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Biomedical subjects

Shunji Mishiro

Publications and source records attributed to Shunji Mishiro.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of clinical features of acute hepatitis caused by hepatitis E virus (HEV) genotypes 3 and 4 in Sapporo, Japan.

In Japan, indigenous acute hepatitis E is not a rare disease, and is mainly caused by hepatitis E virus (HEV) genotypes 3 and 4. Whether there is a difference in clinical features between the two genotypes remains unclear. This study compares the clinical features of patients infected with the two. From January, 1994, to December, 2003, 9 infected with HEV genotype 3 and 27 patients with genotype 4 were enrolled. Patients with genotype 4 had significantly higher peak alanine aminotransferase levels (median 3430IU/L, interquartile range 1747-4763 versus 1052IU/L, 845-2707; p=0.01). The lowest prothrombin time was lower in the genotype 4 group (61%, 42-77 versus 84%, 70-96; p=0.05). In our series, patients with genotype 4 had longer median duration of hospital stay (26.5 days, 18-31 versus 18 days, 12-23.5; p=0.06). The patients with genotype 4 infection tended to have more severe clinical manifestations than those with genotype 3 infection.

Journal Article↗
PubMed2006

Hepatitis E virus infection in wild mongooses of Okinawa, Japan: Demonstration of anti-HEV antibodies and a full-genome nucleotide sequence.

Hepatitis E virus (HEV), a single-strand RNA virus, has been recovered not only from human beings but also from various species of animals. Here we report our results suggesting that mongoose should be added to the list of reservoir animals of HEV. Of 100 mongooses we examined in Okinawa, Japan, 21 were thought to be positive for anti-HEV antibodies, among which one was definitely positive for HEV RNA. Full-genome sequencing of the HEV isolate revealed that it segregates to a unique subgroup within genotype III. Interestingly, this mongoose strain was closely related to a swine isolate previously reported from Okinawa, implicating the possibility of interspecies transmission between these animals.

Journal Article↗
PubMed2006

Molecular tracing of Japan-indigenous hepatitis E viruses.

The ancestor(s) of apparently Japan-indigenous strains of Hepatitis E virus (HEV) was probably of foreign origin, but it remains unclear when and from where it made inroads. In this study, 24 genotype 3 and 24 genotype 4 HEV strains recovered in Japan each showed a significant cluster, clearly distinct from those of foreign strains, in the phylogenetic tree constructed from an 821 nt RNA polymerase gene fragment. The evolutionary rate, approximately 0.8 x 10(-3) nucleotide substitutions per site per year, enabled tracing of the demographic history of HEV and suggested that the ancestors of Japan-indigenous HEV had made inroads around 1900, when several kinds of Yorkshire pig were imported from the UK to Japan. Interestingly, the evolutionary growth of genotype 3 in Japan has been slow since the 1920s, whereas genotype 4 has spread rapidly since the 1980s. In conclusion, these data suggest that the indigenization and spread of HEV in Japan were associated with the popularization of eating pork.

Animals↗
PubMed2005

Serological markers of hepatitis B, C, and E viruses and human immunodeficiency virus type-1 infections in pregnant women in Bali, Indonesia.

Except for hepatitis B virus (HBV), there have been few data on serological markers of hepatitis viruses such as hepatitis C virus (HCV) and E virus (HEV), and human immunodeficiency virus type-1 (HIV) in Bali, Indonesia. During 5 months from April to August 2003, sera were collected from 2,450 pregnant women at eight jurisdictions in Bali, and they were tested for markers of these viruses. Only one (0.04%) was positive for antibody to HCV, but none for antibody to HIV. Hepatitis B surface antigen (HBsAg) was detected in 46 (1.9%) at a prevalence significantly lower than that in 271 of the 10,526 (2.6%) pregnant women in Bali surveyed 10 years previously (P < 0.045). The prevalence of hepatitis B e antigen in pregnant women with HBsAg decreased, also, from 50% to 28% during the 10 years (P < 0.011). Antibody to HEV (anti-HEV) was examined in 819 pregnant women who had been randomly selected from the 2,450. The overall prevalence of anti-HEV was 18%, and there were substantial regional differences spanning from 5% at Tabanan district to 32% at Gianyar district. Furthermore, the prevalence of anti-HEV differed substantially by their religions. In the Sanglah area of Denpasar City, for instance, anti-HEV was detected in 20 of the 102 (20%) Hindus, significantly more frequently than in only 2 of the 101 (2.0%) Muslims (P < 0.001). Swine that are prohibited to Muslims, therefore, is likely to serve as a reservoir of HEV in Bali. In conclusion, HBV is decreasing, HCV and HIV have not prevailed, as yet, while HEV is endemic probably through zoonotic infection in Bali.

Biomarkers↗
PubMed2005

SNPs in the promoter region of the osteopontin gene as a marker predicting the efficacy of interferon-based therapies in patients with chronic hepatitis C.

BACKGROUND: The T-helper (Th)1 immune reaction is essential for the eradication of hepatitis C virus (HCV) during interferon (IFN) therapy in patients with chronic hepatitis C. Osteopontin is a cytokine crucial for the initiation of the Th1 response. Recently, we identified four single-nucleotide polymorphisms (SNPs) in the promoter region of the osteopontin gene (OPN), at nucleotide (nt) -155, -443, -616, and -1748, and suggested that the SNP at nt -443 was a marker reflecting hepatitis activity in patients with HCV. Therefore, we examined the possibility that SNPs in OPN were also markers predicting the therapeutic efficacy of IFN in patients with chronic hepatitis C. METHODS: Blood was collected from 77 patients with chronic hepatitis C who had received either IFN monotherapy or IFN-ribavirin combination therapy (IFN-based therapies). SNPs in OPN, MxA, MBL, and LMP7 were analyzed by Invader assay. RESULTS: Promoter SNPs of OPN at nt -155, -616, and -1748 showed linkage disequilibrium at 100% to each other. Sustained virological response (SVR) was observed in 58% of all patients. The SVR rate was higher in patients with the G/G or G/A alleles in the OPN promoter SNP at nt -1748 than in those with A/A (85% vs 45%; P < 0.05). The SVR rate was also higher in patients with T/T at nt -443 than in those with C/C or C/T (86% vs 47%; P < 0.05). Such differences were particularly evident in patients with HCV genotype 1b who had a pretreatment viral load greater than 100 KIU/ml. All the patients who had G/G or G/A at nt -1748 and T/T at nt -443 obtained an SVR. On the other hand, there was no relationship between the efficacy of IFN-based therapies and SNPs in MxA, MBL, and LMP7, which had been shown to have association with the response to IFN monotherapies. CONCLUSIONS: SNPs in the promoter region of OPN may be useful as a marker to predict the efficacy of IFN-based therapies in patients with chronic hepatitis C, and further investigation regarding their real significance is warranted in a large series of patients.

Adult↗
PubMed2004

Complete or near-complete nucleotide sequences of hepatitis E virus genome recovered from a wild boar, a deer, and four patients who ate the deer.

Zoonosis has been implicated in hepatitis E virus (HEV) transmission. We examined wild boar living in a forest of Hyogo prefecture, Japan, and found HEV RNA in three of seven boars. A full-genome HEV isolate from one of them was revealed to be 99.7% identical to a previous isolate from a wild deer hunted in the same forest and to those from four patients who contracted hepatitis E after eating raw meat of the deer. These findings suggest an interspecies HEV transmission between boar and deer in their wild life, and that both animals might serve as an infection source for human beings as suggested previously.

Animals↗
PubMed2004

Genetic polymorphims in promoter region of osteopontin gene may be a marker reflecting hepatitis activity in chronic hepatitis C patients.

BACKGROUND AND AIMS: Osteopontin, an extracellular matrix protein with RGD motif, is shown to be a cytokine essential for Th1 immune response initiation. Genetic polymorphisms in the osteopontin gene (OPN) determine the magnitude of immunity against rickettsial infection in mice. Similar polymorphisms, if present also in human beings, might affect hepatitis activity in those infected with HCV. METHODS: Blood was collected from 176 patients with chronic hepatitis C. SNPs in the promoter region of OPN were analyzed in 20 patients by direct sequencing of DNA fragments amplified by PCR and in 156 patients by Invader assay. Ninety-five patients compatible to evaluation criteria were classified into three groups depending on maximal serum ALT levels during the observation periods at least for 2 years as follows; lower than 30IU/L (low-activity group), between 30 and 80IU/L with no hepatoprotective treatment (medium-activity group), and higher than 80IU/L irrespective of hepatoprotective treatment (high-activity group). RESULTS: There were 16, 19, and 60 patients in the low-, medium-, and high-activity groups, respectively. Four SNPs (nt -155, -443, -616, and -1748) were detected in the promoter region of OPN. Among them, the SNP at nt -443 (C or T) was a novel one and showed an association with hepatitis activity in our patients: T/T homozygosity was found in 2 (13%), 8 (42%), and 25 (44%), and C/T heterozygosity in 12 (75%), 8 (42%), and 23 (40%), in the low-, medium-, and high-activity groups, respectively. The other 3 SNPs already known showed linkage disequilibrium with D(') and r(2) greater than 0.937 to each other without correlation to disease activity. CONCLUSIONS: OPN promoter region SNP at nt -433 may be a useful marker reflecting hepatitis activity in chronic hepatitis C patients.

Aged↗
PubMed2004

Consumption of uncooked deer meat as a risk factor for hepatitis E virus infection: an age- and sex-matched case-control study.

It was reported previously food-borne transmission of hepatitis E virus (HEV) to humans from deer meat. The present study attempted to clarify whether eating uncooked deer meat is a major epidemiological risk factor for HEV infection in Kasai, a city in western Japan. In total, 45 volunteer subjects with experience of eating raw deer meat were enrolled. An equivalent number of people from the same area who had never eaten raw deer meat served as controls. The subjects and controls had comparable age and sex distributions. Serum anti-HEV IgG and anti-hepatitis A virus (HAV) IgG levels were measured in all 90 volunteers. There was no significant difference in age, overseas travel history, or rate of anti-HAV antibody positivity between the subjects and controls. Eight (17.7%) of the subjects but only one (2.2%) of the controls had measurable serum anti-HEV IgG levels (P = 0.014). Anti-HAV prevalence did not differ between the anti-HEV-positive and negative groups. The results suggest that eating uncooked deer meat is an epidemiological risk factor for HEV infection in the studied area. In countries such as Japan where deer meat is sometimes eaten raw, attention must be paid to this route of HEV infection.

Adult↗
PubMed2004

Estimation of the mutation rate of hepatitis E virus based on a set of closely related 7.5-year-apart isolates from Sapporo, Japan.

Since hepatitis E virus (HEV) does not persist in infected hosts or in cultured cell lines, it has been difficult to know its spontaneous mutation rate. Recently, we identified an HEV isolate in stored serum from a patient having developed hepatitis E in 1995 (JSM-Sap95), nucleotide sequence of which showed a strong resemblance to those obtained from three patients who contracted hepatitis E in 2000 and 2002 (JKK-Sap00, JYW-Sap02, and JTS-Sap02). The remarkable nucleotide similarity together with the fact that all these patients were residents of the same city, Sapporo, prompted us to hypothesize that JKK-Sap00, JYW-Sap02 and JTS-Sap02 are descendants of JSM-Sap95. Then, the mutation rate of HEV was calculated to be 1.72, 1.41, or [Formula: see text] base substitutions per site per year, from JSM-Sap95 to JKK-Sap00, JYW-Sap02 or JTS-Sap02, respectively. Interestingly, these values were very similar to those ( [Formula: see text] to [Formula: see text] ) reported for hepatitis C virus. Because it remains possible that JSM-Sap95 is not the direct ancestor of the other three isolates but was merely a relative of the true ancestor, HEV mutation rate may be a little lower than [Formula: see text] base substitutions per site per year.

Journal Article↗
PubMed2004

Transfusion-transmitted hepatitis E caused by apparently indigenous hepatitis E virus strain in Hokkaido, Japan.

BACKGROUND: In industrialized countries, sporadic cases of hepatitis E have been reported in individuals who have never been in an endemic area. Hepatitis E virus (HEV) infection commonly occurs via the fecal-oral route but a potential risk of transfusion transmission route has been suggested. STUDY DESIGN AND METHODS: A 67-year-old Japanese male patient who had never been abroad received a transfusion of blood from 23 voluntary donors and developed acute hepatitis with unknown etiology after transfusion. His blood samples were tested for viral markers of hepatitis viruses. RESULTS: HAV, HBV, HCV, CMV, and EBV were ruled out as causative agents in this case. The patient's blood sample in the acute phase contained HEV RNA as well as IgM and IgG anti-HEV. HEV RNA was also detected in one of the FFP units transfused. The donor had no history of traveling abroad and had a normal ALT level at the time of donation. The PCR products from the patient and the donor showed complete identity for two distinct regions of HEV within open reading frame 1. CONCLUSION: The patient was infected with HEV via transfused blood from a volunteer donor. A potential risk of posttransfusion hepatitis E should be considered even in nonendemic countries.

Adult↗
PubMed2004

Identification of basal promoter and enhancer elements in an untranslated region of the TT virus genome.

The regulation of TT virus (TTV) gene expression was characterized. Transient-transfection assays using reporter constructs revealed that a 113-nucleotide (nt) sequence within the untranslated region, proximal to the transcription initiation site and containing a TATA box motif, has a basal promoter activity. This sequence is well conserved among different TTV genotypes. Upstream stimulating factor bound to a consensus binding motif within this region and positively regulates TTV transcription. Furthermore, a 488-nt region upstream of the basal promoter exhibited enhancer activity, presumably in a cell type-specific manner. This study illustrates some of the mechanisms involved in the transcriptional regulation of TTV.

Artificial Gene Fusion↗
PubMed2004

[Recent topics on hepatitis E virus: emerging, zoonotic, and animal-to-human transmission in Japan].

Hepatitis E is undoubtedly a zoonosis. Recent observations suggest that the zoonotic food-borne mode of transmission has played an important role in the spread of hepatitis E virus (HEV) among Japanese people (who in general likes eating everything uncooked or undercooked: Sushi, Sashimi, Tataki, Namagimo, Shabu-shabu, etc). Moreover, the situation seems to be worsening. Wild boar (and deer also) has recently been increasing in its number, becoming a more potent HEV reservoir to humans than before. Pork, replacing beef in people's recent fear of BSE, is being consumed increasingly, particularly in Hokkaido. It may be Japanese people that an effective HEV vaccine is most longed for by.

Animals↗