Despite the high prevalence of cutaneous infections, little is known about the role of host immune responsiveness during Staphylococcus aureus dermatitis. We have recently described a murine model of infectious dermatitis induced by superantigen-producing S. aureus. To assess the role of neutrophils in staphylococcal dermatitis, mice were given granulocyte-depleting monoclonal antibody prior to and on several occasions following intracutaneous inoculation with staphylococci. The granulocyte-depleted mice that had been intradermally inoculated with S. aureus developed crusted ulcerations which tended not to heal, whereas animals injected with control monoclonal antibody displayed only minor and transient skin lesions. The finding of severe ulcerations in neutropenic mice correlated with a significantly higher burden of bacteria in the blood and skin during the early phase of the infection. Importantly, while mice with an intact granulocyte population showed only limited skin infection, bacteremia occurred in the great majority of the neutrophil-depleted animals. As a consequence, the latter individuals exhibited significantly increased levels of the proinflammatory cytokine interleukin-6 and specific antibodies to staphylococcal cell wall components and toxic shock syndrome toxin-1 in the serum. Our data point to a crucial protective role of granulocytes in S. aureus dermatitis.Neutrophils are host immune defense cells that are among the first to migrate into the skin in response to invading pathogens. These cells respond to chemotactic signals present at the site of infection. Among the roles played by neutrophils in inflammatory and immune responses are phagocytosis and killing of bacteria via the generation of reactive oxygen intermediates and the release of lytic enzymes stored in granules. In a recently described model of infectious dermatitis induced by the toxic shock syndrome toxin-1 (TSST-1)-producing Staphylococcus aureus strain LS-1 (12), healthy mice inoculated with high doses of staphylococci (10 8 CFU) displayed clinical and histopathological signs of local infection and inflammation within 48 h but lacked clinical or bacteriological signs of sepsis. The aim of this study was to evaluate the role of neutrophils in the induction, progression, and outcome of infectious dermatitis induced by intradermal injection of TSST-1-producing S. aureus. Our results show that depletion of neutrophil granulocytes both increases the severity of the skin lesion and gives rise to generalized infection, including bacteremia. These data demonstrate a crucial protective role for neutrophil granulocytes in S. aureus dermatitis. MATERIALS AND METHODSMice. Male BALB/c mice, 5 to 6 weeks old, were purchased from B&K Universal AB (Sollentuna, Sweden). They were housed in the animal facility of the Department of Rheumatology, University of Göteborg, under standard conditions of light and temperature and fed standard laboratory chow and water ad libitum.Bacterial strain. The BALB/c mice were inoculated intracutaneously with S....

The EWSR1 gene is known to play a crucial role in the development of a number of different bone and soft tissue tumours, notably Ewing's sarcoma. POU5F1 is expressed during early development to maintain the totipotent status of embryonic stem and germ cells. In the present study, we report the fusion of EWSR1 and POU5F1 in two types of epithelial tumours: hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. This finding not only broadens considerably the spectrum of neoplasms associated with EWSR1 fusion genes but also strengthens the evidence for shared pathogenetic mechanisms in the development of adnexal and salivary gland tumours. Reminiscent of the previously reported fusion genes involving EWSR1, the identified transcript is predicted to encode a chimeric protein consisting of the EWSR1 amino‐terminal domain and the POU5F1 carboxy‐terminal domain. We assessed the transcriptional activation potential of the chimera compared to the wild‐type proteins, as well as activation of transcription through the oct/sox composite element known to bind POU5F1. Among other POU5F1 target genes, this element is present in the promoter of NANOG and in the distal enhancer of POU5F1 itself. Our results show that although the chimera is capable of significant transcriptional activation, it may in fact convey a negative regulatory effect on target genes. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Fusion of the CREB regulated transcription coactivator CRTC1 (a.k.a. MECT1, TORC1, or WAMTP1) to the Notch coactivator MAML2 is a characteristic feature of low-grade mucoepidermoid carcinomas of salivary and bronchial glands. The CRTC1-MAML2 fusion protein acts by inducing transcription of cAMP/CREB target genes, and this activity is crucial for the transforming properties of the protein. Here we show that the CRTC1-MAML2 gene fusion is also frequent in benign hidradenomas of the skin. FISH and RT-PCR analyses revealed that hidradenomas are genetically heterogeneous, and that 10 of the 20 tumors analyzed (50%) contained the CRTC1-MAML2 gene fusion and expressed the resulting fusion transcript. Immunohistochemical analysis demonstrated expression of the fusion protein in the majority of tumor cells, including clear cells, poroid cells, and cells with epidermoid and ductal differentiation. In addition, we could show that all fusion-positive tumors were morphologically distinguished by the presence of more or less abundant areas of clear cells whereas all fusion-negative tumors lacked clear cells. Our findings thus demonstrate that the CRTC1-MAML2 gene fusion is frequent in hidradenomas and is associated with clear cell variants of this tumor. Taken together, the present and previous observations indicate that the CRTC1-MAML2 fusion is etiologically linked to benign and low-grade malignant tumors originating from diverse exocrine glands rather than being linked to a separate tumor entity.

In this preliminary study the fluorescence has been compared with the histopathological tumour boundaries. The result implies that the technique can be applied as a useful tool for indicating tumour boundary of aggressive BCCs. Further refinement is needed to be able to indicate the exact tumour border.

Mohs micrographic surgery allows for complete microscopic examination of the surgical margin when treating aggressive and recurrent facial basal cell carcinomas. This leads to the highest cure rates and maximal preservation of healthy tissue. The 5-year recurrence rates of 587 aggressive and/or recurrent facial basal cell carcinomas treated during 1993 to 2003 at our centre were studied retrospectively. The resulting 5-year recurrence rates using Kaplan-Meier survival analysis were 2.1% for primary (previously untreated) tumours, 5.2% for recurrent basal cell carcinomas and 3.3% overall. In total, 87.9% of the tumours required at least two stages of Mohs micrographic surgery. The surgical defect's size after complete excision was, on average, approximately twice the size of the defect after excision of the clinically visible tumour with a 2-3 mm margin. Mohs micro-graphic surgery is underused in Scandinavia despite being the treatment of choice for aggressive and recurrent facial basal cell carcinomas.