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)

The prolonged exposure to formaldehyde induces in the rabbit lung reactional and dystrophic changes involving the intrapulmonary bronchi, the bronchioli and the lung tissue. These changes are represented by bronchial cell hyperplasia with hypermucigenesis, extrusion of bronchial cells, bronchiolar hypermucigenesis, parcellary squamous metaplasia or necrobiosis of epithelia, thickening of bronchial and bronchiolar walls by subepithelial cell accumulations, destruction of musculo-elastic structures with stenosis or ectasia; the vascular reactions are hyperhaemic and proliferative with an obstructive and fibrous tendency; the parenchymal lesions are atelectasias, intralobular emphysema, and cellular thickening of alveolar walls and interlobular areas. The acid phosphatase, Tween-60-esterase, naphthol-AS-D-acetate-esterase, proline-oxidase and hydroxyproline-2-epimerase activities are increasing, while the leucyl-aminopeptidase and beta-glucuronidase ones are decreasing. The qualitative observations are completed and sustained by quanitative studies of mucous cell kinetics, of cell accumulations and differentiations.
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PMID:Experimental chronic obstructive lung disease. I. Bronchopulmonary changes induced in rabbits by prolonged exposure to formaldehyde. 15 Dec 23

In an effort to determine the mechanism of papain action in causing an emphysema-like lesion in hamsters, the number and types of cells and the activities of two lysosomal enzymes in the lung were determined after papain exposure. Three and four weeks after a 3-h exposure to an aerosol of 3% papain the following alterations in lung structure and function were observed: (1) the mean linear intercept, or average distance between adjacent alveoli, was increased; (2) the internal surface area declined; (3) the dynamic compliance was elevated at low breathing frequencies. The numbers of cells present free in the lung increased from a control value of 2.0 +/- 0.2 x 10 (6) to 6.6 +/- 0.5 x 10 (6) 5 days after exposure. The free beta-glucuronidase, alysosomal enzyme, likewise increased over threefold during the first 3 days after exposure. These results are consistent with the hypothesis that papain induces an inflammatory-type responses, and this may be in part responsible for inducing the lesion.
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PMID:Pathogenesis of papain-induced emphysema in the hamster. 68 Sep 50

Evidence is accumulating that cigarette smoking plays an important role in the protease-antiprotease imbalance in alpha 1-antitrypsin-sufficient emphysema. Since most smokers, however, do not develop emphysema, it has to be presumed that other factors in addition to smoking contribute to the origin of the imbalance. The major source of proteases is the polymorphonuclear leucocyte (PMN). We tested the hypothesis that an abnormality in the releasability of PMN might predispose for the development of emphysema. Therefore, the release of elastase, myeloperoxidase, and beta-glucuronidase from PMN was investigated in patients with emphysema and healthy controls, matched for sex, age, and smoking habits. PMN were isolated from peripheral blood and stimulated with calcium-ionophore A23187, formyl-methionyl-leucyl-phenylalanine (FMLP), and serum-treated zymosan (STZ). Total enzyme content of PMN was measured after cell lysis with Triton X-100. Total elastase, myeloperoxidase, and beta-glucuronidase content of PMN were not significantly different in healthy subjects and patients with emphysema. In vitro release of elastase and myeloperoxidase from both stimulated and unstimulated PMN was not significantly different in healthy subjects and emphysematous patients. Moreover, no differences were found between smoking and ex-smoking individuals. Beta-glucuronidase release tended to be lower in patients with emphysema than in healthy controls. We conclude that an abnormality in the releasability of peripheral PMN is unlikely to be a pathogenetic factor in emphysema.
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PMID:In vitro release of neutrophil elastase, myeloperoxidase and beta-glucuronidase in patients with emphysema and healthy subjects. 166 65

In two divisions of a chemical plant producing dust pesticides, employees exposed to dust, containing 28%-65% SiO2, were examined. In the first division (group I, 38 males and 35 females), the average air dust concentration was 5.0 mg/m3, and the active substances were: chlorinated hydrocarbons, captan, carbamates and dodine. In the other division (group II, 26 males and 33 females), the air dust concentration was 4.8-5.2 mg/m3, and the active substances included: carbamates, triazine compounds, cupric oxychloride, captan, lindane, carboxine. Spirographic investigations showed signs of pulmonary emphysema (RV/TLC) in 65.8% males and 60% females of group I and 38.5% males and 40.6% females of group II. In leucocyte concentrate smears, the cytochemical reactions to beta-glucuronidase, acid phosphatase and myeloperoxidase, as well as the nitroblue tetrazolinum (NBT)-dye reduction of neutrophils were performed. The random migration and chemotaxis of isolated neutrophils, washed or incubated in 10% autologous serum, their phagocytic activity and tube adherence test were also investigated. Compared to the controls, the reaction to beta-glucuronidase as well as the NBT reduction were increased, whereas the acid phosphatase and myeloperoxidase reactions were lowered. Impairment of neutrophil chemotaxis stimulated with zymozan-activated serum was observed in all groups of workers; random migration was enhanced in workers of group I and lowered in male workers of group II. Higher phagocytosis of latex particles occurred in workers of group I and in males of group II, while tube adhesion was impaired in group I and enhanced in males of group II.
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PMID:Neutrophil function in chemical plant workers employed in the production of dust pesticides. 181 42

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

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

Homogenates of liver from cases of hepatic cirrhosis due to alpha 1-antitrypsin deficiency (PiZZ) alcoholism were analyzed for their content of various lysosomal enzymes. Also determined were the specific activities of lactate dehydrogenase, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, and creatine phosphokinase in the extracts of liver from cases of both kinds of hepatic cirrhosis: all of these activities were within the range of control values. Similarly, the specific activities of the following lysosomal hydrolases were unremarkable: acid phosphatase, beta-mannosidase, beta-fucosidase, beta-glucuronidase and beta-glucosidase. Hexosaminidase specific activity was increased twofold in livers from the cases of cirrhosis due to alpha 1-antitrypsin deficiency. The specific activity of alpha-mannosidase (measured at pH 4.5) in homogenates of livers from PiZZ individuals with cirrhosis and those with alcoholic cirrhosis was increased two- to four-fold. Chromatography of the high-speed supernatant fraction from homogenates of livers of cirrhotic and noncirrhotic individuals on columns of DEAE-cellulose resolved alpha-mannosidase activity into two components: under the conditions employed, acid pH optimum (pH 4.5) alpha-mannosidase did not bind to the resin, whereas intermediate pH optimum (pH 5.5) alpha-mannosidase could be eluted with 0.1 mol/l NaCl. Liver from one case of (PiZZ) alpha 1-antitrypsin deficiency and emphysema, without demonstrable cirrhosis, was found to contain normal levels of both acid alpha-mannosidase and intermediate alpha-mannosidase. However, cases of cirrhosis due to alpha 1-antitrypsin deficiency contained twice as much acid alpha-mannosidase and only one third to one fourth as much intermediate alpha-mannosidase as controls. The deficiency in hepatic intermediate alpha-mannosidase was also observed in 5 of 5 cases of alcoholic cirrhosis.
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PMID:Altered alpha-mannosidase isoenzymes in the liver in hepatic cirrhosis. 697 51

Klotho gene mutation leads to a syndrome strangely resembling chronic kidney disease patients undergoing dialysis with multiple accelerated age-related disorders, including hypoactivity, sterility, skin thinning, muscle atrophy, osteoporosis, vascular calcifications, soft-tissue calcifications, defective hearing, thymus atrophy, pulmonary emphysema, ataxia, and abnormalities of the pituitary gland, as well as hypoglycemia, hyperphosphatemia, and paradoxically high-plasma calcitriol levels. Conversely, mice overexpressing klotho show an extended existence and a slow aging process through a mechanism that may involve the induction of a state of insulin and oxidant stress resistance. Two molecules are produced by the klotho gene, a membrane bound form and a circulating form. However, their precise biological roles and molecular functions have been only partly deciphered. Klotho can act as a circulating factor or hormone, which binds to a not yet identified high-affinity receptor and inhibits the intracellular insulin/insulin-like growth factor-1 (IGF-1) signaling cascade; klotho can function as a novel beta-glucuronidase, which deglycosylates steroid beta-glucuronides and the calcium channel transient receptor potential vallinoid-5 (TRPV5); as a cofactor essential for the stimulation of fibroblast growth factor (FGF) receptor by FGF23. The two last functions have propelled klotho to the group of key factors regulating mineral and vitamin D metabolism, and have also stimulated the interest of the nephrology community. The purpose of this review is to provide a nephrology-oriented overview of klotho and its potential implications in normal and altered renal function states.
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PMID:Klotho: an antiaging protein involved in mineral and vitamin D metabolism. 2241 41

The discovery that two recently identified molecules, klotho and fibroblast growth factor 23 (FGF23), played an important role in calcium, phosphate, and vitamin D metabolism has transformed our traditional physiological view in which bone and mineral homeostasis was mainly regulated by parathyroid hormone, vitamin D, and calcitonin, according to mineral body needs. FGF23 is a 251-amino acid secreted protein produced by osteoblasts and osteocytes in bone following the stimulation by phosphate and vitamin D or the inhibition by dentin matrix protein 1. Originally isolated from tumoral cells of patients with tumor-induced osteomalacia and hypophosphatemia, FGF23 inhibits phosphate reabsorption in renal proximal tubular cells and 1alpha-hydroxylase activity, resulting in decreased synthesis of calcitriol. To exert these actions, FGF23 requires the conversion, by klotho, of the canonical FGF receptor 1 (IIIc) in a specific high affinity FGF23 receptor. On the other hand, klotho is a putative antiaging gene identified in 1997 when a particular mouse strain, created by random insertion mutagenesis, was found to be short-lived and displayed premature atherosclerosis, osteopenia, skin atrophy, pulmonary emphysema, hyperphosphatemia, hypercalcemia, and high serum calcitriol levels. The gene of klotho encodes a 1012-amino acid cell-surface protein with a short cytoplasmic tail and an extracellular domain that consists in tandem duplicated copies of a beta-glucuronidase-like sequence, which can be released into the circulation as soluble forms after being cleaved by metalloproteinases such as ADAM10 and ADAM17. By modulating FGF23 action, klotho regulates urinary phosphate excretion and calcitriol synthesis. By virtue of its beta-glucuronidase activity, klotho deglycosylates the calcium channel TRPV5 (transient receptor potential vallinoid-5) and regulates urinary calcium excretion. klotho also binds to Na(+),K(+)-ATPase in parathyroid cells and regulates calcium-stimulated PTH secretion. Finally, klotho extends life span via several mechanisms, including the reduction of calcitriol synthesis, serum calcium, and phosphorus levels; the induction of insulin resistance; and by increasing the resistance to oxidative stress.
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PMID:Klotho gene, phosphocalcic metabolism, and survival in dialysis. 1912 71