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The response to wounds until healing requires the activity of many cell types coordinate in space and time, so that the types of cells in a wound and their localization may be of help to date lesions with respect to death, which would be useful in forensic pathology. Cells reacting to injury include dendritic cells; the early reaction of these cells to skin wounding has not yet been investigated in humans, which was the aim of this study. Samples of wounded and control skin were taken at autopsy and analyzed by affinity histochemistry. Both epidermal and dermal MHC-II+ cells increased transiently in number within the first hour after wounding, then decreased. In the epidermis the increase affected also CD1a+ cells, i.e. well differentiated Langherhans cells, which however increased less, earlier and for a shorter time period than MHC-II+ cells. Dermal MHC-II+ cells became part of a perivascular mononuclear cell infiltrate visible in the subpapillary dermis by 60 min after wounding, which contained also mast cells. The immediately perivascular MHC-II+ cells were DC-SIGN- and CD11c-, while MHC-II+, DC-SIGN+, CD11c+ dendritic cells were predominantly located at the periphery of infiltrates and some were near the epidermis. Mast cells underwent degranulation, besides increase in number, in the first hours after wounding. The results suggest that skin dendritic cells, including Langerhans cells, participate to the early response to wounding in concert with mast cells, and that subpapillary blood vessels are primary sites of cell infiltration during that response in humans. The results show that the ratio between CD1a positive and MHC-II positive cells in the epidermis, the degranulation index of mast cells and the relative volume of MHC-II positive cells in the dermis can be added to the tools useful to distinguish vital from post mortem lesions and, the first two of them, to estimate the interval between a lesion and death. [ABSTRACT FROM AUTHOR]

Abstract: Background: The severity of clinical activity of Crohn’s disease is high during the first year after diagnosis and decreases thereafter. Approximately 50% of patients require steroids and immunosuppressants and 75% need surgery during their lifetime. The clinical course of patients with Crohn’s disease first diagnosed at surgery has never been investigated. Aim: To assess the clinical course of Crohn’s disease first diagnosed at surgery for acute abdomen and to evaluate the need for medical and surgical treatment in this subset of patients. Patients and methods: Hospital clinical records of 490 consecutive Crohn’s disease patients were reviewed. Patients were classified according to the Vienna criteria. Sex, extraintestinal manifestations, family history of inflammatory bowel diseases, appendectomy, smoking habit and medical/surgical treatments performed during the follow-up period were assessed. Statistical analysis: Kaplan–Meier survival method and Cox proportional hazards regression model. Results: Of the 490 Crohn’s disease patients, 115 had diagnosis of Crohn’s disease at surgery for acute abdomen (Group A) and 375 by conventional clinical, radiological, endoscopic and histologic criteria (Group B). Patients in Group A showed a low risk of further surgery (Log Rank test p <0.001) and a longer time interval between diagnosis and first operation compared to Group B (10.8 years vs. 5.8 years, p <0.01, respectively). Furthermore, patients in Group A used less steroids and immunosuppressants (OR 0.3, p <0.0001; OR 0.6, p <0.004, respectively). Conclusions: Crohn’s disease patients first diagnosed at surgery for acute abdomen showed a low risk for reintervention and less use of steroids and immunosuppressants during follow-up than those not operated upon at diagnosis. Early surgery may represent a valid approach in the initial management of patients with Crohn’s disease, at least in the subset of patients with ileal and complicated disease. [Copyright &y& Elsevier]

GLI-1 overexpression has been observed in basal cell carcinoma (BCC) and has been considered a key event in its pathogenesis, leading to increased cell proliferation and expression of the anti-apoptotic molecule Bcl-2 as well as to a reduced expression of the adhesion molecule laminin. The aim of the study was to evaluate the expression of the above mentioned molecules in a series of BCCs and in a BCC cell line, TE 354.T. Immunohistochemical expression of GLI-1, Bcl-2, and laminin was evaluated in 15 sporadic BCCs of various subtypes and different clinical behavior (3 nodular, 3 superficial, 3 infiltrating, 3 metatypical, 2 recurrent and 1 metastatic), and, for comparison, in 20 benign hair follicle-related tumors and in 5 cases of basaloid hyperplasia overlying dermatofibromas. Suspended and adherent TE 354.T basal carcinoma cells were fixed with periodate-lysine-paraformaldehyde for immunohistochemistry and with Karnovsky's for electron microscopy. BCCs consistently showed GLI-1 immunoreactivity, the staining being quite heterogeneous in the neoplastic aggregates, with a stronger intensity at the periphery. BCCs also expressed Bcl-2, with a distribution similar to GLI-1. Laminin staining was observed at the interface between tumor nodules and adjacent stroma. Some GLI-1 immunoreactivity was observed in cases of basaloid hyperplasia and benign follicular tumors whereas the normal epidermis was negative. Cultured cells were flat and the cell surface adhering to the substrate was coated by a basal lamina. Different intensity of staining among cultured cells was found for GLI-1, Bcl-2, and laminin. The results support a direct correlation between the expression of GLI-1 and that of Bcl-2. However, GLI-1 expression, although rarely, also in hyperplastic basaloid proliferations and in benign follicular tumors suggests that in the pathogenesis of BCC, besides the deregulation of the patched-hedgehog signaling pathway, other mechanisms are implied. [ABSTRACT FROM AUTHOR]

Abstract: Three surveys have been undertaken in European Union (EU) member states since January 2007, within the European Commission funded Vaccine European New Integrated Collaboration Effort (VENICE) project, to monitor the decision status regarding the introduction of human papillomavirus (HPV) vaccination into national immunisation schedules. A web-based questionnaire was developed and completed online by the 28 countries participating in VENICE. According to the last update (31st December 2008), 15 countries have decided to introduce HPV vaccination into their national immunisation schedule, while another six have started the decision-making process with a recommendation favouring introduction. Varying target populations have been selected by the countries which have introduced vaccination. The number of countries which have made a decision or recommendation has increased from 12 to 21 between October 2007 and December 2008. This survey demonstrates the rapidly evolving nature of HPV vaccine introduction in Europe. A further update should be available in the second half of 2009. [Copyright &y& Elsevier]

The protein product of GLI-1 oncogene mediates the physiological effects of the intercellular signaling molecule Sonic hedgehog (SHH) and controls the cell proliferation and differentiation of subpopulations of epidermal cells during development and in mature organisms. Overexpression of GLI-1 is characteristic of basal cell carcinoma (BCC) and is considered pathogenetic for this disease. Tacrolimus (FK506) has extensive homology and uses the same receptor as rapamycin, which can antagonize the cellular transformation caused by GLI-1 overexpression. We have therefore addressed whether tacrolimus affects the expression of GLI-1 in a basal cell carcinoma cell line, TE 354.T. Total RNA was extracted with Trizol and the expression of GLI-1 was evaluated by quantitative RT-PCR with TaqMan polymerase. Cells lysates were analyzed by gel electrophoresis and Western blotting. Suspended and adherent cells were analyzed by immunohistochemistry and electron microscopy. The cell line TE 354.T had an approximate doubling time of 3.5 days; cells were flat and rich in organelles of the secretory pathway and intermediate filaments; the cell surface adhering to the substrate was coated by a basal lamina. Intermediate filaments contained vimentin. GLI-1, Bcl-2 and laminin were expressed with variable intensity among cells. The expression of GLI-1 was confirmed at the mRNA and protein levels. Three day treatment with Tacrolimus (0.5–50 ng/mL) led to a dose-related drop in the expression of GLI-1 mRNA (significant for 50 ng/mL) and, to a lesser extent, in the number of GLI-1 immunoreactive cells. The cell proliferation rate and fine structure were not affected by treatment. Tacrolimus affects the expression of GLI-1 in a basal carcinoma cell line; this result opens the pathway to investigate whether such effect correlates with altered expression of other genes related to neoplastic behavior. [ABSTRACT FROM AUTHOR]