Mitsuhiko Moriyama

Nihon University, Edo, Tōkyō, Japan

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Publications (141)324.25 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the histopathological findings of type C liver disease to determine risk factors for development of hepatocellular carcinoma (HCC). We studied 232 patients, who underwent liver biopsy for type C chronic liver disease between 1992 and 2009, with sustained virological response (SVR) after interferon therapy. The patients were divided into two groups according to the F stage 0 + 1 + 2 group (n = 182) and F3 + 4 group (n = 50). We prospectively observed and compared the incidence of HCC of the patients with SVR in the F0 + 1 + 2 and F3 + 4 groups. Then, the background factors and liver histopathological findings, including the degree of fibrosis, F stage, inflammation, necrosis, bile duct obstruction, fat deposition, and degree of irregular regeneration (IR) of hepatocytes, were correlated with the risk of developing HCC. HCC developed in three of 182 (1.6%) patients in the F0 + 1 + 2 group, and four of 50 (8.0%) in the F3 + 4 group. The cumulative incidence of HCC in the former group was found to be significantly lower than in the F3 + 4 group (log rank test P = 0.0224). The presence of atypical hepatocytes among IR of hepatocytes in the F3 + 4 group resulted in a higher cumulative incidence of HCC, and was significantly correlated with risk of HCC development (RR = 20.748, 95%CI: 1.335-322.5, P = 0.0303). Atypical hepatocytes among the histopathological findings of type C liver disease may be an important risk factor for HCC development along with progression of liver fibrosis.
    World Journal of Gastroenterology 08/2013; 19(30):4887-96. · 2.55 Impact Factor
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    ABSTRACT: BACKGROUND: Prophylactic treatment for esophageal varices has been performed without adequate supporting evidence. We assessed the feasibility of prophylactic and follow-up treatment for high-risk esophageal varices in patients with hepatocellular carcinoma (HCC). METHODS: Patients with HCC were screened prospectively and followed up for esophageal varices and gastroduodenal ulceration. High-risk esophageal varices (huge F3 varices or intermediate F2 varices positive for red color signs) were treated prophylactically. Follow-up endoscopy was performed to assess the impact of prophylaxis and changes in varices at 1 week, 1 month, and 6 months after operation. If high-risk varices were found during follow-up, secondary prophylaxis was performed according to the same criteria. RESULTS: Among 251 patients with HCC, 81 (32.3 %) had esophageal varices on screening endoscopy. Prophylactic endoscopic treatment was required by 13 patients (1 with F3 varices and 12 with F2 varices positive for red color signs). Ten varices worsened, and 4 varices progressed to high-risk varices requiring endoscopic treatment. No F0 or F1 varices at screening endoscopy progressed to high-risk varices, and no bleeding event occurred during 6 months of preplanned follow-up. A preoperative platelet count of less than 10 × 10(4)/μL (odds ratio: 4.21, 95 % confidence interval 3.11-10.6; p < 0.001), the presence of splenomegaly (2.87, 2.16-21.8; p = 0.011), and an indocyanine green retention rate at 15 min of greater than 30 % (2.31, 1.88-24.6; p = 0.026) were independent predictors of worsening varices. CONCLUSIONS: Our protocol for prophylactic and follow-up treatment of high-risk esophageal varices was feasible in patients with HCC.
    Journal of Gastroenterology 06/2013; · 3.79 Impact Factor
  • Gastrointestinal endoscopy 04/2013; 77(4):674-5. · 6.71 Impact Factor
  • Nihon Naika Gakkai Zasshi 02/2013; 102(2):433-6.
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    ABSTRACT: B-flow is a non-Doppler-based technology for visualizing blood flow and has a high spatial resolution. The aim of this study is to evaluate the blood flow information of liver tumors using B-flow in comparison with color Doppler sonography (CDS).Seventy-nine patients with 82 hepatic nodules were studied using B-flow and CDS. The study group included 45 HCC nodules, 23 liver metastasis nodules, four intrahepatic cholangiocarcinomas (ICC), and 13 hemangiomas. The visualized vascularity and morphological findings of the hepatic tumor vessel were evaluated.B-flow showed multiple vessels in 48 nodules (58.5 %) and a single vessel in 13 nodules (15.9 %). CDS showed multiple vessels in 44 nodules (53.7 %) and a single vessel in 23 nodules (28.0 %). Multivariate analysis showed basket pattern was significant for HCC (OR 49.263; p = 0.0002), and penetrating vessel was significant for liver metastasis or ICC (OR 14.545; p B-flow detects hepatic tumor blood flow with sensitivity as high as that of CDS. Vascular structure information obtained using B-flow could be potentially used to diagnose liver tumors.
    Journal of Medical Ultrasonics 01/2013; 40(4). · 0.64 Impact Factor
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    ABSTRACT: Background: Quantitative electroencephalogram (qEEG) changes in chronic hepatitis C patients treated with interferon-α (IFN-α) have previously been reported. However, whether IFN-α-induced depression is related to changes in qEEG during IFN-α treatment remains unclear. Method: Fifty chronic hepatitis C patients were enrolled and IFN-α was administered intramuscularly at 9 × 10 IU daily for the first 4 weeks and then 3 times a week for the next 20 weeks. Serial EEGs obtained before and at 4 weeks after treatment were assessed. The absolute power for each frequency band was determined using qEEG techniques. Differences in the rate of change in absolute power for each of 6 frequency bands (δ, θ, θ, α, α and β) were assessed between patients with and without major depression using the Mann-Whitney U test. When significant differences in the rate of change in absolute power for each frequency band were observed, differences in the rate of change were also assessed between patients with and without psychological complications using the Mann-Whitney U test. Results: Major depression due to psychological complications during IFN-α treatment was reported in 10 out of 50 patients. In the θ band, the difference in the rate of change was demonstrated to be significant (p = 0.0036). Moreover, at the central, frontal, parietal, and temporal locations, the rates of change were also significantly different. Conclusion: In IFN-α-treated chronic hepatitis C patients who were diagnosed with major depression, qEEG changes were more obvious and widely distributed.
    Neuropsychobiology 01/2013; 67(2):122-6. · 2.37 Impact Factor
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    ABSTRACT: This report describes a case of liver failure secondary to pancreatoduodenectomy and rapid recovery following treatment. A 68-year-old woman with cancer on the ampulla of Vater underwent surgery for pancreatoduodenectomy. The patient developed liver failure 3 months postsurgically. She was hospitalized after presenting with jaundice, hypoalbuminemia and decreased serum zinc. Computed tomography (CT) of the abdomen showed a reduction in CT attenuation values postoperatively. We suspected fatty liver due to impaired absorption caused by pancreatoduodenectomy. We initiated treatment with branched-chain amino acids and a zinc formulation orally. Trace elements were administered intravenously. Two months after treatment, there was a noticeable improvement in CT findings. The patient's jaundice and hypoalbuminemia prompted a liver biopsy, which led to a diagnosis of non-alcoholic steatohepatitis.
    Case Reports in Gastroenterology 01/2013; 7(1):49-55.
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    ABSTRACT: The etiology of Cronkhite-Canada syndrome (CCS) remains unknown and many cases are refractory to treatment. Therefore, new therapies are urgently needed. Furthermore, a number of CCS cases with gastrointestinal carcinoma have been reported. Our patient had rapid onset of CCS and early development of colon carcinoma associated with adenomas. High anterior resection of the sigmoid colon and ileostomy were performed, and her symptoms and endoscopic and histological findings improved. Helicobacter pylori eradication was carried out 2 years later, surgical closure of an ileal fistula the following year. After 4 months, upper gastrointestinal endoscopy and colonoscopy showed that the CCS lesions had completely disappeared, and biopsies confirmed a normal stomach, duodenum, ileum and colon histologically. The patient has maintained remission for 2 years. The clinical course of this case, showing complete regression of CCS lesions following abdominal colectomy and H. pylori eradication, suggests the significance of H. pylori infection in the treatment of CCS.
    Case Reports in Gastroenterology 01/2013; 7(1):140-6.
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    ABSTRACT: Abstract A 62-year-old man was referred to our hospital because of pain in the right upper quadrant. Laboratory tests revealed normal levels of tumor markers. Abdominal ultrasonography showed a hypoechoic mass of approximately 9 cm in diameter in the right lobe of the liver. Computed tomography revealed a low-density mass with peripheral enhancement in the posterior segment of the right lobe. Magnetic resonance imaging showed a low-intensity mass on T(1)-weighted images and a high-intensity mass on T(2)-weighted images. Abdominal angiography showed enhanced staining only at the periphery of the tumor. An open biopsy was performed and intraoperative examination of frozen sections indicated malignant lymphoma. The histopathologic diagnosis was malignant T-cell lymphoma. After combined chemotherapy, the tumor shrank to 4 cm in diameter. To our knowledge, only 15 cases of malignant T-cell lymphoma have been reported previously. Diagnosis is particularly challenging because this type of tumor has no distinctive imaging characteristics or signs or symptoms. This case emphasizes the need to include malignant T-cell lymphoma in the differential diagnosis and demonstrates the importance of open biopsy in patients with a suspected liver tumor.
    International surgery 01/2013; 98(1):13-8. · 0.31 Impact Factor
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    ABSTRACT: We administered zinc supplementation therapy over three years to patients with chronic hepatitis C and reported and that the aspartate aminotransferase (AST) and alanine aminotaransferase (ALT) levels decreased, and platelet counts increased, significantly in the group with increased serum zinc concentrations. We are continuing this treatment to clarify the long-term consequences and report here the changes in serum zinc concentrations over seven years and compare the cumulative incidence of hepatocellular carcinoma (HCC). We administered polaprezinc to 32 patients, randomly selected for zinc therapy (treatment group), while another 30 formed the control group. We measured the serum zinc and albumin concentrations and conducted a prospective study to determine long-term outcomes. The changes and rates of change of serum zinc concentrations after seven years were 76.7 ± 18.2 µg/dl and +0.302 ± 0.30% in the treatment group and 56.7 ± 12.4 µg/dl and +0.033 ± 0.21% in the control group and had increased significantly (p = 0.0002, p = 0.0036). Progression of liver disease seemed to vary, depending on serum albumin concentrations. In the group with baseline serum albumin concentrations of 4.0 g/dl or more, the change and rate of change of serum zinc concentrations increased significantly, and the cumulative incidence of HCC tended to decrease, in the treated group. According to multivariate analysis, the factors that contribute to a reduction in the incidence of HCC are zinc therapy (risk ratio: 0.113, 95% CI: 0.015-0.870, p = 0.0362), and platelet counts (0.766, 0.594-0.989, 0.0409). Zinc supplementation therapy seems to improve liver pathology and reduce the incidence of HCC.
    Journal of Clinical Biochemistry and Nutrition 11/2012; 51(3):178-84. · 2.25 Impact Factor
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    ABSTRACT: PURPOSE: The outcomes of patients with resectable hepatocellular carcinoma (HCC) negative for all virus-related markers have not yet been characterized. This study investigated the outcomes of such patients in comparison to those who had virus-related resectable HCC. METHODS: A total of 398 patients with HCC were divided into 2 groups, comprising patients in which all virus-related markers (HBs-Ag, HBs-Ab, HBe-Ag, HBe-Ab, HBc-Ab, HCV-Ab) were negative (all-negative group, n = 63) and those with at least 1 positive virus-related marker (virus-related group, n = 335). The clinical characteristics, surgical data, and survival rates were compared between the groups. RESULTS: The serum AST (30 vs. 45 IU/l, P < 0.0001) and ALT (21 vs. 42 IU/l, P < 0.0001) levels were significantly lower in the all-negative group than in the virus-related group. The tumor size (4.3 vs. 3.1 cm, P < 0.0001), the prevalence of DM (46.8 vs. 25.4 %, P = 0.001), and BMI (24.8 vs. 22.9, P = 0.0023) were significantly higher in the all-negative group than in the virus-related group. HCC arose from a cirrhotic liver in a significantly higher proportion of patients in the virus-related group than in the all-negative group (20.6 vs. 44.8 %, P = 0.0002). The survival outcomes were not significantly different in the 2 groups (all-negative vs. virus-related: 5-year overall survival rate, 58.2 vs. 55.2 %, P = 0.27), despite such differences in the patients' characteristics. CONCLUSIONS: The postoperative outcomes of patients with HCC are independent of the presence or absence of hepatitis viral infection.
    Surgery Today 08/2012; · 0.96 Impact Factor
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    ABSTRACT: C-reactive protein (CRP) is a major acute-phase protein, which is extremely important in inflammatory disease diagnosis. CRP is rapidly elevated in various diseases as a result of tissue injury, infection and inflammation. Recently, many reports have shown its usefulness as a risk marker for arteriosclerosis and metabolic syndrome. However, the lack of sensitivity of existing CRP assays has hampered CRP testing in conditions associated with viral infections, where CRP levels typically elevate only marginally. In this report, we prepared a novel, ultra-sensitive latex-based CRP test using amino acid spacers with a high sensitivity and a wider assay range. Our method of conjugating latex beads enabled us to measure CRP in the range of 5-500 ng/mL in patient sera. Furthermore, we studied CRP levels in patients with various liver diseases, such as chronic hepatitis, liver cirrhosis and hepatic carcinoma, in order to examine the correlation between severity of liver dysfunction and CRP levels, and to examine the likelihood of recurrence of liver dysfunction. The reagent was simple to prepare and sensitive during clinical investigation, where it discriminated clearly between normal subjects and those with liver diseases. Therefore, we conclude that our ultra-sensitive CRP assay will contribute greatly to the clinical study of hepatic disorders.
    Journal of Bioscience and Bioengineering 07/2012; 114(5):560-3. · 1.74 Impact Factor
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    ABSTRACT: Various convenient and high-sensitivity immunoassays based on luminescent oxygen channeling and chromatographic techniques have been developed in recent years. This study focused on the latex agglutination immunoassay because it is a simple, homogenous immunoassay, which is also cost effective. We developed a highly sensitive latex reagent and examined the method of antibody conjugation on the latex particle surface. We introduced spacer amino acids in the latex surface to investigate the relationship between the amino acid spacer and the binding of an anti-C-reactive protein (anti-CRP) antibody as well as to investigate the resulting reactivity of the latex reagent to antigen. Because the distance between the latex particle and the antibody is equal in each case, differences in immunoreactivity are attributed to the structure of the amino acid side chain (R). Thus, reactivity of the latex reagent depends on the inorganicity and organicity of R. We suggest that a useful amino acid spacer has an inorganicity-to-organicity ratio of approximately 2.
    Journal of immunological methods 08/2011; 373(1-2):63-6. · 2.35 Impact Factor
  • Yasuo Arakawa, Junpei Hayashi, Mitsuhiko Moriyama
    Nippon rinsho. Japanese journal of clinical medicine 05/2011; 69 Suppl 4:128-33.
  • Hitomi Nakamura, Hiroshi Aoki, Okio Hino, Mitsuhiko Moriyama
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    ABSTRACT: Aims:  Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver dysfunction and is closely associated with the development of human hepatocellular carcinoma (HCC). Among HCV components, core protein is implicated in cell growth regulation, and we previously demonstrated that HCV core protein interacted with 14-3-3 protein and activated the kinase Raf-1 and mitogen-activated protein kinase (MAPK)/extracellular regulated kinase (ERK) pathway. In the present study, we investigated the expression levels and function of downstream molecules in the MAPK/ERK signaling pathway in cells expressing HCV core protein. Method:  Heparin-binding EGF-like growth factor (HB-EGF) mRNA, in HepG2 cells stably expressing HCV core protein, was detected by RT-PCR. The soluble HB-EGF in culture media was measured by heparin agarose chromatography/Western blot analysis. Immunodetection of Akt and IKK and IB, in HeLa cells and HepG2 cells expressing HCV core protein, were performed with neutralizing antibody for HB-EGF, phospatidylinositol-3-kinase [PI(3)K] inhibitor and dominant-negative mutant of Ras (DN-Ras). Results:  HB-EGF expression was significantly elevated in cells expressing HCV core protein. HCV core protein activated Akt through the Ras/PI(3)K pathway by autocrine secretion of HB-EGF. Also, HCV core protein activated IKK through Ras/PI(3)K/Akt pathway by autocrine secretion of HB-EGF. As the Ras/PI(3)K/Akt pathway is critical in anti-apoptotic HB-EGF signaling, we examined the possible role of this pathway in cells expressing HCV core protein. In addition, we investigated the relationship between IB kinases (IKK) and Akt in cells expressing HCV core protein, since IKKs are known to be activated by HCV core protein and by Akt in the presence of potent mitogen. We showed that HCV core protein promoted autocrine secretion of HB-EGF and activated Akt through the Ras/PI(3)K pathway. This model indicates a new approach to mechanism of proliferation and anti-apoptosis in HCC. Conclusion:  HCV core protein is a potent activator of mitogenic and anti-apoptotic signaling involved in hepatocarcinogenesis.
    Hepatology Research 03/2011; 41(5):455-62. · 2.07 Impact Factor
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    ABSTRACT: We previously demonstrated that antibiotic combination therapy is effective for induction and maintenance of ulcerative colitis (UC) remission. Herein, we assessed whether antibiotic combination therapy is effective for active UC, including cases with steroid refractory or dependent disease. We enrolled 25 patients with active UC including 17 steroid-dependent or refractory cases. These patients received amoxicillin 500 mg t.i.d., tetracycline 500 mg t.i.d. and metronidazole 250 mg t.i.d. for 2 weeks as well as conventional treatment. Seven colonic segments from the appendiceal region to the rectum were scored for endoscopic activity and histology. Clinical activity indexes (CAI) were also determined. At 3 and 12 months after antibiotic treatment, CAI and endoscopic score were significantly decreased as compared to those before treatment (P < 0.001 and P < 0.05, P < 0.01, respectively). Histological scores were also significantly decreased at 12 months as compared to before treatment (P < 0.01). The clinical response rates in steroid-dependent patients were 60% and 73.3% at 3 and 12 months, respectively, while being 50% at 12 months in steroid-refractory patients. Among the 17 steroid-dependent or refractory patients, 12 (70.6%) were able to discontinue steroid therapy at 12 months. No serious drug-related toxicities were observed during the trial. This long-term follow-up study suggests 2-week antibiotic combination therapy to be effective and safe in patients with active UC including those with steroid-refractory or dependent disease.
    Journal of Gastroenterology and Hepatology 05/2010; 25 Suppl 1:S62-6. · 3.33 Impact Factor
  • Shun Kobayashi, Noriko Nakajima, Yoko Ito, Mitsuhiko Moriyama
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    ABSTRACT: A recent study reported that in addition to their inhibitory effect on gastric acid secretion, some proton pump inhibitors also exert a cytoprotective effect on the gastric mucosa. We investigated the effects of lansoprazole (LPZ) on the epithelial cell cycle, and on the expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2). We examined the effects of 25 and 5 mg/kg LPZ on ulcer healing in an acetic acid-induced ulcer model in rats with and without indomethacin (IND) treatment. On days 14 and 28 after ulcer formation, we compared the ulcer diameter, bromodeoxyuridine (BrdU) uptake, apoptosis, vascular density, and the expressions of VEGF and MMP-2 in the different groups. LPZ administration increased the BrdU uptake that was reduced by IND administration. LPZ administration also increased VEGF expression at the ulcer margin in a dose-dependent manner. However, LPZ administration did not increase VEGF expression following IND pretreatment. Administration of IND alone significantly decreased MMP-2 expression at the ulcer margin; on the other hand, subsequent administration of LPZ increased the MMP-2 expression. One of the mechanisms of ulcer healing brought about by LPZ may be the involvement of endogenous prostaglandin (PG) secretion. The effect of endogenous PG secretion may be related to the induction of VEGF expression. On the other hand, LPZ administration increased MMP-2 expression, and this effect was not influenced by the inhibition of PG synthesis. The mechanisms of LPZ on ulcer healing may be involved by VEGF expression through endogenous PGs secretion. Additionally, the stimulated expression of MMP-2, which is not secreted by endogenous PGs, is another important factor for ulcer healing by LPZ.
    Journal of Gastroenterology 03/2010; 45(8):846-58. · 3.79 Impact Factor
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    ABSTRACT: [This corrects the article DOI: 10.1007/s12072-009-9162-x.].
    Hepatology International 01/2010; 4(4):789-90. · 2.64 Impact Factor
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    ABSTRACT: Lamivudine treatment of chronic hepatitis B (CHB) is associated with frequent resistance and loss of clinical benefit. We present outcomes of lamivudine-refractory Japanese patients treated with entecavir for 3 years. Eighty-two patients refractory to lamivudine therapy received entecavir 0.5 or 1 mg daily for 52 weeks in phase II study ETV-052, directly entered rollover study ETV-060, and received entecavir 1 mg daily. Responses were evaluated among patients with available samples. After 96 weeks in ETV-060 (148 weeks total entecavir treatment time), 55%(36/65) of patients had hepatitis B virus(HBV) DNA of\400 copies/mL, 85% (52/61) had alanine aminotransferase (ALT) of ≤1 × upper limit of normal (ULN), and 14.6% (7/48) achieved HBe seroconversion.A subset of 42 patients received entecavir 1 mg from phase II baseline through 148 weeks: 54% (19/35) had HBV DNA of <400 copies/mL, 84% (27/32) had ALT of ≤1 × ULN, and 15% (4/27) achieved HBe seroconversion.Sixteen patients in the 1-mg subset had baseline and week 148 evaluable biopsy pairs: 81% (13/16) showed histologic improvement and 38% (6/16) showed improvement in fibrosis. Genotypic resistance to entecavir emerged in 31 patients for a 3-year cumulative resistance probability of 35.9%. Entecavir was generally well tolerated during ETV-060, with no on-treatment ALT flares. Long-term entecavir treatment of lamivudine-refractory CHB resulted in virologic suppression, ALT normalization, and improvements in liver histology. Resistance was consistent with that observed in worldwide studies.
    Hepatology International 01/2010; 4(1):414-22. · 2.64 Impact Factor
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    ABSTRACT: We treated patients with C-viral chronic hepatitis (CH) and liver cirrhosis (LC) with polaprezinc and determined prospectively the effect on long-term outcome. 62 patients were enrolled. Of these, 32 were administered 1.0 g polaprezinc and the remainder were not administered polaprezinc. We measured the serum zinc concentrations using conventional atomic absorption spectrometry and conducted a prospective study to determine the long-term outcome of the polaprezinc therapy. Changes of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the polaprezinc administration group were significantly lower than those of the untreated group. The decrease in platelet count was clearly less than that of the untreated group. The factors that inhibited increases in serum zinc concentrations following administration of polaprezinc included low serum zinc concentration states. Furthermore, the reductions of AST and ALT levels in the low zinc group were significantly greater than those of the high zinc group. When the patients who were administered polaprezinc were divided into two groups whose zinc concentrations increased (zinc responders) or remained stable or decreased (zinc non-responders), the zinc responders had a clearly lower cumulative incidence of HCC than the zinc non-responders. We conclude zinc supplementation improved the long-term outcome in C-viral CH and LC patients.
    Journal of Clinical Biochemistry and Nutrition 11/2009; 45(3):292-303. · 2.25 Impact Factor

Publication Stats

2k Citations
324.25 Total Impact Points

Institutions

  • 2000–2013
    • Nihon University
      • • Department of Digestive Surgery
      • • Department of Medicine
      • • Department of Internal Medicine II
      Edo, Tōkyō, Japan
  • 2011
    • Juntendo University
      • Department of Medicine
      Tokyo, Tokyo-to, Japan
  • 1999–2007
    • The University of Tokyo
      • Department of Internal Medicine
      Tokyo, Tokyo-to, Japan
  • 2006
    • Chiba University
      • Department of Medicine and Clinical Oncology
      Chiba-shi, Chiba-ken, Japan
  • 1993
    • Oita University
      • Department of Microbiology
      Ōita, Ōita, Japan