Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe two patients with liver kidney microsomal antibody type 1 (LKM1)-positive autoimmune hepatitis (AIH) with associated endocrinopathies. The first patient had insulin-dependent diabetes (IDDM), and the second patient had Addison's disease and hypoparathyroidism, and is also positive for islet cell antibodies, without overt diabetes. To account for the existence of multiple endocrinopathy in these patients, we investigated whether there is sequence similarity between the target of LKM1 antibodies, cytochrome P4502D6 (CYP2D6), and other human proteins, and if so, whether this structural similarity produces a detectable cross-reactive immune response. Our database search identified two proteins, carboxypeptidase H, an autoantigen in insulin-dependent diabetes, and 21-hydroxylase, the major autoantigen in Addison's disease, that share sequence similarity to the second major LKM1 epitope on CYP2D6. We tested the reactivity of sera from these patients to the homologous regions of the three autoantigens using an enzyme-linked immunosorbent assay (ELISA). The cut-off for positivity was established by testing sera from 22 healthy children. To determine the significance of reactivity to the peptide homologues of the three autoantigens, we investigated 16 additional patients with LKM1 AIH and 20 children with chronic hepatitis B virus infection as pathological controls. We found that reactivity to the second major epitope of CYP2D6 is significantly associated with reactivity to the homologous regions of carboxypeptidase H (CPH) and 21-hydroxylase (21-OHase) in patients with LKM1 AIH, and that this simultaneous recognition is cross-reactive. We suggest that a cross-reactive immune response between homologous autoantigens may contribute to the development of multiple endocrinopathies in LKM1 AIH.
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PMID:Immunological cross-reactivity to multiple autoantigens in patients with liver kidney microsomal type 1 autoimmune hepatitis. 979 98

Coxsackie B virus (CVB-5) infections potentially trigger and accelerate pancreatic beta cell damage leading to type 1 diabetes. In vivo, all viruses face natural resistance mediated by various host factors which restrict the progression of infection. Thus, the aims of this study were to generate a tissue culture model of restricted coxsackie B virus infection in primary islet cells by preventing the production of viral progeny with a selective inhibitor of viral RNA replication and to investigate the mechanisms of virus-induced islet cell death during productive and restricted infective conditions. Cultured foetal porcine islet cells were infected effectively with the prototype strain of coxsackievirus B5 (CVB-5). Nuclear viability stainings and electron microscopy showed productive infection to result in dominantly necrotic cell death with additional slight induction of apoptosis during the 7 days of follow-up. The restricted conditions were created by addition of guanidine-hydrochloride (G-HCl) into culture medium. At 1 mM concentration, it significantly protected the infected cells from necrosis and thus maintained high viability. This was associated with increased significantly apoptosis. In perifusion analysis, the cellular ability to release insulin was reduced, although the metabolic integrity was preserved as shown by MTT-analysis and cellular ATP levels. These data show that restriction of CVB-5 replication with G-HCl protects islet cells against virus-induced necrosis. However, restriction of viral replication shifts the mechanism of cell death from necrosis toward apoptosis. A slowly progressing subclinical infection of islets could thus lead to increased beta-cell apoptosis.
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PMID:Mechanisms of beta cell death during restricted and unrestricted enterovirus infection. 1474 69

A 64-years-old man referred to a hospital because of high-grade fever. He was diagnosed as having influenza B by "POCTEM Influenza A/B", a rapid influenza diagnostic kit which detect some antigens of influenza virus. Six days after medication of oseltamivir phosphate, his flu-symptoms disappeared, but he complained sever thirsty. And after 2days, he suffered from loss of consciousness and was admitted to the hospital. Laboratory data on admission showed diabetes ketoacidosis, slight elevation of HbA1c level despite sever hyperglycemia, and increase of serum amylase concentration. Anti GAD antibody and anti IA-2 antibody were not detected. Urinary C-peptide excretion was undetectable and serum C-peptide levels were also undetectable after glucagon and arginin load, suggesting disappearance of endogeneous insulin secretion. Class II HLA was susceptible to fulminant type1 diabetes. Based on these findings, we diagnosed him with fulminant type1 diabetes. In Japan, only three viruses in three cases have been reported to be the trigger in the development of fulminant type 1 diabetes. They were human herpes virus 6, herpes simplex virus and Coxsackie B3 virus. This is the fourth report of fulminant type 1 diabetes developed after the established diagnosis of viral infection and the first after influenza B virus infection. The fact that fulminant type 1 diabetes developed after the infection of such a common virus suggest that factors within host will play more important roles than virus itself in the etiology of fulminant type 1 diabetes.
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PMID:A case of fulminant type 1 diabetes mellitus after influenza B infection. 1817 74