bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Hypoxia on Succinate Metabolism in Man and the Isolated Perfused Dog Liver
Authors: Iles R. A. , Barnett D. , Strunin L. , Strunin J. M. , Simpson B. R. , Cohen R. D. 
Published: August 2015

1. A marked rise in blood succinate was shown to occur in severely hypoxic patients.
2. A similar effect could be produced in the perfusate of the isolated perfused canine liver subjected to hypoxic hypoxia; in addition, tissue concentrations of succinate in the perfused liver progressively rose during hypoxia.
3. The elevation of succinate concentrations during hypoxia is partly due to reversal of the oxidative pathway from succinate to oxaloacetate.
4. A permeability barrier to succinate and fumarate exists between their locations within the cell and the circulation.
5. The permeability barrier to succinate but not to fumarate is broken down during hypoxia.
The Proteinases of Human Gastric Adenocarcinomata: Their Identification, Separation and Sites of Action on the B-Chain of Oxidized Insulin
Authors: Etherington D. J. , Taylor W. H. 
Published: August 2015

1. Because of the possibility that the proteinases of gastric adenocarcinomata may differ from those of healthy gastric mucosa, an investigation of these enzymes by means of pH-activity studies, agar-gel electrophoresis, column chromatography and the mode of action on the B-chain of oxidized insulin has been undertaken.
2. Agar-gel electrophoresis of extracts at pH 5 revealed a single zone of proteinase activity situated at the equivalent position to the zone 7 of normal gastric mucosal extracts and not activated at pH 2. The typical pepsins of normal mucosal extracts were not present.
3. Agar-gel electrophoresis at pH 8·2 resolved this single zone into three zones. One was located slightly cathodally (proteinase 1) and the other two anodally (a slower proteinase 2A and a faster 2B).
4. Proteinases 2A and 2B were separated by column chromatography and shown to have identical asymmetrical broad pH-activity curves with the maximum at pH 3·3–3·4.
5. Proteinase 1 had a symmetrical narrow pH-activity curve with the maximum at pH 3·7–3·9. Proteinase 1 was purified and resolved into two highly active major components, 1A and 1B, by column chromatography, first on DEAE-cellulose and then on CM-cellulose.
6. The sites of cleavage of the B-chain of oxidized insulin were determined for proteinases 1A and 1B. The same bonds were split by each, with one exception, but several were split at differing rates indicating that the two enzymes had related, but different, modes of action.
7. The tumour proteinases 1 resemble the cathepsins D in certain respects and the pepsins in others. They may represent an enzyme structure of an intermediate form. There is insufficient evidence to indicate whether they are elaborated by partially differentiated cells or whether they are derived from cells which have become dedifferentiated. No enzymes exactly like them have yet been found in normal tissues.
The Role of Angiotensin II in the Control of Aldosterone in Man
Authors: Boyd G. W. , Adamson A. R. , Arnold Marion , James V. H. T. , Peart W. S. 
Published: August 2015

1. The relationship between circulating plasma angiotensin II and plasma aldosterone in man during sodium deficiency has been investigated in normal male subjects by comparing the amounts of the two hormones: (a) after 5 days of sodium restriction with an injection of frusemide on the third day, (b) during intravenous infusions of angiotensin II given in normal sodium balance.
2. The results show that aldosterone and angiotensin II plasma concentrations were both increased by sodium deficiency, but the increase in aldosterone was much greater than was found when angiotensin II was infused during normal sodium balance so as to equal or even exceed the plasma angiotensin II concentrations of sodium deficiency.
3. Other factors capable of increasing aldosterone secretion (plasma Na+, K+ and ACTH) seemed unlikely to account for the discrepancy, nor was there evidence of sufficient increase in adrenal sensitivity during Na+ deficiency.
4. It is suggested that some other unknown factor or factors are necessary to account for the full aldosterone response to this stimulus in man.
Urinary Excretion of Nitrogen from [15N]valine, [15N]leucine and [15N]isoleucine in Malnourished and Recovered Children
Authors: Read W. W. C. , McLaren D. S. , Tchalian Marie 
Published: August 2015

1. l-Valine, l-leucine and l-isoleucine containing 15N were prepared, purified, and fed to marasmic and recovered infants. The excretion of total 15N and [15N]urea in the urine was followed for 72 h.
2. 15N excreted from isoleucine was about 90%, from leucine 70%, and from valine 50% in the recovered child.
3. 15N excreted was lower for leucine and isoleucine in marasmus than in recovery. The clinical state made little difference to 15N excretion from valine.
5. The decrease in excretion was almost entirely due to lowered urea output.
6. The results are discussed in relation to branched-chain amino acid metabolism and dietary requirements for these acids.
Orthostatic Changes of Haemodynamics, Renal Function, Plasma Catecholamines and Plasma Renin Concentration in Normal and Hypertensive Man
Authors: Molzahn M. , Dissmann TH. , Halim S. , Lohmann F. W. , Oelkers W. 
Published: August 2015

1. In eight normal subjects, ten patients with labile hypertension, six with advanced essential hypertension and six with renovascular hypertension, plasma renin concentration, cardiac output, mean arterial pressure, clearances of creatinine and p-aminohippurate (PAH), and sodium excretion were measured before and after 30 min of 45° upright tilting. Changes in plasma adrenaline and noradrenaline concentration were measured in addition in the normal subjects, and in plasma volume in normal subjects and patients with labile essential hypertension.
2. In patients with advanced essential hypertension, heart rate and calculated peripheral resistance increased significantly less than in normal subjects, and plasma renin increased by 15% in this group, in comparison to 37% in normal subjects, 48% in labile essential hypertension, and 57% in renovascular hypertension. There was a positive relationship between changes in renin and noradrenaline concentrations in normal subjects.
3. Apart from a negative correlation between the increases in plasma renin concentration and mean arterial pressure in patients with renovascular hypertension, there were no significant relationships between changes in plasma renin and haemodynamics.
4. A negative correlation between changes in plasma renin and filtration fraction and a positive relationship between changes in renin and sodium excretion were found in normal subjects and patients with labile hypertension. Plasma renin increase was directly related to changes in the tubular rejection fraction of sodium in patients with labile hypertension. In the same group there was a negative correlation between changes of sodium rejection fraction and filtration fraction.
5. The results suggest a role of the adrenergic system in orthostatic renin release, but the functional connection between renal haemodynamics, tubular sodium handling and renin release across orthostasis cannot fully be explained on the basis of our present knowledge of renin releasing mechanisms.
Effects of Acutely Induced Changes in Arterial pH on Pulmonary Vascular Resistance during Normoxia and Hypoxia in Awake Dogs
Authors: Thilenius O. G. , Derenzo Carol 
Published: August 2015

1. Awake dogs with chronically implanted catheters (pulmonary artery, left atrium, aorta) and electromagnetic flow probe (main pulmonary artery) underwent five types of experiments in succession: (1) slow infusion of 0·4 m-hydrochloric acid; (2) rapid infusion of 1·0 m-sodium bicarbonate; (3) exposure to 30 min of hypoxia (10% O2); (4) exposure to hypoxia after arterial pH had been lowered to 7·30; (5) exposure to hypoxia after pH had been increased to 7·55. Intravascular pressures, pulmonary vascular resistance, cardiac output, arterial gas tension and pH were studied.
2. Acute acidosis (pH 7·21) resulted in a small rise in pulmonary artery pressure, cardiac output and pulmonary vascular resistance, associated with a decrease in Pa,co2. Acute alkalosis (pH 7·61) was accompanied by a small rise in pulmonary artery pressure, marked increase in cardiac output, a fall in pulmonary vascular resistance and mild elevation in Pa,co2. During acidosis hypoxia resulted in a more pronounced rise in pulmonary vascular resistance than during alkalosis (P &lt; 0·01).
3. The study provides evidence that in the intact, awake dog with its compensatory mechanisms acute alkalosis decreases pulmonary vascular resistance by decreasing vascular tone and/or recruitment of pulmonary vascular channels; it diminishes the vasoconstrictive response to hypoxia; conversely, mild acidosis increases the pulmonary vascular resistance slightly and enhances vasoconstriction during hypoxia to a small extent.
Insulin Disappearance after Intravenous Injection and its Effect on Blood Glucose in Diabetic and Non-Diabetic Children and Adults
Authors: Stimmler L. , Mashiter K. , Snodgrass G. J. A. I. , Boucher B. , Abrams M. 
Published: August 2015

1. Porcine insulin (0·1 i.u./kg) was injected intravenously into diabetic and non-diabetic subjects.
2. In each group insulin produced a fall in blood glucose within 5 min which was exponential and which continued until approx. 99% of the insulin had left the plasma.
3. In the diabetic subjects both the insulin values and blood glucose fell more slowly than in the controls, when expressed as a proportion of the fasting value. However, both insulin and glucose continued to fall for a longer period, with the result that there was a total fall of blood glucose of 67% in the diabetics and 70% in the non-diabetics. Though in absolute terms considerably more glucose disappeared in diabetics than in the normal subjects, this could be related to the higher initial glucose concentrations in the former.
4. It is suggested that not only does insulin act very rapidly, but it is also rapidly inactivated.
Clinical Studies on Inflammation in Small Diarthrodial Joints. Technetium (99MTc) Percentage Uptakes in Various Arthritides and Studies on the Effect of Aspirin in Rheumatoid Arthritis
Authors: Dick W. C. , Collins K. E. , Buchanan W. W. 
Published: August 2015

1. The uptake of a low dose of intravenously administered 99mTc over the distal and proximal interphalangeal joints was found to be lower in normal subjects than in patients suffering from rheumatoid arthritis, osteoarthritis and psoriatic arthritis.
2. The percentage uptake of technetium over the proximal and distal diarthrodial joints was significantly decreased in patients with rheumatoid arthritis by the oral administration of aspirin (4 g/day for 7 days) and it is proposed that this method may be of value in the routine assessment of anti-inflammatory drug therapy in rheumatoid arthritis.
Vascular Reactivity in Post-Deoxycorticosterone Hypertension in Rats and its Relation to ‘Irreversible’ Hypertension in Man
Authors: Beilin L. J. , Ziakas G. 
Published: August 2015

1. The mechanism by which the blood pressure remains elevated after temporary administration of deoxycorticosterone (DOCA) and saline has been studied by comparing vascular reactivity in the resistance bed of the isolated perfused rat tail in animals with post-DOCA hypertension and normotensive controls.
2. Animals with post-DOCA hypertension showed increased arteriolar responses to noradrenaline and 5-hydroxytryptamine, increased maximum contractile responses to noradrenaline, and increased resistance to flow under conditions of maximum vasodilation.
3. These abnormalities may be explained largely on the basis of arteriolar wall thickening resulting from hypertension and they will lead to a high peripheral resistance.
4. Evidence from experiments on chronic renal hypertension indicates that hypertension only becomes irreversible when the ability of the kidneys to regulate blood pressure is impaired. When this has occurred the high resistance offered by abnormal systemic arterioles will be a significant factor in maintaining a high arterial pressure and the high pressure will in turn continue to exert deleterious effects on resistance vessels, including those of the kidney.
5. It is suggested that persistence of hypertension in patients in whom the initial cause of the hypertension has apparently been removed is due to changes in morphology and reactivity of renal and systemic resistance vessels similar to those described in arterioles of animals with post-DOCA hypertension.
Plasma Volume and Extracellular Fluid Volume during Long-Term Treatment with Propranolol in Essential Hypertension
Authors: Sederberg-Olsen P. , Ibsen H. 
Published: August 2015

1. In ten patients with essential hypertension treated with propranolol (320 mg daily for 4 months) plasma volume and extracellular fluid volume were determined.
2. A significant increase in extracellular fluid volume (ECFV) was found, but there was no significant change in plasma volume.
3. The genesis of the increase found in ECFV is briefly discussed.
The Effects of Chronic Hypokalaemia, Hyponatraemia, and Acid-Base Alterations on Erythrocyte Sodium Transport
Authors: Levin M. L. , Rector F. C. , Seldin D. W. 
Published: August 2015

1. Erythrocyte sodium concentration and fluxes were measured in patients with acid-base disturbances, hypokalaemia and hyponatraemia. Results were similar to those obtained with normal erythrocytes exposed to artificial in vitro alterations.
2. Erythrocyte sodium content and influx varied directly with extracellular bicarbonate which appeared to influence membrane permeability.
3. Hypokalaemia increased the erythrocyte sodium content by decreasing active transport initially. When a new high erythrocyte steady-state sodium concentration was reached, active transport returned to normal but efflux and influx were increased considerably by the appearance of a large component of exchange diffusion in the hypokalaemic environment.
4. Hyponatraemia induced a decrease in sodium influx secondary to the decreased transmembrane sodium concentration gradient. A decrease in erythrocyte sodium content then ensued.
5. The results are discussed in relation to the assessment of cell membrane function in disease states.
Relationship between Dietary Carbohydrates and Fats in Their Influence on Serum Lipid Concentrations
Authors: Macdonald I. 
Published: August 2015

1. Diets containing 45% joules as fat, 45% joules as carbohydrate and 10% joules as calcium caseinate were given for 5 days to ten men and seven women. The fats used were sunflower seed oil or cream, and the carbohydrates were either glucose and fructose, glucose and raw starch or fructose and raw starch.
2. Sunflower seed oil in the diet resulted, after 5 days, in a significant fall in the concentration of triglyceride, cholesterol and phospholipid in the serum taken from subjects fasted for 12 h irrespective of the carbohydrate mixture of the diet.
3. Although there were changes in serum lipid concentrations in relation to the different mixtures of carbohydrate they were much less than those seen after ingesting sunflower seed oil.
4. Men and women differed in their response to carbohydrates, but this distinction was not seen in response to dietary fats.
Studies of the Mechanism of the Jarisch—Herxheimer Reaction in Louse-Borne Relapsing Fever: Evidence for the Presence of Circulating Borrelia Endotoxin
Authors: Bryceson A. D. M. , Cooper K. E. , Warrell D. A. , Perine P. L. , Parry E. H. O. 
Published: August 2015

1. Certain aspects of the Jarisch—Herxheimer reaction (JHR) after treatment of louse-borne relapsing fever have been studied in nine patients. Peripheral vasoconstriction immediately preceded the chill phase and profound vasodilation accompanied the flush phase.
2. From four patients 50–150 ml of blood was taken at the onset of the chill and reinjected intravenously into the same patient the next day. One patient experienced a reaction identical with JHR 40–60 min after reinjection, suggesting that the mediator of JHR was present in that blood.
3. From five patients 40 ml of blood were taken serially throughout JHR and 2-ml samples of plasma, free of cells and spirochaetes, were injected into pairs of normal rabbits. All samples taken while the patients had fever were pyrogenic. After incubation with normal rabbit plasma these samples failed to produce fever in endotoxin-refractory rabbits.
4. These results suggest that in the plasma of patients with relapsing fever there is a powerful endotoxin. We were unable to show that the concentration of endotoxin increased during JHR, nor could we demonstrate the presence of leucocyte pyrogen. This failure could be a problem of quantity of plasma used or of an endotoxin-refractory state.
5. The bearing of these observations on the mechanism of JHR and the uselessness of cortisol in modifying the reaction are discussed.
The Fate of [14C]Carbenoxolone in Patients with Gastric Ulcer
Authors: Parke D. V. , Hunt T. C. , Iveson P. 
Published: August 2015

1. After oral administration of [14C]carbenoxolone (100 mg, 5 μCi) to patients with radiologically-proven gastric ulcers the radioactivity was excreted mostly in the faeces (70–80%) with lesser amounts in the expired CO2 (12–20%) and only traces in the urine (0·2–1%). This is in marked contrast with the metabolism and pattern of excretion of this drug in the rat.
2. Most of the radioactivity excreted in the faeces of patients was present as carbenoxolone, which was probably formed by bacterial hydrolysis of the biliary-excreted conjugate of carbenoxolone.
3. It is concluded that in man orally administered carbenoxolone is absorbed mostly unchanged, in contrast with the rat in which the orally administered drug is substantially hydrolysed to β-glycyrrhetic acid and succinic acid before absorption.
Effect of Vasopressin on the Reabsorption of Phenacetin and its Metabolites from the Tubular Fluid in Man
Authors: Barraclough M. A. 
Published: August 2015

1. Changes in the urine/plasma (U/P) or urinary concentrations of creatinine, urea and phenacetin and its main metabolites, p-acetamidophenol (paracetamol) and p-phenetidine (p-ethoxy aniline), were determined during the transition from water diuresis to vasopressin-mediated antidiuresis in normal subjects given phenacetin (30–45 mg/kg). Studies were performed during both acid (NH4Cl) and alkali (NaHCO3) loading.
2. The U/P ratio of urea, phenacetin and p-acetamidophenol and the urinary concentration of p-phenetidine rose less than that of creatinine during both acid and alkali loading, indicating increased reabsorption of these compounds during vasopressin activity.
3. The mechanism by which phenacetin and its metabolites may cause renal papillary necrosis are discussed.
Intestinal Structure and Function after Small Bowel by-Pass in the Rat
Authors: Gleeson M. H. , Cullen J. , Dowling R. H. 
Published: August 2015

1. To study further the influence of luminal nutrition on small bowel structure and function, segments of rat jejunum and ileum were completely excluded from intestinal continuity by Thiry-Vella by-pass operations. The effect of partial deprivation of luminal nutrition was also studied in jejunal segments that had been surgically transposed to a distal position in the intestinal tract.
2. Macroscopically, by-passed jejunum and ileum both became narrowed and atrophic, whereas the intestine in continuity showed hypertrophic changes similar to those seen after intestinal resection.
3. In by-passed intestine the pattern of villi changed from mucosal ridges to ‘fingers’ and ‘leaves’. Although villous height and total mucosal thickness were both reduced, light microscopy showed that even 6 months after exclusion from intestinal continuity villous morphology was still retained.
4. Epithelial-cell migration rate and turnover time were diminished in both jejunum and ileum after by-pass. In intestine in continuity the migration rate was increased, but the turnover time remained the same as in controls.
5. In by-passed jejunum, in vivo glucose absorption diminished progressively with time, but did not change in excluded ileal segments.
6. After ileo-jejunal transposition, the jejunum showed no major morphological changes, but glucose absorption became significantly depressed.
7. These results further support the concept that intraluminal nutrition exerts a major influence on cell turnover, villous morphology and absorptive function in the small intestine.
The Relationship between the Magnesium Concentration in the Dialysis Fluid Used and in the Plasma and Erythrocytes of Patients with Chronic Renal Failure Being Treated by Regular Haemodialysis
Authors: Heierli Ch. , Hill A. V. L. 
Published: August 2015

1. Plasma and erythrocyte magnesium concentrations have been determined in fifty-five patients on regular haemodialysis and in thirty-two healthy subjects. The dialysis fluid magnesium concentrations of the former were 0·58, 0·9 and 1·73 mm.
2. There was a linear correlation between the plasma and erythrocyte magnesium concentrations of normal subjects and dialysed patients whose dialysis fluid contained 0·58 and 0·9 mm-magnesium and who were treated by dialysis for at least 3 months. This correlation was otherwise independent of the time the patients had been treated by dialysis.
3. There was a linear correlation between the dialysis fluid and the predialysis plasma magnesium concentrations in all dialysed patients, except that, when the dialysis fluid magnesium was increased, a certain period of treatment was necessary before the new equilibrium was reached.
4. An unusually high magnesium concentration in the dialysis fluid for regular haemodialysis may benefit such patients in view of the known effect of an increased plasma magnesium concentration upon the parathyroid function.
Studies on the Nature and Excretion of Biliary Copper in Man
Authors: Gollan J. L. , Deller D. J. 
Published: August 2015

1. Gall-bladder bile was obtained at cholecystectomy from seven patients who had been given [64Cu]cupric acetate intravenously.
2. Studies using dialysis and Sephadex gel filtration indicated that most of the 64Cu in the bile was in a heat-stable complex of molecular weight exceeding 50 000. The remaining biliary 64Cu was in a low-molecular-weight component.
3. Above pH 4, 64Cu could not readily be removed from the macromolecular complex either by excess carrier copper ions, by d-penicillamine or by EDTA.
4. Absorption of 64Cu from 64Cu-labelled bile injected intraduodenally into rats was significantly less than from [64Cu]cupric acetate similarly injected.
5. These observations suggest that limitation of an entero-hepatic circulation of copper by a biliary macromolecule which differs from caeruloplasmin, may be a significant factor in copper homeostasis in man.
The Inhibition of Urokinase by Alpha2-Macroglobulin
Authors: Ogston D. , Bennett B. , Herbert Robyn J. , Douglas A. S. 
Published: August 2015

1. Purified preparations of α2-macroglobulin inhibited the ability of urokinase to induce lysis of a fibrin plate, to activate plasminogen in a purified system, and to hydrolyse N-α-acetyl glycyl-l-lysine methyl ester.
2. Inhibition of urokinase by α2-macroglobulin was immediate: no progressive inhibition could be detected using fibrinolytic and esterolytic assays. Inhibition was competitive.
3. The fibrinolytic activity of euglobulin precipitate prepared from exercise plasma was also inhibited by α2-macroglobulin.
Increase of Plasma Renin-Substrate Concentration after Infusion of Angiotensin in the Rat
Authors: Khayyall M. , MacGregor J. , Brown J. J. , Lever A. F. , Robertson J. I. S. 
Published: August 2015

1. Compared with sixteen control animals infused with saline, plasma renin-substrate concentration increased twofold (P < 0.001) in twenty-two rats following infusion of angiotensin II at a mean rate of 191 ng kg−1 min−1 for 13 h.
2. The change was not attributable to an overall increase of plasma protein concentration.