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Biomedical subjects

H Inoko

Publications and source records attributed to H Inoko.

At least 217 records · Page 12Linked to original sources
PubMed1995

Cloned primed lymphocyte test cells recognize the fourth, fifth, and sixth hypervariable regions at amino acid positions 65-87 of the DPB1 molecule.

Genetic polymorphisms of the HLA-DPB1 gene in Japanese and Caucasian panel cells defined by PLT were analyzed by the PCR-based genotyping technique PCR-RFLP, and suballeles of DPw3 (DPB1*03) and DP"Cp63" (DPB1*09) could be detected. PLT-defined DPw3 cells were typed by PCR-RFLP as either DPB1*0301 or DPB1*1401. On the other hand, PLT-defined DPCp63-typed cells were typed as DPB1*0901 or DPB1*1001. These results indicate that both DPw3 and DPCp63 are split into two subantigens. DPw2 and DPw4 are DPB1*0201 and 0202 and DPB1*0401 and 0402, respectively. Comparative analysis of the amino acid sequences of the DPw2-, DPw4-, DPw3-, and DPCp63-associated alleles revealed that the fourth (C), fifth (D), and sixth (E) hypervariable regions at amino acid positions 65-87 were shared within the same PLT-defined DP antigen groups, suggesting that these three hypervariable regions are recognized by cloned T cells in PLT, thus determining DP antigen specificity. On the basis of this model, 44 DPB1 alleles can be classified into 18 antigen groups, each of which may possibly represent a PLT-defined single DP specificity.

Amino Acid Sequence↗
PubMed1995

Microsatellite polymorphism between the tumor necrosis factor and HLA-B genes in Behçet's disease.

Behçet's disease is associated with the HLA-B51 antigen. However, it has not yet been clarified if the HLA-B51 gene itself is the susceptibility gene related to this disease or if it is some other non-HLA gene in linkage disequilibrium with HLA-B51. Therefore, we screened one of the HSP70 genes, HUM70t (HSP70-Hom), around the class III region and the microsatellite sequence located between the HLA-B and TNF genes for genetic polymorphism in BD. A comparison between patients with BD and healthy controls revealed no significant difference in the frequency of the HUM70t polymorphism. In the microsatellite sequence, Tau-a, in the region between the HLA-B and TNF genes, the frequency of 14 repetitions of GT was increased significantly and that of 11 repetitions was decreased significantly in the patient group. Further, the allelic distributions of the B51 antigen-associated microsatellite polymorphism differed significantly between patients and healthy controls, and in the B51 antigen-negative subjects, analysis of the microsatellite polymorphism also revealed a significant difference in the haplotype frequency between the patient and control groups. These results suggest that the HLA-B51 gene may not be the primary locus responsible for BD, and implicate some other gene(s) located between the TNF and HLA-B genes.

Base Sequence↗
PubMed1995

Determination of HLA class II alleles by genotyping in a Manchu population in the northern part of China and its relationship with Han and Japanese populations.

The genetic polymorphism of the HLA class II loci was investigated in a Manchu population resident in the northern part of China and compared with those of other Asian populations including Japanese and Han. In 8 DQA1 alleles, the most frequent allele was DQA1*03 with the gene frequency of 25.5%. Of 15 DQB1 alleles tested, 11 were observed and the most common allele was DQB1*0301 with the gene frequency of 24.5%. Among 19 DPB1 alleles, 11 were detected and DPB1*0501 (43.8%) was the most frequent allele as observed in other Asian populations such as Japanese, Chinese and Korean. Of 43 DRB1 alleles tested, 21 were detected and DRB1*0901 (14.0%), *1501 (11.0%), *1201 (11.0%), *07 (9.0%) and *1401 (9.0%) were highly predominant and account for the high frequencies of DR9, DR2, DR5, DR7 and DR6. In the DRB3 gene (DR52), DRB3*0202 (18.0%) was the most frequent. With respect to the DRB4 gene (DR53), the gene frequency of DRB4*0101 was 35.0%. Of 3 DRB5 alleles detected, DRB5*0101 (11.0%) was highly predominant. Comparison of HLA class II allele frequencies in Manchu with those in Japanese and Han Chinese populations (South & North) detected some significant differences and genetic divergence between these Oriental populations. The dendrogram constructed by the neighbor-joining (NJ) method based on the allele frequencies of DQA1, DQB1, DPB1 and DRB1 of 10 representative populations over the world suggested that Manchu is the closest, but at the same genetic distance to both Northern and Southern Han Chinese.

Alleles↗
PubMed1995

HLA class II genes associated with anticentromere antibody in Japanese patients with systemic sclerosis (scleroderma).

OBJECTIVE: To define further HLA class II gene associations with anticentromere antibody (ACA), a major serum antinuclear antibody in patients with systemic sclerosis (SSc). METHODS: HLA class II genes were determined using polymerase chain reaction/restriction fragment length polymorphisms in 94 Japanese patients with SSc (22 ACA positive and 72 ACA negative) and 50 race matched normal control subjects. RESULTS: Frequency of DQB1*0501 was increased in ACA positive SSc patients compared with ACA negative SSc patients (36% versus 13%; p = 0.02, odds ratio = 4.0, 95% confidence interval 1.1 to 13.9), but the association of ACA with a polar amino acid at position 26 in the DQB1 beta 1 domain, which was demonstrated in white North Americans, was not observed in Japanese. The DRB1*0101, *0405, and *1302 alleles were associated with high ACA titres, whereas DRB1*1502 was associated with low ACA titres and a low frequency of centromere protein C (CENP-C) reactivity. CONCLUSIONS: These results suggest that the ACA response is associated with multiple HLA class II genes and that ACA positive SSc patients are heterogeneous in terms of immunogenetic background.

Alleles↗
PubMed1995

Clinical features of sarcoidosis in relation to HLA distribution and HLA-DRB3 genotyping by PCR-RFLP.

BACKGROUND: Susceptibility to the development of sarcoidosis has been demonstrated to be associated with HLA-DR5, -DR6, and -DR8 encoded by the DRB1 gene. However, involvement of the DRB3 (HLA-DR52) gene in the development of sarcoidosis remains unclear. METHODS: HLA-DRB3 genotyping was performed using the PCR-RFLP method and the clinical features of the patients with and without the DR3, 5, 6, 8 group antigens were compared. RESULTS: HLA-DRB3 genotyping indicated an association between DRB3*0101 and sarcoidosis. The DR8 haplotype lacking the DRB3 gene has been found to be increased significantly in sarcoidosis, suggesting that the HLA-DRB3 gene is not a primary determinant of predisposition to sarcoidosis. The association of DRB3*0101 with sarcoidosis is attributable to linkage disequilibrium with DR5- and DR6-associated alleles. There were significant decreases in the DR3, 5, 6, 8 group (DR5, DR6, or DR8) antigen frequencies in patients with retinal perivasculitis, high intraocular pressure (or secondary glaucoma), and optic nerve and/or macular lesion. Correlations were observed among the DR3, 5, 6, 8 group antigens, early onset sarcoidosis and disease with fewer intraocular lesions. CONCLUSION: This established a molecular basis for some of the clinical heterogeneity observed in sarcoidosis.

Adolescent↗
PubMed1995

Residual beta-cell function and HLA-A24 in IDDM. Markers of glycemic control and subsequent development of diabetic retinopathy.

To identify risk factors for diabetic retinopathy in insulin-dependent diabetes mellitus (IDDM), we studied the relationships among residual beta-cell function, human leukocyte antigen (HLA), long-term glycemic control, and development of diabetic retinopathy in 128 IDDM patients. Residual beta-cell function was assessed by serum C-peptide immunoreactivity (CPR) response to a 100-g oral glucose load (delta CPR). The patients were stratified into three groups: those with delta CPR of < 0.033 nmol/l (group 1, n = 50), those with delta CPR of 0.033-0.1 nmol/l (group 2, n = 38), and those with delta CPR of > 0.1 nmol/l (group 3, n = 40). The cumulative incidence rate of background retinopathy was higher in the order of groups 1, 2, and 3 (P = 0.032). Group 1 progressed to preproliferative retinopathy at an earlier stage than did groups 2 and 3 combined (P = 0.028). Further progression to proliferative retinopathy tended to be earlier in group 1 than in groups 2 and 3 combined (P = 0.083). The mean HbA1c value rose from 9.01 +/- 1.06% (mean +/- SD) in group 3 to 9.75 +/- 0.79% in group 2 to 10.48 +/- 1.12% in group 1 (P < 0.0001). In group 1, 89.6% of the patients had HLA-A24, whereas 50 and 43.6% of the patients had this antigen in groups 2 and 3 respectively (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3.

Cosmid walking of about 250 kb from MHC class III gene CYP21 to class II was conducted. The gene for receptor of advanced glycosylation end products of proteins (RAGE, a member of immunoglobulin superfamily molecules), the PBX2 homeobox gene designated HOX12, and the human counterpart of the mouse mammary tumor gene int-3 were found. The contiguous RAGE and HOX12 genes were completely sequenced, and the human int-3 counterpart was partially sequenced and assigned to a Notch homolog. This human Notch homolog, designated NOTCH3, showed both the intracellular portion present in the mouse int-3 sequence and the extracellular portion absent in the int-3. It thus corresponds to the intact form of a Notch-type transmembrane protein. About 20 kb of dense Alu clustering was found just centromeric to the NOTCH3.

Amino Acid Sequence↗
PubMed1994

Serologic and nucleotide sequencing analyses of a novel DR52-associated DRB1 allele with the DR 'NJ25' specificity, designated DRB1*1307.

A novel DR52-associated DRB1* allele, designated DRB1*1307, was encountered in the course of our HLA-DRB1 genotyping study in a Japanese population by PCR-RFLP. Comparison of the nucleotide sequence of its second exon with those of the other known DRB1 alleles revealed that DRB1*1307 was most similar to DRB1*1101, differing by two amino acid substitutions. From a family study, DRB1*1307 was found to segregate with a haplotype of DRB3*0202-DQA1*0501-DQB1*0301, which was also observed with DRB1*1101 in a Japanese population. DRB1*1307 was recognized in three of 652 healthy Japanese controls (gene frequency: 0.24%) with the same DR-DQ haplotype, indicating that DRB1*1307 arose from DRB1*1101 by a gene conversionlike event(s) and/or point mutations. Further, it was also observed that this allele had a strong linkage disequilibrium with HLA-B70 (p < 0.001). This new DRB1*1307 allele was serologically defined as DR 'NJ25,' and it gave an almost identical serologic pattern to DRB1*1406. On sequence comparison, however, no unique amino acid residues conserved in DRB1*1406 and DRB1*1307 but absent in all the other DRB1 alleles could be found, indicating that two amino acid changes at positions 47 and 58 abolished the reactivity against the DR11 antisera.

Alleles↗
PubMed1994

Complete association of the HLA-DRB1*04 and -DQB1*04 alleles with Vogt-Koyanagi-Harada's disease.

VKH disease is a bilateral panuveitis and has been known to be closely associated with the particular HLA class II antigens HLA-DR4 and -DQ4, defined by serologic typing. In this study, 63 Japanese VKH patients were analyzed for HLA class II alleles at the DNA level using the PCR-RFLP method. The DRB1*04 alleles encoding the serologic specificity DR4 were found in 100% of the VKH patients carrying DRB1*0405 or DRB1*0410. By statistical analysis, only DRB1*0405 was found to be significantly increased as compared to the healthy controls (RR = 46.7 and pc < 1 x 10(-5)). As to the DQB1 locus, all the patients carried DQB1*0401 or DQB1*0402 expressing the serologic DQ4 specificity, which is in a strong linkage disequilibrium with DRB1*0405 or DRB1*0410 in a Japanese population, respectively. Only DQB1*0401 showed a statistically significant increase as compared to the healthy controls (RR = 41.3 and pc < 1 x 10(-5)). Comparison of the amino acid sequences of these DRB1 and DQB1 alleles indicates that Ser at position 57 of DRB1 and/or Glu at position 70 and Asp at position 71 of DQB1 plays a crucial role in determining the susceptibility to VKH disease.

Adult↗
PubMed1994

Association of HLA-DPB1*0501 with early-onset Graves' disease in Japanese.

To investigate the association between HLA antigens and Graves' disease among Japanese, serologic typing and DPB1 genotyping using the PCR-RFLP method have been performed. HLA alleles of 106 patients with Graves' disease were determined, and the frequency of HLA-B46 was found to be significantly increased. Furthermore, the frequencies of HLA antigens were compared between two age groups: early-onset and late-onset patients (under and over 20 years, respectively). It was found that the frequency of DPB1*0501 (88.9%) was significantly increased (pc < 0.004) in the early-onset group as compared with the healthy controls (55.0%) but not in the late-onset group (60.7%). On the other hand, a significant increase of HLA-B46 was observed in the late-onset patients (pc < 0.0004). These results suggest that the genetic background of Japanese patients with early-onset Graves' disease is different from late-onset patients. Namely, the HLA-DP allele (DPB1*0501) and the HLA-B allele (B46) are primarily involved in the pathogenesis of early-onset and late-onset Graves' disease in Japanese, respectively.

Adolescent↗
PubMed1994

Molecular genetic studies of HLA class II alleles in sarcoidosis.

Previous HLA serological studies showed positive associations of the DR52 antigen, the DR52-associated antigens (DR3, DR5 and DR6) and the DR8 antigen with sarcoidosis. To investigate the HLA alleles that may contribute to the genetic susceptibility to sarcoidosis at the DNA level, HLA-DRB1, -DRB3, -DQA1 and DQB1 genotyping using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed in 63 Japanese patients with sarcoidosis. The frequencies of the DR52-associated DRB1 alleles (DRB1*11, DRB1*12 and DRB1*14 except DRB1*1302), DRB1*08, DRB3*0101, DQA1*0501 and DQB1*0301 were significantly increased in patients compared with healthy controls. The significant increase of DRB3*0101, DQA1*0501 and DQB1*0301 could be explained by linkage disequilibrium with the DR52-associated DRB1 alleles. It must be noted that the DR8 haplotype, which does not possess the DRB3 gene, also showed a significant increase in sarcoidosis. These results suggest that the HLA-alleles responsible for the susceptibility to sarcoidosis are located at the HLA-DRB1 locus rather than the HLA-DRB3, -DQA1 and -DQB1 loci. In contrast, DRB1*1302 may confer resistance to the disease.

HLA-DQ Antigens↗
PubMed1994

HLA-DQA1, -DQB1 and -DRB1 genotyping in Japanese pemphigus vulgaris patients by the PCR-RFLP method.

We performed HLA-DQA1, -DQB1 and -DRB1 genotyping using the PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method for 32 Japanese pemphigus vulgaris (PV) patients. There was a significant association of either DQB1*0503 or DRB1*1405 with PV, and a negative association of either DQA1*0103 or DQB1*0601 with PV was found. Since the DQB1*0503+ patients had various DR14-related alleles, we concluded that the association with DQB1 is primary and that the association with DRB1 is simply due to linkage disequilibrium between the DQ and DR genes. These results may indicate that specific HLA class II antigens confer the susceptibility to PV among Japanese.

Alleles↗