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T Sasazuki

Publications and source records attributed to T Sasazuki.

At least 163 records · Page 9Linked to original sources
PubMed1992

HLA-linked susceptibility and resistance to Takayasu arteritis.

To investigate genetic factors involved in the pathogenesis of Takayasu arteritis, patients in the Japanese population were examined for HLA-A, -B, and -C alleles by serological typing and for HLA-DR, DQ, and DP alleles by DNA typing using polymerase chain reaction (PCR)/sequence-specific oligonucleotide probe (SSOP) analysis. The frequencies of HLA-Bw52, DRB1*1502, DRB5*0102, DQA1*0103, DQB1*0601, and DPB1*0901 alleles were significantly increased and the frequencies of HLA-Bw54, DRB1*0405, DRB4*0101, DQA1*0301, and DQB1*0401 alleles were significantly decreased. Strong linkage disequilibria among the increased alleles and among the decreased alleles were evident in the Japanese population. Therefore, the haplotype of HLA-B252-DRB1*1502-DRB5*0102-DQA1*0103-DQB1++ +*0601-DPA1*02-DPB1*0901 may confer susceptibility to Takayasu arteritis while another haplotype of HLA-Bw54-DRB1*0405-DRB4*0101-DQA1*0301-DQB1++ +*0401 may confer resistance to the disease. These observations clearly indicate that HLA-linked gene(s) are involved in the development of Takayasu arteritis.

Genetic Linkage↗
PubMed1992

Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion.

Crosslinking HLA-DR molecules by monoclonal antibodies (moAbs) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic calcium concentrations in activated human T cells. Binding of bacterial superantigens or moAbs to DR molecules on activated T cells was recently reported to induce homotypic aggregation through activation of protein kinase C (PKC) and mediated by CD11a/CD54 (LFA-1/CAM-1) adhesion molecules. Here, we report that moAbs directed against framework DR, but neither DR1, 2- and DRw52- nor DQ- and DP-specific moABs induced homotypic aggregation of antigen- and alloantigen-activated T cells, antigen-specific CD4+ T-cell lines, a CD8+ T-cytotoxic cell line, and T-leukemia cells (HUT78). Protein tyrosine kinase (PTK) inhibitor herbimycin A partly blocked class-II-induced aggregation responses. In contrast, phorbol ester (PMA)-induced aggregation was essentially unaffected. A potent inhibitor of PKC, staurosporin, inhibited both moAb- and PMA-induced aggregation responses. The aggregation responses were completely inhibited by low temperatures, cytochalasins B and E, and partly inhibited by EDTA and CD18 moAbs, but unaffected by aphidicolin, mitomycin C, an adenylate cyclase inhibitor (2'5'-dideoxyadenosine), and moAbs against other adhesion molecules (CD2/CD58 [LFA-3], CD28/CD28 ligand B7, CD4, and CD44). In conclusion, HLA class-II-induced aggregation responses in activated T cells appear to involve PTK and PKC activation and to be mediated through CD11a-dependent and independent adhesion pathways.

Alkaloids↗
PubMed1992

Polymerase-chain-reaction-based analysis of polymorphism in the HLA-B gene.

The polymerase chain reaction (PCR) in combination with the sequence-specific oligonucleotide probe (SSOP) was applied to analyze the polymorphism in the exon 2 of the HLA-B gene. In this study, genomic DNAs from 85 B-lymphoblastoid cell lines homozygous for HLA and peripheral blood granulocytes of 156 Japanese individuals were investigated. Two HLA-B-specific 5'-sided primers (CG4 and CG5) and two 3'-sided primers (CG2 and CG3) were designed for specific amplification of the exon. HLA-B alleles were classified into two groups (groups I and II) according to specific amplification with two types of the 3'-sided primers. The amplified DNAs were hybridized with 23 nonradioactively labeled SSOPs. Based on the hybridization patterns with the SSOPs, 34 HLA-B specificities were divided into 26 epitope combination (EC) groups. Fifteen HLA-B specificities were classified into four EC groups and these HLA-B specificities could not be distinguished from one another in the same EC group. Another 16 HLA-B specificities corresponded one by one to 16 distinct EC groups, and two subtypes of HLA-Bw75, B27, and Bw48 were also identified enabling the accurate typing of 22 HLA-B alleles at the DNA level. Single-strand conformation polymorphism (SSCP) of the PCR products from group I HLA-B alleles was also investigated. The HLA-B alleles showed distinct electrophoretic patterns in nondenaturing polyacrylamide gels, depending on the nucleotide sequences of the exon 2, indicating that the SSCP analysis may be an alternative, useful and practical HLA-matching system of HLA-B specificity in tissue transplantation.

Alleles↗
PubMed1992

Polymerase chain reaction--single-strand conformation polymorphism analysis of polymorphism in DPA1 and DPB1 genes: a simple, economical, and rapid method for histocompatibility testing.

A new technical trial was carried out to detect polymorphism in HLA-DP genes, based on the diversity in electrophoretic mobility of single-stranded DNA (single-strand conformation polymorphism, SSCP). Genomic DNAs from 31 cell lines homozygous for 2 and 14 different DPA1 and DPB1 alleles, respectively, and from peripheral blood cells of a normal individual homozygous for another DPB1 allele were subjected to polymerase chain reaction (PCR) to amplify the polymorphic exon 2 of DPA1 or DPB1 genes. The PCR samples were denatured by heating in the presence of formamide to obtain single-stranded DNA, electrophoresed in a neutral polyacrylamide gel, and visualized by silver staining. Allelic differences were detected by the distinctive electrophoretic pattern of each single strand, depending on the sequence-specific conformation. Fifteen DPB1 alleles showed 11 distinct electrophoretic patterns, leaving four allelic combinations not distinguished. These four allelic combinations could be further distinguished by using another couple of primers in PCR, with which a part of the exon was amplified, and by subsequent SSCP analysis. The use of four pairs of primers in PCR allowed for discrimination of all the 15 DPB1 alleles tested. Two allelic differences in exon 2 of DPA1 gene could be clearly demonstrated. In addition, putative new alleles of DPA1 and DPB1 genes were detected by SSCP analyses. The PCR-SSCP analysis is simple and rapid, requires neither radioactive materials nor restriction enzymes, and is expected to be a useful tool for investigating the fine HLA-matching required for clinical transplantation of organs.

Alleles↗
PubMed1992

HLA-A and DPB1 loci confer susceptibility to Graves' disease.

To investigate HLA-linked genetic factors involved in the pathogenesis of Graves' disease, 76 patients and 317 healthy controls in the Japanese population were examined for HLA-A, B, C, DR, and DQ specificities by serologic typing and for HLA-DPB1 alleles by DNA typing by using the PCR-SSOP method. The frequencies of HLA-A2, B46, Cw11, and DPB1*0501 were increased and those of HLA-A24, B7, Bw52, and DR1 were decreased in the patients. The increased frequencies of HLA-A2 and DPB1*0501 in the patients were statistically significant when the corrected p value (pc) was applied (pc < 0.02 and pc < 0.002, respectively). ORs for a risk to develop the disease were calculated among individuals positive for DPB1*0501 and/or HLA-A2, and the highest OR (10.5) was observed in individuals possessed both DPB1*0501 and HLA-A2. This observation suggests a synergic involvement of a HLA class II allele (DPB1*0501) and an HLA class I allele (HLA-A2) in the pathogenesis of Graves' disease.

Adolescent↗
PubMed1992

Sequencing and population analysis of four novel HLA-DPA1 alleles.

We determined the base sequences of the HLA-DPA1 gene from four B-lymphoblastoid cell lines (CB6B, LKT3, AMAI, and T7526) that showed distinct electrophoretic patterns of single-stranded polymerase chain reaction products of the HLA-DPA1 gene. The novel HLA-DPA1 alleles of CB6B, LKT3, AMAI, and T7526 were designated DPA1*02021, DPA1*02022, DPA1*0301, and DPA1*0401, respectively. Although there was only one base substitution between DPA1*02021 and DPA1*02022, the single-strand conformation polymorphism of these two alleles was clearly demonstrated by electrophoresis in a nondenaturing polyacrylamide gel containing 10% glycerol. In addition, we genotyped for the HLA-DPA1 gene of healthy unrelated Oriental individuals--i.e., 227 Japanese, 88 Papua New Guineans, and 41 Buyi-Chinese--to demonstrate the ethnic distribution of the HLA-DPA1 alleles.

Alleles↗
PubMed1992

Production of monoclonal antibodies specific to major allergens of Cryptomeria japonica pollen.

Monoclonal antibodies (MAbs) directed against Cryptomeria japonica pollen antigen (CPAg) were prepared. CPAg was precipitated with these MAbs and both MAbs CPA7 (IgG2a) and CPA9 (IgG1) recognized two major glycoproteins (m = 41 kDa and 46 kDa) of CPAg. MAb CPA7 or CPA9 was coupled to CNBr activated sepharose and affinity purification of the major allergen of CPAg from the crude extract was performed. The affinity purified CPAg bound IgE antibody present in patients with Cedar pollinosis.

Allergens↗
PubMed1992

HLA-DP antigen and Takayasu arteritis.

Sixty-four patients with Takayasu arteritis and 317 healthy individuals in the Japanese population were examined for HLA-A, -B and -C alleles by serological typing and for HLA-DR, DQ and DP alleles by DNA typing using PCR/SSOP analysis. The frequencies of HLA-Bw52, DRB1*1502, DRB5*0102, DQA1*0103, DQB1*0601 and DPB1*0901 alleles were significantly increased and the frequencies of HLA-Bw54, DRB1*0405, DRB4*0101, DQA1*0301, DQB1*0401 alleles were significantly decreased. Strong linkage disequilibria among the increased alleles and among the decreased alleles were evident in the Japanese population. Therefore, the combination or haplotype of HLA-Bw52-DRB1*1502-DRB5*0102-DQA1*0103-DQB1*0601 -DPA1*02-DPB1*0901 may confer susceptibility to Takayasu arteritis while another combination or haplotype of HLA-Bw54-DRB1*0405-DRB4*0101-DQA1*0301-DQB1++ +*0401 may confer resistance to the disease. Because this is the first evidence for the association between an HLA-DP allele and Takayasu arteritis, we examined the nucleotide sequences of the DPB1*0901 allele from a patient and her healthy relatives and found no difference. The disease is therefore not caused by a mutated DPB1 gene.

Alleles↗
PubMed1992

DNA typing of HLA class II genes in B-lymphoblastoid cell lines homozygous for HLA.

The HLA class II genotypes were determined in the B-lymphoblastoid cell lines selected for the Tenth International Histocompatibility Workshop. The HLA class II genes were determined by the PCR-SSOP method using the reagents provided by the Eleventh Histocompatibility Workshop. Additional studies have been performed for further characterization of HLA class II polymorphism on these cell lines. It is observed that several cell lines have HLA class II haplotypes with the same DRB1, DQA1 and DQB1 alleles on both haplotypes but different alleles at the other class II loci, confirming that these cell lines are not truly HLA class II-homozygous. Other cell lines carried HLA class II haplotypes which were only different at the DRB1 gene. These results suggest double recombination events or gene conversion-like events in generation of HLA DR, DQ haplotypes. These cell lines provide an important tool as references for HLA DNA typing.

Alleles↗
PubMed1992

Adverse effect of chronic tonsillitis on clinical course of sarcoidosis in relation to HLA distribution.

We examined the effect of chronic inflammatory foci in the upper respiratory tract and/or HLA class 2 antigens on the clinical course of sarcoidosis. Sarcoidosis resolved spontaneously in 6 of 27 (22 percent) patients with CTL and in 19 of 29 (66 percent) without CTL (p less than 0.01). The clinical course became favorable after TLT in 7 of 14 cases with CTL. Patients with HLA-DR9 and DRw8 showed the highest ratio of patients who had protracted clinical course; those with HLA-DR2, DR5 and DR6 showed the lowest; and those with HLA-DR4, DRw52 and Drw53 were between these levels. A high responsiveness to SCW antigens was seen more frequently in sarcoidosis patients with protracted clinical course. The high responsiveness to SCW antigens was related to HLA-DR4, DRw8, DR9 and DRw53 in sarcoidosis patients. HLA antigens, especially HLA-DR, modulate the immune response to inhaled antigenic agents. Immune response seemed to affect the clinical course of sarcoidosis.

Adult↗
PubMed1992

[Contribution of genetic factors to RA].

Multiplex families of rheumatoid arthritis (RA) and concordance of the development of RA in monozygotic twins strongly suggest the relationship of genetic factor to the onset of RA. Among many genetic markers, HLA shows the strongest association with RA and association between RA and HLA-DR4 has been reported in many ethnic groups. DNA typing of HLA class II genes revealed that DRB1 * 0405 (Dw 15) is the most susceptible DRB1 allele for RA in the Japanese. The particular epitope sequence at the third hypervariable region (position 70-74, and 86) and DR beta chain, expressed with the structure of the DR4 molecule seems to be important for the susceptibility to RA.

Arthritis, Rheumatoid↗
PubMed1991

p53 gene mutations in colorectal tumors from patients with familial polyposis coli.

The p53 gene has been elucidated as a tumor suppressor gene, and inactivation of this gene caused by deletion or point mutations may play a crucial role in the development of human malignancies. In colorectal carcinomas with an allelic deletion of the p53 gene, the remaining p53 gene was mutated with considerable frequency. It is most difficult to detect point mutations or small deletions of the gene because the mutations occur in diverse regions, although four hot spots have been observed [J.M. Nigro et al., Nature (Lond.), 342: 705-708, 1989]. The polymerase chain reaction and denaturing gradient gel electrophoresis facilitate detection of mutations in the hot spots of the p53 gene. Using these methods, we detected mutations in three adenomatous polyps and one carcinoma from familial polyposis coli patients and three carcinomas of sporadic cases. The DNA sequence analysis confirmed mutations of the p53 gene in 2 adenomas (13 base-pair deletions in one and a point mutation in the other) and 1 carcinoma (point mutation) from familial polyposis coli patients. These results suggest that the p53 gene mutations may be involved in the formation not only of carcinomas but also of adenomas which occur in familial polyposis coli patients.

Adenomatous Polyposis Coli↗