bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Renin Inhibitors
Authors: Poulsen K. , Burton J. A. , Haber E.
Published: August 2015

1. To examine the substrate specificity of renin a series of analogues of a noctapeptide previously shown to be an effective substrate (Skeggs, Lentz, Kahn & Hochstrasser, 1968) were synthesized.

2. These peptides were studied both with respect to their actions as competitive inhibitors and as substrates.

3. This resulted in the identification of two peptides which were potent competitive inhibitors but could not be cleaved by renin.
Renin Suppression in Hypertension in Relation to Body Fluid Volumes, Patterns of Sodium Excretion and Renal Haemodynamics
Authors: Schalekamp M. A. D. H. , Krauss X. H. , Kolsters G. , Schalekamp M. P. A. , Birkenhäger W. H.
Published: August 2015

1. In patients with essential hypertension plasma renin concentration (PRC) was assessed in relation to age, plasma volume, extracellular fluid volume, aldosterone secretion rate, renal vascular resistance, filtration fraction and excess sodium excretion after acute salt loading.

2. Up to a calculated renal vascular resistance of 20 000 dyn s cm−5, PRC was found to be inversely related with the above-mentioned variables except plasma volume, extracellular fluid volume and aldosterone secretion rate.

3. It is concluded that the phenomenon of renin suppression is not dependent on mineralocorticoid excess. Instead, a decrease in PRC together with hypernatriuresis appears to reflect a progressive switch in intrarenal haemodynamic relationships. Renin suppression should therefore be considered to be a feature of progressive, but still uncomplicated, essential hypertension.
Prognosis in Arteriosclerotic Renovascular Hypertension
Authors: Pinedo H. M. , De Graeff J. , Struyvenberg A.
Published: August 2015

1. A comparison has been made of surgical and medical treatment in patients with arteriosclerotic renal artery stenosis and hypertension.

2. Immediate post-operative blood pressure was often normal, but frequently rose again later. After the sixth year only about 25% of surgical patients were normotensive without drug treatment.

3. Nephrectomy and vascular reconstruction gave similar results.

4. We presently believe that post-operative anticoagulant therapy is indicated in patients undergoing surgery for arteriosclerotic renal artery stenosis.
Effect of Phenobarbitone on Plasma [14C]Bilirubin Clearance in Patients with Unconjugated Hyperbilirubinaemia
Authors: Black M. , Fevery J. , Parker D. , Jacobson J. , Billing Barbara H. , Carson E. R.
Published: August 2015

1. The clearance of a tracer dose of [14C]bilirubin from the plasma was studied in patients with Gilbert's syndrome, congenital non-haemolytic jaundice, haemolytic jaundice and in normal subjects. Clearance was significantly impaired in the patients with Gilbert's syndrome and in those with congenital non-haemolytic jaundice when compared with the normal subjects, and was normal in the patient with haemolytic jaundice.

2. Treatment for 2 weeks with phenobarbitone (180 mg/day) lowered the plasma bilirubin concentration and improved all indices of plasma clearance of the isotope in patients with Gilbert's syndrome, so that they became indistinguishable from those of normal subjects. The improvement in plasma [14C]bilirubin clearance in these patients was associated with modest increases in hepatic bilirubin glucuronyl transferase in some subjects.

3. Phenobarbitone treatment improved plasma bilirubin concentrations and plasma [14C]bilirubin clearance in patients with congenital non-haemolytic jaundice, so that they resembled those seen in patients with untreated Gilbert's syndrome. Despite this improvement hepatic bilirubin glucuronyl transferase activity remained undetectable.

4. These results are compatible with the hypothesis that Gilbert's syndrome is a manifestation of a relative deficiency of hepatic bilirubin glucuronyl transferase, and differs from congenital non-haemolytic jaundice only in severity.
The Effect of Modifying the Combination of Insulin with Rat Adipose Cells on the Intracellular Levels of Cyclic Amp
Authors: Jerums G. , Galton D. J. , Gilbert C.
Published: August 2015

1. Isoprenaline (1 μmol/l) and glucagon (1 μmol/l) raised the levels of cyclic AMP in isolated adipose cells of the rat to a maximum after incubation for approximately 15 min.

2. The effect of glucagon was impaired by pretreatment of adipose cells with trypsin (0.2 mg/ml and 2.0 mg/ml) and N-ethylmaleimide (5 mmol/l). The β-adrenergic receptor was insensitive to such forms of treatment.

3. Insulin (430 μunits/ml) lowered the intracellular levels of cyclic AMP in adipose cells stimulated with isoprenaline (1 μmol/l) and glucagon (1 μmol/l). This effect was observed after incubation for 5 min.

4. Pretreatment of cells with trypsin (0.2 mg/ml and 2.0 mg/ml) and N-ethylmaleimide (0.5 and 5 mmol/l) abolished the effect of insulin in decreasing the intracellular levels of cyclic AMP. At the higher concentration of trypsin a rise in intracellular levels of cyclic AMP was observed in the presence of insulin.

5. Similar concentrations of trypsin and N-ethylmaleimide decreased the disappearance of unlabelled insulin from the incubation medium and also decreased the binding of 125I-labelled insulin to isolated fat cells.

6. The effect of insulin on decreasing the intracellular levels of cyclic AMP in modified adipose cells significantly correlated with the disappearance of unlabelled insulin from the medium and with the percentage of total 125I-labelled insulin bound to cells.

7. The possibility is discussed of using the disappearance of insulin or binding of 125I-labelled insulin to adipose cells as a measure of insulin-receptor availability on the plasma membrane of fat-cells.
The Relationship between Arterial Pco2 and Hydrogen Ion Concentration in Chronic Metabolic Acidosis and Alkalosis
Authors: Bone J. M. , Cowie J. , Lambie Anne T. , Robson J. S.
Published: August 2015

1. An analysis was made of the relationship which exists between arterial [H+], Pco2 and [HCO3−] in twenty-five patients with stable metabolic acidosis and alkalosis and in three normal subjects.

2. Contrary to previous reports, the relationship between Pco2 and [H+] was nonlinear and could best be described in terms of a rectangular hyperbola (Pco2 = 962/([H+]-12).

3. The relationship between Pco2 and [HCO3−] was curvilinear and best described by the quadratic function 23.8 (Pco2)2−12Pco2[HCO3−] −962 [HCO3−] = 0.

4. The small acute changes in [H+],−[HCO3−] and Pco2 produced by infusion of the weak organic acid 5,5−dimethyl 2,4−oxazolidinedione (DMO) could be predicted from the curvilinear regression.
The Effect of Diphenylhydantoin on Insulin Response
Authors: Cudworth A. G. , Cunningham J. L.
Published: August 2015

1. Serum immunoreactive insulin, glucose tolerance and growth hormone levels were estimated in healthy volunteers before and after receiving diphenylhydantoin sodium (DPH) for 14 days.

2. With a standard oral dose of DPH all subjects showed a reduced insulin response to oral glucose (11–44%). This correlated with the serum concentration of the drug, which ranged from 30.5 to 90.0 μmol/l (7.7–22.7 μg/ml).

3. Glucose tolerance remained normal and no changes in growth hormone levels were observed.

4. Different doses of DPH have been employed in the treatment of insulinoma and as a screening test for detecting latent insulin secretory defects. This study confirms the wide inter-individual variation in the metabolism of DPH, and stresses both the importance of measuring the serum concentration of DPH and the comparative irrelevance of dosage levels in these situations.
Haemodynamic Effects of Intravenous Frusemide in Patients with Myocardial Infarction and Left Ventricular Failure
Authors: Tattersfield Anne E. , McNicol M. W. , Sillett R. W.
Published: August 2015

1. Intravenous frusemide has been given to thirty-five patients with myocardial infarction and clinical signs of left ventricular failure. The haemodynamic changes following frusemide were then observed over the subsequent 6 h.

2. Frusemide produced a large diuresis, which was maximal during the first 2 h but fluid depletion was maintained at 24 h. The greatest diuresis occurred in patients with the highest stroke index.

3. All patients showed a fall in pulmonary artery pressure after frusemide. In patients with evidence of poor left ventricular function (low stroke index, high pulmonary artery pressure) this was associated with little change in stroke index. In patients with less severe impairment of left ventricular function there was an initial fall in stroke index at 1 and 2 h.

4. Six hours after frusemide there was a reduction in both pulmonary artery pressure and systemic arterial pressure; the latter correlated with the volume of the diuresis.
Transport of 5-Methyltetrahydrofolic Acid into the Cerebrospinal Fluid in Man
Authors: Chanarin I. , Perry Janet , Reynolds E. H.
Published: August 2015

1. 5-Methyltetrahydrofolate appeared in the CSF when given intravenously to man.

2. The data suggest considerable circulation of folate between CSF and other body compartments.
The Mechanisms by which Sodium Excretion is Increased during a Fast but Reduced on Subsequent Carbohydrate Feeding
Authors: North K. A. K. , Lascelles D. , Coates Pandora
Published: August 2015

1. The excretion of electrolytes was studied in six obese subjects before, during and after a 7 day fast.

2. Despite a constant sodium intake throughout the study, there was a marked but transient increase in sodium excretion during the fast, and a sharp reduction in sodium excretion on resuming the carbohydrate diet.

3. Fasting was associated with an increase in the excretion not only of sodium but also of potassium, magnesium, calcium, ammonium, titratable acid, chloride, phosphate, sulphate and organic acids. Refeeding was associated with a prompt reduction in the excretion of all ions other than chloride.

4. The patterns of electrolyte excretion indicated that a major factor responsible for the increased excretion of sodium on fasting and for the retention of sodium on refeeding was a failure of ammonium excretion to keep pace with the changing output of organic acid.
Effect of Triterpenoids Related to Carbenoxolone upon Human Pepsins and Pepsinogens and upon Bovine Trypsin and Chymotrypsin
Authors: Waft Lesley A. , Roberts N. B. , Taylor W. H.
Published: August 2015

1. Sixteen triterpenoid compounds, related to glycyrrhetic acid, have each been tested for anti-pepsin, anti-pepsinogen, anti-trypsin and anti-chymotrypsin activity. Their actions are compared with the known inhibitory actions of the triterpenoid, carbenoxolone, which is clinically effective in the healing of chronic gastric ulceration in man.

2. One of these compounds, 3-O-lauroyl-11-oxo-18α-olean-12-en-30-oic acid is known to be clinically ineffective in the healing of human gastric ulceration, and is found to have no inhibitory action upon any of the enzymes tested.

3. Anti-pepsin activity is affected by the nature of the side chain in the C-3 position, by substitution in the C-30 position, and by cleaving the A-ring. Anti-pepsinogen activity is affected by substitution into the C-28 position and/or by loss of the 11-oxo group.

4. The results enable suggestions to be made for the synthesis of new anti-pepsin and potential anti-ulcer triterpenoid derivatives.

5. The homologous enzymes, human pepsin 3 and swine pepsin A, are each affected similarly by the sixteen compounds. The correlation between effects of the compounds on pairs of enzymes may thus be used as a measure of the structural similarity of the enzymes. The correlation coefficients are high among the individual pepsins and among the individual pepsinogens.

6. It is also suggested that those triterpenoids which have anti-trypsin and anti-chymotrypsin activity may have a potential value in diseases in which pancreatic enzymes are released.
Hepatic Protein Binding of Folate
Authors: Corrocher R. , De Sandre G. , Pacor M. L. , Hoffbrand A. V.
Published: August 2015

1. Binding of tritiated folic acid to rat liver cell cytoplasmic proteins has been studied in vitro and in vivo by Sephadex G75 column chromatography.

2. Studies in vitro show that folic acid is bound mainly in the ‘Y’ and ‘Z’ protein fractions, which have previously been described as binding other organic anions, e.g. bilirubin, sulphobromophthalein.

3. At 10 min after injection of tritiated folic acid in vivo, radioactive folates in liver cytoplasm were largely bound to X and Z protein fractions, with a smaller fraction bound to the Y fraction. At 24 and 48 h, radioactive folates were bound largely to the X and Y protein fractions.

4. It is suggested that the Y and Z proteins or closely related proteins may be involved in transfer of folates from plasma to liver, the major store of folate in the body.
Plasma Amino Acids in Experimental Acute Hepatic Failure and Their Relationship to Brain Tryptophan
Authors: Buxton B. H. , Stewart D. A. , Murray-Lyon I. M. , Curzon G. , Williams R.
Published: August 2015

1. Sixteen plasma amino acids were measured serially in an experimental model of acute hepatic failure produced in the pig by devascularization of the liver.

2. Significant increases in the concentration of glycine, alanine and methionine were observed.

3. Altered concentrations in plasma of neutral amino acids which compete with tryptophan for transport into the brain had no apparent influence on brain tryptophan concentration.
Cell Sodium, Potassium and Water in Uraemia and the Effects of Regular Dialysis as Studied in the Leucocyte
Authors: Patrick J. , Jones N. F.
Published: August 2015

1. The leucocyte has been used as a model for the study of intracellular sodium, potassium and water in uraemia. The advantages of this cell are described.

2. In undialysed patients with advanced renal failure leucocyte sodium and water contents were significantly greater than normal. Leucocyte potassium content (mmol/kg of dry solids) and concentration (mmol/l of cell water) were reduced.

3. In patients receiving regular dialysis leucocyte water was significantly reduced. Leucocyte potassium content was also reduced in this group, but leucocyte potassium concentration in cell water had returned to normal.

4. In the normal subjects and also in the dialysed patients leucocyte water correlated better with potassium than with sodium content. In contrast, in the undialysed uraemic patients leucocyte water correlated better with sodium than with potassium content, indicating that the increased cell sodium was an important determinant of the increased cell water in this group.
Plasma Tocopherol Levels and the Susceptibility of Erythrocytes to Heinz Body Formation
Authors: Tudhope G. R. , Hopkins J.
Published: August 2015

1. The formation of Heinz bodies, after exposure of erythrocytes to hydrogen peroxide vapour, was significantly greater in cells from patients with plasma tocopherol levels of 11·6 μmol/l (5 mg/1) or less than in those from subjects with plasma tocopherol levels greater than 11·6 μmol/l.

2. Six patients with low plasma tocopherol levels received intramuscular or oral tocopherol for 3–14 days. In four cases, the abnormally great production of Heinz bodies by hydrogen peroxide was much reduced after tocopherol therapy.

3. The addition of tocopherol to suspensions of erythrocytes from such patients markedly reduced the Heinz body formation by hydrogen peroxide in two out of six cases.

4. In one case of erythrocyte glutathione peroxidase deficiency, where the plasma tocopherol concentration was normal, exposure of the erythrocytes to hydrogen peroxide resulted in abnormally great Heinz body formation. On repeating the experiment after the patient had received daily tocopherol injections for 5 days, the production of Heinz bodies by hydrogen peroxide was then no greater than in erythrocytes from normal subjects.

5. The effect of phenylhydrazine in producing Heinz bodies in erythrocytes in vitro was significantly reduced by the addition of tocopherol to the erythrocyte suspension; tocopherol had no significant effect on Heinz body formation by other oxidant drugs tested.
The Effect of Angiotensin upon the Vasculature of the Isolated Perfused Rat Kidney
Authors: Cross R. B. , Trace J. W. , Vattuone J. R.
Published: August 2015

1. The effect of angiotensin II-amide upon the intrarenal distribution of perfusate was studied in the isolated rat kidney.

2. Low concentrations of angiotensin, 4·86 pmol/l (0·005 μg/l), reduced the flow rate through the papilla but did not alter total flow.

3. Higher concentrations of angiotensin, 0·486 nmol/l (0·5 μg/l), reduced total renal flow but did not decrease papillary perfusion.

4. In these experiments the perfusion pressure was maintained constant, indicating that the changes in flow were due to a direct effect of angiotensin upon the renal vasculature.
Post-Heparin Lipolytic Activity and Tissue Lipoprotein Lipase Activity in the Alloxan-Diabetic Rat
Authors: Elkeles R. S. , Williams E.
Published: August 2015

1. Alloxan-diabetic rats showed raised plasma triglyceride levels and low adipose tissue lipoprotein lipase activity compared with controls. Heart lipoprotein lipase activity appeared unaltered by the diabetic state.

2. Plasma post-heparin lipolytic activity was slightly but not significantly increased in the diabetic group. The significance of these findings is discussed.
Competition between Carnosine and other Peptides for Transport by Hamster Jejunum in Vitro
Authors: Addison Jill M. , Matthews D. M. , Burston D.
Published: August 2015

1. This paper reports the results of experiments on competition for transport by hamster jejunum in vitro between carnosine (β-alanyl-l-histidine) and other peptides and amino acids. Carnosine was chosen because this dipeptide is taken up intact with very little hydrolysis, which simplifies interpretation of the results.

2. Jejunal uptake of carnosine was inhibited by equimolar glycylglycine, glycylglycylglycine, glycylsarcosine, glycylproline, methionylmethionine and prolylhydroxy-proline but not by the equivalent free amino acids, or by a mixture of β-alanine and histidine. Inhibition of carnosine uptake by glycylproline was shown to be competitive. It is suggested that carnosine and the dipeptides inhibiting its uptake enter the mucosal cells by a common mechanism which is independent of the entry mechanisms for amino acids. Uptake of carnosine was not inhibited by N-acetylglycylglycine or by glycylglycine amide, suggesting that these substitutions prevent glycylglycine utilizing the dipeptide-uptake mechanism.

3. Carnosine uptake was not inhibited by equimolar lysyllysine or α-glutamylglutamic acid, nor did lysyllysine and α-glutamylglutamic acid affect uptake of each other. Though these results are compatible with the existence of multiple dipeptide-uptake systems in the intestinal mucosa, the evidence at present available is insufficient to permit any conclusion on this point.
Mental Retardation, Megaloblastic Anaemia, Methylmalonic Aciduria and Abnormal Homocysteine Metabolism Due to an Error in Vitamin B12 Metabolism
Authors: Dillon M. J. , England J. M. , Gompertz D. , Goodey Patricia A. , Grant D. B. , Hussein H. A-A. , Linnell J. C. , Matthews D. M. , Mudd S. H. , Newns G. H. , Seakins J. W. T. , Uhlendorf B. W. , Wise Irene J.
Published: August 2015

1. The case is described of a child with retarded physical and mental development, recurrent megaloblastic anaemia, methylmalonic aciduria and abnormal homocysteine metabolism resulting from an inborn error in the metabolism of cobalamins. She died at the age of 7 years. At autopsy there was pulmonary fibrosis and the brain showed lesions typical of those seen in subacute combined degeneration of the cord.

2. A metabolic abnormality was present which resulted in an inability to maintain normal tissue concentrations of the two coenzyme forms of vitamin B12, methylcobalamin and adenosylcobalamin. Lack of methylcobalamin led to deficient activity of N5-methyltetrahydrofolate-homocysteine methyltransferase with reduced ability to methylate homocysteine, and lack of adenosylcobalamin to deficient activity of methylmalonyl-CoA mutase, which accounted for the methylmalonic aciduria.

3. Analyses of total vitamin B12 and of individual cobalamins by a chromatobioautographic technique showed that in organs sampled at autopsy, the content of total vitamin B12 and of methylcobalamin, adenosylcobalamin and hydroxocobalamin were all greatly reduced. The plasma had a high normal total vitamin B12 content, but showed a gross abnormality in the distribution of individual cobalamins, methylcobalamin being decreased and adenosylcobalamin and hydroxocobalamin increased. The erythrocytes showed a reduction in cobalamins resembling that in the solid organs, though less severe.

4. The underlying abnormality in this patient appeared to be either a defect in cellular uptake of vitamin B12, or a defect in a metabolic pathway leading to the formation of a common precursor of methylcobalamin and adenosylcobalamin. Abnormalities in transcobalamins I and II, plasma factors involved in plasma transport and cellular uptake of vitamin B12, were excluded.

5. The clinical and biochemical findings in the patient are compared with those described in three patients previously reported, who had methylmalonic aciduria and homocystinuria, and who were in some respects similar to this patient. The present case is unusual in that previous examples of errors in cobalamin metabolism have not had megaloblastosis or neurological changes typical of vitamin B12 deficiency. It is also the first case in which direct estimations of individual cobalamins have been made.
Peripheral Vitamin C Metabolism in Diabetics and Non-Diabetics: Effect of Intra-Arterial Insulin
Authors: Cox B. D. , Whichelow Margaret J. , Butterfield W. J. H. , Nicholas P.
Published: August 2015

1. Studies of the effect of the local injection of insulin on vitamin C metabolism in the tissues of the forearm and the buffy layer have been carried out in eight normal and eight diabetic subjects. The range of plasma and buffy layer concentrations of vitamin C were wide and overlapped in the two groups.

2. In the fasting state there was an output of vitamin C from the peripheral tissues in both groups and this was increased in the non-diabetics after insulin, whereas the response in the diabetic subjects was variable.

3. It is concluded that insulin influences vitamin C metabolism in the peripheral tissues in man, and that the response is abnormal in many diabetic subjects.
The Control of Aldosterone Secretion in Nephrectomized Man
Authors: Goodwin T. J. , James V. H. T. , Peart W. S.
Published: August 2015

1. The adrenal response to a reduction in extracellular fluid volume (ECFV), sodium depletion, intravenous adrenocorticotrophic hormone (ACTH) and angiotensin II was assessed from changes in plasma aldosterone and plasma cortisol in eleven nephrectomized patients. Five patients were also studied before nephrectomy and six after successful renal transplantation.

2. Before nephrectomy, the resting concentrations of plasma aldosterone were usually raised. In the three patients out of five tested, the response to intravenous ACTH was marked. In two out of four patients, there was a good response to angiotensin II infusion. In one of two patients, there was a good response to a reduction in ECFV and sodium depletion.

3. After nephrectomy, the resting concentrations of plasma aldosterone were negligible or uniformly reduced and the response to ECFV reduction, sodium depletion, ACTH and angiotensin II was universally poor.

4. In all cases there was a normal plasma cortisol response to ACTH.

5. After renal transplantation in six patients, the four to whom an infusion of angiotensin II was given showed a return to a normal aldosterone response and all six showed a normal response to ACTH.

6. No clear correlation was shown between resting concentrations of plasma aldosterone and plasma potassium after nephrectomy.

7. It was concluded that the kidney, through the renin-angiotensin system, may play its main part by sensitizing the zona glomerulosa to other stimuli, but an alternative kidney-dependent mechanism cannot be excluded.
The Antidiuretic Action of Carbamazepine in Man
Authors: Meinders A. E. , Cejka V. , Robertson G. L.
Published: August 2015

1. Carbamazepine had an antidiuretic effect in six patients with neurohypophyseal diabetes insipidus due to various causes. The effect was qualitatively similar to that of antidiuretic hormone.

2. At the time of maximal antidiuresis plasma arginine vasopressin levels, measured by radioimmunoassay, were below the limit of detectability in all patients.

3. In one of two control subjects a temporary decrease in water excretion was observed during administration or carbamazepine.

4. In the two control subjects plasma arginine vasopressin levels dropped from normal to below the level of detectability during administration of the drug.

5. It is concluded that the antidiuretic effect of carbamazepine is not the result of releasing endogenous antidiuretic hormone or of prolonging its half-life.

6. The most likely explanation for the observed results is either a direct effect of carbamazepine on the distal renal tubular cell or an increase of renal responsiveness to endogenous antidiuretic hormone.
Acute Hepatic Encephalopathy in the Rat: The Effect of Cross-Circulation
Authors: Roche-Sicot Jacqueline , Sicot C. , Peignoux Michèle , Bourdiau Denise , Degos Francine , Degos J.-D. , Prandi Danièle , Rueff B. , Benhamou J.-P.
Published: August 2015

1. The effect of cross-circulation on hepatic encephalopathy (evaluated by electroencephalography; EEG) induced by hepatectomy in the rat was examined.

2. Systemic-systemic cross-circulation induced improvement of the altered EEG in only two out of seven liverless rats when the exchange-flow rate was 6.4 ml min−1 kg body wt.−1, and in all seven liverless rats when the exchange-flow rate was 14.0 ml min−1 kg body wt.−1; the difference is statistically significant (P = 0.011).

3. Systemic-portal cross-circulation (systemic blood from the liverless rat being infused into the portal vein of the normal rat) induced improvement of the altered EEG in all seven liverless rats although the exchange-flow rate was only 6.4 ml min−1 kg body wt.−1

4. It is concluded (a) that a certain level of exchange-flow rate is required for cross-circulation to be efficient, and (b) that, for the same exchange-flow rate, systemic-portal cross-circulation is more efficient than systemic-systemic cross-circulation.
Parasympathetic Pathways, Renin Secretion and Vasopressin Release
Authors: Schrier R. W. , Reid I. A. , Berl T. , Earley L. E.
Published: August 2015

1. The interrelationship between parasympathetic neural tone, renin secretion and vasopressin release was examined by observing the effect of bilateral cervical vagotomy on renin secretion in intact and acutely hypophysectomized dogs undergoing a water diuresis.

2. In intact dogs bilateral cervical vagotomy decreased the mean renin secretion from 1245 to 682 units/min (P < 0.01) as urinary osmolality increased from 95 to 414 mosmol/kg (P < 0.001). In contrast, in acutely hypophysectomized dogs cervical vagotomy failed to alter renin secretion significantly (834 to 893 units/min) and urinary osmolality was also unchanged (78 to 71 mosmol/kg).

3. The results suggest that a diminution in vagal tone may significantly alter renin secretion by stimulating vasopressin release. Exogenous vasopressin was associated with changes in urinary osmolality and renin secretion which were qualitatively similar to those seen after cervical vagotomy.

4. We suggest that there is a neurohumoral reflex mechanism by which a fall in parasympathetic tone increases the release of vasopressin, which, in turn, suppresses renin secretion. The results are also compatible with the hypothesis that vasopressin inhibits renin release by a direct effect on the juxtaglomerular cells.
Changes in Physiological Performance of the Lower Limb after Fracture and Subsequent Rehabilitation
Authors: Davies C. T. M. , Sargeant A. J.
Published: August 2015

1. Eight patients who had suffered a fracture of one leg were studied before and after a 7 weeks period of rehabilitation during work with one leg and both legs on a bicycle ergometer.

2. In submaximal exercise minute ventilation for a given carbon dioxide output and tidal volume at a given minute ventilation remained unchanged throughout the period of therapy for both one- and two-leg exercise: oxygen intake for a given work output and cardiac frequency for a given oxygen intake decreased in both the injured and uninjured limb during one-leg work, although in two-leg exercise there was no significant change.

3. Oxygen intake at zero load was subtracted from the maximum oxygen intake measured during loaded exercise to give net values for each limb exercised separately or both legs exercised together. The net maximum oxygen intake thus calculated increased 8.9% (+ 0.17 l/min) in the uninjured leg and 17.4% (+0.29 l/min) in the injured leg during one-leg exercise. In two-leg exercise the increase was 17.2% (+ 0.43 l/min), which approximately equals the increase in the two legs measured separately.

4. In both legs there was an increase in leg muscle (plus bone) volume although this was significant in the injured leg only.

5. The maximum oxygen intake attained in two-leg exercise for a given leg volume in the patients at discharge was not significantly different from that found previously in a cross-sectional survey of young healthy (naval) servicemen. Thus the rehabilitation programme investigated appears to be effective, although the spontaneous recovery without a rehabilitation programme is unknown.
Haematological Status of Middle- and Long-Distance Runners
Authors: Brotherhood J. , Brozović B. , Pugh L. G. C.
Published: August 2015

1. Haematological investigation and blood volume measurements were carried out on forty male middle-and long-distance runners and twelve non-athletes.

2. The distribution of haemoglobin concentration, packed cell volume, erythrocyte count, total iron-binding capacity, serum and erythrocyte folate and serum vitamin B12 concentrations were essentially the same in athletes and non-athletes. The mean serum iron concentration was higher in non-athletes than in athletes. There was no difference in the above measurements between athletes taking iron and/or folate and athletes not taking these supplements.

3. Blood volume and total body haemoglobin were on average 20% higher in the athletes than in the non-athletes.

4. There was no correlation between haemoglobin concentration and blood volume in athletes. The evidence of this study suggests that haemoglobin concentration and blood volume are independently controlled.

5. 2,3-Diphosphoglycerate concentration in the erythrocytes was higher in the athletes than in the non-athletes; the mean values were 15.9 and 14.2 μmol/g of haemoglobin respectively.
Factors Influencing the Entry of Dye into Neutrophil Leucocytes in the Nitroblue Tetrazolium Test
Authors: Segal A. W. , Levi A. J.
Published: August 2015

1. The Nitroblue Tetrazolium (NBT) test is a measure of the phagocytosis of particulate complexes of NBT and heparin and/or fibrinogen by neutrophil leucocytes.

2. Humoral factors in the plasma of ill patients stimulate neutrophil leucocytes of normal subjects to ingest these complexes.

3. The acute phase protein, orosomucoid and endotoxin stimulate reduction of NBT in vitro and could be responsible for some positive NBT tests in vivo.

4. The effect of factors promoting phagocytosis may be masked by an inability of neutrophil leucocytes to respond to stimulation.

5. This defective neutrophil function could result from the replacement of circulating neutrophil leucocytes by less mature, less actively phagocytic cells or by the presence of circulating immune complexes.
Angiotensin-Induced Variations of Receptors in Rat Uterine Membranes
Authors: Chevillotte E. , Devynck M. A. , Fyhrquist F. , Meyer P. , Rouzaire-Dubois B. , Worcel M.
Published: August 2015

1. 3H-labelled angiotensin II specifically binds to plasma membranes of rat uterine smooth muscle cells. Two classes of binding sites differing in their affinity for the hormone were demonstrated. The high-affinity binding sites (KD 29°C ∼ 2.0×10−8 mol/l) probably correspond to the receptors involved in the biological response.

2. Bilateral nephrectomy significantly increases the concentration of 3H-labelled angiotensin-binding sites, a phenomenon which seems unrelated to the freeing of receptor sites secondary to the suppression of plasma angiotensin. This phenomenon may be responsible for the specific hypersensitivity in vitro to angiotensin of uteri excised in anephric rats as compared with normal rats.

3. Angiotensin II infusion in nephrectomized rats reduced the concentration of 3H-labelled angiotensin-binding sites.

4. It is suggested that the angiotensin receptor concentration is regulated by the concentration of circulating angiotensin.
Isolation, Characterization and Function of Cord-Blood Transferrin
Authors: Verhoef N. J. , Van Eijk H. G.
Published: August 2015

1. Transferrin was isolated from umbilical cord blood by means of gel filtration on Sephadex G-150 and ion-exchange chromatography on DEAE-Sephadex A-50, and its properties were compared with those of transferrin isolated from human adult blood.

2. Both glycoproteins were able to bind a maximum of two atoms of iron per molecule and have very similar amino acid and carbohydrate compositions.

3. The molecular weight of cord-blood transferrin, assessed by equilibrium centrifugation, was 78 200, and its sedimentation velocity appeared to be 5.2S.

4. Cord-blood transferrin and adult blood transferrin were found to be immunochemically identical.

5. No differences could be detected between the transferrins in their capacities to deliver iron to immature erythrocytes derived from rat bone marrow, which indicates that the rapid transport of iron across the placenta cannot be explained by differences between foetal and maternal transferrin.
A Comparison of the Effects of Incubation on Cells Containing Haemoglobin S or Haemoglobin A
Authors: Rampling M. W.
Published: August 2015

1. A centrifugal packing technique has been used to investigate the effect of incubation on the flexibility of erythrocytes containing normal (Hb A) or sickle-cell (Hb S) haemoglobin. The effects on cell morphology and on the reversibility of morphological changes were also investigated.

2. The two types of cell reacted similarly to incubation. Sickling of the Hb S-cells was shown not to be responsible for the production of irreversibly deformed cells in these circumstances.

3. It is concluded that for both cell types the membrane inflexibility, cellular deformation and morphological irreversibility induced by the incubation were due to metabolic depletion.
Permanent Hypertension after Renal Homotransplantation in Man
Authors: Grünfeld J. P. , Kleinknecht D. , Moreau J. F. , Kamoun P. , Sabto J. , Garcia-Torres R. , Osorio M. , Kreis H.
Published: August 2015

1. In forty-one patients who underwent renal homotransplantation the following measurements were made: (a) blood flow and its distribution in the transplanted kidney as measured by the 85Kr washout method; (b) renin release in the renal vein of the transplant; (c) arteriovenous difference in plasma renin activity (PRA) of the recipient's remaining left kidney.

2. Eleven transplanted patients were normotensive. Renal haemodynamic data were comparable with those obtained in potential kidney donors.

3. Three hypertensive patients had chronic rejection. The mean renal blood flow and the percentage of flow in the first component of the washout curve were reduced. Renin release from the transplant, however, was normal.

4. Ten hypertensive patients had transplant artery stenosis. In eight of them renin release from the graft as well as peripheral PRA were within normal range. This result is similar to experimental data obtained in Goldblatt renovascular hypertension. The two patients with the tightest artery stenosis had an elevated renin release from the transplant.

5. Thirteen hypertensive patients had elevated arteriovenous difference in PRA of the recipient's own left kidney. Peripheral PRA was significantly higher than in normotensive patients. Left nephrectomy relieved hypertension in ten of them; three have not so far undergone nephrectomy.

6. In four other cases hypertension was also relieved by removal of the patient's own kidney; however, the arteriovenous difference in PRA of that kidney fell within normal range.
Effect of angiotensin II and of an Angiotensin II Analogue (Sar1-Ile8-Angiotensin II) on Blood Pressure, Plasma Aldosterone and Plasma Renin Activity in the Dog
Authors: Beckerhoff R. , Uhlschmid G. , Vetter W. , Armbruster H. , Nussberger J. , Reck G. , Schmied U. , Siegenthaler W.
Published: August 2015

1. The effect of infusions of equimolar doses of angiotensin II (AII) and of the angiotensin analogue Sar1-Ile8-angiotensin II on arterial blood pressure, plasma aldosterone and plasma renin activity were compared in normal anaesthetized dexamethasone suppressed dogs.

2. Angiotensin II induced a significant increase of blood pressure and of plasma aldosterone whereas plasma renin activity decreased. The blood pressure was only slightly affected by large doses of the analogue. Plasma aldosterone, however, increased and plasma renin activity decreased. These changes were significant but less pronounced than after the infusions of angiotensin II. Plasma aldosterone remained high and renin activity low for 40 min after the infusions of the analogue.

3. The results suggest a strong agonistic potency of Sar1-Ile8-angiotensin II at the adrenal and renal angiotensin receptors, and that it is almost ineffective at the vascular receptors. The inhibition of renin secretion by angiotensin seems not to be related to its vasoconstrictive activity.
Total Body Potassium and Body Fat Estimation in Relationship to Height, Sex, Age, Malnutrition and Obesity
Authors: Edmonds C. J. , Jasani B. M. , Smith T.
Published: August 2015

1. Total body potassium was estimated by 40K measurement with a high-sensitivity whole-body counter in normal individuals over a wide age range and in patients who were obese or were grossly wasted as a result of various conditions which restricted food intake.

2. Potassium concentration (mmol/kg body weight) fell with increasing age over 30 years in both normal males and females, but when individuals of different age groups were matched for height, a significant fall in total body potassium with increasing age was observed only in males. Total body potassium of females was about 75% that of males of similar height when young, the sex difference decreasing with ageing. In the normal population, total body potassium was significantly correlated with height and with weight; regression equations for various relationships are given.

3. Fat-free mass was estimated from total body potassium, values of 65 and 56 mmol of potassium/kg fat-free mass being used for males and females respectively. Body fat estimated by this method correlated well with skinfold measurements over a wide range of body weight but in malnourished individuals having inadequate food intake there was considerable discrepancy and present formulae for estimating fat-free mass from total body potassium appear unsatisfactory in malnutrition. Considerable differences between expected and observed values of total body potassium were found in muscular individuals and in normal individuals who were thin but whose body weight was relatively constant.

4. The patients with malnutrition were low both in body fat as estimated by skinfold thickness and in total body potassium estimated on the basis of height. Plasma potassium was, however, normal and potassium supplements did not increase the total body potassium.

5. Total body potassium of obese individuals was not significantly different from that of normal weight individuals on the basis of height. Total body potassium fell on weight reduction with a very low energy diet of 1260 kJ (300 kcal.) daily but changed little with a 3300 kJ (800 kcal.) diet over several months' observation.

6. For overweight, obese individuals, total body potassium was best predicted from the individual's height. For those whose body weight was less than expected, the use of weight gave the best prediction but the error was considerable when the weight deviation was large.
The Characteristics of Ferritin from Human Tissues, Serum and Blood Cells
Authors: Worwood M. , Aherne W. , Dawkins S. , Jacobs A.
Published: August 2015

1. The properties of ferritin in serum have been compared with those of ferritin from a number of tissues including blood cells. On anion-exchange chromatography with DEAE-Sephadex, the behaviour of human heart ferritin is different from that of liver, kidney or spleen ferritin. Reticulocyte ferritin appears to have similar characteristics to heart ferritin.

2. Serum ferritin from normal subjects and patients with various degrees of iron load, leukaemia or liver disease all have a much lower affinity for the anion-exchange column than any tissue ferritin, suggesting a difference in isoelectric point. The elution point of serum ferritin from patients with acute myeloblastic leukaemia is significantly different from normal.

3. Density gradient centrifugation in sucrose showed that ferritin in leucocyte extracts and partially purified ferritin from the serum of two patients with iron overload behaved as apoferritin rather than the iron-rich protein.

4. The results suggest that ferritin is modified during its entry into the plasma and that even in cases of iron overload the iron content of serum ferritin may be low. The findings are of importance in considering the origin of plasma ferritin, the clearance of ferritin from plasma and its role in iron metabolism.
Iron Therapy in Maintenance Haemodialysis
Authors: Baker L. R. I. , Cattell W. R. , Child J. A. , Savdie E.
Published: August 2015

1. Marrow-iron stores were absent or reduced in twenty-three of thirty-nine patients studied within 52 months of starting maintenance haemodialysis.

2. Oral iron was given to twelve patients (group I) with absent or reduced, and to eleven patients (group II) with normal or increased marrow-iron stores.

3. A significant increase in mean haemoglobin concentration and marrow iron was observed in group I. No significant change in mean haemoglobin concentration or marrow iron occurred in group II. Mean haemoglobin concentration after treatment was significantly higher in group I than in group II.

4. The four patients who had normal or increased marrow iron and who received no oral iron all suffered a fall in haemoglobin concentration, and three of them showed a reduction in marrow iron.

5. These findings indicate that continuous oral iron therapy should be given to all patients on maintenance dialysis to correct or prevent iron deficiency.
Yoga and Biofeedback in the Management of ‘stress’ in Hypertensive Patients
Authors: Patel C.
Published: August 2015

1. Psychophysical relaxation exercises based on yogic principles and reinforced by biofeedback instruments were used for behaviour modification in sixteen hypertensive subjects.

2. Preliminary studies indicated that their pressor response to emotional and physical stimuli became less exaggerated and less protracted compared with controls.
Control of High and Low Blood Pressure in the Dog by Aortic and Sinus Nerves
Authors: Clement D. L. , Pelletier L. C. , Shepherd J. T.
Published: August 2015

1. Changes in afferent activity in the aortic and sinus nerves with alterations of blood pressure were studied in anaesthetized dogs. Mean aortic blood pressure was changed from 220 to 50 mmHg by using a pressurized reservoir connected to the abdominal aorta.

2. The stimulus-response curve (defined by measuring the mean impulse frequency at various pressures) from both nerves was S-shaped; the curve for the aortic nerve was shifted to the right of the sinus nerve curve.

3. In the dog, the aortic arch baroreceptors act predominantly as an anti-hypertensive mechanism; at lower pressures, the major control occurs through the sinus baroreflex.
The Brain as a Possible Site for the Cardiovascular Effects of β-Adrenoceptor Blocking Agents in Cats
Authors: Day M. D. , Roach A. G.
Published: August 2015

1. dl-Propranolol, l-propranolol, dl-alprenolol, pindolol (LB46), practolol, ICI 66082, sotalol and oxprenolol all produced prolonged falls in blood pressure and heart rate after intracerebroventricular administration in conscious normotensive cats.

2. Transient initial pressor responses and tachycardias were observed after intracerebroventricular infusions of all the β-adrenoceptor antagonists used, except ICI 66082.

3. d-Propranolol, d-alprenolol, procaine and lignocaine all produced initial increases in blood pressure and heart rate but did not subsequently cause any reduction in either blood pressure or heart rate.

4. The time of maximum hypotension and bradycardia after intracerebroventricular infusion of β-adrenoceptor antagonists coincided with the maximum inhibition of the centrally mediated tachycardia observed after intracerebroventricular isoprenaline.
Relationships between Plasma Renin Activity and Urinary and Plasma Catecholamines
Authors: Werner U. , Günnewig H. , Bock K. D.
Published: August 2015

1. The relations between the changes in plasma renin activity (PRA) and urinary catecholamine excretion (UCA) or plasma noradrenaline concentration have been investigated (a) in patients with benign primary hypertension, with renovascular hypertension and with idiopathic asympatheticotonic hypotension (ASH), and (b) during orthostasis and after administration of frusemide, of the β-blocking agent tenormin, of clonidine and of dihydralazine.

2. In primary hypertension noradrenaline and mean arterial pressure (Pm) showed a close positive correlation.

3. The mean values of both PRA and UCA were higher in renovascular hypertension than in primary hypertension and extremely low in ASH. The overlap of individual values between the patient groups was markedly reduced by using the quotient PRA/UCA. There was a statistically significant positive correlation between PRA and UCA in primary hypertension and in renovascular hypertension, with a different slope of the regression lines.

4. The increase of PRA and of noradrenaline during orthostasis was closely correlated. Frusemide and β-receptor blockade changed the slope of the regression line by additional stimulation or inhibition respectively of PRA.

5. Clonidine decreased, and dihydralazine increased both PRA and noradrenaline concentration. These changes again showed a significant positive correlation. The fall of mean arterial pressure produced by clonidine was correlated with the decrease of PRA and of noradrenaline concentration.
Potassium Changes in Megaloblastic Anaemia
Authors: Hesp R. , Chanarin I. , Tait Christine E.
Published: August 2015

1. Serial measurements of serum potassium and total-body potassium were made on eighteen patients with megaloblastic anaemia before the start of therapy and during the period of recovery.

2. In those patients who presented with an initial packed cell volume of less than 25%, a mean decrease in serum potassium of 0.4 mmol/l occurred on average within 2.5 days of the start of therapy. This was followed by a significant increase in serum potassium during the period of recovery. There was a significant increase in total-body potassium in these patients, but this could be explained by increases in erythrocyte mass, erythrocyte potassium concentration and lean body mass.