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Biomedical subjects

E D Robin

Publications and source records attributed to E D Robin.

At least 73 records · Page 4Linked to original sources
PubMed1985

Increased biosynthesis of pyruvate kinase under hypoxic conditions in mammalian cells.

The rate of biosynthesis of pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) was compared in cells maintained under normoxic or hypoxic conditions. L8 cells (a myoblast cell line) were pulse-labeled with [3H]leucine and incorporation of radioactivity into pyruvate kinase was measured after quantitative affinity separation with anti-pyruvate kinase monoclonal antibody. During chronic hypoxia there is an increased rate of biosynthesis of pyruvate kinase leading to an increase in enzyme content and augmented glycolytic capacity. An inhibitor of the electron transport chain, antimycin A, was used to determine whether changes in pyruvate kinase content occurring during hypoxia are a result of reduction in molecular oxygen directly or an indirect consequence of oxygen depletion. Pyruvate kinase activity increased during chronic antimycin A exposure under normoxic conditions. The increase was quantitatively accounted for by an increase in cellular pyruvate kinase enzyme content. This suggested that decreases in the levels of molecular O2 are not the direct stimulus for the increased content of pyruvate kinase. It is more likely that the increased pyruvate kinase content results from depressed rates of electron transport through the mitochondrial electron transport chain.

Animals↗
PubMed1985

Monitoring hypoxia.

The use of extensive monitoring approaches in patients with various forms of hypoxic disease has flourished extensively during the past decade. When coupled to advanced computer technology, the capacity for generation and storage of data has increased enormously. In addition to clinicians and biomedical scientists, the field has attracted engineers and computer scientists. Most of these developments have occurred without adequate evaluation of the impact of these efforts on the safety and effectiveness of patient management. Moreover this expansion has occurred without a predesigned structural format for either evaluation or for quality control of the various monitoring modalities. Two basic assumptions are widely accepted: 1) That massive data collection is automatically useful; and 2) Monitoring coupled to computerization necessarily leads to better outcome for patients. This paper will challenge both of these assumptions by providing an analysis of monitoring generally with special emphasis on hypoxia. In addition it will describe some current developments in the monitoring of hypoxia.

Catheterization↗
PubMed1985

Prolonged diving and recovery in the freshwater turtle, Pseudemys scripta--IV. Effects of profound acidosis on O2 consumption in turtle vs rat (mammalian) brain and heart slices.

The oxygen consumption of rat versus turtle brain and heart slices was compared as a function of extracellular pH and temperature. At pH = 6.20 rat (mammalian) brain and heart slices show a significant depression of oxygen consumption as compared to pH = 7.50 at temperatures of both 24 degrees and 37 degrees C. In the turtle oxygen consumption in brain and heart slices was not depressed at pH = 6.20 compared to pH = 7.50 at 24 degrees C and brain oxygen consumption was not significantly different at the two pH values at 37 degrees C. Turtle heart QO2 was depressed at 37 degrees C. The results suggest that extracellular acidosis depresses mitochondrial O2 uptake in mammalian brain and heart, playing a role in the bioenergetic manifestations of O2 depletion. Turtle brain mitochondria do not show a depression of QO2 at the acidotic pH. The resistance to acidosis of turtle brain mitochondria presumably enhances the possibility of survival following prolonged diving by maintaining ATP generation during the early diving period and during recovery.

Acidosis↗
PubMed1985

Impact of profound reductions of PaO2 on O2 transport and utilization in congenital heart disease.

A group of eight adult patients with congenital cyanotic heart disease (CCHD) with PaO2 values of less than 32 mm Hg at rest and/or exercise were studied. Four of the patients were re-studied after heart-lung transplantation and restoration of PaO2 to normal values. All eight patients showed increased red cell counts (polycythemia), whereas frankly elevated hemoglobin concentrations were found in only one patient. There was no impressive change in the affinity of hemoglobin for O2 as compared to normal subjects. Blood lactate concentrations were normal at rest before transplantation, rose very modestly during moderate exercise, and were normal following transplantation indicating that the concept of anaerobic threshold is not valid in the present group of patients. Cardiac index was not elevated in the pretransplantation period, indicating that an elevated cardiac output is not an essential adaptive mechanism for dealing with hypoxia. In the pre-transplant period, O2 consumption was elevated as compared to normal values and almost doubled during exercise despite a further decline in PaO2 and SaO2; this establishes that the rate of mitochondrial O2 utilization is maintained despite profound reduction in PaO2. These patients are capable of moderate exercise and normal brain function despite severe hypoxia and the absence or attenuation of various adaptive mechanisms for dealing with hypoxia. Further study of the specifics of O2 transport and utilization in similar patients should prove rewarding.

Adult↗
PubMed1985

The cult of the Swan-Ganz catheter. Overuse and abuse of pulmonary flow catheters.

The use of pulmonary artery flow-directed catheters has assumed epidemic proportions without clinical trials establishing improved outcome as a result of their use. During the past 10 years, however, it has become clear that improved outcome is found only in small groups of patients and that use of these catheters is associated with considerable risks of morbidity and mortality. A clinical trial is urgently needed to assess the balance between risks and benefits. While awaiting such trials, physicians should limit catheter use to circumstances in which there is a large probability that the data will result in more effective management; the measurements should only be used to answer specific questions about patient therapy. This situation will occur in a relatively small number of patients.

Cardiac Catheterization↗
PubMed1984

Hypoxic coordinate regulation of mitochondrial enzymes in mammalian cells.

The effect of hypoxic exposure on various mitochondrial enzymes and on cell mitochondrial genomic content was studied in two types of mammalian cells. Hypoxia depressed the activity of six enzymes to the same degree. The kinetics of depression and of recovery during reexposure to normoxia were statistically similar for three marker enzymes. Despite the global and symmetrical decrease in enzyme activities, mitochondrial DNA remained constant. This suggests either symmetrical loss of mitochondrial enzymes from all mitochondria or complete loss of enzymes from a subpopulation of mitochondria with retention of an intact mitochondrial genome.

Aerobiosis↗
PubMed1984

Coordinate regulation of glycolysis by hypoxia in mammalian cells.

The impact of hypoxic exposure on the activities of all 11 glycolytic enzymes was studied in cell culture into mammalian cells-mouse lung macrophages and L8 rat skeletal muscle cells. During hypoxic exposure, the measured activity of all glycolytic enzymes increased, establishing coordinate regulation. Three nonglycolytic cytoplasmic enzymes showed no change in activity under the same conditions, suggesting a specific mechanism. Hypoxia appears to increase the activities of all glycolytic enzymes whether rate-limiting or not, presumably increasing adenosine triphosphate availability despite decreased O2 supply.

Animals↗
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

Some implications of augmented collagen levels with bleomycin exposure or hyperoxic exposure of lung fibroblasts: fibrosis as altered phenotypic expression.

Bleomycin is a primary fibrogenic agent which increases collagen content in a fibroblast system by a direct effect on fibroblasts. A mechanism for the increase in collagen content is an increase in the rate of collagen biosynthesis. This implies alteration of either collagen transcription or translation. Hyperoxia depresses collagen biosynthesis without changing collagen content. This implies that hyperoxia also depresses collagen degradation. The addition of phagocytes (macrophages) to hyperoxically exposed cells increases both collagen content and the rate of collagen biosynthesis. Hyperoxia is therefore a secondary fibrogenic agent. This suggests that mediators released from phagocytes alter collagen transcription or translation.

Bleomycin↗
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↗
PubMed1982

Clinical management conference. Interstitial lung disease in an elderly woman.

This is a Clinical Management Conference (CMC) presented at a community hospital. It differs from conventional teaching conferences in that (1) the focus of analysis is direct patient benefit and diagnosis is regarded as a secondary process, (2) it seeks to provide an understanding of logical approaches to patient management while confronted with numerous uncertainties caused by an inadequate scientific base, (3) there is no absolute answer provided and (4) the conference involves the entire audience of physicians as direct participants.

Aged↗