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H Yatsuhashi

Publications and source records attributed to H Yatsuhashi.

At least 19 recordsLinked to original sources
PubMed2005

An active metabolite of leflunomide, A77 1726, inhibits the production of serum amyloid A protein in human hepatocytes.

OBJECTIVE: Cytokine-induced hepatic serum amyloid A (SAA) synthesis is the critical step in the pathogenesis of AA amyloidosis secondary to rheumatoid arthritis (RA). This study was conducted to provide more insight into the mechanism of SAA production in hepatocytes and its regulation. METHODS: Primary cultured normal human hepatocytes were stimulated with cytokines (IL-1beta, TNF-alpha and IL-6) and the culture supernatants were analysed for the production of SAA. Human hepatocytes, treated or not treated with A77 1726, were stimulated with IL-1beta and the cellular lysates were analysed by immunoblot using anti-phospho-specific mitogen-activated protein kinase (MAPK) and IkappaB-alpha. Acute phase-SAA (SAA1) mRNA expression was analysed by reverse transcription-polymerase chain reaction. RESULTS: IL-1beta is a most potent inducer of SAA in normal hepatocytes. A77 1726 suppressed the production of SAA in human hepatocytes activated by IL-1beta in a dose-dependent manner (0-50 microM). A77 1726 inhibited IL-1beta-induced p38 and c-Jun N-terminal kinase 1/2 (JNK1/2) activation, whereas A77 1726 did not affect IL-1beta-induced NF-kappaB activation in hepatocytes. CONCLUSION: These results indicate that MAPK signalling pathways are critical in IL-1beta-induced hepatic SAA synthesis. Leflunomide may suppress SAA synthesis by affecting these pathways and may therefore have some beneficial effect on AA amyloidosis secondary to RA.

Aniline Compounds↗
PubMed2005

Reduced blood BDCA-2+ (lymphoid) and CD11c+ (myeloid) dendritic cells in systemic lupus erythematosus.

Type 1 IFN is thought to be implicated in the autoimmune process of SLE. Plasmacytoid dendric cells (DC), which are natural IFN-alpha producing cells, play a pivotal epipathogenic role in SLE. The present study was undertaken to investigate the phenotypic characteristics of peripheral blood DC in SLE patients in comparison with those of healthy controls. Samples from 20 SLE patients and 18 healthy controls were studied. Three-colour flow cytometry was performed to identify myeloid DC, as CD11c(+) lineage marker(-), and HLA-DR(+) cells and plasmacytoid DC, as BDCA-2(+) linage marker(-), and HLA-DR(+) cells. We used the whole blood 'lyse/no-wash' procedure, which allows precise counting of peripheral blood DC. BDCA-2(+) plasmacytoid DC and CD11c(+) myeloid DC were reduced in SLE patients compared with controls. Similarly, BDCA-3(+) DC were reduced in SLE patients. These results indicated that SLE patients had a reduced number of both BDCA-2(+) plasmacytoid DC and CD11c(+) myeloid DC. These alternations of the DC subset may drive the autoimmune response in SLE.

Adult↗
PubMed2005

Ultrasound evaluation of the fibrosis stage in chronic liver disease by the simultaneous use of low and high frequency probes.

A liver biopsy is currently considered the definitive diagnostic modality for establishing the severity of hepatic fibrosis. We analysed the diagnostic sensitivity and accuracy of ultrasound (US) using both low frequency and high frequency probes as a repeatable, inexpensive, and reliable method to determine the fibrosis stage in chronic liver disease and then compared our results with the histological findings. A total of 103 patients with chronic liver disease (60 males and 43 females, average age 51 years old) who had undergone both a liver biopsy and US with 2-5 MHz frequency and 5-12 MHz frequency probes were prospectively evaluated in this study. An US scoring system using both the low frequency and high frequency probes was performed by evaluating the edge, surface and parenchymal texture of the liver. Each score was obtained by evaluating three parameters; the bluntness of the liver edge, the irregularity of the surface and the coarseness of the parenchymal texture were evaluated and then compared with the histological findings. The US scores of the liver edge (rs: 0.6668), liver surface (rs: 0.9007) and liver parenchymal texture (rs: 0.8853) correlated significantly with the fibrosis stage obtained based on the biopsy findings. The accumulated US scores of these three parameters, however, was found to be the most reliable indicator (rs: 0.9524). Patients with an accumulated score of 6.5 or more were all found to have fibrosis stage 4 in which the accuracy of our scoring system for correctly predicting cirrhosis was found to be 100% sensitive. When an accumulated US score of 3 was interpreted to indicate mild fibrosis (a fibrosis score of 0 or 1), all 42 patients with stage 0 or 1 fibrosis were found to have an accumulated US score of 3 or less (a probability of 100%) and 42 of 53 patients with a score of 3 or less were found to have stage 0 or 1 fibrosis (specificity of 79.2%). An ultrasound evaluation of the liver fibrosis stage based on the scoring system using both low and high frequency probes was found to be a reliable and effective alternative to the histological staging in chronic liver diseases.

Biopsy↗
PubMed2004

Suppressive effect of leflunomide metabolite (A77 1726) on metalloproteinase production in IL-1beta stimulated rheumatoid synovial fibroblasts.

Leflunomide, an isoxazol derivative structurally unrelated to other immunomodulatory drugs, has proven to be efficacious in the treatment of rheumatoid arthritis (RA). This study was conducted to elucidate the mechanism by which leflunomide mediated antirheumatic effects. We investigated the effects of A77 1726, leflunomide's active metabolite, on mitogen-activated protein kinase (MAPK) activation in IL-1beta-stimulated rheumatoid synovial fibroblasts. The effects of A77 1726 on the secretion of matrix metalloproteinases (MMPs) from rheumatoid synovial fibroblasts were also examined. A77 1726 partially suppressed IL-1beta-induced ERK1/2 and p38 kinase activation. In contrast, A77 1726 efficiently suppressed IL-1beta-stimulated JNK1/2 kinase activation. Although no suppressive effect was demonstrated on MMP-2, A77 1726 markedly inhibited MMP-1, 3, and 13 secretions from IL-1beta-stimulated rheumatoid synovial fibroblasts. Tissue inhibitor of metalloproteinases-1 (TIMP-1) was constitutively produced from rheumatoid synovial fibroblasts and the suppressive effects of A77 1726 on TIMP-1 production were minimal. Our results suggest that the suppression of the MAPK signalling pathway and MMP synthesis in rheumatoid synovial fibroblasts is a possible mechanism for the inhibitory activity of leflunomide against rheumatoid arthritis.

Aniline Compounds↗
PubMed2001

[The present state and problems of HCV blood screening system in blood products].

After discovering HCV antibody in 1989, the new cases of posttransfusion hepatitis C has been rare. This HCV antibody screening system provided certainly the powerful preventive effect from HCV infection through blood products. But it was possible to infect HCV through the blood products without HCV antibody but with HCV-RNA. This phenomenon seemed to be observed in a window period between time at infection and antibody appearance. To detect the infectious source at a window period in blood products, NAT(nucleic acid amplification) method was adapted recently in Japanese red cross. For safe blood screening system, continuous efforts such as NAT will be needed forever.

Biomarkers↗
PubMed2001

[HCV infection in medical environments].

Since the discovery of the hepatitis C virus(HCV), it has become evident that this infectious agent is a primary cause of posttransfusion and sporadic non-A, non-B hepatitis. Populations at risk for HCV infection include health care workers, infants born to HCV-infected mothers, hemodyalysis patients, and intravenous drug abusers. Because there currently is no HCV vaccine or specific immunoglobulin against HCV, prevention of exposure remains the only possibility for reducing HCV transmission and prevalence. However, the percentage of individuals who are positive for HCV antibody among health care workers is not significantly high, suggesting that health care workers are not at very high risk of HCV infection. Too much fear of HCV infection among the health care workers should be avoided.

Cross Infection↗
PubMed2000

Prospective analysis of risk factors for early intrahepatic recurrence of hepatocellular carcinoma following ethanol injection.

BACKGROUND/AIM: Time-dependent intrahepatic recurrence of hepatocellular carcinoma is frequent after different treatment modalities, including percutaneous ethanol injection. We attempted to prospectively analyze the possible risk factors for early intrahepatic recurrence of hepatocellular carcinoma after percutaneous ethanol injection. METHODS: Sixty-five patients with 65 solitary hepatocellular carcinoma nodules < or =6 cm in diameter underwent initial treatment with percutaneous ethanol injection and were examined to ascertain the factors related to recurrence, local and distant, within the liver. A number of clinical and tumor parameters were analyzed. RESULTS: Cumulative overall recurrence rates 12 and 24 months after percutaneous ethanol injection were 15.6% and 45.1%, respectively, irrespective of clinical and tumor parameters. Overall recurrence rates 12 and 24 months after percutaneous ethanol injection were 40% and 67.5%, for tumor > or =3 cm and 7.5% and 37.5%, for tumor <3 cm. Cumulative local recurrence rates at 12 and 24 months were 26.3% and 43.5%, respectively, for tumor > or =3 cm and 11.7% and 18.2%, respectively, for tumor <3 cm. The log-rank test indicated that a tumor size of > or =3 cm and the presence of capsule for a tumor of <3 cm in diameter were significant risk factors for intrahepatic recurrence. A pretreatment serum PIVKA-II level of > or =0.02 AU/ml was the only clinical parameter associated with overall recurrence (p=0.0041) and distant intrahepatic recurrence (p=0.0307). Distant intrahepatic recurrence rates 12 and 24 months after percutaneous ethanol injection were 22.5% and 31.4%, respectively, for PIVKA-II levels of > or =0.02 AU/ml and 8% and 17.8%, for PIVKA-II of <0.02 AU/ml. Cox's proportional hazard model identified that tumor size, tumor capsule and baseline serum PIVKA-II levels were independently related to intrahepatic recurrence. CONCLUSIONS: These data demonstrate that tumor size and peritumoral capsule were associated with overall and local recurrence of hepatocellular carcinoma. Moreover, pretreatment serum levels of PIVKA-II can indicate the risk of early intrahepatic recurrence and may assist in patient selection and appropriate therapy.

Adult↗
PubMed2000

Detection of HBV RNA in peripheral blood mononuclear cells in patients with and without HBsAg by reverse transcription polymerase chain reaction.

We examined RNA of hepatitis B virus (HBV) in peripheral blood mononuclear cells (PBMCs) by the reverse transcription polymerase chain reaction (RT PCR) in 61 patients associated with HBV infection, in order to analyze the relationship between the transcriptional activity of HBV in PBMCs and the clinical characteristics. The presence of HBV RNA in PBMCs was detected in 19/51(37.1%) patients with HBsAg positive and in 1/10 (10.0%) patient with HBsAg negative patients. Six healthy controls were all negative. The frequency of HBV RNA positivity was detected in patients with high ALT level (P<0.05), serum HBeAg positivity (P<0.01) and serum HBV DNA level>/=0.7 Meq/ml (P<0.05). Moreover, HBV RNA in PBMCs was detected in one patient followed up for 2 years after HBsAg disappearance in serum, who had not HBV DNA but anti-HBc IgG, in serum. These results suggested that the transcription of HBV in PBMCs, was frequently detected in the patients with higher replication of the virus, but HBV RNA in PBMCs might be detected in a few patients who had no evidence of HBV replication serologically.

Journal Article↗
PubMed2000

Proposed abdominal sonographic staging to predict severity of liver diseases: analysis with peritoneoscopy and histology.

Abdominal sonography is a routinely used noninvasive modality for screening and treatment of liver diseases. We attempted to establish a morphological sonographic staging to predict the severity of liver diseases with their consequent analysis with morphological staging of peritoneoscopy and histology. In all, 136 patients were enrolled for the final confirmation of disease state by peritoneoscopy and histology preceded by abdominal sonography. All patients were categorized from stage 0 to stage 5, depending on a proposed criterion of sonographic features based on surface pattern of liver and the appearance of internal echogenic bands relating to the irregularity of the liver texture. A digitized computer quantitation of histogram-based standard deviation (SD) values from different stages of sonographic images was analyzed, and their values were justified by correlation with the definite appearance of an internal echogenic band. The association of different sonographic stages with disease progression was also demonstrated by their relation with peritoneoscopy and histology. In all patients, the different sonographic staging results were significantly correlated with hepatic surface features of peritoneoscopic staging (r = 0.939, P < 0.0001) graded from stage 0 to stage 5 and were also correlated with biopsy-proven staging of fibrosis (r = 0.739, P < 0.0001). The greater SD values of histogram-based echo levels, as analyzed from digitized sonographic images of 90 patients, were associated with the appearance of internal echogenic bands (P < 0.0001). Furthermore, the corresponding SDS were significantly correlated with the qualitative staging of sonographic features (r = 0.781, P < 0.0001), peritoneoscopy (r = 0.786, P < 0.0001) and histology (r = 0.779, P < 0.0001). We concluded that our proposed sonographic staging is well correlated with peritoneoscopic and histological staging of liver diseases, with only a small discrepancy, and can be used clinically to demonstrate the ongoing severity of liver diseases.

Abdomen↗
PubMed2000

Natural history of chronic hepatitis C.

The natural history of chronic hepatitis C is one of a slow progression from early stage chronic hepatitis without fibrosis to cirrhosis or hepatocellular carcinoma (HCC). The disease progresses to advanced stage chronic hepatitis C over 10-30 years. Data from Japan indicate that mortality associated with chronic hepatitis C results mainly from the development of HCC. We studied 186 patients referred between 1968 and 1994. The mean follow-up interval was 8.6 (2-23) years. HCC developed in 34 patients (18%). The cumulative probability of HCC development was 4% at 5 years, 18% at 10 years and 45% at 15 years. Univariable analysis indicated that age at entry, fibrosis stage, inflammation activity and the status of IFN treatment (treated vs untreated) were predictive risk factors for developing HCC in patients with chronic hepatitis C. Multivariable analysis of these risk factors indicated that age at entry (> 50 vs < 50; Risk Ratio = 3.2, P< 0.005) and fibrosis stage (F3 vs F0; Risk Ratio= 5.6, P< 0.005) are independent risk factors for HCC. From these results it was concluded that (1) 20% of patients referred to liver clinics with chronic hepatitis C in Japan can be expected to develop HCC over a 10 year period; (2) the risk of HCC increases with progression of liver fibrosis (F3, F4) and age (greater than 50 years old) at the time of diagnosis and (3) the degree of liver fibrosis is a critical predictive factor for the occurrence of HCC.

Adolescent↗
PubMed1999

Immunohistochemical analysis of hepatic interferon alpha-beta receptor level: relationship between receptor expression and response to interferon therapy in patients with chronic hepatitis C.

BACKGROUND/AIMS: This study aimed to determine the expression level of interferon alpha/beta (IFN-alpha/beta) receptor in the liver immunohistochemically and evaluate its usefulness in predicting the outcome to IFN therapy in patients with chronic hepatitis C. METHODS: The level of IFN-alpha/beta receptor expression was determined in immunoperoxidase-stained pretreatment sections of 55 chronic hepatitis C patients later treated with IFN. We used liver biopsy specimens and mouse monoclonal anti-human IFN-alpha/beta receptor antibody. Quantitative analysis of immunostaining was performed by image analysis software. The level of IFN-alpha/beta receptor was expressed as Unit (U). Sustained responders were patients who showed persistent disappearance of serum HCV-RNA during the 6-month period after treatment, while non-responders showed persistence of viremia after therapy. RESULTS: Positive immunostaining was observed in the cytoplasm of hepatocytes. The mean expression level of hepatic IFN-alpha/beta receptor in sustained responders (2.65+/-1.11 U, n = 15) was significantly (p<0.001) higher than in non-responders (1.61+/-1.05 U, n = 40). A significant decrease in IFN-alpha/beta receptor expression level was observed in patients with advanced liver fibrosis. In patients with low level viremia (pretreatment serum HCV-RNA <1 Meq/ml, n = 18), the level of IFN-alpha/beta receptor in sustained responders (2.89+/-1.12 U, n = 11) was significantly (p<0.01) higher than in non-responders (0.93+/-0.33 U, n = 7). CONCLUSIONS: Our results suggest that measurement of the level of hepatic IFN-alpha/beta receptor in patients with chronic hepatitis C might be useful for predicting the response to IFN therapy. Resistance to IFN therapy in patients with chronic hepatitis C might be due to low levels of hepatic IFN-alpha/beta receptor.

Adult↗
PubMed1999

Prevalence and clinical characteristics of TT virus (TTV) in patients with sporadic acute hepatitis of unknown etiology.

BACKGROUND/AIMS: Recently, a novel DNA virus was isolated from the serum of a patient with post-transfusion non-A-G hepatitis and named TT virus. The aim of this study was to determine the prevalence and clinical characteristics of TT virus infection in patients with sporadic acute hepatitis of unknown etiology. METHODS: TT virus was investigated in the serum of 66 patients with sporadic acute hepatitis non-A-G and 50 healthy controls by semi-nested PCR with previously published primers. RESULTS: TT virus was detected in 17 (26%) of the 66 patients with sporadic acute hepatitis non-A-G and in a slightly higher rate (34%,17/50) in the control group. No significant differences in alanine aminotransferase or bilirubin concentrations were observed between the groups of patients with or without TT virus infection. Eighty per cent (12/15) of patients for whom follow up was possible had persistent viremia from 4 to 36 months, and 67% (8/12) of these patients had already normalized their levels of alanine aminotransferase. A phylogenetic tree constructed by the Neighbor Joining Method revealed that all isolates in this study were grouped within genotype 1a and 1b, without showing any association between genetic type and development of hepatic disease. CONCLUSIONS: Our results suggest that TT virus DNA is present not only in patients with sporadic acute hepatitis non-A-G but also in a large proportion of the general population. This virus was not likely to be the causative agent of hepatitis among the patients in this study.

Acute Disease↗
PubMed1999

[Clinical characteristics and incidence in acute non A-G hepatitis].

We investigated clinical characteristics and incidence of patients with acute non-A-G hepatitis, who were all registered in 17 Japanese National Hospitals. Seven hundreds thirty-one (24.0%) of 3052 patients with sporadic acute hepatitis and 73 (21.2%) of 344 patients with posttransfusion acute hepatitis were diagnosed as acute non-ABC hepatitis. Patients with acute non-ABC hepatitis were older (Mean +/- SD, 44 +/- 15 years) and male/female ratio was 0.70. Although mean levels of liver function abnormality was generally mild, 4(1.8%) of 250 patients with acute non-ABC hepatitis were died of fulminant hepatitis.

Acute Disease↗
PubMed1999

[HBV-DNA].

Explore the source record for details and available documents.

DNA, Viral↗
PubMed1998

Association of mutations in the core promoter and precore region of hepatitis virus with fulminant and severe acute hepatitis in Japan.

It was recently reported that mutations in the precore and core promoter region of hepatitis B virus (HBV) are associated with fulminant hepatitis. The aim of this study was to investigate the association of mutations in the precore and core promoter region of HBV with fulminant and severe acute hepatitis. We studied Japanese patients with acute HBV infection, including seven patients with fulminant hepatitis, 12 with severe acute hepatitis and 41 with acute self-limited hepatitis. The presence of HBV mutants was examined by using a point mutation assay to detect a G to A transition at position 1896 in the precore region and an A to T transition at position 1762 and a G to A transition at position 1764 in the core promoter region. Significant differences in the proportion of mutations in the precore or core promoter region were present between patients with fulminant hepatitis and self-limited acute hepatitis (7/7 (100%) vs 4/41 (9.8%), P<0.01) and between severe acute hepatitis and self-limited acute hepatitis (6/12 (50.0%) vs 4/41 (9.8%), P<0.01). The frequency of mutation increased proportionately with the severity of disease in patients with acute HBV infection. Fulminant hepatitis B in Japan is closely associated with mutations in the core promoter and precore gene of HBV. Point mutation assays for HBV precore and core promoter analysis may be useful to predict the outcome of liver disease in patients with acute HBV infection.

Acute Disease↗
PubMed1997

Quantitative analysis of interferon alpha/beta receptor mRNA in the liver of patients with chronic hepatitis C: correlation with serum hepatitis C virus-RNA levels and response to treatment with interferon.

We analysed the expression of interferon (IFN) alpha/beta receptor mRNA in the liver of patients with chronic hepatitis C and examined the relationship between the expression of this receptor gene and the level of hepatitis C virus (HCV)-RNA as well as the response to 16 weeks of 6 x 10(6) units IFN. The mean level of IFN alpha/beta receptor mRNA in patients with chronic HCV infection (expressed as delta cycle; 10.8 +/- 1.9 (mean +/- SD); n = 39) was significantly higher than that of control subjects (9.4 +/- 0.5; n = 6; P < 0.01). There was a significant negative correlation between the level of IFN alpha/beta receptor mRNA and serum HCV-RNA in 39 patients with chronic hepatitis C (R = -0.546; P < 0.01). The mean level of IFN alpha/beta receptor mRNA in six patients who showed a complete response to IFN therapy (12.3 +/- 1.6) was higher than that of 15 patients who failed to respond to therapy (10.1 +/- 1.5; P < 0.01). Our results are consistent with the suggestion that the anti-viral activity of IFN depends on the level of the IFN alpha/beta receptor on hepatocytes in patients with chronic hepatitis C.

Adult↗