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Biomedical subjects

H Inoko

Publications and source records attributed to H Inoko.

At least 19 recordsLinked to original sources
PubMed2001

Association between CagA+ Helicobacter pylori infection and p53, bax and transforming growth factor-beta-RII gene mutations in gastric cancer patients.

We assessed the possible association between CagA+ Helicobacter pylori infection and gastric carcinogenesis in gastric cancer patients. Gastric biopsy specimens were obtained from 64 patients with gastric cancer and were histologically classified into intestinal and diffuse types. H. pylori infection was determined by cultivation, flaA-PCR and serum antibody against CagA. p53, BAX and transforming growth factor-beta-RII (TGFbeta-RII) gene mutations were analyzed by PCR-SSCP and direct sequencing. Intestinal and diffuse types of cancer were detected in 45 and 19 patients, respectively. H. pylori infection was found in 55 (85.9%) of 64 patients. There was no significant difference in H. pylori positivity between intestinal and diffuse types. However, the CagA antibody was positive in 15 (78.9%) of 19 patients with the diffuse type and in 22 (48.9%) of 45 patients with the intestinal type (p = 0.030). Among the 55 H. pylori-positive cases, 11 (29.7%) of the 37 patients in the CagA+ group were found to have p53 alterations, compared with 2 (11.1%) in the 18 CagA- group (p = 0.182). Moreover, among the 64 gastric cancer patients, p53 alterations were more frequently found in the CagA+ group (29.7%) than in the H. pylori-positive CagA- and H. pylori-negative groups (7.4%; p = 0.033). BAX gene mutations were found in 19 (29.7%) of 64 patients and there was no relationship among CagA seropositivity, cancer stages and histopathological phenotypes. In contrast, the TGFbeta-RII gene mutation was only detected in one CagA- patient. The results suggest that CagA+ H. pylori infection may have an important role in the development of gastric cancer patients with p53 mutations

Antigens, Bacterial↗
PubMed2001

A second susceptibility gene for developing rheumatoid arthritis in the human MHC is localized within a 70-kb interval telomeric of the TNF genes in the HLA class III region.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with a multifactorial genetic basis. However, pathogenic genes for RA other than the human leukocyte antigen (HLA)-DRB1 gene have yet to be identified. Here, we investigated whether there is a second susceptibility locus for RA within the human major histocompatibility complex using 18 microsatellite markers distributed from the centromeric (HSET) to the telomeric end (P5-15) of the 3.6-Mb HLA region. Statistical studies of associated alleles on each microsatellite locus showed that one pathogenic gene for RA in the HLA region is localized in the DRB1 gene, as expected. Further, a second susceptibility gene of RA was suggested to be present in the HLA class III region, narrowed to 70 kb, that is just telomeric of the TNF gene cluster (TNFA and LTA) and that is located between the microsatellites TNFa and C1-2-A. In this critical segment, four expressed genes have been thus far identified, NFKBIL1 (IkappaBL), ATP6G, BAT1, and MICB, all of which are candidate genes for determining susceptibility to RA. These results exclude the possibility of involvement of the TNFA genes (TNF-alpha) in the development of RA, which was suggested previously to be a strong candidate for RA in the class III region.

Alleles↗
PubMed2001

Microsatellite mapping of a susceptible locus within the HLA region for Behçet's disease using Jordanian patients.

Behçet's disease (BD) has been established to be associated with HLA-B51. However, it has not been revealed whether the HLA-B51 gene itself or another gene located near the HLA-B gene is directly involved in the pathogenesis of BD. Previously, using Japanese BD patients, our group has narrowed down a BD-causative gene to 46 kb between the MICA and HLA-B genes by means of fine mapping analysis with eight microsatellite markers distributed within a 1100 kb segment around the HLA-B gene. To know whether this mapping result is generally observed in BD of another population we have investigated repeat polymorphisms of the same microsatellite markers in Jordanian BD patients. Furthermore, we have evaluated these data by Mantel-Haenzel stratified analysis to find out a primarily associated locus for BD. As a result, HLA-B51 was found to be the most strongly and primarily associated marker. This result suggests that the pathogenic gene of BD is HLA-B51 itself, but unlikely to be other genes located in the vicinity of HLA-B.

Adolescent↗
PubMed2001

A close relationship of triplet repeat polymorphism in MHC class I chain-related gene A (MICA) to the disease susceptibility and behavior in ulcerative colitis.

Major histocompatibility complex (MHC) class I chain-related gene A (MICA) has been found near the HLA-B gene. The MICA molecule is exclusively expressed on gastrointestinal epithelium and recognized by intestinal epithelial gamma delta T cells, where it exhibits a triplet repeat polymorphism in the transmembrane region. We investigated the possible correlation between MICA genetic polymorphism and ulcerative colitis (UC). Eighty-three patients with UC and 132 unrelated controls were included in this study. All subjects were Japanese. A triplet repeat polymorphism in the transmembrane region of the MICA was determined by direct sequencing procedures after amplification by a polymerase chain reaction. A significantly higher allele and phenotype frequencies of MICA A6 allele were observed in patients with UC than controls (allele frequency: P(c)=0.000011, phenotype frequency: P(c)=0.0049 odds ratio=2.62). A6 homozygous patients with UC showed significantly earlier onset of UC than patients without the A6 allele ((P)c=0.0042). Phenotypes of MICA A6 allele in Japanese are closely related to the disease susceptibility and behavior in UC. Examinations of MICA polymorphism in other ethnic groups may provide important information about the locus of primary responsible gene for UC.

Adolescent↗
PubMed2000

Mapping of the HLA-linked genes controlling the susceptibility to Takayasu's arteritis.

To further define the HLA-linked genes controlling the susceptibility to Takayasu's arteritis, polymorphisms in five microsatellites around the HLA-B and MICA genes, C1-2-A, MIB, C1-4-1, C1-2-5, and C1-3-1, were investigated in 91 Japanese patients with Takayasu's arteritis and 248 healthy Japanese controls. It was found that allele 238 of C1-2-A [60.4% in patients vs. 29.8% in controls, odds ratio (OR)=3.59, P(c)<0.000004], allele 332 of MIB (22.0% vs. 6. 1%, OR=4.32, P(c)<0.0003), allele 208 of C1-2-5 (47.3% vs. 24.6%, OR=2.75, P(c)=0.001), and allele 291 of C1-3-1 (62.6% vs. 44.8%, OR=2.07, P(c)<0.02) were significantly associated with the disease. Combined analyses of polymorphisms in the HLA-B and MICA genes with those in the microsatellites suggest that there are two different disease-susceptible loci for Takayasu's arteritis; one is mapped near the C1-2-A locus and the other is more closely linked to the HLA-B gene than to the MICA gene, because there are at least two different disease-associated HLA-B haplotypes, HLA-B*52 and -B*39.2 haplotypes, in which the disease-associated C1-2-A allele is shared in common.

Alleles↗
PubMed2000

Replication timing of the human X-inactivation center (XIC) region: correlation with chromosome bands.

The human genome is composed of long-range G+C% mosaic structures, which are thought to be related to chromosome bands. Replication timing during S phase is associated with chromosomal band zones; thus, band boundaries are thought to correspond to regions where replication timing switches. The proximal limit of the human X-inactivation center (XIC) has been localized cytologically to the junction zone between Xq13.1 and Xq13.2. Using PCR-based quantification of the newly replicated DNA from cell-cycle fractionated THP-1 cells, the replication timing in and around the XIC was determined at the genome sequence level. We found two regions where replication timing changes from the early to late period during S phase. One is located near a large inverted duplication proximal to the XIC, and the other is near the XIST locus. We propose that the 1Mb late-replicated zone (from the large inverted duplication to XIST) corresponds to a G-band Xq13.2. Several common characteristics were observed in the XIST region and the MHC class II-III junction which was previously defined as a band boundary. These characteristics included differential high-density clustering of Alu and LINE repeats, and the presence of polypurine/polypyrimidine tracts, MER41A, MER57 and MER58B.

Animals↗
PubMed2000

Variants of NOS1, NOS2, and NOS3 genes in asthmatics.

Nitric oxide (NO) gas concentrations are higher in expired air in asthmatics. NO is synthesized by three isoforms of NO synthase (NOS) encoded by three distinct genes, NOS1, NOS2, and NOS3. Genome-wide searches have identified linkages to asthma on chromosomes 7, 12, and 17 where these three genes are localized. No association study, however, has been reported to date. To test whether variants of NOS1, NOS2, and NOS3 relate to asthma, a genetic association study was conducted in a British population (n = 300). Intragenic microsatellite variants of NOS1 were significantly associated with asthma [odds ratio (OR) = 2.08, 95% CI: 1.20-3.57 (95% CI), P = 0.008 (Pc = 0.048)], but not with IgE levels. Neither NOS2 nor NOS3 variants showed any association with asthma nor IgE levels. These findings suggest that NOS1 variants may be a significant contributor to asthma in a British population.

Alleles↗
PubMed2000

The SH2D2A gene encoding the T-cell-specific adapter protein (TSAd) is localized centromeric to the CD1 gene cluster on human Chromosome 1.

The SH2D2A gene encoding the T-cell-specific adapter protein (TSAd), was isolated from a human Chromosome (Chr) 1 cosmid library (LLNL, UK HGMP). The gene spans 11 kilobases and contains nine exons and eight introns. Four alternative transcript variants were observed in activated T cells. Three single-nucleotide polymorphisms were identified within intron 2. A variable number of GA repeats was found at position -340 from the first coding ATG. Linkage analysis using this marker in eight CEPH families showed that the SH2D2A gene is located close to the D1S2624 marker on Chr 1q21-1q22. Physical mapping of a PAC and BAC contig containing the CD1 gene cluster telomeric to D1S2624 failed to identify a clone harboring the SH2D2A gene. Thus the SH2D2A gene is located centromeric to the CD1 gene cluster on Chr 1.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Significance of transporter associated with antigen processing gene polymorphism in living related renal transplantation.

The HLA class I and class II mediated antigen presentation plays a major role in the initiation of immune response and the development of acute rejection after transplantation. The purpose of this study was to examine whether MHC-encoded antigen processing (TAP1, TAP2, LMP2, DMA and DMB) gene polymorphisms were associated with the incidence and the severity of acute rejection after renal transplantation. We studied a selected population of 112 pairs of donors and recipients who underwent living-related renal transplantation. They were divided into 3 groups: rejection-free (Group A, n = 51), steroid-sensitive rejection (Group B, n = 31) and steroid-resistant rejection (Group C, n = 30). The frequency of TAP2*0103 (41.2%) was significantly higher in the donors of Group A than that of Group B (12.9%, p = 0.0070, pc = 0.0280) or Group C (16. 7%, p = 0.0225, pc = 0.0900). No significant difference was observed in the allelic frequencies of the TAP1, LMP2, DMA, and DMB genes in the donors or recipients among Groups A, B, and C. This result supported the idea that the TAP2 gene polymorphism might be functionally related to antigen presentation. It also suggested that donor's antigen presenting cells with the TAP2*0103 allele would have the attenuated efficacy in the presentation of allospecific antigens to recipient's T cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

A unique monoclonal antibody mNI-11 rapidly enhances spread formation in human umbilical vein endothelial cells.

We previously reported a novel monoclonal antibody (MAb), designated mNI-11, recognizing an adhesion-associated antigen distinct from any previously reported ones. In this article, this adhesion-associated antigen with a molecular weight of about 97 kDa was found to be strongly expressed on human umbilical vein endothelial cells (HUVECs) by fluorescence-activated cell sorter (FACS) analysis. Expression of this antigen on HUVECs was slightly increased in response to the exposure to tumor necrosis factor-alpha (TNF-alpha) or phorbol myristate acetate (PMA). As a biological function exerted by this antigen, it was of great interest that immobilized mNI-11 directly and rapidly enhanced the spread formation of HUVECs, whereas MAbs binding other adhesion-associated antigens such as mNI-58A (anti-CD11a), L130 (anti-CD18), L133.1 (anti-CD31), L178 (anti-CD44), L25.3 (anti-CD49d), or LB-2 (anti-CD54) did not carry such activity under the same conditions. The HUVECs spread formation enhanced by mNI-11 was completely blocked in the presence of a microfilament formation inhibitor, cytochalasin D (CyD), a Ca2+ calmodulin inhibitor, W-7, EDTA, and was partially blocked by a microtubule formation inhibitor, nocodazole, a protein kinase C (PKC) inhibitor, H-7, and a protein synthesis inhibitor, cycloheximide (CHX). However, a protein tyrosine kinase (PTK) inhibitor, genistein, did not affect the spread formation under the same conditions. Taken together, it was suggested that the spread formation of HUVECs enhanced by mNI-11 was mainly associated with the influx of Ca2+ and microfilament reorganization. In addition, the novel property associated with mNI-11 to enhance the spread formation of HUVECs was possibly mediated through its reaction against a unique epitope on HUVECs.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

A microfilament formation inhibitor, cytochalasin strongly enhances the low-affinity Fc epsilon receptor II (CD23) expression on the human monocyte-like cell line, U937.

Enhancement of the low-affinity Fc epsilon receptor (CD23) expression by cytochalasin was analyzed on the human monocytelike cell line, U937. The CD23 expression on the U937 cells was enhanced at 24 hr after culture with cytochalasin B, D, or E, especially cytochalasin E having the most remarkable effect on it at the low concentration. This enhanced expression was found to be associated with a concomitant increase of a CD23 (about 45-kDa) protein on the U937 cells as assessed by Western blotting analysis. On the other hand, CD11a, CD18, CD31, CD49d, or CD54 was not markedly enhanced on the U937 cells by culture with cytochalasin E, although the mean fluorescence intensities (MFIs) of CD11a, CD18, and CD54 on U937 was partially up-regulated. Cell growth of U937 cultured with cytochalasin E was completely suppressed for 72 hr, but cell viability was sufficiently maintained (more than 95%). Soluble-formed CD23 (sCD23) also was released from the U937 cells at 24 to 72 hr after culture with cytochalasin E. In addition, the protein tyrosine kinase activity was detected in the U937 cells cultured with cytochalasin E for 24 hr using the enzyme immunoassay. Enhancement of the CD23 expression on the U937 cells at 24 to 72 hr cultured with cytochalasin E was sufficiently blocked by protein tyrosine kinase inhibitors herbimycin A and genistein, and a protein synthesis inhibitor, cychloheximide. On the other hand, protein kinase C inhibitors such as H-7 and H-8 had no effect on this CD23 expression. These results suggest that a mechanism underlying enhancement of the CD23 expression on the U937 cells cultured with cytochalasin E is mediated through tyrosine phosphorylation and protein synthesis.

Actin Cytoskeleton↗
PubMed2000

Genetic polymorphisms in the cell growth regulated gene, SC1 telomeric of the HLA-C gene and lack of association of psoriasis vulgaris.

Psoriasis vulgaris is associated with the HLA-Cw6 and Cw7 antigens. We have previously narrowed down the critical region most likely to contain the psoriasis vulgaris gene to 111 kb spanning 89 kb to 200 kb telomeric of the HLA-C locus by microsatellite mapping. This segment includes three known genes (POU5F1, SC1 and S) and four new expressed genes. Among them, SC1 (TCF19) is the cell growth regulated gene possibly with trans-activator activity. Since psoriasis vulgaris is a common skin disorder characterized by hyperproliferation of epidermal cells, it is tempting to speculate that the SCI gene is one of the strong candidate genes responsible for the development of psoriasis vulgaris. Here, we investigated genetic polymorphisms in the SC1 gene by direct DNA sequencing and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) techniques. Three single nucleotide polymorphisms in exon 2, two of which are accompanied by amino-acid substitutions, were identified. Further, one 4-bp deletion polymorphism was detected around the acceptor site of the lariat-shaped structure necessary for RNA splicing in intron 2. No significant difference in the dimorphic or haplotypic distribution at these four polymorphic sites was observed between the patients with psoriasis vulgaris and healthy controls. This suggests that the susceptible gene for psoriasis vulgaris is not the SC1 gene itself, although a unique homozygous haplotype was identified in the patients.

Base Sequence↗
PubMed2000

HLA-DQB1*0601 is primarily associated with the susceptibility to cardiac sarcoidosis.

Cardiac sarcoidosis occurs in 1-5% of sarcoidosis patients. We previously reported a significant increase of the uncommon TNFA (tumor necrosis factor alpha) allele, TNFA2 with cardiac sarcoidosis in Japanese. In order to precisely localize the susceptible locus for cardiac sarcoidosis within the HLA region, genetic polymorphisms of classical HLA genes, non-classical HLA class II genes such as HLA-DMA and -DMB genes and several genes involved in the class I-mediated antigen presentation pathway (TAP1, TAP2, LMP2 and LMP7) were investigated. Further, association analyses using four polymorphic microsatellite markers located around the TAP1 and TNFA genes were also carried out. As a result, HLA-DQB1*0601 was found to be the most significantly associated allele, being more significantly increased than TNFA2. No significant increase of the DR52-associated DRB1 alleles (DRB1*03, 05, 06 and 08), which was suggested to be primarily associated with lung sarcoidosis, was observed in cardiac sarcoidosis. A primary role of DQB1*0601 in determination of the susceptibility to cardiac sarcoidosis was supported by association analysis using four polymorphic microsatellite markers, in which only the TAP1 microsatellite locus, the nearest marker to the DQB1 gene among the microsatellites tested, displayed a significant positive association with cardiac sarcoidosis. On the other hand, the HLA-DQB1*0501-DQA1*0101-DRB1*0101-B7 haplotype showed a negative association with the disease, as similarly observed in lung sarcoidosis. Thus, molecular mechanism for controlling the development of the disease related to HLA molecules are different between cardiac and lung sarcoidosis, whereas those for conferring a resistant trait may be similar to each other.

Alleles↗
PubMed2000

Polymorphism of the ABO blood group genes in Han, Kazak and Uygur populations in the Silk Route of northwestern China.

Genetic polymorphism in the ABO blood group gene of Han, Kazak and Uygur populations inhabiting the most northwestern part of China was investigated using polymerase chain reaction-based techniques. The present study enrolled 43 healthy unrelated Han, 37 Kazak and 59 Uygur volunteers. The allele in A1 blood group is distinguished A0101 and A0102 in difference of nucleotide position 467. The A0101 allele is more frequent in Caucasian and the A0102 allele is characteristic in Mongoloid. It must be notable that A0201 in the A2 group (with a single base deletion at nucleotides 1059 to 1061) which was characteristic of Caucasian was observed in Kazak and Uygur populations but not in Han. Further, 00201 (with no nucleotide deletion at 261 and three nucleotide differences), which is frequent in different races including Caucasian except for Mongoloid, was detected also in Kazak and Uygur populations. The frequencies of B0101 in Kazak, Uygur and Han were comparable to those of other Asian populations but higher than those of Caucasian populations. Collectively, these results reveal that the allele frequencies of Kazak and Uygur at the ABO blood group locus are an intermediate between those of Mongoloid and Caucasian, suggesting the admixed feature of Kazak and Uygur with Mongoloid and Caucasian.

ABO Blood-Group System↗
PubMed2000

Polymorphisms in the TNFA promoter region is not associated with palmoplantar pustulosis.

Polymorphisms of the 5'-flanking promoter/enhancer region of the TNAFA gene were determined in 80 Japanese patients with pulmoplantar pustulosis (PPP). The 5'-flanking region of the TNFA gene from -1107 to 66 was amplified by polymerase chain reaction (PCR) method. Nucleotide sequencing data from the PCR products revealed that 5 single nucleotide polymorphisms at position 1031, -863, -857, -307 and -237. None of the nucleotide substitutions were significantly increased in PPP patients when compared with those in controls. To clarify the linkage among the neighboring genetic marker, we analyzed the association between the polymorphisms in the TNFA promoter region and the NcoI polymorphism in the first intron of the TNFB gene as well as HLA-DR9. The genotype at 1031C is strongly associated with TNFB1 and negatively associated with TNFB2 which is reported to be associated with PPP. These data indicate that TNFA gene centromeric to TNFB is not associated with PPP and the susceptible gene of PPP is located between TNFB and HLA-B.

Genotype↗
PubMed2000

On the MICA deleted-MICB null, HLA-B*4801 haplotype.

A 100-kb deletion including the MICA gene was recently reported in the HLA-B48 (B*4801)-associated haplotype in Japanese. Interestingly, this MICA deletion is accompanied by a MICB null allele, MICB0107N. In order to further investigate the universality of the apparent tight linkage between these two events, we present data on high-resolution deletion mapping of eight HLA-B48-homozygous individuals. Among these, five carried the MICA deletion linked to MICB0107N, as originally reported. Conversely, the remaining three possessed an intact MICA gene of MICA008 or MICA010 allelic variant associated this time with a putative expressed MICB allele, MICB0102. These results may imply that the expression of both MICA and MICB molecules is indispensable to viability through a yet-to-be understood mutual interaction in immune surveillance.

Alleles↗
PubMed2000

HLA class II alleles in Japanese patients with immune thrombocytopenic purpura. Associations with anti-platelet glycoprotein autoantibodies and responses to splenectomy.

HLA class II alleles and immunoglobulin allotypes were determined in 83 Japanese patients with immune thrombocytopenic purpura (ITP) and 114 race-matched healthy controls. Distribution of DRB and DQB1 alleles as well as G1M(f, z), G2M(n+, n-), and KM(1, (1,2), 3) were not different between ITP patients and healthy controls, while DPB1*0201 was marginally increased in ITP patients vs. healthy controls (51% vs. 28%, Pc= 0.04, OR=2.6 [1.4-4.8]). In contrast, strong associations between anti-glycoprotein autoantibodies and HLA class II genes were found as follows: antiGPIIb-IIIa antibody with DRB1*0405 and DQB1*0401; and anti-GPIb-IX antibody with DRB1*0803 and DQB1*0601. When factors influencing therapeutic responses to splenectomy were examined, a poor response was correlated with the presence of DRB1*0405, DQB1*0401 and anti-GPIIb-IIIa antibody (P=0.01, 0.002, and 0.03, respectively). Our results indicate that HLA class II genes influence the production of anti-glycoprotein antibody specificities rather than the development of ITP. In addition, HLA class II genotyping could be useful in predicting therapeutic responses to splenectomy in Japanese patients with ITP.

Adult↗