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M Ota

Publications and source records attributed to M Ota.

At least 127 records · Page 7Linked to original sources

Major histocompatibility complex class II alleles in an Uygur population in the Silk Route of Northwest China.

HLA class II (DRB1, DQA1, DQB1 and DPB1) genotyping was performed in 57 unrelated Uygur individuals inhabiting the northwestern China area by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Among 98 DRB1 alleles tested, 23 alleles were detected, and DRB1*0701 (16.7%) and DRB1*0301 (14.0%) were the most and the second most common alleles, respectively. In 8 DQA1 alleles detected, DQA1*05 (26.3%), DQA1*03 (21.9%) and DQA1*0201 (21.1%) were very frequent. Of 21 DQB1 alleles tested, 13 were observed. Among them, DQB1*02 was highly predominant with the gene frequency of 32.5%. Of 46 DPB1 alleles tested, 15 were detected, among which DPB1*0401 (31.6%) was the most frequent. Two haplotypes predominate clearly; DRB1*0701-DQA1*0201-DQB1*02 (15.5%) and DRB1*0301-DQA1*05-DQB1*02 (12.6%). The dendrogram constructed by the neighbour-joining (NJ) method based on the allele frequencies of the DRB1, DQA1, DQB1 and DPB1 genes of 13 representative populations all over the world suggested that Uygur belonged to the Asian group and lay at the closest genetic distance to a Kazak population inhabiting the same area.

Alleles↗

Cytotoxic T lymphocyte clone specific for autologous human hepatocellular carcinoma cell line SUHC-1.

We established a cytotoxic T lymphocyte (CTL) clone directed against an autologous hepatocellular carcinoma (HCC) cell line SUHC-1 which had been established in our department from a patient with HCC associated with hepatitis C virus infection. The CTL clone lysed autologous SUHC-1 cells but did not lyse autologous Epstein-Barr (EB) virus-transformed B cells, natural killer (NK) cell-sensitive erythroleukaemia cell line K562, the NK-resistant B cell line Daudi, or allogeneic HCC cell lines, Hep-G2, Hep-3B, Mahlavu and PLC/PRF/5. The CTL clone expressed CD3 and CD8 molecules. The cytotoxic activity of the clone was inhibited by anti-CD3, anti-CD8 and anti-histocompatibility antigen (HLA) class I monoclonal antibodies. These results indicated that the CTL clone recognized HCC tumour antigen in an HLA class I-restricted manner. Furthermore, we investigated the T cell receptor (TCR) gene usage of the CTL clone. The CTL clone expressed TCR alphabeta. We searched for expression of TCR variable (V) alpha and beta regions and sequenced complementary determining region (CDR) 3 of the clone. The clone expressed V alpha14, junctional (J) region alpha9.7 and V beta7, J beta2.1. The amino acid sequence of the N region of the of chain was S-P-G-G-G-G-A-D-G-L-T and of the N-D-N region of the beta chain was S-W-T-G-A-S-T-D-T-Q-Y. These results suggested that HLA class I-restricted CTL play an important role in the elimination of human HCC cells.

Carcinoma, Hepatocellular↗

[Aging of macular function as seen in multifocal electroretinograms].

Multifocal electroretinograms were recorded from 32 eyes of 32 young and aged healthy volunteers to investigate the change in electrophysiological functions with age in the central, nasal, temporal, superior, and inferior retina. The amplitude and latency of the first negative and positive waves were analyzed statistically in correlation with age. In all regions, amplitudes of focal responses tended to diminish with age. There was significant inverse correlation between amplitude and age in the central retina at 2 and 8 degrees, but no significant correlation was found in the other regions. These facts suggest that the macular retina tends to show functional deterioration with age when compared with other retinal areas.

Adolescent↗

MICA gene polymorphisms and HLA-B27 subtypes in Japanese patients with HLA-B27-associated acute anterior uveitis.

PURPOSE: HLA-B27-associated acute anterior uveitis (HLA-B27 AAU) seems to be triggered by external factors in persons with a particular genetic background. It is still uncertain whether HLA-B27 or other gene(s) near the HLA-B region predisposes to uveitis in a linkage disequilibrium with B27. The authors investigated microsatellite polymorphism within the transmembrane region of the MICA gene, located 47 kb centromeric of the HLA-B gene, and HLA-B27 subtypes. METHODS: Seventeen HLA-B27-positive Japanese patients with HLA-B27 AAU, 51 Japanese controls, and 20 B27-positive Japanese controls were examined for MICA gene polymorphism within the transmembrane region using polymerase chain reaction (PCR) and subsequent automated fragment detection by fluorescent-based technology. Furthermore, B27-positive patients with HLA-B27 AAU and B27-positive controls were examined for HLA-B27 subtypes by the PCR-sequence-specific primer method. RESULTS: The microsatellite allele in the MICA gene, consisting of four repetitions of GCT/AGC (designated A4 allele), was present at a significantly higher phenotype frequency in the patient group (64.7%) than in the control group (25.5%) (chi 2 = 6.95, Pc = 0.042). Furthermore, the frequency of the A4 allele was significantly higher, even when compared with 20% in the B27-positive control group (chi 2 = 5.88, Pc = 0.042). The frequency of HLA-B27 subtypes was not significantly different between B27-positive patients with HLA-B27 AAU and B27-positive controls. CONCLUSIONS: These results suggest that the MICA gene itself, or other nearby gene(s), linked to the MICA A4 allele may be involved in the development of HLA-B27 AAU and that HLA-B27 subtypes are not important in the development of HLA-B27 AAU in a Japanese population.

Acute Disease↗

Accumulation of p300 mediates transcriptional repression of simian virus 40 enhancer in undifferentiated F9 embryonal carcinoma cells.

The SV40 enhancer is repressed in embryonal carcinoma (EC) cells, and it is also repressed by the adenovirus E1A oncoprotein. Repression by E1A is mediated by the binding of E1A to the p300 transcriptional coactivator. Thus, we examined the role of p300 in the repression of the SV40 enhancer activity in EC cells. We demonstrated that high levels of p300 protein are accumulated in undifferentiated EC cells and that the levels decline dramatically upon differentiation because of the changes of protein stability. Furthermore, we showed that overexpression of p300 does not stimulate the SV40 enhancer activity in undifferentiated F9 cells. However, the activity of a p300 mutant deficient for E1A binding can be restored by the presence of excess E1A. In addition, low-level expression of E1A causes derepression of the enhancer activity in F9 cells. These results indicate that the accumulation of p300 protein participates in repression of the SV40 enhancer activity in undifferentiated F9 cells.

Activating Transcription Factor 1↗

[A case of untreatable progressive bladder carcinoma effectively treated by single administration of tegafur and uracil].

Bloody urine was grossly observed and multinodular shadow confirmed in both lungs of an 81-year-old male, who had been referred to our department. The diagnosis was bladder cancer (TCC, G3, T4N3M1) from detailed examination. With his advanced age and lowered ADL, the family did not wish for aggressive treatment, so no combination multidrug chemotherapy was attempted. Instead he was given 300 mg/day UFT per os. After 4 weeks administration, the metastatic focus decreased and tended to contract; at the same time gross observation revealed no more bloody urine. Moreover, following 7 weeks of administration, the bladder tumor disappeared, the lung metastatic focus showed overall shrinkage of over 50%, the lymph node metastasis also was more than 50% less, and the case was considered to be PR. The literature reveals UFT was efficacious in only 2 other cases of progressive bladder carcinoma. Since UFT has fewer complications, such as myelosuppression, among antitumor agent, it is considered worth trying in cases where intensive treatment is not feasible.

Aged↗

Structural requirement of highly-conserved residues in globins.

Globins have remarkable sequence diversity, and yet maintain a common fold. In spite of the diversity, there are highly-conserved residues at several sites. The conserved residues were examined in terms of the structural stability, by employing the pseudo-energy functions of the structure/sequence compatibility method. The fitness of each residue type to the structural environment was evaluated at seven highly-conserved sites: the Leu (at the B10 site), Phe (CD1), and Leu (F4) residues were found to fit their respective sites due to hydrophobic interactions; Pro (C2) stabilizes the N-terminal edge of an alpha-helical structure; and Phe (CD4) is stabilized by backbone hydrogen-bonding to Phe (CD1). On the other hand, the other two residues, His (E7) and His (F8), are poorly suited to the sites from a structural viewpoint, suggesting that their conservation clearly results from a heme-related functional requirement. The invariant Phe residue (CD1) has been suggested to be important for supporting the heme. The present analysis revealed that this residue is also well suited to the site in terms of energy.

Amino Acid Sequence↗

Triplet repeat polymorphism in the transmembrane region of the MICA gene: a strong association of six GCT repetitions with Behçet disease.

A member of a novel family of the human major histocompatibility complex (MHC) class I genes termed MIC (MHC class I chain-related genes), MICA, has been recently identified near the HLA-B gene on the short arm of human chromosome 6. The predicted amino acid sequence of the MICA chain suggests that it folds similarly to typical class I chains and may have the capacity to bind peptides or other short ligands. Therefore, MICA is predicted to have a specialized function in antigen presentation or T cell recognition. During nucleotide sequence analyses of the MICA genomic clone, we found a triplet repeat microsatellite polymorphism of (GCT/AGC)n in the transmembrane (TM) region of the MICA gene. In 68 HLA homozygous B cell lines, 5 distinct alleles of this microsatellite sequence were detected. One of them contained an additional one base insertion that created a frameshift mutation resulting in a premature termination codon in the TM region. This particular allele may encode a soluble, secreted form of the MICA molecule. In addition, we have investigated this microsatellite polymorphism in 77 Japanese patients with Behcet disease, which is known to be associated with HLA-B51. The microsatellite allele consisting of 6 repetitions of GCT/AGC was present at significantly higher frequency in the patient group (Pc = 0.00055) than in a control population. Furthermore, the (GCT/AGC)6 allele was present in all B51 positive patients and in an additional 13 B51 negative patients. These results suggest the possibility of a primary association of Behcet disease with MICA rather than HLA-B.

Asian People↗

Sequence variation of allele 27 at the D1S80 locus.

In 180 unrelated Japanese individuals 18 examples of allele 27 were detected at the locus D1S80 (MCT118). On 6% polylacrylamide gels 5 out of these 18 alleles were found to migrate between allele 26 and allele 27, but closer to allele 27, and thus were labelled variants of allele 27. All 18 examples of allele 27 were sequenced and the results were compared. Although all had the same number of base pairs (578 bp) the five variants could be subdivided into three types. V1, V2 and V3. The variants and the standard allele were composed of the same kinds of repeat units, but the order of arrangement was different. We investigated whether it was possible to distinguish the standard allele 27, and the variants V1, V2, and V3 by PCR-RFLP. EcoRII and MspI which have restriction sites within the repeat units were adopted as restriction enzymes. The variants could be discriminated from each other after treatment of the PCR fragments with EcoRII or MspI, followed by PAG electrophoresis.

Base Sequence↗

Allelic variants of the human MHC class I chain-related B gene (MICB).

The human major histocompatibility complex (MHC) is located within a 4 megabase segment on chromosome 6p21.3. Recently, a highly divergent MHC class I chain-related gene family, MIC was identified within the class I region. The MICA and MICB genes in this family have unique patterns of tissue expression. The MICA gene is highly polymorphic, with more than 20 alleles identified to date. To elucidate the extent of MICB allelic variations, we sequenced exons 2 (alpha 1), 3 (alpha 2), 4 (alpha 3), and 5 (transmembrane) as well as introns 2 and 4 of this gene in 46 HLA homozygous B-cell lines. We report the identification of eleven alleles based on seven non-synonymous, two synonymous, and four intronic nucleotide variations. Interestingly, one allele has a nonsense mutation resulting in a premature termination codon in the alpha 2 domain. Thus, MICB appears to have fewer alleles than MICA, not unlike the allelic ratio between the HLA-C and -B loci. A preliminary linkage analysis of the MICB alleles with those of the closely located MICA and HLA-B genes revealed no conspicuous linkage disequilibrium between them, implying the presence of a potential recombination hotspot between the MICB and MICA genes.

Alleles↗

ACTBP2 gene frequency distribution and sequencing of the allelic ladder and variants in the Japanese and Chinese populations.

The human beta-actin related pseudogene H-beta-Ac-psi-2 (ACTBP2) gene frequency distributions in the Japanese and Chinese Han populations were investigated and compared. Analysis was carried out by applying fluorescently labeled samples and a differently labeled sequenced allelic ladder within the same lanes in denaturing gels, followed by laser detection and automated analysis using Genescan software 672. The discrimination index and the heterozygosity index were calculated to be 0.993 and 0.916 in the Japanese population, and 0.993 and 0.944 in the Chinese Han population, respectively. No deviation from Hardy-Weinberg equilibrium was observed in these two populations. The allelic ladder, which ranged from 233 bp to 319 bp, was constructed from a combination of 23 regularly occurring alleles. The allelic ladder and 12 variants observed in 24 individuals in these two populations were sequenced. The variants could be divided into three types according to their structural variation characteristics. These variants differed from the alleles of the same repeats in the allelic ladder by the presence or absence of hexanucleotides in the central repeat regions, base deletions in the flanking regions, and base insertions in the repeat units.

Actins↗

Assessment of pseudo-energy potentials by the best-five test: a new use of the three-dimensional profiles of proteins.

We propose a new assessment, called the best-five test, for the pseudo-energy potential empirically derived from the protein structural database. The object of the test is the three-dimensional (3D) profiles of proteins, which are directly connected to the pseudo-energy potentials. In the 3D profile, the fitness of each amino acid type is ranked at each residue site of a protein. A site whose native residue type is ranked within the best-five out of 20 amino acids is regarded as satisfactory and the ratio of the satisfactory sites over all the sites of all the proteins examined is indicative of the efficiency of the pseudo-energy potential employed. We applied the test to our potential function consisting of four terms; side-chain packing, hydration, backbone hydrogen-bonding and local conformation, by setting various kinds of definitions for each term. Through this test, the validity of the minus average operation is confirmed, where the energy level of potential functions is adjusted by referring to the random-environmental state of the proteins. Especially in the side-chain packing function, the success ratio increases from about 30 to 50% with this operation. Failure without the operation is ascribed to bulky hydrophobic residues, which almost always occupy higher ranking positions in the 3D profile table. A maximum success ratio of 55.6% was attained with the final potential set consisting of the above four terms. The efficiency of the final set was further checked in the fold-recognition test for distantly related proteins. The best-five test is a new use of the 3D profile table for assessing the ability of the pseudo-energy potentials.

Amino Acid Sequence↗

Trinucleotide repeat polymorphism within exon 5 of the MICA gene (MHC class I chain-related gene A): allele frequency data in the nine population groups Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian.

We recently identified a trinucleotide repeat polymorphism, (GCT)n, within the transmembrane (TM) segment of the human MHC class I MICA gene (MHC class I chain-related gene A). Five distinct alleles (A4, A5, A5.1, A6, A9) corresponding to 4, 5, 5 with one nucleotide insertion, 6 and 9 repetitions, respectively, have been detected in various HLA-homozygous B cell lines. Here we present allele frequencies for this trimeric short tandem repeat (STR) in 604 unrelated individuals collected from nine human populations (Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian) determined using the polymerase chain reaction (PCR) combined with fluorescent-based automated fragment detection technology. All alleles were present in each population, but allelic distributions varied from one population to another. No new alleles (such as A7 or A8) were identified. The evolutionary and structural significance of these data as well as the potential application to forensic medicine is discussed.

Alleles↗

MICA gene and ankylosing spondylitis: linkage analysis via a transmembrane-encoded triplet repeat polymorphism.

In order to address the possibility that the MICA gene located 47 kb upstream from HLA-B is involved in the pathogenesis of ankylosing spondylitis (AS), we have investigated microsatellite polymorphism in the transmembrane region of MICA in Caucasian patients with AS. The microsatellite allele consisting of 4 repetitions of GCT/AGC was present at significantly higher frequency in the patient group (Pc<0.0000001) than in the ethnically matched control group. However, the frequency of the (GCT/AGC)4 allele was significantly low in the B27-positive patients than in the B27-positive healthy controls (Pc=0.0145). These observations suggest that B27 itself remains the primary genetic marker for AS, although the significantly dissimilar phenotype frequency of the (GCT/AGC)4 allele in B27-positive patients and healthy individuals may reflect the existence of other genetic factor(s) in the HLA-B27 haplotype involved in the development of AS.

Alleles↗

Major histocompatibility complex class II alleles in Kazak and Han populations in the Silk Route of northwestern China.

Genetic polymorphism of the HLA class II loci including the DRB1, DQA1, DQB1 and DPB1 genes was investigated by the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method in a Kazak population inhabiting the most northwestern part of China, Urümqi in the Xinjiang Uygur Zizhiqu as well as in a Han population in the same area. Forty-two Kazak and 59 Han unrelated volunteers were enrolled in this study. Among 51 DRB1 alleles tested, 29 alleles were detected, and DRB1*0301 (13.1%) and DRB1*07 (10.7%) in Kazak and DRB1*0901 (11.9%), DRB1*1501 (11.0%) and DRB1*07 (11.0%) in northwestern Han were highly predominant. In 8 DQA1 alleles detected, DQA1*0501 (29.8%) and DQA1*0301 (23.8%) in Kazak, and DQA1*0301 (28.8%) and DQA1*0102 (19.5%) in northwestern Han were the most and the second most common alleles, respectively. Of 18 DQB1 alleles tested, 14 were observed, among which DQB1*0201 and DQB1*0301 were very frequent both in Kazak (23.8% and 21.4%, respectively) and northwestern Han (18.6% and 16.9%, respectively) populations. Of 37 DPB1 alleles tested, 14 were detected. Among them, the frequencies of DPB1*0401 (21.4%), DPB1*0501 (20.2%), DPB1*0402 (19.0%) and DPB1*0201 (16.7%) in Kazak, and those of DPB1*0501 (38.1%) and DPB1*0201 (16.1%) in northwestern Han were highly increased. Several three-locus haplotypes were recognized to predominate significantly, namely DRB1*0301-DQA1*0501-DQB1*0201 (13.1%) and DRB1*0701-DQA1*0201-DQB1*0201 (8.3%) in Kazak; and DRB1*0901-DQA1*0301-DQB1*0303 (11.9%) and DRB1*0701-DQA1*0201-DQB1*0201 (10.2%) in northwestern Han. The dendrogram constructed by the neighbor-joining (NJ) method based on the allele frequencies of the DRB1, DQA1, DQB1 and DPB1 genes of 12 representative populations all over the world including northern Han, southern Han, Manchu and Japanese suggested that Kazak and northwestern Han were the closest to each other, but Kazak was a little farther from the Asian ethnic groups than northwestern Han.

Alleles↗