Dihydroxyacetone, the active browning ingredient in sunless tanning lotions, induces DNA damage, cell-cycle block and apoptosis in cultured HaCaT keratinocytes.

Dihydroxyacetone (DHA), the active substance in sunless tanning lotions reacts with the amino groups of proteins to form a brown-colored complex. This non-enzymatic glycation, known as the Maillard reaction, can also occur with free amino groups in DNA, raising the possibility that DHA may be genotoxic. To address this issue we investigated the effects of DHA on cell survival and proliferation of a human keratinocyte cell line, HaCaT.

CD56+ lymphoma with skin involvement: clinicopathologic features and classification.

Background: Extranodal lymphomas expressing CD56 (neuronal cell adhesion molecule) are characterized by a high incidence of cutaneous involvement and a very aggressive clinical course. Knowledge about the prognosis and clinicopathologic features of CD56(+) lymphomas with skin involvement is very limited.

Objectives: To determine survival and prognostic factors for extranodal CD56(+) lymphomas with skin involvement and to describe their clinicopathologic features.

Skin aging and natural photoprotection.

Aging of skin is a continuous process that may be enhanced by sun exposure. Photoaging may provoke changes different from aging. Epidermal changes involve thinning of stratum spinosum and flattening of the dermo-epidermal junction.

Melanoma diagnosis by Raman spectroscopy and neural networks: structure alterations in proteins and lipids in intact cancer tissue.

Melanoma is the most aggressive skin cancer. The specificity and sensitivity of clinical diagnosis varies from around 40% to 80%. Here, we investigated whether the chemical changes in the melanoma tissue detected by Raman spectroscopy and neural networks can be used for diagnostic purposes.

In vivo UVB irradiation induces clustering of Fas (CD95) on human epidermal cells.

In vitro studies with human cell lines have demonstrated that the death receptor Fas plays a role in ultraviolet (UV)-induced apoptosis. The purpose of the present study was to investigate the relation between Fas expression and apoptosis as well as clustering of Fas in human epidermis after a single dose of UVB irradiation. Normal healthy individuals were irradiated with three minimal erythema doses (MED) of UVB on forearm or buttock skin.

Intracellular calcium pool emptying induces DNA synthesis in HaCaT keratinocytes.

Calcium signaling provides a central control mechanism for growth, differentiation and apoptosis of epidermal keratinocytes. Moreover, calcium signaling is important for carcinogenesis in view of the observations suggesting that emptying of intracellular stores in keratinocytes [e.g.

Flotillas of lipid rafts in transit amplifying cell-like keratinocytes.

Lipid rafts are dynamic membrane microdomains enriched in cholesterol and sphingolipids and are involved in the regulation of a variety of cellular processes, such as proliferation, apoptosis and cell motility. We have previously described that large lipid raft aggregates are readily detectable on cultured keratinocyte cell line HaCaT by staining with the fluorescein-tagged cholera toxin (CTx-FITC). In this paper we adopted this method for the detection of lipid rafts in human epidermis and keratinocytes in culture.

Bone marrow precursor of extranodal T-cell lymphoma.

The development of extranodal lymphomas is thought to be initiated by the transformation event in peripheral organs. Lymphomatoid papulosis (LyP) is a low-grade cutaneous lymphoma and may progress into the cutaneous anaplastic lymphoma. We identified 2 patients who 3 and 4 years before the development of LyP were treated for an unrelated malignancy (Burkitt lymphoma and small-cell B-cell lymphoma).

Expression of T-cell activation marker CD134 (OX40) in lymphomatoid papulosis.

Background: CD134/OX40 and CD30 are transmembrane proteins from the tumour necrosis factor receptor (TNFR) family present selectively on activated T cells. TNFR-related proteins are crucially involved in the regulation of proliferation and survival of normal and malignant lymphohaematopoietic cells. CD30 has been used for the immunophenotyping and subclassification of cutaneous lymphomas; virtually nothing is known, however, about the expression pattern of CD134 in lymphoid skin malignancies.

IgA pemphigus: the first two Scandinavian cases.

IgA pemphigus is a rare neutrophilic acantholytic skin disorder with only approximately 70 cases reported in the indexed literature to date. Here we describe two patients with IgA pemphigus (subcorneal pustular dermatosis type and intraepithelial neutrophilic type) that to our knowledge are the first Scandinavian patients with this disease. Initially, both patients were misdiagnosed as subcorneal pustular dermatosis of Sneddon and Wilkinson and only subsequent careful immunofluorescence studies (in one case with confocal laser scanning microscopy) led to the correct diagnosis.

Phototoxicity to diuretics and antidiabetics in the cultured keratinocyte cell line HaCaT: evaluation by clonogenic assay and single cell gel electrophoresis Comet assay).

Background: Potential phototoxicity has been described for a number of drugs and chemical substances. Psoralens, chlorpromazines and fluoroquinolones have been described as inducing photomutagenicity and photocarcinogenicity in vitro and in vivo. We wanted to investigate oral antidiabetics and diuretics for potential phototoxicity and possible DNA damage in the HaCaT cell line.

Deletion of deoxyribonucleic acid binding domain of the vitamin D receptor abrogates genomic and nongenomic functions of vitamin D.

The vitamin D hormone 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], the biologically active form of vitamin D, is essential for an intact mineral metabolism. Using gene targeting, we sought to generate vitamin D receptor (VDR) null mutant mice carrying the reporter gene lacZ driven by the endogenous VDR promoter. Here we show that our gene-targeted mutant mice express a VDR with an intact hormone binding domain, but lacking the first zinc finger necessary for DNA binding.

Cholesterol-rich plasma membrane domains (lipid rafts) in keratinocytes: importance in the baseline and UVA-induced generation of reactive oxygen species.

The biologic effects of ultraviolet radiation such as DNA damage, mutagenesis, cellular aging, and carcinogenesis are in part mediated by reactive oxygen species. In unirradiated cells the major known sources of reactive oxygen species are the mitochondrial respiratory chain and the membrane oxidases functionally coupled to several membrane growth factor receptors. There is evidence that mitochondria also play a role in oxidative stress after ultraviolet irradiation; however, it is unknown whether the biochemical processes at the level of the plasma membrane contribute to the regulation of reactive oxygen species synthesis.

Calcipotriol for erythema annulare centrifugum.

: Erythema annulare centrifugum (EAC) is an uncommon inflammatory skin disease of unknown aetiology. No therapy is currently available. We describe a 73-year-old woman with a 3-year history of EAC that was resistant to topical and systemic glucocorticoids, antifungals, and psoralen plus ultraviolet A treatment.

Differences in activation of G2/M checkpoint in keratinocytes after genotoxic stress induced by hydrogen peroxide and ultraviolet A radiation.

Long-wave ultraviolet radiation (UVA) may cause extensive DNA damage via reactive oxygen species (ROS). In this study we examined whether UVA- and H2O2-mediated DNA damage have equivalent effects on the induction of G2/M phase checkpoint and cell cycle progression in a transformed keratinocyte cell line HaCaT. By employing single cell gel electrophoresis (comet assay) we determined the equipotent doses of UVA and H2O2 with respect to the induction of alkali-labile sites (an indicator of oxidative DNA decay).

Induction of endothelial nitric oxide synthase in perivascular mast cells in rat neurohypophysis after ischemia.

An electron microscopic immunocytochemical study was performed in order to determine the expression pattern of endothelial nitric oxide synthase (eNOS) in rat neurohypophysis after ischemia. In basal conditions eNOS was found to be weakly expressed on the endothelial cells and on single activated neurohypophyseal mastocytes. After cerebral ischemia, the number of mast cells increased in the neurohypophysis.

Hydrogen peroxide is responsible for UVA-induced DNA damage measured by alkaline comet assay in HaCaT keratinocytes.

We investigated the role of different reactive oxygen species (ROS) in ultraviolet A (UVA)-induced DNA damage in a human keratinocyte cell line, HaCaT. UVA irradiation increased the intracellular levels of hydrogen peroxide (H2O2), detected by a fluorescent probe carboxydichlorodihydrofluorescein, and caused oxidative DNA damage, single strand-breaks and alkali-labile sites, measured by alkaline single cell gel electrophoresis (comet assay). Superoxide anion (O2*-) was a likely substrate for H2O2 production since diethyldithiocarbamate (DDC), a superoxide dismutase blocker, decreased the level of intracellular H2O2.

Changes in the ultrastructure of cytoskeleton and nuclear matrix during HaCaT keratinocyte differentiation.

The cellular scaffold that comprises nuclear matrix and cytoskeleton provides mechanical support for the cell and plays a crucial role in motility, cellular signaling, regulation of gene transcription and DNA replication. In this study we examined the structure of cytoskeleton and nuclear matrix in the keratinocyte cell line HaCaT using a recently developed technique, embedment-free electron microscopy. With this method the three-dimensional structure of cellular scaffold is visualized in the cells extracted from soluble proteins and the chromatin.

[Why skin cancer?].

Basal cell carcinoma, squamous cell carcinoma, and malignant melanoma are the most prevalent types of skin cancer. Recent developments in skin cancer research have made it possible to identify environmental factors involved in cutaneous carcinogenesis and to describe the molecular pathology of skin cancer. The alterations in the sonic hedgehog signalling pathway are responsible for the development of basal cell carcinoma, whereas deactivation of the p53 protein is an important step in the pathogenesis of squamous cell carcinoma.

Role of mitochondria in ultraviolet-induced oxidative stress.

The biological effects of ultraviolet radiation (UV), such as DNA damage, mutagenesis, cellular aging, and carcinogenesis, are in part mediated by reactive oxygen species (ROS). The major intracellular ROS intermediate is hydrogen peroxide, which is synthesized from superoxide anion ((*)O(2)(-)) and further metabolized into the highly reactive hydroxyl radical. In this study, we examined the involvement of mitochondria in the UV-induced H(2)O(2) accumulation in a keratinocyte cell line HaCaT.

Structural association of Bax with nuclear matrix and cytomatrix revealed by embedment-free immunogold electron microscopy.

Bax is a cellular protein functioning as a promoter of apoptosis. It is ultrastructurally associated with mitochondrial membranes, where it participates in permeability transition pore formation. By employing embedment-free electron microscopy (EFEM), we present evidence that Bax is also associated with the nuclear matrix and cytomatrix of cultured human tumour cells (COLO 205, PA-1, U-373 MG).