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Biomedical subjects

B D Ross

Publications and source records attributed to B D Ross.

At least 181 records · Page 10Linked to original sources
PubMed1976

Effect of inhibition of gluconeogenesis on ammonia production in the perfused rat kidney.

1. Gluconeogenesis from lactate or from glutamine is inhibited by 90-100% by sodium quinolinate (1 mmol/l) or 3-mercaptopicolinate (150 nmol/l) in the perfused rat kidney. L-Tryptophan is not metabolized and is without effect. 2. Lactate uptake and glucose production are inhibited to the same degree by 3-mercaptopicolinate in the kidneys of well-fed or starved rats. 3. Inhibition of gluconeogenesis from glutamine (1 mmol/l) by 3-mercaptopicolinate is accompanied by 50% inhibition of ammonia production, and 34% inhibition of glutamine uptake, in the kidneys of acidotic rats. Ammonia production from glutamine was not inhibited in kidneys from non-acidotic rats. 4. It is concluded that the increased rate of gluconeogenesis from glutamine which occurs in acidotic rats is an essential and primary event regulating all of the increase in ammonia formation.

Ammonia↗
PubMed1976

Energy requirements for metabolic and excretory activities of perfused rat kidney.

A ratio 34.5 NA+/O2, or 5.8 Na+/ATP is obtained for the ouabain sensitive sodium pump, which accounts for 50% of sodium transport in the perfused kidney. Na-K-ATP'ase activity accounts for 15% of renal O2 uptake and sodium transport may account for only 30% of renal oxygen uptake. 2. Hydrogen ion secretion requires little extra energy. An increase in respiration produced by increasing the filtered load of potassium was not prevented by ouabain and active potassium secretion produced no detectable increases in oxygen consumption. 3. In general, the rate of oxidation substrates presented individually does not correlate well with the theoretical energy requirement for sodium transport. Exceptions were the low rate of oxidation of glutamine, which is consistent with limited sodium transport, and glucose, where the expected and observed rates of glucose oxidation are in close agreement. 4. The difference between substrates cannot be explained by activity of pyruvate kinase, by pyruvate dehydrogenase activation, by futile cycling between PFK/FDP'ase, or by involvement of the malate-aspartate shuttle.

Aminooxyacetic Acid↗
PubMed1975

Effect of human lysozyme (muramidase) on potassium handling by the perfused rat kidney. A mechanism for renal damage in human monocytic leukaemia.

Purified human lysozyme (muramidase) stimulated potassium excretion by the isolated perfused rat kidney. Lysozyme is filtered and reabsorbed, without a tubular maximum. Over 90% of lysozyme filtered is retained within the kidney; 50% was recovered by enzymic assay and histologically localized to the proximal tubular cells. Hypokalaemia seen in some patients with myelomonocytic leukaemia may be directly attributed to an elevated circulating lysozyme level.

Animals↗
PubMed1975

Potassium transport by the isolated perfused kidney.

Rat kidneys perfused outside of the body with an artificial medium are able to increase their fractional excretion of potassium in response to a rising concentration of potassium in the medium but never show net secretion of potassium. By contrast, isolated perfused kidneys from chronically potassium-loaded rats regularly secrete potassium in excess of the amount filtered. Ouabain completely blocks the secretion of potassium by these isolated kidneys, suggesting that Na-K-ATPase mediates potassium secretion by potassium-adapted rats. Neither sodium deprivation, pretreatment with deoxycorticosterone, nor pretreatment with methylprednisolone prepared the kidney to secrete potassium, despite stimulation of Na-K-ATPase activity in cortex or outer medulla. Potassium loading was the only maneuver tested that increased the activity of Na-Katpase in the inner medulla (white papilla) and also produced potassium secretion by the isolated kidney. Surgical ablation of the papilla abolished the net secretion of potassium normally seen in perfused kidneys of potassium-adapted rats, thus underlining the importance of the papilla in the process of potassium adaptation.

Adaptation, Physiological↗
PubMed1967

The rate of gluconeogenesis from various precursors in the perfused rat liver.

1. The rates of gluconeogenesis from many precursors have been measured in the perfused rat liver and, for comparison, in rat liver slices. All livers were from rats starved for 48hr. Under optimum conditions the rates in perfused liver were three to five times those found under optimum conditions in slices. 2. Rapid gluconeogenesis (rates of above 0.5mumole/g./min.) were found with lactate, pyruvate, alanine, serine, proline, fructose, dihydroxyacetone, sorbitol, xylitol. Unexpectedly other amino acids, notably glutamate and aspartate, and the intermediates of the tricarboxylic acid cycle (with the exception of oxaloacetate), reacted very slowly and were not readily removed from the perfusion medium, presumably because of permeability barriers which prevent the passage of highly charged negative ions. Glutamine and asparagine formed glucose more readily than the corresponding amino acids. 3. Glucagon increased the rate of gluconeogenesis from lactate and pyruvate but not from any other precursor tested. This occurred when the liver was virtually completely depleted of glycogen. Two sites of action of glucagon must therefore be postulated: one concerned with mobilization of liver glycogen, the other with the promotion of gluconeogenesis. Sliced liver did not respond to glucagon. 4. Pyruvate and oxaloacetate formed substantial quantities of lactate on perfusion, which indicates that the reducing power provided in the cytoplasm was in excess of the needs of gluconeogenesis. 5. Values for the content of intermediary metabolites of gluconeogenesis in the perfused liver are reported. The values for most intermediates rose on addition of lactate. 6. The rates of gluconeogenesis from lactate and pyruvate were not affected by wide variations of the lactate/pyruvate ratio in the perfusion medium.

Journal Article↗
PubMed1967

Metabolic activities of the isolated perfused rat kidney.

1. A technique for perfusing the isolated rat kidney is described. It is primarily designed for the study of renal metabolism but is also suitable for studying some aspects of the secretory function; this was normal with respect to minimal glucosuria. The glomerular filtration rate as measured by creatinine clearance was lower than in vivo and slowly decreased with time. 2. Gluconeogenesis from a variety of precursors was rapid and similar to that in kidney-cortex slices, in contrast with liver where the perfused organ is more effective than slices. Whereas the maximal rates of gluconeogenesis from glycerol and pyruvate were similar in liver and kidney, the rates from succinate, malate and fumarate were 14-20 times, and those from glutamate and aspartate about three times, as high in the kidney. 3. The oxygen consumption of the perfused organ was about twice that of cortex slices, presumably because of the secretory work done in the perfused organ but not in slices. 4. The rate of acetoacetate oxidation was about the same in the perfused organ and in slices but, because of the higher rate of oxygen consumption, the percentage contribution of acetoacetate to the fuel of respiration was lower in the perfused organ. The results suggest that acetoacetate can supply energy for the basal requirements and for gluconeogenesis but not for the secretory work. 5. Glutamine was formed at a high rate from glutamate and at a lower rate from aspartate. The high rates indicate that, in the rat, the kidney is a major source of body glutamine.

Acetoacetates↗
PubMed1967

Carbohydrate metabolism of the perfused rat liver.

1. The rates of gluconeogenesis from most substrates tested in the perfused livers of well-fed rats were about half of those obtained in the livers of starved rats. There was no difference for glycerol. 2. A diet low in carbohydrate increased the rates of gluconeogenesis from some substrates but not from all. In general the effects of a low-carbohydrate diet on rat liver are less marked than those on rat kidney cortex. 3. Glycogen was deposited in the livers of starved rats when the perfusion medium contained about 10mm-glucose. The shedding of glucose from the glycogen stores by the well-fed liver was greatly diminished by 10mm-glucose and stopped by 13.3mm-glucose. Livers of well-fed rats that were depleted of their glycogen stores by treatment with phlorrhizin and glucagon synthesized glycogen from glucose. 4. When two gluconeogenic substrates were added to the perfusion medium additive effects occurred only when glycerol was one of the substrates. Lactate and glycerol gave more than additive effects owing to an increased rate of glucose formation from glycerol. 5. Pyruvate also accelerated the conversion of glycerol into glucose, and the accelerating effect of lactate can be attributed to a rapid formation of pyruvate from lactate. 6. Butyrate and oleate at 2mm, which alone are not gluconeogenic, increased the rate of gluconeogenesis from lactate. 7. The acceleration of gluconeogenesis from lactate by glucagon was also found when gluconeogenesis from lactate was stimulated by butyrate and oleate. This finding is not compatible with the view that the primary action of glucagon in promoting gluconeogenesis is an acceleration of lipolysis. 8. The rate of gluconeogenesis from pyruvate at 10mm was only 70% of that at 5mm. This ;inhibition' was abolished by oleate or glucagon.

Animal Nutritional Physiological Phenomena↗
PubMed1966

Gluconeogenesis in the perfused rat liver.

1. A modification of the methods of Miller and of Schimassek for the perfusion of the isolated rat liver, suitable for the study of gluconeogenesis, is described. 2. The main modifications concern the operative technique (reducing the period of anoxia during the operation to 3min.) and the use of aged (non-glycolysing) red cells in the semi-synthetic perfusion medium. 3. The performance of the perfused liver was tested by measuring the rate of gluconeogenesis, of urea synthesis and the stability of adenine nucleotides. Higher rates of gluconeogenesis (1mumole/min./g.) from excess of lactate and of urea synthesis from excess of ammonia (4mumoles/min./g. in the presence of ornithine) were observed than are likely to occur in vivo where rates are limited by the rate of supply of precursor. The concentrations of the three adenine nucleotides in the liver tissue were maintained within 15% over a perfusion period of 135min. 4. Ca(2+), Na(+), K(+), Mg(2+) and phosphate were found to be required at physiological concentrations for optimum gluconeogenesis but bicarbonate and carbon dioxide could be largely replaced by phosphate buffer without affecting the rate of gluconeogenesis. 5. Maximal gluconeogenesis did not decrease maximal urea synthesis in the presence of ornithine and ammonia and vice versa. This indicates that the energy requirements were not limiting the rates of gluconeogenesis or of urea synthesis. 6. Addition of lactate, and especially ammonium salts, increased the uptake of oxygen more than expected on the basis of the ATP requirements of the gluconeogenesis and urea synthesis.

Adenosine Triphosphate↗
PubMedDate not supplied

Endorectal surface coil MR imaging of prostatic carcinoma with the inversion-recovery sequence.

The value of inversion-recovery (IR) sequences in the diagnosis and staging of prostatic carcinoma with magnetic resonance (MR) imaging was studied. Twenty-six patients with carcinoma of the prostate were imaged at 1.5 T with an endorectal surface coil and with a variety of IR sequences and a set of spin-echo (SE) sequences for comparison. Ex vivo prostate specimens were imaged again at the same field strength. The two images were correlated with histologic sections. Cancer was identified with MR imaging in 96% of patients. Of the tumors more than 4 mm in diameter, 87% were identified on T2-weighted SE images, whereas only 26% were identified on IR images. However, IR images may be more useful in local staging of carcinoma. Gross capsular infiltration was present in only two patients; however, it was detectable (and excluded in five other patients) by means of IR images. It was not detectable on SE images. The high quality of images obtained with the endorectal coil was confirmed. The authors conclude that addition of the IR sequence to MR imaging with the endorectal coil may improve the usefulness of this examination.

Adult↗
PubMedDate not supplied

Quantitative P-31 MR spectroscopy of the liver in alcoholic cirrhosis.

To determine the cause of reduced urea synthesis in cirrhosis, absolute concentrations of phosphorus metabolites in the human liver have been measured in vivo with magnetic resonance (MR) spectroscopy. One-dimensional chemical shift imaging was used to obtain phosphorus-31 spectra from five healthy volunteers and five patients with alcoholic cirrhosis. A reference standard included in all studies enabled the calculation of absolute concentrations. In contrast to hepatic metabolite ratios, absolute concentrations reveal that in the cirrhotic patients, concentrations of adenosine triphosphate (ATP) were significantly reduced and concentrations of phosphomonoesters slightly reduced. Intracellular pH was unchanged. Histologic evidence suggests that the amount of ATP per cell was unchanged and could not account for the reduced urea production. Instead, urea synthesis depends on the functional liver cell mass, which was reduced by 31% in alcoholic cirrhosis. Quantitative in vivo P-31 MR spectroscopy of liver has potential clinical applications and can supplement the more generally used P-31 metabolite ratios.

Adenosine Triphosphate↗
PubMedDate not supplied

Dialysis and transplantation affect cerebral abnormalities of end-stage renal disease.

Localized short echo time proton magnetic resonance spectroscopy was performed to determine whether chronic and end-stage renal failure, hemodialysis, continuous ambulatory peritoneal dialysis, or renal transplantation result in alterations of cerebral water and metabolites in humans. Hemodialysis patients show an increased cerebral concentration of myo-inositol (+ 14%; P < .05). Increased metabolite ratios are found for myo-inositol/creatine (+14%; P <.01) and choline containing compounds choline/creatine (+10%; P < .01) and are more marked in gray than in white matter. N-acetylaspartate and total creatine concentrations are unaffected. Compared to hemodialysis, continuous ambulatory peritoneal dialysis patients show a larger increase in choline and less elevated myo-inositol. Acutely, hemodialysis significantly decreases the cerebrospinal fluid content of the examined brain regions, but metabolite changes are small compared to the persistent alterations in patients receiving hemodialysis or continuous ambulatory peritoneal dialysis. Undialyzed patients with chronic renal failure do not differ from patients on hemodialysis, but cerebral metabolite changes are completely reversed by transplantation. Cerebral metabolic effects of end-stage renal disease differ from Alzheimer's disease, which is associated with markedly reduced N-acetylaspartate, increased myo-inositol, and normal choline concentrations. The small but significant cerebral metabolic disorders associated with renal failure and dialysis may be a consequence of osmotic dysregulation.

Adult↗
PubMedDate not supplied

1H MRS in acute traumatic brain injury.

The objective of this study was to demonstrate 1H MR spectroscopy (MRS) changes in cerebral metabolites after acute head trauma. Twenty-five patients (12 children, 13 adults) were examined with quantitative 1H MRS after closed head injury. Clinical grade (Glasgow Coma Scale [GCS]) and outcome (Rancho Los Amigos Medical Center Outcome Score [ROS]) were correlated with quantitative neurochemical findings. N-acetylaspartate (NAA), a neuronal and axonal marker, was reduced (P < .03-.001). In children, a reduced NAA/creatine plus phosphocreatine (Cr) level and the presence of detectable lipid/lactate predicted bad outcome (sensitivity, 89%; specificity, 89%). The first MRS examination of all patients correlated with ROS versus NAA (r = .65, P < .0001). Although most patients showed MRS abnormalities, striking heterogeneity of 1H MRS characterized the individual patients. 1H MRS identifies multiple patterns of diffuse brain injury after blunt head trauma. There was a strong correlation between MRS and outcome. Future prospective studies will be needed to determine the clinical usefulness of MRS in predicting outcome from closed head injury.

Adult↗