Diabetes and Viruses
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This book will assemble the views of many of the world's experts in the field of viruses and diabetes. It will look critically at some unanswered questions, in the field. Among these, How do viruses destroy or modify the pancreatic islet? Which viruses are involved? What is the role of virus-induced cytokines> Could vaccines prevent virus-induced diabetes? Until recent technological advances, progress in the understanding of the relationship between viruses and diabetes has been hampered. New technologies are helping shed new light on these mysteries. This will be the first comprehensive volume on this topic.
appearance of or an increase in the concentration of islet autoantibodies. Islet autoantibodies were not detected before RV infection. 5. Dose–response (increased effect with increasing dose or exposure): demonstrated by repeated RV infection being associated with islet autoantibodies. 6. Plausibility (observed associations explained by the biology): supported by the demonstration that CD4+ T-cell autoepitope peptides in GAD65 and IA-2 have strong sequence similarities to T-cell epitopes in
using the VMD 1.8.7 program (Protein Data Bank access code 1D4M). Courtesy of Vesa Hytönen, University of Tampere, Finland. Fig. 3 Assembly of the enterovirus capsid. A) The four capsid proteins represented as Van der Waals spheres (VP1, blue; VP2, red; VP3, yellow; VP4, green) are shown as assembled in the capsid. B) The four capsid proteins are shown as assembled in a pentamer. C) Side view of capsid proteins assembled in a single pentamer. As in Figures 1 and 2, the models are based on the
CTLA4 molecule could be a factor that predisposes to type 1 diabetes, but this issue remains unclear. The PTPN22 Gene The PTPN22 gene (1p13) encodes a lymphoid protein tyrosine phosphatase (the protein product called LYP) that is expressed in lymphocytes and is acting through binding intracellular kinases. LYP is involved directly in setting thresholds for T-cell receptor signaling (Cloutier and Veillette 1999). The Arg620Trp polymorphism of this gene is associated with type 1 diabetes in many
subject to evolutionary forces, such as selection, drift, and penetrance. It has been observed in the Finnish population that the penetrance of HLA on the phenotype of type 1 diabetes gradually changed during the last few decades. The frequency of risk HLA Class II genotypes has decreased among newly diagnosed patients, while the proportion of newly diagnosed subjects carrying neutral or protective genotypes has increased considerably (Hermann et al. 2003a). This has since been confirmed in
cells. In some cases, each pancreatic lobe had slightly atrophied islets composed of islet cells with scanty cytoplasm. Mild or severe lymphocytic inﬁltration at both the periphery and inner part of the islets was observed frequently in all cases (Fig. 10.1d). Most inﬂammatory cells consisted of small lymphocytes and, occasionally, few large mononuclear cells and plasma cells. In some lobes, mitoses were seen in the enlarged islets composed of hypertrophic cells. In the exocrine glands, focal