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K Tadokoro

Publications and source records attributed to K Tadokoro.

At least 91 records · Page 5Linked to original sources
PubMed1997

Characterization of T-cell clones derived from peripheral blood lymphocytes of a patient with transfusion-associated graft-versus-host disease: Fas-mediated killing by CD4+ and CD8+ cytotoxic T-cell clones and tumor necrosis factor beta production by CD4+ T-cell clones.

Transfusion-associated graft-versus-host disease (TA-GVHD) is one of the most serious adverse effects of blood transfusion. It is generally thought to be caused by the infused lymphocytes. Donor-derived cytotoxic T lymphocytes (CTLs) directed against the recipient's HLAs, which have escaped the recipient's immune system and are proliferating, are considered to attack recipient organs and tissues. Despite the seriousness of the disease, the precise mechanism of its development remains unclear and no definitive treatment has been developed. With the aim of developing an effective treatment, we established and characterized T-cell clones from peripheral blood lymphocytes (PBLs) of a TA-GVHD patient. Three types of clones were established. Type I clones were CD8+ and specifically lyse cells that express HLA B52. Type II clones were CD4+, specifically lysed cells that express HLA DR15, and proliferated in response to stimulation with cells that express DR15. Type III clones were also CD4+, showed no cytotoxic activity toward any HLA-expressing cells, and proliferated in response to stimulation with cells that express DR15. Furthermore, we found that the Fas/Fas-ligand (Fas-L) system is involved in the cytotoxicity of the type I and II clones and that the type III clones produce and secrete a large amount of tumor necrosis factor beta (TNFbeta) after antigen stimulation. Based on our results, these three types of clones can be classified into two categories: those that have the ability to induce GVHD directly by cytolysis and that show no cytotoxic activity and those that have the ability to cause GVHD indirectly through secretion of cytotoxic lymphokines.

Aged↗
PubMed1997

Association of Campylobacter jejuni serotype with antiganglioside antibody in Guillain-Barré syndrome and Fisher's syndrome.

Using Penner's method and Lior's scheme, we serotyped 31 isolates from patients with Guillain-Barré syndrome, 7 isolates from those with Fisher's syndrome, and isolates from patients with sporadic enteritis. PEN 19 of Campylobacter jejuni was isolated more frequently from the Guillain-Barré syndrome patients (16/31 isolates, 52%) than from the sporadic enteritis patients (5%). LIO 7 of C. jejuni also was isolated more frequently from the Gillain-Barré syndrome patients (14/31 isolates, 45%) than from the enteritis patients (3%). One reason why Guillain-Barré syndrome is rare, despite the high incidence of C. jejuni enteritis, may be the low frequencies of PEN 19 and LIO 7. The frequency of positive anti-GM1 antibody titers in the Guillain-Barré syndrome patients with PEN 19 isolates was higher than that in the Guillain-Barré syndrome and Fisher's syndrome patients without PEN 19 isolates. We speculate that the serotypic determinant of PEN 19 aids in the production of anti-GM1 antibody by a GM1-like lipopolysaccharide. In contrast, 5 of the 7 isolates from the Fisher's syndrome patients belonged to PEN 2:LIO 4. The IgG anti-GQ1b antibody was associated with PEN 2 and LIO 4. These serotypic determinants may aid in the production of IgG anti-GQ1b antibody by a GQ1b-like lipopolysaccharide.

Antibodies↗
PubMed1997

Large-scale comparative mapping of the MHC class I region of predominant haplotypes in Japanese.

In order to further our understanding of major histocompatibility complex (MHC) class I gene organization, we began a comparative analysis of the large scale organization of the class I region in diverse haplotypes. For these studies, the MHC in healthy Japanese donors who have the predominant MHC haplotypes and/or HLA-A or -B alleles was examined by pulsed field gel electrophoresis and Southern analysis using probes spanning the class I region. Hybridization with probes from the HLA-A to HLA-G region revealed that individuals expressing HLA-A30, -A31, or -A33 have an approximately 70 kilobase (kb) insertion near the HLA-A gene as compared with haplotypes containing the HLA-A11 or -A26 allele. Conversely, HLA-A24-containing haplotypes appear to have an approximately 50 kb deletion from the same region. Further, it appears that chromosomes carrying closely related alleles are similar to each other in this region, consistent with their presumed evolutionary relationship. While little is known about the gene content between the HLA-A and HLA-G region, it will be interesting to examine the prospect that functional genes do in fact reside within the inserted or deleted portions, thereby raising the possibility that distinct functional differences are conferred by different haplotypes. Overall, the results reported here should contribute to furthering our understanding of the association between diseases and HLA as well as provide new insights into the evolution of the MHC.

Alleles↗
PubMed1997

Sequence-based association analysis of HLA class I and II alleles in Japanese supports conservation of common haplotypes.

Alleles of HLA-A, B, C, DRB1, DQB1, and DPB1 loci were fully determined in 117 healthy Japanese. A*2402, A*3303, A*1101, A*0201, B*4403, B*5201, Cw*0102, Cw*1403, Cw*0304, Cw*0702, Cw*0801, and Cw*1202 showed frequencies of over 10%. Multi-locus haplotype frequencies were estimated by the maximum likelihood method. Strength of association between C and B loci was comparable with that between DRB1 and DQB1 loci. Alleles unidentified by a serological method and having very similar nucleotide sequences (A2: A*0201, A*0206, A*0207, B61: B*4002, B*4006) were carried by different haplotypes. Several frequent five-locus haplotypes were identified including A*3303-Cw*1403-B*4403-DRB1(*)1302-DQB1(*)0604, and A*2402-Cw*1202-B*5201-DRB1(*)1502-DQB1(*)0601. These sequence-based haplotypes corresponded to serology-based common haplotypes which have already been described in Japanese. These findings indicate that common HLA haplotypes consist of particular sets of HLA alleles and that these haplotypes have been conserved through recent human evolution.

Alleles↗
PubMed1997

Proliferative effect of postapheresis platelet donor plasma on a megakaryoblastic leukemia cell line.

Platelet donors sometimes show an increased platelet count following apheresis. We analyzed the effect of plasma obtained from such donors, along with thrombopoietin (Tpo), for growth and differentiation-inducing activity on a megakaryoblastic leukemia cell line, Meg-J. Colony formation was stimulated by donor plasma for Meg-J cells in a dose-dependent manner, and the time course of the sampling peaked 1 day after apheresis. Neither the donor plasma nor Tpo induced morphological differentiation. Donor plasma from any sampling time decreased CD41 and CD42b expression by more than 10%, and more than a 10% decrease of CD41 was induced by Tpo. The measurement of plasma Tpo showed no statistically significant increase after platelet donation. Our data suggest that, following apheresis, donor plasma contains factor(s) that: (a) stimulate growth rather than induce differentiation of a megakaryoblastic cell line; (b) are present in increased levels after apheresis; and (c) are different from Tpo.

Blood Donors↗
PubMed1997

Detection and quantitation of HBV DNA by semi-nested PCR in donated blood: comparison with HBV serological markers.

To detect and quantitate hepatitis B virus (HBV) DNA, semi-nested polymerase chain reaction (PCR) method was designed for amplifying the HBV core region DNA. Cloned HBV core region DNA was used as a quantitation control, and upon electrophoresis of the semi-nested PCR product, one, two, or three bands of amplified DNA were observed using a small (< 50 mol), moderate (around 200 mol), or large (> or = 1250 mol) quantity of the template DNA, respectively. Using this semi-nested PCR method, HBV DNA was quantitated in donated blood and tested for HBV serological markers. Most of the HBV surface antigen (HBsAg) high titer samples showed three bands on the electrophoresis, indicating a high level of HBV DNA, while most of the HBsAg low titer samples showed one band, indicating a low level of HBV DNA. HBV DNA was detected in 7 out of 36 HBsAg-undetectable and anti-HBc-positive samples (19.4%) but all 7 showed one band, indicating a low level of HBV DNA. In almost all of the HBV e antigen-positive samples the HBsAg titer was high, and three bands were observed indicating a high level of HBV DNA.

Blood Donors↗
PubMed1997

Identification of HLA class II antigens as the targets of effector clones which may cause transfusion-associated graft-versus-host disease.

We established T cell clones, which were considered to be the possible cause of transfusion-associated graft-versus-host disease (TA-GVHD), from the peripheral blood lymphocytes (PBLs) of two patients. In both cases, several CD4+ cytotoxic T-cell (CTL) clones were established. In case I, the target antigen of the established CD4+ clones was a DRB1*0403-related antigen serologically typed as HLA DR4, which was one of the patient HLA antigens. In case II, the target of four out of five established CD4+ CTL was a DRB1*1302-related antigen. One CD4+ CTL clone showed cytotoxicity against cells carrying A*2402, B*4403, Cw*1403 and DPB1*0401. A monoclonal antibody (mAb) blocking study showed only anti-DP mAb inhibited the cytotoxicity of this clone. Thus, it might be considered that this clone recognizes HLA-DP with its binding peptides derived from either A*2402, B*4403, Cw*1403 or DRB1*1302. Our findings indicate that CD4+ CTLs may play important roles in the aetiology of TA-GVHD and that the antigens of patients recognized by donor-derived effector cells may not always recognize a single HLA antigen.

Aged↗
PubMed1997

Activation of the contact system by filtration of platelet concentrates with a negatively charged white cell-removal filter and measurement of venous blood bradykinin level in patients who received filtered platelets.

BACKGROUND: Several recent reports have described hypotensive transfusion reactions in patients receiving platelet concentrates (PCs) filtered through white cell-reduction filters. It is well known that a negatively charged surface activates the contact system, consisting of factor XII, prekallikrein, and high-molecular-weight kininogen. STUDY DESIGN AND METHODS: To clarify the mechanisms of these hypotensive reactions, the possibility that white cell-reduction filtration activates the contact system was examined. Venous blood plasma bradykinin levels were also measured in patients receiving PC transfusions through filters. RESULTS: None of the measured values were changed by filtration through a positively charged filter. However, filtration through a negatively charged filter resulted in a decrease in the amounts of prekallikrein and an increase in the amount of bradykinin generated, which indicated the activation of the contact system. The bradykinin level was inversely related to the activity of angiotensin-converting enzyme (ACE) in the PCs and was elevated by addition of an ACE inhibitor. Although the venous blood plasma bradykinin level did not change in two patients with a normal ACE activity during PC transfusion through the negatively charged filter, two patients who had decreased ACE activity, showed a significant increase in bradykinin during the transfusion. CONCLUSION: These results suggest that the generation of a large amount of bradykinin by filtration of PCs through a negatively charged filter might cause hypotensive reactions in patients with decreased ACE activity. The clinical significance of bradykinin generation requires further study.

Aged↗
PubMed1997

Identification of HLA-C alleles using PCR-single-strand-conformation polymorphism and direct sequencing.

Alleles encoding HLA-C antigens in Japanese were identified by polymerase chain reaction followed by single strand conformation polymorphism (PCR-SSCP) and nucleotide sequencing analyses. The results showed that at least sixteen different alleles code for eight serologically detectable antigen groups and undetectable blanks. Cw1 was mainly encoded by Cw*0102, whereas two split antigens of Cw3, Cw9 and Cw10, were encoded by Cw*0303 and Cw*0304, respectively. Cw4 and Cw6 were encoded by Cw*0401 and Cw*0602, respectively. Seven alleles, Cw*0801, Cw*0803, Cw*1202, Cw*1203, Cw*1402, Cw*1403 and Cw*1502, were found to encode serological HLA-C "blanks" in Japanese. Moreover, errors in the published nucleotide sequences of Cw*0501 and Cw*1201 were corrected. Twenty-one HLA-C alleles were distinguished from each other by means of group-specific PCR amplification followed by the SSCP method developed in the present study. The system using genomic DNAs can be used effectively for identification of new HLA-C alleles.

Alleles↗
PubMed1997

[Possible involvement of donor-derived B cells in development of post-transfusion graft-versus-host disease].

Post-transfusion graft-versus-host disease(PT-GVHD) is one of the most severe side effects of blood transfusion. To clarify the mechanism of development PT-GVHD, we characterized possible effector lymphocyte clones, presumably involved in the occurrence of PT-GVHD. By lymphocyte cloning from peripheral blood of a PT-GVHD patient, not only donor-derived cytotoxic T cell clones but also donor-derived B cell clones were established. The B cell clones produce cytotoxic IgG, directed against the patient's class II HLA. It was strongly suggested that donor-derived B cells, through production of cytotoxic IgG directed against the patient's HLA, were involved in the pathogenesis of the PT-GVHD in this case.

B-Lymphocytes↗
PubMed1996

Eosinophil degranulation in the presence of bronchial epithelial cells. Effect of cytokines and role of adhesion.

It has been suggested that eosinophils (Eos) are responsible for damage to bronchial epithelial cells by releasing toxic eosinophil granule proteins in bronchial asthma. We examined eosinophil cationic protein (ECP) release from human Eos cultured in the presence of human bronchial epithelial cell line BEAS-2B (Ep). ECP release was potentiated only when both Eos and Ep were activated by IL-5 and TNF, respectively, while it was not potentiated when either Eos or Ep were activated. ECP release from Eos activated by IL-5 was also enhanced when Ep was stimulated by IFN-gamma. Paraformaldehyde fixation of Ep had no effect on ECP enhancement, excluding the possibility that soluble factors from Ep contribute to ECP potentiation. Coculture of Eos and Ep with cytokine treatment resulted in the enhancement of eosinophil adhesion and ECP release, and eosinophil adhesion preceded ECP release in the kinetic study. The enhancement of ECP release was partially inhibited by anti-CD18 mAb, which caused partial and comparable inhibition on the potentiation of eosinophil adhesion. These results suggest that the activation of Ep may profoundly affect the ability of cocultured Eos to release ECP and that CD18-dependent adhesion of Eos to Ep may be considered as one of the mechanisms of ECP enhancement.

Antibodies, Monoclonal↗
PubMed1996

HLA-A null allele with a stop codon, HLA-A*0215N, identified in a homozygous state in a healthy adult.

A healthy adult having no serologically detectable HLA class I A locus antigens was identified. The parents of the individual are consanguineous. Results of a family study indicated that the individual is homozygous for the B46-Cw1-DR8.1 haplotype, which was shown to be positively associated with A*0207 in our previous study. The HLA-A null individual is healthy and exhibits no apparent immunological abnormality. Total RNAs extracted from peripheral blood were converted to cDNAs. The reverse transcriptase-polymerase chain reaction (PCR) product, which is of the same size as the normally expressed gene, was easily obtained from the cDNAs with HLA-A locus-specific primers. The nucleotide sequence of this null allele (A*0215N) was the same as that of A*0207 except for a single nucleotide substitution which resulted in a stop codon in exon 4. From its nucleotide sequence, a truncated molecule was expected to be produced; however, the immunoprecipitation study failed to detect the predicted product. Genomic DNAs from 29 unrelated individuals who expressed only one HLA-A antigen with HLA-B46, were analyzed by a PCR-sequence-specific oligonucleotide method. None of the samples possessed this stop codon. Therefore, A*0215N is likely to be a rare allele generated by a single point mutation from A*0207.

Adult↗
PubMed1996

Identification and DNA typing of two Cw7 alleles (Cw*0702 and Cw*0704) in Japanese, with the corrected sequence of Cw*0702.

Two alleles encoding HLA-Cw7 antigens, tentatively called C7J1 and C7J2, have been identified in Japanese using a PCR-SSCP method. The nucleotide sequence of full-length C7J1 cDNAs showed a high degree of homology to the reported Cw*0702 sequence except in exon 1. We then resequenced the allele carried by the cell line JY in which Cw*0702 was first identified, according to a request from the WHO Nomenclature Committee. The results revealed complete identity between the corrected Cw*0702 sequence and the C7J1 sequence. On the other hand, the C7J2 sequence was completely identical to the reported Cw*0704 sequence. Sequences specific for Cw*0702 and Cw*0704 were confirmed using PCR-RFLP and PCR-SSO methods. Moreover, association analysis with other HLA locus alleles showed positive associations of Cw*0702 with HLA-B7, -B39, and -B67 and of Cw*0704 with HLA-B70 in Japanese.

Alleles↗
PubMed1996

Evidence of involvement of cytotoxic antibodies directed against patients's HLA class II produced by transfused donor-derived B cells in post-transfusion graft-versus-host disease.

Post-transfusion graft-versus-host disease (PTGVHD) is one of the most severe side-effects of blood transfusion. To characterize the effector cells causing this disease, we cloned lymphocytes from a PTGVHD patient's peripheral blood. T-cell and B-cell clones were established, the origins of which were proven to be transfused donor lymphocytes. It was found that the B cells produced IgG that mediated complement-dependent cytotoxicity to the cells bearing the patient's HLA class II genotype. Our results suggest, for the first time, the involvement of B-cell-produced cytotoxic antibodies directed against patient's HLA class II in the pathogenesis of PTGVHD.

Antibodies↗