bluuebunny/crossref_metadata_2025 huggingface dataset:
Demography of Serum Immunoglobulins: Differences in IgG and IgM Levels in two Normal Mexican Adult Populations
Authors: Alarcón-Segovia D. , Fishbein Eugenia
Published: August 2015

1. The three major immunoglobulins were quantitatively determined in the serum of 112 healthy Mexico City residents by the single radial immunodiffusion method.

2. Mean levels of IgG and particularly of IgM were unusually low as compared to (a) mean levels reported from elsewhere, (b) a group of thirty-eight healthy residents of Acapulco, Mexico of similar racial background and income and (c) a ‘British’ standard reference serum.

3. It is suggested that low IgG and IgM levels in Mexico City residents may be related to its high altitude.

4. Diminished immunoglobulin levels, particularly those of IgM, might be a compensatory mechanism for the increase in blood viscosity caused by high altitude erythrocytosis.
Protein Turnover in Skeletal Muscle. I. The Measurement of Rates of Synthesis and Catabolism of Skeletal Muscle Protein Using [14C]Na2CO3 to Label Protein
Authors: Millward D. J.
Published: August 2015

1. The turnover of rat skeletal muscle protein was studied using [75Se]selenomethionine, [6-14C]arginine and [14C]Na2CO3 to label protein.

2. In rats labelled with both [75Se]selenomethionine and [14C]Na2CO3 the 14C activity of mixed skeletal muscle protein fell rapidly with a half-life of 6·0 days for the specific activity and 10·5 days for the total activity. There was no loss of 75Se activity from muscle protein during the 12 days of the experiment.

3. Following the injection of [6-14C]arginine both sarcoplasmic and myofibrillar proteins continued to incorporate label for 6 days after which time the label was lost fairly rapidly.

4. Following the injection of [14C]Na2CO3 muscle protein was maximally labelled by 6 h, at which time specific activity of the free amino acids had fallen to a very low level. Aspartate and glutamate in particular had lost over 99% of their maximum activity by this time in comparison to arginine which was still highly labelled after 24 h.

5. 14C activity was lost more rapidly from aspartate and glutamate isolated from sarcoplasmic and myofibrillar protein than from the other labelled amino acids. The half-lives of the two protein fractions were 3·9 and 7·2 days from the specific activity curves and 6·0 and 19·0 days from the total activity curves.

6. The differences between the half lives of muscle proteins labelled with different amino acids are discussed in terms of the effects of reutilization of the labelled amino acid used. It is postulated that aspartate and glutamate labelled by the injection of [14C]CO=3 are only reutilized to a very small extent and therefore afford the means by which the rates of protein synthesis and catabolism in skeletal muscle can be measured with reasonable accuracy.
Exercise Tolerance Breathing a Low Density Gas Mixture, 35% Oxygen and Air in Patients with Chronic Obstructive Bronchitis
Authors: Raimondi A. C. , Edwards R. H. T. , Denison D. M. , Leaver D. G. , Spencer R. G. , Siddorn J. A.
Published: August 2015

1. We have examined the effects of (a) reducing the density of the inspired gas and of (b) increasing inspired oxygen concentration on the exercise performance of eight men with chronic obstructive bronchitis (COB).

2. Each subject performed two types of exercise test breathing three different gas mixtures: air, 35% oxygen in nitrogen and 21% oxygen in helium. The exercise capacity, ventilation and heart rate were recorded. Indices of pulmonary mechanics were measured to determine where and how any change in ventilatory capacity might have been achieved.

3. (a) Effort tolerance at a constant load (70% capacity breathing air) was greater when the inspired gas mixture was 35% oxygen in nitrogen than when air or 21% oxygen in helium was breathed.

(b) Peak expiratory flow (PEF) was greater when the helium mixture was breathed, but the forced expiratory volume in 1 s (FEV1) and maximum expiratory flow at 50% vital capacity (MEF50%) were the same as when breathing air. Effort tolerance was the same breathing the helium mixture and air in both the progressive and constant load tests.

(c) PEF, FEV and MEF50% were greater immediately after than before exercise on all gas mixtures.

4. It is concluded that a reduction in the density of the inspired gas does not improve effort tolerance in patients with COB. Possible reasons for this lack of benefit are discussed.
Relationships between Potassium, Chloride, Intracellular and Extracellular pH in Dogs
Authors: Wilson A. F. , Simmons D. H.
Published: August 2015

1. Total body, intracellular, and extracellular electrolyte and acid-base changes were studied following sodium nitrate-induced potassium and chloride depletion and subsequent selective chloride repletion.

2. It was found that potassium and chloride depletion was associated with markedly decreased extracellular Na, K, Cl and water content. Intracellular Na increased, intracellular K decreased and there was a large transcellular redistribution of acid, i.e. extracellular alkalosis and intracellular acidosis ensued.

3. Selective chloride repletion was associated with return of extracellular pH towards normal. Extracellular K and intracellular parameters showed very little change. Further chloride administration was followed by extracellular acidosis, but extracellular K remained low.

4. There was close relationship between extracellular chloride and hydrogen ion concentrations ([Cl−]e and [H+]e) and extracellular potassium and intracellular hydrogen ion ([K+]e and [H+]i) but not between any of the other parameters. The close relationship between [H+]e and [Cl−]e may be explained by the chemical relationship between [H+]e, Pco2, and [HCO3−]e and empirical relationships between [Cl−]e and [HCO3−]e, and Pco2 and [HCO3−]e.
Role of Circulating Catecholamines in Human Eccrine Sweat Gland Control
Authors: Foster K. G. , Ginsburg Jean , Weiner J. S.
Published: August 2015

1. Intra-arterially as well as intradermally administered adrenaline or noradrenaline produces a sweat response.

2. The intensity of the intradermal response is always considerably less than that due to acetylcholine and the threshold of effective concentration is considerably greater than for acetylcholine. The glands also fail to respond to repeated small doses of intradermal catecholamine and to continued arterial catecholamine infusion.

3. Intradermal administration of a mixture of adrenaline and acetylcholine did not indicate that adrenaline potentiates the cholinergic response.

4. Intravenous infusions of 20 μg/min adrenaline neither produce a response by the resting glands nor affect the response of the active glands. Whilst intra-arterial infusions of high doses of adrenaline or noradrenaline produce a response by the resting glands they reduce the response of the active glands.

5. The results show that even though the catecholamine levels in a discharge of a phaeochromocytoma can be high enough to cause a discharge by resting glands, as the glands are likely to be secreting in response to neural stimulation, the effect of the secreted catecholamine would be inhibitory.
Different Effects of Frusemide Administered during Hypertonic Saline Infusion in Healthy Subjects and Hypertensive Patients
Authors: Radó J. P. , Szende L. , Borbély L. , Báanos Cs. , Takó J. , Fischer J.
Published: August 2015

1. The effects of hypertonic saline and frusemide administered during hypertonic saline infusion were studied during antidiuresis and infusion of lysine-vasopressin in fifteen healthy subjects and seventeen patients with hypertension.

2. Rates of excretion of water and sodium were higher during salt loading in the hypertensive patients as compared to the healthy persons. On the other hand, frusemide administered during saline infusion had a greater effect in the normal subjects.

3. Free water reabsorption increased markedly in the first 10-min clearance period after frusemide injection in the healthy subjects, while in the hypertensive group there was no significant change. This suggested that the diuretic may have a more marked proximal tubular effect in the healthy persons and/or a more intensive Henle's loop action in the hypertensives. However, the latter possibility was not supported by data concerning the correlation between solute excretion and free water reabsorption.

4. It is suggested that sodium transport is competitively inhibited in the same segment(s) of the nephron by frusemide and hypertonic saline and that this may explain the decreased effect of frusemide in the hypertensives.
Transferable Pyrogen in Human Experimental Fever
Authors: Rawlins M. D. , Cranston W. I. , Luff R. H.
Published: August 2015

1. Steady-state fever has been produced in normal volunteers by an intravenous priming injection followed by a sustaining infusion of leucocyte pyrogen. During this fever, volumes of up to 550 g blood were withdrawn, and separated into cells and plasma.

2. No febrile responses were observed when on subsequent days the cells or the plasma was re-infused.

3. These findings are compatible with the hypothesis that the inability to detect a circulating pyrogen in patients with inflammatory fever, reflects the difficulty of obtaining sufficiently large volumes of blood.

4. Transfusion of blood is unlikely to be a useful means of establishing whether circulating endogenous pyrogen is concerned in naturally occurring fever.
Forearm Circulation in Man at High Altitude
Authors: Weil J. V. , Byrne-Quinn E. , Battock D. J. , Grover R. F. , Chidsey C. A.
Published: August 2015

1. Several phenomena observed in man during acute exposure to high altitude could be explained in part by a decrease in compliance of systemic capacitance vessels.

2. Serial measurements of forearm venous compliance were made with a water-filled plethysmograph in healthy men during a 24 h stay at 4300 m.

3. A decrease in venous compliance (increase in venous tone) occurred in all subjects and averaged 17·0 ± 6·2% (SEM).

4. In seven normal men during 1 week at 4300 m, a decrease in venous compliance again occurred in all subjects and was sustained throughout the 1 week period. There was also a rise in forearm blood flow and a fall in forearm vascular resistance. Increases in urinary excretion of noradrenaline and vanilmandelic acid suggested that these responses are mediated by the sympathetic nervous system.

5. Acute laboratory studies suggest that the response is primarily triggered by hypocapnia and potentiated by hypoxia; it cannot be duplicated by hyperventilation or by mild hypoxia in the absence of hypocapnia.

6. This decrease in systemic venous compliance may play an important role in the increased central blood volume and cardiac output which are seen acutely following ascent to high altitude.
Reactions of Arterial and Venous Vessels in the Human Forearm and Hand to Deep Breath or Mental Strain
Authors: Delius W. , Kellerová E.
Published: August 2015

1. Arterial and venous reactions in forearm and hand to a deep breath or to mental strain (a 50 s period of arithmetic) were measured in fourteen individuals. Blood flow and tissue volume change were measured by venous occlusion plethysmography, and venous tone by the occluded limb technique.

2. A deep breath caused cutaneous vasoconstriction which was short-lasting in resistance (arterial) vessels and long-lasting in capacitance vessels.

3. Mental strain caused cutaneous venous constriction and muscular arterial dilatation with a similar time-course, while the cutaneous arterial reaction was variable.
The Causes of Hypocalcaemia in Chronic Renal Failure
Authors: Cochran M. , Nordin B. E. C.
Published: August 2015

1. Serum calcium and phosphate, calcium absorption and calcium excretion were measured in twenty-seven cases of chronic renal failure.

2. Hypocalcaemia was present in thirteen cases and tended to be more severe in patients with the most severe degree of renal failure.

3. The hypocalcaemia could not be attributed to hyperphosphataemia since many of the patients with hypocalcaemia had normal serum phosphate concentrations.

4. Malabsorption of calcium was observed in all but three patients, and was significantly related to the degree of renal failure, but there was only a weak correlation between absorption and the serum calcium concentration. The 24 h calcium excretion was not significantly related to creatinine clearance or to calcium absorption.

5. The relation between serum calcium concentration and fasting urine calcium excretion, expressed in mg per 100 ml of glomerular filtrate, was grossly abnormal. Instead of the positive correlation previously established in normal subjects, plasma calcium and urine calcium expressed in this way were inversely related, signifying a severe reduction in the tubular reabsorption of calcium.

6. Calcium and sodium excretion (each expressed in units per 100 ml of glomerular filtrate) were significantly related, but calcium excretion and serum bicarbonate were not. However, examination of the urine calcium/sodium relationship at urine sodium excretion rates below 1·5 mEq per 100 ml of glomerular filtrate indicated that, within this range, urine calcium excretion was inversely related to serum bicarbonate concentration and positively related to urine sodium excretion.

7. We conclude that there is reduced tubular reabsorption of calcium in renal failure, and this is attributable both to metabolic acidosis and to the increased rate of sodium excretion per nephron, and that it could be a significant contributory factor in the hypocalcaemia which may be observed in renal failure without hyperphosphataemia.
Metabolism of Palmitic and Linoleic Acids in Man: Differences in Turnover and Conversion to Glycerides
Authors: Nestel P. J. , Barter P.
Published: August 2015

1. The metabolism of palmitic acid (a saturated fatty acid) and linoleic acid (a polyunsaturated fatty acid) was compared in seven subjects during constant infusions of the radioactive tracers.

2. The studies were repeated in some subjects after the turnover of the free fatty acids and the size of the fatty acid and glyceride pools had been altered with sucrose or polyunsaturated fat diets.

3. The fractional turnover of linoleic acid was nearly always greater than that of palmitic acid, though its total turnover rate was less.

4. A lesser proportion of the turnover of linoleate than of palmitate was incorporated into plasma triglyceride over a range of turnover rates of free fatty acids and glyceride fatty acid pools. This may be a factor in the lowering of plasma triglyceride concentrations with diets rich in polyunsaturated fatty acids.
A Study of the Metabolism of Fibrinogen after Surgical Operations
Authors: Hickman J. A.
Published: August 2015

1. The turnover of fibrinogen was studied in twenty-eight patients after moderate and major surgical operations and in a contrast group of thirteen patients suffering from miscellaneous chronic disorders.

2. After operation the mean biological half-life of fibrinogen was 60.1 h (SD 16.4) and the mean plasma loss of fibrinogen was 40.1% (SD 12.6) of the intravascular fibrinogen pool each 24 h. In the contrast group, respective values of 96.2 h (SD 13.1) and 22.5% (SD 2.0) were obtained, which are in agreement with published values for the normal catabolism of fibrinogen.

3. When the post-operative increase in the plasma fibrinogen pool was taken into account, a massive increase in the absolute plasma loss of fibrinogen was observed with values approaching those reported for albumin turnover.

4. Possible sites of loss and the relevance of this investigation to the detection of disseminated intravascular coagulation and venous thrombosis are discussed.
Ragweed Pollen: Morphological Changes on Incubation with Saliva from Ragweed-Allergic and Non-Allergic Humans
Authors: Mayron L. W. , Loiselle R. J.
Published: August 2015

1. The interactions between ragweed pollen and the saliva from ragweed-sensitive and non-sensitive humans have been examined. A number of morphological changes of the pollen grains take place under the conditions of the incubation. Of these changes, two occur only with incubation in allergic saliva and one occurs with the use of ‘inflammatory’ saliva, allergic or non-allergic.

2. The two changes that are associated only with incubation in saliva from an individual who is ragweed-sensitive appear to be related. They consist of a clearing of the background material surrounding the pollen grain and the formation of a halo of white, mat-like material around the grain.

3. The incubation of pollen with ‘congestive’ or ‘inflammatory’ saliva resulted in the exudation of granular material, encased in a membrane, from the pollen grain.

4. Kinetic studies give the development time of particular changes and their duration.
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 < 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.
Cardio-Pulmonary Responses and Gas Exchange during Exercise in Adults with Homozygous Sickle-Cell Disease (Sickle-Cell Anaemia)
Authors: Miller G. J. , Serjeant G. R. , Sivapragasam S. , Petch M. C.
Published: August 2015

1. Cardio-pulmonary responses and gas exchange during progressive exercise, the ventilatory response to hypercapnia and anthropometric indices were measured in twenty-two Jamaican adults with homozygous sickle-cell disease. Their anthropometric indices and exercise performances were compared with those observed in healthy but sedentary adults in the Caribbean.

2. The patients had long lower limbs for their height; their body fat, proportion of lean body mass as muscle and vital capacity were reduced. Haemoglobin concentrations ranged from 4 to 10 g/100 ml. Heart rate and ventilation were normal at rest.

3. During exercise in the male patients haemoglobin concentrations below about 8 g/100 ml were associated with an increased demand for anaerobic metabolism. This resulted in excessive lacticacidaemia and increased ventilation at standard oxygen uptake (hyperpnoea). The ventilation-tidal volume relationship was normal. When allowance was made for differences in body muscle, anaemia did not appear to affect the heart-rate response to exercise.

4. Hyperventilation with respect to carbon dioxide output, increased alveolar-arterial oxygen-tension gradients and abnormal deadspace ventilation during exercise indicated a pulmonary perfusion disturbance with mixed venous shunting. The most likely basis for this disorder was considered to be the sickling phenomenon. Arterial hypoxaemia produced by the pulmonary shunt probably accounted for some of the exercise hyperpnoea, partly by increasing the chemoreceptor drive and partly by encouraging lacticacidaemia.

5. Reduced arterial carbon dioxide tensions and bicarbonate concentrations had lowered the threshold and increased the sensitivity of the ventilatory response to carbon dioxide as measured by rebreathing. Increased chemosensitivity was not thought to have contributed towards the exercise hyperpnoea since arterial carbon dioxide tensions were below the threshold value for ventilatory drive.

6. Exertional dyspnoea in sickle-cell disease was attributed to the combination of hyperpnoea and a reduced maximum breathing capacity (MBC) owing to small lung-volumes. The fraction of MBC used at standard work was therefore abnormally large, and the increased ventilatory effort produced a sensation of breathlessness in some patients.
The Effect of Cold on Blood Flow in the Hand of Patients with Raynaud's Phenomenon
Authors: Downey J. A. , Frewin D. B.
Published: August 2015

1. The response of hand blood flow to a measured controlled cold stimulus was determined using venous occlusion plethysmography in normal subjects and patients exhibiting Raynaud's phenomenon.

2. Comparisons of percentage and absolute falls in hand blood flow, and also the recovery times after removal of the cold stimulus, were made in both the normal subjects and the patients and found to be similar.

3. The nature of the abnormality causing Raynaud's phenomenon was not elicited, but it did not appear to be due to an increased sensitivity of the hand vasculature to cold.
The Direct Interconversion of Glucose and Fructose in Human Skeletal Muscle with Special Reference to Childhood Muscular Dystrophy
Authors: Ellis D. A. , Strickland Jennifer M. , Eccleston J. F.
Published: August 2015

1. Acid extracts of muscle-fibre preparations from human biopsies incubated with [U-14C]glucose were chromatographically analysed.

2. Radioactivity of fructose was significantly greater in muscle from childhood dystrophy patients and also in female carriers of the disease compared with normal, foetal, neurogenic muscle disease and polymyositis control groups.

3. Measurements of the activity of polyol-NADP oxidoreductase (EC 1.1.1.21) and L-iditol-NAD oxidoreductase (EC 1.1.1.14) in muscle extracts compared with the ability of extracts to dephosphorylate fructose 6-phosphate, indicated that the probable route of fructose formation from glucose is via glucitol. The mean activities of the two specified enzymes in dystrophic muscle showed 13- and 3–5-fold increases respectively compared with normal muscle, and smaller increases compared with other controls.

4. Direct comparison of labelling patterns following incubation of muscle-fibre preparations with d-[U-14C]glucose, d-[U-14C]fructose and d-[U-14C]glucitol showed that these three substances are rapidly interconvertible mutual major metabolic products, confirming the glucitol pathway as a major route of fructose formation.

5. [U-14C]fructose is readily metabolized by dystrophic muscle, excluding the possibility of its accumulation being the result of poor utilization.

6. Inhibition of polyol oxidoreductase in dystrophic muscle preparations by 3,3′-tetramethyleneglutarate drastically reduces the ability of the fibres to utilize [U-14C]-glucose, and prevents the formation of [14C]fructose.

7. Some implications of these results are discussed in relation to the pathogenesis of childhood muscular dystrophy.
Effect of Prostaglandins A1, A2, B1, E2 and F2α on Forearm Arterial Bed and Superficial Hand Veins in Man
Authors: Robinson B. F. , Collier J. G. , Karim S. M. M. , Somers K.
Published: August 2015

1. The effects of local infusions of prostaglandins (PG) A1, A2, B1, E2 and F2α have been studied in the forearm arterial bed and superficial hand veins of man.

2. Prostaglandins A1, A2, B1, E2 and F2α all gave rise to a dose-dependent increase in forearm blood flow when infused into the brachial artery. At dosages just below the dilator range, PGF2α caused a transient fall in forearm flow, but this was not seen with any of the other prostaglandins.

3. Prostaglandins A1, A2 and E2 had no effect when infused locally into relaxed veins but caused dose-dependent dilatation when given into veins preconstricted with either noradrenaline or 5-hydroxytryptamine. Prostaglandins B1 and F2α caused dose-dependent constriction when given into relaxed veins and had no dilator effect when infused into preconstricted veins.

4. The results suggest that there are at least two types of receptors mediating responses to prostaglandins in peripheral blood vessels.
Comparison of Absorption Rates of Glucose and Maltose in Man in Vivo
Authors: Cook G. C.
Published: August 2015

1. Using a double-lumen tube perfusion technique in vivo, the absorption rates of glucose from a glucose (200 mmol l−1) and from a maltose (100 mmol l−1) solution were measured in the proximal jejunum of six Zambian African adults.

2. In all of the subjects the rate of glucose absorption from the maltose solution was greater than that from the glucose solution. The difference between the mean rates was approximately 15% and is significant (P < 0.01).