[Show abstract][Hide abstract] ABSTRACT: We report on a comparative study by Transmission Electron Microscopy (HRTEM) and Scanning Transmission Ion Microscopy (STIM) combined with Rutherford Backscattering Spectrometry (RBS) and Particle Induced X-Ray Emission (PIXE) on ultra-thin and thin cross-sections, respectively, of various skin samples (porcine skin, healthy human skin, human skin grafted on a severe combined immuno-deficient mouse model) to which we applied topically various formulations containing titanium dioxide (TiO2) nanoparticles with primary particle sizes in the range from 20–100 nm. Whereas the HRTEM and STIM/PIXE images reveal clear differences – mainly related to the different thickness of the cross-sections – they unambiguously show that penetration of TiO2 nanoparticles is restricted to the topmost 3–5 corneocyte layers of the stratum corneum (SC).
[Show abstract][Hide abstract] ABSTRACT: In recent years, possible health hazards due to radiofrequency radiation (RFR) emitted by mobile phones have been investigated. Because several publications have suggested that RFR is stressful, we explored the potential biological effects of Global System for Mobile phone communication at 900 MHz (GSM-900) exposure on cultures of isolated human skin cells and human reconstructed epidermis (hRE) using human keratinocytes. As cell stress markers, we studied Hsc70, Hsp27 and Hsp70 heat shock protein (HSP) expression and epidermis thickness, as well as cell proliferation and apoptosis. Cells were exposed to GSM-900 under optimal culture conditions, for 48 h, using a specific absorption rate (SAR) of 2 W x kg(-1). This SAR level represents the recommended limit for local exposure to a mobile phone. The various biological parameters were analysed immediately after exposure. Apoptosis was not induced in isolated cells and there was no alteration in hRE thickness or proliferation. No change in HSP expression was observed in isolated keratinocytes. By contrast, a slight but significant increase in Hsp70 expression was observed in hREs after 3 and 5 weeks of culture. Moreover, fibroblasts showed a significant decrease in Hsc70, depending on the culture conditions. These results suggest that adaptive cell behaviour in response to RFR exposure, depending on the cell type and culture conditions, is unlikely to have deleterious effects at the skin level.
[Show abstract][Hide abstract] ABSTRACT: We report on an apparently previously undescribed neonatal diffuse congenital hyperkeratosis with spontaneous improvement. The child, born to consanguinous parents, presented at birth with a verrucous hyperkeratosis involving face, trunk, and limbs, but sparing palms and soles. No visceral or skeletal abnormality was associated and neurosensory status was normal. The skin condition improved dramatically during the first month of life. At age 7 years, the child was healthy with normal psychomotor development and growth. He had an abnormal curvature of nose, ulerythema ophryogenes, and large ears. The skin was moderately dry. This favorable clinical outcome led us to propose the term "regressive congenital hyperkeratosis" until further molecular characterization of this new phenotype.
American Journal of Medical Genetics Part A 11/2004; 130A(3):303-6. DOI:10.1002/ajmg.a.30236 · 2.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the development of congenital nevi, how nevus cells migrate in the dermis remains unclear. As shown in an earlier study designed to investigate Unna's Abtropfung hypothesis, dermal invasion does not occur when nevus cells are seeded on epidermal reconstructs. In melanoma, the decrease of E-cadherin expression is associated with the dermal invasion of melanoma cells.
To study the expression of E-cadherin in dermal-cultured nevus cells from congenital nevi and its relevance to explain the absence of dermal invasion noted in epidermis reconstructed with cultured nevus cells.
Comparison of the immunohistochemical expression pattern of E-cadherin in congenital nevi in vivo and after culture in monolayers and in a three-dimensional system.
E-cadherin was not expressed in vivo by dermal nevus cells, either isolated or in nests. However, in monolayer cultures, dermal nevus cells expressed E-cadherin. When these cells were used in reconstructed epidermis, nevus cells did not invade the dermis and they expressed E-cadherin when isolated and just weakly or not when grouped in junctional nests.
The absence of dermal invasion of nevus cells could be due to the expression of E-cadherin in these cells in reconstructed epidermis. Our experiments suggest, a restoration of the control of keratinocytes, that nevus cells escape in the dermal compartment.
[Show abstract][Hide abstract] ABSTRACT: Since Unna's Abtropfung hypothesis, the process of migration of nevus cells in the dermis remains unknown. To investigate its mechanisms, we studied the role of gelatinases in dermal nevus cells obtained from congenital pigmented nevi, which are major actors in the remodeling of basement membrane proteins. Our previous studies have shown that dermal nevus cells express pro-matrix metalloproteinase (MMP)-2 exclusively and cannot return to the dermis when seeded together with keratinocytes on top of the dermis in a skin reconstruction model. To examine why MMP-2 was not in its active form, we used Western blot to study the expression of members of the MMP-2 activation pathway (membrane type 1-MMP and tissue inhibitor of metalloproteinase-2), which proved to be normally expressed. To induce the dermal passage of nevus cells artificially, we also tried to activate gelatinases with phorbol-12-myristate-13-acetate and epidermal growth factor, using epidermis reconstructed with nevus cells. No migration in the dermis could be triggered. We conclude that the absence of active MMP-2 is due to a functional blockade of its activation pathway and may prevent dermal nevus cells from reaching the dermal compartment in skin reconstructs. Furthermore, our findings reinforce the concept that dermal nevus cells originating from congenital nevi are in a quiescent status.
Pigment Cell Research 09/2003; 16(4):366-73. DOI:10.1034/j.1600-0749.2003.00058.x · 4.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Congenital nevi are composed of pigment cells bearing common features with melanocytes but showing altered differentiation which leads to nesting and dermal involvement. Using a dead de-epidermized dermis seeded with a combination of keratinocytes and various sources of pigment cells (normal melanocytes, dermal nevus cells from congenital nevi, Bowes melanoma cells), we have studied the formation of nests and the dermal migration of pigment cells together with their secretion profiles of matrix metalloproteinases (MMP). Dermal fibroblasts were also used as control cells in epidermal reconstructs. Besides their morphologic features, the absence of pigment donation to keratinocytes was the major characteristic of dermal nevus cells. A positive correlation was established between the increasing percentage of seeded nevus cells and the patchy pigmentation of reconstructs, as well as the clustering of cells in junctional nests. However, the presence of nevus cells in the dermis of reconstructs was never detected, whereas melanoma cells and dermal fibroblasts could invade the dermis during the time span of the experiments. MMP9 was never expressed in congenital dermal nevus cells but pro-MMP2 was constitutively expressed by all strains of congenital nevus cells and dermal fibroblasts. Melanocytes produced comparable amounts of both pro-MMP2 and pro-MMP9, and Bowes melanoma cells secreted a marginal level of pro-MMP2. In view of their three-dimensional behaviour and secretion of MMPs, we propose that dermal congenital nevus cells correspond to an intermediate status of differentiation between normal melanocytes and melanoma cells. Activation of MMPs by a cofactor or the activation of another signalling pathway seems necessary to induce the dermal passage of nevus cells.
Pigment Cell Research 03/2002; 15(1):41-8. DOI:10.1034/j.1600-0749.2002.00065.x · 4.29 Impact Factor