Biomedical subjects

Shuji Mori

Publications and source records attributed to Shuji Mori.

47 records · Page 3Linked to original sources

PubMed2003

Nafamostat mesilate is an extremely potent inhibitor of human tryptase.

Previously, nafamostat mesilate was found to be a potent inhibitor of human tryptase. In present study, we performed a kinetic study to determine its K(i) value for tryptase and compared it with that of gabexate mesilate. Nafamostat mesilate inhibited human tryptase in a competitive manner. The apparent K(i) value was estimated to be 95.3 pM, which was 1000 times lower than that of gabexate mesilate (95.1 nM). These results strongly indicated that nafamostat mesilate is an extremely potent inhibitor of tryptase and suggested that some of its beneficial effects in the treatment of clinical status may be due to tryptase inhibition.

Benzamidines↗

PubMed2003

The regulation of ICAM-1 and LFA-1 interaction by autacoids and statins: a novel strategy for controlling inflammation and immune responses.

Histamine, prostaglandin E(2), and catecholamines have been demonstrated to regulate the innate and acquired immune responses. In this review, we describe one of the mechanisms common to the action of these agonists; the regulation of the expression of costimulatory adhesion molecules such as ICAM-1 and B7 antigens on monocytes/macrophages. The specific receptor subtypes involved in the action of each agonist were H(2) for histamine, EP(2)/EP(4) for prostaglandin E(2), and beta(2) for catecholamines, all of which are coupled with adenylate cyclase via Gs protein. The regulation of the expression of adhesion molecules by these agonists in turn leads to the modulation of subsequent cytokine production mediated by cell-cell interaction under different stimuli. Histamine is synthesized in monocytes and T cells by the induction of histidine decarboxylase. The inducible histamine has different dynamics from that in storage granules of mast cells and basophils. Also, noradrenaline appears to be synthesized in lymphocytes. Thus, immune cells can produce histamine, prostaglandins, and noradrenaline by themselves and modulate the cell-cell interaction between monocytes and other cells. Some of the inhibitors of HMG-CoA reductase were shown to bind to the ICAM-1-binding domain of LFA-1, reducing the interaction mediated by ICAM-1/LFA-1. The regulation of interaction mediated by adhesion molecules may provide a new target for controlling inflammatory and immune responses.

Animals↗

PubMed2002

Prostaglandin E(2) inhibits IL-18-induced ICAM-1 and B7.2 expression through EP2/EP4 receptors in human peripheral blood mononuclear cells.

Costimulatory molecules play important roles in immune responses. In the present study we investigated the effects of PGE(2) on the expression of ICAM-1, B7.1, and B7.2 on monocytes in IL-18-stimulated PBMC using FACS analysis. Addition of PGE(2) to PBMC inhibited ICAM-1 and B7.2 expression elicited by IL-18 in a concentration-dependent manner. We examined the involvement of four subtypes of PGE(2) receptors, EP1, EP2, EP3, and EP4, in the modulatory effect of PGE(2) on ICAM-1 and B7.2 expression elicited by IL-18, using subtype-specific agonists. ONO-AE1-259-01 (EP2R agonist) inhibited IL-18-elicited ICAM-1 and B7.2 expression in a concentration-dependent manner with a potency slightly less than that of PGE(2), while ONO-AE1-329 (EP4R agonist) was much less potent than PGE(2). The EP2/EP4R agonist 11-deoxy-PGE(1) mimicked the effect of PGE(2) with the same potency. ONO-D1-004 (EP1R agonist) and ONO-AE-248 (EP3R agonist) showed no effect on IL-18-elicited ICAM-1 or B7.2 expression. These results indicated that EP2 and EP4Rs were involved in the action of PGE(2). Dibutyryl cAMP and forskolin down-regulated ICAM-1 and B7.2 expression in IL-18-stimulated monocytes. As EP2 and EP4Rs are coupled to adenylate cyclase, we suggest that PGE(2) down-regulates IL-18-induced ICAM-1 and B7.2 expression in monocytes via EP2 and EP4Rs by cAMP-dependent signaling pathways. The fact that anti-B7.2 as well as anti-ICAM-1 Ab inhibited IL-18-induced cytokine production implies that PGE(2) may modulate the immune response through regulation of the expression of particular adhesion molecules on monocytes via EP2 and EP4Rs.

Antibodies↗

PubMed2002

Essential role of ICAM-1/LFA-1 interaction in synergistic effect of IL-18 and IL-12 on IFN-gamma production in human PBMC.

IL-18 (0-100 ng/ml) specifically upregulated ICAM-1 expression on monocytes in human PBMC as demonstrated in our previous study. In the present study, we examined whether the synergistic upregulation of ICAM-1 occurred after the stimulation with the combination of IL-18 and IL-12 and whether the synergistic production of IFN-gamma was dependent on the interaction between ICAM-1 on monocytes and LFA-1 on NK/T cells. The effect of IL-12 on ICAM-1 expression on monocytes was marginal even at the highest concentration (100 ng/ml). However, in the presence of IL-12 (100 ng/ml), the expression of ICAM-1 induced by IL-18 was significantly enhanced as compared with that obtained by IL-18 alone. In addition to the expression of ICAM-1 on monocytes, IFN-gamma production was synergistically stimulated by IL-18 and IL-12. Anti-ICAM-1 and anti-LFA-1 Abs exhibited significant inhibitory effect on enhanced production of IFN-gamma by the combination of two cytokines, in particular, anti-ICAM-1 showing the complete inhibition. These results as a whole indicated that synergistic effect of IL-18 and IL-12 on IFN-gamma production in human PBMC is ascribed to the synergism of the effect of two cytokines on ICAM-1 expression on monocytes and that the subsequent ICAM-1/LFA-1 interaction plays an important role in the enhanced production of IFN-gamma.

Antibodies, Monoclonal↗

PubMed2002

Reaction times and anticipatory skills of karate athletes.

Two experiments were conducted to investigate the reaction times (RTs) and anticipation of karate athletes. In Experiment 1, choice RTs and simple RTs were measured with two types of stimuli. One was videotaped scenes of opponent's offensive actions, which simulated the athletes' view in real situations, and the other was static filled circles, or dots. In the choice RT task, participants were required to indicate as soon as possible whether the offensive actions would be aimed at the upper or middle level of their body, or the dot was presented either at a higher or a lower position. In the simple RT task, they were required to respond as soon as possible when the offensive action started from a static display of the opponent's ready stance, or a dot appeared on the display. The results showed significant differences between the karate athletes and the novices in the choice RT task, the difference being more marked for the video stimuli than for the dot stimuli. There was no significant difference in simple RT between the two groups of participants, for either type of stimuli. In Experiment 2, the proportions of correct responses (PCRs) were measured for video stimuli which were cut off at the seventh frame from the onset of the opponent's offensive action. The athletes yielded significantly higher PCRs than the novices. Collectively the results of the two experiments demonstrate the superior anticipatory skills of karate athletes regarding the target area of an opponent's attack (Scott, Williams, & Davids, Studies in perception and action II: Posters presented at the VIIth International conference on Event Perception and Action, Erlbaum, Hillsdale, NJ, 1993, p. 217; Wiiliams & Elliot, Journal of Sport & Exercise Psychology 21 (1999) 362), together with their advantage over novices in non-specific sensory functions (e.g., vertical discrimination).

Adult↗

PubMed2002

Lateralized effects of target location on reaction times when preparing for manual aiming at a visual target.

To elucidate the temporal characteristics of information processing for motor action differing in complexity in relation to both perceptual and cognitive information processing, we investigated whether the reaction times (RTs) to a visual target would be affected by task complexity (finger lifting or manual aiming), pre-cueing (with a pre-cue or without a pre-cue), or target location (five horizontal positions). Using the right hand, seven right-handed subjects performed two tasks, finger lifting and manual aiming at a target, with or without a pre-cue. The pre-cue announced the location of the target to be presented. An ANOVA showed significant interactions between task and location and between pre-cue and location with no significant interaction between task and pre-cue, indicating that the task-location interaction does not depend on whether or not a pre-cue is given. The manual-aiming RTs were longer than the finger-lifting RTs, and the effects of the target location on the RTs differed for finger lifting and manual aiming. It can be assumed that the longer RTs of manual aiming reflect the time for information processing that is needed when preparing for the aiming action per se, which is an extra movement performed in addition to the simple initiation of finger lifting. Differential RTs (DRTs) calculated by subtracting the finger-lifting RTs from the aiming RTs were therefore examined. The DRTs significantly differed for target locations (i.e., a lateralized effect), with the DRTs for an ipsilateral target appearing to be significantly shorter than those for contralateral and central targets. The lateralized effect appearing on the DRTs may be mediated by the processing of visual-spatial information about visual targets as motor preparations are made for manual aiming.

Adult↗

PubMed2002

Histamine regulation of interleukin-18-initiating cytokine cascade is associated with down-regulation of intercellular adhesion molecule-1 expression in human peripheral blood mononuclear cells.

In the previous study, we demonstrated that interleukin (IL)-18 up-regulated intercellular adhesion molecule-1 (ICAM-1) expression on monocytes in human peripheral blood mononuclear cells (PBMC) and that heterotypic interaction between monocytes/T or NK cells through ICAM-1/LFA-1 intensified the production of IL-12, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) in PBMC. In the present study, we demonstrate that histamine inhibited the ICAM-1 expression in monocytes induced by IL-18 using flow cytometry and that the responses of IL-12, IFN-gamma, and TNF-alpha induced by IL-18 were concentration dependently inhibited by coexisting histamine, whereas IL-18-inhibited IL-10 production was reversed by the same concentrations of histamine. The modulatory effects of histamine on ICAM-1 expression and cytokine production were all concentration dependently antagonized by famotidine but not by d-chlorpheniramine and thioperamide, and were mimicked by selective H(2)-receptor agonists but not by H(1)- and H(3)-receptor agonists, indicating the involvement of H(2)-receptors in histamine action. The inhibition of IL-18-induced IFN-gamma by histamine was ascribed to the strong inhibition of IL-12 production by histamine. Histamine thus operates the negative feedback mechanism against IL-18-activated cytokine cascade through the strong inhibitory effect on ICAM-1 expression and IL-12 production in monocytes, contributing to the formation of diverse pattern of cytokine activation from Th1 to Th2, depending on the monocyte/macrophage activation and cytokine environment.

Cell Aggregation↗

PubMed2002

Spatial-frequency uncertainty and cuing effects on psychometric functions for contrast detection.

In the present study, the effects of spatial-frequency uncertainty and cuing on psychometric functions for contrast detection of sinusoidal gratings are examined. For this purpose, psychometric functions were collected from 4 subjects under fixed-frequency, randomized-frequency, and cued-frequency conditions. The experiment was conducted with a temporal two-alternative forced-choice task, and five spatial frequencies in the range of 0.5 and 8.0 c/deg and seven contrast levels for each frequency were used. The results showed that the psychometric functions for the randomized-frequency condition were shallower than those for the fixed-frequency condition, supporting the single-band model for the uncertainty effects (Hübner, 1993a, 1993b). For the cued-frequency condition, the slopes of the functions were not clearly different from those for the randomized condition. These results clearly differ from those of Hübner (1996b), which showed, in the spatial two-alternative forced-choice task, steeper psychometric functions for the randomized-frequency condition than those for the fixed- and cued-frequency conditions, supporting the multiple-band model (Hübner, 1993a, 1993b). The difference suggests that the single-band model applies to the uncertainty effects in the temporal forced-choice task, whereas the multiple-band model does so in the spatial forced-choice task.

Adult↗

PubMed2002

Elevation of antioxidant potency in mice brain by low-dose X-ray irradiation and its effect on Fe-NTA-induced brain damage.

The increase in lipid peroxide levels in mice brain following Fe3+ administration was about 50% of that when 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) was administered. This may be due to excessive oxidation by Fe3+, and was supported by the decrease in activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX), Na+,K(+)-ATPase activity and membrane fluidity after Fe3+ administration. Relatively low-dose X-ray irradiation (0.5 Gy) inhibited lipid peroxidation associated with Fe3+ administration and restored the decreased activities of the above antioxidant enzymes and Na+,K(+)-ATPase, and membrane fluidity to the levels in the non-Fe(3+)-administered group. In the purine metabolism system, uric acid decreased after Fe3+ administration, which may be due to transient impairment of the system for production of uric acid from xanthine by excessive oxidation by Fe3+. However, 0.5 Gy irradiation inhibited this decrease in uric acid, increasing its level to that in the non Fe(3+)-administrated group. This may be due to factors such as rapid recovery of the activities of the above antioxidant enzymes and Na+,K(+)-ATPase, and membrane fluidity after 0.5 Gy irradiation. In addition, since no changes were observed in xanthine and uric acid, increased inosine and hypoxanthine may have advanced to a salvage pathway leading to not xanthine but inosine 5'-monophosphate (IMP).

Animals↗

PubMed2002

Adjustment function among antioxidant substances in acatalasemic mouse brain and its enhancement by low-dose X-ray irradiation.

The catalase activities in blood and organs of the acatalasemic (C3H/AnLCsbCsb) mouse of the C3H strain are lower than those of the normal (C3H/AnLCsaCsa) mouse. We conducted a study to examine changes in the activities of antioxidant enzymes, such as catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPX), the total gluathione content, and the lipid peroxide level in the brain, which is more sensitive to oxidative stress than other organs, at 3, 6, or 24 hr following X-ray irradiation at doses of 0.25, 0.5, or 5.0 Gy to the acatalasemic and the normal mice. No significant change in the lipid peroxide level in the acatalasemic mouse brain was seen under non-irradiation conditions. However, the acatalasemic mouse brain was more damaged than the normal mouse brain by excessive oxygen stress, such as a high-dose (5.0 Gy) X-ray. On the other hand, we found that, unlike 5.0 Gy X-ray, a relatively low-dose (0.5 Gy) irradiation specifically increased the activities of both catalase and GPX in the acatalasemic mouse brain making the activities closer to those in the normal mouse brain. These findings may indicate that the free radical reaction induced by the lack of catalase is more properly neutralized by low dose irradiation.

Acatalasia↗

PubMedDate not supplied

alpha1-Adrenergic receptor antagonists induce production of IL-18 and expression of ICAM-1 and CD40 in human monocytes.

The activation of T cells plays a role in antitumor response. Monocytes activate T cells by inducing the cell-to-cell interaction that involves the engagement of adhesion molecules with their ligands, and the production of IL-18. The authors examined the effect of the quinazoline-based alpha1-adrenergic receptor antagonists bunazosin, doxazosin, prazosin, and terazosin on the expression of adhesion molecules such as ICAM-1, B7.1, B7.2, CD40, and CD40L on monocytes isolated from human peripheral blood mononuclear cells. Doxazosin, prazosin, and terazosin induced the expression of ICAM-1 and CD40 but had no effect on the expression of B7.1, B7.2, and CD40L. Moreover, IL-18 was detected in the medium of incubated monocytes treated with doxazosin, prazosin, and terazosin. Bunazosin did not affect adhesion molecule expression and IL-18 production, suggesting that the chemical structure of quinazoline might not be related to the effect of doxazosin, prazosin, and terazosin. Although caspase-1 inhibitor completely abolished the production of IL-18, anti-IL-18 mAb and caspase-1 inhibitor partially inhibited the increase in ICAM-1 and CD40 expression induced by doxazosin, prazosin, and terazosin. Doxazosin, prazosin, and terazosin can induce monocyte activation with a specific pattern of expression of adhesion molecules and IL-18 production, and this may lead to T-cell activation through the cell-to-cell interaction. The activation of T cells induced by the increase of the expression of ICAM-1 and CD40 and the production of IL-18 may be involved in the anti-cancer effects of doxazosin, prazosin, and terazosin.

Adrenergic alpha-1 Receptor Antagonists↗