Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)  

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Authorship：Lead author   Language：Japanese  

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Language：Japanese   Publisher：Japan Society for Science Education  

DOI： 10.14935/jsser.35.6_31

CiNii Research

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Authorship：Corresponding author   Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)  

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Trans Tech Publications Ltd  

Self-organized TiO2 nanotubes were generated on the surface of the designed alloy Ti- 4.7Mo-4.5Fe (TMF55) by electrochemical anodization process to investigate the effect of nanostructured on the biocompatibility. The biocompatibility of the designed alloys showed very promising results compared to those of Ti-6Al-4V ELI alloy, especially for the untreated and nanostructured surfaces of the specimens with diameter size less than 35 nm. By increasing the diameter of nanotube, the biocompatibility is decreased. The most convenient compatible alloy was in favor of TMF8 alloy, making this V-free low-cost alloy is a promising candidate for replacing the commercial Ti-6Al-4V ELI alloy in biomedical applications.

DOI： 10.4028/www.scientific.net/MSF.1016.458

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Authorship：Last author   Language：English   Publishing type：Research paper (international conference proceedings)  

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Authorship：Last author   Language：English   Publishing type：Research paper (international conference proceedings)  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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DOI： 10.1016/j.msec.2019.01.133

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

We investigated whether Cirsium maritimum Makino can inhibit immunoglobulin-E-mediated allergic response in rat basophilic leukemia (RBL-2H3) cells and passive cutaneous anaphylaxis (PCA) in BALB/c mice. In vitro, the ethyl acetate extract of C. maritimum Makino (ECMM) significantly inhibited beta-hexosaminidase release and decreased intracellular Ca2+ levels in RBL-2H3 cells. Moreover, ECMM leaves more strongly suppressed the release of beta-hexosaminidase than ECMM flowers. ECMM leaves also significantly suppressed the PCA reaction in the murine model. High-performance liquid chromatography and H-1 and C-13 nuclear magnetic resonance indicated that cirsimaritin, a flavonoid, was concentrated in active fractions of the extract. Our findings suggest that ECMM leaves have a potential regulatory effect on allergic reactions that may be mediated by mast cells. Furthermore, cirsimaritin may be the active anti-allergic component in C. maritimum Makino.

DOI： 10.1021/acs.jafc.7b03322

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Language：Japanese   Publisher：(公社)日本栄養・食糧学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

CiNii Books

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Other Link： http://id.nii.ac.jp/1299/00000420/

Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

We examined the inhibitory effects of HAQ (His-Ala-Gln) peptide on type-1 allergy in vitro and in vivo. HAQ peptide inhibited -hexosaminidase release and intracellular Ca2+ levels of rat basophilic leukemia RBL-2H3 cells. Oral administration of a HAQ peptide-added diet (1mg/mouse/administration) to C3H/HeJ mice for 14days led to significant suppression of allergic symptoms, but did not reduce allergen-specific IgE or IgG(1).

DOI： 10.1080/09168451.2016.1243984

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Language：Japanese   Publisher：(株)北隆館  

1989年米国で、トリプトファンサプリメント摂取による好酸球増多筋痛症(EMS)と呼ばれる健康障害が起きた。EMS発症原因の1つとして、特定のロット中に含有していた不純物3-phenylamino-L-alanine(PAA)の関与が報告されている。そこで本稿では、ヒト好酸球の走化性および炎症性ケモカインの一種であるIL-8の各種レセプター発現に及ぼす不純物PAAの影響を検討し、トリプトファン事故品摂取によるアレルギー反応誘発機構を紹介する。(著者抄録)

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Language：Japanese   Publisher：四国公衆衛生学会  

本研究では、ヒト好酸球性白血病由来細胞株EoL-3が健康食品の安全性評価系としてなり得るか否かを調査するため、トリプトファンサプリメント事故品中に含まれた不純物3-phenylamino-L-alanine(PAA)による好酸球の反応性をモデルに、EoL-3細胞株ならびにヒト末梢血由来好酸球における各種ケモカインレセプター発現レベルの比較検討を行った。各種細胞にPAAを一定時間曝露し、ケモカインレセプターの発現レベルをSDS-PAGE法ならびにWestern Blotting法を用いて検出した。PAA濃度依存的にヒト末梢血由来好酸球におけるCXCR2発現は増大し、CCR3発現は抑制した。EoL-3細胞株においても同様の傾向が確認された。これらの結果から、Eosinophilia-Myalgia Syndrome(EMS)発症機序の一つとして、PAA曝露により好酸球に好中球の性質が一部付与され、インターロイキン(IL)-8への走化性を強めたことにより、更なる炎症が惹起されEMS発症に至ったのではないかと推察された。また、ヒト末梢血由来好酸球は採血量に対して細胞の回収率が非常に低く、大規模な健康食品の安全性評価に対して利用することは難しい。しかし、PAAによる各種ケモカインレセプター発現調節がEoL-3細胞株でも同様に認められたことから、健康食品の安全性評価の一つとしてEoL-3細胞株を利用できるのではないか考えられた。(著者抄録)

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

We have already reported that lactate dehydrogenase (LDH) activates lymphocytes in vitro and in vivo. In this paper, we report the activating effects of LDH on the macrophage-like cell line J774.1. LDH was found to enhance production of IL-6 and TNF-alpha by J774.1 cells in a dose-dependent manner. Transcription levels of IL-6 and TNF-alpha in J774.1 cells were also enhanced by supplementation with LDH. From immunoblot analysis, it was revealed that LDH enhances the phosphorylation level of JNK in J774.1 cells. Moreover, the JNK inhibitor SP600125 decreased production of IL-6 and TNF-alpha induced by LDH. NF-kappa B translocation to the nucleus was also facilitated by LDH. These results was revealed that LDH enhances production of IL-6 and TNF-alpha by J774.1 cells via the increase of JNK phosphorylation and NF-kappa B translocation to the nucleus. Our data indicated that macrophages may be activated by LDH released from damaged tissues and cells in our body.

DOI： 10.1007/s10616-013-9646-3

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Language：Japanese  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

The effects of four ellagitannin metabolites (M1-M4) and ellagic acid on immunoglobulin E-mediated allergic responses in rat basophilic leukemia-2H3 cells were investigated. M1-M4 inhibited the antigen-induced degranulation and secretion of interleukin-4 and tumor necrosis factor-alpha, but ellagic acid only slightly, did so under the same experimental conditions. M1 inhibited the activation of the mitogen-activated protein kinases in antigen-stimulated cells.

DOI： 10.1271/bbb.120448

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Lactate dehydrogenase (LDH) has been demonstrated to have an immunoglobulin production-stimulating effect on an IgM-producing human hybridoma cell line and on human peripheral blood lymphocytes in vitro. Here, we examined the immunostimulatory activity of LDH on mouse immune system in vitro and in vivo. LDH stimulated IgA, IgG, and IgM production by lymphocytes from spleen, mesenteric lymph node, and Peyer's patch in vitro. BALB/c mice were administered with LDH at 1.0 or 5.0 mg/kg/day for 2 weeks to examine the immunostimulatory activity of LDH in vivo. The IgA level in mouse serum was increased by administration at 5.0 mg/kg/day. Moreover, IgA and IgG production by Peyer's patch lymphocytes from mice administered at 1.0 mg/kg/day of LDH was accelerated. IgA, IL-4, IL-5, IL-10, IFN-gamma, and TNF-alpha production by spleen lymphocytes were also facilitated by administration of LDH. It was revealed that oral administration of LDH stimulates immunoglobulin and cytokine production by lymphocytes in vivo. (C) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jff.2012.07.005

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Immunostimulating effects of water extract from bulbus arteriosus in tuna were examined and found to enhance IgM production by human hybridoma HB4C5 cells. When tuna bulbus arteriosus extract was heated, the IgM production-stimulating activity was decreased or lost. To identify the active substance, the extract was partially purified by anion-exchange chromatography, and proteins contained in positive fractions were analyzed by LC-MS/MS. The positive fractions contained lactate dehydrogenase, triosephosphate isomerase, enolase, and haemoglobin. Each of these four proteins was verified to enhance IgM production by HB4C5 cells with the commercially available purified proteins, suggesting that all of these four proteins are active substances in the extract. The immunostimulatory effect of these proteins was also examined on mouse primary spleen lymphocytes in vitro. Lactate dehydrogenase enhanced IgA, IgG, and IgM production and triosephosphate isomerase enhanced IgA and IgG production. In particular, lactate dehydrogenase had the strongest Ig production-stimulating effect on HB4C5 cells and on mouse primary lymphocytes. Thus, fish viscera may serve as an important raw material for the enhancement of the acquired immune system, once processed. (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jff.2011.12.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER TOKYO  

In response to atherogenic stimuli, blood monocytes transmigrate across the vascular endothelium not only through endothelial cell-cell junctions (para-cellular) but also through endothelial cells themselves (trans-cellular). The molecular mechanism of the latter is mostly unknown, because it rarely happens, especially in vitro. Although many reports have recognized trans-cellular migration from snapshot images of leukocytes halfway across the endothelium at non-junctional locations, it often produces a false-positive result, because some leukocytes that initiate trans-cellular migration withdraw and return to the apical endothelial surface. Thus, analyzing the entire process is essential. In this study, complete monocyte trans-cellular migration was successfully captured for live cells, with simultaneous visualization of endothelial PECAM-1. We suggest the possible existence of both PECAM-1-related migration at peri-junctional sites and PECAM-1-unrelated migration at sites remote from junctions. This is the first report to describe the entire process of monocyte trans-cellular migration for live cells and its relationship with endothelial PECAM-1.

DOI： 10.1007/s12576-011-0181-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Epidemiological studies have indicated a correlation between homocysteinemia and dementia, including Alzheimer's disease. However, the mechanism by which homocysteine (Hcy) induces neuronal cell death remains unknown. We found that micromolar concentrations of Hcy induced neuroblastoma SH-SY5Y cell death only when co-cultured with glioblastoma U251MG cells. In this culture system, cysteine had no effect on SH-SY5Y cell death. There was an increase in TUNEL-positive cells and loss of mitochondrial membrane potential following treatment with 100 mu M Hcy. Addition of conditioned medium prepared from U251MG cells in the presence of 100 mu M Hcy also reduced SH-SY5Y cell viability, while this effect was prevented when using conditioned medium from U251MG cells exposed to 100 mu M Hcy + apocynin, a specific NADPH oxidase inhibitor. Following exposure to 100 mu M Hcy in U251MG cells, expression of Rac1, a compartment of NADPH oxidase, was translocated to the plasma membrane, and the active form of Rac1 was increased. There was no change in peroxide concentration in the medium of U251MG cells after addition of Hcy. Overall, these data suggest that Hcy stimulates Rac1 activation and NADPH oxidase, resulting in superoxide anion production that may induce SH-SY5Y cell apoptosis. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2011.09.010

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC FOOD SCIENCE TECHNOLOGY  

In this study, we aimed to search for peptides derived from casein with new anti-allergic action, and to examine the degranulation inhibitory effects associated with this anti-allergic action. Furthermore, amino acids making up the peptide with anti-allergic action were investigated for degranulation inhibitory effects, cytokine production and electron density. The peptides tested were low molecular weight HAQ, DMES, EQPI and KIKE, which are present in CE90GMM, a peptide mixture derived from casein. Using rat basophilic leukemia RBL-2H3 cells, we measured beta-hexosaminidase levels released during degranulation in the antigen-antibody reaction in the presence of these peptides, and evaluated the anti-allergic effects. Cytokine production (TNF-alpha, IL-4) was evaluated by ELISA. Optimized structure and electron density of amino acids were analyzed using a three-dimensional of electrostatic potential. Significant inhibition of,beta-hexosaminidase release was seen with CE90GMM stimulation at 0.25 mg/mL. With the four types of peptide at levels ranging from 0.01 to 0.5 mg/mL, significant inhibition of beta-hexosaminidase release was observed, but the effect varied with the dose. Our analysis also suggested that the peptides with anti-allergic action possess aromatic rings and neutral/hydrophobic amino acids in the side chain. (Received May 22, 2012: Accepted Jul. 19, 2012)

DOI： 10.3136/nskkk.59.556

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Language：Japanese   Publisher：(公社)日本生化学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Background: Although the importance of monocyte trans-endothelial migration in early atherogenesis is well recognized, it is unclear whether and how one transmigration event affects endothelium to facilitate subsequent ones. In this study, we tested the hypothesis that monocyte transmigration alters endothelial junctional organization to facilitate subsequent transmigration.
Methods and results: When human monocytes were added twice at intervals of approximate to 30 min to IL-1 beta-prestimulated human umbilical vein endothelial cells in vitro, significant augmentation of transmigration was observed at the second addition (approximate to 1.5-fold, analyzed from a total of 231 monocytes in 3 experiments). Endothelial surface expressions of two major junctional molecules, PECAM-1 and VE-cadherin, increased and decreased respectively, in response to monocyte addition, which could facilitate subsequent transmigration. To further investigate spatiotemporal dynamics of the increasing molecule, PECAM-1, we constructed a PECAM-1-GFP expression system and found that monocyte transmigration induced local accumulation of endothelial PECAM-1 around the transmigration spot, which was followed by transmigration of subsequent monocyte around the same location. Detailed analysis revealed that within the defined region around one transmigration event, 50% of later transmigrating monocytes used the same or similar location as the previous one (10 out of 20 transmigrating monocytes in 11 experiments).
Conclusions: These findings show that monocyte trans-endothelial migration alters endothelial junctional organization to a more monocyte-permeable state (increased PECAM-1 and decreased VE-cadherin), resulting in the augmented transmigratory activity at a later stage. This positive feedback mechanism is partially associated with monocyte transmigration-induced local accumulation of endothelial PECAM-1, which promotes transmigration of following monocytes at the same location. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2010.12.018

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

The immunostimulation effects of yellowtail heart extracts were examined. Screening various parts of the yellowtail viscera, we found that extracts from the yellowtail heart enhanced IgM production by human hybridoma HB4C5 cells. Yellowtail heart extracts heated at 121 degrees C for 20 min and dialyzed showed the highest IgM production-stimulating activity toward HB4C5 cells. Also, immunoglobulin production by mouse spleen lymphocytes was stimulated by yellowtail heart extracts in vitro, and lymphocytes derived from mice administered the extract for 20d were activated in vivo. Yellowtail heart extracts were partially purified by anion-exchange chromatography, and fractions containing a 33 kDa-protein exhibited immunostimulating activity. LC-MS/MS analysis revealed that the 33 kDa-protein was most similar to tropomyosin-4 from various fishes. Purified tropomyosin from porcine muscle enhanced IgM production by HB4C5 cells. This means that tropomyosin-4 is one of the immunostimulating substances in the yellowtail heart.

DOI： 10.1271/bbb.100713

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

The water-soluble fraction of kale (Brassica oleracea L. var. acephala DC.) had immunoglobulin (Ig) production stimulating activity in human hybridoma HB4C5 cells and human peripheral blood lymphocytes. The biochemical and physical properties of the main active substance in kale were found to be a heat-stable protein with a molecular weight higher than 50 kDa. The Ig production-stimulating factors were assumed to act on the translational and/or secreting processes of Igs. This Ig production-stimulating effect was also observed in lymphocytes from the mesenteric lymph node and Peyer's patches of mice that had been administered with the kale extract for 14 d. The partially purified kale extract was analyzed by LC-ESI-MS/MS, the result indicating ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) as an active substance. Rubisco from spinach indeed exhibited Ig production-stimulating activity in HB4C5 cells. These findings provide another beneficial aspect of kale as a health-promoting foodstuff.

DOI： 10.1271/bbb.100490

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Language：Japanese   Publishing type：Research paper (conference, symposium, etc.)  

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Monocyte accumulation in the arterial intima is a hallmark in early atherosclerosis. Monocyte extravasation involves sequential processes including rolling, adhesion, and transmigration across vascular endothelial cells (ECs), where abundant mechanical interactions between these two cells exist. Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is a junctional protein expressed on both cells, and participates in paracellular transmigration via homophilic binding between these cells, while PECAM-1 binds homophilically between neighboring ECs in the absence of monocytes. During monocyte transmigration, PECAM-1-bearing membrane can be recruited to the transmigration spot from intracellular pools. The mechanism by which PECAM-1 binding between ECs in control state is switched to that between monocytes and ECs during transmigration, and its relationship with recruited PECAM-1 remain unclear. In this study, we built an experimental model in vitro for studying molecular behavior of PECAM-1 during monocyte transmigration. A plasmid vector containing PECAM-1 tagged with green (GFP) or red (DsRed) fluorescent protein was constructed, and separately transfected into ECs. The mixture of both transfectants in culture achieved a monolayer that contains an intercellular PECAM-1 boundary between PECAM-1-GFP- and PECAM-1-DsRed-expressing cells which is visualized as yellow in merged image. Using this model together with confocal laser scanning microscope-based system, molecular behavior of PECAM-1 on neighboring ECs during monocyte transmigration was observed in live cells. This model can be essential to directly visualize binding/dissociation state of PECAM-1 between neighboring ECs during monocyte trans-endothelial migration in relation to mechanical monocyte-EC interactions. © 2010 by JSME.

DOI： 10.1299/jbse.5.281

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Alpha-lipoic acid has been shown to possess cancer-cell-killing activity via activation of the apoptosis pathway. In this study, the cytotoxic activities of alpha-lipoic and dihydro-alpha-lipoic acid were compared in HL-60 cells. The cell-killing activity of dihydro-alpha-lipoic acid was higher than that of alpha-lipoic acid. Both alpha-lipoic and dihydro-alpha-lipoic acid induced caspase-3 cleavage and internucleosomal DNA fragmentation in treated cells. On the other hand, apparent necrotic or late-stage apoptotic cell populations could be detected in dihydro-alpha-lipoic acid cells but not in those treated with alpha-lipoic acid. Moreover, dihydro-alpha-lipoic acid, but not alpha-lipoic acid, induced marked mitochondrial permeability transition. Antioxidants could not prevent dihydro-alpha-lipoic- or alpha-lipoic-acid-induced cell death. In addition, dihydro-alpha-lipoic and alpha-lipoic acid did not up-regulate cellular reactive oxygen level. These results indicated that dihydro-alpha-lipoic acid exerts more potent cytotoxicity than alpha-lipoic acid through different cytotoxic actions.

DOI： 10.1007/s11626-008-9164-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Indoleamine 2,3-dioxygenase (IDO; EC 1.13.11.42) is a rate-limiting enzyme involved in the catabolism of tryptophan, which is an essential amino acid. It is induced under pathological conditions, such as the presence of viral infections or tumour cells. This enzyme is induced by IFN-gamma in the mouse rectal carcinoma cell line CMT-93. It is known that both 1-methyl-L-tryptophan (1-MT) and methylthiohydantoin-DL-tryptophan (MTH-trp) are tryptophan analogues, and are authentic inhibitors of the enzymatic activity of IDO. In this study, we examined the effects of both 1-MT and MTH-trp on the IFN-gamma inducible IDO expression of CMT-93. As a result, the IFN-gamma inducible IDO mRNA and the protein levels in CMT-93 were suppressed by 1-MT and MTH-trp, independently. Moreover, tryptophan (Trp), as a substrate of IDO, also suppressed IDO induction by IFN-gamma at the transcriptional level. These results suggest that 1-MT and MTH-trp are as inhibitors of IDO enzymatic activity, and Trp suppresses IDO induction by IFN-gamma at the transcriptional level.

DOI： 10.1007/s10616-007-9081-4

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We previously identified perchloric acid-soluble protein (PSP) in the rat liver, kidney, brain and lung, and reported that it appeared to be related to repression of cell proliferation. In the present study, we clarified that PSP was expressed in the intestine, and found that the amino acid sequence of the intestinal PSP was consistent with those of other PSPs present in other tissues. An immunohistochemical study revealed that PSP was expressed in enterocytes and goblet cells, but not in other cell types among the lamina propria epithelial cells. A comparison of the expressions of PSP and proliferating cell nuclear antigen demonstrated that the proliferating cells did not express PSP. Intestinal PSP expression was induced by approximately 3-fold by oral administration of dietary fat. These findings indicate that the proliferation repression activity may be related to renewal of the intestinal epithelium, and that PSP is one of the fatty acid-inducible proteins.

DOI： 10.1016/j.bbagen.2006.03.023

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

We previously identified perchloric acid-soluble protein (PSP) in the rat liver, kidney, brain and lung, and reported that it appeared to be related to repression of cell proliferation. In the present study, we clarified that PSP was expressed in the intestine, and found that the amino acid sequence of the intestinal PSP was consistent with those of other PSPs present in other tissues. An immunohistochemical study revealed that PSP was expressed in enterocytes and goblet cells, but not in other cell types among the lamina propria epithelial cells. A comparison of the expressions of PSP and proliferating cell nuclear antigen demonstrated that the proliferating cells did not express PSP. Intestinal PSP expression was induced by similar to 3-fold by oral administration of dietary fat. These findings indicate that the proliferation repression activity may be related to renewal of the intestinal epithelium, and that PSP is one of the fatty acid-inducible proteins. (c) 2006 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.bbagen.2006.03.023

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

We examined the expression of perchloric acid-soluble protein (PSP) during liver regeneration after partial hepatectomy (PH) in rats. Liver regeneration was almost complete at 7-d after PH. Expression of PSP protein and mRNA decreased and then gradually increased during liver regeneration. An immunohistochemical study showed that PSP is distributed in cytosol and nuclei in normal liver, but localization in the nuclei was not be recognized in the regenerated liver.

DOI： 10.1271/bbb.70.290

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER INST NUTRITION  

We evaluated the effect of cis-9, trans-11 (9c, 11t) and trans-10, cis-12 (10t, 12c) conjugated linoleic acid (CLA) on the immune system in C57BL/6J mice. Mice were fed experimental diets containing 0% CLA (controls), 1% 9c, 11t-CLA, 1% 10t, 12c-CLA or a 1:1 mixture (0.5% + 0.5%) of these two CLA isomers for 3 wk. Relative spleen weights of all CLA fed mice were greater than the controls. Spleen lymphocytes isolated from the mice fed 10t, 12c-CLA produced more immunoglobulin (1g)A and IgM but not IgG when stimulated with concanavalin A (ConA) compared with controls. IgA production from unstimulated spleen lymphocytes was greater in the 10t, 12c-CLA group than in controls. Conversely, 9c, 11t-CLA did not affect the production of any of the Ig subclasses. Lymphocytes isolated from 9c, 11t-CLA fed mice produced more tumor necrosis factor-a than the control group. The proportion of B cells in the spleen lymphocyte population was significantly lower in the 9c, 11t-CLA group, and higher in the 10t,12c-CLA group than in the controls. Compared with the control group, the percentage of CD4(+) T cells was lower in the 1 Ot, 12c-CLA group, and the percentage of CD8(+) T cells was higher in the 9c,11t-CLA group. Furthermore, the percentage of CD8(+) T cells was higher in the 1:1 mixture group than in controls. The CD4(+)/CD8(+) ratio was lower in the 1:1 mixture group than in controls. These results suggest that 9c,11t and 10t, 12c-CLA can stimulate different immunological effects and that the simultaneous intake of the two isomers can change the T cell population.

DOI： 10.1093/jn/133.3.784

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC FOOD SCIENCE TECHNOLOGY  

We investigated the effects of Casein, whey protein, soybean protein, wheat gluten and their peptides on the proliferation and immunoglobulin (Ig) production of mouse spleen lymphocytes. Among them, bovine, beta-Casein remarkably enhanced the production of IgA, IgG and IgM. In addition, some peptides from Casein enhanced IgA production and a peptide from wheat gluten enhanced IgA, IgG and IgM production. On the other hand, whey and soybean proteins exerted no immunoregulatory activity, as well as peptides derived from these proteins. beta-Casein elevated Ig producing cell population in mouse spleen lymphocytes, but peptides derived from casein did not increase Ig producing cell population. These data suggest that immunoglobulin production stimulating effect of beta-Casein takes part in increasing of Ig producing cells. Therefore, Casein and wheat gluten peptides may well be available as immunoregulatory food materials.

DOI： 10.3136/nskkk.50.72

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：SPRINGER  

We showed beta-Casein derived from bovine milk dose-dependently enhanced interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha productions but not interleukin (IL)-4 production by mouse spleen lymphocytes. Furthermore, beta-Casein increased the percentage of CD4(+) T cell ratio but not CD8(+) T cell ratio. That is, beta-Casein significantly increased CD4(+)/CD8(+) ratio. It is supposed from these results that beta-Casein activates CD4(+) T cells, especially Th1 type cells. And, the effects of beta-Casein on the mRNA expressions of various cytokines in spleen lymphocytes were performed using RT-PCR method. RT-PCR analysis showed that spleen lymphocytes expressed the mRNA for IFN-gamma, IL-2, IL-4, IL-6, IL-10 and IL-12p40 under Concanavalin A (ConA) stimulation. In addition, beta-Casein stimulus increased the mRNA level of IFN-gamma, IL-4 and IL-6 under ConA stimulation. And beta-Casein stimulus increased the mRNA level of IL-12p40 under none stimulation. These results suggested that beta-Casein activated not only IFNgamma production but also transcription activity of IFN-gamma and spleen T cell response to the beta-Casein is of the Th1 type. Moreover, the binding of the beta-Casein to spleen lymphocytes was assessed by flow cytometory. beta-Casein was strongly bound to some spleen lymphocytes, which were expected to be beta-Casein sensitive population.

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Language：Japanese   Publisher：九州大学大学院農学研究院  

To clarify the lipid metabolism and immune function of soybean extracts, Sprague-Dawley rats were fed diets with sample powders containing 3％ level. After soybean homogenate was fed to rats for 3 weeks, IgG productivity of spleen lymphocytes was enhanced and HDL-Chol level for T-Chol level in serum was increased. The immunoglobulin production stimulating effects by soybean homogenate may be useful for activation of host defenses. On the other hand, feeding of enzyme digested soybean homogenate decreased GOT and GPT activities in serum. These results suggested that enzyme digested soybean homogenate may be prevention against lesion of hepatic function. In this study, it is clear that soybean hornogenate and digestive products have novel biological and physiological regulatory function.大豆抽出物の脂質代謝および免疫機能を明らかにするために，それらのサンプルを食餌重量に対し3％レベルでSprague-Dawley系ラットに摂食させた．その結果 大豆ホモジェネート摂食群において，全身免疫系に属する脾臓リンパ球のIgG抗体生産能の増強効果および血清中のT-Cholに対するHDL-Cholの割合の上昇が認められた．これにより，大豆ホモジェネート摂食による抗体産生促進作用は宿主免疫の活性化に有用である可能性が期待された．一方，酵素処理大豆ホモジェネート摂食により，GOTおよびGPT活性が減少することより肝機能障害予防効果が期待された．本研究により，大豆ホモジェネートおよび大豆ホモジェネートから派生する分解物の新規生理機能が明らかとなった．

DOI： 10.15017/21119

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

A histone mixture (H1, H2A, H2B, H3, and H4) derived from calf thymus stimulated IgM production by human-human hybridoma HB4C5 cells. On the contrary, the histone mixture did not increase IgM production by the human Burkitt's lymphoma cell line NAT-30, IgG production by the human B lymphoblastoid cell line HMy-2, and IgE production by the human myeloma cell line U266. The immunoglobulin pro duction-stimulating activity of the histone mixture was inactivated by trypsin or chymotrypsin digestion. In addition, confocal laser microscopic analysis had shown that HB4C5 cells incorporated a lot of histone but other cell lines did not incorporate it as much.
These facts strongly suggest that histone acts as an immunoglobulin pro duction-stimulating factor (IPSF) after internalization into the human B cell lines and the native structure of histone is required for the IPSF activity.

DOI： 10.1271/bbb.66.1241

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Alcohol dehydrogenase-I (ADH-I; EC 1.1.1.1) derived from horse liver stimulated IgM production by human-human hybridoma, HB4C5 cells and human peripheral blood lymphocytes. The immunoglobulin production stimulating activity of ADH-I was inactivated by chymotrypsin digestion, even though the enzymatic activity was completely preserved. This fact suggests that the immunoglobulin production stimulating effect of ADH-I is irrelevant to its enzymatic function. This also means that the effect is a novel function of this enzyme. ADH-I enhanced IgM production by transcription-suppressed HB4C5 cells treated with actinomycin D. Moreover, the enzyme was effective to accelerate IgM production by translation-suppressed HB4C5 cells treated with sodium fluoride and cycloheximide. Although the secretion of IgM by HB4C5 cells treated with monensin for suppression of the post-transcription process was inhibited, the intracellular IgM content of the cells was obviously increased by the addition of ADH-I. It is supposed from these results that ADH-I accelerates the translation activity to enhance immunoglobulin productivity. In addition, a laser confocal microscopic analysis revealed that ADH-I from horse liver was subsequently incorporated by HB4C5 cells. (C) 2001 Elsevier Science Inc. All rights reserved.

DOI： 10.1016/S0141-0229(01)00371-4

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Language：Japanese   Publisher：(公社)日本農芸化学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KLUWER ACADEMIC PUBL  

Alcohol dehydrogenase-I (ADH-I) derived from horse liver stimulated IgM production by human-human hybridoma, HB4C5 cells and lymphocytes. The IPSF activity of ADH-I was suppressed by coexistence of short DNA whose chain length is less than 200 base pairs (bp) and fibrous DNA in a dose-dependent manner. These DNA preparations completely inhibited the IPSF activity at the concentration of 250 mu g/ml and 1.0 mg/ml, respectively. DNA sample termed long DNA whose average chain length is 400-7000 bp slightly stimulated IPSF activity at 0.06 mu g/ml. However, long DNA suppressed IPSF activity by half at 1.0 mg/ml. The laser confocal microscopic analysis had revealed that ADH-I was incorporated by HB4C5 cells. The uptake of ADH-I was strongly inhibited by short DNA and fibrous DNA. However, long DNA did not suppress the internalization of ADH-I into HB4C5 cells. These findings indicate that short DNA and fibrous DNA depress IPSF activity of ADH-I by inhibiting the internalization of this enzyme. According to the gel-filtration analysis using HPLC, ADH-I did not directly interact with short DNA. It is expected from these findings that short DNA influences HB4C5 cells to suppress the internalization of ADH-I. Moreover, these facts also strongly suggest that ADH-I acts as IPSF after internalization into the cell.

DOI： 10.1023/A:1008024322602

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Language：Japanese   Publisher：The Japan Society of Home Economics  

<b>目的</b> 沖縄県の特産柑橘であるシークヮーサーは主にジュース加工に用いられているが，搾汁効率は50%程度であり，ポリメトキシフラボン類であるノビレチン等を多く含有する搾汁残渣「葉」および「果皮」の用途開発が課題である. 昨年，我々は，<i>in vitro</i>でシークヮーサー葉・果皮抽出物に脱顆粒抑制効果を見出してきた. 本研究では，<i>in vitro</i>における葉・果皮抽出物による脱顆粒抑制効果の熱安定性および作用機序を検討するとともに，マウスを用いた<i>in vivo</i>で抗アレルギー効果を明らかにすることで，葉や果皮などの未利用部位に新たな機能性を付与することを目的とした. <br> <b>方法</b> <i>in vitro</i>での抗アレルギー作用は，抗DNP-IgE抗体で感作させたラット好塩基球様細胞株RBL-2H3細胞からのDNP-HSA抗原刺激により惹起される脱顆粒現象をβ-hexosaminidase放出活性および細胞内Ca<sup>2+</sup>濃度により評価した. また，<i>in vivo</i>での抗アレルギー作用は，各抽出物をBALB/c雌マウスに経口投与後，受動皮膚アナフィラキシー（PCA）反応により評価した. <br> <b>結果 </b>シークヮーサー葉・果皮抽出物は，60分の煮沸処理下でも脱顆粒抑制効果を保持したことから，活性成分は強い熱安定性を有し，細胞内へのCa<sup>2+</sup>流入を抑制することで脱顆粒抑制効果を発現することが明らかになった. また，葉および果皮抽出物投与群は，コントロール群と比較すると有意にPCA反応を抑制したことから，マウスにおいても抗アレルギー効果を示すことが確認された. さらに，葉・果皮抽出物によるPCA反応の抑制レベルは，<i>in vitro</i>での結果と異なったため，ノビレチン以外の抗アレルギー活性成分の存在が示唆された. 

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Language：Japanese   Publisher：The Japan Society of Home Economics  

<b>目的</b> 食中毒菌を選択的に培養できるフードスタンプを用いた培養実験において,食中毒菌の採取に適切な時期や食品などは明らかになっていない.そこでフードスタンプを用いた食中毒菌培養実験を構築し,その実験を取り入れた実践授業を実施することで,教育効果や食中毒菌培養実験の有用性を検討することを目的とした.<br><b>方法</b> 食中毒菌を採取する食品を6種類選定し,8～12月の間に毎月,フードスタンプを用いて採取・培養実験を行うことで,培養実験に適する採取時期や食品群を検討した.得られた結果をもとに,実践授業を構築し,愛媛県立Ｍ高校理数科36名を対象に実施し,授業前後のアンケートによって教育効果や有用性を検討した.  <br> <b>結果</b> 食中毒菌培養実験には,気温が20℃以上ある1学期後半から2学期前半が良いと考えた.また,モヤシから大腸菌・大腸菌群,鶏ミンチからサルモネラ,アサリから腸炎ビブリオが一定量採取できることを確認した.さらに,食中毒予防法における加熱の重要性を示す実験において,加熱時間よりも,加熱温度を変化させる方が,コロニー数の減少を観察しやすいことが分かった.以上の実験結果を用いた実験授業を実践すると,食中毒菌や食中毒予防の三原則の認知度が向上し,食中毒予防法の実践意欲も高まった.授業後に実施したアンケートでは,フードスタンプに対して生徒全員から「面白かった」「分かりやすかった」と回答され,フードスタンプに対して高評価であることが確認された.

DOI： 10.11428/kasei.69.0_321

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Language：Japanese   Publishing type：Rapid communication, short report, research note, etc. (bulletin of university, research institution)  

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Language：Japanese   Publisher：The Japan Society of Home Economics  

<b>目的</b> 近年、マウスにビタミン E を過剰摂取させると破骨細胞の巨大化を伴いつつ活性化することで骨吸収を促進し、骨粗鬆症を誘発する危険性があると報告された。しかし、骨芽細胞に与えるビタミンEの影響に関する詳細な検討はなされていない。そこで本研究では、ビタミンEで骨芽細胞を刺激することで、骨芽細胞自身ならびに破骨細胞活性化メカニズムにどのような影響を与えるのかについて検討した。<br><b>方法</b> マウス頭蓋冠由来骨芽細胞 MC3T3-E1 を、ビタミン E の主成分であるα-tocopherol(α-toc)で刺激し、細胞増殖に与える影響を検討した。また、骨芽細胞から産生される破骨細胞活性化因子である IL-6 および IL-1βの量を ELISA 法で測定した。<br><b>結果および考察</b> MC3T3-E1 にα-toc を作用させたところ、濃度依存的に細胞増殖が抑制され、継続的なα-toc 刺激により、その効果は維持された。また、骨芽細胞 1 個あたりの IL-6 および IL-1β生産性を評価した結果、α-toc 濃度依存的に高値を示した。さらに、α-toc(50μM)刺激によって MC3T3-E1 の付着ならびに増殖時に認められる細胞突起の伸展が顕著に抑制された。したがって、α-toc は骨芽細胞の増殖を抑制しつつ、骨芽細胞からの破骨細胞活性化因子の生産性を促進することで破骨細胞の活性化を誘導し、骨粗鬆症の発症を誘起しているのではないかと推察された。

DOI： 10.11428/kasei.68.0_283

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Language：Japanese   Publisher：愛媛大学教育学部  

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Language：Japanese   Publisher：愛媛大学教育学部  

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Language：Japanese   Publisher：愛媛大学教育学部附属教育実践総合センター  

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J-GLOBAL

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Language：Japanese   Publisher：愛媛大学教育学部  

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Language：Japanese   Publishing type：Research paper, summary (national, other academic conference)  

J-GLOBAL

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J-GLOBAL

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Publisher：The Japan Society of Home Economics  

<b>目的</b> これまでに，アンセリンやカルノシンなどのイミダゾールジペプチドに花粉症抑制効果，疲労回復効果，抗加齢効果等を持つことが報告されている．また我々は，HAQ(His-Ala-Gln)ペプチドが，RBL-2H3細胞の脱顆粒を抑制することを明らかにしてきた．そこで本研究では，他のイミダゾールジ・トリペプチドの脱顆粒抑制効果を検討するとともに，動物実験系を用いてHAQペプチドの抗アレルギー効果を評価した． <br><b>方法</b> 抗体感作されたラット好塩基球様細胞株RBL-2H3に，化学合成した各種ペプチド（HH，HHH，HAQ，QHA，AQH）を10分間作用させた後，抗原との共刺激30分後のβ-hexosaminidase放出活性を測定し，脱顆粒レベルを評価した．また，卵白リゾチーム（LHE）感作マウスを用いて，14日間のHAQペプチド継続投与による血清中LHE特異IgE及びIgG1産生，ならびにLHE投与後のアナフィラキシー症状に与える影響を検討した．アナフィラキシー評価の指標として直腸温とスコアを測定した. <br><b>結果</b> HH，HHH，HAQ ペプチドをRBL-2H3細胞に作用させたところ，それぞれ濃度依存的に脱顆粒抑制効果が認められ，その抑制強度は，HAQ≒HHH＞HHであった．また，HAQ，QHA，AQHペプチドで同様に検討したところ，その抑制強度はHAQ＞AQH＞QHAであった．よって，イミダゾールペプチドによる脱顆粒抑制効果のレベルはヒスチジン残基の数に依存し，配列特異性も有することが明らかになった．また，LHE感作マウスを用いた実験においてHAQペプチドの継続投与による各種抗体産生の低下は認められなかったもののアナフィラキシー症状の抑制傾向が認められ，動物実験系においても抗アレルギー効果を有することが示唆された.

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Publisher：The Japan Society of Home Economics  

<b>目的</b> トリプトファンサプリメント事故品摂取による好酸球増多筋痛症候群(EMS)発症の原因物質の一つとして、不純物3-phenylamino-L-alanine(PAA)が知られている。ヒト好酸球における走化性およびIL-8レセプター(CXCR1およびCXCR2)の発現レベルに及ぼすPAAの影響を検討し、トリプトファン事故品摂取によるアレルギー反応誘発機構の解明を目的とした。<br><b>方法</b> 健常者男性よりヒト末梢血(100mL)を採取し、Eosinophil isolation kitを用いて磁気細胞分離法(MACS法)により好酸球の分離を行った。分離された好酸球に対してPAAで曝露し、遊走活性を細胞動態解析装置(EZ-TAXIScan)を用いて評価した。また、各種IL-8レセプターの発現レベルに関しては、SDS-PAGE法ならびにWestern Blotting法を用いて検出した。<br><b>結果</b> ヒト好酸球の走化性に及ぼすPAA曝露の影響について検討したところ、PAA濃度依存的に遊走活性が惹起された。また、各種IL-8レセプターの発現レベルに関しては、好酸球にPAAを6時間曝露したところ、PAA濃度依存的(0.005～0.5μM)に、CXCR2レセプターの発現が増強された。一方、PAAを12時間曝露すると、低濃度(0.005μM)においてCXCR2レセプター発現の増強が認められた。また、PAA曝露によるCXCR1レセプターの発現は、CXCR2レセプターの発現より弱いが、同様の増強傾向が見られた。これらの結果から、PAA曝露による好酸球のIL-8に対する走化性の誘導には、IL-8レセプターの発現の増大が関与していると示唆された。

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Language：Japanese   Publisher：(公社)日本生化学会  

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Language：Japanese   Publisher：診断と治療社  

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Language：Japanese   Publisher：The Japan Society of Mechanical Engineers  

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Language：Japanese   Publisher：緑書房  

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Publisher：一般社団法人 日本家政学会  

【目的】近年，特に先進国においてI型アレルギー患者が急増し，大きな社会問題となっている。これまでに，茶カテキンなどのポリフェノール類が抗アレルギー効果を示すことが報告されているが，食品由来ペプチドについての報告例は少ない。本研究では，抗アレルギー作用を有する新規ミルク由来ペプチドの検索を目的とし，数種のペプチドによる脱顆粒抑制効果を検討した。【材料および方法】ペプチドサンプルは，ミルク由来ペプチド混合物であるCE90GMM（平均分子量；640）および CE90GMMに含有する４種のペプチド，HAQ（His-Ala-Gln），DMES（Asp-Met-Glu-Ser），EQPI（His-Gln-Pro-Ile），KIKE（Lys-Ile-Lys-Glu）を用いた。RBL-2H3細胞に各種ペプチドを１０分間作用させた後，抗原との共刺激３０分後のβ-hexosaminidase放出活性を測定した。【結果および考察】ミルク由来ペプチド混合物CE90GMM刺激下では，有意なβ-hexosaminidase放出抑制効果が認められ，CE90GMMに含まれる4種のペプチド刺激下では，全てのペプチドにおいて用量依存的に有意なβ-hexosaminidase放出抑制効果が認められた。その抑制効果の強度は，HAQ≧EQPI≧DMES＞KIKEの順であった。さらに，HAQペプチドおよびKIKEペプチドを蛍光標識し，RBL-2H3細胞へ作用させたところ，HAQペプチドが強く細胞内へ取り込まれていることが明らかとなった。よって，ペプチドによる抗アレルギー効果の発現には，細胞内への取り込みが関与するのではないかと示唆された。

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Language：Japanese   Publisher：日本産科婦人科学会  

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Language：Japanese   Publisher：Kawasaki Medical School  

DOI： 10.11482/KMJ-LAS(35)1-9

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：SPRINGER TOKYO  

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DOI： 10.11482/KMJ-LAS(35)1-9

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Indoleamine 2,3-dioxygenase (IDO
EC 1.13.11.42) is a rate-limiting enzyme involved in the catabolism of tryptophan, which is an essential amino acid. It is induced under pathological conditions, such as the presence of viral infections or tumor cells. This enzyme is induced by IFN-γ in the mouse rectal carcinoma cell line CMT-93. It is known that both 1-methyl-l-tryptophan (1-MT) and methylthiohydantoin-dl-tryptophan (MTH-trp) are tryptophan analogues, and are authentic inhibitors of the enzymatic activity of IDO. In this study, we examined the effects of both 1-MT and MTH-trp on the IFN-γ inducible IDO expression of CMT-93. As a result, the IFN-γ inducible IDO mRNA and the protein levels in CMT-93 were suppressed by 1-MT and MTH-trp, independently. Moreover, tryptophan (Trp), as a substrate of IDO, also suppressed IDO induction by IFN-γ at the transcriptional level. These results suggest that 1-MT and MTH-trp as inhibitors of IDO enzymatic activity, and Trp suppress IDO induction by IFN-γ at the transcriptional level. © 2007 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ics.2007.07.015

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One hundred and fifty crushed eggs of Hymenolepis nana were administrated to 5-6 week old ddY mice, and the animals were killed at 0, 7, 14, 21 or 28 days post-infection (dpi). The small intestines were recovered, and both halves, proximal and distal, were examined, observed for immunohistochemistry, and assayed on enzyme activity of IDO. Enzyme activity of IDO was increased by H. nana infection, and was parallel to a decrease of recovered worms. The expression pattern of IDO-positive cells in the proximal intestine was also the same as those of IDO activity with a little change earlier. Furthermore, IDO-positive cells coincided with goblet cells, but not all goblet cells were IDO-positive. Present findings apparently suggest that IDO might be involved in the mucous excretion process in the expulsion of worms. © 2007 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ics.2007.07.051

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Language：Japanese   Publisher：JAPAN SOC FOOD SCIENCE TECHNOLOGY  

We investigated the effects of Casein, whey protein, soybean protein, wheat gluten and their peptides on the proliferation and immunoglobulin (Ig) production of mouse spleen lymphocytes. Among them, bovine, beta-Casein remarkably enhanced the production of IgA, IgG and IgM. In addition, some peptides from Casein enhanced IgA production and a peptide from wheat gluten enhanced IgA, IgG and IgM production. On the other hand, whey and soybean proteins exerted no immunoregulatory activity, as well as peptides derived from these proteins. beta-Casein elevated Ig producing cell population in mouse spleen lymphocytes, but peptides derived from casein did not increase Ig producing cell population. These data suggest that immunoglobulin production stimulating effect of beta-Casein takes part in increasing of Ig producing cells. Therefore, Casein and wheat gluten peptides may well be available as immunoregulatory food materials.

DOI： 10.3136/nskkk.50.72

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Language：Japanese   Publisher：九州大学  

大豆抽出物の脂質代謝および免疫機能を明らかにするために、それらのサンプルを食餌重量に対し3％レベルでSprague-Dawley系ラットに摂食させた。その結果、大豆ホモジェネート摂食群において、全身免疫系に属する脾臓リンパ球のIgG抗体産生能の増強効果および血清中のT-Cholに対するHDL-Cholの割合の上昇が認められた。これにより、大豆ホモジェネート摂食による抗体産生促進作用は宿主免疫の活性化に有用である可能性が期待された。一方、酵素処理大豆ホモジェネート摂食により、GOTおよびGPT活性が減少することにより肝機能障害予防効果が期待された。本研究により、大豆ホモジェネートおよび大豆ホモジェネートから派生する分解物の新規生理機能が明らかとなった。

DOI： 10.15017/21119

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Event date： 2024.5

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<b>目的</b> これまでに，アンセリンやカルノシンなどのイミダゾールジペプチドに花粉症抑制効果，疲労回復効果，抗加齢効果等を持つことが報告されている．また我々は，HAQ(His-Ala-Gln)ペプチドが，RBL-2H3細胞の脱顆粒を抑制することを明らかにしてきた．そこで本研究では，他のイミダゾールジ・トリペプチドの脱顆粒抑制効果を検討するとともに，動物実験系を用いてHAQペプチドの抗アレルギー効果を評価した． <br><b>方法</b> 抗体感作されたラット好塩基球様細胞株RBL-2H3に，化学合成した各種ペプチド（HH，HHH，HAQ，QHA，AQH）を10分間作用させた後，抗原との共刺激30分後の&beta;-hexosaminidase放出活性を測定し，脱顆粒レベルを評価した．また，卵白リゾチーム（LHE）感作マウスを用いて，14日間のHAQペプチド継続投与による血清中LHE特異IgE及びIgG1産生，ならびにLHE投与後のアナフィラキシー症状に与える影響を検討した．アナフィラキシー評価の指標として直腸温とスコアを測定した. <br><b>結果</b> HH，HHH，HAQ ペプチドをRBL-2H3細胞に作用させたところ，それぞれ濃度依存的に脱顆粒抑制効果が認められ，その抑制強度は，HAQ≒HHH＞HHであった．また，HAQ，QHA，AQHペプチドで同様に検討したところ，その抑制強度はHAQ＞AQH＞QHAであった．よって，イミダゾールペプチドによる脱顆粒抑制効果のレベルはヒスチジン残基の数に依存し，配列特異性も有することが明らかになった．また，LHE感作マウスを用いた実験においてHAQペプチドの継続投与による各種抗体産生の低下は認められなかったもののアナフィラキシー症状の抑制傾向が認められ，動物実験系においても抗アレルギー効果を有することが示唆された.

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<b>目的</b> トリプトファンサプリメント事故品摂取による好酸球増多筋痛症候群(EMS)発症の原因物質の一つとして、不純物3-phenylamino-L-alanine(PAA)が知られている。ヒト好酸球における走化性およびIL-8レセプター(CXCR1およびCXCR2)の発現レベルに及ぼすPAAの影響を検討し、トリプトファン事故品摂取によるアレルギー反応誘発機構の解明を目的とした。<br><b>方法</b> 健常者男性よりヒト末梢血(100mL)を採取し、Eosinophil isolation kitを用いて磁気細胞分離法(MACS法)により好酸球の分離を行った。分離された好酸球に対してPAAで曝露し、遊走活性を細胞動態解析装置(EZ-TAXIScan)を用いて評価した。また、各種IL-8レセプターの発現レベルに関しては、SDS-PAGE法ならびにWestern Blotting法を用いて検出した。<br><b>結果</b> ヒト好酸球の走化性に及ぼすPAA曝露の影響について検討したところ、PAA濃度依存的に遊走活性が惹起された。また、各種IL-8レセプターの発現レベルに関しては、好酸球にPAAを6時間曝露したところ、PAA濃度依存的(0.005～0.5&mu;M)に、CXCR2レセプターの発現が増強された。一方、PAAを12時間曝露すると、低濃度(0.005&mu;M)においてCXCR2レセプター発現の増強が認められた。また、PAA曝露によるCXCR1レセプターの発現は、CXCR2レセプターの発現より弱いが、同様の増強傾向が見られた。これらの結果から、PAA曝露による好酸球のIL-8に対する走化性の誘導には、IL-8レセプターの発現の増大が関与していると示唆された。

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<b>目的</b> 近年、マウスにビタミン E を過剰摂取させると破骨細胞の巨大化を伴いつつ活性化することで骨吸収を促進し、骨粗鬆症を誘発する危険性があると報告された。しかし、骨芽細胞に与えるビタミンEの影響に関する詳細な検討はなされていない。そこで本研究では、ビタミンEで骨芽細胞を刺激することで、骨芽細胞自身ならびに破骨細胞活性化メカニズムにどのような影響を与えるのかについて検討した。<br><b>方法</b> マウス頭蓋冠由来骨芽細胞 MC3T3-E1 を、ビタミン E の主成分である&alpha;-tocopherol(&alpha;-toc)で刺激し、細胞増殖に与える影響を検討した。また、骨芽細胞から産生される破骨細胞活性化因子である IL-6 および IL-1&beta;の量を ELISA 法で測定した。<br><b>結果および考察</b> MC3T3-E1 に&alpha;-toc を作用させたところ、濃度依存的に細胞増殖が抑制され、継続的な&alpha;-toc 刺激により、その効果は維持された。また、骨芽細胞 1 個あたりの IL-6 および IL-1&beta;生産性を評価した結果、&alpha;-toc 濃度依存的に高値を示した。さらに、&alpha;-toc(50&mu;M)刺激によって MC3T3-E1 の付着ならびに増殖時に認められる細胞突起の伸展が顕著に抑制された。したがって、&alpha;-toc は骨芽細胞の増殖を抑制しつつ、骨芽細胞からの破骨細胞活性化因子の生産性を促進することで破骨細胞の活性化を誘導し、骨粗鬆症の発症を誘起しているのではないかと推察された。

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<b>目的</b> 食中毒菌を選択的に培養できるフードスタンプを用いた培養実験において,食中毒菌の採取に適切な時期や食品などは明らかになっていない.そこでフードスタンプを用いた食中毒菌培養実験を構築し,その実験を取り入れた実践授業を実施することで,教育効果や食中毒菌培養実験の有用性を検討することを目的とした.<br><b>方法</b> 食中毒菌を採取する食品を6種類選定し,8～12月の間に毎月,フードスタンプを用いて採取・培養実験を行うことで,培養実験に適する採取時期や食品群を検討した.得られた結果をもとに,実践授業を構築し,愛媛県立Ｍ高校理数科36名を対象に実施し,授業前後のアンケートによって教育効果や有用性を検討した. &nbsp;<br> <b>結果</b> 食中毒菌培養実験には,気温が20℃以上ある1学期後半から2学期前半が良いと考えた.また,モヤシから大腸菌・大腸菌群,鶏ミンチからサルモネラ,アサリから腸炎ビブリオが一定量採取できることを確認した.さらに,食中毒予防法における加熱の重要性を示す実験において,加熱時間よりも,加熱温度を変化させる方が,コロニー数の減少を観察しやすいことが分かった.以上の実験結果を用いた実験授業を実践すると,食中毒菌や食中毒予防の三原則の認知度が向上し,食中毒予防法の実践意欲も高まった.授業後に実施したアンケートでは,フードスタンプに対して生徒全員から「面白かった」「分かりやすかった」と回答され,フードスタンプに対して高評価であることが確認された.

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当日参加が難しかったため動画による視聴（2023.12.23）

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本科研費申請説明会を企画・運営した。

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科研費獲得セミナーを企画した。コロナ禍ということもあり、遠隔非同期型で実施した。

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教育学部より若手研究者として、井上昌善先生、中村依子先生を紹介した。

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