Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A radioimmunoassay for the detection of antibodies in human serum to tritium-labeled HeLa cell cytoplasmic ribosomes was developed with the use of Macaloid for the inhibition of endogenous ribonuclease activity. Antibodies were observed in the serum of patients with systemic lupus erythematosus in high incidence and titer. Patients with rheumatoid arthritis and chronic active hepatitis manifested a lower incidence and titer of antibodies to ribosomes, whereas serums from normal individuals and from patients with sarcoidosis, chronic glomerulonephritis, and malignant tumors showed no significant reactivity with cytoplasmic ribosomes. Maximum inhibition of the reaction was achieved with unlabeled HeLa cell ribosomes or rat liver ribosomes and partial inhibition by purified ribosomal RNA.
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PMID:Radioimmunoassay for antibodies to cytoplasmic ribosomes in human serum. 91 Jan 57

Autoantibody reactive with tRNA was identified by immunoprecipitation of Hela cell extract. Four out of 56 sera from patients with autoimmune chronic active hepatitis (CAH), and four out of 35 sera from patients with primary biliary cirrhosis (PBC) contained antibody directed against gel-purified tRNA in Hela cell extract, but no sera obtained from CAH type B, CAH non-A, non-B, or healthy volunteers did. Further studies on these eight anti-tRNA sera disclosed that 6 of the 8 sera that immunoprecipitated tRNA from Hela cell extract, reacted with purified tRNA, but reacted with neither 5sRNA nor ribosomal RNA species. After proteinase and deoxyribonuclease digestion of Hela cell extract, the epitope for these 6 sera was conserved, and the antigen was sensitive to ribonuclease (anti-tRNA serum). Purified Hela cell DNA digested with Eco RI or Hind III (denatured or non-denatured) could not be immunoprecipitated by these sera. In a patient with autoimmune CAH, the anti-tRNA antibody was weakly positive at week 2 and disappeared 2 months after steroid therapy started, "in parallel" with disappearance of anti-nuclear antibody. In the other 2 sera, the antigen was sensitive to proteinase.
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PMID:Autoantibody specific for transfer ribonucleic acid (tRNA) in patients with autoimmune chronic active hepatitis and primary biliary cirrhosis. 177 87

Antinucleolar antibody (ANoAb) was tested for in sera from 25 patients with systemic lupus erythematosus (SLE), 61 with progressive systemic sclerosis (PSS), 22 with chronic active hepatitis (CAH) and 28 healthy persons, using immunofluorescence reactivity with acetone-fixed monolayers of cultured human fibroblasts, and a procedure to reveal ANoAb when other antinuclear antibodies were concurrently present. ANoAb was found on direct testing in sera from 6 patients with SLE, 15 with PSS and 7 with CAH, but not in any of 28 sera from healthy persons; homogeneously reactive antinuclear antibody was also present in the serum of these 6 cases of SLE, in 6 of the 15 with PSS and in 3 of the 7 with CAH and, in SLE specifically, pre-treatment of fibroblast monolayers with DNase "unmasked" the presence of ANoAb in a further 7 sera which had shown only homogeneous nuclear staining in fibroblasts. ANoAb belonged to the IgG, IgM and IgA class in sera from cases of SLE and PSS, and to only the IgG and IgM class in sera from cases of CAH. ANoAb titres were highest in patients with PSS. ANoAb were sensitive to RNase in 5 cases, to RNase and DNase in 6, and were sensitive to combinations of RNase, DNase, NaC1, and trypsin in the remaining cases. We conclude that (i) fibroblast monolayers are a suitable substrate for the demonstration of ANoAb, (ii) homogeneous staining of cell nuclei may mask ANoAb, so that the incidence of ANoAb becomes higher in SLE than in PSS, (iii) low-titre ANoAb in CAH not visualized in frozen tissue sections may be detected on fibroblast monolayers, and (iv) nucleolar antigens probably include RNA, RNA bound to DNA, and RNA bound to proteins.
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PMID:Antinucleolar autoantibodies demonstrated by monolayers of human fibroblasts in sera from patients with systemic lupus erythematosus, progressive systemic sclerosis and chronic active hepatitis. 674 43

1. Activated hepatic lipocytes are central to the pathogenesis of liver fibrosis as the principal source of both interstitial collagens and matrix-degrading metalloproteinases. In progressive fibrosis there is a failure to degrade interstitial collagens with a reported decrease in collagenase activity. In these studies we investigate expression of the potent collagenase inhibitor, tissue inhibitor of metalloproteinase-1, and interstitial collagenase in end-stage autoimmune chronic active hepatitis and activated human hepatic lipocytes in culture. 2. Messenger RNA transcripts for interstitial collagenase and tissue inhibitor of metalloproteinase-1 in explanted human liver were quantified by ribonuclease protection assay and densitometric analysis. This indicated that tissue inhibitor of metalloproteinase-1 and interstitial collagenase expression in autoimmune chronic active hepatitis were also coordinately up-regulated. 3. Using Northern analysis of RNA from human lipocytes in primary culture on plastic, mRNA for interstitial collagenase could not be detected in unstimulated cells but was present after stimulation with tumour necrosis factor alpha. Tissue inhibitor of metalloproteinase-1 mRNA was present in unstimulated lipocytes and up-regulated fivefold in response to tumour necrosis factor alpha. Using activity assay of serum-free conditioned media, interstitial collagenase could not be detected in unstimulated primary cultures, primary cultures stimulated with tumour necrosis factor alpha or transforming growth factor beta-1 (n = 3 and n = 4 respectively) or in passaged lipocytes (n = 6). In contrast, free tissue inhibitor of metalloproteinase-1 activity was present in unstimulated and passaged cultures and this was increased in response to tumour necrosis factor alpha and transforming growth factor beta-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue inhibitor of metalloproteinase-I and interstitial collagenase expression in autoimmune chronic active hepatitis and activated human hepatic lipocytes. 767 71

Congenial lipoid adrenal hyperplasia (lipoid CAH) is the most severe form of CAH. Affected individuals can make no adrenal or gonadal steroids. All affected individuals are phenotypic females irrespective of gonadal sex, and frequently die in infancy if mineralocorticoid and glucocorticoid replacements are not instituted. Recent data implicate the steroidogenic acute regulatory (StAR) protein in this disorder. We now describe a 46,XY patient of Vietnamese ancestry with lipoid CAH who had a somewhat milder form of the disease. Diagnosis was at 10 weeks of age, and low levels of plasma progesterone, corticosterone, 180H-corticosterone and androstenedione were detectable. Testicular RNA for StAR was reverse transcribed, amplified, cloned and sequenced, revealing a 185 bp deletion corresponding to all of exon 5. The corresponding mRNA did not encode active protein in transfected cells. Cloned genomic DNA from the patient revealed only a T-->A transversion in intron 4,11 bp from the splice acceptor site of exon 5. This transversion destroys an NcoI site; digestion of PCR-amplified genomic DNA from the patient and both parents confirmed that the patient was homozygous and the parents were heterozygous. Expression vectors for StAR minigenes were constructed containing all StAR exons plus introns 4, 5 and 6 either with or without the T-->A mutation in intron 4. RNase protection assays showed that expression of the vector with normal intron 4 yielded correctly spliced StAR mRNA in transfected COS-1 cells, while most, but not all StAR mRNA from the vector with the T-->A transversion in intron 4 was abnormally spliced. RNase protection of the patient's testicular RNA confirmed that most, but not all StAR mRNA was similarly spliced abnormally. Splicing errors appear to be a rare cause of genetic diseases, but subtle intronic mutations may be missed when genomic DNA is the only material available for study. The low level of normal StAR mRNA produced may account for the later clinical presentation and low levels of steroid hormones detected in this patient.
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PMID:T-->A transversion 11 bp from a splice acceptor site in the human gene for steroidogenic acute regulatory protein causes congenital lipoid adrenal hyperplasia. 863 2

Cultured hepatic stellate cells (HSCs), the cell type primarily involved in the progression of liver fibrosis, secrete insulin-like growth factor-I (IGF-I) and IGF binding protein (IGFBP) activity. IGF-I exerts a mitogenic effect on HSCs, thus potentially contributing to the fibrogenic process in an autocrine fashion. However, IGF-I action is modulated by the presence of specific IGFBPs that may inhibit and/or enhance its biologic effects. Therefore, we examined IGFBP-1 through IGFBP-6 mRNA and protein expression in HSCs isolated from human liver and activated in culture. Regulation of IGFBPs in response to IGF-I and other polypeptide growth factors involved in the hepatic fibrogenic process was also assessed. RNase protection assays and ligand blot analysis demonstrated that HSCs express IGFBP-2 through IGFBP-6 mRNAs and release detectable levels of IGFBP-2 through IGFBP-5. Because IGF-I, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-beta (TGF-beta) stimulate HSC proliferation and/or matrix production, we tested their effect on IGFBPs released by HSCs. IGF-I induced IGFBP-3 and IGFBP-5 proteins in a time-dependent manner without an increase in the corresponding mRNAs. IGFBP-4 protein levels decreased in response to IGF-I. TGF-beta stimulated IGFBP-3 mRNA and protein but decreased IGFBP-5 mRNA and protein. In contrast, PDGF-BB failed to regulate IGFBPs compared with controls. Recombinant human IGFBP-3 (rhIGFBP-3) was then tested for its effect on IGF-I-induced mitogenesis in HSCs. rhIGFBP-3 inhibited IGF-I-stimulated DNA synthesis in a dose-dependent manner, with a peak effect observed at 25 nM IGFBP-3. Because TGF-beta is highly expressed in cirrhotic liver tissue, we determined whether IGFBP-3 mRNA expression is increased in liver biopsies obtained from patients with an active fibroproliferative response due to viral-induced chronic active hepatitis. In the majority of these samples, IGFBP-3 mRNA was increased compared with normal controls. These findings indicate that human HSCs, in their activated phenotype, constitutively produce IGFBPs. IGF-I and TGF-beta differentially regulate IGFBP-3, IGFBP-4, and IGFBP-5 expression, which, in turn, may modulate the in vitro and in vivo action of IGF-I.
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PMID:Characterization and regulation of insulin-like growth factor binding proteins in human hepatic stellate cells. 942 10