跳到主要內容

臺灣博碩士論文加值系統

(34.204.169.230) 您好!臺灣時間:2024/02/21 23:59
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:蔡慧頻
研究生(外文):Huey-Pin Tsai
論文名稱:1999年至2004年南台灣流行性感冒病毒之研究分析
論文名稱(外文):Analysis of influenza virus in southernTaiwan from 1999 to 2004
指導教授:王貞仁王貞仁引用關係
指導教授(外文):Jen-Ren Wang
學位類別:碩士
校院名稱:國立成功大學
系所名稱:醫事技術學系
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:116
中文關鍵詞:流行性感冒病毒
外文關鍵詞:influenza virus
相關次數:
  • 被引用被引用:1
  • 點閱點閱:188
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:1
  流行性感冒病毒(流感病毒) 之感染在老年人及小孩中常造成極高的罹病率及死亡率。是否能成功地使用疫苗來控制流感病毒之感染主要決定於當季所流行的病毒株以及流感病毒感染之季節型態。雖然A型及B型流感病毒之感染在溫帶地區流行的季節主要是在冬季,不過在台灣它們依然可活躍於春天、夏天及早秋。Amantadine 這個藥物主要是用來治療及預防A型流感病毒之感染,倘若產生具有抗amantadine 之A型流感病毒株,其可能會引起大規模之流行。因此,對A型流感病毒對此藥物之抗藥性之了解有助於對流感病毒之流行的預防提供良好的線索。所以本研究的目地包括(1) A型及B型流感病毒的分子流行病學分析(2) A 型流感病毒H1N2亞型的出現率(3) 監測A型流感病毒中產生amantadine 抗藥性之比例,以了解南台灣流病毒流行之情形。
  我們所分析的病毒株包括來自1999 年至2004 年南台灣A型流感病毒(H3N2 及H1N1) 及B型流感病毒等。在分析H3、H1A型流感病毒的HA (Hemagglutinin, HA)基因及抗原性之變化顯示,其HA1的區域與prototype之疫苗株相比不管在核? 酸或是胺基酸的變化中呈現出逐年連續性漂變(drift)的情形。2002 年三月至2004 年的H3病毒株與疫苗株(A/Panama/2007/99) 相比,發現於B抗原決定位中有一至三個胺基酸陸續被取代的病毒株;而這三個胺基酸被取代之病毒株在分子流行病學的分析中與疫苗株(A/Fujian/411/02) (WHO 2004/2005 北半球所推薦之疫苗株)是屬於同一個clade。此結果顯示福建株早在2003 年3月即在南台灣出現。在1999/2000 季節的H1病毒株(A/New Caledonia/20/99-like) 中,與疫苗株北京株(A/Beijing/262/95)相比其胺基酸分別在3個抗原決定位(Sa, Sb, Ca)產生改變,這被認為是那個季節造成台灣H1大流行的原因。B型流感病毒方面,1998-2000 年間病毒株均屬於Yamagata 系源,但自2001 年3月我們開始發現流行於1980 年代的B/Victoria/2/87 系源之病毒株。此外,發現自2002 年4月之部份病毒株其HA與NA(Neuraminidase, NA) 之間有來自Victoria 及Yamagata 不同系源之基因重組(genetic reassortmant)的現象,所測試之2002 年的病毒株中重組病毒佔46% (5/11)。對基因重組之B型流感病毒做HA 的基因分析,發現它們皆來自B/Victoria/2/87 系源的一個分支且與B/Hong Kong/1351/02 疫苗株相類似,而其NA基因則來自Yamagata 系源。另外從我們所分析的病毒株中,顯示到目前為止南台灣還未出現H1N2 病毒株。此外,1999 年至2002 年間我們利用了PCR-RFLP 方法偵測53 株A型流感病毒株(20 株H3N2、33 株H1N1)之amatadine 抗藥性之能力。由PCR-RFLP之結果發現雖然有兩株病毒株為具抗藥性之型態,不過經由序列之分析發現其突變的位置是位於第3個核? 乾酸屬於nonsense的突變。以上這些結果針對南台灣流感病毒株有深一層的了解,並且可供我們在全球監控流感病毒的資訊上提供進一步之訊息。
  Infection with influenza viruses can cause severe morbidity and mortality in the elderly and children. Successful application of vaccine for influenza control in a particular region depends on the circulating strains and seasonal pattern of influenza infection. Although infections with influenza virus A and B predominate in winter seasons, they were also observed in the spring, summer, and early fall in Taiwan. Amantadine has shown effect in treatment and preventing influenza A virus infections. Amantadine resistant influenza A virus may result in epidemic infection. Therefore, well understanding the variation of influenza viruses can give the clues for viral prophylaxis. In this study, we examined (1) the molecular epidemiology of influenza A and B viruses (2) the occurrence of H1N2 of influenza A virus (3) monitoring the incidence of amantadine resistance influenza A virus in southern Taiwan.
  The isolates of influenza A (H3N2 and H1N1) and B viruses between 1999 and 2004 from southern Taiwan were used for this study. In the genetic and antigenic analysis in HA (Hemagglutinin, HA) gene of influenza A (H3, H1), the results showed continuous drift of nucleotide and amino acid in the HA1 region increased year by year when compared with the prototype vaccine strains. There were 1, 2, and 3 amino acid substitutions in antigenic site B of H3 isolates found between 2002 March-2004 Jan when compared to A/Panama/2007/99 vaccine strain. The isolates with 3 amino acid changes and A/Fujian/411/02 (WHO 2004/2005 northern hemisphere vaccine strain) belonged to the same clade in the phylogenetic analysis, indicating Fujian-like strains occurrence in southern Taiwan since March 2003. Among 1999/2000 H1 isolates, the amino acid showed changes in the three antigenic sites (Sa, Sb, and Ca1), when compared with A/Beijing/262/95 vaccine strain, which was considered as the reason for the burst outbreak. Most influenza B viruses between 1998 to 2000 belonged to B/Yamagata lineage, since March 2001, B/Victoria/2/87 lineage isolates were identified cocirculating with Yamagata lineage. More interestingly, genetic reassortants of influenza B with different lineage of HA and NA (Neuraminidase, NA) genes were found since April 2002, and 46% (5/11) reassortment virus of 2002 influenza B virus were found. Genetic analysis of the HA gene showed that the B reassortant viruses formed a separate branch from Victoria lineage and were most closely related to B/Hong Kong/1351/02 vaccine strain and NA gene was reassorted from Yamagata lineage. In addition, our study showed lack of H1N2 viruses in Taiwan to date. Furthermore, between 1999 and 2002, fifty-three influenza A viruses isolates (20 H3N2, 33 H1N1) were examined by PCR-RFLP method to screen the single amino acid substitution at position 27, 30 and 31 in the transmembrane domain of the M2 protein in amatadine resistant influenza A viruses. There were two isolates with resistant patterns but the sequence analysis showed nonsense mutations at the third nucleotide. In conclusions, these results provide the better understanding of the influenza viruses in southern Taiwan, and they will serve us as the baseline information for continued worldwide surveillance of influenza viruses.
中文摘要1
英文摘要3
致謝5
目錄6

第一章緒論11
第一節流行性感冒的歷史背景與流行病學11
1.1 流行性感冒病毒之易突變性12
1.2 人類新興的流感病毒13
1. 3 流行性感冒病毒之預防與治療17
1.3.1 流行性感冒病毒疫苗17
1.3.2 流行性感冒病毒抗病毒藥物18
第二節流行性感冒病毒的特性21
2.1 流行性感冒病毒的型態構造21
2.2 流行性感冒病毒之基因體組成及其蛋白質22
2.2.1 聚合脢蛋白及其基因22
2.2.2 核蛋白及其基因23
2.2.3 血球凝集素及其基因23
2.2.4 神經胺酸脢及其基因25
2.2.5 基質蛋白及其基因26
2.2.6 非結構性蛋白及其基因27
2.3 流感病毒的複製28
第三節本研究之動機、目標與實施策略之背景30
3.1 動機及目標30
3.2 實施策略之背景31
3.2.1 南台灣A型及B型流感病毒的分子流行31
病學分析
3.2.2 南台灣A型流感病毒H1N2 亞型的發生率34
3.2.3 監測南台灣A型流感病毒amamtadine 抗藥性36
之發生率

第二章材料及方法38
第一節流行性感冒病毒分子流行病學之分析及38
A型流感病毒H1N2之發生率
(一) 細胞培養38
(二) 病毒培養39
(三) 免疫螢光染色40
(四) 血球凝集抑制試驗41
(五) 病毒核酸之萃取51
(六) 反轉錄、聚合脢連鎖反應52
(七) 定序前之PCR產物純化53
(八)定序54
(九) 本實驗所使用引子序列之目錄54
(十) 分子演化分析55
1. GCG alignment 55
2. 演化樹之描繪56
3. Nucleotide sequence accession number 57
第二節監測南台灣A型流感病毒amamtadine之抗藥性58
之發生率
(一) 實驗規劃流程圖58
(二) 反轉錄聚合脢反應(RT-PCR) 58
(三) Restriction fragment length polymorphism method 59
(四) 定序59

第三章結果60
第一節南台灣流感病毒株之流行概況60
第二節南台灣流感病毒之分子流行病學61
1. A型流感病毒之分子流行病學61
1.1 A 型流感病毒分子演化之分析61
1.2 A 型流感病毒分子及抗原性分析62
2. B 型流感病毒之分子流行病學65
2.1 B 型流感病毒分子演化之分析65
2.2 B 型流感病毒HA胺基酸序列差異之比較67
2.3 B 型流感病毒之血球凝集抑制試驗(HI) 67
及分子演化系源種類之比較
第三節南台灣A型流感病毒H1N2 的發生率68
第四節監測A型流感病毒amamtadine 抗藥性之發生率69

第四章討論71

第五章參考文獻82
陳志豪, 2000。A型及B型流行性感冒病毒的基因分析。陽明大學博士論文。台
北。台灣。
林智暉、邱淑君、賴淑寬、陳豪勇, 2004。全球流感的流行病學。疫情報導。20,
123-135。
Abed, Y., Hardy, I., Li, Y., Boivin, G., 2002. Divergent evolution of hemagglutinin
and neuraminidase genes in recent influenza A:H3N2 viruses isolated in Canada. J
Med Virol 67, 589-595.
Almond, J. W., 1977. A single gene determines the host range of influenza. Nature
270, 617-618.
Ansaldi, F., D’Agaro, P., Florentiis, D., Puzelli, S., Lin, Y. P., Gregory, V., Bennett,
M., Donatelli, I., Gasparini, R., Crovari, P., Hay, A., Campello, C., 2003. Molecular
characterization of influenza B viruses circulating in northern Italy during the 2001-
2002 epidemic season. J. Med. Virol. 70, 463-469.
Anonymous, 1999. Influenza. Wkly. Epidemiol. Rec. 74, 111.
Anonymous, 2003. Influenza. Wkly. Epidemiol. Rec 78, 57-64.
Anonymous, 2000. Update: Influenza activity— United States, and worldwide, 1999--
2000 season, and composition of the 2000-01 influenza vaccine. MMWR 49, 375-381.
Anonymous, 2001. Update: Influenza activity— United States, and worldwide, 2000--
2001 season, and composition of the 2001-02 influenza vaccine. MMWR 50, 466-470.
Anonymous, 2002. Update: Influenza activity— United States, and worldwide, 2001--
2002 season, and composition of the 2002-03 influenza vaccine. MMWR 51, 503-506.
Anonymous, 2003. Update: Influenza activity— United States, and worldwide, 2002--
2003 season, and composition of the 2003-04 influenza vaccine. MMWR 52, 516-521.
Anonymous, 2004. Update: Influenza activity— United States, 2003/2004 season.
MMWR 53, 284-287.
Barr, I. G., Komadina, N., Hurt, A., Shaw. R., Durrant, C., Iannello, P., Tomasov, C.,
Sjogren, H., Hampson, A. W., 2003. Reassortants in recent human influenza A and B
isolates from South East Asia and Oceania. Virus Res. 98, 35-44.
Barrett, T., Wolstenholme, A. J., Mahy, B. W. J., 1979. Transcription and replication
of influenza virus RNA. Virology 98, 211-225.
Beaton, A. R., Krug, R. M., 1986. Transcription antitermination during influenza
viral template RNA synthesis requires the nucleocapsid protein and the absence of a
5’ capped end. Proc. Natl. Acad. Sci. USA 83, 6282-6286.
Belshe, R. B., Smith, M. H., Hall, C. B., Betts, R., Hay, A. J. 1988. Genetic basis of
resistance to rimantadine emerging during treatment of influenza A virus infection. J.
Virol. 62, 1508-12.
Biswas, S. K., Nayak, D. P., 1994. Mutational analysis of the conserved motifs of
influenza A virus polymerase basic protein 1. J. Virol. 68, 1819-1826.
Bush, R. M., Fitch, W. M., Bender, C. A., Cox, N. J., 1999. Positive selection on the
H3 hemagglutinin gene of human influenza virus A. Mol. Biol. Evol. 16, 1457-1465.
Bush, R. M., Bender, C. A., Subbarao, K., Cox, N. J., Fitch, W. M., 1999. Predicting
The evolution of human influenza A. Science 286, 1921-1925.
Caton, A. J. , Brownlee, G. G., 1982. The antigenic structure of the influenza virus
A/PR/8/34 hemagglutinin (H1 subtype). Cell 31, 417-427.
Chi, X. S., Bolar, T. V., Zhao, P., Rappaport, R., Cheng, S. M., 2003. Cocirculation
and evolution of two lineages of influenza B viruses in Europe and Israel in the 2001-
2002 season. J. Clin. Microbiol. 41, 5770-5773.
Class, E, Osterhaus, A., Van Beek R, et al., 1998. Human influenza A H5N1 virus
related to a highly pathogenic avian influenza virus. Lancet 351, 472-77.
Colman, P. M., 1989. Neuraminidase:enzyme and antigen. In: Krug, R. M., ed. The
influenza viruses. New York: Plenum Press. P. 175-218.
Cough, R.B., Kasel, J.A., 1983. Immunity to influenza in man [review]. Annu. Rev.
Microbiol. 37, 529-49.
Cough, R. B., 2000. Prevention and treatment of influenza. N. Engl. J. Med. 343,
1778-1787.
Cox, N. J., Brammer, T.L., Rehnery, H.L., 1994. Influenza: global surveillance for
epidemic and pandemic variants. Eur. J. Epidemiol. 10, 467-470.
Cox, N. J., Bender, C. A., 1995. The molecular epidemiology of influenza viruses.
Sem Virol. 6, 359-370.
Cox, N. J., Regnery, H.L., 1996. Global influenza surveillance: tracking a moving
target in a rapidly changing world. In options for the control of influenza III, Cairns,
Australia, ed. LE Brown, AW Hampson, RT Webster, pp. 591-98.
Cox, N. J., Subbarao, K., 2000. Global epidemiology of influenza: past and present.
Annu. Rev. Med. 51, 407-421.
Crosby AW., 1989. America’s forgotten pandemic. Cambridge, UK: Cambridge
Univ. Press
Davies, W. L., Grunert, R. R., Haff, R. F., McGahen, J. W., Neumayer, E. M.,
Paulshock M., Watts J. C., Wood, T. R., Herrman, E. C., Hoffman, C. E., 1964.
Antiviral activity of 1-Adamantanamine (Amantadine). Science 144, 862-863.
Degelau, J., Somani, S. K., Cooper, S. L., Guay, D., Crossley, K. B., 1992.
Amantadine-resistant influenza A in a nursing facility. Arch. Intern. Med. 152, 390-
392.
Dolin, R., Reichman, R. C., Madore, H. P., Maynard, R., Linton, P. N., Webber-Jone,
J., 1982. A controlled trial of amantadine and rimantadine in the prophylaxis of
influenza A infection. N. Engl. J. Med. 307, 580-584.
Ellis, J. S., Alvarez-Aguero, A., Gregory, V., Lin, Y. P., Hay, A., Zambon, M. C.
2003. Influenza A (H1N2) viruses and their impact during the 2001-02 influenza
season in the United Kingdom. Emerg. Infect. Dis. 9, 304-310.
Ellis, J., Zambon, M. C., 2002. Molecular diagnosis of influenza. Rev. Med. Virol. 12,
357-89.
Englund, J. A., Champlin, R. E., Wyde, P. R., Kantarjian, H., Atmar, R. L., Tarrand,
J., Yousuf, H., Regnery, H., Klimov, A. J., Cox, N. J., Whimbey, E., 1998. Common
emergence of ama ntadine- and rimantadine-resistant influenza A viruses in
symptomatic immunocompromised adults. Clin. Infect. Dis. 26, 1418-1424.
Fitch, W. M., Bush, R.M., Bender, C. A., Cox, N. J., 1997. Long term trends in the
evolution of H3 HA1 human influenza type A. Proc. Natl. Acad. Sci. USA 94, 7712-
7218.
Fouchier R, 2003. Avian influenza human-Netherlands (09):fatal case. Reported in:
ProMed-mail [online]. Boston: International Society for Infectious Disease, report no
20030419.0959, April 19. (www.promedmail.org)
Frank, A. L., Taber, L. H., 1983. Variation in frequency of natural infection with
influenza A viruses. J. Med. Virol. 12, 17-23.
Glezen, W. P., Paredes, A., Taber, L. H., 1980. Influenza in children. JAMA 243,
1345-1349.
Gregory, V., Bennett, M., Orkhan, M. H., Al Hajjar, S., Varsano, N., Mendelson, E.,
Zanbon, M., Ellis, J., Hay, A., Lin, Y P, 2002. Emergence of influenza A H1N2
reassortment viruses in the human population during 2001. Virology 300, 1-7.
Guan, Y., Shortridge, K.F., Krauss, S., Webster, R,G., 1999. Molecular
characterization of H9N2 influenza viruses: Were they the donors of “internal” genes
of H5N1 viruses in Hong Kong? Proc. Natl. Acad. Sci. 96, 9363-67.
Guo, Y., Xu, X., Cox, N.J., 1992. Human influenza A (H1N2) viruses isolated from
China. J Gen Virol 73:383-88.
Hall, C. B., Dolin, R., Gala, C. L., Markovitz, D. M., Zhang, Y. Q., Madore, P. H.,
1987. Children with influenza A infection: treatment with rimantadine. Pediatrics 80,
275-282.
Hardy, I., Li, Y., Coulthart, M.B., Goyette, N., Boivin, G., 2001. Molecular evolution
of influenza A/H3N2 viruses in the province of Québec (Canada) during the 1997-
2000 period. Virus Research 77, 89-96.
Hay, A. J., 1992. The action of amantadine against influenza A viruses: inhibition of
the M2 ion channel protein. Semin. Virol. 3, 21-30.
Hay, A. J., Gregory, V., Douglas, A. R., Lin, Y. P., 2001. The evolution of human
influenza viruses. Philo. Trans. R. Soc. London [Biol] 356, 1861-1870.
Hayden, F. G., Belshe, R. B., Clover, R. D., Hay, A. J., Oakes, M. G., Soo, W., 1989.
Emergence and apparent transmmision of rimantadine-resistant influenza A virus in
families. N. Engl. J. Med. 321, 696-1702.
Hayden, F. G., Sperber, S. J., Belshe, R. B., Clover, R. D., Hay, A. J., Pyke, S., 1991.
Recovery of drug-resistant influenza A virus during therapeutic use of rimantadine.
Antimicrob. Agents Chemother. 351, 1741-1747.
Hemophil M. L., Rota, P. A., Ivanova, V. T., et al., 1993. Antigenic and genetic
analyses of influenza type B viruses isolated in Russia. 1987-91. Epidemiol. Infect.
111, 539-546.
Hiromoto, Y., Saito, T., Lindstorm, S. E., Li, Y., Nermone, R., Sugita, S., Shinjoh,
M., Nerome, K., 2000. Phylogenetic analysis of the three polymerase genes (PB1,
PB2 and PA) of influenza B virus. J. Gen. Virol. 81, 929-937.
Hirst GK., 1941. Agglutinination of red cells by allantoic fluid of chick embryos
infected with influenza virus. Science 94, 22-23.
Houck, P., Hemphill, S., Lacroix, S., Hirsh, D., Cox, N. J., 1995. Amantadineresistant
influenza in nursing homes. Arch. Intern. Med. 155, 533-537.
Ina, Y., Gojobori, T., 1994. Statistical analysis of nucleotide sequence of the
hemagglutinin gene of human influenza A viruses. Proc. Natl. Acad. Sci. USA 91,
8388-8392.
Ito, T., Couceiro, J. N., Kelm, et al., 1998. Molecular basis for the generation in pigs
of influenza A viruses with pandemic potential. J. Virol. 72, 7367-7373.
Jefferson, T. O., Demicheli, V., Deeks, J. J., Rivetti, D., 2001. Amantadine and
rimantadine for preventing and treating influenza A in adults (Cochrane Review). In:
The Cochrane library, issue 4, Oxford: Update Software.
Kanegae, Y., Suqita, S., Endo, A., Ishida, M., Senya, S., et al., 1990. Evolutionary
pattern of the hemagglutinin gene of influenza B viruses isolated in Japan:
Cocirculating lineages in the same epidemic season. J. Virol. 64, 2860-2865.
Kendal, A. P., Cox, N. J., 1985. Forecasting the epidemic potential of influenza virus
variants based on their molecular properties. Vaccine 3, 263-266.
Klimov, A. J., Rocha, E., Hayden, F. G., Shult, P. S., Roumillat, L. F., Cox, N. J.,
1995. Prolonged shedding of amantadine-resistant influenza A viruses by
immunodeficient patients: detection by polymerase chain reaction-restriction analysis.
J. Infect. Dis. 172, 1352-1355.
Krug, R. M., 1981. Priming of influenza viral RNA transcription by capped
heterologous RNAs. Curr. Top. Microbiol. Immunol. 93, 125-149.
Lam, R. A., and Krug, R. M., 1996. In fields Virology, 3rd ed. Lippincott-Raven Press,
Philadelphia. Pp. 1353-1395.
Levandowski, R. A., Regnery, H. L, Staton, E., et al., 1991. Antibody responses to
influenza B viruses in immunologically unprimed children. Pediatrics 88, 1031-1036.
Li, X. S., Zhao, C. Y., Gao, H. M., Zhang, Y. Q., Ishida, M., Kanegae, Y., Endo, A.,
Nerome, R., Omoe, K., Nerome, K., 1992. Origin and evolutionary characteristics of
an antigenic reassortment (H1N2) virus isolated from man in China. J. Gen. Virol. 73,
1329-37.
Lindstorm, S. E., Hiromoto, Y., Nerome, R., Omoe, K., Sugita, S., Yamazaki, Y.,
Takahashi, T., Nerome, K., 1998. Phylogenetic analysis of the entire genome of
influenza A (H3N2) viruses from Japan: evidence for genetic reassortment of the six
internal genes. J. Virol. 72, 8021-8031.
Mast, E. E., Harmon, M. W., Gravenstein, S., Wu, S. P., Arden, N. H., Circo, R.,
Tyszka, G., Kendal, A. P., Davis, J. P., 1991. Emergence and possible transmmsion of
amantadine-resistant viruses during nursing home outbreaks of influenza A (H3N2).
Am. J. Epidemiol. 134, 988-997.
Marsh, M., Helenius, A., 1989. Viral entry into animal cells. Adv. Virus Res. 36,
107-151.
Martin, K., Helenius, A., 1991. Nuclear transport of influenza virus
ribonucleoproteins: the viral matrix protein (M1) promotes export and inhibit import.
Cell 67, 117-130.
Masuda, H., Suzuki, H., Oshitani, H., Saito, R., Kawasaki, S., Nishikawa, M., Satoh,
H., 2000. Incidence of amantadine-resistant influenza A viruses in sentinel
surveillance sites and nursing homes in Niigata, Japan. Microbiol. Immunol. 44, 833-
839.
McClelland L, Hare R., 1941. The adsorption of influenza virus by red cells and a
new in vitro method of measuring antibodies for influenza virus. Can. J. Public health.
32, 530-538.
McCullers, J. A., Wang, G. C., He, S., Webster, R. G., 1999. Reassortment and
insertion-deletion are strategies for the evolution of influenza B viruses in nature. J.
Virol. 73, 7343-7348.
Mounts, A.W., Kwang, H., Izurieta, H.S., et al. 1999. Case-control study of risk
factors for avian influenza A(H5N1) disease, Hong Kong, 1997. J. Infect. Dis. 180,
505-8.
Murphy, B. R., Kasel, J. A., Chanock, R. M., 1972. Association of serum antineuraminidase
antibody with resistance to influenza in man. N. Engl. J. Med. 286,
1329-1332.
Murphy, B. R., Buckler-White, A. J, London, W. T., Snyder, M. H., 1989.
Characterization of the M protein and nucleoprotein genes of an influenza A virus
which are involved in host range restriction in monkeys. Vaccine 7, 557-561.
Nerome, R., Hiromoto, Y., Sugita, S., Tanabe, N., et al., 1998. Evolutionary
characteristics of influenza B virus since its first isolation in 1940: Dynamic
circulation of deletion and insertion mechanism. Arch. Virol. 143, 1569-1583.
Nicholson, K.G., Wood, J.M., Zambon, M., 2003. Influenza. Lancet 362, 1733-45.
Nishikawa, F., Sugiyama, T., 1983. Direct isolation of H1N2 recombinat virus from a
throat swab of a patient simultaneously infected with H1N1 and H3N2 influenza A
viruses. J. Clin. Microbiol. 18, 425-427.
Noble GR., 1982. Epidemiological and clinical aspects of influenza. In basic and
applied influenza research, ed. As Beare, pp. 11-50. FL: CRC.
Oxford, J. S., Galbraith, A., 1980. Antiviral activity of amantadine: A review of
laboratory and clinical data. Pharmacol Ther 11, 181-262.
Palese, P., Tobita, K., Ueba, M., Compans, R. W., 1974. Characterization of
temperature sensitive influenza virus mutants defective in neuraminidase. Virology 61,
397-410.
Plakokefalos, E. T., Markoulatos, P., Spyrous, N., Bei, T. A., Vamvakopoulos, N. C.,
2001. Molecular and phylogenetic analysis of haemagglutinin and neuraminidase
sequences from recent human influenza type A (H3N2) viral isolates in Southern
Greece. Arch. Virol. 146, 1899-1918.
Raymond, F. L., Caton, A. J., Cox, N. J., Kendal, A. P., Brownlee, G. G., 1986. The
antigenic and evolution of influenza H1 Haemagglutinin, from 1950-1957 and 1977-
1983: two pathways from one gene. Virology 148, 275-287.
Rota, P. A, Hemphil, M. L., Whistler, T., Regnery, H. T., Kendal, A. P., 1992.
Antigenic and genetic characterization of the hemagglutinins of recent cocirculating
strains of influenza B virus. J. Gen. Virol. 73, 2737-2742.
Rota, P., Wallis, T.P., Harmon, M. W., Rota, J. S. et al., 1990. Cocirculation of two
distinct evolutionary lineages of influenza type B viruse since 1983. Virology 175, 5-
68.

Rogers, G. N., Paulson, J. C., Daniel, R. S., Skehel, J. J., Wilson, I. A., Wiley, D. C.,
1983. Single amino acid substitutions in influenza haemagglutinin change receptor
binding specificity. Nature 304, 76-78.
Ruutu, P., Halonen, P., Meurman, O., Torres, C., Paladin, F., Yamaoka, K., Tupasi, T.
E., 1990. Viral lower respiratory tract infections in Filipino children. J. Infec. Dis. 161,
175-179.
Saito, T., Taylor, G., Laver, W. G., Kawaoka, Y., Webster, R. G., 1994. Antigenicity
of the N8 influenza A virus neuraminidase:exstence of an epitope at the subunit
interface of the neuraminidase. J. Virol. 68, 1790-1796.
Saito, P., Oshitani, H., Masuda, H., Suzuki, H., 2002. Detection of amantadineresistant
influenza A viruse strains in nursing homes by PCR-restriction fragment
length polymorphism analysis with nasopharyngeal swabs. J. Clin. Microbiol. 40, 84-
88.
Scholtissek, C., Burger, H., Kistner, O., et al., 1985. The nucleoprotein as a possible
major factor in determining host specificity of influenza H3N2 viruses. Virology 147,
287-294.
Shaw, M. W., Xu, X., Li, Y., Normand, S., Ueki, R., Kunimoto, G. Y., Hall, H.,
Klimov, A., Cox, N. J., Subbarao, K., 2002 Reappearance and global spread of
variants of influenza B/Victoria/2/87 lineage viruses in the 2000-2001 and 2001-2002
seasons. Virology 303, 1-8.
Shih, S. R., Lee, C. N., Tasi, H. R., Chen, G. W., Tsao, K. C., 2001. Amantadineresistant
influenza A virus in Taiwan. J. Formos. Med. Assoc. 100, 608-612.
Smith, C. B., Cox, N. J., Subbarao, K., Taber, L. H., Glezen., 2002. Molecular
epidemiology of influenza A (H3N2) virus reinfections. J Infect Dis 185, 980-5.
Stuarford, Harris, C.H., Schild, G.C., Oxford, J.S., 1985. Influenza. The viruses and
the Disease, pp. 118-38. Victoria, Can.: Edward Arnold. 2nd ed.
Sugrue, R. J., Hay, A. J., 1991. Structural characteristics of the M2 protein of the
influenza A viruses: evidence that it forms a tetrameric channel. Virology 180, 617-
624.
Tsai, H. P., Kuo, P. W., Liu, C. C., Wang, J. R., 2001. Respiratory viral infections
among pediatric inpatients and outpatients in Taiwan from 1997 to 1999. J. Clin.
Microbiol. 39, 111-118.
Ulmanen, I., Broni, B. A., Krug, R. M., 1981. Role of two of the influenza virus core
P proteins in recognizing cap 1 structure (m7GpppNm) on RNAs and in initiating viral
RNA transcription. Proc. Natl. Acad. Sci. USA 78, 7355-7359.
Wang, C., Takeuchi, K., Pinto, L. H., Lamb, R. A. 1993. Ion channel activity of
influenza A virus M2 protein: characterization of the amantadine block. J. Virol. 67,
5585-94.
Wanger, R., Matrosovich, M., Klenk, H, D., 2002. Functional balance between
haemagglutinin and neuraminidase in influenza virus infections. Rev. Med. Virol. 12,
159-166.
Webster, R. G., Bean W. J. J., 1998. Evolution and ecology of influenza viruses:
interspecies transmission. In Nicholson, K, G., Hay, A. J. (Eds) Textbook of influenza.
Blackwell, Oxford, pp. 109-119.
Webster, R.G., Geraci, J., Petursson, G., Skirnisson, K., 1981. Conjunctivitis in
human beings caused by influenza A virus of seals. N. Engl. J. Med. 304, 911.
WHO Wkly. Epidemiol. Rec, 2004. (http://www.who.int/en/)
Wiley, D. C., Wilson, I. A., Skehel, J.J., 1981.Structural identification of the
antibody-binding sites of Hong Kong influenza hemagglutinin and their involvement
in antigenic variation. Nature 289, 373-8.
Wiley, D. C., Skehel, J. J., Waterfield, M. D., 1977. Evidence from studies with a
cross- linking reagent that the hemagglutinin of influenza virus is a trimer. Virology
79, 446-448.
William, G., 1999. New influenza vaccine. Blackwell Science Ltd. Advanced
influenza. International Medical Forum, 104, 19-26.
Wilson, IA., Cox, N. J., 1990. Structural basis of immune recognition of influenza
virus hemagglutinin. Annu Rev Immuno 8, 737-71.
Wright, K. E., Wilson, G. A., Novosad, D., Dimock, C., Tan, D., Weber, J. M.,1995.
Typing and subtyping of influenza viruses in clinical samples by PCR. J. Clin.
Microbiol. 33, 1180-1184.
Xu, X., Guo, Y., Rota, P. A., Hemphil, M., Kendal, A. P., Cox, N.J., 1993. Genetic
reassortment of human influenza virus in nature. In: Hannoun, C., Kendal, A. P.,
Klenk, H. D., Rudenko, L. G. (Eds), Options for the control of influenza, vol. II.
Elsevier, Amsterdam, The Netherlands, pp. 203-207.
Xu. X., Smith, C. B., Mungall, B. A., Lindstorm, S. E., Hall, H. E., Subbarrao, K.,
Cox, N. J., Klimov, A., 2002. Intercontinental circulation of human influenza A
(H1N2) reassortment viruses during the 2001-2002 influenza season. J. Infect. Dis.
186, 490-493.
Yewdell JW, Hackett CJ., 1989. Specificity and function of T lymphocytes induced
by influenza A viruses. In: Krug RM, ed. The influenza viruses. New York: Plenum
Press, 361-429.
Ziegler, T., Hemphill, M. L., Ziegler, M. L., Perez-Oronoz, G., Klimov, A. I.,
Hampson, A. W., Regnery, H. L., Cox, N. J., 1999. Low incidence of rimantadine
resistance in field isolates of influenza A viruses. J. Infect. Dis. 180, 935-939.
連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
1. 楊媛絢。1996。Lactobacillus acidophilus之降膽固醇及抗癌性。食品工業 28(9):39-45。
2. 劉心綺。1998。Resistant starch─抗性澱粉的特性和應用。食品資訊 150:52-55。
3. 廖宏儒。1999。抗酵素水解澱粉。烘焙工業 88:69-74。
4. 5.吳清基(1995),我國學校行政的政策新取向,學校行政創刊號,P.3-10。
5. 3.何金銘、李安民(2002年冬季號),組織政治知覺與工作滿足及工作壓力關係,人力資源管理學報,第二卷第四期,P.81-106。
6. 邵貽沅。2002。難消化澱粉對大白鼠血脂與肝脂的影響。中華民國營養學會雜誌 27:16-23。
7. 王怡晶。1997。淺談抗性澱粉。食品工業 29(5):38-49。
8. 8.許士軍(1972),有關黎史二氏「組織氣候」尺度在我國企業機構之適用性之探討,國立政治大學學報,第26期,P.103-138。
9. 1.王政彥(1998),成人隔空學習主題的延伸─從自我調控學習的分析,成人教育雙月刊,56,P.9-21。
10. 27.陳郁汝(2002),行政人員自我導向學習能力、工作投入與學校行政效能之研究,高雄師範大學成人教育研究所碩士論文。
11. 丁懷謙。2000。益生菌與胃腸保健功效。食品工業 32(10):1-5。
12. 12.藍瑞霓(1998),國小教師工作滿意度調查研究,屏東師院學報,11期,P.55-79。
13. 10.張紹勳、林介鵬(2003),工作滿足之因果模式─以台灣日商銷售人員為例,管理學報,第二十卷第三期,P.547-577。
14. 9.許士軍(1977),工作滿意、個人特徵與組織氣候─文獻探討及實證研究,國立政治大學學報,第35期,P.13-56。