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Biomedical subjects

M Mizokami

Publications and source records attributed to M Mizokami.

At least 73 records · Page 4Linked to original sources
PubMed1998

GB virus C/hepatitis G virus infection among Colombian native Indians.

To elucidate the prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) infection in Colombian native Indians, serum GBV-C/HGV RNA was assayed in 163 native Indians and 67 members of the general population in Colombia. The native Indians (males:females = 40:123) and the members of the general population (males:females = 20:47) were tested by reverse transcription-semi-nested polymerase chain reaction. Of the 163 native Indians, 10 (6.1%) were positive for GBV-C/HGV RNA, compared with one (1.5%) of 67 from the general population. All Indians were negative for hepatitis B surface antigen and antibody to hepatitis C virus. Of 10 Indians with GBV-C/HGV RNA, the genotype of nine subjects was the Asian type. These data indicated that 1) the prevalence of GBV-C/HGV RNA in Colombian native Indians is high, and 2) GBV-C/HGV was probably brought from Asia and inherited for generations in some native Indian groups.

Adolescent↗
PubMed1998

Heterogeneity in E2 region of GBV-C/hepatitis G virus and hepatitis C virus.

GB virus C/hepatitis G virus (GBV-C/HGV) is related distantly to hepatitis C virus (HCV). HCV has a hypervariable region (HVR), and exists as quasispecies in vivo. Although GBV-C/HGV also has replaceable amino acids in the presumed antigenic region, the existence and fluctuation of population of heterogeneous virus have not been evaluated. In this study, the heterogeneity of GBV-C/HGV and HCV was investigated by the single-strand conformation polymorphism (SSCP) analysis in six concomitantly infected patients. Two patients were observed for 4 years without any treatment, and four were treated with interferon-alpha (IFN). By SSCP analysis, amplicons of GBV-C/HGV RNA were separated into 1-5 bands on gels for each patient. The amplicons had different nucleotide but the same amino acid sequences in the presumed antigenic region. The amplicons of HCV RNA, separated into 1-4 bands, had different nucleotide and amino acid sequences in the HVR. In the two patients without treatment, the predominant strain of GBV-C/HGV was unchanged for the 4 years. In the four patients administered IFN, some strains of GBV-C/HGV disappeared after IFN therapy, whereas other strains persisted. The mean genetic distance among GBV-C/HGV strains represented by SSCP analysis was significantly lower than that of HCV (P < 0.05). The data indicate that: 1) GBV-C/HGV can be devoid of antigenic drift unlike HCV; 2) GBV-C/HGV has no HVR as seen in HCV in the presumed antigenic region; and 3) the sensitivity to IFN differs among GBV-C/HGV strains in the same hosts, as with HCV.

Adult↗
PubMed1998

GB virus C/hepatitis G virus infection among patients with hepatocellular carcinoma in the inshore area of the Yangtze River, China.

To investigate the association between GB virus C/hepatitis G virus (GBV-C/HGV) infection and the development of hepatocellular carcinoma (HCC) in H city, in the inshore area of the Yangtze River, where high prevalence of HCC has been reported, we determined hepatitis B virus (HBV) and hepatitis C virus (HCV) markers, GBV-C/HGV-RNA and GBV-C/HGV E2 antibody (anti-HG E2) among 114 HCC patients and the same number of age- and sex-matched controls. There were no significant differences in the clinical and demographic characteristics between them, except for serum alanine aminotransferase level and history of liver diseases. There was a significant difference of hepatitis B virus surface antigen (HBsAg) prevalence between the HCC patients (75.4%) and the controls (20.2%; P<0.01). Hepatitis C virus antibody was detected in 4.4% of the HCC patients, compared with 1.7% of the controls. GB virus-C/HGV-RNA and anti-HG E2 were detected in 14.9 and 1.7% of the HCC patients, respectively, compared with 7.0 and 1.7% of the controls, respectively. Nucleotide sequences and molecular evolutionary analysis showed the strains of GBV-C/HGV-RNA were classified into genotype 2 and 3 (HG and ASIA type). An effect analysis showed an odds ratio (OR) for developing HCC from GBV-C/HGV infection among HBsAg-positive subjects was 14.9, with a 95% CI of 4.9-45.4. HBsAg infection alone was 13.83 (95% CI 7.4-25.9) and GBV-C/HGV infection alone, 3.74 (95% CI 1.1-13.1), respectively. These data indicate that HBV infection is considered to be one of the major risk factors in patients with HCC and although GBV-C/HGV infection was observed in both the HCC and the control groups, it might not play an important role in the development of HCC in this area.

Adult↗
PubMed1997

Hepatitis C virus infection in patients with B-cell non-Hodgkin lymphoma.

BACKGROUND: Several studies from Europe have reported a high prevalence (9% to 32%) of chronic hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin lymphoma. It has been suggested that HCV plays a role in the pathogenesis of B-cell non-Hodgkin lymphoma. OBJECTIVE: To determine the prevalence of HCV infection in patients with B-cell lymphoma in the United States. DESIGN: Controlled, cross-sectional analysis. SETTING: University medical center. PATIENTS: 120 patients with B-cell lymphoma (78% were Hispanic, 9% were black, 7% were Asian, and 6% were white), 154 patients with other malignant hematologic conditions (control group 1), and 114 patients with nonmalignant conditions (control group 2). MEASUREMENTS: Samples were tested for antibodies to HCV by enzyme-linked immunosorbent assay. Hepatitis C virus RNA was detected by reverse-transcription polymerase chain reaction. Genotyping for HCV was done with genotype-specific primers from the HCV core region. RESULTS: Infection with HCV was detected in 26 patients (22% [95% CI, 15% to 30%]) with B-cell lymphoma compared with 7 of 154 patients (4.5%) in control group 1 and 6 of 114 patients (5%) in control group 2 (P < 0.001). Risk factors for HCV infection were present in 15 patients (60%) with B-cell lymphoma and occurred a median of 15 years before diagnosis of lymphoma. Monocytoid B-cell lymphoma was the most common type of lymphoma found in HCV-positive patients (23% compared with 7% in HCV-negative patients) (P = 0.034). CONCLUSIONS: The prevalence of HCV infection was higher in patients with B-cell non-Hodgkin lymphoma than in controls. The possible role of HCV in the pathogenesis of B-cell lymphoma warrants further investigation.

Adult↗
PubMed1997

Clonal selection of HIV type 1 variants associated with resistance to foscarnet in vitro: confirmation by molecular evolutionary analysis.

Foscarnet (trisodium phosphonoformate, PFA) is an effective inhibitor of retroviral reverse transcriptase (RT) and is known to block the replication of human immunodeficiency virus type 1 (HIV-1). In this article we analyzed the evolutionary process in generating HIV-1 strains related to drug resistance, using PFA as a selective pressure. PFA inhibited virus replication and protected the virus-induced cell killing, but it did not completely eliminate HIV-1 during the course of 7 weeks of treatment. The nucleotide sequence of the 859-bp DNA fragment spanning the core region of the HIV-1 pol gene was determined for 51 clones obtained from genomic DNA of the HIV-1-infected cells at different time points during PFA treatment. The nucleotide sequence analysis documented the presence of a minor HIV-1 variant prior to the PFA treatment. Molecular evolutionary techniques were utilized to analyze how the minor HIV-1 clones became predominant during this evolutionary process under the selective pressure of PFA. A phylogenetic tree analysis divided these 51 HIV-1 clones into 3 groups. One of the groups consisted of the clones associated with the resistance to PFA. The clones belonging to this group became predominant over time during the course of PFA treatment. Thus, the acquisition of PFA resistance by HIV-1 was considered to be due to clonal selection. Furthermore, among the various amino acid substitutions observed, the substitution of arginine at position 172 by lysine (Arg172Lys) clearly distinguished this group from the others. Since the consistent amino acid substitution observed here has not been identified in the HIV-1 strains resistant to other RT inhibitors, PFA in combination with other RT inhibitors is considered to be a feasible candidate for a convergent combined chemotherapy against HIV-1 in the treatment of patients with AIDS and related conditions.

Amino Acid Sequence↗
PubMed1997

Three different GB virus C/hepatitis G virus genotypes. Phylogenetic analysis and a genotyping assay based on restriction fragment length polymorphism.

The 5'-untranslated region (5'-UTR) sequences of 33 GB virus C/hepatitis G virus (GBV-C/HGV) obtained from different geographic areas were determined through reverse-transcription polymerase chain reaction and dideoxy chain termination sequencing, the alignment of sequences, the estimation of the number of nucleotide substitution per site, and construction of phylogenetic trees. The 5'-UTR of GBV-HGV was found to be heterogeneous, with 70.9-99.5% homology. Three distinct phylogenetic branches were observed consistently in all phylogenetic trees. GBV-C is the prototype for one, HGV for another, and there is a new branch which consisted of GBV-C/HGV isolates from Asia. Genotype-specific restriction sites for the restriction enzymes, ScrFI and BsmFI, were identified, and a simple restriction fragment polymorphism analysis was developed for genotyping. These data provide evidence that GBV-C/HGV consists of three different genotypes. Our simple genotyping assay will also provide a tool for epidemiological studies of GBV-C/HGV infection.

Base Sequence↗
PubMed1997

Antibody to the host cellular gene-derived epitope GOR-1 in liver transplant recipients with hepatitis C virus infection.

The presence of anti-GOR was determined in paired pre-orthotopic liver transplantation (pre-OLT) and post-OLT sera from 87 OLT patients with hepatitis C virus infection. Before OLT, 48/87 patients were seropositive for anti-GOR, but this marker had no relationship with the clinical and biochemical parameters, or viremia level. Anti-GOR was less commonly detected in patients infected with genotype 3a, compared with genotypes 1 and 2, which might be related to the less conserved nature of the proposed shared epitope (amino acid sequence 9-18) in genotype 3a isolates. After OLT (median follow-up 16 months), anti-GOR was detected in 31/87 patients and it had no correlation with the clinical and biochemical parameters, viremia level, histologic disease activity, and clinical outcome. Changes in anti-GOR status (before OLT versus after OLT) were also not related to any of the clinical parameters. Although anti-GOR is commonly detected in OLT patients infected with hepatitis C virus genotypes 1 and 2, it has no clinical or prognostic significance.

Adult↗
PubMed1997

Detection of GB virus-C/hepatitis G virus RNA in serum by reverse transcription polymerase chain reaction.

Three PCR methods based on the GB virus-C/hepatitis G virus (GBV-C/HGV) 5'UTR and NS3 genomic region were used for the detection of GBV-C/HGV RNA in serum of 62 patients with chronic hepatitis C virus (HCV) infection. Ten of 62 (16%) patients were found to have GBV-C/HGV RNA, which was confirmed by sequence analysis of the 5'UTR PCR amplicon. All methods appear to be specific, but methods based on the 5'UTR appear to be more sensitive.

Adult↗
PubMed1997

Constrained evolution with respect to gene overlap of hepatitis B virus.

With the aim of elucidating the evolution of a hepadnavirus family, we constructed molecular phylogenetic trees for 27 strains of hepatitis B virus (HBV) using both the unweighted pair-grouping and neighbor-joining methods. All five gene regions, P, C, S, X, and preS, were used to construct the phylogenetic trees. Using the phylogenetic trees obtained, we classified these strains into five major groups in which the strains were closely related to each other. Our classification reinforced our previous view that genetic classification is not always compatible with conventional classification determined by serological subtypes. Moreover, constraints on the evolutionary process of HBV were analyzed for amino-acid-altering (nonsynonymous) and silent (synonymous) substitutions, because two-thirds of the open reading frame (ORF), P, contains alternating overlapping ORFs. In our unique analysis of this interesting gene structure of HBV, the most frequent synonymous substitutions were observed in the nonoverlapped parts of the P and C genes. On the other hand, the number of synonymous substitutions per nucleotide site for the S gene was quite low and appeared a strongly constrained evolution. Because the P gene overlaps the S gene in a different frame, the low rate of synonymous substitution for the S gene can be explained by the evolutionary constraints which are imposed on the overlapping gene region. In other words, synonymous substitutions in the S gene can cause amino acid changes in its overlapping region in a different frame. Thus, the evolution of HBV is constrained evolutionarily by the overlapping genes. We propose calling this mode of viral evolution "constrained evolution." The evolution of HBV represents a typical constrained evolution.

Amino Acid Sequence↗
PubMed1997

High prevalence of GB virus C/hepatitis G virus infection among the Jewish population in Uzbekistan.

Although a new virus, GB virus C/hepatitis G virus (GBV-C/HGV), has been isolated from patients with hepatitis by two different research groups, its prevalence in the world and pathogenesis are still unknown. In this study, 92 samples from the Jewish population of Uzbekistan were investigated for the prevalence of GBV-C/HGV. GBV-C/HGV RNA was detected by reverse transcription polymerase chain reaction (RT-PCR) using specific primers derived from the 5'-untranslated region (5'-UTR). Sequences were analyzed by a molecular evolutionary method. Of 92 samples, GBV-C/HGV RNA was detected in ten (10.9%), HCV RNA was present in two (2.2%), and HBsAg in eight (8.7%). HTLV-I and HIV infection was not detected. Single GBV-C/HGV infection was detected in eight (80%), and co-infection with HBV or HCV was detected in only two of the GBV-C/HGV infections. Alanine aminotransferase (ALT) levels were elevated in three (3.3%), but none with single GBV-C/HGV infection had an elevated ALT level. Nine people (90%) with GBV-C/HGV infection were distributed under the mean age of the population (P < 0.05). Molecular evolutionary analysis showed all GBV-C/HGV strains in this study were related to the HGV derived from the US. These results indicate that (1) GBV-C/HGV infection is highly prevalent among the Jewish population in Uzbekistan; (2) single GBV-C/HGV infections without persistent hepatitis are common; and (3) GBV-C/HGV infection is present among the younger generation.

Adolescent↗
PubMed1997

Genotype of GB virus C/hepatitis G virus by molecular evolutionary analysis.

GB virus C/hepatitis G virus is a newly described virus. Classification of GB virus C/hepatitis G virus into genotypes has not been established. We analyzed nucleotide sequences within the 5' untranslated region of GB virus C/hepatitis G virus isolates and segregated these isolates into genotypes. Twenty serum samples with GB virus C/hepatitis G virus RNA from Australia, Cameroon, the Congo, Japan, Mongolia, and Bangladesh were studied. Reverse transcription and polymerase chain reaction were used to obtain GB virus C/hepatitis G virus RNA. After nucleotide sequences from the 5' untranslated region were determined, 68 nucleotide sequences, including 48 previously reported sequences, were analyzed by molecular evolutionary methods. The phylogenetic tree of the 5' untranslated region showed that all strains could be divided into three major genotypes, GB type (type 1), HG type (type 2), and Asian type (type 3). Bootstrap analysis indicated that the strains could be divided into three major genotypes but could not be further subdivided. Moreover, frequency histograms of pairwise distances between nucleotide sequences demonstrated only one peak. These result indicated that GB virus C/hepatitis G virus can be classified into three major genotypes, GB type (type 1), HG type (type 2), and Asian type (type 3), and should not be divided into minor subtypes.

Base Sequence↗
PubMed1997

GB virus C/hepatitis G virus infection among Korean patients with liver diseases and general population.

GB virus C and hepatitis G virus (GBV-C/HGV) have been identified from the patients with acute or chronic liver diseases as possible agents of non-B, non-C hepatitis by two different groups, independently. To investigate whether GBV-C/HGV plays a role among Korean patients with liver diseases, GBV-C/HGV RNA were evaluated in 337 sera by the reverse transcription polymerase chain reaction (RT-PCR) using specific primers derived from 5'-noncoding region of GBV-C/HGV genome. GBV-C/HGV RNA was identified in 11/337 (3.3%). They consisted of 1/160 (0.6%) and 10/177 (3.3%) among the general population and patients with liver diseases, respectively (P < 0.01). Nucleotide sequences of all PCR amplicons were determined by the dideoxy chain termination method and analyzed by molecular evolutionary methods. The phylogenetic tree showed all sequences could be divided into three genotypes. These results indicate that: (1) GBV-C/HGV already exist in Korea; (2) GBV-C/HGV may play some role as an etiologic factor among the Korean patients with liver diseases; (3) GBV-C/HGV infection is rare among Korean general population; and (4) there are at least three different types of GBV-C/HGV in Korea.

Adolescent↗
PubMed1997

GB virus C (GBV-C)/hepatitis G virus (HGV) infection among intravenous drug users in Japan.

A sero-epidemiologic survey of 74 IVDUs and 86 age-matched controls was performed to investigate the prevalence, clinical significance, and genetic distribution of GB virus C (GBV-C)/hepatitis G virus (HGV) infection among intravenous drug users (IVDUs) in Japan. GBV-C/HGV RNA was detected by reverse transcriptase-hemi-nested polymerase chain reaction (RT-hemi-nested PCR) for the 5'-untranslated region (5'-UTR) in 43.2% (32/79) of the IVDUs compared with 1.2% (1/86) of the controls (P < 0.001). The duration of drug use did not correlate with the prevalence of GBV-C/HGV. Thirteen subjects positive for GBV-C/HGV RNA without HCV RNA had normal serum aminotransferase concentrations. Phylogenetic tree showed that the 32 GBV-C/HGV-positive isolates from IVDUs were classified within a new GBV-C/HGV group, which has been identified mainly in Asian subjects (type 3). The present study illustrated, (1) the high incidence of GBV-C/HGV infection among Japanese IVDUs, (2) GBV-C/HGV alone may not be an important pathogenic factor for hepatic injury, and (3) type 3 GBV-C/HGV was the most prevalent among IVDUs in Japan.

Adolescent↗
PubMed1997

Interferon-alpha therapy in patients dually infected with hepatitis C virus and GB virus C/hepatitis G virus--virological response of HGV and pretreatment HGV viremia level.

BACKGROUND/AIMS: The response to interferon-alpha (IFN) therapy of recently isolated GB virus C and hepatitis G virus (HGV) is still unclear. To investigate the biochemical and virological response to IFN therapy in patients with chronic hepatitis C virus (HCV) infection concomitantly infected with HGV, 196 patients with HCV who had received IFN therapy were retrospectively studied. METHODS: HGV and HCV RNA were detected by reverse transcription nested polymerase chain reaction (RT-PCR). Serum HGV RNA levels were quantified by competitive RT-PCR. The HGV genotype was detected by restriction fragment length polymorphism analysis using the PCR products. RESULTS: Of 196 patients, 16 (8.2%) were positive for both HCV and HGV RNA before IFN therapy. There were no significant clinical and virological differences between the patients with dual infection and those with only HCV infection. During the therapy, a decrease or loss of serum HGV RNA level was observed in these patients. Six months after cessation of the therapy, five of 16 patients became negative for HGV RNA by RT-PCR. The pretreatment HGV RNA level of the patients who lost HGV RNA after cessation of IFN was low (median=10(3) copies/ml), compared to the level (median=10(7) copies/ml, p<0.01) in the patients with positive HGV RNA after the therapy. The HGV genotype of these 16 patients was the same type. CONCLUSIONS: These data suggest that: 1) there is no significant difference in response to IFN therapy between patients with dual and single infection; 2) HGV shows sensitivity to IFN therapy; and 3) in the patients who show a low pretreatment HGV RNA level, serum HGV RNA becomes undetectable by RT-PCR after cessation of IFN therapy.

Adult↗
PubMed1997

Study of needlestick accidents and hepatitis C virus infection in healthcare workers by molecular evolutionary analysis.

In the five-year period between 1989 and 1993, 87 needlestick accidents occurred among healthcare workers at our hospital. Thirty-seven (43%) of these needlestick accidents involved blood contaminated with hepatitis C virus (HCV), and two of them (5.4%) led to the occurrence of hepatitis C infection. Case 1 was a 43-year-old nurse who was accidentally injured by a needle contaminated with blood from a patient who had cirrhosis and hepatocellular carcinoma due to hepatitis C. Acute hepatitis C occurred after five weeks and HCV RNA was positive after eight weeks. Case 2 was a 33-year-old nurse who was injured by a needle contaminated with blood from a patient who had chronic hepatitis C. Liver function was normal at 11 days after the accident. However, hepatitis C was diagnosed 21 months later after she had successfully given birth to her baby. The nucleotide sequence of the HCV E2/NS1 region was determined in the two patients and the needlestick victims, and phylogenetic trees were constructed by molecular evolutionary analysis. On the basis of these trees, transmission of HCV could be confirmed in both cases. This method of analysis may be useful for confirming the transmission of HCV even long after the event.

Adult↗
PubMed1997

Prevalence of hepatitis C virus infection in Nanjing, southern China.

There is little information on the prevalence of hepatitis C virus (HCV) infection in China. The prevalence of HCV infection was determined in 998 subjects (398 with liver disease and 600 without) in the city of Nanjing in southern China. Subjects were tested for anti-HCV antibodies by a second generation assay. We also determined serological HCV genotypes and HCV RNA sequences. Among the 600 subjects without liver disease, 3 (0.5%) were seroreactive for anti-HCV. All were less than 12 years of age and had a history of transfusion. Of the 398 liver disease patients, 20 (5.0%) were seroreactive for anti-HCV. Of 16 patients in whom serological HCV genotype was determined, 10 (62.5%) were infected with HCV type 1, 5 (31.3%) with type 2 and 1 (6.3%) undetermined. HCV genomes sequenced from 2 patients belonged to genotype 2 and were closely related to strains in Beijing and Japan by molecular evolutionary analysis. These results suggest that HCV infection is rare and not a major cause of liver disease in southern China.

Adult↗
PubMed1997

Sequence variation and phylogenetic analysis of the 5' terminus of hepatitis G virus.

We determined the nucleotide and deduced amino acid sequence of the 5' terminus of the hepatitis G virus (HGV) genome from isolates of varied geographical origins. Our analysis showed that the putative 5' non-coding region (NCR) contains several blocks of highly conserved sequences that may be useful for the development of a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for detection of HGV RNA. Overall, the degree of conservation within the 669-nucleotide (nt) 5'terminal sequence was found to range from 99.5% to 86% sequence identity. We also showed that the HGV NCR from some isolates contained conserved insertions or deletions that altered the translational reading frames at the 5'-end of the genome, resulting in different sizes of predicted polyproteins encoded by genomes of individual isolates. Specifically, the insertions/deletions affected the size of the peptide preceding the putative first envelope (E1) protein. Phylogenetic analysis of the nucleotide sequences suggested that the isolates examined can be classified into distinct groups that may be useful for studying the molecular evolution of HGV and possible relationships between isolate sequence characteristics and infection patterns.

Adenovirus E1 Proteins↗