Dr. Hajime  Higuchi
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Dr. Hajime Higuchi

Professor
International University of Health and Welfare, Japan


Highest Degree
PostDoc Fellow in Medicine from Mayo Clinic Graduate School, USA

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Area of Interest:

Medicine
100%
Immunology
62%
Physiology
90%
Hepatology
75%
Gastroenterology
55%

Research Publications in Numbers

Books
0
Chapters
0
Articles
0
Abstracts
0

Selected Publications

  1. Suzuki, K., H. Higuchi, S. Shimizu, M. Nakano, H. Serizawa and S. Morinaga, 2015. Endoscopic snare papillectomy for a solitary Peutz-Jeghers-type polyp in the duodenum with ingrowth into the common bile duct: Case report. World J. Gastroenterol., 21: 8215-8220.
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  2. Soma, H., N. Miyata, S. Hozawa, H. Higuchi and Y. Yamagishi et al., 2015. Ampullary adenoma treated by endoscopic double-snare retracting papillectomy. Gut Liver, 9: 689-692.
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  3. Mayanagi, S., M. Kitago, T. Sakurai, T. Matsuda and T. Fujita et al., 2015. Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer. Cancer Sci., 106: 397-406.
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  4. Sugimoto, S., Y. Yamagishi, H. Higuchi and T. Kanai, 2014. Endoscopic ultrasound-guided drainage for a mediastinal pancreatic pseudocyst. Internal Med., 53: 2651-2652.
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  5. Nakamura, S., T. Yaguchi, N. Kawamura, A. Kobayashi and T. Sakurai et al., 2014. TGF-β1 in tumor microenvironments induces immunosuppression in the tumors and sentinel lymph nodes and promotes tumor progression. J. Immunother., 37: 63-72.
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  6. Nakamura, Y., T. Kanai, K. Saeki, M. Takabe and J. Irie et al., 2013. CCR2 knockout exacerbates cerulein-induced chronic pancreatitis with hyperglycemia via decreased GLP-1 receptor expression and insulin secretion. Am. J. Physiol.-Gastrointest. Liver Physiol., 304: G700-G707.
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  7. Matsuzaki, J., H. Suzuki, S. Okuda, A. Tanimoto and K. Asakura et al., 2013. Biliary findings assist in predicting enlargement of intraductal papillary mucinous neoplasms of the pancreas. Clin. Gastroenterol. Hepatol., 11: 548-554.
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  8. Kabashima-Niibe, A., H. Higuchi, H. Takaishi, Y. Masugi and Y. Matsuzaki et al., 2013. Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor progression of pancreatic cancer cells. Cancer Sci., 104: 157-164.
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  9. Funakoshi, S., A. Hashiguchi, K. Teramoto, N. Miyata and S. Kurita et al., 2013. Second-line chemotherapy for refractory small cell neuroendocrine carcinoma of the esophagus that relapsed after complete remission with irinotecan plus cisplatin therapy: Case report and review of the literature. Oncol. Lett., 5: 117-122.
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  10. Chang, J., T. Hisamatsu, K. Shimamura, K. Yoneno and M. Adachi et al., 2013. Activated hepatic stellate cells mediate the differentiation of macrophages. Hepatol. Res., 43: 658-669.
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  11. Akagi, H., H. Higuchi, H. Sumimoto, T. Igarashi and A. Kabashima et al., 2013. Suppression of myeloid cell leukemia-1 (Mcl-1) enhances chemotherapy-associated apoptosis in gastric cancer cells. Gastric Cancer, 16: 100-110.
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  12. Sakai, G., T. Yajima, H. Takaishi, T. Mori and H. Higuchi et al., 2012. Colon neoplastic cells do not originate from bone marrow-derived cells after sex-mismatched bone marrow transplantation. Anticancer Res., 32: 4097-4103.
    Direct Link  |  
  13. Miyoshi, J., T. Yajima, K. Shimamura, K. Matsuoka and S. Okamoto et al., 2012. 5-aminosalicylic acid mediates expression of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase to suppress colorectal tumorigenesis. Anticancer Res., 32: 1193-1202.
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  14. Miyata, N., T. Azuma, S. Hozawa, H. Higuchi and A. Yokoyama et al., 2012. Transforming growth factor β and Ras/MEK/ERK signaling regulate the expression level of a novel tumor suppressor Lefty. Pancreas, 41: 745-752.
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  15. Izumiya, M., A. Kabashima, H. Higuchi, T. Igarashi and G. Sakai et al., 2012. Chemoresistance is associated with cancer stem cell-like properties and epithelial-to-mesenchymal transition in pancreatic cancer cells. Anticancer Res., 32: 3847-3853.
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  16. Ichikawa, R., T. Takayama, K. Yoneno, N. Kamada and M.T. Kitazume et al., 2012. Bile acids induce monocyte differentiation toward interleukin-12 hypo-producing dendritic cells via a TGR5-dependent pathway. Immunology, 136: 153-162.
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  17. Yamagishi, Y., H. Higuchi, M. Izumiya, G. Sakai and H. Iizuka et al., 2010. Gemcitabine as first-line chemotherapy in elderly patients with unresectable pancreatic carcinoma. J. Gastroenterol., 45: 1146-1154.
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  18. Kurita, S., H. Higuchi, Y. Saito, N. Nakamoto and H. Takaishi et al., 2010. DNMT1 and DNMT3b silencing sensitizes human hepatoma cells to TRAIL-mediated apoptosis via up-regulation of TRAIL‐R2/DR5 and caspase-8. Cancer Sci., 101: 1431-1439.
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  19. Kabashima, A., H. Higuchi, H. Takaishi, Y. Matsuzaki and S. Suzuki et al., 2009. Side population of pancreatic cancer cells predominates in TGF-β-mediated epithelial to mesenchymal transition and invasion. Int. J. Cancer, 124: 2771-2779.
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  20. Takaishi, H., T. Matsuki, A. Nakazawa, T. Takada and S. Kado et al., 2008. Imbalance in intestinal microflora constitution could be involved in the pathogenesis of inflammatory bowel disease. Int. J. Med. Microbiol., 298: 463-472.
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  21. Iwai, H., T. Hisamatsu, H. Iizuka, T. Oyama and H. Higuchi et al., 2007. Microscopic colitis with granuloma which responded to steroid therapy. Internal Med., 46: 1551-1555.
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  22. Nakamoto, N., H. Higuchi, H. Kanamori, S. Kurita and S. Tada et al., 2006. Cyclooxygenase-2 inhibitor and interferon-β synergistically induce apoptosis in human hepatoma cells in vitro and in vivo. Int. J. Oncol., 29: 625-635.
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  23. Taniai, M., A. Grambihler, H. Higuchi, N. Werneburg and S.F. Bronk et al., 2004. Mcl-1 mediates tumor necrosis factor-related apoptosis-inducing ligand resistance in human cholangiocarcinoma cells. Cancer Res., 64: 3517-3524.
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  24. Higuchi, H., A. Grambihler, A. Canbay, S.F. Bronk and G.J. Gores, 2004. Bile acids up-regulate death receptor 5/TRAIL-receptor 2 expression via a c-Jun N-terminal kinase-dependent pathway involving Sp1. J. Biol. Chem., 279: 51-60.
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  25. Adachi, M., H. Higuchi, S. Miura, T. Azuma and S. Inokuchi et al., 2004. Bax interacts with the voltage-dependent anion channel and mediates ethanol-induced apoptosis in rat hepatocytes. Am. J. Physiol.-Gastrointest. Liver Physiol., 287: G695-G705.
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  26. Werneburg, N.W., J.H. Yoon, H. Higuchi and G.J. Gores, 2003. Bile acids activate EGF receptor via a TGF-α-dependent mechanism in human cholangiocyte cell lines. Am. J. Physiol.-Gastrointest. Liver Physiol., 285: G31-G36.
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  27. Taimr, P., H. Higuchi, E. Kocova, R.A. Rippe, S. Friedman and G.J. Gores, 2003. Activated stellate cells express the TRAIL receptor-2/death receptor-5 and undergo TRAIL-mediated apoptosis. Hepatology, 37: 87-95.
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  28. Natori, S., H. Higuchi, P. Contreras and G.J. Gores, 2003. The caspase inhibitor IDN-6556 prevents caspase activation and apoptosis in sinusoidal endothelial cells during liver preservation injury. Liver Transplant., 9: 278-284.
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  29. Janssen, H.L., H. Higuchi, A. Abdulkarim and G.J. Gores, 2003. Hepatitis B virus enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) cytotoxicity by increasing TRAIL-R1/death receptor 4 expression. J. Hepatol., 39: 414-420.
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  30. Higuchi, H., J.H. Yoon, A. Grambihler, N. Werneburg, S.F. Bronk and G.J. Gores, 2003. Bile acids stimulate cFLIP phosphorylation enhancing TRAIL-mediated apoptosis. J. Biol. Chem., 278: 454-461.
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  31. Higuchi, H. and G.J. Gores, 2003. Mechanisms of liver injury: An overview. Curr. Mol. Med., 3: 483-490.
    CrossRef  |  PubMed  |  Direct Link  |  
  32. Higuchi, H. and G.J. Gores, 2003. Bile acid regulation of hepatic physiology: IV. Bile acids and death receptors. Am. J. Physiol.-Gastrointest. Liver Physiol., 284: G734-G738.
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  33. Grambihler, A., H. Higuchi, S.F. Bronk and G.J. Gores, 2003. cFLIP-L inhibits p38 MAPK activation: An additional anti-apoptotic mechanism in bile acid-mediated apoptosis. J. Biol. Chem., 278: 26831-26837.
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  34. Feldstein, A.E., A. Canbay, M.E. Guicciardi, H. Higuchi, S.F. Bronk and G.J. Gores, 2003. Diet associated hepatic steatosis sensitizes to Fas mediated liver injury in mice. J. Hepatol., 39: 978-983.
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  35. Canbay, A., P. Taimr, N. Torok, H. Higuchi, S. Friedman and G.J. Gores, 2003. Apoptotic body engulfment by a human stellate cell line is profibrogenic. Lab. Invest., 83: 655-663.
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  36. Canbay, A., M.E. Guicciardi, H. Higuchi, A. Feldstein and S.F. Bronk et al., 2003. Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis. J. Clin. Invest., 112: 152-159.
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  37. Canbay, A., A.E. Feldstein, H. Higuchi, N. Werneburg, A. Grambihler, S.F. Bronk and G.J. Gores, 2003. Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine expression. Hepatology, 38: 1188-1198.
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  38. Yoon, J.H., N.W. Werneburg, H. Higuchi, A.E. Canbay and S.H. Kaufmann et al., 2002. Bile acids inhibit Mcl-1 protein turnover via an epidermal growth factor receptor/Raf-1-dependent mechanism. Cancer Res., 62: 6500-6505.
    Direct Link  |  
  39. Yoon, J.H., H. Higuchi, N.W. Werneburg, S.H. Kaufmann and G.J. Gores, 2002. Bile acids induce cyclooxygenase-2 expression via the epidermal growth factor receptor in a human cholangiocarcinoma cell line. Gastroenterology, 122: 985-993.
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  40. Torok, N.J., H. Higuchi, S. Bronk and G.J. Gores, 2002. Nitric oxide inhibits apoptosis downstream of cytochrome C release by nitrosylating caspase 9. Cancer Res., 62: 1648-1653.
    Direct Link  |  
  41. Taniai, M., H. Higuchi, L.J. Burgart and G.J. Gores, 2002. p16INK4a promoter mutations are frequent in Primary Sclerosing Cholangitis (PSC) and PSC-associated cholangiocarcinoma. Gastroenterology, 123: 1090-1098.
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  42. Takeuchi, T., S. Miura, L. Wang, K. Uehara and M. Mizumori et al., 2002. Nuclear factor-κB and TNF-α mediate gastric ulceration induced by phorbol myristate acetate. Dig Dis. Sci., 47: 2070-2078.
    CrossRef  |  PubMed  |  Direct Link  |  
  43. Kishikawa, H., S. Miura, H. Yoshida, M. Hirokawa and H. Nakamizo et al., 2002. Transmural pressure induces IL-6 secretion by intestinal epithelial cells. Clin. Exp. Immunol., 129: 86-91.
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  44. Higuchi, H., S.F. Bronk, M. Taniai, A. Canbay and G.J. Gores, 2002. Cholestasis increases tumor necrosis factor-related apoptotis-inducing ligand (TRAIL)-R2/DR5 expression and sensitizes the liver to TRAIL-mediated cytotoxicity. J. Pharmacol. Exp. Therapeut., 303: 461-467.
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  45. Canbay, A., H. Higuchi, S.F. Bronk, M. Taniai, T.J. Sebo and G.J. Gores, 2002. Fas enhances fibrogenesis in the bile duct ligated mouse: A link between apoptosis and fibrosis. Gastroenterology, 123: 1323-1330.
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  46. Hirokawa, M., S. Miura, H. Kishikawa, H. Yoshida and H. Nakamizo et al., 2001. Loading of mechanical pressure activates mitogen-activated protein kinase and early immediate gene in intestinal epithelial cells. Dig. Dis. Sci., 46: 1993-2003.
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  47. Higuchi, H., S.F. Bronk, Y. Takikawa, N. Werneburg, R. Takimoto, W. El-Deiry and G.J. Gores, 2001. The bile acid glycochenodeoxycholate induces trail-receptor 2/DR5 expression and apoptosis. J. Biol. Chem., 276: 38610-38618.
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  48. Higuchi, H., M. Adachi, S. Miura, G.J. Gores and H. Ishii, 2001. The mitochondrial permeability transition contributes to acute ethanol-induced apoptosis in rat hepatocytes. Hepatology, 34: 320-328.
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  49. Higuchi, H., H. Miyoshi, S.F. Bronk, H. Zhang, N. Dean and G.J. Gores, 2001. Bid antisense attenuates bile acid-induced apoptosis and cholestatic liver injury. J. Pharmacol. Exp. Therapeut., 299: 866-873.
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  50. Han, J.Y., S. Miura, Y. Akiba, H. Higuchi and S. Kato et al., 2001. Chronic ethanol consumption exacerbates microcirculatory damage in rat mesentery after reperfusion. Am. J. Physiol.-Gastrointest. Liver Physiol., 280: G939-G948.
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  51. Higuchi, H., S.F. Bronk, A. Bateman, K. Harrington, R.G. Vile and G.J. Gores, 2000. Viral fusogenic membrane glycoprotein expression causes syncytia formation with bioenergetic cell death: Implications for gene therapy. Cancer Res., 60: 6396-6402.
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  52. Sakaguchi, A.A., S. Miura, T. Takeuchi, R. Hokari and M. Mizumori et al., 1999. Increased expression of inducible nitric oxide synthase and peroxynitrite in Helicobacter pylori gastric ulcer. Free Radic. Biol. Med., 27: 781-789.
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  53. Hokari, R., S. Miura, H. Fujimori, S. Koseki and Y. Tsuzuki et al., 1999. Altered migration of gut-derived T lymphocytes after activation with concanavalin A. Am. J. Physiol.-Gastrointest. Liver Physiol., 277: G763-G772.
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  54. Higuchi, H., D.N. Granger, H. Saito and I. Kurose, 1999. Assay of antioxidant and antiinflammatory activity of nitric oxide in vivo. Methods Enzymol., 301: 424-436.
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  55. Shigematsu, T., S. Miura, M. Hirokawa, R. Hokari and H. Higuchi et al., 1998. Induction of endothelin-1 synthesis by IL-2 and its modulation of rat intestinal epithelial cell growth. Am. J. Physiol.-Gastrointest. Liver Physiol., 275: G556-G563.
    CrossRef  |  Direct Link  |  
  56. Shigematsu, T., S. Miura, M. Hirokawa, R. Hokari and H. Higuchi et al., 1998. Endothelins promote egg albumin-induced intestinal anaphylaxis in rats. Gastroenterology, 115: 348-356.
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  57. Kimura, H., R. Hokari, S. Miura, T. Shigematsu and M. Hirokawa et al., 1998. Increased expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in colonic mucosa of patients with active ulcerative colitis. Gut, 42: 180-187.
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  58. Hokari, R., S. Miura, H. Fujimori, Y. Tsuzuki and T. Shigematsu et al., 1998. Nitric oxide modulates T-lymphocyte migration in Peyer's patches and villous submucosa of rat small intestine. Gastroenterology, 115: 618-627.
    CrossRef  |  Direct Link  |  
  59. Hirokawa, M., S. Miura, H. Yoshida, I. Kurose and T. Shigematsu et al., 1998. Oxidative stress and mitochondrial damage precedes gastric mucosal cell death induced by ethanol administration. Alcoh. Clin. Exp. Res., 22: 111S-114S.
    PubMed  |  
  60. Tsuzuki, Y., S. Miura, I. Kurose, M. Suematsu and H. Higuchi et al., 1997. Enhanced lymphocyte interaction in postcapillary venules of Peyer's patches during fat absorption in rats. Gastroenterology, 112: 813-825.
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  61. Miura, S., H. Serizawa, Y. Tsuzuki, I. Kurose and M. Suematsu et al., 1997. Vasoactive intestinal peptide modulates T lymphocyte migration in Peyer's patches of rat small intestine. Am. J. Physiol.-Gastrointest. Liver Physiol., 272: G92-G99.
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  62. Kimura, H., S. Miura, T. Shigematsu, N. Ohkubo and Y. Tsuzuki et al., 1997. Increased nitric oxide production and inducible nitric oxide synthase activity in colonic mucosa of patients with active ulcerative colitis and Crohn's disease. Digestive Dis. Sci., 42: 1047-1054.
    CrossRef  |  
  63. Hirokawa, M., S. Miura, T. Shigematsu, H. Yoshida and R. Hokari et al., 1997. Pressure stimulates proliferation and DNA synthesis in rat intestinal epithelial cells. Life Sci., 61: 667-672.
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  64. Higuchi, H., I. Kurose, D. Fukumura, H.J. Yan and H. Saito et al., 1997. Active oxidants mediate IFN-alpha-induced microvascular alterations in rat mesentery. J. Immunol., 158: 4893-4900.
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  65. Tsuzuki, Y., S. Miura, M. Suematsu, I. Kurose and T. Shigematsu et al., 1996. α4 integrin plays a critical role in early stages of T lymphocyte migration in Peyer's patches of rats. Int. Immunol., 8: 287-295.
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  66. Saito, H., I. Kurose, H. Ebinuma, D. Fukumura and H. Higuchi et al., 1996. Kupffer cell-mediated cytotoxicity against hepatoma cells occurs through production of nitric oxide and adhesion via ICAM-1/CD18. Int. Immunol., 8: 1165-1172.
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  67. Miura, S., Y. Tsuzuki, I. Kurose, M. Suematsu and T. Shigematsu et al., 1996. Endotoxin stimulates lymphocyte-endothelial interactions in rat intestinal Peyer's patches and villus mucosa. Am. J. Physiol.-Gastrointest. Liver Physiol., 271: G282-G292.
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  68. Miura, S., D. Fukumura, I. Kurose, H. Higuchi and H. Kimura et al., 1996. Roles of ET-1 in endotoxin-induced microcirculatory disturbance in rat small intestine. Am. J. Physiol.-Gastrointest. Liver Physiol., 271: G461-G469.
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  69. Kimura, H., S. Miura, H. Higuchi, I. Kurose and Y. Tsuzuki et al., 1996. Effect of chronic ethanol feeding on nitric oxide synthesis by rat Kupffer cells. Alcoholism: Clin. Exp. Res., 20: 69a-72a.
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  70. Higuchi, H., I. Kurose, S. Kato, S. Miura and H. Ishii, 1996. Ethanol-induced apoptosis and oxidative stress in hepatocytes. Alcoh.: Clin. Exp. Res., 20: 340A-346A.
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  71. Fukumura, D., Y. Yonei, I. Kurose, H. Saito and T. Ohishi et al., 1996. Role in nitric oxide in Kupffer cell-mediated hepatoma cell cytotoxicity in vitro and ex vivo. Hepatology, 24: 141-149.
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  72. Fukumura, D., S. Miura, I. Kurose, H. Higuchi and H. Suzuki et al., 1996. IL-1 is an important mediator for microcirculatory changes in endotoxin-induced intestinal mucosal damage. Dig. Dis. Sci., 41: 2482-2492.
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