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Biomedical subjects

K Tadokoro

Publications and source records attributed to K Tadokoro.

At least 37 records · Page 2Linked to original sources
PubMed2000

TGF-beta 1 reciprocally controls chemotaxis of human peripheral blood monocyte-derived dendritic cells via chemokine receptors.

We examined the effect of TGF-beta 1 on the chemotactic migratory ability of human monocyte-derived dendritic cells (DCs). Treatment of immature DCs with TGF-beta 1 resulted in increased expressions of CCR-1, CCR-3, CCR-5, CCR-6, and CXC chemokine receptor-4 (CXCR-4), which were concomitant with enhanced chemotactic migratory responses to their ligands, RANTES (for CCR-1, CCR-3, and CCR-5), macrophage-inflammatory protein-3 alpha (MIP-3 alpha) (for CCR-6), or stromal cell-derived growth factor-1 alpha (for CXCR-4). Ligation by TNF-alpha resulted in down-modulation of cell surface expressions of CCR-1, CCR-3, CCR-5, CCR-6, and CXCR-4, and the chemotaxis for RANTES, MIP-3 alpha, and stromal cell-derived growth factor-1 alpha, whereas this stimulation up-regulated the expression of CCR-7 and the chemotactic ability for MIP-3beta. Stimulation of mature DCs with TGF-beta 1 also enhanced TNF-alpha-induced down-regulation of the expressions of CCR-1, CCR-3, CCR-5, CCR-6, and CXCR-4, and chemotaxis to their respective ligands, while this stimulation suppressed TNF-alpha-induced expression of CCR-7 and chemotactic migratory ability to MIP-3 beta. Our findings suggest that TGF-beta 1 reversibly regulates chemotaxis of DCs via regulation of chemokine receptor expression.

CCR5 Receptor Antagonists↗
PubMed2000

Simple PCR detection of haptoglobin gene deletion in anhaptoglobinemic patients with antihaptoglobin antibody that causes anaphylactic transfusion reactions.

Two anhaptoglobinemic patients showing anaphylactic transfusion reactions by antihaptoglobin antibody were found. Southern blot analysis indicated that 2 patients were homozygous for the deleted allele of the haptoglobin gene (Hp(del)) as reported previously. We have identified the junction region of the deletion from genomic DNA of 1 patient using cassette-mediated polymerase chain reaction (PCR). Then, the deleted region from the 5' breakpoint to the promoter region of the Hp was amplified from genomic DNA of a control individual using PCR. DNA sequence analysis of these regions indicated that the 5' breakpoint of the Hp(del) allele was located 5. 2 kilobase (kb) upstream of exon 1 of the Hp and the 3' breakpoint was positioned between 52 and 53 base pair (bp) upstream of exon 5 of the haptoglobin-related gene. There was no significant homology between the DNA sequences flanking the 5' and 3' breakpoints, except for a 2-bp (TG) identity. To examine the gene frequency, we have developed a simple PCR method to detect the gene deletion. We found 8, 16, and 17 Hp(del) alleles in 157 Koreans, 523 Japanese, and in 284 Chinese, respectively, but did not find the Hp(del) in 101 Africans or in 100 European-Africans. The incidence of individuals homozygous for the Hp(del) allele was therefore expected to be 1/4000 in Japanese, 1/1500 in Koreans, and 1/1000 in Chinese. This incidence is higher than that of IgA deficiency in Japanese. More attention should be paid on haptoglobin deficiency and antihaptoglobin antibody as the cause of transfusion-related anaphylactic reactions in Asian populations. (Blood. 2000;95:1138-1143)

5' Untranslated Regions↗
PubMed2000

Autocrine activation-induced cell death of T cells by human peripheral blood monocyte-derived CD4+ dendritic cells.

Mature T cells activated by antigen (Ag)-presenting cells are subject to various downmodulatory processes designed to maintain T cell homeostasis. Here we describe experiments in which mature T cells were subjected to apoptosis following stimulation with CD4(+) dendritic cells (DCs) during Ag presentation. The proliferative response of allogeneic T cells was increased by DCs at stimulator to responder (S/R) ratios ranging from 10(-3) to 1, whereas this response was decreased at S/R ratios ranging from 2 to 10. Allogeneic T cells stimulated with DCs at an S/R ratio of 5 underwent apoptosis, whereas this event was not observed in allogeneic T cells stimulated with DCs at an S/R ratio of 0.5. Stimulation of T cells with DCs at an S/R ratio of 5 induced a higher level of expression of CD95 ligand (CD95L) than stimulation of T cells cultured with DCs at an S/R ratio of 0.5, whereas similar levels of expression of CD28 and CD154 were observed in both cells. The abortive proliferation of mature T cells stimulated with DCs was prevented by blocking the CD95-CD95L system. Our results suggest that the CD4(+) DCs play counterregulatory roles in dictating T cell responses during Ag presentation.

Antigen Presentation↗
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

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

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

Guidelines for irradiation of blood and blood components to prevent post-transfusion graft-vs.-host disease in Japan.

The Japanese Red Cross analysed the results of questionnaires sent in 1993 regarding post-transfusion graft-vs.-host disease (PT-GVHD) from hospitals; the majority of patients with PT-GVHD in 1993 were transfused for cardiovascular or cancer surgery, and about 10 patients had died yearly from PT-GVHD in the following few years. The Japan Society of Blood Transfusion (JSBT) organized a subcommittee for the prevention of PT-GVHD, and issued a fourth version of guidelines for the irradiation of blood to prevent PT-GVHD. These guidelines recommended transfusion of irradiated blood for cardiosurgery, cancer surgery, elderly recipients and severe trauma, as well as congenital immunodeficient recipients, newborn infants and other immunocompromised patients. Also recommended was irradiation not only of blood within 72 h after collection but also of blood stored for 14 days. Reported PT-GVHD has diminished to a few cases in recent years.

Blood↗
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

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

Gamma-ray-irradiated red blood cells stored in mannitol-adenine-phosphate medium: rheological evaluation and susceptibility to oxidative stress.

BACKGROUND AND OBJECTIVES: To evaluate the rheological properties and the oxidative susceptibility of gamma-ray-irradiated red blood cells (RBCs). MATERIALS AND METHODS: RBCs in mannitol-adenine-phosphate (MAP) medium were irradiated with 35 Gy and stored at 4 degrees C for 4 weeks. The deformability of the RBCs was examined under shear flow in relation to the morphological and biochemical changes. The RBCs were further exposed to 1 mM FeSO(4) and 5 mM ascorbate to examine the oxidative susceptibility. RESULTS: The RBC deformability was decreased during storage, and the impairment was further enhanced by the irradiation, which promoted cell shrinkage and intracellular hemoglobin condensation accompanying potassium loss. Lipid peroxidation and protein aggregation of the RBC membrane as well as echinocytosis were not enhanced by the irradiation. The exposure to free iron did not stimulate the oxidation of the irradiated RBC membrane. CONCLUSION: The decreased deformability of gamma-ray-irradiated RBCs in MAP medium was mainly induced by dehydration due to potassium loss, and the membrane lipids and proteins were stably preserved against oxidative stress.

Adenine↗
PubMed2000

Synthesis of four stereoisomers of 1,4-thiazane-3-carboxylic acid 1-oxide via the asymmetric transformation (combined isomerization-preferential crystallization) of 1,4-thiazane-3-carboxylic acid.

In order to synthesize four stereoisomers of 1,4-thiazane-3-carboxylic acid 1-oxide (TCA SO), (S)-1,4thiazane-3-carboxylic acid [(S)-TCA], which is one of the precursors, was prepared by the asymmetric transformation (combined isomerization-preferential crystallization) of (RS)-TCA. This asymmetric transformation was used (2R, 3R)-tartaric acid [(R)-TA] as a resolving agent and salicylaldehyde as the epimerization catalyst in propanoic acid at 110 degrees C to afford a salt of (S)-TCA with (R)-TA in 100% de with a yield of over 90%. Optically pure (S)-TCA was obtained by treating the salt with triethylamine in methanol in a yield of over 80%, based on (RS)-TCA as the starting material. In addition, asymmetric transformation of (R)-TCA gave (S)-TCA in a yield of 60-70%. (S)-TCA was oxidized by hydrogen peroxide in dilute hydrochloric acid to selectively crystallize (1S, 3S)-TCA.SO. (1R, 3S)-TCA SO of 70% de from the filtrate was allowed to form a salt with (R)-TA after a treatment with triethylamine to give (1R, 3S)-TCA SO as a single diastereoisomer. (1R, 3R)- and (1S, 3R)-TCA.SO were also prepared by starting from (R)-TCA that had been synthesized from L-cysteine.

Crystallization↗
PubMed2000

Decreased deformability of the X-ray-irradiated red blood cells stored in mannitol-adenine-phosphate medium.

X-ray irradiation of blood is an effective way to prevent transfusion-associated graft-versus-host disease. Red blood cells (RBCs) from normal donors suspended in mannitol-adenine-phosphate (MAP) medium were irradiated with X-ray of 15 and 35 Gy in minimum dose. The change of deformability of the RBCs during storage at 4 degrees C for 4 weeks was examined under shear stress of 13-130 dyn/cm2 using a rheoscope, in relation to the hematological and biochemical properties. (1) The deformability of RBCs was decreased during the storage, and it was further decreased by the irradiation. In addition, the number of undeformable RBCs against a given shear stress increased after the irradiation. (2) The cell volume gradually decreased, while the intracellular hemoglobin concentration increased. These changes were accelerated by the irradiation. The echinocytic transformation during the storage was not accelerated by the irradiation. (3) The content of aggregated proteins reducible with beta-mercaptoethanol in RBC membrane increased during the storage, but was not increased by the irradiation. Membrane lipid peroxidation was not increased during the storage and by the irradiation. (4) Leakage of potassium ions from RBCs during the storage was accelerated by the irradiation. In conclusion, shear-induced deformation of RBCs stored in MAP medium was impaired by X-ray irradiation, mainly due to dehydration caused by excess leakage of potassium ions from RBCs.

Adenine↗
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↗
PubMed1999

Extracellular signal-regulated kinase, stress-activated protein kinase/c-Jun N-terminal kinase, and p38mapk are involved in IL-10-mediated selective repression of TNF-alpha-induced activation and maturation of human peripheral blood monocyte-derived dendritic cells.

TNF-alpha or IL-10 has been implicated to reversibly regulate physiological states of dendritic cells (DCs). However, little is known about dual stimulations of these cytokines on DC properties and the intracellular signaling events that are responsible for the regulation of these states. Here, we show that a family of mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase 2 (ERK2), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38mapk, are potentially involved in IL-10-mediated selective suppression of TNF-alpha-induced changes of the monocyte-derived DC properties. TNF-alpha induced the cluster formation of the cells and the enhancement of cell surface expression levels of CD83, CD86, and HLA-DR, and T cell stimulatory capacity, whereas the capacities for the endocytosis and the chemotactic migration were suppressed in these cells. Treatment of monocyte-derived DCs with IL-10 resulted in the reduction of the cell surface expression levels of CD86, HLA-DR, and T cell stimulatory capacity, whereas both endocytic and chemotactic migratory capacities were increased by IL-10. Dual stimulations of monocyte-derived DCs with TNF-alpha and IL-10 selectively antagonized their respective effects on these DC properties. TNF-alpha induced tyrosine phosphorylation and enzymatic activation of ERK2, SAPK/JNK, and p38mapk, whereas IL-10 did not induce these events. Dual stimulations of TNF-alpha plus IL-10 abolished TNF-alpha-induced changes of these MAPKs in DCs. These results suggest that the blockage in the MAPKs cascades contributes to IL-10-mediated repression of TNF-alpha-induced changes of DC properties.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1999

CC chemokine receptors, CCR-1 and CCR-3, are potentially involved in antigen-presenting cell function of human peripheral blood monocyte-derived dendritic cells.

We examined the potential involvement of two CC chemokine receptors (CCRs), CCR-1 and CCR-3, in the functional activation of granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4)-generated human peripheral blood monocyte-derived immature dendritic cells (DCs). Flow cytometric analysis showed that CCR-1, CCR-3, CCR-5, and CXC chemokine receptor (CXCR)-4 were expressed on the cell surface of monocyte-derived DCs. Treatment with a monoclonal antibody (MoAb) to either CCR-1 or CCR-3 but not MoAbs to CCR-5 and CXCR-4 abolished chemotactic migration of monocyte-derived DCs. The DCs treated with either the anti-CCR-1 MoAb or anti-CCR-3 MoAb were less efficient than untreated DCs in proliferation of allogeneic T cells (TCs) and TC-derived secretion of interferon-gamma (IFN-gamma). The homotypic aggregation of DCs and heterotypic aggregation of DCs with TCs were suppressed by the anti-CCR-1 MoAb or anti-CCR-3 MoAb. These results indicate that CCR-1 and CCR-3 specifically regulate interaction of TCs and DCs in the process of antigen presentation.

Antibodies, Monoclonal↗