bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Hypokalaemia on the Ouabain-Sensitive Sodium Transport and the Ouabain-Binding Capacity in Human Erythrocytes
Authors: Rubython E. Jill , Morgan D. B.
Published: August 2015

1. The sodium content, the ouabain-sensitive sodium efflux and efflux rate constant and the ouabain-binding capacity were measured in the erythrocytes of 53 patients with hypokalaemia and in 37 healthy controls. The sodium content alone was measured in a further 57 patients with hypokalaemia.

2. In the patients with hypokalaemia there was an increase in the average sodium content of the erythrocytes, which was entirely due to a reduction in the ouabain-sensitive efflux rate constant.

3. The ratio of the ouabain-sensitive efflux rate constant to the number of sodium pumps was decreased in the patients with hypokalaemia, and was directly related to the plasma potassium.

4. Many patients with moderate hypokalaemia had normal erythrocyte sodium and potassium contents and normal ouabain-sensitive efflux rate constant. These patients had an increased number of sodium pumps, which compensated for the inhibitory effect of hypokalaemia on each sodium pump.

5. This increase in the number of sodium pumps was common even in patients who had probably had hypokalaemia for less than 2 weeks. This finding suggests that there are latent sodium pumps within the circulating erythrocytes.
Effects of Dietary Sodium on Circadian Rhythm and Physiological Responses of 18-Hydroxycorticosterone
Authors: Sowers James R. , Martin Victor I. , Beck Frances W. J.
Published: August 2015

1. The effects of dietary sodium intake on plasma 18-hydroxycorticosterone (18-OHB) responses to physiological stimuli and recumbent 24-h-plasma 18-OHB levels have been examined in nine normal male subjects.

2. Basal supine levels of 18-OHB during a 40 mmol of sodium intake period (62.5 ± 6.0 ng/dl) were considerably greater (P < 0.0001) than the levels during a 200 mmol of sodium intake period (9.8 ± 1.2 ng/dl). Further incremental and percentage changes of 18-OHB in response to graded dose infusions of angiotensin II and adrenocorticotropic hormone (ACTH) were greater during the 40 mmol of sodium intake period.

3. Although the mean 24 h levels of plasma 18-OHB during the 40 mmol of sodium intake period (43.9 ± 4.0 ng/dl) were greater (P < 0.001) than those during the 200 mmol of sodium intake period (9.4 ± 1.2 ng/dl), the circadian rhythm of 18-OHB secretion was similar under the two extremes of sodium intake.

4. Factors which increase angiotensin II levels, such as sodium restriction, isometric exercise and angiotensin infusion, selectively increase 18-OHB and aldosterone, suggesting that angiotensin II increases 18-OHB and aldosterone secretion, in part, by modulation of the 18-hydroxylation reaction involved in conversion of corticosterone into 18-OHB.
Binding of Testosterone and Oestradiol to Sex Hormone Binding Globulin, Human Serum Albumin and other Plasma Proteins: Evidence for Non-Specific Binding of Oestradiol to Sex Hormone Binding Globulin
Authors: Iqbal M. Jawed , Dalton Maureen , Sawers Robert S.
Published: August 2015

1. The percentage binding of testosterone (T) and oestradiol (E2) to sex hormone binding globulin (SHBG) and human serum albumin (HSA) was determined over a range of SHBG concentrations of 16–250 nmol of dihydrotestosterone (DHT) bound/l. It was found that the binding of both T and E2 to HSA was a function of their binding to SHBG and bore an inverse relationship to it. After removal of both SHBG and HSA from plasma by affinity chromatography a ‘residual’ binding of about 11% for T and 12% for E2 was still apparent. in addition to the specific high-affinity, low capacity binding of E2 to SHBG, non-specific low-affinity binding of 7–12% was demonstrated after selective denaturation of the specific binding site of the latter.

2. Competition studies indicated that although at the relatively higher levels of SHBG found in the normal female the physiological concentrations of E2, T and DHT need not be taken into account in estimating the unbound fractions of steroids, at the relatively lower levels of SHBG found in normal men and hirsute women, the physiological concentrations of T and DHT are effective in causing statistically significant displacement of E2 from the common, specific binding site on SHBG.

3. A simple computerized technique is described for the determination of fractions of E2 and T respectively, that are unbound to SHBG, unbound to SHBG and HSA, and unbound to all plasma proteins, when the total plasma levels of E2, T, DHT and SHBG are known.
Alterations in Tyrosine and Protein Kinetics Produced by Injury and Branched Chain Amino Acid Administration in Rats
Authors: Sakamoto Akio , Moldawer Lyle L. , Palombo John D. , Desai Sukumar P. , Bistrian Bruce R. , Blackburn George L.
Published: August 2015

1. To determine whether the alterations in amino acid metabolism after injury were a result of changes in protein synthesis, whole body tyrosine and individual tissue protein kinetics were estimated 24 h after three different forms of stress in rats.

2. in addition, injured rats were either starved or infused with 180 mg of nitrogen/day (as branched chain amino acids or l-alanine) to ascertain whether the mechanism and degree of nitrogen sparing were unique to branched chain amino acid administration or whether they could be attributed to the infusion of α-amino nitrogen.

3. in the more catabolic types of injury, increased nitrogen loss during starvation appeared to be due to both an increased plasma amino acid appearance and a greater percentage being oxidized. Rates of tyrosine incorporation into whole body protein were also enhanced and could be explained in part by increases in the fractional synthesis rate of hepatic non-secretory protein.

4. Both branched chain amino acid and l-alanine administration reduced endogenous tyrosine oxidation and improved nitrogen balance. However, branched chain amino acid administration significantly increased amino acid incorporation into whole body protein and fractional synthetic rates of skeletal muscle, kidney and hepatic non-secretory protein.

5. It is concluded that the catabolic response to severe injury is consistent with increased rates of plasma amino acid appearance and branched chain amino acid administration spares body protein by improving amino acid utilization for whole body protein synthesis.
Effect of Aspirin on Urinary Excretion of 6-Ketoprostaglandin F1α
Authors: Jones P. B. B. , Russell R. G. G.
Published: August 2015

1. We studied the effect of oral administration of acetylsalicylic acid (1200 mg/day for 3 days) on the urinary excretion of 6-ketoprostaglandin F1α in normal human subjects as an index of prostacyclin production in vivo.

2. The concentrations and excretion rate in urine fell to 45% of pretreatment levels in 3 days, but returned to pretreatment values after 7 days.

3. These results suggest that production of prostacyclin in vivo is only partially inhibited by high doses of aspirin and that there are sites of production of prostacyclin which are protected from inhibition by aspirin and which contribute to urinary 6-ketoprostaglandin F1α. The measurement of 6-ketoprostaglandin F1α in urine may therefore be of only limited value as an index of the metabolism of vascular tissue in vivo.
Insulin-Induced Glucose Utilization Influences Triglyceride Metabolism
Authors: Bazelmans J. , Nestel P. J. , Nolan C.
Published: August 2015

1. We have investigated the possibility that the effect of insulin on triglyceride metabolism is related to the individual's responsiveness to insulin-mediated glucose utilization. Changes in plasma triglyceride levels were determined during 2 h infusions of insulin with glucose that maintained euglycaemia in 17 subjects, some of whom were overweight and/or hypertrigly-ceridaemic.

2. Plasma triglyceride concentrations fell in most subjects (mean ± sd: 19.9 ± 13.0%). The percentage fall in plasma triglyceride was inversely related to body mass index (r = −0.64, P < 0.01) and to basal triglyceride concentration (r = −0.69, P < 0.005), but directly to insulin sensitivity (r = +0.48, P < 0.05), and was unrelated to plasma free fatty acid concentration.

3. Since insulin sensitivity was also related to body mass index and basal triglyceride level stepwise regression analysis was carried out to determine the influence of these three variables on insulin-mediated lowering of plasma triglyceride. The percentage fall in plasma triglyceride remained independently related to insulin sensitivity (P < 0.05) and to body mass index (P < 0.05), and these two variables accounted for 44% of the fall in triglyceride.

4. Resistance to insulin (in terms of glucose utilization) may therefore be one significant, independent factor determining the plasma triglyceride concentration.
Ferroxidase and Ascorbate Oxidase Activities of Caeruloplasmin in Synovial Fluid from Rheumatoid Patients
Authors: Blake D. R. , Blann A. , Bacon P. A. , Farr M. , Gutteridge J. M. C. , Halliwell B.
Published: August 2015

1. The protein caeruloplasmin inhibits certain free radical reactions, in part probably due to its ability to oxidize Fe2+ into Fe3+ (ferroxidase activity). Since caeruloplasmin is present in synovial fluid from rheumatoid patients, we investigated its properties in relation to protection of the joint from damage by oxygen radicals produced by activated phagocytes.

2. The ferroxidase and ascorbate oxidase activities of serum from both normal and rheumatoid patients could be accounted for by the caeruloplasmin present, as determined immunologically. More caeruloplasmin is present in the serum of rheumatoid patients than in normal serum.

3. Synovial fluid from rheumatoid patients contains caeruloplasmin protein but its ferroxidase and ascorbate oxidase activities are abnormally low. It is suggested that ferroxidase deficiency contributes to radical damage in the rheumatoid joint.
Platelet Function and Lipoprotein Levels after Plasma-Exchange in Patients with Familial Hypercholesterolaemia
Authors: Brook Gerald , Winterstein Giora , Aviram Michael
Published: August 2015

1. Repeated plasma exchange was carried out on three young patients with severe familial hypercholesterolaemia. There was a 3 week interval between each exchange. After a single exchange, plasma cholesterol, apolipoprotein B and low density lipoprotein-cholesterol levels decreased markedly, but pre-exchange levels were not achieved within 2 weeks. High density lipoprotein-cholesterol and apolipoprotein A-I levels also fell but returned to the original concentration after only 5 days.

2. Platelet aggregation and [14C]serotonin release were increased in all three patients and dropped by 20% and 13% respectively after a single plasma exchange. Platelet function in vitro returned to pre-exchange levels with similar kinetics to that observed with the low density lipoprotein concentration. On removal of 100 g of plasma cholesterol, after repeated exchanges, low density lipoprotein concentration and platelet function were significantly decreased in comparison with values before initiation of plasma exchange. in addition there was a marked regression of xanthoma in all three patients.

3. Since this procedure is instrumental in achieving a negative cholesterol balance as well as inhibiting hypersensitive platelets, it may well result in a downgrading of the atherosclerotic risk.
Changes in the Binding of Radioactive Conjugated Bile Salts to Serum Proteins in Cholestatic Jaundice
Authors: Chitranukroh A. , Billing B. H.
Published: August 2015

1. A micro-partition centrifugal ultrafiltration technique has been used to monitor the percentage of[14C]glycocholate,[3H]glycochenodeoxycholate and[3H]glycochenodepxycholate-3-sulphate bound to serum proteins of patients with cholestatic liver disease.

2. in comparison with normal individuals the percentage of binding of [14C]glycocholate and, to a lesser extent, of [3H]glycochenodeoxycholate and [3H]glycochenodeoxycholate-3-sulphate was reduced.

3. The binding of [14C]glycocholate was inversely related to the serum bile salt and bilirubin concentrations. in contrast, the binding of [3H]glycochenodeoxycholate and [3H]glycochenodeoxycholate-3-sulphate were not altered by the severity of the cholestasis.

4. Studies in vitro indicated that the reduction in the binding of [14C]glycocholate in cholestatic liver disease was not due to high concentrations of bile salts, unconjugated bilirubin or fatty acids.
Decreased Neutrophil Cyclic AMP Response to Isoprenaline Stimulation in the Elderly
Authors: Cotter T. G. , O'Malley K.
Published: August 2015

1. Neutrophils from drug-free elderly subjects produced approximately 50% less cyclic AMP in response to isoprenaline than did neutrophils from young subjects. A significant difference in basal cyclic AMP levels was also evident (elderly 2.8 ± 0.37; young 4.9 ± 0.36 pmol of cAMP/107 cells; P < 0.05).

2. With a range of anti-neutrophil monoclonal antibodies no evidence of age-related neutrophil population heterogeneity was found.

3. These findings indicate that the age-related decline in β-adrenoceptor responsiveness is not due to changes in the neutrophil population.

4. The present results support the hypothesis that there is a generalized decline in β-adrenoceptor-mediated responsiveness in the elderly.
The Physiological Effects of Insulin-Induced Hypoglycaemia in Man: Responses at Differing Levels of Blood Glucose
Authors: Gale E. A. M. , Bennett T. , MacDonald I. A. , Holst J. J. , Matthews J. A.
Published: August 2015

1. The aim of this study was to describe hormonal, cardiovascular and thermoregulatory responses to insulin-induced hypoglycaemia of differing levels of severity.

2. Five normal male volunteers were rendered hypoglycaemic at intervals of 1 week by intravenous infusions of 3, 4 or 6 units of insulin/h, or by intravenous injection of 0.15 unit/kg body weight.

3. Plasma glucose reached nadir values of 2.08 ±0.10, 1.82 ± 0.21, 1.24 ±0.08 and 0.92 ± 0.06 mmol/l (means ± sem) in the four experiments. Non-esterified fatty acid levels fell equally in all experiments but recovery was more rapid with severe hypoglycaemia. In contrast the rate of recovery of plasma glucose was slower with deeper hypoglycaemia and this appeared unrelated to the counter-regulatory response.

4. Plasma glucagon, adrenaline and prolactin levels increased in proportion to the severity of hypoglycaemia, but peak concentrations of cortisol, growth hormone (somatotropin) and noradrenaline did not vary, suggesting that moderate hypoglycaemia had elicited maximal responses. When the areas under the curves were calculated, the cortisol responses were greater for the 6 units infusion and bolus injection than for the other infusions, and the growth hormone responses were similar for all three infusions but significantly greater with the bolus injection.

5. Increases in heart rate and systolic blood pressure were related to the severity of hypoglycaemia, but changes in diastolic blood pressure and peripheral vascular resistance (assessed from calf and from hand blood flow) were not.

6. Central temperature fell by 0.13 ± 0.06°C, 0.30 ± 0.10°C, 0.65 ± 0.14°C and 1.15 ± 0.30°C (means ± sem) in the four experiments, and the fall in skin temperature had a similar gradation.

7. Many physiological responses to hypoglycaemia are not ‘all-or-none’, but vary according to the intensity of stimulus; some are already maximal at mild degrees of hypoglycaemia. Other changes are more complex, reflecting an interplay between opposing endocrine and neural responses.
The Combined Effects of Infection and Malnutrition on Protein Metabolism in Children
Authors: Tomkins A. M. , Garlick P. J. , Schofield W. N. , Waterlow J. C.
Published: August 2015

1. Twenty-two children were studied as in-patients at a Nigerian Hospital.

2. They were divided into four groups on the basis of weight for age: I, adequately nourished, acutely infected; II, moderately under weight, acutely infected; III, malnourished, chronically infected; IV, malnourished, uninfected.

3. Urinary nitrogen excretion was highest in group I and lowest in groups III and IV. Urinary creatinine was highest in group I, but did not differ significantly in groups II, III and IV. The excretion of 3-methylhistidine closely paralleled that of creatinine. It is suggested that the high rates of creatinine and methylhistidine excretion in group I resulted in part from destruction of muscle.

4. Rates of whole body protein turnover were measured by administration of a single dose of [15N]glycine with measurement of the excretion of 15N in urinary NH3 for the next 9 h.

5. Rates of protein synthesis and breakdown were very high in infected children of groups I and II. Although rates were lower in the malnourished groups, in infected children of group III they were nearly twice as high as in the uninfected group IV. The net balance of protein (synthesis minus breakdown) was negative in group I, less negative in group II, zero in group III and positive in group IV.

6. Repeat measurements in group I during recovery from infection showed a decline in rates of excretion of nitrogen, creatinine and 3-methylhistidine. Rates of protein synthesis and breakdown declined and the protein balance became less negative, but these changes were not statistically significant.

7. Multiple regression analysis of the results of all groups taken together showed independent contributions to rates of protein metabolism from infection and nutritional state, especially plasma albumin.

8. It was concluded that infection caused a rise in protein breakdown which was larger than the concomitant rise in synthesis, leading to net loss of protein, and that these responses were reduced by malnutrition.
The Transport of Thyroid Hormones
Authors: Hoffenberg R. , Ramsden D. B.
Published: August 2015

1. Hormones have to be transported from their sites of synthesis to their target organs. For lipophilic hormones, such as steroids and thyroid hormones, transport is accomplished by binding to specific serum proteins, in the case of thyroxine (T4) and tri-iodothyronine (T3) to thyroxine-binding globulin (TBG) and prealbumin (PA). Normally about 70% of circulating T4 and 75–80% of T3 is bound to TBG, about 20% of T4 and 10% of T3 to PA and 10–15% of each to albumin, which has a low affinity but high capacity for both hormones [1, 2]. Apart from facilitating transport, binding to serum protein prevents excessive loss of hormone into the urine by glomerular filtration or flooding into cells, and may provide a readily available reservoir in times of need. The union between binding proteins and their ligands is reversible, so that a small proportion of hormone is non-protein-bound or ‘free’, in equilibrium with that which is protein-bound. For T4 this free fraction is normally 0.02-0.04% of the total serum T4 concentration, for T3 about 0.3% [3, 4].

2. The major binding proteins of T4 and T3 will briefly be described and the nature of free T4 and T3 considered.
Estimation of Non-Fat Body Tissues from Measurements of Skinfold Thickness, total Body Potassium and Total Body Nitrogen
Authors: Morgan D. B. , Burkinshaw L.
Published: August 2015

1. Many previous reports have shown that the ratio of total body potassium to fat-free tissue mass is, on average, higher in men than in women.

2. In an attempt to explain this finding we have re-examined our own data and data taken from the literature. Our own data comprise measurements on 333 healthy people (196 men and 137 women). In all subjects we measured total body potassium and estimated fat-free mass from body weight and skinfold thickness; in 91 of them (62 men and 29 women) we measured, in addition, total body nitrogen.

3. We have used the statistical technique of factor analysis to obtain unbiased estimates of the relationships between the three quantities measured in the smaller group. The validity of the relationships is supported by the results from the larger group and by data from the literature.

4. The average values of total body potassium and fat-free mass are greater in men than in women, but the relationship between the two variables is identical in men and women. The relationship has a positive intercept on the axis of fat-free mass, so that the ratio of total body potassium to fat-free mass increases with fat-free mass. The higher ratio in men compared with women can therefore be explained by a difference in size alone.

5. The relationship between total body potassium and total body nitrogen has a negligible intercept. Therefore the ratio of total body potassium to total body nitrogen does not change with size.

6. These findings suggest that, on average, the fat-free mass is made up of a fixed component of approximately 9 kg of tissue containing no potassium or nitrogen, and a variable component with a potassium to nitrogen ratio of about 1.81 mmol/g.
Hypoxia-Induced Cardiovascular Changes and Plasma Electrolytes before and after β-Adrenoceptor Blockade
Authors: Mengesha Yoseph Assen , Woreta Ambachew , Mariam Belay Tesfa
Published: August 2015

1. The forearm blood flow responses to hypoxia obtained from ten subjects (ages 26–37 years) before and after propranolol showed no relation with either plasma osmolality or plasma concentrations of K+, Na+, Ca2+, Pi and Cl−. The average oral dose of 3.3 mg of propanolol/kg body weight decreased the overall mean flow response to hypoxia by 42.2% (P < 0.025). This reflects some β-adrenoceptor involvement. The residual vasodilatation observed after β-blockade by propranolol could be attributed to activation of cholinergic vasodilator fibres by hypoxic stress.

2. The mean heart rate during acute hypoxia before and after propranolol administration was 95 and 89 beats/min respectively. The residual tachycardia could be due to reduction of vagal tone during the hypoxic stress.

3. The response of arterial blood pressure to the hypoxic stress before and after propranolol administration, on the other hand, was found to be negligible in most subjects. This lack of response during emotional stress is in agreement with previous findings. In the present circumstances the possible increase in baroreceptor activity is probably masked by the general peripheral vasodilatation.
The Influence of Neonatal Treatment with Guanethidine on the Development of Isolation-Induced Hypertension in Adult Rats
Authors: Gardiner S. M. , Bennett T.
Published: August 2015

1. Rats housed individually in glass metabolism cages develop hypertension. Since previous experiments have provided some evidence for the involvement of the sympathetic nervous system in the maintenance of the hypertension, the present work was designed to explore the possible involvement of the sympathetic nervous system in the genesis of isolation-induced hypertension.

2. Male and female Wistar rats were treated neonatally with guanethidine, with a protocol designed to produce an extensive peripheral sympathectomy; control rats received saline.

3. The effects of isolation on systolic blood pressure and fluid and electrolyte balances were studied when the rats were mature.

4. Guanethidine-treated rats did not develop hypertension in response to isolation whereas control rats did.

5. There were no significant differences between the fluid and electrolyte balances of the guanethidine-treated rats compared with controls throughout the period of isolation.

6. It is concluded that a fully functional sympathetic nervous system is required for the development of isolation-induced hypertension, but its involvement is not through a modulation of renal function.
Amino Acid and Protein Metabolism in Hospitalized Patients as Measured by l-[U-14C]Tyrosine and l-[1-14C]Leucine
Authors: Desai Sukumar P. , Moldawer Lyle L. , Bistrian Bruce R. , Blackburn George L.
Published: August 2015

1. Plasma amino acid kinetics were determined in hospitalized patients receiving one of three intravenous solutions: isotonic amino acids, isotonic sodium chloride, or total parenteral nutrition.

2. Whole body amino acid appearance, oxidation and incorporation into protein were estimated with two different isotopically labelled amino acids: l-[1-14C]leucine and l-[U-14C]tyrosine.

3. A positive correlation was obtained between whole body amino acid appearance, oxidation and incorporation into protein with the two isotopically labelled amino acids.

4. Derivation of whole body protein kinetics with l-[U-14C]tyrosine consistently gave higher values than those obtained from l-[1-14C]leucine, presumably due in part to the contribution of phenylalanine hydroxylation to plasma tyrosine appearance. However, the percentages of amino acid appearance oxidized and used for protein synthesis were similar.

5. It can be concluded that estimates of whole body protein kinetics are qualitatively similar when measured with l-[U-14C]tyrosine and l-[1-14C]leucine in hospitalized patients receiving either isotonic sodium chloride solutions or balanced amino acid intakes.
Altered Behaviour of Erythrocytes in Scleroderma
Authors: Kovacs I. B. , Sowemimo-Coker S. O. , Kirby J. D. T. , Turner P.
Published: August 2015

1. Filterability (deformability) of erythrocytes of patients with Raynaud's phenomenon together with progressive systemic sclerosis (PSS) was decreased compared with the filtration of erythrocytes from normal subjects.

2. PSS erythrocytes showed lower electrophoretic velocity and about 23% less neuraminidase-removable sialic acid density on their surface than the normal erythrocytes.

3. PSS erythrocytes showed more adherence to cultured endothelial cells than the control normal erythrocytes.

4. It is concluded that the increased rigidity and adherence of PSS erythrocytes-5-have pathological significance in the mechanism of vascular abnormalities in PSS.
Vitamin a and its Transport Proteins in Patients with Chronic Renal Failure Receiving Maintenance Haemodialysis and after Renal Transplantation
Authors: Kelleher J. , Humphrey C. S. , Homer Dana , Davison A. M. , Giles G. R. , Losowsky M. S.
Published: August 2015

1. Serum vitamin A, retinol binding protein, prealbumin and transferrin have been studied in chronic renal failure patients receiving maintenance haemodialysis and after renal transplantation.

2. Vitamin A and retinol binding protein were uniformly raised in haemodialysis patients and this was unrelated to the period on dialysis. There was a molar excess of retinol binding protein to both vitamin A and prealbumin as compared with normal individuals.

3. Renal transplantation significantly reduces serum vitamin A and retinol binding protein concentrations but has no effect on prealbumin concentrations. The reduction in vitamin A and retinol binding protein is variable in individual patients and cannot be predicted either by the allograft function or time since transplantation.

4. Several years after transplantation, with normal serum creatinine, both serum vitamin A and retinol binding protein levels may still be greatly increased. Despite the very high vitamin A and retinol binding protein concentrations, the close correlation between the two seen in normal individuals is well maintained.

5. The continuing high vitamin A and retinol binding protein levels in patients with satisfactorily functioning transplants is unexplained.
Extracellular Release of Hydrogen Peroxide by Human Alveolar Macrophages: The Relationship to Cigarette Smoking and Lower Respiratory Tract Infections
Authors: Greening A. P. , Lowrie D. B.
Published: August 2015

1. It has been suggested that oxidants from pulmonary inflammatory cells may contribute to the development of emphysema by (i) direct tissue toxicity and (ii) inhibition of α1-antitrypsin, thus diminishing protection of the lung from proteolytic damage.

2. The extracellular release of hydrogen peroxide (H2O2) by human alveolar macrophages (AM) has been measured. AM were obtained by bronchoalveolar lavage and adherence from 24 smokers and 17 non-smokers.

3. Smokers' AM released significantly more H2O2 (3.83 nmol h−1 üg−1 of DNA; sem 0.44) than those of non-smokers' (2.33 nmolh−1 μg−1 of DNA; sem 0.40) (P <0.05).

4. AM from donors with a recent lower respiratory tract infection released increased quantities of H2O2 (5.22 nmol h−1 μg−1 of DNA; sem 0.72; P <0.01) even when allowance was made for smoking habits.

5. These findings are consistent with the hypothesis that H2O2 of AM origin contributes to the development of emphysema in smokers.
Trends in Trabecular and Cortical Bone in the Radius Compared with Whole Body Calcium Balance in Osteoporosis
Authors: Hesp R. , Deacon A. C. , Hulme Patricia , Reeve J.
Published: August 2015

1. Mean linear attenuation coefficients for trabecular bone (T) in the distal radius and total absorption coefficients (TA) in the radial mid-shafts of 22 patients with crush fracture osteoporosis were measured serially for a year by using computed tomography. After approximately 6 months, each patient was admitted to a metabolic ward for an 18-day calcium balance study.

2. The rate of change (trend) in trabecular bone (T) in the distal radius was a better predictor of calcium balance than the trend in mid-shaft cortical bone (TA).

3. The scatter in the regressions of the trends of T and TA on calcium balance could be accounted for by known methodological uncertainties.
Release of Active and Inactive Kallikrein from the Isolated Perfused Rat Kidney
Authors: Van Leeuwen B. H. , Grinblat S. M. , Johnston C. I.
Published: August 2015

1. The release of kallikrein into the perfusate and urine of the isolated perfused rat kidney was studied.

2. Comparison between enzymic and immunological assays for kallikrein demonstrated the presence of an enzymically inactive form of kallikrein.

3. Of kallikrein found in normal rat urine 77 ± 4% is active and 23% is in an inactive form.

4. In the isolated perfused rat kidney a similar proportion of active kallikrein (84%) was excreted into the urine but very little enzymically active kallikrein (2%) could be detected in the perfusate.

5. However, significant amounts of enzymically inactive but immunologically reactive kallikrein could be found in the kidney perfusate. The rate of release of kallikrein into the perfusate was approximately one-fifth of the rate of release into the urine.

6. Renin showed a similar pattern of release into the perfusate and urine but the lysosomal enzyme marker acid phosphatase was not detectable.

7. These results show that kallikrein is secreted from the kidney into the circulation as well as being excreted in the urine. However, in urine the enzyme is predominantly in an enzymically active form whereas it is secreted into the circulation in an inactive form.
Absorption and Metabolism of Allopurinol and Oxypurinol by Rat Jejunum in Vitro: Effects on Uric Acid Transport
Authors: Shaw M. I. , Parsons D. S.
Published: August 2015

1. The transport and metabolism of allopurinol and oxypurinol have been examined in a preparation of adult rat jejunum in vitro. When present in the lumen (50–500 μmol/l) allopurinol appeared in the serosal secretions at lower concentrations, together with its metabolite oxypurinol and an unidentified substance. Oxypurinol in the lumen (1.4–430 μmol/l) was transported into the serosal secretions and at luminal concentrations below approximately 150 μmol/l was concentrated in the secretions. The transport of oxypurinol into serosal secretions was greater than that of allopurinol.

2. Allopurinol and oxypurinol decreased the appearance of urate, in the serosal secretions and the luminal fluid, by an amount which was greater than the concomitant increase in oxypurines; they increased the rate constant of the mono-exponential washout of endogenous urate and induced purine secretion into the lumen.

3. The transport of uric acid from the lumen into the serosal secretions was inhibited by allopurinol and oxypurinol. With allopurinol the specific radioactivity (14C) of urate in the serosal secretions approached that in the lumen; with oxypurinol the specific radioactivity was approximately 70% that in the lumen. There was no evidence for the uphill movement of urate from the lumen.
The Stimulation of Na+, K+-ATPase Activity in the Medulla of the Rat Kidney by [arginine] Vasopressin and Its Analogues
Authors: Pippard Corinna , Baylis P. H.
Published: August 2015

1. Total and Na+,K+-ATPase activities have been measured in sections (10 μm thick) from blocks of rat kidney cultured for 5 h at 37°C, pH 7.5, in Glasgow Eagle's Minimum Essential Medium.

2. Synthetic [arginine]vasopressin ([Arg]VP) stimulated ATPase activity in the thick tubular cells of the renal outer medulla over the concentration range 0.01-10 fmol/l, but failed to affect ATPase activity in the proximal and distal convoluted tubules of the cortex.

3. The increase in medullary total ATPase activity induced by [Arg]VP and its analogues was wholly due to stimulation of Na+,K+-ATPase activity.

4. Stimulation of medullary ATPase activity was blocked by [Arg]VP antiserum.

5. The [Arg]VP analogues desmopressin, [lysine]vasopressin, [arginine]vasotocin and oxytocin stimulated medullary Na+,K+-ATPase activity, the three last-named analogues being considerably less potent than [Arg]VP.
A Method for the Study of Cation Transport in vivo: Effects of Digoxin Administration and of Chronic Renal Failure on the Disposition of An Oral Load of Rubidium Chloride
Authors: Boon N. A. , Aronson J. K. , Hallis K. F. , White N. J. , Raine A. E. G. , Grahame-Smith D. G.
Published: August 2015

1. In order to study cation transport in vivo we have measured the changes in plasma and intra-erythrocytic rubidium concentrations following an oral load of rubidium chloride. The changes in plasma rubidium concentration are related to the distribution of rubidium to all the body tissues and the changes in intra-erythrocytic rubidium concentrations provide an example of rubidium uptake by one particular tissue.

2. In eight healthy volunteers pretreatment with a loading dose of digoxin (20 μg/kg) enhanced the rise in plasma rubidium concentrations and attenuated the rise in intra-erythrocytic rubidium concentrations after the oral load of rubidium chloride.

3. Ten patients with chronic renal failure, compared with a well-matched control group, were found to have changes similar to, but more marked than, those caused by digoxin, i.e. a much greater rise in plasma rubidium concentrations and a much smaller rise in intra-erythrocytic rubidium concentrations, after the oral load of rubidium chloride.

4. These findings are consistent with widespread reduction in Na+,K+-ATPase activity in subjects who have taken a loading dose of digoxin and patients with chronic renal failure. They are, therefore, consistent with the findings of previous studies in vitro and show that it is possible to demonstrate changes in cation transport in vivo.
Slowly digested carbohydrate food improves impaired carbohydrate tolerance in patients with cirrhosis
Authors: Jenkins D. J. A. , Thorne M. J. , Taylor R. H. , Bloom S. R. , Sarson D. L. , Jenkins A. L. , Blendis L. M.
Published: August 2015

1. To test whether impaired carbohydrate tolerance in cirrhosis could be modified by dietary means ten cirrhotic patients, five of them taking insulin, took as breakfast either lentils or whole-meal bread and cottage cheese containing the same amount of carbohydrate and protein.

2. Lentils resulted in significantly diminished blood glucose, insulin (in those not on insulin) and gastric inhibitory peptide responses.

3. Enteroglucagon and neutrotensin levels were high with lentils, suggesting that absorption of lentil carbohydrate continued into the ileum with perhaps some malabsorption, so confuming the results of earlier studies in vitro.

4. However, breath hydrogen studies on a separate group of eight healthy volunteers indicated that the difference in carbohydrate malabsorption between lentil, and wholemeal bread was insignificant.

5. It is suggested that slowly digested carbo-hydrate foods, such as leguminous seeds, may minimize carbohydrate intolerance in patients with cirrhosis.
Receptors for angiotensin I1 on platelets from man
Authors: Ding Yuan , Kenyon Christopher J. , Semple Peter F.
Published: August 2015

1. Platelets were prepared from peripheral venous blood on iso-osmotic density gradients of Percoll, resulting in a good recovery of cells (50–80%) which were relatively free of contaminating blood cells (erythrocyte <0.1%, leucocyte <0.1%).

2. At 22°C, specific binding of 125labelled angiotensin II (300 pmol/l) was time and temperature dependent, saturable, reversible and linear with cell concentration.

3. Scatchard analysis of saturation curves revealed a single class of binding sites with Kd 1.5 ± 0.4 × 10−10 mol/l and total binding capacity 6.3 ± 1.2 receptorslplatelet. Similar values (Kd 2.4 ± 0.7 × 10−10 mol/l and binding capacity 6.5 ± 1.0 receptors/cell) were obtained by displacement analysis. From kinetic studies the forward and reverse rate constants were 3.1 × 108 mol min−1 1−1 and 3.6 × 10−2/min giving a Kd of 1.2 × 10−10mol/l.

4. The relative binding potencies for angiotensin I1 and analogues were: [Sar1, Thr8]ANC II > ANG II > ANG III > [Sar1, Ala8]ANG II > ANG I.

5. Incubation with an extracellular marker (51Cr-labelled EDTA) demonstrated that binding of angiotensin II to platelets was not due to free fluid endocytosis.
Forearm Arterial Compliance: The Validation of a Plethysmographic Technique for the Measurement of Arterial Compliance
Authors: Fitchett D. , Bouthier J. D. , Simon A. Ch. , Levenson J. A. , Safar M. E.
Published: August 2015

1. Arterial compliance was determined in eight normal subjects and 23 patients with hypertension and vascular disease by two independent techniques: (a) with a plethysmographic strain gauge (to measure pulsatile forearm volume changes as representing intra-arterial volume changes) and an automated sphygmomanometric system (to measure pulse pressure) and (b) calculation from the local pulse wave velocity and dimension of the brachial artery measured by pulsed wave Doppler ultrasound.

2. Arterial compliance measured both by the plethysmographic technique and calculated from the pulse wave velocity was reduced in subjects with hypertension and vascular disease as compared with normal subjects.

3. The regression equation between the compliance determined by the plethysmographic technique (x) and that calculated (y) from the pulse wave velocity and brachial arterial diameter was y = 3.35x + 1.53, r = 0.77, P < 0.001. The good correlation appears to validate the plethysmographic technique as a method of determining arterial compliance.
Whole Body Cellular and Collagen Nitrogen in Healthy and Wasted Man
Authors: James H. M. , Dabek J. T. , Chettle D. R. , Dykes P. W. , Fremlin J. H. , Hardwicke J. , Thomas B. J. , Vartsky D.
Published: August 2015

1. The classical literature shows that wasting of body protein takes place mainly from the cellular compartment leaving high proportions of extracellular collagen. Whole body nitrogen (WBN) is proportional to whole body protein (cellular + extracellular) while whole body potassium (WBK) is almost entirely intracellular. WBK might be an adequate index of cellular wasting.

2. WBN was measured by neutron activation and WBK by counting 40K in 29 healthy males and 131 male and female patients with wide ranges of body composition.

3. Our wasted patients with Crohn's disease or ulcerative colitis, had higher WBN/WBK ratios than matched healthy controls and the difference between the two groups was in the cellular ratio (23.6 mol of N/mol of K, 0.33 g of N/mmol of K, 3 mmol of K/g of N). A multiple regression model for all the subjects represented cellular nitrogen by a term in WBK and extracellular nitrogen by simple anthropometric measurements. The partial regression coefficient of WBN on WBK was 22.6 ± 1.1 (se) mol of N/mol of K; this was also similar to the cellular ratio.

4. Our results were compatible with extracellular protein (mainly collagen, which is 35% of normal whole body protein) remaining resistant to wasting even when severe loss of cellular protein occurs. The high ratios of WBN/WBK in wasted patients can be explained by this disproportionate wasting of cellular substances and they do not imply alterations in the cellular N/K ratio.

5. We suggested that the stable ratio of WBK to cellular protein makes it an effective index of cellular wasting. The resistance of collagen to wasting and the preponderance of extracellular mass in the fat-free mass of wasted subjects, make WBN and fat-free mass unreliable guides to the extent of wasting.
Effect of Intraluminal Hydrocortisone on Solute and Water Absorption in the Human Jejunum
Authors: Crake T. , Crisp A. J. , Shearing M. , Record C. O. , Sandle G. I.
Published: August 2015

1. To compare the effects of intravenous and intraluminal hydrocortisone on jejunal transport, the proximal jejunum was perfused with glucose (28 mmol/l) in saline in two groups of normal subjects.

2. In the first group of seven subjects, compared with the control period results there were no changes in sodium, water and glucose absorption during the intravenous administration of hydrocortisone. In contrast, intraluminal hydrocortisone (100 mg/l) increased sodium, water and glucose absorption by 169%, 223% and 81% respectively (P < 0.001 in each case) above the control values, when peripheral plasma cortisol levels were similar to those achieved with intravenous hydrocortisone.

3. In the second group of three subjects, intraluminal hydrocortisone (10 mg/l and 30 mg/l), followed by an intravenous infusion of hydrocortisone, had no effects on sodium, water and glucose absorption.

4. In a third group of six normal subjects perfused with fructose (28 mmol/l) in saline and bicarbonate (28 mmol/l) in saline intraluminal hydrocortisone (100 mg/l) had no effect on solute and water absorption.

5. These results suggest that intraluminal hydrocortisone stimulates glucose-coupled sodium transport by exerting a topical effect on the apical membrane of the jejunal mucosa.
The Relationship between Human Adipocyte and Monocyte Insulin Binding
Authors: Taylor Roy , Proctor Steven J. , James Oliver , Clark Frederick , Alberti K. George M. M.
Published: August 2015

1. The assumption that insulin binding to monocytes reflects that of insulin binding to adipocytes has been examined.

2. In normal, diabetic, thyrotoxic and cirrhotic subjects no correlation was observed between monocyte and adipocyte insulin binding.

3. Extrapolation is not justified from monocyte binding data to conclusions about insulin-sensitive tissues.
Oesophageal Motility: Recent Advances and Implications
Authors: Blackwell John N. , Castell Donald O.
Published: August 2015

Recent technological advances have brought oesophageal motility investigations within the scope of gastrointestinal departments in all major hospitals. The techniques are now well-tried, straightforward and reproducible [1]. Their use in research has contributed greatly to our understanding of the normal physiology of the oesophagus, and to our knowledge of the abnormalities that occur in reflux oesophagitis. In clinical practice, motility studies are required most often for diagnosis of the oesophageal motility disorders, which have been shown to be more common than was once thought.
Leukotrienes and the Lung
Authors: Leitch A. G.
Published: August 2015

Background: Feldberg & Kellaway [1] were the first to demonstrate the formation and release from envenomed dog and monkey lungs of a substance which caused a delayed and slow contraction of the guinea-pig jejunum; subsequently, Kellaway & Trethewie [2] described release of a slow-reacting substance (SRS) during acute anaphylaxis of the guinea-pig lung. Brocklehurst [3, 4] later reported the formation of an SRS, which he called slow-reacting substance of anaphylaxis (SRS-A), during anaphylaxis of guinea-pig, rabbit, monkey and human lungs. This substance had similar activity to SRS on guinea-pig ileum and was unaffected by the newly developed antihistamine, mepyramine. Release of SRS-A was demonstrated during antigen-induced constriction of bronchioles from subjects with asthma [5], suggesting that SRS-A might be of importance in the pathogenesis of human asthma [6, 7]. The development of techniques for the generation and partial purification of SRS-A from the rat peritoneal cavity [6] and intact guinea-pig lungs [8] permitted characterization of its biological properties.
The effect of Fasting and Hypocaloric Diets on the Functional and Metabolic Characteristics of rat Gastrocnemius Muscle
Authors: Russell David McR. , Atwood Harold L. , Whittaker J. Scott , Itakura Takeo , Walker Paul M. , Mickle Donald A. G. , Jeejeebhoy Khursheed N.
Published: August 2015

1. Previous observations have shown that in human subjects with malnutrition and after prolonged fasting, there are characteristic changes in the force-frequency response, relaxation rate and power of muscle during a 30 s stimulus (fatigue). In order to characterize these findings under carefully controlled conditions, in different types of muscle and to correlate them with changes in muscle structure, composition and biochemical status, we developed an animal model in rats.

2. In this model, nutrient restriction, both after an acute fast and after chronic hypocaloric feeding, resulted in: (a) loss of force during high frequency stimulation but preservation of contraction-relaxation characteristics during low frequency stimulation; (b) slower muscle relaxation rate at high frequency stimulation; (c) increased muscle fatiguability at high frequency stimulation.

3. Measurements of muscle enzymes showed that acute fasting resulted in a reduced content of glycolytic enzymes, but preservation of oxidative enzymes, while chronic hypocaloric dieting resulted in a reduction in both classes of enzyme.

4. There was no significant change in ATP, AMP or energy charge, or in intracellular sodium, potassium and magnesium levels. Creatine phosphate was normal in acutely fasted animals but low in those fed hypocalorically. By contrast, increased intracellular calcium and ADP levels were seen in both fasted and hypocalorically fed animals. These findings suggest that subtle disturbances of intracellular energy states with altered calcium flux may be of importance in the genesis of muscle dysfunction caused by malnutrition.