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Yasushi Seo

Publications and source records attributed to Yasushi Seo.

16 recordsLinked to original sources

Genotype and variations in core promoter and pre-core regions are related to progression of disease in HBV-infected patients from Northern Vietnam.

Vietnam is one of the countries with a high rate of hepatitis B virus (HBV) infection, but there are only a few reports about relation of HBV genotypes and mutations to clinical course in Northern Vietnam. The characteristics of HBV and its relationship to clinical outcome in patients from Northern Vietnam were analyzed. Serum samples were collected from 183 HBV-infected Vietnamese patients. They were clinically categorized into 4 groups: hepatocellular carcinoma (HCC), liver cirrhosis (LC), chronic hepatitis (CH), and asymptomatic carriers (ASC). HBV serology, alpha-fetoprotein, HBV genotypes, HBV-DNA level and mutations in the core promoter and pre-core regions of HBV-DNA were examined. The majority of sera contained HBV genotype B (67.8%) and C (27.9%). The median age was matched between genotype B and C (38.2 vs. 42.9 years). The rates of HBeAg seroconversion and G1896A for genotype B were significantly higher than those for genotype C (P<0.05). Genotype C had a higher HBV-DNA level than genotype B. C1858 was frequent, especially in genotype C (62.7%). The most prevalent genotype in ASC and CH was genotype B. The presence of the mutation A1762T/G1764A correlated with disease progression. The triple mutation T1753C/A1762T/ G1764A was quite common and was more prevalent in LC and HCC than in CH and ASC. In Northern Vietnamese, HBV genotypes B and C were prevalent. Genotype C and mutations in the core promoter region were associated with progressive, severe liver diseases.

Adolescent↗

ADC measurement of abdominal organs and lesions using parallel imaging technique.

OBJECTIVE: The purpose of our study was to assess the reliability and usefulness of parallel imaging for apparent diffusion coefficient (ADC) measurement of abdominal organs and lesions. MATERIALS AND METHODS: Single-shot spin-echo echo-planar diffusion-weighted MRI (TE = 66, b = 0, 600 s/mm2) was performed in phantom and clinical studies. The b value was set to minimize the effects of perfusion in tissue and to maintain signal-to-noise ratio. Bottle phantoms were scanned with and without parallel imaging and with various parallel imaging factors and at various positions to evaluate the effects of parallel imaging on ADCs. In 200 consecutive clinical patients (122 men and 78 women: mean age, 61.9 years), ADCs were calculated for liver (four segments), spleen, pancreas (head, body, tail), gallbladder, renal parenchyma, and back muscle, and then compared to evaluate the reliability of clinical ADC measurements with parallel imaging. ADCs were also calculated for diffuse diseases and focal lesions (94 malignant and 93 benign) of abdominal organs to evaluate the clinical usefulness of ADC. RESULTS: Location-dependent changes in water ADCs were minimal with parallel imaging factors first of 3, then of 4, and were small except for measurements at the image periphery. Acetone ADCs were saturated at 4.00 x 10(-3) mm2/s. Degraded image quality prevented ADC measurement of the left hepatic lobe and pancreas in 7-18 patients. There was no significant difference among ADCs of four liver segments (1.50 +/- 0.24 [SD] x 10(-3) mm2/s - 1.56 +/- 0.31 x 10(-3) mm2/s) and between ADCs of the right and left kidneys (2.65 +/- 0.30 x 10(-3) mm2/s, 2.59 +/- 0.33 x 10(-3) mm2/s). ADC of the pancreas tail (1.65 +/- 0.37 x 10(-3) mm2/s) was significantly lower than those of the head (1.81 +/- 0.40 x 10(-3) mm2/s) and body (1.81 +/- 0.41 x 10(-3) mm2/s) (p < 0.005). Renal ADCs were significantly lower in patients with renal failure (right: 2.15 +/- 0.30 x 10(-3) mm2/s; left: 2.11 +/- 0.25 x 10(-3) mm2/s) than in those without disease (right: 2.67 +/- 0.29 x 10(-3) mm2/s; left: 2.60 +/- 0.32 x 10(-3) mm2/s) (p < 0.005). ADC of pancreatic cancer was significantly higher than that of healthy pancreas (p < 0.05). ADC of renal angiomyolipoma was significantly lower than those of renal cell carcinoma and healthy renal parenchyma (p < 0.0005). CONCLUSION: Clinical ADC measurements of abdominal organs and lesions using parallel imaging appear to be reliable and useful, and the effect of parallel imaging on calculated values is considered to be minimal.

Adult↗

Expression of thioredoxin and thioredoxin-binding protein-2 in the liver of patients with chronic hepatitis C as a predictor of response to interferon therapy.

Oxidative stress contributes to the pathogenesis of various hepatic injuries. Thioredoxin (TRX) is an indicator of oxidative stress, reported to be increased in the serum of patients with chronic hepatitis C with the progression of fibrosis. The aim of this study was to evaluate the clinical significance of the expression of TRX and thioredoxin-binding protein-2 (TBP-2), which is a negative regulator of TRX function, in the liver of patients with chronic hepatitis C and the relationship of this to the efficacy of interferon (IFN) treatment. A retrospective study was performed using the liver biopsy specimens obtained before IFN treatment from 69 patients with chronic serotype 1 hepatitis C virus (HCV) infection. TRX and TBP-2 mRNA levels in the liver biopsy specimens were amplified by real-time RT-PCR. The serum TRX protein level was estimated with a sandwich enzyme-linked immunosorbent assay kit, and the expression of TRX protein in the liver was examined immunohistochemically in 19 patients. There was no association between the serum TRX level and the TRX level in the liver. There was a significant correlation between the expression level of TRX protein in the liver and the TRX mRNA level in the liver. TRX and TBP-2 levels in the liver tended to decrease slightly with increased fibrosis stage, although not significantly. The TRX level in the liver tended to increase with hepatitis activity index, although not significantly. TBP-2 mRNA levels in the liver were significantly higher in responders than non-responders to the IFN therapy (p<0.05). Among patients who had a high viral load of >850 KIU/ml, the TRX level in the livers of non-responders was significantly lower than that in the livers of responders (p<0.05). TRX and TBP-2 mRNA levels in the liver before IFN therapy may predict the outcome of IFN therapy in patients with chronic serotype 1 HCV infection.

Adult↗

Serum hepatitis B virus DNA levels differentiating inactive carriers from patients with chronic hepatitis B.

OBJECTIVE: We compared serum hepatitis B virus (HBV)-DNA levels in different states of hepatitis B infection, and investigated whether there is an HBV-DNA value that can be used for differentiating inactive carriers from patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis. METHODS: A retrospective study using sera at a followed endpoint from 64 Japanese patients with chronic HBV infection seen in Kobe University Hospital between 1989 and 2002. Sera of patients were assayed using a polymerase chain reaction-based assay. RESULTS: Genotype C was dominant (95.4%). Patients with chronic hepatitis with an elevation of the serum alanine aminotransferase (ALT) level had significantly higher HBV-DNA levels than patients with persistently normal ALT. For one time observation at a followed endpoint, the mean HBV-DNA level of HBeAg-negative inactive carriers was significantly lower than that of HBeAg-negative chronic hepatitis patients (3.6+/-1.0 versus 4.8+/-1.5 log copies/ml, P<0.005). The use of a cutoff value of 4.5 or 5.0 log copies/ml misclassified 23 and 18% of HBeAg-negative inactive carriers and 50 and 55% of patients with HBeAg-negative chronic hepatitis. If testing were performed on two occasions with approximately a 4-month interval, the cutoff values of 4.5 and 5.0 log copies/ml would misclassify 20 and 10% of HBeAg-negative inactive carriers and 28.6 and 28.6% of patients with HBeAg-negative chronic hepatitis. CONCLUSIONS: The measurement of serum HBV DNA more than twice is useful for assessing chronic hepatitis B surface antigen carriers and confirms that 10 copies/ml may be an appropriate level of HBV for characterizing the inactive carrier state.

Adult↗

Long-term follow-up of Japanese patients with chronic hepatitis B treated with interferon-alpha.

The long-term usefulness of interferon-alpha (IFN-alpha) in chronic hepatitis B remains controversial. To investigate the long-term efficacy of IFN-alpha therapy in chronic hepatitis B, 62 Japanese patients, including 27 patients treated with IFN-alpha (IFN group) and 35 patients without antiviral therapy matched by age and sex as controls (control group), were followed up for 2-14 years. At entry, the serum alanine aminotransferase (ALT) level in the IFN group was significantly higher than that in the control group (238.6+/-250.1 vs. 142.3+/-152.1 IU/l, P < 0.05). The prevalence of genotype C was 89%, with no difference between the two groups (93 vs. 86%). There was no significant difference in the presence of the precore mutation or the dual core promoter mutations between the IFN and control groups (37 vs. 46%, 74 vs. 66%). After long-term follow-up, the rate of sustained HBeAg seroconversion was comparable in the two groups (33 vs. 31%). Normalization of serum ALT level was seen in 44% of the IFN group and 51% of the control group, with no difference. There was also no difference in the percentage of cases with loss of serum HBV-DNA by PCR assay between the two groups (33 vs. 29%). During follow-up, two patients of the control group and three patients of the IFN group developed cirrhosis, and one of the IFN- treated patients progressed to hepatocellular carcinoma. The results of this long-term follow-up study showed that no benefit of IFN-alpha treatment was detectable during long-term follow-up in Japanese patients with chronic hepatitis B.

Adult↗

High expression of PRL-3 promotes cancer cell motility and liver metastasis in human colorectal cancer: a predictive molecular marker of metachronous liver and lung metastases.

PURPOSE: Overexpression of PRL-3 has been implicated in colorectal cancer metastases. We investigated the significance of PRL-3 expression in the progression and development of colorectal cancer. EXPERIMENTAL DESIGN: We transfected PRL-3-specific small interfering RNA into human colon cancer DLD-1 cells and analyzed its effect on proliferation, motility, and hepatic colonization. Using an in situ hybridization method, we examined the levels of PRL-3 expression in both primary (177 cases) and metastatic (92 cases) human colorectal cancers and elucidated the relationships with clinicopathological parameters including the incidence of metachronous liver and/or lung metastasis after curative surgery for primary tumor. RESULTS: Transient down-regulation of PRL-3 expression in DLD-1 cells abrogated motility (in vitro) and hepatic colonization (in vivo), but no effect on the proliferation of these cells was observed. In human primary colorectal cancers, the frequency of up-regulated PRL-3 expression in cases with liver (84.4%) or lung (88.9%) metastasis was statistically higher than that in cases without either type of metastasis (liver, 35.9%; lung, 42.3%). In metastatic colorectal cancer lesions, high expression of PRL-3 was frequently detected (liver, 91.3%; lung, 100%). Interestingly, metachronous metastasis was observed more frequently in the cases with high PRL-3 expression (P < 0.0001). CONCLUSIONS: These results indicate that PRL-3 expression in colorectal cancers may contribute to the establishment of liver metastasis, particularly at the step in which cancer cells leave the circulation to extravasate into the liver tissue. In addition, PRL-3 is expected to be a promising biomarker for identifying colorectal cancer patients at high risk for distant metastases.

Aged↗

Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-1 (E-NPP1/PC-1) and -3 (E-NPP3/CD203c/PD-Ibeta/B10/gp130(RB13-6)) in inflammatory and neoplastic bile duct diseases.

Ecto-nucleotide pyrophosphatase/phosphodiesterase-I enzyme (E-NPP) consists of three closely related molecules: E-NPP1, E-NPP2 and E-NPP3. We investigated the expression and localization of E-NPP1 and -3 in human inflammatory and neoplastic bile duct diseases. Immunohistochemically E-NPP1 was located on the apical cytoplasmic side of cancer cells, whereas E-NPP3 was located in the apical plasma membrane. Western blot analysis revealed that the expression of E-NPP3, but not E-NPP1, was higher in tumor tissues than in surrounding tissues and the specific form of the E-NPP3 protein was readily detected in the sera of bile duct carcinoma (BDC) patients. Furthermore, it was confirmed that E-NPP3 was associated with migration ability by using of NIH3T3 cells that stably transfected with E-NPP3 cDNA. These results suggest that E-NPP3 is involved in the infiltration of neoplastic BDC and is possible to be a tumor marker.

Animals↗

Apoptotic pathway related to oval cell proliferation.

BACKGROUND AND AIM: Oval cells, liver stem cell-derived cells, are generated from the liver periportal region and spread into the parenchyma by an autocrine signaling pathway. The mechanism behind how oval cells take their place among packed silent hepatocytes, however, is not well understood. We hypothesized that apoptosis involves a decrease in hepatocytes surrounding oval cells. METHODS: Male Fisher rats were treated using the AAF/PH protocol to induce oval cells in the liver. Apoptosis was assessed by measuring the activity of caspase-3, -8 and -9, and apoptosis-related molecules such as caspase-3, Fas, Fas-L and Bax were also assessed by immunohistochemical analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). Apoptosis was confirmed by TUNEL staining. Regarding antiapoptotic factors, nuclear factor-kappaB (NF-kappaB) DNA binding activity and proliferating cell nuclear antigen (PCNA) expression were examined. RESULTS: NF-kappaB elevated at the early stage of oval cell proliferation. Conversely, caspase activity increased after NF-kappaB elevation. The mRNA of caspase-3, Fas, Fas-L and Bax was induced during and after AAF/PH treatment. Immunohistochemically, oval cells lacked the expression of these proteins, whereas the hepatocytes, particularly those surrounding oval cells, expressed strongly. CONCLUSIONS: The present study suggests that the apoptosis in hepatocytes through both extrinsic and intrinsic pathways mediates oval cell proliferation.

Animals↗

Early response to interferon alpha treatment and long-term clinical outcome in Japanese patients with chronic HBV genotype C infection.

Genotype C of hepatitis B virus (HBV) has been shown to be associated with a poor clinical outcome and less favorable response to interferon (IFN) alpha therapy compared to genotype B. We evaluated the response to IFN alpha therapy and long-term clinical outcome in Japanese patients with chronic active HBV genotype C infection. Thirty Japanese patients with chronic active hepatitis who received natural IFN alpha therapy were followed for 2-12 years (mean 5.9 years). Twenty-four patients were treated short-term (daily for 4 weeks at a mean total dosage of 174 million units) and 6 patients were treated long-term (total of 26 weeks at a mean total dosage of 687 million units). Twelve of 30 (40%) patients had an antiviral response at 6 months after therapy. Clinical data before treatment in both responders and non-responders were comparable. Although not significant, responders tended to have younger age, a higher serum transaminase level, a lower frequency of precore mutation (G1896A) (67% vs. 92%) and a higher frequency of core promoter mutation (A1762T/G1764A) (89% vs. 58%) than non-responders. The patients treated long-term responded significantly better than those treated short-term (83% vs. 29%, P=0.026). Up to 12 years after therapy, a higher percentage of responders than non-responders had sustained clearance of HBeAg with seroconversion and normalization of transaminase concentration at the followed end point (83% vs. 17%, P<0.001). Two non-responder patients had cirrhosis after long-term follow-up. One non-responder patient died of hepatocellular carcinoma 8 years after IFN therapy; except in this patient there was no development of decompensated cirrhosis. Early responsiveness to IFN alpha therapy in Japanese patients with chronic active HBV genotype C infection improves the long-term clinical outcome.

Adult↗

IFN-alpha prevents the growth of pre-neoplastic lesions and inhibits the development of hepatocellular carcinoma in the rat.

Interferon (IFN)-alpha treatment is a common therapy for chronic viral hepatitis and contributes to preventing hepatocarcinogenesis. However, it is not clear whether IFN-alpha directly inhibits the clonal expansion of pre-neoplastic hepatocytes. To clarify the mechanism by which IFN-alpha prevents hepatocarcinogenesis, we examined the effect of IFN-alpha in a chemically induced hepatocarcinogenesis model initiated by diethylnitrosamine (DEN) and promoted by 2-acetylaminofluorene (2-AAF) and partial hepatectomy, in which hepatocellular carcinoma (HCC) arises through pre-neoplastic foci without inflammation or fibrosis. The protocols of IFN-alpha administration were started simultaneously with chemical initiation and lasted for either 4 or 40 weeks. The pre-neoplastic foci and neoplastic HCC were evaluated at 4 or 40 weeks after chemical initiation, respectively. The effects of IFN-alpha were assessed by the expression of tumor-related genes and cell cycle-related genes in the pre-neoplastic foci, using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). As a result of IFN-alpha treatment, the numbers and average volume of pre-neoplastic foci were reduced. The proliferating cell nuclear antigen index and the expression of G(1) cyclins were also reduced in the pre-neoplastic foci in the IFN-treated group. The expression of p21, which is an inhibitor of cyclin-kinase complexes was higher in the foci of the IFN-treated group, while p53 expression was not altered in this group, compared with the control group. IFN-alpha also suppressed the tumor development at 40 weeks after initiation. And in the long-term IFN-alpha-treated group, both the tumor numbers and average tumor size were markedly more reduced than those in the short-term-treated group. Therefore, it was demonstrated that longer treatment with IFN-alpha was more effective, compared with shorter treatment. In conclusion, it was shown that IFN-alpha directly prevented and delayed hepatocarcinogenesis through the suppression of pre-neoplastic cell proliferation and that it may partially depend on p21 induction through a p53-independent pathway.

Animals↗

Hepatitis B virus DNA in anti-HBe-positive asymptomatic carriers.

OBJECTIVES: We examined the level of hepatitis B virus (HBV) DNA and the mutations in the precore, core and polymerase regions of HBV in sera from anti-HBe-positive asymptomatic carriers (ASC). METHODS: The amount of HBV DNA was determined semiquantitatively by mutation site-specific assay in sera from 19 anti-HBe-positive ASC and 31 HBeAg-positive patients with chronic liver disease (CLD). The mutations in the precore, core and polymerase (terminal protein) regions, spanning 1,037 nucleotides, of HBV in sera from three cases each of anti-HBe-positive ASC, HBeAg-positive ASC and HBeAg-positive CLD were examined by directly sequencing the amplified HBV DNA. RESULTS: The level of HBV viremia in anti-HBe-positive ASC was significantly lower than that in HBeAg-positive CLD patients (p < 0.01). By sequence analysis, there were a few missense mutations detected in HBeAg-positive ASC and HBeAg-positive CLD patients. In contrast, many mutations, especially in the central or N-terminal half of the core region and N-terminal part of the polymerase region, were detected in anti-HBe-positive ASC. CONCLUSION: Mutations not only in the precore/core region, but also in the polymerase region of HBV might cause damage to some important functions for efficient replication of HBV and be involved in the reduced amount of HBV in anti-HBe-positive ASC.

Adult↗

Different apoptotic regulation of TRAIL-caspase pathway in HBV- and HCV-related hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) appears to be strongly associated with apoptosis and its breakdown may be involved in the occurrence of HCC. Like the Fas/Fas-L system, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) transduces apoptosis in a number of cancers; it is also a clinical candidate for cancer therapy. To examine its applicability in future therapy, the apoptotic pathway through TRAIL was investigated in HBV- and HCV-related HCC that have different mechanisms of hepatocarcinogenesis. Caspase-3 activity and the expression of four types of TRAIL receptor mRNAs were quantitated in tumor and contiguous non-tumor tissues obtained from 27 patients with HCC (HBV-related in 10; HCV-related in 17). The expression of caspase-3 and TRAIL receptors was also examined immunohistochemically. A significantly positive correlation was observed between caspase-3 activity and TRAIL-R1, -R2. Caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue were significantly lower than those in non-tumor tissue in HBV-related HCC. Some HCV-related HCC cases, however, demonstrated elevated caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue. HBV-related HCC demonstrated significantly suppressed caspase-3 activity, signifying apoptosis. Both TRAIL-R1 and -R2 showed coefficient correlation with caspase-3 activity, and were strongly associated with apoptosis in human HCC.

Apoptosis↗

A case of well-differentiated hepatocellular carcinoma arising in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic progressive, autoimmune liver disease that increases the risk of hepatobiliary malignancies at a late stage. We report a 66-year-old woman with PBC combined with hepatocellular carcinoma (HCC) accompanied by hypoglycemia. Two large tumors were detected on admission and the patient died because of tumor rupture and subsequent liver failure. Histological analysis revealed well-differentiated HCC in both of the tumors. Sometimes the patient had suffered from hypoglycemic attacks of unknown origin, but serum immunoreactive insulin (IRI) was within the normal range. It was interesting that such large well-differentiated hepatocellular carcinomas were generated in PBC.

Aged↗

Histological grading and staging in chronic hepatitis: its practical correlation.

Although the histological features of various causes of chronic liver disease have been well described, usually the inflammatory activity of the disease is important after the cause has been established. Some patients have co-infection or concomitant liver disease and on occasion it is difficult to decide the treatment. In order to clarify the histological differences, we investigated the inflammatory activity among autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), chronic hepatitis C (CHC) and chronic hepatitis B (CHB) in a standardized way using the modified histological activity index (HAI). According to the modified HAI, inflammatory activity is divided into four categories; categories A/D explains portal/periportal inflammation and categories B/C explains lobular activity. The inflammatory score of AIH tended to be greater in all categories from the early stage of fibrosis, whereas scores of PBC were lower, except for portal inflammation. Chronic hepatitis C patients had portal or periportal inflammation, and their inflammatory scores were linked to the development of fibrosis. Chronic hepatitis B patients tended to have severe lobular injury, but did not have a relationship between the inflammatory score and their stage. To know the distribution of inflammation using the modified HAI scoring system may be helpful and convenient in evaluating patients with chronic inflammatory liver disease.

Adult↗

Response to interferon-alpha in chronic hepatitis B with and without precore mutant strain detected by mutation site-specific assay.

GOALS: We investigated whether the presence of precore mutant (stop codon mutation at codon 28) affects the response to interferon-alpha in patients with chronic hepatitis B. BACKGROUND: Mutations of hepatitis B virus (HBV) may influence the response to treatment. The association of precore mutant with the response to interferon is controversial. STUDY: Thirty-one Japanese patients with hepatitis B e antigen-positive chronic hepatitis were treated with natural interferon-alpha. HBV DNA with the precore mutation was assayed in serum using a mutation site-specific assay before and after treatment. RESULTS: Before treatment, precore mutant was detected in 22 cases (group A) and not detected in 9 cases (group B). Serum HBV DNA level before treatment was not different between the 2 groups. At the end of treatment, serum HBV DNA was decreased to undetectable levels in 13% (4 of 31). Six months after treatment, the percentage of cases with loss of hepatitis B e antigen and a decrease in the transaminase level to within the normal range was significantly higher in group B than in group A (67%, 18%, P = 0.015). CONCLUSIONS: Chronic hepatitis without precore mutant strain before treatment is more responsive to IFN-alpha.

Adult↗

Evaluation of the therapeutic effect using MD-CT immediately after RFA for HCC.

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is an effective modality for treatment of hepatocellular carcinoma (HCC), because it can induce large coagulation necrosis in a few sessions. The aim of this study is to evaluate whether we can assess the therapeutic effect of RFA immediately after RFA. METHODOLOGY: Twenty-one patients (25 nodules) with HCC undergoing RFA treatment were enrolled in this study. Fourteen patients were treated with combination therapy of lipiodol chemoembolization and RFA, while 7 patients were treated with RFA alone. Dynamic computed tomography (CT) using multidetector row helical CT (MD-CT) was performed before, immediately after and 1 week after RFA. Simultaneously, multiplanar reconstruction (MPR) images were also obtained for comparison. RESULTS: With or without chemoembolization, the size of coagulated necrosis was almost the same between the time immediately after and 1 week after RFA. The therapeutic effect was able to be evaluated by dynamic CT scans immediately after RFA in all patients. Moreover, MPR images facilitate the detailed evaluation of the therapeutic effect. CONCLUSIONS: Examination of dynamic CT using MD-CT immediately after RFA is useful to evaluate the therapeutic effect and may enable a shorter hospital stay.

Aged↗