Biomedical subjects
Publications and source records attributed to M Lowry.
Students who drop out of pre-registration nurse education not only represent a lost opportunity, but also a waste of time, effort and precious resources. The changes heralded by Project 2000 make this an ideal time to re-evaluate attitudes towards recruitment.
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Explore the source record for details and available documents.
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The provision of seating in the wards is something we all take for granted. However, poor seating design can exacerbate patient injury and illness, and so require extra nursing time.
The purpose of this review is to examine the factors regulating ammonium production in the kidney and to place these factors in the perspective of acid-base balance. Renal ammonium production and excretion are required to maintain acid-base balance. However, only a portion of renal ammonium production is specifically stimulated by metabolic acidosis. One should examine urinary ammonium excretion at three levels: distribution of ammonium between blood and urine, augmented glutamine metabolism, and an energy constraint due to ATP balance considerations. With respect to the biochemical regulation of acid-base renal ammonium production, an acute stimulation of alpha-ketoglutarate dehydrogenase by a fall in pH seems to be important but this may not be the entire story. In chronic metabolic acidosis augmented glutamine entry into mitochondria (dog) or increased phosphate-dependent glutaminase activity (rat) become critical to support a high flux rate. Metabolic alterations, which diminish the rate of oxidation of alternate fuels, might also be important. The above principles are discussed in the ketoacidosis of fasting, the clinically important situation of high rates of renal ammonium production.
The pathway of serine synthesis by the rat kidney has been investigated in vivo by measuring the net flux in the presence and absence of specific inhibitors of the glycine cleavage system, phosphoenol-pyruvate carboxykinase and gamma-glutamyltranspeptidase. In normal animals serine release was 705 +/- 187 nmol X min-1 X animal-1, whereas glycine uptake was only 28% of this value. Inhibition of the glycine cleavage system (cysteamine infusion) resulted in a reversal of glycine flux with no change in serine production. In similar experiments with mercaptopicolinate serine release was decreased by 55% with no change in glycine removal. AT-125, a potent inhibitor of gamma-glutamyltranspeptidase, had no effect on renal serine and glycine fluxes. In chronically acidotic rats serine synthesis was unchanged, but there were significant increases in the uptake of glutamine (fourfold) and glycine (2.5-fold). Infusion of cysteamine into these animals caused a 50% decrease in serine release with a significant reversal of the glycine flux. Infusion of mercaptopicolinate had effects similar to those observed in normal animals. These results show that renal serine synthesis can occur by both the phosphorylated-intermediate pathway and serine hydroxymethyltransferase in vivo. Furthermore, they demonstrate that glycine can contribute significantly to ammoniagenesis during acidosis.
Renal serine synthesis was studied in the isolated perfused kidney and in isolated cortical tubules. Serine was produced by the perfused kidney from both glycine and aspartate, indicating flux through at least two separate pathways: serine hydroxymethyltransferase and either the nonphosphorylated or phosphorylated intermediate pathways. The precise nephron site of serine production was determined by measuring serine synthesis from various precursors and the activities of enzymes of both pathways in isolated tubules fractionated on a Percoll gradient into proximal tubule and distal tubule fractions. Both pathways of serine synthesis were located in proximal tubules. Detailed studies of serine synthesis from glycine demonstrated extremely tight coupling between the glycine cleavage enzyme and serine hydroxymethyltransferase, since the rate of 14CO2 production from [2-14C]glycine was less than 5% of that of [1-14C]glycine, whereas the rate of incorporation of 14C into serine from [2-14C]glycine was double that from [1-14C]glycine. These studies demonstrate that the kidney can synthesize serine by two separate pathways, both located in the cells of the proximal tubule.
Glycine is metabolized in isolated renal cortical tubules to stochiometric qualities of ammonia, CO2 and serine by the combined actions of the glycine-cleavage-enzyme complex and serine hydroxymethyltransferase. The rate of renal glycine metabolism by this route is increased in tubules from acidotic rats, but is not affected in vitro by decreasing the incubation pH from 7.4 to 7.1. Metabolic acidosis caused an increase in the renal activity of the glycine-cleavage-enzyme complex, but there were no changes in the activity of serine hydroxymethyltransferase or of methylenetetrahydrofolate dehydrogenase. This enzymic adaptation permits increased ammoniagenesis from glycine during acidosis. The physiological implications are discussed.
Isolated perfused rat kidneys removed considerable quantities of glycyltyrosine, glycylhydroxyproline, tetraglycine and prolylhydroxyproline from the perfusate. The component amino acids are released into the perfusate and, in the case of the glycine-containing peptides, there is increased synthesis of serine. Removal of peptides was more than could be accounted for on the basis of filtration, so antiluminal metabolism is indicated. Metabolism of such peptides by the kidney may contribute to renal serine synthesis in vivo.
The metabolism of hydroxyproline by the rat kidney leads to the production of significant quantities of both glycine and serine. This process was observed in both the isolated perfused kidney and in isolated cortical tubule suspensions. The rate of hydroxyproline metabolism was increased in both preparations by the addition of alanine. The distribution of hydroxyproline oxidase, hydroxyoxoglutarate aldolase and alanine-glyoxalate transaminase were determined in detail. All three enzymes were found exclusively in the renal cortex where they were restricted to the mitochondria. Cortical tubule fractionation studies indicated that the enzymes are located in the proximal convoluted and proximal straight segments at the nephron. The results suggest that hydroxyproline degradation could contribute significantly to the renal synthesis of serine.
Branched-chain-amino-acid:alpha-ketoglutarate transaminase and branched-chain alpha-ketoacid dehydrogenase have been assayed in brains of control and of streptozotocin-induced diabetic rats. Enzyme activities were measured in five distinct regions of the brain: cerebellum, pons + medulla, midbrain, thalamus + hypothalamus, and telencephalon. Subcellular distribution of these enzymes in whole brain was assessed by fractionating brain homogenate into cytoplasm, free mitochondria, and synaptosomes. The following enzymes were used as markers: lactate dehydrogenase for cytoplasm, glutamate dehydrogenase for mitochondria, and glutamate decarboxylase for synaptosomes. The activity of the branched-chain amino acid transaminase in all brain regions was considerably higher than that of the branched-chain alpha-ketoacid dehydrogenase. While the highest activity of the transaminase occurred in brain-stem regions, the highest activity of the dehydrogenase was present in cerebellum and telencephalon. Diabetes did not affect the activity of the transaminase, but it caused a decrease in the total activity of the dehydrogenase in midbrain and in thalamus + hypothalamus. The transaminase was localized in the cytoplasmic fraction of whole brain, while the dehydrogenase was enriched in the free mitochondria.
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Metabolic rates and adenine nucleotide content of liver and kidney from hibernating ground squirrels were measured and compared to rats to study the biochemical adaptation to hibernation. High rates of renal and hepatic gluconeogenesis were observed in squirrels, particularly from propionate and glycerol compared to rat. During hibernation and starvation soluble phosphoenolpyruvate carboxykinase activity was increased in both liver and kidney. Although metabolic rates are decreased during hibernation the results suggest that the enzymic complement is maintained at high activity even during torpor.
Of a group of 288 depressed female inpatients, 43 (15%) had secondary panic attacks. Compared to other depressives, the subgroup with panic attacks had significantly higher frequencies of anorexia, weight loss, gastrointestinal disturbances, hypochondriasis, and psychomotor agitation, and significantly lower frequencies of melancholic symptoms, including loss of interest in usual activities, guilt feelings, delusional thinking, psychomotor retardation, and orientation or memory impairment. Patients with panic attacks were less likely to have a depressed parent and were more likely to be described as having been nervous, worrisome, sensitive, and sexually dysfunctional before the onset of depression. Phenomenologically, they resembled "anxious depressives" as described by other authors.