Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine deaminase (ADA) deficiency typically causes severe combined immunodeficiency (SCID) in infants. We report metabolic, immunologic, and genetic findings in two ADA-deficient adults with distinct phenotypes. Patient no. 1 (39 years of age) had combined immunodeficiency. She had frequent infections, lymphopenia, and recurrent hepatitis as a child but did relatively well in her second and third decades. Then she developed chronic sinopulmonary infections, including tuberculosis, and hepatobiliary disease; she died of viral leukoencephalopathy at 40 years of age. Patient no. 2, a healthy 28-year-old man with normal immune function, was identified after his niece died of SCID. Both patients lacked erythrocyte ADA activity but had only modestly elevated deoxyadenosine nucleotides. Both were heteroallelic for missense mutations: patient no. 1, G216R and P126Q (novel); patient no. 2, R101Q and A215T. Three of these mutations eliminated ADA activity, but A215T reduced activity by only 85%. Owing to a single nucleotide change in the middle of exon 7, A215T also appeared to induce exon 7 skipping. ADA deficiency is treatable and should be considered in older patients with unexplained lymphopenia and immune deficiency, who may also manifest autoimmunity or unexplained hepatobiliary disease. Metabolic status and genotype may help in assessing prognosis of more mildly affected patients.
 ...
PMID:Adenosine deaminase deficiency in adults. 910 4

Adenosine deaminase acting on RNA 1 (ADAR1) is a double-stranded RNA binding protein and RNA-editing enzyme that modifies cellular and viral RNAs, including coding and noncoding RNAs. This interferon (IFN)-induced protein was expected to have an antiviral role, but recent studies have demonstrated that it promotes the replication of many RNA viruses. The data from these experiments show that ADAR1 directly enhances replication of hepatitis delta virus, human immunodeficiency virus type 1, vesicular stomatitis virus, and measles virus. The proviral activity of ADAR1 occurs through two mechanisms: RNA editing and inhibition of RNA-activated protein kinase (PKR). While these pathways have been found independently, the two mechanisms can act in concert to increase viral replication and contribute to viral pathogenesis. This novel type of proviral regulation by an IFN-induced protein, combined with some antiviral effects of hyperediting, sheds new light on the importance of ADAR1 during viral infection and transforms our overall understanding of the innate immune response.
 ...
PMID:Enhancement of replication of RNA viruses by ADAR1 via RNA editing and inhibition of RNA-activated protein kinase. 2149 91

Serum Adenosine deaminase (ADA) activity in normal healthy control subjects increases upto 30 years, remains steady between 31-60 years of age and shows a steep increase in the age group of 61-70 years. This was compared with serum aspartate transaminase (AST) and alanine transaminase (ALT) activity which also showed a gradual increase upto 40 years of age and decreased thereafter. The activities of serum ADA, AST and ALT increased in patients with hepatitis of all age groups compared to their respective controls. The degree of increase in the activities of the above enzymes in hepatitis, decreased with age. The present study also shows that while studying serum ADA activity in hepatitis for diagnostic purposes, the value obtained in a particular age group should be compared with normal range of values for the respective age group only.
 ...
PMID:Studies on the age dependent changes in serum adenosine deaminase activity and its changes in hepatitis. 2310 81

Adenosine deaminase acting on RNA 1 (ADAR1) is an essential protein for embryonic liver development. ADAR1 loss is embryonically lethal because of severe liver damage. Although ADAR1 is required in adult livers to prevent liver cell death, as demonstrated by liver-specific conditional knockout (Alb-ADAR1(KO)) mice, the mechanism remains elusive. We systematically analyzed Alb-ADAR1(KO) mice for liver damage. Differentiation genes and inflammatory pathways were examined in hepatic tissues from Alb-ADAR1(KO) and littermate controls. Inducible ADAR1 KO mice were used to validate regulatory effects of ADAR1 on inflammatory cytokines. We found that Alb-ADAR1(KO) mice showed dramatic growth retardation and high mortality because of severe structural and functional damage to the liver, which showed overwhelming inflammation, cell death, fibrosis, fatty change, and compensatory regeneration. Simultaneously, Alb-ADAR1(KO) showed altered expression of key differentiation genes and significantly higher levels of hepatic inflammatory cytokines, especially type I interferons, which was also verified by inducible ADAR1 knockdown in primary hepatocyte cultures. We conclude that ADAR1 is an essential molecule for maintaining adult liver homeostasis and, in turn, morphological and functional integrity. It inhibits the production of type I interferons and other inflammatory cytokines. Our findings may provide novel insight in the pathogenesis of liver diseases caused by excessive inflammatory responses, including autoimmune hepatitis.
...
PMID:ADAR1 Prevents Liver Injury from Inflammation and Suppresses Interferon Production in Hepatocytes. 2645