bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analytical Subcellular Fractionation of Human Granulocytes with Special Reference to the Localization of Enzymes Involved in Microbicidal Mechanisms
Authors: Segal A. W. , Peters T. J. 
Published: August 2015

1. Granulocytes were isolated from 40–400 ml of human blood, disrupted and subjected to analytical subcellular fractionation by centrifugation on sucrose density gradients.
2. The principal subcellular organelles, characterized by their respective marker enzymes, were resolved on the density gradients. The subcellular localization of hitherto unassigned enzymes was determined by comparison with the marker enzymes.
3. NAD(P)H-dependent reduction of nitroblue tetrazolium at high nucleotide concentration (2·5 mmol/l) and NAD(P)H/cytochrome c reduction has a complex distribution with activity in the plasma membrane, mitochondria and cytosol fractions.
4. At a lower, physiological concentration of pyridine nucleotides (25 μmol/l), NADH-dependent nitroblue tetrazolium reduction was confined to the plasma membrane whereas NADPH dependent-reduction of the dye was undetectable. NAD(P)H/nitroblue tetrazolium reductase activity was partially inhibited by superoxide dismutase.
5. NADPH and NADH oxidase activities, measured by the production of oxidized nucleotide, were localized with the azurophil granules.
6. Superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase were localized predominantly to the cytosol.
7. Neutral α-glucosidase and γ-glutamyl transpeptidase showed a bimodal distribution with localizations to both endoplasmic reticulum and specific granule components.
8. It is suggested that the plasma membrane, and thus the wall of phagocyte vacuoles, contains a free radical generating NADH-dependent enzyme which plays a primary bactericidal role. The cytosol contains mechanisms which detoxify hydrogen peroxide, superoxide and free radicals and protect the granulocyte from these compounds.
Proline and Hydroxyproline Excretion and Vitamin C Status in Elderly Human Subjects
Authors: Bates C. J. 
Published: August 2015

1. Plasma and buffy-coat vitamin C, urinary proline, hydroxyproline, creatinine and total amino acid concentrations were measured in 23 healthy elderly subjects at intervals of 3 months.
2. There was a strong positive correlation between plasma vitamin C and buffy-coat vitamin C.
3. There were no significant correlations between plasma or buffy-coat vitamin C and total urinary hydroxyproline, whether expressed on a creatinine basis or on a total amino acid basis. Similarly, no significant correlations could be detected involving the proline/hydroxyproline ratio in urine hydrolysates.
4. There was a significant negative correlation between plasma or buffy-coat vitamin C and total urinary proline, when expressed per unit of total amino acids in the hydrolysates. This correlation was not observed with unhydrolysed urine, and it appeared to reside in the diffusible fraction, part of whose proline could be liberated by prolidase digestion. In addition, in the men, there was some evidence for a positive correlation between plasma or buffy-coat vitamin C and the ratio of total urinary amino acids to creatinine.
5. These results support the view that poor vitamin C status in elderly humans may be associated with a defect in collagen proline hydroxylation, reflected by increased excretion of proline-rich, collagen-derived peptides. If this interpretation is correct, it indicates a potential defect in connective tissue repair, and could form the basis of a functional test for subclinical vitamin C deficiency.
Intestinal Absorption of Glycine and Glycyl-L-Proline in the Rat
Authors: Heading R. C. , Schedl H. P. , Stegink L. D. , Miller D. L. 
Published: August 2015

1. Absorption of [3H]glycine and [14C]-glycyl-l-proline at concentrations between 0·5 and 4 mmol/l was studied by perfusion in vivo of rat jejunal and ileal segments. Absorption was defined as net removal of radioisotope from the perfusate. Radioactivity assays and amino acid analyses were performed on perfusates and on mucosal tissue samples obtained from the perfused segments.
2. At the concentrations studied, absorption rates of glycine and glycylproline were proportional to concentration. Ileal rates were approximately 60% of jejunal rates. Glycylproline absorption was slightly faster than glycine absorption and was associated with the appearance in the perfusate of free glycine and proline in the ratio approximately 3:1. Intraluminal hydrolysis was insufficient to account for the amounts of free amino acids found and glycylproline hydrolase activity at the brush border is known to be minimal.
3. Glycylproline absorption apparently occurred by transport of the intact peptide followed by its intracellular hydrolysis. However, more than one-third of absorbed glycine and one-eighth of absorbed proline returned to the lumen as free amino acid. This reflux of glycine and proline was not proportional to their concentrations in the mucosa.
The Effect of Chronic Frusemide Administration on Intracellular Potassium, Sodium and pH of Cardiac and Skeletal Muscle
Authors: Hall R. J. C. , Cameron I. R. 
Published: August 2015

1. Chronic administration of frusemide in large doses of 4 mg day−1 kg−1 for 3 weeks caused a significant reduction of cell water in rabbit cardiac and skeletal muscle. Intracellular Na+ concentration, intracellular pH and extracellular space were unchanged in both tissues. Intracellular K+ concentration increased slightly in both cardiac and skeletal muscle.
2. It is concluded that frusemide does not reduce intracellular K+ concentration in cardiac or skeletal muscle of normal animals receiving a normal oral potassium intake.
Effect of Pharmacological Inhibitors on Urate Transport during Induced Uricosuria
Authors: Diamond H. S. , Meisel A. D. 
Published: August 2015

1. The effect on urate excretion of administration of probenecid and pyrazinamide was observed in normal subjects under control conditions and after induction of uricosuria by exogenous urate loading by ribonucleic acid feeding in seven subjects, by volume loading with hypertonic sodium chloride solution infusion in 11 subjects and by partial inhibition of net urate reabsorption with uricosuric drugs in 20 subjects.
2. After ribonucleic acid feeding, the uricosuric response to probenecid was intact and ribonucleic acid feeding did not produce uricosuria after pyrazinamide.
3. After volume loading, the uricosuric response to probenecid was again intact, but infusion of sodium chloride solution still produced uricosuria after pyrazinamide administration.
4. After uricosuric drugs, the uricosuric response to probenecid was diminished.
5. These responses to probenecid and pyrazinamide may reflect different mechanisms of uricosuria. Response to pharmacological inhibitors of urate reabsorption or urate secretion may be useful for classification of induced and clinical uricosuric states.
The Association between Fasting Hyperbilirubinaemia and Serum Non-Esterified Fatty Acids in Man
Authors: Cowan R. E. , Thompson R. P. H. , Kaye J. P. , Clark Gillian M. 
Published: August 2015

1. The concentrations of plasma total and unconjugated bilirubin and of serum non-esterified fatty acids (NEFA) have been measured in two healthy subjects during fasts of up to 21 h.
2. Fasting was either continuous or interrupted by various procedures that altered the concentrations of NEFA and total bilirubin.
3. When NEFA concentrations were increased by the administration of noradrenaline, heparin or caffeine, bilirubin concentrations also rose.
4. When NEFA concentrations were lowered by insulin, bilirubin concentrations fell.
5. Meals of 3·138 kJ and more, taken during the fasting period, lowered total bilirubin and NEFA concentrations in both subjects, whereas the effects of smaller meals were less consistent.
6. These studies demonstrate a statistically significant correlation between total bilirubin and NEFA during uninterrupted fasting and an association between these variables under other experimental conditions. They suggest that the control of bilirubin concentrations in the blood is linked to lipid metabolism.
Nitrogen Metabolism in Neonatal Citrullinaemia
Authors: Walser M. , Batshaw M. , Sherwood G. , Robinson B. , Brusilow S. 
Published: August 2015

1. The pathways of disposition of waste nitrogen were studied in a male infant with neonatal citrullinaemia during 3 months of normal growth on a protein-restricted diet supplemented by a mixture of amino acids and nitrogen-free analogues of amino acids.
2. The rate of excretion of urea averaged one-sixteenth, and the rate of excretion of total urinary nitrogen one quarter, of that reported in normal infants retaining the same amount of nitrogen per kg. Thus the efficiency of retention of dietary nitrogen for growth in this infant was very high. Plasma urea varied from 0·35 to 1·30 mmol/l.
3. The small amount of urea formed was apparently derived entirely from dietary arginine via arginase, as indicated by the observation that urea excretion and plasma urea were linear functions of arginine intake with intercepts of zero or less. These relationships imply that urea synthesis would cease at zero arginine intake. This hypothesis could not be verified because arginine intakes below 2·2 mmol day−1 kg−1 led to hyperammonaemia.
4. The high intake of arginine was required chiefly to replenish ornithine skeletons lost as citrulline in the urine (0·7 mmol day−1 kg−1). Smaller amounts of arginine were estimated to be required for protein synthesis and for creatine synthesis. The rate at which ornithine was utilized in reactions other than citrulline synthesis appeared to be excessively high.
5. Citrulline was the principal end-product of nitrogen metabolism, accounting for 51% of urinary nitrogen.
6. The results suggest that normal growth can be obtained in the virtual absence of the ability to dispose of waste nitrogen as urea.
The Role of Alanine and Glutamine in Steroid-Induced Nitrogen Wasting in Man
Authors: Sapir D. G. , Pozefsky T. , Knochel J. P. , Walser M. 
Published: August 2015

1. Administration of dexamethasone, 8 mg/day (0·02 mmol/day), for 5 days to normal subjects produced negative nitrogen balance, due to early and sustained increases in urinary urea nitrogen excretion.
2. In eight subjects ingesting 0·9–1·6 g of protein day−1 kg−1 body weight the cumulative increment in urea nitrogen excretion averaged + 12·5 g (sem 2·8, P < 0·01) over the 5 days of glucocorticoid administration.
3. Increases in urinary urea nitrogen excretion could be related to both plasma alanine and blood glutamine changes by using a multiple regression equation.
4. These results suggest that corticosteroids induce increased release of alanine and glutamine by peripheral tissues, which may augment urea formation and negative nitrogen balance.
5. The correlation between increments in urea nitrogen excretion and increases in plasma arginine remains unexplained.
Effects of Adrenaline Injection on Human Plasma Tryptophan and Non-Esterified Fatty Acids
Authors: Gentil V. , Lader M. H. , Kantamaneni B. D. , Curzon G. 
Published: August 2015

1. Subcutaneous injection of adrenaline into normal male volunteer subjects caused large increases of plasma non-esterified fatty acids and free tryptophan, but plasma total tryptophan fell considerably. Therefore increases of the percentage of plasma tryptophan in the free state were more marked than absolute increases of free tryptophan.
2. Plasma tyrosine fell slightly and plasma phenylalanine and cortisol were unaffected.
3. It is suggested that catecholamine release could lead to abnormalities of tryptophan disposition in stress and psychiatric illness.
The Effect of Certain Chelating Compounds on the Urinary Excretion of Copper by the Rat: Observations on their Clinical Significance
Authors: Gibbs Kathleen , Walshe J. M. 
Published: August 2015

1. A screening procedure is described to assess rapidly the clinical potential of chelating agents for the treatment of Wilson's disease.
2. Rats were used as the test animal; they were kept in metabolic cages and the urine was collected in copper-free containers. The compounds investigated were given by mouth as a standard dose of 100 mg. Copper was determined by atomic absorption spectrophotometry.
3. Basal urine copper excretion was 65·1 ± se 2·93 nmol/24 h (4·1 μg ± 0·185). After penicillamine this rose to 367·1 nmol and after trien to 305·9 nmol.
4. Certain compounds caused a reduction in the amount of copper excreted in the urine, probably by forming insoluble chelates with the metal, hence rendering it unavailable for excretion at the glomerulus.
Sodium Homeostasis in Patients with Autonomic Failure
Authors: Wilcox C. S. , Aminoff M. J. , Slater J. D. H. 
Published: August 2015

1. The renal excretion of sodium by five patients with autonomic failure (Shy—Drager syndrome) was compared with a matched control group who had normal autonomic reflexes (Parkinson's disease). For 8 or 9 days the daily sodium intake was reduced to 17 mmol, and for 5 subsequent days it was increased to 189 mmol.
2. The sodium excretion of the patients with autonomic failure was not significantly reduced during 7 days of restricted intake whereas that of the control group fell rapidly to values comparable with their sodium intake. Patients with autonomic failure had a larger fall in body body weight than the control subjects.
3. Both lying and standing values of mean blood pressure fell during salt restriction in the patients with autonomic failure, but not in the control subjects.
4. Values of plasma renin activity (PRA) were significantly depressed in patients with autonomic failure. However, PRA rose to values similar to those of control subjects while standing during the period of restricted sodium intake. At this time the patients with autonomic failure had a large orthostatic fall in blood pressure and creatinine clearance.
5. Aldosterone secretion rates were measured in three patients with autonomic failure at both levels of sodium intake and were considerably lower than the rates found in the control group.
6. A mineralocorticoid drug (9α-fludrocortisone; 2 mg/day), given on the last 2 days of restricted sodium intake, failed to correct fully the negative sodium balance of the patients with autonomic failure, since an excessive sodium excretion persisted during the period of recumbency at night.
7. These results demonstrate a severe defect in renal salt conservation in certain patients with autonomic failure. They suggest that the defect may not be entirely due to deficient secretion of mineralocorticoid hormones.
Mechanisms of the Uricosuric Effect of the Diuretic Tienilic Acid (Ticrynafen) in Man
Authors: Lau K. , Stote R. M. , Goldberg M. , Agus Z. S. 
Published: August 2015

1. We have studied the effects of the diuretic tienilic acid (Ticrynafen) upon renal tubular transport of urate, in 11 healthy volunteers on a constant dietary intake.
2. Daily administration of tienilic acid for 10 days to six subjects reduced the mean body weight from 67·1 ± 4·7 kg to 64·5 ± 4·7 kg and a reversible fall in serum urate from a mean value of 0·34 ± 0·04 to 0·16 ± 0·01 mmol/l. Fractional urate excretion in the six subjects on the first day of therapy was 30·3 ± 5·6% and then fell to reach a new steady-state mean value of 17·4 ± 2·0%.
3. To evaluate the mechanism of the uricosuria, studies were performed during acute sustained water diuresis in five subjects to assess the effects of tienilic acid, pyrazinamide, probenecid and their combinations.
4. Fractional urate excretion increased markedly with tienilic acid from 11·2 ± 1·3% to 47·5 ± 5·7%. Pyrazinamide, 24·4 mmol (3 g) orally, decreased urate excretion to 5·1 ± 0·7% and markedly blunted the uricosuric effects but not the natriuresis of tienilic acid. Probenecid increased urate excretion to 26 ± 6·0 % and when given with tienilic acid increased urate excretion to 66·4 ± 2·6%. Addition of pyrazinamide to this combination decreased urate excretion to 19·6 ± 4·0%, which was greater than the effect with pyrazinamide alone.
5. We suggest that tienilic acid increased urate excretion by inhibiting reabsorption of both filtered and secreted urate. We have used our results to construct semi-quantitative estimates of the various components of urate transport in man.
Vitamin D Metabolism in Adult Rats at Low and Normal Calcium Intake and the Effect of Cadmium Exposure
Authors: Lorentzon R. , Larsson S.-E. 
Published: August 2015

1. Chromatography measurements indicated that adult rats converted 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol at a lower rate than that reported earlier for young animals. In serum, less-polar metabolites were found which probably represented vitamin D esters and vitamin D3.
2. A low dietary intake of calcium resulted in an evident increase in the fraction corresponding to 1,25-dihydroxycholecalciferol in the kidneys and also in the intestinal mucosa and serum.
3. Inclusion of 0·67 mmol of cadmium/l of drinking water at a low dietary intake of calcium resulted in an increased accumulation of both cadmium and zinc in the kidneys and liver compared with values at a normal dietary calcium intake.
4. At a normal dietary calcium intake, cadmium exposure caused inhibited production of 1,25-dihydroxycholecalciferol by the kidneys and an increased accumulation of 24,25-dihydroxycholecalciferol, vitamin D3 and vitamin D esters in the serum.
5. The inhibitory effect of cadmium on the renal conversion of 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol was almost completely counteracted by a simultaneous low dietary calcium intake. Cadmium-exposed, calcium-deficient animals also showed a maintained accumulation of 1,25-dihydroxycholecalciferol in the intestinal mucosa.
Excretion of Salt and Water by Patients with Sickle-Cell Anaemia: Effect of a Diuretic and Solute Diuresis
Authors: Forrester T. E. , Alleyne G. A. O. 
Published: August 2015

1. Patients with sickle-cell anaemia were unable to increase free water reabsorption (TcH2O) in response to intravenous hypertonic sodium chloride solution.
2. Ethacrynic acid caused a brisk natriuresis in patients with sickle-cell anaemia but fractional sodium excretion was lower in these patients.
3. These findings could be explained by abnormal function of the loop of Henle.
Anaemia, Iron Deficiency and Exercise: Extended Studies in Human Subjects
Authors: Charlton R. W. , Derman D. , Skikne B. , Torrance J. D. , Lynch S. R. , Sayers M. H. , Zwi S. , Goldman H. I. , Van As A. , Margo G. , Schneider J. T. , Bothwell T. H. 
Published: August 2015

1. Ventilation and cardiac frequency were measured during repeated treadmill exercise in three healthy subjects over 36 weeks, before, during and after iron-deficiency anaemia was produced and after iron treatment. The haemoglobin and 2,3-diphosphoglycerate concentrations and the oxygen-binding (P50) were measured.
2. There was an inverse relationship between the haemoglobin concentrations and the 2,3-diphosphoglycerate concentrations and the P50 values.
3. The mean cardiac frequencies during the fourth to tenth minutes of exercise showed a negative correlation with the haemoglobin concentrations in all three subjects, and the mean minute ventilations in two of them.
Oxygen Transport in Children on Maintenance Haemodialysis
Authors: Bursaux E. , Broyer M. , Poyart C. , Bohn B. , Jean G. 
Published: August 2015

1. Adaptive mechanisms of oxygen transport by blood have been studied in severely anaemic young patients on maintenance haemodialysis, in conditions of hyperphosphataemia (P1 ≥ 2·2 mmol/l) or normophosphataemia.
2. In hyperphosphataemia whole-blood affinity for oxygen was slightly decreased, as measured by an increase in P50 (the partial pressure of oxygen necessary to half saturate haemoglobin). 2,3-Diphosphoglycerate was increased by 10% (P < 0·10) whereas P1, total erythrocyte phosphate and ATP were increased by 100%, 47% and 36% respectively, compared with control values.
3. After correction of hyperphosphataemia a small but significant decrease in P50 and 2,3-diphosphoglycerate, to normal values, was observed whereas the other variables, although significantly lowered, remained above control values.
4. In these severely anaemic and hyperphosphataemic patients P50 and 2,3-diphosphoglycerate are only slightly increased. ATP synthesis appears to be favoured over that of 2,3-diphosphoglycerate. This is possibly due to alterations in the erythrocyte membrane elicited by bi-weekly extracorporeal circulation. Adequate oxygen transport can be achieved only through a drastic increase in blood flow. Correction of hyperphosphataemia adds further to the abnormality. It is concluded that this condition could induce a long-term myocardial fatigue, which might be prevented with occasional small blood transfusions.
The Measurement of Calcium Absorption and Absorption Rate with an External Arm Radioactivity Counter
Authors: Smart R. C. , Holdsworth C. D. 
Published: August 2015

1. A large-volume scintillation counter was used to measure calcium absorption from the ratio of forearm uptake of 47Ca after oral 47CaCl2 (administered with milk) to forearm uptake after intravenously administered 47CaCl2.
2. In some subjects serial measurements of both forearm uptake of 47Ca and blood 47Ca radioactivity were also recorded, and by using deconvolution both total calcium absorption and calcium absorption rate were determined.
3. The forearm ratio determination of 47Ca absorption correlated well with that obtained by deconvolution of either serial blood 47Ca or forearm 47Ca measurements provided that the forearm radioactivity measurements were made at least 8 h after the administrations of 47CaCl2.
4. Although the two deconvolution techniques gave similar estimates of total calcium absorption there were discrepancies between their measurements of calcium absorption rate. These discrepancies were reduced but not eliminated by the use of additional lead shielding around the Armac counter.
Bone Blood Flow and Age in the Rat
Authors: MacPherson J. N. , Tothill P. 
Published: August 2015

1. The proportion of the cardiac output delivered to the skeleton and individual bones has been determined in rats of differing ages and weights with radioactive microspheres.
2. There was a decrease in the blood flow to the tibia—fibula, jaw, femur, pelvis, humerus, radius and ulna, and scapula with increase in age and weight of rats, but no change was seen in blood flow to the ribs, spine, skull or whole skeleton.
3. The proportion of the cardiac output delivered to the whole skeleton was approximately 3%.
4. The derived values for skeletal blood flow agree well with estimates by other authors using the technique of bone uptake and blood clearance of 45Ca.
Comparative Effects of Oestrogen and a Progestogen on Bone Loss in Postmenopausal Women
Authors: Lindsay R. , Hart D. M. , Purdie D. , Ferguson M. M. , Clark A. S. , Kraszewski A. 
Published: August 2015

1. The value of progestogen therapy in the prevention of postmenopausal bone loss was assessed in 30 women, by a preliminary randomized controlled trial of gestronol or mestranol, in comparison with a placebo.
2. When the skeletal response was measured by photon absorptiometry, bone mineral loss was prevented by both the oestrogen and the progestogen.
3. We confirm that mestranol significantly reduced the urinary output of hydroxyproline-containing peptide, but this did not occur during gestronol therapy, suggesting that progestogen has a different action on bone, perhaps stimulating bone formation.