1,720,986 research outputs found
Neonatal syndromes of polyendocrinopathy.
No full textFetal and newborn mammals have a limited ability to mount an immune response, both qualitatively and quantitatively, leading to an increased susceptibility to bacterial or viral infections. The incomplete development in the neonate of both innate and acquired immune system may well explain this increased susceptibility; however, the neonatal immune system, under certain circumstances, can mount an efficient immune response. Various immune-mediated disorders, including autoimmune syndromes, can take place in the early postnatal life, a period during which the immune system acquires key functions and undergoes a complex maturation and education process. Neonatal autoimmune syndromes involving endocrine glands include: IPEX/XLAAD/XPID, neonatal hyperthyroidism, Di George syndrome, ALPS, and Kabuki syndrome
MicroRNAs as new tools for exploring type 1 diabetes: relevance for immunomodulation and transplantation therapy
No full textType 1 diabetes (T1D) is a polygenic disorder where loci within the human leukocyte antigen (HLA) account for most of the genetic susceptibility. Nongenetic factors, most likely environmental, are also involved in the pathogenesis of the disease, resulting in T-cell-mediated autoimmune attack against pancreatic beta cells. Although our understanding of the natural history of T1D has significantly improved during the last decades, the pathogenesis of the disease remains elusive as are successful strategies for primary intervention. Interesting findings are expected from the emerging field of microRNAs (miRNAs), a family of endogenous small noncoding RNA molecules that regulate gene expression. They play a key role in post-transcriptional regulation by selectively binding complementary messenger RNAs, thus affecting translation. miRNAs affect key biological processes including cell proliferation, differentiation, development, and metabolism. In addition, miRNAs are also involved in the regulation of the immune system and insulin secretion. Interestingly, miRNAs have been identified in both normal and pathological conditions, functioning as predictive markers in certain human diseases. Herein, we have discussed the potential application of this new field to T1D. Research in this area may help to identify variations in genes coding for selected miRNAs that may contribute to diabetes susceptibility. In addition, mechanistic studies on the role of miRNAs in the modulation of the immune system may elucidate important regulatory mechanisms, identifying potential therapeutic targets to ameliorate responses to islet transplantation
Comment on: Meagher et al. Neutralization of interleukin-16 protects nonobese diabetic mice from autoimmune type 1 diabetes by a CCL4-dependent mechanism. Diabetes 2010;59:2862-2871
No full textMarkers of beta cell function in type 1 diabetes mellitus
No full textType 1 diabetes mellitus is a multifactorial autoimmune disease characterized by destruction of insulin producing pancreatic beta cells that results in insulin deficiency and fasting hyperglycemia. It is now well known that the clinical onset of the disease represents the end stage of an immunological process that occurs over a course of months to years. During this period the presence of autoantibodies against different islet antigens can be detected by the use of standardized assays. The rate of beta cell loss is quite variable among different individuals and at onset ketoacidosis represents still a life threatening complication of the disease. The Diabetes Control and Complication Trial (DCCT) has clearly shown that the preservation of beta cell function in type 1 diabetic subjects results in a better metabolic control and significantly reduces the risk of microvascular complications. Consequently, markers of beta cell function represent important tools to make an early diagnosis and to evaluate the impact of new therapies on the natural history of the disease. The present review will focus on clinical markers currently available (intravenous glucose tolerance test, i.v.GTT, oral glucose tolerance test, OGTT, basal and stimulated C-peptide) to assess the beta cell function in type 1 diabetes
Hidden Cointegration in Financial Time Series
No full textL'obiettivo principale di questo lavoro è di analizzare la non stazionarietà di serie storiche finanziarie mutivariate. La non linearità dei processi sottostanti a tali serie storiche ha indotto a considerare l'estensione non ineare del concetto di cointegrazione introdotto da Engle e Granger (1987). In particolare si farà riferimento al concetto di cointegrazine nascosta proposto da Granger e Yoon (2002) che rappresenta un sempice esempio di cointegrazione non lineare e una generalizzazione della cointegrazione lineare applicandolo a dati simulati e ad alcune serie storiche di quotazioni di titoli azionari
Virus infections: lessons from pancreas histology
No full textType 1 diabetes mellitus is a chronic autoimmune disease resulting from the progressive immune-mediated destruction of pancreatic beta cells in genetically susceptible individuals, with the likely contribution of environmental factors, among which viruses have been extensively studied. The pathologic hallmark of the disease is insulitis-a process characterized by islet infiltration of immunocompetent cells that has been well characterized in animal models of islet autoimmunity, and to a lesser extent, in humans. Insulitis characterization has provided valuable information to gain insights into the disease pathogenesis. We review the recent literature on the viral contribution to beta-cell destruction and dysfunction in type 1 diabetes, with particular reference to the pathology of the pancreatic islet in humans and in animal models of the disease
Pathological changes in human islets
No full textPurpose of review: This paper reviews the most recent articles on human islet inflammation in type 1 and type 2 diabetes, in recurrent autoimmunity and alloimmunity, which can result in pancreatic graft failure. Finally, we examine data supporting the hypothesis that islet destruction is accompanied by regenerative phenomena aimed at restoring beta cell mass. Recent findings: Type 1 diabetes: Application of high-resolution magnetic resonance imaging and fluorescence of long circulating nanoparticles was successfully used in evaluating islet inflammation in animal models of autoimmune diabetes. Among environmental factors in type 1 diabetes, enteroviral beta-cell infection was reported in some Finnish type 1 diabetic patients. Finally, a family of modulators of cytokine signaling was reported to occur in human islets. Pancreatic islet transplantation: Several observations suggested that (a) interventions to activate, amplify, or sustain intra-islet endothelial cells may facilitate islet revascularization; and (b) the development of strategies aimed at preventing upregulation of proinflammatory molecules can improve islet transplantation. Type 2 diabetes: Multiple factors such as proinflammatory cytokines, high glucose and free fatty acids can contribute to islet inflammation in type 2 diabetes. Accordingly, type 2 diabetic islets show increased apoptotic phenomena and a series of functional defects. Beta-cell regeneration: A number of reports observed beta-cell neogenesis in rodent and in human pancreas. Newly formed beta-cells likely derive either from ductal cells or as results of proliferation phenomena from pre-existing beta cells. Summary: Increasing evidence supports the hypothesis that islet inflammation together with beta-cell dysfunction is a common feature to both type 1 and type 2 diabetes
Innate immunity and the pathogenesis of type 1 diabetes
No full textType 1 diabetes mellitus is an autoimmune disease caused by the immune-mediated destruction of insulin-producing pancreatic beta cells occurring in genetically predisposed individuals, with consequent hyperglycemia and serious chronic complications. Studies in man and in experimental animal models have shown that both innate and adaptive immune responses participate to disease pathogenesis, possibly reflecting the multifactorial pathogenetic nature of this autoimmune disorder, with the likely involvement of environmental factors occurring at least in a subset of individuals. As a consequence, components of both innate and adaptive immune response should be considered as potential targets of therapeutic strategies for disease prevention and cure. Here we review the contribution of innate immune response to type 1 diabetes, with a particular emphasis to Toll-like receptors (TLR) and NK cells
CD4+CD25high regulatory T cells in human autoimmune diabetes
No full textIn mouse models, CD4+CD25+ T cells are involved in maintenance of peripheral tolerance. In humans, a subset of CD4+CD25+ T cells expressing high levels of CD25 (CD4+CD25high) with characteristics identical to murine CD4+CD25+ was recently described. We evaluated the characteristics of CD4+CD25high T cells in peripheral blood of type 1 diabetic subjects (T1D) and normal controls (NC). In contrast to a previous report, we found no difference in the number of CD4+CD25high and CD4+CD25+ T cells between T1D and NC. We confirmed previous studies that demonstrated that human CD4+CD25high cells can suppress the proliferation of co-cultured CD4+CD25- cells stimulated in conditions of sub-maximal cross-linking by anti-CD3 either with or without anti-CD28. However, we did not observe statistical differences between the normal controls and the chronic diabetic subjects we tested. Culturing of these cell populations did not appear to affect their ability to suppress proliferation in both groups. In conclusion, we found no significant differences in number or in vitro regulatory function of CD4+CD25high in chronic human T1D subjects
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