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T Fukunishi

Publications and source records attributed to T Fukunishi.

At least 37 records · Page 2Linked to original sources

Gene frequencies and haplotypic associations within the HLA region in 916 unrelated Japanese individuals.

The gene frequencies and haplotypic associations within the HLA region have been investigated in 916 unrelated Japanese individuals. HLA class I and class II antigens were studied by conventional serology, and class II alleles, DRB1, DRB3, DQA1, DQB1 and DPB1 were typed by using polymerase-chain reaction amplification and sequence-specific oligonucleotide probe (PCR-SSOP) method. Thirty DRB1, 3 DRB3, 8 DQA1, 15 DQB1 and 13 DPB1 alleles were found in our population. DR-NJ25, a characteristic antigen in the native American and Asian populations, was observed at 3.0%. This antigen was observed mainly with the DRB1*1403 and 1406 alleles. Twenty-seven out of 30 DRB1 alleles found in this study had a high positive linkage disequilibrium with DQB1 alleles and 20 of them had an exclusive association with one specific DQA1-DQB1 combination. The strong association between DRB1 alleles and HLA-B antigens was the most striking finding in this study. Twenty-eight out of 30 DRB1 alleles had a positive linkage disequilibrium with 24 HLA-B antigens (p < 0.01). The other two alleles, DRB1*0404 and 1402, were very rare, and their frequencies were 0.2% and 0.1%, respectively. The data presented in this population study should be useful for the studies on anthropology, organ transplantation and disease susceptibility.

Gene Frequency↗

Striking conservation of three extended HLA-DR13 haplotypes in the Japanese population.

HLA class II DNA typing was conducted for 1335 unrelated Japanese individuals. The study on the linkage disequilibrium revealed a striking conservation of HLA DR13 haplotypes. Among these Japanese, 155 were typed for HLA-DR13 serologically, and they were correspondent to three DRB1 alleles, DRB1*1301, 1302 and 1307 defined by using the polymerase-chain reaction and sequence-specific oligonucleotide probe (PCR-SSOP) method. The two alleles, DRB1*1301 and 1307 were exclusively associated with each specific DRB3-DQA1-DQB1 combination which was DRB1*1301-DRB3*0101-DQA1*0103-DQB1*0603, and DRB1*1307-DRB3*0202-DQA1*0501-DQB1*0301, respectively. DRB1*1302, the most common DR13 allele in Japanese, had two significant associations with DRB3*0301-DQA1*0102-DQB1*0604 (DRB1*1302A) and with DRB3*0301-DQA1*0102-DQB1*0605 (DRB1*1302B). In this study, no other DR13 class II combinations were found. Only the DRB1*1302A halotype was associated with the DPB1*0401 allele while the DRB1*1302B haplotype was not. The complete conservation of these DR13 class II haplotypes was found to extend toward the HLA class I region. They were HLA A3-B44-DRB1*1301, A33-B44-DRB1*1302A and A33-B17-DRB1*1302B. Japanese could be characterized with these three extended haplotypes which were remarkably different from those in Caucasian, Black and Asian other than Korean populations.

DNA Primers↗

Long-term graft survival rate of zero-mismatch kidney transplants for HLA-DRB1.

The study of a two-locus association between HLA-B and -DRB 1 revealed a significant 43 linkage disequilibrium. Donor-recipient HLA-DRB1 was determined by these 43 linkages. Zero-mismatch for HLA-DRB1 had a significant effect on the graft survival rate in living related and cadaver transplants. The 5-year graft survival rate was 94% in the zero-mismatch group for HLA-DRB1, 96% for related transplants, 92% for cadaver cases, and 94% in HLA identical siblings. A statistically significant difference was found between the zero-mismatch group for HLA-DRB1 and mismatch groups for HLA-DRB1 or HLA-DR (P < 0.01). The zero-mismatch group for HLA-DRB1 had mismatches for HLA-A and/or HLA-B in 46 of 70 cases (66%). No significant differences in the rejection rate was observed between zero-mismatch and mismatch cases for HLA-A and/or -B in the zero-mismatch group for HLA-DRB1. In the second step, genotyping was conducted in 118 cases. The 5-year graft survival rate was 93% in the zero-mismatch group for HLA-DRB1 and 86% in mismatch group (not a significant difference). We concluded that zero-mismatch transplant for HLA-DRB1 had a better long-term graft survival rate regardless of HLA class I.

Cyclosporine↗

The impact of hepatitis C virus infection on liver disease in renal transplant recipients.

To assess the prevalence of hepatitis C virus (HCV) infection in renal transplant recipients and its impact on posttransplant liver disease, the sera from 176 recipients who had been followed for 1-20 years (mean 8.3 years) were tested for HCV-specific antibody using enzyme immunoassay. HCV-specific antibody was detected in 53 patients (30.1%) including 2 patients also positive for hepatitis B surface antigen (HBsAg). Among 167 HBsAg-negative patients, the presence of HCV-specific antibody was associated with an increased incidence of chemically significant hepatitis (70.6% vs. 9.5% in anti-HCV-negative patients, P < 0.01). Hepatitis was more likely to be chronic in anti-HCV-positive patients than in anti-HCV-negative patients (P<0.05). Serious liver disease developed in 4 of 51 anti-HCV-positive, HBsAg-negative patients: liver failure causing death in 3 and hepatoma in 1. Liver biopsy specimens from anti-HCV-positive patients showed more aggressive histological lesions compared with those from anti-HCV-negative patients. We conclude that HCV infection is quite prevalent in our renal transplant recipients and plays a major role in posttransplant chronic liver disease.

Alanine Transaminase↗

[Expression of integrin molecule in urological tumor cell lines by using RT-PCR method].

Integrins are heterodimer molecule that are composed of one alpha subunit and one beta subunit. Integrins appear to be the major receptors by which cells attach to extracellular matrices, and some integrins also mediate important cell-cell adhesion event. In recent years signaling pathway via beta subunit of integrin molecule has been clarified, and 8 kinds of integrin beta subunit are known to exist. And so we investigated the expression of integrin beta subunit in various urological tumor cell lines by using RT-PCR method. Materials are composed of 8 renal cell carcinoma cell lines, 2 urinary bladder carcinoma cell lines, a testicular tumor cell line and a prostate tumor cell line. All 12 cell lines express integrin beta 1 subunit. The expression rate of beta 4 subunit in renal cell carcinoma lines are lower than that in other urological tumor cell lines. The expression of beta 6 subunit was observed in renal cell carcinoma cell lines and testicular tumor line. In testicular tumor cell line we also found the expression of beta 2 subunit which expression had been believed to be specific in leukocyte.

Base Sequence↗

The significant effect of HLA-DRB1 matching on long-term kidney graft outcome.

Serotyping and genotyping (polymerase chain reaction with sequence-specific oligonucleotide probes method) were conducted on 520 unrelated individuals to determine the linkage disequilibrium of HLA-B and HLA-DRB1. Analyses of 511 kidney transplants (300 related and 211 cadaver recipients) were carried out at 4 transplant centers using the linkage disequilibrium of HLA-B and HLA-DRB1 established previously. All transplant recipients received CsA immunosuppression and were transplanted from June 1983 to December 1991. There were 51 significant linkages formed between HLA-B and HLA-DRB1 alleles (P < 0.05). DRB1-compatible transplants experienced a comparable 5-year graft success rate of 94% as did the HLA-identical recipients with a 100% 5-year success rate. However DRB1-incompatible recipients displayed a significantly reduced 5-year graft survival rate of 73% (73% vs. 94% P < 0.01). The 5-year graft survival rate of HLA-DR-incompatible recipients of 71% was compatible to the 73% for HLA-DRB1-incompatible recipients. No variation of rejection rate for DRB1-compatible grafts was seen in any of the 4 transplant centers. The results also indicated that HLA-DRB1 compatibility was essential for optimal success rate, regardless of HLA class I mismatches. The overall conclusion was that matching for HLA-DR was important to achieve optimal kidney graft survival on the molecular level but not on the serotyping level.

Alleles↗

Early diagnosis of kidney transplant rejection and cyclosporin nephrotoxicity by urine cytology.

A total of 2000 urine samples from 53 kidney transplant recipients were studied to develop a routine method for the early diagnosis of rejection and cyclosporin (CSA) nephrotoxicity in urine. New-Sternheimer staining and an immunocytochemical technique were used together with classical Papanicolaou staining to differentiate cells in the urine. After cell count and differentiation of second morning urine samples with New-Sternheimer and Papanicolaou stains, immunocytochemistry was performed using antibodies against the following antigens: CD2, CD4, CD8, CD25, CD71 (transferrin receptor), HLA-DR and cytokeratin (Lu-5). Cell counts were obtained for the positively-reacting cells per millilitre of urine. By New-Sternheimer and Papanicolaou staining, CSA nephrotoxicity was characterized by the predominance of proximal tubular cells. During rejection episodes, increased numbers of mononuclear cells and renal epithelial cells were found. Immunocytochemical analysis showed a significant increase in CD2-, CD4-, CD8-, CD25-, CD71-, and HLA-DR-positive epithelial cells and in the ratio HLA-DR/cytokeratin-positive epithelial cells in rejection. CD25-positive cells had the highest sensitivity and specificity for the diagnosis of rejection. Our urine cytology technique proved to be a useful and non-invasive method for the early diagnosis of rejection and CSA nephrotoxicity.

Adolescent↗

A preliminary pharmacokinetic study of cyclosporine A in 10 Japanese renal transplant patients.

A pharmacokinetic study of cyclosporine A (CyA) was performed in ten Japanese renal transplant patients. The peak blood CyA concentration appeared at about 2.5 h after oral administration of CyA 180-360 mg, and the mean peak CyA concentration was 582 +/- 238 (SD) ng/ml. The apparent clearance was 39.9 +/- 16.9 (SD) ml/min/kg which is almost the same as reported in European transplant patients. The apparent distribution volume was 5.34 +/- 3.05 (SD) l/kg. The wide variations observed both in the apparent clearance and in the apparent distribution volume are ascribed to the wide variation of the area under the curve (AUC). No correlation was found between the oral dose per body weight and peak blood CyA level or AUC in the 10 subjects. However, a linearity was ascertained between blood CyA concentrations and oral CyA doses (250 mg and 500 mg), though in one patient. Especially, in one patient, blood CyA level was under the lower detection limit of our assay method, 50 ng/ml, over 20 h after oral administration of CyA. This study strongly supports the need of the blood monitoring in the CyA therapy after renal transplantation.

Adult↗