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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Combined exposure of hamsters to 60% hyperoxia and the carcinogen diethylnitrosamine for 6 wk resulted in the development of lung tumors. This was associated with progressive loss of body weight as well as increases in the pulmonary-associated peptides, mammalian bombesin (MB) and immunoreactive calcitonin (iCT). After 3 wk of exposure, multiple bronchial epithelial hyperplastic foci were noted, along with increased lung levels of MB and iCT as well as increased serum levels of MB. At this time, immunocytochemistry revealed the presence of MB and iCT within hyperplastic pulmonary neuroendocrine (PNE) cells. In addition, the localization of MB to alveolar type II cells was noted, along with the presence of lamellar bodies and secretion granules in these cells on electron microscopy. After 6 wk of exposure, distinctive microscopic pulmonary tumorlets were seen. These tumorlets were associated with a marked increase in lung and serum MB, and to a lesser extent lung and serum iCT. At this time, MB and iCT were localized exclusively to these abnormal PNE cell sites. These results, which may have relevance in humans, suggest that endogenous peptides may be important components in the process of development of neuroendocrine cancer.
Am J Respir Cell Mol Biol 1990 Jan
PMID:Pulmonary bombesin and calcitonin in hamsters during exposure to hyperoxia and diethylnitrosamine. 230 67

The concomitant treatment of rats with bleomycin and hyperoxia results in synergistic development of pulmonary injury. We exposed rats to 70% oxygen for 72 hr following an intratracheal instillation of bleomycin (0.2 U/kg body wt). Animals were killed 15, 30, 60 and 90 days after treatment for hydroxyproline, cell kinetics, and histopathologic analysis. A 16% increase in hydroxyproline over controls was seen 15 days after treatment which was manifested by the proliferation phase of diffuse alveolar damage and an increase in cell labeling by tritiated thymidine. Thirty days after treatment the hydroxyproline remained elevated while lung injury appeared to be healing with a residual focal interstitial pneumonitis and a drop in cell labeling. Between 60 and 90 days, there was an additional significant increase in hydroxyproline to 44% over controls. Diffuse interstitial pneumonitis with fibrosis was observed. Cell labeling remained constant between 60 and 90 days. We conclude that the treatment of rats with bleomycin and hyperoxia results in slowly progressive pulmonary fibrosis. The increase in hydroxyproline in the chronic phase was not accompanied by an increase in cell proliferation, and therefore may have resulted from an increase in cellular production of hydroxyproline rather than increased number of cells producing collagen.
Exp Mol Pathol 1985 Dec
PMID:Progressive pulmonary fibrosis in rats: a biochemical, cell kinetic, and morphologic analysis. 241 89

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.
Am J Respir Cell Mol Biol 1989 Aug
PMID:Increased synthesis and mRNA of surfactant protein A in oxygen-exposed rats. 261 99

Several aspects of tissue response to injury, including cell proliferation, cell migration, and deposition of extracellular matrix, have been attributed to platelet-derived growth factor (PDGF)-like cytokines. Because these responses play key roles in lung injury, PDGF-B (c-sis) gene expression was measured by Northern blot analysis of lung total RNA prepared after oxidant injury was induced by chronic exposure of rats to 85% oxygen for zero, 1, 3, and 7 days. Constitutive but low levels of PDGF-B mRNA (4.0 kb) were observed in the lungs of control animals exposed to 21% oxygen. Steady-state levels of PDGF-B mRNA in lung were elevated 2.5-fold by day 3 of hyperoxia and remained so up to at least day 7. The early increase in PDGF-B mRNA expression after 3 days of hyperoxic exposure preceded several other aspects of the reparative response. DNA synthesis measured by in vivo incorporation of [3H]thymidine into lung DNA was unchanged at day 3 but markedly elevated by day 7. A similar increase in extractable lung RNA implies a quantitative or qualitative change in extractable RNA at this later phase of tissue injury. Subtle changes in actin mRNA expression were also noted late in the course of lung injury. The content of cytoplasmic (beta,gamma) actin mRNA (2.1 kb) in lung was doubled after 7 days of hyperoxia (P less than 0.05). In addition, increased expression of an actin cDNA-hybridizing mRNA, which co-migrates with muscle-specific alpha-actin mRNA (1.7 kb), was detected on day 7, suggesting hyperplasia of smooth muscle and myofibroblasts. These data show that PDGF-B transcripts are constitutively expressed in rat lung tissue. The expression of PDGF-B mRNA increases early in the course of hyperoxic lung injury and precedes an increase in DNA synthesis and other responses that reflect tissue remodeling. These results suggest that the production of PDGF-like cytokines by cells within the lung itself initiates or modulates various aspects of lung injury and repair.
Am J Respir Cell Mol Biol 1989 Sep
PMID:Increased expression of PDGF-B (c-sis) mRNA in rat lung precedes DNA synthesis and tissue repair during chronic hyperoxia. 269 12

Changes in lung structure and collagen metabolism were studied at 1, 2, 3, 4, 6, and 8 weeks in a model of pulmonary fibrosis induced in rats with paraquat plus hyperoxia. Morphologic examination of the lungs revealed that the earliest lesions consisted of severe and irreversible endothelial and alveolar epithelial cell damage. Afterward, an inflammatory process took place, initially dominated by polymorphonuclear leukocytes and then by mononuclear cells, but with the constant presence of granulocytes. From the fourth week on there were fibroblast proliferation and a moderate increase of mast cells. In the early stages alveolitis was focal, but from the second week the lungs were diffusely affected with severe distortion of the architecture. Collagen content was moderately increased in the first 2 weeks and then showed a progressive increment until the end of the experiment. Collagen synthesis was significantly elevated from the fourth week, coinciding with interstitial fibroblast proliferation, although there were some animals that showed increased collagen production from the first week. Collagenolytic activity occurred in 3 stages: at 2 weeks there was increased collagen degradation, at 3, 4, and 6 weeks the values showed a trimodal behavior, and at 8 weeks almost all experimental rats presented an important decrease of collagenolysis. Thus, the development of lung fibrosis was associated first with increased rates of collagen synthesis and later with a decrease of collagen degradation.
Exp Mol Pathol 1989 Apr
PMID:Experimental pulmonary fibrosis induced by paraquat plus oxygen in rats: a morphologic and biochemical sequential study. 270 80

We have tested the effects of hyperbaric oxygen on necrosis of rat liver induced by the administration of several toxins. The extent of liver necrosis was determined 24 h after the administration of the toxins by measurement of serum levels of alanine and aspartate amino-transferases and by histologic and ultrastructural analyses. Treatment with hyperbaric oxygen decreases carbon tetrachloride (CCl4)-induced necrosis in a manner dependent upon duration and pressure of oxygen exposure. Pretreatment of rats with phenobarbital diminishes this protective effect. Hyperbaric oxygen treatment before or immediately after CCl4 intoxication is protective. Loss of protection is rapid; hyperbaric oxygen treatment 6 h after CCl4 intoxication augments the liver necrosis. No delayed necrogenic effects of CCl4 are seen in the animals treated with hyperbaric oxygen immediately. Hyperbaric oxygen augments the liver necrosis induced by acetaminophen, bromobenzene, dimethylnitrosamine or thioacetamide. This augmented necrosis is averted by prolonged treatment with hyperbaric oxygen. Hyperbaric oxygen has no effect on liver injury induced by galactosamine or lipopolysaccharide. We conclude that hyperoxia decreases the hepatic necrosis induced by compounds which undergo reductive biotransformation by the cytochrome P-450 monooxygenase system; hyperoxia augments the necrosis induced by compounds which undergo oxidative biotransformation by this system. Biotransformation of toxins appears to be nonspecifically inhibited by hyperoxic exposure of long duration.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:Effect of hyperoxia on liver necrosis induced by hepatotoxins. 287 23

Hyperoxia impairs cytoskeleton-dependent phagocytic functions in polymorphonuclear leukocytes (PMNs) and alveolar macrophages (AMs). To investigate the effect of different oxygen concentrations on the cytoskeleton, in particular the microtubule (MT) and microfilament (MF) system, the fluorescence pattern of Concanavalin A (Con A) receptors in AMs and PMNs was observed. Cells were obtained from guinea-pigs exposed to different oxygen concentrations. The exposure of guinea-pigs to oxygen concentrations of up to 50% induced in AMs and PMNs mainly spontaneous Con A capping, demonstrating an altered MT system. Oxygen tensions above 50% lead to an increased number of AMs and PMNs exhibiting a patchy Con A fluorescence distribution. Even in the presence of the microtubule-disrupting agent colchicine most AMs and PMNs were unable to form a Con A cap fluorescence distribution under these high oxygen tensions. This study demonstrates that the exposure of guinea-pigs to an oxygen concentration greater than 50% increases the relative number of AMs and PMNs demonstrating a patchy distribution of Con A. This patchy fluorescence pattern is associated with a severe cytoskeletal defect, i.e. MT and MF disruption. The various leukocyte function defects induced by hyperoxia, demonstrated in previous studies, are based on this MT and MF alteration in AMs and PMNs, representing an additional sepsis-promoting factor during hyperoxia.
Virchows Arch B Cell Pathol Incl Mol Pathol 1983
PMID:Concanavalin A distribution in polymorphonuclear leukocytes and alveolar macrophages during hyperoxia. 613 6

An early proliferative response of mesothelial and subpleural cells has been reported in animals after inhalation or intratracheal (I.T.) instillation to the lung of long asbestos fibers, which also induce pulmonary fibrosis. To determine whether this cell proliferation is directly related to asbestos exposure or is a nonspecific response to injury, we examined [3H]thymidine (3HT) uptake by cells at the pleura after exposing mice to 5 days of hyperoxia, to intravenous (I.V.) (3 mg) or I.T. (0.15 mg) bleomycin, to I.T. (1 mg) silica, and to I.T. (0.1 mg) crocidolite asbestos of mixed length. All exposures induced acute lung injury, as shown by high levels of protein in lavage fluid. After hyperoxia, the percentage of total lung cells labeled by 3HT in autoradiographs was high for only a few days, as repair took place with no increase in fibroblast growth and no subsequent development of fibrosis. Particle or bleomycin exposure induced a prolonged increase in 3HT uptake with enhanced fibroblast labeling over a 4- to 6-wk period. In each case, labeled subpleural cells, mainly fibroblasts, increased up to 10-fold in the first 2 to 4 wk. At the same time, 3HT uptake by mesothelial cells ranged from 1.4 to 3% compared with almost zero in controls and in oxygen-exposed mice after a few days upon return to air. These results indicate that mesothelial and subpleural cell proliferation occurs after various types of injury to the lung. The close temporal association between 3HT uptake by mesothelial cells and fibroblasts during the reparative phase suggests that mesothelial cells may respond to the same cytokines that trigger interstitial fibrosis.
Am J Respir Cell Mol Biol 1994 Mar
PMID:Mesothelial cell proliferation: a nonspecific response to lung injury associated with fibrosis. 750 11

Destruction of pulmonary endothelial cells is characteristic of hyperoxic lung injury. During recovery from hyperoxia, pulmonary endothelial cells proliferate to regenerate the vascular endothelium. Vascular endothelial growth factor (VEGF) is a peptide growth factor that is mitogenic specifically for endothelial cells. We hypothesized that VEGF messenger RNA (mRNA) increases during recovery from acute hyperoxic lung injury. Adult rabbits were exposed to 100% oxygen for 64 h and allowed to recover in air for 0, 1, 3, and 5 days. In situ hybridization showed increased VEGF expression in alveolar epithelial cells beginning at 1 day recovery. By 3 days recovery the message was in alveolar epithelial cells throughout the lung. Compared with alveolar epithelial cells, little or no expression was noted in large vessel endothelial cells, airway cells, or smooth muscle cells. Combined in situ hybridization for VEGF and immunostaining for macrophages and other mesenchymal cells found no VEGF message in those cell types. Isolated alveolar macrophages had no detectable VEGF message. Cells expressing VEGF mRNA were enriched in alveolar type II cell preparations from recovering lung. Double in situ hybridization for VEGF and surfactant protein-C (SP-C) showed co-expression in a population of type II cells, but with an inverse relationship: cells with abundant VEGF mRNA did not have abundant SP-C mRNA. Type II cells in vitro expressed VEGF message, but only when the SP-C message abundance was relatively low. We conclude that alveolar type II cells express increased VEGF mRNA during recovery from acute hyperoxia. These findings are consistent with a role for VEGF in regulating microvascular endothelial repair after oxidant injury.
Am J Respir Cell Mol Biol 1995 Oct
PMID:Vascular endothelial growth factor mRNA increases in alveolar epithelial cells during recovery from oxygen injury. 754 67

Tissue injury that occurs as a result of ischemia and subsequent reperfusion is characterized by endothelial cell injury, edema formation, and the influx of inflammatory leukocytes. Two macrophage-derived proinflammatory cytokines which may play a critical role in cellular injury and leukocyte recruitment/activation that occurs in the setting of ischemia-reperfusion injury are tumor necrosis factor alpha (TNF) and macrophage inflammatory protein-1 alpha (MIP-1 alpha). To determine if modulation of ambient oxygen tensions in vitro alters the expression of proinflammatory cytokines from activated macrophages, murine alveolar macrophages (AMO) were cultured in various combinations of ambient oxygen concentrations, then the supernatant fluid and cell pellet assayed for the presence of TNF and MIP-1 alpha messenger RNA (mRNA) and protein. We demonstrated that conditions of anoxia (95% nitrogen/5% CO2) or hyperoxia (95% oxygen/5% CO2) independently resulted in the increased expression of both TNF and MIP-1 alpha mRNA and protein from lipopolysaccharide (LPS)-stimulated AMO, as compared with cells cultured in room air. The specific culture condition of anoxia (x 6 h) followed by hyperoxia (x 18 h) produced the greatest increases in both TNF and MIP-1 alpha, suggesting that when following a period of anoxic priming, oxygen stress results in exaggerated cytokine production. A period of at least 4.5 to 6 h of anoxia prior to hyperoxic exposure was found to be the minimal time required for anoxic priming. Furthermore, the coincubation of LPS-treated AMO with dimethyl sulfoxide (DMSO) attenuated the anoxia-hyperoxia-induced increases in TNF and MIP-1 alpha mRNA by 23% and 34%, respectively. These findings suggested that alterations in ambient oxygen tension can regulate the expression of TNF and MIP-1 alpha from activated AMO, and that oxidant-related cytokine production may represent an important mechanism by which inflammation occurs in the clinical settings of ischemia-reperfusion injury and hyperoxia.
Am J Respir Cell Mol Biol 1995 Oct
PMID:Alterations of ambient oxygen tension modulate the expression of tumor necrosis factor and macrophage inflammatory protein-1 alpha from murine alveolar macrophages. 754 69


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