Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of mercuric chloride on phagocytic capacity, formation of toxic oxygen species and release of lysosomal enzymes of human polymorphonuclear leukocytes (PMNL). Our results show that HgCl2 may alter these microbicidal functions of human PMNL without remarkable damage of cell viability. The phagocytic capacity was markedly depressed in a concentration-dependent manner. The formation of toxic oxygen species was also diminished by mercuric chloride when induced by phagocytosis. It was furthermore reduced when the PMNL were activated without phagocytosis by binding of IgG to Fc-receptors or by binding of phorbol myristate acetate to the membrane. In contrast, the release of the lysosomal enzyme lysozyme was enhanced in the presence of mercuric chloride, but not the release of beta-glucuronidase. These effects may lead to impaired defense against infections and possibly to inflammatory reactions in adjacent tissues induced by released lysosomal enzymes.
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PMID:Effect of mercuric chloride on microbicidal activities of human polymorphonuclear leukocytes. 339 53

The interactions between subinhibitory concentrations of cephalosporins and polymorphonuclear leukocytes in the killing of a strain of Escherichia coli are described and an attempt is made to define the responsible mechanism. Ceftizoxime was the most potent agent tested. Pretreatment of the E. coli strain with subinhibitory concentrations of ceftizoxime increased the susceptibility to both; phagocytic killing activity of the polymorphonuclear leukocytes and bactericidal activities of the oxygen metabolites and the granule extracts. A most interesting result was the increased susceptibility of the ceftizoxime-treated E. coli to killing by beta-glucuronidase which normally is not bactericidal. It is suggested that the augmented killing could be due to bacteriolysis by beta-glucuronidase.
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PMID:Synergism of cephalosporins at subinhibitory concentrations and polymorphonuclear leukocytes on phagocytic killing of Escherichia coli and its mode of action. 351 64

Considerable progress has been made in the localization of chemical substances within the gas-exchange zones of vertebrate lungs since cytochemical techniques suitable for use with the electron microscope have been developed. The light microscope, an instrument with an effective resolution limit of about 0.2 micron, is ill-suited for studying regions such as these where small tissue elements are arranged in a complex manner. A wide range of acid hydrolases have been detected in the vacuoles and dense bodies of alveolar macrophages by means of cytochemical techniques. The enzymes demonstrated in this way include acid phosphatase, aryl sulphatase, cathepsin D, beta-glucuronidase, acetyl glucosaminidase, nonspecific esterase, dipeptidyl peptidase II and dipeptidyl peptidase IV. Such enzymes are, of course, to be expected in the lysosomes of cells which have a primary phagocytic role. Nevertheless, it must be confessed that very little is yet known about the actual mechanism of phagocytosis or of the fate of the digested material. It is fortunate, however, that some of the tools which are likely to be of value in research on these aspects of macrophage function are currently being developed. Of particular interest in this connection are the immunocytochemical techniques which permit the localization of surface-associated antigens and intracellular contractile proteins. It must be emphasized that phagocytosis is not the only function of macrophages in the gas-exchange zone of the lung. These cells are thought to be involved in the presentation of exogenous antigenic material to the reactive cells of the lymphoid system. Recent research has also indicated that mammalian alveolar macrophages synthesize a diverse range of substances. Furthermore, the elastases associated with pulmonary macrophages are now thought to be involved in the pathogenesis of emphysema. All of the above-mentioned activities are of great biological and clinical significance and, consequently, merit the cytochemists' attention in future. The epithelial lining of the greater part of the pulmonary gas-exchange area is composed of type I pneumonocytes. In terms of ultrastructure, these are very specialized cells; their extensive and highly-attenuated cytoplasmic processes form the outer layer of the air-blood barrier. No special carrier systems have been identified within type I pneumonocytes and this is in keeping with the claims that oxygen is transferred across the alveolar tissue barrier by a process of simple diffusion. Type II pneumonocytes, in contrast, have considerable metabolic activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytochemistry of the gas-exchange area in vertebrate lungs. 355 66

Culture medium conditioned by mononuclear leucocytes (MNL) stimulated by formalin-fixed heat-killed Staphylococcus aureus (sCM) modulated a number of neutrophil functions. The sCM inhibited the locomotion of human neutrophils in both the presence and absence of a chemotactic gradient generated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). It also stimulated the oxygen-dependent respiratory burst as assessed by its ability to stimulate basal H2O2, superoxide and chemiluminescence production by neutrophils. Neutrophils treated with sCM also showed increased release of lysozyme but not beta-glucuronidase. In addition, the sCM-treated neutrophils showed a potentiated response to stimuli that bind surface receptors, i.e. FMLP and opsonized zymosan. The effects of sCM and either of the stimuli were synergistic. Examination of lysosomal enzyme release showed that sCM enhanced the release of lysozyme and beta-glucuronidase induced by either FMLP/cytochalasin B or zymosan. The response to phorbol myristate acetate (PMA), which bypasses the surface receptor, was also stimulated but compared poorly with the FMLP response. The sCM effects on the FMLP-induced chemiluminescence response occurred even when FMLP addition was delayed for 4 hr. Cells treated with sCM and washed retained the ability to show an enhanced FMLP response. The neutrophil-modulating activity was not produced by MNL cultured in the absence of bacteria.
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PMID:Staphylococcus aureus-stimulated human mononuclear leucocyte-conditioned medium augments the basal and stimuli-induced neutrophil respiratory burst and degranulation. 357 Mar 57

Metabolism of tamoxifen by rat hepatocytes and hydrolysis of the resulting polar metabolites corresponding to conjugates with beta-glucuronidase gave a major component which was identified as 1-[4-(2-hydroxyethoxy)phenyl]-1-(4-hydroxyphenyl)-2-phenyl-1-butene by comparison of mass spectral properties with those of synthetic material. This compound, which was not observed as a phase I metabolite, is believed to have been found previously in rat bile and in human faeces (metabolite F) but its structure had been incorrectly assigned. Its binding affinity for the estrogen receptor was greater than that of tamoxifen but less than that of 4-hydroxytamoxifen, and it possessed a corresponding degree of antitumour activity against the MCF-7 breast cancer cell line. By carrying out the hepatocyte incubation separately under oxygen and air, it has been shown that the N-oxidation of tamoxifen is favoured by a high concentration of oxygen during in vitro metabolism but that the rate of 4-hydroxylation is not dependent on oxygen availability.
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PMID:Metabolism of tamoxifen by isolated rat hepatocytes. Identification of 1-[4-(2-hydroxyethoxy)phenyl]-1-(4-hydroxyphenyl)-2-phenyl-1-butene and the dependence of N-oxidation on oxygen availability. 357 87

The concentration of lipid peroxides in the plasma and synovial fluid of 65 arthritic patients was determined using a new ion-pairing reverse phase HPLC technique. Patients with rheumatoid arthritis receiving only non-steroidal anti-inflammatory drugs, had a significantly higher mean concentration of lipid peroxides in synovial fluid samples (162 +/- 22.0 micrograms/l) than osteoarthritic patients (40.0 +/- 8.0 micrograms/l, p less than 0.0001). Mean concentrations in both groups correlated strongly with the level of beta-glucuronidase activity as a measure of lysosomal enzyme release (r = 0.71, p less than 0.0001). Contrary to previous reports by investigators using less specific methods, we were unable to demonstrate any increase in plasma levels of lipid peroxides in the rheumatoid patient. Treatment of rheumatoid arthritis with D-penicillamine was associated with a significant reduction of lipid peroxide levels (83.2 +/- 11.5 micrograms/ml, p less than 0.002), suggesting that this drug may function as an oxygen radical scavenger in the joint cavity. These results give further support to the concept of oxygen-free radicals playing an important role in the pathogenesis of chronic inflammatory disorders.
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PMID:Lipid peroxidation and malondialdehyde in the synovial fluid and plasma of patients with rheumatoid arthritis. 359 15

An influx of polymorphonuclear and mononuclear cells into the lungs of smokers and patients with chronic obstructive lung disease (COLD) is thought to be an important factor in the development of pulmonary emphysema. Next to the synthesis and release of toxic oxygen radicals and mediators, an enhanced production and activity of proteolytic enzymes could play an important role in the pathogenesis of emphysema. In the present study changes were investigated in the broncho-alveolar lavage (BAL) fluid and BAL-cells, especially in alveolar macrophages. Pulmonary lavages were performed in the middle lobe with sterile saline of 37 degrees C in individuals, who could be divided on the basis of their history and lung function into normal/nonsmokers, normal/smokers, COLD-patients/nonsmokers and COLD-patients/smokers. Alveolar macrophages obtained by BAL were stained for different lysosomal enzymes. Isolated BAL-fluid and BAL-cells were assayed for elastolytic activity. In alveolar macrophages of smoking COLD-patients significantly more beta-glucuronidase could be demonstrated. Elastolytic activity changed with smoking habits, suggesting an enhanced release of elastolytic enzymes. No correlation was found between elastolytic activity and the amount of polymorphonuclear cells in the BAL-fluid. From these results it may be concluded that enzymes from alveolar macrophages play a more important role in the pathogenesis of emphysema than those from polymorphonuclear cells.
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PMID:Changes in alveolar macrophage enzyme content and activity in smokers and patients with chronic obstructive lung disease. 359 69

Eosinophils from the blood of normal individuals were purified by centrifugation over discontinuous Percoll gradients. Eosinophil suspensions were obtained with a mean purity of 96% and a mean recovery of 64% (n = 19). When incubated with phorbol-myristate acetate, eosinophils consumed twice as much oxygen as did neutrophils from the same donors. With serum-treated zymosan, 70% and 100% of the maximal oxidative response (i.e. the response to phorbol-myristate acetate) was obtained with eosinophils and neutrophils, respectively. The calcium ionophore A23187 is a weak stimulus that triggered only 2.5% of the eosinophil and 10% of the neutrophil oxidative capacity. The response of both cell types to formyl-methionyl-leucyl-phenylalanine (fMLP) was rapid, with a maximum after 3 min. The magnitude of this eosinophil reaction was half that of neutrophils. Although the activities of the granule enzymes beta-glucuronidase and arylsulphatase were 2.5 and 6 times higher in eosinophils than in neutrophils, respectively, the exocytosis of these enzymes in response to various stimuli was lower in eosinophils. The high yield of eosinophils from our separation method enabled us to prepare eosinoplasts by centrifugation of eosinophils over discontinuous Ficoll gradients that contained cytochalasin B. Eosinoplasts are plasma membrane vesicles derived from eosinophils, filled with cytoplasm but devoid of granules and nucleus. The eosinoplasts contained 30% of the cytoplasm and plasma membrane present in intact eosinophils. Eosinoplasts still possessed a functionally intact oxidase enzyme that could be stimulated with various stimuli. Therefore, eosinoplasts may provide a valuable tool to study separately the role of the oxidase products and that of the granule contents in eosinophil functions.
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PMID:Purification of eosinophils from normal human blood, preparation of eosinoplasts and characterization of their functional response to various stimuli. 381 66

Although a number of skin diseases are characterized by the presence of an increased number of phagocytes in their lesions, the effects of alcohol on phagocytic functions are not clearly understood. Therefore, we measured the influence of ethanol and acetaldehyde on the generation of oxygen radicals, chemotaxis and the release of lysosomal enzymes from human phagocytes. We added 0.03%-3% ethanol and 0.005%-0.25% acetaldehyde to cell cultures. We found that both ethanol and acetaldehyde suppressed the generation of oxygen radicals from granulocytes and monocytes; the ID50 was achieved at concentrations of approximately 0.25% for ethanol and 0.03% for acetaldehyde. A significant inhibition of granulocyte chemotaxis was first noted with 0.063% ethanol and 0.016% acetaldehyde. Ethanol and acetaldehyde inhibited the release of the lysozyme of monocytes at concentrations of greater than 0.75% and greater than 0.03% respectively, but granulocytes were unaffected; the release of beta-glucuronidase and lactate dehydrogenase remained stable. Due to the high volatility of the agents, especially acetaldehyde, under the experimental procedures employed, the actual concentrations of the agents were probably lower and similar to those measured in vivo. Our results indicate that defined phagocytic functions are strongly inhibited by concentrations of ethanol and acetaldehyde which are associated with moderate to severe inebriation.
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PMID:Effects of ethanol and acetaldehyde on phagocytic functions. 398 69

Perturbation of the neutrophil membrane by opsonized zymosan particles activates the cell's "respiratory burst." Associated with this activation process is the generation of highly reactive oxygen products, including superoxide, and the release of lysosomal enzymes. Membrane activation also stimulates arachidonic acid metabolism and the generation of a wide variety of products through both the lipoxygenase and cyclooxygenase pathways. In isolated human neutrophils, we have evaluated the effects inhibitors of cyclooxygenase and lipoxygenase upon opsonized zymosan stimulated chemiluminescence, superoxide generation, oxygen consumption, and beta-glucuronidase release. Nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase enzyme, suppressed chemiluminescence, superoxide generation, oxygen consumption, and beta-glucuronidase release. Both indomethacin, a cyclooxygenase inhibitor, and 5,8,11,14 - eicosatetraynoic acid (ETYA) an inhibitor of both cyclooxygenase and lipoxygenase, inhibited all tested neutrophil functions. However, when compared to NDGA, indomethacin and ETYA were considerably less potent. Our observations suggest that the lipooxygenase derived metabolites play a predominant regulatory role in these neutrophil inflammatory functions.
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PMID:Regulation of the human polymorphonuclear leukocyte inflammatory response by inhibitors of arachidonic acid metabolism. 609 11


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