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Biomedical subjects

J Theodore

Publications and source records attributed to J Theodore.

At least 127 records · Page 7Linked to original sources
PubMed1979

Effects of high oxygen exposure on bioenergetics in isolated type II pneumocytes.

O2-mediated alterations in cell energy metabolism may play a role in structural and functional abnormalities described in type II pneumocytes (T-II-P) following in vivo hyperoxia. Bioenergetic alterations produced by hyperoxia (95% O2) were therefore examined in a culture-maintained cell line derived from T-II-P. Exposure of cell monolayers to 95% O2 for 96 h results in a significant decrease in O2 consumption (from 0.52 +/- 0.07 to 0.30 +/- 0.08, P less than 0.01), suggesting impaired mitochondrial energy provision. In addition, there are increased rates of aerobic lactate production (from 2.89 +/- 0.52 to 3.84 +/-0.80, P less than 0.05) with loss of Pasteur effect, indicating a shift to glycolytic metabolism at relatively high PO2's. These metabolic changes are not accompanied by altered activities of critical mitochondrial (cytochrome oxidase) or glycolytic (pyruvate kinase, phosphofructokinase) enzymes. Altered cell bioenergetics following hyperoxia may this represent an important secondary mechanism leading to functional abnormalities in T-II-P.

Aerobiosis↗
PubMed1978

Bioenergetic pattern of isolated type II pneumocytes in air and during hypoxia.

The bioenergetic pattern of a cell clone derived from rat lung with ultrastructural and biochemical characteristics like those of type II pneumocytes (T-II-P), has been studied in a tissue culture system. During air cultivation, these cells have a high rate of aerobic and anaerobic glycolysis associated with high activities of two rate-limiting enzymes in glycolysis (pyruvate kinase [PyKi] and phosphofructokinase [PFK]). This is present despite the rates of oxygen consumption and activities of cytochrome oxidase (CyOx) similar to other lung cells. Presumably the high rate of aerobic glycolysis explains the substantial lactate production previously described in lung slices and in the intact perfused lung. Hypoxic cultivation results in a decrease in CyOx. Acute re-exposure to air does not restore the oxygen consumption to normal, presumably as a result of decreased mitochondrial O(2) utilization associated with decreased CyOx activity. As a result, hypoxically cultivated T-II-P cells have a decreased capacity for mitochondrial ATP generation in air as compared to air-cultivated cells. During hypoxia, aerobic and anaerobic glycolysis are further increased as well as the activities of PyKi and PFK. The high rate of glycolysis and high activities of PyKi and PFK in cultivated T-II-P appear to reflect intrinsic genetic regulation. The decreased CyOx activity and increased PyKi and PFK activities in hypoxic T-II-P appear to reflect alterations in enzyme biosynthesis/biodegradation regulated by O(2) availability.

Animals↗
PubMed1977

Some comparative aspects of the organ distribution of superoxide dismutase activity in the freshwater turtle, Pseudemys scripta elegans.

1. Superoxide dismutase activities in five tissues of the relatively anaerobic freshwater turtle were compared with SOD activities in the same tissues of two mammalian species (mouse and rabbit) with a more usual pattern of dependence on O2 availability. 2. SOD activities in brain, lung and skeletal muscle, but not liver or cardiac muscle, are significantly lower in the turtle. The turtle also shows differences in the pattern of relative SOD activities in various tissues as compared to the two mammalian species. 3. The data indicate that a relationship does exist between SOD activities and O2 exposure in intact vertebrate systems, and is consistent with a physiological role for SOD in tissue O2 metabolism.

Animals↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1977

Acute cyanide poisoning complicated by lactic acidosis and pulmonary edema.

Massive cyanide poisoning occurred in a 21-year-old man who had ingested 600 mg of potassium cyanide. The clinical course was marked by acute pulmonary edema and lactic acidosis. Because the poison was unidentified until nine hours after ingestion, the patient received only supported treatment which included diuresis, oxygen, bicarbonate, and assisted ventilation. A review of the literature shows that many case reports are poorly documented and do not provide a firm basis for evaluating therapy. To our knowledge, only four patients, including ours, have had blood levels of cyanide measured. In the absence of a suitable history, diagnosis of cyanide poisoning is difficult. A simple chemical test which can be performed on gastric aspirate is available. Hydroxocobalamin may be used as a nontoxic specific antidote. Nonspecific supportive therapy is of great importance.

Acidosis↗
PubMed1976

Intracellular edema and dehydration: effects on energy metabolism in alveolar macrophages.

The effects of intracellular edema and dehydration on energy metabolism in alveolar macrophages were studied. Intracellular edema increased lactate production and reversibly decreased oxygen consumption. Dehydration caused no significant change in lactate production but irreversibly decreased oxygen consumption. These phenomena may be applicable to a wide variety of clinical problems including lung and brain edema.

Animals↗
PubMed1976

Intracellular and subcellular oedema and dehydration.

Changes in intracellular water content appear to be common abnormalities induced by a wide variety of pathogenic mechanisms. Such changes in cell water produce changes in the water in various subcellular organelles bound by semipermeable membranes. Cell and subcell functions then alter in their turn. In isolated alveolar macrophages (rabbit), intracellular and intramitochondrial oedema reduces mitochondrial O2 utilization. Metabolic control is maintained because lactate production reverses (Pasteur effect). On reconstitution, O2 utilization and lactate production return towards normal, indicating reversibility. Cellular and intramitochondrial dehydration also reduces mitochondrial O2 utilization but metabolic control is lost because lactate production also decreases. Osmotic reconstitution does not reverse the abnormality. Exposure to hypotonic media leads to release of lysosomal enzymes (beta-glucuronidase, EC 3.2.1.31) to the extracellular phase of isolated alveolar macrophages. Some of this release is caused by exocytosis although, at low osmotic concentrations, intralysosomal oedema ultimately ruptures lysosomes, with extensive discharge of enzyme. In turn, lysosomal enzymes may injure more normal cells. Impairment of energy metabolism caused by hypoxia leads to intracellular oedema, because Na+ accumulates in the cells when ATP is no longer available for the sodium pump. Continued studies of the disorders in cell physiology caused by changes in cell and subcell water should provide important new insights into a wide variety of disease states (including pulmonary oedema).

Adenosine Triphosphate↗
PubMed1976

Speculations on neurogenic pulmonary edema (NPE).

Evidence suggests the following pathogenesis for neurogenic pulmonary edema. The initial phase results from a centrally mediated, massive, sympathetic discharge. This produces intense, generalized, but transient, vasoconstriction with a resultant shift of blood from the high-resistance systemic circulation to the lowresistance pulmonary circulation. Marked increases in pulmonary vascular pressures and marked increases in pulmonary blood volume then produce pulmonary edema because of the hydrostatic effect of increased pulmonary capillary pressure. In addition, pulmonary hypertension and hypervolemia injure pulmonary blood vessels, altering pulmonary capillary permeability and producing lung hemorrhage. After the transient systemic and pulmonary vascular hypertension subside, the patient is left with abnormal pulmonary capillary permeability, so that pulmonary edema persists in the face of normal hemodynamics and normal cardia function.

Animals↗
PubMed1975

Pathogenesis of neurogenic pulmonary oedema.

Evidence suggests that the initial phase of neurogenic pulmonary oedema results from a centrally mediated, massive, sympathetic discharge. It is postulated that this produces intense, generlised, but transient, vasoconstriction with a resultant shift of blood from the high-resistance systemic circulation to the low-resistance pulmonary circulation. Pronounced increases in pulmonary vascular pressures and blood-volume then produce pulmonary oedema because of the hydrostatic effect of increased pulmonary capillary pressure. In addition, pulmonary hypertension and hypervolaemia injure pulmonary blood-vessels, altering pulmonary capillary permeability and producing lung haemorrhage. After the transient systemic and pulmonary vascular hypertension subside, the patient is left with abnormal pulmonary capillary permeability, so that pulmonary oedema persists in the face of normal haemodynamic and cardiac function.

Blood Pressure↗
PubMed1975

Total eosinophil counts in the management of bronchial asthma.

Total eosinophil counts were investigated in asthmatic patients to determine their usefulness in the diagnosis and management of steroid-dependent asthma. Counts averaged 122 plus or minus 74 (S.D.) per mm-3 (65 untreated normal subjects) and 43 plus or minus 22 per mm-3 (six prednisone-treated normal subjects). Fifty-two patients with active bronchial asthma showed significant eosinophilia (greater than 350/mm-3 off and greater than 85/mm-3 on steroids), suggesting that eosinophilia is an important diagnostic feature of bronchial asthma. In 14 patients (60 observations), the counts showed significant inverse correlation with specific airway conductance--r equals 0.74, p less than 0.001--and with a variety of other measurements of bronchial dynamics and lung volumes, suggesting that the total eosinophil count reflects asthmatic activity and is useful for regulating steroid dosage and for early detection of exacerbations.

Adrenal Cortex Hormones↗
PubMed1975

Transalveolar transport of large polar solutes (sucrose, inulin, and dextran).

The in vivo transalveolar transport of three large polar solutes, sucrose, inulin, and dextran (mol wt 60,000-90,00), was compared with the transport of urea in saline-filled dog lung. Apparent permeability coefficents (p', in cm X sec-1 X 10(6)) were as follows; urea: 2.4 +/- 0.28 (SD) greater than sucrose: 0.64 +/- 0.31 (P less than 0.001) greater than inulin: 0.12 +/- .05 (P less than 0.001)--not different from dextran (mol wt 60,000-90,000): 0.08 +/- .02 (P greater then .01). Calculation of the resistance of the alveolar epithelium compared to total barrier resistance for the various solutes indicates that approximately 90% of the total resistance resides in the alveolar epithelium. Comparison of the ratio of permeability coefficients to the ratio of free-diffusion coefficients in water shows similar values for the three large polar solutes, suggesting that permeation through the alveolar epithelium occurs by means of water-filled channels. The values for permeability coefficients of alveolar epithelium fit into the spectrum of values reported for other epithelial structures (including gall bladder, frog skin, and toad bladder); it seems to have a system of channels with a small number of wide "pores" (greater than 80 A) that permit permeation of large polar solutes and is not a relatively homogeneous structure.

Animals↗