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Biomedical subjects

Y Morimoto

Publications and source records attributed to Y Morimoto.

602 records · Page 34Linked to original sources

Effect of steroids on lipopolysaccharide/interleukin 2-induced interleukin 18 production in peripheral blood mononuclear cells.

Interleukin (IL) 18, a powerful inducer of the immunoregulatory cytokine interferon-gamma (IFN-gamma), presents upstream of the cytokine activation cascade in the inflammatory response. The anti-inflammatory properties of steroids permit their use in various conditions, although effects are transient and pathological states are not fully relieved by short-term steroidal use. We examined the effect of lipopolysaccharide (LPS)/IL-2 on the cytokine cascade in human peripheral blood mononuclear cells (PBMCs). We also examined the effect of steroids on LPS/IL-2-induced cytokine production in human PBMCs taken from healthy volunteers. Cell-free supernatant fractions were assayed for IL-18, IL-12, IL-2, IFN-gamma and IL-10 protein, using enzyme-linked immunosorbent assays, and synergy between LPS and IL-2 in enhanced production of IL-18 was observed. Steroids suppressed the production of IL-18 and other secondary cytokines in LPS/IL-2-stimulated PBMCs, in a concentration- and time-dependent manner, although inhibition was incomplete even at high concentrations. Effects of steroid treatment on expression of membrane-bound LPS receptor antigen (mCD14) and intercellular adhesion molecule-1 (ICAM-1) in PBMCs were studied by flow cytometric analysis. Steroid treatment up-regulated mCD14 expression in a concentration-dependent manner, with no effect on ICAM-1 expression. These results suggest that the incomplete counteraction of steroids in the LPS/IL-2-initiating cytokine cascade is due, at least partly, to the up-regulation of mCD14 by steroid preparations, which increases susceptibility to bacterial endotoxins.

Animals↗

Activated T cells and soluble molecules in the portal venous blood of patients with cholestatic and hepatitis C virus-positive liver cirrhosis. Possible promotion of Fas/FasL-mediated apoptosis in the bile-duct cells and hepatocyte injury.

We investigated the immune responses of patients with cholestatic and hepatitis C virus-positive (HCV-positive) liver cirrhosis by analysing T-cell subsets and cytokine levels in the portal and peripheral veins, using flow cytometry and enzyme-linked immunosorbent assay. In cholestatic liver cirrhosis, the proportion of natural-killer (NK) T cells and interleukin (IL) 6 and IL-18 levels in the portal venous blood were significantly higher than those in the peripheral venous blood. In HCV-positive liver cirrhosis, the proportions of NK T cells and Fas+ T cells and IL-6 and soluble Fas levels in the portal venous blood were significantly higher than those in the peripheral venous blood. These results suggest that in these diseases, activated T cells and soluble molecules in portal venous blood may promote Fas/FasL-mediated apoptosis of the bile-duct cells and hepatocytes, and contribute to the deterioration in liver function as an inevitable result of positive feedback.

Adult↗

Cyclosporin in psoriasis: continuous monotherapy versus intermittent long-term therapy.

Using two methods (continuous monotherapy and intermittent therapy) for the treatment of psoriasis with cyclosporine, we observed the clinical efficacy and adverse reactions of each treatment method for more than 36 months to evaluate the clinical usefulness of both methods. Thirty-seven cases were analyzed and the following results were obtained: 1) The PASI score evaluated at each visit was maintained between 5 and 10 by both treatment methods and the improvement rate was more than 70%, while there was no difference in the daily dose between the two treatment methods; 2) The period required to achieve remission tended to be prolonged by intermittent therapy, while no change was observed with continuous monotherapy; 3) The period up to relapse tended to become shorter with both treatment methods but this tendency was more marked with intermittent therapy; 4) E-PAP(evaluation for prognosis with averaged PASI) was lower in the continuous monotherapy group and the patients were more satisfied; 5) The incidence of adverse reactions was similar to that reported in previous studies, with no difference between the two treatment methods in this regard; 6) A significant increase in BUN levels was observed in elderly patients; 7) There were only three cases in which the drug was discontinued due to exacerbation and adverse reactions. Based on the above findings, continuous monotherapy seems to be of greater clinical usefulness than intermittent therapy.

Adult↗

A generational comparison of changes in mandibular third molars.

Due to recent increases in the number of cases of embedded mandibular third molars, the Department of Dental Radiology, Kyushu Dental College decided to investigate generational differences in their occurrence. For the purpose of investigation, 670 panoramic radiographs, obtained from two different generations (1970s and 1999s) of Kyushu Dental College students, wer used. There were significant statistical differences in the angle of eruption of the third molar between the 1970s and 1990s groups. The mandibular third molars in the 1990s group were growing at an abnormal angle (P < 0.05) and were closer to the mandibular canal (P < 0.05) than those in the 1970s group.

Adaptation, Physiological↗

Blood transfusion and postoperative plasma cytokine antagonist levels in colorectal cancer patients.

BACKGROUND/AIMS: Postoperative cytokine antagonist response affects various factors. However, excessive stress responses are deleterious as increased plasma concentration of cytokine antagonists may induce an impaired immune system. METHODOLOGY: We determined plasma levels of cortisol, IL-1ra, and sTNF-R55 in 20 patients who had undergone resection of colorectal carcinoma. Ten patients had a blood transfusion during the operation (invasive group), but 10 patients had received no blood transfusion (less invasive group). Plasma levels of cytokine antagonists were determined before operation (POD 0) and POD-1, -2 and -7. RESULTS: Postoperative plasma cortisol and sTNF-R55 levels were significantly elevated on POD-1 in the invasive group. Plasma IL-1ra levels were significantly increased on POD-1 in both the invasive and less invasive groups. CONCLUSIONS: The present study demonstrated that perioperative allogeneic blood transfusion can induce an excessive production of cortisol and sTNF-R55, and might be deleterious.

Adult↗

Maxillary sinus floor in edentulous and dentate patients.

To compare the depth of the maxillary sinus floor on panoramic radiographs between the edentulous and dentate patients. Thirty panoramic radiographs of edentulous female patients and 47 panoramic radiographs of female dentate patients were used for the sample. To measure the depth of the maxillary sinus floor, the outline of the maxillary sinus on the panoramic radiograph was traced on transparent paper. An apparent difference in depth of the maxillary sinus floor was recognized only in comparing the left sides of the edentulous and dentate jaws(P < 0.05). However, there was no statistical difference in the depth of the maxillary sinus floor between the right and left sides in the edentulous and dentate jaws. In this study there seems to be no difference in the depth of maxillary sinus floor between the right and left sides of either the edentulous or dentate jaws. It is not clear as to why, on the other hand, there is a statistical difference in between only the left maxillary sinus floor of the edentulous and dentate jaws, this apparent contradiction might be further investigated statistically.

Aged↗

Down-regulation of IL-18 receptor in cancer patients: its clinical significance.

Interleukin-18 (IL-18) is a powerful inducer of interferon-gamma (IFN-gamma), a key immunoregulatory cytokine. Cellular immune responsiveness, as measured by IL-18-induced IFN-gamma production from peripheral blood mononuclear cells (PBMCs) in ELISA assay, was evaluated in 10 patients with advanced cancer and in 10 normal controls. Supernatant levels of IFN-gamma were detected at 2 hours after PBMCs culture and markedly increased thereafter in healthy volunteers. In contrast, IFN-gamma production in cancer patients was not detected during the culture period (0-72 hours). We also measured IL-18-stimulated IL-12 production in healthy volunteers and null response was observed in cancer-bearing patients. Next, we studied mRNA expressions of IL-18 receptor (IL-18R) and IFN-gamma in PBMCs in cancer patients and healthy volunteers by RT-PCR assay. Both mRNA levels of IL-18R and IFN-gamma were significantly decreased in cancer-bearing patients compared with normal controls. These results suggested that IL-18 responsiveness for IFN-gamma production in cancer-bearing patients was impaired. Using flow cytometric analysis, we studied T-cell subsets, CD3- CD56+ (NK cell), CD3+ CD45RO+ (memory T-cell), CD3+ CD95+ (Fas+ T-cell), CD3+ CD4+ (helper T-cell), CD3+ CD8+ (cytotoxic T-cell: CTL) and CD3+ V alpha24+ (NKT-cell), in cancer patients and normal controls. The NK and cytotoxic T-cells significantly decreased and NKT-cells had decreased tendency in cancer patients compared with normal controls. In contrast, memory T cells, Fas+ T-cells and helper T-cells were all significantly increased in cancer patients compared with normal controls. These results suggested that the underlying mechanism of impaired IL-18 responsiveness in PBMCs from cancer-bearing patients was, at least in part, ascribed to a drastic decrease of NK cells and CTL which constitutively and highly express IL-18R and also attributed to null production of IL-12 which up-regulates IL-18R.

Adult↗

Effect of Y-25130, a selective 5-hydroxytryptamine3 receptor antagonist, on gastric emptying in mice.

The effect of Y-25130 on gastric emptying of nutrient test meals (solid chow) was examined in mice. In a dose range of 0.01-1 mg/kg, p.o., Y-25130 significantly accelerated gastric emptying of solid meals in a dose-dependent manner, at an ED30 of 0.021 mg/kg. Other 5-hydroxytryptamine3 receptor antagonists and prokinetic agents having 5-hydroxytryptamine3 receptor antagonistic properties accelerated the emptying of solid meals in the following rank order of potency: Y-25130 = granisetron > or = tropisetron > ondansetron > cisapride > metoclopramide. The acceleration of the gastric emptying showed a good correlation with the antagonistic potencies of these compounds on 5-hydroxytryptamine3 receptors, determined by the inhibition test of the von Bezold-Jarisch reflex in anesthetized rats (r2 = 0.99). Domperidone (1 and 10 mg/kg, p.o.) and trimebutine (10 and 100 mg/kg, p.o.) failed to increase the rate of emptying from the stomach. Cisplatin (30 mg/kg, i.p.), a chemotherapeutic agent, significantly delayed the gastric emptying of solid meals, and Y-25130 (0.1-1 mg/kg, p.o.) prevented such a delay in emptying in a dose-dependent manner. These results suggest that Y-25130 accelerates the gastric emptying in mice by antagonism of the 5-hydroxytryptamine3 receptor.

Animals↗