[The skin. Anatomic and physiological review].
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Biomedical subjects
Publications and source records attributed to A Taïeb.
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The primary cellular or molecular targets accounting for melanocytes loss in vitiligo are not clearly identified. To study a putative latent epidermal defect in the epidermis of vitiligo patients, we performed in vitro studies using cultured vitiligo melanocytes and keratinocytes transplanted on to a dead de-epidermized dermis according to a variant of Pruniéras' technique. Control autologous constructs were made with keratinocytes and melanocytes of normal adult epidermis and vitiligo epidermis from perilesional skin. For heterologous reconstructs we combined vitiligo-derived melanocytes or keratinocytes with their normal phototype-matched counterpart. After 15 days of culture at the air-liquid interface, epidermal reconstructs were studied macroscopically and microscopically. Immunohistochemistry was performed using antibodies to TRP-1 and NKI-beteb. All heterologous and autologous reconstructs made with melanocytes and keratinocytes from vitiligo patients had a normal histology and ultrastructure. For vitiligo melanocytes or normal melanocytes submitted to the influence of vitiligo keratinocytes, immunophenotype and function (pigment production and transfer) were similar to normal controls. So, without additional noxious stimuli, we could not discriminate between melanocytes and keratinocytes as inducers of the disease. Our data suggest that the basic abnormality in vitiligo vulgaris needs extrinsic factors to be macroscopically revealed or requires a longer period of culture to develop. Our model will allow analysis of the various pathophysiological mechanisms of vitiligo, e.g. autoantibodies or oxidative stress, at the cellular, biochemical or molecular level.
Sexually transmitted diseases in children include vertically transmitted diseases responsible for severe fetopathy and neonatal diseases as well as infections acquired in the postnatal period. Sexually transmitted diseases in children raise the question of possible of sexual abuse, which has major medicolegal, social and psychological implications. The proof of sexual abuse is further complicated by the fact that some neonatal infections can be revealed only at a later stage. Moreover in rare cases venereal diseases are transmitted by non sexual contact. Early sexual activity, should also be included (10% of children have their first sexual intercourse before the age of 15).
BACKGROUND AND DESIGN: Longitudinal melanonychia is rare in white children and represents a difficult clinical challenge. Because of the fear of malignant melanoma, a surgical excision is usually performed, sometimes with definitive aesthetic and functional consequences. Eight children with longitudinal melanonychia who were between the ages of 2 and 14 years underwent follow-up. Surgical excision was performed in five cases. For three children, a wait-and-see policy was adopted, because their longitudinal melanonychia had been unchanged for years at the time of their examination. RESULTS: Melanoma was never observed in our cases (follow-up, 5.5 years). Histologic examinations performed in five cases showed junctional nevi of the nail matrix, often with dysplasia as commonly seen in juvenile nevi. Two children had postoperative nail dystrophy. CONCLUSION: In white children, longitudinal melanonychia rarely disappears. Since an ungual melanocytic band can appear at the age when other nevi appear, surgical excision should not be undertaken on different grounds than for other congenital or acquired nevi in children.
Calcitriol or 1.25 (OH)2-vitamin D3 is used in the treatment of psoriasis as an inhibitor of cell proliferation. We studied the action of calcitriol ex vivo on the growth of psoriatic and normal human keratinocytes, and on the expression of the EGF receptor. Third passaged normal and psoriatic keratinocytes were seeded (10(4)/cm2) in 24-well dishes in serum-free medium (MCDB supplemented with amino acids, with either 0.1 or 1.1 mM of calcium) and 10(-9) M calcitriol. When subconfluence was reached, cell counts and 125I-EGF binding studies were performed. Cell counts showed at least a 50% decrease in growth under all conditions studied (normal or psoriatic keratinocytes; 0.1 or 1.1 mM calcium) when calcitriol was added. 125I-EGF binding studies showed a decrease in total receptor numbers in the presence of calcitriol with acceleration of binding at low concentrations of 125I-EGF. Scatchard plot analysis showed only one type of high affinity receptor. Receptor sites were decreased (30% to 40% of controls) in the presence of calcitriol together with a decrease in the dissociation constant. In conclusion, at almost physiological concentrations ex vivo, calcitriol strongly decreased normal and psoriatic keratinocyte growth. This potent antiproliferative effect could in part be explained by the capacity of calcitriol to downregulate EGF receptor expression.
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We studied skin phototypes ex vivo to validate a model of epidermal reconstruction with melanocytes. We made autologous epidermal reconstructs with keratinocytes and melanocytes of healthy donors of skin phototypes I to VI. Keratinocytes and melanocytes were seeded on a dead de-epidermized dermis (Pruniéras type) at a 1:20 melanocyte/keratinocyte ratio. Reconstructed epidermis was grown for 15 d at the air-liquid interface with or without ultraviolet B irradiation. A macroscopic, chromometric. histologic, and ultrastructural evaluation was performed. Reconstructs reproduced the initial phototype with few modifications. The intensity of melanin transfer correlated with the in vivo situation and was stimulated after ultraviolet B irradiation in reconstructs of all categories of skin phototypes.
8 children aged 1 to 13 years, clinically suspected of having contact dermatitis due to footwear, have been studied in our Paediatric Dermatology Unit from January 1980 to September 1995. Patch tests have been performed with the European standard series and with constituents of the patients' own shoes. In our study, patients appeared to be predominantly sensitive to rubber chemicals. Avoiding shoes or materials that had been identified improved the symptoms in most cases.
To understand the contribution of epidermal melanocytes in the proteolytic potential of human skin, we have studied melanocytes grown in a low-serum medium deprived of phorbol esters, cholera toxin, and other non-physiological supplements. We focused on the plasminogen activation system and certain matrix metalloproteinases (gelatinases). Supposing that the proteolytic activity of cells can influence binding to collagen matrix and its reorganization, we have analyzed these parameters as well. We found that human melanocytes secreted tissue-type plasminogen activator and utilised it to generate cell-bound plasmin. No urokinase-type plasminogen activator was detected in the cultures but its receptor was found in cell extracts. Both the 72 kDa and 92 kDa gelatinases were secreted by the cells and in equal amounts. In addition, melanocytes secreted the wide-spectrum proteinase inhibitor alpha-2-macroglobulin. Melanocytes cast into collagen matrices retained a rounded morphology, did not extend processes, and were unable to contract collagen lattices. As a control, these parameters were investigated in parallel in cultures of human keratinocytes, dermal fibroblasts, and two melanoma cell lines. The obtained characteristics suggest that normal human melanocytes are proteolytically active cells. This function may pertain to skin physiology and pathophysiology.
BACKGROUND: Papulopustular eruptions of the face in neonates are frequently referred to as neonatal acne or sebaceous miliaria. Our findings suggest that there is an association between this type of eruption and Malassezia furfur infection. OBSERVATIONS: Direct examination of pustule smears showed M furfur yeasts in eight of 13 cases involving neonates with erythema and papulopustules of the face, neck, and scalp (mean age at onset, 22 days [range, 7 to 30 days]). The pustules were predominantly neutrophilic. Treatment with 2% ketoconazole cream applied topically twice daily was effective in 1 week. CONCLUSION: Malassezia furfur is frequently associated with a common nonfollicular pustulosis of the newborn, probably improperly termed neonatal acne.
A deficiency in uroporphyrinogen decarboxylase (UROD) enzyme activity, the fifth enzyme of the heme biosynthetic pathway, is found in patients with sporadic porphyria cutanea tarda (s-PCT), familial porphyria cutanea tarda (f-PCT), and hepatoerythropoietic porphyria (HEP). Subnormal UROD activity is due to mutations of the UROD gene in both f-PCT and HEP, but no mutations have been found in s-PCT. Genetic analysis has determined that f-PCT is transmitted as an autosomal dominant trait. In contrast, HEP, a severe form of cutaneous porphyria, is transmitted as an autosomal recessive trait. HEP is characterized by a profound deficiency of UROD activity, and the disease is usually manifest in childhood. In this study, a strategy was designed to identify alleles responsible for the HEP phenotype in three unrelated families. Mutations of UROD were identified by direct sequencing of four amplified fragments that contained the entire coding sequence of the UROD gene. Two new missense mutations were observed at the homoallelic state: P62L (proline-to-leucine substitution at codon 62) in a Portuguese family and Y311C (tyrosine-to-cysteine substitution at codon 311) in an Italian family. A third mutation, G281E, was observed in a Spanish family. This mutation has been previously described in three families from Spain and one from Tunisia. In the Spanish family described in this report, a paternal uncle of the proband developed clinically overt PCT as an adult and proved to be heterozygous for the G281E mutation. Mutant cDNAs corresponding to the P62L and Y311C changes detected in these families were created by site-directed mutagenesis. Recombinant proteins proved to have subnormal enzyme activity, and the Y311C mutant was thermolabile.
INTRODUCTION: The cause of chronic urticaria remains unknown very often. Having noted several cases of chronic urticaria associated with antibodies to Toxocara canis, and lacking any other explanation, we set-up a case-control study. PATIENTS AND METHODS: Between November 1992 and April 1993, 51 adults or children with chronic urticaria (cases) who had been examined at least once at one of the three dermatology units of the Bordeaux University Hospital were matched to controls who had neither signs nor symptoms of chronic urticaria. The presence of antibodies to T. canis was measured by ELISA and Western blot. RESULTS: The frequency of T. canis was 64.7 p. 100 in cases and 21 p. 100 in controls (p < 0.0001) with an odds ratio of 6.9 (95 p. 100 CI: 2.9-16.3). Cases with antibodies to T. canis were more frequently in contact with pets (84 vs 50 p. 100, p < 0.001). Of the 33 cases of chronic urticaria with antibodies to T. canis, 14 have been treated with thiabendazole or ivermectin and after a one-year follow-up, 5 (36 p. 100) were cured and 4 (29 p. 100) had improvement. No improvement occurred in the 12/19 cases not specifically treated. CONCLUSION: The strong association between the presence of antibodies to Toxocara canis and chronic urticaria is unlikely to be due to chance. A causal relation is difficult to establish, however. Our findings should prompt further investigation of a role for Toxocara canis in chronic urticaria and the evaluation of therapeutic interventions. Preventive measures include deworming pets (dogs particularly), enclosing kitchen gardens, and handwashing before meals. A systematic measure of Toxocara canis in patients with chronic urticaria is recommended especially when in contact with dogs. Early and specific treatments can be applied on knowledge we already have.
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