跳到主要內容

臺灣博碩士論文加值系統

(44.200.175.255) 您好!臺灣時間:2022/08/11 14:21
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:陳泓志
研究生(外文):Mark Hung-Chih Chen
論文名稱:第一型和第二型類胰島素生長因子基因及其接受器在斑馬魚發育之研究
論文名稱(外文):The insulin-like growth factor 1 gene, insulin-like growth factor 2 gene and their receptor involve in zebrafish(danio rerio) development
指導教授:吳金洌吳金洌引用關係
指導教授(外文):Jen-Leih Wu
學位類別:博士
校院名稱:國防醫學院
系所名稱:生命科學研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:英文
論文頁數:160
中文關鍵詞:類胰島素生長因子斑馬魚軟骨硫化胸部的發育E胜月太
外文關鍵詞:Insulin-like growth factorzebrafishcartilage sulfationThorax developmentMorpholinoE polypeptide
相關次數:
  • 被引用被引用:0
  • 點閱點閱:401
  • 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
斑馬魚(Danio rerio)由於易於飼養、成長快速、繁殖容易、胚胎透明,是作為脊椎動物基礎研究指標性的國際性模式魚種,而相關的基因功能研究技術皆相當成熟,如基因轉殖、基因去活化(morpholinos knock-down)等。類胰島素生長因子(IGF)的反應或由類胰島素生長因子本身的旁分泌、自分泌(paracrine/autocrine)的一連串訊息傳遞反應來調控生長,而IGF基因家族在旁分泌及自分泌調控仍有許多未知待發掘,透過旁分泌和自分泌機制所產生的IGF對個體生長和胚胎發育扮演了非常重要角色。
所以類胰島素生長因子基因家族(IGF-1, IGF-2, IGF-1 receptor(IGF-1R))是生長系統最重要的成員之一,因此本論文研究主要是找出與類胰島素生長因子相關之基因群組,再進而探討其功能性的研究。
斑馬魚的第一型類胰島素生長因子基因在本研究至少發現有二個,但仍只轉譯出一種相同的蛋白質冪嚆(TM)胰島素生長因子(proIGF-1 Ea-2),而此二基因轉譯出的蛋白質相同程度達100%,至於蛋白質的成熟機制至今仍尚不清楚,其proIGF-1之E 胜月太究竟是演化上冗長多餘的,還是像原胰島素(proInsulin) 能有研究發現其C peptide有重要功能,尤其最近研究指出C peptide在第一型糖尿病上扮演重要角色,基於上述理由,本實驗假設proIGF-1之E 胜月太有模擬IGF-1之功能,尤其在軟骨生長上,所以本研究闡述了Ea-2 胜月太在斑馬魚和吳郭魚的鰓軟骨上皆具有軟骨硫化之功能,其硫化程度比控制組高達三倍以上,除了硫化功能外Ea-2 胜月太尚有[3H]thymidine嵌合DNA之能力並有荷爾蒙濃度依存之效果。為了更進一步了解其Ea-2 胜月太之作用機制,在本研究中採用了IGF-1之頡抗劑(aIR-3),此一aIR-3可有效的結合IGF-1接受器,使IGF-1訊息無法傳遞,研究發現以aIR-3並無法抑制Ea-2 胜月太之硫化功能,但郤能抑制IGF-1之硫化功能,在此闡述了Ea-2 胜月太之硫化功能可非經由IGF-1接受器,而可能有另外的特有接受器或其他作用機制而使Ea-2 胜月太擁有軟骨硫化之生化功能。
IGF基因在胚胎中胚層扮演極重要的角色,如骨骼系統,心血管系統及真皮組織和皮下脂肪皆由中胚層衍生出來,而間葉細胞則屬於中胚層的衍生物,其可分化為纖維母細胞、免疫母細胞、軟骨母細胞和成骨母細胞等。IGF-1和IGF-2都是普遍性的細胞生長因子並透過IGF-1R接受器來傳達訊息,並可透過自分泌或旁分泌來抑制或擴增其IGF的生物活性。所以IGF-2和IGF-1R是本論文不可少之成員,本論文亦將IGF-2a cDNA和IGF-2b基因選殖出來,並從斑馬魚網站找到一個高相似度的IGF-1R EST選殖株取得其5UTR區域,透過基因功能研究技術:基因轉殖及基因去活化(morpholinos knock-down)來研究IGF基因嚴重影響斑馬魚胸部的發育。
本論文結論是希望能以斑馬魚IGF基因在生長機制上提供一些新的見解,以促進對生長的瞭解,希望能在未來建立調節生長的工程基因網路。
The characteristics of high growth rate, easy breeding and maintenance have made the zebrafish (Danrio rerio) as world-wide recognized species and important embryo model for functional genomics and proteomics research in the post-genomics era.
This dissertation focused on the zebrafish growth related genes and its function, especially IGF-1, IGF-2 and IGF-1R. In this study, we plan to dissect the mechanisms of paracrine/autocrine modes of IGF action in the thorax development.
We cloned zebrafish (Danio rerio) IGF-1 cDNA and its genomic sequence from zebrafish brain cDNA library and an adult zebrafish genomic library, respectively. These two cDNA sequences differ from with each other in different length of 5- and 3-untranslated region (5UTR and 3UTR) and one nucleotide difference at glutamine (A9, CAG/IGF-1a and CAA/IGF-1b) of the A domain. The results of IGF-1 mRNA expression and genomic Southern blotting, RPA, 5悐ACE suggested that the zebrafish have more than two IGF-1 genes. All these findings suggest that the expression of pro-IGF-1 Ea-2 is not controlled by alternative splicing but alternative gene usage in the zebrafish.
Results of RT-PCR and Southern blot analysis showed that, only one form of IGF-1 Ea-2 mRNA was expressed in all tested adult tissues of zebrafish, even under condition of growth hormone, prolactin or insulin administration and fasting. The encoding proIGF-1a Ea-2 protein is 100% identity to proIGF-1b Ea-2. So, we tested the hypothesis whether E domain can mimic IGF-1 function.
In this research, a synthetic peptide of the predicted zebrafish Ea-2 polypeptide (designated as zfEa-2) was not only increased 3 fold of branchial cartilage specific sulfate uptake in vitro compared with control group but also increased the [3H]thymidine incorporation into DNA on the mouse spleen cell. For further understanding the zfEa-2 polypeptide action mechanism, the aIR-3 was used to block the IGF-1 signal transduction. We demonstrated that aIR-3 couldn掐 inhibit the zfEa-2 signal but inhibit the IGF-1 sulfate uptake capability. These findings strongly suggest that the zfEa-2 can mimic IGF-1 function as a local mediator in zebrafish. These findings strongly suggest that the zfEa-2 polypeptide has another receptor to trigger the sulfation signal in zebrafish.
Finally, The IGFs system exhibits an important role on the zebrafish development. So, we are further cloning the IGF-2a cDNA and IGF-2b gene from library. Meantime, we are search one zebrafish IGF-1Ra EST clone and get the 5UTR sequence for morpholino gene knock-down functional assay.
In conclusion, this dissertation hopes to provide a new vision on the IGF gene family (IGF-1, IGF-2, IGF-1R) to distribute onto the growth regulation mechanism. Based on these researches, it can provide some information to construct the growth gene-chip network in the future.
謝辭 ............................................
CONTENTS ........................................ I
LIST OF FIGURES AND LEGENDS ..................... IV
LIST OF MATERIALS AND METHODS ..................... V
ABSTRACT (English) .............................. 1
ABSTRACT (Chinese) .............................. 3
INTRODUCTION .................................... 5
1. Theory about the growth .......................... 5
a. GH-IGF-1 axis (Somatomedin Hypothesis) ......... 5
b. Modify Somatomedin Hypothesis .................. 6
2. IGF-1 genes, IGF-2 genes and IGF-1 receptor ...... 8
a. The IGF-1 ligand family ........................ 8
b. Functional domains of preproIGF-1 protein ...... 12
c. Regulation network between IGFs ligand and IGF-1R 15
3. Zebrafish development ............................ 22
a. The zebrafish fish as a model system of postfertilization development .................. 22
4. Scope of this thesis ............................. 23
MATERIALS AND METHODS ........................... 25
RESULTS ......................................... 47
1. The novelty of preproIGF-1 genes ................. 47
2. One form proIGF-1 Ea-2 mRNA is expressed ......... 52
3. Biological activity of Synthetic zfEa-2 polypeptide ...................................... 55
4. The novelty of the zebrafish IGF-2 genes ......... 57
5. Spatial and temporal expression pattern of IGF-1, IGF-2a and IGF-2b mRNA during zebrafish embryogenesis and tissue distribution in adult zebrafish ........................................ 58
FIGURES AND LEGENDS ............................. 61
DISCUSSION ...................................... 105
1. More than two IGF-1 genes exist in zebrafish ..... 105
2. The zfEa-2 polypeptide mimic IGF-1 function ...... 109
CONCLUSION ...................................... 114
REFERENCES ...................................... 116
APPENDIX ........................................ 129
1. Publication List ................................. 129
a. Major publication .............................. 131
2. Abbreviations .................................... 140
3. BMI index ........................................ 142
4. Results of IGFs system on the thorax development of zebrafish ......................... 142
VITAE ........................................... 155
1. Adachi, T., Takiya, S., Suzuki, Y., Iwami, M., Kawakami, A., Yahahashi, S.Y., Ishizaki, H., Nagasawa, H., Suzuki, A., 1989. cDNA structure and expression of bombyxin, an insulin-like brain secretory peptide of the silkmoth Bombyx Mori J. Biol. Chem. 264, 7681-7685.
2. Adamo, M.L., Newenschwander, S., LeRoith, D., Roberts, C.T.Jr., 1993. Structure, expression, and regulation of the IGF-I gene. In: LeRoith, D., Raizada, M.K., (eds.), Current Direction in Insulin-Like Growth Factor Research. Plenum, New York, pp. 1-11.
3. Allan, G. J., Flint, D. J., and Patel, K., 2001 Insulin-like growth factor axis during embryonic development. Reproduction 122, 31-39.
4. Arnqvist, H. J., Bornfeldt, K. E., Chen, Y. and Lindstrom, T. (1995) The Insulin-Like Growth Factor System in Vascular Smooth Muscle: Interaction With Insulin and Growth Factors. Metabolism 44(10, Suppl 4), 58-66.
5. Bach, M. A., Werner, H., Bondy, C., Leroith, D. and Roberts, Jr. C. T. (1991) Regulation of Type I IGF Receptor Gene Expression. In "Modern Concepts of Insulin-Like Growth Factors" (E. Martin Spencer, Eds.), 671-679. Elsevier Science Publishers, New York.
6. Baker, J., Liu, J. P., Robertson, E. J., and Efstratiadis, A. (1993). Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75, 73-82.
7. Butler, A.A. and LeRoith, D.: Minireview: tissue-specific versus generalized gene targeting of the igf1 and igf1r genes and their roles in insulin-like growth factor physiology. Endocrinology 142 (2001) 1685-8.
8. Cao, Q. P., Duguay, S. J., Plisetskaya, E., Steiner, D. F. and Chan, S. J., 1989. Nucleotide sequence and growth hormone-regulated expression of salmone insulin-like growth factor I mRNA. Mol. Endocrinol. 3: 2005-2010.
9. Chen, J.Y., Chang, C.Y., Chen, J.C., Shen, S.C. and Wu, J. L., 1997. Production of biologically active recombinant tilapia insulin-like growth factor-II polypeptides in E.coli cells and characterization of the genomic structure of the coging region. DNA and Cell Biology. 16: 883-892.
10. Chen. J.Y., Chen, J. C., Chang, C. Y., Shen, S. C., Chen, M. S. and Wu, J. L., 2000. Expression of recombinant tilapia insulin-like growth factor-I and stimulation of juvenile tilapia growth by injuction of recombinant IGFs polypeptides. Aquaculture : 181, 347-360.
11. Chen, J.Y., Tsai, H.L., Chang, C.Y., Wang, J.I., Shen, S.C., Wu, J.L., 1998a Isolation and Characterization of Tilapia (Oreochromis mossambicus) Insulin Like Growth Factors Gene and Proximal Promoter Region. DNA Cell Biol. 17, 359-376.
12. Chen, M.H.C., Lin, G.H., Gong, H.Y., Lee, C.Y., Chang, C.Y., Chen, T.T., Wu, J.L., 1998b. Cloning and characterization of insulin-like growth factor I cDNA from black seabream (Acathopagrus schlegeli). Zool. Stud. 37, 213-221.
13. Chen, M.H.C., Lin, G.H., Gong, H.Y., Weng, C.F., Chang, C.Y. and Wu, J.L. 2001. The characterization of prepro-insulin-like growth factor-1 Ea-2 expression and insulin-like growth factor-1 genes (devoid 81bp) in the zebrafish (Danio rerio). Gene 268: 67-75.
14. Chew, S.L., Lavender, P., Clark, A.J.L., Ross, R.J.M., 1995. An alternatively spliced human insulin-like growth factor-1 transcript with hepatic tissue expression that diverts away from the mitogenic IBE1 peptide. Endocrinology 136, 1939-1944.
15. Conover C.A., Baker, B.K., Hintz, R.L., 1989. Cultured human fibroblasts secrete insulin-like growth factor IA prohormone. J. Clin. Endocrinol. Metab. 69, 25-30.
16. Daughaday, W.H. and Rotwein, P., 1989. Insulin-like growth factors I and II peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentration. Endocrin. Rev. 10: 68-91.
17. Delafontaine, P., 1995. Insulin-like growth factor I and its binding proteins in the cardiovascular system. Cardiovasc Res 30, 825-34.
18. D帾rcole, A.J., 1996. Growth and growth disorders: Insulin-like growth factors and their receptors in growth (Endocrinol and Metab Clin of North America, vol 25), pp. 573-590, WB Saunders, Philadelphia.
19. Detrich, III H.W., Westerfield, M. and Zon, L.I., 1999. in: Methods in Cell Biology (Wilson, L. and Matsudaira, P., Eds.) The zebrafish: Biology. vol. 59, Academic press, California.
20. Diatchenko, L., Lau, Y.F.C., Campell, A.P., Chenchik, A., Moqadam, F., Huang, B., Lukyanov, S., Lukyanov, K., Gurskaya, N., Sverdlov, E.D. and Siebert, P.D., 1996. Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc. Natl. Acad. Sci. USA 93: 6025-6030.
21. Duan, C., Duguay, S.J. and Plisetskaya, E.M., 1993. Fish Physiol. Biochem. 11, 371-379.
22. Duguay, S.J., Lai-Zhang, J., Steiner, D.F., 1995. Mutational Analysis of the Insulin-like Growth Factor I Prohormone Processing Site. J. Biol. Chem. 270, 17566-17574.
23. Duguay, S.J., Lai-Zhang, J., Steiner, D.F., Funkenstein, B., Chan, S.J., 1996. Developmental and tissue-regulated expression of IGF-1 and IGF-2 mRNAs in Sparus aurata. J. Mol. Endocrinol. 16, 123-132.
24. Duguay, S.J., Park, L.K., Samadpour, M. and Dickhoff, W.W., 1992. Mol. Endocrinol. 6, 1202-1210.
25. Duguay, S.J., Swanson, P. and Dickhoff, W.W., 1994. Differential expression and hormonal regulation of alternatively spliced IGF-I mRNA transcripts in salmon. J. Mol. Endocrinol. 12: 25-37.
26. Foyt, H.L., Roberts, Jr. C.T., 1991. The IGF-1 gene: Structure, expression and gene products. In: LeRoith, D. (ed.), Insulin-like Growth Factor: Molecular and Cellular Aspects. CRC, Florida, pp. 1-16.
27. Geffner, M.E., Bailey, R.C., Bersch, N., Vera, J.C. and Golde, D.W.: Insulin-like growth factor-I unresponsiveness in an Efe Pygmy. Biochem Biophys Res Commun 193 (1993) 1216-23.
28. Gray, E. S., and Kelley, K. M., 1991. Growth regulation in the gobiid teleost Gillichthys mirabilis: roles of growth hormone, hepatic growth hormone receptors and insulin-like growth factor-I. J of Endocrinol. 131, 57-66.
29. Greene, M.W., Chen, T.T., 1997. Temporal expression pattern of insulin-like growth factor mRNA during embryonic development in a teleost, rainbow trout (Onchorynchus mykiss). Mol. Mar. Biol. Biotech. 6, 144-151.
30. Hashimoto, H., Mikawa, S., Takayama, E., Yokoyama, Y., Yoyohara, H., Sakaguchi, M., 1997. Molecular cloning and growth hormone-regulated gene expression of carp insulin-like growth factor-I. Biochem. Mol. Biol. Inter. 41, 877-886.
31. Holly, J. M. P. and Wass, J. A. H., 1989. Insulin-like growth factors : autocrine, paracrine or endocrine ? New perspectives of the somatomedin hypothesis in light of recent developments. J. Endocrinol. 122, 611-618.
32. Howard, A. D., Feighner, S. D., Cully, D. F., 1996. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273:974-977.
33. Huang, W.T., Gong, H.Y., Lin, C.J.F., Weng, C.F., Chen, M.H.C., Wu, J.L., 2001. Hepatocyte nuclear factor (HNFs)-1a, -1b and -3b expressed in the gonad of tilapia (Oreochromis mossambicus). Biochem. Bioph. Res. Co. 288: 833-840.
34. Ido, Y., Vindigni, A., Chang, K., Stramm, L., Chance, R., Heath, W.F., DiMarchi, R.D., Di Cera, E. and Williamson, J.R.: Prevention of vascular and neural dysfunction in diabetic rats by C- peptide. Science 277 (1997) 563-6.
35. Kagawa, H., Kobayashi, M., Hasegawa, Y. and Aida, K., 1994. Gen. Comp. Endocrinol. 95, 293-300.
36. Kavsan, V.M., Grebenjuk, V.A., Koval, A.P., Skorokhod, A.S., Roberts, Jr. C.T., Leroith, D., 1994. Isolation of a second nonallelic insulin-like growth factorⅠgene from the salmon genome. DNA Cell Biol. 13, 555-559.
37. Kavsan, V.M., Koval, A.P., Grebenjuk, V.A., Chan, S.J., Steiner, D.F., Roberts, Jr. C.T., Leroith, D., 1993. Structure of the chum salmon insulin-like growth factor I gene. DNA Cell Biol. 12, 729-737.
38. Kelley, K.M., Gray, E.S., Siharath, K., Nicoll, C.S. and Bern, H.A., 1993. Endocrinol. 132, 2696-2702.
39. Kermouni, A., Mahmound, S.S., Wang, S., Moloney, M., Habibi, H.R., 1998. Cloning of a full-length insulin-like growth factor-I complementary DNA in the goldfish liver and ovary and development of a quantitative PCR method for its measurement. Gen. Comp. Endocrinol. 111, 51-60.
40. Kim, S.W., Lajara, R., Rotwein, P., 1991. Structure and function of a human insulin-like growth factor-I gene promoter. Mol. Endocrinol. 5, 1964-1972.
41. Kopchick, J.J. and Okada, S., 2001. Growth hormone receptor antagonists: discovery and potential uses. Growth Horm IGF Res Suppl A:S103-109.
42. Le Roith, D., Bondy, C., Yakar, S., Liu, J. L. and Butler, A., 2001. The somatomedin hypothesis: 2001. Endo. Rev. 22, 53-74.
43. Leroith, D., Werner, H., Beitner-Johnson, D. and Roberts, Jr. C. T. (1995) Molecular and Cellular Aspects of the Insulin-Like Growth Factor I Receptor. Endocr Rev 16(2), 143-163.
44. Leroith, D., Werner, H., Newenschwander, S., Kalebic, T. and Helman, L. J. (1995) The Role of the Insulin-like Growth Factor-I Receptor in Cancer. Ann NY Acad Sci 766, 402-408.
45. Liang, Y.H., Cheng, C.H.K. and Chan, K.M., 1996. Mol. Mar. Biol. Biotechnol. 5, 145-152.
46. Liu, G., Mang''era, K., Liu, N., Gupta, S., Rusckowski, M., and Hnatowich, D. J., 2002. Tumor pretargeting in mice using (99m)Tc-labeled morpholino, a DNA analog. J Nucl Med 43, 384-91.
47. Liu, J. P., Baker, J., Perkins, A. S., Robertson, E. J., and Efstratiadis, A., 1993. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75, 59-72.
48. Loffing-Cueni, D., Schmid, A.C., Graf, H., Reinecke, M., 1998. IGF-1 in the bony fish Cottus scorpius: cDNA, expression and differential localization in brain and islets. Mol. Cell. Endocrinol. 141, 187-194.
49. Lund, P.K., 1994. Insulin-like growth factor 1: molecular biology and relevance to tissue-specific expression and action. In: Bardin, C.W. (ed.), Rescent progress in hormone research, vol 49. Academic, London, pp. 125-148
50. Lupu, F., Terwilliger, J.D., Lee, K., Segre, G.V., and Efstratiadis, A., 2001. Roles of Growth Hormone and Insulin-like Growth Factor 1 in Mouse Postnatal Growth. Developmental Biology 229, 141-162.
51. Manley, J.L., Tacke, R., 1996. SR proteins and splicing control. Genes Dev. 10, 1569-1579.
52. Maures, T., Chan S.J., Xu B., Sun H., Ding, J. and Duan, C. (2002) Structural, biochemical, and expression analysis of two distinct Insulin-like growth factor 1 receptors and their ligands in zebrafish. Endocrinology 143(5), 1858-1871.
53. McRory, J.E. and Sherwood, N.M., 1994. J. Biol. Chem. 269, 18588-19592.
54. McRory, J.E., Sherwood, N.M., 1997. Ancient divergence of insulin and insulin-like growth factor. DNA Cell Biol. 16, 939-949.
55. Merchav, S., 1998. The haematopoietic effects of growth hormone and insulin-like growth factor-I. J Pediatr Endocrinol Metab 11, 677-85.
56. Morali, O.G., Jouneau, A., McLaughlin, K.J., Thiery, J.P. and Larue, L.: IGF-II promotes mesoderm formation. Dev Biol 227 (2000) 133-45.
57. Nagamatsu, S., Chan, S.J., Falkmer, S. and Steiner, D.F., 1991. J. Biol. Chem. 266, 2397-2402.
58. Nasevicius, A. and Ekker, S. C., 2000. Effective targeted gene 剬nockdown in zebrafish. Nat. Genetics 26: 216-220.
59. Nolten, L.A., Van Schaik, F.M.A., Steenbergh, P.H. and Sussenbach, J.S., 1994. Expression of the insulin- like growth factor I gene is stimulated by the liver-enriched transcription factor C/EBPa and LAP. Mol. Endocrinol. 8: 1636-1645.
60. Nolten, L.A., Steenbergh, P.H. and Sussenbach, J.S. 1995. Hepatocyte nuclear factor 1a activates promoter 1 of the human insulin- like growth factor I gene via two distinct binding sites. Mol. Endocrinol. 9: 1488-1499.
61. Nolten, L.A., Steenbergh, P.H. and Sussenbach, J.S. 1996. The hepatocyte nuclear factor 3b stimulates the transcription of the human insulin- like growth factor I gene in a direct and indirect manner. J. Biol. Chem. 271: 31846-31854.
62. Pedrini, M. T., Giorgino, F. and Smith, R. J. (1994) cDNA cloning of the rat IGF-I receptor: structural analysis of rat and human IGF-I and insulin receptors reveals differences in alternative splicing and receptor-specific domain conservation. Biochem Biophys Res Commun 202, 1038-1046.
63. Pietrzkowski, Z., Wernicke, D., Porcu, P., Jameson, B. A. and Baserga, R. 1992 Inhibition of Cellular Proliferation by Peptide Analogues of Insulin-like Growth Factor 1 Cancer Res 52, 6447-6451.
64. Plisetskaya, E. M. and Duan C., 1994. Insulin and insulin-like growth factor I in coho salmon Oncorynchus kisutch injected with streptozotocin. Am. J. Physiol. 267 (Regulatory Integrative Comp. Physiol. 36):R1408-R1412.
65. Roberts, C.T. Jr., Brown, A.L., Graham, D.E., Seelig, S., Berry, S., Gabbay, K.H., Rechler, M.M., 1986. Growth hormone regulates the abundance of insulin-like growth factor I RNA in adult rat liver. J. Biol. Chem. 261: 10025-10028.
66. Rotwein P., Pollock K.M., Didier D.K., Krivi G.G., 1986. Organization and sequence of the human insulin-like growth factor I gene. J. Biol. Chem. 261, 4828-4832
67. Rubin, R. and Baserga, R. 1995. Biology of Disease Insulin-Like Growth Factor-I Receptor: Its Role in Cell Proliferation, Apoptosis, and Tumorigenicity. Lab Invest 73(3), 311-331.
68. Salmon, W. D., Daughaday, W.H., 1957. A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med 49:825826.
69. Sambrook, J., Fritsch, E.F., Maniatis, T., 1989. Molecular cloning. A Laboratory Manual, 2nd ed. Cold Spring Harbor Laboratory, Cold Spring Harbor press, NY.
70. Schally, A. V. and Varga, J. L., 1999. Trends Endocrinol. Metab. 10:383-391.
71. Shamblott, M.J. and Chen, T.T., 1992. Proc. Natl. Acad. Sci. USA 89, 8913-8917.
72. Shamblott, M.J., Chen, T.T., 1993. Age-related and tissue-specific levels of five forms of insulin-like growth factor mRNA in a teleost. Mol. Mar. Biol. Biotechnol. 2, 351-361.
73. Shamblott, M.J., Cheng, C.M., Bolt, D. and Chen, T.T., 1995. Proc. Natl. Acad. Sci. USA 92, 6943-6946.
74. Shimatsu, A., Rotwein, P., 1987 Mosaic evolution of the insulin-like growth factors. J. Biol. Chem. 262: 7894-7900.
75. Shuldiner, A. R., Barbetti, F., Raben, N., Scavo, L. and Serrano, J. (1991) Insulin. in LeRoith D (ed): Insulin-Like Growth Factors: Molecular and Cellular Aspects. Boca Raton, CRC press. 181-219.
76. Siegfried, J.M., Kasprzyk, P.G., Treston, A.M., Mulshine, J.L., Quinn, K.A., Cuttitta, F., 1992. A mitogenic peptide amide encoded within the E peptide domain of the insulin-like gorwth factor IB prohormone. Proc. Natl. Acad. Sci. USA 89, 8107-8111.
77. Sjogren, K., Bohlooly, Y. M., Olsson, B., Coschigano, K., Tornell, J., Mohan, S., Isaksson, O. G., Baumann, G., Kopchick, J., and Ohlsson, C., 2000. Disproportional skeletal growth and markedly decreased bone mineral content in growth hormone receptor -/- mice. Biochem Biophys Res Commun 267, 603-608.
78. Smit, A.B., Vreugdenhil, E., Ebberink, R.H.M., Geraerts, W.P.M., Klootwijk, J., Joosse, J., 1988. Growth-controlling molluscan neurons produce the precursor of an insulin-related peptide. Nature 331, 535-538.
79. Sussenbach J.S., Steenbergh P.H., H?lthuizen P., 1992. Structure and expression of the human insulin-like growth factor genes. Growth Regulation 2, 1-9.
80. Tian, X.C., Chen, M.J., Pantschenko, A.G., Yang, T.J., Chen, T.T., 1999. Recombinant E-peptides of pro-IGF-1 have mitogenic activity. Endocrinology 140, 3387-3390.
81. Tsai, H.J., Chi, W.K., Chang, C.C., Kao, K.K. and Chang, C.F., 1993. Fish Soc. Taiwan 20, 271-277.
82. Ullrich, A., Gray, A., Tam, A. w., Yang-Feng, T., Tsubokawa, M., Collins, C., Henzel, W., Le Bon, T., Kathuria, S., Chen, E., Jacobs, S., Francke, U., Ramachandran, J. and Fujita-Yamaguchi, Y. 1986 Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests determinants that define functional specificity. EMBO J 5, 2503-2512
83. Wallis, A.E., Devlin, R.H., 1993. Duplicated insulin-like growth factor I genes in salmon display alternative splicing pathways. Mol. Endocrinol. 7, 409-422.
84. Westerfield, M., 1994. The zebrafish book: A guide for the laboratory use of zebrafish (Danio rerio), 2nd ed. University of Oregon press, Eugene.
85. Yakar, S., Liu, J. L., Stannard, B., Butler, A., Accili, D., Sauer, B., and LeRoith, D., 1999. Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc Natl Acad Sci U S A 96, 7324-7329.
86. Yayon, A., Klagsbrun, M., Esko, J.D., Leder, P. and Ornitz, D.M. 1991. Cell surface, Heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell 64, 841-848.
87. Zhou, Y., Xu, B. C., Maheshwari, H. G., He, L., Reed, M., Lozykowski, M., Okada, S., Cataldo, L., Coschigamo, K., Wagner, T. E., Baumann, G., and Kopchick, J. J., 1997. A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/ binding protein gene (the Laron mouse). Proc Natl Acad Sci U S A 94, 13215-13220.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
1. 洪正芳、詹志賢(1999).以戴明之管理原則-評估醫院全面品質管理實施的障礙.醫院,32(1),11-21。
2. 于克瑞、郭春花(1999).病房醫材管理改進方案.醫院,32(2),48-56。
3. 余嘉鵬(2000).高績效團隊應用於南部某一區域醫院水質檢驗室實例探討.醫院,33(2),56-59。
4. 洪正芳、王麗菁曹淑珍石錦鑾林宜怡(1999).全面品質管理對員工工作滿足感、組織認同感與組織管理原則認知之探討.醫院,32(4),41-53。
5. 洪正芳、王麗菁曹淑珍石錦鑾林宜怡(1999).全面品質管理對員工工作滿足感、組織認同感與組織管理原則認知之探討.醫院,32(4),41-53。
6. 洪正芳、王麗菁曹淑珍石錦鑾林宜怡(1999).全面品質管理對員工工作滿足感、組織認同感與組織管理原則認知之探討.醫院,32(4),41-53。
7. 周鴻儒、陳淑樺、蕭世榮、王蓉敏(2001).醫院員工之工作滿意度及組織承諾調查-以某家地區醫院為例.醫院,34(6),45-53。
8. 于克瑞、郭春花(1999).病房醫材管理改進方案.醫院,32(2),48-56。
9. 周鴻儒、陳淑樺、蕭世榮、王蓉敏(2001).醫院員工之工作滿意度及組織承諾調查-以某家地區醫院為例.醫院,34(6),45-53。
10. 余嘉鵬(2000).高績效團隊應用於南部某一區域醫院水質檢驗室實例探討.醫院,33(2),56-59。
11. 余嘉鵬(2000).高績效團隊應用於南部某一區域醫院水質檢驗室實例探討.醫院,33(2),56-59。
12. 吳淑惠、溫信財、何國章(1999).利用品管圈活動縮短現場掛號病歷調閱時間之研究.醫院,32(2),54-60。
13. 吳淑惠、溫信財、何國章(1999).利用品管圈活動縮短現場掛號病歷調閱時間之研究.醫院,32(2),54-60。
14. 吳淑惠、溫信財、何國章(1999).利用品管圈活動縮短現場掛號病歷調閱時間之研究.醫院,32(2),54-60。
15. 李惠齡、鍾國彪、陳慧敏、陳美華、林瑞明(2001).以品管圈活動降低健保抽樣送審資料不完整率.醫院,34(6),54-68。