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Featured researches published by Ken-ichi Toda.


Immunology Letters | 1994

Adult T cell leukemia-derived factor/human thioredoxin protects endothelial F-2 cell injury caused by activated neutrophils or hydrogen peroxide.

Hajime Nakamura; Mitsuhiro Matsuda; Keizo Furuke; Yuki Kitaoka; Satoshi Iwata; Ken-ichi Toda; Takashi Inamoto; Yoshio Yamaoka; Kazue Ozawa; Junji Yodoi

Adult T cell leukemia-derived factor (ADF), originally defined as an interleukin 2 receptor/alpha (alpha) chain inducer produced by human T-lymphotropic virus type-I transformed cells, is identical to human thioredoxin (TRX). In this study, the protective effect of ADF/TRX on the cytotoxicity of endothelial cells caused by phorbol myristate acetate (PMA)-activated neutrophils or hydrogen peroxide (H2O2) was examined. When murine endothelial F-2 cells established from an ultraviolet light-induced tumor on a nude mouse were incubated with PMA-activated neutrophils or with 1 mM H2O2 for 6 hours, the cytotoxicity of F-2 cells was respectively 51 +/- 4% or 40 +/- 8% by the 51Cr releasing assay. Recombinant ADF/TRX (rADF/TRX) inhibited this cytotoxicity in a dose-dependent manner, although mutant ADF/TRX (cysteine 31 to serine), 2-mercaptoethanol and dithiothreitol did not. On a molar basis, rADF/TRX was more effective than glutathione but less effective than catalase. Immunoblotting analysis showed that treatment with 0.1 mM H2O2 induced murine TRX on F-2 cells. These findings indicate that ADF/TRX is an oxidative stress-inducible endogenous protein and rADF/TRX plays a protective role against activated neutrophils- or H2O2-induced endothelial cytotoxicity.


Immunology Letters | 1995

Induction of ADF/TRX by oxidative stress in keratinocytes and lymphoid cells

Yoshifumi Sachi; Kiichi Hirota; Hiroshi Masutani; Ken-ichi Toda; Takashi Okamoto; Masahiro Takigawa; Junji Yodoi

Adult T-cell leukemia-derived factor (ADF)/human thioredoxin (TRX) has thiol-dependent reducing activities and is known to have regulatory roles on the DNA-protein interaction and cell activation. Inducive effect of ultraviolet (UV) has been indicated because of the enhanced expression of ADF/TRX in epidermal cells of sun-exposed skin, as determined by immunohistochemical staining with antibody against recombinant ADF (rADF). We studied the effect of UVB irradiation and other oxidative stress on the expression of ADF/TRX in epithelial cells as well as lymphoid cells, as HTLV-1 and Epstein-Barr virus-transformed lymphoid cells constitutively produce ADF/TRX. Using immunohistochemical staining anti-ADF antibody, the enhancement of ADF/TRX expression on primary culture of human keratinocytes was demonstrated, 12 h after 20 mJ/cm2 UVB irradiation. Western blot analysis of the ADF/TRX protein in the cell lysates also showed the significant induction. In in situ hybridization, induction of ADF/TRX mRNA was detected after 4 h of UV exposure. ADF/TRX was also induced in a HTLV-1 (+) T-cell line, MT-1, by UVB or H2O2 dose dependently. The augmentation of ADF/TRX was observed 6 h after treatment of H2O2.


Plastic and Reconstructive Surgery | 1994

A new skin equivalent : keratinocytes proliferated and differentiated on collagen sponge containing fibroblasts

Tomoko Maruguchi; Yukiya Maruguchi; Shigehiko Suzuki; Kazuya Matsuda; Ken-ichi Toda; Nobuhiko Isshiki

Three types of artificial skin containing keratinocytic components were prepared and tested for comparison. Keratinocytes were cultured on the artificial skin dermis (collagen sponge) by the air-liquid interface culture method. In order to create continuous keratinocytic layers on the artificial skin dermis, pores of its uppermost layer were filled beforehand with type I collagen gel, Matrigel, or fibroblasts. A band of keratinocytes consisting of two to six cell layers was formed on collagen gel-coated artificial skin dermis. On Matrigel-coated artificial skin dermis, keratinocytes were piled up into about 20 cell layers, but cell differentiation was incomplete; cornified material was not fully developed, and the proportion of cuboidal cells was very high compared with normal epidermis. Keratinocytes formed continuous layers on the fibroblasts-artificial skin dermis complex without gel coating. Keratinocytes proliferated well and differentiated properly on this matrix, and their histologic appearance was similar to that of normal epidermis. Thus keratinocytes cultured on the fibroblast-artificial skin dermis complex seem to be a good skin equivalent.


Microscopy Research and Technique | 1997

Roles of E- and P-cadherin in the human skin.

Fukumi Furukawa; Kimio Fujii; Yuji Horiguchi; Norihisa Matsuyoshi; Mayumi Fujita; Ken-ichi Toda; Sadao Imamura; Hisashi Wakita; Shigeho Shirahama; Masahiro Takigawa

The Ca2+‐dependent cell‐cell adhesion molecules, termed cadherins, are subdivided into several subclasses. E (epithelial)‐ and P (placental)‐cadherins are involved in the selective adhesion of epidermal cells.


Photodermatology, Photoimmunology and Photomedicine | 2001

Near‐infrared irradiation stimulates cutaneous wound repair:laboratory experiments on possible mechanisms

Kiichiro Danno; Noriko Mori; Ken-ichi Toda; Takashi Kobayashi; Atsushi Utani

Background/Aims: Several physical agents such as low‐energy lasers have been used in the treatment of chronic skin ulcers. This study was performed to investigate potential effects of a newly‐developed, specific near‐infrared light source on wound repair.


American Journal of Dermatopathology | 1998

Basal cell carcinoma cells resemble follicular matrix cells rather than follicular bulge cells: immunohistochemical and ultrastructural comparative studies.

Satoshi Kore-Eda; Yuji Horiguchi; Masamichi Ueda; Ken-ichi Toda; Sadao Imamura

To detail the histogenetic relationship between basal cell carcinoma (BCC) and hair follicles, we immunohistochemically compared BCC cells to follicular matrix cells and follicular bulge cells using a panel of monoclonal antibodies against melanocytes, cytokeratins, subepidermal extracellular matrix components, and bullous pemphigoid (BP) sera, as well as using electron microscopy. Cytokeratin expression patterns were not consistent with the variety in types of cytokeratins and in cases of BCC. The distribution of some extracellular matrix components was not only linear along the interfaces of BCC tumor nests and stroma, and follicular matrix and follicular papilla; granular deposits were also seen in the stroma and follicular papilla, whereas they were only linearly distributed along the follicular bulge. The BP antigens and integrin alpha 6, which were absent in BCC and follicular matrix, were expressed in the follicular bulge area. Electron microscopically, hemidesmosomes were poorly organized in these three tissues, but the lamina densa was incomplete in BCC and follicular matrix, whereas the lamina densa in the follicular bulge area was continuous. These morphologic similarities between BCC and follicular matrix cells, and coexistence of melanocytes in the BCC tumor nest strongly suggest the differentiation of BCC toward the follicular matrix cells.


Journal of The American Academy of Dermatology | 1986

Immunoelectron microscopic observations in a case of linear IgA bullous dermatosis of childhood

Yuji Horiguchi; Ken-ichi Toda; Hiroyuki Okamoto; Sadao Imamura

A 16-month-old boy exhibited vesicobullous skin lesions on the lower part of his abdomen, in his genital region, and on the buttocks and extremities. The eruptions presented small, tense bullae with or without erythematous changes of the surrounding skin, some of which clustered around the resolving lesions. Histologic examination of the eruptions showed subepidermal, ultrastructurally suprabasal laminar blister formation with infiltration of the polymorphonuclear cells and large mononuclear cells in the blister cavity. Immunoelectron microscopy revealed IgA deposits at the basilar surface of the basal keratinocytes of the lesional skin, as well as the presence of circulating IgA-class antibodies reacting to the basilar surface of the hemidesmosomes. The eruptions responded well to a combination therapy of small doses of a corticosteroid agent and a sulfonamide. There were neither clinical nor laboratory findings suggesting dermatitis herpetiformis. This case, diagnosed as linear IgA bullous dermatosis of childhood by immunofluorescence microscopy, ultrastructurally had a pathogenic site close to that observed in bullous pemphigoid.


British Journal of Dermatology | 2006

Soluble E-cadherin : a novel cutaneous disease marker

Norihisa Matsuyoshi; Toshihiro Tanaka; Ken-ichi Toda; Hiroyuki Okamoto; Fukumi Furukawa; Sadao Imamura

E‐cadherin is a major homophilic cell‐cell adhesion molecule of the skin. There are two forms of E‐cadherin—membrane and soluble types. Although various abnormalities of the former type have been identified in some cutaneous diseases, information relating to the latter is sparse. We measured the concentrations of soluble E‐cadherin in several cutaneous diseases, and found higher levels in sera from patients with bullous pemphigoid, pemphigus vulgaris, psoriasis vulgaris and inflammatory skin diseases, compared with controls. In psoriasis vulgaris the levels of soluble E‐cadherin in sera correlated with the PASI score. In normal individuals, levels in suction blister fluid were double those in sera. These findings suggest that changes occur in circulating levels of soluble E‐cadherin in skin disease, possibly reflecting increased turnover and/or proteolysis of cell‐surface molecules in the epidermis.


Archives of Dermatology | 1992

Amyloidosis cutis dyschromica : DNA repair reduction in the cellular response to UV light

Shinichi Moriwaki; Chikako Nishigori; Yuji Horiguchi; Sadao Imamura; Ken-ichi Toda; Hiraku Takebe

BACKGROUND Amyloidosis cutis dyschromica, a special type of primary cutaneous amyloidosis, is assumed to be a congenital disorder and sun exposure is thought to be the major causal factor. Herein we report a case of this rare disease and DNA repair characteristics of UV damages in the fibroblasts derived from the patient. OBSERVATIONS A 24-year-old Japanese woman showed hyperpigmented and hypopigmented xerotic lesions in sun-exposed skin since she was 10 years old; deposits of amyloid material were detected in the papillary dermis. The fibroblasts were hypersensitive to UV-B, but not so sensitive to UV-C. Unscheduled DNA synthesis of the patients cells after UV-C exposure was lower than that of normal cells at 3 hours and both reached the same level at 6 hours. After UV-B exposure, unscheduled DNA synthesis of the patients cells was lower than that of normal cells at least until 6 hours after UV exposure. CONCLUSION Although the origin of amyloidosis cutis dyschromica is unknown, hypersensitivity to UV-B with possible DNA repair defects is suggested to be the cause of this disease.


FEBS Letters | 2006

Cyclophosphamide enhances TNF-α-induced apoptotic cell death in murine vascular endothelial cell

Toshio Ohtani; Tomoyuki Nakamura; Ken-ichi Toda; Fukumi Furukawa

Cyclophosphamide (CPA) is one of the therapeutic agents for systemic inflammatory disorders. In murine dermal endothelial cells (F‐2), 4‐hydroxycyclophosphamide (4‐HC), which is active metabolite of CPA, enhanced TNF‐α‐induced DNA fragmentation. In addition, 4‐HC was shown to elevate TNF‐α‐induced caspase‐3 activation. Caspase‐8 activation was identified by the treatment of TNF‐α, whereas 4‐HC was no effect. In contrast, only when treated with 4‐HC, caspase‐9 activation and the increase in the intracellular expression of Bax were detected. These results suggest that CPA may sensitize endothelial cells to TNF‐α‐induced apoptosis through a mitochondria‐dependent pathway and clinically may contribute to the limitation of inflammatory process.

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Kiichiro Danno

Shiga University of Medical Science

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Fukumi Furukawa

Wakayama Medical University

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Takeshi Horio

Kansai Medical University

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