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S Mishiro

Publications and source records attributed to S Mishiro.

At least 19 recordsLinked to original sources
PubMed1998

Mother-to-infant transmission occurs more frequently with GB virus C than hepatitis C virus.

A total of 107 hepatitis C virus (HCV)-infected pregnant women were screened for GB virus C (GBV-C) RNA in their sera, and 11 (10.3%) were positive. Among 11 infants born to these HCV/GBV-C co-infected mothers, GBV-C RNA was detected in 7 (63.6%) while HCV RNA was found in 1 (9.1%) within 1 year after birth: this difference was statistically significant (p = 0.023). The mothers of infected infants had significantly higher serum titers of GBV-C RNA than those of uninfected infants: 10(6.7 +/- 0.5) vs 10(4.0 +/- 1.0) copies/ml in average (p = 0.001). The baby in whom HCV RNA was found was also positive for GBV-C RNA, and had an elevation in serum transaminase levels, whereas all the other GBV-C infected infants showed no evidence for hepatitis. A family study, performed on 2 of the 7 infected cases, revealed that all the elder siblings of the index infants were also GBV-C RNA-positive. Nucleotide sequence of GBV-C RNA, amplified by PCR from an NS3 region, was completely identical between the mother and the infant within each family, but varied significantly across different families. These results suggest that GBV-C is more easily transmitted from mother to infant than HCV, although hepatitis is not caused thereby.

Base Sequence↗
PubMed1996

Prevalence of hepatitis C virus and distribution of its genotypes in Northern Eurasia.

We tested hepatitis C virus (HCV) antibody in 4216 sera collected from healthy people living in European part of Russia (including Northern, North-Western, Central, Central-Blacksoil, Volga-Vyatka, Volga, and North-Caucasian regions), non-European part of Russia (the Urals, East-Siberia, and the Far-East regions) and Mongolia. Prevalence of HCV antibody varied significantly by regions, ranging from 0.7% in Central region of European part of Russia to 10.7% in Mongolia. Genotyping of HCV (into 1a, 1b, 2a, 2b, and 3a) was performed on 469 sera from blood donors and patients (in Russia, Moldova, Turkmenistan, and Mongolia) who were positive for both HCV antibody and RNA. Genotype 1b was the most dominant genotype irrespective of regions (68.9%), with the highest rate in Moldova (96%). HCV unclassifiable into genotypes 1a-to-3a was found in 28 (6.0%) samples: particularly 4 of 10 samples from Lipetzk were untypable. Overall, HCV genotypes in European part of Russia were more similar to those in European countries, while those in Eastern part of Russia more similar to China or Japan. Genotype distribution was not associated with the clinical expression of HCV disease: acute hepatitis, chronic hepatitis or liver cirrhosis.

Adult↗
PubMed1996

Very low incidence rates of community-acquired hepatitis C virus infection in company employees, long-term inpatients, and blood donors in Japan.

To assess the contemporary rate of hepatitis C virus (HCV) propagation in Japanese community, we conducted a sentinel study on three groups of people: company employees, long-term inpatients, and blood donors. A total of 3079 company employees negative for anti-HCV were followed thereafter, and seroconversion to anti-HCV was found in 5 per 5786 person-years. None of them was positive for HCV RNA. In the group of 703 long-term inpatients (25 of whom were initially positive for anti-HCV) none showed seroconversion to anti-HCV per 2712 person-years. As for 114,266 repeated blood donors who were initially antibody-negative, 227 became anti-HCV positive later. Of these seroconverted donors, 83 were found to have anti-HCV with titers of 2(6) or greater. HCV RNA was positive in only 3 of them. Thus, the incidence rates of acquired HCV viremia in these three groups were 0 for both company employees and long-term inpatients, and 1.78 (95% C.I.: 0.37-5.19) per 100,000 person-years in blood donors. These results suggest that community-acquired HCV infection is now rare in Japan, and that even if it occurred it hardly leads to persistent viremia.

Adolescent↗
PubMed1995

Detection of the GBV-C hepatitis virus genome in serum from patients with fulminant hepatitis of unknown aetiology.

Hepatitis viruses A, B, C, D, and E have not accounted for all cases of hepatitis, hence "non A-E" agent(s) might be implicated. A set of new viruses (GBV-A, -B, and -C) whose genomes have been sequenced, are being investigated as possible causes of non A-E hepatitis. We investigated six cases of fulminant hepatitis of unknown aetiology for the presence of GBV-C genome in their serum, and three showed positive signals by semi-nested PCR using primers derived from the NS3/helicase region. Nucleotide sequence analyses confirmed these signals to be derived from a GBV-C sequence. The results suggest the importance of GBV-C in the aetiology of fulminant hepatitis.

Adolescent↗
PubMed1995

Influence of the genotypes of hepatitis C virus on the severity of recurrent liver disease after liver transplantation.

BACKGROUND/AIMS: Several genotypes of hepatitis C virus (HCV) have been identified by phylogenetic analysis, but their clinical relevance remains elusive. Liver transplantation for HCV-related cirrhosis offers a unique opportunity for prospective studies of this issue. METHODS: Sixty anti-HCV-positive liver recipients with precise virological and histological assessments were included. HCV genotype was determined with both type-specific capsid primers and a line probe genotyping assay. RESULTS: HCV genotype 1b was the predominant type before transplantation (40 of 60 patients); after liver transplantation, acute and chronic active hepatitis developed more frequently in these patients than in patients infected by other genotypes (31 of 40 and 24 of 40 vs. 8 of 20 and 4 of 20 patients). Actuarial rates of acute hepatitis and chronic active hepatitis were 77% and 59%, respectively, 3 years after transplantation in patients infected by type 1b and 40% (P = 0.008) and 22% (P = 0.004) in those infected by other types. There was no statistical relation between the level of HCV viremia and HCV genotypes both before and after transplantation. In contrast, after transplantation, serum HCV RNA values were significantly increased in patients who developed hepatitis after transplantation. CONCLUSIONS: This study provides direct evidence that HCV 1b is associated with more aggressive recurrent liver disease than other genotypes.

Actuarial Analysis↗
PubMed1995

Transmission of hepatitis C virus from mothers to infants: its frequency and risk factors revisited.

A total of 16,714 pregnant Japanese women were tested for antibodies against hepatitis C virus (HCV), and 163 (0.98%) were positive. None of these were infected with human immunodeficiency virus-1 (HIV-1). We conducted a prospective study to discover the rate of HCV infection in babies born to mothers who were HCV RNA-positive but had no evidence for hepatitis (so called "asymptomatic carriers"), and only 2 (2.3%) of 87 such babies became infected during follow-up. This rate was considerably lower than those from other reports which included mothers with clinically overt chronic hepatitis C. We conducted another study to follow babies born to mothers with chronic hepatitis C, and found two babies infected. All of the four infected babies were born to mothers who had HCV RNA in their circulations around delivery at high titers (greater than 5.0 x 10(6) Eq/ml by branched DNA assay). This confirmed the previous finding that virus load was an important risk factor. In addition, we found three families where mother-to-infant HCV transmission was suspected in a retrospective study by indexing HCV-infected pediatric patients. Throughout the seven families, siblings of infected babies were free from HCV infection, suggesting that maternal infection of HCV owes much to chance. Breast milk feeding was not regarded as a risk factor. We also assessed the prevalence of anti-HCV antibody among 6-year old children, and only 10 of 10,446 (0.1%) were positive, suggesting low frequency of HCV infection during the period from birth to this age.

Carrier State↗
PubMed1995

The precore/core promoter mutant (T1762A1764) of hepatitis B virus: clinical significance and an easy method for detection.

Recently, a new hepatitis B virus (HBV) mutant with HBe antigen-negative phenotype has been characterized, in which one TATA box-like motif of the precore/core promoter had degenerated: most frequently by both A-->T and G-->A mutations at positions 1762 and 1764, respectively. The clinical significance of this mutant is as yet unknown. In our present study, the T1762 A1764 mutant was sought in sera from HBV-infected blood donors and chronic liver disease patients by directly sequencing a PCR-amplified region of HBVDNA. Also, because the A1764 mutation generates a Sau3AI cleavage site (GGTC-->GATC), we digested the PCR products with Sau3AI to see if cleavage would occur at this specific site. Our results mostly corroborated the earlier report but we found a higher-than-predicted frequency of HBe antigen-positive blood donors positive for the mutant (22%). The titres of HBe antigen in these mutant-positive sera were slightly decreased compared to the titres in wild-type HBV infection. In addition, these blood donors had relatively high (though within the normal range) serum alanine aminotransferase (ALT) levels, suggesting that the T1762 A1764 mutation could be used as a sensitive laboratory marker for insidious hepatitis in these otherwise 'asymptomatic' carriers. The Sau3AI assay, which is much more convenient than sequencing, was shown to be useful for the detection of the T1762 A1764 mutant in an extensive number of clinical samples.

Alanine Transaminase↗
PubMed1994

A redox factor protein, ref1, is involved in negative gene regulation by extracellular calcium.

A rise in extracellular calcium (Ca2+e) suppresses not only secretion of parathyroid hormone (PTH) but also expression of the PTH gene to ensure constant plasma Ca2+ level. A nuclear protein(s) in a wide variety of cells bound to the specific DNA elements (negative Ca2+ responsive elements, nCaREs) in the human PTH gene in sequence-specific and Ca2+e concentration-dependent manners. Our Southwestern cloning revealed that a redox factor protein (ref1), which was known to activate several transcription factors via alterations of their redox state, belonged to an nCaRE binding protein. The level of ref1 mRNA as well as of its protein was elevated by an increase in Ca2+e concentration. In gel shift assay, anti-ref1 antibody eliminated formation of the nCaRE-protein complex. We also found that there was another protein(s) interacting with nCaREs and ref1. Further, experiments with an antisense-ref cDNA expression vector introduced into cultured cells suggested that DNA (nCaRE)-ref1 interaction led to Ca2+e-mediated transcriptional suppression. Thus, it is concluded that ref1 possesses transcription repressor activity in addition to its function as a transcriptional auxiliary protein.

Animals↗
PubMed1994

Hepatitis C virus variants from Vietnam are classifiable into the seventh, eighth, and ninth major genetic groups.

Thirty-four (41%) of 83 hepatitis C virus (HCV) isolates from commercial blood donors in Vietnam were not classifiable into genotype I/1a, II/1b, III/2a, IV/2b, or V/3a; for 15 of them, the sequence was determined for 1.6 kb in the 5'-terminal region and 1.1 kb in the 3'-terminal region. Comparison of the 15 Vietnamese isolates among themselves and with reported full or partial HCV genomic sequences indicated that they were classifiable into four major groups (groups 6-9) divided into six genotypes (6a, 7a, 7b, 8a, 8b, and 9a). Vietnamese HCV isolates of genotypes 7a, 7b, 8a, 8b, and 9a were significantly different from those classified into groups 4, 5, and 6 based on divergence within partial sequences; those of genotype 6a were homologous to a Hong Kong isolate (HK2) of genotype 6a. Phylogenetic trees based on the envelope 1 (E1) gene (576 bp) of 55 isolates and a part of the nonstructural 5 (NS5) region (1093 bp) of 43 isolates revealed at least nine major groups, three of which (groups 7, 8, and 9) were identified only in Vietnamese blood donors. With a prospect that many more HCV isolates with significant sequence divergence will be reported from all over the world, the domain of the HCV genome to be compared and criteria for grouping/typing and genotyping/subtyping will have to be determined, so that they may be correlated with virological, epidemiological, and clinical characteristics.

Base Sequence↗
PubMed1994

Hepatitis C virus infection in spouses of patients with type C chronic liver disease.

OBJECTIVE: Survey for markers of hepatitis C virus (HCV) infection in spouses of patients with HCV-related chronic liver disease. DESIGN: Cross-sectional clinical, serologic, and molecular biological study of spouses of patients with HCV viremia and chronic liver disease. SETTING: University and city hospitals. PARTICIPANTS: Spouses (52 men and 102 women; mean age, 56 +/- 11 years) of 154 patients with HCV viremia (102 men and 52 women; mean age, 58 +/- 10 years), of whom 66 had chronic hepatitis, 49 had liver cirrhosis, and 39 had primary hepatocellular carcinoma. METHODS: Tests for HCV-associated antibodies were done using a second-generation enzyme immunoassay and immunoassays with synthetic oligopeptides deduced from the HCV core gene. Hepatitis C virus RNA was detected by polymerase chain reaction with primers deduced from the 5'-noncoding region and HCV genotypes by reaction with type-specific primers deduced from the HCV core gene. RESULTS: Hepatitis C virus-associated antibodies were detected in 42 (27%) spouses, of whom 25 were also positive for HCV RNA. Of 112 (73%) spouses without detectable antibodies, 2 had chronic liver disease. The development of markers of HCV infection in spouses increased with the duration of marriage, ranging from 1 to 60 years (30 +/- 11 years). CONCLUSIONS: Spouses of patients with HCV viremia and chronic liver disease have an increased risk for acquiring HCV, which is proportional to the duration of marriage. They should be followed routinely for markers of HCV infection and liver disease.

Aged↗
PubMed1994

Safety and efficacy of a recombinant yeast-derived pre-S2 + S-containing hepatitis B vaccine (TGP-943): phase 1, 2 and 3 clinical testing.

A recombinant yeast-derived pre-S2 + S-containing hepatitis B vaccine (TGP-943) was clinically evaluated through three phases of testing in a total of 2137 volunteers. We observed the immunogenic purity of TGP-943 (phase 1), the inter-lot reproducibility of both safety and immunogenicity (phase 2), no significant side-effects, a high capability of inducing both anti-HBs and anti-pre-S2 antibodies (phases 1, 2 and 3), and an ability to induce seroconversion in the majority of vaccines who had been non-responsive to conventional hepatitis B vaccines (phases 2 and 3). In conclusion, TGP-943 is a safe and tolerable vaccine, with special merits: the ability to induce an early anti-pre-S2 response that circumvents the problem of delayed appearance of anti-HBs, and efficacy in non-responders to previous vaccination.

Adolescent↗
PubMed1994

Genetic heterogeneity of hepatitis C virus.

There are four hierarchical strata in the genetic heterogeneity of hepatitis C virus (HCV): group above subgroup above isolates above quasispecies. The entire genome sequence has so far been reported for 16 isolates which are classifiable into 3 groups and 6 subgroups. Provisional classification of HCV is also possible using a partial sequence of the HCV genome. With the E1 region sequence for example, the present collection of HCV isolates can be classified into 9 groups and 23 subgroups. The rationale for these classifications and the epidemiological and clinical implications of genotyping HCV are reviewed.

Amino Acid Sequence↗
PubMed1994

Superinfection of chimpanzees carrying hepatitis C virus of genotype II/1b with that of genotype III/2a or I/1a.

Three chimpanzees persistently infected with hepatitis C virus of genotype II/1b were challenged with hepatitis C virus of genotype III/2a and 6 wk later with hepatitis C virus of genotype I/1a. They were tested for titers of total and genotype-specific hepatitis C virus RNA, as well as for serum transaminase levels, until 52 wk after the first challenge. One chimpanzee (CH489) with intermittent low hepatitis C virus RNA titers of genotype II/1b in serum was superinfected with hepatitis C virus of genotype III/2a between wk 1 and 7 after the challenge; superinfection was accompanied by fluctuating high transaminase levels. Later, the animal was superinfected with hepatitis C virus of genotype I/1a. Superinfection was accompanied by persistently high transaminase levels immediately after the challenge. Hepatitis C virus of genotype I/1a persisted, whereas hepatitis C virus of genotype II/1b was undetectable 22 wk after the challenge and thereafter. In another chimpanzee (CH353) with intermittent low hepatitis C virus RNA titers of genotype II/1b, hepatitis C virus of genotype III/2a induced fluctuating high levels of serum transaminases without revealing itself in serum. Then, HCV of genotype I/1a superinfected her, induced persistently high transaminase levels and took over HCV of genotype II/1b at 22 wk after the challenge and thereafter. The third chimpanzee (CH451) with persistently high HCV RNA titers of genotype II/1b did not reveal HCV RNA of genotype III/2a in serum after the challenge, although transaminases sharply increased. Low-titered HCV RNA of genotype I/1a was detected at 18 wk after the challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗