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Biomedical subjects

H Yotsuyanagi

Publications and source records attributed to H Yotsuyanagi.

31 records · Page 2Linked to original sources
PubMed1997

Hepatitis C virus core protein induces hepatic steatosis in transgenic mice.

Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide, which finally leads to development of hepatocellular carcinoma. Chronic hepatitis C is characterized by several histological features in the liver which discriminate it from other forms of hepatitis: bile duct damage, lymphoid follicles and steatosis (fatty change). Little is known, however, about the role of HCV or its viral proteins in the pathogenesis of hepatitis. Recently, the core protein of HCV has been suggested to have a transcriptional regulatory function, and thereby to be involved in inducing phenotypic changes in hepatocytes. To clarify whether or not the HCV core protein has an effect on pathological phenotypes in the liver, two independent transgenic mouse lines carrying the HCV core gene were established. These mice developed progressive hepatic steatosis, indicating that the HCV core protein plays a direct role in the development of hepatic steatosis, which characterizes hepatitis C. This transgenic mouse system would be a good animal model for the study of pathogenesis in human HCV infection.

Animals↗
PubMed1996

Chronic hepatitis A with persistent viral replication.

Hepatitis A virus (HAV) usually causes an acute self-limited illness. This report describes a patient with hepatitis A whose serum aminotransferase activities remained above normal and whose serum was persistently positive for immunoglobulin (Ig) M class anti-hepatitis A 31 months after the onset of hepatitis. Liver biopsy carried out 11 months after the onset of hepatitis showed histological changes consistent with chronic hepatitis of moderate severity. HAV RNA was detected by polymerase chain reaction (PCR) in feces collected at the time of the liver biopsy. Furthermore, the patient developed esophageal varices 25 months after the onset of hepatitis. We believe this to be the first reported case in which persistent replication of HAV is implicated in chronic hepatitis with the potential to develop into liver cirrhosis.

Hepatitis A↗
PubMed1996

Prolonged fecal excretion of hepatitis A virus in adult patients with hepatitis A as determined by polymerase chain reaction.

In hepatitis A virus (HAV) infection, fecal excretion of the virus has been reported to cease shortly after symptoms occur. Although there have been several reports on detection of HAV in feces using polymerase chain reaction (PCR), the duration of fecal HAV shedding in human adult hepatitis A has not been well described. In the present study, we applied the reverse-transcription (RT)-PCR system to the detection of fecal HAV RNA in 10 patients with sporadic hepatitis A. The viral genomic RNA was detected in the stools from five patients after the onset of clinical symptoms. All stool samples collected within 10 days of onset of illness were HAV-RNA-positive, and the duration of positivity lasted from a few days to as long as 3 months. In four patients, HAV RNA was detected in the stool even after the serum alanine transaminase (ALT) levels had peaked, and in one patient well after ALT levels fell to normal. These results show that fecal shedding of HAV can last for months after resolution of symptoms and such patients could be a source of further spreading of the virus in the community.

Adult↗
PubMed1995

Hepatitis C virus genotypes and development of hepatocellular carcinoma.

BACKGROUND: Among several genotypes of hepatitis C virus (HCV), genotypes 1b (or II) and 2a (or III) are predominant in Japan. Although it has been shown that the efficacy of interferon treatment of patients with chronic hepatitis C varies with the HCV genotype, the relationship between HCV genotype and the development of hepatocellular carcinoma (HCC) has not been well described. METHODS: The genotypes and serum levels were determined for HCV-RNA in 72 patients with HCC and 131 patients without HCC, all of whom were positive for second-generation HCV antibody and HCV-RNA. In addition, clinical data from 34 patients with HCC who each had a history of blood transfusion were analyzed. RESULTS: Fifty-seven (79.2%) of 72 patients with HCC had genotype 1b HCV, whereas 101 (77.1%) of 131 patients without HCC had genotype 1b, indicating that there was no significant difference in the prevalence of genotype 1b HCV between the patients with and without HCC. Furthermore, comparison of patients with HCC with genotype 1b HCV with those with genotype 2a who had a history of blood transfusion did not differ significantly in the number of years from blood transfusion to diagnosis of HCC. Levels of HCV-RNA were not significantly different among patients with liver diseases of various stages. CONCLUSIONS: Hepatocellular carcinoma develops in patients with either genotype 2a HCV or genotype 1b HCV. A difference in genotype is not likely to be responsible for the difference in development of HCC.

Carcinoma, Hepatocellular↗
PubMed1995

Dominant replication of either virus in dual infection with hepatitis viruses B and C.

To characterize the state of dual infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), HBV-DNA and HCV-RNA levels were determined by spot hybridization or polymerase chain reaction in the sera of patients who were positive for both hepatitis B surface antigen and HCV antibody. Among 27 patients who showed evidence of double infection, 21 (77.8%) had detectable levels of only either HBV or HCV genome in their sera, 2 (7.4%) showed none of the viral genomes, and 4 (14.8%) had both HBV-DNA and HCV-RNA. In the 4 patients with both HBV-DNA and HCV-RNA, the titers of HCV-RNA or HBV-DNA were lower than those in the patients with HCV-RNA or HBV-DNA alone. In some patients with chronic hepatitis, the viruses appeared to replicate in turn in the course of the disease. These results indicate that the viruses show alternating dominance in replication in most of the patients who have dual infection with HBV and HCV, probably due to interference of the viruses.

Adolescent↗
PubMed1995

Takayasu's arteritis in prepulseless stage manifesting lymph node swelling and hepatosplenomegaly.

A 17-year-old male had fever of unknown origin (FUO) for 3 months with positive c-reactive protein, lymph node swelling, and hepatosplenomegaly. Biopsy specimens of the liver and lymph node disclosed nonspecific inflammation. Lymph node swelling and hepatosplenomegaly subsided gradually, while vascular murmur and pulselessness appeared. Computerized tomography and magnetic resonance imaging showed thickened arterial wall, while angiography disclosed arterial narrowing. From these findings he was diagnosed to have Takayasu's arteritis. The therapy with prednisolone was effective. Takayasu's arteritis is rarely manifested by hepatosplenomegaly and lymphadenopathy in its prepulseless stage.

Adolescent↗
PubMed1994

Induction of interstitial pneumonitis during interferon treatment for chronic hepatitis C.

A 48-year-old woman developed interstitial pneumonitis while receiving interferon treatment for chronic hepatitis C. Laboratory studies prior to treatment showed elevated serum alanine aminotransferase levels, but chest X-rays and physical examination revealed no abnormalities suggestive of interstitial pneumonitis. At the 9th week of interferon treatment (total dose, 380 MU of recombinant interferon-alpha, without other medications), the patient began to complain of cough and exertional dyspnea. A chest X-ray film revealed diffuse reticulo-nodular shadows in bilateral lung fields, suggesting a diagnosis of interstitial pneumonitis. A marked increase in lymphocyte count was observed in bronchoalveolar lavage fluid and a diagnosis of interstitial pneumonitis was made as a result of transbronchial lung biopsy. Her clinical symptoms and abnormal lung shadows were reversible, improving within a month of the discontinuation of interferon, and disappearing promptly after exogenous corticosteroid was instituted. This may be the first case of drug-induced interstitial pneumonitis occurring during the course of treatment with interferon alone. We should be aware of the possibility of interstitial pneumonitis developing during treatment of chronic hepatitis C with interferon.

Biopsy↗
PubMed1994

Induction of cell cycle progression by hepatitis B virus HBx gene expression in quiescent mouse fibroblasts.

The HBx gene of hepatitis B virus has been shown to induce hepatic tumors in transgenic mice and is implicated in hepatocarcinogenesis in human hepatitis B virus infection. To further characterize the role of HBx gene in carcinogenesis, we established mouse fibroblast cell lines in which the expression of HBx gene could be controlled by glucocorticoid hormone and examined the effect of HBx gene expression on cell growth in vitro. Along with the expression of HBx gene, most cells in the G0/G1 phase moved into the S phase in 24 h, and the cell cycle progressed further toward 48 h. Induction of DNA synthesis was also demonstrated by bromo-deoxyuridine labeling analysis. These results indicate that HBx gene has a function to trigger the synthesis of cellular DNA and suggest that HBx gene may play a role in hepatocarcinogenesis in human infection by driving deregulated cell cycle progression.

3T3 Cells↗
PubMed1994

High-level expression of hepatitis B virus HBx gene and hepatocarcinogenesis in transgenic mice.

We studied the development of liver tumors in male HBx gene transgenic mice. Of two lineages studied, in the lineage with the lowest HBx gene expression liver tumors developed only in an incidence comparable with that in normal CD-1 strain, whereas 84% of male mice with a high level of the HBx gene product succumbed to liver neoplasia, indicating that continued HBx gene expression higher than a certain threshold level may be necessary for the development of hepatic neoplasia. Sixty-five mice from a lineage with a high level of HBx expression were then followed throughout their 24-mo lifespan. The livers of transgenic mice showed foci of cellular alteration with cytoplasmic vacuolations around the central veins from the age of 2 mo, but these foci did not expand progressively by the age of 12 mo. Immunostaining demonstrated such hepatocytes had higher expression of HBx protein than surrounding cells. Neoplastic lesions including liver cell adenomas and hepatocellular carcinomas developed from the age of 13 mo. By bromodeoxyuridine labeling analysis, hepatocytes in altered foci were found to have increased DNA synthesis, whereas no labeling was observed in age- and sex-matched nontransgenic littermate controls. Furthermore, DNA content analysis revealed the existence of several small aneuploid peaks in the transgenic liver before the age of tumor development. These results suggest that the continued expression of HBx gene may initiate a complex process to hepatocellular carcinoma by inducing DNA synthesis and placing large numbers of hepatocytes subjective to secondary events for transformation.

Adenoma, Liver Cell↗
PubMed1993

Duration of viremia in human hepatitis A viral infection as determined by polymerase chain reaction.

Viremia in hepatitis A viral (HAV) infection is said to be limited to pre-symptomatic period. However, it is not clear how long viremia lasts in human infection due to the lack of a simple and sensitive detection system. In an attempt to find HAV genome in patients' sera, we used the RT-PCR method by setting a pair of primers in the 5' non-coding region. While in most cases HAV-RNA was detected only before alanine aminotransferase (ALT) reached peak levels with this sensitive system, the viral genome was observed in some patients' sera even after ALT reached peak levels. Some patients also had HAV viremia after seroconversion to HAV antibody. These results show that viremia in HAV infection lasts longer than has been previously thought, and give a warning of possible secondary blood-borne infection.

Adult↗
PubMed1991

Interferon therapy for non-A, non-B chronic hepatitis.

We report the results of our study on 8-week consecutive interferon (IFN) treatment for chronic non-A, non-B hepatitis. In the 6 MIU/day group, most cases had continuously normalized alanine-aminotransferase (ALT) levels even after IFN treatment was discontinued. In responders whose ALT levels remained normal, not only the degree of inflammation, as seen from HAI scores, but also liver histopathological features were improved. Moreover, antibody to hepatitis C virus (anti-HCV) titer in responders was continuously decreased. Antiviral effects of IFN were observed by detection of HCV-RNA using the PCR technique. HCV-RNA became negative with IFN treatment, however, in some patients who relapsed after discontinuation of IFN treatment, re-elevation of ALT levels was usually preceded by re-appearance of HCV-RNA.

Alanine Transaminase↗
PubMedDate not supplied

Subcellular localization of hepatitis C virus structural proteins in the liver of transgenic mice.

Hepatitis C virus (HCV) core and envelope proteins are suggested to be responsible for the pathogenesis of hepatic and extrahepatic manifestations in chronic hepatitis C. Moreover, the core protein is implicated in the regulation of the transcription of cellular genes including c-myc, RB and p53. Determining the subcellular localization of the core and envelope proteins is therefore necessary to elucidate their behaviors, particularly in vivo ones, regarding the interaction with transcriptional regulatory proteins or gene elements. We defined the subcellular localization of HCV envelope and core proteins which were expressed in substantial levels in the liver of transgenic mice. Subcellular fractionation by ultra-centrifugation revealed that the envelope proteins were present principally in the microsomes of the liver, while a small amount of the protein was detected also in the nuclei. Immunohistochemistry confirmed the localization of envelope proteins in the nuclei. In contrast, the core protein was detected principally in the cytoplasmic fraction, where it was closely associated with lipids. A low level of the core protein was detected also in the nuclei and microsomal fraction. These results suggest possible interaction of the HCV structural proteins with some factors in hepatocytes thereby perturbing intracellular circumstances.

Animals↗