Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eosinophilic endocarditis is a potentially lethal complication of chronic peripheral blood hypereosinophilia. We hypothesized that eosinophil peroxidase (EPO), an abundant eosinophil (EO) cationic granule protein, promotes eosinophilic endocarditis by binding to negatively charged endocardium, and there generating cytotoxic oxidants. Using an immunocytochemical technique, we demonstrated endocardial deposition of EPO in the heart of a patient with hypereosinophilic heart disease. Because EPO preferentially oxidizes Br- to hypobromous acid (HOBr) rather than Cl- to hypochlorous acid (HOCl) at physiologic halide concentrations, we characterized the Br(-)-dependent toxicity of both activated EOs and purified human EPO towards several types of endothelial cells and isolated working rat hearts. In RPMI supplemented with 100 microM Br-, phorbol myristate acetate-activated EOs, but not polymorphonuclear leukocytes, caused 1.8-3.6 times as much 51Cr release from four types of endothelial cell monolayers as in RPMI alone. H2O2 and purified human EPO, especially when bound to cell surfaces, mediated extraordinarily potent, completely Br(-)-dependent cytolysis of endothelial cells that was reversed by peroxidase inhibitors, HOBr scavengers, and competitive substrates. We further modeled eosinophilic endocarditis by instilling EPO into the left ventricles of isolated rat hearts, flushing unbound EPO, then perfusing them with a buffer containing 100 microM Br- and 1 microM H2O2. Acute congestive heart failure (evidenced by a precipitous decrement in rate pressure product, stroke volume work, aortic output, and MVO2 to 0-33% of control values) ensued over 20 min, which deletion of EPO, Br-, or H2O2 completely abrogated. These findings raise the possibility that EPO bound to endocardial cells might utilize H2O2 generated either by overlying phagocytes or endogenous cardiac metabolism along with the virtually inexhaustible supply of Br- from flowing blood to fuel HOBr-mediated cell damage. By this mechanism, EPO may play an important role in the pathogenesis of eosinophilic endocarditis.
 ...
PMID:Bromide-dependent toxicity of eosinophil peroxidase for endothelium and isolated working rat hearts: a model for eosinophilic endocarditis. 198 18

We examined factors that may limit degradation of bacterial protein of Escherichia coli S15 killed by polymorphonuclear leukocytes (PMN). Both human and rabbit PMN degraded up to 40% of [14C]amino acid-labeled protein of ingested and killed E. coli in 2 h as determined by loss of acid-precipitable radioactivity. In contrast, equally bactericidal broken-PMN preparations or isolated granules degraded only about 10% of bacterial protein regardless of pH. To determine whether activation of the respiratory burst contributes to digestion, we compared degradation by intact PMN in room air and under N2. Depletion of O2 by N2 flushing had no effect on the bactericidal activity of either human or rabbit PMN but reduced degradation by approximately 50%. Protein degradation during phagocytosis was also reduced in the presence of cyanide or azide, inhibitors of myeloperoxidase (MPO). PMN of two patients with chronic granulomatous disease ingested and killed E. coli S15 as well as did normal PMN but degraded bacterial protein as did normal PMN incubated under N2. The low degradative activity of PMN disrupted by sonication could be raised to nearly the level of intact PMN incubated in room air by preincubation of the PMN with 10(-7) M formyl-methionyl-leucyl-phenylalanine (fMLP) before sonication and by pretreatment of E. coli with MPO. Depletion of O2 or chloride during these preincubations with formyl-methionyl-leucyl-phenylalanine respectively, virtually abolished and markedly diminished stimulation of bacterial protein degradation. We conclude that enhanced MPO-mediated O2 metabolism of intact PMN plays a role in the digestion of killed E. coli.
 ...
PMID:Respiratory burst facilitates the digestion of Escherichia coli killed by polymorphonuclear leukocytes. 330 66

An autopsy case of systemic mastocytosis without cutaneous involvement in a 76-year-old woman was described. The patient presented with general malaise, chest and epigastric discomfort, flushing of the face and progressive hepatosplenomegaly, and she terminated in hemorrhagic complications of DIC within 2 months. There was neither rash nor urticaria pigmentosa recognizable in the entire course. The diagnosis was made by the histologic identification of abnormal aggregates of mast cells in a bone marrow aspirate. These mast cell granules were chloroacetate esterase-positive, peroxidase-negative, and electronmicroscopically they were composed of fine granular materials containing variable numbers of lamellar structures. At autopsy, diffuse infiltration of the mast cells was found in the liver, spleen, bone marrow, lymph nodes, lungs, kidneys, stomach, and adrenal glands.
 ...
PMID:Systemic mastocytosis without cutaneous involvement. 355 89

Lectins conjugated with either peroxidase or ferritin were used to detect specific monosaccharide residues on the luminal front of he fenestrated endothelium in the capillaries of murine pancreas and intestinal mucosa. The lectins tested recognize, if accessible, the following residues: alpha-N-acetylgalactosaminyl (soybean lectin), beta-D-galactosyl (peanut agglutinin [PA] and Ricinus communis agglutinin-120 [RCA]), beta-N-acetylglucosaminyl and sialyl residues (wheat germ agglutinin [WGA]), alpha-L-fucosyl (lotus tetragonolobus lectin), and alpha-D-glucosyl and beta-D-mannosyl (concanavalin A [ConA]). Thi labeled lectins were introduced by perfusion in situ after thoroughly flushing with phosphate-buffered saline the microvascular beds under investigation. Specimens were fixed by perfusion, and subsequently processed for peroxidase detection and electron microscopy. Control experiments included perfusion with: (a) unlabeled lectin before lectin conjugate; (b) labeled lectin together with the cognate hapten sugar, and (c) horseradish peroxidase or ferritin alone. Binding sites were found to be relatively homogeneously distributed on the plasmalemma proper, except for Lotus tetragonolobus lectin and Con A, which frequently bound in patches. Plasmalemmal vesicles, transendothelial channels, and their associated diaphragms were particularly rich in residues recognized by RCA and PA (beta-D-galactosyl residues) and by WGA (beta-N-acetylglucosaminyl residues). Receptors for all lectins tested appeared to be absent or considerably less concentrated on fenestral diaphragms. The results reported here extend and complement previous findings on the existence of microdomains generated by the preferential distribution of chemically different anionic sites (Simionescu et al., 1981, J. Cell Biol., 9:605-613 and 614-621).
 ...
PMID:Differentiated microdomains on the luminal surface of capillary endothelium: distribution of lectin receptors. 710 6

Enhanced nitric oxide (NO) generation by stimulated NO synthase (NOS) activity may, through its oxidative metabolism contribute to tissue injury in experimental colitis. In this study the possible amelioration of experimental colitis by NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS activity, was evaluated. Colitis was induced in rats by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB) dissolved in 0.25 ml 50% ethanol or by flushing the colon of capsaicin pretreated rats with 2 ml of 5% acetic acid. In several experiments, L-NAME 0.1 mg/ml was added to the drinking water at the time of colitis induction with TNB or seven days before acetic acid treatment. Rats were killed at various time intervals after induction of colitis. A 10 cm distal colonic segment was isolated, weighed, lesion area measured, and explants organ cultured for 24 hours for determination of NO generation by the Greiss reaction. The rest of the mucosa was scraped for determination of myeloperoxidase and NOS activities and leukotriene generation. In TNB treated rats mean arterial pressure was also determined up to 72 hours after damage induction, with or without cotreatment with nitroprusside. L-NAME significantly decreased the extent of tissue injury in TNB treated rats. Seven days after TNB treatment lesion area was reduced by 55%, colonic weight by 37%, and myeloperoxidase and NOS activity by 59% and 42%, respectively. Acetic acid induced colitis in capsaicin pretreated rats was also significantly decreased by L-NAME. Twenty four hours after acetic acid treatment lesion area was reduced by 61%, colonic weight by 21% and NOS activity by 39%. Mean (SEM) arterial blood pressure in TNB+L-NAME treated rats was 37.6 (8.1) mm Hg higher than in TNB treated rats, an effect that was only partially abolished by nitroprusside. These results show that inhibition of NO synthesis by an L-arginine analogue significantly ameliorates the extent of tissue injury in two models of experimental colitis, an effect that is not due only to its vasoconstrictor properties. Modulation of NO generation may be a novel therapeutic approach in inflammatory bowel disease.
 ...
PMID:Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity. 867 8

The immunohistochemical and ultrastructural localization of prostaglandin H synthase (PGH synthase) was studied in the Albino Swiss CF-1 mouse at different stages of embryonic development (two-cell stage, four-eight cell stage, morula and blastocyst). Flushed embryos and sections of uteri and oviducts containing embryos were treated with a mouse IgG monoclonal anti-PGH synthase antibody. The second antibody (rabbit anti-mouse) was conjugated with peroxidase or fluorescein isothiocyanate for light microscopy, fluorescence microscopy and confocal scanning. For reflection contrast microscopy and transmission electron microscopy a second antibody, goat anti-mouse, was conjugated with ultrasmall gold particles. Controls without anti-PGH synthase were used concurrently. All embryos demonstrated PGH synthase reactivity. Immunostaining appeared to be more intense at the two-cell stage, four-eight cell stage embryos and morulae than in blastocysts. Further examination indicated an intracytoplasmic location for PGH synthase, which was confirmed by stereoscopic photographs made during confocal scanning microscopy and by the immunostaining patterns observed with reflection contrast microscopy and transmission electron microscopy. Transmission electron microscopy immunostaining patterns support the localization of PGH synthase in the endoplasmic reticulum. This is the first demonstration of the ultrastructural localization of PGH synthase in the mouse embryo. Its presence before the apposition with the endometrial epithelium supports the hypothesis that arachidonic acid metabolism via the PGH synthase pathway may be crucial for implantation.
 ...
PMID:Immunohistochemical and ultrastructural localization of prostaglandin H synthase in the preimplantation mouse embryo. 888 80

Effects of artificial defoliation on defensive needle chemistry in Scots pine (Pitus sylvestris L.) were evaluated with particular emphasis on peroxidases, phenolic compounds, soluble sugars, polyamines, and foliar nitrogen levels. The study was carried out on a nutrient-poor Scots pine stand with 8- to 25-year-old trees. Defoliation treatment consisted of repeated defoliation in two successive years with respective control trees. Defoliation was done before needle flushing by removing all mature needles. Guaiacol peroxidase activity increased in the needles after the first defoliation. The difference between treatments diminished towards autumn, and disappeared before the second defoliation in the next summer. After the second defoliation, the activities showed a similar trend. Apparently, peroxidases are involved in inducible chemical changes and recovery reactions that occur in the intact needles shortly after defoliation. After the second defoliation, total nitrogen concentration in the current year needles was about 20% lower, and free putrescine (a polyamine) concentration was 40% lower in the defoliated trees than in control needles. These changes indicate a loss of nitrogen due to defoliation. Specific phenolic compounds such as quercitrin, (+)-catechin, and two catechin derivatives increased in current year needles in response to defoliation. Accumulation of starch and sucrose in the current year needles of repeatedly defoliated trees may imply decreased assimilate transport. The results are indicative that changes in needle phytochemistry in response to defoliation accompany changes in needle nitrogen metabolism.
 ...
PMID:Defoliation-induced responses in peroxidases, phenolics, and polyamines in scots pine (Pinus sylvestris L.) needles. 1295 14

Ulcerative colitis is associated with altered contractile activity and transit time of colon. On the other hand, cholecystokinin (CCK) has been shown to play an important role in regulation of gastrointestinal motor function including colonic contraction and transit. In the present study, an attempt was made to study the effect of proglumide, a CCK receptor antagonist on experimental colitis in rats. Experimental colitis was induced in male Sprague-Dawley rats by instilling 1 ml of 4% acetic acid followed by flushing with 0.5 ml air. The rats were kept in a head-down position for 30s. Finally, each rat received 1.5 ml colonic wash with 1.5 ml saline. Four groups of rats received proglumide orally (0, 250, 500 and 1000mg/kg). The first dose of proglumide was given 1 h before acetic acid challenge, whereas the second dose of proglumide was given 25 h after the first dose. Sham control rats received an equal volume of saline instead of acetic acid. Forty-eight hours after the acetic acid challenge, the colon was removed, weighed and split longitudinally and scored for injury. Part of the colon was used for histopathological study as well as analysis of myeloperoxidase (MPO) activity (as a marker of neutrophil activity). Acetic acid produced severe diarrhea and exfoliation of the colonic epithelium accompanied by extensive destruction of the mucosal interstitium. Proglumide dose dependently protected rats against acetic acid-induced increase in colon weight, diarrhea, MPO activity and colonic injury. Inhibition of CCK exerts a beneficial effect in experimental colitis. Further studies are warranted to determine the mechanism of protection and the therapeutic potential of CCK inhibitors.
 ...
PMID:Proglumide attenuates experimental colitis in rats. 1581 62

Clostridium acetobutylicum and Clostridium aminovalericum, both obligatory anaerobes, grow normally after growth conditions are changed from anoxic to microoxic, where the cells consume oxygen proficiently. In C. aminovalericum, a gene encoding a previously characterized H2O-forming NADH oxidase, designated noxA, was cloned and sequenced. The expression of noxA was strongly upregulated within 10 min after the growth conditions were altered to a microoxic state, indicating that C. aminovalericum NoxA is involved in oxygen metabolism. In C. acetobutylicum, genes suggested to be involved in oxygen metabolism and genes for reactive oxygen species (ROS) scavenging were chosen from the genome database. Although no clear orthologue of C. aminovalericum NoxA was found, Northern blot analysis identified many O2-responsive genes (e.g., a gene cluster [CAC2448 to CAC2452] encoding an NADH rubredoxin oxidoreductase-A-type flavoprotein-desulfoferrodoxin homologue-MerR family-like protein-flavodoxin, an operon [CAC1547 to CAC1549] encoding a thioredoxin-thioredoxin reductase-glutathione peroxidase-like protein, an operon [CAC1570 and CAC1571] encoding two glutathione peroxidase-like proteins, and genes encoding thiol peroxidase, bacterioferritin comigratory proteins, and superoxide dismutase) whose expression was quickly and synchronously upregulated within 10 min after flushing with 5% O2. The corresponding enzyme activities, such as NAD(P)H-dependent peroxide (H2O2 and alkyl hydroperoxides) reductase, were highly induced, indicating that microoxic growth of C. acetobutylicum is associated with the expression of a number of genes for oxygen metabolism and ROS scavenging.
 ...
PMID:Adaptive responses to oxygen stress in obligatory anaerobes Clostridium acetobutylicum and Clostridium aminovalericum. 1633 33

Suspension arrays for protein-based assays have been developed using shape-coded poly(ethylene glycol) (PEG) hydrogel microparticles to overcome the problems with current systems which use color-coded rigid microparticles as protein supports. Various shapes of hydrogel microparticles were fabricated by a two-step process consisting of photopatterning and flushing using a poly(dimethylsiloxane) (PDMS) channel as a molding insert. Hydrogel microparticles with lateral dimensions ranging from 50 to 300 micrometers were fabricated using different molecular weights of PEG (700, 3,400, and 8,000 Da), by which the water content and swelling behavior of the hydrogel microparticles could be controlled. Protein-entrapped hydrogel microparticles were prepared in a suspension array format, and PEG hydrogel could encapsulate proteins without deactivation for a week due to its high water content and soft nature. The sequential bienzymatic reaction of hydrogel-entrapped glucose oxidase (GOX) and peroxidase (POD) was successfully investigated using fluorescence detection, demonstrating one possible application of suspension arrays. Furthermore, a mixture of two different shapes of hydrogel microparticles containing GOX/POD and alkaline phosphatase (AP), respectively, was prepared and the shape-coded suspension array was used for simultaneous characterization of two different enzyme-catalyzed reactions.
 ...
PMID:Suspension arrays of hydrogel microparticles prepared by photopatterning for multiplexed protein-based bioassays. 1856 Oct 28


1 2 Next >>