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)

The purpose of the studies described here was to test the hypothesis that overexpression of the human interleukin-1 receptor antagonist (IL-1ra) in the distal airway epithelia of mice would result in amelioration of the inflammatory effects of IL-1alpha. The coding region of the human IL-1ra gene was placed under transcriptional control of the 5' flanking region of the human SP-C gene. Transgenic mice were generated by pronuclear injection of the transgene and identified by Southern blot analysis of genomic DNA. RNA expression of the transgene was confirmed by Northern blot analysis. In order to determine whether expression of the transgene conferred protection against inflammatory stimuli, control and transgenic mice were treated with IL-1alpha by intratracheal instillation. Six hours after treatment, bronchoalveolar lavage was performed, which revealed a statistically significant decrease in the degree of neutrophilia in the transgenic mice as compared with control mice. Furthermore, there was a significant reduction in the whole-lung myeloperoxidase concentration. Reverse transcription-polymerase chain reaction analysis of whole-lung RNA revealed a significant reduction in the messenger RNA/beta-actin ratio of macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-2 in the transgenic animals as compared with controls. The results of these studies indicate that distal airway epithelial cell expression of human IL-1ra results in partial protection from IL-1alpha-induced airway inflammation and injury.
Am J Respir Cell Mol Biol 1998 Mar
PMID:Generation of a transgenic mouse with lung-specific overexpression of the human interleukin-1 receptor antagonist protein. 949 Jun 61

It is now recognized that ultraviolet (UV) radiation is a potent environmental insult capable of interfering with immunity to skin cancers and modifying certain immunologic reactions within both locally irradiated skin and distant, unexposed sites. Exposure to UVB light (290-320 nm) induces a potent cutaneous inflammatory response that involves the infiltration of leukocytes into the dermis as well as the production of proinflammatory cytokines by both resident epidermal keratinocytes and dermal cells. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has been shown to be a major mediator of UVB light effects on cutaneous immunity. Recent studies have demonstrated that pentoxifylline (PTX), a xanthine-derived phosphodiesterase inhibitor, has the ability to inhibit synthesis of TNF-alpha. To examine the effects of PTX on UVB-mediated cutaneous inflammation, Skh/hr hairless mice were injected intraperitoneally with either phosphate-buffered saline or 50 microg/g PTX 1 h before exposure to 2240 J/m2 UVB. Reverse transcription-polymerase chain reaction and immunohistochemical techniques were used to demonstrate that 24 h to 1 wk after UVB-light irradiation, PTX inhibited UVB-induced TNF-alpha gene expression, inhibited the increase in epidermal TNF-alpha protein synthesis, blocked the increase in epidermal proliferation observed after exposure to UVB light, and decreased production of myeloperoxidase by neutrophils infiltrating into the dermis. These studies demonstrated that PTX modifies epidermal responses after acute UVB light exposure and suggest that PTX treatment may be used clinically to modulate the deleterious effects of long-term UVB-light irradiation.
Mol Carcinog 1998 May
PMID:Inhibitory effects of pentoxifylline on ultraviolet B light-induced cutaneous inflammation. 960 97

Covalent binding of a reactive metabolite of clozapine to neutrophils or their precursors is thought to play a role in the development of clozapine-induced agranulocytosis. Immunoblotting studies with an anti-clozapine antiserum detected covalent binding of clozapine to human neutrophils in vitro when HOCl was used to generate clozapine reactive metabolite (major clozapine adducts of 31, 49, 58, 78, 86, 126, 160, and 204 kDa). In addition, incubating neutrophils with clozapine and H2O2 (major clozapine adducts of 49 and 58 kDa) or clozapine, H2O2, and human myeloperoxidase (major clozapine adducts of 31, 49, 58, and 126 kDa) also resulted in covalent binding of clozapine to the neutrophils. The covalent binding of clozapine to neutrophils was inhibited by extracellular glutathione when HOCl, but not H2O2 was used to generate reactive metabolite. We found that the antiserum against clozapine also recognized olanzapine, an antipsychotic drug that forms a similar reactive metabolite to clozapine but has not been associated with induction of agranulocytosis. Repeating the in vitro experiments with olanzapine revealed that the major olanzapine-modified polypeptides had molecular masses of 96, 130-170, and 218 kDa. Only relatively low levels of 31, 49, and 58 kDa adducts were observed. Clozapine-modified polypeptides also were detected in neutrophils from patients being treated with clozapine. A major 58-kDa clozapine-modified polypeptide was detected in all patients tested. In contrast, no drug-modified polypeptides were detected in neutrophils from patients taking olanzapine. The differences in covalent binding exhibited by the two compounds and, in particular, the lack of olanzapine binding to human neutrophils in vivo may help to explain the difference in toxicity of these two drugs.
Mol Pharmacol 1998 Jun
PMID:A comparison of the covalent binding of clozapine and olanzapine to human neutrophils in vitro and in vivo. 961 1

Chromatography of human myeloperoxidase (MPO) on a heparin-agarose column demonstrated a tight association of the protein with the resin. The electrophoretic mobility of mixtures of MPO and heparin in polyacrylamide gels under nondenaturing conditions was consistent with a strong interaction of the cationic enzyme with the polyanionic polysaccharide. Purified MPO prebound to bovine aorta endothelial cells (BAEC) and supplemented with hydrogen peroxide dose- and time-dependently abrogated the interaction of coagulation factor IX (FIX) with factor IX-binding protein (FIXBP) on the surface of BAEC reflecting oxidative modification of the binding protein. This inactivation of FIXBP required the presence of chloride implicating hypochlorite in the reaction. Hypochlorite and activated neutrophils exerted a similar effect. The oxidative modification of FIXBP was only partially dependent on the addition of hydrogen peroxide and was abolished by exogenous heparin which displaced MPO from the cell surface, emphasizing the functional differences between cell-bound and free enzyme.
Mol Cell Biochem 1998 Jun
PMID:Association of myeloperoxidase with heparin: oxidative inactivation of proteins on the surface of endothelial cells by the bound enzyme. 965 78

Taurine prevents tissue damage in various models of inflammation through a mechanism postulated to involve taurine monochloramine (Tau-Cl). Tau-Cl is formed through the action of a halide-dependent myeloperoxidase system associated with polymorphonuclear leukocytes (PMN), eosinophils, and basophils. Production of nitric oxide (NO), PGE2, and other proinflammatory mediators by activated macrophages is inhibited by Tau-Cl. Since glial cells may be activated to produce NO, PGE2 and other proinflammatory mediators, similar to macrophages, we examined the effects of Tau-Cl on the production of NO and PGE2 by rat C6 glioma cells. C6 cells were seeded to grow over 2-3 days to approximately 90% confluency before exposure to various concentrations of Tau-Cl in HBSS for 2 h (37 degreesC, 5% CO2). The HBSS was replaced, after washing the cells, with DMEM containing 4% fetal calf serum and activators (LPS, 10 microgram/ml; rat rIFN-gamma, 50 U/ml; and human rTNF-alpha, 50 ng/ml). Media content of NO2- and PGE2 was measured 48 h after activation and cell lysates were subjected to SDS-PAGE followed by Western blot analyses to determine the relative expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. Media accumulation of NO2- and PGE2 was inhibited by Tau-Cl in a concentration dependent manner and this was accompanied by decreased amounts of iNOS and COX-2 proteins in cell lysates. Additional experiments determined the effects of Tau-Cl on the kinetics of iNOS and COX-2 mRNA expression. Expression of iNOS mRNA was markedly inhibited in activated C6 cells that were previously exposed to Tau-Cl and this persisted for at least 24 h. In contrast, inhibition of COX-2 mRNA expression was only transiently reduced in Tau-Cl exposed cells during the first 4 h of activation and was relatively unimpaired thereafter (8-24 h). These results suggest that Tau-Cl inhibits the transcriptional expression of the iNOS gene but inhibits expression of COX-2 protein by post-transcriptional mechanisms.
Brain Res Mol Brain Res 1998 Aug 31
PMID:Taurine chloramine inhibits production of nitric oxide and prostaglandin E2 in activated C6 glioma cells by suppressing inducible nitric oxide synthase and cyclooxygenase-2 expression. 972 77

Several studies report that among the antioxidant agents used to reduce injury after myocardial ischemia/reperfusion, analogues of vitamin E (VE) seem to have a significant efficacy. Raxofelast is a potent antioxidant agent under investigation, structurally related to VE, having an excellent bioavailability and favourable physicochemical properties. We assessed raxofelast in a rat model of myocardial damage induced by 1 h of left coronary artery occlusion followed by 6 h of reperfusion. Myocardial ischemia/reperfusion produced: wide tissue necrosis (50.3+/-10.3%); membrane peroxidation, evaluated by assessing cardiac malondialdehyde (MAL) (87.8+/-15.8 nmol/g tissuev 9.53+/-2.4 nmol/g tissue) and plasma conjugated dienes (CD) (8.73+/-1.86 DeltaABS/mlv 1.61+/-0.45 DeltaABS/ml); endogenous antioxidant wasting [cardiac VE=23.5+/-10.2 nmol/g tissuev 61.4+/-13.4 nmol/g tissue, cardiac reduced glutatione (GSH)=2.15+/-1.23 micromol/g proteinv 7.34+/-0.92 micromol/g protein and cardiac superoxide dismutase (SOD)=8.9+/-4.1 U/mg proteinv 17. 5+/-4.2 U/mg protein]; depressed mean arterial blood pressure (MAP) (61.4+/-5.8 mmHgv 85.3+/-6.2 mmHg); heart rate (HR) (275+/-35 beats/minv 368+/-34 beats/min) and left-ventricular derivative developed force (LV dP/dtmax) (1050+/-187 mmHg/sv 2520+/-194 mmHg/s); and cardiac neutrophil accumulation, evaluated by assessing cardiac myeloperoxidase (MPO) (9.23+/-2.1 U/g tissuev 0.92+/-0.12 U/g tissue). Administration of raxofelast (25, 50 and 100 mg/kg i.p. 5 min after occlusion) limited myocardial necrosis (22.3+/-14.8%P<0. 005, following the highest dose), reduced lipid peroxidation (MAL=43. 5+/-14.7 nmol/g tissueP<0.001 and CD=4.01+/-2.21 DeltaABS/mlP<0.001, following the highest dose), restored the endogenous antioxidants VE (52.8+/-14.2 nmol/g tissueP<0.001, following the highest dose), SOD (14.2+/-2.7 U/mg proteinP<0.001, following the highest dose) and GSH (4.92+/-1.33 micromol/g proteinP<0.005, following the highest dose), improved hemodynamic parameters (MAP=68.1+/-5.3 mmHgP<0.05, HR=317+/-27 beats/minP<0.05, LV dP/dtmax=1427+/-143 mmHg/sP<0.05, following the highest dose) and reduced myocardial neutrophil infiltration (MPO=5.1+/-1.5 U/g tissueP<0.001, following the highest dose). These data suggest that raxofelast could be considered a useful drug to reduce myocardial infarction.
J Mol Cell Cardiol 1998 Aug
PMID:Beneficial effect of raxofelast, an hydrophilic vitamin E analogue, in the rat heart after ischemia and reperfusion injury. 973 36

The Bayer-Technicon hematological devices differentiate leukocytes by their peroxidase activity and their volume, displaying them as separate clusters. Peroxidase deficiencies are manifested by the irregular location of these clusters. This makes it possible to identify persons totally or partially lacking myeloperoxidase. The deficiency is quantified by the myeloperoxidase index, which is expressed for every routine analysis and for which normal values were determined. Values of the myeloperoxidase index confirm varying degrees of deficiency and prevalence. Family studies using these degrees show that the hereditary pattern must be more complicated than the classical autosomal-recessive mode. A bigenic mode is suggested. While about half of the totally deficient individuals detected were free of typical symptoms, in the other half we found infectious complications that were sometimes life-threatening. The hematological devices allow the identification of persons suffering from eosinoperoxidase deficiency and from MPO deficiency of the monocytes. The latter symptom seems to indicate immaturity of these cells and may lead to unexpected diagnosis of malignancy.
J Mol Med (Berl) 1998 Sep
PMID:Prevalence of myeloperoxidase deficiency: population studies using Bayer-Technicon automated hematology. 976 44

Autoantibodies to MPO are associated with various forms of systemic vasculitis, including the renal limited form described as idiopathic crescentic glomerulonephritis. In vitro the antibodies are able to further activate primed neutrophils to the production of reactive oxygen species and the release of lysosomal enzymes. In vivo experimental studies in which an autoimmune response to MPO was induced in rats have demonstrated the in vivo potential of the autoantibodies to aggravate subclinical inflammatory lesions. In the right context, vasculitis and glomerulonephritis can ensue. Further studies are being directed to the precise characterization of autoimmune responses in order to obtain clues for the etiopathogenesis of the associated diseases.
J Mol Med (Berl) 1998 Sep
PMID:Autoantibodies to myeloperoxidase: clinical and pathophysiological significance. 976 46

Phenotypic conversion from acute myeloid leukemia (AML) to acute lymphoblastic leukemia (ALL) is rare. A 38-year-old man was initially diagnosed as having AML (FAB-M2) associated with the t(8;21)(q22;q22) chromosomal abnormality. The blasts showed myeloperoxidase (MPO) activity and CD13 antigen expression. He showed complete remission after standard chemotherapy for AML. However, the patient relapsed with blasts showing ALL morphology (FAB-L1), MPO negativity, and CD19 antigen expression 33 months after cessation of AML therapy. Cytogenetic analysis at relapse was unsuccessful. Molecular analysis of ALL blasts revealed immunoglobulin heavy-chain gene and MLL gene rearrangements but no AML1 gene. MLL gene rearrangement or the 11q23 chromosomal abnormality has been associated with therapy-related leukemia. The subsequent ALL in our patient may have been induced by the chemotherapy including daunorubicin, known as a topoisomerase II inhibitor.
Hematopathol Mol Hematol 1998
PMID:Phenotypic conversion from t(8;21) acute myeloid leukemia to MLL gene rearrangement-positive acute lymphoblastic leukemia. 984 25

The preventive effects of the dietary germinated barley foodstuff (GBF), which increases the contents of protein, RNA and DNA in the intestinal mucosa of rats on the mucosal damage and diarrhea were examined in a methotrexate (MTX)-induced enteritis model in rats. Sprague-Dawley rats intraperitoneally injected with MTX (10 mg/kg body weight) were used as an enteritis model. After consumption of diets containing GBF, glutamine or a glutamine-rich stuff (gluten), mucosal damage, contents of mucosal protein, RNA and DNA, myeloperoxidase (MPO) activity, bacterial translocation and DNA synthetic activity in the small intestine were assessed. GBF more effectively prevented diarrhea and mucosal damages, and increased mucosal protein, DNA and RNA contents than glutamine or gluten. The bacterial trans-location and elevation of MPO activity induced by MTX were depressed only by the consumption of GBF. GBF has a potential as therapeutic diet to decrease the adverse effects of anti-cancer chemotherapy.
Int J Mol Med 1998 Jun
PMID:Preventive effects of germinated barley foodstuff on methotrexate-induced enteritis in rats. 985 31


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