacter jejuni human isolates using a low-cost microarray reveals extensive genetic diversity. Genome Res. 11, 1706- 1715.
    
    78. Johnson, J.R., Stell, A.L., 2000. Extended virulence genotypes of Escherichia coli strains from patients with urosepsis in relation to phylogeny and host compromise. J. Infect. Dis. 181, 261 - 272.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700