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)

The clinical and laboratory features of 29 patients who had one of three anti-aminoacyl-tRNA synthetase autoantibodies, anti-Jo1 (histidyl-tRNA synthetase), anti-PL12 (alanyl-tRNA synthetase) or anti-PL7 (threonyl-tRNA synthetase) were analysed and compared with the findings of other published reports. These autoantibodies were found to be associated with a syndrome delineated by inflammatory myositis (24 patients) and pulmonary fibrosis (23 of 29), but also including inflammatory arthritis (26/29), keratoconjunctivitis sicca (17/29), sclerodactyly (21/29), Raynaud's phenomenon (27/29), hepatitis (8/29) and subcutaneous calcinosis (7/29). The most important clinical determinant of outcome in this group of patients was the severity of the interstitial pulmonary disease. No patient fulfilled the classification criteria for systemic lupus erythematosus, although 10 had autoantibodies to extractable nuclear antigens including Ro, La, RNP, and Sm, and two patients had anti-dsDNA antibodies. Although it seems unlikely that anti-aminoacyl-tRNA synthetase antibodies are directly responsible for causing disease, they may provide an important clue to the aetiology of this unusual syndrome.
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PMID:Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes. 226 80

Isozyme patterns of S-adenosylmethionine synthetase have been measured with or without dimethylsulfoxide in liver of LEC rat hereditary hepatitis. The activities of the alpha- and beta-forms are decreased with age after birth, and decreased to a half level of 36 weeks after birth. Concentration of S-adenosylmethionine in the liver is almost a half level of control rat. However, the activity of glycine- and tRNA-methyltransferases in the liver shows no significant change.
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PMID:Decreased activities of S-adenosylmethionine synthetase isozymes in hereditary hepatitis in Long-Evans rats. 236 43

The structure of an RNA hairpin containing a seven-nucleotide loop that is present in the self-cleaving sequence of hepatitis delta virus antigenomic RNA was determined by high resolution NMR spectroscopy. The loop, which is composed of only one purine and six pyrimidines, has a suprisingly stable structure, mainly supported by sugar hydroxyl hydrogen bonds and base-base and base-phosphate stacking interactions. Compared with the structurally well-determined, seven-membered anticodon loop in tRNA, the sharp turn which affects the required 180 degrees change in direction of the sugar-phosphate backbone in the loop is shifted one nucleotide in the 3' direction. This change in direction can be characterized as a reversed U-turn. It is expected that the reversed U-turn may be found frequently in other molecules as well. There is evidence for a new non-Watson-Crick UC base pair formed between the first and the last residue in the loop, while most of the other bases in the loop are pointing outwards making them accessible to solvent. From chemical modification, mutational and photocrosslinking studies, a similar picture develops for the structure of the hairpin in the active ribozyme indicating that the loop structure in the isolated hairpin and in the ribozyme is very similar.
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PMID:The structure of the isolated, central hairpin of the HDV antigenomic ribozyme: novel structural features and similarity of the loop in the ribozyme and free in solution. 921 9

The coronavirus mouse hepatitis virus (MHV) is an enveloped positive stranded RNA virus. In infected cells MHV produces a 3' coterminal nested set of subgenomic messenger RNAs. Only the genomic RNA, however, is encapsidated by the nucleocapsid protein and incorporated in infectious MHV virions. It is believed that an RNA packaging signal (Ps), present only in the genomic RNA, is responsible for this selectivity. Earlier studies mapped this signal to a 69-nt stem-loop structure positioned in the 3' end of ORF1b. The selective encapsidation mechanism probably initiates by specific interaction of the packaging signal with the nucleocapsid protein. In this study we demonstrate the in vitro interaction of the MHV-A59 nucleocapsid protein with the packaging signal of MHV using gel retardation and UV cross-linking assays. This interaction was observed not only with the nucleocapsid protein from infected cells but also with that from purified virions and from cells expressing a recombinant nucleocapsid protein. The specificity of the interaction was demonstrated by competition experiments with nonlabeled Ps containing RNAs, tRNA, and total cytoplasmic RNA. The results indicated that no virus specific modification of the N-protein or the presence of other viral proteins are required for this in vitro intervention. The assays described in this report provide us with a powerful tool for studying encapsidation (initiation) in more detail.
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PMID:Identification of a specific interaction between the coronavirus mouse hepatitis virus A59 nucleocapsid protein and packaging signal. 942 48

Antibodies (Abs) hydrolyzing proteins, DNA, and RNA are detected in the blood of patients with various autoimmune diseases. In the present work, homogeneous preparations of IgG Abs from the blood of the healthy donors as well as patients with A, B, C, and delta types of viral hepatitis, influenza, pneumonia, tuberculosis, tonsillitis, duodenal ulcer, and some types of cancer were purified. For the first time, the fraction of IgG and its Fab fragments of patients with viral hepatitis were shown to have high DNA- and RNA-hydrolyzing activity. In case of Abs from the healthy donors and patients with other diseases, high activity of Abs was not detected. The data obtained by various methods indicate that the activity of hepatitis Abs is an intrinsic property of the immunoglobulins. The relative rates of hydrolysis of cCMP, poly(U), poly(A), poly(C), and tRNA(Phe) by hepatitis Abs were compared with those of RNase A and other RNases from human blood. Significant differences in activities of Abs and nucleases in hydrolysis of model substrates were demonstrated. Thus, catalytically active Abs can appear in the blood of patients not only with autoimmune disorders, but with viral diseases as well.
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PMID:DNA- and RNA-hydrolyzing antibodies from the blood of patients with various forms of viral hepatitis. 948 69

In order to evaluate uranyl photocleavage as a tool to identify and characterize structural and dynamic properties in RNA, we compared uranyl cleavage sites in five RNA molecules with known X-ray structures, namely the hammerhead and hepatitis delta virus ribozymes, the P4-P6 domain of the Tetrahymena group I intron, as well as tRNA(Phe) and tRNA(Asp) from yeast. Uranyl photocleavage was observed at specific positions in all molecules investigated. In order to characterize the sites, photocleavage was performed in the absence and in increasing amounts of MgCl(2). Uranyl photocleavage correlates well with sites of low calculated accessibility, suggesting that uranyl ions bind in tight RNA pockets formed by close approach of phosphate groups. RNA foldings require ion binding, usually magnesium ions. Thus, upon the adoption of the native structure, uranyl ions can no longer bind well except in flexible and open to the solvent regions that can undergo induced-fit without disrupting the native fold. Uranyl photocleavage was compared to N-ethyl-N-nitrosourea and lead-induced cleavages in the context of the three-dimensional X-ray structures. Overall, the regions protected from ENU attack are sites of uranyl cleavage, indicating sites of low accessibility which can form ion binding sites. On the contrary, lead cleavages occur at flexible and accessible sites and correlate with the unspecific cleavages prevalent in dynamic and open regions. Applied in a magnesium-dependent manner, and only in combination with other backbone probing agents such as N-ethyl-N-nitrosourea, lead and Fenton cleavage, uranyl probing has the potential to reveal high-affinity metal ion environments, as well as regions involved in conformational transitions.
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PMID:Evaluation of uranyl photocleavage as a probe to monitor ion binding and flexibility in RNAs. 1087 69

We previously described autoantibodies against a UGA serine tRNA-protein complex (tRNP(Ser)Sec) in patients with type-1 autoimmune hepatitis [1] and now define the specificity and frequency of this autoantibody and the DNA sequence encoding the tRNA(Ser)Sec-associated antigenic protein. The presence of anti-tRNP(Ser)Sec antibodies was highly specific for type-1 autoimmune hepatitis, as 47.5% of patients were positive compared with none of the control subjects. To characterize the antigenic protein(s), we immunoscreened a human cDNA library with anti-tRNP(Ser)Sec-positive sera. Two clones (19 and 13) were isolated. Clone 19 encodes a protein with a predicted molecular mass of 48.8 kD. Clone 13 is a shorter cDNA, almost identical to clone 19, which encodes a 35.9-kD protein. Expression of both cDNAs was accomplished in Escherichia coli as His-tagged recombinant proteins. Antibodies eluted from both purified recombinant proteins were able to immunoprecipitate the tRNA(Ser)Sec from a HeLa S3 cell extract, demonstrating their cross-reactivity with the mammalian antigenic complex. Recent cloning data relating to the target antigen(s) of autoantibodies in autoimmune hepatitis patients that react with a soluble liver antigen (SLA) and a liver-pancreas antigen (LP) have revealed that these two autoantibodies are identical and that the cloned antigen shows 99% amino acid sequence homology with tRNP(Ser)Sec.
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PMID:Isolation and characterization of cDNA encoding the antigenic protein of the human tRNP(Ser)Sec complex recognized by autoantibodies from patients withtype-1 autoimmune hepatitis. 1093 Nov 55

Autoantibodies to soluble liver antigen (SLA) are considered a specific marker of autoimmune hepatitis. We have performed immunoscreening of a human liver gene expression library with an anti-SLA-positive serum. A reactive clone with a 35-kd open reading frame (ORF) and a 563 base pair (bp) 3' untranslated region (UTR) was isolated (soluble liver antigen [SLA]-p35), showing strong homology to an independently isolated putative SLA/liver-pancreas antigen (LP) sequence (Acc. No. AF146396), and a UGA serine tRNA-protein complex (tRNP)((Ser) Sec) related protein (AJ238617), as well as different expression sequence tag (EST)-clones from lymphatic and oncofetal tissues. Expressed in Escherichia coli, SLA-p35 showed dose-dependent and complete blocking of reactivity to native SLA antigen after preabsorption with the 35-kd recombinant protein. It recognized 67/85 (78.8%) precharacterized anti-SLA-positive sera in dilutions up to 1:40,000 in immunoblot, without detectable cross reactivity in the controls. The commercially available SLA/LP enzymelinked immunosorbent assay (ELISA), by comparison, recognized 63/85 samples (74.1%). Of the negative samples, 18% showed strong inhibition rates (80% and above) in the polyclonal inhibition ELISA. We conlude that the complementary DNA now isolated by 3 independent approaches encodes for the major but not sole antigenic component of soluble liver antigen. Although its truncated form presented here may serve to improve diagnostics based on the new recombinant polypeptide, it currently cannot fully replace the polyclonal inhibition ELISA.
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PMID:Soluble liver antigen: isolation of a 35-kd recombinant protein (SLA-p35) specifically recognizing sera from patients with autoimmune hepatitis. 1123 Jul 39

Nineteen different functional RNAs were synthesized for an investigation of the actions of ribozymes, in vitro and in vivo, under the control of two different promoters, tRNA or U6, which localize transcripts either in the cytoplasm or in the nucleus. No relationships were found between the activities of these RNAs in cultured cells and the kinetic parameters of their respective chemical cleavage reactions in vitro, indicating that in no case was chemical cleavage the rate-limiting step in vivo. For example, a hepatitis delta virus (HDV) ribozyme, whose activity in vitro was almost 3 orders of magnitude lower than that of a hammerhead ribozyme, still exhibited similar activity in cells when an appropriate expression system was used. As expected, external guide sequences, the actions of which depend on nuclear RNase P, were more active in the nucleus. Analysis of data obtained with cultured cells clearly demonstrated that the cytoplasmic ribozymes were significantly more active than the nuclear ribozymes, suggesting that mature mRNAs in the cytoplasm might be more accessible to antisense molecules than are pre-mRNAs in the nucleus. Our findings should be useful for the future design of intracellularly active functional molecules.
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PMID:Relationships between the activities in vitro and in vivo of various kinds of ribozyme and their intracellular localization in mammalian cells. 1127

The liver is continuously exposed to a large antigenic load that includes pathogens, toxins, tumor cells and dietary antigens. A loss of tolerance against its own antigens may result in autoimmune hepatitis (AIH). The current paradigm holds that the disease is the result of self-perpetuating autoimmune process triggered by yet unknown factors (infections, chemicals, drugs) in a genetically susceptible host. To date, several putative hepatocellular surface antigens have been identified: P450-IID6 (recognized by the anti-LKM-1 autoantibodies) a membrane bound asialoglycoprotein receptor (a liver-specific membrane protein), a cytosolic UGA-suppressor tRNA associated protein (recognized by anti-SMA and anti-LP antibodies) and argininosuccinate lysate and formiminotransferase cyclodeaminase (recognized by ant-LC1 antibodies). In contrast to other chronic hepatitides patients with AIH display significant T cell hypereactivity to autologous liver antigens. Tissue injury seems to be mediated by CD4+ or CD8+ T cells and/or by antibody-dependent cell mediated cytotoxicity.
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PMID:Autoimmune hepatitis: evolving concepts. 1511 Feb 33


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