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Biomedical subjects

J Theodore

Publications and source records attributed to J Theodore.

At least 109 records · Page 6Linked to original sources
PubMed1983

Increased phosphofructokinase content during chronic hypoxia in cultured skeletal muscle (L8) cells.

Chronic hypoxia results in increased measured activity of all of the glycolytic enzymes and is associated with an increase in glycolytic capacity. Phosphofructokinase, a rate-limiting glycolytic enzyme, was measured under normoxic and hypoxic conditions to determine the relationship between increased activity and enzyme content. Monoclonal antibodies were used to isolate pure enzyme in rat skeletal muscle cells (L8) cultured hypoxically (PO2 = 14 torr) and normoxically (PO2 = 142 torr). Phosphofructokinase content per cell in cultures maintained under chronic (96 h) hypoxic conditions was twice that of cells cultured under normoxic conditions (0.0675 +/- 0.008 (S.E.) and 0.0345 +/- 0.003 micrograms enzyme protein/microgram DNA, P less than 0.01). Phosphofructokinase activity increased proportionately (hypoxia, 0.020 +/- 0.003; normoxia, 0.010 +/- 0.001 units/microgram DNA). The specific activity (units/mg enzyme protein) of phosphofructokinase in the hypoxic (296 +/- 32) versus the normoxic (290 +/- 15) cultures was not significantly different, indicating that the increased activity was accounted for by an increase in enzyme content. Glycolytic rate appears to be regulated at the level of enzyme content.

Animals↗
PubMed1983

Combined heart and lung transplantation.

Combined heart and lung transplantation was carried out in ten patients at Stanford University Medical Center between March, 1981, and December, 1982. All patients had end-stage pulmonary hypertension. 7 of them had Eisenmenger's syndrome and 3 primary pulmonary hypertension. 3 patients died within a month of operation, but the remaining recipients are well 2 months to 2 years after transplantation. The hospital stay of the survivors ranged from 38 to 85 days. All survivors have returned to normal activity. The results of heart and lung transplantation have thus been considerably superior to those reported previously for lung transplantation. It is suggested that cardiopulmonary replacement is suitable treatment for end-stage pulmonary hypertension with or without associated congenital heart disease and that its application to other forms of advanced pulmonary failure may be warranted.

Adult↗
PubMed1982

Hyperoxic-induced alterations in lung cell structure and function. Effects on cellular cyclic AMP content and comparison to alterations produced by exogenous cyclic AMP.

Hyperoxic exposure in vitro of two lung-derived cell types (the epithelial-derived L2 cells and WI-38 fibroblasts) inhibits cellular replication, produces striking morphologic changes and may result in cell death; these effects have been observed consistently in other cell types. Hyperoxic exposure of L2 cells is associated with an increase in cellular cyclic AMP content (cellular cyclic AMP content 454 +/- 115 fmol/micrograms DNA in cells exposed to pO2 677 Torr for 96 h compared to 136 +/- 17 fmol/microgram DNA in air-grown cells). Hyperoxic exposure of WI-38 fibroblasts is not associated with increased cyclic AMP content. Although cultivation of L2 cells in the presence of exogenous dibutyryl cyclic AMP does inhibit replication and produce morphologic alterations, similar effects are produced by sodium butyrate alone. Hyperoxic exposure alters cyclic AMP metabolism in some cell types, but the structural and functional alterations observed in L2 cells and WI-38 fibroblasts following hyperoxic exposure are not produced by changes in cellular cyclic AMP content.

Anaerobiosis↗
PubMed1982

Hormonal changes and enforced diving in the harbor seal Phoca vitulina. II. Plasma catecholamines.

Plasma epinephrine and norepinephrine concentrations were measured in five harbor seals, Phoca vitulina, during a control period, during a 6-min dive, and during a 30-min postdiving recovery period. Measurements were performed with and without prior glucose administration. Control epinephrine concentrations [189 +/- 118 (SD) pg/ml] and norepinephrine concentrations (340 +/- 191 pg/ml) were similar to resting values in humans. During diving there are dramatic increases in both epinephrine and norepinephrine concentrations, which returned to control values by 30 min of the postdiving recovery period. A similar pattern was found after glucose infusion. The increased catecholamines were not the primary mechanism responsible for arterial constriction during the dive. Persistent diving bradycardia suggests obliteration of the chronotropic effects of catecholamines during the dive. An unchanged stroke volume suggests obliteration of the inotropic effects of catecholamines during the dive. Catecholamines do not appear to be involved in postdiving hyperglycemia and hyperglucogenemia. Neither the regulatory role of increased catecholamines nor the physiological function of increased catecholamines was apparent from the studies. However, dramatic increases in plasma catecholamines during diving appear to be an important component of the hormonal response to prolonged diving in aquatic mammals.

Animals↗
PubMed1981

Endothelial mosaic in Fuchs' dystrophy. A qualitative evaluation with the specular microscope.

The progressive morphological changes of cornea guttata in Fuchs' endothelial dystrophy have been characterized by clinical specular photomicroscopy. Five specific stages in the development of excrescences can be discerned using this in vivo technique. Several stages can be observed in the same cornea at a given time, although in most cases the majority of guttate changes seemed to have progressed to the same stage of development. All five stages of cornea guttata discerned in this study can occur in a cornea clinically free of edema. Two types of cornea guttata can be identified in vivo. One has a smooth, regular posterior surface, whereas the posterior contour of the second is irregular.

Cornea↗
PubMed1981

Corneal edema secondary to vitreocorneal contact.

Aphakic eyes, some with edematous corneas, and others with corneas free of edema, but all with formed vitreous humor in contact with the corneal endothelium, were studied. Removal of vitreous humor from the anterior chamber by closed vitrectomy resulted in substantial improvement in the state of corneal hydration and, in some cases, in the elimination of clinically notable corneal edema. Specular microscopy showed endothelial abnormalities in the edematous corneas that were not present in corneas with vitreous contact that remained free of edema. However, those endothelial changes seen in edematous corneas before vitrectomy seemed to persist after vitrectomy and corneal deturgescence. Thus, elimination of vitreous contact may result in clinical reversal of corneal edema despite a prolonged period of vitreous contact and in the face of seemingly irreversible endothelial changes.

Aged↗
PubMed1981

Differences in oxygen-dependent regulation of enzymes between tumor and normal cell systems in culture.

Metabolic studies in tumor cells have indicated that bioenergetic regulatory mechanisms geared to acute changes in oxygen availability are abnormal. In the present studies we have examined bioenergetic adaptations to chronic oxygen depletion in culture maintained tumor cells in comparison to normal cell lines. Activities of two key glycolytic enzymes (pyruvate kinase (PyKI) and phosphofructokinase (PFK)) were measured in two tumor cell lines (fibrosarcoma (FS) and Hela) and two normal cell lines (rat lung fibroblasts (RLF) and WI-38) maintained in culture for up to 96 hours under aerobic (PO2 approximately 140) and hypoxic PO2 approximately 15) conditions. Exposure to low O2 tensions for 96 hours resulted in significant increases in PyKi and PFK in both RLF and WI-38, ut did not alter activities of these enzymes in either FS or HeLa cell systems. Activities of two enzymes involved in O2 metabolism (cytochrome oxidase (CyOx) and superoxide dismutase (SOD) were also measured in the two tumor cell lines and in RLF. chronic hypoxia significantly decreased the activities of CyOx and SOD in RLF cell systems but did not alter the activities of these enzymes in the tumor cells. In these studies, the tumor-derived cell lines do not demonstrate specific enzymatic responses to sustained oxygen depletion in vitro noted in normal cell systems, suggesting significant abnormalities in regulatory mechanisms geared to chronic changes in molecular O2.

Cell Line↗
PubMed1981

Glucoregulation and simulated diving in the harbor seal Phoca vitulina.

Plasma glucose, glucagon, and insulin concentrations were measured in the harbor seal, Phoca vitulina, during a 6-min dive and a 30-min recovery period. Studies were performed in the fasting state and following intravenous glucose. During diving in the fasting state, values of plasma glucose, glucagon, and insulin are not significantly different from prediving values, presumably because of the loss of perfusion to the pancreas. In the postdiving period, plasma glucagon increases significantly. The increased glucagon levels reach a peak at 6 min into the postdiving period. By 4 min postdiving, plasma glucose values increase. The hyperglycemia appears to be at least partially related to hyperglucagonemia. Despite hyperglycemia, insulin levels do not change significantly. The net effect is to increase glucose availability, particularly for non-insulin-requiring tissues (brain). Preadministration of glucose eliminates the postdiving increase in glucagon. Plasma glucose and insulin concentrations also show no significant changes during the diving and postdiving periods. These results suggest that hormonally mediated glucose conservation serves to maintain brain glucose supplies and to restore peripheral carbohydrate stores during the postdiving period.

Animals↗
PubMed1981

Regulation of intracytoplasmic pH and "apparent" intracellular pH in alveolar macrophages.

An approach for determining the permeability of cell and subcell membranes to H+/HCO3- has been applied to alveolar macrophages. The approach uses analysis of substrate ratios which are compartment specific and involved in pH-dependent reactions. By determining the changes in substrate pair ratios produced by perturbations of CO2, the effects of intracellular acidosis and alkalosis can be determined. By measuring substrate pair ratios at a constant PCO2 and variable H+/HCO3- it is possible to determine the permeability of the macrophage plasma membrane to these ions qualitatively. Measurements of intracellular lactate/pyruvate ratios showed that the alveolar macrophage plasma membrane is permeable to H+/HCO3-. Previous studies have shown that alveolar macrophages are freely permeable to Cl-. pHi was determined from measurements of pHe and Cli-/Cle- following changes of external PCO2 at a constant HCO3- concentration and following changes in pHe produced by changes of external HCO3- concentration at a constant PCO2. The data show that the relationship between pHi and Phe is: pHi = 0.973 pHe - 0.027 (r = 0.99, P less than 0.001). Thus at pHe = 7.40, macrophage intracellular pHi = 7.17. Alveolar macrophages appear to be permeable to H+/HCO3- and thus resemble erythrocytes, platelets, and lymphocytes and not brain and muscle cells.

Acid-Base Equilibrium↗
PubMed1981

Bioenergetic alterations in cultivated pulmonary artery and aortic endothelial cells exposed to normoxia and hypoxia.

Endothelial cells function under conditions of different oxygen availability under physiologic conditions and a variety of pathologic states. We determined the effect of normal and low O2 tensions on three key bioenergetic enzymes [pyruvate kinase (ATP:pyruvate phosphotransferase, EC 2.7.1.40), phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 27.1.11) and cytochrome aa3] in culture-maintained endothelial cells derived from calf pulmonary artery and aorta. Endothelial cells derived from pulmonary artery and aorta demonstrate similar bioenergetic enzyme activities when exposed to the same PO2 in vitro. Endothelial cells exposed to hypoxia in vitro for 48-96 hr show significantly increase activities of 2 key glycolytic enzymes: pyruvate kinase, and phosphofructokinase. Freshly isolated intimal strips from calf pulmonary artery (normal PO2 = 40 torr) show significantly greater activities of PyKi than aortic intimal strips (normal PO2 = 90 torr), suggesting that a similar pattern occurs in vivo. The data suggest that both cell types have a common bioenergetic pattern which is genetically determined and that this pattern is modified by regulatory mechanisms geared to ambient O2 tension. As endothelial cells of both types are not uncommonly exposed to hypoxic conditions, these regulatory mechanisms may play an important role in maintaining vascular integrity.

Animals↗
PubMed1980

Regulation of glycolytic enzyme activity during chronic hypoxia by changes in rate-limiting enzyme content. Use of monoclonal antibodies to quantitate changes in pyruvate kinase content.

Monoclonal antibodies were prepared against pyruvate kinase (PyKi; ATP: pyruvate phosphotransferase, EC 2.7.1.40) and used to quantitate PyKi content in L2 lung cells and WI-38 fibroblasts cultivated under hypoxic and normoxic conditions. After 96 h of hypoxic cultivation, PyKi activity was significantly increased in both cell types (L2: normoxia [Po2 = 142 torr], 0.11 +/- 0.01 [SD]; hypoxia [Po2 = 14 torr], 0.25 +/- 0.04 U/microgram DNA, P < 0.01). PyKi content increased proportionately in both cell lines (L2: normoxia, 0.44 +/- 0.13; hypoxia, 0.94 +/- 0.13 microgram enzyme protein/microgram DNA). Specific activity was not significantly different after 96 h (L2: normoxia, 261 +/- 11; hypoxia, 261 +/- 14 U/mg enzyme protein). These results indicate that regulation of glycolysis during chronic hypoxia occurs at the level of enzyme content. Chronic O2 depletion leads to either an increased rate of biosynthesis or a decreased rate of biodegradation of PyKi, causing augmented glycolytic capacity. Monoclonal antibodies provide a highly specific, convenient approach to charcterizing enzymes, as well as quantitating cellular enzyme content.

Animals↗
PubMed1980

Impairment of phagocytosis by moderate hyperoxia (40 to 60 per cent oxygen) in lung macrophages.

Exposure of isolated mouse lung macrophages to 40 and 60 per cent oxygen in tissue culture for 48 hours resulted in significant depression of phagocytosis as compared to air-exposed controls. The impairment of phagocytosis was reversed when the cells were reexposed to normoxic conditions for 48 hours. The impairment of phagocytosis occurred despite significant increases in intracellular superoxide dismutase activity, an enzyme felt to play a protective role in oxygen toxicity. Exposure to 40 and 60 per cent oxygen increased the susceptibility of lung macrophages to functional impairment by 95 per cent oxygen, rather than producing tolerance. The precise biologic and clinical significance of these findings will require additional studies in integrated systems. However, these studies show unequivocal lung macrophage injury with moderate hyperoxic exposure.

Animals↗
PubMed1979

External ocular toxicity of dipivalyl epinephrine.

Of 26 patients enrolled in a study designed to assess the usefulness of dipivalyl epinephrine 0.1%, administered topically at 12-hour intervals, for lowering intraocular pressure in patients with glaucoma and ocular hypertension, six patients (23.1%) developed adverse external ocular side effects severe enough to require that the drug be discontinued. Four of these six patients had a history of previous intolerance to epinephrine. The other two had successfully used epinephrine HCl 2% for more than two years before being treated with dipivalyl epinephrine and developed an adverse reaction after taking the drug 18 and 22 months, respectively. One patient with a history of epinephrine intolerance has successfully used dipivalyl epinephrine for 26 months to date. Our observations suggest that duration of exposure is an important factor in the development of sensitization to topically applied dipivalyl epinephrine.

Administration, Topical↗
PubMed1979

Effects of sustained oxygen depletion on tissue pyruvate kinase activities in the freshwater turtle, Pseudemys scripta elegans.

1. The effect of sustained (48 hr) oxygen depletion on tissue (brain, heart, skeletal muscle) pyruvate kinase (PyKi) activities was examined in the pond turtle (Pseudemys scripta elegans). 2. PyKi activities in skeletal muscle are significantly increased (from 322 +/- 84 to 450 +/- 95) following 48 hr of tissue hypoxia. PyKi activities in brain may already be elevated under ambient conditions but do not change following prolonged submersion (334 +/- 75 vs 325 +/- 77). Cardiac muscle PyKi is actually decreased (from 135 +/- 35 to 94 +/- 18) under anaerobic conditions. 3. The data suggest that prolonged O2 depletion may increase PyKi biosynthesis in turtle skeletal muscle (subserving enhanced glycolysis), but also demonstrate that factors other than oxygen availability are involved in the regulation of tissue PyKi activities in intact vertebrates.

Animals↗
PubMed1979

Bioenergetic pattern of turtle brain and resistance to profound loss of mitochondrial ATP generation.

The adaptations in the freshwater turtle that permit survival despite prolonged loss of mitochondrial ATP generation were investigated by comparing the bioenergetics of turtle brain slices with rat brain slices. Aerobic turtle brain shows no significant difference in basal levels of total ATP generation compared to rat brain; levels in turtle brain and rat brain were 18.4 +/- 2.8 (SD) and 19.4 +/- 2.2 mumol (100 mg of tissue)-1 hr-1, respectively. However, in turtle brain, a significantly greater fraction of ATP is derived from glycolysis both under aerobic and anaerobic conditions [aerobic turtle (24%) and rat (13%), P less than 0.02; anaerobic, turtle (28%) and rat (18%), P less than 0.05]. The increased glycolytic capacity is related to high levels of rate-limiting glycolytic enzymes, such as pyruvate kinase (EC 2.7.1.40). Turtle brain operates close to glycolytic capacity even under aerobic conditions, and no Pasteur effect can be demonstrated. Quantitatively, anaerobic glycolysis accounts for a maximum of 28% of basal aerobic ATP generation, suggesting that prolonged diving is also accompanied by a reduction in brain energy requirements. The adaptation subserving short-term (natural) diving is an increase in brain glycolytic capacity. The adaptation subserving prolonged diving (days to weeks) may be a reduction in the energy requirements of brain (and other cells).

Animals↗