Search PubMed⌕ Search

Biomedical subjects

S Kuwata

Publications and source records attributed to S Kuwata.

125 records · Page 7Linked to original sources

T3 surface molecules on adult T cell leukemia cells are modulated in vivo.

Cells from eight patients with adult T cell leukemia (ATL) and from four patients with non-ATL were examined to see if the T3 antigen of these cells could be modulated in vitro. We found a low density of T3 antigen and the presence of Tac antigen on cells from all patients with ATL. The density of T3 antigen on non-ATL cells was normal, and Tac antigen was not detected. Modulation of T3 antigen and an increase in Tac antigen-positive cells occurred when cells from patients with T4 non-ATL were cultured with OKT3 monoclonal antibody (mAb). Those changes in T3 antigen density and the appearance of Tac antigen-bearing cells by OKT3 mAb were not so marked when ATL cells were used. But the modulation of T3 antigen and the increase in Tac antigen-bearing cells by OKT3 mAb were closely related in cells from six ATL patients. These findings suggest that T3 T cell antigen receptor complexes on ATL cells are not functionally "frozen" by leukemic changes and might be modulated in vivo. In addition, modulation of T3 surface antigen on ATL cells was not induced by cultivation with human T cell leukemia virus type I particles and envelope proteins obtained by gene technology.

Acute Disease↗

Immunoregulatory role in gamma interferon production by a T cell growth factor-dependent experimental malignant glioma-specific cytotoxic T lymphocyte clone.

The authors have established a murine malignant glioma-specific cytotoxic T lymphocyte clone (G-CTLL 1) by T cell growth factor (TCGF) using 203-glioma (a methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin). The cloned cells were found to release a large amount of gamma interferon (IFN) in response to glioma-associated antigen-specific stimulation. The authors have investigated whether the IFN produced can contribute to killing the target cells. Adding anti-mouse gamma IFN antibody to the mixed clone-target cell culture inhibited IFN production by the cloned cells but the toxicity of the cells was minimally diminished. Therefore, it is suggested that the endogenous gamma IFN produced by the TCGF-dependent cloned cytotoxic T lymphocyte line does not have direct cytotoxic action on the target cells. Furthermore, IFN production as well as cytotoxicity was blocked by anti-Lyt-2 monoclonal antibody in the absence of complement. This suggests that IFN plays a role in the process of antigen recognition of target cells because the Lyt-2 molecule is involved in an antigen-specific function on the cytotoxic T lymphocyte receptor. The role of TCGF in gamma IFN production was also investigated. The spontaneous production of gamma IFN by the cloned cells paralleled the amounts of exogenous TCGF added to the cultures, but TCGF had no synergistic effect on IFN production in the presence of mitogen or tumor antigen. Accordingly, it is possible that TCGF stimulates the cloned cells to proliferate, causing IFN release.

Animals↗

Establishment of experimental malignant glioma-specific cytotoxic T lymphocyte clone by T cell growth factor.

In an attempt to facilitate the long-term proliferative growth and subsequent cloning of cytotoxic T lymphocytes (CTL's) against syngeneic murine 203-glioma (20-methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin), sensitized T lymphocytes from tumor-bearing mice were cultured in the presence of T cell growth factor (TCGF). Of five clones established by a limiting dilution technique, two clones (G-CTLL 1 and 2) exhibited tumor-specific cytotoxicity. G-CTLL 1 cells, which possessed much higher cytotoxic activity than G-CTLL 2 cells, were further analyzed. G-CTLL 1 cells were maintained in a TCGF-dependent exponential proliferative culture for over 18 months and continued to mediate an extremely high cytotoxic activity with the target specificity (50- to 100-fold increases over the peak cytotoxic activity of sensitized T lymphocytes in tumor-bearing mice). Their phenotypes of surface antigens were Thy-1+ (weak positive), Lyt-1.-2.+3+, and asialo-GM1-, and their cytotoxicity was blocked by adding only anti-Lyt-2 monoclonal antibodies. These results indicated that the cloned cells originated from CTL's. The cloned cells were characterized by the production of immune interferon with the glioma antigen-stimulation, suggesting that the immune interferon could enhance the cytotoxic activity of the CTL clone at the site of a clone-target cell recognition event.

Animals↗

Fluctuation of antigen binding activity during the cell cycle in the synchronized population of the murine T hybridoma cell line.

The murine T cell hybridoma line which specifically binds antigen (ovalbumin) was established using a cell fusion technique with Sendai virus. Regional lymph node cells from ovalbumin (OVA) immunized C57BL/6 mice were fused with thymidine kinase deficient variant cells of the EL-4 cell line (originating from a thymoma of a C57BL/6 mouse). Approximately one hundred cell lines were established and the antigen binding activity was determined by rosette formation with OVA coated sheep red blood cells (SRBC). One hybridoma cell line, MMH-77, could form rosettes and this formation was specifically inhibited by the addition of free OVA. The ability of the cell line to form rosettes varied from one stage of the cell cycle to the other with the maximum ability in the S phase.

Animals↗

Effect of immunoglobulin G on membrane-bound enzyme activity of sarcoma 180 cells.

Changes in the activity of membrane bound ATPase of Sarcoma 180 cells caused by immunoglobulin G (IgG) of anti-Sarcoma 180 was investigated in relation to the incorporation of amino acid by the cells. Enzymatic activity of ATPase was increased up to 160% of the original activity upon incubation of the cell with IgG. Kinetic studies showed that IgG did not change the affinity of this enzyme for the substrate, but exerted influence upon catalytic efficiency of the enzyme. The rate of incorporation of leucine into Sarcoma 180 cells was also affected by IgG, as observed in the effect of IgG on the enzymatic reaction of the cells.

Animals↗

Plasma level and transfer capacity of thiamin in patients undergoing long-term hemodialysis.

Water-soluble vitamins have a molecular size small enough to pass through the membrane of an artificial kidney. This fact has led to the suggestion that these vitamins be substituted in patients undergoing long-term hemodialysis. In sharp contrast to this general belief, our study has shown that the plasma thiamin levels in patients on long-term hemodialysis were not different from those found in normal subjects. It also remained unchanged before and after the dialysis, althoug thiamin was obviously removed in in vitro dialysis. Accordingly, dietary thiamin appears to be sufficient, making further supplementation unnecessary.

Erythrocytes↗

Ethnic differences in allele frequencies of two microsatellite markers closely linked to the locus for polycystic kidney disease 1 (PKD1).

Two microsatellite markers, D16S283 and D16S284, closely linked to the locus of autosomal polycystic kidney disease (PKD1), were amplified in a Japanese population sample by the polymerase chain reaction to investigate differences in allele frequencies between Japanese and Caucasian populations. Ten D16S283 alleles and four D16S284 alleles were discerned among 53 Japanese. The observed heterozygosities of D16S283 and D16S284 in this study were 76.8 and 9.1%, and the polymorphism-informative contents were 0.75 and 0.09, respectively. Several allele frequencies of D16S283 exhibited significant differences. The Y9 allele (19 CA repeats, 91 bp) was the most frequent in both populations but its frequency in Caucasians was higher. The second most frequent allele was different: Y6 (22 CA repeats, 97 bp) in Japanese and Y10 (18 CA repeats, 89 bp) in Caucasians. Y8 (20 CA repeats, 93 bp) and Y11 (17 CA repeats, 87 bp) alleles also showed different frequencies. For D16S284, no differences in allele frequencies were observed between the two populations. As we observed differences in allele frequencies for D16S283, an association study with this polymorphism should carefully control for the ethnic origin of subjects.

Alleles↗

The genetic contribution of the TNFa11 microsatellite allele and the TNFb + 252*2 allele in Japanese RA.

OBJECTIVES: The contribution of the microsatellite polymorphisms of TNFa and TNFb, and the TNFB + 252 (TNFB) dimorphism to the pathogenesis of rheumatoid arthritis (RA) was studied among Japanese patients. METHODS: The TNFa and TNFb microsatellite polymorphisms, and the TNFB dimorphism were determined in Japanese RA patients and normal subjects using electrophoresis followed by specific PCR amplification. HLA-DRB1*04 typing was carried out by the PCR-SSCP method. RESULTS: The allele frequency of TNFa11 showed a significant increase in RA with DRB1*0405 when compared to that in RA without DRB1*0405 (28.5% Vs 12.9%, respectively, p = 0.022). An association analysis indicated that TNFa11 was not primary, but secondary to the increase in HLA-DRB1*0405, because TNFa11 showed a strong positive association with HLA-DRB1*0405 in Japanese controls. The slight increase in the TNFb4 allele observed in RA with DRB1*0405 (50.0%) may be reflective of the increase in TNFa11 and DRB1*0405. In RA with DRB1*0405, the allele frequency of TNFB*2 significantly increased compared to that of normal controls (75.0% Vs 55.3%, respectively, p = 0.007) and compared to that of RA without DRB1*0405 (45.0%, p = 0.001). No significant positive association of TNFB*2 with HLA-DRB1*0405 or TNFa11 in Japanese controls might suggest that the increase in the TNFB*2 allele might not be secondary to the increase in DRB1*0405, and that TNFB*2 might contribute additively to DRB1*0405-positive RA in Japanese. CONCLUSION: TNFB*2 may contribute additively to Japanese RA with HLA-DRB1*0405, while TNFa11 and TNFb4 are not independent genetic markers of RA among Japanese.

Alleles↗

Association of TAP1 and TAP2 with systemic sclerosis in Japanese.

OBJECTIVE: The contribution of polymorphism of transporter associated with antigen processing 1 and 2 (TAP1 and 2) alleles to the pathogenesis of Japanese SSc was studied. METHODS: TAP1 and TAP2 typing was carried out in 55 Japanese SSc patients and 95 normal Japanese subjects by the PCR-RFLP (restriction fragment length polymorphism) method. HLA-DR typing and HLA DRB1*15, *16 and *08 genotyping were carried out by the PCR and the PCR-SSCP (single-stranded DNA conformation polymorphism) methods, respectively. RESULTS: The frequencies of the TAP1A and TAP2A alleles were significantly increased in SSc with diffuse scleroderma (100%, p < 0.005; 80.0%, p < 0.001, respectively) and in SSc with antitopoisomerase 1 antibody (a-Scl-70), (93.2%, p = not significant (NS); 63.6%, p < 0.05). In contrast, the TAP1B allele was significantly decreased in diffuse scleroderma (0%, p < 0.005) and SSc with a-Scl-70 (4.5%, p < 0.05), and TAP2B was decreased in diffuse scleroderma (12.5%, p < 0.01). CONCLUSION: Association analysis among TAP1A, TAP2A and DRB1*1502 indicated that increases in TAP1A and TAP2A were not primary, but were reflective of an increase in HLA DRB1*1502 in Japanese SSc patients with diffuse scleroderma and SSc with a-Scl-70.

ATP-Binding Cassette Transporters↗

Association of DMA and DMB with RA in Japanese.

OBJECTIVE: The contribution of polymorphism of DMA and DMB alleles to the pathogenesis of Japanese RA was studied. The association of DM alleles with HLA-DRB1*0405 and *0802, which were positively and negatively susceptible to Japanese RA, respectively, is also discussed. METHODS: DMA and DMB typing was carried out in 91 Japanese RA patients and in 77 normal subjects by the PCR-RFLP (restriction fragment length polymorphism) method. HLA-DRB1*04 and *08 genotyping were carried out by the PCR-SSCP (single-stranded DNA conformation polymorphism) method. RESULTS: Allele frequencies of DMB*0101 and DMB*0102 were slightly higher (52.2% and 27.0%) and the allele frequency of DMB*0103 was slightly lower (25.8%) in RA, but these differences were not significant. The increase of DMB*0102 was due to a negative association with HLA-DRB1*0802 [p < 0.05, pc = not significant (NS)]. The decrease of DMB*0103 was due to a positive association with DRB1*0802 (p < 0.005, pc < 0.05). The increase of DMB*0101 was possibly due to a weak association with HLA-DRB1*0405, (p = NS). Positivity of rheumatoid factor did not affect the prevalence of DMA and DMB alleles. CONCLUSION: Association analysis among DMA, DMB and DRB1 (*0405 and *0802) indicate that slight increases or decreases in DMB*0101, DMB*0102 and DMB*0103 are not primary indicators but reflect an increase in HLA-DRB1* 0405 and a decrease in HLA-DRB1*0802 in Japanese RA.

Adult↗