Ryoji Tsuboi

Tokyo Medical University, Edo, Tokyo, Japan

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Publications (324)877.93 Total impact

  • T. Kariya · Y. Kato · A. Kanzaki · Y. Kanda · T. Ohara · R. Tsuboi
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    ABSTRACT: Deoxy-2-[18F] fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) is known to be highly accurate in differentiating benign from malignant lesions. In rare cases, benign tumors, viral infections, and sarcoidosis of the skin have been reported to show FDG uptake, but the mechanism remains unclear. Here we report the first documented case of seborrheic keratosis (SK) showing increased FDG uptake. FDG PET can be used to detect enhanced glycolysis of tumor cells by measuring increased levels of glucose transporters (GLUTs) indicative of higher glucose uptake. GLUT1 and GLUT3 expression in this case was compared with that in PET-negative SK and two normal skin samples using quantitative PCR with paraffin-embedded tissue. The expression of GLUT1 and GLUT3 was higher in PET-positive SK than in PET-negative SK or normal skin. More specifically, the expression of GLUT3 was observed only in the PET-positive case. This study revealed that high GLUT1 and GLUT3 expression in SK might be associated with the uptake of FDG. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2016 · British Journal of Dermatology
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    ABSTRACT: Infection by Trichophyton tonsurans is an emerging fungal epidemic in Japan. Itraconazole (ITZ) and terbinafine have been used for the treatment of this infection for 15 years. However, patients with T. tonsurans infections have been shown to remain uncured or to become reinfected, suggesting that subclinical infection or polyphyletic strains and/or antifungal drug-resistant strains might be occurring in Japan. In this study, PCR analysis was performed to confirm the presence of the mating type locus MAT in genomic DNA from 60 Japanese clinical isolates of T. tonsurans, and to assess the previously postulated clonal origin of clinical isolates of this species. Antifungal susceptibility testing on isolates also was performed to confirm the absence of strains resistant to ITZ. PCR analysis proved that all 60 strains contained the MAT1-1 allele, while none contained the MAT1-2 allele. As determined by E-test, the mean MIC of ITZ in the 60 strains was 0.023 mg/L (range 0.002-0.125 mg/L). All strains of T. tonsurans isolated in Japan were clonal and were not resistant to ITZ. Therefore, dermatophytosis due to T. tonsurans is expected to respond to ITZ, since clinical isolates of T. tonsurans tested to date have been susceptible to this antifungal. This infection is proliferating as a subclinical infection in Japan.
    No preview · Article · Jan 2016 · Mycopathologia
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    ABSTRACT: Objective: To compare drug concentrations in the stratum corneum following daily application of luliconazole and terbinafine cream in a guinea pig tinea pedis model. METHODS: Luliconazole 1% cream or terbinafine 1% cream were topically applied once daily to hind limbs of guinea pigs for 14 days. Drug concentration in stratum corneum of plantar skin was measured by HPLC-UV on days 1, 3, 7, 10, and 14. Separately, creams were applied daily for 5 days to the hind limbs of guinea pigs and skin drug release determined. In addition, drug retention in the stratum corneum was assessed by infecting guinea pigs with Trichophyton mentagrophytes, 14 and 21 days after a single application of luliconazole or terbinafine creams. RESULTS: Luliconazole stratum corneum concentrations were higher than those of terbinafine throughout the study. Concentrations of luliconazole and terbinafine were 71.6μg/g and 36.6μg/g, respectively, after a single application (P<.05), reaching steady state after 10 days. Cumulative release of luliconazole from the stratum corneum was 4.5 times greater than with terbinafine. Unlike terbinafine, no fungal invasion of the stratum corneum was seen 14 days post-treatment with luliconazole. CONCLUSIONS: Drug concentrations of luliconazole in the stratum corneum and subsequent release are greater than those achieved with terbinafine and may contribute to clinical efficacy. Luliconazole may also provide greater protection against disease recurrence. J Drugs Dermatol. 2016;15(1):104-108.
    No preview · Article · Jan 2016 · Journal of drugs in dermatology: JDD
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    ABSTRACT: We herein report a case of hair follicle nevus, a rare hamartoma found on the face and showing follicular differentiation, which was associated with sebaceous hyperplasia. Dermoscopy of the lesion showed yellow globules surrounded by crown vessels/telangiectasias and scattered tiny hairs. Histopathological investigation revealed hyperplasia of the sebaceous glands and proliferation of well-differentiated vellus hair follicles. These pathological findings were thought to correspond to the yellowish globules and tiny hairs observed under dermoscopy. Hair follicle nevus associated with sebaceous hyperplasia is extremely rare; however, dermoscopic examination can suggest an appropriate diagnosis. The present case proved the diagnostic usefulness of dermoscopy for cutaneous tumors with hair follicular and sebaceous glandular differentiation.
    No preview · Article · Dec 2015 · Case Reports in Dermatology
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    ABSTRACT: Bleomycin-induced scleroderma in mice is an established model for human scleroderma. Making use of this, we have established a new model for wound retardation. After inducing dermal sclerosis by local bleomycin treatment in nude mice, a full-thickness wound was made by punch excision on the bleomycin application site. Mice pretreated with bleomycin showed a significant delay in wound closure, as compared with mice pretreated with phosphate-buffered saline. Proliferation of keratinocytes was significantly inhibited and the number of Ki-67-positive keratinocytes was significantly lower in the bleomycin-pretreated skin. Also, the number of CD31-positive blood vessels was markedly reduced in the bleomycin-treated skin. The topical daily application of basic fibroblast growth factor (bFGF) significantly promoted wound closure, while increasing blood vessel formation and reducing transforming growth factor-β and alpha-smooth muscle actin mRNA levels. Furthermore, only two applications of PG-FGF1, a fusion protein of FGF1 with heparan sulfate proteoglycan, overcame the delay in wound closure. Wound delay in this model mainly occurred as a result of decreased vessel formation and keratinocyte migration following bleomycin treatment. It is expected that this model will provide novel insights into the pathogenesis of wound healing and the exploration of possible candidate drugs for refractory or chronic wounds in the clinical setting.
    No preview · Article · Dec 2015 · Archives for Dermatological Research

  • No preview · Article · Nov 2015 · International journal of dermatology
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    ABSTRACT: Background: IL-33, a member of the IL-1 cytokine family, binds to heterodimeric receptors ST2 and IL-1 receptor accessory protein, and activates Th2-type immune responses. The signals from the ST2 receptor are mediated by the two major pathways, including AP-1 and NF-κB molecules. The present study examined whether IL-33 induced ICAM-1 expression in bone marrow-derived mast cells (BMMCs). Methods: BMMCs from C57BL/6J mice, cultured in media containing IL-3 (20 ng/ml), were treated with IL-33 (50 ng/ml) for up to 72 h. ICAM-1 expression with mRNA and protein, degranulation of siRNA ICAM-1 transfected BMMCs, and cell adhesion were analyzed. In the in vivo part of the experiment rIL-33 (500 ng) was injected intradermally into the ear pinnae of mice and any resulting pathological changes were assessed. Results: ICAM-1 mRNA expression was increased one hour after IL-33 stimulation while ICAM-1 protein attained maximum expression levels 24 h after IL-33 stimulation. Moreover, IL-33-treated BMMCs showed increased cell adhesion to the LFA-1-coated plate. However, siRNA ICAM-1 transfected BMMCs did not affect Ag/IgE-mediated degranulation level compared to the wild control siRNA. Pre-treatment with a NF-κB inhibitor dramatically reduced ICAM-1 expression in IL-33-treated BMMCs, suggesting the involvement of NF-κB in the process. In vivo study, at 6 h after IL-33 treatment, MCs histologically showed up-regulated ICAM-1 expression though the number of tryptase-positive cells did not change. Conclusions: These data suggest that MCs increase ICAM-1 expression and activate LFA-1 positive cells in the early phase of skin inflammation in response to IL-33.
    Preview · Article · Nov 2015 · Allergology International
  • Yukihiko Kato · Chizu Egusa · Tatsuo Maeda · Ryoji Tsuboi
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    ABSTRACT: Background: Retinoids exert anti-proliferative, differentiative, and apoptosis-inducing effects through their receptors. Retinoic acid receptor (RAR) β2 behaves as a tumor suppressor gene, and its expression is suppressible by DNA methylation in many malignancies. Objective: We aimed to determine whether combining a retinoid, Am 80, with a histone deacetylase inhibitor, MS-275, could suppress tumor growth in a RARβ2-negative human cutaneous T cell lymphoma (CTCL) cell lines and freshly isolated primary CTCL cells, and to elucidate the epigenetic mechanism behind the phenomena. Methods: SeAx cells were implanted subcutaneously in NOD-SCID mice which were randomly divided into four groups and treated with either Am80, MS-275 by oral gavage (five days/week), or a combination of the two agents. Cell proliferation assay, methylation-specific PCR, flow cytometric analysis of cell cycle and apoptosis and chromatin immunoprecipitation assay were employed. Results: Quantitative PCR analysis revealed that RARβ2 gene expression was restored only by this combination rather than by either of the agents singly. Restored retinoid sensitivity was observed in combining retinoid with a histone deacetylase inhibitor significantly inhibited cell growth in vitro, suppressed subcutaneously transplanted tumor growth, and prolonged survival of tumor-bearing mice in vivo by more strongly inducing apoptosis and p21 expression in CTCL cells than either agent alone. In the combination treatment, the histone H4 acetylation level at lysine 12 and 16 in the promoter region increased after restoration of RARβ2 expression although the DNA methylation of RARβ2 remained unchanged. Conclusion: This is the first report of histone acetylation as the primary event in the restoration of RARβ2. Inducible RARβ2 expression may serve as a reliable predictor for tumor response in patients undergoing 'epigenetic & differentiation' therapy.
    No preview · Article · Oct 2015 · Journal of dermatological science
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    ABSTRACT: Erythema dyschromicum perstans (EDP) and ashy dermatosis (AD) are pigmentary disorders of unknown etiology. EDP is usually considered to be identical to AD; however, a new clinical classification for EDP was proposed in the recent literature. Herein, we report a typical case of EDP observed in an African-American man. Interestingly, the late skin lesions in this case fit the criteria of AD as well. While there appear to be a few clinical cases that can be diagnosed as both EDP and AD based on the clinical course, the preponderance of the evidence in the published reports of EDP and AD and the clinical findings reported here strongly suggest that they are two distinct entities in terms of the extent of the inflammation, albeit on the same spectrum of pigment disorders.
    Preview · Article · Sep 2015 · Case Reports in Dermatology

  • No preview · Conference Paper · Sep 2015
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    ABSTRACT: Regarding appropriate timings of discontinuation and resumption of biologics for psoriasis patients before and after elective surgeries, an international consensus has yet to be reached. The Japanese Dermatological Association of Guideline and Safety Manual for the use of Biologic Agents in Psoriasis 2013 states that infliximab (IFX) and adalimumab (ADA) should be withheld at least 4 and 2 weeks, respectively, before surgery and can be restarted as neither postoperative infection nor delayed wound healing is recognized. We experienced three generalized pustular psoriasis (GPP) patients and one plaque-type psoriasis patient undergoing surgeries during tumor necrosis factor (TNF)-α blocker therapy. Three GPP cases experienced uneventful post-surgical course. One psoriasis vulgaris patient on IFX had a wound healing delay with deterioration of psoriatic plaques which was restored by restarting IFX. The timing of suspension and resumption of TNF-α blockers in all cases were determined following the Japanese guideline.
    No preview · Article · Sep 2015 · The Journal of Dermatology
  • R Jo · T Ito · C Egusa · T Maeda · T Numata · K Mae · M Saito · K Harada · R Tsuboi

    No preview · Article · Aug 2015 · Journal of the European Academy of Dermatology and Venereology
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    Preview · Article · Jul 2015
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    ABSTRACT: Vitamin D3 ointment and corticosteroid ointment are both used for the treatment of palmoplantar pustulosis (PPP). However, to date there is no systematic study of the efficacy of combination therapy for the treatment of PPP. We compared the efficacy of a topical combination therapy with vitamin D3 and a topical corticosteroid with that of topical corticosteroid alone in the treatment of PPP. We evaluated left-right comparison study of the efficacy of a combination therapy consisting of maxacalcitol ointment and betamethasone butyrate propionate ointment (BBP), and monotherapy with BBP alone in 27 patients with PPP for 8 weeks. The improvement in the symptom (erythema, pustules/vesicles, hyperkeratosis/scales) scores was high for the combination therapy. In particular, the improvement rate for pustules/vesicles at week 8 after the combination therapy was significantly higher than for the monotherapy (p < 0.05). This combination regimen demonstrated that not only topical corticosteroids, but also topical vitamin D3 ointment, is useful for the treatment of PPP.
    No preview · Article · Jun 2015 · Journal of Dermatological Treatment
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    ABSTRACT: Glupearl 19S, an acid-hydrolyzed wheat protein (HWP), is used widely in Japan as a moisturizing ingredient in facial soaps. Since 2010, there has been an increasing number of reports of contact urticaria and wheat allergy resulting from the use of products containing this substance. Sixty-one patients who had used HWP-containing facial soap visited our hospital. Thirty-five of these experienced urticaria or anaphylaxis after consuming wheat-containing food. Eighteen of the 35 patients tested positive to 0.01% Glupearl 19S solution. Wheat-specific IgE and serum gluten-specific IgE were higher in the patients with HWP allergy than in non-HWP allergy patients. Among the patients who tested positive to Glupearl 19S on the skin prick test, nine experienced HWP-wheat-dependent exercise-induced anaphylaxis, and four experienced food-dependent anaphylaxis. Moreover, four of these patients not only experienced food-dependent anaphylaxis but also a worsening of the symptoms during exercise. The clinical symptomology was so variable that the patients were classified into six groups. We found that patients with HWP allergy tended to manifest symptoms of both HWP-wheat-dependent exercise-induced anaphylaxis and contact urticaria. The etiology of hydrolyzed wheat protein allergy is unknown. Patients with a history of these symptoms need to be informed about the risk of consuming wheat-containing foods and the importance of excluding such items from their diet. © 2015 The International Society of Dermatology.
    No preview · Article · Jun 2015 · International journal of dermatology
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    ABSTRACT: Legius syndrome (Online Mendelian Inheritance in Man no. 611431) or neurofibromatosis type 1 (NF1)-like syndrome was first reported by Legius et al. in 2007. We herein report the first instance of Legius syndrome occurring in two female siblings in Japan. Both individuals presented cafe-au-lait macules and freckling. Mutation analysis revealed a mutation of c.349C>T resulting in p.Arg117* in the SPRED1 gene as the cause of the Legius syndrome. The National Institutes of Health criteria for NF1 are insufficient to rule out the condition. For this reason, and because the clinical course of each condition is quite different, we stress the need to differentiate Legius syndrome from NF1 clearly. © 2015 Japanese Dermatological Association.
    No preview · Article · May 2015 · The Journal of Dermatology

  • No preview · Article · May 2015 · Contact Dermatitis
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    ABSTRACT: Mast cells (MCs), recognized as tissue-resident cells of hematopoietic origin, are involved in cellular and pathological manifestations of allergic disorders including atopic dermatitis. IL-33, a member of the IL-1 cytokine family, activates Th2-type immune responses, and promotes the degranulation and maturation of MCs. However, it is uncertain whether IL-33 treatment induces mature mast cells to acquire the characteristics of the monocyte-dendritic cell lineage.We investigated the effect of IL-33 on the MHC class II expression and function of murine mast cells. IL-33-treated mature murine bone marrow-derived mast cells (BMMCs) were analyzed by FACS, real-time PCR, chromatin immunoprecipitation (ChIP) assay, and Western blotting. The morphology and degranulation activity of BMMCs and T-cell activation by BMMCs were also examined. BMMCs treated with IL-33 for 10 days induced cell surface expression of the MHC class II protein, whereas the expression of FcεRI and c-kit was not affected by IL-33. The expression of CIITA, driven from pIII and pIV, was up-regulated in IL-33-treated BMMCs. The amount of PU.1 mRNA and protein significantly increased in IL-33-treated BMMCs. The ChIP assay showed PU.1 binding to CIITA pIII, and enhanced histone acetylation due to IL-33 treatment. Syngeneic T cells were activated by co-culture with IL-33-treated BMMCs, although the expression of the co-stimulatory molecules, CD40, CD80, CD86, and PDL-1, was not detected. Mast cells express MHC class II after prolonged exposure to IL-33, probably due to enhanced recruitment of PU.1 to CIITA pIII, resulting in transactivation of CIITA and MHC class II. IL-33 is an important cytokine in allergic disorders. Mast cells have the ability to express MHC class II after prolonged exposure to IL-33 in a murine model. IL-33 holds a key to understanding the etiology of atopic dermatitis.
    Full-text · Article · May 2015
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    ABSTRACT: We analyzed the S100A9 protein expression level during wound healing in mouse excisional wounds applied basic fibroblast growth factor (bFGF). We prepared 6 mm, round, full-thickness wounds on the back skin of mice and applied bFGF (1.0 μ g/cm2) once daily for three days. The mRNA level of TNF-α and ILIβ in granulation tissues extracted from the bFGF-applied group was determined higher than from the vehicle group by quantitative RT-PCR. The mRNA level of S100A9 extracted from the bFGF-applied group and vehicle group on day 5, day 7, and day 11 was expressed three times higher than in the vehicle group (p = 0.0397). The S100A9 protein in granulation tissues from the bFGF-applied group was increased more than that from the vehicle group. We speculate that S100A9 protein plays an important role in wound healing, particularly in the inflammatory reaction.
    No preview · Article · Mar 2015
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    ABSTRACT: Malassezia spp. are lipophilic fungi that occur on all skin surfaces of humans and animals as commensal and pathogenic organisms. In the 2000s, several new species were added to the Malassezia genus by Japanese researchers. The genus Malassezia now includes 14 species of basidiomycetous yeast. Culture-independent molecular analysis clearly demonstrated that the DNA of Malassezia spp. was predominantly detected in core body and arm sites, suggesting that they are the dominant fungal flora of the human body. Malassezia spp. have been implicated in skin diseases including pityriasis versicolor (PV), Malassezia folliculitis (MF), seborrheic dermatitis (SD) and atopic dermatitis (AD). While Malassezia spp. are directly responsible for the infectious diseases, PV and MF, they act as an exacerbating factor in AD and SD. The fatty acids generated by Malassezia lipase can induce inflammation of the skin, resulting in development of SD. Patch and serum immunoglobulin E tests revealed that AD patients were hypersensitive to Malassezia. However, these findings only partially elucidated the mechanism by which Malassezia spp. induce inflammation in the skin; understanding of the pathogenetic role of Malassezia spp. in SD or AD remains incomplete. In this article, the latest findings of Malassezia research are reviewed with special attention to skin diseases. © 2015 Japanese Dermatological Association.
    No preview · Article · Mar 2015 · The Journal of Dermatology

Publication Stats

5k Citations
877.93 Total Impact Points


  • 2002-2016
    • Tokyo Medical University
      • Division of Dermatology
      Edo, Tokyo, Japan
  • 2012-2013
    • Tokyo Medical and Dental University
      • Department of Dermatology
      Edo, Tokyo, Japan
  • 2010
    • Meiji University
      Edo, Tokyo, Japan
  • 1984-2007
    • Juntendo University
      • • Department of Dermatology
      • • Atopy (Allergy) Research Center
      Edo, Tokyo, Japan
  • 2003
    • Meiji Pharmaceutical University
      Edo, Tōkyō, Japan
  • 2001
    • Kinki University
      • Faculty of Agriculture
      Ōsaka, Ōsaka, Japan
  • 1992
    • Complutense University of Madrid
      • Department of Microbiology III
      Madrid, Madrid, Spain
  • 1989-1990
    • CUNY Graduate Center
      New York City, New York, United States