I.臺灣地區各年齡層受人類多瘤性病毒感染之研究 II.人類多瘤性病毒與中樞神經系統腫瘤相關性之研究

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Title:	I.臺灣地區各年齡層受人類多瘤性病毒感染之研究 II.人類多瘤性病毒與中樞神經系統腫瘤相關性之研究 Investigation of human polyomavirus infection in individuals of various ages in TaiwanInvestigation of correlation between human polyomavirus and central nervous system tumors
Authors:	林惠生 Hui-Sheng Lin
Contributors:	中山醫學院：生物化學研究所;張德卿;郝菊
Keywords:	多瘤性病毒;T抗原 T-antigen
Date:	1999
Issue Date:	2010-04-02T07:47:12Z (UTC)
Abstract:	人類多瘤性病毒包括JC病毒及BK病毒兩種。本論文是以Polymerase chain reaction（PCR）的方法放大各年齡層尿液檢體中JC病毒及BK病毒的核甘酸，藉核甘酸序列之不同以限制酉每切割方式進行基因圖譜分析，以期瞭解在臺灣不同年齡層受人類多瘤性病毒感染的情形。我們收集了874位3歲到84 歲個體之尿液檢體，PCR結果顯示人類多瘤性病毒尿液排放率在3至7歲幼稚園學童約有1% （1/104），而8至13歲國小學童則為3.2% （7/216），14至19歲國高中生則為6.5%（17/261），20至30歲大學生則為13.3%（10/75），31至50歲成人則為30.0%（6/20），51至60歲成人則為41.7%（5/12），61至70歲老人則為45.1%（37/82），而大於70歲之老人則病毒尿液排放率為58.7%（61/104）。這個結果顯示隨著年齡的增長，人類多瘤性病毒尿液排放率也有漸行增高之趨勢，這或許是因為年齡的增高使得人體的某些免疫機制開始退化的關係，除此之外也發現JC病毒CY亞型（44.8%）及TW-1亞型（55.2%）為台灣地區主要分佈之兩種亞型。另外我們也針對臺灣地區的原住民族群布農族，受人類多瘤性病毒感染情形進行調查，同時利用血球凝集抑制方法偵測血清中抗JC病毒抗體之陽性率的調查結果發現布農族尿液中JC病毒排放率為50.8%（68/134）而抗JC病毒抗體陽性率為92% （124/136），該族群中JCV CY亞型佔91.2%（62/68），比起8.8%（6/68）的JCV TW-1來得多。這些結果顯示JCV CY為臺灣原住民族群布農族主要之亞型。中文摘要中樞神經系統的腦瘤佔人類腫瘤近2%，其主要分佈於小孩及老人，而腦瘤的真正原因至今未明。人類嗜神經性JC病毒可感染人類腦細胞是引起進行性多病灶腦白質病的因素，為一種致命性的脫髓鞘疾病，其導致神經系統產髓質細胞的溶解破壞，但JCV也在許多動物實驗上顯示其有促成腫瘤的潛在性。轉殖基因老鼠表現JCV之早期蛋白T-抗原進而發展出未分化之腫瘤，類似人類神經膠質性衍生之腫瘤。在許多病例報告中有伴隨PML或無PML的情況下，亦偵測到JCV與中樞神經系統腫瘤之相關性。本篇研究探討人類腦腫瘤與JCV之間的相關性，我們收集腦腫瘤檢體共47個及非腦瘤病變9個，使用蘇木精伊紅染色做為病理診斷以及免疫組織化學染色做為輔助確認診斷，所有檢體均使用病毒早期蛋白T抗原免疫組織化學染色，陽性反應者為源自於神經膠質性衍生之腫瘤(glial-derived tumor) 11個(11/29)，轉移性腫瘤(metastatic tumors) 3個(3/11)及非腫瘤性腦組織3個(3/9)，非神經膠質衍生腫瘤(non-glial-derived tumor) 7個則均為陰性反應。這些觀察提供了JCV T抗原與神經膠質性衍生之腫瘤並包含轉移後之腫瘤有關，而非神經膠質衍生之腫瘤則無T抗原之呈現，另外非腫瘤性腦組織則可在部份星狀細胞內發現T抗原。 To investigate the prevalence of human polyomavirus in normal population with various ages in Taiwan, 874 urine samples were collected for analysis. Polymerase chain reaction (PCR) and DNA endonuclease digesting were performed to detect the viral DNA and identify genotype. The results showed that 1% (1/104) of age range 3-7, 3-2% (7/216) of age range 8-13, 6.5% (17/261)，13.3% (10/75) of age range 20-30, 30.0% (6/20) of age range 31-50, 41.7% (5/12) of age range 51-60, 45.1% (37/82) of age range 60-70 and 58.7% (61/104) of age greater than 70 were JCV positive. The results indicate that the incidence of JC viruria is increased with age, which may be correlated with immunity. In addition, CY (44.8%) and TW-1 (55.2%) are the predominant genotypes of JCV prevalent in Taiwan. Prevalence of human polyomavirus in Bunun aboriginal tribe was also investigated. Urine sample were collected for virus genotype analysis. Blood sample was used for anti-JC antibody determination by hemagglutination inhibition assay. The results showed that JC viruria were 50.8% (68/134), and anti-JC antibody positivity were 91.2% (124/136). The predominance of CY genotype [91.2% (62/68)] were more than TW-1 genotype [8.8% (6/68)] in Bunun tribe. Abstract Brain tumors represent near 2% of human neoplasm is preferentially affect children and older adults. The etiology of brain tumors in humans remains unknown. Human neurotropic JC virus is able to infect human brain glial cells. The causative agent of the fatal human demyelinating disease progressive multifocal leukoencephalopathy(PML), that cytolyses and destroys oligodendrocytes, the myelin-producing cells of the central nervous system. Also results from several experiments have indicated the JCV is able to induce neoplasms. Transgenic mice expressing the JCV early protein, T-antigen, develop neoplasms that exhibit a phenotype similar to that of human glial-derived tumors. Several case reports have detected JCV with human CNS tumors in patients with or without concomitant PML. In this study, we have examined the possible association of JCV with human brain tumor. We collected 47 specimens of brain tumor and 9 brain non-neoplasms specimens. By using pathological diagnosis in Hematoxylin-Eosion stain with auxiliary confirm immunohistochemistry stain of tissue section. Immunochemistry stain was used for viral early protein T-antigen. Positive samples included 11 of 29 glial-derived tumors, 3 of 11 metastatic tumors, and 3 of 9 non-neoplasms change. All of 7 non-glial-derived tumors showed negative results. These results provided evidence for a possible association of JCV T-antigen with glial-derived tumors and metastatic tumors. In addition, samples with non-neoplasm showed JCV LT positive in some astrocytes
URI:	http://140.128.138.153:8080/handle/310902500/1138
Appears in Collections:	[The Institute of Biochemistry, Microbiology and Immunology ] Electronic Theses of Dissertation

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