K Arima

Kagawa University, Takamatu, Kagawa, Japan

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Publications (30)79.7 Total impact

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    ABSTRACT: Because the underlying mechanism of hepatocellular damages in autoimmune hepatitis (AIH) still remains unclear, analysis of CD28 and bcl-2 molecules, which are critical for T cell activation and survival, was performed in patients with AIH. The number of CD28(+)CD4(+) peripheral blood mononuclear cells (PBMC) in corticosteroid (CS)-treated patients was comparable to normal control individuals but decreased in untreated AIH patients. In contrast, the number of CD28(+)CD8(+) PBMC was decreased in both CS-treated and untreated AIH patients. Analysis of liver-infiltrating mononuclear cells (LIMC) showed that the number of CD28(+)CD4(+) and CD28(-)CD8(+) LIMC were positively correlated with the histology activity index score. Bcl-2(+)CD4(+) LIMC were observed in the portal area of the liver and the numbers fluctuated with disease activity during the time course after CS administration. By contrast, CD8(+) LIMC were shown not to express bcl-2. Taken collectively, these results suggest that bcl-2(+)CD28(+)CD4(+) and bcl-2(-)CD28(-)CD8(+) cells may play critical and distinct roles in hepatocellular damage in AIH.
    Journal of Clinical Immunology 08/2006; 26(4):323-30. · 3.38 Impact Factor
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    ABSTRACT: The pathogenic mechanism for hepatocellular damage in hepatitis C virus (HCV) infection has not been clearly understood. Analysis of costimulatory molecules on lymphocytes may give us insight into the pathogenic mechanism of hepatocellular damage in HCV infection. Peripheral blood mononuclear cells (PBMCs) and liver infiltrating mononuclear cells (LIMCs) isolated from the HCV-infected patients were analyzed with antibodies directed against a variety of costimulatory molecules by flow cytometry. Blocking experiment against HLA-A24-restricted HCV-specific CTLs and immunohistochemical analysis were also performed. PBMCs expressing CD8, CD28, CD80, or CD154 were significantly reduced in HCV-infected patients compared with the healthy controls. CD28(+)CD8(+) PBMCs in the patients inversely correlated with ALT levels. Conversely, levels of CD28(-)CD8(+) LIMCs correlated with ALT levels. HCV-specific CTL activity was blocked by the treatment with anti-CD8 antibody, but not with anti-CD4 or anti-CD28 antibody. Immunohistochemical analysis revealed the accumulation of CD28(+) cells around the portal area in the liver of a patient with chronic active hepatitis C. These results suggest that CD28(+)CD8(+) T cells leave the circulation, move to the livers, and are activated in the portal area in proportion to the extent of liver diseases. CD28(-)CD8(+) T cells may finally function as effector T cells causing the hepatocellular damage in HCV infection.
    Journal of Clinical Immunology 12/2003; 23(6):518-27. · 3.38 Impact Factor
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    ABSTRACT: Recently we have demonstrated the existence of anti-cytokeratin 19 (CK19) antibodies in sera of patients with autoimmune hepatitis (AIH). In the present study, we examined the existence of T lymphocytes specific for CK19 in patients with AIH. The frequency of responders having CK19-specific T lymphocytes was significantly higher in AIH patients than in chronic hepatitis C (CH-C) patients and normal subjects. Furthermore, the stimulation index of proliferative responses of peripheral blood mononuclear cells (PBMCs) was significantly higher in AIH patients than in CH-C patients and normal subjects. The phenotype of proliferating PBMCs specific for CK19 was shown to be predominantly CD4(+) T lymphocytes and these CD4(+) T lymphocytes had a Th1 subtype. The present findings demonstrate that there is some population of CD4(+) T lymphocytes with a Th1 subtype specific for CK19 in peripheral blood of patients with AIH. The Th1-predominat pattern of cytokines may induce cytotoxic T lymphocytes (CTLs) specific for the antigenic peptides derived from the autoantigen, including CK19. In addition, these CTLs may attack the hepatocytes and this may be one of the important etiologies of AIH.
    Hepatology Research 05/2003; 25(4):415-422. · 2.07 Impact Factor
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    ABSTRACT: Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) therapy are currently used for the treatment of hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the usefulness of combination therapy of PEI and RFA (PEI-RFA). Seventy-three patients with biopsy-proven HCC and liver cirrhosis underwent RFA after a bolus injection of ethanol into HCC. The volume of coagulated necrosis in the liver caused by PEI-RFA was estimated and compared with that by RFA alone. Coagulated necrosis areas in the liver of patients treated with PEI-RFA were significantly larger than those of patients treated with RFA alone. In PEI-RFA group, the volume of coagulated necrosis was significantly correlated with the amounts of ethanol injected into HCC. No major complications were observed during and after the PEI-RFA treatment. These results indicate that PEI-RFA is more effective than RFA alone and can make dramatic improvement of therapeutic effects in RFA therapy for HCC with fewer sessions of treatments. Therefore, PEI-RFA is considered to be a practical and promising option and may open up new avenues for the treatment of HCC.
    International Journal of Oncology 11/2002; 21(4):841-6. · 2.66 Impact Factor
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    ABSTRACT: Radiofrequency ablation (RFA) is an effective modality for the treatment of hepatocellular carcinoma (HCC), because it can induce large coagulated necrosis in a few sessions. We have recently reported that the combination therapy of percutaneous ethanol injection (PEI) with RFA (PEI-RFA) created enhancement of coagulated necrosis compared with RFA alone. In the present study, we adopted PEI-RFA for the treatment of HCCs located in the regions that are difficult to treat with RFA alone. Five patients with biopsy-proven HCC and liver cirrhosis underwent PEI-RFA therapy. In these patients, HCCs were located beside the gallbladder, inferior vena cava or portal vein or kidney, or immediately under the diaphragm. Prior to RFA, 99.5% ethanol was injected into the region of HCC located in the regions where RFA energy appears to be difficult to reach. In all cases, HCC was totally coagulated by PEI-RFA. Injecting ethanol prior to RFA therapy caused no major side effects. These results indicate that PEI-RFA may be effective for the treatment of HCCs located in the regions that are difficult to treat with RFA alone as well as large-sized HCCs.
    International Journal of Oncology 10/2002; 21(3):611-5. · 2.66 Impact Factor
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    ABSTRACT: The Bcl-2 family proteins are important regulators of apoptosis and have been implicated in the occurrence of autoimmune diseases. There have been reports that Bcl-2-positive lymphocytes play important roles in pathogenesis of at least some types of autoimmune diseases, including autoimmune hepatitis. In this study, we examined the role of Bcl-2-positive lymphocytes in the development of primary biliary cirrhosis (PBC). The expression of Bcl-2 in lymphocytes infiltrating into the liver was evaluated from liver biopsy specimens of 25 patients with PBC (stage I/II/III/IV, 11/3/8/3) and 24 controls with chronic hepatitis B (CH-B) or chronic hepatitis C (CH-C). Bcl-2 expression in lymphocytes infiltrating into the liver was investigated by immunohistochemistry using a monoclonal antibody to Bcl-2 with an avidin-biotin complex system. Significant overexpression of Bcl-2 in lymphocytes infiltrating into the liver was observed in the early stage of PBC, especially in areas of destructed bile ducts. Most of Bcl-2-positive cells were CD45RO-positive helper T-cells visualized by the double staining method. These results suggest that Bcl-2-positive helper T-cells may have important roles in the pathogenesis of PBC.
    International Journal of Molecular Medicine 07/2002; 9(6):571-7. · 1.96 Impact Factor
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    ABSTRACT: alpha-fetoprotein (AFP) is an important marker for the diagnosis of hepatocellular carcinoma (HCC) and has been widely used in clinical settings. Recently, the importance of lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) has been indicated. However, the clinical significance of the level of AFP-L3 protein in relation to the characteristics of HCC has not been fully evaluated. In the present study, both the ratio of AFP-L3 (AFP-L3%) and the absolute value of AFP-L3 (AFP-L3-AV) were examined in 80 patients with HCC, and evaluated with respect to characteristics of HCC such as grade of differentiation, size of tumor and morphological findings. Among HCC-specific tumor markers, AFP, AFP-L3% and protein induced in vitamin K absence (PIVKA-II), AFP showed the highest positive rate in patients with HCC, while AFP-L3% showed the lowest rate. AFP-L3% and AFP-L3-AV were, however, most significantly correlated with the grade of HCC differentiation, while AFP showed the least significant correlation. Furthermore, AFP-L3% was most significantly correlated with the size of HCC in patients with solitary HCC. Conversely, neither AFP-L3-AV nor PIVKA-II showed a significant correlation with the size of HCC. In relation to morphological differences of HCC, although AFP-L3%, AFP-L3-AV and PIVKA-II were significantly higher in the diffuse type of HCC than in the nodular type of HCC, AFP was most significantly correlated with the morphological differences of HCC. These results indicate that tumor markers for HCC, such as AFP, AFP-L3%, AFP-L3-AV and PIVKA-II, may play different roles in predicting the characteristics of HCC.
    International Journal of Oncology 03/2002; 20(2):305-9. · 2.66 Impact Factor
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    ABSTRACT: It has been suggested that cytotoxic T lymphocytes (CTL) have crucial roles for the hepatocellular damage in hepatitis C virus (HCV) infection. A series of CTL epitopes located in the HCV protein have been identified. However, no CTL epitopes restricted by HLA-A24, a common HLA allele in humans, has been identified. Peripheral blood and liver infiltrating mononuclear cells from the patients with hepatitis C virus infection and healthy controls were stimulated with a series of peptides containing HLA-A24 binding motifs located in HCV protein. An immunodominant HLA-A24 restricted CTL epitope (A24-4; AYSQQTRGL, amino acids 1031-1039) presented by HLA-A24 molecule was identified using a series of synthetic peptides containing the HLA-A24 binding motifs. The CTL activity against this peptide was induced both in peripheral blood and liver infiltrating mononuclear cells from HLA-A24-positive chronic hepatitis C patients, not from HLA-A24-negative patients and HLA-A24-positive healthy controls. CTL activity was blocked by anti-HLA-A24 and anti-CD8 antibodies, not by anti-CD4 antibody. Furthermore, the A24-4-specific CTL recognized the HCV gene transfected target cells. Because this peptide is presented by a common HLA class I molecule, it might be useful for protection against hepatocellular damage and vaccine development in large population of the HCV-infected patients.
    Journal of Hepatology 07/2001; 34(6):930-5. · 9.86 Impact Factor
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    ABSTRACT: The present study aimed to investigate whether antimitochondrial antibody (AMA)-positive primary biliary cirrhosis (PBC) and AMA-negative PBC with autoantibodies differ histologically, especially with respect to infiltrating cells in portal tracts involved by chronic non-suppurative destructive cholangitis. Liver specimens were stained from 15 primary biliary cirrhosis with AMA (group 1), nine patients consistently negative for AMA but positive for antinuclear antibodies (ANA) (group 2). Group 2 showed overlapping features of PBC and autoimmune hepatitis type 1, in a pattern recently termed autoimmune cholangiopathy (AIC). We analyzed the cell population, including lymphocytes, plasma cells, large histiocytes, eosinophils and neutrophils, which had infiltrated portal tracts involved by destructive lesions. Although serum immunoglobulin M levels were higher in group 1 compared to those in group 2 (P=0.0282), patients of both groups were broadly comparable with respect to clinical features and laboratory data. Histologically, the number of plasma cell and its percentage among inflammatory infiltrating cells in the portal tract were higher in group 2 than in group 1 (P=0.0015, P=0.0070, respectively). The percentage of lymphocyte infiltration among inflammatory infiltrating cells in the portal tract were higher in group 1 than in group 2 (P=0.0052). The percentage of plasma cell infiltration among inflammatory infiltrating cells in the portal tract was correlated to immunoglobulin G levels in group 2 (r=0.949, P=0.0016). In conclusion, AMA-positive PBC and AIC showed differences in inflammatory cell population in involved portal tracts in this preliminary study.
    Hepatology Research 02/2001; 19(1):41-51. · 2.07 Impact Factor
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    ABSTRACT: To determine whether spleen size is related to the severity of esophageal varices or associated gastric varices and liver functions in patients with cirrhosis. The authors retrospectively studied spleen size on CT (splenic index [SI] = length x width x height of the spleen), liver functions, and the results of esophagogastric endoscopy in 110 patients with cirrhosis. They also analyzed SI in 112 controls. In controls, body weight, height, and age affected the SI. The SI in patients with uncompensated cirrhosis was greater compared with the SI in those with well-compensated disease (p = 0.0363). The SI in patients with esophageal varices was greater than in patients without esophageal varices (p<0.0001), but patients with and without gastric varices had similar SI values. The SI in patients with the red color signs (red wale marking, cherry red spot, and hematocystic spot) on esophageal varices or with risky varices (enlarged tortuous varices with beady, nodular, or tumor shape associated with red color signs) was greater than in patients without these signs (p = 0.0029 and p = 0.0030, respectively). The SI is a good indicator of the severity of esophageal varices and hepatic functional reserve in patients with cirrhosis.
    Journal of Computer Assisted Tomography 08/2000; 24(5):788-94. · 1.58 Impact Factor
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    ABSTRACT: The proto-oncogene product bcl-2 is known to inhibit apoptotic cell death, and its dysregulation might play a critical role in the development of autoimmune disease. To elucidate the role of bcl-2 in autoimmune hepatitis (AIH), its expression in peripheral blood mononuclear cells (PBMC) and in liver-infiltrating lymphocytes (LIL) was investigated. Increased bcl-2 expression in PBMC was found in AIH patients compared with that in chronic hepatitis C (CHC) patients and in healthy controls. The level of bcl-2 expression significantly correlated with serum ALT level. Further analysis showed that CD4+ T cells are enriched in bcl-2-expressing PBMC. To characterize the Th1/Th2 profile of bcl-2-expressing CD4+ T cells, intracellular interferon-gamma (IFN-gamma) and IL-4 were analysed. The results revealed that most of the bcl-2-expressing cells were found to be IFN-gamma-secreting Th1 cells. In three patients for whom their clinical courses could be followed, bcl-2 expression was decreased after the initiation of immunosuppressive therapy with corticosteroids. However, the level of IFN-gamma + cells was not altered. Immunohistochemical analysis also showed that large amounts of bcl-2+ cells were observed in periportal area in the liver. In conclusion, bcl-2-expressing cells were shown to be increased in peripheral blood and liver in AIH and the bcl-2 product was expressed mainly in CD4+ Th1-type cells, suggesting that these cells might promote the cellular immune response and contribute to the development of hepatitis and hepatocellular damage in AIH.
    Clinical & Experimental Immunology 05/1999; 116(1):140-5. · 3.41 Impact Factor
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    ABSTRACT: Liver/kidney microsomal type 1 (LKM-1) antibodies described by indirect immunofluorescence using frozen sections of kidney, stomach and rat liver define a group of patients with type 2 autoimmune hepatitis. Sera react with a non-glycosylated 50-kD protein of the endoplasmic reticulum, which was recently identified as cytochrome P4502D6 (CYP2D6). LKM-1 antibodies may also be associated with hepatitis C virus infection (HCV+/LKM-1+). For this subset of patients, the choice of steroids or interferon alpha therapy may be difficult because of the association of hepatitis C virus infection and autoimmune manifestations. Recently we developed a quantitative immunoprecipitation radioligand assay using 35S-methionine-labeled CYP2D6 protein produced by in vitro transcription and translation reaction. This method detects antibodies against linear and conformational epitopes in both AIH-2 and HCV+/LKM-1+ patients. The aim of this study was to analyze the time-course of HCV+/LKM-1+ patients, applying our radioligand assay over a long follow-up. We studied five patients who were positive for CYP2D6 antibodies from among 235 chronic hepatitis C virus hepatitis patients (2.1%) treated with interferon alpha for a minimal follow-up of 2 years. We analyzed LKM-1 antibody titer sequentially by radioligand assay, HCV RNA titer and alanine aminotransferase activity in these patients. We found no aggravation of liver disease in this group of patients. Three of these patients showed a sustained biochemical and virological response after interferon. Two others responded partially to interferon therapy. Alanine aminotransferase levels and HCV-RNA decreased during interferon therapy in responder patients. CYP2D6 antibodies did not change in three responder patients during follow-up. One responder patient decreased CYP2D6 antibody level by radioligand assay, but indirect immunofluorescence titers showed a similar pattern. One partial responder patient decreased CYP2D6 antibody level but was negative by indirect immunofluorescence. Our results show that patients with hepatitis C virus who are positive for CYP2D6 antibodies may be treated with interferon, and respond in the same way as CYP2D6 antibody negative patients. Radioligand assay could be helpful for monitoring HCV+/LKM-1+ patients receiving interferon therapy.
    Journal of Hepatology 07/1998; 28(6):965-70. · 9.86 Impact Factor
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    ABSTRACT: To assess whether demography is one of the important factors determining antibody response to nuclear antigens [ANA: SSA-Ro (52K and 60K), SSB-La, snRNPs (A, 70K, B'/B), and Cenp-B], we investigated 95 and 47 sera of autoimmune hepatitis (AIH) from North America and Asia, respectively, by immunofluorescent (IF) and recombinant ELISA. Correlations among nuclear IF patterns, ELISA, and disease indices were analyzed. The frequency and titer of individual antibodies differed significantly between the groups. Patients with speckled patterns were younger in both regions and had higher aspartate aminotransferase levels only in North America. HLA-A1, B8, DQ2, and DR4 or DR3 or both in North America, and A2, B61, DQ7, and DR4 in Asia were predominant. In Asia, B61 correlated with anti-70K, and DQ7 correlated with antibodies to 52K, Cenp-B, and B'/B. In North America, A1, B8, DR3 haplotype, and DQ2 correlated with antibodies to A and 70K. Anti-B'/B and DR4 in North America, and A2 in Asia, were associated with concurrent immunologic disorder. Individual ANA clusters correlated with individual HLA in the demography, and different HLA alleles might determine disease expression as well as different ANA being produced in AIH.
    Digestive Diseases and Sciences 07/1998; 43(6):1322-31. · 2.26 Impact Factor
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    ABSTRACT: We have recently found that antibodies to total histones are common in a group of American patients with type 1 autoimmune hepatitis (AIH). In an attempt to determine the profile and clinical association of anti-histone antibody (AHA), 45 Japanese AIH patients were studied for serum isotypic reactivity with individual histones (H1, H2A, H2B, H3, H4) by enzyme-linked immunosorbent assay and western blotting. The results revealed that 40% of sera had reactivities with at least one of individual histones and that the antibodies were detected in all three classes of immunoglobulins (IgG, IgM, IgA). Immunoglobulin G type anti-H3 showed the dominant reactivity and it characterized 72% of sera with AHA. The titre of anti-H3 decreased significantly (P < 0.0075) after steroid therapy and the index of decrease for anti-H3 was correlated in individuals with that for serum aminotransferase. In general, patients with AHA showed higher serum level of alanine aminotransferase (P < 0.05), immunoglobulin G (P < 0.025), and higher frequency of A2-DR4 haplotype (53 vs 17%) than their seronegative counterparts. However, the titre of AHA was low in this disease condition and histone class-specific antibodies did not distinguish patients with distinctive clinical features, although patients with anti-H3 tended to be younger than those without AHA.
    Journal of Gastroenterology and Hepatology 06/1998; 13(5):483-9. · 3.33 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/1998; 28:140-140.
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    ABSTRACT: The aims of the current study were to assess the frequency and the significance of antibodies to cytochrome P450IID6 protein (anti-P450IID6) in various diseases among Japanese patients. Sera from 541 patients were tested by indirect immunofluorescence, and the specificity of anti-P450IID6 was ascertained by either enzyme immunoassay (ELISA) or Western blot using recombinant antigen or rat liver microsomes. Anti-P450IID6 was found in only 6 of 235 patients (2.6%) with chronic active hepatitis (CAH) positive for hepatitis C virus (HCV) antibody and quantitative HCV-RNA with genotypes II and IV. The predominant epitopes on immunoblots were 66 and 50KD, a 10KD band being the newly underfined microsomal antigen. Even in the patients negative for autoantibodies to nuclear antigens (ANA) by routine indirect immunofluorescence test, various ANA were detected by the newly developed recombinant ELISA. These patients were younger, with lower gamma-globulin and IgG levels than patients with autoimmune hepatitis. Three of five patients with anti-P450IID6 responded well to interferon therapy and one received prednisone when interferon was ineffective. Interestingly, only this patient was diagnosed as definite autoimmune hepatitis according to the criteria proposed by the International Autoimmune Hepatitis Group (IAHG). The other five patients who did not satisfy the IAHG criteria might be considered as CAH-C with autoimmune features. No autoimmune hepatitis patients positive for anti-P450IID6 were identified in the current study, indicating that the variant is very rare in Japan. Anti-P450IID6 in CAH-C patients in Japan is not as rare as expected. Anti-P450IID6 among Japanese patients has uncertain significance and precludes further characterization of CAH-C with autoimmune features, which might require interferon therapy.
    Journal of Hepatology 06/1997; 26(5):992-1000. · 9.86 Impact Factor
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    ABSTRACT: In order to determine the factors responsible for the differentiation of cytomegalovirus (CMV) hepatitis and Epstein-Barr virus (EBV) hepatitis, the clinical features and laboratory data of both types of hepatitis were retrospectively analyzed in 20 patients with CMV and 11 patients with EBV. While most signs and symptoms of CMV and EBV hepatitis showed no significant differences, we found that cervical lymph- adenopathy was more common in EBV hepatitis than in CMV hepatitis (p < 0.01). Frequency of epigastralgia was more common in CMV hepatitis than EBV hepatitis (p < 0.05). The percentage of peripheral blood monocytes in the white blood cell count in CMV hepatitis was greater than in EBV hepatitis (p < 0.01). Low CD4 levels and high CD8 levels made CD4/CD8 low in peripheral lymphocytes of both groups of hepatitis. Ten EBV hepatitis patients received antibiotics in the early stage of the disease in which two (25%) developed severe erythematous rashes. Four CMV hepatitis patients received antibiotics and did not develop rashes. Identification of early clinical parameters capable of differentiating CMV hepatitis from EBV hepatitis is important.
    Liver International 04/1997; 17(2):63-9.
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    ABSTRACT: Annexin (AX) constitutes a new family of Ca2+-dependent membrane-binding proteins; 13 of them have been described. Among these, annexin-1 (AX-I) has displayed many biological functions in vitro. Its actual role in vivo, however, remains unknown. We already reported that AX-I was expressed in proliferating (regenerating) hepatocytes at both protein and messenger RNA (mRNA) levels. The role of AX-I in human hepatocellular carcinoma (HCC) remains obscure. In this study, the amounts of AX-I at protein and mRNA levels, as well as its localization, have been determined in the normal human liver, chronic hepatitis liver, and nontumorous and tumorous portions of HCC. AX-I was rarely found in normal and chronic liver tissues, whereas it is overexpressed at both the transcriptional and translational levels in tumorous and nontumorous regions of HCC. In addition, more AX-I was expressed in the tumorous portion than the nontumorous portion of HCC. AX-I was present in the hepatocytes and HCC cells, localized mainly in the cytoplasm. AX-I was expressed in poorly differentiated cancer cells. Furthermore, AX-I was tyrosine-phosphorylated in HCC. We also found that some of the AX-I- positive hepatocytes in the nontumorous tissues were derived from a particular subset of parenchymal cells (stem or oval cells). These results indicate that AX-I plays an important role in the malignant transformation process leading to HCC and that it is closely related to the histological grade of HCC. HCC would offer a novel tool with which to study the function of AX-I in malignant transformation.
    Hepatology 08/1996; 24(1):72-81. · 12.00 Impact Factor
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    ABSTRACT: It is believed that blind introduction of an endoscope into the esophagus causes less patient discomfort. The aim of this study was to evaluate the yield and usefulness of endoscopic screening of the hypopharyngeal and laryngeal regions. A total of 1623 patients who underwent upper gastrointestinal endoscopy for gastrointestinal disease between 1987 and 1992 had the instrument introduced under visual guidance, and were retrospectively studied. We found 15 pathological conditions in the throat (0.92%): two small cancers (0.12%), one advanced cancer (0.06%), two hypopharyngeal polyps (0.12%), one cyst (0.06%), and eight cases of lymphoid hyperplasia (0.49%) in the hypopharyngeal region. A large Zenker's diverticulum was detected in one patient (0.06%). All of these cases could have been overlooked if the instrument had been passed blindly through the throat. In patients undergoing upper gastrointestinal endoscopy, the procedure of screening the hypopharyngeal and laryngeal region is justified to detect earlystage disease in these regions.
    Endoscopy 04/1996; 28(3):295-8. · 5.74 Impact Factor
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    International Hepatology Communications 02/1996; 4(5):299.