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Biomedical subjects

K Tadokoro

Publications and source records attributed to K Tadokoro.

At least 73 records · Page 4Linked to original sources
PubMed1998

Guillain-Barré and Fisher's syndromes subsequent to Campylobacter jejuni enteritis are associated with HLA-B54 and Cw1 independent of anti-ganglioside antibodies.

The frequencies of human leukocyte antigens (HLA)-class I (A, B and Cw) were determined serologically and those of HLA-class II (DRB1 and DQB1) at the genomic level in 35 Japanese patients with Guillain-Barré syndrome (GBS), 58 with Fisher's syndrome (FS), and 112 healthy controls. HLA-B54 and -Cw1 antigens were found in GBS and FS patients from whom Campylobacter jejuni had been isolated more often than found in the healthy controls. No HLA types were related to GBS or FS as a whole, except for the B54 antigen which often was significant in the entire GBS group. This relation, however, may depend on the high population of C. jejuni-isolate patients in our GBS group. There were no relationships between the frequencies of HLA types and the presence of serum IgG antibodies to GM1, GQ1b, GD1a, or GalNAc-GD1a. Our findings suggest that HLA types are associated with the onset of GBS and FS after C. jejuni enteritis and that the HLA types in distinct GBS and FS subgroups of a single etiological origin need to be examined.

Antibodies↗
PubMed1998

Crystallization and preliminary diffraction studies of the extracellular region of human p58 killer cell inhibitory receptor (KIR2).

Molecules of the human killer cell inhibitory receptor (KIR) family, which belong to the immunoglobulin superfamily (IgSF), are expressed on the surface of natural killer (NK) cells and some subsets of T cells. These receptors function to mediate the inhibition or activation of cytotoxic activity by recognizing HLA class I molecules on the target cell. The extracellular region of a p58 KIR specific for HLA-Cw1,3,7 (KIR2) has been overproduced in Escherichia coli and purified. The recombinant KIR2 has been crystallized in 9-10% poly(ethylene glycol) methyl ether (average Mr = 8000), 50mM HEPES, 8% ethylene glycol, 0.5% octyl-beta-glucoside, pH 7.5, at 294 K using the sitting-drop vapour-diffusion method. Preliminary X-ray diffraction studies reveal the space group to be hexagonal (P6122 or P6522) with lattice constants a = b = 95.3, c = 130.8 A. A native data set (3 A resolution) has been collected at the Photon Factory (lambda = 1.0 A).

Crystallization↗
PubMed1998

Dendritic cells stimulate the expansion of bcr-abl specific CD8+ T cells with cytotoxic activity against leukemic cells from patients with chronic myeloid leukemia.

The role of T lymphocytes in the control of chronic myeloid leukemia (CML) after bone marrow transplantations has been clearly shown. This effect closely correlates with graft-versus-host disease (GVHD). A specific graft-versus-leukemia (GVL) effect separate from GVHD has been postulated but has been difficult to show. One possible target for specific GVL activity is the bcr-abl fusion protein characteristic of CML. We have investigated the use of normal peptide-pulsed dendritic cells for the generation of cytotoxic, bcr-abl-specific T cells from normal donors. T cells (CD3+, CD8+, TCR alpha beta+, and NK receptor-negative) generated from a normal donor (HLA A24, B52, B59, Cw1) after stimulation with autologous dendritic cells, primed with a 16 mer peptide spanning the b3a2 breakpoint of bcr-abl, lysed CML cells from the peripheral blood of seven patients with CML with the b3a2 breakpoint. CML cells from four patients with only the b2a2 breakpoint were not lysed. Phytohemagglutinin (PHA) blasts derived from peripheral blood of patients with CML were not lysed, suggesting that cytotoxicity was not due to alloreactivity. Blocking experiments with anti-HLA-A,B,C indicated that cytotoxicity was dependent on recognition of major histocompatibility complex (MHC) class I molecules, although cytotoxicity was not MHC-restricted because not all patients shared HLA types with the T-cell donor. Specificity for bcr-abl and absence of alloreactivity was confirmed by the presence of lytic activity against autologous and allogeneic class I HLA-A matched monocytes pulsed with the 16 mer bcr-abl fusion peptide, but not against unpulsed monocytes or monocytes pulsed with other peptides. These results show that bcr-abl-specific T cells with marked cytotoxic activity against CML cells can be generated and amplified from normal donor peripheral blood. Recognition of HLA molecules is essential for cytotoxicity but strict HLA identity is not required.

Antigens↗
PubMed1998

Molecular cloning and characterization of decay-accelerating factor deficiency in Cromer blood group Inab phenotype.

An additional decay-accelerating factor (DAF) mutation, designated as Inab phenotype in the Cromer blood group system, was recently identified in a 28-year-old Japanese woman (H.A.). The red blood cells of H.A., like those of other Inab phenotype individuals, were negative for Cromer system antigens, Cra, Tca, Dra, UMC, and IFC. The deficiency of DAF on the red blood cells of H.A. has been shown by immunoblotting with a murine monoclonal antibody to DAF. Molecular analysis has shown that H.A. is homozygous for a single nucleotide substitution, C1579-->A, at the position 24 bp upstream of the 3'-end of exon 2 of the DAF gene. This substitution causes the activation of a novel cryptic splice site and results in the production of mRNA with a 26 bp deletion. The deletion introduces a reading frame shift and creates a stop codon immediately downstream of the deletion. Translation of mRNA would be terminated at the first amino acid residue of the second short consensus repeat (SCR2) domain (exon 3) of DAF. The functional domains of DAF's complement regulatory activity and the carboxy-terminal signal domains for glycosylphosphatidylinositol (GPI) anchoring are predicted to be lacking in H.A. Thus, there would be no DAF present on the cell surface.

Adult↗
PubMed1998

A nested PCR-RFLP method for high-resolution typing of HLA-A alleles.

We developed a nested polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method for high-resolution typing of HLA-A alleles. HLA-A alleles can be identified by this method without the need for other information such as serological type. The first PCR was performed using outer primers, ASP5 and ASP3, specific for the HLA-A gene, and a 991-bp DNA fragment extending from exon 1 through exon 3 was amplified. In the second PCRs, exon 2 and exon 3 of the HLA-A gene were amplified separately from the diluted first PCR product using nested primers. Computer analysis of cleavage patterns for 78 HLA-A alleles showed that 31 RFLP patterns could be obtained by digestion of the exon 2 PCR product using eight restriction endonucleases and 42 RFLP patterns by digestion of the exon 3 PCR product using 11 restriction endonucleases, and all alleles could be discriminated based on combinations of these RFLP patterns except for nine allele groups or pairs: A*0201/0207/0215N/0220/0222, A*0205/0208/0214, A*0206/0221, A*0212/0213, A*2402/2405, A*2406/2413, A*2601/2605, A*2603/2606 and A*7401/7402. Thus, 65 PCR-RFLP patterns were predicted from the results of analysis of digestion patterns of 78 HLA-A alleles. Among 2145 possible homozygous and heterozygous combinations of the 65 distinguishable PCR-RFLP patterns, 82 combinations were predicted to have the same PCR-RFLP patterns. In PCR-RFLP analysis, although the nested primers were not specific for the HLA-A gene, clear RFLP banding patterns were obtained because specificity was guaranteed by the use of the outer primers, ASPS and ASP3 in the first PCR. A*0201 and A*0207 occur relatively frequently in the Asian populations among indistinguishable allele groups or pairs using the present PCR-RFLP method. We also developed a PCR sequence-specific primers (PCR-SSP) method for distinguishing between A*0201/0220/0222 and A*0207/0215N. We could identify 39 alleles (groups) upon HLA-A typing of 50 Japanese individuals, 40 cell lines of the Fourth Asia-Oceania Histocompatibility Workshop, and 80 cell lines of the UCLA International Cell Exchange Program using the present PCR-RFLP and PCR-SSP methods.

Alleles↗
PubMed1998

Immunosuppressive effects of chloroquine: potential effectiveness for treatment of post-transfusion graft-versus-host disease.

Post-transfusion graft-versus-host disease (PT-GVHD) is a fatal adverse effect of blood transfusion. In spite of its severity, there is no effective treatment at present for PT-GVHD. Previously, we reported that chloroquine (CH) inhibited the cytotoxicity of cytotoxic T-cell (CTL) clones and tumour necrosis factor beta (TNF beta) production by TNF beta-producing clones in vitro, both the clones being derived from peripheral blood lymphocytes (PBMCs) of PT-GVHD patients. To explore the possibility of utilizing CH for the treatment of PT-GVHD, we extended our investigation of the immunosuppressive effects of CH in vitro to PBMCs derived from healthy donors. Our results show that CH inhibits the mixed lymphocyte reaction (MLR) between allogeneic PBMCs, production of inflammatory cytokines such as TNF alpha, interleukin-1 beta (IL-1 beta) and interferon gamma (IFN gamma) in mixed lymphocyte culture and natural killer cell activity, and, further, reduces the number of alloreactive CTL precursors.

Chloroquine↗
PubMed1998

Release of granule proteins from human eosinophils stimulated with mast-cell mediators.

BACKGROUND: It has been suggested that mast cells and eosinophils are major effector cells in the pathogenesis of allergic diseases. However, the interaction of these cells has not been thoroughly elucidated. We examined eosinophil cationic protein (ECP) release and cytosolic free calcium concentration ([Ca2+]i) in human eosinophils induced by the major mast-cell mediators including cytokines. METHODS: Eosinophils from healthy donors were stimulated with the major mast-cell mediators for 20 min after preincubation with cytochalasin B for 10 min. ECP in supernatants was measured by radioimmunoassay. Moreover, to examine changes of [Ca2+]i in eosinophils, Fura-2-loaded eosinophils were monitored for fluorescence changes after stimulus addition. RESULTS: Of the tested mediators (prostaglandin [PG]D2, leukotriene (LT)B4, platelet-activating factor (PAF), histamine, LTC4, and eosinophil chemotactic factor of anaphylaxis [ECF-A]), LTB4 and PAF induced ECP release from eosinophils. Any cytokines produced by human mast cells, i.e., interleukin (IL)-4, IL-5, IL-8, tumor necrosis factor (TNF), or granulocyte-macrophage colony-stimulating factor (GM-CSF), did not induce ECP release in our system. ECP release triggered with LTB4 and PAF occurred at concentrations of 10(-8)-10(-6) M concentration-dependently. LTB4 and PAF also elicited a rise in [Ca2+]i in eosinophils. Neither PGD2, histamine, nor LTC4 induced ECP release, although they increased cytosolic calcium in eosinophils. CONCLUSIONS: Of mast-cell mediators, LTB4 and PAF induced eosinophil degranulation. The contribution of LTB4 and PAF from mast cells to eosinophil degranulation may be important in the pathogenesis of allergic inflammatory diseases.

Blood Proteins↗
PubMed1998

Detection of IgE antibody to a radiocontrast medium.

BACKGROUND: Very little is known about the mechanisms underlying adverse reactions to radiocontrast medium. On the basis of the clinical features of the adverse reactions, it has generally been considered that an IgE-dependent mechanism is not involved in these adverse reactions, and only a few studies have demonstrated the presence of IgE antibody to radiocontrast medium in patient sera. METHODS: We assayed for IgE antibody to ioxaglic acid (Hexabrix), a representative radiocontrast medium, in the sera of patients who had developed adverse reactions to ioxaglic acid. A conjugate was prepared by coupling succinyl ioxaglic acid to human serum albumin. Enzyme immunoassay and radioimmunoassay for the detection of IgE antibody to ioxaglic acid in patient sera were constructed by physical adsorption or by covalent coupling of the conjugate on solid supports. RESULTS: When the radioactivity or the absorbance exceeding the mean plus 3 SD for normal healthy subjects was regarded as positive, IgE antibody was detected in the sera of 47.1% of the patients who had a past history of adverse reactions to ioxaglic acid and 16.2% of those who had experienced adverse reactions to ioxaglic acid within 24 h before the blood collection, although the IgE antibody levels were low. On the other hand, IgE antibody to ioxaglic acid was not detected in the sera of patients with no history of adverse reactions to ioxaglic acid. Inhibition experiments revealed the presence of IgE antibody specific to ioxaglic acid in the serum defined as positive for IgE antibody to ioxaglic acid. The presence of IgE antibody to ioxaglic acid did not always correlate with the activation of mast cells due to the occurrence of adverse reactions to ioxaglic acid. CONCLUSIONS: A small amount of IgE antibody to ioxaglic acid was detected in the sera of some patients with a history of adverse reactions to ioxaglic acid, and these adverse reactions may be partly explained by the presence of IgE antibody in the serum of at least some patients.

Antibodies↗
PubMed1998

Diversity of HLA-B61 alleles and haplotypes in East Asians and Spanish Gypsies.

The distribution of HLA-B61 alleles and their association with HLA-C and DRB1 alleles were investigated in six East Asian populations (South Korean, Chinese Korean, Man (Manchu), Northern Han, Mongolian and Buryat) and Spanish Gypsies and compared to our previous report on the Japanese population. The alleles were identified using a group-specific polymerase chain reaction (PCR) and genomic DNA followed by hybridization with sequence-specific oligonucleotide probes (SSOP). Both HLA-B*4002 and B*4006 were commonly detected in the South Korean, Chinese Korean, Man, Northern Han and Japanese populations, while HLA-B*4002 was predominant in the Mongolian and Buryat populations. Strong associations of B*4002 with Cw*0304 and of B*4006 with Cw*0801 were commonly observed in these East Asian populations. In contrast, in Spanish Gypsies, only HLA-B*4006 was found and the allele exhibited a strong association with Cw*1502. HLA-B*4003 was also identified in the South Korean, Chinese Korean, Northern Han, Mongolian and Japanese populations at relatively low frequencies, and exhibited an association with Cw*0304. Moreover, the association of these B61 alleles with the DRB1 alleles revealed considerable diversity among the different populations. HLA-B*4004 and B*4009 were not observed in these populations. Consequently, the frequencies of the B61 alleles varied among the different East Asian populations, but the individual B61 alleles were carried by specific haplotypes often regardless of the ethnic differences.

Alleles↗
PubMed1998

Polymorphism of TAPASIN and its linkage disequilibria with HLA class II genes in the Japanese population.

Tapasin plays an important role in HLA class I assembly. The gene has been mapped on the human MHC region. We identified two alleles of TAPASIN in the Japanese population and analyzed the association of the alleles with HLA-DPB1, -DQB1 and -DRB1 alleles. The allele frequencies of TAPASIN*01 and *02 were estimated to be 0.37 and 0.63, respectively, in the Japanese population. TAPASIN showed strong linkage disequilibrium with the HLA-DPB1 locus. Several frequent four-locus haplotypes were identified, including DRB1*0901-DQB1*0303-DPB1*0501-TAPASIN*02, DRB1*0901-DQB1*0303-DPB1*0201-TAPASIN*02 and DRB1*1302-DQB1*0604-DPB1*0401-TAPASIN*02.

Antiporters↗
PubMed1998

Human lymphocytes obtained from decidual tissue express killer activatory receptors as well as killer inhibitory receptors: analysis using a single strand conformation polymorphism method.

PROBLEM: The objective was to clarify whether lymphocytes in decidual tissue express only killer inhibitory receptors (KIRs) or both KIRs and killer activatory receptors (KARs). METHOD OF STUDY: A polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis method, using cDNA as a template, was applied to detect as many natural killer receptors (NKRs) expressed on natural killer (NK) cells as possible and to distinguish between KIRs and KARs. Using this method, we analyzed NKRs on lymphocytes in decidual tissue and maternal peripheral blood mononuclear cells (PBMCs) (n = 10) from the same individuals. RESULTS: More than 20 SSCP bands were detected for NKRs on both the lymphocytes in decidual tissue and the maternal PBMCs. The SSCP band patterns were different for each individual. KARs mRNA was detected in lymphocytes in decidual tissue according to the SSCP analysis results. CONCLUSION: Lymphocytes in decidual tissue express not only KIRs but also KARs; this finding suggests their roles in placentation and the maintenance of pregnancy.

Abortion, Induced↗
PubMed1998

Differential effect of azidothymidine on resting and activated cells: potentiality of this drug for treatment of post-transfusion graft-versus-host disease.

The key factor for the treatment of post-transfusion graft-versus-host disease (PT-GVHD) is the successful eradication of donor-derived cytotoxic T cells (CTLs) which are thought to be a main cause of the disease, with no effects on either peripheral blood mononuclear cells (PBMCs) or tissues of the recipient. In this study, we examined the effect of azidothymidine (AZT: Zidovudine) on resting PBMCs and cultured fibroblast cells which are assumed to be patient cells, and alloreactive CD8(+)-CTL clones which are imagined to be donor-derived activated CTLs, in vitro. We show here that AZT has no effect on resting PBMCs and cultured fibroblast cells, but greatly inhibited the growth of CTL clones.

Anti-HIV Agents↗
PubMed1998

[Standardization of hemopoietic colony assay reagents].

Several Japanese Red Cross blood centers have begun cooperating with hospitals in peripheral blood stem cell transplantation research. However, most have not yet standardized their techniques or reagents for that purpose yet. Consequently, wide variations are often observed in data from different blood centers, especially for hemopoietic colony assays. We compared our colony assay reagent set with those in three commercial colony assay kits. The best results were obtained with the kit from a manufacturer referred to here as company A. Although our reagent set obtained lower colony values, the CFU-GM, BFU-E, and total colony values correlated well with those obtained using company A's kit (r = 0.74, 0.80, and 0.97, respectively). Company A's kit gave reproducible results even with the use of different lots, and includes reagents that can be stored for up to two years at -20 degrees C. These features highlighted its advantages as a standard reagent set.

Colony-Forming Units Assay↗
PubMed1998

[A case report of selective IgA deficiency in rheumatoid arthritis and anti-IgA antibody induced anaphylactic transfusion].

We described a case of rheumatoid arthritis (RA) with selective IgA deficiency. A 69 year-old female with RA was admitted because of gall bladder cancer, and also had selective IgA deficiency which serum IgA level was less than 5.0 mg/dl, and IgA 1 and IgA 2 subclasses were not detected. Prior to the operation, she was given red cell compatible blood transfusion because of severe anemia. After 30 min of transfusion, she developed chill, nausea, vomiting and hypotension. These anaphylactic reactions might be induced by the presence of anti-IgA antibody, since the level of this antibody titers in her serum was elevated, assessed by the methods of ELISA and Western blotting. Although a case of RA associated with selective IgA deficiency, and also with elevated serum anti-IgA antibody level is extremely uncommon, attention should be paid to the presence of anti-IgA antibody in patients with selective IgA deficiency to avoid any unexpected anaphylactic reactions.

Aged↗
PubMed1997

Bradykinin generation in RC-MAP during storage at 4 degrees C and leukocyte removal filtration.

We investigated contact system activation in red cell concentrate in mannitol-adenine-phosphate (MAP) solution (RC-MAP) during storage and leukocyte removal filtration. The contact system activation was assessed in terms of bradykinin (BK) generation. The BK level in the RC-MAP transiently but significantly (p < 0.05) increased at 7 to 14 days of storage. Moreover, the BK level in 21-day-stored RC-MAP was approximately 10 times higher than that in other blood components. The BK level in mannitol-containing MAP solutions, but not that in mannitol-free MAP solution, saline or whole blood, increased during storage. The plasma angiotensin-converting enzyme (ACE) activity decreased significantly only in mannitol-containing MAP solutions. These findings suggest that mannitol plays an essential role in the increase in BK level in RC-MAP. Furthermore, the BK level in RC-MAP increased 10 minutes after the start of filtration through a negatively charged filter, either a BPF-4 or an RN-40, and reached a maximum of 6,000 pg/ml. Hypotensive reactions are rare in RC-MAP transfusion in comparison to their incidence in platelet concentrate (PC) transfusion in spite of the higher BK level in RC-MAP than in PC. Therefore, BK generation in various blood components is not likely to be the main cause of hypotensive reactions. However, the level of BK in RC-MAP is sufficiently high to cause site pain. Further investigation on the clinical significance of a high BK level in blood components is necessary.

Adenine↗