bluuebunny/crossref_metadata_2025_split huggingface dataset:
Some problems associated with adenylate cyclase bioassays for parathyroid hormone
Authors: Seshadri M. S. , Chan Y. L. , Wilkinson M. R. , Mason R. S. , Posen S. 
Published: August 2015

1. A renal adenylate cyclase system was assessed for its suitability in the performance of parathyroid hormone (PTH) bioassays. Membrane preparations from 1 week old chicks were found to be more sensitive to PTH than material from humans, dogs or rats.
2. Because of the presence of non-specific inhibitors and stimulators of adenylate cyclase in human serum, each serum sample was assayed in the presence and in the absence of a specific PTH inhibitor and the difference was used to calculate PTH activity.
3. Calcium, an inhibitor of adenylate cyclase, was either removed from serum samples by pretreatment with Chelex resin or chelated during assay by means of EGTA.
4. Human and bovine PTH (1-34) stimulated adenylate cyclase in this system to the same extent. The lower limit of detectability was 19.5 pg/ml (final concentration). The intra-assay coefficient of variation at a final concentration of 45 pg/ml was 18%. The index of precision was 0.08 ± 0.04 (n = 7).
5. When synthetic human PTH (1-34) was infused into three normal volunteers, the mean biological half-life of this material was found to be 3.2 min.
6. PTH-like bioactivity could be routinely detected in sera from normal rats, while such activity was significantly decreased in rats subjected to thyroparathyroidectomy.
A comparison of body protein determination in rats by in vivo neutron activation and carcass analysis
Authors: Preston T. , Reeds P. J. , East B. W. , Holmes P. H. 
Published: August 2015

1. Total body nitrogen (TBN) was determined in 16 rat carcasses ranging in weight from 55 to 550 g, by non-destructive 14 MeV neutron activation analysis (NAA).
2. The rat carcasses were subsequently analysed for TBN by Kjeldahl digestion, for total body water (TBW) by loss of weight after freeze-drying and for body fat by adiabatic bomb calorimetry after subtraction of protein energy.
3. TBN results by the two methods were in good agreement, the precision by NAA (coefficient of variation = 1.5%) being superior to that by chemical analysis (coefficient of variation = 2.8%).
4. Body fat calculated by difference from a combination of measured TBW and NAA data agreed closely with bomb calorimetry measurements. The use of indirect estimates of TBW to determine fat gave poor results.
5. A group of four growing rats was analysed sequentially by NAA four times in 2 weeks. The maximum total radiation dose received by each animal was &lt; 50 rem (&lt; 500 mSv) and no significant differences in growth rate were observed compared with non-irradiated control groups.
6. 14 MeV NAA in vivo can be conducted with sufficient precision to measure 0.14 g TBN changes in growing rats at 2 weeks post-weaning.
A comparison of cobalamin binding by liver and kidney in rat and man
Authors: Scott J. S. D. , Bowman E. P. W. , Cooksley W. G. E. 
Published: August 2015

1. Binding of cobalamin (Cbl) was compared in liver and kidney plasma membranes prepared from rat and human tissues.
2. Single, high-affinity, saturable (200 pmol/l), binding sites for TC II-Cbl were found in all tissues; by contrast no receptors were present for free cobalamin, for which only non-specific adsorption occurred.
3. Binding constants for TC II-CNCbl determined for liver and kidney plasma membranes were of a similar magnitude. Mean values for Ka (litre/nmol) were 16.7 (rat liver), 18.8 (rat kidney), 8.0 (human liver) and 7.5 (human kidney).
4. Results for binding TC II-OHCbl instead of TC II-CNCbl showed no difference in Ka and Bmax. values, although the non-specific adsorption was decreased to a third.
5. Competitive inhibition results showed that the receptors are specific for the TC II molecule and that binding is unaffected either by the cobalamin moiety or by the presence of free cobalamin. Degradation of the receptor protein molecules by trypsin (10 μg/ml) resulted in 90% inhibition of binding.
6. It is concluded that differences between liver and kidney in cobalamin uptake and accumulation cannot be attributed to differences in their TC II receptors.
Some observations on the role of the abdomen in breathing in patients on peritoneal dialysis
Authors: Bush Andrew , Miller Juliet , Peacock Andrew J. , Sopwith Tom , Gabriel Roger , Denison David 
Published: August 2015

1. We studied a total of 29 patients on continuous ambulatory peritoneal dialysis (CAPD), who had no present or past respiratory impairment, before and after drainage of dialysate (2.324 ± se 0.033 litres).
2. We measured spirometry, lung volumes and carbon monoxide transfer sitting and supine in 20 patients. The only statistically significant changes on drainage were a small increase in supine functional residual capacity (+ 214 ± se 61 ml, P&lt;0.01) and a small fall in supine peak expiratory flow rate (−26.6 ± se 12.1 litres/min, P&lt;0.05).
3. Measurement of maximal mouth and transdiaphragmatic pressures in ten patients made under the same circumstances showed no statistically significant changes on drainage.
4. A model of the abdomen demonstrates that fluid distension is likely to be better tolerated than gaseous distension, and review of previous studies suggests that a wide range of changes in intraabdominal fluid volume can be tolerated without respiratory embarrassment.
5. These results suggest that fluid volumes used for CAPD do not interfere with breathing in patients with previously normal lungs. The nature of the mechanisms compensating for the fluid suggests that patients with chest disease should be able to tolerate this form of dialysis.
Low-molecular-weight iron complexes and oxygen radical reactions in idiopathic haemochromatosis
Authors: Gutteridge J. M. C. , Rowley D. A. , Griffiths E. , Halliwell B. 
Published: August 2015

1. The sera of patients with idiopathic haemochromatosis and iron-overload have been found to contain low-molecular-weight iron complexes detectable in the ‘bleomycin assay'.
2. These complexes stimulate both the peroxidation of membrane lipids and the formation of the highly reactive and damaging hydroxyl radical.
3. The iron chelator desferrioxamine interferes with these reactions.
4. We suggest that oxygen radical reactions stimulated by iron salts are important in the pathology of idiopathic haemochromatosis.
Assessment in vitro and in vivo of muscle degradation in chronic skeletal muscle myopathy of alcoholism
Authors: Martin Finbarr C. , Peters Timothy J. 
Published: August 2015

1. Muscle protein breakdown in vivo has been studied by measurements of urinary 3-methylhistidine/creatinine ratios. No differences were found between control subjects and chronic alcoholics either with or without proximal muscle wasting or cirrhosis.
2. Calculation of muscle turnover rates, with the correction of Afting et al. (1981, Biochemical Journal, 200, 449-452) for non-skeletal muscle contributions of 3-methylhistidine and creatinine, showed lower values for alcoholics compared with controls.
3. Tissue activities of a neutral protease, assayed by a novel, rapid and sensitive fluorimetric method, were similar in patients and controls. The activity did not vary with severity of atrophy or the presence of cirrhosis.
4. No evidence was therefore obtained to suggest that alcoholic myopathy is due to increased muscle breakdown.
Commentary on Workshop on α-Adrenoceptors
Authors: McGrath J. C. , Reid J. L. 
Published: August 2015

1. A Workshop on α-Adrenoceptors was held at Loch Lomond, Scotland in July 1984. Forty participants from different disciplines in the pharmacological, biochemical, physiological and clinical fields considered the questions:
(i) How many subtypes of α-receptor do we need at present?
(ii) What are the activation steps set in motion by α-adrenoceptors?
(iii) What are the physiological roles of α-adrenoceptors in circulatory control?
(iv) What are the pathophysiological roles and how can α-receptors be manipulated in disease?
2. This paper reviews the major points which arose and is intended as a guide to the papers in this Supplement.
Factors determining α-adrenoceptor-mediated responses of human digital arteries and metacarpal veins
Authors: Stevens M. J. , Moulds R. F. W. 
Published: August 2015

We have previously suggested that differences in α-adrenoceptor-mediated responses of human digital arteries and metacarpal veins cannot be completely reconciled with mixed populations of postsynaptic α1- and α2-adrenoceptors in these tissues [1, 2].
These suggestions were based on the following observations: (a) the Arunlakshana and Schild plots constructed on the basis of antagonism of either phenylephrine or noradrenaline by yohimbine had slopes which were less than unity, thus confirming that the receptors could not be a homogeneous population; (b) prazosin reduced the maximal responses to noradrenaline in both veins and arteries, but to a greater extent in the former than in the latter; (c) pD2 values for the α1-adrenoceptor agonists methoxamine and phenylephrine, and for the α2-adrenoceptor agonists clonidine and oxymetazoline, were the same in arteries and veins, whereas pD2 values for noradrenaline and adrenaline were significantly higher in veins than in arteries; (d) the difference between the arteries and veins in their pD2 values for noradrenaline was maintained in the presence of neuronal and extraneuronal uptake blockade and α-adrenoceptor blockade, thus suggesting it was due to differences in the α-adrenoceptors themselves rather than reflecting differences in populations of other receptors or of neurotransmitter uptake mechanisms [3].
The second of these observations would suggest that if there was a mixed population of typical α1- and α2-adrenoceptors in the arteries and veins the proportion of prazosin-resistant (α2-) receptors was greater in arteries than in veins. This conclusion, however, was not compatible with the observation of the greater sensitivity of veins than arteries to noradrenaline, but not phenylephrine or methoxamine, which would indicate a greater proportion of α2-adrenoceptors in veins than in arteries.
Electrical membrane events in response to α-adrenoceptor stimulation
Authors: Haeusler G. , Peyer J. E. De 
Published: August 2015

1. Strips of rabbit main pulmonary artery (RMPA) were used to study the effects of several agonists on tension development and membrane potential of the vascular smooth muscle cells.
2. The following α-adrenoceptor agonists were employed: methoxamine and St 587 (α1-selective), B-HT 920 (α2-selective) and clonidine, which stimulates preferentially α2-adrenoceptors. By the use of the selective antagonists prazosin and yohimbine it was not possible to differentiate convincingly between α1- and α2-adrenoceptors in the RMPA. Methoxamine and B-HT 920 produced depolarization of similar magnitude of the membrane of the vascular smooth muscle cells. In spite of these results, which point to a uniform α-adrenoceptor in the RMPA, contractions to α1-and α2-agonists differed in some important aspects.
3. Contractions in response to α2-agonists were highly susceptible to the inhibitory effects of calcium withdrawal and calcium antagonists whereas contractions to α1-agonists were much less so. Reduction of the membrane potential of the vascular cells by K+ at 12 mmol/l had no effect on the concentration-contraction curve of methoxamine but shifted that of B-HT 920 to the left. Conversely hyperpolarization of the membrane of the vascular smooth muscle cells by strychnine totally suppressed contraction to B-HT 920 and caused only a rightward shift of the concentration-contraction curve of methoxamine and St 587.
4. Interaction of α1- and α2-agonists with an apparently uniform α-adrenoceptor induces in the RMPA contraction which seems to be triggered by different membrane processes.
Role of endothelium in the contractile response of rat aorta to α-adrenoceptor agonists
Authors: Godfraind ThéOphile , Egleme Cécile , Osachie Iyad Al 
Published: August 2015

1. The influence of endothelium on the response of rat isolated aorta to α-adrenergic agonists has been studied by comparing the response of intact and denuded preparations before and after treatment with calcium entry blockers flunarizine and nifedipine.
2. Endothelium removal enhanced the response of the preparations, especially to α2-agonists that had a weak effect in intact preparations. In the absence of endothelium, about 80% of the maximum response to clonidine was blocked by calcium entry blockers, whereas only 25% of the maximum response to noradrenaline was sensitive to them. In contrast about 40% of maximum noradrenaline-evoked contractions was sensitive to calcium entry blockers in the presence of endothelium. This may be attributed to an increase in the intracellular exchangeable calcium fraction, likely to be due to a slight depolarization of smooth muscle membrane of denuded preparations, which are highly sensitive to the calcium agonist BAY K 8644.
3. The results indicate that a factor liberated by endothelial cells controls both calcium entry and calcium release evoked by α-adrenoceptor agonists in vascular smooth muscle.
Lack of differential inhibition by nifedipine of pressor responses induced by α1- and α2-adrenoceptor agonists and by angiotensin II in anaesthetized cats
Authors: Alabaster V. A. , Solca A. M. 
Published: August 2015

1. The effect of nifedipine on pressor dose-response curves to phenylephrine, α-methylnoradrenaline and angiotensin II was determined in anaesthetized cats pretreated with propranolol and atropine.
2. The selectivity of phenylephrine and α-methylnoradrenaline for postjunctional α1- and α2-adrenoceptors respectively was demonstrated by using the selective α1-adrenoceptor antagonist doxazosin and the relatively selective α2-adrenoceptor antagonist rauwolscine.
3. Nifedipine infused intravenously produced a degree of inhibition of rises in diastolic blood pressure similar to that induced by all three agonists.
4. It is concluded that α1- and α2-adrenoceptor activation induced by phenylethanolamine derivatives is equally dependent on extracellular calcium for vascular smooth muscle contraction. Antagonism of sympathetically mediated or angiotensin-induced vasoconstriction could contribute to the vasodilator effects of nifedipine.
Influence of blood gases, Ca2+-entry blockade and angiotensin converting enzyme inhibition on pressor responses to α-adrenoceptor agonists: evidence in vivo for subtypes of response independent of receptor subtype?
Authors: O'Brien J. W. , Flavahan N. A. , Grant T. L. , McGrath J. C. , Marshall R. J. 
Published: August 2015

1. The pressor responses in the pithed rat to α-adrenoceptor agonists can be modified by alterations in arterial blood gas levels or by drugs which interfere with excitation-contraction coupling processes in the vascular smooth muscle, e.g. Ca2+-entry blockers or angiotensin converting enzyme (ACE) inhibitors. However, the extent of these influences depends on which agonist is used.
2. The pressor response to intravenous injection of α-adrenoceptor agonists consists of two phases: an initial rapid but transient response (phase I) is followed by a response of slower onset but longer duration (phase II). We have examined the effects of manipulation of arterial blood gases, a Ca2+-entry blocker, nifedipine, and an ACE inhibitor, teprotide, on the pressor responses to a series of α-adrenoceptor agonists. In each case, the effects showed selectivity for one or other of the two phases and the differences in susceptibility between agonists could be explained by the relative sizes of the two phases in their responses. In general, phase II was more susceptible to alkalosis, nifedipine and teprotide, so that drugs in which this component predominated were more susceptible to these factors. In contrast there was no direct correlation with the receptor subtypes activated by the agonists.
3. The results are discussed in relation to the modulation of adrenergic responses by physiological factors and drugs which disturb them.
Acute and chronic regulation of α2-adrenoceptor number and function in man
Authors: Jones C. R. , Hamilton C. A. , Whyte K. F. , Elliott H. L. , Reid J. L. 
Published: August 2015

1. Agonist regulation of platelet α2-adrenoceptors was examined in human volunteers after acute elevations of adrenoceptor agonist and during chronic elevation of plasma catecholamines in two patients with phaeochromocytoma.
2. Platelet α2-adrenoceptor number was measured by radioligand binding ([3H]yohimbine) and α2-adrenoceptor function measured by turbidimetric platelet aggregation.
3. Short term infusion of adrenoceptor agonists with α2 activity caused reductions in the platelet response to adrenaline in vitro; conversely an increase in activity was observed postoperatively in two patients after removal of phaeochromocytoma.
4. The changes in platelet response were not accompanied by changes in α2-adrenoceptor number.
5. It is proposed that a process of receptor inactivation occurs during desensitization and this is responsible for the dynamic regulation of platelet responses.
Effect of Bromocriptine Treatment on Prolactin, Noradrenaline and Blood Pressure in Hypertensive Haemodialysis Patients
Authors: Esposti Ezio Degli , Sturani Alessandra , Santoro Antonio , Zuccalà Alessandro , Chiarini Carla , Zucchelli Pietro 
Published: August 2015

1. Bromocriptine (2.5 mg/day orally) produced a significant fall in supine mean arterial pressure in nine hypertensive haemodialysis patients with high serum prolactin levels, without causing significant changes in heart rate.
2. On bromocriptine, there was a significant decrease in the mean value of both serum prolactin and plasma noradrenaline, without significant changes in the mean value of plasma renin activity.
3. A significant relationship was found between the changes in supine plasma noradrenaline and the changes in supine mean arterial pressure induced by bromocriptine.
4. The increase in mean arterial pressure in response to the tilt test was greater on bromocriptine than on placebo although the changes in plasma noradrenaline were reduced by bromocriptine. Similar results were observed during the cold pressor test.
5. These findings suggest that the arterial pressure-lowering effect of bromocriptine is related to the reduction in sympathetic out-flow. The parallel decrease in serum prolactin raises the question of the possible involvement of dopaminergic mechanisms in the development of hypertension in our patients.
6. Moreover, bromocriptine seems to enhance the vascular response to endogenous noradrenaline.
Antigenic Reactivity of Peptides Derived from Wheat Gluten with Sera from Patients with Coeliac Disease
Authors: Rawcliffe P. M. , Priddle J. D. , Jewell D. P. 
Published: August 2015

1. Fraction B from a peptic-tryptic digest of gluten from Scout 66 wheat has already been shown to cause histological damage to the jejunal mucosa of coeliac patients. Peptide fractions, designated P1-P4, have been prepared from it by a combination of gel filtration (producing an intermediate fraction pseudo-B2: ψ B2) and reverse-phase high pressure liquid chromatography.
2. An enzyme-linked immunosorbent assay (ELISA) has been used to measure IgG antibodies to fraction B in sera from untreated coeliac patients, patients with inflammatory bowel disease (IBD) and healthy individuals. The coeliac group had significantly higher (P &lt; 0.05) antibody levels to fraction B than either of the control groups [medians: coeliac disease (n = 21), 0.247; IBD (n = 17) 0.019; healthy controls (n = 13) 0.020]. Five coeliac sera which gave high absorbance values in the ELISA were chosen and pre-incubated with fraction B in a range of concentrations, before assay by ELISA: a dose-dependent inhibition of binding was found.
3. Two sera which gave high ELISA values were preincubated with fractions B2 and P1-P4. B2, P1, P2 and P4 gave a dose-dependent inhibition, with P1 being the most potent. Absolute values were different for the two sera but the same relative pattern of reactivity was observed for each. With the serum giving the higher ELISA value the concentration of fraction (μg/ml) giving a 50% inhibition of binding when 0.5 ml was added to 0.5 ml of a 1/500 dilution of the serum (IC50) was 2.6 for fraction B, 61 for P1, 155 for B2 and 285 and 295 for P4 and P2 respectively. Fraction P3 had negligible inhibitory effect at the doses tested. With the second serum, P1 was again the most active inhibitor.
4. It is concluded that different peptide fractions of wheat gluten have differing reactivity with antibodies to gluten fraction B present in the sera of two patients with untreated coeliac disease.
A study of Erythrocyte Membrane Proteins and Urinary Polypeptides in Conga Drumming Haemoglobinuria
Authors: Levy Richard D. , Khaleeli Ali A. , Griffiths Beatrice L. , Edwards Yvonne H. 
Published: August 2015

1. The erythrocyte membrane proteins and glycoproteins and urinary polypeptides have been examined in a patient exhibiting intermittent pigmenturia associated with conga drumming.
2. Significant excretion of haemoglobin, albumin and probably erythrocyte carbonic anhydrase but not myoglobin occurred during the acute phase of the conga drumming-induced pigmenturia. This usually ceased within 24-48 h.
3. We found no evidence of aberrant erythrocyte membrane components on electrophoresis with either protein staining or a range of 125I-labelled lectins used for detection.
Blood Pressure and Dietary Polyunsaturated and Saturated Fats: A Controlled Trial
Authors: Margetts Barrie M. , Beilin Lawrence J. , Armstrong Bruce K. , Rouse Ian L. , Vandongen Robert , Croft Kevin D. , Mcmurchie Edward J. 
Published: August 2015

1. Fifty-four healthy, omnivore normotensive volunteers aged 20-59 years were randomly allocated either to a control group eating a low polyunsaturated to saturated fat ratio (P/S ratio) diet (0.3) throughout, or to one of two experimental groups eating a high P/S ratio diet (1.0) for one of two 6-week experimental periods. Changes in other components were avoided.
2. Twenty-four hour diet records showed substantial changes in the P/S ratio for experimental groups when on the high P/S ratio diet (0.3 to 1.0).
3. There were significant increases in relative concentrations of linoleic acid in plasma phospholipids when on the high P/S ratio diet.
4. There was no consistent effect of dietary P/S ratio elevation from 0.3 to 1.0 on group mean systolic and diastolic blood pressures. Adjustment of blood pressure changes for changes in electrolytes, other dietary components, plasma lipids, weight and other lifestyle variables did not alter this result.
5. It was concluded that the blood pressure lowering effect of a vegetarian diet reported previously was unlikely to have been due to changes in dietary P/S ratio.
Demonstration of methionine synthetase in intestinal mucosal cells of the rat
Authors: Keating J. N. , Weir D. G. , Scott J. M. 
Published: August 2015

1. Methionine synthetase was measured in the mucosal cells of the rat duodenum, jejunum and ileum by a previously employed method for mucosal cell isolation. No activity was found in these cells.
2. When a dual buffer system for the isolation of villous and crypt cell population was substituted, however, methionine synthetase was found to be active in the duodenum, jejunum and ileum, both in the villous and crypt cell populations. The activity was significantly higher in the crypt cells than in the villous cells throughout the intestine, and higher levels were found in the ileum than in the duodenum or jejunum.
3. As had been previously reported for the rat liver, nitrous oxide in vivo reduced the enzyme activity in both the villous and crypt cell populations, suggesting a role in vivo for the enzyme. We conclude that methionine synthetase is both present and active in the small intestinal mucosal cells of the rat.