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

DOI： 10.1111/cup.13891

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

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

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

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

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

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

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

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

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

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

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

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

DOI： 10.1111/exd.12794

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

症例1:64歳女、症例2:75歳女で、いずれも全身のそう痒を伴う皮疹および水疱を主訴とした。いずれの症例も臨床検査でBP180抗体陽性を認め、病理組織像より水疱性類天疱瘡と診断した。中等量以上のプレドニゾロン(PSL)内服を開始したものの皮疹が拡大し、紅皮症を呈したため、メチルプレドニゾロン(mPSL)によるパルス療法を施行した。以後、慎重にPSLを漸減し、症例2は皮疹の良好なコントロールが得られた。症例1はPSL漸減中に口腔びらんが出現し、再度mPSLパルス療法を併用し皮疹は良好にコントロールされた。

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

The integrity of the epidermis depends on the cohesion between keratinocytes, and desmosomes are the main adhesion structures. When cells become cornified, desmosomes are modified and transformed into corneodesmosomes. Mutations in the genes encoding desmosomal components underlie several skin diseases including palmoplantar keratoderma and forms of epidermolysis bullosa, indicating the importance of desmosomes as mechanical stress-bearing structures. Other types of genetic defects in a desmosome component (desmoglein 1), a corneodesmosome component (corneodesmosin), and an inhibitor for proteases involved in corneodesmosome degradation (LEKTI) result in three clinically overlapping conditions: SAM syndrome, an inflammatory type of peeling skin disease, and Netherton syndrome. All three result in allergies to multiple allergens due to severe barrier impairment. Conversely, impaired corneodesmosomal degradation due to matriptase mutations could lead to ichthyosis. By discovering the diverse clinical phenotypes of these diseases, we can enrich our understanding of the multifunctional roles of desmosomes and corneodesmosomes in skin biology. © 2014 Japanese Society for Investigative Dermatology.

DOI： 10.1016/j.jdermsci.2014.02.005

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

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease, which is characterized by recurrent and paroxysmal fever, peritonitis, arthritis, myalgia, and skin rashes. Although various skin lesions such as "erysipelas-like erythema", urticaria, nonspecific purpura, and subcutaneous nodules have been described, cutaneous vasculitis is rare. We report a Japanese case of sporadic FMF accompanied by cutaneous arteritis at the time of febrile attacks of FMF. Gene analysis revealed M694I mutation in a single allele of the MEFV gene, and oral colchicine successfully controlled both periodic fever and subcutaneous nodules of arteritis. Cutaneous necrotizing vasculitis repeatedly emerging with febrile attacks should be included among the skin manifestations of FMF. © 2014 Japanese Dermatological Association.

DOI： 10.1111/1346-8138.12588

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

The stratum corneum of the epidermis is composed of stacked dead corneocytes embedded in lipid layers and is the main protective shield of the skin. The thickness of the stratum corneum is maintained fairly constantly through the balance between new cell creation and old cell removal. Corneodesmosomes are the main intercellular adhesive structures in the stratum corneum. They are transformed from desmosomes at the most superficial layer of the stratum granulosum of the epidermis. The major compositional distinction from desmosomes is the presence of corneodesmosin in the extracellular portion. Furthermore, corneodesmosomes are structurally different from desmosomes in that (1) they do not have a tri-lamellar desmoglea but rather one that is homogeneously electron-dense and (2) attachment plaques are integrated into a part of the cornified cell envelopes. When the extracellular regions of corneodesmosomes are fully degraded, desquamation occurs. The degradation process of corneodesmosomes is carefully controlled by a number of proteases and their inhibitors. The most important proteases involved in this process are the kallikrein-related peptidases. Their main inhibitor is the lympho-epithelial Kazal-type related inhibitor. Other regulators of this process include matriptase, meprin and mesotrypsin. © 2014 Springer-Verlag Berlin Heidelberg

DOI： 10.1007/s00441-014-2037-z

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Peeling skin syndrome (PSS) type B is a rare recessive genodermatosis characterized by lifelong widespread, reddish peeling of the skin with pruritus. The disease is caused by small-scale mutations in the Corneodesmosin gene (CDSN) leading to premature termination codons. We report for the first time a Japanese case resulting from complete deletion of CDSN. Corneodesmosin was undetectable in the epidermis, and CDSN was unamplifiable by PCR. QMPSF analysis demonstrated deletion of CDSN exons inherited from each parent. Deletion mapping using microsatellite haplotyping, CGH array and PCR analysis established that the genomic deletion spanned 49-72 kb between HCG22 and TCF19, removing CDSN as well as five other genes within the psoriasis susceptibility region 1 (PSORS1) on 6p21.33. This observation widens the spectrum of molecular defects underlying PSS type B and shows that loss of these five genes from the PSORS1 region does not result in an additional cutaneous phenotype. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

DOI： 10.1111/exd.12292

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

Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm characterized by clonal proliferation of Langerhans cells in multi-organ systems including skin, bone, pituitary gland, liver and spleen. Skin-limited involvement of LCH usually indicates an indolent clinical course; however, in rare cases, LCH is accompanied by other myeloproliferative disorders, which may determine the prognosis. An 82-year old Japanese man presented with numerous asymptomatic facial papules clinically simulating rhinophyma. Although findings of histopathology and general examination including bone marrow biopsy led to the diagnosis of cutaneous LCH, he died from chronic myelomonocytic leukemia, which emerged 10 months after the initial diagnosis of LCH. The previously reported cases of LCH concomitant with other hematological disorders are also summarized and described compared with the present case. © 2014 Japanese Dermatological Association.

DOI： 10.1111/1346-8138.12417

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

Background Chronic wounds are a major source of morbidity and mortality in generalized severe recessive dystrophic epidermolysis bullosa (RDEB-GS). Objective This was a phase II double-blinded randomized controlled trial of intralesional allogeneic cultured fibroblasts in suspension solution versus suspension solution alone for wound healing in RDEB-GS. Methods Adult patients with RDEB-GS were screened for chronic ulcers and reduced collagen VII expression. Up to 6 pairs of symmetric wounds were measured and biopsied at baseline, then randomized to cultured allogeneic fibroblasts in a crystalloid suspension solution with 2% albumin or suspension solution alone. Ulcer size, collagen VII protein and messenger RNA expression, anchoring fibril numbers, morphology, and inflammatory markers were measured at 2 weeks and at 3, 6, and 12 months. Results All wounds healed significantly more rapidly with fibroblasts and vehicle injections, with an area decrease of 50% by 12 weeks, compared with noninjected wounds. Collagen VII expression increased to a similar degree in both study arms in wounds from 3 of 5 patients. Limitations The number of patients with RDEB-GS who met inclusion criteria was a limitation, as was 1 trial center rather than multicenter. Conclusions The injection of both allogeneic fibroblasts and suspension solution alone improved wound healing in chronic nonhealing RDEB-GS wounds independently of collagen VII regeneration. This may provide feasible therapy for wound healing in patients with RDEB-GS. © 2013 by the American Academy of Dermatology, Inc.

DOI： 10.1016/j.jaad.2013.08.014

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

Barrett's esophagus (BE) is metaplastic columnar epithelium converted from normal squamous epithelia in the distal esophagus that is thought to be a precancerous lesion of esophageal adenocarcinoma. BE is attributed to gastroesophageal reflux disease (GERD), and therefore gastric acid or bile acids are thought to be factors that cause epithelial cell damage and inflammation in the gastro-esophageal junction. The decrease of adherent junction molecules, E-cadherin has been reported to be associated with the progression of the Barrett's carcinoma, but the initiation of BE is not sufficiently understood. BE is characterized by the presence of goblet cells and occasionally Paneth cells are observed at the base of the crypts. The Paneth cells possess dense granules, in which human antimicrobial peptide human defensin-5 (HD-5) are stored and secreted out of the cells. This study determined the roles of HD-5 produced from metaplastic Paneth cells against adjacent to squamous cells in the gastro-esophageal junction. A human squamous cell line Het-1A, was incubated with the synthetic HD-5 peptide as a model of squamous cell in the gastro-esophageal junctions, and alterations of E-cadherin were investigated. Immunocytochemistry, flowcytometry, and Western blotting showed that the expression of E-cadherin protein was decreased. And a partial recovery from the decrease was observed by treatment with a CD10/neprilysin inhibitor (thiorphan). In conclusion, E-cadherin expression in squamous cells was reduced by HD-5 using in vitro experiments. In gastro-esophageal junction, HD-5 produced from metaplastic Paneth cells may therefore accelerate the initiation of BE. © 2013 Elsevier Inc.

DOI： 10.1016/j.bbrc.2013.08.026

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Background: Atopic dermatitis (AD), Netherton syndrome (NS) and peeling skin syndrome type B (PSS) may show some clinical phenotypic overlap. Corneodesmosomes are crucial for maintaining stratum corneum integrity and the components' localization can be visualized by immunostaining tape-stripped corneocytes. In normal skin, they are detected at the cell periphery. Objective: To determine whether AD, NS, PSS and ichthyosis vulgaris (IV) have differences in the corneodesmosomal components' distribution and corneocytes surface areas. Methods: Corneocytes were tape-stripped from a control group (n=12) and a disease group (37 AD cases, 3 IV cases, 4 NS cases, and 3 PSS cases), and analyzed with immunofluorescent microscopy. The distribution patterns of corneodesmosomal components: desmoglein 1, corneodesmosin, and desmocollin 1 were classified into four types: peripheral, sparse diffuse, dense diffuse and partial diffuse. Corneocyte surface areas were also measured. Results: The corneodesmosome staining patterns were abnormal in the disease group. Other than in the 3 PSS cases, all three components showed similar patterns in each category. In lesional AD skin, the dense diffuse pattern was prominent. A high rate of the partial diffuse pattern, loss of linear cell-cell contacts, and irregular stripping manners were unique to NS. Only in PSS was corneodesmosin staining virtually absent. The corneocyte surface areas correlated significantly with the rate of combined sparse and dense diffuse patterns of desmoglein 1. Conclusion: This method may be used to assess abnormally differentiated corneocytes in AD and other diseases tested. In PSS samples, tape stripping analysis may serve as a non-invasive diagnostic test. © 2013 Japanese Society for Investigative Dermatology.

DOI： 10.1016/j.jdermsci.2013.05.004

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

DOI： 10.1111/j.1346-8138.2011.01345.x

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

Background Extramammary Paget's disease (EMPD) is an uncommon skin tumor that usually occurs in the genital area. Few studies on EMPD have been conducted. Objective To evaluate the clinical and pathologic features, treatments, recurrence, survival rates, and prognostic factors of EMPD. Methods A total of 35 (27 men and 8 women) patients with EMPD was analyzed. The average age of the patients was 73.4 years. Result Twenty nine Of the 35 patients had lesions in the genital area, one in the genital and perianal area, three in the axillary area and two in the perianal area. Eighteen patients had in situ lesions, five had inguinal lymph node metastases and two had distant metastases at the time of diagnosis. Surgical resection was performed in 30 cases and radiation therapy, was administered in three cases. Six patients died of EMPD, and the overall 5 year survival rate was 75%. Conclusion The presence of a nodule on the primary lesion, clinically palpable lymph nodes, the level of tumor invasion, and lymph node metastases were found to be significant prognostic factors in the 35 EMPD cases at our institution. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

DOI： 10.1111/j.1524-4725.2012.02584.x

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

Epidermal cornified cells are attached to each other with modified desmosomes, namely corneodesmosomes. Changes in the corneodesmosome degradation process influence the total thickness of the stratum corneum and surface appearance of the skin. The major extracellular constituents of corneodesmosomes are desmoglein 1, desmocollin 1 and corneodesmosin. The intracellular part of corneodesmosomes is cross-linked into cornified cell envelopes. Corneodesmosomes are degraded from the central surface area of each cell. Peripheral corneodesmosomes retain structural integrity up to the skin surface. A hypothesis where tight junctions in the stratum corneum play a role in this spatial difference in corneodesmosome degradation has recently been proposed. Genetic defects in corneodesmosin and inhibitors for proteases involved in corneodesmosome degradation result in accelerated desquamation and severe barrier impairment, presenting as the inflammatory type of peeling skin syndrome and Netherton syndrome, respectively. Abnormal corneodesmosome degradation is also found in more common skin diseases including ichthyosis vulgaris, atopic dermatitis, psoriasis vulgaris, lichen planus and soap-induced xerosis. © 2011 Japanese Dermatological Association.

DOI： 10.1111/j.1346-8138.2011.01227.x

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To maintain stratum corneum integrity while simultaneously desquamating at a steady rate, degradation of corneodesmosomes must proceed in a controlled manner. It is unknown why corneodesmosomes are present only at the cell periphery in the upper stratum corneum. To explore this, we studied distributions of three major corneodesmosomal components, corneodesmosin, desmoglein 1 and desmocollin 1 in normal adult human epidermis. Immunofluorescent microscopy studies of skin surface corneocytes detected all three components only at the cell edges. Immunoelectron microscopy revealed selective loss of these components at the central areas starting from the deep cornified layers. We hypothesized that tight junctions (TJs) formed in the superficial granular layer may prevent protease access by functioning as a barrier between the peripheral and the central intercellular spaces in the stratum corneum. Ultrastructural examination demonstrated TJs up to the junctions between the seventh and the eighth deepest cornified layers. Immunoelectron microscopy also detected clusters of occludin and claudin1 immunolabels at the cell periphery, and kallikrein 7 immunolabels outside of TJs in the lower cornified layers. With colloidal lanthanum nitrate perfusion assay of stripped stratum corneum, the tracer was excluded from TJ domains. Taken together, we propose that TJs inhibit access of proteases to the peripheral corneodesmosomes forming the structural basis for the basket-weave-like appearance of the stratum corneum. © 2010 John Wiley & Sons A/S.

DOI： 10.1111/j.1600-0625.2010.01170.x

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Event date： 2020.11

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2020.10

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2020.9

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2019.11

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.11

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2019.8

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.5

Language：English   Presentation type：Poster presentation  

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Event date： 2019.5

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Event date： 2018.5 - 2019.5

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Event date： 2017.12

Language：English   Presentation type：Poster presentation  

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Event date： 2016.7

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2014.5 - 2014.6

Language：Japanese  

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