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Biomedical subjects

M Mizokami

Publications and source records attributed to M Mizokami.

At least 55 records · Page 3Linked to original sources
PubMed1999

Seroprevalence of hepatitis B virus, hepatitis C virus and GB virus-C infections in Siberia.

We studied the seroprevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and GB virus-C (GBV-C) infections in 348 Siberian natives who lived in the Kamchatka Peninsula of Russia. Of 348 samples studied, the seroprevalence of HBsAg and anti-HBs were 11.8% (41 of 348 samples) and 35.9% (125 of 348 samples), respectively. The prevalence of HCV infection was 1.4% (5 of 348 samples), and that of GBV-C RNA, using RT-PCR methods, was 7.5% (26 of 348 samples). In Siberia, the prevalences of HBV and GBV-C infections were about tenfold higher than those in Japan. The prevalence of HBsAg in subjects under 50 years of age was significantly higher than that in those over 50 years old (P < 0.05). Because HBV infection is highly endemic in Siberia, we propose that the community-based mass immunization must be conducted as soon as possible in this area.

Adolescent↗
PubMed1999

Prevalence of TT virus and GBV-C infections among patients with liver diseases and the general population in Shanghai, China.

To determine the prevalence of TT virus (TTV) and GB virus C/hepatitis G virus (GBV-C) infections among patients with liver disease and the general population in Shanghai, China, we studied 90 patients with liver diseases (acute hepatitis, 28; chronic hepatitis, 27; liver cirrhosis, 20; hepatocellular carcinoma, 15) and 90 age, sex matched healthy blood donors as controls. There were no significant differences in the clinical and demographic characteristics between the two groups, except for liver function test values. There was a statistical difference between the patient group and the control group with regard to the prevalence of TTV DNA (23.5% in patient group, 11.1% in control group, P < 0.05), although no differences in clinical features could be found between TTV DNA-positive and negative subjects. Also, no differences in TTV DNA prevalence among various categories of liver diseases were noted (P = NS). The prevalence of HBsAg was significantly different between the patient group (36.7%) and the control group (3.3%) (P0.01), whereas the prevalence of anti-HCV and GBV-C RNA were not significantly different between the two groups. The nucleotide sequences were determined in the TTV DNA-positive samples and evaluated using phylogenetic analysis which suggested that they could be divided into two main genotypes designated as genotype 1 and 2. There were five samples clustered into 3 hitherto unknown subtypes of genotype 2. We concluded that (1) although TTV infection is widespread among both groups and there is a statistical difference of TTV infection between them, no hepatic damaging evidence and correlation with certain liver disease could be found in this study, suggest that TTV may not be major cause of liver disease, (2) GBV-C infection is frequent, but the virus is not the cause of liver diseases, and (3) new subtypes of TTV may exist in Shanghai, China.

Adult↗
PubMed1999

Hepatitis G virus infection in renal transplant recipients.

To determine the prevalence and clinical significance of hepatitis G virus (HGV)/GB virus C (GBV-C) infection in renal transplant recipients, prospectively collected serum samples from a cohort of cadaveric renal transplant patients were studied for the presence of HGV RNA using a sensitive reverse transcription 'nested'-polymerase chain reaction (RT-PCR) based on primers derived from the 5' untranslated region. All positive PCR amplicons were sequenced bidirectionally and aligned. The nucleotide substitution rate was estimated by the 6-parameter method, and a phylogenetic tree was constructed using the Neighbour-joining method. HGV RNA was detected in 11/93 (12%) patients pretransplant and in 15/90 (17%) patients 1-4 years post-transplant. All PCR amplicons were confirmed to be specific for HGV by sequencing. Phylogenetic tree construction revealed that 17 PCR amplicons had sequences related to HGV and one had a sequence related to GBV-C. Two HGV RNA-positive patients pretransplant became HGV RNA negative post-transplant, and seven HGV RNA-negative patients pretransplant became HGV RNA positive post-transplant. There was no relationship between hepatitis C virus (HCV) and HGV infection. There were also no differences in age, gender distribution, ethnic origin, the total number of blood units transfused and either graft or patient survival between patients who were positive or negative for HGV RNA. We conclude that HGV infection is common among renal transplant candidates and recipients. Most of the isolates had sequences related to the HGV prototype. HGV infection does not appear to adversely affect clinical outcome in renal transplant recipients during early follow-up.

5' Untranslated Regions↗
PubMed1999

TT virus infection among IVDUs in south western China.

To elucidate the prevalence and clinical implications of infection with the newly described TT virus (TTV) among intravenous drug users (IVDUs) in Yunnan, southwest China, serum samples from 158 IVDUs (129 M, 29 F; mean age 26.1 +/- 5.5 years) were examined for TTV DNA by semi-nested polymerase chain reaction (PCR) using primers derived from the open reading frame (ORFI) of TTV DNA. The seroprevalence of viral markers of HIV, HBV, HCV and GB virus C/hepatitis G virus (GBV-C) infection was also examined. A molecular evolutionary analysis was performed. Thirty one (20%) of the IVDUs were positive for TTV DNA, and 34 (22%), 6 (4%), 98 (62%), 76 (48%), 136 (86%) and 65 (41%) were positive for anti-HIV, HBsAg, anti-HBs, anti-HBc, anti-HCV and GBV-C RNA, respectively. When all the subjects were classified according to TTV DNA positivity, no significant differences were observed in demographic, biochemical or virological characteristics between the 2 groups. TTV infection was in all cases associated with co-infection with 1 or more of the other aforementioned viruses. There were no significant differences in the various combinations of co-infection between TTV positive and negative groups. Phylogenetic analysis revealed that the TTV isolates obtained in the study could be grouped mainly into TTV genotype 1, and that some of the isolates belonged to subgroups other than those previously described. These results indicate that: 1) TTV infection is prevalent among IVDUs in China; 2) TTV probably has minor liver pathogenicity; and 3) new subgroups of genotype 1 and 2 exist in China.

Adult↗
PubMed1999

Human IgM monoclonal antibody to ganglioside GM2 and complement suppress virus propagation in ex vivo cultures of lymphocytes from HIV-1 infected patients.

HIV-1 infection induces aberrant ganglioside GM2 expression on infected cell lines, and human IgM anti-GM2 monoclonal antibody (L55 Ab) together with normal fresh human serum (FHS) as a source of complement causes complement mediated cytolysis of HIV-1 infected cells as well as HIV-1 particles. We report here that high expression of GM2 was also detected on HIV-1 infected lymphocytes from HIV-1 seropositive patients. L55 Ab effectively suppressed the generation of HIV in the presence of FHS in primarily cultured lymphocytes from HIV-1 infected patients in ex vivo experiments, and the suppression was enhanced additively by AZT. These data suggest that L55 Ab may increase the therapeutic effect of chemotherapy.

Antibodies, Monoclonal↗
PubMed1999

Beta-catenin accumulation and mutation of exon 3 of the beta-catenin gene in hepatocellular carcinoma.

A study was conducted to clarify the contribution of beta-catenin accumulation and mutation of the beta-catenin gene to hepatocarcinogenesis. Beta-catenin accumulation was examined immunohistochemically in 38 paired samples of hepatocellular carcinoma (HCC) and corresponding non-cancerous liver tissue. Gene mutation was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing using intronic primers encompassing exon 3. Neither accumulation nor mutation was detected in non-cancerous liver tissues that showed no remarkable histological features, chronic hepatitis or liver cirrhosis. Accumulation of beta-catenin was seen in the nucleus, cytoplasm or cell membrane in 15 of 38 (39%) HCC samples, and gene mutation was seen in 9 of 38 (24%) HCC samples. Although there was a significant correlation between accumulation and mutation (P<0.01), six HCCs without mutation also showed accumulation. Samples of early HCC showed neither accumulation nor mutation, and accumulation and mutation were each correlated significantly with portal vein tumor involvement (P<0.05). The present results indicate that (1) mutation of exon 3 of the beta-catenin gene can lead to beta-catenin accumulation, although other mechanisms of accumulation may also operate in HCC, and (2) beta-catenin accumulation and mutation of the beta-catenin gene are not early events in hepatocarcinogenesis, and may be associated with the malignant progression of HCC.

Adult↗
PubMed1999

Intraspousal transmission of GB virus C/hepatitis G virus in an hepatitis C virus hyperendemic area in Japan.

OBJECTIVE: An immunoassay for antibodies against an hepatitis G virus (HGV) protein (anti-E2) was recently developed that might serve as a useful marker for diagnosing recovery from HGV infection. METHODS: We investigated the intraspousal transmission of GB virus C/hepatitis G virus (GBV-C/HGV) using both reverse transcription hemipolymerase chain reaction (RT-hemi-PCR for the 5' untranslated region) and a recently developed anti-E2. RESULTS: Thirty-two GBV-C/HGV-infected index subjects were selected from an hepatitis C virus hyperendemic area in Japan. Of the 32 subjects, seven (6.4%) were GBV-C/HGV RNA-positive, 24 (21.8%) were anti-E2-positive, and one (0.9%) was both GBV-C/HGV RNA- and anti-E2-positive. Among the 32 spouses of these subjects, GBV-C/HGV RNA, anti-E2, and both GBV-C/HGV RNA and anti-E2 positivity were detected in 0, 6, (18.8%), and one (3.1%) spouses, respectively (the total prevalence of GBV-C/HGV was 7 spouses [21.9%]). Thus, the intraspousal transmission of GBV-C/HGV was undeniable in these seven couples. The respective positive rates of 175 sex- and age-matched controls were 7 (4.0%), 26 (14.9%), and 0 (the total prevalence of GBV-C/HGV was 34 [19.4%]). No significant difference in positive rates was observed between the subjects/spouses and the controls. Five spouses among the seven couples who were positive for any of GBV-C/HGV markers had parenteral risk factors such as blood transfusion, acupuncture, and major surgery. CONCLUSION: Based on these observations, we cannot draw a definitive conclusion that intraspousal transmission of GBV-C/HGV had occurred among these seven couples.

Aged↗
PubMed1999

Molecular evolution of hepatitis viruses.

Methods and models for analytical and quantitative researches on the evolution of hepatitis viruses using nucleotide sequences and amino acids of hepatitis viruses are described. Methods for the calculation of evolutionary rates and the construction of molecular evolutionary trees, especially by estimating the number of nucleotide substitutions and the number of amino acids, are introduced hereinafter. In addition, the evolution of the hepatitis virus is discussed by applying these methods to hepatitis B virus and hepatitis C virus.

Biological Evolution↗
PubMed1999

Molecular epidemiology of hepatitis C virus infection in an area endemic for community-acquired acute hepatitis C.

The southern district of N city (U area), Yamagata Prefecture, is highly endemic for hepatitic C virus (HCV) infection. Around 20% of the general population are positive for antibodies to HCV (anti-HCV). Community-acquired, acute non-A, non-B hepatitis was epidemic from 1967 to 1972 in this area. Our previous study revealed that these people are actually infected with HCV, but a relationship between this outbreak and the high positivity rate of anti-HCV in the U area has not been shown. We followed up 15 anti-HCV-positive individuals who developed hepatitis during the epidemic and used the serum collected to conduct molecular evolutional analysis to reveal the characteristics of the HCV epidemic in the U area. HCV genotypes in the U area were also analyzed. Phylogenetic analysis of the HCV core gene sequences showed that the subjects' HCV sequences were closely related and derived from the same cluster. All subjects were infected with HCV genotype 1b, which was frequently detected with a high positivity of over 80% of HCV-infected individuals in the U area. These results confirm that the community-acquired hepatitis C epidemic occurred around three decades ago through an unidentified route, and suggest that this episode may result in a continuing increase in the number of HCV-1b positive patients in this small area.

Acute Disease↗
PubMed1999

[Molecular evolution and genotype classification of TT virus].

Based on sequences data, TTV have a partial Rep protein motifs found among Circoviridae and the conserved region of parvoviral nonstructural polypeptides (NS)-1 genes, however we could not perform phylogenetic analyses among TTV and other viruses because of few similar sequences. Putative ORF2 among G2 and G4 encoded 49 aa because of in-frame stop codon, although that of G1 encoded 202 aa. Just down-stream of the stop codon, another putative new ORF(ORF3) were found around 150 aa. A phylogenetic analysis, using the ORF1 sequences of 93 TTV obtained from various geographical areas, indicated that the virus could be classified into six different genotypes. Further studies using more than 350 isolates obtained from DDBJ showed at least nine genotypes.

Amino Acid Sequence↗
PubMed1999

Interferon-alpha therapy exerts selective pressure on hepatitis C virus quasispecies equilibrium.

Two patients with chronic hepatitis C virus (HCV) genotype 2b infection were studied. They responded biochemically to interferon (IFN) but had early virological and later biochemical relapse. The HCV quasispecies equilibrium in these patients was studied by a combination of cloning, sequencing and construction of phylogenetic trees. Another patient with chronic HCV genotype 2b infection was followed every 6 months for 30 months (including one episode of biochemical exacerbation) to serve as the control. Quasispecies equilibrium drifted during IFN therapy but moved back in the direction of the original equilibrium during biochemical relapse. In the control patient, there was no significant drifting throughout the follow-up period. These data suggest that IFN therapy exerts selective pressure on HCV quasispecies equilibrium.

Adult↗
PubMed1998

New genotypes of TT virus (TTV) and a genotyping assay based on restriction fragment length polymorphism.

A phylogenetic analysis, using the open reading frame I sequence of 93 TT viruses (TTV) obtained from various geographical areas, indicated that the virus could be classified into six different genotypes including three hitherto unreported genotypes. The high reliability of the six clusters was confirmed by bootstrap analysis. On the basis of these sequence data, a new simple genotyping assay based on a restriction fragment length polymorphism of TTV was developed. Using the enzymes NdeI and PstI, followed by cleavage with NlaIII or MseI, it was possible to distinguish between the six TTV genotypes. This system will provide the framework for future detailed epidemiological and clinical investigations.

Base Sequence↗
PubMed1998

African origin of GB virus C/hepatitis G virus.

Ninety-four GB virus C/hepatitis G virus (GBV-C/ HGV) RNA-positive serum samples were obtained from all over the world. We found that all 15 GBV-C/HGV isolates from the Pygmies and the Bantu in the Central African region had a 12-amino acid indel (i.e. insertion or deletion) in the non-structural protein (NS) 5A region. Phylogenetic analyses of the NS5A region, using GBV-A as an outgroup, showed that these 15 isolates had diverged from the common ancestor much earlier than the remaining isolates, indicating an African origin of GBV-C/HGV.

Africa↗
PubMed1998

Lack of anti-GOR antibody among subjects with GB virus C/hepatitis G virus RNA.

Homologies were sought between the putative amino acid sequences of GB virus C/hepatitis G virus (GBV-C/HGV) and the GOR epitope or the liver/kidney microsome-1 (LKM-1) epitope, which share partial sequence identity with the hepatitis C virus (HCV) polyprotein. Anti-GOR antibody (anti-GOR) was assayed among 100 subjects with GBV-C/HGV RNA. Twenty-one and 25 subjects were coinfected with hepatitis B virus (HBV) or HCV, respectively. Homologies were found between the NS5 or E2 polyproteins of GBV-C/HGV and the GOR epitope or the LKM-1 epitope, respectively. These segments of GBV-C/HGV polyproteins sharing identity with the GOR or the LKM-1 epitope were well conserved among three genotypes of GBV-C/HGV. However, only 1 of 55 subjects (1.8%) with GBV-C/HGV RNA, but not with HBV or HCV, was positive for anti-GOR. The positivity for anti-GOR among the group with GBV-C/HGV RNA alone was significantly lower than that among the groups with HCV RNA (P < 0.01 and P < 0.05, respectively). Only 2 of 55 subjects (3.6%) with GBV-C/HGV RNA alone exhibited elevation of alanine aminotransferase. The incidence of liver dysfunction among the group with GBV-C/HGV RNA alone was significantly lower than the incidence among the groups with GBV-C/HGV RNA and hepatitis B surface antigen (HBsAg) or HCV RNA (P< 0.01 and P< 0.01, respectively). These data indicate that 1) there is no association between GBV-C/HGV infection and the presence of anti-GOR, and 2) GBV-C/HGV infection is not related to chronic liver dysfunction.

Adult↗
PubMed1998

A pilot randomized, controlled trial of the effect of iron depletion on long-term response to alpha-interferon in patients with chronic hepatitis C.

BACKGROUND/AIMS: Some studies have suggested that hepatic iron may influence the response to interferon therapy in chronic hepatitis C patients. We conducted this randomized, controlled trial to evaluate the effect of iron depletion on: (1) aminotransferase activity and hepatitis C RNA levels; and (2) response to interferon therapy in 38 patients with elevated alanine aminotransferase levels and who were HCV RNA positive. METHODS: Seventeen patients underwent a 500-ml phlebotomy every 2 weeks until iron deficiency was achieved. Patients were then started on a 6-month course of alpha-interferon 2b (3 mu tiw). Controls were 21 patients who were monitored for a 6- to 8-week period without phlebotomy prior to interferon therapy. Response to interferon was defined as loss of serum HCV RNA by reverse transcriptase-polymerase chain reaction. Serum HCV RNA was quantitated by bDNA technique. RESULTS: Alanine aminotransferase levels decreased in 15/17 patients after phlebotomy. Mean alanine aminotransferase fell from 156.8 to 89.7 U/l (p=0.008). Changes in iron indices and alanine aminotransferase after phlebotomy were not accompanied by changes in HCV RNA levels. In control patients, neither alanine aminotransferase nor HCV RNA levels changed during the observation period. At the end of 24 weeks of interferon therapy, 7/17 phlebotomized patients had a response, compared to 6/21 control patients (p=ns). After 6 months of follow-up, 5/17 phlebotomized patients remained HCV RNA negative, in contrast to only 1/21 controls (p=0.07). CONCLUSIONS: Iron depletion led to a reduction in aminotransferase levels; this was not accompanied by changes in levels of hepatitis C RNA. There may be an improvement in the sustained response to interferon therapy, but this requires confirmation.

Adult↗
PubMed1998

Analysis of conserved ambisense sequences within GB virus C.

No analysis has been done of the ambisense of GB virus C (GBV-C). When the anti-genomes of 16 reported sequences of GBV-C were analyzed, nucleotide codons 1758 and 1402 within the anti-genome were conserved initiation and stop codons, respectively. Nucleotide sequences were also determined within the same region of 22 GBV-C strains. The anti-genomes of 38 sequences were translated and a consensus sequence was determined. In accordance with the consensus sequence, overlapping peptides were synthesized and used for the detection of anti-synthetic peptide antibodies by ELISA. The positivity of antibodies among sera with GBV-C RNA was significantly higher than among sera without GBV-C RNA (66.7% vs. 15.6%), regardless of the simultaneous presence of hepatitis B surface antigen or antibodies to hepatitis C virus (P < .05). These results indicated that a novel protein associated with GBV-C might be expressed from the ambisense of this virus.

Antibodies, Viral↗