Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Surfactant protein A (SP-A) is an abundant glycoprotein in surfactant that is synthesized and secreted by alveolar type II cells and likely has important roles in mediating surfactant function and metabolism. In the present study, we demonstrate that exposure to 85% oxygen increased alveolar lavage and lung SP-A, and that these increases were related to increased SP-A synthesis and mRNA. Adult rats were exposed to room air or to 85% oxygen for 3, 5, or 7 days. Continuous exposure to hyperoxia progressively increased SP-A content, with a 20-fold increase in alveolar lavage and a 10-fold increase in lung SP-A content observed after 7 days. SP-A-specific mRNA increased in the lungs of rats exposed to oxygen, occurring with a time course similar to the increase in tissue SP-A. SP-A mRNA was increased 7-fold after 7 days of oxygen exposure. Synthesis of SP-A was increased 2- to 3-fold and secretion was increased 6- to 7-fold by type II epithelial cells isolated from oxygen-exposed rats. We conclude that exposure to hyperoxia increased lung and alveolar SP-A pool sizes. Increased expression of SP-A was related, at least in part, to increased SP-A mRNA and increased SP-A synthesis and secretion by type II epithelial cells.
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PMID:Increased synthesis and mRNA of surfactant protein A in oxygen-exposed rats. 261 99

The use of therapeutic hyperoxia has greatly improved the survival of infants born prematurely. However, high concentrations of oxygen cause pulmonary injury, leading to decreased pulmonary compliance and decreased oxygen diffusion. This injury can result in chronic pulmonary insufficiency. It has been hypothesized that the adverse effects of hyperoxia are mediated, in part, through changes in the pulmonary surfactant system. We investigated the effects of hyperoxia on surfactant-associated protein A (SP-A), the abundant surfactant-specific glycoprotein. Adult male rats were exposed to 85% oxygen for 72 h. Total lung volume and pulmonary compliance were measured, and alveolar surfactant material recovered by lavage. Hyperoxia decreased total lung capacity, and altered inflation and deflation hysteresis patterns. Disaturated phosphatidylcholine and SP-A content were significantly increased in alveolar surfactant material isolated from oxygen-treated rats. SP-A content was also significantly increased in lung tissue from oxygen-treated rats. The SP-A in the lavage of oxygen-treated rats appeared to be intact protein as no proteolytic fragments were detected and the SP-A migrated identically to that recovered from room air animals when analyzed by two-dimensional isoelectric focusing. We conclude that the decreased pulmonary compliance associated with pulmonary oxygen injury is not due to quantitative decreases in two major surfactant components, disaturated phosphatidylcholine and SP-A.
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PMID:Effects of pulmonary oxygen injury on airway content of surfactant-associated protein A. 320 7

The pathogenesis of pulmonary oxygen toxicity is postulated to be related in part to neutrophil-mediated injury. This study examined the effect of a monoclonal antibody directed against the CD11a,b,c/CD18 glycoprotein complex (beta 2 leukocyte integrins) on oxygen-induced lung injury. M8, a monoclonal antibody that binds to the beta chain of the guinea pig leukocyte integrins that facilitate neutrophil adherence to vascular endothelium, was injected into adult guinea pigs prior to and during exposure to > 98% oxygen. Control oxygen-exposed animals were injected with a noninhibitory antibody to the CD18 complex or with saline. Survival in oxygen was similar for animals treated with M8 when compared with those treated with saline (102 versus 105 h, respectively, NS). Pulmonary edema as assessed by protein in the supernatant of bronchoalveolar lavage fluid (BALF) was higher in the three groups of oxygen-exposed animals than in the air-exposed groups (p < 0.01), but it did not differ between the M8 antibody treatment group and the other oxygen-exposed groups. M8 antibody treatment did not decrease hyperoxia-induced neutrophil accumulation into the lung as assessed by myeloperoxidase activity (MPO) in lung homogenates or by neutrophil counts in histologic specimens. M8 antibody also did not decrease neutrophil counts or MPO in alveolar lavage fluid, both of which were significantly elevated in all oxygen-exposed groups. These results suggest that hyperoxia-induced neutrophil migration into the lung and acute lung injury occurs by CD18-independent processes in the guinea pig model of pulmonary oxygen toxicity.
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PMID:Oxygen-induced lung injury in the guinea pig proceeds through CD18-independent mechanisms. 790 67

Hyperoxic stress alters expression of genes involved in extracellular matrix (ECM) remodeling. To identify novel ECM-associated gene products positively regulated by hyperoxia, rat kidney cells were exposed to 95% O2, and the complement of [35S]methionine-labeled, saponin-resistant, ECM-associated proteins was compared with normoxic controls. O2-stressed cells accumulated significantly greater ECM levels (approximately 3- to 4-fold that of control cells) of a 52-kDa glycoprotein (p52), recently identified as the matrix form of plasminogen activator inhibitor type 1 (PAI-1) (P.J. Higgins, P. Chaudhari, and M.P. Ryan. Biochem. J. 273: 651-658, 1991; P. J. Higgins, M. P. Ryan, R. Zeheb, T. D. Gelehrter, P. Chaudhari. J. Cell. Physiol. 143:321-329, 1990), which peaked at 48 h of exposure. Hyperoxia-associated increases in ECM p52(PAI-1) content reflected parallel elevations in p52(PAI-1) mRNA abundance. Similar results were obtained using secondary cultures of rat pulmonary fibroblasts. This 48-h period of maximal hyperoxia-induced p52(PAI-1) expression in vitro was used to design subsequent in vivo studies. Adult rats were exposed to 99% O2 for 24-50 h, and RNA was extracted from the pulmonary tissue of stressed and control animals. A 5- to 8-fold and 6- to 15-fold increase in lung p52(PAI-1) mRNA content was evident in hyperoxia-treated rats at 24 and 50 h, respectively. All of this increase occurred in the defined 3.2-kb species of rat p52(PAI-1) mRNA. Actin mRNA levels increased three- to sevenfold as a function of hyperoxic stress, whereas catalase and glyceraldehyde-3-phosphate dehydrogenase mRNA abundance was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperoxic stress elevates p52(PAI-1) mRNA abundance in cultured cells and adult rat pulmonary tissue. 836 24

The oxygen partial pressure of middle ear gas increases more than 3-fold upon insertion of ventilation tubes, while the carbon dioxide partial pressure decreases. Whereas the middle ear gas is normally equilibrated to venous gases and has an oxygen partial pressure of 43 mmHg, 138 mmHg is measured in ventilated ears. The present study was undertaken to compare the effects of these oxygen tensions on in vitro growth and glycoprotein secretion of rabbit middle ear epithelium and for comparison auditory meatal epithelium. Cultures were incubated in atmospheres of 7, 21 or 75% O2 in 5% CO2 and the remnant N2. The cell layer protein mass, [3H]thymidine-incorporation, DNA content and [3H]glucosamine-incorporation was measured in identical subcultures every third day during a 15-day period. In middle ear epithelium the DNA content, DNA synthesis and cell layer protein mass were significantly higher at 7% oxygen compared to 21% and 75%. In conclusion hyperoxia leads to decreased growth of middle ear epithelium in vitro. If applicable to in vivo conditions, this might contribute to the mechanism of action of ventilation tubes. Moreover the proliferation rate of auditory meatal epithelium exceeds that of middle ear epithelium both at 7 and 21% oxygen, an interesting point with regards to cholesteatoma pathogenesis.
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PMID:Influence of hyperoxia on in vitro growth of rabbit middle ear epithelium and auditory meatal epithelium. 935 Apr 87

The major function of the erythrocyte is to transport oxygen from the lungs to the other tissues, a function ensured by the glycoprotein hormone erythropoietin which couples red cell production to long term tissue oxygen requirements. Tissue hypoxia is the only physiological mechanism for increasing erythropoietin production but there are a variety of mechanisms for its down regulation including hyperoxia, increased catabolism by an expanded erythroid progenitor cell pool, blood hyperviscosity independently of its oxygen content, renal disease and the cytokines produced in inflammatory, infectious and neoplastic disorders. Erythropoietin lack results in severe and often transfusion-dependent anemia but if bone marrow function is otherwise normal, recombinant human erythropoietin therapy can restore the red cell mass and alleviate the transfusion need. However, elevation of the red cell mass by recombinant human erythropoietin is associated with a reduction in plasma volume and in some patients, hypertension is induced. Elevation of the red cell mass is also associated with a reduction in cerebral blood flow. When used to gradually elevate the hematocrit to 36% in anemic patients, recombinant human erythropoietin therapy is usually uneventful. However, when the normal hematocrit level is exceeded, the risk for thrombotic events increases since blood viscosity varies exponentially with the hematocrit. Increasing the hematocrit by autologous blood transfusions can enhance athletic performance in fit individuals and recombinant human erythropoietin administration is an obvious surrogate for autologous blood transfusions. However, paradoxically, its effects are the opposite of those of endurance training, namely a change in red cell mass without an increase in the total blood volume. Thus, the use of recombinant human erythropoietin as a performance-enhancing agent is dangerous, particularly in the less fit athlete, and probably of little benefit in the highly conditioned one. Differences in the carbohydrate content of native and recombinant human erythropoietin are identifiable by isoelectric focusing, providing a direct means for detecting erythropoietin abuse using urine specimens; a panel of surrogate blood markers of enhanced erythropoiesis such as soluble transferrin receptors, serum erythropoietin, reticulocyte hematocrit and percent macrocytes provide an indirect means for this purpose. Timing of surveillance is, of course, critical due to biological limitations on the physical presence of the hormone. However, education about its dangers may prove to be the most valuable solution to abuse of recombinant human erythropoietin for competitive advantage.
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PMID:Erythropoietin use and abuse: When physiology and pharmacology collide. 1195 Jan 39

Extracellular superoxide dismutase (SOD3) is a homotetrameric copper- and zinc-containing glycoprotein with affinity for heparin. The level of SOD3 is particularly high in blood vessel walls and in the lungs. The enzyme has multiple roles including protection of the lungs against hyperoxia and preservation of nitric oxide. The common mutation R213G, which reduces the heparin affinity of SOD3, is associated with increased risk of myocardial infarctions and stroke. We report the first crystal structure of human SOD3 at 1.7 A resolution. The overall subunit fold and the subunit-subunit interface of the SOD3 dimer are similar to the corresponding structures in Cu-Zn SOD (SOD1). The metal-binding sites are similar to those found in SOD1, but with Asn180 replacing Thr137 at the Cu-binding site and a much shorter loop at the zinc-binding site. The dimers form a functional homotetramer that is fashioned through contacts between two extended loops on each subunit. The N- and C-terminal end regions required for tetramerisation and heparin binding, respectively, are highly flexible. Two grooves fashioned by the tetramer interface are suggestive as the probable sites for heparin and collagen binding.
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PMID:The structure of human extracellular copper-zinc superoxide dismutase at 1.7 A resolution: insights into heparin and collagen binding. 1928 27