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Biomedical subjects

M Takeno

Publications and source records attributed to M Takeno.

At least 37 records · Page 2Linked to original sources
PubMed1998

Q wave and non-Q wave myocarditis with special reference to clinical significance.

This study was designed to evaluate the differences in clinical findings between patients with and without Q waves in acute myocarditis. Among a total of 24 patients, eleven patients had Q waves and thirteen did not. Echocardiographic findings, in-hospital complications and follow-up results were compared between the two groups. In the acute stage, the Q wave group showed significantly higher creatine kinase (CK) values and a more impaired left ventricular ejection fraction than the non-Q wave group (40 +/- 11% vs 57 +/- 10%, p < 0.001). Transient left ventricular hypertrophy was also prominent in the Q wave group. The incidence of cardiogenic shock (55%) and conduction disturbances (64%) were higher in the Q wave group than in the non-Q wave group (0% and 15%, respectively). In-hospital mortality rate was 27% in the Q wave group and 8% in the non-Q wave group, respectively. Since rapid improvement occurred in survivors with Q waves, long-term prognosis was favorable for the two groups. In conclusion, Q waves might indicate a more severe course in early illness.

Adrenal Cortex Hormones↗
PubMed1997

Autoreactive T cell clones from patients with systemic lupus erythematosus support polyclonal autoantibody production.

This work examines the functional properties and TCRbeta gene utilization of 15 autoreactive T cell clones derived from five patients with systemic lupus erythematosus. All these clones proliferated and secreted cytokine when stimulated in vitro by autologous (but not allogenic) B cells. Individual T cell clones used diverse TCRbeta genes and did not show skewing toward the preferential usage of anionically charged receptors. Autoreactive T cell clones supported polyclonal B cell activation, as characterized by the production of anti-DNA, anti-Sjögren syndrome A, and anti-tetanus toxoid (anti-TT) Abs. This T cell help was mediated through the production of immunostimulatory cytokines, especially IL-6. Although stimulation of the autoreactive clones was blocked by anti-HLA class II Abs, the T cell clones did not proliferate, nor did they support polyclonal IgG production by HLA class II-matched normal B cells. Unlike the autoreactive clones, TT-specific clones derived from the same patients provided help selectively to B cells secreting anti-TT Abs. These findings suggest that autoreactive T cells from systemic lupus erythematosus patients are triggered to provide help following cognate interactions with self-peptides presented in the context of HLA class II molecules expressed on autologous B cells regardless of their specificities.

Amino Acid Sequence↗
PubMed1997

Modulation of synovial cell function by somatostatin in patients with rheumatoid arthritis.

OBJECTIVE: To elucidate the role of neurologic, endocrine, and immune system interactions in the development of pathologic responses in patients with rheumatoid arthritis (RA), we studied somatostatin (SOM) production and somatostatin receptor (SOMR) expression in RA synovium and its function in patients with RA. METHODS: The effects of SOM on proinflammatory cytokine (interleukin-6 [IL-6] and IL-8) and collagenase production by RA synovial cells were estimated by enzyme-linked immunosorbent assay, and their messenger RNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) using limiting dilutions of the complementary DNA. The expression of SOMR by RA synovial cells was also studied by RT-PCR. Local production of SOM was estimated by RT-PCR and immunohistochemical staining. RESULTS: Physiologic concentrations (approximately 10(-10)M) of SOM inhibited proliferation of RA synovial cells. The production of proinflammatory cytokines and matrix metalloproteinases by RA synovial cells was also modulated by SOM. SOMR subtypes 1 and 2 were expressed on fibroblast-like synovial cells, and the expression of SOMR-2 was up-regulated by proinflammatory cytokine treatment of the synovial cells from patients with RA. RA fibroblast-like cells synthesized SOM by themselves, suggesting that SOM acts as an autocrine regulator of synovial cell function in patients with RA. CONCLUSION: SOM inhibited aberrant synovial cell function in patients with RA, suggesting possible clinical applications of this neuropeptide.

Activating Transcription Factor 1↗
PubMed1997

DNA vaccines: safety and efficacy issues.

DNA technology has been harnessed to produce a variety of plasmid-based vaccines designed to prevent viral, bacterial and parasitic infections. The rapid adoption and implementation of this novel vaccine strategy carries with it important safety and efficacy concerns. This review will focus on whether DNA vaccines (1) are likely to induce systemic or organ-specific autoimmune disease, (2) have the potential to induce tolerance rather than immunity, and (3) are as effective in individuals with depressed immune function as they are in healthy adults.

Aging↗
PubMed1997

Therapeutic effects of preferential induction of mite-specific T helper 0 clones.

The predominance of Th2 cytokine-secreting pattern in allergic asthma has been known as a cause and an accelerating factor, and Th1 suppresses these allergic phenomena, but the role of Th0 clones is obscure. Because Th1/Th2 differentiation has been determined by cytokine environment, we investigated how mite-specific helper T cells stimulated in different cytokine environments actually influenced IgE and IgG4 synthesis, which are known to be regulatory immunoglobulins for allergic response. Th0 clones, which were mainly established in the presence of IL-12, provided a great deal of help for IgG4 and IgG1 synthesis, but did not provide help for IgE synthesis, whereas Th2 clones helped IgE synthesis prominently, and IgG4 and IgG1 synthesis marginally. These characteristics of Th0 clones were also true for Th0 clones obtained from patients who were successfully treated with desensitization therapy. Furthermore, the differences in helper activity between Th0 and Th2 clones were not ascribed solely to soluble factors. These data indicate that IgE and IgG4 synthesis is differentially regulated by antigen-specific T cells, and that conversion or selection from Th2 to Th0 by the addition of IL-12 may exhibit therapeutic effects.

Adult↗
PubMed1997

Role of gammadelta T lymphocytes in the development of Behçet's disease.

Phenotypic and functional properties of gammadelta T cells, which play an important role in mucocutaneous immunity, were examined to elucidate whether immunological abnormality in Behcet's disease may be related to a specific T cell population. We found that CD45RA+ Vgamma9+ Vdelta2+ gammadelta T cells, which constitute a minor population of gammadelta T cells in healthy individuals, were increased in number in Behçet's disease irrespective of disease activity. This CD45RA+ subset of gammadelta T cells in the active, but not inactive, phase of this disease expressed IL-2Rbeta and HLA-DR, suggesting that they are activated in vivo in active Behçet's disease. In addition, the CD45RA+ gammadelta T cells produced extreme amounts of tumour necrosis factor and contained perforin granules. These data indicate that a phenotypically distinct subset of gammadelta T cells, CD45RA+ CD45RO- Vgamma9+ Vdelta2+, may contribute to immunological abnormalities which may lead to complexity of pathophysiology in Behçet's disease.

Adult↗
PubMed1997

[Monoclonal antibodies for treating autoimmune diseases].

Monoclonal antibodies (mAbs) directed to selected cell surface antigens, cytokines and their receptors, and adhesion molecules have been shown to inhibit autoimmune responses in preclinial animal models. Therapeutic trials using the chimeric or humanized mAbs have already been undergoing in patients with rheumatoid arthritis (RA). Effects of anti-CD4 mAb are controversial, but anti-TNF-alpha mAb reveals encouraging results. Although it is too early to determine the efficacy, mAbs are new hopeful therapeutic strategies for autoimmune diseases.

Animals↗
PubMed1996

Induction of neonatal tolerance by plasmid DNA vaccination of mice.

Plasmid DNA vaccines capable of preventing viral, bacterial, and parasitic infections are currently under development. Our labs have shown that a plasmid DNA vaccine encoding the circumsporozoite protein of the malaria parasite elicits protective immunity against live sporozoite challenge in adult BALB/c mice. We now find that the same DNA vaccine induces tolerance rather than immunity when administered to 2-5 d-old mice. Neonatally tolerized animals were unable to mount antibody, cytokine or cytotoxic responses when rechallenged with DNA vaccine in vitro or in vivo. Tolerance was specific for immunogenic epitopes expressed by the vaccine-encoded, endogenously produced antigen. Mice challenged with exogenous circumsporozoite protein produced antibodies against a different set of epitopes, and were not tolerized. These findings demonstrate important differences in the nature and specificity of the immune response elicited by DNA vaccines versus conventional protein immunogens.

Age Factors↗
PubMed1995

Excessive function of peripheral blood neutrophils from patients with Behçet's disease and from HLA-B51 transgenic mice.

OBJECTIVE: To elucidate the role played by HLA-B51 in the neutrophil hyperfunction of Behçet's disease, we determined the superoxide production by purified peripheral blood neutrophils from Behçet's disease patients, from HLA-B51 positive healthy individuals, and from HLA-B51 transgenic mice. METHODS: Neutrophil function was evaluated by flow cytometric analysis, detecting the conversion of 2',7'-dichlorofluorescin diacetate into dichloroflurescein, induced by superoxide in the neutrophils. RESULTS: A significant correlation between the neutrophil hyperfunction and the possession of HLA-B51 phenotype, regardless of the presence of the disease, was observed in humans. FMLP-stimulated neutrophils (without in vitro priming) from HLA-B51 transgenic mice, but not those from HLA-B35 transgenic mice or from nontransgenic mice, produced substantial amounts of superoxide. CONCLUSION: The HLA-B51 molecule itself may be responsible, at least in part, for neutrophil hyperfunction in Behçet's disease.

Animals↗
PubMed1994

Fine antigen specificity of human gamma delta T cell lines (V gamma 9+) established by repetitive stimulation with a serotype (KTH-1) of a gram-positive bacterium, Streptococcus sanguis.

We have established human gamma delta T cell lines specific for Streptococcus sanguis (S. sanguis) KTH-1 present in normal oral cavity flora. The CD4-CD8-CD3+V gamma 9+V delta 1-CD45RO+ CD25+ T cell lines showed a proliferative response to the streptococcal antigen (Ag) in the presence of autologous antigen-presenting cells without apparent evidence of HLA restriction. The proliferative response of the gamma delta T cell lines was completely blocked by anti-TcR gamma delta monoclonal antibody (mAb) and anti-HLA class I mAb (W6/32), whereas anti-HLA classical class Ia mAb (B-H9; anti-HLA-A,B,C), anti-HLA class II mAb (anti-DR, anti-DQ, and anti-DP) and anti-CD4 mAb did not have any inhibitory effects. Surprisingly, the gamma delta T cell lines showed the proliferative response against the original bacterial Ag KTH-1 exclusively, and exhibited no cross-reactivity with nominal Ag such as purified protein derivative of tuberculin, tetanus toxoid and Mycobacterium tuberculosis, or the same species but different strain of S. sanguis, American Type Culture Collection (ATCC) standard strain (10556), or even with the same strain but different serotype of S. sanguis, KTH-3. Moreover, cytokine production of the gamma delta T cell lines was similar to the Th1 pattern [interferon-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta]. They also produced interleukin-8 that functions as one of chemoattractants for polymorphonuclear cells. Using direct sequencing technique of the polymerase chain reaction products, we found that junctional diversity of the T cell receptor (TcR) used by the parental KTH-1 specific gamma delta T cell line and its subclones is rather limited. It is suggested that gamma delta T cells with canonical TcR could preferentially respond to KTH-1 Ag. Thus, in addition to a broad or cross-reactivity of gamma delta T cells against phylogenetically conserved stress/heat-shock protein, which is well characterized by others, some peripheral blood gamma delta T cells could recognize and kill exogenous agents with fine antigenic specificity to protect the body against them.

Antigens, Bacterial↗
PubMed1991

T cell interactions in active rheumatoid arthritis: insights from the human autologous mixed lymphocyte reaction as a model of T cell activation cascade.

The autologous mixed lymphocyte reaction (AMLR) represents the activation, proliferation and differentiation of T cells in response to signals from autologous non-T cells. Using monoclonal anti-Leu8 antibody to isolate subpopulations of human CD4+ and CD8+ T cells, we have investigated the role of these subpopulations in the T cell activation cascade during the course of AMLR. In normal subjects, CD4+Leu8+ cells are necessary for the initiation of the AMLR response, and sequentially lead to activation and proliferation of both CD4+Leu8- cells and CD8+Leu8+ cells. The activated CD8+Leu8+ cells, in turn, induce CD8+Leu8- cells to generate proliferation of the latter cells. Soluble mediators could be involved in the T cell activation cascade induced by the AMLR. Patients with active rheumatoid arthritis have a profound defect in the AMLR. Further analysis indicates that rheumatoid arthritis CD8+ T cells are markedly defective as responding cells in the AMLR. The impaired AMLR response by CD8+ cells cannot be reconstituted with AMLR-derived supernatants from normal T cells. The data suggest that the defective CD8+ T cell function may contribute to the pathogenesis of the disease.

Adult↗
PubMed1990

[Abnormalities in autologous mixed lymphocyte reaction-induced T cell activation cascade in rheumatoid arthritis and their possible correction by methyl-B12].

We have previously shown that when patients with active rheumatoid arthritis (RA) were examined for the ability of their lymphocytes to respond in the autologous mixed lymphocyte reaction (AMLR), profoundly reduced AMLR responses were found in the RA patients. The defects were mainly due to the impaired response of CD8+ and CD4+ Law8- subsets; however, both CD4+Leu8+ and CD4+ + Leu8- cells functioned normally as responding cells. The present study demonstrated that the abnormalities of RA CD8+ T cells in the AMLR were corrected when the AMLR cultures were set up in the presence of methyl-B12. In addition, a main target of the methyl-B12 effect observed was both CD8+Leu8+ and CD8+Leu8- cells. Thus, methyl-B12 may become a potential agent that would be able to control the pathophysiology of RA.

Adult↗
PubMed1990

[Multiple myeloma causing obstructive jaundice by extramedullary plasmacytoma after Bence Jones protein loss--an autopsy case report].

A 63-year-old man was admitted to our hospital with a chief complaint of general malaise in March 1986. A diagnosis of Bence Jones protein (kappa) type of multiple myeloma was made from increased atypical plasma cells in the bone marrow, urinary BJP (kappa) and osteolytic lesions. Urinary BJP (kappa) was decreased by MP and VENP therapies. In April 1987, he visited us again with the complaint of pain on the left shoulder. An examination revealed multiple osteolytic lesions and bilateral pleural effusion containing atypical plasma cells. Jaundice was developed at the end of July 1987. An ultrasound examination revealed a hypoechoic mass in the area of pancreatic head. The effusion was gradually increased without response to the treatment. He died of respiratory failure on July 31, 1987. On autopsy, extramedullary plasmacytoma was found in the head of pancreas. It was a rare case of multiple myeloma in which pleural effusion and multiple plasmacytomas, and finally obstructive jaundice were developed although urinary BJP (kappa) was reduced by treatment.

Bence Jones Protein↗
PubMed1983

Isozymes of glycogen phosphorylase in human cartilage and cartilage tumors.

Isozyme patterns of glycogen phosphorylase in normal fetal and adult human cartilage and benign and malignant cartilage tumors were investigated by means of polyacrylamide gel disc electrophoresis. In both normal cartilage and cartilage tumors four distinct bands were observable: these were of the liver, liver-like and fetal types and of a hybrid type between the muscle and fetal types judging by their mobilities in the small-pore gels containing 0.01% and 0.1% glycogen. The isozyme pattern of benign cartilage tumors was almost identical with that of normal cartilage. In normal fetal and adult cartilage and benign cartilage tumors, the liver and liver-like types were predominant, whereas in malignant cartilage tumors they were minor and the fetal type was predominant. These results indicate fetal deviation of phosphorylase isozymes in malignant transformation of cartilage cells.

Adult↗
PubMedDate not supplied

Involvement of cAMP responsive element binding protein (CREB) in the synovial cell hyperfunction in patients with rheumatoid arthritis.

OBJECTIVE: To elucidate a possible role of cAMP responsive element binding protein (CREB) in rheumatoid arthritis (RA) synovial cell function, we have studied CREB expression of synovial cells and the effects of an inhibitor of the cAMP/CREB signal pathway on synovial cell function in patients with RA. METHODS: We examined CREB expression by immunohistochemical staining, immunocytochemical staining, and gel shift assays. Effects of cAMP/CREB inhibitor on the proliferation of RA synovial cells were assessed by [3H]-TdR incorporation, and those on proinflammatory cytokine and matrix metalloproteinase (MMP) production by reverse transcription PCR and ELISAs. RESULTS: Immunohistochemical staining of synovial tissue revealed that CREB is expressed mainly in the lining and sublining layers of synovium in patients with RA. DNA binding activity of CREB was ascertained by a gel shift assay. We also confirmed nuclear translocation and phosphorylation of CREB in TNF-alpha stimulated RA fibroblast-like synovial cells by immunocytochemical staining. Modulators of cAMP/CREB signaling pathway, such as Rp-cAMP, had an inhibitory potential on RA synovial cell proliferation in vitro. Rp-cAMP also inhibited the proinflammatory cytokine and MMP production. CONCLUSION: CREB is involved in the synovial cell activity in patients with RA. Inhibition of CREB activity by its inhibitor brings about the correction of aberrant synovial cell functions in patients with RA, thus suggesting a possible clinical application of cAMP/CREB inhibitors.

Aged↗