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研究生:劉君恕
研究生(外文):Chinsu Liu
論文名稱:利用單株抗體研究膽道閉鎖病人肝臟膽小管及肝內膽管上皮細胞之抗原表現-探討與膽道閉鎖預後及病理機轉之關係
論文名稱(外文):Studies on the Expression of Antigens of Bile Canaliculi and Bile Ductule Epithelia of Livers in Biliary Atresia Using monoclonal Antibodies-Discussion of the Prognosis and Pathogenesis in Biliary Atresia
指導教授:邱仁輝邱仁輝引用關係魏拙夫魏拙夫引用關係
指導教授(外文):Jen-Hwey ChiuChoufu Wei
學位類別:博士
校院名稱:國立陽明大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:中文
論文頁數:102
中文關鍵詞:膽道閉鎖膽小管肝內膽管單株抗體aminopeptidase NFasFas ligand9B2
外文關鍵詞:biliary atresiabile canaliculusintrahepatic bile ductulemonoclonal antibodyaminopeptidase NFasFas ligand9B2
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膽道閉鎖(Biliary Atresia)是小兒外科領域中最令人困惑的一個疾病。在臨床上的表現為新生兒黃膽,直接型膽紅素升高,解灰白便,肝臟外膽管閉鎖。在1957年以前大家對此疾病仍是束手無策,直到日本外科醫師葛西氏(Kasai)發明葛西氏手術將肝外閉鎖之膽管切除到肝門處(Liver hilum),再以空腸套在肝門處以期待膽汁的排出,才開始有治療的一個希望。這四十年來由於對於此疾病之病因的探討研究,在病因學以及預後因子的了解有一些進步。在病因的研究上,有許多種假說,包括先天性肝內膽管發育畸型 (Congenital ductal plate malformation),病毒感染,自體免疫系統功能失調,肝動脈畸型等等,但是莫衷一是。在預後因子的研究上,包括接受手術的年齡,接受手術時肝臟肝門處膽管直徑大小及肝臟纖維化程度,肝臟細胞以及肝內膽管上皮細胞的炎性介質抗原的表現與否等等。在我們的研究中,我們希望能更進一步探討膽道閉鎖的病因以及預後因子。
大部份對於膽道閉鎖的研究都是著重於肝外膽管(Extrahepatic bile duct),少部份探討肝內膽管(Intrahepatic bile duct, ductule),很少有探討到膽小管(Bile canaliculus)的層次。我們了解肝臟細胞是一具有極性的上皮細胞,含有血管竇,基底側和膽小管三種功能團。利用抗人類肝細胞中膽小管功能團的單株抗體(9B2),以人類肝癌細胞株為模式發現分化良好的肝癌細胞株如:HepG2,HuH-7等可以在肝細胞之間形成膽小管的構造,但是在分化不良的細胞株如:HA22T/VGH,SK-HEP-1則無法形成。我們的研究假設人類胎兒肝臟中膽小管的發育應該是漸漸成熟,而不成熟的情況可能在某些膽道閉鎖的病患可以發現。而呈現不成熟膽小管發育的膽道閉鎖病患其致病原因可能含有先天性的問題,而非只有後天的問題。其他,膽小管發育成熟的膽道閉鎖可能是後天問題為主。
我們利用9B2單株抗體藉著免疫組織化學染色以及流式細胞計數法 (Flow cytometry) 在人類胎兒,早產兒,足月新生兒及兒童肝臟切片的檢驗,發現膽小管在足月新生兒的發育已漸趨完整,而32週大的早產兒仍發育較差,20週大的胎兒發育極不成熟。另外比較總膽管囊腫病患的膽小管抗原表現,可以發現阻塞性黃疸可以使9B2抗原表現增強。而在我們所研究的膽道閉鎖病患,有一部份的9B2抗原表現相當強,比足月新生兒高得多,有一部份病患的9B2抗原表現和足月新生兒強度相當,甚至有一小部份病患的9B2抗原表現強度與32週大的早產兒相近。有趣的是9B2抗原表現愈強的病患接受葛西氏手術失敗機率愈高。由這些結果我們認為做葛西氏手術前的9B2表現強弱可以預測肝外膽管阻塞的嚴重程度以及時間長短,除此之外表現9B2強度低於足月新生兒的病例其病因可能合併有先天性發育的問題。
此外,由於免疫功能失調可能是膽道閉鎖病因之一,而許多報告曾指出Fas-Fas ligand系統所造成的細胞計劃性死亡 (Apoptosis) 可以在許多肝臟疾病扮演肝細胞壞死的角色,而在動物實驗上也發現將肝外膽管紮住引起阻塞性黃疸可以誘發由Fas-Fas ligand系統所引起的肝細胞Apoptosis。所以我們將膽道閉鎖病患的肝臟切片作關於Fas,Fas ligand表現的研究。發現Fas ligand蛋白質以及訊息核醣核酸 (mRNA) 可以表現在某一部份的膽道閉鎖病患的肝內膽管上皮細胞,而這些病患的肝內膽管上皮細胞(Intrahepatic bile duct epithelium)有Apoptosis的現象,而且這些病患的浸潤淋巴球(Infiltrating lymphocytes)呈現Apoptosis的量也高於其他病患。更有趣的是這些肝內膽管上皮細胞有Fas ligand蛋白質及mRNA表現者,其手術預後在統計上,有顯著的高失敗率。此結果讓我們推論肝內膽管上皮細胞可能分泌Fas ligand來攻擊浸潤淋巴球而卻造成Autocrine或Paracrine suicide而破壞肝內膽管而使得手術後仍使肝內膽管持續破壞,Fas/Fas ligand系統可能不是起始病因,但可以反應免疫系統功能失調在膽道閉鎖病因中扮演一個相當重要的角色。比較9B2的表現可以發現那一小部份9B2表現強度與早產兒相近者,其肝內膽管上皮細胞都沒有表現FAS ligand蛋白質及mRNA,也沒有Apoptosis的情況。
從我們的研究中,我們認為膽道閉鎖可能合併多種病因,先天發育及後天免疫功能失調都可能為其中的原因之一。9B2抗原的表現強度和肝內膽管上皮是否分泌Fas ligand都可以作為術後成功與否的預後因子。
Biliary atresia (BA) is the most puzzled disease in the field of pediatric surgery. Clinical manifestations are neonatal jaundice, direct hyperbilirubinemia, passage of clay stool and obliteration of extrahepatic bile duct. This disease was incurable until Dr. Kasai, a Japanese surgeon, reported his portoenterostomy in 1957, which was the procedure of excision of extrahepatic fibrotic bile duct to liver hilum and roux-en-y portojejunostomy. During the past four decades, many investigations have been made to figure out the etiologies of BA and the predictors for post-Kasai outcome. There are many hypotheses about the etiology, including congenital ductal plate malformation, viral infection, immunological/inflammatory system disorder and defect in fetal/perinatal circulation. There are also many predictors for post-Kasai outcome, including age at Kasai operation, diameter of bile duct at hilum, severity of liver fibrosis and the presentation of some inflammatory mediators on hepatocytes and intrahepatic bile ductule epithelia. In this study, we try to further study the etiology and clinical predictors of BA.
Most studies on BA focused on the extrahepatic bile duct and intrahepatic bile duct and ductule, very few studies discussed about bile canaliculi, which is the most cephalic part of bile secretory apparatus. The hepatocyte is known as a polarized epithelial cell, composed of sinusoid, basolateral and bile canalicular domains. Previous studies used monoclonal antibodies (9B2), shown to react with the antigens on the bile canalicular domain of human hepatocytes, and the human hepatoma cell lines as in vitro model to study the biliary polarity of human hepatocytes. In Hep G2 and HuH-7, known as well differentiated hepatoma cell lines, the 9B2 antigen could be located on the bile canaliculus structure; whereas in HA22T/VGH and SK-HEP-1, known as poorly differentiated lines, no 9B2 antigen located on the bile canaliculus structure. In this study, we hypothesize the bile canaliculus of human fetal hepatocytes is progressively developed and the under-developed status could be found in some cases of BA. Congenital malformation could be one of the causative factors of BA in the cases with under-development of bile canaliculi while the postnatal insults should be responsible for the cases without under-development of bile canaliculi.
When comparing the expression of 9B2 antigens in the livers of 20-weeks fetuses, premature babies, term neonates and children by means of semiquantitative analysis of immunohistochemistry staining and quantitative analysis of flow cytometry, we find that bile canaliculi are well developed in term neonates, under-developed in premature babies and even less developed in 20 week fetuses. We also find the fact that obstructive jaundice rather than hepatitis will induce 9B2 antigen expression stronger by examining the livers of choledochal cysts and neonatal hepatitis. In the livers of BA patients, some cases have much stronger 9B2 expression than term neonates, some cases have about the same expressive intensity as term neonates but a few cases have the intensity as premature babies. We also find that the more intensive expression of 9B2 antigens, the higher failure rate of Kasai operation. Based on the results, we suggest the intensity of 9B2 expression in the pre-Kasai livers could reflect the severity and duration of extrahepatic obstruction before Kasai operation. In the cases showing premature development of bile canaliculi, congenital malformation may be a causative factor of BA.
The disorder of immunological system had been proposed to be one of the etiologies in BA. Many reports indicated that apoptosis induced by Fas/Fas ligand (FasL) system may play a role on various types of hepatitis and some animal studies indicated ligation of extrahepatic bile duct would cause hepatocytes apoptosis by Fas/FasL system. So, we question whether the Fas/FasL system is involved in the persistent liver damage of BA by examining the expression of FasL proteins and FasL mRNA on the livers of BA patients. We find that positive expression of FasL protein and mRNA is noted on some intrahepatic bile ductule epithelia in some BA patients. In these cases, apoptosis of intrahepatic bile ductule epithelia is noted and larger amount of apoptosis of infiltrating lymphocytes as compared with the cases without expression of FasL on bile ductule epithelia. We also note that the post-Kasai outcome in the cases with positive FasL expression had a significantly higher failure rate. This result suggests intrahepatic bile ductule epithelia could secret FasL to attack the infiltrating lymphocytes and result in apoptotic suicide/fratricide and these leads to persistent destruction of intrahepatic bile ductule after Kasai-operation. Although Fas/
FasL system should not be the initiating cause of BA, it may play a significant role in the pathogenesis of BA. Very interestingly, in the cases of BA with under- development of 9B2, there is neither expression of FasL on intrahepatic bile ductile epithelia nor the phenomenon of apoptosis.
From our study, we conclude that the etiology of BA is multiple and congenital malformation and post-natal disorder of immunological system may play a role in the pathogenesis. Both the expression intensity of 9B2 and FasL on bile ductule epithelia could serve as the prognostic factors of Kasai operation.
封面
中文摘要     
英文摘要
第一章 概論  
第二章 材料與方法  
第三章 肝臟APN表現與膽道閉鎖的關聯
第一節 人類胎兒到新生兒以及兒童其膽小管抗原的表現
第二節 膽道閉鎖病患, 新生兒肝炎病患以及兒童阻塞性黃疸病患的膽小管抗原的表現
第三節 圖及表
第四章 Fas以及Fas ligand系統與膽道閉鎖的關聯
第一節 Fas以及Fas ligand系統所引發的細胞凋亡在膽道閉鎖可能扮演的角色
第二節 預後因子和可能病因
第三節 圖及表
第五章 結語   
參考文獻
附錄
參考文獻
1. Kasai M, Suzuki A. A new operation for “non-correctable” biliary atresia: hepatic portoenterostomy. Shujyutsu 1959; 13:733-737.
2. Kasai M. Treatment of biliary atresia with special reference to hepatic porto-enterostomy and its modifications. Prog Pediatr Surg 1974; 6:5-52.
3. Balistreri WF, Grand R, Hoofnagle JH, Suchy FJ, Ryckman FC, Perlmutter DH, Sokol RJ. Biliary atresia: current concepts and research directions. Summary of a symposium. Hepatology 1996; 23:1682-1692.
4. Vazquez-Estevez J, Stewart B, Shikes R, Hall R, Lilly J. Biliary atresia: early determination of prognosis. J Pediatr Surg 1989; 24:48-50.
5. Tagge DU, Tagge EP, Drongowski RA, Oldham KT, Coran AG. A long-term experience with biliary atresia: Reassessment of prognostic factors. Ann Surg 1991; 214:590-598.
6. Suruga K, Miyano T, Kitahara T. Treatment of biliary atresia: a study of our operative results. J Pediatr Surg 1981; 16:621-626.
7. Suruga K, Miyano T, Arai T. A study of patients with long-term bile flow after hepatic portoenterostomy for biliary atresia. J Pediatr Surg 1985; 20:252-255.
8. Kojima Y. Clinical and histo-pathologic studies on congenital biliary atresia. Part I: Liver cell damage and prognosis. University of Juntendo Press 1981; 27:305.
9. Okasora T, Toyosaka A, Muraji T. The use of ultrasoonography in the diagnosis of biliary atresia. Pediatr Surg Int 1987; 2:231-234.
10. Vazquez-Estevez J, Stewart B, Shikes RH, Hall RJ, Lilly JR. Biliary atresia: early determination of prognosis. J Pediatr Surg 1989; 24:48-51.
11. Kasai M. The present status and problems in the treatment of biliary atresia. J Jpn Surg Soc 1986; 88:1401-1406.
12. Laurent J, Gauthier F, Bernard O, Hadchouel M, Odievre M, Valayer J, Alagille D. Long-term outcome after surgery for biliary atresia-study of 40 patients surviving for more than 10 years. Gastroenterology 1990; 99:1793-1797.
13. Altman RP, Lilly JR, Greenfeld J, Weinberg A. van Leeuwen K. Flanigan L. A multivariable risk factor analysis of the portoenterostomy (Kasai) procedure for biliary atresia: twenty-five years of experience from two centers. Ann Surg 1997; 226:348-353.
14. Matsuo S, Suita S, Kubota M, Shono K. Long-term results and clinical problems after portoenterostomy in patients with biliary atresia. Eur J Pediatr Surg 1998; 8:142-145.
15. Schweizer P, Lunzmann K. Extrahepatic bile duct atresia: how efficient is the hepatoporto-enterostomy? Eur J Pediatr Surg 1998; 8:150-154.
16. Davenport M, Kerkar N, Mieli-Vergani G, Mowat AP, Howard ER. Biliary atresia: the King’s College Hospital experience (1974-1995). J Pediatr Surg 1997; 32:479-485.
17. Azarow KS, Phillips MJ, Sandler AD, Hagerstrand I, Superina RA. Biliary atresia: should all patients undergo a portoenterostomy? J Pediatr Surg. 1997; 32:168-172.
18. Endo M, Masuyama H, Hirabayashi T, Ikawa H, Yokoyama J, Kitajima M. Effects of invaginating anastomosis in Kasai hepatic portoenterostomy on resolution of jaundice, and long-term outcome for patients with biliary atresia. J Pediatr Surg 1999; 34:415-419.
19. Nio M, Ohi R, Hayashi Y, Endo N, Ibrahim M, Iwami D. Current status of 21 patients who have survived more than 20 years since undergoing surgery for biliary atresia. J Pediatr Surg 1996; 31:381-384.
20. Mowat AP. Biliary atresia into the 21st century: a historical perspective. Hepatology. 1996; 23:1693-1695.
21. Oh M, Hobeldin M, Chen T, Thomas DW, Atkinson JB. The Kasai procedure in the treatment of biliary atresia. J Pediatr Surg 1995; 30:1077-1080.
22. Aronson DC, de Ville de Goyet J, Francois D, Otte JB. Primary management of biliary atresia: don’t change the rules. Br J Surg. 1995; 82:672-673.
23. Inomata Y, Oike F, Okamoto S, Uemoto S, Asonuma K, Egawa H, Kiuchi T, Okajima H, Tanaka K. Impact of the development of a liver transplant program on the treatment of biliary atresia in an institution in Japan. J Pediatr Surg 1997; 32:1201-1205.
24. Balistreri WF. Transplantation for childhood liver disease: an overview. Liver Transplant Surg 1998; 4:S18-23.
25. Uryuhara K, Egawa H, Uemoto S, Inomata Y, Asonuma K, Shapiro AM, Kiuchi T, Tanaka K. Application of living related auxiliary partial liver in an adult recipient with biliary atresia. J Am Coll Surgeons 1998; 187:562-564.
26. Losay J, Piot D, Bougaran J, Ozier Y, Devictor D, Houssin D, Bernard O. Early liver transplantation is crucial in children with liver disease and pulmonary artery hypertension. J Hepatol 1998; 28:337-342.
27. Van der Werf WJ, D’Alessandro AM, Knechtle SJ, Pilli G, Hoffmann RM, Judd RH, Odorico JS, Kirk AD, Rayhill SC, Sollinger HW, Kalayoglu M. Infant pediatric liver transplantation results equal those for older pediatric patients. J Pediatr Surg 1998; 33:20-23.
28. Maksoud JG, Fauza DO, Silva MM, Porta G, Miura I, Zerbini CN. Management of biliary atresia in the liver transplantation era: a 15-year, single-center experience. J Pediatr Surg 1998; 33:115-118.
29. Wayman KI, Cox KL, Esquivel CO. Neurodevelopmental outcome of young children with extrahepatic biliary atresia 1 year after liver transplantation. J Pediatr 1997; 131:894-898.
30. Hasegawa T, Fukui Y, Tanano H, Kobayashi T, Fukuzawa M, Okada A. Factors influencing the outcome of liver transplantation for biliary atresia. J Pediatr Surg 1997; 32:1548-1551.
31. Sandler AD, Azarow KS, Superina RA. The impact of a previous Kasai procedure on liver transplantation for biliary atresia. J Pediatr Surg 1997; 32:416-419.
32. Chardot C, Carton M, Spire-Bendelac N, Le Pommelet C, Golmard JL, Auvert B. Prognosis of biliary atresia in the era of liver transplantation: French national study from 1986 to 1996. Hepatology. 1999; 30:606-611.
33. Casas A, Falkenstein K, Gallagher M, Dunn SP. Living donor liver transplantation in critically ill children. Pediatr Transplant 1999; 3:104-108.
34. Ryckman FC, Alonso MH, Bucuvalas JC, Balistreri WF. Long-term survival after liver transplantation. J Pediatr Surg 1999; 34:845-849.
35. Gridelli B, Lucianetti A, Melada E, Colledan M, Paone G, Albani AP, Caccamo L, Nebbia G, Bracaloni D, Fassati LR. Pediatric liver transplantation: indications, risk factors, and results. Transplant Proc 1994; 26:3647-3648.
36. Tracy TF Jr, Dillon P, Fox ES, Minnick K, Vogler C. The inflammatory response in pediatric biliary disease: macrophage phenotype and distribution. J Pediatr Surg 1996; 31:121-126.
37. Ohya T, Fujimoto T, Shimomura H, Miyano T. Degeneration of intrahepatic bile duct with lymphocyte infiltration into biliary epithelial cells in biliary atresia. J Pediatr Surg 1995; 30:515-518.
38. Vasiliauskas EA, Targan SR, Cobb L, Vidrich A, Rosenthal P. Biliary atresia- an autoimmune mediated disorder? Hepatology 1995; 22:87A.
39. Broome U, Nemeth A, Hultcrantz R, Scheynius A. Different expression of HLA-DR and ICAM-1 in livers from patients with biliary atresia and Byler''s disease. J Hepatol 1997; 26:857-862.
40. Kobayashi H, Puri P, O''Briain DS, Surana R, Miyano T. Hepatic overexpression of MHC class II antigens and macrophage-associated antigens (CD68) in patients with biliary atresia of poor prognosis. J Pediatr Surg 1997; 32:590-593.
41. Petersen C, Biermanns D, Kuske M, Schakel K, Meyer-Junghanel L, Mildenberger H. New aspects in a murine model for extrahepatic biliary atresia. J Pediatr Surg 1997; 32:1190-1195.
42. Tamatani T, Kobayashi H, Tezuka K, Sakamoto S, Suzuki K, Nakanishi T, Takigawa M, Miyano T. Establishment of the enzyme-linked immunosorbent assay for connective tissue growth factor (CTGF) and its detection in the sera of biliary atresia. Biochem Bioph Res Co 1998; 251:748-752.
43. Bates MD, Bucuvalas JC, Alonso MH, Ryckman FC. Biliary atresia: pathogenesis and treatment. Semin Liver Dis 1998; 18:281-293.
44. Kobayashi H, Miyano T, Horikoshi K, Orihata K, Watanabe S, Futagawa S. Clinical significance of plasma endothelin levels in patients with biliary atresia. Pediatr Surg Int 1998; 13:491-493.
45. Petersen C, Kuske M, Bruns E, Biermanns D, Wussow PV, Mildenberger H. Progress in developing animal models for biliary atresia. Eur J Pediatr Surg 1998; 8:137-141.
46. Fischler B, Ehrnst A, Forsgren M, Orvell C, Nemeth A. The viral association of neonatal cholestasis in Sweden: a possible link between cytomegalovirus infection and extrahepatic biliary atresia. J Pediatr Gastroenterol Nutr 1998; 27:57-64.
47. Tyler KL, Sokol RJ, Oberhaus SM, Le M, Karrer FM, Narkewicz MR, Tyson RW, Murphy JR, Low R, Brown WR. Detection of reovirus RNA in hepatobiliary tissues from patients with extrahepatic biliary atresia and choledochal cysts. Hepatology. 1998; 27:1475-1482.
48. Desmet VJ. Ludwig symposium on biliary disorders--part I. Pathogenesis of ductal plate abnormalities. Mayo Clin Proc 1998; 73:80-89.
49. Bobo L, Ojeh C, Chiu D, Machado A, Colombani P, Schwarz K. Lack of evidence for rotavirus by polymerase chain reaction/enzyme immunoassay of hepatobiliary samples from children with biliary atresia. Pediatr Res 1997; 41:229-234.
50. Shneider BL, Fox VL, Schwarz KB, Watson CL, Ananthanarayanan M, Thevananther S, Christie DM, Hardikar W, Setchell KD, Mieli-Vergani G, Suchy FJ, Mowat AP. Hepatic basolateral sodium-dependent-bile acid transporter expression in two unusual cases of hypercholanemia and in extrahepatic biliary atresia. Hepatology 1997; 25:1176-1183.
51. Tanano H, Hasegawa T, Kawahara H, Sasaki T, Okada A. Biliary atresia associated with congenital structural anomalies. J Pediatr Surg 1999; 34:1687-1690.
52. Lamireau T, Le Bail B, Boussarie L, Fabre M, Vergnes P, Bernard O, Gautier F, Bioulac-Sage P, Rosenbaum J. Expression of collagens type I and IV, osteonectin and transforming growth factor beta-1 (TGFbeta1) in biliary atresia and paucity of intrahepatic bile ducts during infancy. J Hepatol 1999; 31:248-255.
53. Jevon GP, Dimmick JE. Biliary atresia and cytomegalovirus infection: a DNA study. Pediatr Devel Pathol 1999; 2:11-14.
54. Funaki N, Sasano H, Shizawa S, Nio M, Iwami D, Ohi R, Nagura H. Apoptosis and cell proliferation in biliary atresia. J Pathol. 1998; 186:429-433.
55. Drut R, Drut RM, Gomez MA, Cueto Rua E, Lojo MM. Presence of human papillomavirus in extrahepatic biliary atresia. J Pediatr Gastroenterol Nutr 1998; 27:530-535.
56. Rosenthal P. The association of reovirus 3 and biliary atresia: finally resolved?. Am J Gastroenterol 1995; 90:1895-1896.
57. Tan CE, Davenport M, Driver M, Howard ER. Does the morphology of the extrahepatic biliary remnants in biliary atresia influence survival? A review of 205 cases. J Pediatr Surg 1994; 29:1459-1464.
58. Tan CE, Moscoso GJ. The developing human biliary system at the porta hepatis level between 29 days and 8 weeks of gestation: a way to understanding biliary atresia. Part 1. Pathol Int 1994; 44:587-599.
59. Tan CE, Moscoso GJ. The developing human biliary system at the porta hepatis level between 11 and 25 weeks of gestation: a way to understanding biliary atresia. Part 2. Pathol Int 1994; 44:600-610.
60. Wilson GA, Morrison LA, Fields BN. Association of the reovirus S1 gene with serotype 3-induced biliary atresia in mice. J Virol 1994; 68:6458-6465.
61. Liu CS, Chin TW, Wei CF. Value of gamma-glutamyl transpeptidase for early diagnosis of biliary atresia. Chin Med J (Taipei) 1998; 61:716-720.
62. Endo M, Masuyama H, Watanabe K, Hagane K, Ikawa H, Yokoyama J, Kitajima M. Calculation of biliary atresia prognostic index using a multivariate linear model. J Pediatr Surg 1995; 30:1575-1579.
63. Muraji T, Higashimoto Y. The improved outlook for biliary atresia with corticosteroid therapy. J Pediatr Surg 1997; 32:1103-6.
64. Ramm GA, Nair VG, Bridle KR, Shepherd RW, Crawford DH. Contribution of hepatic parenchymal and nonparenchymal cells to hepatic fibrogenesis in biliary atresia. American J Pathol 1998; 153:527-535.
65. Minnick KE, Kreisberg R, Dillon PW. Soluble ICAM-1 (sICAM-1) in biliary atresia and its relationship to disease activity. J Surg Res 1998; 76:53-56.
66. Kobayashi H, Puri P, O''Briain DS, Surana R, Miyano T. Hepatic overexpression of MHC class II antigens and macrophage-associated antigens (CD68) in patients with biliary atresia of poor prognosis. J Pediatr Surg 1997; 32:590-593.
67. Kobayashi H, Miyano T, Horikoshi K, Tokita A. Prognostic value of serum procollagen III peptide and type IV collagen in patients with biliary atresia. J Pediatr Surg 1998; 33:112-114.
68. Kobayashi H, Horikoshi K, Yamataka A, Yamataka T, Okazaki T, Lane GJ, Miyano T. Hyaluronic acid: a specific prognostic indicator of hepatic damage in biliary atresia. J Pediatr Surg 1999; 34:1791-1794.
69. Kinugasa Y, Nakashima Y, Matsuo S, Shono K, Suita S, Sueishi K. Bile ductular proliferation as a prognostic factor in biliary atresia: an immunohistochemical assessment. J Pediatr Surg 1999; 34:1715-1720.
70. Kardorff R, Klotz M, Melter M, Rodeck B, Hoyer PF. Prediction of survival in extrahepatic biliary atresia by hepatic duplex sonography. J Pediatr Gastroenterol Nutr 1999; 28:411-417.
71. Kobayashi H, Narumi S, Tamatani T, Lane GJ, Miyano T. Serum IFN-inducible protein-10: a new clinical prognostic predictor of hepatocyte death in biliary atresia. J Pediatr Surg 1999; 34:308-311.
72. Kawahara H, Kamata S, Okada A, Hasegawa T, Wasa M, Fukui Y. The importance of the plasma amino acid molar ratio in patients with biliary atresia. Surgery. 1999; 125:487-497.
73. Hossain M, Murahashi O, Ando H, Iio K, Kaneko K, Ito T. Immunohistochemical study of proliferating cell nuclear antigen in hepatocytes of biliary atresia: a parameter to predict clinical outcome. J Pediatr Surg 1995; 30:1297-1301.
74. Fujimoto T, Ohya T, Miyano T. A new clinical prognostic predictor for patients with biliary atresia. J Pediatr Surg 1994; 29:757-760.
75. Park WH, Kim SP, Park KK, Choi SO, Lee HJ, Kwon KY. Electron microscopic study of the liver with biliary atresia and neonatal hepatitis. J Pediatr Surg 1996; 31:367-374.
76. Segawa O, Miyano T, Fujimoto T, Watanabe S, Hirose M, Fujiwara T. Actin and myosin deposition around bile canaliculi: a predictor of clinical outcome in biliary atresia. J Pediatr Surg 1993; 28:851-856.
77. Biava CG. Studies on cholestasis: a re-evaluation of the fine structure of normal human bile canaliculi. Lab Invest 1964; 12: 840-848.
78. Steiner JW, Carruthers JS. Studies on the fine structure of the terminal branches of the biliary tree. I. The morphology of normal bile canaliculi, bile preductules (ducts of Hering) and bile ductules. Am J Pathol 1961; 38:639-645.
79. Steiner JW, Canuthers JS. Studies on the fine structure of the terminal branches of the biliary tree. II. Observations of pathologically altered bile canaliculi. Am J Pathol 1961; 39: 41-50.
80. Oda M, Price VM, Fisher MM, Phillips MJ. Ultrastructure of bile canaliculi, with special reference to the surface coat and the pericanalicular web. Lab Invest 1974; 31:314-323.
81. Arias IM, Che M, Gatmaitan Z, Leveille C, Nishida T, St. Pierre M. The biology of the bile canaliculus, 1993. Hepatology. 1993; 17:318-329.
82. Hu CP, Han SH, Lui WY, Hsu HC, Lin YM, Lin PH, Chen LR, Hsieh HG, Kuo PT, P’eng FK. Monoclonal antibodies against antigens expressed on human hepatocellular carcinoma cells. Hepatology 1986; 6:1396-1402.
83. Lin YM, Hu CP, Chou CK, O-Lee TW, Wu KT, Chen TY, P’eng FK, Liu TJ, Ko JL, Chang CM. A new human hepatoma cell line: establishment and characterization. Chin J Microbiol Immunol. 1982; 15:193-201.
84. Chiu JH, Hu CP, Lui WY, Lo SC, Chang CM. The formation of bile canaliculi in human hepatoma cell lines. Hepatology 1990; 11:834-842.
85. Chiu JH, Hu CP, Lui WY, Chang HM, Chang C. Different processing of bile canalicuiar antigen in well and poorly differentiated human hepatoma cell lines. J.Gastroenterol. Hepatol 1993; 8: 59-66.
86. Lian WN, Tsai JW, Yu PM, Wu TW, Yang SC, Chau YP, Lin CH. Targeting of aminopeptidase N to bile canaliculi correlates with secretory activities of the developing canalicular domain. Hepatology 1999; 30:748-760.
87. Moore KL. The digestive system. In: Moore KL, ed. The Developing Human, clinically oriented embryology. 3rd ed. Philadelphia: Saunders, 1982.Pp. 227-254.
88. Langman J. Digestive tube and its derivatives. In: Langman J, ed. Medical Embryology. 3rd ed. Baltimore: Williams and Wilkins, 1975.Pp. 258-302.
89. Rapoport B. Pathophysiology of Hashimoto''s thyroiditis and hypothyroidism. Ann Rev Med 1991; 42:91-96.
90. Kotani T, Aratake Y, Hirai K, Fukazawa Y, Sato H, Ohtaki S. Apoptosis in thyroid tissue from patients with Hashimoto’s thyroiditis. Autoimmunity 1995; 20:231-236.
91. Mitsiades N, Poulaki V, Kotoula V, Mastorakos G, Tseleni-Balafouta S, Koutras DA, Tsokos M. Fas/Fas ligand up-regulation and Bcl-2 down-regulation may be significant in the pathogenesis of Hashimoto’s thyroiditis. J Clin Endocrinol Metab 1998; 83:2199-2203.
92. Giordano C, Stassi G, De Maria R, Todaro M, Richiusa P, Papoff G, Ruberti G, Bagnasco M, Testi R, Galluzzo A. Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto''s thyroiditis. Science 1997; 275:960-963.
93. Leithauser F, Dhein J, Mechtersheimer G, Koretz K, Bruderlein S, Henne C, Schmidt A, Debatin KM, Krammer PH, Moller P. Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells. Lab Invest 1993; 69:415-429.
94. Rouvier E, Luciani MF, Golstein P. Fas involvement in Ca 2+-independent T cell-mediated cytotoxicity. J Exp Med 1993; 177:195-200.
95. Hanabuchi S, Koyanagi M, Kawasaki A, Shinohara N, Matsuzawa A, Nishimura Y, Kobayashi Y, Yonehara S, Yagita H, Okumura K. Fas and its ligand in a general mechanism of T-cell-mediated cytotoxicity. Proc Natl Acad Sci USA 1994; 91:4930-4934.
96. Kojima H, Shinohara N, Hanaoka S, Someya-Shirota Y, Takagaki Y, Ohno H, Saito T, Katayama T, Yagita H, Okumura K. Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes. Immunity 1994; 1:357-364.
97. Lowin B, Hahne M, Mattmann C, Tschopp J. Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature 1994; 370:650-652.
98. Mita E, Hayashi N, Iio S, Takehara T, Hijioka T, Kasahara A, Fusamoto H, Kamada T. Role of Fas ligand in apoptosis induced by hepatitis C virus infection. Biochem Bioph Res Co 1994; 204:468-474.
99. Yonehara S, Ishii A, Yonehara M. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med 1989; 169:1747-1756.
100. Arase H, Arase N, Saito T. Fas-mediated cytotoxicity by freshly isolated natural killer cells. J Exp Med 1995; 181:1235-1238.
101. Galle PR, Hofmann WJ, Walczak H, Schaller H, Otto G, Stremmel W, Krammer PH, Runkel L. Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage. J Exp Med 1995; 182:1223-1230.
102. Kondo T, Suda T, Fukuyama H, Adachi M, Nagata S. Essential roles of the Fas ligand in the development of hepatitis. Nat Med 1997; 3:409-413.Kondo T, Suda T, Fukuyama H, Adachi M, Nagata S. Essential roles of the Fas ligand in the development of hepatitis. Nat Med 1997; 3:409-413.
103. Ergaz Z, Arad I. Hyperbilirubinemia in premature infants: relevance to blood transfusion. Biol Neonate 1994; 66:71-76.
104. Ullrich D, Fevery J, Sieg A, Tischler T, Bircher J. The influence of gestational age on bilirubin conjugation in newborns. Eur J Clin Invest 1991; 21:83-89.
105. Vlahcevic ZR, Miller JR, Farrar JT, Swell L. Kinetics and pool size of primary bile acids in man. Gastroenterology 1971; 61: 85-89.
106. Watkins JB, Ingall D, Szczepanik P, Klein P, Lester R. Bile-salt metabolism in the newborn. Measurement of pool size and synthesis rate by stable isotope technic. N Engl J Med 1973; 288:431-432.
107. Watkins JB, Szczepanik P, Gould JB, Klein P, Lester R. Bile salt metabolism in the human premature infant. Preliminary observations of pool size and synthesis rate following prenatal administration of dexamethasone and phenobarbital. Gastroenterology 1975; 69: 706-709.
108. Hollander M, Schaffner F. Electron microscopic studies in biliary atresia: I. Bile ductular proliferation. Am J Dis Child 1968; 116:49-56.
109. Hollander M, Schaffner F. Electron microscopic studies in biliary atresia: II. Hepatocellular alternations. Am J Dis Child 1968; 116:57-65.
110. Landing BH, Wells TR, Reed GB. Consideration of the pathogenesis of neonatal hepatitis, biliary atresia and choledochal cyst-The concept of infantile obstructive cholangiopathy. Prog Pediatr Surg 1974; 6:113-139.
111. O’Connell J, O’Sullivan GC, Collins JK. The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. J Exp Med 1996; 184:1075-1082.
112. Miyoshi H, Rust C, Roberts PJ, Burgart LJ, Gregory JG. Hepatocyte apoptosis after bile duct ligation in the mouse involves Fas. Gastroenterology 1999; 117:669-675.
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