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Biomedical subjects

F Tsuda

Publications and source records attributed to F Tsuda.

At least 37 records · Page 2Linked to original sources
PubMed1998

Infection with an unenveloped DNA virus (TTV) associated with posttransfusion non-A to G hepatitis in hepatitis patients and healthy blood donors in Thailand.

An unenveloped single-stranded DNA virus (TTV) has been reported in association with posttransfusion and acute and chronic hepatitis of unknown etiology. DNA of TTV was tested for by polymerase chain reaction with heminested primers in 127 patients with chronic liver disease and 105 healthy blood donors in Thailand. TTV DNA was detected in 23 (59%) of the 39 patients without hepatitis B surface antigen or RNA of hepatitis C virus, at a frequency significantly higher than the detection in 21 (36%) of the 59 patients with HBsAg (P < 0.05) or in 38 (36%) of the 105 blood donors (P< 0.05). Among patients with chronic liver disease, TTV DNA occurred in those with liver cirrhosis and hepatocellular carcinoma more frequently than in those with chronic hepatitis (35 of 65 or 54% vs. 20 of 62 or 32%, P< 0.05). There were no differences in age, sex, or markers of infection with hepatitis B, C and GBV-C/HGV viruses, indicating a mode of transmission of TTV different from those of the other hepatitis viruses. Phylogenetic analysis indicated three different genotypes of TTV with six distinct subtypes in Thailand. Based on these results, TTV would have a role in the development of chronic liver disease of unknown etiology in Thailand.

Base Sequence↗
PubMed1998

Incidence and influence of GB virus C and hepatitis C virus infection in patients undergoing bone marrow transplantation.

Markers of GB virus C (GBV-C) and hepatitis C virus (HCV) were sought in 80 patients before and after they underwent BMT in a metropolitan hospital in Tokyo between 1990 and 1996. RNA of GBV-C was detected in 14 (18%) patients before BMT. Of the 55 patients who had been transfused, 14 (25%) possessed GBV-C RNA at a frequency significantly higher than in the 25 untransfused patients who were all negative (P < 0.01). HCV RNA was detected in three of the 55 (5%) transfused patients, but in none of the 25 untransfused patients. Sera at 3 months after BMT were available for 57 patients. GBV-C RNA persisted in all 10 patients who were infected before BMT, while it was detected in five of the remaining 47 (11%) patients who were not. However, persistent and/or ongoing GBV-C infection had no appreciable influence on patient morbidity or mortality. Two of the 57 patients were positive for HCV RNA before BMT and this persisted after BMT in both. HCV RNA became positive in eight of the remaining 55 (15%) patients who were negative before BMT. Of the 14 patients who received transfusions screened by the first-generation test at BMT, seven (50%) became positive for HCV RNA, a rate significantly higher than the one of 41 (2%) patients who received transfusions screened by the second-generation test (P < 0.001). These results indicate that BMT patients are at increased risk of GBV-C infection transmitted by transfusions received before and at the time of BMT, and that the risk of HCV infection has decreased after the implementation of the second-generation anti-HCV test.

Adolescent↗
PubMed1998

The entire nucleotide sequences of three hepatitis C virus isolates in genetic groups 7-9 and comparison with those in the other eight genetic groups.

We have proposed that hepatitis C virus should be classified into eleven genetic groups (types) which further divide into more than 80 genotypes (subtypes). However, only eight genetic groups (1-6, 10 and 11) have been defined on the basis of the full-length sequence. Hence, the entire nucleotide sequences of three HCV isolates in genetic groups 7-9 have now been determined. Phylogenetic analysis over the full-length sequences of these three isolates, along with 30 more in the other eight genetic groups, indicated that genetic groups 6-9 and 11 have bifurcated from a common branch and groups 3 and 10 from another. In the former branch groups 7 and 11, and groups 8 and 9, are closely related. Consequently, HCV can be classified into either eleven (1-11) or six groups (1; 2; 3 and 10; 4; 5; 6-9 and 11), allowing a clear separation of group and genotype similarity within the NS5b region or a subregion of 1093 nt. When pairwise comparison of 1093 nt in the NS5b sequence was performed on 106 HCV isolates of 36 genotypes in eleven genetic groups, they were classified into either eleven (1-11) or six (1; 2; 3 and 10; 4; 5; 6-9 and 11) genetic groups. However, group and genotype similarities were not clearly separable in either classification. The overlapping range was smaller using the classification into eleven genetic groups as compared to six genetic groups (2.7 vs 4-7%). These results indicate that HCV might not have evolved in the two-tiered fashion, at least in a strict sense.

Base Sequence↗
PubMed1998

Prevalence of anti-hepatitis C antibodies in a rural community without high mortality from liver disease in Niigata prefecture.

The prevalence of hepatitis C virus (HCV) infection and factors relating to the HCV transmission were evaluated in a community without high mortality from chronic liver disease in Niigata prefecture. A total of 2,231 subjects were examined to detect anti-HCV core antibodies by enzyme-linked immunosorbent assay with synthetic peptides CP14 and CP9. The prevalence was 1.66% (95% CI; 1.17% to 2.29%) and tended to increase with age. The values were lower than those reported from districts with hepatic disease endemic. Histories of blood transfusion (relative risk (RR) 5.51; 95% CI 2.90 to 10.48) and surgery with hospital admission (RR 4.43; 95% CI 2.04 to 9.65) were significantly associated with the anti-HCV core antibodies positive. Multiple logistic analysis corroborated independency of these factors. Among 188 subjects who experienced surgery and/or blood transfusion after 1990, only one (0.5%) had HCV infection. By contrast, 8 (3.5%) were positive in subjects who experienced first acupuncture therapy after 1990. The acupuncture therapy in alternative medicine could be still related to the HCV transmission.

Acupuncture Therapy↗
PubMed1998

Infection with GB virus C, hepatitis C and B viruses in 1,044 cases autopsied at the Medical Examiner's Office in Tokyo.

Markers of GB virus C (GBV-C), hepatitis C virus (HCV) and hepatitis B virus (HBV) were sought in sera from 1,044 cases autopsied at the Medical Examiner's Office, Tokyo Metropolitan Government. GBV-C RNA was detected in 35 (3%) cases at a frequency significantly higher (P < 0.05) than in blood donors in Tokyo (4 of 448 or 1%). Three genotypes of GBV-C provisionally designated G1, G2 and G3 were determined by selective amplification with type-specific primers, and G3 (Asian type) was detected in 31 (89%), G2 (European/American type represented by the prototype hepatitis G virus) in three (9%) and G1 (West African type represented by the prototype GBV-C) in one (3%). Antibody to HCV (anti-HCV) was detected in 116 (11%) cases and accompanied by HCV RNA in 88. HCV genotypes were I/1a in one (1%), II/1b in 55 (63%), III/2a in 17 (19%) and IV/2b in 13 (15%). Antibodies to hepatitis B virus (HBV) was detected in 335 (32%) cases and hepatitis B surface antigen in 14 (1%). Subtypes were determined in 12 of them, adw was found in seven (58%), adr in four (33%) and adyr in one (8%). GBV-C RNA was detected significantly more frequently (P< 0.01) in the cases with liver disease (9 of 70 or 13%) than in those with the other causes of death (26 of 974 or 3%). Anti-HCV was more frequent in the cases with GBV-C RNA than in those without it (15 of 35 or 43% vs. 101 of 1,009 or 10%, P< 0.001). These results indicate that infection with GBV-C as well as HCV was common, while infection with HBV was not common in the Medical Examiner's autopsy cases in Tokyo.

Adolescent↗
PubMed1998

An enzyme-linked immunosorbent assay with monoclonal antibodies for the determination of phosphorylated hepatitis B core protein (p21c) in serum.

An enzyme-linked immunosorbent assay (ELISA) was developed for the determination of hepatitis B virus (HBV) core protein (p21c) using monoclonal antibody (mAb) directed to a phosphorylated C-terminal amino acid sequence that is not present in hepatitis B e antigen (HBeAg). HBV virions in the test serum were precipitated with horse polyclonal antibody to hepatitis B surface antigen (HBsAg), dissolved with Tween 20 and NaOH, and then neutralized. HBV core protein (p21c), released from HBV cores by this procedure, was sandwiched between immobilized mAb C33 directed to amino acids (aa) 133-140 of the core protein, fixed on a solid support and labeled mAb T2212 that recognizes aa 165-175, only when they are phosphorylated. The method was applied for the detection of phosphorylated p21c in sera from symptom-free carriers and patients with chronic hepatitis. The results indicated a higher extent of phosphorylation in p21c of HBV cores from symptom-free carriers than hepatitis patients.

Animals↗
PubMed1998

Fecal excretion of a nonenveloped DNA virus (TTV) associated with posttransfusion non-A-G hepatitis.

Five patients with type B or C hepatocellular carcinoma were found to be infected with a nonenveloped DNA virus (TTV) associated with posttransfusion hepatitis of non-A-G etiology. Paired feces and serum samples from these patients were tested for TTV DNA by polymerase chain reaction with seminested primers and their sequences were compared. TTV DNA was detected in sera from all of the patients, while it was detected in feces from three patients, including two with high viral titers in serum. When feces and serum from one patient were subjected to floatation ultracentrifugation in CsCl, TTV in feces banded at a peak density of 1.35 g/cm3 and that in serum at 1.31-1.32 g/cm3. TTV isolates in three pairs of feces and serum had the identical sequence of 222 base pairs. The excretion of TTV into feces indicates that TTV would be transmitted not only parenterally but also nonparenterally by a fecal-oral route.

Base Sequence↗
PubMed1997

Mutation rate of GB virus C/hepatitis G virus over the entire genome and in subgenomic regions.

A patient on maintenance hemodialysis was infected with a recently discovered putative non-A to -E hepatitis virus designated GB virus C (GBV-C) or hepatitis G virus (HGV) by transfusion. The viral isolate was recovered from the patient soon after she turned positive for GBV-C/HGV RNA in serum (GS185) and 8.4 years thereafter (GS193), and the entire nucleotide sequences were determined. They both had a genomic length of 9391 nucleotides with a defective C gene made of only 42 nucleotides. Between GS185 and GS193, 31 (0.33%) nucleotides were different, which changed 5 (0.18%) of the encoded 2842 amino acids. Thus, GBV-C/HGV was estimated to have a mutation rate of 3.9 x 10(-4) base substitutions per site per year. Nucleotide conversions were distributed over subgenomic regions, except in the 5' untranslated region of 552 nucleotides and a defective short C gene, which were conserved in sequence. The change in the putative envelope genes (E1 and E2) was no different from that in the entire genome with only 6 (0.35%) nucleotide substitutions among the 1730, just 1 of which induced an amino acid conversion. Taken along with the comparison of the two isolates with the reported five GBV-C or HGV isolates, these results indicate that GBV-C/HGV would not have hypervariable regions and would use a strategy for viral persistence that is different from immune escape.

Amino Acid Sequence↗
PubMed1997

Infection with GB virus C and hepatitis C virus in hemodialysis patients and blood donors in Beijing.

RNAs of GB virus C (GBV-C) and hepatitis C virus (HCV) were sought by reverse-transcription polymerase chain reaction with nested primers deduced from the 5' untranslated region: 79 patients on maintenance hemodialysis, 205 commercial blood donors, and 205 voluntary donors in Beijing were studied. GBV-C RNA was detected in 43 (54%) patients and 17 (8%) commercial donors, and HCV RNA in 43 (54%) patients and 13 (6%) commercial donors, respectively. By contrast, GBV-C RNA was detected only in 2 (1%) and HCV RNA in none among 205 volunteer blood donors serving as controls. Thus both patients and commercial blood donors were at higher risk for infection with GBV-C (P < 0.001) than controls. HCV RNA was detected more often in patients with GBV-C RNA than without (29/43 or 67%, vs. 14/36 or 39%, P < 0.05) as well as in commercial donors with GBV-C RNA than without (5/17 or 29% vs. 8/188 or 4%, P < 0.01). A phylogenetic tree constructed on a sequence of 100 base pairs in the helicase region indicated that GBV-C isolates from Beijing are more similar to Japanese isolates than to isolates from the United States and Africa. Sequences from certain hemodialysis patients and those from some commercial donors were similar, suggesting nosocomial infection and spread among restricted groups.

Adult↗
PubMed1997

Infection with GB virus C and hepatitis C virus in drug addicts, patients on maintenance hemodialysis, or with chronic liver disease in Nepal.

Infection with GB virus C (GBV-C) and hepatitis C virus (HCV) was surveyed in various populations in Kathmandu, Nepal. GBV-C RNA and HCV RNA were detected in four (2%) and none, respectively, of 181 normal controls. Viral RNAs were detected significantly more frequently (P < 0.001) in 32 (44%) and 43 (60%), respectively, of 72 users of illicit intravenous drug, and in three (14%) and one (5%) of 22 patients on maintenance hemodialysis. The three hemodialysis patients with GBV-C RNA had been transfused with more blood units than the 19 without GBV-C RNA (51 +/- 21 vs. 5 +/- 3 units, P < 0.01), and one was co-infected with HCV. Of 145 patients with chronic liver disease, GBV-C RNA was detected in four (3%) and HCV RNA in 12 (8%); only one patient with GBV-C RNA was without markers of HCV or hepatitis B virus infection. In the 32 drug addicts infected with GBV-C, genotypes were G1 in two (6%), G2 in 26 (81%), G3 in three (9%), and the remaining one (3%) was coinfected with G2 and G3. GBV-C genotypes in the 13 individuals in the populations other than drug addicts were G2 in 11 (85%) and G3 in two (15%). HCV genotypes in the 43 drug addicts with viremia were l/1a in 21 (49%), V/3a in 19 (44%) and l/1a plus V/3a in two (5%); these genotypes were not prevalent in normal controls and patients with chronic liver disease in Nepal. These results indicate that GBV-C infection is prevalent in healthy subjects in Nepal at a frequency (2%) comparable with those in the other countries and that GBV-C transmits efficiently by intravenous drug abuse among drug addicts and by transfusion in hemodialysis patients.

Adult↗
PubMed1997

Molecular investigation of GB virus C infection in hemophiliacs in Japan.

RNA of a putative non-A, -B, -C, -D, or -E hepatitis virus named GB virus C (GBV-C) was detected by reverse transcription-polymerase chain reaction with primers deduced from the 5' untranslated region in 15 (24%) of 63 men with hemophilia in Japan at a frequency higher (P < .001) than that in 2 (0.6%) of 337 controls. By phylogenetic analysis, GBV-C isolates from some patients were similar in sequence, indicating infection with closely related strains, and those from certain patients resembled sequences reported from foreign countries. All patients were infected with hepatitis C virus, and genotypes that are rare in Japan were detected in 36 (57%) of them. These results indicate that patients with hemophilia in Japan would be at increased risk for infection with GBV-C and hepatitis C virus, some of which would have been transmitted via imported coagulation factor concentrates in the past.

Adolescent↗
PubMed1997

Response to interferon-alpha 2a in patients with e antigen-negative chronic hepatitis B.

Sixty-eight consecutive patients with chronic hepatitis B received 702 million units of recombinant interferon-alpha 2a. Of the 24 patients negative for hepatitis B e antigen (HBeAg) in serum, the normalization of serum transaminase occurred in 14 (58%) at the completion of interferon therapy and in 13 (54%) at 12 months thereafter; it was normalized in 17 (39%) and 13 (30%), respectively, of the 44 HBeAg-positive patients. Of the HBeAg-negative patients, hepatitis B virus DNA was cleared from serum in six (25%) at the completion and in one (4%) at 12 months thereafter, in contrast to only one (2%, p < 0.05) and none of the HBeAg-positive patients, respectively. The 1896th nucleotide of G (G1896) for codon 28 for tryptophan or A (A1896) for the stop codon 28 in the precore region was determined by restriction fragment length polymorphism. The ten HBeAg-negative patients with A1896 only in the precore region had lower pretreatment levels of viral markers, which decreased more rapidly and extensively after interferon than in the 14 HBeAg-negative patients with a mixture of G1896 and A1896 or in the 44 HBeAg-positive patients. These results indicate that patients with HBeAg-negative chronic hepatitis B may respond better to interferon than HBeAg-positive patients, and that the precore mutant with the stop codon 28 may be sensitive to interferon.

Adult↗
PubMed1997

The entire nucleotide sequences of two GB virus C/hepatitis G virus isolates of distinct genotypes from Japan.

Recently, putative viral agents responsible for human non-A to E hepatitis have been independently reported by two groups of investigators and designated GB virus C (GBV-C) and hepatitis G virus (HGV), respectively. The entire nucleotide sequences were determined for two viral genomes isolated from Japanese blood donors with GBV-C RNA. One of them (GT230) had a total genomic length of 9390 nucleotides (nt) with 5' and 3' untranslated regions of 551 and 313 nt, while the other (GT110) had genomic lengths of 9395, 281 and 315 nt, respectively. They both had a single long open reading frame, encoding 2842 amino acids (aa) in GT230 and 2933 aa in GT110. Surprisingly, they both lacked a clearly identifiable core gene, and possessed the E1/E2 gene with only four potential N-linked glycosylation sites. Pairwise comparison and phylogenetic analysis of the entire sequence indicated that the prototype GBV-C and two HGV isolates reported, as well as GT230 and GT110, are the same virus possibly of different genotypes. The five GBV-C/HGV isolates were variable up to 13.8% in the genomic nucleotide sequence, and contained deletions and insertions within the 5'-terminal 518-593 nt, which resulted in four different sizes of predicted polyproteins encoded by genomes of individual isolates. By contrast, the 3' untranslated region was well conserved. The high degree of sequence conservation within this region would favour it as a target for sensitive detection of GBV-C/HGV RNA.

Amino Acid Sequence↗
PubMed1997

Antibodies to hepatitis C virus and elevated transaminase levels in a town of hyperendemicity in Iwate, Japan.

In an annual survey for liver function tests in persons aged > 35 years in Iwate Prefecture, Japan, a town was identified where high levels of alanine aminotransferase abounded. Of 5152 inhabitants aged > 35 years in this town, antibodies to hepatitis C virus (HCV) determined by enzyme-linked immunosorbent assay with HCV core peptides were detected in 798 (15.5%) people, hepatitis B surface antigen was detected in 47 (0.9%) people and antibodies to hepatitis B surface antigen and/or hepatitis B core antigen unaccompanied by surface antigenaemia were detected in 1748 (33.9%) people. Antibodies to HCV core peptides correlated closely with the antibodies detected by passive haemagglutination with recombinant HCV proteins of the second generation. Antibodies to HCV core peptides were particularly common in one of the nine districts of the town (district 8), where 276 (45.3%) of 609 inhabitants tested positive; there were no differences in the frequency of serological markers of hepatitis B virus (HBV) infection among residents in the nine districts. Of the 798 individuals with antibodies to HCV core peptides, 257 (32.2%) were found to have elevated transaminase levels. A history of transfusion was associated with a high frequency of antibodies to HCV core peptides, except in district 8 where such antibodies were equally frequent in residents irrespective of transfusions. These results indicate an epidemiology of HCV distinct from that of HBV in this town and a very local spread of HCV, as well as a high frequency of hepatic injuries in individuals with antibodies to HCV.

Adult↗
PubMed1997

GB virus C and hepatitis C virus infections in hemodialysis patients in eight Japanese centers.

RNA of a putative non-A to E hepatitis virus, designated GB virus C (GBV-C), was detected in 40 (6.2%) of 645 hemodialysis patients, at a frequency significantly higher than in 3 (0.9%) of 336 blood donors in Japan (p < 0.001). A history of transfusion was more frequent (88 vs. 58%, p < 0.001), the duration of dialysis was longer (13.2 +/- 7.9 vs. 7.9 +/- 6.5 years, p < 0.001), and the detection of hepatitis C virus RNA was more often (38 vs. 18%, p < 0.01) in the 40 patients with GBV-C RNA than in the 605 patients without it. The prevalence of GBV-C RNA varied widely from 0 to 10% among the 8 dialysis centers. These results indicate that hemodialysis patients would be at increased risk of GBV-C transmitted by transfusions. The detection of GBV-C RNA in the 5 patients without a history of transfusion and a high prevalence restricted to certain dialysis centers would reflect nosocomial infection.

Alanine Transaminase↗
PubMed1997

Loss of circulating hepatitis C virus in children who developed a persistent carrier state after mother-to-baby transmission.

Of the 15 babies born to mothers infected with hepatitis C virus (HCV) and followed since birth, three developed HCV RNA in their serum. HCV RNA disappeared in two infants within 2 mo, but it persisted in the remaining infant. Mother-to-baby transmission was diagnosed retrospectively in an additional eight children aged 0.8-13.6 y. The eight children were followed for 1.4-5.0 y (mean +/- SD: 3.2 +/- 1.3 y) until they were 3.3-16.7 y old (8.5 +/- 4.3 y). Serum HCV RNA disappeared and antibodies to HCV decreased in the titer in two of the children when they were 3 y old. The spontaneous loss of serum HCV RNA was not observed in any of the other 14 children with posttransfusion infection who were followed for 2.6-6.1 y (4.0 +/- 1.1 y), until 3-22 y from the time they received transfusions and when they were 8.4-22.8 y old (15.4 +/- 4.1 y). These results indicate that the vertical transmission of HCV is rare, and some children can resolve the infection after a few years, whereas the infection persists in children who are infected by transfusion.

Adolescent↗
PubMed1997

Infection with GB virus C in patients with chronic liver disease.

Infection with putative non-A to E hepatitis virus, designated GB virus C (GBV-C), was surveyed in 286 patients with chronic liver disease in Japan. RNA of GBV-C was detected, by reverse-transcription polymerase chain reaction with nested primers from the 5'-noncoding region, in 19 patients (6.6%) at a frequency higher (P < 0.001) than in three of 275 (1.1%) normal controls. It was detected in three of 83 (4%) patients with hepatitis B virus infection, 15 of 188 (8%) patients with hepatitis C virus infection, and one of 12 (8%) patients without evidence of ongoing infection with hepatitis B or C virus. GBV-C RNA was detected in nine of 186 (5%) patients with chronic hepatitis aged 51.2 +/- 13.3 years, six of 64 (9%) with liver cirrhosis aged 62.9 +/- 11.4 years, and four of 36 (11%) with hepatocellular carcinoma aged 62.0 +/- 11.1 years. Nucleotide sequences of 100 base pairs in the helicase region of GBV-C isolates from the 19 patients varied up to 21%, while sequences of 33 deduced amino acids were conserved and differed only by up to 6%. These results indicate that infection with GBV-C in patients with non-B, non-C chronic liver disease would not be frequent, although the sensitivity of the detection method could be improved. Coinfection of GBV-C with hepatitis B or C virus, as well as the duration of infection, might accelerate the progression of chronic liver disease.

Amino Acid Sequence↗