Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476273 (respiratory distress)
 19,632 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In untreated patients with inoperable lung cancer, serum levels of alpha1-antitrypsin were found significantly increased in comparison to patients with non malignant diseases of the lung, alpha2-macroglobulin levels were unchanged in both groups of patients. There was also no difference in alpha2-macroglobulins in cancer patients reacting with DNCB and in non-reactors. Thus alpha2-macroglobulin levels do not seem to correlate with the immunestatus of cancer patients. Proteinase inhibitors are involved in a variety of biological processes including blood, clotting, digestion, and sperm capacitation. alpha1-antitrypsin, a alpha-globulin with a molecular weight of about 60,000 has been found to be decreased in patients' serum under several pathological conditions. A clear correlation exists between alpha1-antitrypsin deficiency and hereditary pulmonary emphysema (1, 2), respiratory distress syndrome (3), and juvenile cirrhoses of the liver (4). Elevated serum levels of alpha1-antitrypsin have also been found in some cancer cases. Thirty years ago a cancer test was developed on the basis of differences in the antiproteolytic activity in cancer patients' sera and in patients with other non-neoplastic diseases (5, 6). Several authors have tried to confirm these early data regarding specifity and sensitivity with respect to a screening test for cancer (7, 8). Methods of these authors were based mainly on enzyme substrate inhibition assays by addition of the patients' sera. Recently a commercially available test, based on immune-precipitation according to Mancini (9), has been developed (Behring-Werke, Partigen). By using this standardized method for determinating alpha1-antitrypsin, Harris et al. have recently demonstrated that patients with inoperable lung cancer have significantly elevated levels of this antiprotease in their sera (10), in comparison to patients with non malignant diseases of the lung. alpha2-macroglobulin is a serum protein with a molecular weight of 800,000 and with known antiprotease activity and can therefore bind trypsin, plasmin, elastase, and collagenase and it is known that alpha2-macroglobulin decreases with increasing of age. Changes of alpha-macroglobulin have also been observed in several pathological conditions (11). James et al. 4ave found decreases in serum of myeloma patients (12). An association between the development and function of lymphocytes and alpha2-macroglobulin has been suggested by several authors (13, 14). This alpha2-globulin has also been demonstrated on the surface of peripheral blood lymphocytes (15) and there is evidence that it is synthesized by lymphocytes (16). The purpose of the present study was to determine serum alpha1-antitrypsin levels in patients with inoperable lung cancer and to determine whether there is also an inverse correlation to alpha2-macroglobulin. It was further attempted to correlate alpha2-macroglobulin with general immunological parameters, as it is known that patients with lung cancer show a decreased general immune-reactivity (17).
 ...
PMID:Serum levels of alpha1-antitrypsin and alpha2-macroglobulin in lung cancer. 6 86

An imbalance of proteolytic enzymes and protease inhibitors may contribute to the development of bronchopulmonary dysplasia. We studied secretory leukocyte protease inhibitor (not previously addressed), and alpha 1-antitrypsin, alpha 1-antichymotrypsin, alpha 2-macroglobulin and elastase. Albumin was used as an internal reference. Infants with pneumonia had higher concentrations of secretory leukocyte protease inhibitor (p = 0.02) and elastase (p = 0.04) in bronchoalveolar lavage fluid than those with respiratory distress syndrome; those who also developed bronchopulmonary dysplasia had intermediate values. A decreased concentration of alpha 1-antitrypsin was found in the second and third postnatal weeks (p = 0.002). Further detailed studies of the balance between proteases and protease inhibitors and of the importance of pulmonary infections in the pathogenesis of bronchopulmonary dysplasia are suggested. Secretory leukocyte protease inhibitor is important both as an elastase inhibitor of bronchial mucus and as a marker of infection in the bronchi.
 ...
PMID:Protease inhibitors in bronchoalveolar lavage fluid from neonates with special reference to secretory leukocyte protease inhibitor. 138 26

1. Research into the pathogenesis of acute and chronic neonatal lung disease has been hampered by the lack of a suitable small-animal model of prematurity. We describe such a model that has been developed and validated in the guinea-pig. 2. Pre-term guinea-pigs delivered by Caesarian section at 65 days gestation (normal gestation 68 days) exhibited transient respiratory distress. The survival of pre-term animals was lower than that of term animals after exposure to 95% O2 (pre-term 42% versus term 79% at 96 h, P less than 0.05). 3. Pulmonary histology in pre-term animals exposed to both 21% O2 and 95% O2 revealed evidence of acute lung injury with atelectasis, pulmonary oedema, fibrin deposition and inflammatory cell infiltration. No evidence of lung injury was observed in term animals exposed to 21% O2, whereas those exposed to 95% O2 showed a similar, but less pronounced, injury to that seen in pre-term pups. 4. The protein concentration in bronchoalveolar lavage fluid was similar in pre-term and term animals exposed to 95% O2, but neutrophil numbers in bronchoalveolar lavage fluid tended to be greater in pre-term pups. 5. Elastase-like activity, measured against succinyl-1-trialanine p-nitroanilide, was higher in bronchoalveolar lavage fluid from control pre-term animals compared with that from control term animals. Exposure to 95% O2 increased the elastase-like activity significantly in both groups. The majority of the elastase-like activity was EDTA-sensitive and thus is possibly due to metallo-elastase. Fractionation of bronchoalveolar lavage fluid indicated that the elastase-like activity was associated with a high-molecular-mass complex.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The pre-term guinea-pig: a model for the study of neonatal lung disease. 165 47

In this experiment, rabbit model with smoke inhalation injury was used. The study was designed to observe the dynamic changes of elastase activities of polymorphonuclear leukocytes (PMN), alveolar macrophages (AM) and bronchoalveolar lavage fluid (BALF); and trypsin inhibitory capacities of serum and BALF (STIC & BTIC). The relationships between these changes and acute lung injury, as well as the concomitant changes of arterial blood gas levels, lung water volume and pathomorphology of trachea and lung tissues were also observed. It was found that after injury the elastase activities of PMN and AM were markedly reduced, and the elastase activity of BALF was rapidly increased. STIC was also reduced. PaO2 progressively dropped and PaCO2 progressively increased. Animals showed respiratory distress. Pathomorphological phagocytes aggregations in lungs, pulmonary edema and pneumorrhagia were found. There were serious destructions of capillary endothelial cells, alveolar epithelial cells, basement membranes and interstitial fibers. The number of elastic fibers of parenchyma decreased. The lung water volume was markedly increased, and there was a significant correlation between the increment of extravascular lung water and the rising of elastase activity of BALF. On the basis of our observation, it is proposed that the imbalance of elastase-antiprotease may play an important role in the development of acute lung injury after smoke inhalation.
 ...
PMID:[Experimental study of dynamic changes in elastase-antiprotease in rabbits in the early stage of inhalation injury]. 251 41

Pulmonary effluent from infants who received exogenous human surfactant for severe respiratory distress syndrome was evaluated for inflammatory changes previously identified with lung injury during the first 2 weeks after birth. The number of pulmonary effluent inflammatory cells was higher only on day 1 in infants given surfactant. No other evidence of enhanced inflammation was detected in cytologic assessment of tracheal secretions. The classical pathway of complement was not activated in infants given surfactant or in control infants 2 weeks after birth. Albumin content of airway secretions was higher on the first day but not significantly altered on subsequent days. Human surfactant treatment was not associated with increased proteolytic activity, measured as neutrophilic elastase per milligram of albumin in lung effluent, but was associated with significantly higher alpha 1-proteinase inhibitor levels than in control infants from days 2 to 7 after birth. These findings provide evidence that exogenous human surfactant instilled into the lungs of preterm infants with severe respiratory distress syndrome is not associated with enhanced lung inflammation, compared with conventional mechanical ventilation alone. These data support additional clinical trials using human surfactant.
 ...
PMID:Human surfactant treatment of severe respiratory distress syndrome: pulmonary effluent indicators of lung inflammation. 348 64

Group B beta-hemolytic Streptococcus (GBS) is a major pathogen affecting newborns. We have investigated the molecular mechanism underlying the respiratory distress induced in sheep after intravenous injection of a toxin produced by this organism. The pathophysiological response is characterized by pulmonary hypertension, followed by granulocytopenia and increased pulmonary vascular permeability to protein. 31P NMR studies of GBS toxin and model components before and after reductive alkaline hydrolysis demonstrated that phosphodiester residues are an integral part of the GBS toxin. Reductive alkaline treatment cleaves phosphate esters from secondary and primary alcohols and renders GBS toxin nontoxic in the sheep model and inactive as a mediator of elastase release in vitro from isolated human granulocytes. We propose that the interaction of cellular receptors with mannosyl phosphodiester groups plays an essential role in the pathophysiological response to GBS toxin.
 ...
PMID:Molecular basis for group B beta-hemolytic streptococcal disease. 354 Sep 59

Neutrophils secrete of variety of biologically active compounds, especially when they accumulate at sites of inflammation. Secretory products are delivered to the tissues both by exocytosis of cytoplasmic granules and by metabolic events taking place at the plasma membrane. The release of lysosomal constituents, such as lactoferrin, elastase and collagenases, is associated with the regulation of the turnover of neutrophils, their participation and activity in the inflammatory reaction, and breakdown of cartilage and connective tissues, for example. Generation of cytotoxic oxygen radicals and compounds, e.g. the superoxide anion, hydrogen peroxide and the hydroxyl radical, is initiated by many inflammatory mediators. These two systems, either individually or in collaboration, can cause damage to many types of structures. For instance, when endothelial cells are injured, increased vascular permeability may occur. If such injury involves the pulmonary capillary system a respiratory distress syndrome may supervene. Leukotrienes are potent mediators of inflammation, formed in neutrophils after exposure to various other chemotactic or perturbating compounds. Leukotriene B4 is the most potent of the hitherto described compounds, being a promotor of neutrophil adherence, aggregation and chemotaxis in vitro of similar potency as the formylated synthetic chemotactic peptides, e.g. fMLP, and as the C5a fragment. However, the ability of LTB4 to induce a release of lysosomal enzymes is only half of that of fMLP, and, finally, the capacity to initiate a chemiluminescence response, being a measure of the oxidative metabolism, is only one-tenth of that of fMLP. Thus, leukotrienes of the B series seem to be a signal system whereby activated neutrophils can recruit cellular reinforcements, and, possibly, to act as an intracellular, second messenger system.
 ...
PMID:The role of granulocytes in inflammation. 633 Aug 85

Evidence is presented indicating that oxidants are generated in lungs of patients with the adult respiratory distress syndrome (ARDS). The evidence was derived from observations that alpha-1-PI, recovered in bronchoalveolar lavage (BAL) fluid, had been inactivated by oxidation, presumably oxidation of the methionyl residue in the reaction site of the molecule. This was indicated by findings that activity of the alpha-1-PI could be restored by exposure to the reducing agent, dithiothreitol in the presence of methionyl sulfoxide peptide reductase. The amount of activity restored was proportional to the amount of inactive alpha-1-PI present at 52,000 D. Oxidation of the 52,000-D alpha-1-PI was also revealed by the finding that the inactive molecule was subject to proteolytic cleavage to 47,000 D when exposed to porcine pancreatic elastase, a characteristic of alpha-1-PI with oxidized methionyl residues in the reactive site. Inactivation of the alpha-1-PI in vivo also resulted from complexing to an active enzyme, shown previously to be neutrophil elastase, and from proteolytic cleavage in vivo, that produced a fragment of 47,000 mol wt. In contrast to that in BAL fluids, the alpha-1-PI in plasma of patients with respiratory distress syndrome was found to be greater than 90% active in 14 of 22 cases and 50-90% active in 8 cases. This suggested that for the most part, alpha-1-PI was inactivated after leaving the vessels and entering the lung. The circulating alpha-1-PI in patients with the respiratory distress syndrome was found to be equally susceptible to oxidative inactivation as alpha-1-PI from normal individuals. It seems improbable therefore that patients develop ARDS because of labile alpha-1-PI inhibitor.
 ...
PMID:Pathogenesis of the adult respiratory distress syndrome. Evidence of oxidant activity in bronchoalveolar lavage fluid. 660 Jul 48

Pulmonary effluent samples were obtained from 26 preterm or term infants throughout the period of endotracheal intubation. Infants with respiratory distress syndrome, infants with this disorder developing bronchopulmonary dysplasia, and intubated infants without lung disease were compared daily in terms of lung effluent cellularity, albumin, elastase activity, alpha 1-proteinase content and activity, and elastase inhibitory capacity. The elastase activity was determined to be neutrophilic in origin. Polyacrylamide gel electrophoresis of pulmonary effluents from two infants with respiratory distress syndrome and exposed to FiO2 greater than or equal to 0.6 up to 6 d revealed cleavage of alpha 1-proteinase inhibitor to a 47,000-mol weight fragment suggestive of oxidation. Pulmonary effluent neutrophils, macrophages, and elastase activity were increased by day 3 of life in infants with respiratory distress syndrome eventually developing bronchopulmonary dysplasia. Elastase inhibitory capacity and alpha 1-proteinase inhibitor activity were reduced in infants developing chronic lung disease. Bronchopulmonary dysplasia developed in infants with enhanced inflammatory response, but with less or inhibited antiprotease activity.
 ...
PMID:Elastase and alpha 1-proteinase inhibitor activity in tracheal aspirates during respiratory distress syndrome. Role of inflammation in the pathogenesis of bronchopulmonary dysplasia. 660 78

Neonatal guinea pig pulmonary response to oxygen exposure FiO2 greater than 0.9 resulted in an increase in total cell number in lung lavage. Alveolar macrophages initially increased within 48 h of exposure. Polymorphonuclear leukocytes and macrophages exceeded age-matched neonatal control values by 72 h of oxygen exposure. By 144 h of life, total inflammatory cell number still exceeded control cell populations. Chemotaxis of alveolar macrophages to N-formyl-methionyl-phenylalanine (1 x 10(-5) M) exceeded chemotaxis of air-exposed controls. Although initially depressed, by 72 h of FiO2 greater than 0.9 polymorphonuclear leukocyte chemotaxis increased 6-fold. Endogenous chemotactic peptides were demonstrated in lung lavage supernatant of oxygen-exposed neonatal guinea pigs. Elastase activity rose in oxygen exposed guinea pigs by 72 h of life. Lung lavage disaturated phosphatidylcholine in oxygen-exposed neonates exceeded control values 4-fold. In a preliminary study, lung effluent elastase activity was found to be increased in human neonates with respiratory distress syndrome over the first days of life compared to infants intubated but without lung disease. In infants developing bronchopulmonary dysplasia, tracheal aspirate protease activity remained greater than 10(-3) U for over 10 days and up to 5 weeks of age.
 ...
PMID:Oxygen exposure in the newborn guinea pig lung lavage cell populations, chemotactic and elastase response: a possible relationship to neonatal bronchopulmonary dysplasia. 692 85


1 2 3 4 5 Next >>