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The Journal of Dermatology 03/2013; · 1.49 Impact Factor
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ABSTRACT: Biologics such as tumor necrosis factor (TNF) inhibitors are highly effective for treating severe psoriasis, and an increasing number of patients benefit from them. However, subsidiary subjects have arisen in the course of treatment which may directly impact the continued use of these drugs in a given case. In this article, we report two cases of psoriasis vulgaris refractory to treatment with both adalimumab and infliximab. We measured the serum drug concentration and absorbance value of antidrug antibodies using the sandwich enzyme-linked immunoassay method. Antibodies to adalimumab and infliximab were detected in both patients. The low drug concentration and adverse clinical response observed corroborated these findings. Dosage and concomitant medication are considered to be important factors influencing the development of antibody formation. Therapeutic drug monitoring and measurement of antidrug antibodies will assist in maintaining a clinical response and in optimizing the response of patients being treated with biological therapies. The use of concomitant immunosuppressive medication should be considered for patients who will be treated with their second TNF inhibitor after having developed antidrug antibodies against their first TNF inhibitor.
The Journal of Dermatology 02/2013; · 1.49 Impact Factor
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ABSTRACT: Malassezia species of lipophilic yeasts account for most fungal microbiota. Although they colonize healthy skin, they are also associated with several skin diseases, including pityriasis versicolor, seborrheic dermatitis, Malassezia folliculitis, and atopic dermatitis. To date, 14 members of the Malassezia genus have been identified. Of these, both M. globosa and M. restricta predominate, regardless of skin-disease type. Comprehensive analysis of fungal microbiota in the skin of patients with atopic dermatitis using an rRNA clone library method revealed that fungal microbiota cluster according to disease severity. The external ear canal and sole of the foot are colonized by specific Malassezia microbiota.
Nippon Ishinkin Gakkai Zasshi 01/2013; 54(1):39-44.
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ABSTRACT: We found that the yeast species Cryptococcus albidus var. albidus more often colonized more on the skin surface of patients with atopic dermatitis (AD) (77.0%, 47/61) compared with that of healthy subjects (37.5%, 15/40). The intergenic spacer (IGS) 1 region of the rRNA gene of this species consists of four sequence types: I, II, III, and IV. Types I and II were predominant among healthy subjects and AD patients, respectively.
Microbiology and Immunology 11/2012; · 1.30 Impact Factor
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ABSTRACT: The calcium binding proteins S100A8 and S100A9 can dimerize to form calprotectin, the release of which during tissue damage has been implicated in inflammation and metastasis. However, receptor(s) mediating the physiological and pathophysiological effects of this damage-associated 'danger signal' are uncertain. In this study, searching for candidate calprotectin receptors by affinity isolation-mass spectrometry, we identified the cell surface glycoprotein EMMPRIN/BASIGIN (CD147/BSG). EMMPRIN specifically bound to S100A9 but not S100A8. Induction of cytokines and matrix metalloproteases (MMPs) by S100A9 was markedly downregulated in melanoma cells by attenuation of EMMPRIN. We found that EMMPRIN signaled utilized the TNF receptor-associated factor TRAF2 distinct from the known S100 binding signaling pathway mediated by RAGE (AGER). S100A9 strongly promoted migration when EMMPRIN was highly expressed, independent of RAGE, whereas EMMPRIN blockade suppressed migration by S100A9. Immunohistological analysis of melanomas revealed that EMMPRIN was expressed at both the invasive edge of lesions as well as the adjacent epidermis, where S100A9 was also strongly expressed. In epidermal-specific transgenic mice, tail vein-injected melanoma accumulated in skin expressing S100A9 but not S100A8. Together, our results establish EMMPRIN as a receptor for S100A9 and suggest the therapeutic utility in targeting S100A9-EMMPRIN interactions.
Cancer Research 11/2012; · 7.86 Impact Factor
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ABSTRACT: The maturation and activation mechanisms of caspases are generally well understood, except for those of caspase-14, which is activated at the onset of keratinocyte terminal differentiation. We investigated the possible involvement of epidermal proteases expressed in the late stage of differentiation, and found that the chymotrypsin-like serine protease kallikrein-related peptidase-7 (KLK7) cleaved procaspase-14 at Tyr(178), generating an intermediate form that consists of a large (20 kDa) and a small subunit (8 kDa). We prepared an antibody directed to this cleavage site (h14Y178 Ab), and confirmed that it recognized a 20-kDa band formed when procaspase-14 was incubated with chymotrypsin or KLK7. We then constructed a constitutively active form of the intermediate, revC14-Y178. The substrate specificity of revC14-Y178 was completely different from that of caspase-14, showing broad specificity for various caspase substrates except WEHD-7-amino-4-trifluoromethylcoumarin (AFC), the preferred substrate of active, mature caspase-14. K(m) values for VEID-AFC, DEVD-AFC, LEVD-AFC, and LEHD-AFC were 0.172, 0.261, 0.504, and 0.847 μm, respectively. We confirmed that the mature form of caspase-14 was generated when procaspase-14 was incubated with KLK7 or revC14-Y178. Expression of constitutively active KLK7 in cultured keratinocytes resulted in generation of both the intermediate form and the mature form of caspase-14. Immunohistochemical analysis demonstrated that the intermediate form was localized at the granular layer. Our results indicate that regulation of procaspase-14 maturation during terminal differentiation is a unique two-step process involving KLK7 and an activation intermediate of caspase-14.
Journal of Biological Chemistry 07/2012; 287(39):32825-34. · 4.77 Impact Factor
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ABSTRACT: Selecting an appropriate treatment for a given case of skin wound is crucial for inducing optimal healing. We used an animal model consisting of normal rabbit ears in order to assess the efficacy of treatments for skin wounds with/without a wet dressing, anti-microbial reagent, or topical wound-stimulatory reagents. The degree of healing in each group was evaluated and compared using four histological parameters: (i) degree of reepithelialisation, (ii) amount of granulation tissue formation and (iii) the number of capillary lumens and (iv) fibroblasts in the granulation tissue. Treatment using wet dressings presented an increase in capillary number compared to the open dry wound. Although the retention of PI in wound tissue after application significantly inhibited reepithelialisation (P < 0·05), rinsing povidone-iodine (PI) off with saline after application was comparable in effect to using only a wet dressing. The three topical reagents, namely, basic fibroblast growth factor, prostaglandin E1 and dibutyryl cyclic adenosine monophosphate, significantly improved reepithelialisation (P < 0·05). In conclusion, wounds should be kept hydrated by applying topical reagents. If there are any signs of bacterial infection, PI can be applied if rinsed later with saline in order to minimise its cytotoxic effects.
International Wound Journal 07/2012; · 1.46 Impact Factor
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The Journal of Dermatology 07/2012; · 1.49 Impact Factor
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International journal of dermatology 05/2012; · 1.18 Impact Factor
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ABSTRACT: Topical treatment with betamethasone butyrate propionate lotion on 37 patients with scalp psoriasis was replaced with a combination therapy using maxacalcitol lotion (on weekdays) and BBP (on the weekends). This combination therapy was later switched to MXA monotherapy. To identify the optimum duration of the combination therapy, the patients were divided into two groups: a 4-week group and an 8-week group, which were given combination therapy and monotherapy. In both groups, the total mean scores for the skin symptoms had significantly improved in comparison with that obtained at the outset of the study (p < 0.01). In terms of overall improvement, 20.0% of the 4-week group and 72.7% of the 8-week group yielded scores reflecting moderate or greater improvement. The treatment administered to the 8-week group was significantly more effective than that given to the 4-week group at the end of the trial (p < 0.01). This study also suggests that a 4-week combination therapy is an option before switching to monotherapy, but that an 8-week therapy is preferable in severe cases.
Journal of Dermatological Treatment 04/2012; · 1.23 Impact Factor
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ABSTRACT: Of the fungal skin microbiota, the lipophilic yeast genus Malassezia predominates at all body sites. Of the members of this genus, M. globosa, M. restricta, and M. sympodialis are the most common on the face, limbs, and trunk. In the present study, the Malassezia microbiotas in the external auditory canal and on the sole of the foot were characterized. M. slooffiae was the most common species in both the external auditory canal and on the sole of the foot, followed by M. restricta. Principal component analysis further revealed that the Malassezia microbiota in the external auditory canal and on the sole of the foot constitute a different cluster from those on the scalp and cheek and in the nasal cavity. Additionally, five new Malassezia phylotypes were detected on the sole of the foot and in the external auditory canal. Our results suggest that a distinctive Malassezia microbiota is present in the external auditory canal and on the sole of the foot, although the clinical significance of this finding remains unknown.
Microbiology and Immunology 04/2012; 56(4):238-44. · 1.30 Impact Factor
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ABSTRACT: Luliconazole is a novel topical antifungal imidazole with broad-spectrum and potent antifungal activity. The drug is under clinical development in the United States for management of dermatophytosis with a short-term treatment regimen. The present study was undertaken to investigate the clinical benefit of short-term therapy with luliconazole cream in guinea pig models of tinea corporis and tinea pedis induced with Trichophyton mentagrophytes. The dose-dependent therapeutic efficacy of topical luliconazole cream (0.02 to 1%), measured by macroscopic improvement of skin lesions and by fungal eradication as determined by a culture assay, was demonstrated using a tinea corporis model. The improvement in skin lesions seen with luliconazole cream was observed even at a concentration of 0.02%, and its efficacy at 0.1% was equal to that of 1% bifonazole cream. The efficacy of short-term therapy with 1% luliconazole cream, which is used for clinical management, was investigated using the tinea corporis model (4- and 8-day treatment regimens) and the tinea pedis model (7- and 14-day treatment regimens). The 1% luliconazole cream completely eradicated the fungus in half or less of the treatment time required for 1% terbinafine cream and 1% bifonazole cream, as determined by a culture assay for both models. These results clearly indicate that 1% luliconazole cream is sufficiently potent for short-term treatment for dermatophytosis compared to existing drugs. Luliconazole is expected to be useful in the clinical management of dermatophytosis.
Antimicrobial Agents and Chemotherapy 03/2012; 56(6):3138-43. · 4.84 Impact Factor
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02/2012; , ISBN: 978-953-51-0110-9
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ABSTRACT: Of the fungal skin microbiota, the lipophilic yeast genus Malassezia predominates at all body sites. Of the members of this genus, M. globosa, M. restricta, and M. sympodialis are the most common on the face, limbs, and trunk. In the present study, we characterized the Malassezia microbiota in the external ear canal and on the sole of the foot. M. slooffiae was the most common species in both the external ear canal and on the sole of the foot, followed by M. restricta. Principal component analysis further revealed that the Malassezia microbiota in the external ear canal and on the sole of the foot constituted a different cluster from those on the scalp and cheek and in the nasal cavity. Additionally, five new Malassezia phylotypes were detected on the sole of the foot and in the external ear canal. Our results suggest that a distinctive Malassezia microbiota is presented in the external ear canal and on the sole of the foot, although its clinical significance remains unknown.
Microbiology and Immunology 01/2012; · 1.30 Impact Factor
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European journal of dermatology: EJD 01/2012; 22(2):269-70. · 2.53 Impact Factor
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ABSTRACT: Porokeratosis plantaris palmaris et disseminata (PPPD) is a quite rare variant of porokeratosis. We report a 56-year-old male patient. He first noted brownish, asymptomatic, annular macules scattered on the trunk and extremities at about age 31 and these skin lesions, continued to increase in number. Ten years prior to presentation, similar lesions appeared on the palms. About one to two years ago, the patient noted painful wart-like, keratotic punctuate papules 2-3 mm in diameter on the soles, which disturbed walking. Histological examination showed the characteristic feature of the cornoid lamella. The family tree of this patient showed an autosomal dominant mode of transmission. We review sixteen typical cases of PPPD previously reported in the English literature.
Dermatology online journal 01/2012; 18(8):5.
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ABSTRACT: To improve the ability of dermatologists to diagnose cutaneous mycoses, we have proposed a list of the minimum mycological knowledge and skills required by senior residents of dermatology. The list includes ability to select the most appropriate sampling method, knowledge of the basic method of potassium hydroxide (KOH) examination and skill in performing fungal cultures and identifying the most prevalent fungal species isolated from skin lesions. It is not possible for the Japanese Society of Medical Mycology to train every senior resident directly, and it is difficult for them to acquire sufficient expertise independently. Consequently, training and advice given by instructors in residents' home institutes is essential. A project of an advanced course for instructors, who are in charge of educating senior residents in their own institute, may be possible. Therefore, we have proposed here a list for instructors of the knowledge and skills required to educate senior residents. Employing this list should realize improved skill in dermatologists.
Nippon Ishinkin Gakkai Zasshi 01/2012; 53(2):109-16.
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The Journal of Dermatology 12/2011; 39(2):113-20. · 1.49 Impact Factor
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The Journal of Dermatology 12/2011; 39(8):736-8. · 1.49 Impact Factor
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ABSTRACT: Churg-Strauss syndrome (CSS) is a vasculitis usually thought to affect comparatively young individuals, however, elderly cases of CSS are being reported increasingly. We report two elderly cases of CSS and review 123 cases of CSS reported in Japan between 2003 and 2010. The two patients showed typical features of CSS such as asthma, chronic sinusitis, purpura and mononeuritis multiplex. The biopsy specimens demonstrated leukocytoclastic vasculitis with infiltration of eosinophils. Both patients responded well to oral prednisolone. The age of the CSS cases we reviewed ranged from the teens to the 80s, with 47.2% of the patients aged 60 years or older. These patients tended more frequently to have complications such as gastrointestinal involvement, and a higher mortality rate. Elderly cases of CSS are not rare. Correct diagnosis at an earlier stage and careful, long-term follow up are of particular importance in preventing a fatal outcome.
The Journal of Dermatology 12/2011; 39(1):76-9. · 1.49 Impact Factor
