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T Sumida

Publications and source records attributed to T Sumida.

At least 145 records · Page 8Linked to original sources
PubMed1995

[T cell receptor repertoire of infiltrating T cells in the interstitial nephritis of patients with Sjögren's syndrome].

We examined the T cell receptor (TCR) repertoire of infiltrating T cells in the kidney, labial salivary glands (LSGs) and peripheral blood lymphocytes (PBLs) in Sjögren's syndrome (SS) patients with interstitial nephritis. The TCR V beta gene repertoire in kidney was more restricted compared with that in LSGs and PBLs. The TCR V beta 2 gene was predominantly expressed in six of seven kidneys (86%). Junctional sequence of TCR V beta 2 gene shows that some of these cells expanded clonally. The identical TCR clones in the kidneys were not detected in LSGs and the amino acid (Arg96) in the CDR3 region of V beta 2 gene was conserved specifically in kidneys. These findings suggest that T cells infiltrating in the kidneys from SS patients with interstitial nephritis identify different autoantigens from LSGs rather than superantigen.

Autoantigens↗
PubMed1995

Identification of Ro(SSA) 52 kDa reactive T cells in labial salivary glands from patients with Sjögren's syndrome.

OBJECTIVE: To identify the self-antigens recognized by autoreactive T cells in labial salivary glands from patients with Sjõgren's syndrome (SS). METHODS: T cells lines were established from infiltrating T cells in the labial salivary glands from 6 patients with SS, using interleukin 2 and phytohemagglutinin. Bulk cultured T cells and T cell lines were examined for the proliferative response to recombinant Ro(SSA) 52 kDa and SSB proteins. The usage of T cell receptor (TCR) V beta and V alpha genes from Ro(SSA) 52kDa reactive T cells was analyzed by family polymerase chain reaction. The sequences of complementary determining region 3 of TCR V beta genes were also examined. RESULTS: Three of 6 bulk cultured T cells and 4 of 16 T cell lines showed a significant proliferative response to Ro(SSA) 52 kDa protein. All T cell lines represented CD4+ alpha beta T cells by flow cytometry analysis. All 4 RO(SSA) 52 kDa reactive T cell lines utilized the V beta 2 gene and 3 lines used the V beta 13 gene, suggesting preferential usage of the V beta 2 and the V beta 13 genes in Ro(SSA) 52 kDa reactive T cells. Junctional sequences of TCR V beta genes from Ro(SSA) 52 kDa reactive T cell lines showed the conserved amino acid sequences in CDR3 region. CONCLUSION: These findings support the notion that Ro(SSA) 52 kDa is a possible autoantigen recognized by autoreactive T cells and that limited epitope is present on the Ro(SSA) 52 kDa antigen.

Amino Acid Sequence↗
PubMed1994

Expression of sequences homologous to HTLV-I tax gene in the labial salivary glands of Japanese patients with Sjögren's syndrome.

OBJECTIVE: To address the question of whether the human T cell leukemia virus type I (HTLV-I) gene is associated with the etiology of Sjögren's syndrome (SS). METHODS: RNA expression of HTLV-I gag, pol, env, and tax genes in labial salivary glands (LSGs) from SS patients who were seronegative for antibodies to HTLV-I was examined using reverse transcription and polymerase chain reaction techniques. RESULTS: The HTLV-I tax gene, but not the HTLV-I gag, pol, or env genes, was detected in LSG samples from 4 of 14 patients (29%). The nucleotide sequences of the HTLV-I pXIV region in these 4 patients' LSGs showed 100% homology to the HTLV-I pXIV gene from the MT-2 cell line. CONCLUSION: These findings suggest that products encoding sequences homologous to the HTLV-I pXIV gene in SS patients' LSGs might be candidates for self-antigen and/or lead to activation of autoreactive T lymphocytes through trans-acting transcriptional activation.

Base Sequence↗
PubMed1994

Prevention of insulitis and diabetes in beta 2-microglobulin-deficient non-obese diabetic mice.

beta 2-Microglobulin (beta 2m)-deficient non-obese diabetic (NOD) mice were established by crossing beta 2m-deficient 129/Sv mice with NOD mice, and used to examine the possible involvement of MHC class I molecules and CD8+ T cells in the development of insulitis and diabetes. In these mice, MHC class I molecules were not expressed, resulting in no generation of CD8+ T cells. None of eight lines of beta 2m-deficient NOD mice (-/-) established developed overt diabetes by 32 weeks, while control littermates (+/+) became diabetic by 22 weeks. histological studies showed no significant lymphocyte infiltration of the islets (insulitis score: 0.03 +/- 0.03) in any of the beta 2m-deficient NOD mice (-/-) compared with littermate NOD mice (+/+) with overt insulitis (1.42 +/- 0.28). These findings support the notion that the expression of MHC class I molecules and/or CD8+ T cells plays an essential role in the infiltration of CD4+ T cells in islets as well as the development of diabetes in NOD mice.

Animals↗
PubMed1994

HLA-DR alleles in patients with Sjögren's syndrome over-representing V beta 2 and V beta 13 genes in the labial salivary glands.

To identify genetic factors that play a role in the pathogenesis of patients with SS over-representing V beta 2 and V beta 13 genes in the lips, HLA-DR and -DQ alleles of 10 primary SS patients with predominant expression of V beta 2 and V beta 13 genes in the lips were analysed, using the polymerase chain reaction (PCR) and sequence specific oligonucleotide probes. The CDR3 amino acid sequences of cDNA clones encoding V beta 2 and V beta 13 genes were also determined by PCR. The results showed that the DRB4*0101 allele was significantly increased (80%) and that the frequency of DRB3 allele was decreased (0%) when compared to findings in healthy subjects (35.6 and 26%, respectively). Sequencing analyses demonstrated that 75% of V beta 2 cDNA clones and 87% of V beta 13 cDNA clones had a glutamine residue at position 106, in the CDR13 region. Moreover, the conserved sequences (Y*TLRNEQ) in the CDR3 of V beta 13-positive T cell were detected in two different clones (27%) from the two individual SS patients. These findings suggest that the decreased DRB3 and increased DRB4*0101 alleles may be associated with the antigens recognized by V beta 2- and V beta 13-positive T cells.

Alleles↗
PubMed1994

T cell receptor V alpha repertoire of infiltrating T cells in labial salivary glands from patients with Sjögren's syndrome.

OBJECTIVE: To analyze the T cell receptor (TCR) V alpha repertoire of infiltrating T cells in labial salivary glands of patients with Sjögren's syndrome (SS). METHODS: TCR V alpha genes of infiltrating T cells in lips from 2 patients with SS were examined, using the double step inverse polymerase chain reaction. Four and 7 clones encoding the VJC alpha region were established and sequenced, respectively. RESULTS: All 4 clones used the V alpha 17.1 gene in one patient, while 3 (42.8%) of 7 clones from the other patient used the V alpha 2 family gene (V alpha 2.1, V alpha 2.2, V alpha 2.4), and the other 3 clones used the V alpha 11.1 family gene. A comparison using labial salivary glands and peripheral blood showed that the predominant expression of V alpha 2, V alpha 11.1, and V alpha 17.1 gene segments is specific in the salivary glands. CONCLUSION: The TCR V alpha repertoire of infiltrating T cells from the lips of 2 patients with SS was relatively restricted in individual patients, thereby suggesting the limited heterogeneity of these cells in salivary glands.

Amino Acid Sequence↗
PubMed1994

T-cell receptor V beta repertoire of L3T4+ regulatory T cells in anti-L3T4 antibody-induced tolerant NOD mice.

In ongoing studies, we have found that short-term administration of anti-L3T4 monoclonal antibodies (mAb) prevents the development of overt diabetes in non-obese diabetic (NOD) mice. In the present work, we asked whether L3T4+ T cells or Lyt-2+ T cells can suppress the diabetes in these mice. L3T4+ T cells or Lyt-2+ T cells were sorted using a magnetic cell sorter, then were transferred into cyclophosphamide-induced male NOD mice. We obtained evidence that the L3T4+ but not Lyt-2+ T cells did inhibit the diabetes, thereby indicating that the former can regulate diabetes in anti-L3T4 mAb-induced tolerant NOD mice. Further analysis on T-cell receptor (TCR) V beta genes on splenic T cells from anti-L3T4 mAb-treated NOD mice revealed that V beta 4-positive T cells expanded predominantly, while L3T4+ T cells represented heterogeneity of the TCR V beta gene, hence, V beta 4-positive Lyt-2+ T cells generate predominantly. Our findings suggest that both L3T4+ and Lyt-2+ T cells renew and function as regulatory cells, through clonotypic interaction in tolerant NOD mice.

Animals↗
PubMed1994

[Phase I study of paclitaxel].

Paclitaxel, a novel antimicrotubule agent that enhances tubulin polymerization and microtubule stability, was administered as a 24-hour infusion in a phase I study. Twelve patients received 32 courses at 50, 100, 150, and 200 mg/m2. A premedication regimen of dexamethasone, diphenhydramine, and ranitidine was used to prevent the acute hypersensitivity reactions (HSRs). The dose-limiting factor was leukopenia (granulocytopenia) associated with Grade 4 infection. The maximum tolerated dose was 200 mg/m2. Other non-hematological effects included peripheral neuropathy, myalgia, alopecia, and elevations of transaminase and alkaline phosphatase. Severe HSRs were not observed. The paclitaxel plasma concentration declined with a half-life of 10.0 to 24.9 hours. Excretion into urine within 72 hours was in the range of 7.28 to 11.34% of paclitaxel dosage. Two patients with breast cancer at the 200 mg/m2 dose level had partial responses. The recommended dose of paclitaxel for phase II study, when administered as a 24-hour infusion, is considered to be 150 mg/m2 every 3 weeks.

Adolescent↗
PubMed1994

V gene analysis of anti-cardiolipin antibodies from (NZW x BXSB) F1 mice.

In (NZW x BXSB) F1 (W/B F1) male mice, systemic lupus-like disease, thrombocytopenia and coronary vascular disease with myocardial infarction occur, due to the presence of platelet-associated antibodies, anti-platelet antibodies and anti-cardiolipin antibodies (aCL). We developed monoclonal aCL and analysed the specificity of aCL. In the W/B F1 mice, there are aCL with pathogenic properties, which have an IgG isotype and reveal a cofactor-dependent binding to CL, binding activity to platelets, and lupus anti-coagulant (LA) activity. Here, we analysed the usage of VH and V kappa genes of six aCL, including two pathogenic aCL, from W/B F1 mice, in an attempt to address the question of whether or not aCL with pathogenic properties use restricted Ig V genes. Sequence analysis of VH and V kappa genes of aCL showed that the pathogenic aCL had VHJ558 and V kappa 21 or V kappa 23 genes, whereas the other aCL without pathogenic features used mainly the 7183 VH family and the random V kappa gene group. However, two pathogenic aCL showed a 86.6% homology with the IgV region, each other, indicating that they were not closely related clones. Thus, these findings suggest the possibility that usage of Ig VH genes in pathogenic aCL is not random, but that there may exist a few epitopes of antigen recognized by the pathogenic aCL.

Amino Acid Sequence↗
PubMed1993

V gene analysis of anticardiolipin antibodies from MRL-lpr/lpr mice.

We analyzed the VH and V kappa genes of 14 hybridomas producing anticardiolipin antibodies (aCL) from MRL-lpr/lpr mice, in an attempt to address the question of whether aCL are generated by Ag-driven stimulation or by polyclonal B cell activation. Five of six aCL from one mouse and both aCL from the other mouse carried 98 to 100% homologous VH and V kappa genes, respectively, thereby indicating that aCL were derived from the oligoclonal B cell precursor in that individual mouse. Of nine clones, six (67%) used the VH gene of the J558 family, and three (43%) of seven clones used the V kappa gene of the V kappa 23 group. Three to five somatic mutations were detected in all VH and V kappa genes of the examined aCL. These results suggest the possibility that usage of VH/V kappa genes in aCL is not random and that aCL consist of somatically mutated Ig genes.

Amino Acid Sequence↗
PubMed1993

Fentanyl antagonizes diazepam on carotid sinus baroreflex control of circulation in rabbits.

To investigate the effects of a combination of fentanyl and diazepam on carotid sinus baroreflex in conscious rabbits, we examined the responses of mean systemic arterial pressure (MAP), heart rate (HR) and total peripheral resistance (TPR) to bilateral carotid occlusion (BCO). Seven rabbits were given 0.5 mg.kg(-1) of diazepam i.v. followed by 10 mg.kg(-1) of fentanyl i.v. at 5 min intervals (group 1), and the drugs were given in the reverse order to 5 other rabbits (group 2). BCO was repeated in conscious state (control) and after each drug injection. MAP responses did not differ from control response in either group when both drugs were given. In group 1, however, diazepam decreased HR response to 71.4% of control, and increased TPR response by 36%. Fentanyl administration reversed diazepam-induced changes in BCO responses to the control level. In group 2, fentanyl decreased TPR response to 61.6% of control and increased HR response by 41.5%. Administration of diazepam following fentanyl restored HR and TPR responses to control levels. Carotid sinus baroreflex gain was 3.1 +/- 0.4 (mean +/- SEM) in control and 3.1 +/- 0.4 after administration of both drugs in 12 rabbits. The results suggest that a sedative dose of either fentanyl or diazepam antagonizes the other drug's action on the carotid sinus baroreflex. The combination of fentanyl and diazepam has little influence on carotid sinus baroreflex control of the circulation in rabbits.

Journal Article↗
PubMed1993

Effects of halothane on carotid occlusion in rabbits.

Effects of halothane on the carotid sinus baroreflex control of circulation were studied in chronically instrumented rabbits. The carotid sinus baroreflex was evaluated by the hemodynamic responses to bilateral carotid occlusion (BCO). Either 0.5 or 1.0 MAC of halothane inhalation did not alter mean arterial pressure (MAP) or total peripheral resistance (TPR), but significantly increased heart rate (HR). Carotid occlusion produced a significant increase in MAP and HR, and both responses were attenuated dose-dependently by halothane. Halothane depressed the reflex gain of arterial pressure from 3.5 +/- 0.3 at conscious state to 1.3 +/- 0.2 at 1.0 MAC halothane. Response of cardiac output (CO) to BCO was attenuated significantly only at 1.0 MAC compared with those responses at conscious state and at 0.5 MAC. Response of TPR was attenuated at both 0.5 and 1.0 MAC halothane as compared with at conscious state but no significant difference existed between the two concentrations of halothane. These data suggested that halothane could attenuate the carotid occlusion responses to various degrees in the involved effector components. 0.5 MAC halothane attenuated MAP response to BCO predominantly by attenuating reflex peripheral vasoconstriction. The reduced CO response was mainly responsible for further attenuation of MAP response at 1.0 MAC halothane.

Journal Article↗
PubMed1993

Effects of vasopressin on the response to carotid occlusion in conscious rabbits.

To investigate the interaction between arginine vasopressin and the carotid sinus baroreflex, hemodynamic responses to bilateral carotid occlusion and to controlled reductions in carotid sinus pressure were examined. In the control state and during vasopressin infusion in conscious rabbits, mean arterial pressure, heart rate, mean aortic flow and total peripheral resistance were measured. Vasopressin infusion at 5 or 10 ng/kg/min did not raise arterial pressure, but increased resistance, and decreased heart rate and aortic flow in a dose-dependent manner. The pressure and resistance responses to carotid occlusion or changes in carotid pressure were not altered by vasopressin. The heart rate response was augmented significantly from 23 +/- 5 (mean +/- S.E.) to 40 +/- 8 and 43 +/- 8 beats/min with infusion of 5 and 10 ng/kg/min of vasopressin. Vasopressin did not augment the gain of carotid sinus reflex control of arterial pressure (3.7 +/- 0.5 in control and 3.5 +/- 0.5 during 5 ng/kg/min of vasopressin). With vasopressin infusion at 5 ng/kg/min, following vagal blockade with methylatropine both the arterial pressure and the heart rate responses to carotid pressure changes decreased to 73% and 32% of the response before blockade. The data indicate that vasopressin has little effect on control of arterial pressure by the carotid sinus baroreflex in conscious rabbits when vagal responses are activated.

Animals↗
PubMed1993

Short-term administration of anti-L3T4 MoAb prevents diabetes in NOD mice.

We treated 2-week-old and 8-week-old non-obese diabetic (NOD) mice with 1 mg of anti-L3T4 MoAb weekly for 4 weeks. This short-term treatment of anti-L3T4 MoAb prevented the development of overt diabetes in NOD mice, in both groups, even after cessation of the therapy. However, there were overt mononuclear cell infiltrations in the majority of islets, and no appreciable differences in the degree of insulitis between treated and control mice. There were also no significant differences in the percentage of L3T4+ T cells expressing V beta 5, V beta 8 and V beta 11 antigens between the treated and the control group. In contrast, most of the male NOD mice injected with 200 mg/kg of cyclophosphamide did not become diabetic when the spleen cells from the MoAb-treated female NOD mice were transferred to these animals 48 h before the cyclophosphamide injection. Thus, the tolerance induced by the short-term administration of anti-L3T4 MoAb to NOD mice may not be due to clonal deletion, but rather to newly generated suppressor cells in the animals.

Animals↗
PubMed1992

Novel positive inotropic agents: synthesis and biological activities of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinone derivatives.

A series of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinones has been synthesized and evaluated for positive inotropic activity on the canine heart. Some of these derivatives have a potent activity with none or negative chronotropic effect in isolated, blood-perfused dog heart preparations. They also display a high selectivity for positive inotropic effect over chronotropic and vasodilatory effects in anesthetized dogs. (+/-)-6-[2-Hydroxy-3-[(3-methoxybenzyl)amino]propoxy]-2(1H)-quinolinone (39) and (+/-)-6-[3-(3,4-dimethoxybenzyl)amino]-2-hydroxypropoxy]-2 (1H)-quinolinone (40) were further investigated in conscious dogs. After iv administration, they did not affect heart rate or mean blood pressure at the dose producing a 50% increase in the peak of the first derivative of the left ventricular pressure. The compounds (39, OPC-18750, and 40, OPC-18790) are the most promising agents with desirable biological activities, and now are currently undergoing clinical evaluation.

Animals↗
PubMed1992

Anticardiolipin antibodies in NZW x BXSB F1 mice. A model of antiphospholipid syndrome.

NZW x BXSB F1 (W/B F1) male mice develop systemic lupus-like disease, and several autoantibodies, circulating immune complexes, and lupus nephritis become apparent. The abnormally high incidence of degenerative coronary vascular disease with myocardial infarction and thrombocytopenia due to the presence of both platelet-associated antibodies and circulating antiplatelet antibodies in this animal has been reported. We found that W/B F1 male mice produced autoantibodies against cardiolipin (aCL) and that the titer of aCL increases with age. aCL from W/B F1 male mice were mainly IgG and binding activity to cardiolipin was aCL-cofactor (beta 2-glycoprotein I (beta 2-GPI)) dependent. We developed monoclonal aCL from these animals and examined specificity of the autoantibodies. All the mAb used reacted with the negatively charged phospholipids, cardiolipin, phosphatidylserine, and phosphatidylinositol, and some reacted with platelets and DNA. The addition of human or mouse beta 2-GPI enhanced the titer for monoclonal aCL from the W/B F1 mice. From the results of competitive inhibition enzyme immunoassay with monoclonal aCL and purified beta 2-GPI, aCL from the W/B F1 mice recognized the complex of CL and beta 2-GPI. The W/B F1 male mouse may be an appropriate model for use in studies on the pathologic significance of aCL in patients with antiphospholipid syndrome.

Animals↗
PubMed1992

Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor.

Anticardiolipin antibodies (aCL) found in sera from patients with SLE react with cardiolipin (CL) in the presence of a 50-kDa serum cofactor. The cofactor, which was identified to be beta 2-glycoprotein I by sequencing the N-terminal amino acids, not only enhances CL binding by antibodies in SLE but also depresses it by antibodies associated with syphilis. Cofactor-dependent binding of aCL in SLE to solid phase CL was competitively inhibited by the simultaneous addition of fluid phase CL but was unaffected by either prior or simultaneous addition of a high excess of the cofactor. Binding of aCL in syphilis to solid phase CL was competitively inhibited by either addition of the cofactor or fluid phase CL. aCL in SLE reacted with CL, PS, and PA in the presence of cofactor. In contrast, biotinyl-cofactor bound directly to these anionic phospholipids (PL) and also to PG. These results show that the cofactor-CL complex bears an epitope that confers recognition specificity for aCL in SLE, in contrast with direct CL recognition by syphilitic aCL. The direct binding of the cofactor to PL suggests that the cofactor dependence of aCL binding to PL is due to recognition by aCL of a unique epitope generated upon the formation of the cofactor-CL complex.

Amino Acid Sequence↗