Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary human amnion cell monolayers which had been treated with DEAE-dextran, washed, and then inoculated with sonicated cells of the EB3 line of Burkitt's lymphoma cells developed foci of transformed amnion cells 7 to 14 days later. When either the DEAE-dextran or the sonicate was omitted, no significant transformation was found. The foci consisted of enlarging mounds of rapidly dividing cells, which upon subculturing continued their high miotic activity; and strains or lines of the transformed amnion cells were thus readily established. The modal number of chromosomes in such lines was 65 instead of the normal 46. Not all human amnions yielded cells transformable by EB3 cell sonicate, as determined by direct comparisions using the same cultural conditions and testing with the same fresh sonicate preparation in the same experiment. Overall, it appeared that only about 40 to 50% of the amnions yielded transformable cell monolayers; the rest gave monolayers apprently completely refractory to the transformation. The transformed amnion cells contained nuclear and cytoplasmic Epstein-Barr virus (EBV) antigen(s), as revealed by indirect immunofluorescence tests. EB3 cell sonicate also caused the appearance of rapidly growing transformed cell foci on secondary rat embryo cell monolayers which had been sensitized with DEAE-dextran. Calcium in the cell maintenance medium decreased the number of transformed foci found, both on the human and on the rat cell monlayers. Sonicates of cultured normal human leucocytes had no such transforming activity for either the human or the rat cells. The transforming agent in EB3 cell sonicate was completely destructible by either deoxyribonuclease or trypsin, but not by ribonuclease, and was not neutralizable by anti-EBV serum. The simplest interpretation of these results is that the transforming agent is part of all of the EBV DNA plus some necessary protein, with both the DNA and the protein accessible to hydrolytic enzyme action.
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PMID:Use of a transfection method to demonstrate a monolayer cell transforming agent from the EB3 line of Burkitt's lymphoma cells. 18 Feb 48

Serine-threonine protein kinases in the ribosomal S6 kinase (rsk or p90rsk) family have been implicated as signaling intermediates in the cellular response to several growth factors. To investigate the molecular diversity of human p90rsk isoforms, mixed degenerate oligonucleotide polymerase chain reaction was used to isolate partial rsk cDNAs (1.1 kb). Three closely related human rsk cDNAs were obtained (HU-1, HU-2, HU-3). These cDNAs are encoded by separate genes based on DNA sequence diversity and distinct patterns seen with genomic Southern blots. Northern analysis revealed different sized mRNA transcripts for each isoform. A full-length HU-1 cDNA (3.1 kb) was subsequently isolated from a HeLa cell library. 5'-cDNA clones for HU-2 and HU-3 were isolated using the "rapid amplification of cDNA ends" strategy. Experiments using human x hamster somatic cell hybrids localized the HU-1 gene to human chromosome 3; HU-2 is on chromosome 6; and HU-3 is on the X chromosome. The tissue distribution of human rsk mRNAs was determined using ribonuclease protection assays. HU-3 mRNA was present in multiple RNA samples. HU-2 was expressed in fibroblast > muscle > lymphocyte = placenta > liver. HU-1 was expressed in Epstein-Barr virus lymphocyte > > muscle = liver > fat = placenta. These results indicate that the multiplicity of p90rsk isoforms is increased to at least three for humans and that marked tissue-/cell-specific differences in p90rsk isoform expression are present.
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PMID:Human rsk isoforms: cloning and characterization of tissue-specific expression. 814 Dec 49

The Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorders that arise in immunosuppressed individuals are considered to resemble EBV-transformed in vitro lymphoblastoid cell lines (LCLs) with a mature activated B-cell phenotype. In this study of human lymphoproliferative disorders in the severe combined immunodeficiency mouse model, however, we demonstrate that EBV-infected tumor cells are not LCL-like but are predominantly plasmacytoid and that this phenotype correlates with reduced expression of EBV latent genes. B-cell tumors developed within 3-6 weeks after injection of LCLs into severe combined immunodeficiency mice. The tumors and the injected LCLs were analyzed by flow cytofluorometry for B-cell differentiation and activation markers and by ribonuclease protection assay for cellular and viral gene expression. No differences in the expression of CD19 and CD21 were observed. However, a decrease in CD23, CD11a (lymphocyte function-associated antigen LFA-1), and CD58 (LFA-3) expression and an increase in CD38 (a plasma-cell-associated antigen), CD54 (intracellular adhesion molecule ICAM-1), and HLA class I in the tumor cells relative to the LCLs was observed. Two-color flow cytofluorometric analysis showed that the predominant population (> 80%) in LCLs was CD23hi/CD38lo and that the major population in LCL-derived tumors was CD23lo/CD38hi. Cell cycle analysis showed that, in contrast to actively cycling LCLs, the majority of tumor cells had exited the cell cycle and were restricted to G0/G1 phase. Finally, and most important, a reduction in mRNA for the EBV latent genes EBV nuclear antigen 2 (EBNA2) and latent membrane protein (LMP1) was observed in the tumors.
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PMID:Plasmacytoid differentiation of Epstein-Barr virus-transformed B cells in vivo is associated with reduced expression of viral latent genes. 838 Apr 97

Point mutations of the donor splice site of intron 3 of the human GH-1 gene cause autosomal dominant inherited isolated growth hormone deficiency (IGHD II). The mechanism by which a defect in one GH-1 allele results in GH deficiency is obscure. Previously reported reverse transcription-nested PCR data suggested an overexpression of the mutant GH-1 allele. We employed alternative methods to determine the relative expression of mutant (C for G at +1 of intron 3) and normal GH-1 allele. The use of a second round PCR primer bridging exons 2 and 3 and specific for normal GH-1 messenger ribonucleic acid (mRNA) indicated equal quantities in mutant and control cells. Large scale messenger RNA extraction from Epstein-Barr virus-transformed lymphoblasts permitted assay by ribonuclease protection. In normal pituitary, there were three GH-1 mRNA species. The variant lacking exon 3 comprised 5% of the total GH-1 mRNA. The proband's lymphoblasts contained equal amounts of mRNA with and without exon 3. Only normal GH-1 mRNA was detected in controls. Secreted GH, measured by enzyme-linked immunosorbent assay was present in equal concentrations in media from normal and mutant cells. Thus, GH-1 mRNA lacking exon 3 was expressed in proportion to the dosage of the mutant gene, and dominant effects on GH secretion were not observed in lymphoblasts. These findings are compatible with a dominant negative mechanism involving interaction between normal and mutant proteins in secretory vesicles of somatotropes.
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PMID:Mechanisms responsible for dominant expression of human growth hormone gene mutations. 892 59

Increased extraglandular aromatization has been reported as the cause of familial gynecomastia. We studied a kindred with aromatase excess inherited in an autosomal dominant manner, in which affected males had heterosexual precocity and/or gynecomastia, and affected females had isosexual precocity and/or macromastia. The propositus was a 9-yr-old boy with gynecomastia. His 7.5-yr-old sister had precocious puberty, and their father and paternal grandmother had peripubertal gynecomastia and macromastia, respectively. Serum concentrations of gonadal and adrenal steroid hormones were determined before and after the administration of corticotropin and/or hCG. Aromatase activity was determined by [3H]delta4-androstenedione to [3H]estrone conversion by cultured skin fibroblasts and/or Epstein-Barr virus-transformed lymphocytes and was detected by immunohistochemistry and/or Western analysis. Linkage was examined with a polymorphism of the aromatase (P450arom) gene. The P450arom messenger ribonucleic acid was analyzed by rapid amplification of complementary DNA (cDNA) ends, ribonuclease protection assay, and RT-PCR. hCG testing demonstrated a high rate of conversion of delta4-androstenedione to estrone and of testosterone to estradiol in the propositus and his father. Treatment of the propositus and his sister was initiated with an aromatase inhibitor (testolactone) and a GnRH analog, which successfully delayed skeletal and pubertal development in both children. Markedly increased aromatase activity was found in the patients' fibroblasts and Epstein-Barr virus-transformed lymphocytes. The P450arom polymorphism segregated with the disease in the family. A new 5'-splice variant was present in the patients' P450arom messenger ribonucleic acid, thus identifying yet another first exon of this gene, which appears to be aberrantly expressed in this family. In conclusion, a family with the aromatase excess syndrome is described, in which the condition was inherited in an autosomal dominant manner, led to feminizing manifestations in both sexes, and was associated with the aberrant utilization of a novel transcript of the P450arom gene.
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PMID:The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant P450 aromatase gene transcription. 954 66

Hepatitis C virus (HCV) infection is usually treated with the combination of interferon and ribavirin, but only a small fraction of patients develop a sustained remission. There is need for the development of specific molecular approaches for the treatment of chronic HCV infection. We propose that RNA interference is highly effective antiviral strategy that offers great potential for the treatment of HCV infection. Three plasmid constructs expressing small interfering RNAs (siRNAs) targeted to sequences encoding the structural gene (E2) and non-structural genes (NS3, NS5B) of HCV1a genome were prepared. Antiviral properties of siRNAs against the HCV1a strain were studied in a transient replication model that involved the use of a transcription plasmid containing the full-length HCV genome and an adenovirus expressing T7 RNA polymerase. We found that siRNAs targeted to the E2, NS3 and NS5B regions of the HCV genome efficiently inhibited expression of the HCV core and NS5A protein measured by Western blot analysis and immunocytochemical staining. Intracytoplasmic immunization of siRNAs in HCV-transfected cells efficiently degraded genomic positive strand HCV RNA, as shown by ribonuclease protection assay (RPA). All three siRNAs efficiently inhibited synthesis of replicative negative strand HCV RNA in the transfected cells. A control siRNA plasmid against a Epstein--Barr virus latency gene did not inhibit protein expression and negative strand HCV RNA. These results suggest that RNAi is an effective and alternative approach that can be used to inhibit HCV expression and replication.
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PMID:Small interfering RNA effectively inhibits protein expression and negative strand RNA synthesis from a full-length hepatitis C virus clone. 1597 38