Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RNA polymerase of E. coli (EC 2.7.7.6) is able to bind certain oligoribonucleotides with the length greater than or equal to 5 from the corresponding isoplith mixtures (Knorre V.L., Vasilenko S.V., Salganik R.I., FEBS Letters 30, 229, 1973). It has been shown in this study that all pentaribonucleotides able to be bound by RNA polymerase can be extracted from the random mixture by the enzyme saturation procedure. Loosely and tightly bound pentaribonucleotides subfractions were isolated and each was separated by chromatography into 3-4 isopliths. Blocking of the enzyme SH groups by p-chloromercurium benzoate (10(-3) M) and denaturation by urea (6.3 M) prevent formation of the enzyme-pentaribonucleotides complexes. Complexes are destroyed by heat denaturation. Removal of sigma-subunit does not influence the enzyme capacity for pentaribonucleotides binding.
Mol Biol (Mosk)
PMID:[Conditions for specific oligoribonucleotide binding with E. coli RNA-polymerase]. 78 22

Inflammation of the human airways in diseases such as chronic bronchitis, cystic fibrosis with Pseudomonas endobronchial infection, and possibly asthma during late-phase reactions involves a local influx of neutrophils (PMN) that may participate in airway epithelial injury. PMN-mediated cellular injury is most efficient under conditions of PMN-target cell adhesion. PMN express adhesive glycoproteins of the CD11/CD18 family that are counter-receptors for intercellular adhesion molecule-1 (ICAM-1), found on various cell types. We proposed that adherence by PMN to human airway epithelial cells via ICAM-1 might be an important mechanism in inflammatory airway diseases. We found that although PMN adhere poorly (less than 5%) to monolayers of human tracheal epithelial cells (TEC) in primary culture, they adhere readily (45 to 50%) to an SV40-immortalized line of human TEC, designated 9HTEo-. We also found 6-fold greater surface expression of ICAM-1 on 9HTEo- compared with primary TEC. Blocking surface ICAM-1 on 9HTEo- cells with specific monoclonal antibody inhibited PMN adherence by about 50%. Thus, ICAM-1 plays a major role in this adherence, although it is possible that other epithelial ligands contribute also. Antibodies to CD11a, CD11b, and CD18 on PMN also inhibited PMN-epithelial adherence. Treatment of primary TEC monolayers with the proinflammatory cytokines interleukin-1 (IL-1) or tumor necrosis factor-alpha (TNF-alpha) caused a 3- to 4-fold increase in both cell surface ICAM-1 expression and support of PMN adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Aug
PMID:Induction of ICAM-1 expression on human airway epithelial cells by inflammatory cytokines: effects on neutrophil-epithelial cell adhesion. 135 76

Only recently has the mechanism for lipopolysaccharide (LPS) recognition by macrophages been elucidated. In contrast to many ligand receptor interactions, the interaction of LPS with its receptor, CD14, on myeloid cells is greatly enhanced by prior complexation of LPS with LPS-binding protein (LBP), a recently discovered plasma glycoprotein. LBP is found in normal serum or plasma in the 5 to 10 micrograms/ml range. In plasma, it reacts rapidly but transiently with LPS. LPS-LBP complexes then react with CD14 bearing cells. Blocking CD14 with monoclonal antibodies or removal of LBP from plasma blocks the ability of the cells to react with LPS-LBP complexes and also blocks release of cytokines and other mediators from the cells. In the normal lung, bronchoalveolar lavage fluid contains low levels of LBP. However, during acute lung injury, LBP levels may rise by transudation and enhance activation of alveolar macrophages to release injurious mediators. Description of this pathway for LPS recognition by macrophages and other leukocytes offers the possibility of developing new reagents to block LPS recognition and prevent the development of endotoxemia.
Am J Respir Cell Mol Biol 1992 Sep
PMID:Participation of lipopolysaccharide-binding protein in lipopolysaccharide-dependent macrophage activation. 138 94

The murine myeloid precursor cell line FDC-P1/MAC simultaneously expresses receptors for multi-colony-stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, and macrophage (M)-CSF. Growth of FDC-P1/MAC cells in either multi-CSF or GM-CSF results in the posttranscriptional suppression of M-CSF receptor (c-fms proto-oncogene) expression. We use the term transregulation to describe this control of receptor expression and have further characterized this regulatory process. The removal of FDC-P1/MAC cells from GM-CSF stimulation resulted in the re-expression of c-fms mRNA independent of M-CSF stimulation and new protein synthesis. Switching FDC-P1/MAC cells from growth in M-CSF to GM-CSF caused the selective degradation of c-fms mRNA within 6 h after factor switching. Blocking protein synthesis or gene transcription with metabolic inhibitors effectively prevented GM-CSF stimulated degradation of c-fms mRNA. These results suggest that the transregulation of c-fms transcripts by GM-CSF requires the transcriptional activation of a selective mRNA degradation factor. In vitro analysis, the use of cytoplasmic cell extracts, provided evidence that a ribonuclease is preferentially active in GM-CSF stimulated cells, although the specificity for mRNA degradation in vitro is broader than seen in vivo. Together, these data suggest that GM-CSF can dominantly transregulate the level of c-fms transcript through the transcriptional activation of a ribonuclease degradation system.
Mol Biol Cell 1992 May
PMID:A GM-colony-stimulating factor (CSF) activated ribonuclease system transregulates M-CSF receptor expression in the murine FDC-P1/MAC myeloid cell line. 153 42

Construction of the shuttle cloning vectors for Escherichia coli-Brevibacterium flavum system is described. Expression of the Sp/Sm resistance determinant derived from the Corynebacterium plasmid pCG4 was registered in Escherichia coli cells. The genetic determinant for Sp/Sm resistance was shown to be located in a 2.2 kb PstI-SphI fragment by the deletion analysis mapping in Escherichia coli cells. Using Escherichia coli as a host we cloned the unique 0.8 kb EcoRI-EcoRI fragment of Brevibacterium flavum bacteriophage phi BSh6 in the plasmids with dual replication origins. Blocking of the shuttle vector transfer to Brevibacterium flavum by the insertion of bacteriophage phi BSh6 DNA was observed. The deletion of entire phage fragment or a specific part of it made it possible introduction of plasmids harboured by Escherichia coli cells into Brevibacterium flavum. A potential vector for homologous DNA cloning in Brevibacterium flavum was constructed.
Mol Gen Mikrobiol Virusol 1991 Nov
PMID:[Potential vectors for molecular cloning in Brevibacterium flavum]. 180 11

Relationship between pyrimidine distribution patterns and radiosensitivity (Z) of DNA molecules of different species was derived by computer analysis of recurrence frequency of pyrimidine clusters. Blocking factors (beta) and Z for coding and non-coding DNA sequences of species from different taxonomic classes have been calculated within a new model. The radiosensitivity of coding DNA sequences practically does not vary whereas Z values were increased during evolution from simplest to higher organisms. The beta and Z values calculated for several groups of individual genes were shown to vary considerably.
Mol Biol (Mosk)
PMID:[Radiosensitivity of coding and noncoding DNA sequences of various organisms]. 181 7

The oxysterol 25-hydroxycholesterol acts both as a regulatory sterol determining the expression of genes governed by sterol regulatory elements and as a substrate for 7-alpha-hydroxylase, the first and rate-limiting enzyme in the bile acid synthetic pathway. Most wild-type nonhepatic cells are killed by the cytotoxic action of 25-hydroxycholesterol. In contrast, liver cells, which express 7-alpha-hydroxylase activity, are resistant to killing by 25-hydroxycholesterol. We examined the possibility that selection for resistance to 25-hydroxycholesterol might lead to the derivation of a cell line expressing 7-alpha-hydroxylase. A rat hepatoma cell line (7-alpha-hydroxylase minus) was transfected with human DNA and screened for resistance to 25-hydroxycholesterol. Although parental hepatoma cells were all killed within a week, a 25-hydroxycholesterol-resistant cell line (L35 cells) which showed stable expression of 7-alpha-hydroxylase activity and mRNA was obtained. These cells exhibited normal inhibition of cholesterol biosynthesis by 25-hydroxycholesterol. Blocking 7-alpha-hydroxylase activity with ketoconazole also blocked the resistance of L35 cells to 25-hydroxycholesterol. Isolation of microsomes from these cells showed levels of 7-alpha-hydroxylase activity (22.9 pmol/min/mg of protein) that were comparable to the activity (33.2 pmol/min/mg) of microsomes isolated from the livers of rats killed during the high point of the diurnal cycle. Parental cells had no detectable activity. These data show a new complementation group for 25-hydroxycholesterol resistance: expression of 7-alpha-hydroxylase. Dexamethasone increased both the activity and the cellular content of mRNA coding for 7-alpha-hydroxylase. Since dactinomycin blocked the ability of dexamethasone to induce mRNA, active transcription is required. Southern analysis of genomic DNA showed that L35 cells contain the rat (endogenous) gene but not the human gene. Furthermore, the RNA expressed by L35 cells is similar in size to rat RNA and is distinct from the human form of 7-alpha-hydroxylase. The combined data indicate that L35 cells are resistant to 25-hydroxycholesterol because they express 7-alpha-hydroxylase. The mechanism responsible involves activation of the endogenous (silent) gene of the parental rat hepatoma cell.
Mol Cell Biol 1991 Apr
PMID:Activation of the silent endogenous cholesterol-7-alpha-hydroxylase gene in rat hepatoma cells: a new complementation group having resistance to 25-hydroxycholesterol. 200 96

A small portion of human lung mononuclear cells are very potent stimulators of allogeneic resting T cells. Although several-fold more effective than phagocytic alveolar macrophages (AM) and blood monocytes (Mo), they do not produce more of the lymphocyte co-stimulators interleukin-1-alpha (IL-1 alpha), interleukin-1-beta (IL-1 beta), or tumor necrosis factor-alpha (TNF-alpha) than did Mo. Blocking antibodies against IL-1 alpha, IL-1 beta, TNF-alpha, and IL-6 did not reduce T cell proliferation. These potent antigen-presenting cells (APC) are loosely adherent and do not have phagocytic inclusions. Most of them have the marker RFD1 of dendritic cells (DC) rarely present on Mo or AM and have a strong tendency to form clusters with T cells like murine DC. Thus, we demonstrate an example in the human system of a dissociation between T cell activation and IL-1 or TNF-alpha production by DC or Mo, implying a major role for other "co-stimulating signals" by lung APC with dendritic features. The presence of different APC with various co-stimulating signals may be of importance for T cell subsets modulation.
Am J Respir Cell Mol Biol 1990 Jun
PMID:Dissociation between allogeneic T cell stimulation and interleukin-1 or tumor necrosis factor production by human lung dendritic cells. 234 59

Monoclonal antibodies were made against a truncated form of human laminin isolated from placenta. 12 antibodies were isolated and characterized. All antibodies stained basement membranes in placenta and immunoprecipitated laminin from media of cultured choriocarcinoma cells. Three antibodies, 3E5, 4C7, and 4E10, partially blocked the neurite-promoting activity of laminin. Addition of a second antibody, goat anti-mouse IgG, caused more complete blocking of the activity. Two of the blocking antibodies, 4C7 and 4E10, reacted with epitopes within the globular domain at the end of the long arm of laminin, and the third one, 3E5, reacted at the end of the rod-like portion of the long arm adjacent to the globular domain, as shown by electron microscopy after rotary shadowing. Five nonblocking antibodies used in the same test reacted with epitopes in other domains of the molecule. Blocking antibodies 3E5 and 4E10 could be used in immunoblotting and both antibodies reacted with the same polypeptides in pepsin fragments of human laminin, the predominant polypeptides being approximately 400 kD. When a crude extract of human amnion was used as a source of intact laminin, the 4E10 antibody detected a single polypeptide of approximately 400 kD. A nonblocking antibody, 2E8, which reacted at the center of the laminin cross, reacted predominantly with a 200-kD polypeptide in human laminin fragments and exclusively with a 200-kD polypeptide in amnion extract and in rat laminin. Our results with human laminin match the results by Edgar, D., R. Timpl, and H. Thoenen, 1984, EMBO (Eur. Mol. Biol. Organ.) J., 3:1463-1468, in which the neurite-promoting activity of mouse laminin resides at the end of the long arm, which is also the site for heparin binding. However, since the active fragments of human laminin did not bind to heparin, the neurite-promoting site should be different from the heparin-binding site. Our results further suggest that the neurite-promoting site may be contained in or close to the 400-kD component of laminin.
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PMID:Mapping of domains in human laminin using monoclonal antibodies: localization of the neurite-promoting site. 243 Sep 84

Different class 1 antiarrhythmic drugs have differing capabilities for producing a rate-dependent modulation of cardiac excitability. Structural hypotheses regarding these drug actions, both in terms of their widely differing abilities for blocking myocardial sodium channels during individual action potentials and their associated repriming kinetics, have been proposed. Recent studies on the channel blocking actions of these drugs, assessed using maximum upstroke velocities of intracellularly recorded actions potentials (APs), are reviewed in order to test these hypotheses. The size/solubility hypothesis, which says that smaller antiarrhythmic drugs with good lipid distribution capabilities provide more rapid repriming kinetics, is supported by results on 36 of 40 drugs having molecular weights up to 350. Blocking abilities during individual APs are also examined, with lipid distribution coefficients describing this blocking capability within selected classes of drug structures. However overall "potency" must include consideration of drug repriming kinetics which allows for accumulation of excitability block. Evidence which suggests that the kinetically slower drugs may be more cardiotoxic (arrhythmogenic) is presented. A model for the steep size dependence of drug recovery times is provided by a cylindrical pore having a radius of 4.1 Angstroms. Finally the different drug pools that drive the hypothesized hydrophilic and hydrophobic pathways to the receptor are considered in order to explain why drug lipid distribution characteristics might play a role in recovery kinetics.
J Mol Cell Cardiol 1987 Mar
PMID:Quantitative structure/activity relations based on use-dependent block and repriming kinetics in myocardium. 243 97


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