Fumiko Sakamoto

Niigata University, Niahi-niigata, Niigata, Japan

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Publications (6)17.67 Total impact

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    ABSTRACT: It has been recognized that ceramides are decreased in the epidermis of patients with psoriasis as well as atopic dermatitis. Here, we generated Sptlc2 (serine palmitoyltransferase long chain base subunit 2) targeted mice (SPT-cKO mice), thereby knocking out serine palmitoyltransferase (SPT), the critical enzyme for ceramide biosynthesis, in keratinocytes. SPT-cKO mice showed decreased ceramide levels in the epidermis, which impaired water-holding capacity and barrier function. From 2 weeks of age, they developed skin lesions with histologic aberrations including hyperkeratosis, acanthosis, loss of the granular layer, inflammatory cell infiltrates. Epidermal Langerhans cells showed persistent activation and enhanced migration to lymph nodes. Skin lesions showed up-regulation of psoriasis-associated genes, such as IL-17A, IL-17F, IL-22, S100A8, S100A9 and β-defensins. In the skin lesions and draining lymph nodes, there were increased numbers of γδ T cells that produced IL-17 (γδ-17 cells), most of which also produced IL-22, as do Th17 cells. Furthermore, IL-23-producing CD11c(+) cells were observed in the lesions. In vivo treatment of SPT-cKO mice with an anti-IL-12/23p40 antibody ameliorated the skin lesions and reduced the numbers of γδ-17 cells. Therefore, we conclude that a ceramide deficiency in the epidermis leads to psoriasis-like lesions in mice, likely mediated by IL-23-dependent IL-22-producing γδ-17 cells.Journal of Investigative Dermatology accepted article preview online, 30 April 2013; doi:10.1038/jid.2013.199.
    Journal of Investigative Dermatology 04/2013; · 6.19 Impact Factor
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    ABSTRACT: The gene encoding human desmoglein 4 (DSG4) was recently cloned, and a mutation in this gene has been reported in several consanguineous Pakistani families affected with localized autosomal recessive hypotrichosis (LAH). In addition, various mutations in the Dsg4 gene have been identified in animal models of hypotrichosis that share a characteristic phenotype called "lanceolate hair". To date, the features of the hair-shaft anomaly in patients with LAH have not been well described. We report a Japanese patient affected with congenital hypotrichosis that was originally diagnosed as monilethrix because she had a hair-shaft abnormality that resembled moniliform hair. However, no mutations were found in the type II hair keratin genes, hHb1, hHb3, and hHb6, whose mutations cause monilethrix. Instead, we identified novel compound heterozygous mutations in the DSG4 gene of our patient. On the maternal allele is a novel S192P transition within the extracellular cadherin II domain of DSG4; on the paternal allele is a novel 2039insT mutation leading to the generation of unstable transcripts. Here we present the observation that mutations in the DSG4 gene can cause monilethrix-like congenital hypotrichosis. Based on our findings, we propose that LAH and monilethrix could overlap.
    Journal of Investigative Dermatology 07/2006; 126(6):1281-5. · 6.19 Impact Factor
  • Ying Song, Fumiko Sakamoto, Masaaki Ito
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    ABSTRACT: Previous studies indicate that FXIIIa+ proliferative cells are the cells constituting DFs, however, in spite of the high incidence of DFs, there is a little information in the literature regarding ultrastructural characteristics of the FXIIIa+ dendritic cells on DFs. In this study, we examined the fine structures and potential heterogeneity among the subgroup of factor XIIIa (FXIIIa) positive dendritic cells consisted of eleven cases of dermatofibroma (DF). Immunohistochemical, electron microscopical, and immunoelectron microscopical techniques were utilized. We demonstrated (i) the immunohistochemical labeling of FXIIIa and CD68 in the DFs. The reactivity was stronger in histiocytic lesions than in fibroblastic lesions. On the other hand, the labeling of HHF35 was mainly in fibroblastic lesions. (ii) The fibroblastic and histiocytic cells on DFs displayed the same basic fine structures; moderate or abundant rough endoplasmic reticulum (RER), lipid droplets and/or bundles of myofilaments in varying proportions. Macular adherence connections between neighboring cells were common. (iii) They also showed the similar features to dermal dendritic cells (DDC), which have been well characterized with long cytoplasmic processes, abundant RER, fibronexus-like plaques and pinocytotic vesicles. (iv) FXIIIa expressions were found within the cytoplasm of both fibroblastic and histiocytic cells in association with the nucleus by immunoelectron microscopy. The labeling was stronger in the histiocytic cells and the cells expressing elongated cytoplasmic processes than in the fibroblastic cells. The FXIIIa+ dendritic cells might be an essential cell of DF, and might have potential to develop HHF35+ fibroblastic or CD68+ histiocytic cells, under appropriate stimuli. The FXIIIa+ dendritic cells might be originated from DDC.
    Journal of Dermatological Science 09/2005; 39(2):89-96. · 3.52 Impact Factor
  • Fumiko Sakamoto, Masaaki Ito, Ryuzo Saito
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    ABSTRACT: Acquired structural hair defects are caused by various physical and chemical manipulations. Plucked hairs and hair follicle biopsy specimens of pili torti-like hairs that arose from pseudopelade scalp were studied. In scanning electron microscopy, the hair shafts had a segmental pili torti-like appearance, accompanied by oblique or longitudinal grooves and ridges. In light microscopy, the hair follicles showed an asymmetric hair bulb and inner root sheath, and a shortened keratogenous zone within sclerosing fibrous connective tissue. In transmission electron microscopy, the numbers and thickness of the hair cuticle cells were different on the opposite sides of the hair shaft. The hair cuticle was irregularly shaped and formed asymmetric waves. The tonofilaments in the hair cortex ran almost parallel to the hair axis. From these findings, it was clear that the grooves and ridges were produced by the deformed hair cuticle and cortex, whose shapes were modulated by the asymmetric inner root sheath. This asymmetry most likely resulted from a dysfunctional dermal papilla, which was affected by fibrosis. The pili torti-like appearance appeared to be caused by the grooves and ridges that ran obliquely on the hair shaft surface.
    The Journal of Dermatology 05/2002; 29(4):197-201. · 1.77 Impact Factor
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    ABSTRACT: A case of cutaneous adnexal carcinoma arising on the cheek of an 87-year-old woman was studied by light and electron microcopy. This tumor showed a histologic architecture resembling trichilemmal carcinoma. The tumor was composed of lobular nests showing peripheral cell palisading, and trichilemmal keratinization having central keratinous masses and/or cyst-like structures. Electron microscopy showed that the tumor cells represent a combined differentiation toward follicular, sebaceous, and apocrine apparatus.
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    ABSTRACT: The present study demonstrated the structure of the multiple nodules of trichoepithelioma papulosum multiplex (TPM) with sweat duct differentiation taken from a 74-year-old woman. Histologically, the tumor was wellcircumscribed, and composed of several basaloid nests with palisading at the periphery, keratinous cysts, and occasional follicular papillae. Another prominent finding was the presence of some small duct-like structures, which were proven by immunohistochemistry and electron microscopy to be sweat ducts. Typically, trichoepithelioma is considered a benign neoplasm showing differentiation toward the hair follicle. We here report a unique case which showed combined differentiation toward the hair follicle and sweat duct.