Dermatophytes cause intractable superficial infections in humans. Arthroderma benhamiae, a zoophilic dermatophyte, triggers severe inflammatory responses in humans, while Trichophyton tonsurans, an anthropophilic dermatophyte, triggers minimal ones. Cytokines and other factors derived from keratinocytes play important roles in inflammatory and immune responses in the skin. The authors performed an in vitro investigation to determine the human keratinocyte cytokine profiles during dermatophyte infection. The human keratinocyte cell line PHK16-0b was infected with A. benhamiae or T. tonsurans for 24 h, and the cytokines secreted were analysed using a human cytokine antibody array. Marked differences were observed in the cytokine profiles of the cells infected with the two dermatophytes. A. benhamiae infection resulted in the secretion of a broad spectrum of cytokines, including proinflammatory cytokines, chemokines, and immunomodulatory cytokines. In contrast, T. tonsurans-infected keratinocytes secreted only limited cytokines, including eotaxin-2, interleukin (IL)-8 and IL-16. cDNA microarray analysis confirmed that A. benhamiae infection upregulated genes encoding IL-1β, IL-2, IL-4, IL-6, IL-10, IL-13, IL-15, IL-16, IL-17 and interferon (IFN)-γ, while T. tonsurans infection upregulated only a few genes, such as those encoding IL-1β and IL-16. RT-PCR demonstrated that infection by both dermatophytes enhanced IL-8 mRNA expression in keratinocytes. These results suggest that A. benhamiae-induced secretion of several cytokines from keratinocytes may be involved in a severe inflammatory response, and that the limited cytokine secretion from keratinocytes in response to T. tonsurans infection may result in a minimal inflammatory response in the skin. These cytokine profiles may aid in proving the clinical features of dermatophytosis.
Fungal microbiota colonization of neonates began on day 0, and the fungal microbiota of neonates had changed to the adult type by day 30. To our knowledge, this is the first report of a molecular analysis of the fungal microbiota of neonates.
Proteinase activity is increased in psoriatic epidermis. To elucidate the involvement of enzymes in psoriatic epidermis, the expression of cathepsins, L, B and D was investigated by Western blotting and immunohistological studies. Normal epidermis contained abundant inactive precursors (39 kDa) of cathepsins L and B and an inactive intermediate form (45 kDa) of cathepsin D. Cathepsin L in psoriasis was processed to a variable extent from the precursor to a single-chain form (30 kDa) and a mixture of single- and heavy-chain (25 kDa) forms of the active mature enzyme, corresponding to the immunohistological staining patterns 'diffuse dense', 'small granular', and unevenly distributed 'condensed granular'. Cathepsin B showed a mixture of precursor form (39 kDa) and single-chain (30 kDa) forms and was expressed as a 'diffuse dense' staining pattern in the mid-spinous layer and as a 'condensed' pattern in the upper spinous and granular layers. Cathepsin D was processed to the heavy-chain (31 kDa) form of activated mature enzyme with small granular staining and a mixture of heavy-chain and degraded protein (28 kDa) with larger and more condensed granular staining. The distribution patterns of 'small granular' cathepsin L, and of cathepsins B and D expression in suprabasal keratinocytes were very similar to that of involucrin. After complete clinical resolution of psoriasis by 8-methoxypsoralen plus UVA treatment, the expression of the three cathepsins was normalized. These results suggest that cathepsins L, B and D in forms activated to a variable extent may be involved in the pathology of psoriasis.
Oligosaccharides, involved in regulation of plant developmental and defensive processes, were tested to determine their ability to enhance proliferation of human keratinocytes. A mixture of alginate oligosaccharides remarkably stimulated keratinocyte growth and [ 3 H]thymidine uptake in the presence of epidermal growth factor (EGF). The activity was comparable to bovine pituitary extract, a common complement in keratinocyte culture, and additive on BPE-induced stimulation. The most effective oligosaccharide in the mixture was identified and its chemical structure was determined. These findings demonstrate a novel activity of alginate oligosaccharide(s) in keratinocyte growth and suggest a possible co-factor for EGF-dependent stimulation in medium for keratinocytes. © 1997 Federation of European Biochemical Societies.
There has been no epidemiological survey of foot diseases in Japan. In this study we determined the prevalence of foot diseases, especially tinea pedis (TP) and tinea unguium (TU) in Japan. We conducted a randomized survey of outpatients who visited a dermatologist during the third week of May in 1999, 2000 and 2006. The most frequently reported condition was "fungal infection" in 8737 (40.0%) of 21 820 patients in 1999/2000, and 3848 (49.4%) of 7783 patients in 2006. The patients who visited a dermatologist for reasons other than superficial fungal infection but were diagnosed with TP or TU comprised 18.6% of the study population in 2000 and 24.1% in 2006. Of the patients with TP or TU, 63.2% used topical medication only. This survey showed that often patients are not aware of fungal infections and that their treatment is sometimes insufficient. Dermatologists should actively examine and treat patients with TP and TU.
Cutaneous Malassezia is an exacerbating factor in patients with atopic dermatitis. We analysed the Malassezia microbiota of adult patients with head and neck atopic dermatitis of different severities (mild, moderate and severe). Of the nine human-associated Malassezia species, the number detected was similar (3.5-4.2 species per case) among the members of all severity groups. However, the ratio of the two major Malassezia species, M. globosa and M. restricta, was different in the severe group.
Summary. We report a case of systemic phaeohyphomycosis due to Exophiala dermatitidis in a 24‐year‐old man. At the age of 17, the patient had noticed cervical swellings. On palpation at his initial examination, more than a dozen firm lymph nodes between 1 and 5 cm in diameter were found on both sides of the neck and in both axillae. Examination of biopsy specimens of lymph nodes revealed pale brown hyphae in granulomatous lesions and Exophiala dermatitidis was isolated from mycological cultures of the local tissues. The clinical course was marked by an episode of jaundice six months later, and surgery disclosed a fist‐sized inflammatory mass in the region of the head of the pancreas and the duodenum. The patient was treated by providing external biliary drainage and by the administration of antifungal agents, but two years later complained of diplopia and a slight heaviness in the head. Computed tomographic scans were made of the head, revealing multiple plum‐sized masses in the brain. The patient died a year later. In Japan, 10 cases of systemic infection by this organism (including the present one) have been reported, all in patients of up to 30 years of age, with lesions appearing in the brain, lung, liver, digestive organs and lymph nodes. The prognosis is grave. Zusammenfassung. Unser Bericht beschreibt einen Fall von systemischer Phäohyphomykose, verursacht durch Exophiala dermatitidis, bei einem 24‐jährigen Mann. Im Alter von 17 Jahren hatte dieser Patient Schwellungen am Hals festgestellt. Bei der Palpation während der ersten Unter‐suchung wurde uber ein Dutzend fester Lymph‐knoten (1–5 cm Durchmesser) an beiden Seiten des Halses und in beiden Achselhöhlen gefunden. Die Gewebsuntersuchung eines Lymphknotens zeigte hellbraune Hyphen in einer granulomatö‐sen Verletzung, und Exophiala dermatitidis wurde von einer mykologischen Kultur des lokalen Gewebes isoliert. Der klinische Verlauf war durch das Auftreten von Gelbsucht sechs Monate später gekennzeichnet, und bei einer Operation wurde eine faustgroße entzündete Masse im Bereich des Pankreaskopfes und des Zwälffingerdarms festgestellt. Der Patient wurde mit einer externen Gallengangdrainage versehen und mit Antimyko‐tika behandelt. Aber zwei Jahre später klagte er über Doppeltsehen und ein Schweregefuhl im Kopf. Der Kopf wurde mittels Computertomo‐graphie untersucht, und dabei wurden im Gehirn mehrere pflaumengroße Massen festgestellt. Der Patient starb ein Jahr spater. In Japan wurden bisher über 10 Fälle von systemischer Infektion durch diesen Organismus (den hier beschriebenen Fall eingeschlossen) berichtet. Alle traten bis zum Alter von 30 Jahren auf und waren gekenn‐zeichnet durch Läsionen im Gehirn, in Lunge, Leber, Verdauungsorganen und Lymphknoten. Die Prognose ist ernst.
Although the lipophilic yeasts of the genus Malassezia are part of the cutaneous microbiota in healthy individuals, they are also associated with several skin diseases, such as seborrheic dermatitis. However, the effects of age and gender on the Malassezia microbiota have not been completely elucidated. We analyzed the cutaneous Malassezia microbiota of 770 healthy Japanese using the highly accurate real-time PCR with a TaqMan probe to investigate the effects of age and gender on the Malassezia population. The numbers of Malassezia cells increased in males up to 16-18 years of age and in females to 10-12 years old, and subsequently decreased gradually in both genders until senescence. Malassezia restricta overwhelmingly predominated at ages over 16-18 years in males and 23-29 years in females. M. globosa and M. restricta together accounted for more than 70% of Malassezia spp. recovered regardless of gender. The total colonization of Malassezia and the ratio of the two major species change with age and gender in humans.
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