Graduate School of Medicine ＞ Medical Sciences
＞ Medicine(Gastroenterology,Nephrology,Hematology)



Professor: Eiji TANAKA Gastroenterology and Hepatology
Associate Professor: Fumihiro ISHIDA　Hematology
Senior Assistant Professor: Hideaki HAMANO　Pancreatology
Senior Assistant Professor: Takeji UMEMURA Hepatology
Assistant Professor: Tetsuya ICHIJO　Hepatology
Assistant Professor: Toshiro ITO　Hematology
Assistant Professor: Yuji KAMIJO　Nephrology
Assistant Professor: Tomoaki SUGA Gastroenterology

◎Summary of Activity
We have worked on the basic and clinical research of Gastroenterology, Hepatology, Pancreatology, Hematology and Nephrology.

Gastroenterology, Hepatology, and Pancreatology
There are several projects in each field. We have published many papers especially on viral hepatitis, autoimmune liver diseases, Helicobacter pilori,cancers of liver, pancreas, and stomach, and IgG4 related diseases.

Hematology
We have worked on the pathologic phenomena of various disorders of granular lymphocytes. 　We have shown the relationships of chemokine system and aggressive NK cell leukemia (ANKL) or T-cell large granular lymphocyte leukemia. Currently, we focused on the molecular aspects of proliferative mechanism of ANKL. 
Another our recent concern  is  to  characterize Celiac disease and its complications among non Caucasian populations.　After reporting the first Japanese case of Celiac disease complicated with diffuse large B cell lymphoma, epidemiological research of Celiac disease is underway. 

Nephrology
One of the pillars of the research in our department is to clarify the factors which develop chronic kidney disease (CKD). To investigate the progressive mechanism in CKD, we use cultured mesangial cells and several animal models. Also, we investigate the laboratory and histological findings in CKD patients.

◎Research Projects
The specific current research interests are as follows:
Gastroenterology, Hepatology, and Pancreatology
*Clinical research of hepatitis C virus, especially treatment with interferon and ribavirin.
*HBV core-related antigen.
*Radio-frequency ablation of hepatocellular carcinoma
*Genetic analysis of autoimmune liver diseases.
*Establishment of suitable management for various type of gastrointestinal malignant lymphoma such as MALT lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, and T-cell lymphoma.
*Clinical, pathological, epidemiological, and bacteriological study for Helicobacter pylori infection in collaboration with Clinical Laboratories of Shinshu University Hospital.
*Long-time follow-up study of patients with early gastric cancer that were treated using endoscopic mucosal resection and/or endoscopic submucosal dissection.
*Clinical study of pancreatic cancer.
* Basic and Clinical study of autoimmune pancreatitis and IgG4-related diseases.

Hematology
*Development of new therapies for the hematological malignancies with multicenter　clinical trials as a member of Japan Adult Leukemia study group(JALSG)
*Novel therapeutic approach for NK cell lymphoma with multicenter clinical trial as a member of NK tumor study group(NKTSG)
*Pathobiology of aggressive NK-cell leukemia
*Characterization and classification of granular lymphocyte-proliferative disorders (GLPD)
*Prevalence of Celiac disease and  its complications among non Caucasian populations
*Molecular basis of macrothormbocytopnic disorders

Nephrology
*Reaction of cultured mesangial cells after the stimulation of high glucose state and the addition of immune-complex
*Expression of hepatocyte growth factor induced by the interaction between human mesangial cells and monocytes
*Role of nitric oxide in diabetic nephropathy rats
*Interaction between parietal and visceral epithelial cells in experimental nephritis models
*Role of peroxisome proliferator-activated receptor α (PPARα) in rat renal proximal tubular cells
*Role of macrophage in uremic condition
*Incidence and prevalence of several hepatic virus infection in hemodialysis and CAPD patients   
*Relationship between effluent levels of β2-microglobulin and peritoneal injury markers in 7.5 % icodextrin-based peritoneal dialysis solution
*Investigation of clinical and histological progressive factors in IgA nephropathy
*Search for more adequate equation about estimated glomerular filtration rate (eGFR)
*Case-based clinical research in renal transplantation
*Pharmacokinetics and Pharmakodynamics of mitiglinide calcium hydrate in end-stage renal failure patients

References
Division of Hepatology
  1. Matsumoto A, Tanaka E. (2009) Pretreatment prediction of virological response to peginterferon plus ribavirin therapy in patients with chronic hepatitis C, using viral and host factors: some concerns (reply). Hepatology 49: 2125-2126.

  2. Okiyama W, Tanaka N, Nakajima T, Tanaka E, Kiyosawa K, Gonzalez FJ, Aoyama T. (2009) Polyenephosphatidylcholine prevents alcoholic liver disease in PPARalpha-null mice through attenuation of increases in oxidative stress. J Hepatol 50: 1236-1246.

  3. Umemura T, Ichijo T, Yoshizawa K, Tanaka E, Kiyosawa K. (2009) Epidemiology of hepatocellular carcinoma in Japan. J Gastroenterol 44: 102- 107.

  4. Umemura T, Katsuyama Y, Hamano H, Kitahara K, Takayama M, Arakura N, Kawa S, Tanaka E, Ota M. (2009) Association analysis of Toll-like receptor 4 polymorphisms with autoimmune pancreatitis. Hum Immunol 70: 742- 746.

  5. Komatsu M, Yazaki M, Tanaka N, Sano K, Hashimoto E, Takei Y, Song YZ, Tanaka E, Kiyosawa K, Saheki T, Aoyama T, Kobayashi K.(2008) Citrin deficiency as a cause of chronic liver disorder mimicking non-alcoholic fatty liver disease. J Hepatol.49: 810-820.

  6. Shirakawa H, Matsumoto A, Joshita S, Komatsu M, Tanaka N, Umemura T, Ichijo T, Yoshizawa K, Kiyosawa K, Tanaka E (2008) Nagano Interferon Treatment Research Group: Pretreatment prediction of virological response to peginterferon plus ribavirin therapy in chronic hepatitis C patients using viral and host factors. Hepatology 48: 1753-1760.

  7. Tanaka E, Umemura T. (2008) History and prevention of de novo hepatitis B virus-related hepatitis in Japan and the world. Clin J Gastroenterol 1: 83-86.

  8. Tanaka N, Nagaya T, Komatsu M, Horiuchi A, Tsuruta G, Shirakawa H, Umemura T, Ichijo T, Matsumoto A, Yoshizawa K, Aoyama T, Kiyosawa K, Tanaka E. (2008) Insulin resistance and hepatitis C virus: a case-control study of non-obese, non-alcoholic and non-steatotic hepatitis virus carriers with persistently normal serum aminotransferase. Liver Int 28: 1104-1111.

  9. Umemura T, Ota M, Hamano H, Katsuyama Y, Muraki T, Arakura N, Kawa S, Kiyosawa K. (2008)Association of autoimmune pancreatitis with cytotoxic T-lymphocyte antigen 4 gene polymorphisms in Japanese patients. Am J Gastroenterol 103: 588-594.

  10. Umemura T, Ota M, Yoshizawa K, Katsuyama Y, Ich Tanaka E, Kiyosawa K.ijo T. (2008) Association of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with type 1 autoimmune hepatitis in Japanese. Hepatol Res 38: 689-695.

  11. Umemura T, Tanaka E, Kiyosawa K, Kumada H; Japan de novo Hepatitis B Research Group. (2008) Mortality secondary to fulminant hepatic failure in patients with prior resolution of hepatitis B virus infection in Japan. Clin Infect Dis 47: e52-56.

  12. Yoshizawa K, Shirakawa H, Ichijo T, Umemura T, Tanaka E, Kiyosawa K, Imagawa E, Matsuda K, Hidaka E, Sano K, Nakazawa Y, Ikegami T, Hashikura Y, Miyagawa S, Ota M, Nakano M.(2008) De novo autoimmune hepatitis following living-donor liver transplantation for primary biliary cirrhosis. Clin Transplant 22: 385-390.

  13. Yokosawa S, Yoshizawa K, Ota M, Katsuyama Y, Kawa S, Ichijo T, Umemura T, Tanaka E, Kiyosawa K. (2007) A genomewide DNA microsatellite association study of Japanese patients with autoimmune hepatitis type 1. Hepatology 45: 384-90.

  14. Umemura T, Muto H, Tanaka E, Matsumoto A, Ichijo T, Yoshizawa K, Akamatsu T, Kiyosawa K, and the Nagano Interferon Treatment Research Group. (2007) Anti-Helicobacter seropositivity: influence on severity and treatment response in patients with chronic hepatitis C. J Viral Hepatitis 14: 48-54.

  15. Umemura T, Ota M, Yoshizawa K, Katsuyama Y, Ichijo T, Tanaka E, Kawa S, Kiyosawa K. (2007) Lack of association between FCRL3 and FcγRII polymorphisms in Japanese type 1 autoimmune hepatitis. Clin Immunol 122: 338-342.

  16. Tanaka N, Horiuchi A, Yamaura T, Komatsu M, Tanaka E, Kiyosawa K. (2007) Efficacy and safety of 6-month iron reduction therapy in patients with hepatitis C virus-related cirrhosis: a pilot study. J Gastroenterol 42: 49-55.

  17. Matsumoto A, Tanaka E, Minami M, TOkanoue T, Yatsuhashi H, Nagaoka S, Suzuki F, Kobayashi M, Chayama K, Imamura M, Yotsuyanagi H, Nakaoka S, Maki N, Kawata S, Kumada H, Iino S, Kiyosawa K. (2007) Low serum level of hepatitis B core-related antigen indicates unlikely reactivation of hepatitis after cessation of lamivudine therapy. Hepatol Res 37: 661-666.

  18. Umemura T, Zen Y, Hamano H, Kawa S, Nakanuma Y, Kiyosawa K. (2007) Immunoglobin G4-hepatopathy: association of immunoglobin G4-bearing plasma cells in liver with autoimmune pancreatitis. Hepatology 46: 463-471.

  19. Umemura T, Zen Y, Hamano H, Ichijo T, Kawa S, Nakanuma Y, Kiyosawa K. (2007) IgG4 associated autoimmune hepatitis: a differential diagnosis for classical autoimmune hepatitis. Gut. 56: 1471-1472.

  20. Tanaka E, Matsumoto A, Suzuki F, Kobayashi M, Mizokami M, Tanaka Y, Okanoue T, Minami M, Chayama K, Imamura M, Yatsuhashi H, Nagaoka S, Yotsuyanagi H, Kawata S, Kimura T, Maki N, Iino S, Kiyosawa K. (2006) HBV Core-Related Antigen Study Group. Measurement of hepatitis B virus core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistance. Liver Int 26(1): 90-96.

  21. Misawa N, Matsumoto A, Tanaka E, Rokuhara A, Yoshizawa K, Umemura T, Maki N, Kimura T, Kiyosawa K. (2006) Patients with and without loss of hepatitis B virus DNA after hepatitis B e antigen seroconversion have different virological characteristics. J Med Virol 78: 68-73.

  22. Tanaka N, Tanaka E, Sheena Y, Komatsu M, Okiyama W, Misawa N, Muto H, Umemura T, Ichijo T, Matsumoto A, Yoshizawa K, Horiuchi A, Kiyossawa K. (2006) Useful parameters for distinguishing nonalcoholic steatohepatitis with mild steatosis from cryptogenic chronic hepatitis in the Japanese population. Liver Int 26:956-963.

  23. Rokuhara A, Matsumoto A, Tanaka E, Umemura T, Yoshizawa K, Kimura T, Maki N, Kiyosawa K. (2006) Hepatitis B virus RNA is measurrable in serum and can be a new marker for monitoring lamivudine therapy. J Gastroenterol 41: 785-790.

  24. Matsumoto A, Tanaka E, Rokuhara A, Kiyosawa K, Kumada H, Omata M, Okita K, Hayashi N, Okanoue T, Iino S, Tanikawa K; the Inuyama Hepatitis Study Group. (2005) Efficacy of lamivudine for preventing hepatocellular carcinoma in chronic hepatitis B: A multicenter retrospective study of 2795 patients. Hepatol Res 14: 173-184

  25. Tanaka E, Matsumoto A, Takeda N, Li TC, Umemura T, Yoshizawa K, Miyakawa Y, Miyamura T, Kiyosawa K (2005) Age-specific antibody to hepatitis E virus has remained constant during the past 20 years in Japan. J Viral Hepat 12: 439-442

  26. Yoshizawa K, Ota M, Katsuyama Y, Ichijo T, Matsumoto A, Tanaka E, Kiyosawa K. (2005) Genetic analysis of the HLA region of Japanese patients with type 1 autoimmune hepatitis. J Hepatol. 42: 578-584.


Division of Gastroenterology
  1. Arakura N, Ozaki Y, Muraki T, Maruyama M, Chou Y, Kodama R, Takayama M, Hamano H, Tanaka E, Kawa S. (2009) Pancreaticobiliary fistula associated with pansreatolithiasi. Clin J Gastroenterol 2: 226- 231.

  2. Arakura N, Takayama M, Ozaki Y, Maruyama M, Chou Y, Kodama R, Ochi Y, Hamano H, Nakata T, Kajikawa S, Tanaka E, Kawa S. (2009) Efficacy of preoperative endoscopic nasobiliary drainage for hilar cholangiocarcinoma. J Hepatobiliary Pancreat Surg 16: 473- 477.

  3. Ozaki Y, Oguchi K, Hamano H, Arakura N, Muraki T, Kiyosawa K, Momose M, Kadoya M, Miyata K, Aizawa T, Kawa S. (2008) Differentiation of autoimmune pancreatitis from suspected pancreatic cancer by fluorine-18 fluorodeoxyglucose positron emission tomography. J Gastroenterol 43: 144-151.

  4. Hamano H, Umemura T, Uehara T, Kawa S, Kiyosawa K. (2007) IgG4-related sclerosing cholangitis should be included as an exclusion criterion for the diagnosis of primary sclerosing cholangitis. Am J Gastroenterol 102: 691-692.

  5. Ota M, Katsuyama Y, Hamano H, Umemura T, Kimura A, Yoshizawa K, Kiyosawa K, Fukushima H, Bahram S, Inoko H, Kawa S. (2007) Two critical genes (HLA-DRB1 and ABCF1) in the HLA region are associated with the susceptibility to autoimmune pancreatitis. Immunogenetics 59: 45-52.

  6. Hamano H, Arakura N, Muraki T, Ozaki Y, Kiyosawa K, Kawa S. (2006) Prevalence and distribution of extrapancreatic lesions complicating autoimmune pancreatitis. J Gastroenterol 41: 1197-205.

  7. Umemura T, Ota M, Hamano H, Katsuyama Y, Kiyosawa K, Kawa S. (2006) Genetic association of Fc receptor-like 3 polymorphisms with autoimmune pancreatitis in Japanese patients. Gut 55: 1367-1368.

  8. Muraki T, Hamano H, Ochi Y, Komatsu K, Komiyama Y, Arakura N, Yoshizawa K, Ota M, Kawa S, Kiyosawa K. (2006) Autoimmune pancreatitis and complement activation system. Pancreas 32: 16-21.

  9. Kawa S, Yoshizawa K, Nikaido T, Kiyosawa K. (2005) Inhibitory effect of 22-oxa-1,25-dihydroxyvitamin D3, maxacalcitol, on the proliferation of pancreatic cancer cell lines. J Steroid Biochem Mol Biol 97: 173-177.

  10. Hamano H, Kawa S, Uehara T, Ochi Y, Takayama M, Komatsu K, Muraki T, Umino J, Kiyosawa K, Miyagawa S. (2005) Immunoglobulin G4-related lymphoplasmacytic sclerosing cholangitis that mimics infiltrating hilar cholangiocarcinoma: part of a spectrum of autoimmune pancreatitis? Gastrointest Endosc 62: 152-157.

  11. Komatsu K, Hamano H, Ochi Y, Takayama M, Muraki T, Yoshizawa K, Sakurai A, Ota M, Kawa S. (2005) High prevalence of hypothyroidism in patients with autoimmune pancreatitis. Dig Dis Sci 50: 1052-1057.


Division of Nephrology
  1. Kono K, Kamijo Y, Hora K, Takahashi K, Higuchi M, Kiyosawa K, Shigematsu H, Gonzalez FJ, Aoyama T. (2009) PPAR{alpha} attenuates the proinflammatory response in activated mesangial cells. Am J Physiol Renal Physiol 296: F328-F336.

  2. Li G, Hu R, Kamijo Y, Nakajima T, Aoyama T, Ehara T, Shigematsu H, Kannagi R, Kyogashima M, Hara A. (2009) Kidney dysfunction induced by protein overload nephropathy reduces serum sulfatide levels in mice. Nephrology 14: 658- 662.

  3. Zhang X, Nakajima T, Kamijo Y, Li G, Hu R, Kannagi R, Kyogashima M, Aoyama T, Hara A. (2009) Acute kidney injury induced by protein-overload nephropathy down-regulates gene expression of hepatic cerebroside sulfotransferase in mice, resulting in reduction of liver and serum sulfatides. Biochem Biophys Res Commun 390: 1382- 1388.

  4. Kamijo Y, Hora K, Kono K, Takahashi K, Higuchi M, Ehara T, Kiyosawa K, Shigematsu H, Gonzalez FJ, Aoyama T. (2007) PPARalpha protects proximal tubular cells from acute fatty acid toxicity. J Am Soc Nephrol. 18:3089-3100.

  5. Kamijo Y, Hora K, Nakajima T, Kono K, Takahashi K, Ito Y, Higuchi M, Kiyosawa K, Shigematsu H, Gonzalez FJ, Aoyama T. (2007) Peroxisome proliferator-activated receptor alpha protects against glomerulonephritis induced by long-term exposure to the plasticizer di-(2-ethylhexyl)phthalate. J Am Soc Nephrol. 18:176-88.

  6. Minami, S., Hora, K., Kamijo, Y. and Higuchi, M. (2007) Relationship between effluent levels of β2-microglobulin and peritoneal injury markers in 7.5 % icodextrin-based peritoneal dialysis solution. Therapeutic Apheresis and Dialysis 11: 296-300.

  7. Kamijo, H., Higuchi, M., Hora, K. (2006) Chronic inhibition of nitric oxide production aggravates diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats. Nephron Physiol 104: 12-22.

  8. Chowdhury, A.R., Ehara, T., Higuchi, M., Hora, K., Shigematsu, H. (2005) Immunohistochemical detection of immunoglobulins and complements in formaldehyde-fixed and paraffin-embedded renal biopsy tissues; an adjunct for diagnosis of glomerulonephritis. Nephrology 10: 298-304

  9. Ehara, T., Yazawa, M., Konishi, K., Hora, K., Shigematsu, H. (2005) Renal cholesterol embolism: analysis of two spontaneous autopsy cases. Nephrology 10: 90-96.

  10. Higuchi, M., Hata, T., Furuya, S., Hosaka, S., Kamijo, Y., Kiyosawa, K., Ishizuka, O., Nishizawa, O., Hora, K. (2005) Epstein-Barr virus-related primary central nervous system lymphoma after cadaveric renal transplantation improved by treatment with high-dose methotrexate followed by irradiation. Nephrology 10: 321-324.

Division of Hematology
  1. Asano N, Yamamoto K, Tamaru J, Oyama T, Ishida F, Ohshima K, Yoshino T, Nakamura N, Mori S, Yoshie O, Shimoyama Y, Morishima Y, Kinoshita T, Nakamura S. (2009) Age-related Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorders: comparison with EBV-positive classic Hodgkin lymphoma in elderly patients. Blood 113: 2629-2636.

  2. Ito T, Makishima H, Nakazawa H, Kobayashi H, Shimodaira S, Nakazawa Y, Kitano K, Matsuda K, Hidaka E, Ishida F. (2008) Promising approach for aggressive NK cell leukaemia with allogeneic haematopoietic cell transplantation. Eur J Haematol.81: 107-111.

  3. Makishima　H, Ito T, Momose K, Nakazawa H, Shimodaira S, Kamijo Y, Nakazawa Y, Ichikawa N, Ueno M, Kobayashi H, Kitano K, Saito H, Kiyosawa K, Ishida F. (2007) Chemokine system and tissue infiltration in aggressive NK-cell leukemia. Leukemia Res 31: 1245-1253.

  4. Momose　K, Makishima H, Ito T, Nakazawa H, Shimodaira S, Kiyosawa K, Ishida F. (2007) Close resemblance　between chemokine receptor expression profiles of lymphoproliferative disease of granular lymphocytes and their normal counterparts in association with elevated serum concentrations of IP-10 and MIG. Int J Hematol 86: 174-179.

  5. Asano N Suzuki R, Matsuo K, Kagami Y, Ishida F, Tamaru J, Jin GS, Sato Y, Shimoyama Y, Yoshino T, Morishima Y, Nakamura S. (2007) Cytotoxic molecule expression is predictive of prognosis in Hodgkins-like anaplastic large cell lymphoma. Histopathology 50: 705-715.

  6. Nakazawa H, Ito T, Makishima H, Misawa N, Okiyama W, Uehara T, Hidaka E, Kiyosawa K, Ishida F. (2006) Adenovirus fulminant hepatic failure after unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia. Internal Med　45: 975-980.

  7. Asano N, Oshiro A, Matsuo K, Kagami Y, Ishida F, Suzuki R, Kinoshita T, Shimoyama Y, Tamaru J, Yoshino T, Kitamura K, Fukutani H, Morishima Y, Nakamura S. (2006) Prognostic significance of T-cell or cytotoxic molecules phenotype in classical Hodgkin’s lymphoma: a clinicopathologic study. J Clin Oncol 24: 2646-2633.

  8. Makishima H, Ito T, Kodama R, Asano N, Nakazawa H, Hirabayashi K, Nakamura S, Ota M, Akamatsu T, Kiyosawa K, Ishida F. (2006) Intestinal diffuse large B cell lymphoma associated with celiac disease -a Japanese case. Int J Hematol 83: 63-65.

  9. Makishima H, Ito T, Asano N, Nakazawa H, Shimodaira S, Kamijo Y, Nakazawa Y, Suzuki T, Kobayashi H, Kiyosawa K, Ishida F. (2005) Significance of chemokine receptor expression in aggressive NK cell leukemia. Leukemia 19:1169-1174.

  10. Asano N, Suzuki R, Kagami Y, Ishida F, Kitamura K, Fukutani H, Morishima Y, Takeuchi K, Nakamura S. (2005) Clinicopathologic and prognostic significance of cytotoxic molecule expression in nodal peripheral T-cell lymphoma, unspecified. American Journal of Surgical Pathology 29:1284-1293.