Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum levels of IgM, IgG and IgG-antibody subclasses directed against cell envelopes, lipopolysaccharides and cytoplasmic fractions from Capnocytophaga sputigena, C. gingivalis and C. ochracea were examined in age-, race- and sex-matched periodontally healthy (n = 25) subjects and subjects with adult periodontitis (n = 25). The envelopes and cytoplasmic fractions were obtained by ballistic disintegration of the cells and ultracentrifugation. Cell envelopes were treated with DNase, RNase and lysozyme. Lipopolysaccharides were obtained by hot phenol-water extraction and treated with DNase and RNase. The relative levels of the antibodies in response to the cell fractions were measured by the streptavidinbiotin micro enzyme-linked immunosorbent assay. Both groups showed IgM and IgG antibodies to each fraction of the three Capnocytophaga species, but the frequency of positive IgG subclass responses varied. The IgG4 responses were lower than the other subclasses. There were no significant differences between the IgM antibody levels of the two groups. However, the adult periodontitis group had significantly lower IgG antibody titres to the cell envelopes and cytoplasmic fractions of C. gingivalis and C. ochracea, and lipopolysaccharide of C. gingivalis. These results were reflected in the depressed levels of IgG1 and/or IgG2 to these cellular fractions from the same bacterial species. The adult periodontitis group also showed a lower level of IgG1 to the cytoplasmic fractions of C. sputigena without any depression in the total IgG antibody level. There were no significant differences between the groups in IgG3 and IgG4 antibody levels to any of the cellular fractions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum antibody responses in human periodontitis to cellular components of Capnocytophaga. 141 21

The myelin deficient shimld mouse is an autosomal recessive mutant, characterized by hypomyelination in the central nervous system. The expression of the myelin basic protein (MBP) gene is inhibited transcriptionally. The MBP gene is duplicated tandemly in mld, and exons 3 to 7 of the upstream copy is inverted. In the present studies, we determined the approximate position of the 5' boundary and the nucleotide sequence surrounding the 3' boundary of the inversion and found a number of sequences homologous to the switching regions of mouse immunoglobulin heavy chain gene and J regions of human T cell receptor genes. Antisense RNA complementary to exons 3 and 7, which correspond to the inverted segment, was detected by RNase protection studies. This abnormal transcript was also shown to elongate through the inverted segment to reach the transcription initiation site of the downstream gene.
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PMID:Recombination within the upstream gene of duplicated myelin basic protein genes of myelin deficient shimld mouse results in the production of antisense RNA. 246 59

We report a simple type of reciprocal chromosomal translocation in the LOU rat IgE-secreting immunocytoma cell line, IR162, involving the c-myc protooncogene and the switch region of the epsilon immunoglobulin heavy chain, c-myc/S epsilon. By cloning and sequencing the translocation-associated and the homologous normal c-myc and S epsilon DNAs, we have identified the position of the translocational junction in both the c-myc 5'-flanking region and the repetitive elements of the S epsilon region. The translocational recombination was precise, and no insertion or N-addition was found in the junctional region, leaving all the c-myc exons, together with two promoter sites, intact. RNase mapping confirmed that the same promoters were utilized in IR162 and normal LOU spleen cells. No point mutation was found in the 5'-flanking region and the 3'-portion of exon 1 of the translocated c-myc gene. However, the putative silencer region was lost with the translocation. It was also noticed that a strikingly AT-rich sequence associated with S epsilon region had translocated to the 5'-flanking region of c-myc gene. We discuss the possibility that a change of DNA topology, perhaps either due to the juxtaposition of an AT-rich sequence of the S epsilon region, or to the loss of the putative silencer element, may contribute to c-myc gene deregulation in IR162.
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PMID:A simple and precise aberrant translocation of the rat c-myc gene into the epsilon-heavy chain switch region of the IgE-producing immunocytoma, IR162. 249 84

The heterogeneity of the PC-specific IgG response of Proteus morganii (Potter) was systematically analyzed. Serum samples from individual mice were focused in paired adjacent tracks, PC-specific antibodies were detected with 125I-PC-RNase, and the resulting autoradiographs were examined for co-focusing bands. Both the number of different antibody band groups and their frequency of expression were determined. Varying qualitatively from simple to complex, the spectrotypes of 38 BALB/c and 19 A/HeJ each appeared unique. However, after thorough analysis for co-focusing bands. It was evident that each spectrotype reflected a unique combination of shared band groups rather than numerous uniquely focusing band groups. The responses of A/HeJ and BALB/c showed striking similarities qualitatively in the appearance of individual spectrotypes. The heterogeneity of the two strains was also similar quantitatively. The basis for this finite though complex heterogeneity was examined by in situ subclass analysis after IEF and idiotype analysis of IEF bands by using antibodies purified from individual BALB/c and A/HeJ. Each mouse primarily expressed IgG3, and antibody bands of this subclass ranged from pI of 6.75 to 8.2. IgG1-positive bands ranged from pI of 6 to 7. Minimal amounts of IgG2 and IgM were detected. In comparisons of individual mice, there was more heterogeneity apparent in the IgG3 subclass than in the IgG1. The idiotype, IdX-M603, was found in both subclasses and also in multiple band groups focusing at different positions within each subgroup. Possible explanations for this heterogeneity among these idiotypically related antibodies are discussed.
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PMID:Clonotypes of anti-phosphocholine antibodies induced with Proteus morganii (Potter). II. Heterogeneity, class, and idiotypic analyses of the repertoires in BALB/c and A/HeJ mice. 705 90

Three major components of the plasminogen activators (PA)/plasmin system are synthesized physiologically in glomeruli, and can be involved in glomerular proteolysis and extracellular matrix metabolism: tissue-type PA (tPA), urokinase (uPA) and PA inhibitor type 1 (PAI-1). To explore the possible role of a dysregulation of the plasmin protease system in the development and progression of lupus-like glomerulonephritis, we studied the expression of the renal plasmin protease components during the course of the disease, either acute, induced by IgG3 monoclonal cryoglobulins, or chronic, occurring spontaneously in three different lupus-prone mice: (NZBxNZW)F1, BXSB and MRL-lpr/lpr. RNase protection assays and in situ hybridizations revealed a marked glomerular induction of PAI-1 mRNA abundance without any significant changes in renal tPA and uPA mRNA levels in the two different types of lupus-like glomerulonephritis. The overexpression of PAI-1 mRNA occurred in parallel with a significant decrease in glomerular tPA-catalyzed enzymatic activity as determined by zymographic analysis. In addition, a concomitant increase in glomerular expression of transforming growth factor beta 1 (TGF-beta 1) mRNA was observed. The demonstration of a close correlation between the PAI-1 and TGF-beta 1 mRNA levels and the severity of lupus-like glomerular lesions suggests that a pertubation of the glomerular PA/PAI balance, resulting from a marked TGF-beta 1-mediated induction of PAI-1 gene expression, plays an important role in the progression of lupus-like glomerular lesions, leading to glomerulosclerosis.
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PMID:Induction of plasminogen activator inhibitor type 1 in murine lupus-like glomerulonephritis. 854 2

Protease nexin 1 (PN-1), a potent serpin-class antiprotease, is thought to be synthesized in the murine kidney. However, neither the cellular localization of PN-1 synthesis nor its role has yet been defined. To address these questions, we determined by in situ hybridizations RNase protection assay and immunoblotting, the sites of PN-1 mRNA accumulation in normal mouse kidneys and the modulation of PN-1 expression in several pathological conditions. In normal kidneys, PN-1 mRNA was detected primarily in glomeruli, most likely in mesangial cells. The glomerular expression of PN-1 was substantially enhanced not only in lupus-like glomerulonephritis (induced by IgG3 monoclonal rheumatoid factors or occurring spontaneously in lupus-prone mice), but also in mild glomerular lesions associated with intracapillary thrombi induced by IgG3 anti-trinitrophenyl monoclonal antibodies. In contrast, no modulation of PN-1 mRNA levels was observed during the course of lipopolysaccharide-induced acute tubular necrosis. A constitutive PN-1 gene expression and its up-regulation during glomerular injury suggest a possible role for PN-1 in glomerular biology. In view of its high inhibitory activity towards thrombin, mesangial PN-1 may be involved in the control of glomerular coagulation following initial glomerular injuries.
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PMID:Protease nexin 1 in the murine kidney: glomerular localization and up-regulation in glomerulopathies. 894 77

The human immunodeficiency virus type-1 (HIV-1) long terminal repeat (LTR) initiates transcription efficiently but produces only short transcripts in the absence of the trans-activator protein, Tat. To determine whether a cellular enhancer could provide the signals required to recruit an elongation-competent polymerase to the HIV-1 LTR, the B cell-specific immunoglobulin heavy chain gene enhancer (IgHE) was inserted upstream of the LTR. The enhancer increased transcription in the absence of Tat between 6- and 7-fold in transfected B cells, but the full-length transcripts remained at basal levels in HeLa cells, where the enhancer is inactive. RNase-protection studies showed that initiation levels in the presence and absence of the enhancer were constant, but the enhancer significantly increased the elongation capacity of the polymerases. Tat-stimulated elongation is strongly inhibited by the nucleoside analogue 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), which inhibits the Tat-associated kinase, TAK (CDK9). However, polymerases initiating transcription from LTRs carrying the enhancer were able to efficiently elongate in the presence of DRB. Specific repression of TAK by expression in trans of the CDK9 kinase also inhibited Tat-stimulated elongation but did not inhibit enhancer-dependent transcription significantly. Thus, the activation of polymerase processivity by the IgHE involves a unique mechanism which is independent of TAK.
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PMID:Stimulation of Tat-associated kinase-independent transcriptional elongation from the human immunodeficiency virus type-1 long terminal repeat by a cellular enhancer. 1006 3

Borrelia burgdorferi, the spirochetal bacterium that causes human Lyme disease, encodes numerous lipoproteins which have the capacity to trigger the release of proinflammatory cytokines from a variety of host cell types, and it is generally believed that these cytokines contribute to the disease process in vivo. We previously reported that low-passage-number infectious B. burgdorferi spirochetes express a novel lipidation-independent activity which induces secretion of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) by the mouse MC/9 mast cell line. Using RNase protection assays, we determined that mast cells exposed in vitro to low-passage-number, but not high-passage-number, B. burgdorferi spirochetes show increased expression of additional mRNAs representing several chemokines, including macrophage-inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and TCA3, as well as the proinflammatory cytokine interleukin-6. Furthermore, mast cell TNF-alpha secretion can be inhibited by the phosphatidylinositol 3-kinase inhibitor wortmannin and also by preincubation with purified mouse immunoglobulin G1 (IgG1) and IgG2a, but not mouse IgG3, and by a mouse Fc gamma receptor II and III (FcgammaRII/III)-specific rat monoclonal antibody, suggesting the likely involvement of host FcgammaRIII in B. burgdorferi-mediated signaling. A role for passively adsorbed rabbit or bovine IgG or serum components in B. burgdorferi-mediated FcgammaR signaling was excluded in control experiments. These studies confirm that low-passage-number B. burgdorferi spirochetes express a novel activity which upregulates the expression of a variety of host cell chemokine and cytokine genes, and they also establish a novel antibody-independent role for FcgammaRs in transduction of activation signals by bacterial products.
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PMID:Role of Fc gamma receptors in triggering host cell activation and cytokine release by Borrelia burgdorferi. 1111 32

We have previously demonstrated that an antibody-avidin fusion protein could be used to deliver biotinylated enzymes to tumor cells for antibody-directed enzyme prodrug therapy. However, the presence of the chicken protein avidin suggests that immunogenicity may be a problem. To address this concern, we developed a new delivery system consisting of human proteins. The amino-terminal 15-amino-acid peptide derived from human ribonuclease 1 (human S*tag) can bind with high affinity to human S*protein (residues 21-124 of the same ribonuclease). We constructed an antibody-S*protein fusion protein in which S*protein was genetically linked to an anti-rat transferrin receptor IgG3 at the carboxyl terminus of the heavy chain. We also constructed an enzyme-S*tag fusion protein in which S*tag was genetically linked to the carboxyl terminus of Escherichia coli purine nucleoside phosphorylase (PNP). When these two fusion proteins were mixed, S*tag and S*protein interacted specifically and produced homogeneous antibody/PNP complexes that retained the ability to bind antigen. Furthermore, in the presence of the prodrug 2-fluoro-2'-deoxyadenosine in vitro, the complex efficiently killed rat myeloma cells overexpressing the transferrin receptor. These results suggest that human ribonuclease-based site-specific conjugation can be used in vivo for targeted chemotherapy of cancer.
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PMID:An interaction between S*tag and S*protein derived from human ribonuclease 1 allows site-specific conjugation of an enzyme to an antibody for targeted drug delivery. 1591 91