Search PubMed⌕ Search

Biomedical subjects

T Juji

Publications and source records attributed to T Juji.

At least 55 records · Page 3Linked to original sources
PubMed2000

Involvement of receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor in osteoclastogenesis from synoviocytes in rheumatoid arthritis.

OBJECTIVE: To clarify the mechanism by which osteoclasts are formed in culture of rheumatoid synoviocytes by exploring the involvement of receptor activator of nuclear factor kappaB ligand (RANKL)/osteoclast differentiation factor (ODF). METHODS: Osteoclast formation was evaluated in cocultures of rheumatoid synovial fibroblasts and peripheral blood mononuclear cells (PBMC) in the presence of macrophage colony stimulating factor and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) utilizing separating membrane filters. RANKL/ODF expression was examined by Northern blotting in synovial tissues from 5 rheumatoid arthritis (RA) patients and tissues from patients with giant cell tumor (GCT), osteosarcoma (OS), and osteoarthritis (OA). RANKL/ODF expression and the ability of synovial fibroblasts to support osteoclastogenesis were investigated in coculture with PBMC in the presence or absence of 1,25(OH)2D3, and soluble RANKL/ODF and osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) were measured by enzyme-linked immunosorbent assay. The effects of OPG/OCIF on the osteoclastogenesis in the primary culture of rheumatoid synoviocytes and the coculture system were determined. RESULTS: Synovial fibroblasts did not induce osteoclastogenesis when separately cocultured with PBMC. Northern blotting revealed that RANKL/ODF was highly expressed in all tissues from RA and GCT patients, but not from OA or OS patients. Cultured rheumatoid synovial fibroblasts efficiently induced osteoclastogenesis in the presence of 1,25(OH)2D3, which was accompanied by up-regulated expression of RANKL/ODF and decreased production of OPG/OCIF. Osteoclastogenesis from synoviocytes was dose-dependently inhibited by OPG/OCIF. CONCLUSION: RANKL/ODF expressed on synovial fibroblasts is involved in rheumatoid bone destruction by inducing osteoclastogenesis and would therefore be a good therapeutic target.

Arthritis, Rheumatoid↗
PubMed2000

Identification of a telomeric boundary of the HLA region with potential for predisposition to human narcolepsy.

We report on a study performed to determine a boundary of the region with the potential to contribute to the predisposition to human narcolepsy (the susceptibility region) in the human leukocyte antigen (HLA) region. We investigated a Japanese narcolepsy family, in which a de novo chromosomal recombination occurred between the HLA-DRB1 and HLA-B genes in the proband. The recombinant chromosome carrying HLA-DRB1*1501 was transmitted to the affected child and grandchild, suggesting that a strong genetic factor(s) predisposing to the disorder was (were) present on the chromosome, and that the recombination breakpoint could be regarded as a boundary to the susceptibility region. To search for the breakpoint, we carried out allele typing at various polymorphic sites, e.g., microsatellite repeat polymorphisms, restriction fragment length polymorphisms, and single-nucleotide polymorphisms in the HLA region, and examined haplotypes with the polymorphic sites in the family members. Haplotype analyses revealed that the recombination breakpoint was present approximately 50 kb to the telomeric side of the palmitoyl-protein thioesterase-2 (PPT2) gene in the HLA class III region. From the gene map of the HLA region, the cyclic AMP response element-binding protein-related protein gene (CREB-RP) appeared to be located at the telomeric end in the 50-kb region. Therefore, the data presented here suggest that the susceptibility region for the disorder in the family is present on the centromeric side of the CREB-RP gene in the recombinant Chromosome 6 carrying HLA-DRB1*1501.

Female↗
PubMed2000

Gene organization and rearrangements at the human Rhesus blood group locus revealed by fiber-FISH analysis.

The human Rhesus (Rh) blood group locus is composed of two highly homologous genes, the RHD and RHCE genes on chromosome 1, encoding the D, C/c, and E/e antigens in common Rh-positive phenotypes. In general, the RHD gene is either absent or grossly deleted in Rh-negative individuals. In this study, gene organization at the RH locus of Japanese donors with different serological phenotypes was directly analyzed by two-color fluorescence in situ hybridization on DNA fibers released from their lymphocytes (fiber-FISH) and by using DNA probes of introns 3 and 7 of the RHCE and RHD genes. Six Rh-positive samples (two with the D+C-c+E+e-, two with the D+C+c-E-e+, and two with the D+C+c+E+e+ phenotype) showed the presence of two RH genes within a region of less than 200 kb on chromosome 1p36.1. Of great interest was the finding that the genes were arranged in the antidromic order of the telomere -RHCE (5'--> 3') -RHD (3'-->5') - centromere. On the other hand, two typical Rh-negative samples (D-C-c+E+e+) showed the presence of only one RHCE gene, as expected. Moreover, further analysis combined with a locus-specific assay of three Rh-negative samples (D-C+c+E+e+, D-C+c+E-e+, and D-C+c-E-e+) showed the possible presence of the RHD gene(s) and complex rearrangements, including partial deletion, duplication, and recombination, in this region; these could be responsible for the Rh-negative phenotype.

Base Sequence↗
PubMed2000

Dendritic cells are targets for human invariant Valpha24+ natural killer T-cell cytotoxic activity: an important immune regulatory function.

OBJECTIVE: Human invariant Valpha24+ natural killer T (NKT) cells, a subpopulation of NK cell-receptor (NKR-P1A)-expressing T cells with an invariant Valpha24JalphaQ T-cell receptor (TCR), are stimulated by the glycolipid a-galactosylceramide (KRN7000), in a CD1d-dependent, TCR-mediated fashion. Little is known about invariant Valpha24+ NKT cell function or mechanisms of effector activity. Evidence suggests this cell population protects against autoimmunity and has antitumor effects against leukemia and solid tumors. MATERIALS AND METHODS: We compared the phenotype and function of invariant Valpha24+ NKT cells, from patients with chronic myeloid leukemia (CML) and normal donors, generated by stimulation of peripheral blood mononuclear cells with alpha-galactosylceramide pulsed monocyte-derived dendritic cells. The CD4(-)CD8(-) (double negative) population was studied further. RESULTS: Activated human invariant Valpha24+ NKT cells were cytotoxic against autologous and allogeneic peripheral blood dendritic cells and monocyte-derived dendritic cells but not against autologous or allogeneic T-cell PHA blasts, B-cell lymphoblastoid cell lines, monocytes, or leukemic cells from patients with CML. The findings are consistent with previous observations showing the importance of CD1d in target cell recognition. None of the Valpha24+ NKT cell lines expressed the NK markers CD16, CD56, CD94, or killer inhibitory receptors, but all expressed NKR-P1A. There was no difference in phenotype, function, or ease of generation of invariant Valpha24+ NKT cells between normal donors and patients with CML. CONCLUSION: Based on our results and the previous evidence linking reduced Valpha24+ NKT cells to autoimmunity, we propose that double-negative Valpha24+ NKT cells have important immune regulatory functions, including contribution to the prevention of excessive antigen stimulation by virtue of cytotoxic activity against antigen presenting cells, particularly in dendritic cells.

Cytotoxicity, Immunologic↗
PubMed2000

Heterogeneity of Taiwan's indigenous population: possible relation to prehistoric Mongoloid dispersals.

Taiwan's 9 indigenous tribes (Tsou, Bunun, Paiwan, Rukai, Atayal, Saisiat, Ami, Puyuma, Yami) are highly homogeneous within each tribe, but diversified among the different tribes due to long-term isolation, most probably since Taiwan became an island about 12,000 years ago. Homogeneity of each tribe is evidenced by many HLA-A,B,C alleles having the world's highest ever reported frequencies, e.g. A24 (86.3%), A26 (18.8%), Cw10 (36.8%), Cw7 (66%), Cw8 (32.1%), B13 (27.9%), B62 (37.4%), B75 (18%), B39 (53.5%), B60 (33.3%), and B48 (24%). Also, all of these tribes have HLA class I haplotype frequencies greater than 10%, with A24-Cw7-B39 in Saisiat (44.5%) being the highest, suggesting Taiwan's indigenous tribes are probably the most homogeneous ( the "purest") population in the world. A24-Cw8-B48, A24-Cw10-B60 and A24-Cw9-B61 found common to many Taiwan indigenous tribes, have also been observed in Maori, Papua New Guinea Highlanders, Orochons, Mongolians, Inuit, Japanese, Man, Buryat, Yakut, Tlingit, Tibetans and Thais. These findings suggest Taiwan's indigenous groups are more or less genetically related to both northern and southern Asians. Principal component analysis and the phylogenetic tree (using the neighbor-joining method) showed close relationship between the indigenous groups and Oceanians. This relationship supports the hypothesis that Taiwan was probably on the route of prehistoric Mongoloid dispersals that most likely took place along the coastal lowland of the Asian continent (which is under the sea today). Cultural anthropology also suggests a relationship between Taiwan's indigenous tribes and southern Asians and to a lesser extent, northern Asians. However, the indigenous groups show little genetic relationship to current southern and northern Han Chinese.

Alleles↗
PubMed2000

Analysis of HLA genes and haplotypes in Ainu (from Hokkaido, northern Japan) supports the premise that they descent from Upper Paleolithic populations of East Asia.

The Ainu people are assumed to be the descendants of pre-agricultural native populations of northern Japan, while the majority of population of present-day Japan (Hondo-Japanese) is considered to have descended mainly from post-neolithic migrants. Sequence-level polymorphisms of the HLA-class I (HLA-A and HLA-B) genes were investigated in DNA samples of 50 Ainu living in Hidaka district, Hokkaido. HLA-A*2402, A*0201, A*0206, A*2601, A*3101, B*1501, B*5101, B*3901, and B*3501 were observed at frequencies of more than 10% and most of these have previously been found in populations of not only Asians but also North and South American Indians. A*68012, which has not so far been detected in Hondo-Japanese, was found in the Ainu (3%). On the other hand, several alleles common in Hondo-Japanese, including HLA-A*3303, A*1101, B*4403, B*5201, B*5401, B*4601, and B*0702 were infrequent in Ainu (0-1%). Correspondence and neighbor-joining analyses of various populations based on HLA-A, -B and -DRB1 gene frequencies enabled distinction between Asian, Native South American, European, and African populations. The Ainu, as well as Tlingit (Na-Dene), were placed midway between other East Asians, including Hondo Japanese, and Native South Americans (Amerindians) in the correspondence analysis. Furthermore, several HLA-A-B and HLA-B-DR-DQ haplotypes common in the Ainu, are shared with some Native American populations. These observations strongly suggest a unique place for the Ainu as descendants of some Upper Paleolithic populations of East Asia, from whom some Native Americans may have descended.

Alleles↗
PubMed2000

Identification of a novel HLA-B46 allele, B*4602, in Japanese.

The B*4602 was identified in a healthy Japanese donor. The B46 variant antigen differed serologically from B46. The nucleotide sequence of B*4602 differed from that of B*4601 by a single base (from A to G) at position 293 in exon 2. The substitution changed the amino acid Asp at position 74 to Gly. The gene frequency of B*4602 in the Japanese population is extremely low. The presumed haplotype of B*4602 was HLA-A2-Cw1-B*4602-DRB1*09. This is the first report of polymorphism of the B46 antigen.

Alleles↗
PubMed2000

Nucleotide sequence of a new Fc gamma receptor IIIB allele that codes for a neutrophil antigen.

A new allele of the human neutrophil antigen (HNA) system (tentatively called NA2M) was discovered and its nucleotide sequence was determined. NA2M differs in a single nucleotide (193G-->A) from FCGR3B*2(NA2), resulting in an amino acid change (54Glu-->Lys). The frequency of the NA2M gene in the Japanese population was estimated to be 0.008. Granulocytes of individuals possessing NA2M reacted with HNA-1b(NA2)-specific monoclonal antibody (TAG2) in the GIFT assay.

Alleles↗
PubMed2000

Generation of HLA-DRB1*1501-restricted p190 minor bcr-abl (e1a2)-specific CD4+ T lymphocytes.

A small population of cells in acute lymphoblastic leukaemia is characterized by a specific translocation of the c-abl oncogene on chromosome 9 to the break point cluster lesion (bcr) on chromosome 22, t(9; 22)(q34; q11) (e1a2). Theoretically, the junction-spanning sequences of oncogene fusion proteins might be ideal targets for immunotherapy because these are not present in normal cells. In this study, we show for the first time that in vitro immunization with a 17-mer e1a2 peptide representing the p190 minor bcr-abl fusion protein resulted in HLA-DRB1*1501-restricted peptide-specific proliferative CD4+ T lymphocytes, using peptide-pulsed monocyte-derived dendritic cells as the antigen-presenting cells.

CD4-Positive T-Lymphocytes↗
PubMed2000

Human invariant valpha24+ natural killer T cells activated by alpha-galactosylceramide (KRN7000) have cytotoxic anti-tumour activity through mechanisms distinct from T cells and natural killer cells.

Human Valpha24 + NKT cells, a subpopulation of natural killer cell receptor (NKR-P1A) expressing T cells with an invariant T-cell receptor (TCR; Valpha24JalphaQ) are stimulated by the glycolipid, alpha-galactosylceramide (KRN7000), in a CD1d-dependent, TCR-mediated fashion. Little is known about Valpha24 + NKT-cell function. The murine counterpart, Valpha14 + NKT cells, appear to have an important role in controlling malignancy. There are no human data examining the role of Valpha24 + NKT cells in controlling human malignancy. We report that Valpha24 + NKT cells have perforin-mediated cytotoxicity against haemopoietic malignancies. Valpha24 TCR, CD1d and alpha-galactosylceramide may all play a role in cytotoxicity but are not absolute requirements. The greatest cytotoxicity was observed against the U937 tumour cell line (95 +/- 5% lysis). THP-1, Molt4, C1R cells and allogeneic mismatched dendritic cells were also sensitive to Valpha24 + NKT cytotoxicity but neither the NK target, K562, nor lymphokine-activated killer-sensitive Daudi cells, were sensitive. These results indicate a killing pattern distinct from conventional major histocompatibility complex-restricted T cells, NK cells and other cytotoxic lymphoid cells previously described. We conclude that human Valpha24 + NKT cells have cytotoxic anti-tumour activity against haemopoietic malignancies through effector mechanisms distinct from conventional T cells and NK cells and that their specific stimulator KRN7000 may have therapeutic potential.

Adjuvants, Immunologic↗
PubMed2000

Immunotherapy prevents recurrent abortion without influencing natural killer receptor status.

PROBLEM: We assessed the expression of natural killer (NK) receptors in recurrent aborters before and after immunotherapy using their husbands' peripheral blood mononuclear cells (PBMCs). METHOD OF STUDY: Using stored PBMCs from recurrent aborters before and after the immunotherapy, the expression of NK receptors, CD158a, CD158b, CD159 and CD94, were analyzed using monoclonal antibodies for respective receptors. The diversity of killer activatory receptors (KARs) and killer inhibitory receptors (KIRs) was also examined using reverse transcriptase-polymerase chain reaction (RT-PCR)-single strand conformation polymorphism (SSCP) method. RESULTS: In recurrent aborters, no apparent changes in NK receptor expression and the balance between KARs and KIRs were found before and after the immunotherapy. CONCLUSION: The allo-human leukocyte antigen (HLA)-stimulation caused by the immunotherapy for recurrent aborters did not affect the expression of NK receptors and the ratio of KARs to KIRs regardless of the outcome of subsequent pregnancies, suggesting that recurrent aborters may benefit from the immunotherapy through mechanisms unrelated to alteration in NK receptor status.

Abortion, Habitual↗
PubMed2000

Polymorphisms of RhD(Va) and a new RhD(Va)-like variant found in Japanese individuals.

BACKGROUND AND OBJECTIVES: Red cell type RhD(Va) lacks epD1 and 5 and is encoded by hybrid RHD-CE(5)-D alleles. We analyzed RhD(Va) and RhD(Va)-like samples in Japanese blood donors. MATERIALS AND METHODS: Ten RhD(Va) samples lacked epD1 and 5 and 3 RhD(Va)-like variants also lacked, epD2 and a part of 6/7. We identified the full-length nucleotide sequences of the complementary DNA (cDNA) synthesized from 4 samples: 3 of type D(Va) and the 4th a D(Va)-like variant. RESULTS: Although their sequences differed from each other, all the substitutions were exclusively in exon 5. Three D(Va) samples had hybrid RHD-CE(5)-D alleles, but the D(Va)-like variant had a unique nucleotide substitution with a single amino acid change, E233K. Exon 5 of the genomic DNA from all 13 samples was analyzed by sequencing. No other sequences were identified. CONCLUSION: All RhD(Va) and RhD(Va)-like variants had the substitution for E233. E233 seems to be a determinant of epD1 and 5. A new category of RhD variant, DYO, was identified.

Amino Acid Substitution↗
PubMed2000

Improved sensitivity in the measurement of residual leukocytes in platelet products using an automated leukocyte counter.

BACKGROUND AND OBJECTIVES: Leukocytes remaining in platelet concentrates may be responsible for side effects caused by platelet transfusion. A simple method of high sensitivity for determining trace numbers of leukocytes is currently needed. MATERIALS AND METHODS: An automated leukocyte counter, the LD-1000, the principle of which is a combination of spinning down on the observation field of stained nuclei derived from a 100 microl neat sample and image digitization with a charge coupled device camera, was newly developed and tested for sensitivity and reproducibility. RESULTS: While the theoretical lower limit of detection was 0.01 cells/microl, the limit of detection of the LD-1000 was verified to be 0.2 cells/microl. A good correlation (r = 0.86) was observed between the results obtained using the Nageotte method and the LD-1000. Repeated measurements also confirmed satisfactory reproducibility. CONCLUSIONS: The instrument provides a new method of enumerating residual leukocytes in platelet products with better sensitivity and easier procedure compared to the Nageotte method and will be useful for quality assurance purposes at blood centers.

Humans↗
PubMed2000

Analysis of HLA-DRB1 polymorphism in the Gidra of Papua New Guinea.

The genetic structure of the Gidra-speaking population inhabiting 13 villages in Papua New Guinea was investigated, based on the analysis of HLA-DRB1 polymorphism. Nei's fixation indices (F(IS), F(IT), and F(ST)) showed that the Gidra villages were genetically differentiated. The genetic distances significantly correlated with the geographic distances among the 13 villages. Thus, it is likely that a low intervillage migration rate has been maintained since the Gidra community was established. Correspondence analysis revealed that the Gidra, who belong to non-Austronesian-speaking groups, are genetically located at the intermediate point between the Aboriginal Australian groups and the Austronesian-speaking groups. Moreover, the HLA-DRB1*0802 allele, which has been observed in only two Polynesian groups (Austronesian-speaking groups) of Oceanian populations, was also found in the Gidra. These results suggest that the admixture of Austronesian and indigenous non-Austronesian groups beyond the linguistic boundary occurred partly in Papua New Guinea before Austronesian groups spread to the Pacific.

Black People↗
PubMed2000

Treatment of post transfusion graft-versus-host disease.

BACKGROUND AND OBJECTIVES: In Japan, so many cases of post-transfusion graft-versus-host disease (PT-GVHD) have been reported, and no effective treatment has been reported. MATERIALS AND METHODS RESULTS: Totally 61 cases of PT-GVHD have been collected, and their background were analyzed. A serine protease inhibitor, nafamostat mesilate(N.M.) was examined as a drug for treatment of PT-GVHD using 4 patients. RESULTS: N.M. was confirmed to inhibit cytotoxic activities of established cytotoxic T cell (CTL) clones in vitro. Simultaneously it was confirmed that fever and skin rash disappeared and liver function tests were normalized soon after the administration of N.M. in all four cases. Leukopenia and thrombocytopenia simultaneously improved. CONCLUSION: The effects of N.M. seem to be limited to inhibit cytotoxic activity of CTL. In addition to this drug, how to remove the CTL from the patients will be the essentially important theme for the future.

Aged↗
PubMed1999

Killer cell immunoglobulin receptors and T cell receptors bind peptide-major histocompatibility complex class I with distinct thermodynamic and kinetic properties.

Human natural killer cells and a subset of T cells express a repertoire of killer cell immunoglobulin receptors (KIRs) that recognize major histocompatibility complex (MHC) class I molecules. KIRs and T cell receptors (TCRs) bind in a peptide-dependent manner to overlapping regions of peptide-MHC class I complexes. KIRs with two immunoglobulin domains (KIR2Ds) recognize distinct subsets of HLA-C alleles. Here we use surface plasmon resonance to study the binding of soluble forms of KIR2DL1 and KIR2DL3 to several peptide-HLA-Cw7 complexes. KIR2DL3 bound to the HLA-Cw7 allele presenting the peptide RYRPGTVAL with a 1:1 stoichiometry and an affinity (K(d) approximately 7 microM at 25 degrees C) within the range of values measured for other cell-cell recognition molecules, including the TCR. Although KIR2DL1 is reported not to recognize the HLA-Cw7 allele in functional assays, it bound RYRPGTVAL/HLA-Cw7, albeit with a 10-20-fold lower affinity. TCR/peptide-MHC interactions are characterized by comparatively slow kinetics and unfavorable entropic changes (Willcox, B. E., Gao, G. F., Wyer, J. R. , Ladbury, J. E., Bell, J. I., Jakobsen, B. K., and van der Merwe, P. A. (1999) Immunity 10, 357-365), suggesting that binding is accompanied by conformational adjustments. In contrast, we show that KIR2DL3 binds RYRPGTVAL/HLA-Cw7 with fast kinetics and a favorable binding entropy, consistent with rigid body association. These results indicate that KIR/peptide-MHC class I interactions have properties typical of other cell-cell recognition molecules, and they highlight the unusual nature of TCR/peptide-MHC recognition.

Amino Acid Sequence↗