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T Sumida

Publications and source records attributed to T Sumida.

At least 37 records · Page 2Linked to original sources
PubMed2001

Identification of Th2-type suppressor T cells among in vivo expanded ocular T cells in mice with experimental autoimmune uveoretinitis.

Experimental autoimmune uveoretinitis (EAU), which is a T cell mediated organ specific autoimmune disease, is induced by immunization with interphotoreceptor retinoid binding protein (IRBP) in susceptible strains of mice. It has been found that IRBP-derived peptide 518-529 (p518-529) generates Th2-type responses and inhibits IRBP-induced EAU, indicating that the p518-529 might be an epitope for suppressor T cells in IRBP-induced EAU. First, we observed that there were T cells producing the Th2 type cytokines such as IL-4 and IL-10 in late phase of EAU. Furthermore, to examine whether p518-529-reactive T cells expand in the eye during EAU, T cell receptor (TCR) of ocular T cells was compared with that of p518-529 reactive T cells in spleen from mice with EAU by PCR-single strand conformation polymorphism (PCR-SSCP) and nucleotide sequence analysis. SSCP and sequence analyses indicated that p518-529 reactive TCR BV10+ T cells bearing amino acid motif(PWG) and TCR BV13+ T cells bearing amino acid motif(PGLGGY) in their complementary-determining region 3 (CDR3) region were clonally expanding in ocular tissues on day 28 after immunization, although these T cells were not detected on day 14. These findings demonstrate that p518-529 reactive Th2-type T cells expand oligoclonally in the uveitic eyes in the late stage of EAU and may function as Th2-type suppressor T cells for improvement of the disease.

Amino Acid Motifs↗
PubMed2001

Selective reduction and recovery of invariant Valpha24JalphaQ T cell receptor T cells in correlation with disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: To study the regulatory role of CD4-CD8- double-negative (DN) invariant T cell receptor (TCR) Valpha24JalphaQ T cells, a human counterpart of murine NK 1 + T cells, in the autoimmune process of systemic lupus erythematosus (SLE). METHODS: We carried out a 2 step frequency analysis of DN Valpha24JalphaQ T cells in patients with SLE before and after prednisolone therapy; the frequency of DN Valpha24+ T cells was determined by 3 color FACS analysis and subsequently the frequency of Valpha24JalphaQ rearrangement among DN Valpha24+ T cells was determined by sequencing. RESULTS: DN Valpha24+ T cells were significantly increased in patients with active SLE compared to healthy subjects. In healthy subjects, invariant Valpha24JalphaQ TCR dominated in DN Valpha24+ T cells at a high frequency (93-100%). However, the invariant Valpha24JalphaQ TCR was not detected in DN Valpha24+ T cells from patients with active SLE, and instead 2 to 9 Jalpha genes other than the invariant JalphaQ were oligoclonally expanded in the patients. In inactive SLE induced by prednisolone therapy, the invariant Valpha24JalphaQ TCR could be detected in DN Valpha24+ T cells from all the patients and dominated in most of the patients. Further, oligoclonally expanded Valpha24+ clones other than the invariant JalphaQ gene in active disease states were significantly decreased by prednisolone therapy. CONCLUSION: The selective reduction of DN invariant Valpha24JalphaQ T cells is related to the disease progression of SLE, while DN TCR Valpha24 T cells other than Valpha24JalphaQ T cells constitute autoaggressive T cells in SLE.

Adult↗
PubMed2001

Interferon-gamma enhances interleukin 12 production in rheumatoid synovial cells via CD40-CD154 dependent and independent pathways.

OBJECTIVE: To determine the role of interferon-gamma (IFN-gamma) in CD40-CD154 dependent production of interleukin 12 (IL-12) by synovial cells of patients with rheumatoid arthritis (RA). METHODS: We examined the effects of IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony stimulating factor (GM-CSF) on CD40 expression on CD68+ synovial macrophage-lineage cells (SMC). The effects of IFN-gamma and soluble CD154 (sCD154) on IL-12 production by RA synovial cells were determined by ELISA. RESULTS: CD68+ SMC expressed substantial levels of CD40. IFN-gamma, but not TNF-alpha or GM-CSF, markedly upregulated CD40 expression on CD68+ SMC. IFN-gamma also dose dependently increased IL-12 production by synovial cells. The effects of IFN-gamma on CD40 expression (EC50 = 127.4 U/ml) were observed at a concentration 19 times lower than the effects on IL-12 production (EC50 = 6.8 U/ml). Treatment with IFN-gamma at a concentration low enough to augment CD40 expression but not IL-12 production enhanced spontaneous IL-12 production synergy with sCD 154. The synergistic enhancement of spontaneous IL-12 production was abrogated by CD40-Fc. In contrast, IL-12 production induced by high concentration of IFN-gamma was not neutralized by CD40-Fc. CONCLUSION: IFN-gamma enhanced IL-12 production via both CD40-CD154 dependent and independent pathways in RA synovium. IFN-gamma may play a crucial role in the development of RA synovitis through regulation of IL-12 production.

Antigens, CD↗
PubMed2000

Gene expression of GLUT isoforms and VHL in oral squamous cell carcinoma.

In human oral squamous cell carcinoma (OSCC) cell lines, we detected atypical mRNA expression of GLUT2 and/or GLUT4 in addition to enhanced expression of GLUT1 mRNA using RT-PCR. In semi-quantitative reverse transcription-polymerase chain reaction analysis of mRNA expression in OSCC cell lines, we found an inverse relationship between mRNA expression of von Hippel-Lindau (VHL) and that of GLUT1, with no apparent influence on the expression of other GLUTs. These findings suggest that the reduction of VHL may play a critical role in glucose uptake of OSCC cell lines, with enhancement of GLUT1 expression.

Carcinoma, Squamous Cell↗
PubMed2000

Keratin mRNA for detecting micrometastasis in cervical lymph nodes of oral cancer.

We studied three keratin (K) gene candidates, K13, K19, and K20 mRNAs, for detecting micrometastases in cervical lymph nodes (LNs) by reverse transcriptase-polymerase chain reaction (RT-PCR). Of 166 histologically metastasis-negative nodes, 24 micrometastatic LNs (14. 4%) were detected based on K13 gene expression. Keratin 19 mRNA is an inadequate marker for the genetic diagnosis due to not only illegitimate gene expression from lymphatic tissue but also gene expression from the ectopic salivary gland. Keratin 20 mRNA showed low sensitivity. It is suggested that K13 mRNA may be a promising tumor marker among these keratin genes for detecting the micrometastases in cervical LNs of oral cancer.

Gene Expression Regulation, Neoplastic↗
PubMed2000

Suppression of azoxymethane-induced colon carcinogenesis in male F344 rats by mandarin juices rich in beta-cryptoxanthin and hesperidin.

We have reported protective effects of dietary administration of a powder "CHRP" containing high amounts of beta-cryptoxanthin and hesperidin prepared from a Satsuma mandarin (Citrus unshiu Marc.) juice on azoxymethane (AOM)-induced rat aberrant crypt foci through suppression of crypt cell proliferation and/or induction of detoxifying enzymes. In the present study, we investigated the modifying effects of a commercial Satsuma mandarin (Citrus unshiu Marc.) juice (MJ) and those of MJ2 and MJ5, which were prepared from MJ and are richer in beta-cryptoxanthin and hesperidin than MJ, on the occurrence of colonic tumors induced by AOM in male F344 rats. Rats were given 2 weekly s.c. injections of AOM (20 mg/kg body weight) to induce colonic neoplasms. They also received MJ, MJ2, or MJ5 as a drinking water at night for 36 weeks, starting 1 week after the last dosing of AOM. AOM exposure produced colonic adenocarcinoma with an incidence of 69% and a multiplicity of 0.76 +/- 0.57/rat at week 38. MJ, MJ2, and MJ5 administration significantly reduced the frequency of colonic carcinoma [MJ: 35% (49% reduction), p < 0.02; MJ2: 20% (64% reduction), p = 0.0028; and MJ5: 15% (78% reduction), p < 0.00021] and multiplicity [MJ: 0.40 +/- 0.58 (47% reduction), p < 0.05; MJ2: 0.25 +/- 0.43 (67% reduction), p < 0.005; and MJ5: 0.15 +/- 0.36 (80% reduction), p < 0.001]. Also, the numbers of cancer cells positive for proliferative cell nuclear antigen (PCNA) and cyclin D1 in colonic tumors were lowered by these treatments. In addition, treatment with MJ, MJ2, or MJ5 significantly increased apoptotic index in colonic adenocarcinoma. These findings might suggest effective chemopreventive ability of MJs, especially MJ5, in colon tumorigenesis.

Adenocarcinoma↗
PubMed2000

Alternative splicing forms of the human CD1D gene in mononuclear cells.

CD1d is a critical molecule for the presentation of lipid antigens to natural killer (NK) T cells. To investigate the molecular complexity of CD1d, alternatively spliced transcripts in peripheral blood mononuclear cells from three healthy subjects were analyzed by PCR and sequencing methods. We found eight alternatively spliced variants of the CD1D gene (V1-V8), seven of which are newly established variants (V2-V8). V1 and V4 are in-frame; however, the other six variants (V2, V3, V5-V8) are out-of-frame. V1, V2, V4, and V5 lack a beta(2)-microglobulin binding site (alpha3 domain), indicating the unstable presentation of the CD1d molecule on the surface. In V2 and V5, the transmembrane region is absent, supporting a soluble CD1d. In the V3-V8 variants, the antigen binding region (alpha1 and alpha2 domains) is partially defective, suggesting incomplete functional products. In contrast, the V1 and V2 transcripts bear the complete antigen binding site, resulting in functional proteins. Especially, the V2 splicing variant might function as an inhibitory soluble CD1d molecule and regulate the presentation of antigens on APC to NKT cells.

Alternative Splicing↗
PubMed2000

Light chain determines the binding property of human anti-dsDNA IgG autoantibodies.

We have previously prepared human anti-double-stranded (ds) DNA IgG Fab clones using phage-display technology. Nucleotide sequence analysis of genes of immunoglobulin (Ig) heavy and light chain variable regions in these Fab clones suggested that the DNA-binding activity of the clones depended on light chain usage. To confirm the role of the light chain in antibody binding to DNA, we constructed in the present study's new recombined Fab clones by heavy and light chain shuffling between the original anti-dsDNA Fab clones. Clones constructed by pairing Fdgamma fragments with the light chain from a high DNA-binding clone showed high DNA-binding activities, whereas other constructed clones using light chains from low DNA-binding clones showed low DNA-binding activities. Our results indicate that light chains in anti-dsDNA antibodies can determine the DNA-binding activity of the antibodies. Ig chain shuffling of phage-display antibodies may be useful for investigating the molecular mechanisms for antigen-antibody binding of human autoantibodies.

Amino Acid Sequence↗
PubMed2000

Modifying effects of carotenoids on superoxide and nitric oxide generation from stimulated leukocytes.

Excessive and prolonged generation of superoxide (O2-) and nitric oxide (NO) from inflammatory leukocytes is associated with several lifestyle-related diseases, including cancer. In the present study, we screened 19 natural carotenoids for their modifying effects on O2- and NO generation from differentiated human promyelocytic HL-60 cells and mouse macrophage RAW 264.7 cells, respectively. Of the carotenoids tested, halocynthiaxanthin, isolated from oysters, showed the highest suppressive effect on the generation of both free radicals. The inhibitory potencies of certain carotenoids on radical generation markedly exceeded that of beta-carotene. In addition, some important structural moieties regulating radical generation suppression are discussed.

Animals↗
PubMed2000

Platelet-activating factor (PAF)-like oxidized phospholipids: relevance to atherosclerosis.

Lipid peroxidation is involved in the pathogenesis of chronic diseases including atherosclerosis. Oxidized lipoprotein has diverse biological activities and is believed to initiate atheroma formation and maturate fatty plaque. The active components of oxidized lipoproteins still remain to be clarified, but a likely candidate is the phosphatidylcholine (PC) having an sn-2-short-chain acyl group with a methyl, hydroxyl, aldehydic or carboxylic terminal. These unique PCs, formed by oxidative fragmentation of the polyunsaturated acyl group of the parent PC in liposomes, low density lipoproteins and blood plasma, induce platelet aggregation through the activation of the receptor for platelet-activating factor (PAF), due to their resemblance in structure with PAF. We have found that PAF-like lipids regulate DNA synthesis and production of nitric oxide independently of the activation of the PAF receptor in vascular smooth muscle cells. Regulation of vascular cell function through two distinct signaling pathways mediated by PAF-like lipids provides new insight into the mechanism of induction of atherosclerosis.

Animals↗
PubMed2000

Bypass graft material and myocardial protective procedure in combined coronary artery bypass grafting and valve surgery.

OBJECTIVE: The aortic cross clamping time is prone to be longer when coronary artery bypass grafting (CABG) is combined with valve surgery. Therefore, the myocardium that is revascularized by in-situ internal thoracic artery graft is at risk to ischemia, and, myocardial protection is especially important in such operation. In this study, the effect of myocardial preservation of combined antegrade, retrograde and terminal warm blood cardioplegia during combined valve surgery and CABG using the internal thoracic artery as a bypass conduit was evaluated. METHODS: From November 1992 to August 1999, 15 patients received combined CABG and valve surgery. Among these 15 patients, 13 patients who did not need hemodialysis were divided into 2 groups, and a comparative study was done. In Group I (n = 5), only the saphenous vein graft was employed for combined CABG and valve surgery, and myocardial protection was done by combined antegrade and terminal warm blood cardioplegia. In Group II (n = 8), at least 1 in-situ internal thoracic artery graft was employed for CABG and valve surgery, and myocardial protection was done by combined antegrade, retrograde and terminal warm blood cardioplegia. RESULTS: Despite longer aortic cross clamping time in Group II, the peak creatine kinase-MB of Group II was significantly lower. In addition, the postoperative administration of dopamine tended to be less in Group II. CONCLUSION: Myocardial protection by combined antegrade, retrograde and terminal warm blood cardioplegia may be an effective adjunct to combined valve surgery and CABG employing the in-situ internal thoracic artery graft.

Aged↗
PubMed2000

Histological study on pN upgrading of oral cancer.

The International Union Against Cancer (UICC) does not define the number of sections required from each regional lymph node to record pTNM classification. This study was designed to clarify the incidence of occult metastasis and to assess the pN upgrading of patients with oral cancer. Ultimately, this study led to a proposal for appropriate semiserial sectioning guidelines. Five hundred fifty-four nonmetastatic cervical lymph nodes taken from 73 patients with oral cancer were subjected to hematoxylin-eosin (HE) staining and keratin immunohistochemistry. Micrometastases, defined as foci < or =3 mm, were detected in 29 sites of 23 lymph nodes (4.2%) of 16 patients (21.9%). In 9 patients (12.3%) pN upgrading was needed: in 6 from pN0 to pN1, in 1 from pN0 to pN2b, and in 2 from pN1 to pN2b. The remaining 13 lymph nodes with occult metastasis were found in 5 pN2b and 2 pN2c patients, resulting in no pN upgrading. Occult metastasis was also detected in 6 small lymph nodes < or =5 mm in diameter. The average minor axis of the micrometastasis was 1.36-/+0.85 mm. We propose that the lymph nodes should be cut and examined at 1-mm intervals to detect micrometastatic foci and to evaluate the pN classification accurately.

Humans↗
PubMed2000

Clonally accumulating T cells in the anterior chamber of Behçet disease.

PURPOSE: To clarify the nature of infiltrating T cells into the anterior chamber of a patient with Behçet disease. METHODS: Aqueous humor was obtained from a patient with ocular Behçet disease by paracentesis. RNA isolated from the cells in aqueous humor was reverse transcribed into complementary DNA. Complementary DNA encoding the variable (V) diversity (D) joining (J) (junctional) region of T-cell receptor beta chain V domain (TCR BV) chain was amplified by T-cell receptor BV family polymerase chain reaction. RESULTS: Polymerase chain reaction Southern blot analysis showed that T-cell receptor BV3, BV5, and BV7 were dominantly expressed on ocular T cells of this patient. In addition, DNA sequencing revealed that monoclonal or oligoclonal T-cell accumulation was found in T-cell receptor BV3(+), BV5(+), and BV7(+) T cells. CONCLUSION: These findings suggest that some T cells infiltrating into the anterior chamber of a patient with ocular Behçet disease expand by antigen-driven stimulation, indicating the pivotal role of T cells in the pathogenesis of ocular Behçet disease.

Adult↗
PubMed2000

Induction of apoptosis and inhibition of DNA topoisomerase-I in K-562 cells by a marine microalgal polysaccharide.

We have previously purified an extracellular polysaccharide, D-galactan sulfate associated with L(+)-lactic acid, produced from a marine microalga Dinoflagellate Gymnodinium sp. A3 (GA3). The GA3 polysaccharide, irrespective of presence or absence of lactic acid, exhibited significant cytotoxicity, which is based on an induction of apoptotic cell death, toward human myeloid leukemia K562 cells. Furthermore, we found that the GA3 polysaccharide with or without lactic acid possesses an inhibitory effect on topoisomerase-I (topo-I). The potent cytotoxic effect of GA3 polysaccharide may result from its inhibitory effect on topo-I, because the topo-I inhibition is known to trigger apoptotic cell death.

Animals↗