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

Ring-expanded (ldauo;fat") nucleosides (RENs) described in this review are analogues of purine nucleosides containing a 5:7-fused imidazodiazepine or imidazotriazepine ring system. They are both of natural and synthetic origin, and are of chemical, biochemical, biophysical, as well as medicinal interest. The important natural RENs include coformycin, pentostatin, azepinomycin, adechlorin, and adecypenol. A majority of them are synergistic antitumor and/or antiviral antibiotics which potentiate the effects of other antitumor or antiviral compounds through inhibition of key enzymes such as adenosine deaminase or guanase which would otherwise metabolically degrade the active compounds into therapeutically less potent or totally inactive counterparts. However, despite the fact that some of the natural RENs such as coformycins are the strongest known enzyme inhibitors, they have not been proven as effective clinically as anticipated because of the extremely high toxicity associated with their use. Nevertheless, pentostatin (2'-deoxycoformycin) is a conspicuous exception as it is gaining wide attention in recent years as a clinically effective therapeutic agent against leukemias and lymphomas. Many of the recently reported synthetic RENs, by contrast, possess biological activities of their own, in particular against a wide spectrum of cancers and viruses with little toxicity to the host cells, and thus hold considerable promise as chemotherapeutic agents. The promising preliminary in vitro data concerning the effects of RENs on human cancers, in particular prostate and breast cancer cells, support their further pursuit in animal and clinical studies. RENs also carry promise against many viral infections belonging to the families of hepatitis, herpes, and respiratory infections, most notable being the hepatitis B (HBV), hepatitis C (HCV), and the West Nile (WNV) viruses.
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PMID:Ring-expanded ("Fat") nucleosides as broad-spectrum anticancer and antiviral agents. 1217 69

Intrinsic to the life cycle of hepatitis delta virus (HDV) is the fact that its RNAs undergo different forms of posttranscriptional RNA processing. Transcripts of both the genomic RNA and its exact complement, the antigenomic RNA, undergo ribozyme cleavage and RNA ligation. In addition, antigenomic RNA transcripts can undergo 5' capping, 3' polyadenylation, and even RNA editing by an adenosine deaminase. This study focused on the processing of antigenomic RNA transcripts. Two approaches were used to study the relationship between the events of polyadenylation, ribozyme cleavage, and RNA ligation. The first represented an examination under more controlled conditions of mutations in the poly(A) signal, AAUAAA, which is essential for this processing. We found that when a separate stable source of deltaAg-S, the small delta protein, was provided, the replication ability of the mutated RNA was restored. The second approach involved an examination of the processing in transfected cells of specific Pol II DNA-directed transcripts of HDV antigenomic sequences. The DNA constructs used were such that the RNA transcripts were antigenomic and began at the same 5' site as the mRNA produced during RNA-directed HDV genome replication. A series of such constructs was assembled in order to test the relative abilities of the transcripts to undergo processing by polyadenylation or ribozyme cleavage at sites further 3' on a multimer of HDV sequences. The findings from the two experimental approaches led to significant modifications in the rolling-circle model of HDV genome replication.
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PMID:Alternative processing of hepatitis delta virus antigenomic RNA transcripts. 1507 32

Previous studies have defined a novel cell culture system in which a modified RNA genome of hepatitis delta virus (HDV) is able to maintain a low level of continuous replication for at least 1 year, using a separate and limited DNA-directed source of mRNA for the essential small delta protein. This mode of replication is analogous to that used by plant viroids. An examination was made of the nucleotide changes that accumulated on the HDV RNA during 1 year of replication. The length of the RNA genome was maintained, except for some single-nucleotide deletions and insertions. There was an abundance of single-nucleotide substitutions, with a 22-fold excess of these being base transitions rather than transversions. Of the detected transitions, at least 70% were consistent with being the consequences of posttranscriptional RNA editing by an adenosine deaminase acting on RNA. The remainder of the changes, including the single-nucleotide insertions and deletions, are likely to be the consequence of misincorporation during transcription. In addition, an intermolecular competition assay was used to show that the majority of the genomes present after 1 year of replication were essentially as competent in replication as the original single HDV RNA sequence that was used to initiate the genome replication. A model is provided to explain how, in this experimental system, the observed single-nucleotide changes were essentially neutral in terms of their effect on the ability of the HDV genome to carry out continued rounds of replication.
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PMID:Evolution of hepatitis delta virus RNA genome following long-term replication in cell culture. 1622 53

Hepatitis delta virus (HDV) RNA editing controls the formation of hepatitis-delta-antigen-S and -L and therefore indirectly regulates HDV replication. Editing is thought to be catalysed by the adenosine deaminase acting on RNA1 (ADAR1) of which two different forms exist, interferon (IFN)-alpha-inducible ADAR1-L and constitutively expressed ADAR1-S. ADAR1-L is hypothesized to be a part of the innate cellular immune system, responsible for deaminating adenosines in viral dsRNAs. We examined the influence of both forms on HDV RNA editing in IFN-alpha-stimulated and unstimulated hepatoma cells. For gene silencing, an antisense oligodeoxyribonucleotide against a common sequence of both forms of ADAR1 and another one specific for ADAR1-L alone were used. IFN-alpha treatment of host cells led to approximately twofold increase of RNA editing compared with unstimulated controls. If ADAR1-L expression was inhibited, this substantial increase in editing could no longer be observed. In unstimulated cells, ADAR1-L suppression had only minor effects on editing. Inhibition of both forms of ADAR1 simultaneously led to a substantial decrease of edited RNA independently of IFN-alpha-stimulation. In conclusion, the two forms of ADAR1 are responsible almost alone for HDV editing. In unstimulated cells, ADAR1-S is the main editing activity. The increase of edited RNA under IFN-alpha-stimulation is because of induction of ADAR1-L, showing for the first time that this IFN-inducible protein is involved in the base modification of replicating HDV RNA. Thus, induction of ADAR1-L may at least partially cause the antiviral effect of IFN-alpha in natural immune response to HDV as well as in case of therapeutic administration of IFN.
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PMID:The large form of ADAR 1 is responsible for enhanced hepatitis delta virus RNA editing in interferon-alpha-stimulated host cells. 1647 90

Cytosolic enzymes AMP deaminase and adenosine deaminase (ADA) catalyze AMP and adenosine deamination, constitute rate-limiting steps of adenine nucleotide catabolism and play important roles in cellular energy metabolism. In this study, AMP deaminase and ADA activities of rat liver, neocortex, cerebellum, striatum and hippocampus were investigated in acute ammonia intoxication and subacute CCl(4)-induced hepatitis. Activities of both AMP deaminase and ADA in the liver were elevated by 2.4-4.2-fold (p<0.0001) in both models of hepatotoxic injury as compared with controls. In acute hyperammonemia activities of AMP, deaminase and ADA increased by 46-59% (p<0.02) in the neocortex and did not change in the striatum. In the hippocampus of hyperammonemic rats, only AMP deaminase activity was increased by 48% (p=0.0004), and in the cerebellum only ADA activity was increased significantly (by 26%, p<0.05). The adenylate pool size and energy charge were greatly reduced in the neocortex of hyperammonemic rats. Results suggested that two parallel pathways of AMP breakdown, including AMP deaminase and ADA, respectively, are up-regulated under pathological conditions, probably in order to overcome compensatory synthesis of adenylates, to ensure prompt adenylate pool depletion and reduce the adenylate energy charge in liver and selected brain regions.
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PMID:AMP deaminase and adenosine deaminase activities in liver and brain regions in acute ammonia intoxication and subacute toxic hepatitis. 1990 Apr 20

We studied the effect of acute ammonia poisoning and CCl4-induced subacute hepatitis on activities of AMP deaminase and adenosine deaminase in rat liver. Both models of liver failure were accompanied by an increase in activities of AMP deaminase and adenosine deaminase in the cytoplasmic fraction of the liver (by 2.4-4.2 times compared to the control). A direct correlation was found between activities of AMP deaminase and adenosine deaminase. We believe that two parallel pathways of AMP degradation are activated simultaneously, which leads to rapid depletion of adenylate reserves under pathological conditions.
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PMID:Activation of AMP deaminase and adenosine deaminase in the liver during ammonia poisoning and hepatitis. 2116 Oct 45

Serum adenosine deaminase (ADA), 5' nucleotidase (5'NT) and malondialdehyde (MDA) were estimated in patients with acute infective hepatitis (AIH) along with the routine parameters of liver disease. Present study is done to evaluate these special parameters in patients with clinical history of AIH and to assess the utility of these parameters as diagnostic/ prognostic indices of liver function and to correlate special parameters with routine live function tests (LFT). ADA, 5'NT and MDA along with routine LFT was estimated in 25 patients with AIH and 25 samples from healthy voluntary blood donars served as the control group. Routine LFT was estimated by standard clinical chemistry procedures on dade behring analyser and ADA, 5'NT and MDA were estimated by berthlot reaction, fiske and subbarao method and thiobarbituric acid method respectively.Statistical analysis showed that serum ADA, 5'NT and MDA were significantly higher in patients as compared with the controls. There was a significant positive correlation between ADA and total bilirubin and MDA and total bilirubin. Hence we can conclude that these tests would be more sensitive to diagnose the patients with AIH and that the raised bilirubin levels could be looked upon, as a protective mechanism which the liver has evolved in order to combat oxidative stress.
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PMID:Serum adenosine deaminase, 5' nucleotidase and malondialdehyde in acute infective hepatitis. 2310 70


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