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M Yoshiba

Publications and source records attributed to M Yoshiba.

At least 19 recordsLinked to original sources
PubMed2006

Intracellular-diced dsRNA has enhanced efficacy for silencing HCV RNA and overcomes variation in the viral genotype.

RNA interference (RNAi) can be used to inhibit viral replication in mammalian cells and therefore could be a powerful new antiviral therapy. Small interfering RNA (siRNA) may be effective for RNAi, but there are some technical problems that must be solved in each case, for example, predicting the effective siRNA target site and targeting heterogeneous sequences in a virus population. We show here that diced siRNA generated from long double-stranded RNA (dsRNA) is highly effective for inducing RNAi in HuH-7 cells harboring hepatitis C virus (HCV) replicons and can overcome variations in the HCV genotype. However, in mammalian cells, long dsRNA induced an interferon response and caused cell death. Here we describe an improvement of this method, U6 promoter-driven expression of long hairpin-RNA with multiple point mutations in the sense strand. This can efficiently silence HCV RNA replication and HCV protein expression without triggering the interferon response or cell death normally caused by dsRNA. In conclusion, intracellular-diced dsRNA efficiently induces RNAi, and, despite the high rate of mutation in HCV, it should be a feasible therapeutic strategy for silencing HCV RNA.

Base Sequence↗
PubMed2005

Interferon combined with cyclosporine treatment as an effective countermeasure against hepatitis C virus recurrence in liver transplant patients with end-stage hepatitis C virus related disease.

Hepatitis C virus (HCV) is the most common cause of end-stage liver disease in transplant recipients. Progression of recurrent HCV infection is accelerated. Cyclosporine is not only an immunosuppressive drug, but also an anti-HCV drug. We reported here the beneficial effect of combined interferon and cyclosporine treatment for chronic hepatitis C. We recommend this protocol for established HCV-related graft disease.

Adult↗
PubMed2001

The presence of a newly identified infectious agent (SEN virus) in patients with liver diseases and in blood donors in Japan.

The existence of the newly discovered SEN virus (SENV) was investigated in 379 Japanese patients with liver diseases and in 277 blood donors, to determine whether SENV is associated with non-A-E hepatitis. SENV DNA was detected by seminested polymerase chain reaction, with primers directed to 2 SENV strains: SENV-H and SENV-D. SENV was detected in 7 (32%) of 22 patients with fulminant hepatitis, in 15 (17%) of 86 patients with acute hepatitis, in 38 (27%) of 139 patients with chronic hepatitis, in 29 (31%) of 93 patients with liver cirrhosis, in 5 (33%) of 15 patients with autoimmune hepatitis, in 11 (46%) of 24 patients with primary biliary cirrhosis, and in 27 blood donors (10%). Infection occurred more frequently in patients with liver diseases than in blood donors; however, there were no significant differences in SENV-positive rates between patients with non-A-C hepatitis and those with acute or chronic hepatitis due to known hepatitis virus or nonviral liver disease. This study did not suggest SENV as a possible causative agent of non-A-C hepatitis.

Adolescent↗
PubMed2001

[IFN combined cyclosporin A therapy].

Current therapy of chronic hepatitis C with a 6 months course of alpha interferon shows limited effectiveness for patients with chronic hepatitis C. In particular more effective therapy is needed to treat patients who have high serum level of group 1-HCV RNA. We previously reported that a combination of interferon and cyclosporin A was more effective than interferon monotherapy. We also examined whether CsA has an antiviral effect on HCV using cultured human hepatocyte cell line. Propagation of HCV seems to be inhibited by CsA in a dose dependent manner. Further study is needed to clarify the action of cyclosporin A.

Clinical Trials as Topic↗
PubMed2001

[Overview of hepatitis C virus from its discovery to now].

Hepatitis C was first recognized as a form of viral hepatitis that was distinct from disease caused by hepatitis A virus and hepatitis B virus. The etiologic agent of hepatitis C was proposed to be a small, enveloped virus based on demonstrations of its transmissibility to chimpanzees, electron microscopic studies, and sensitive to chloroform. Successful molecular cloning of viral genome in the late 1980's led to the development of assay for serological diagnosis of HCV and it is currently estimated that at least 170 million people are chronically infected with the hepatitis C virus. HCV evades host antiviral defenses by mechanisms that remain to be identified and establishes a persistent infection in a majority of patients. Persistent infection of HCV is a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Therefore development of antiviral treatment for HCV is an urgent worldwide health problem. Although much has been learned about HCV genome organization, polyprotein processing, protein function and structure, many key questions remain to be answered. Major efforts of Japanese investigators should now be directed at establishing cellular system and animal models appropriate for dissecting the various steps in HCV replication cycle and strategies for blocking them.

Animals↗
PubMed2000

Microwave coagulation therapy for hepatocellular carcinoma.

The efficacy and safety of microwave coagulation therapy (MCT) in patients with hepatocellular carcinoma (HCC) and impaired hepatic reserve were studied. Preoperative background factors, postoperative results, and prognostic factors were compared in 51 patients who underwent hepatic resection (HR group) and 38 patients who underwent microwave coagulation therapy (MCT group). Before surgery, measures of hepatic function, including level of albumin (P = 0.0072), prothrombin time (P<0.0001), hepaplastin test (P = 0.0088), and the radioactivity of technetium-99m galactosyl-human serum albumin 15 min in the liver after injection divided by that in both liver and heart (P <0.0001) were significantly lower in the MCT group than in the HR group. The indocyanine green dye retention rate at 15 min was significantly greater (P<0.0001) in the MCT group than in the HR group, and a significant difference was noted in Child-Pugh grade between the groups (P<0.0001). Operative time (P = 0.0014) and blood loss during surgery (P = 0.0005) were significantly lower in the MCT group than in the HR group. In contrast, no significant differences were recognized between the groups in the changes in postoperative liver function, or in the rates of morbidity, mortality, local recurrence, and survival. Moreover, the type of treatment (HR or MCT) was not a prognostic factor. The results indicate that MCT can be used safely as an alternative to hepatic resection in patients with poor liver function without reducing the efficacy of local control.

Aged↗
PubMed2000

TT virus infection in patients with fulminant hepatic failure.

OBJECTIVE: A new DNA virus, which has been designated the TT virus, was discovered in 1997. It is not clear whether TT virus is a cause of any of the types of hepatitis. We conducted a case-control study to test the hypothesis that the presence of TT virus is a necessary condition for the development of fulminant hepatic failure in people who have non-A, -B, or -C hepatitis. METHODS: We studied 55 patients with fulminant hepatic failure [28 men, 27 women, mean (+/- SD) age, 47 +/- 15 yr], 32 patients with acute hepatitis (18 men, 14 women, mean age, 38 +/- 15 yr), and 200 healthy subjects (106 men, 94 women, mean age, 42 +/- 14 yr). TT virus DNA was detected in sera by a nested polymerase chain reaction using a primer set for genotype 1. RESULTS: TT virus was more frequently detected in patients with fulminant hepatic failure [in 33 of 55 (60%); 95% confidence interval (CI), 47-73%] than in those with acute hepatitis [in 8 of 32 (25%); 95% CI, 10-40%; p = 0.0016] or in healthy subjects [in 50 of 200 (25%); 95% CI, 19-31%; p < 0.0001]. TT virus was detected at a significantly higher rate in non-A, -B, or -C fulminant hepatic failure [in 18 of 22 (82%); 95% CI, 66-98%] than in fulminant hepatic failure of A, B, or C type [45%, 28-62%, 15/33; p = 0.007] or in non-A, -B, or -C acute hepatitis [24%, 3-44%, 4/17; p = 0.0003]. The logistic regression analysis selected TT virus (p = 0.0009), age (p = 0.0116), and etiology (p = 0.0309) as independent variables associated with fulminant hepatic failure (coefficient of determination, 0.2335). CONCLUSIONS: TT virus comparatively plays a role in the pathogenesis of non-A, -B, or -C fulminant hepatic failure.

Acute Disease↗
PubMed1999

Possible association between serum GB virus C RNA level and disease activity in fulminant hepatitis type G.

BACKGROUND/AIMS: Whether GB virus C causes serious liver diseases remains controversial. The aim of the present study was to determine whether there is an etiological relationship between GB virus C and fulminant hepatitis. METHODS: The level of GB virus C RNA in the sera of three patients with fulminant hepatitis was quantitatively determined using the newly developed real-time detection polymerase chain reaction method, which is based on Taq Man chemistry. The NS 3 region of the viral genome isolated from the sera was sequenced at several time points to confirm whether the same virus was responsible for fulminant hepatitis during the patients' clinical courses. RESULTS: The sensitivity of the PCR was comparable to that of nested PCR and a linear relationship between RNA copy number and threshold cycle was observed for 10(1) and 10(6) RNA copies/ml (r = 0.99). The serum level of GB virus C RNA closely paralleled that of ALT in all patients. Sequence analysis of the NS3 region isolated from the patients' sera revealed that the same GB virus C strain infected the patients during their entire clinical courses, despite plasma exchange therapy. CONCLUSIONS: These observations suggest that GB virus C may be etiologically associated with fulminant hepatic failure, and is not merely an inactive bystander introduced by therapeutic plasma exchange.

Adult↗
PubMed1999

Quantitation of hepatitis B virus genomic DNA by real-time detection PCR.

Quantitation of hepatitis B virus (HBV) DNA in serum is a useful method for the monitoring of HBV replication. We attempted to develop a quantitative assay system for HBV DNA that is more sensitive, accurate, and reproducible than existing systems. We detected HBV DNA by real-time detection PCR (RTD-PCR) based on Taq Man chemistry. The efficacy of this assay was evaluated by quantitatively measuring sequential levels of synthetic DNA and DNA in clinical serum samples. The detection limit of this system was as few as 10 DNA copies/reaction. A linear standard curve was obtained between 10(1) and 10(8) DNA copies/reaction. The coefficient of variation for both intra- and interexperimental variability indicated remarkable reproducibility. This system detected HBV DNA in 100% of chronic hepatitis B patients tested and never detected HBV DNA in healthy volunteers who were negative for HBV markers. These observations suggest that RTD-PCR is an excellent candidate for a standard HBV quantification method.

Adult↗
PubMed1999

[Serial hepatic and splenic volumetry in acute severe hepatitis].

In this study, we elucidate a relationship between final outcome and changes in hepatic and splenic volume in patients with acute severe hepatitis. The subjects were 40 patients: 10 with sever acute hepatitis (prothrombin time < 40%) and 30 with fulminant hepatic failure (acute type in 12 and subacute type in 18). Liver and spleen volume were measured by CT initially on hospitalization and subsequently 1 to 40 days after hospitalization, and the scans were analyzed retrospectively. Liver volume decreased in 15 of 26 survivors, and all 14 non-survivors. Among 15 survivors and 14 non-survivors whose liver volume decreased, spleen volume increased in none of the survivors, whereas it increased in 11 of the 14 non-survivors. In survivors there was a close parallelism between changing rates of the liver volume and that of the spleen volume (r = 0.82, p < 0.0001). These observations suggest that the decrease of liver volume accompanied by that of spleen volume implies a good prognosis, while the decrease without such accompaniment implies a bad prognosis.

Acute Disease↗
PubMed1998

Clinical and molecular virological differences between fulminant hepatic failures following acute and chronic infection with hepatitis B virus.

Clinical and molecular biological characteristics were compared between patients who presented with fulminant hepatic failure following acute infection with hepatitis B virus (HBV) and those who developed hepatic failure during they carried HBV. The 11 patients with acute HBV infection had higher levels of alanine aminotransferase (mean +/- SD: 4943 +/- 2867 vs 1157 +/- 678 IU/L, P < 0.01), more often with a single peak (91% vs. 0%, P < 0.001), and lower total bilirubin level (15.3 +/- 4.4 vs 28.1 +/- 14.3 mg/1000 ml, P < 0.01) than the 13 patients with chronic HBV infection. Hepatitis B surface antigen was detected less often (55% vs. 100%, P < 0.05) and viral DNA polymerase less frequently (0% vs. 46%, P < 0.05) in the patients with acute than chronic HBV infection. Hepatitis B e antigen was detected in one (9%) patient with acute infection, less frequently than in six (46%) patients with chronic infection (P < 0.05). Mutations in the precore region was detected in HBV DNA clones from ten (91%) patients with acute infection and only in those from eight (62%) patients with chronic infection. All HBV DNA clones from the five (38%) patients with chronic infection that did not have precore mutations, however, possessed mutations in the core promoter. These results indicate that HBV mutants incapable of translating hepatitis B e antigen would play a major role in fulminant hepatic failure occurring after acute HBV infection. In contrast, HBV variants with core promoter mutations for reducing the transcription of hepatitis B e antigen would play an additional role in fulminant hepatic failure developing during chronic infection.

Acute Disease↗
PubMed1998

[A close association of prognosis with effect of interferon in HBV carriers developing acute severe exacervation].

We have treated 19 HBV carriers who developed acute severe exacerbation using interferon and immunosuppressive agents. Of these 14 patients developed fulminant hepatic failure. Of 10 patients with positive result for serum HBV DNA polymerase before the start of te treatment, five patients in whom HBV DNA polymerase turned negative and one patient whose HBV DNA polymerase level fluctuated in a low abnormal range after the start of the treatment survived. While, four patients whose HBV DNA polymerase level remained high after the start of interferon treatment died. Thus, it is suggested that suppression of HBV virus replication is closely related to prognosis in HB carriers developing acute severe exacervation of hepatitis.

Acute Disease↗
PubMed1997

Case report: primary hepatic lymphoma associated with chronic liver disease.

We report on a case of primary hepatic lymphoma that developed in a patient with chronic hepatitis C. Given that Japan is an area endemic for both hepatitis B and C viruses, we reviewed 51 Japanese cases of primary hepatic lymphoma, addressing the question as to whether the Japanese cases have unique characteristics and whether there is a causal relationship to the presence of chronic liver disease. Primary hepatic lymphoma most commonly affected middle-aged males. Presenting symptoms and physical findings were non-specific. Aminotransferases tended to stay in the low range compared with marked increases in lactate dehydrogenase. Sixteen patients (31%) had chronic liver disease, eight had liver cirrhosis and eight had chronic hepatitis, suggesting that there is a possible aetiological link between chronic liver disease and primary hepatic lymphoma.

Adult↗
PubMed1997

Fulminant hepatic failure: observation with serial CT.

PURPOSE: To determine the imaging characteristics of fulminant hepatic failure at serial computed tomography (CT) and to assess if any CT findings have prognostic value. MATERIALS AND METHODS: In 40 patients, 207 CT scans were analyzed retrospectively. Thirty-four patients had fulminant hepatic failure (acute in seven and subacute in 27), and six had late-onset hepatic failure. Twenty-one patients died of hepatic failure. CT was performed soon after the onset of coma and repeated weekly. Liver volume was measured by tracing the hepatic contour and summing the areas to estimate whole-liver volume. RESULTS: Liver volumes in survivors (n = 19) and nonsurvivors (n = 21), respectively, were 1,090 cm3 +/- 300 and 830 cm3 +/- 240 at initial CT and 1,130 cm3 +/- 310 and 700 cm3 +/- 280 at last CT (P = .0001). III-defined hypoattenuating areas were noted in 20 patients and were distributed in a solitary (n = 13), multiple (n = 6), or diffuse (n = 1) pattern. At follow-up CT, the area of hypoattenuation increased in six patients (five nonsurvivors) and disappeared or markedly decreased in four survivors. An increase in or late occurrence of ascites was noted in 15 patients (14 nonsurvivors, P = .0001). CONCLUSION: Liver volumes at the initial and last CT examinations and an increase in or late occurrence of ascites are useful prognostic findings.

Adolescent↗