Universit& and x00E0
PAOLINI L.,Universit& and x00E0 |
PICCOLO M.,University of Bologna |
RONCHI DELLA ROCCA S.,Universit& and x00E0
Mathematical Structures in Computer Science | Year: 2015
Intersection type assignment systems can be used as a general framework for building logical models of λ-calculus that allow to reason about the denotation of terms in a finitary way. We define essential models (a new class of logical models) through a parametric type assignment system using non-idempotent intersection types. Under an interpretation of terms based on typings instead than the usual one based on types, every suitable instance of the parameters induces a λ-model, whose theory is sensible. We prove that this type assignment system provides a logical description of a family of λ-models arising from a category of sets and relations. Copyright © Cambridge University Press 2015
Orciani M.,Universit& and x00E0
Journal of biological regulators and homeostatic agents | Year: 2013
Scleroderma is a chronic systemic autoimmune disease (primarily of the skin) characterized by fibrosis (or hardening), vascular alterations and autoantibodies production.There are currently no effective therapies against this devastating and often lethal disorder. Despite the interest for the immunomodulatory effects of mesenchymal stem cells (MSCs) in autoimmune diseases, the role of MSCs in scleroderma is still unknown. A pivotal role in scleroderma onset is played by oxidative stress associated with the accumulation of great amounts of reactive oxygen species (ROS). This study depicts some phenotypic and functional features of MSCs isolated from the skin of healthy and scleroderma patients; the ROS production and accumulation, the expression of ERK1/2 and the effects of the stimulation with PDGF, were analyzed in MSCs; results were compared to those observed in primary fibroblasts (Fbs) isolated from the same subjects. We found that the pro-oxidant environment exerted by scleroderma affects MSCs, which are still able to counteract the ROS accumulation by improving the antioxidant defenses. On the contrary, scleroderma fibroblasts show a disruption of these mechanisms, with consequent ROS increase and the activation of the cascade triggered by scleroderma auto-antibodies against PDGFR.
Esposito S.,Universit& and x00E0 |
Ascolese B.,Universit& and x00E0 |
Senatore L.,Universit& and x00E0 |
Bosis S.,Universit& and x00E0 |
And 3 more authors.
International journal of immunopathology and pharmacology | Year: 2014
Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory metabolic disease that is caused by mutations in the MVK gene. Patients with MKD typically have an early onset in infancy. MKD is characterized by recurrent episodes of high fever, abdominal distress, diffuse joint pain, and skin rashes. In a subset of patients, MKD is also associated with elevated serum immunoglobulin D (IgD) levels (hyperimmunoglobulinemia D syndrome, HIDS). The clinical phenotype of MKD varies widely and depends on the severity of the impaired mevalonate kinase activity. Complete impairment results in the severe metabolic disease, mevalonic aciduria, while a partial deficiency results in a broad spectrum of clinical presentation, including HIDS. The precise molecular mechanisms behind the elevated serum IgD levels and inflammation that occurs in MKD remain unknown. Children who exhibit symptoms of MKD should be tested for mutations in the MKD gene. However, the complexity of MKD often results in delays in its definitive diagnosis and the outcome in adult age is not completely known. Therapeutic options for MKD are based on limited data and include non-steroidal anti-inflammatory drugs, corticosteroids, and biological agents that target specific cytokine pathways. In recent years, some studies have reported promising results for new biological drugs; however, these cases have failed to achieve satisfactory remission. Therefore, further studies are needed to understand the pathogenesis of MKD and identify innovative therapeutic tools for its management.
PubMed | Universit& and x00E0
Type: Journal Article | Journal: International journal of immunopathology and pharmacology | Year: 2012
Salivary gland tumors, most of which are rare benign tumors, represent a histologically heterogenous group with the greatest diversity of morphological and cellular features. The aim of this study is to analyse the expression and possible interactions between gelatinases (MMP-2, MMP-9) and cyclooxygenases (COX-1, COX-2) in some benign salivary gland tumors. We investigated the expression of gelatinases and cyclooxigenases in control salivary gland, Pleomorphic adenoma and Warthins tumor through immunohistochemistry and Reverse Transcription - Polymerase Chain Reaction (PCR). We identified the expression of both classes of enzyme in normal samples and in the two types of pathological samples without any quantitative differences. From the present data no significant differences emerge in the expression of these enzymes among the different pathologies examined. Nevertheless, due to the small number of samples included in this study, general statements regarding correlation between the degree of severity of the tumoral pathology and the quantitative expression of these potential tumoral markers can not be made.
PubMed | Universit& and x00E0
Type: Journal Article | Journal: International journal of immunopathology and pharmacology | Year: 2011
Cross-Reacting Material 197 (CRM197) is a diphtheria toxin non-toxic mutant that has shown antitumor activity in mice and humans. It is still unclear whether this anti-tumorigenic effect depends on its strong inflammatory-immunological property, its ability to inhibit heparin-binding epidermal growth factor (HB-EGF), or even its possible weak toxicity. CRM197 is utilized as a specific inhibitor of HB-EGF that competes for the epidermal growth factor receptor (EGFR), overexpressed in colorectal cancer and implicated in its progression. In this study we evaluate the effects of CRM197 on HT-29 human colon cancer cell line behaviour and, for CRM197 recognized ability to inhibit HB-EGF, its possible influence on EGFR activation. In particular, while HT-29 does not show any reduction of viability after CRM197 treatment (MTT modified assay), or changes in cell cycle distribution (flow cytometry), in EGFR localization, phospho-EGFR detected signals (immunohistochemistry) or in morphology (scanning electron microscopy, SEM) they show a change in the gene expression profile by microarray analysis (cDNA microarray SS-H19k8). The overexpression of genes like protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA), guanine nucleotide-binding protein G subunit alpha-1(GNAI1) and butyrophilin, subfamily 2, member A1 (BTN2A1) has been confirmed with real-time-qPCR. This is the first study where the CRM197 treatment on HT-29 shows a possible scarce implication of endogenous HB-EGF on EGFR expression and cancer cell development. At the same time, our results show the alteration of a specific and selected number of genes.
PubMed | Universit& and x00E0
Type: Journal Article | Journal: Journal of biological regulators and homeostatic agents | Year: 2012
Alzheimers Disease implies memory and cognitive impairment due to beta amyloid accumulation, presence of reactive microglia and astrocytes, loss of synapses, neural network dysfunctions and modifications of neuronal signalling. A key role in such events is played by astrocytes, which actively secrete high levels of beta amyloid protein originating from sequential cleavage of APP by alpha, beta and gamma secretases. Since inhibition of such process could represent an important strategy against the occurrence of Alzheimers Disease, in this paper the role played by pPKC alpha in the in vitro beta amyloid production in response to gamma secretase inhibitor in rat cortical astrocytes is reported. pPKC alpha increased expression seems to be related to decreased beta amyloid production in parallel to increased astrocytes viability and decreased iNOS expression in the presence of 10 microM LY411575. Thus gamma secretase inhibitor, activating pPKC alpha intracellular pathway could be suggested to prevent or reduce downstream toxic events, representing a useful strategy to counteract Alzheimers disease.