Papers by KIYOSHI HIGASHI
L'invention concerne un biomarqueur pour un trouble d'un microdomaine et une technologie ... more L'invention concerne un biomarqueur pour un trouble d'un microdomaine et une technologie diagnostic associee a un procede permettant de detecter, entre autres, un trouble d'un microdomaine de maniere simple et bon marche.
Journal of Investigative Dermatology, 2019
Thimerosal has been used as a preservative in a variety of products which may cause contact derma... more Thimerosal has been used as a preservative in a variety of products which may cause contact dermatitis. It is the second most common allergen in positive patch test reactions, though being a clinical irrelevant allergen. It is believed that thimerosal may cause contact dermatitis through delayed-type hypersensitivity response. However, recent studies have demonstrated the association between Mas-related G protein coupled receptor X2 (MRGPRX2) on mast cells and pseudo-allergic reaction. It is possible that thimerosal may cause contact dermatitis via MRGPRX2 mediated mechanism. To investigate the role of MRGPRX2/MrgprB2 in contact dermatitis induced by thimerosal, we developed a novel skin pseudo-allergic reaction mouse model, footpad swelling and extravasation assays in vivo and mast cell degranulation assay in vitro were studied. The results showed that thimerosal induced contact dermatitis in dorsal skin and footpad swelling in wild-type mice, but had no significant effect in MrgprB2knockout mice. Thimerosal-induced dermatitis is characterized by infiltration of inflammatory cells and elevation of serum histamine and inflammatory cytokines, rather than elevation of serum IgE level. Moreover, thimerosal increased the intracellular Ca 2+ concentration in HEK293 cells overexpressing MrgprB2/MRGPRX2. Downregulation of MRGPRX2 resulted in the reduced degranulation of human mast cells from LAD2 cell line. Collectively, we demonstrate that MrgprB2 mediated thimerosal-induced mast cell degranulation and pseudoallergic reaction in mice, thimerosal also activated human mast cell via MRGPRX2, indicating that MRGPRX2 may be a key contributor to human contact dermatitis.
Connective Tissue, Dec 25, 2003
Journal of Dermatological Science, 2013
Low-dose ionizing radiation exposure represses the cell cycle and protein synthesis pathways in i... more Low-dose ionizing radiation exposure represses the cell cycle and protein synthesis pathways in in vitro human primary keratinocytes and U937 cell lines
Journal of Biomechanics, 1990
Compressive stress-strain properties of an elastic ligament of a bivalve, Pseudocardium sachaline... more Compressive stress-strain properties of an elastic ligament of a bivalve, Pseudocardium sachalinensis were investigated in the swollen state in water. The ligament is a calcified tissue, composed of calcium carbonate and insoluble protein which is rich in methionine S-oxide residue [Kikuchi, Y. and Tamiya, N., J. Biochem. (Tokyo) 89, 1975-1976 (1981)]. X-ray diffraction study showed that calcium carbonate existed only in orthorhombic aragonite form, and that all the crystal c-axes of the unit cell orientate nearly in the growing direction of the ligament. The uniaxial compression modulus for the growing direction was appreciably larger than those for the other two directions, while the anisotropy of the modulus was absent for a decalcified ligament. Thus the mechanical anisotropy of the ligament could be explained by means of the uniaxially oriented structure of aragonite crystals being dispersed in a nearly isotropic protein matrix.
Gastroenterology, 2008
The authors thank Dr Benoit de Crombrugghe for his generous gift of transgenic collagen promoter ... more The authors thank Dr Benoit de Crombrugghe for his generous gift of transgenic collagen promoter reporter mice; Drs Marcos Rojkind and Patricia Greenwel for providing us with CFSC-2G cells; Dr Peter ten Dijke for the valuable anti-Smad2 and anti-Smad3 antibodies; and Drs Fu-Tong Liu and Ko Fujimori for their helpful suggestions. Conflicts of interest: No conflicts of interest exist with the submitting manuscript.
Journal of Dermatological Science, 2013
Dermokine-β is abundant in stratified epithelia and in differentiating keratinocytes in culture. ... more Dermokine-β is abundant in stratified epithelia and in differentiating keratinocytes in culture. We have recently shown that treatment of keratinocytes with dermokine-β attenuates phosphorylation of extracellular signal-regulated kinase, however, the roles of dermokine-β in vivo remain unknown. Dermokine-β is overexpressed in marginal keratinocytes during wound healing. This study was conducted to investigate the roles of dermokine-β in the wound healing process. Recombinant human dermokine-β or its active peptide was topically applied to excisional wounds in mice and the relative wound area was calculated. Histological and chemokine expression analyses in wounds were also performed. The chemokine expression levels as well as the chemotactic activity of dermokine-β in cultured keratinocytes were determined. Topical application of recombinant dermokine-β as well as its carboxy-terminal domain peptide inhibited mouse wound healing at an early phase, reduced infiltration of neutrophils and macrophages into the wounds, inhibited angiogenesis, and decreased the number of myofibroblasts in the wounds. Treatment with dermokine-β augmented IL-10 expression, but attenuated expression of transforming growth factor-β and tumor necrosis factor-α. In addition, application of dermokine-β to skin wounds reduced the expression of CXCL1 and CXCL5, both of which are chemoattractant for neutrophils into wounds. Both dermokine-β and its active peptide decreased the expression of CXCL1, CXCL6, and CXCL8 in cultured human keratinocytes. Treatment of human keratinocytes with dermokine-β inhibited neutrophil chemotaxis. These results suggest that dermokine-β delays early cutaneous wound healing in part by inhibiting expression of CXC chemokines containing the ERL-sequence motif.
Supplemental material, revised_figure_Higashi_et_al for Carbohydrate 3′-sialyllactose as a novel ... more Supplemental material, revised_figure_Higashi_et_al for Carbohydrate 3′-sialyllactose as a novel target for theranostics in pancreatic ductal adenocarcinoma by Kiyoshi Higashi, Keiko Maeda, Kaori Miyata, Saori Yoshimura, Keita Yamada, Daijiro Konno, Taro Tachibana and Koichi Saito in Tumor Biology
Review of gastroenterology & clinical gastroenterology and hepatology, 2008
Cancer Biomarkers, 2019
BACKGROUND: Pancreatic ductal adenocarcinoma is a devastating malignancy with an extremely poor p... more BACKGROUND: Pancreatic ductal adenocarcinoma is a devastating malignancy with an extremely poor prognosis. Although the most widely used biomarker for pancreatic cancer is carbohydrate antigen CA19-9, it is elevated mainly in the late stage of pancreatic cancer. Some serum natural antibodies against carbohydrates have been shown to be possible diagnostic markers for cancer. OBJECTIVE: This study was conducted to determine whether the level of natural antibodies against carbohydrates fluctuates in pancreatic ductal adenocarcinoma. METHODS: Serum from pancreatic cancer subjects (n = 55) and 43 subjects free of malignant disease were studied. The contents of natural antibodies against sialyl glycans and CA19-9 in serum were determined by enzyme-linked immunosorbent assay. RESULTS: The level of serum anti-3'-sialyllactose antibodies in pancreatic cancer subjects was significantly lower than that in healthy controls. In contrast, the amounts of serum antibodies against other sialyl glycans were comparable between the two groups. Concentration of serum anti-3'-sialyllactose IgG provided excellent AUC of 0.86, with sensitivity 82%, specificity 81%, and accuracy 82%. The combination of serum anti-3'-sialyllactose IgG with CA19-9 improved the sensitivity of pancreatic cancer detection at an early stage. CONCLUSIONS: Natural antibodies against 3'-sialyllactose constitute a promising biomarker for pancreatic cancer detection. The measurement of serum anti-3'-sialyllactose antibodies could play a supportive role in diagnostics and complement the performance of CA19-9 for the early detection of pancreatic ductal adenocarcinoma.
Tumor Biology, 2020
We previously demonstrated that the carbohydrate 3′-sialyllactose is overexpressed in cancer stem... more We previously demonstrated that the carbohydrate 3′-sialyllactose is overexpressed in cancer stem-like cells such as metastatic pancreatic and poorly differentiated gastric cancer cells, and undifferentiated human embryonic stem cells. In this study, we investigated the possibility of 3′-sialyllactose as a target for theranostics in cancers using a recombinant mouse monoclonal antibody r3B1E2 that binds to 3′-sialyllactose. Immunohistochemistry analysis confirmed an elevated expression of 3′-sialyllactose in tumors of pancreas, stomach, and testis, while no expression of 3′-sialyllactose was observed in corresponding normal controls. In addition, a stage-independent expression of 3′-sialyllactose was observed, especially in pancreatic ductal adenocarcinoma (PDAC). The level of serum 3′-sialyllactose in PDAC subjects was significantly higher than that in healthy controls, providing excellent AUC of 0.88. We next explored the therapeutic potential of r3B1E2 for PDAC in vitro. Treatmen...
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Papers by KIYOSHI HIGASHI