Showing papers in "Clinical Science in 1976"
TL;DR: The mean activity of post-heparin plasma lipo-protein lipase was significantly lower in subjects with hyperprebetalipoproteinaemia than in normal individuals, however, many hypertriglyceridaemic patients had lipoprotein lipase within the normal range and there was no correlation between serum triglyceride concentration and the activity ofPost- heparin lipases.
Abstract: 1. A selective immunochemical method was used to measure post-heparin plasma lipoprotein lipase and hepatic lipase activity in eighty-two normal subjects and in twenty patients with type IIb, IV or V hypertriglyceridaemia. In twenty-six normal subjects the activity of post-heparin plasma lipases was compared with the kinetic parameters of endogenous plasma triglyceride metabolism. 2. The activity of post-heparin lipoprotein lipase was significantly higher in normal females than in males, whereas the activity of hepatic lipase showed an opposite sex ratio. The activity of lipoprotein lipase decreased with age both in males and females, whereas no significant age variation was observed in the activity of hepatic lipase. 3. In normal subjects a highly significant negative correlation was present in both sexes between the activity of post-heparin plasma lipoprotein lipase and fasting serum triglyceride concentration, but not between the activity of post-heparin hepatic lipase and serum triglycerides. 4. The fractional removal rate of endogenous triglycerides was positively correlated to the activity of lipoprotein lipase but not to the activity of hepatic lipase. No relationship was found between the activities of post-heparin plasma lipases and the absolute turnover of serum triglycerides. 5. The mean activity of post-heparin plasma lipoprotein lipase was significantly lower in subjects with hyperprebetalipoproteinaemia than in normal individuals. However, many hypertriglyceridaemic patients had lipoprotein lipase within the normal range and there was no correlation between serum triglyceride concentration and the activity of post-heparin lipases. 6. All three patients with fasting chylomicronaemia had low post-heparin lipoprotein lipase activity. Several subjects with high post-heparin plasma hepatic lipase activity were present in the group with hyperprebetalipoproteinaemia, but the mean value of the hepatic lipase was not significantly different from normal.
225 citations
TL;DR: Alveolar hydrogen concentration showed a highly significant correlation with hydrogen production measured either by a rebreathing technique or by a total collection procedure.
Abstract: 1. A simple method is described for measuring the hydrogen concentration in alveolar air by end-expiratory sampling, by using a modified Haldane—Priestley tube and gas chromatography. Hydrogen was generated in vivo by ingestion of the non-absorbable sugar lactulose. 2. Alveolar hydrogen concentration showed a highly significant correlation with hydrogen production measured either by a rebreathing technique or by a total collection procedure. 3. The coefficient of variation of the end-expiratory method, assessed by comparing sixty-one paired results, was 11·6%. The coefficient of variation in ten measurements in one subject at 1 min intervals was 17·6%.
215 citations
TL;DR: The concept of a key position for alpha2-macroglobulin in the protective mechanisms against endogenous proteases is supported, which suggested a breakdown of complexes by cells in the reticuloendothelial system.
Abstract: 1. Complexes of human trypsin and human granulocyte elastase with alpha1-anti-trypsin and alpha2-macroglobulin were isolated and injected intravenously into human volunteers. 2. The elimination of alpha2-macroglobulin complexes with trypsin and elastase followed single-exponential functions with half-lives of 9 and 12 min respectively. The complexes showed no tendency to dissociate. 3. Complexes of alpha1-anti-trypsin with trypsin persisted in the circulation much longer, with a half-life of 3-5 h; complexes of alpha1-anti-trypsin with elastase had an intermediate half-life of 1 h. 4. Dissociation was observed of alpha1-anti-trypsin complexes with transfer of trypsin and elastase to alpha2-macroglobulin. 5. Dialysable radioactivity appeared in the urine soon after the injection of alpha2-macroglobulin complexes, which suggested a breakdown of complexes by cells in the reticuloendothelial system. Radioactivity over the liver achieved maximum values within 30-40 min after the injection of alpha2-macroglobulin complexes but not until 50-70 min after the injection of alpha1-anti-trypsin comlexes. 6. These results support the concept of a key position for alpha2-macroglobulin in the protective mechanisms against endogenous proteases.
177 citations
TL;DR: A new method of destroying thrombi in blood vessels by ultrasound and simultaneously removing them is reported, and no significant changes were seen in the fibrinolytic system or microscopic structure of the vessel wall after ultrasound.
Abstract: 1. A new method of destroying thrombi in blood vessels by ultrasound and simultaneously removing them is reported. 2. Experiments were performed in twenty dogs with artificial thrombi in the iliac and femoral arteries and veins. The length of the thrombi ranged from 4 to 5 cm and the age from 12 h to 10 days. The unit used consisted of a generator, a frequency counter, an ultrasonic transducer with the hollow waveguide and a vacuum pump. For protection of the vessel wall the guide is surrounded by a plastic tube. The ultrasonic frequency is 26-5 kHz, the amplitude 25-30 micronm. The time needed to destroy the thrombus by ultrasound and suck out the thrombotic material ranged from 2-5 to 5 min. 3. To check side effects, experiments were performed in forty-four dogs. No significant changes were seen in the fibrinolytic system or microscopic structure of the vessel wall after ultrasound.
171 citations
TL;DR: Kidney weight and content of protein, RNA and DNA were measured in rats with streptozotocin diabetes of varying duration and insulin treatment decreased the renal weight gain during the first 8 days of diabetes, but did not prevent the increase in DNA.
Abstract: 1. Kidney weight and content of protein, RNA and DNA were measured in rats with streptozotocin diabetes of varying duration. 2. Diabetic rats had larger kidneys than control rats: after 3 days of diabetes the weight increase was 15% and after 42 days of diabetes it was 90%. The protein content rose in parallel to the weight. 3. RNA content was already increased after 36 h of glycosuria, whereas DNA content was unchanged for the first 3 days of diabetes, and increased thereafter. The protein/DNA ratio increased rapidly during the first 3 days but remained constant thereafter. 4. Insulin treatment decreased the renal weight gain by about 67% during the first 8 days of diabetes, but did not prevent the increase in DNA. When insulin was started after 25 days of diabetes there was only a slight regression of kidney growth.
167 citations
TL;DR: At least three distinct populations of lysosomes with different modal densities and enzyme content were demonstrated and this analytical fraction technique can be used to study the subcellular pathology of human jejunum.
Abstract: 1. Portions of closed jejunal biopsies were gently homogenized in isotonic sucrose or sorbitol and centrifuged at 800 g for 10 min to prepare a cell extract. 2. The extract was fractionated in a single-step procedure by isopycnic centrifugation on a continuous sucrose or sorbitol density gradient with the Beaufay automatic zonal rotor. 3. The subcellular organelles were located in the density gradient by assay of marker enzymes and previously unassigned enzymes were localized to particular organelles. 4. The following organelles were characterized by their modal equilibrium densities in sucrose density gradients: brush borders (1·21), peroxisomes (1·18), mitochondria (1·16), endoplasmic reticulum (1·16), basal—lateral membranes (1·12). At least three distinct populations of lysosomes with different modal densities and enzyme content were demonstrated. 5. This analytical fraction technique can be used to study the subcellular pathology of human jejunum.
107 citations
TL;DR: The administration of glucose, but not of fructose or sucrose, to starved rats alters the response to heparin injection towards that found in rats in the fed state, and the effect of changes in nutritional status on the activity of clearing factor lipase in rat post-heparin plasma depends on theHeparin dosage used.
Abstract: 1. In rats in a variety of nutritional states, the adipose tissue clearing factor lipase activity is strongly, positively correlated with fat-cell triglyceride fatty acid uptake. 2. In the same animals, muscle clearing factor lipase activity is inversely correlated with the activity of the enzyme in adipose tissue and with the plasma insulin concentration. 3. In starved animals that are given glucose, adipose tissue clearing factor lipase activity is positively correlated with the plasma insulin concentration. 4. The effect of changes in nutritional status on the activity of clearing factor lipase in rat post-heparin plasma depends on the heparin dosage used. The administration of glucose, but not of fructose or sucrose, to starved rats alters the response to heparin injection towards that found in rats in the fed state.
101 citations
TL;DR: In this article, an exercise test for elderly or frail subjects was developed which is based on free walking at three different speeds on a level indoor course of 256m, where each subject sets his own pace in accord with simple instructions.
Abstract: 1. An exercise test has been developed which is suitable for elderly or frail subjects. It is based on free walking at three different speeds on a level indoor course of 256m. The subject sets his own pace in accord with simple instructions. 2. Twenty-four elderly men and ten young men took part in the study. 3. The time and number of paces taken to cover two sections of 100m within the course were used to establish that the subjects walked steadily. Walking speed, pace frequency and stride length were then calculated. 4. Heart rate was obtained with body-borne tape recorders and related to the walking speed. The heart rate at a standard walking speed could then be obtained by interpolation. This is an assessment of the cardiovascular response to exercise (physical condition). The variation on repeating the test was +/-5 per cent and there was no significant difference between the two age groups. 5. The assessment was found to correlate moderately well with a conventional assessment of physical condition based on oxygen uptake from tests on a bicycle ergometer. 6. The test could also be used as a performance index since walking speed was characteristic for the subject. The younger group walked significantly faster than the older group. As a performance index the test is therefor sensitive to age differences.
97 citations
TL;DR: A striking increase of arginine vasopressin concentration was seen within 4 min of syncope, but there was no change of plasma osmolality, cortisol concentration or renin activity.
Abstract: 1. Fourteen mildly hydropenic normal volunteers were slowly tilted at a constant rate from the horizontal to the 85 degrees head-up position in order to study the interrelationship between plasma arginine vasopressin concentration, plasma renin activity and the change of plasma volume. 2. Nine subjects did not develop vaso-vagal symptoms and were studied for 45-60 min. Arginine vasopressin rose biphasically in all subjects: a small initial rise, which was seen at 3 min and persisted for 30 min, was followed by a striking rise between 30 and 45 min, when the fall of plasma volume had reached its maximum (17%). 3. Plasma renin activity reached a maximum at 30 min but fell by 45 min, as plasma concentration of arginine vasopressin rose. 4. Five subjects developed vaso-vagal symptoms 4-24 min after reaching 85 degrees when the study was terminated. A striking increase of arginine vasopressin concentration was seen within 4 min of syncope, but there was no change of plasma osmolality, cortisol concentration or renin activity.
96 citations
TL;DR: It is suggested that hexachlorobenzene or a metabolite acts directly to decrease the activity of the enzyme, which is suggested to cause porphyria in female Wistar rats.
Abstract: 1. A new method for the measurement of uroporphyrinogen decarboxylase (EC 4.1.1.37) in rat liver homogenates, with 5-carboxyl porphyrinogen as substrate, is described. 2. The administration of a diet containing 0·3% (w/w) hexachlorobenzene produces porphyria in female Wistar rats after a delay of at least 4 weeks. The development of porphyria is accompanied by a progressive fall in hepatic uroporphyrinogen decarboxylase activity to 18% of control values after 11 weeks. The features of hexachlorobenzene porphyria are consequences of this enzyme defect. 3. Feeding with hexachlorobenzene did not lead to the accumulation of iron in the liver. It is suggested that hexachlorobenzene or a metabolite acts directly to decrease the activity of the enzyme.
94 citations
TL;DR: A safe reversible anaesthesia of the airways in man lasting for a period of 10-20 min is demonstrated, and the afferent pathway of a reflexly elicited bronchoconstriction in one subject was abolished.
Abstract: 1. The effect of breathing an anaesthetic aerosol of 5% bupivacaine hydrochloride has been assessed in dog and man. 2. In the dog, the cough reflex was abolished and the Hering—Breuer inflation reflex severely impaired or abolished; breathing became slower and deeper; no pathological changes were found in the lungs of these dogs. 3. In man, no untoward effects resulted from a 10 min period of aerosol inhalation; there were no systematic effects on airway resistance or lung volumes and the cough reflex in response to either tactile or chemical (citric acid aerosol) stimulation was invariably abolished. The Hering—Breuer inflation reflex was impaired, but this was not associated with any change in resting ventilation. The V E /CO 2 response was enhanced after aerosol anaesthesia; subjects felt an exaggerated dyspnoea. The aerosol anaesthesia abolished the afferent pathway of a reflexly elicited bronchoconstriction in one subject. There was no effect on the ability to hold the breath, or on the quality of the associated sensation. 4. Control aerosols of sodium chloride solution or phosphate buffer produced no effects. Control experiments with intravenous infusions of bupivacaine proved that none of the effects could have been produced by systemic effects of the absorbed anaesthetic. 5. Plasma concentrations of bupivacaine in man did not exceed a recognized toxic level. The experiments demonstrate a safe reversible anaesthesia of the airways in man lasting for a period of 10–20 min.
TL;DR: Nocturnal hypertension in pre-eclampsia is of theoretical interest and practical importance and patients with uncomplicated essential hypertension in pregnancy retained a normal diurnal blood pressure pattern.
Abstract: 1 Reversal of the normal diurnal blood pressure pattern has been demonstrated in women with severe hypertension and renal impairment in pregnancy (pre-eclampsia) 2 Maximum arterial pressure occurred at night in these women The phenomenon was not due to hypotensive drug therapy or posture Patients with uncomplicated essential hypertension in pregnancy retained a normal diurnal blood pressure pattern 3 Nocturnal hypertension in pre-eclampsia is of theoretical interest and practical importance
TL;DR: Five normal subjects were given 100 ml of aluminium hydroxide gel per day for 28 days and the phosphorus balance became more positive in one subject, less negative in two and changed from negative to positive in the other two subjects.
Abstract: 1. Five normal subjects were given 100 ml of aluminium hydroxide gel per day for 28 days. 2. The phosphorus balance became more positive in one subject, less negative in two and changed from negative to positive in the other two subjects. This was accompanied by a rise in the concentration of the fasting morning plasma phosphorus. Calcium balance did not change. 3. The normal subjects absorbed 0·3–3·6 mmol of aluminium/day, which is significantly less than that absorbed by five patients with chronic renal failure, three of whom were studied before, and two after, the observations on the normal subjects had been completed. 4. In a further five normal subjects on 100 ml of aluminium hydroxide gel/day the 08.00 hours concentration of plasma phosphorus did not fall, though there was a fall at 11.00, 14.00 and 17.00 hours.
TL;DR: A new method for measurement of skeletal blood flow is described which depends on the complete extraction of 18F in a single passage through bone, suggesting that improved precision depends on closer control of physiological variables.
Abstract: 1. A new method for measurement of skeletal blood flow is described which depends on the complete extraction of 18 F in a single passage through bone. 2. Plasma concentration and urinary excretion are measured over a 2 h period. The technique of impulse analysis is used to determine the initial transfer rate of 18 F to bone and extravascular extracellular fluid (ECF). The ECF component is evaluated by using a second tracer ( 51 Cr-EDTA or 82 Br) and the bone transfer rate obtained by difference. The 51 Cr-EDTA data also provide an estimate of glomerular filtration rate and enable a correction to be applied for urinary bladder retention when necessary. 3. Duplicate measurements of skeletal blood flow in eight normal male volunteers gave mean flows between 4·4 and 5·9% of blood volume/min, or about 4 ml min −1 100 g −1 of bone. The variation between normal subjects was least when the results were expressed as % of blood volume/min rather than ml/min, ml min −1 kg −1 or ml min −1 1·73 m −2 body surface area. The precision of the technique was estimated to be 16·4%. 4. Addition of 1·5% random noise to the input data resulted in an uncertainty of 8·5% in the measurement of skeletal blood flow, suggesting that improved precision depends on closer control of physiological variables. 5. In six patients with severe untreated Paget9s disease of bone, skeletal blood flow was 8·4–15·3% of blood volume/min. The increase was significant in all cases. 6. The absorbed radiation dose is low, so that the measurement can be repeated.
TL;DR: Estimating the rates of protein breakdown from the tyrosine flux involved some assumptions about pathways of phenylalanine metabolism and the use of a labelled essential amino acid would therefore give more accurate values for short-term measurements of whole body protein turnover.
Abstract: 1. Six men were infused intravenously for 10 h with a tracer amount of L-[U-14C]tyrosine while on a standardized food intake. 2. Measurements of plasma L-[14C]-tyrosine specific radioactivity and the excretion rate of 14CO2 were made at frequent intervals and showed plateau labelling of plasma and expired carbon dioxide within 6-8 h. The tyrosine flux was calculated from the specific radioactivity in plasma at plateau value. 3. The excretion rate of 14CO2, corrected for retention of label within the bicarbonate pool, showed that oxidation accounted for 20% of the tyrosine flux. Urinary excretion of label was negligible. 4. Rates of protein synthesis were calculated from the flux of tyrosine after subtracting the proportion oxidized. Although the mean rate of synthesis was consistent with other measurements of protein turnover, the individual values ranged from 284 to 387 g/day. The variation was not reduced by relating turnover to body weight, lean body mass or energy expenditure. 5. Estimating the rates of protein breakdown from the tyrosine flux involved some assumptions about pathways of phenylalanine metabolism. The use of a labelled essential amino acid would therefore give more accurate values for short-term measurements of whole body protein turnover.
TL;DR: It is suggested that iron accumulation damages lysosomal membrane, releasing acid hydrolases into the cytoplasm and thus initiating cell damage in patients with a wide variety of chronic liver diseases.
Abstract: 1. Iron, acid phosphatase and N -acetyl-β-glucosaminidase were assayed in liver biopsies from control subjects and patients with primary and secondary haemochromatosis. 2. The activities of the lysosomal enzymes were significantly higher in liver biopsies from patients with iron overload than in those from other patient groups. 3. Lysosomes from the livers of patients with iron overload were strikingly more fragile than those of control subjects as demonstrated by assays of latent and sedimentable N -acetyl-β-glucosaminidase. 4. Lysosomal integrity was essentially normal in biopsies from patients with a wide variety of chronic liver diseases. 5. It is suggested that iron accumulation damages the lysosomal membrane, releasing acid hydrolases into the cytoplasm and thus initiating cell damage.
TL;DR: It was concluded that the presence of propranolol had prevented more or caused fewer infarctions than had the older hypotensive agents unsupported by beta-receptor blockade.
Abstract: 1. After some exclusions, 169 severe uncomplicated essential hypertensive patients presenting consecutively were divided into two groups according to their treatment. Of these, 121 had been given longterm treatment containing propranolol (PC group) and forty-eight had been treated with hypotensive agents excluding any beta-receptor-blocker group, the non-beta-receptor-blocker (NBB) group. 2. There were no significant differences in myocardial infarction risk factors between the two groups. 3. After a mean follow-up of 5-25 years, nine of the 121 subjects (7-5%) in the PC group had suffered first infarctions and fifteen of the forty-eight subjects (31%) in the NBB group, a significant difference (P less than 0-01). 4. It was concluded that the presence of propranolol had prevented more or caused fewer infarctions, perhaps a combination of both, than had the older hypotensive agents unsupported by beta-receptor blockade.
TL;DR: The haemodynamic effects of intravenously administered hydrallazine, diazoxide and nitroprusside and orally administered minoxidil suggest that drugs producing both venodilatation and arteriolar dilatation may be more specific therapy for hypertensive complications associated with cardiac failure.
Abstract: 1. We investigated the haemodynamic effects of intravenously administered hydrallazine, diazoxide and nitroprusside and orally administered minoxidil to determine whether vasodilators (such as nitroprusside) which do not increase cardiac output might be better treatment for hypertensive complications associated with, or caused by, myocardial failure than those that do. 2. Hydrallazine and diazoxide caused increases in heart rate, cardiac output, cardiopulmonary blood volume, the ratio of cardiac output to cardiopulmonary volume, and pulmonary artery pressure. Nitroprusside, although decreasing pressure and vascular resistance, caused no significant change in the other functions except for reducing pulmonary artery pressure. Minoxidil, when given orally, had the potential for causing pulmonary hypertension. This seemed explained by increased flow (hyperdynamic type) in some but by congestive cardiac failure in others; the latter condition was probably intensified by the marked fluid retention that the drug can cause. 3. On the basis of these results a classification of vasodilators was constructed which depends on the presence or absence of a venodilating effect. Vasodilators which produce no (or little) venodilatation, increase heart rate, cardiac output, cardiopulmonary blood volume and pulmonary artery pressure. In this class are diazoxide, hydrallazine and minoxidil. Those that cause venodilatation do not stimulate the heart nor do they cause pulmonary hypertension. Nitroprusside and nitroglycerine are drugs of this type. 4. These results suggest that drugs producing both venodilatation and arteriolar dilatation may be more specific therapy for hypertensive complications associated with cardiac failure than those that cause only arteriolar dilatation.
TL;DR: The results confirm the presence of an intracellular labile iron pool which is available for chelation, and demonstration that different iron chelators have different metabolic effects.
Abstract: 1. The effect of iron chelators on iron uptake, ferritin and total protein synthesis was studied in cultured Chang cells. Desferrioxamine depressed ferritin synthesis and completely inhibited iron uptake by ferritin protein. Rhodotorulic acid reduced iron uptake by the cells but had little effect on ferritin synthesis. Diethylenetriamine pentaacetic acid produced complete inhibition of iron uptake and all protein synthesis. 2,3-Dihydroxybenzoic acid (2,3-DHB) had no effect in this system. 2. When 2,3-DHB was incubated with a liver homogenate, its subsequent addition to a Chang cell culture resulted in depression of ferritin synthesis, iron uptake into the protein and some depression of total protein synthesis. Pretreatment of rhodotorulic acid did not affect its properties. 3. Non-ferritin iron in the Chang cell cytosol was dialysable, available for binding to transferrin and formed chelates which appeared, on gel chromatography, to be of low molecular weight. Gel chromatography of cytosol after incubation of the cells with chelating agents showed non-ferritin iron to be in a similar form. 4. Loss of non-ferritin iron from the cells occurred only when the transferrin in the medium was unsaturated. In the presence of chelating agents non-ferritin iron was lost from the cells even when transferrin was 100% saturated. 5. The results confirm the presence of an intracellular labile iron pool which is available for chelation, and demonstrate that different iron chelators have different metabolic effects.
TL;DR: The results suggest that the increased sensitivity in corticosterone-treated rats may be due to the number of receptors, receptor affinity to noradrenaline, or changes in the functional link between receptor and contractile apparatus.
Abstract: 1. Isolated hind limbs of rats were perfused and vascular smooth muscle sensitivity to noradrenaline, methoxamine and potassium chloride was measured and dose-response curves were obtained. 2. The sensitivity of vascular smooth muscle to noradrenaline is attenuated by adrenalectomy and low sodium diet; it is enhanced by corticosterone. High sodium diet or administration of deoxycorticosterone did not alter the dose—response curve significantly. 3. The increased sensitivity of vascular smooth muscle after corticosterone treatment is not related to changes in the contractile protein or alterations in the neuronal uptake and extraneuronal metabolism of noradrenaline. 4. These results suggest that the increased sensitivity in corticosterone-treated rats may be due to the number of receptors, receptor affinity to noradrenaline, or changes in the functional link between receptor and contractile apparatus.
TL;DR: The uptake of bilirubin was studied in the perfused rat liver by a multiple-indicator dilution technique employing the three-compartment model of Goresky, indicating that the hepatic uptake system for bilirubs under normal conditions is operating far below saturation.
Abstract: 1. The uptake of bilirubin was studied in the perfused rat liver by a multiple-indicator dilution technique employing the three-compartment model of Goresky. 2. The kinetics of hepatic bilirubin uptake could be described by the Michaelis—Menten equation. 3. The maximal uptake velocity ( V max .) and the apparent half-saturation constant ( K m ) were 4·4 ± 0·5 nmol s −1 g −1 of liver and 58 ±16 nmol/g of liver respectively, indicating that the hepatic uptake system for bilirubin under normal conditions is operating far below saturation. 4. Sodium taurocholate did not compete with bilirubin for hepatic uptake. 5. These findings are consistent with the concept that carrier-mediated transport is responsible for hepatocellular uptake of bilirubin and that bilirubin and bile acids enter the hepatocyte via separate pathways.
TL;DR: The results raise the possibility that coronary-risk can be more simply estimated from the plasma HDL cholesterol concentration than from a consideration of other major lipid risk factors and blood pressure.
Abstract: 1. The relation between plasma high-density lipoprotein (HDL) cholesterol concentration and multiple coronary-risk factor status has been assessed in fifty-two middle-aged clinically healthy men from urban and rural Jamaica. 2. Rural hill-farmers had a superior exercise performance (assessed by the responses to submaximal test exercise), less body fat, and lower fasting levels for plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, total triglyceride and blood glucose than urban businessmen. Mean plasma HDL cholesterol was considerably higher in farmers then businessmen. 3. Multilinear regression analysis showed HDL cholesterol concentration to be independently and inversely correlated with plasma triglyceride, LDL cholesterol and diastolic blood pressure and that these relationships applied across the urban and rural sub-groups. There was also some evidence that HDL cholesterol concentration increased with stature. When these factors were taken into account, age, ethnic group, adiposity, weight, exercise performance, smoking history and blood glucose made no further significant contribution to the prediction of HDL cholesterol concentration. 4. Thus plasma HDL cholesterol concentration was highest in those subjects with the lowest coronary-risk as predicted by their multiple risk-factor status, an observation which supported other evidence that coronary-risk is inversely related to plasma HDL concentration. 5. The results raise the possibility that coronary-risk can be more simply estimated from the plasma HDL cholesterol concentration than from a consideration of other major lipid risk factors and blood pressure.
TL;DR: Bacterial generation of organic solute in faeces which have left the body is sufficiently rapid to cast serious doubts on the validity of faecal centrifugation, or other time-consuming techniques involving lengthy handling of faes, as methods of obtaining extracellular faecic fluid for measurements of organic constituents or ammonia.
Abstract: 1. A 25% faecal suspension in sodium chloride solution, incubated anaerobically at 37 degrees C for 48 h, showed excellent survival of all the main groups of faecal bacteria. 2. All faecal incubation systems studied generated large amounts of ammonia, particularly those in which bacterial counts fell during incubation. As normal faeces contain negligible amounts of urea this ammonia must have been generated from sources other than urea. 3. Ammonia was also generated by faeces delivered by sodium chloride enema, and by ileostomy fluid, indicating that the phenomenon is not confined to distal colonic contents. 4. Ammonia generation by incubated faeces was inhibited by prior autoclaving of the sample, but not by sterilization with gamma-irradiation. 5. Generation of ammonia by incubated stool was accompanied by release of large amounts of organic anion and a fall in pH. 6. These observations are interpreted as evidence that ammonia generated within the colon in situ is not derived exclusively from urea, but also from bacterial deamination of amino acids, peptides and proteins. Simultaneously bacterial activity generates large amounts of organacid. The presence of living bacteria is not essential for ammonia generation, provided that bacterial enzymes are present. 7. Bacterial generation of organic solute in faeces which have left the body is sufficiently rapid to cast serious doubts on the validity of faecal centrifugation, or other time-consuming techniques involving lengthy handling of faeces, as methods of obtaining extracellular faecal fluid for measurements of organic constituents or ammonia.
TL;DR: Both BRS and ACI appear to decrease with increasing age and systolic blood pressure, probably due at least in part to the observed reduction in arterial distensibility.
Abstract: 1. The relationship between baroreflex sensitivity (BRS) and arterial compliance index (ACI) has been investigated (a) in paired subjects matched in one instance for systolic blood pressure with differing ages, and (b) in another instance matched for age with differing systolic blood pressures. 2. There was a significant negative correlation between BRS and age and between ACI and age in the twelve systolic blood pressure-matched subjects. 3. A significant negative correlation of systolic blood pressure with both BRS and ACI was observed in the fourteen age-matched subjects. 4. Both BRS and ACI appear to decrease with increasing age and systolic blood pressure. This decrease in BRS is probably due at least in part to the observed reduction in arterial distensibility.
TL;DR: Normal subjects showed a highly reproducible, rapid increase in plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) after an intravenous injection of 200 MRC units of highly purified bovine parathyroid hormone, and it seems unlikely that circulating hormone fragments could account for the prolonged impairment in the responsiveness to the intact hormone.
Abstract: 1. Normal subjects showed a highly reproducible, rapid increase in plasma adenosine 3′:5′-cyclic monophosphate (cyclic AMP) after an intravenous injection of 200 MRC units of highly purified bovine parathyroid hormone. 2. No significant increase in plasma cyclic AMP was observed after administration of bovine parathyroid hormone to patients with severe chronic renal failure. 3. Even when renal function was not impaired, some patients with primary hyperparathyroidism, who had high concentrations of endogenous parathyroid hormone, showed resistance to bovine parathyroid hormone and when this was injected intravenously it caused only a small increase in plasma cyclic AMP. This resistance was reversible since there was marked improvement in the response after parathyroidectomy, when endogenous parathyroid hormone concentration had fallen. 4. It was possible to reproduce this resistance to the hormone by intravenous infusion of bovine parathyroid hormone into normal subjects. When the hormone (1000 MRC units) was infused over 2 h, after an initial increase there was a progressive decline in plasma cyclic AMP concentration and a fall in urinary cyclic AMP excretion. The response to a standard test stimulus (200 MRC units of bovine parathyroid hormone given as a rapid intravenous injection) was examined at intervals after 1000 units of bovine parathyroid hormone had been infused. Initially, the response was severely impaired; at 4 h, partial recovery had occurred and, 24 h after the infusion, recovery of the response was complete. The resistance was therefore reversible. Infusion of the amino -terminal peptide, fragment 1–34, gave the same effect as infusion of intact hormone. Region-specific assays for the hormone were used to show that the concentration of immuno-assayable hormone remained high during the infusions. 5. The mechanism of this reversible resistance to parathyroid hormone remains to be elucidated; it seems unlikely that circulating hormone fragments could account for the prolonged impairment in the responsiveness to the intact hormone. It is possible that alteration in the formation, intracellular degradation or, perhaps, release of cyclic AMP from the cells, is the cause. Changes in the characteristics of the hormone receptor sites might also explain the phenomenon.
TL;DR: Young Wistar rats were used as an experimental model to determine the effects of protein-energy malnutrition on glucose tolerance and insulin release and the impairment of insulin release demonstrated in the malnourished rats cannot be ascribed to a 'functional immaturity' of the pancreas.
Abstract: 1. Young Wistar rats were used as an experimental model to determine the effects of protein-energy malnutrition on glucose tolerance and insulin release. 2. Malnourished rats presented some of the features commonly found in human protein-energy malnutrition, such as failure to gain weight, hypoalbuminaemia, fatty infiltration of the liver and intolerance of oral and intravenous glucose loads. 3. The rate of disappearance of glucose from the gut lumen was greater in the malnourished rats but there was no significant difference in portal blood glucose concentration between normal and malnourished rats 5 and 10 min after an oral glucose load. 4. Insulin resistance was not thought to be the cause of the glucose intolerance in the malnourished animals since these rats had a low fasting plasma insulin concentration with a normal fasting blood glucose concentration and no impairment in their hypoglycaemic response to exogenous insulin administration. Furthermore, fasting malnourished rats were unable to correct the insulin-induced hypoglycaemia despite high concentrations of hepatic glycogen. 5. Malnourished rats had lower peak plasma insulin concentrations than normal control animals after provocation with oral and intravenous glucose, intravenous tolbutamide and intravenous glucose plus aminophyllin. This was not due to a reduction in the insulin content of the pancreas or potassium deficiency. Healthy weanling rats, like the older malnourished rats, had a diminished insulin response to intravenous glucose and intravenous tolbutamide. However, their insulin response to stimulation with intravenous glucose plus aminophyllin far exceeded that of the malnourished rats. Thus the impairment of insulin release demonstrated in the malnourished rats cannot be ascribed to a 'functional immaturity' of the pancreas.
TL;DR: Exercise is a physiological stimulus to HGH secretion and the mechanism is independent of blood [H+] and lactate concentrations.
Abstract: 1. Seven healthy males were studied during cycle ergometer exercise at 33%, 66% and 90% of Vo 2 max. on three occasions when NH 4 Cl, NaHCO 3 or CaCO 3 (as a control substance) were administered in gelatin capsules double blind and in randomized order. Plasma growth hormone (HGH), lactic acid and hydrogen ion concentration ([H + ])weremeasured at frequent intervals. 2. Ammonium chloride produced highest blood [H + ] and NaHCO 3 the lowest. These differences were maintained during exercise and in recovery. Plasma lactic acid concentrations were similar at rest. At 66%, 90% Vo 2 max. and recovery lactic acid was highest with NaHCO 3 and lowest with NH 4 Cl. 3. Exercise stimulated HGH secretion in all studies and the elevation was proportional to the intensity of the exercise. NH 4 Cl caused a variable elevation of HGH at rest and 33% Vo 2 max. At 66% Vo 2 max., plasma HGH was significantly elevated to similar concentrations in all studies and, at 90% Vo 2 max., HGH was highest with NaHCO 3 . 4. An infusion of sodium l(+)-lactate producing plasma lactate concentrations of 3–5 mmol/l did not influence HGH secretion. 5. Exercise is a physiological stimulus to HGH secretion and the mechanism is independent of blood [H + ] and lactate concentrations.
TL;DR: Lactation hyperphagia was chosen as a model for increased luminal nutrition and the changes in small-bowel mucosal structure and function seen in lactation are probably due to hormonal factors.
Abstract: 1. To study the relative contributions of luminal nutrition, bile and pancreatic secretions and hormonal factors in intestinal adaptation, lactation hyperphagia was chosen as a model for increased luminal nutrition, either alone (intestinal transection control group) or in combination with (i) exclusion of bile and pancreatic secretions from the jejunum (by transposition of the jejunum above the Ampulla of Vater) or (ii) exclusion of bile, pancreatic secretions and exogenous luminal nutrition from the jejunum (proximal Thiry—Vella by-pass group). 2. The results confirm that in lactation there is mucosal hyperplasia with increases in villus height and crypt depth, and in small-bowel wet and defatted dry-tissue weights per unit length of intestine. 3. There are corresponding changes in absorptive function with increased glucose and water absorption per unit length of intestine. 4. These structural and functional adaptive changes are proportionately greater in ileum than in jejunum. 5. The exclusion of exogenous luminal nutrition, bile and pancreatic secretions from the jejunum did not diminish the degree of intestinal mucosal hyperplasia and functional adaptation seen in lactation. 6. Diversion to the ileum of greater than normal amounts of bile, pancreatic secretions and luminal nutrition did not further increase the degree of mucosal hyperplasia and enhanced absorption seen in the lactating intestinal transection control group. 7. Unlike other models of intestinal adaptation, the changes in small-bowel mucosal structure and function seen in lactation are problaby due to hormonal factors.
TL;DR: The results raised the possibility that kallikrein could be an aldosterone-induced protein and the effects of inhibitors, biological activity and immunological properties.
Abstract: 1. A technique has been developed for the measurement of kallikrein 'production' in rat renal cortical cells in suspension. 2. After preparative steps, column chromatography on DEAE-cellulose yielded a peak of alpha-N-tosyl-L-arginine methyl ester (Tos-Arg-OMe) esterase activity identical with kallikrein isolated from rat urine in respect of pH optimum, effects of inhibitors, biological activity and immunological properties. 3. The nutrient medium surrounding incubated cells contained measurable kallikrein activity, which was increased by aldosterone and decreased by spironolactone. 4. The results raised the possibility that kallikrein could be an aldosterone-induced protein.
TL;DR: During intravenous infusions of 3H-labelled AII at pressor doses small amounts of radioactivity were found in cerebrospinal fluid perfusate, and the radioactivity of cerebroSpinal fluid outflow could not be related to AII.
Abstract: 1. Anaesthetized, nephrectomized rats were infused intravenously with unlabelled angiotensin II (AII) or with [ 3 H]angiotensin II ( 3 H-labelled AII). The brain ventricular system was perfused with artificial cerebrospinal fluid. The perfusate was collected from the cisterna magna and analysed for AII by radioimmunological and biochemical methods. 2. No increase of immunoreactive AII in cerebrospinal fluid could be shown during intravenous infusion of AII. 3. During intravenous infusions of 3 H-labelled AII at pressor doses small amounts of radioactivity were found in cerebrospinal fluid perfusate. 4. The radioactivity of cerebrospinal fluid outflow could not be related to AII.