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Biomedical subjects

T Ichimaru

Publications and source records attributed to T Ichimaru.

At least 37 records · Page 2Linked to original sources

[Inhibitory effects of saiboku-to and compornent herbs on the production of peptide leukotrienes (LTs) and LTB4].

We investigated the effects of Saiboku-to, Syoseiryu-to and compornent herbs of these two Kampo-Medicines (Saiko, Hange, Bukuryo, Ogon, Koboku, Taiso, Ninjin, Kanzo, Soyo, Syokyo, Keihi, Gomisi, Saisin, Syakuyaku, Mao and Kankyo) on the production of peptide leukotrienes (LTs) and LTB4 in cultured rat basophilic leukemia (RBL)-1 cells. Cultured RBL-1 cells were stimulated with Ca ionophore, A23187, at 10(-5) M in the absence or presence of various concentrations of these substances, and the production of peptide LTs and LTB4 was measured by reversed phase-high performance liquid chromatography (RP-HPLC). The production of LTs was dose-dependently suppressed by the addition of Saibokuto. Saiboku-to (100 micrograms/ml) showed 35% and 30% inhibition on the production of peptide LTs and LTB4, respectively. These inhibitory actions of Saiboku-to on LT-synthesis were attributable to the effects of its component herbs, Ogon, Koboku and Kanzo. On the other hand, Syoseiryu-to showed no inhibitory action on LT-production. these results indicate that anti-allergic action of Saiboku-to is, at least in part, attributable to its inhibitory action on LT-synthesis.

Animals↗

Saiboku-To, a herbal extract mixture, selectively inhibits 5-lipoxygenase activity in leukotriene synthesis in rat basophilic leukemia-1 cells.

Saiboku-To, a mixture of extracts from 10 medicinal herbs, has been used for the treatment of bronchial asthma in Japan. Inhibitory action of this drug on arachidonate 5-lipoxygenase (5-LO) metabolism in rat basophilic leukemia cells (RBL-1 cells) was examined. Saiboku-To significantly inhibited calcium ionophore-stimulated synthesis of cysteinyl leukotrienes (cLTs) and leukotriene B4 (LTB4). Inhibition appeared 10 min after addition of the substance and reached a maximal value after 3 h. Saiboku-To did not inhibit the release of [3H]arachidonic acid (AA) from cell membrane by calcium ionophore stimulation, or the production of cLTs and LTB4 when LTA4-free acid was used as the substrate. However, it significantly inhibited the production of cLTs and LTB4 when free AA was used as the substrate. The production of thromboxane A2 (TXA2). a cyclooxygenase metabolite, was not inhibited when AA was used as the substrate in cell free study. These results indicate that Saiboku-To selectively inhibits 5-LO activity in the metabolic pathway of AA.

Animals↗

Cyclosporin A inhibits leukotriene production in intact RBL-1 cells without inhibiting leukotriene biosynthetic enzymes.

The effects of cyclosporin A (CSA) on arachidonic acid (AA) metabolism were investigated in intact rat basophilic leukemia-1 (RBL-1) cells and cell lysates. Calcium ionophore (A23187)-stimulated synthesis of cysteinyl leukotrienes (LTC4, LTD4, and LTE4), LTB4, and 5-hydroxyeicosatetraenoic acid (5-HETE) in intact cells in the absence or presence of CSA was measured by reversed-phase high-performance liquid chromatography (HPLC). CSA inhibited the production of cysteinyl LTs, LTB4, and 5-HETE in intact cells in a dose-dependent manner. The synthesis of cysteinyl LTs, LTB4, and 5-HETE was also measured after the incubation of cell lysates with free AA in the absence or presence of CSA. CSA did not inhibit synthesis of cysteinyl LTs, but rather stimulated production of LTB4 and 5-HETE in cell lysate. A23187-stimulated release of incorporated [3H]AA from intact cells was not inhibited by CSA. CSA did not inhibit the synthesis of cysteinyl LTs and LTB4 when cells incubated with LTA4 as the substrate. These results indicate that the inhibitory effects of CSA on the synthesis of LTs and 5-HETE in intact cells are attributable to a modulatory action on a step in the series of intracellular events that includes the activation of 5-lipoxygenase, which are initiated by Ca2+ influx and end in the release of metabolites from the cell membrane, rather than to a direct inhibitory action on enzymes in the LT biosynthetic pathway.

Animals↗

IL-3 and IL-5 enhance the production of LTB4 stimulated by calcium ionophore in rat basophilic leukemia cells.

To determine the regulatory mechanism of Leukotriene (LT) B4 synthesis by cytokines, we investigated the regulation of LTB4 generation by short-term (30 min) priming and long-term (15 h) enzyme-inducing actions of the four cytokines interleukin (IL)-3, IL-5, tumor necrosis factor alpha (TNF-alpha), and transforming growth factor alpha (TGF-alpha) in rat basophilic leukemia-1 (RBL-1) cells. Pretreatment of cells with IL-3 or IL-5 for 30 min increased A23187- (5x10(-9)M) stimulated synthesis of LTB4 by three to four times over control levels. However, IL-3 or IL-5 lacked this effect when stimulated with exogenous arachidonic acid A at 10(-4)M. TNF-alpha and TGF-alpha had no priming effect on LTB4 synthesis following stimulation with either A23187 (5x10(-9)M) or AA(10(-4)M). Stimulation with the calcium ionophore (A23187)(10(-5)M) or AA(10(-4)M) following 15-h exposure to these cytokines had no effect. These results suggest that IL-3 and IL-5 increase the production of LTB4 by priming the activity of phospholipase A2(PLA2) without inducing enzymes in the arachidonate 5-lipoxygenase pathway. Such a priming effect may be important in regulating the development of allergic and other diseases involving the inflammatory reaction.

Animals↗

Inhibition of leukotriene production by FK506 in rat basophilic leukemia-1 cells.

We investigated the inhibitory action of FK506 (0.0005-5 micrograms/ml) on the metabolism of arachidonate 5-lipoxygenase in rat basophilic leukemia-1 cells. Cells were stimulated with A23187 (10(-5) mol/l) for 15 min in the absence or presence of various concentrations of FK506. Arachidonate 5-lipoxygenase metabolites, peptide leukotrienes (LTs), leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) were measured by high-performance liquid chromatography. FK506 inhibited A23187-stimulated production of peptide LTs, LTB4 and 5-HETE in intact cells by up to 77, 73 and 60%, respectively. Phospholipase A2 activity, measured by the release of 3H-arachidonic acid (AA), was not significantly inhibited by FK506. The synthesis of peptide LTs and LTB4 was not inhibited by FK506 when leukotriene A4-free acid was added to the culture medium. The synthesis of peptide LTs, LTB4 and 5-HETE was not affected by FK506 in a cell lysate study using AA as the substrate. These results indicate that FK506 inhibits the production of peptide LTs, LTB4 and 5-HETE by inhibiting 5-lipoxygenase activity in intact cells. The inhibition is not a direct action on 5-lipoxygenase but results from the activating processes of this enzyme.

Animals↗

Specific induction of LTC4 synthase by retinoic acid in rat basophilic leukemia-1 cells.

Overnight (10-16 h) incubation of retinoic acid (RA), a derivative of vitamin A, specifically induced LTC4 synthase activity (5 to 10-fold), but not LTA4 hydrolase activity in the lysate of rat basophilic leukemia-1 (RBL-1) cells. A time course study revealed that the increase of LTC4 synthase activity was time dependent and that the peak value was obtained after a 24-hour incubation with RA. The induction of enzyme activity was specifically localized to the microsomal fraction. Glutathione (GSH) S-transferase activity measured by using the same cell lysate as an enzyme source and 1-chloro-2,4-dinitrobenzene (DNCB) as a substrate was not influenced by RA treatment, indicating that the induction by RA is specific for membrane-bound LTC4 synthase. The induction of LTC4 synthase may be an important regulatory mechanism of peptide-LT synthesis in allergy and inflammatory diseases.

Animals↗

Inhibition by dexamethasone of retinoic acid-induced enhancement of leukotriene C4 synthesis in rat basophilic leukemia-1 cells.

We investigated inhibitory actions of dexamethasone (DEX) on retinoic acid (RA)-induced enhancement of leukotriene C4 (LTC4) synthesis in rat basophilic leukemia-1 (RBL-1) cells. Cultured cells were preincubated with RA for 16 h with or without DEX, and generation of LTC4 was measured by high performance liquid chromatography in cell-free and intact cell systems. RA (0.1 microgram/ml) significantly potentiated calcium ionophore-stimulated production of LTC4 synthesis. DEX inhibited the RA-induced enhancement of LTC4 synthesis by up to approximately 95% in intact cells when stimulated with calcium ionophore. RA-induced LTC4 synthase activity, which was determined by enzyme assay, was also inhibited by DEX by 65% in a cell-free system. This discrepancy of inhibition between the intact and cell-free systems was due to a partial inhibition of phospholipase A2 activity by DEX in the intact cells. These results indicate that the production of LTC4 is predominantly regulated at a level of LTC4 synthase. The induction of new LTC4 synthase activity by RA and inhibition of the RA-induced activity by DEX are important regulatory mechanisms of LTC4 synthesis.

Animals↗

Treatment of severe pertussis by administration of specific gamma globulin with high titers anti-toxin antibody.

Our patient presented with severe respiratory distress and marked pleocytosis. She was mechanically ventilated and received gamma globulin with high titers of anti-pertussis toxin and anti-filamentous hemagglutinin. Her clinical signs improved and a notable decrease in white blood cell count was observed. Ten months after treatment, the patient showed normal physical and mental development and anti-pertussis toxin and anti-filamentous hemagglutinin titers were significantly increased. Recently, the effectiveness of gamma globulin therapy has been emphasized again. Our experience supports the use of iv gamma globulin infusion. Also, gamma globulin did not influence the patient's own immunologic response to pertussis. Gamma globulin therapy with high anti-pertussis toxin titers could be considered for treatment of severe pertussis.

Antitoxins↗

Alteration of platelet activating factor (PAF) metabolism in rat pulmonary alveolar macrophages and plasma by cigarette smoking.

The pathophysiological role of platelet activating factor (PAF) in smoking-induced disorders was examined in rats exposed daily to smoke for 10, 18 and 26 weeks. The concentration of PAF in bronchoalveolar lavage fluid and the activities of PAF biosynthetic and catabolic enzymes in alveolar macrophages and in plasma were determined. The concentration of PAF in lavage fluid of the smoke-exposed group was significantly lower than that in the sham group for each duration of smoke exposure. The PAF biosynthetic enzyme, acetyl transferase, activity in alveolar macrophages of smoked group was less than that in the sham group although the difference was not statistically significant. PAF catabolic enzyme, acetyl hydrolase, activities in alveolar macrophages and in plasma were all significantly higher in every smoked group than in the sham group. These data indicate that cigarette smoking alters PAF metabolism in the respiratory tract and in plasma and such an alteration may contribute, at least in part, to smoking induced cardiopulmonary disorders.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

[Application of fluoro-resins on the tissue surface of pontic].

The purpose of this study was to investigate the applicability of fluoro-composite resins for clinical usage. Polychlorotrifluoroethylene (PCTFE) resin was applied to the tissue surface of pontic for 7 days in the oral cavity, and the amount of plaque accumulation was measured. The plaque retaining capacity of PCTFE was compared with Au-Ag-Pd alloy and porcelain. In order to survey the endurance of PCTFE-resin, the surface of PCTFE-coating was observed under SEM. The results were as follows: 1. Plaque accumulation on the PCTFE-coating was less than that of metal, and was equivalent to or less than that of porcelain. 2. Pin-point like plaque formation similar to that found on porcelain surfaces were observed on the PCTFE-coating. 3. SEM observations of the PCTFE-coating revealed some traces made by the toothbrush. As a result, PCTFE-coating was found to be useful for decreasing the amount of plaque formation on those pontic surfaces where mechanical cleaning can not be maintained.

Composite Resins↗

[Plaque accumulation (S. mutans) in various dental restorative materials and fluoro-resins (in vitro)].

The quantities of in vitro accumulated plaque (S. mutans), cultured in 5% sucrose BHI broth, to the surface of PMMA, Co-Cr alloy, porcelain, PTFE, PCTFE, Composite PCTFE, and detachment time as an indicator of plaque retaining capacity, were measured. The former increased with the increase in surface roughness on all materials, except for the Co-Cr alloy, and with contact angles, which suggests that hydrophobic interaction may play an important role for formation of plaque on materials. By contrast, the quantities of accumulated plaque, cultured in 5% sucrose BHI broth containing synthetic saliva constituents, to the surface of various materials, also increased with the increase in surface roughness, but decreased with values of contact angles, which suggest that the effect of hydrophobic interaction on forming plaque to materials seems to be weakened by constituents of synthetic saliva.

Composite Resins↗

Mass screening for heart disease of school children in Saga city: 7-year follow up study.

1. At the initial screening, 6.11% of elementary school children and 6.28% of junior high school students were picked up for the second screening. At the second screening, 0.49% of elementary school children and 0.85% of junior high school students were referred to the final screening. The pick-up ratio was significantly higher in junior high school children. The ratio of children needing medical management was also significantly higher for junior high school students (2.96%) than for elementary school children (2.26%). 2. The reexamination system was useful for management of a group of children with minimal findings of ECG at minimal cost and effort and without giving rise to unnecessary anxiety for the children and their families. 3. In order to manage children from elementary school to junior high school without any risk, it is essential to establish more sophisticated systems of managing patient-records, such as computer managing systems. 4. In order to increase the reliability of questionnaires, it is necessary to explain the significance of the mass screening system for the prevention of cardiac accidents, to refine the questions and to give more easily understood instructions.

Child↗