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Biomedical subjects

K Ohba

Publications and source records attributed to K Ohba.

At least 91 records · Page 5Linked to original sources
PubMed1995

Seroprevalence of hepatitis C virus infection and its genotype in Lanzhou, western China.

The seroprevalence of hepatitis C virus (HCV) infection in Lanzhou, Western China was studied. HCV genotypes in 20 patients with HCV infection was determined by genotype-specific primer for polymerase chain reaction (PCR) based on HCV core region and compared with the genotype assigned by sequence comparison and molecular evolutionary analysis based on the same region. Antibody to HCV (anti-HCV) was present in 2.5% of volunteer blood donors and in 35.0% of paid blood donors (P < 0.01). HCV infection is uncommon in patients with liver disease who attended liver clinics in this locality; 4.0% with acute hepatitis and 4.0% with chronic hepatitis, 10.0% with liver cirrhosis, and none with hepatocellular carcinoma were seropositive for anti-HCV. Genotype 1b and 2a were both found to be prevalent. Together, they accounted for 19 of 20 (95%) patients with HCV infection. Sequencing of the HCV core region from two patients showed that the assignment of HCV genotype by genotype-specific primers for PCR matched well with the genotyping results based on sequence comparison and molecular evolutionary analysis. These data showed that HCV is present in Western China, HCV infection is more common in paid blood donors, and HCV genotypes 1b and 2a are both prevalent in Western China.

Amino Acid Sequence↗
PubMed1995

Loss of serum HCV RNA at week 4 of interferon-alpha therapy is associated with more favorable long-term response in patients with chronic hepatitis C.

To determine the virological factors associated with a favorable long-term response to interferon-alpha (IFN) therapy in chronic hepatitis C virus (HCV) infection, 61 Japanese patients with chronic HCV infection were treated with IFN for 24 weeks (780 million units in total) and followed for 8 to 16 months after cessation of therapy. Ten patients dropped out because of severe side effects. Of the 51 patients who completed IFN therapy, 23 showed complete and sustained response (CR --> SR), 13 complete response with early relapse (CR --> Rel), and 15 no response to IFN (NR). For the pretreatment serum HCV RNA level, 20/23 who had CR --> SR had < 10(6) eq/ml compared to 3/13 CR --> Rel and 1/15 NR (P < 0.01). Serologically defined HCV type 2 infection was also associated with a better opportunity to develop CR --> SR compared to CR --> Rel of NR (P < 0.01). Loss of serum HCV RNA at week 4 of IFN therapy was also associated with a more favorable long-term response [17/19 CR --> SR were HCV RNA negative compared to 3/11 CR --> Rel (P < 0.01) and 2/13 NR (P < 0.01)]. In contrast, normalization of serum alanine aminotransferase (ALT) levels at week 4 was found in 9/19 CR --> SR compared to 8/11 CR --> Rel (P = NS), and 0/13 in NR (P < 0.01). Six months after cessation of IFN therapy, 3/25 CR --> SR patients were HCV RNA positive despite normalization of serum ALT levels. These data indicated that in addition to pretreatment serum HCV RNA levels and HCV type, the kinetics of response to IFN (at week 4) were also predictive of subsequent long-term response to IFN in patients with chronic HCV infection.

Adult↗
PubMed1995

Genotype distribution in Nagoya and new genotype (genotype 3a) in Japanese patients with hepatitis C virus.

We evaluated hepatitis C virus (HCV) genotype distribution among Japanese patients in the city of Nagoya and the possible existence of any other genotype not determined by Okamoto's method. Eighty-five of 93 (91.4%) anti-HCV-positive patients had detectable HCV RNA. The genotype of the HCV isolate was determined in 84 of 85 (98.8%) of these HCV RNA-positive patients by Okamoto's method but determination was not possible in one (1.2%). Genotype 1b was detected in 58 of the 85 patients (68.2%), genotype 2a in 20 (23.5%), genotype 2b in 3 (3.5%), and genotype 1b + 2a in 3 (3.5%). In the remaining 1 patient in whom the genotype could not be determined, we determined the nucleotide sequence of the core region in HCV RNA extracted from this patient and evaluated it by molecular evolutionary analysis. This HCV isolate was then classified as genotype 3a. These results suggest that genotype 3a is rare among Japanese patients with HCV; thus, when classifying Japanese isolates, we should take more care because genotype 3a is not determined by current typing systems.

Amino Acid Sequence↗
PubMed1995

Classification of hepatitis C virus into major types and subtypes based on molecular evolutionary analysis.

Molecular evolutionary analysis was applied to determine the number of hepatitis C virus (HCV) types and subtypes based on all the HCV nucleotide sequences available from the DNA data banks (DDBJ, GenBank (NCBI), EMBL) and the literature. There was an excellent concordance among the types and subtypes assigned based on different HCV genomic regions. Only one HCV isolate was assigned to different HCV types based on the 5' non-coding (NC) and envelope 1 (E1) regions. The 5' NC region was well conserved and could be used to assign only types and not subtypes. From the sequence data available there were 13 subtypes based on the core region and 14 subtypes based on the E1 and non-structural protein 5 (NS5) regions.

Biological Evolution↗
PubMed1995

Relationships between serotypes and genotypes of hepatitis B virus: genetic classification of HBV by use of surface genes.

Hepatitis B virus (HBV) surface antigen (HBsAg), which is encoded by the HBV S gene, is conventionally classified into 4 serological subtypes, adw, adr, ayw and ayr. To determine the relationship between the HBsAg seroreactivity and the nucleotide sequence diversity of the HBV S gene, the nucleotide sequences of S genes for HBV isolates reported so far were aligned with each other. The numbers of nucleotide substitutions were then estimated by the 6-parameter method, and a phylogenetic tree was constructed by the unweighted paired grouping method with arithmetic mean (UPGMA) and the neighboring-joining (NJ) method. The phylogenetic trees constructed showed that all isolates were grouped into 4 genotypes (gyw, gdw-1, gdw-2, and gdr). More importantly, the genotypes did not necessarily correspond to the conventional serotypes. In particular, serotype 'adw' can be any of genotypes gdw-1, gdw-2, or gdr. Thus, genotyping by S genes gives more accurate information about genetic variation of HBV.

Amino Acid Sequence↗
PubMed1995

Treatment of brachymetatarsia using a semicircular lengthener. 1-3 years results in 6 patients.

6 women with brachymetatarsia involving 9 bones were treated by the use of the Ilizarov semicircular lengthener. The affected bones were the second, third and fourth metatarsals. Ilizarov half-rings were applied on the foot with 5 or 6 half-pins (3 mm in diameter) and a percutaneous osteotomy was done. The short metatarsals were lengthened 0.25 mm twice a day by the patient. The lengthened distance was 15 (10-22) mm and the overall treatment time was 15 (12-25) weeks. The postoperative course was uneventful, with smooth bone regeneration. No bone-grafting was needed. During treatment, the patients could bear full weight and tolerated the fixators well. We conclude that this technique is useful in the treatment of brachymetatarsia.

Adolescent↗
PubMed1994

New genotype of hepatitis C virus in South Africa.

Partial nucleotide sequences in the core region of the hepatitis C viral genome were determined by reverse transcription followed by polymerase chain reaction, in a patient with chronic hepatitis from South Africa. These nucleotide sequences showed a low degree of homology with known types of HCV: the degree of homology between the nucleotide sequences of these clones with HC-J1, J4, J6, J7, Tr, and Eb-1 were 86.1-87.3%, 87.3-87.9%, 83.0-83.9%, 81.1-82.0%, 81.0-82.2%, and 82.8-83.4%, respectively, and that the deduced amino acid sequence homologies between these clones and HC-J1, J4, H6, J7, Tr, and Eb-1 were 90.7-91.6%, 89.7-91.6%, 91.6-93.5%, 90.7-91.6%, 81.5-82.4%, and 89.2-90.2%, respectively. The nucleotide sequence homologies of these clones with HC-J1, J4, J6, J7, Tr, and Eb-1 were very low, compared to those between the same genotype. Further comparison using molecular evolutionary methods suggested that this sequences should be classified in a new genotype.

Amino Acid Sequence↗
PubMed1994

Nucleotide sequence of the core region of hepatitis C virus in Pakistan and Bangladesh and the geographic characterisation of hepatitis C virus in south Asia.

A large number of complete and partial hepatitis C virus (HCV) sequences have been reported and classified into several genotypes, although none have been reported from South Asia. We have determined and evaluated partial sequences in the core region of HCV obtained from patients with chronic hepatitis in Pakistan and Bangladesh. Nucleotide sequences from these viruses show significant homology with the Japanese HCV-TR isolate (91.7%-97.9%) and low homology with other Japanese, American, and UK isolates including HCV-1, HC-J4, HC-J6, HC-J8, and E-b1 (79.3%-86.2%). The homologies of their deduced amino acids sequence with HCV-1, HC-J4, HC-J6, HC-J8, E-b1, and HCV-TR were 84.3%-89.8%, 85.0-87.9%, 84.1%-86.9%, 84.3%-87.0%, 90.2%-93.1%, and 89.8%-93.5%, respectively. These results suggest that our clones might be classified into the same genotype as HCV-TR. Further analysis using molecular evolutionary methods strongly supported the classification of these sequences with the HCV-TR genotype. Moreover, we could not detect any isolates which were closely related to our clones or HCV-TR in countries outside the South Asian area. These data further support the association of HCV genotypes with distinct geographic regions.

Amino Acid Sequence↗
PubMed1994

Reduction of synonymous substitutions in the core protein gene of hepatitis C virus.

Molecular evolutionary analyses were carried out to elucidate the phylogenetic relationships, the evolutionary rate, and the divergence times of hepatitis C viruses. Using the nucleotide sequences of the viruses isolated from various locations in the world, we constructed phylogenetic trees. The trees showed that strains isolated from a single location were not necessarily clustered as a group. This suggests that the viruses may be transferred with blood on a worldwide scale. We estimated the evolutionary rates at synonymous and nonsynonymous sites for all genes in the viral genome. We then found that the rate (1.35 x 10(-3) per site per year) at synonymous sites for the C gene was much smaller than those for the other genes (e.g., 6.29 x 10(-3) per site per year for the E gene). This indicates that a special type of functional constraint on synonymous substitutions may exist in the C gene. Because we found an open reading frame (ORF) with the C gene region, the possibility exists that synonymous substitutions for the C gene are constrained by the overlapping ORF whose reading frame is different from that of the C gene. Applying the evolutionary rates to the trees, we also suggest that major groups of hepatitis C viruses diverged from their common ancestor several hundred years ago.

Biological Evolution↗
PubMed1994

Analysis of the core and E1 envelope region sequences of a novel variant of hepatitis C virus obtained in Indonesia.

Hepatitis C virus (HCV) is currently classified into 6 major types, HCV-1 through -6, each of which can be further divided into a few subtypes, e.g., HCV-1a, -1b, -1c, etc., on the basis of sequence variation of the viral genome. The core and E1 envelope regions of HCV genome were amplified from sera of Indonesian patients using reverse transcription-polymerase chain reaction. Sequence analysis of both core and E1 regions followed by molecular evolutionary phylogenetic analysis identified a novel sequence variant of HCV-1 (Td-6). Antibodies in the serum from which Td-6 was isolated reacted only marginally to the core protein of HCV-J, a representative strain of HCV-1b, despite strong antibody response against a mixture of the core, NS3 and NS4 proteins of HCV-1a. The possible mechanism for the diminished reactivity of the antibodies in the serum to the core protein of HCV-J is discussed.

Amino Acid Sequence↗
PubMed1994

Hepatitis C virus serotype II responds more favorably to interferon-alpha therapy.

To determine whether serological typing of hepatitis C virus correlated with the response to interferon-alpha therapy, hepatitis C virus serotypes were determined by subtype-specific antibody to NS4 polypeptide by enzyme-linked immunosorbent assay in 55 Japanese patients with chronic active hepatitis C who subsequently received recombinant interferon-alpha 2a therapy. Response to interferon-alpha was defined as complete and sustained (n = 12), complete response followed by relapse (n = 26), and no response (n = 17). There was no difference in the clinical biochemical parameters between these patients groups. However, a higher proportion (50.0%) of patients with hepatitis C virus serotype II showed complete and sustained response to interferon-alpha, compared to serotype I (11.1%, p < 0.01). These data indicate that this simple hepatitis C virus serotyping assay is a useful predictor of response to interferon-alpha therapy in patients with chronic hepatitis C virus infection.

Adult↗
PubMed1994

Application of the RLGS method to large-size genomes using a restriction trapper.

We developed a method for producing restriction landmark genomic scanning (RLGS) profiles of large-size genomes, such as those of higher plants or amphibians using a restriction trapper. Use of the conventional RLGS method is limited to genomes smaller than 3 x 10(9) bp, because the larger genomic DNAs, especially those of more than 1 x 10(10) bp, produce high background due to incorporation of radioactivity at non-specifically damaged sites. Our new method reduces the background levels by reducing genome complexity to 1/200-1/300 using a purification step to enrich DNA fragments carrying specific restriction landmarks at their ends using a restriction trapper. This step makes it possible to obtain RLGS patterns of larger genomes. Our paper describes the practical application for the RLGS method using a restriction trapper with the pine tree genome (3 x 10(10) bp/haploid genome; Pinus koraiensis Sieb. et Zucc.) as an example.

DNA, Plant↗
PubMed1994

Full-length sequence of the genome of hepatitis C virus type 3a: comparative study with different genotypes.

Hepatitis C virus (HCV) type K3a (type 3a), which represents a minor genotype in Europe, the U.S.A. and Asia, appears to be significantly distributed throughout Australia and Brazil. We amplified the HCV-K3a/650 genome by reverse transcription polymerase chain reaction in ten overlapping fragments and determined the nucleotide sequences. The total sequence was 9454 bases in length and contained an open reading frame of 3021 amino acids, which is 10 or 11 amino acids longer than in HCV type 1 and 12 amino acids shorter than the sequence of type 2. These differences were due to the different lengths of both the putative envelope protein E2 and the NS5A regions, whose nucleotide lengths differ between types 1 and 2 also. Phylogenetic analysis of the putative core region and a portion of NS5B encoding the Gly-Asp-Asp motif indicated that HCV-K3a closely matched the corresponding type 3a group. The deletion and addition of amino acids in both E2 and NS5A may be associated with their pathobiological features.

Amino Acid Sequence↗