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T Minagawa

Publications and source records attributed to T Minagawa.

At least 19 recordsLinked to original sources
PubMed1992

Cardiovascular responses induced in free-moving rats by immune cytokines.

1. We investigated the effect of intraperitoneal (I.P.) injections of the immune cytokines, interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) on cardiovascular responses in free-moving rats, using a biotelemetry system. 2. The I.P. injection of a small dose of IL-1 beta (1 microgram/kg) induced a monophasic increase in the heart rate, and that of a large dose (10 micrograms/kg) induced biphasic increases in the blood pressure and heart rate. However, the I.P. injection of any of several doses of TNF (1, 10 and 50 micrograms/kg) had no effect on cardiovascular responses in rats. 3. Pre-treatment with I.P. injection of indomethacin (10 mg/kg), an inhibitor of cyclo-oxygenase, significantly suppressed the cardiovascular responses and the increase in the plasma noradrenaline (NA) concentration induced by I.P. injection of IL-1 beta. 4. Microinjection of IL-1 beta (1 and 10 ng) into the preoptic and anterior hypothalamic (PO-AH) region induced dose-dependent increases in the blood pressure and heart rate in rats. These responses were also suppressed by pretreatment with I.P. indomethacin (10 mg/kg). In addition, microinjection of prostaglandin E2 (20 and 100 ng) into the PO-AH region increased blood pressure and heart rate, but that of prostaglandin D2 (100 ng) had no effect. 5. The present results suggest that IL-1 beta stimulates the release of prostaglandins, presumably E series, near regions of the hypothalamus, which act on the hypothalamus to induce activation of the sympathetic nervous system. Subsequently, the blood pressure, heart rate and the plasma level of NA increase.

Animals↗
PubMed1992

Endogenous tumor necrosis factor, interleukin-6, and gamma interferon levels during Listeria monocytogenes infection in mice.

Mice were infected intravenously with a sublethal dose of Listeria monocytogenes cells and then levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), and gamma interferon (IFN-gamma) in the bloodstreams, spleens, and livers were monitored. The maximum level of TNF was detected at 72 h in the spleens and livers, but TNF was never detected in the bloodstreams. IL-6 appeared in the bloodstreams and spleens and peaked at 48 h. The maximum level of IFN-gamma could be detected in all three specimens, and the highest titer was shown in the spleens. Endogenous TNF production was suppressed by in vivo administration of anti-CD4 monoclonal antibody (MAb) or anti-asialo GM1 antibody but not by anti-CD8 MAb, whereas none of these antibodies suppressed endogenous IL-6 production. Endogenous production of neither IL-6 nor IFN-gamma was inhibited in rabbit anti-recombinant mouse TNF-alpha antibody-treated mice. Similarly, production of TNF and IL-6 did not decrease in anti-mouse IFN-gamma MAb-treated animals, but TNF production was augmented in these animals. These results suggest that the these endogenous cytokines are produced by different mechanisms in L. monocytogenes infection.

Animals↗
PubMed1992

Role of cell-mediated immune reaction in blister formation of bullous pemphigoid.

In patients with bullous pemphigoid (BP), early lesions appear as exudative erythematous patches. Histologically, the inflammatory infiltrate is composed mainly of mononuclear cells (MNCs) in the erythematous lesion, although eosinophils and neutrophils are also present. The MNCs are predominantly helper/inducer T cells even in the bullous lesions. Some of the MNCs infiltrated were stained in cytoplasm by antihuman gamma-interferon (IFN-gamma) monoclonal antibody (MoAb) immunohistologically. These infiltrates are considered to produce IFN-gamma. In the bullous fluids of early BP lesions, high levels of IFN-gamma are detected by radioimmunoassay using antihuman IFN-gamma MoAb. The results suggest that infiltrating lymphocytes are stimulated immunologically in BP bullous lesions. Cell-mediated immune reaction as well as autoantibody to the basement membrane zone may also play an important role in blister formation in BP.

B-Lymphocytes↗
PubMed1992

[The distribution and localization of alpha 1-adrenoceptor agonist on the bladder and urethra of female rats].

The distribution of selective alpha 1-adrenoceptor agonist 1-(2',5'-dimethoxyphenyl)-2-glycinamidoethanol hydrochloride, midodrine, and its active metabolite 1-(2',5'-dimethoxyphenyl)-2-aminoethanol, DMAE, was evaluated on bladder and urethra of 8-weeks and 52-weeks old female rats. Prior to the intravenous injection of 14C-labeled midodrine and DMAE, bilateral ureters were ligated to prevent drug uptake from the urinary tract. In 8-weeks rats, 14C-midodrine activity was significantly (p less than 0.01) higher in the bladder than in the femoral muscle, which served as a control for drug distribution. Similarly, higher uptake of 14C-DMAE was observed in the bladder than in the femoral muscle (p less than 0.01) and the urethra (p less than 0.05). In 52-weeks rats, there was no significant difference of midodrine uptake among these tissues. However, significantly higher uptake of 14C-DMAE was observed in the urethra than in the femoral muscle (p less than 0.05). Compared with midodrine, the concentration of DMAE was significantly increased in the bladder of 8-weeks rat and in the urethra of 52-weeks rats (respectively, p less than 0.05). In autoradiogram, the grains corresponding to midodrine and DMAE were diffusely distributed on the smooth muscles of bladder (mainly bladder neck and trigone) and urethra. The grains were also recognized on the vessels and perivascular areas of these tissues. These findings support that midodrine and DMAE could be effective for stress incontinence, because these drugs are known to bind specifically to alpha 1-adrenoceptor.

Adrenergic alpha-Agonists↗
PubMed1991

Functional evaluation of tumor-infiltrating mononuclear cells. Detection of endogenous interferon-gamma and tumor necrosis factor-alpha in human colorectal adenocarcinomas.

Quantitative evaluation of the levels of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the extracts of tumors and their corresponding normal tissues resected from 43 patients with colorectal adenocarcinoma was done using solid-phase, sandwich radioimmunoassay. The levels of both IFN-gamma and TNF-alpha detected in the tumor tissues were higher than those in the corresponding normal colorectal tissues obtained from each patient. A significant negative correlation was observed between the level of IFN-gamma and TNF-alpha in each tumor extract. The decrease of the level of IFN-gamma in the tumor correlated with the advance of clinical stage, and the levels of IFN-gamma of the patients with distant metastases were significantly lower than those of the patients without distant metastases. However, an increase in the level of TNF-alpha correlated not only with an enlarged diameter but also with the extent of the primary tumor. Immunohistochemical staining of IFN-gamma and TNF-alpha producing cells in tumor tissues showed that IFN-gamma was mainly produced by CD4+ CD8- T-lymphocytes and TNF-alpha was mainly produced by CD11c+ cells with macrophage-like morphology. These results suggest that CD4+ T-lymphocytes that produce IFN-gamma might play an important role in the antitumor response against cancer progression in human colorectal adenocarcinomas.

Adenocarcinoma↗
PubMed1991

Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells.

We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL.

Cytokines↗
PubMed1991

Immunoregulatory cytokine release in rat spleen cell cultures after treatment with bleomycin and its analogues in vivo.

We have studied the immunological effects that accompany a change in the chemical structure of a group of antineoplastic antibiotics by comparing the immunoregulatory cytokine release during mitogen-stimulated spleen cell culture after in vivo drug treatment. Whereas bleomycin and peplomycin increased cytokine levels in culture supernatants when compared with supernatants from untreated control rat spleen cell cultures, liblomycin generally reduced cytokine levels under the same culture conditions. We then compared these results with the antitumor effects of equivalent doses of the three drugs against a highly antigenic rat fibrosarcoma, KMT-17, both in vivo and in vitro. The results suggest that the immunoaugmenting effects of these antitumor antibiotics are essential for an optimal antitumor effect in vivo, and that these effects can be drastically altered by modification of the chemical structure of the drugs employed.

Animals↗
PubMed1991

Analysis of benzophenones by gas chromatography/Fourier transform-infrared spectrometry.

A gas chromatograph/Fourier transform-infrared spectrometric analysis of benzophenones, as hydrolyzed products of benzodiazepine, was evaluated and the vapor phase spectra obtained were compared with those measured in the condensed phase. Each infrared spectrum obtained in the vapor phase showed a much greater difference in comparison to differences found in those in the condensed phase, especially in the fingerprint region. The identification of 14 benzophenones by their infrared spectra in the vapor phase was possible. The detection limits for these benzophenones were between 50-100 ng with high signal-to-noise ratios. The vapor phase spectra of the benzophenones were unique and the analytical method allowed the differentiation of closely related classes of drugs, such as benzophenones.

Benzodiazepines↗
PubMed1991

Detection of endogenous cytokines in sera or in lymph nodes obtained from patients with sarcoidosis.

To investigate the possible role of endogenous cytokines in the immunopathogenesis of sarcoidosis, a study of cytokines in lymph nodes obtained from patients with active pulmonary sarcoidosis was carried out using immunoperoxidase staining and radioimmunoassays (RIA). Cells stained for interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), which appeared to be CD3+ cells and CD14+ cells, respectively, were seen scattered around granulomas. In contrast, cells positive for interleukin-1 beta (IL-1 beta) were located in CD11c+ cells within granulomas. Lymph nodes of patients with sarcoidosis contained significantly higher amounts of IFN-gamma, TNF-alpha and IL-1 beta than control lymph nodes. The levels of IFN-gamma and TNF-alpha in extracts of lymph nodes were correlated with the histological status of the granulomas. IFN-gamma was detected in all stages, while the highest level of TNF-alpha was obtained from lymph nodes containing many active granulomas. The level of serum IFN-gamma was always lower than in lymph node extract and correlated significantly with either serum angiotensin-converting enzyme or serum lysozyme. Patients with positive gallium-67 uptake or bilateral hilar lymphadenopathy had high levels of either serum IFN-gamma or lysozyme. These results suggest that quantitative analyses of IFN-gamma and TNF-alpha in sera and lymph nodes may serve to elucidate the pathophysiology of sarcoidosis.

Cytokines↗
PubMed1991

Endogenous gamma interferon-independent host resistance against Listeria monocytogenes infection in CD4+ T cell- and asialo GM1+ cell-depleted mice.

The effects of in vivo administration of antibodies against T-cell subsets and asialo GM1 (ASGM1)-bearing cells on endogenous gamma interferon (IFN-gamma) production and host defense in Listeria monocytogenes-infected mice were investigated. Endogenous IFN-gamma titers in the bloodstreams and spleen extracts of mice on day 2 of infection were partially suppressed by administration of rabbit anti-ASGM1 antibody, but not by anti-CD4 monoclonal antibody (MAb) or anti-CD8 MAb. Of the different combinations of these three antibodies, the most suppressive effect on IFN-gamma production was observed after administration of anti-CD4 Mab and anti-ASGM1 antibody, although anti-CD8 MAb combined with anti-CD4 MAb partially inhibited IFN-gamma production. In contrast, antilisterial resistance was suppressed by the administration of anti-CD8 MAb but not by anti-CD4 MAb or anti-ASGM1 antibody. Antilisterial resistance in mice in which both CD4+ cells and ASGM1+ cells had been depleted was performed as efficiently as in normal mice in spite of the fact that endogenous IFN-gamma production was markedly suppressed. Furthermore, these mice also eliminated L. monocytogenes cells efficiently from the spleens even when they were pretreated with anti-mouse IFN-gamma MAb. These results indicate that CD4+ T cells, CD8+ T cells, and ASGM1+ cells are all responsible for endogenous IFN-gamma production and that antilisterial resistance and endogenous IFN-gamma production are not absolutely correlated.

Animals↗
PubMed1991

[The role of gamma-interferon in blister formation of bullous pemphigoid].

Recently it has been reported that cell-mediated immune (CMI) reaction is related to the blister formation as well as the reaction of autoantibody against the basement membrane zone (BMZ-Ab) in bullous pemphigoid (BP). Previously we reported that T-cells infiltrated were producing gamma-interferon (IFN-gamma) and that high levels of IFN-gamma were detected in the blister fluids of BP. In the present study, in order to find the effect of IFN-gamma on the skin, we have done the organ culture of normal skin explants with IFN-gamma. The dermal-epidermal separation (DES) was histologically observed in skin explants which were incubated with high level of IFN-gamma after 24 hours. The DES was found to be located between the basal layer and the site of laminin and type IV collagen. It is considered that IFN-gamma alters the antigenicity and mediates to release some other cytokines in CMI reaction. In addition to these, IFN-gamma seems to directly work on the DES in normal skin. Around the DES of the skin explants, plasminogen activator was accelerated immunohistologically. The results suggest that IFN-gamma mediated by CMI response also plays an important role as well as the autoantibody in the blister formation of BP.

Adult↗
PubMed1990

Immunohistopathologic studies in the development of psoriatic lesion influenced by gamma-interferon and the producing cells.

Immunological studies on psoriasis have been done using monoclonal antibodies (MoAbs) to elucidate the relation between gamma-interferon (IFN-gamma) secreted from inflammatory infiltrate, and the expression of HLA-DR molecule on epidermal keratinocytes in the lesion. In highly inflamed psoriatic lesions, IFN-gamma producing cells were found in the inflammatory infiltrate of the dermal papillae, while keratinocytes located near IFN-gamma+ cells expressed HLA-DR molecules on the surface. In fully developed psoriatic lesions, HLA-DR+ keratinocytes were mainly found in the thin epidermis over the elongated dermal papillae where IFN-gamma deposited not only at infiltrates but also in teh dermal components. The IFN-gamma+ cells were activated T cells which exhibited HLA-DR and interleukin 2 receptor. Munro's microabscess under the horny layer also included IFN-gamma producing cells. A radioimmunoassay by the sandwich method with anti-human IFN-gamma and anti-recombinant IFN-gamma MoAbs found that extracts from psoriatic scales contained IFN-gamma. The results suggest that HLA-DR+ keratinocytes are due to the effect of IFN-gamma secreted by activated T cells in psoriatic lesions. The proliferation of keratinocytes over the dermal papillae in fully developed lesions seemed to be inhibited by IFN-gamma from the inflammatory infiltrate. We consider that cell-mediated immune reaction plays an important role in the development of psoriatic eruption.

Adult↗
PubMed1990

Interferon induction by human herpesvirus 6 in human mononuclear cells.

Interferon (IFN) production after inoculation with human herpesvirus 6 (HHV-6) was studied in peripheral blood mononuclear cells from 10 HHV-6-seropositive healthy adults and five samples of cord blood mononuclear cells. When the cells were exposed to HHV-6 at a multiplicity of infection of 10(-2) 50% tissue culture infectious doses/cell, IFN activity was detected as early as 12 h after exposure to HHV-6, plateaued at days 2-5, and gradually decreased thereafter. IFN was also induced by ultraviolet-inactivated but not heat-inactivated HHV-6. The response of cord blood mononuclear cells was lower than that of the cells from healthy adults. The activity of all IFN samples was stable to acid and exclusively neutralized by anti-human IFN-alpha. The IFN-producing cell population was mainly non-T cells and monocytes. Furthermore, exogenous IFN suppressed HHV-6 replication. Production of IFN-alpha may be an important part of the host response to HHV-6.

Cell Separation↗
PubMed1990

Evidence that endogenous gamma interferon is produced early in Listeria monocytogenes infection.

It has been presumed that gamma interferon (IFN-gamma), which plays an essential role in antilisterial resistance, is produced late in Listeria monocytogenes infection. In the present study, however, IFN-gamma was detected in the bloodstreams and spleens of mice from days 1 to 4 of L. monocytogenes infection by both a double-sandwich enzyme-linked immunosorbent assay and an immunohistochemical technique, suggesting that endogenous IFN-gamma is produced early but not late in L. monocytogenes infection.

Animals↗
PubMed1990

Suppression of host resistance against Listeria monocytogenes infection by 15-deoxyspergualin in mice.

The effects of 15-deoxyspergualin (DSG), an immunosuppressive agent, on host resistance against Listeria monocytogenes were studied in mice. Administration of DSG in the early phase of infection resulted in fatal listeriosis by preventing acquired anti-listerial resistance, even though the infectious dose was sublethal for the untreated controls. In contrast, DSG treatment started after development of the acquired immunity was ineffective. Endogenous production of interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) in the bloodstreams induced by the infection was normal in DSG-treated mice. Nevertheless, augmentation of macrophage functions such as expression of major histocompatibility complex (MHC) class II antigens, phagocytic activity and listericidal activity induced by the infection was abrogated by DSG treatment. These results suggest that the inhibitory effect of DSG on anti-listerial resistance might be different from cyclosporine A (CsA).

Animals↗
PubMed1989

Synergistic action of three recombination gene products of bacteriophage T4, uvsX, uvsY, and gene 32 proteins.

Previously we proved that uvsX protein catalyzes reactions similar to those thought to occur during T4 recombination (Yonesaki, T., Ryo, Y., Minagawa, T., and Takahashi, H. (1985) Eur. J. Biochem. 148, 127-134; Yonesaki, T., and Minagawa, T. (1985) EMBO J. 4, 3321-3327). Now we have found that uvsY protein stabilizes binding of uvsX protein and single-stranded DNA and weakly stimulates those reactions catalyzed by uvsX protein, although it has little activity, if any, by itself. Gene 32 protein also stimulates them weakly at low concentrations, but is strongly inhibitory at high concentrations (Yonesaki, T., and Minagawa, T. (1985) EMBO J. 4, 3321-3327; Formosa, T., and Alberts, B. M. (1986) J. Biol. Chem. 261, 6107-6118). This inhibition is counteracted by uvsY protein. The highest efficiency of uvsX protein is achieved by the co-existence of a small amount of uvsY protein and a large amount of gene 32 protein. We discuss the mechanism and the role of the three proteins in recombination.

Adenosine Triphosphate↗