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)

To reveal the dependence of the efficacy of the treatment of tick-borne encephalitis (TBE) on the patient's HLA phenotype and to elaborate recommendations for individual treatment, 98 subjects who suffered TBE and who received different types of therapy in the acute period (isolated or combined use of specific homologous immunoglobulin and RNase) were subjected to immunogenetic examinations. The clinical follow-up and immunological examination of the subjects indicated made it possible to distinguish groups with a favorable and unfavourable outcome due to the treatment carried out in the acute period. Computer processing of the immunogenetic data on the patients with TBE allowed the deriving of individual predictors of the efficacy of the symptomatic and etiotropic therapy of TBE. The final effect due to the application of agents possessing an immunomodulating effect on specific humoral immune response is determined not only by the gravity of viral infection but is also associated with a number of allele variants of HLA complex genes which the patient has.
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PMID:[Evaluation of the effectiveness of various methods of the treatment of tick-borne encephalitis in the acute period]. 132 75

Enhancer-like sequences have previously been identified in the promoter region of the mouse major histocompatibility complex (MHC) class I genes. We have screened for such sequences in and around a human MHC class I gene, HLA-B7. Various restriction fragments of the B7 gene were assayed for their ability to enhance transcription of a bacterial chloramphenicol acetyltransferase gene from a simian virus 40 promoter in transiently transfected mouse LTA cells. Our results demonstrate that enhancer activity is located in introns 3 and 5 as well as 5' to the transcription initiation site. RNase protection experiments corroborate the results. Preliminary experiments indicate that B7 enhancers are active in various cell types. The role of these enhancers in B7 gene expression is not known at present. We speculate that the position of the enhancer elements may be related to the occurrence of Hpa II tiny fragment islands.
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PMID:Multiple enhancer-like sequences in the HLA-B7 gene. 250 82

The major histocompatibility complex of the rat (RT1 complex) encodes two sets of class II molecules referred to as RT1.B and RT1.D. The complete structure of the RT1.D alpha u chain of the diabetes prone BB rat was determined by the isolation and characterization of a full size cDNA. Comparisons of the nucleotide and protein sequences of RT1.D alpha with the analogous molecules, H-2 I-E alpha and HLA DR alpha, revealed that these alpha chains have been highly conserved during evolution. Southern blot analysis indicated an association of the RT1 haplotypes, 'u' and 'l', with Bam H1 DNA bands of 9.8 kb and 11.7 kb, respectively. The BB rat develops insulin dependent diabetes as an autoimmune abnormality. Accumulating evidence suggests a cellular mediated etiology and the involvement of class II molecules. The steady state levels of RT1.D alpha mRNA were measured in splenic lymphocytes of diabetes prone BB rats and age matched histocompatible normal nondiabetic WF rats by a RNase protection assay. Compared to WF rats, elevated transcripts of RT1.D alpha were found in lymphocytes of young BB rats (approximately 4x and approximately 2.5x greater at 20-40 and 40-75 d, respectively). In lymphocytes of older diabetic and nondiabetic BB rats (greater than 75 d) the levels of RT1.D alpha mRNA were lower than in the young BB rats and were found at the WF control levels. The increased steady state RT1.D alpha mRNA levels in the young BB rats may reflect differences in the proportion of splenic lymphocytes expressing this gene (activated lymphocytes), and thus differences in splenic lymphocyte populations. The steady state RT1.D alpha mRNA levels in lymphocytes of the normal rats were found to be relatively similar at all ages examined. The increased class II gene transcripts found in lymphocytes of young BB rats indicates that they possess a highly activated immune system.
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PMID:The complete sequence of the MHC class II chain RT.1D alpha u of the diabetic BB rat: mRNA levels of RT1.D alpha in lymphocytes. 312 83

We undertook a large sample census of the TCR-beta repertoire from a single human thymus (300 clones from an unamplified cDNA library), to establish the statistics of the rearranged V, D, J, and C gene segments. The assortments of all germ-line segments are subject to significant biases and thus critically reduce the effective germ-line contribution to beta-chain diversity. Thirty-two V genes characterize the whole sample, but surprisingly as few as seven genes from different families encompass half of the beta-chain repertoire. Furthermore, a Spearman rank order correlation test of the thymic V beta frequencies with those inferred in other studies using RNase protection assays shows a statistically significant similarity. Thus, in the establishment of thymic V beta frequencies in man, rearrangement preferences intrinsic to the progenitors of TCR-beta expressing cells override HLA- and Ag-dependent biasing factors. By implication, a large enough pool of direct progenitor cells (maybe as high as thousands) must exist to secure V beta frequencies against large random fluctuations. Uncorrelated with the V gene bias, the representation of D beta and J beta segments is also far from even. Notably, D beta 1 and J beta 2.1 and 1.2 predominate. Using the above mentioned rank order statistic, we also find that unlike V genes, the bias in the J segment usage carries over into the frequencies of peripheral T lymphocyte populations.
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PMID:Few V gene segments dominate the T cell receptor beta-chain repertoire of the human thymus. 824 54

Cells expressing HLA DR7 contain two functional DR beta genes, DRB1 and DRB4, whose mRNA is present at different levels. We examined whether the mRNA levels are due to differential transcriptional regulation or post-transcriptional regulation. As part of this analysis, a novel series of upstream elements was identified. Analysis of the proximal promoter activity, using a transient expression system, showed that the isomorphic promoter activities of B1 and B4 are about equal. RNase protection analysis of steady-state pre-mRNA and mRNA levels shows that the DR7 B1 pre-mRNA levels are 3 to 4 fold higher than B4 pre-mRNA levels. However, the B1 mRNA levels are increased seven fold relative to the B4 mRNA levels. The disproportionate increase of the mRNA levels relative to the corresponding pre-mRNA levels indicates that regulation also occurs at the post-transcriptional level.
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PMID:Differential expression of isomorphic HLA-DR beta genes is not a sole function of transcription. 889 34

Tenascin-X (TN-X) is an extracellular matrix protein encoded by a large gene that overlaps the steroid 21-hydroxylase (P450c21) gene in the HLA locus on chromosome 6p21.3. This may be the most complex locus in the human genome identified to date, containing 13 overlapping transcription units in 160 kb of DNA. Previous studies determined the sequence of 39 TN-X exons, encoding a 12 kb open reading frame, but the promoter(s) of the gene had not been located. We identify the principal TN-X promoter and a previously unknown 5' untranslated exon that lies more than 10 kb upstream from the previously known exons. This promoter, which is substantially different from the promoter for TN-C, initiates transcription in human fetal adrenal and muscle, but expression in human NCI-H295 adrenocortical carcinoma cells is initiated by two other promoters lying further upstream. One of these is the same as the promoter for a recently identified Creb-related protein (Creb-rp), but transcripts initiated form this promoter in human adrenal NCI-H295 tumor cells are spliced differently from Creb-rp, and are largely retained in the nuclei of these cells. By analogy with the other two members of the tenascin family, TN-C and TN-R, it has been predicted that TN-X should undergo alternate splicing in its fibronectin-like domains. RACE cloning and RNase protection experiments reveal no such alternate splicing. The TN-X gene appears to be unique in having both its 5' and 3' ends buried in other genes.
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PMID:Alternate promoters and alternate splicing of human tenascin-X, a gene with 5' and 3' ends buried in other genes. 892 3

The ability of intact protein antigens to bind to purified class II histocompatibility molecules was investigated. Intact bovine ribonuclease (RNase) inhibited peptide binding to DR1 with a potency similar to that of a high affinity peptide or irreversibly denatured RNase. Similarly, horse myoglobin (Mb) was a potent inhibitor of peptide binding to I-E(k). I-E(k)-Mb complexes were directly visualized as a distinct band with reduced mobility on SDS PAGE. Direct binding experiments with biotin-labeled proteins demonstrated that Mb and RNase bind to class II molecules through the peptide-binding groove with high affinity, and that binding occurs in the absence of detergent. The possibility that HLA-DM can catalyse the binding of intact protein antigens was supported by the observation that DM enhances the binding of biotin-RNase to DR1. Our results provide further support for the hypothesis that intact, partially unfolded protein antigens can act as ligands for initial interaction with class II molecules.
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PMID:Intact proteins can bind to class II histocompatibility molecules with high affinity. 930 63

Zinc-alpha 2-glycoprotein (Zn alpha 2gp) is widely distributed in body fluids and in various epithelia; its gene has been completely sequenced, but its function has long remained elusive. We have found that Zn alpha 2gp has RNase activity, comparable to onconase but two orders of magnitude less than RNase A. The RNase activity of Zn alpha 2gp is characterized by maxima in pH at 7.5, in ionic strength at 50 mM NaCl, and in temperature at 60 degreesC. It is strongly inhibited by ZnCl2, but unaffected by MgCl2. It is partially inactivated (down to 20%) by the placental RNase inhibitor. On synthetic polyribonucleotide substrates, the RNase activity of Zn alpha 2gp is specific for pyrimidine residues [poly(C) and poly(U) equally] and cleaves only single-stranded RNA. For onconase, it has been demonstrated that the RNase activity depends on pyroglutamic acid (pyr 1) as the N-terminus; Zn alpha 2gp also has pyr 1, while RNase A does not. Alignment of the amino acid sequences of Zn alpha 2gp and onconase or RNase A reveals only modest matches. Despite the more substantial overall structural homology of Zn alpha 2gp to class I major histocompatibility complex proteins, Zn alpha 2gp has not been proven to be associated with the immune response and, conversely, we could not detect RNase activity in six class I HLA heavy chains.
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PMID:Zinc-alpha 2-glycoprotein has ribonuclease activity. 967 22

The mechanism of resistance of malignant melanoma to treatment with interferon-alpha is unknown, and currently there is no reliable method of predicting response. Signalling via the JAK/STAT pathway is known to mediate many interferon-regulated events and has been implicated in mediating the antiproliferative response. The objective of this study was to determine whether defects in JAK/STAT signalling may be responsible for interferon resistance. The in vitro response to interferon was determined in a panel of established melanoma cell lines, and the components and functioning of the JAK/STAT pathway were examined in sensitive and resistant cell lines. Two melanoma cell lines, characterized as sensitive (MM418) and resistant (MeWo) to the antiproliferative effect of interferon, were both shown by Western blotting to possess all the protein components of the JAK/STAT pathway, and were shown to be capable of producing functional transcription factors using an electrophoretic mobility shift assay and a ribonuclease protection assay of known interferon-induced genes. In addition, both cell lines had intact antiviral and HLA upregulation responses. These data suggest that there is no defect in the JAK/STAT pathway per se in the MeWo cell line, and that the substantial resistance to interferon must be mediated through components either downstream or additional to this signalling pathway. Others have shown JAK/STAT defects to be responsible for interferon resistance in some melanoma cell lines. However, our results highlight the likely heterogeneity in the mechanisms leading to interferon resistance both in cell lines and tumours, and suggest that a clinical assay based on analysis of components of the JAK/STAT pathway may have only limited use as a predictor of interferon response.
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PMID:The JAK/STAT pathway is not sufficient to sustain the antiproliferative response in an interferon-resistant human melanoma cell line. 1277 75

We report a child with short stature since birth who was otherwise well, presenting at 2.8 years with progressive granulomatous skin lesions when diagnosed with severe T cell immunodeficiency. When previously investigated for short stature, and at the time of current investigations, she had no radiological skeletal features characteristics for cartilage hair hypoplasia, but we found a disease causing RMRP (RNase mitochondrial RNA processing endoribonuclease) gene mutation. Whilst search for HLA matched unrelated donor for haematopoietic stem cell transplantation (HSCT) was underway, she developed rapidly progressive EBV-related lymphoproliferative disorder requiring laparotomy and small bowel resection, and was treated with anti-B cell monoclonal antibody and eventually curative allogeneic HSCT. Screening for RMRP gene mutations should be part of immunological evaluation of patients with 'severe and/or combined' T cell immunodeficiency of unknown origin, especially when associated with short stature and regardless of presence or absence of radiological skeletal features.
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PMID:Phenotypic variations of cartilage hair hypoplasia: granulomatous skin inflammation and severe T cell immunodeficiency as initial clinical presentation in otherwise well child with short stature. 2421 15


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