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Biomedical subjects

L M Simon

Publications and source records attributed to L M Simon.

44 records · Page 3Linked to original sources

Superoxide dismutase (SOD) activity in hypoxic mammalian systems.

Superoxide Dismutase (SOD) activity was compared in rabbit peritoneal macrophages (ambient PO2 approximately 15 Torr) and alveolar macrophages (ambient PO2 approximately 100 Torr) and in brain, lung, cardiac muscle, and skeletal muscle of chromically hypoxic mice(ambient PO2 approximately 50 Torr) and normoxic mice (ambient PO2 approximately 150 Torr). Peritoneal macrophages (PM) have significantly less SOD activity than alveolar macrophages (AM) (PM: 2.94 +/- 0.49 (mean +/- SD); AM:6.03 +/- 1.60 units-mg protein -1 (P less than 0.01)). SOD activity of lung and brain homogenates from the hypoxic mice was significantly less than from the normoxic controls. Heart and skeletal muscle SOD activities were not significantly different. These studies show that limitations of O2 supply are associated with reductions in SOD and are consistent with the thesis that SOD plays an important role in protection against oxygen toxicity in mammalian systems.

Animals↗

Effect of hyperoxia, hypoxia, and maturation on superoxide dismutase activity in isolated alveolar macrophages.

The influence of ambient O2 tensions and of cell maturation on superoxide dismutase activity were studied in tissue culture--maintained mouse alveolar macrophages. Cultivation under hyperoxic conditions (PO2 about 640 mmHg) for 24 hours was associated with a significant increase in superoxide dismutase activity as compared with normoxic conditions (PO2 approximately 150 mmHg). (Hyperoxia: superoxide dismutase = 7.9 +/- 4.0 (SD); normoxia: superoxide dismutase = 4.4 +/- 1.7 units X mg cell protein-1 P less than 0.05). Hypoxic exposure (PO2 approximately 15 mmHg) was associated with a significant decrease in superoxide dismutase compared to normoxic controls (hypoxia: 2.2 +/- 0.6; normoxic: 3.8 +/- 0.6 units X mg protein-1 P less than 0.01). This decrease was found only after 168 hours of in vitro hypoxia. The in vitro maturation of alveolar macrophages cultivated in air was associated with a progressive increase in superoxide dismutase activity per 10(6) cells, although superoxide dismutase activity per unit protein remained constant. Molecular O2 may modify cell superoxide dismutase activity by altering intrinsic enzyme regulation. The increase in superoxide dismutase activity with hyperoxia and the decrease with hypoxia are consistent with but not unequivocally establish an important role for superoxide dismutase in protecting against cellular O2 toxicity.

Animals↗

Enzymatic basis for bioenergetic differences of alveolar versus peritoneal macrophages and enzyme regulation by molecular O2.

Alveolar macrophages (AM) and peritoneal macrophages (PM) originate from common precursor cells, but function in different O2 environments. In the present studies, the impact of different O2 tensions on cell metabolism has been quantitatively determined, an enzymatic basis for these differences established, and a mechanism which regulates enzymatic differences demonstrated. O2 consumption and lactate production were compared in rabbit AM and PM in air and nitrogen. In air, AM demonstrate significantly greater O2 utilization. In nitrogen, (where glycolysis is the major source of energy provision) lactate production is two- to threefold greater in the PM. A comparison of several enzymes of energy metabolism in AM and PM indicate that one basis for the differences in cell energetics is a difference in activity of key enzymes of both the oxidative phosphorlyative and the glycolytic sequences. Exposure of cultivated AM to hypoxic conditions results in changes in the activity of these enzymes such that the AM closely resembles the PM. A key enzyme in oxidative phosphorylation (cytochrome oxidase) shows decreased activity and reaches values similar to those found in the PM. A key enzyme in glycolysis (pyruvate kinase) shows increased activity to values resembling those found in the PM. These alterations in enzyme pattern occur in isolated cell systems, suggesting that molecular O2 modifies the intrinsic cellular regulation of some enzymes of energy metabolism. Alterations in O2 tension may lead to alterations of the rate of biosynthesis and (or) the rate of biodegradation of key enzymes involved in oxidative phosphorylation and glycolysis. In turn, the alteration of enzyme patterns leads to a more suitable bioenergetic pattern as a function of O2 availability.

Animals↗

Adaptations of energy metabolism in the cultivated macrophage.

Adaptive changes in energy metabolism, as reflected by pyruvate kinase and cytochrome oxidase activities, were examined during in vitro differentiation of the cultivated macrophage. Serum concentrations of tissue culture media, which directly influence endocytic activity, and ambient oxygen tension were both shown to influence pyruvate kinase and cytochrome oxidase activities. Cells maintained in high serum concentrations (30% newborn calf serum [NBCS]) exhibited a 300-400% increase in pyruvate kinase activity and a 40% increase in cytochrome oxidase activity, whereas cells maintained in low serum concentrations (2% NBCS) exhibited a lesser increase (65%) in pyruvate kinase activity and no change in cytochrome oxidase activity. Anaerobiosis resulted in additional alterations in pyruvate kinase and cytochrome oxidase activities. Cells maintained for 48-72 h under anaerobic conditions exhibited a 500-600% increase in pyruvate kinase activity and a 40% decrease in cytochrome oxidase activity. Increased pyruvate kinase activity was dependent on continued protein synthesis. Enzyme increases occurred in anaerobically cultured cells despite an overall reduction in cell protein synthesis. It is suggested that adaptive changes in pyruvate kinase and cytochrome oxidase activity resulting from alterations in either serum concentration or ambient oxygen tension are regulated by two independent mechanisms. One mechanism is aimed at providing energy for endocytic activity and the other in compensating for impaired oxidative metabolism during anaerobiosis.

Aerobiosis↗

Acute injuries in off-road bicycle racing.

A descriptive study was conducted to investigate injuries sustained at a major off-road bicycling race at Mammoth Mountain, California, July 6 to 10, 1994. A total of 4027 individual starts in five events during the race were reported. Overall, the total number of competitors in the 5 events was 3624, with some cyclists participating in multiple events. Injuries were considered significant if they occurred during competition and prevented the rider from completing the event. Sixteen cyclists had injuries that met these criteria for an overall injury rate of 0.40%. These 16 cyclists had 44 injuries. Abrasions were the most common injury, followed by contusions, lacerations, fractures, and concussions. The mean injury severity score was 3.0 (range, 1 to 5) with 81.2% of the injuries resulting from cyclists going downhill. Injuries were more severe when the riders were thrown from the bicycles (P = 0.03). We observed different mechanisms of injury in various events, suggesting that the risk factors for sustaining a traumatic injury may vary according to the type of competition involved.

Adolescent↗