Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two molecularly and kinetically distinct major species of the extracellular nuclease BAL 31 from Alteromonas espejiana, previously characterized as the "fast" (F) and "slow" (S) BAL 31 nucleases, have been evidenced to derive from proteolysis starting from a still larger (approximately 120 kDa) precursor nuclease. The expected protease activity in the culture fluid has been confirmed and is strongly dependent on the cell growth phase. The disappearance of the largest nuclease species with the concomitant sequential appearance of first the F and then the S species has been demonstrated for nuclease obtained from culture supernatants as a function of cell growth phase. Nuclease from periplasmic extracts displayed very little of the F and S nucleases. Treatment of purified F nuclease with Pronase or subtilisin readily converted it to species with only a few percent of the native exonuclease activity against duplex DNA but retaining much of the initial activity against single-stranded DNA. Electrophoresis in nuclease-detecting gels demonstrated a parallel conversion of the larger species to one indistinguishable in molecular weight from the S species. The observed loss of exonuclease activity could correspond to the conversion of the F to the S nuclease. However, treatment of S nuclease with subtilisin resulted in a drastic reduction of exonuclease activity of this enzyme on duplex DNA with retention of most of the activity against single-stranded and nicked circular duplex DNA substrates. Evidence of internal proteolysis of the S nuclease could be seen after electrophoresis in denaturing gels but only after the denaturation buffer was adjusted to 6 M in urea. The preferential removal of the exonuclease activity may enhance the usefulness of the BAL 31 nuclease in such applications as heteroduplex mapping.
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PMID:Precursor-product relationship of larger to smaller molecular forms of the BAL 31 nuclease from Alteromonas espejiana: preferential removal of duplex exonuclease relative to endonuclease activity by proteolysis. 230 7

Idiopathic pulmonary fibrosis (IPF) is characterized by an increased oxidant burden and by a deficiency of glutathione, a major antioxidant, in the lung epithelial lining fluid (ELF). Therefore, a rational therapeutic approach is to reverse the imbalance between oxidants and antioxidants in the lung by enhancing the antioxidant screen. With this background, the aim of our study was to evaluate oral N-acetylcysteine (NAC) as a strategy to augment lung glutathione levels in patients with IPF. Concentrations of total glutathione in bronchoalveolar lavage fluid (BALF) were quantified spectrophotometrically, before and following oral therapy with 3 x 600 mg NAC per day for 5 days, in 17 nonsmoking patients with biopsy-proven IPF. The volume of ELF recovered by BAL was determined using the urea method. Pretherapy, total glutathione levels in ELF in IPF patients were significantly less than normal (187 +/- 36 vs 368 +/- 60 microM), in contrast to levels in BALF (0.99 +/- 0.12 vs 1.18 +/- 0.19 microM). Following therapy with oral NAC, glutathione levels in BALF were 1.54 +/- 0.24 microM (a significant increase compared to pretherapy), whereas the increase in ELF levels (319 +/- 92 microM) did not reach significance. The therapy was well-tolerated, and all routine clinical and bronchoscopic parameters remained unchanged. It is thus feasible and safe to augment deficient lung glutathione levels in patients with IPF; thereby, potentially augmenting pulmonary antioxidant protection.
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PMID:The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis. 801 95

Plasma protein exudation into the airways is an important pathophysiological event in asthma. The effect of 12 wk of treatment with inhaled fluticasone propionate (FP; 250 microgram twice a day) or salbutamol (Sb; 400 microgram twice a day) on plasma protein leakage was compared in a double-blind, randomized parallel-group study of 30 patients with asthma. Primary outcomes were plasma protein leakage and size selectivity of the blood-airway lumen barrier, cell differentials in BAL fluid, and bronchial responsiveness to histamine (PC20histamine). Two independent procedures to account for the effect of variable dilution of BAL on the levels of albumin (Alb) and alpha2-macroglobulin (A2M) in BAL fluid consisted of correction based on urea levels and on the application of the relative coefficient of excretion [RCE = ([A2M] in BAL fluid/[A2M] in serum)/([Alb] in BAL fluid/[Alb] in serum)]. In the FP group a significant decrease was found in the A2M level and the RCE, and in the percentage of eosinophils in BAL fluid. The PC20histamine increased significantly (mean increase, 2.4 doubling doses), whereas PC20histamine decreased in the Sb group. Differences between groups were significant except for the decrease in eosinophils. We conclude that 12 wk of FP (250 microgram twice a day) decreased the permeability of the blood-airway lumen barrier, in particular for high molecular weight proteins.
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PMID:A double-blind study on the effect of inhaled corticosteroids on plasma protein exudation in asthma. 1022 17

Definitive analysis of solute concentrations in lung lavage fluid involves the use of a marker of dilution to correct for variable recovery of epithelial lining fluid (ELF), but the question of the most appropriate dilutional marker remains unresolved. In lavage fluid collected from infants with lung disease and healthy control subjects, we examined ELF concentration of protein, albumin, sphingomyelin (SM), and IgA secretory component (SC), and critically appraised the relative validity of SC and urea as dilutional markers in the context of lung infection and lung injury. Protein, albumin, and SM were found not to be valid dilutional markers, as their ELF concentration varied significantly between the diseased, recovering, and normal lung. Differences in concentration were noted in both tracheal aspirate samples (TA, 4 x 0.5 ml) and nonbronchoscopic bronchoalveolar lavage fluid (NB-BAL, 3 x 1 ml/kg), but were not uniform (e.g., TA-disease versus control: albumin 2.8 versus 0.68 mg/ml, SM 45 versus 16 microgram/ml, both p < 0.05; NB-BAL-disease versus recovery: protein 8.1 versus 4.8 mg/ml, albumin 2.9 versus 1. 4 mg/ml, both p < 0.05). Overall, SC concentrations in ELF were not different between the diseased and normal lung, but in the NB-BAL samples, significantly higher SC concentration was noted in viral bronchiolitis and pneumonia than in noninfective lung diseases. No clear evidence of additional influx of urea into lavage fluid in association with epithelial disruption was found in the diseased lung. Comparative analysis of SC and urea revealed no difference in TA samples, but in NB-BAL specimens, urea best standardized the lavage concentration of surfactant indices to correspond to the degree of lung dysfunction as indicated by oxygenation index. We conclude that SC and urea, but not protein, albumin, or SM, are valid dilutional markers with which to estimate ELF recovery during small volume lung lavage. Urea appears a more appropriate choice in return fluid derived from the distal tracheobronchial tree, and SC should not be used in the context of lung infection.
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PMID:Validity of markers of dilution in small volume lung lavage. 1047 96

An important application of primary hepatocyte cultures is for hepatotoxicity research. In this paper, gel entrapment culture of rat hepatocytes in miniaturized BAL system were evaluated as a potential in vitro model for hepatotoxicity studies in comparison to monolayer cultures. After exposure for 24 and 48 h to acetaminophen (2.5 mM), gel entrapped hepatocytes were more severely damaged than hepatocyte monolayer detected by methyl thiazolyl tetrazolium (MTT) reduction, intracellular glutathione (GSH) content, reactive oxygen species (ROS) levels, urea genesis and albumin synthesis. CYP 2E1 activities detected by 4-nitrocatechol (4-NC) formation were higher in gel entrapped hepatocytes than in hepatocyte monolayers while the addition of CYP 2E1 inhibitor, diethyl-dithiocarbamate (DDC), more significantly reduced acetaminophen-induced toxicity in gel entrapped hepatocytes. In addition, protective effects of GSH, liquorice extract and glycyrrhizic acid against acetaminophen hepatotoxicity were clearly observed in gel entrapped hepatocytes but not in hepatocyte monolayer at an incubation time of 48 h. Overall, gel entrapped hepatocytes showed higher sensitivities to acetaminophen-induced hepatotoxicity than hepatocyte monolayer by a mechanism that higher CYP 2E1 activities of gel entrapped hepatocytes could induce more severe acetaminophen toxicity. This indicates that gel entrapped hepatocytes in hollow fiber system could be a promising model for toxicological study in vitro.
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PMID:Acetaminophen-induced hepatotoxicity of gel entrapped rat hepatocytes in hollow fibers. 1679 10

Sepsis is still a major cause of the high mortality rate in the intensive care unit. Many studies have been published about the severity of sepsis, but the cause of mortality in sepsis and multiorgan failure is still obscure. This study investigated the effects of caffeic acid phenethyl ester (CAPE) particularly on the inflammatory and related histopathological changes in the lung, liver and kidney in an experimental sepsis model. Forty Sprague Dawley rats were used in this study, and were divided into four groups of ten rats each, as follows: Group I was given intraperitoneal saline infusion treatment. Group II was given intraperitoneal CAPE infusion treatment. Sepsis was induced in the animals in Group III (sepsis with saline infusion), while Group IV rats underwent induced sepsis plus CAPE infusion treatment (sepsis with CAPE infusion). Sampling was performed 48 h after treatment. The induction of sepsis resulted in a significant increase in serum glucose, leukocytes, urea, creatinine, LDH levels in BAL, plasma MDA, AST and ALT levels in the sepsis + saline group. The use of CAPE significantly decreased these parameters. Histopathological examination revealed less congestion, portal inflammation, and focal necrosis of the liver, and less congestion, edema, and emphysematous and inflammatory changes in the lung in the sepsis + CAPE group than in the other groups. These results support that CAPE may be used for the treatment of organ failure during sepsis.
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PMID:Effects of caffeic acid phenethyl ester (CAPE) on sepsis in rats. 1860 6

Acute chest syndrome (ACS) is the leading cause of ICU admission in patients with sickle cell disease and is characterized by golden sputum, which is commonly attributed to the presence of bilirubin. Three young consecutive patients with homozygous sickle cell disease were admitted for severe acute respiratory syndrome due to ACS. In all 3 patients, tracheal secretions and bronchoalveolar lavage fluid (BALF) showed a yellowish plasma-like stain. After normalization for the plasma-to-BAL urea ratio, BALF protein and lactate dehydrogenase levels were consistent with an exudative process. BALF bilirubin concentrations were very low, implying that the yellowish stain was not related to bilirubin content. The yellowish coloration of tracheal secretions and BALF observed during ACS appears to be related to an intense exudative process rather than to the presence of bilirubin.
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PMID:Golden tracheal secretions and bronchoalveolar fluid during acute chest syndrome in sickle cell disease. 2531 91