bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Bendrofluazide and Frusemide on the Ventilatory Response to Carbon Dioxide and Hypoxia in Normal Man
Authors: Leitch A. G. , Clancy L. , Flenley D. C. 
Published: August 2015

1. We have determined the ventilatory response to CO2 at two levels of end-tidal O2 tension in eight normal subjects before and after (1) 4 days of 0.242 mmol (80 mg) oral frusemide daily and (2) 4 days of 0.024 mmol (10 mg) bendrofluazide daily.
2. Frusemide produced no significant alkalosis, change in end-tidal CO2 tension or alteration in the CO2 response line. However, we did demonstrate a linear relationship between the change in plasma total CO2 content and the change in intercept of the CO2 response line in hyperoxia after frusemide.
3. Bendrofluazide produced a metabolic alkalosis with no significant change in end-tidal CO2 tension. The CO2 response line after the drug showed a decrease in slope in hyperoxia and a shift to the right of the intercept in hypoxia. There was no relationship between change in plasma total CO2 content and change in the intercept of the CO2 response line in hyperoxia.
4. If these results obtained on normal subjects are applicable to patients with chronic bronchitis and emphysema, frusemide might be the diuretic of choice for use with controlled oxygen therapy in the management of acute exacerbations of this disease when it is complicated by ventilatory failure.
Vitamin E Protection of the Liver from Paracetamol in the Rat
Authors: Walker B. E. , Kelleher J. , Dixon M. F. , Losowsky M. S. 
Published: August 2015

1. Control, vitamin E-deficient, vitamin E-supplemented (deficient with added ‘normal’ intake) and vitamin E-treated rats were given paracetamol at a dose of 25.5 mmol (4 g)/kg body weight. Control rats were also given paracetamol with or without simultaneous vitamin E.
2. Plasma aspartate aminotransferase and alanine aminotransferase activities increased to very high values (mean 2842 and 1241 i.u./l respectively) in the control group, and even higher (mean 8220 and 2320 i.u./l respectively) in the vitamin E-deficient group.
3. In the vitamin E-supplemented group the rises in activity were similar but rather less than in the control group (mean 2417 and 815 i.u./l) and in the vitamin E-treated group only very small rises (mean 177 and 98 i.u./l) were seen.
4. Histological evidence of hepatic necrosis correlated closely with plasma enzyme activities.
5. It appears that paracetamol-induced hepatic necrosis is potentiated in vitamin E deficiency and reduced by prior treatment with α-tocopherol.
6. Vitamin E administered simultaneously with paracetamol at 12.8 or 19.2 mmol/kg also greatly reduced the expected rise in serum enzyme activities.
7. These observations may shed some light on the mechanism of paracetamol-induced hepatic necrosis, and may form a basis for preventing or reducing this lesion in man.
Muscle Metabolism during Exercise in Patients with Parkinson's Disease
Authors: Landin S. , Hagenfeldt L. , Saltin B. , Wahren J. 
Published: August 2015

1. Arterial concentrations and leg exchange of carbohydrate substrates and non-esterified fatty acids (NEFA) were examined together with concentrations of intramuscular metabolites at rest and during exercise in six patients with Parkinson's disease and in a group of five healthy control subjects.
2. Heart rate, pulmonary oxygen uptake and ventilatory exchange ratio were all significantly higher in the group of patients during exercise. The release of lactate by the exercising leg in the patients exceeded that of the control subjects and was associated with a significantly elevated arterial lactate concentration. Glucose uptake by the leg was greater in the patients during exercise. Arterial NEFA was higher and fractional NEFA turnover lower in the patients both at rest and during exercise, whereas oxidation of NEFA by the leg muscles during exercise was similar in the two groups.
3. ATP, creatine phosphate and glycogen content of muscle were significantly reduced in the basal state in the patients. During exercise, ATP fell markedly but the lactate content of muscle was within the normal range. Muscle glycogen utilization during exercise exceeded that of the controls. As in normal subjects, the reduction of glycogen content was most marked in type I (presumably slow-twitch) muscle fibres.
4. It is concluded that, in relation to controls, muscle metabolism in patients with Parkinson's disease (a) is associated with lower content of phosphagens, (b) is altered towards greater utilization of carbohydrate substrates, and (c) is associated with a low efficiency in the peripheral utilization of NEFA.
Hepatic Vitamin B12 Release and Transcobalamin II Synthesis in the Rat
Authors: Cooksley W. G. E. , England J. M. , Louis L. , Down M. C. , Tavill A. S. 
Published: August 2015

1. The release of 57Co-labelled vitamin B12 ([57Co]B12) and synthesis of transcobalamin II (TCII) by the isolated perfused rat liver were studied 10–42 days after the parenteral administration of a trace dose of 15 pmol (approximately 20 ng) of radioactive cyanocobalamin.
2. The rate of release of [57Co]B12 into plasma and bile was linear and constituted approximately 0.9% and 0.3% respectively of the initial hepatic radioactivity per hour of perfusion.
3. [57Co]B12 released into plasma was bound to TCII. Saturation of the total TCII by the addition of cyanocobalamin before perfusion resulted in the appearance of the hepatic [57Co]B12 in the free form.
4. These data were found to be compatible with the following observations in vivo: (i) rates of [57Co]B12 release as measured by urinary [57Co]B12 excretion after saturation of plasma binders with non-labelled cyanocobalamin; (ii) rates of biliary excretion of [57Co]B12.
5. Liver damage produced by hypoxaemia was associated with a fall in the rate of release of [57Co]B12.
6. TCII release occurred at a linear rate of almost twenty times that required for the binding of newly released hepatic vitamin B12.
7. Cycloheximide at a dose sufficient to inhibit release of TCII did not prevent the release of [57Co]B12 from the liver into plasma or bile.
8. Alteration of perfusate composition to contain either high plasma concentrations of vitamin B12 and low concentrations of unsaturated TCII or high plasma concentrations of vitamin B12 and high concentrations of unsaturated TCII had no effect on the rate of [57Co]B12 release into plasma or bile.
9. It is concluded that the fluxes of hepatic vitamin B12 and TCII are very rapid and that the release of vitamin B12 by the rat liver is controlled in the short term by factors other than the synthesis of TCII and the concentration of vitamin B12 or unsaturated transcobalamin in the plasma.
2,3-Diphosphoglycerate Concentrations and the Dissociation of Oxyhaemoglobin in Ventilatory Failure
Authors: Fairweather L. J. , Walker J. , Flenley D. C. 
Published: August 2015

1. The position of the oxygen-haemoglobin dissociation curve has been related to erythrocyte 2,3-diphosphoglycerate (2,3-DPG) concentrations in twenty-seven patients with both acute and chronic respiratory failure.
2. The average values of both 2,3-DPG concentration and of the oxygen tension for one-half full saturation (P50) in these patients were normal, but values both above and below the normal range were encountered.
3. P50 values correlated positively with erythrocyte 2,3-DPG concentrations, but negatively correlated with the mean corpuscular haemoglobin concentration in these patients.
4. Multiple regression, including the above two variables and also the blood oxygen capacity as major factors, accounted for just under half of the variance in the position of the dissociation curve, and this was little improved by addition of the minor effects of the arterial oxygen and carbon dioxide tensions.
5. The intraerythrocytic pH bore a similar relationship to plasma pH, in both studies in vitro of blood from normal subjects and patients with chronic hypercapnia, and studies in vivo in hypercapnic subjects.
The Effect of Vitamin B12 Deficiency on Methylfolate Metabolism and Pteroylpolyglutamate Synthesis in Human Cells
Authors: Lavoie A. , Tripp E. , Hoffbrand A. V. 
Published: August 2015

1. The uptake of 14C from [methyl-14C]methyItetrahydrofolate was significantly reduced in the phytohaemagglutinin (PHA)-stimulated lymphocytes from nine patients with untreated pernicious anaemia compared with the uptake in seven normal subjects.
2. The uptake of 14C from [14C]methyltetrahydrofolate by the lymphocytes from seven of the patients with pernicious anaemia was consistently increased by addition of vitamin B12in vitro.
3. The proportion of 14C taken up from [14C]methyltetrahydrofolate transferred to non-folate compounds was found to be significantly reduced in the PHA-stimulated lymphocytes from nine patients with untreated pernicious anaemia compared with the proportion transferred in the PHA-stimulated lymphocytes from seven normal subjects. Addition of vitamin B12in vitro consistently increased the transfer in vitamin B12-deficient cells but had no consistent effect in normal cells.
4. Normal and vitamin B12-deficient PHA-stimulated lymphocytes took up [3H]folic acid and after 72 h incubation converted this largely into pteroylpolyglutamate forms.
5. The proportion of labelled lymphocyte folate as pteroylpolyglutamate after incubation with [3H]folic acid was the same in vitamin B12-deficient as in normal lymphocytes and the proportion of pteroylpolyglutamates formed in vitamin B12-deficient lymphocytes was unaffected by addition of vitamin B12in vitro.
6. No radioactivity could be decteted in pteroylpolyglutamates after incubating normal PHA-stimulated lymphocytes with [14C]methyltetrahydrofolate for 72 h, suggesting that pteroylpolyglutamate forms of folate cannot be made directly from methyltetrahydrofolate.
7. These results are consistent with the ‘methyltetrahydrofolate trap’ hypothesis in vitamin B12 deficiency. It is suggested that reduced synthesis of pteroylpolyglutamates reported by others in vitamin B12-deficient cells may be secondary to the failure of removal of the methyl group from methyltetrahydrofolate rather than to a direct effect of vitamin B12 deficiency on the enzyme responsible for pteroylpolyglutamate synthesis.
8. Reduced entry of methyltetrahydrofolate into vitamin B12-deficient cells may be secondary to failure of conversion of this compound into tetrahydrofolate.
Seasonal Variation of Lipoprotein Lipase Activity in Human Subcutaneous Adipose Tissue
Authors: Persson B. 
Published: August 2015

1. In 126 normotriglyceridaemic and in seventy-three hypertriglyceridaemic subjects there was a similar seasonal variation of adipose tissue lipoprotein lipase activity, the lowest activity being noted during the summer months.
2. There was no seasonal variation of the serum triglyceride or free fatty acid concentrations in the normotriglyceridaemic group.
3. In the same group the highest blood acetoacetate concentration was noted in March–April, the lowest in November–December.
4. There was no seasonal variation of the blood glucose concentration for women, but for men the lowest concentration was noted in July–August.
The Metabolism of Low-Density Lipoprotein in a Patient with Familial Hyperbetalipoproteinaemia
Authors: Reichl D. , Simons L. A. , Myant N. B. 
Published: August 2015

1. Plasma low-density lipoprotein (LDL) from a patient with homozygous familial hyperbetalipoproteinaemia was labelled with 125I and LDL from a matched normal subject was labelled with 131I. The two samples of LDL were injected simultaneously into the patient and into a second normal subject.
2. In each subject the fractional rate of turnover of the two LDL samples was the same, but the fractional rate in the patient was less than half that in the normal subject.
3. It is concluded that the hyperbetalipoproteinaemia in the patient was not due to an abnormality in her LDL protein recognizable by her own body or by that of the normal recipient.
Polyglutamate Forms of Folate in Resting and Proliferating Mammalian Tissues
Authors: Lavoie A. , Tripp Edith , Parsa K. , Hoffbrand A. V. 
Published: August 2015

1. Tritiated folic acid (pteroylglutamic acid) was injected into rats whose livers were undergoing regeneration after partial hepatectomy, and into normal control rats.
2. The major form of labelled liver folate was found to be pteroylpentaglutamate in both hepatectomized and normal rats and there was no difference in the proportion of pteroylpentaglutamate to other forms of folate in the regenerating or resting liver.
3. Folate concentrations were also measured in leucocytes from normal and leukaemic patients.
4. Pteroylpolyglutamates constituted the main form of folate in both sets of cells. There was again no difference in proportion of pteroylpolyglutamate to pteroylmonoglutamate forms of folate between normal mature cells and primitive blast cells.
5. It is therefore suggested that pteroylpolyglutamates, which constitute nearly all the folates in cells actively synthesizing DNA and protein as well as in resting cells, probably act as the coenzymes in vivo for the folate-dependent reactions in DNA, RNA and protein synthesis in mammalian systems.
Control of Phosphorylative Activity in Human Liver Mitochondria through Changes in Respiratory Enzyme Contents
Authors: Ozawa K. , Honjo I. 
Published: August 2015

1. Oxidative phosphorylation and respiratory enzyme activities were measured in the mitochondria from the non-involved lobe of the liver in eighteen patients with massive tumour mainly localized to one lobe and from the regenerating livers of partially hepatectomized rats treated with chloramphenicol.
2. In patients, the concentrations of cytochrome a(+ a3) varied from 40 to 170 pmol/mg of protein. In mitochondria with cytochrome a(+ a3) concentrations more than 70 pmol/mg of protein, the phosphorylative activity per mg of mitochondrial protein was considerably higher than in controls. The mitochondrial oxidative and phosphorylative activities per unit of cytochrome a(+a3) were negatively correlated with the concentration of cytochrome a(+ a3). These patients with mitochondrial cytochrome a(+a3) exceeding 70 pmol/mg of protein tolerated partial hepatectomy well. On the other hand, in patients with mitochondrial cytochrome a(+ a3) less than 60 pmol/mg of protein, phosphorylative activity was very low and there was a high surgical mortality.
3. In the regenerating liver of rats treated with chloramphenicol, the oxidative and phosphorylative activities per unit of cytochrome a(+ a3) were negatively correlated with the concentration of cytochrome a(+a3).
4. It is suggested that an increase in ATP-synthesizing activity per unit of respiratory assemblies is the most basic homeostatic mechanism maintaining energy production in response to an increased metabolic load upon hepatic cells.
Enhancement of the Antihypertensive Effect of Hydrochlorothiazide in Dogs after Suppression of Renin Release by Beta-Adrenergic Blockade
Authors: Sweet C. S. , Mandradjieff M. 
Published: August 2015

1. Renal hypertensive dogs were treated with hydrochlorothiazide (8−2 μmol/kg or 33 μmol/kg daily for 7 days), or timolol (4.6 μmol/kg daily for 4 days), a potent β-adrenergic blocking agent, or combinations of these drugs). Changes in mean arterial blood pressure and plasma renin activity were measured over the treatment period.
2. Neither drug significantly lowered arterial blood pressure when administered alone. Plasma renin activity, which did not change during treatment with timolol, was substantially elevated during treatment with hydrochlorothiazide.
3. When timolol was administered concomitantly with hydrochlorothiazide, plasma renin activity was suppressed and blood pressure was significantly lowered.
4. These observations suggest that compensatory activation of the renin-angiotensin system limits the antihypertensive activity of hydrochlorothiazide in renal hypertensive dogs and suppression of diuretic-induced renin release by timolol unmasks the antihypertensive effect of the diuretic.
Modifications of Plasma Post-Heparin Lipolytic Activity and Tissue Lipoprotein Lipase Activity Induced in the Rat by Acute Administration of Ethanol or Propan-2-ol
Authors: Giudicelli Y. , Nordmann R. , Nordmann J. 
Published: August 2015

1. The oral administration of propan-2-ol [isopropanol; 100 mmol (6 g)/kg body weight] or ethanol [130 mmol (6 g)/kg body weight] to starved rats produced no change in plasma post-heparin lipase activity (PHLA) compared with that observed in 154 mmol/l sodium chloride (saline)-treated rats.
2. An increase of adipose tissue lipoprotein lipase (LLA) and a decrease of heart LLA occurred in isopropanol-treated animals, whereas no significant changes were found in these activities after ethanol administration.
3. Since administration of isopropanol produces hyperglycaemia, observations were also made in rats receiving glucose infusion rather than saline. In these animals a rise in PHLA and adipose tissue LLA, and a fall in heart LLA, occurred.
4. It is suggested that the changes in tissue LLA produced by isopropanol are mediated by the rise in blood glucose.
Mechanisms of Post-Obstructive Diuresis in the Solitary Hydronephrotic Kidney of the Rat
Authors: Wilson D. R. 
Published: August 2015

1. In order to clarify further the phenomenon of post-obstructive diuresis, clearance and micro-puncture experiments were done before and after relief of partial ureteral obstruction in rats with a solitary hydronephrotic kidney.
2. Glomerular filtration rate, urine flow and sodium excretion increased markedly, whereas surface nephron glomerular filtration rate increased only slightly and intratubular pressure, proximal and distal tubular water reabsorption did not change significantly. Decreased tubular reabsorption in deeper nephrons and collecting ducts appeared to be of major importance in the post-obstructive diuresis after relief of chronic obstruction.
3. In order to examine further the distinctive functional characteristics of the chronically hydronephrotic kidney, the results were compared with control rats having a solitary normal kidney or a solitary remnant kidney with an intact renal medulla. Urine flow rate and sodium excretion were higher and urine osmolality was lower (P < 0.01) in post-obstructive kidneys when compared with either control group. There were no differences in glomerular filtration rate or surface nephron function which could account for the greater diuresis and natriuresis from the hydronephrotic kidney, thus confirming the importance of an abnormality in deep nephron or medullary function in post-obstructive diuresis.
4. There was a greater diuresis in post-obstructive rats with a marked increase in blood urea concentration. Water reabsorption in the distal nephron was decreased in such animals, as well as in urea-loaded rats with a remnant kidney, indicating the probable mechanism by which urea diuresis potentiates the phenomenon of post-obstructive diuresis.
Maximal Oxygen Uptake, Lung Volume and Ventilatory Response to Carbon Dioxide and Hypoxia in a Pair of Identical Twin Athletes
Authors: Leitch A. G. , Clancy L. , Flenley D. C. 
Published: August 2015

1. Maximal oxygen uptake (V̇o2 max.), lung volumes, and ventilatory responses to carbon dioxide and hypoxia have been measured in identical twin athletes, who were trained to a similar high degree.
2. The results confirm previous findings for V̇o2 max. and lung volumes in identical twins, and are in keeping with the suggestion that genetic factors play a major part in determining the ventilatory response to carbon dioxide and hypoxia.
Correlation of Peak Aortic and Carotid Flow Acceleration during Coronary Occlusion in Conscious Baboons
Authors: Chimoskey J. E. , Flanagan W. J. , Huntsman L. L. , Gams E. , Rushmer R. F. 
Published: August 2015

1. Peak blood flow acceleration measured in the common carotid artery was compared with peak flow acceleration measured in the ascending aorta of three baboons.
2. The response to occlusion for 60 s of the circumflex branch or the anterior descending branch of the left coronary artery was investigated.
3. Both accelerations decreased approximately to the same extent. Peak aortic flow velocity, stroke volume and cardiac output also decreased but to a smaller extent.
4. It is concluded that peak aortic flow acceleration is a sensitive index of myocardial function during acute coronary occlusion in conscious primates and that peak carotid flow acceleration is an indirect measure of myocardial performance under the same conditions.
Human Platelet Monoamine Oxidase Activity in Iron-Deficiency Anaemia
Authors: Moussa B. H. , Woods H. F. , Mitchell B. , Grahame-Smith D. G. , Callender Sheila 
Published: August 2015

1. The activity of monoamine oxidase, when assayed with four substrates, was significantly lowered in platelets prepared from the blood of patients with iron-deficiency anaemia.
2. Treatment with oral iron preparations restored platelet monoamine oxidase activity to normal in those patients whose serum iron concentrations also returned to normal.
3. Platelet monoamine oxidase activity remained low if treatment failed to restore serum iron concentration to within normal limits.
Efficiency of Utilization of Urea Nitrogen for Albumin Synthesis by Chronically Uraemic and Normal Man
Authors: Varcoe R. , Halliday D. , Carson E. R. , Richards P. , Tavill A. S. 
Published: August 2015

1. The relation between endogenous urea metabolism and albumin synthesis has been studied in ten patients with chronic renal failure and in four normal subjects, after single intravenous injections of [14C]urea, [15N]urea and 125I-labelled albumin.
2. The rate of urea synthesis was determined from the dynamics of plasma [14C]urea specific radioactivity and the rate of urea metabolism was estimated from the relative rates of urea synthesis and urea appearance in urine and body water. Deconvolution analysis of plasma [15N]albumin enrichment and 125I-labelled albumin radioactivity yielded the cumulative incorporation of 15N into total exchangeable albumin and enabled calculation of the absolute rate of urea nitrogen utilization for albumin synthesis.
3. Although the mean absolute rate of urea degradation in uraemic patients (3.7 mmol/h) was higher than in normal subjects (2.3 mmol/h) there was no significant positive correlation between urea degradation and plasma urea concentration.
4. In uraemic subjects, there was a significant positive correlation between urea synthetic rate and urea degradation rate.
5. The rate of utilization of urea nitrogen for albumin synthesis was low, but was very much higher in uraemic subjects (mean 83.8 μmol/h) compared with normal subjects (mean 6.4 μmol/h), as was the provision by urea of the nitrogen required for albumin synthesis in uraemic subjects (2.37%) compared with normal subjects (0.13%).
6. The efficiency of utilization of urea nitrogen for albumin synthesis was higher in the uraemic patients (1.3%) than the normal subjects (0.2%), and was higher in those patients with chronic renal failure who received a 30 g protein diet than those on 70 g of protein. A significant negative correlation was noted between efficiency of urea nitrogen utilization and the rate of synthesis of albumin.
7. These studies suggest the presence of a mechanism for the conservation of urea nitrogen in chronic renal failure which is unrelated to the extent of urea degradation, and which can only be partly explained by the higher proportion of intraluminal gut nitrogen derived from urea.