Insulin Binding Properties of Normal and Transformed Human Epidermal Cultured Keratinocytes

Insulin binding to its receptors was studied in cultured normal and transformed (A431 line) human epidermal keratinocytes. The specific binding was a temperature-dependent, saturable process. Normal keratinocytes possess a mean value of about 80,000 receptors per cell. Fifteen hours exposure of the cells to insulin (2 × 10−7M) lowered their receptor number (about 65% loss in available sites); these reappeared when the hormone was removed from the culture medium (“down-regulation” process). In the A431 epidermoid carcinoma cell line, there is a net decrease in insulin binding (84% of the initial bound/free hormone ratio in comparison with normal cells) essentially related to a loss in receptor affinity for insulin. Thus, cultured human keratinocytes which express insulin receptors may be a useful tool in understanding skin pathology related to insulin disorders

Neprilysin, a Novel Target for Ultraviolet B Regulation of Melanogenesis Via Melanocortins

SummaryCompelling evidence suggest a role for melanocortins in the regulation of melanogenesis by ultraviolet radiation. Within the epidermis, melanocytes and keratinocytes produce α-melanocyte-stimulating hormone and adrenocorticotropic hormone. The persistence and the strength of the biologic signal delivered by these peptides depend on their local concentration, which is controlled by the rate of peptide production and by the rate of its degradation. In this study, we investigated the mechanism of melanocortin degradation by melanocytes and the effect of ultraviolet on this process. We have focused our attention on a neutral endopeptidase, neprilysin, which has been implicated in the ending of numerous peptidergic signals. We have shown that this enzyme is expressed at the surface of human melanocytes. Interestingly, its activity and its expression are dramatically downregulated by ultraviolet B treatment. Moreover, in the presence of phosphoramidon, a stable inhibitor of neprilysin, we observed an increased efficiency of α-melanocyte-stimulating hormone and adrenocorticotropic hormone to stimulate both tyrosinase activity and microphthalmia expression. Taken together, these data indicate that neprilysin expressed by melanocytes has a physiologic role in the regulation of melanogenesis by proopiomelanocortin peptide. Further, its downregulation by ultraviolet B irradiation shed light on a new and appealing mechanism of ultraviolet B induced melanogenesis via the control of melanocortins degradation

Dermatitis herpetiformis arising within vitiligo in a patient with autoimmune polyendocrine syndrome type 3

Non peer reviewe

Mélanocytes épidermiques et mélanocytes folliculaires

International audienc

Role of Thiol Compounds in Mammalian Melanin Pigmentation: Part I. Reduced and Oxidized Glutathione

Evidence for the postulated role of glutathione reductase in melanin pigmentation has been obtained by determinations of the glutathione concentrations in Tortoiseshell guinea pig skin of different colors (black, yellow, red, and white). As expected, the lowest levels of reduced glutathione (GSH) were found associated with eumelanin type pigmentation, whereas the highest ones were found in the skin with phaeomelanin producing melanocytes. On the other hand, white skin of guinea pig having no active melanocytes showed GSH levels which were intermediate between those of the black and yellow areas.These results are consistent with the view that the activity of the enzyme glutathione reductase, though not primarily related to pigmentation, plays an important role in the regulation and control of the biosynthetic activity of melanocytes leading to various types of melanin pigments

Syringomatous carcinoma: Case report of a rare tumor entity

Syringomatous carcinoma is a rare cutaneous neoplasm, most frequently situated on the face and scalp and histologically characterised by aninfiltrative pattern of basaloid or squamous cells, a desmoplastic stromal reaction and keratin filled cysts. We report the case of a 76-year-oldwoman who presented an ulcerative interscapular lesion measuring 3x4cm. After resection, the histological examinations of the specimens haveidentified a basal cell carcinoma. However, a local recurrence was observed 18 months later; histopathological findings showed a syringomatouspattern and neoplastic epithelial cells arranged in interconnecting cords with microcystic areas. Nests, cords, and tubules of the tumour extendedinto the dermis and into the adjacent muscle. Sclerosis of stroma around the cords was present. Tumour cells were not connected to the epidermis. The immunohistochemical analysis showed positivity for anti-CK7, AE1/AE3 and negativity for anti CEA and anti CK20. These histological and immunohistochemical analyses were consistent with the diagnosis of syringomatous eccrine carcinoma. Syringomatous carcinoma is an extremely invasive tumor, locally destructive and slowly growing adnexal tumour, derived from eccrine sweat glands. It is often mistaken, both clinically and microscopically, for other benign and malignant entities. The tumour recurrence is high due to extensive perineural invasion, butregional or distant metastases are rare. The local aggressive nature of the tumour and the high recurrence rate may necessitate mutilating procedures. Optimal treatment consists of a complete microscopically controlled surgical excision with clear surgical margins. Key words: Syringomatous carcinoma, histopathology, immunohistochemistry, differential diagnosi

PSS25 COST-EFFECTIVENESS OF ETANERCEPT AND EFALIZUMAB IN THE MANAGEMENT OF MODERATE AND SEVERE PLAQUE PSORIASIS

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Identification of a Lethal Form of Epidermolysis Bullosa Simplex Associated with a Homozygous Genetic Mutation in Plectin

Genetic mutations in plectin, a cytoskeleton linker protein expressed in a large variety of tissues including skin, muscle, and nerves, cause epidermolysis bullosa simplex with muscular dystrophy, a recessive inherited disease characterized by blistering of the skin and late onset of muscular dystrophy, and Ogna epidermolysis bullosa simplex, a rare dominant inherited form of epidermolysis bullosa simplex with no muscular involvement. Here we report a novel homozygous genetic mutation (2727del14) in the plectin gene (PLEC1) associated with a lethal form of recessive inherited epidermolysis bullosa in a consanguineous family with three affected offspring. This new clinical variant of epidermolysis bullosa is characterized by general skin blistering, aplasia cutis of the limbs, developmental complications, and rapid demise after birth. Mutation 2727del14 is the first genetic defect described in PLEC1 that disrupts the plakin domain of plectin. The severe phenotype of the patients may be linked to the role of the N-terminal domain in the function of plectin and develops the understanding of the genotype-phenotype correlations in the genodermatoses affecting the dermal-epidermal junction