Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Human monocytes isolated from peripheral blood responded with increased thromboplastin expression upon stimulation in vitro with three mycobacterial antigens: tuberculin purified protein derivative and sonicates of Mycobacterium boviS BCG and Mycobacterium leprae. The stimulating principle of mycobacteria is probably a cell wall constituent since crude extracts of cell walls were 2.5 to 25 times more potent in stimulating thromboplastin synthesis than were whole sonicates. This thromboplastin response was inhibited by inhibitors of RNA and protein synthesis, dexamethasone, and agents that caused elevation of intracellular cyclic AMP. The presence of lymphocytes did not enhance the monocyte thromboplastin response significantly during the first 24 h of incubation. For M. bovis BCG and M. leprae sonicates, the thromboplastin response correlated with general activating effects measured by determining the release of lysozyme and beta-glucuronidase. The role of thromboplastin in chronic inflammatory reactions is discussed.
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PMID:Effect of purified protein derivative and sonicates of Mycobacterium leprae and Mycobacterium bovis BCG on thromboplastin response in human monocytes in vitro. 618 26

12-O-Tetradecanoylphorbol 13-acetate (TPA), phorbol 12,13-diacetate and phorbol 12,13-didecanoate were all potent inducers of thromboplastin activity in human monocytes in vitro, whereas 4 alpha-phorbol 12,13-didecanoate and 4 alpha-phorbol had no such effect. A concomitant increase in titrable apoprotein III antigen was found (apoprotein III is the protein component of thromboplastin). The increase was inhibited by cycloheximide and actinomycin D and partly by alpha-amanitin. The increase of thromboplastin activity was therefore most likely due to synthesis de novo of apoprotein III. The response was approximately halved in the absence of serum or Ca2+. Retinol had a weak inhibitory effect, and retinoic acid was inhibitory only at concentrations that also induced signs of cytotoxicity. TPA caused an initial rise in monocyte cyclic AMP concentration of about 90-120 min duration. No increase in 45Ca2+ influx was induced over 2 h. Good correlation exists between induction of apoprotein III synthesis in monocytes in vitro and mouse skin-tumour promotion in vivo by the various phorbol derivatives. Substances inactive in tumour promotion do not induce the synthesis of apoprotein III. General activating and cytotoxic effects of TPA were monitored by determining release of lysozyme, beta-glucuronidase and lactate dehydrogenase.
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PMID:Phorbol esters induce synthesis of thromboplastin activity in human monocytes. 627 36

C5a is an inflammatory mediator that evokes a variety of immune effector functions including chemotaxis, cell activation, spasmogenesis, and immune modulation. It is well established that the effector site in C5a is located in the C-terminal region, although other regions in C5a also contribute to receptor interaction. We have examined the N-terminal region (NTR) of human C5a by replacing selected residues in the NTR with glycine via site-directed mutagenesis. Mutants of rC5a were expressed as fusion proteins, and rC5a was isolated after factor Xa cleavage. The potency of the mutants was evaluated by measuring both neutrophil chemotaxis and degranulation (beta-glucuronidase release). Mutants that contained the single residue substitutions Ile-6-->Gly or Tyr-13-->Gly were reduced in potency to 4-30% compared with wild-type rC5a. Other single-site glycine substitutions at positions Leu-2, Ala-10, Lys-4, Lys-5, Glu-7, Glu-8, and Lys-14 showed little effect on C5a potency. The double mutant, Ile-6-->Gly/Tyr-13-->Gly, was reduced in potency to < 0.2%, which correlated with a correspondingly low binding affinity for neutrophil C5a receptors. Circular dichroism studies revealed a 40% reduction in alpha-helical content for the double mutant, suggesting that the NTR contributes stabilizing interactions that maintain local secondary or tertiary structure of C5a important for receptor interaction. We conclude that the N-terminal region in C5a is involved in receptor binding either through direct interaction with the receptor or by stabilizing a binding site elsewhere in the intact C5a molecule.
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PMID:Site-specific mutations in the N-terminal region of human C5a that affect interactions of C5a with the neutrophil C5a receptor. 840 Dec 25

We found a new, highly selective plasma kallikrein inhibitor, trans-4-aminomethyl-cyclohexanecarbonylphenylalanine 4-carboxymethylanilide hydrochloride, called PKSI-527 in our laboratories. This study was conducted to evaluate PKSI-527, on thromboplastin (TP)- and endotoxin (LPS)-induced disseminated intravascular coagulation (DIC) in rats. PKSI-527 was infused intravenously at 0.1 mg/kg/min for 250 min. Three of the parameters of the coagulation and fibrinolysis system, fibrinogen level, platelet counts and fibrin(ogen) degradation products (FDP) level were assayed. PKSI-527 prevented the change in the coagulation and fibrinolysis system in LPS-induced DIC, however it was not clearly effective in TP-induced DIC. The parameters of organ failure, such as serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), creatine phosphokinase (CPK), lactate, blood urea nitrogen and beta-glucuronidase, were assayed. Although the changes in the fibrinogen level, platelet counts and FDP level were almost the same in both models, the parameters of organ failure apparently increased in LPS-induced DIC more so than in TP-induced DIC. PKSI-527 significantly suppressed the increases in GOT and GPT in LPS-induced DIC. These results indicate that plasma kallikrein may play a significant role in LPS-induced DIC. Therefore, PKSI-527, as a synthetic plasma kallikrein inhibitor may be a valuable tool to explore the mechanism of DIC and the accompanying organ failure.
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PMID:Effects of a highly selective synthetic inhibitor of plasma kallikrein on disseminated intravascular coagulation in rats. 874 31

In neonatal respiratory distress syndrome activation of inflammation and clotting is demonstrated. High frequency oscillatory ventilation (HFOV) is considered to be less damaging to the human preterm lung, resulting in less activation of inflammation and clotting compared with conventional ventilation (CV). To assess the sequence of events of activation of inflammation and clotting and to compare the impact of HFOV to CV, we ventilated preterm lambs delivered by cesarean section at 132 d gestational age (term 145 d) for 8 h by CV (n = 10) or HFOV (n = 11). Fifteen minutes after birth and at 2-h intervals thereafter blood samples, from umbilical catheters, were analyzed for AP50 (complement activation), number of polymorphonuclear leukocytes, beta-glucuronidase, platelet function, activated partial thromboplastin time, thrombin time and thrombin inhibition, and bronchoalveolar lavage fluid was analyzed for elastase, thrombin and protein. We found complement activation, low number of polymorphonuclear leukocytes and high levels of beta-glucuronidase already at 15 min after birth. Within 2 to 4 h after birth platelet function deteriorated, activated partial thromboplastin time prolonged, and thrombin inhibition decreased. Activation of inflammation and clotting in the lungs was demonstrated by increased levels of elastase and thrombin in bronchoalveolar lavage fluid. In the HFOV group, AP50 remained significantly higher than in the CV group, reflecting less complement activation, and platelet function analysis remained significantly lower, reflecting better platelet function. We conclude that systemic activation of inflammation can be found in the ventilated preterm lamb with respiratory distress syndrome within 15 min after birth. Afterward, or due to activation of inflammation, clotting is activated. HFOV possibly attenuates activation of inflammation.
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PMID:Early activation of inflammation and clotting in the preterm lamb with neonatal RDS: comparison of conventional ventilation and high frequency oscillatory ventilation. 1164 62

Recently we have shown that activation of inflammatory reaction and clotting can be found immediately after delivery in preterm lambs ventilated for respiratory distress syndrome (RDS). To investigate whether antenatal glucocorticoids would attenuate postnatal activation of the inflammatory reaction and clotting, we studied ventilated preterm lambs delivered by cesarean section, 24 h after antenatal administration of betamethasone or placebo. Blood was sampled before clamping the cord, 5, 10, and 15 min after delivery, and 2-hourly afterwards. Blood was used to determine oxygenation index, alveolar - arterial partial O(2) difference (AaDO(2)), AP50 titer (see text), polymorphonuclear leukocytes (PMNs), beta-glucuronidase, thrombin inhibition, activated partial thromboplastin time, and clot lysis time. Bronchoalveolar lavage fluid was sampled before clamping the cord and 30 min and 1, 2, 4, 6 and 8 h after delivery and was analyzed for elastase, thrombin, and protein. After removal of the lungs, static compliance and water content of the lungs were determined. We found that betamethasone-treated lambs had lower oxygenation index and AaDO(2) than controls. At birth, PMN levels were higher, and the beta-glucuronidase level was lower after betamethasone treatment. PMNs and beta-glucuronidase did not change in betamethasone-treated lambs, in contrast to controls. Thrombin inhibition, activated partial thromboplastin time, and clot lysis time did not change in betamethasone-treated lambs, in contrast to controls. In both groups, elastase and protein levels in bronchoalveolar lavage fluid increased; the thrombin level increased in controls. The static compliance was better, and the water content of the lung was lower in the betamethasone-treated lambs. We conclude that early systemic activation of inflammatory reaction and clotting in preterm lambs with RDS are attenuated by antenatal betamethasone administration. Whether this is a direct effect of betamethasone on the inflammatory reaction or a result of a reduced ventilatory support because of less severe RDS after antenatal betamethasone treatment remains to be elucidated.
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PMID:Antenatal glucocorticoids attenuate activation of the inflammatory reaction and clotting in preterm lambs. 1463 Nov 53

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