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Biomedical subjects

M Toda

Publications and source records attributed to M Toda.

At least 109 records · Page 6Linked to original sources
PubMed1995

Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.

Approximately 10% of peripheral CD4+ cells and less than 1% of CD8+ cells in normal unimmunized adult mice express the IL-2 receptor alpha-chain (CD25) molecules. When CD4+ cell suspensions prepared from BALB/c nu/+ mice lymph nodes and spleens were depleted of CD25+ cells by specific mAb and C, and then inoculated into BALB/c athymic nude (nu/nu) mice, all recipients spontaneously developed histologically and serologically evident autoimmune diseases (such as thyroiditis, gastritis, insulitis, sialoadenitis, adrenalitis, oophoritis, glomerulonephritis, and polyarthritis); some mice also developed graft-vs-host-like wasting disease. Reconstitution of CD4+CD25+ cells within a limited period after transfer of CD4+CD25- cells prevented these autoimmune developments in a dose-dependent fashion, whereas the reconstitution several days later, or inoculation of an equivalent dose of CD8+ cells, was far less efficient for the prevention. When nu/nu mice were transplanted with allogeneic skins or immunized with xenogeneic proteins at the time of CD25- cell inoculation, they showed significantly heightened immune responses to the skins or proteins, and reconstitution of CD4+CD25+ cells normalized the responses. Taken together, these results indicate that CD4+CD25+ cells contribute to maintaining self-tolerance by down-regulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage; elimination/reduction of CD4+CD25+ cells relieves this general suppression, thereby not only enhancing immune responses to non-self Ags, but also eliciting autoimmune responses to certain self-Ags. Abnormality of this T cell-mediated mechanism of peripheral tolerance can be a possible cause of various autoimmune diseases.

Animals↗
PubMed1995

Effect of a neuron-specific actin-binding protein, drebrin A, on cell-substratum adhesion.

Drebrin A expression was induced in non-neuronal L cells via transfection with a vector containing the cDNA of rat drebrin A. Following treatment with colcemid (5 micrograms/ml) and cytochalasin D (0.5 micrograms/ml), most L cells collapsed into round cells, while drebrin expressing cells were resistant to the treatment, keeping their cell shapes. Simultaneously, actin filaments and microtubules were disrupted in both cell lines. By quantitative analysis, in the presence of cytochalasin D, the extent of cell spreading and cell attachment in drebrin expressing cells was significantly higher than that in control cells. These results suggest that drebrin A modulates cell-substratum adhesion.

Actins↗
PubMed1995

[Appearance of antibacterial activity of oxacillin against methicillin resistant Staphylococcus aureus (MRSA) in the presence of catechin].

We previously reported that tea catechin shows bactericidal activity against various bacteria including methicillin resistant Staphylococcus aureus (MRSA) and that bactericidal catechin damages the lipid bilayer of bacterial cell membranes. Here we describe that oxacillin (MPIPC) shows antibacterial activity against MRSA in the presence of catechin below MIC. Twenty clinical isolates of MRSA were examined by a cup method. In the absence of catechin, MPIPC even at a concentration of 40 micrograms/ml did not show antibacterial activity against all isolates of MRSA. However, when catechin below MIC (25-100 micrograms/ml) was mixed with the agar medium, MPIPC (5-12.5 micrograms/ml) showed antibacterial activity against all MRSA isolates. By counting the numbers of viable bacteria in a broth culture, only MPIPC (5 micrograms/ml) or catechin (100 micrograms/ml) showed similar growth curves to the control. But addition of both MPIPC and catechin reduced the number of viable bacteria to 1/100-1/10000 after 24 hours of cultures. Besides MPIPC, in the presence of catechin below MIC methicillin (12.5 micrograms/ml), aminobenzylpenicillin (32 micrograms/ml), tetracycline (2.5 micrograms/ml), and chloramphenicol (12.5 micrograms/ml) showed antibacterial activities against multiple drug resistant MRSA to antibiotics mentioned above. These findings suggest a possible use of catechin in the treatment of MRSA infection.

Catechin↗
PubMed1995

[Polymorphism of 3,9-bis-(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2- c]quinoline-6-one(KCA-098), a new benzofuroquinoline derivative].

Physicochemical properties of polymorphism of 3,9-bis-(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinol ine-6-one (KCA-098) have been investigated. The existence of four crystalline forms (designated as hydrate, I, II and III) was confirmed by X-ray powder diffraction, IR spectroscopy and thermal analysis (DSC and TG). The hydrate was found to be a monohydrate by elemental analysis and water content measurement. DSC measurement found that the hydrate was transformed fo form III at about 93 degrees C, and then to form II at about 152 degrees C, and finally to form I at about 260 degrees C. On the other hand, when suspended in water the forms I, II and III were transformed into hydrate. The transition rate from form III to hydrate was higher than those from form II to hydrate and from form I to hydrate. Form III as a metastable form showed higher solubility than any of form I, II and hydrate.

Chemical Phenomena↗
PubMed1995

Development of oligodendrocyte and myelination in the central nervous system.

We demonstrated the cell lineage of oligodendrocytes from the glial precursor cells to mature oligodendrocytes forming myelin sheath around the axon. There are several different stages of oligodendrocyte development in vito. So far there are no precise data about their morphological changes during oligodendrocyte development, but by the analysis using SEM and immunostaining, the characteristic morphological changes with serial expression of cell markers were observed in each developmental steps of oligodendrocyte. We have also clearly demonstrated how oligodendrocytes wrap around the axon by using video time-lapse movies. These results will be useful for understanding the exact cellular mechanism of myelination in the CNS.

Animals↗
PubMed1995

Inhibition of leukotriene C4 and B4 release by human eosinophils with the new 5-lipoxygenase inhibitor 6-hydroxy-2(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazo le hydrochloride.

Eosinophils generate and release leukotrienes C4 and B4 (LTC4, LTB4) and platelet activating factor (PAF), all of which have the capacity to cause inflammation and tissue injury in the airways. This study has examined the effects of a new 5-lipoxygenase inhibitor, 6-hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazo le hydrochloride (CAS 120164-49-0, E6080) on the release of LTC4, LTB4 and PAF by human eosinophils, Eosinophils stimulated by 1 mumol/l calcium ionophore A23187 for 15 min released 37.5 +/- 2.2 ng, 2.3 +/- 0.3 ng and 4.0 +/- 0.3 pmol per 10(6) cells of immunoreactive LTC4, LTB4 and PAF, respectively (mean +/- SEM, n = 4). LTC4 and LTB4 releases were inhibited dose-dependently by the addition of E6080 to the cell suspension. The IC50 values were 0.26 mumol/l for LTC4 and 0.23 mumol/l for LTB4. PAF release was not inhibited. These results suggest that E6080 is a potent inhibitor of LTC4 and LTB4 release from eosinophils and may provide a protective effect against bronchoconstriction during late-phase asthmatic responses.

Asthma↗
PubMed1994

GFAP transfected cells produce laminin, leading to neurite outgrowth promotion.

Accumulating evidence indicates the importance of astrocytes in neuronal development and regeneration. While glial fibrillary acidic protein (GFAP) is believed to mediate the morphology of developing astrocytes, its precise function remains unknown. To analyse the function of GFAP in astrocytes, we established GFAP-expressing cell lines by transfection of mouse GFAP cDNA into mouse fibroblast L cells. Stable transfectants expressed GFAP uniformly in the cytoplasm with no phenotypic changes and exhibited extended processes rich in GFAP. GFAP-expressing cells significantly promoted the neurite outgrowth of rat cerebral cortex neurones in the co-culture system. Analysis of the products of GFAP-expressing cells revealed an increase in production of laminin, but not fibronectin. These results suggest that L cells expressing GFAP increase laminin production, leading to promotion of neurite outgrowth.

Animals↗
PubMed1994

Induction of autoimmune disease in mice by germline alteration of the T cell receptor gene expression.

Germline expression of rearranged TCR alpha-chain transgenes with the Ig H chain enhancer reproducibly elicits T cell-mediated autoimmune disease in the thyroid gland, gastric mucosa, Langerhans islets, salivary gland, ovaries, and testes in selected strains of normal mice. Multiple organs are destroyed in a single transgenic mouse and the same organ in transgenic strains with different MHC background, suggesting the transgene expression can elicit self-reactive T cell clones having different Ag specificities and MHC restrictions. Construction of this autoimmune-inducing TCR alpha EH transgene does not require particular V alpha J alpha gene segments or Ag specificities. Moreover, the autoimmune disease can be adoptively transferred to syngeneic normal mice by T cells expressing endogenous TCR alpha-chains. Taken together, these results indicate that the TCR alpha EH transgene expression does not suppress endogenous alpha-chain gene rearrangement and may trigger the expansion/activation of various self-reactive T cells expressing endogenous TCR alpha- and beta-chains. Furthermore, it appears that the transgene-induced autoimmune T cells are not deleted in the normal thymus or rendered anergic upon contact with the normal target self Ag, but can be controlled by a T cell-dependent mechanism, since transfer of the transgenic bone marrow cells to histocompatible SCID mice produces the same autoimmune disease as in the donors, and the autoimmune development in the SCID mice is effectively prevented by co-transfer of syngeneic nontransgenic T cells. This novel autoimmune model produced by genetic manipulation of the T cell lineage, not the target self Ag or the environment of T cell differentiation/selection, should be useful for elucidating the immunologic and genetic basis of autoimmune disease.

Age Factors↗
PubMed1994

Cell growth suppression of astrocytoma C6 cells by glial fibrillary acidic protein cDNA transfection.

The cellular functions of the intermediate filament family including glial fibrillary acidic protein (GFAP) are not well known yet beyond their roles as structural elements of cells. Expression of GFAP, which is specific in astrocytes and regulated developmentally, suggests its involvement in cell growth and differentiation of astrocytes. We transfected murine GFAP cDNA into a rat astrocytoma C6 cell line to assess the specific effect of GFAP on cells. Two stable GFAP-transfected cell lines, GFC6-5 and GFC6-6, exhibited a series of morphological and growth characteristics that distinguish them from their counterparts, i.e., NeoC6 cells transfected only with the neomycin-resistant gene, and native C6 cells. Both GFC6-5 and GFC6-6 cells showed elongated cell shapes with extended processes rich in GFAP, markedly suppressed cell growth, and decreased bromodeoxyuridine uptake. Western blot analysis revealed a remarkable increase of GFAP expression in GFC6-5 and GFC6-6 compared with that in NeoC6 and C6, in contrast to similar vimentin expression in all cell lines. The results indicate that the expression of GFAP has dramatic effects on cell morphology and cell growth suppression in C6 cells, suggesting that GFAP may function as a tumor suppressor in astrocytoma.

Animals↗
PubMed1994

[Effect of catechin on the ultrastructure of Trichophyton mentagrophytes].

The effects of (-) epigallocatechin gallate (EGCg) on the morphology of hyphae and conidia of Trichophyton mentagrophytes were examined using scanning and transmission electron microscopy. EGCg inhibited the germination of conidia and subsequent hyphal growth. After being treated with EGCg for 3 days, conidia showed morphological changes such as deformation, swelling, wrinkles, exfoliation of the surface layer and accumulation of granular, amorphous materials on the conidia and short hyphae surfaces. These morphological changes became apparent day by day. After 5 days, most of the ungerminating conidia were broken down. The hyphal cell walls were also exfoliated and the cytoplasm in most of the cells disappeared completely. Inner organellas were variable in size and shape. Many high electron dense particles, greatly enlarged vacuoles appeared in the cytoplasm. The degradation of cells occurred. These observations indicates that EGCg causes lysis of the conidia and hyphae. These findings suggest that EGCg may be used as an antidermatophytic agent against T. mentagrophytes infection.

Catechin↗
PubMed1994

[Inhibition of the infectivity of influenza virus by black tea extract].

We determined whether black tea extract inhibits the infectivity of influenza virus to mice. When mice were inoculated intranasally with 10(5.3) PFU influenza viruses (10(1.3) LD50), their body weight decreased and all died within 10 days. Whereas, when mice were inoculated i.n. with the mixture of influenza viruses and 2% (w/w) black tea extract, 5 min after mixing, all mice showed normal body-weight increase and survived. Neutralizing antibody to influenza virus was not detected in nine of 10 survived mice. The results indicate that black tea extract at beverage concentration (2% w/w) inhibits almost completely the infectivity of influenza virus to mice and that in vivo reversion of the tea-inactivated influenza virus does not occur.

Animals↗
PubMed1994

[Rearing related stress and depressive severity].

Mothers' difficulties concerning child-rearing were conceptualized as a rearing-related stress (RRS). Eight hundred and seventeen mothers who had six month-olds infants were asked to rate 28 RRS items and 20 items on the depressive severity scale (Zung, 1956). The main results were summarized as follows: (1) Twenty-two items of RRS were analyzed by Hayashi's quantification (type-III) method, and two hypothesized dimensions were extracted. These are named children-related rearing stress (CRRS) and mothers-related rearing stress (MRRS). (2) RRS was related to mothers depressive severity. (3) Linear relationships of "CRRS-MRRS-depression severity" was examined by partial correlation analysis. (4) Primiparae experienced more RRS than multiparae. These results suggested that RRS could be considered as a process, i.e., CRRS influences MRRS and then MRRS influences depressive severity. The RRS model is an accord with the psychological stress model of Lazarus and Folkman (1986). Lastly, possible preventive strategies for mothers' RRS were discussed in the light of RRS model.

Adolescent↗
PubMed1993

Molecular cloning of cDNA encoding human drebrin E and chromosomal mapping of its gene.

Drebrins are novel actin-binding proteins in the brain which are developmentally regulated. Three isoforms: two embryonic types (E1 and E2) and an adult type (A) are generated by alternative RNA splicing from a single debrin gene in the chicken brain. A full length cDNA clone of human drebrin E has been isolated from a cDNA library of human fetus brain. The clone is 2596 base pairs in length and contains an open reading frame of 1947 nucleotides encoding a protein of 649 amino acids. The deduced amino acid sequence, except for the internal 138-nucleotide sequence (ins2), exhibits 88% homology with rat drebrin A. Spot blot hybridization using flow-sorted human chromosomes provides evidence that the gene encoding human drebrin protein locates on human chromosome 5.

Amino Acid Sequence↗
PubMed1993

Characterization of the T cell receptor repertoire causing collagen arthritis in mice.

Collagen type II-induced arthritis (CIA) is generated in susceptible rodent strains by intradermal injections of homologous or heterologous native type II collagen in complete Freund's adjuvant. Symptoms of CIA are analogous to those of the human autoimmune disease, rheumatoid arthritis. CIA is a model system for T cell-mediated autoimmune disease. To study the T cell receptor (TCR) repertoire of bovine type II-specific T cells that may be involved in the pathogenesis of CIA in DBA/1Lac.J (H-2q) mice, 13 clonally distinct T cell hybridomas specific for bovine type II collagen have been established and the alpha and beta chains of their TCRs have been analyzed. These T cell hybridomas recognize epitopes that are shared by type II collagens from distinct species and not by type I collagens, and exhibit a highly restricted TCR-alpha/beta repertoire. The alpha chains of the TCRs employ three V alpha gene subfamilies (V alpha 11, V alpha 8, and V alpha 22) and four J alpha gene segments (J alpha 42, J alpha 24, J alpha 37, and J alpha 32). The V alpha 22 is a newly identified subfamily consisting of approximately four to six members, and exhibits a high degree of polymorphism among four mouse strains of distinct V alpha haplotypes. In addition, the beta chains of the TCRs employ three V beta gene subfamilies (V beta 8, V beta 1, and V beta 6), however the V beta 8.2 gene segment is preferentially utilized (58.3%). In contrast, the J beta gene segment usage is more heterogeneous. On the basis of the highly limited TCR-alpha/beta repertoire of the TCRs of the panel of bovine type II-specific T cell hybrid clones, a significant reduction (60%) of the incidence of arthritis in DBA/1Lac.J mice is accomplished by the use of anti-V beta 8.2 antibody therapy.

Amino Acid Sequence↗