Yoshimi Ito

Chiba University Hospital, Tiba, Chiba, Japan

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Publications (33)141.59 Total impact

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    ABSTRACT: Abstract Although the vast majority of hepatitis B surface antigen (HBsAg) carriers of the world inhabit South-east Asia, very little is known about delta infection in this area. Therefore, a serological and immunohistological study was made in the Tokyo-Chiba area. One of 58 (1.7%) HBsAg carriers had anti-delta antibody in a high titre in serum. Delta antigen was immuno-histologically localized in the liver in two of 146 (1.4%) HBsAg carriers studied. The antigen was strongly stained in the nuclei, and positive cells were diffusely scattered throughout the liver in both cases. Neither subject was an illicit drug user: one had travelled to Italy 10 years earlier and the other had a blood transfusion during a 5-year residence in Bangkok in the past. Thus, there is delta infection among non-intravenous drug users in Japan. Delta infection has been linked to severe liver damage, occasionally fatal. Once introduced, it could become epidemic in a country where hepatitis B virus infection is endemic, and might spread among non-drug users.
    Journal of Gastroenterology and Hepatology 03/2008; 1(1):33 - 38. DOI:10.1111/j.1440-1746.1986.tb01753.x · 3.50 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the effects of being overweight on autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) patients. 44 AIH and 95 PBC patients were enrolled in this study. Body weight and body mass index (BMI) of AIH (57.6 +/- 10.4 kg and 23.8 +/- 2.9 kgm(-2), respectively) were higher than those of PBC (51.6 +/- 7.0 kg and 22.0 +/- 2.6 kgm(-2), respectively) (P < 0.001). The prevalence of overweight patients in AIH was also higher than those in PBC (P < 0.005). Being overweight and having 25 < or = BMI < 30 did not affect the progression of hepatic fibrosis in AIH and PBC. In comparison with the non-overweight with PBC, overweight patients with PBC tended not to be symptomatic, such as having itching or fatigue (P = 0.027). Clinicians should be aware that not only non-alcoholic fatty liver disease but also PBC patients might be included among the overweight hepatic disease patients with unknown etiology.
    Hepato-gastroenterology 09/2007; 54(78):1758-60. · 0.93 Impact Factor
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    ABSTRACT: The precore region of hepatitis B virus (HBV) is indispensable for secretion of e antigen protein. Therefore, the precore stop codon mutants may play an important role in the process of e antigen seroconversion. However, the presence of the mutants in hepatitis B e antigen positive carriers has not been fully studied because of difficulties in detecting the mutants in the presence of large amounts of wild-type viruses. To overcome this, a sensitive method has been developed to detect the presence of G to A stop codon mutants at codon 28 of precore region. Primers for polymerase chain reaction (PCR) were devised to introduce restriction enzyme site Sty I for wild-type viruses and Dde I for the mutants. The amplification products with these primers were digested with Sty I to exclude the products from wild-type viruses. The remaining amplicon from precore mutants were re-amplified, and the presence of precore mutant was confirmed with Dde I digestion. The presence of precore mutants was examined in 61 HBV carriers by the method combining PCR and restriction enzyme digestion. Approximately 0.1% of precore mutant DNA among 106 copies of wild-type virus DNA was detectable by this method. The presence of the precore mutants was detected in seven of 10 (70%) e antigen positive asymptomatic carriers, and in 29 of 36 (81%) e antigen positive patients with chronic liver diseases, and in all 15 (100%) anti-e antibody positive patients with chronic liver diseases. This study revealed that a small amount of the precore mutants was present in the majority of HBV carriers.
    Journal of Gastroenterology and Hepatology 07/1995; 10(4):419 - 425. DOI:10.1111/j.1440-1746.1995.tb01594.x · 3.50 Impact Factor
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    ABSTRACT: The effect of ursodeoxycholic acid on liver function tests and on bile acid metabolism was investigated in a multi-center randomized controlled dose study for chronic hepatitis C. Twenty, 18 and 19 patients were administered 150, 600 and 900 mg/day, respectively of ursodeoxycholic acid every day for 16 wk. Serum liver parameters and bile acid composition in the treatment groups were compared with 17 control patients. A similarly significant decrease of serum alanine aminotransferase and serum gamma-glutamyltransferase was observed in patients administered 600 and 900 mg of ursodeoxycholic acid. Serum bile acid composition was determined by high-performance liquid chromatography. At entry, the relative proportions of major bile acids were similar to those observed in normal individuals. Maximal concentrations of total ursodeoxycholic acid were 0.30 mumol/L, 5.59 mumol/L, 21.42 mumol/L and 14.73 mumol/L in the control, 150, 600 and 900 mg/day groups, respectively. The fraction of the total ursodeoxycholic acid increased in a dose-dependent manner, and it was significantly higher than in controls (p < 0.001). The hydrophobicity index of bile acids was calculated by the method of Heuman, and its correlation with serum parameter levels was analyzed. In the 600 and 900 mg/day dose groups, serum alanine aminotransferase decreased in the cases in which hydrophobicity index significantly decreased during treatment. The same correlation was observed between the hydrophobicity index and serum gamma = glutamyltransferase in these two groups. There was no correlation between these parameters in the control and 150-mg groups. There was no correlation between reduction rate of serum alanine aminotransferase and initial liver histology.(ABSTRACT TRUNCATED AT 250 WORDS)
    Hepatology 09/1994; 20(3):558-64. DOI:10.1002/hep.1840200303 · 11.06 Impact Factor
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    ABSTRACT: We developed a quantitative method of hepatitis C virus RNA by competitive reverse transcription-polymerase chain reaction. With this method, 36 patients with type C chronic liver disease were analyzed for the copy number of circulating hepatitis C virus in 50 microliters of serum. The amounts of hepatitis C virus RNA ranged from 10(1) to 10(7) copies in the 36 patients. The average amount of hepatitis C virus RNA was 10(3.3 +/- 2.2) copies in 12 patients with chronic persistent hepatitis, 10(5.7 +/- 1.6) copies in 12 patients with chronic active hepatitis and 10(6.0 +/- 1.6) copies in 12 patients with cirrhosis (including 4 patients with hepatocellular carcinoma). The amount of hepatitis C virus RNA in serum was significantly less in patients with chronic persistent hepatitis than in patients with chronic active hepatitis or cirrhosis (p < 0.01), and it tended to increase according to the progression of histopathological changes of the liver. Furthermore, it was revealed that the amount of hepatitis C virus RNA became exponentially larger as the term from infection became longer. Quantification of hepatitis C virus RNA by competitive reverse transcription-polymerase chain reaction may have many applications for the study of clinical features of hepatitis C virus infection.
    Hepatology 07/1993; 18(1):16-20. DOI:10.1016/0270-9139(93)90500-M · 11.06 Impact Factor
  • Osamu Yokosuka · Yoshimi Ito · Masao Ohto · Masao Omata ·
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    ABSTRACT: Putative hepatitis C virus E2 protein was applied for detection of anti-E2 antibody in patients with type C hepatitis. The Putative E2 sequence was expressed in E. coli and approximately 38 KDa hepatitis C E2 protein fused with 42 KDa maltose binding protein was obtained. The HCV E2 antibody was detected in 2 of 7 acute hepatitis cases, in 8 of 12 chronic persistent hepatitis, in 17 of 25 chronic active hepatitis, and in 2 of 4 cirrhosis. It was not detected in 10 normal subjects. Anti-E2 antibody became undetectable after successful interferon treatment in patients with type C hepatitis. The High detection rate of E2 antibody in chronic hepatitis C and disappearance of the antibody after the interferon treatment indicate that the E2 antibody is related to viral replication and is unlikely to be a neutralizing antibody.
    Gastroenterologia Japonica 06/1993; 28 Suppl 5(S5):52-4. DOI:10.1007/BF02989206
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    ABSTRACT: To assess the effects of interferon treatment on chronic hepatitis C, histological changes long after treatment were compared with normalization of aminotransferases and seroconversion of hepatitis C virus RNA. Twenty one histologically proven chronic hepatitis C patients received alpha-interferon, 3 million units 3 times weekly for 12 months. Hepatitis C virus RNA was detected by reverse transcription/polymerase chain reaction method. Follow-up liver biopsies were performed 3 to 5 years after treatment. Fourteen of 21 (67%) patients showed normal aminotransferases for 3 to 5 years after treatment. HCV RNA seroconversion was observed in 12 of these patients. These responders showed improvement in histological activity indices and in histological findings. Two patients improved from chronic active hepatitis 2a to nonspecific changes, 1 from chronic active hepatitis 2a to portal fibrosis, 1 from chronic active hepatitis 2a to chronic persistent hepatitis and 1 from chronic active hepatitis 2b to chronic persistent hepatitis. Histological improvement of the liver correlated well with normalization of aminotransferases and seroconversion of hepatitis C virus RNA. These data indicate that complete histological resolution of chronic hepatitis C can be achieved by elimination of the virus with interferon treatment.
    Journal of Gastroenterology 04/1993; 28:115-117. DOI:10.1007/BF02989220 · 4.52 Impact Factor
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    ABSTRACT: Putative hepatitis C virus core sequence was amplified from a serum sample positive for anti-C-100-3 and expressed inEscherichia coli. Approximately 62 kDa fusion protein with maltose binding protein containing 20 kDa hepatitis C core protein was obtained. The antibody to this protein was detected in 53 of 54 (98%) sera from hepatitis C virus ribonucleic acid-positive patients including 40 sera positive for anti-C-100-3 and 13 sera negative for anti-C-100-3. The antibody was also detected in all of 12 patients with acute hepatitis C showing the earlier detectability of the antibody than anti-C-100-3. Thus, the protein expressed from the amplified hepatitis C core sequence by the polymerase chain reaction would be useful for the diagnosis of hepatitis C.
    Digestive Diseases and Sciences 03/1993; 38(4):626-630. DOI:10.1007/BF01316791 · 2.61 Impact Factor
  • Osamu Yokosuka · Yoshimi Ito · Fumio Imazeki · Masao Ohto · Masao Omata ·
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    ABSTRACT: Putative E2/NS1 sequence of hepatitis C virus was expressed in E. coli as a fusion protein with maltose binding protein. Approximately 80 kDa protein was obtained containing 38 kDa E2/NS1 protein. The antibody to this protein was detectable in the same serum from which the sequence was amplified. It was also detectable in none of 7 acute hepatitis, in 2 of 12 chronic persistent hepatitis, in 3 of 25 chronic active hepatitis, and in 2 of 4 cirrhosis. It was detectable in none of 10 normal subjects. In 3 cases who were positive for the antibody before the interferon treatment, it became undetectable after the treatment. Thus, it seems that the antibody is not a neutralizing antibody and is related to active viral replication.
    Biochemical and Biophysical Research Communications 12/1992; 189(1):565-71. DOI:10.1016/0006-291X(92)91595-H · 2.30 Impact Factor
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    ABSTRACT: Forty-nine Japanese patients were enrolled in a randomized, placebo-controlled, doubleblind trial of -interferon for chronic non-A, non-B hepatitis: 24 patients received 3 million units of recombinant human alpha -interferon (-2a) thrice weekly for eight weeks, and 25 patients received placebo in a similar schedule. The mean serum alanine aminotransferase (ALT) dropped from 15591 (sd) to 6972 during interferon treatment, but remained unchanged (158140 to 147130) during placebo treatment (P-interferon induces biochemical and histological improvement in more than half the patients with chronic non-A, non-B hepatitis.
    Digestive Diseases and Sciences 01/1991; 36(9):1217-1222. DOI:10.1007/BF01307512 · 2.61 Impact Factor
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    ABSTRACT: Replication of duck hepatitis B virus in extrahepatic tissue such as pancreas, kidney and spleen has been well documented. To assess whether there is more widespread extraheptic virus replication, we assayed brain, heart, lung, thymus, pancreas, kidney, spleen and intestine of 1- to-wk-old ducklings for the presence of duck hepatitis B virus DNA and mRNA by blotting in in situ methods. Replicative intermediates and single-stranded duck hepatitis B virus DNA and RNA transcripts were detected in the brain, lung, heart, intestine, kidney, pancreas and spleen. In situ hybridization showed evidence of viral replication in the lung epithelium, germinal center of spleen, acinar cell of pancreas and tubular epithelium of kidney. These data suggest that extrahepatic duck hepatitis B virus replication is more widespread than previously thought. It is yet to be determined whether widespread extrahepatic replication is unique to duck hepatitis B virus infection or is a common feature of other mammalian hepatitis B-like viruses. (HEPATOLOGY 1990; 11: 44–48.)
    Hepatology 01/1990; 11(1):44-8. DOI:10.1002/hep.1840110109 · 11.06 Impact Factor
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    ABSTRACT: We have treated 17 patients with non-A, non-B chronic hepatitis by recombinant interferon alpha (0.3–9 megaunits for 4–28 weeks). In six patients, serum aminotransferase levels fell to normal or near-normal range during treatment. The mean levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in 17 patients fell from 15680 (meansd) and 213135 at the beginning of treatment to 9449 and 11271, respectively, at the end of treatment. In 12 patients, liver biopsies were performed before and after (or during) the treatment, and histological activity indices (HAI) were blindly examined by two independent observers. For comparison, we examined histological changes of pre- and posttreatment liver biopsies of 19 patients who were treated by recombinant interferon for chronic hepatitis B. Mean HAI scores improved from 10.0 to 5.4 after treatment in non-A, non-B chronic hepatitis. The most marked reduction was noted in scores of portal inflammation and hepatocellular degeneration and/or necrosis. No such reduction was observed in B- viral chronic hepatitis. These data indicated that rapid biochemical resolution by the treatment was related to histological improvement of the liver in our patients with non-A, non-B hepatitis.
    Digestive Diseases and Sciences 01/1989; 34(3):330-337. DOI:10.1007/BF01536251 · 2.61 Impact Factor

  • Kanzo 01/1989; 30(2):178-181. DOI:10.2957/kanzo.30.178
  • Osamu Yokosuka · Masao Omata · Yoshimi Ito ·
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    ABSTRACT: We have examined the expression of duck hepatitis B virus (DHBV)-associated proteins in experimentally infected ducks by an immunoblot (Western) method. The DHBV-related core protein, C protein, was identified at the position of 35,000 Da (P35). Pre-S proteins were recognized as two major bands (P37 and P28), the former representing pre-S1 and the latter pre-S2 protein. Expression of the proteins was examined in the early phase of infection in ducklings sequentially sacrificed from 6 hr postinoculation to 10 days. C protein (P35) was detected as early as 24 hr postinoculation. This timing coincided with the exponential increase of RNA transcripts and double-stranded viral DNA. Pre-S1/S2 proteins were detected at 3 days postinoculation. The early appearance of C protein suggested that the proteins were utilized for nucleic acid packaging. On the other hand, the late appearance of pre-S1/S2 proteins suggested that they were utilized in the production of virions near the end of the replication cycle.
    Virology 12/1988; 167(1):82-6. DOI:10.1016/0042-6822(88)90056-6 · 3.32 Impact Factor

  • Kanzo 01/1988; 29(3):301-305. DOI:10.2957/kanzo.29.301
  • Yoshimi Ito · Masao Omata · Osamu Yokosuka · Naoko Hayashi · Masao Ohto ·

    Kanzo 01/1988; 29(9):1165-1170. DOI:10.2957/kanzo.29.1165

  • Kanzo 01/1988; 29(4):463-467. DOI:10.2957/kanzo.29.463

  • Kanzo 01/1988; 29(6):742-746. DOI:10.2957/kanzo.29.742

  • Kanzo 01/1987; 28(2):149-153. DOI:10.2957/kanzo.28.149
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    ABSTRACT: To study the relation between gene expression of hepatitis B virus (HBV) and liver disease, we studied HBV RNA transcripts and DNA in liver-biopsy specimens from 30 patients with chronic liver disease (17 seropositive for hepatitis B surface antigen and 13 seronegative). HBV-specific RNA was found in all the seropositive patients and in none of the seronegative patients. Two major RNAs, sizes 29S (long) and 21S (short), were found in nine seropositive patients, of whom seven had free HBV DNA and eight were seropositive for hepatitis B e antigen. Six of the nine patients had hepatitis B core antigen in hepatocytes and active liver disease. In contrast, inactive liver disease was noted in the remaining eight seropositive patients, who had only one (21S) RNA. None of these patients had free HBV DNA (five of eight had integrated DNA) or hepatitis B core antigen in hepatocytes. Hybridization analysis suggested that 29S and 21S RNAs are messenger RNAs of hepatitis B core antigen and hepatitis B surface antigen, respectively. These data indicate that the free DNA and its products are causally related to the activity of liver disease and that once HBV DNA has been integrated, the disease will become quiescent. None of the determinants were identified in patients seronegative for hepatitis B surface antigen.
    New England Journal of Medicine 12/1986; 315(19):1187-92. DOI:10.1056/NEJM198611063151903 · 55.87 Impact Factor

Publication Stats

700 Citations
141.59 Total Impact Points


  • 1981-2008
    • Chiba University Hospital
      Tiba, Chiba, Japan
  • 1993
    • The University of Tokyo
      Tōkyō, Japan
    • Chiba University
      • Department of Medicine and Clinical Oncology
      Chiba-shi, Chiba-ken, Japan