bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Autologous Serum on Human Leucocyte Na+/H+ Exchange and Intracellular pH
Authors: Goldsmith D. J. A. , Poston L. , Watson M. , Morris J. , Hilton P. J. , Cragoe E. J. 
Published: August 2015

1. Leucocyte Na+/H+ exchange and intracellular pH were investigated in physiological buffer containing bicarbonate.
2. The amiloride analogue 5-(N,N-hexamethylene) amiloride (1 × 10−5 mol/l), an inhibitor of Na+/H+ exchange, had no significant effect on resting leucocyte pH, Na+ influx or Na+ content.
3. Ammonium chloride washout induced a profound intracellular acidosis, stimulating Na+/H+ exchange. This led to a 236% increase in Na+ influx. Eighty-eight per cent of this increase was inhibited by 5-(N,N-hexamethylene) amiloride. This demonstrates that 5-(N,N-hexamethylene) amiloride is an effective inhibitor of Na+/H+ exchange in human leucocytes.
4. The recovery from intracellular acidosis was shown to be dependent entirely on the presence of extracellular Na+. The Ki for inhibition by 5-(N,N-hexamethylene) amiloride of the recovery was 0.5 μmol/l.
5. Incubation with serum increased Na+ influx and Na+ content: the maximal effect was reached at 20% dilution. Serum (10%, v/v) increased influx by 40%, and 20% (v/v) serum by 102%, over resting levels. Only 43% of the serum-induced increase in Na+ influx was inhibited by 5-(N,N-hexamethylene) amiloride. This represented one-fifth of total Na+ influx.
6. Leucocyte intracellular pH increased on incubation with serum. This alkalinization was inhibited using 5-(N,N-hexamethylene) amiloride.
7. Studies of Na+/H+ exchange in leucocytes in physiological and pathological states are more likely to reflect the state in vivo if carried out in the presence of autologous serum.
Increased Erythrocyte Sodium-Lithium Countertransport Activity in essential Hypertension is Due to an Increased Affinity for Extracellular Sodium
Authors: Rutherford P. A. , Thomas T. H. , Wilkinson R. 
Published: August 2015

1. Sodium-lithium countertransport activity in a standard assay, its sodium affinity constant and maximum velocity were measured in erythrocytes from normal subjects and from essential hypertensive patients with and without a family history of hypertension.
2. In normal subjects the sodium concentration used in the standard assay was similar to the sodium affinity constant so that the activity measured in this assay was less than the maximum velocity.
3. In patients with essential hypertension and a positive family history, 33% had a sodium-lithium countertransport activity greater than the upper limit of the normal control range (0.4 mmol of Li+ h−1 l−1 of cells).
4. The reason for the raised sodium-lithium countertransport activity was an increased sodium affinity (lower sodium affinity constant) at the outside ion-binding site.
5. Of the patients with essential hypertension and a positive family history but sodium-lithium countertransport activity within the normal range in the standard assay, 30% also had a low sodium affinity constant.
6. A low sodium affinity constant at the outside site of the sodium-lithium countertransporter may be a more specific indicator for a group of patients with inherited hypertension than the standard sodium-lithium countertransport activity assay.
Elevated Plasma Noradrenaline Concentrations in Patients with Low-Output Cardiac Failure: Dependence on Increased Noradrenaline Secretion Rates
Authors: Abraham William T. , Hensen Johannes , Schrier Robert W. 
Published: August 2015

1. Plasma noradrenaline concentrations are elevated in patients with congestive heart failure; however, the pathogenesis of these elevated noradrenaline levels is controversial.
2. Possible mechanisms for elevated noradrenaline concentrations in patients with congestive heart failure include increased noradrenaline secretion, decreased clearance of noradrenaline, and a combination of increased secretion and decreased clearance.
3. In the present study, plasma noradrenaline clearance and apparent secretion rates were determined using a whole-body steady-state radionuclide tracer method in six otherwise healthy patients with moderate degrees of low-output cardiac failure and in six normal control subjects.
4. The venous plasma noradrenaline level was elevated in the patients with congestive heart failure as compared with the control subjects (4.18±1.34 versus 1.54 ± 0.16 nmol/l, P &lt; 0.05). There was no stimulation of the adrenal medulla as evident by normal plasma adrenaline levels in both groups (0.19 ±0.04 versus 0.1810.02 nmol/l, not significant). The apparent secretion rate of noradrenaline was elevated in the patients with congestive heart failure (4.75 ±1.95 versus 1.78±0.18 nmol min−1 m−2, P &lt; 0.05), whereas the clearance rate of noradrenaline was similar in the two groups (1.26±0.27 versus 1.16±0.02 1 min−1 m−2, not significant).
5. We conclude that the high peripheral venous plasma noradrenaline concentrations in patients with mildly decompensated low-output cardiac failure are initially due to increased secretion, rather than to decreased metabolic clearance, perhaps in response to diminished effective arterial blood volume.
Effect of Infused Branched-Chain Amino Acids on Muscle and Whole-Body Amino Acid Metabolism in Man
Authors: Louard Rita J. , Barrett Eugene J. , Gelfand Robert A. 
Published: August 2015

1. Using the forearm balance method, together with systemic infusions of l-[ring-2,6-3H]phenylalanine and l-[1-14C]leucine, we examined the effects of infused branched-chain amino acids on whole-body and skeletal muscle amino acid kinetics in 10 postabsorptive normal subjects; 10 control subjects received only saline.
2. Infusion of branched-chain amino acids caused a four-fold rise in arterial branched-chain amino acid levels and a two-fold rise in branched-chain keto acids; significant declines were observed in circulating levels of most other amino acids, including phenylalanine, which fell by 34%. Plasma insulin levels were unchanged from basal levels (8 ± 1 μ-units/ml).
3. Whole-body phenylalanine flux, an index of proteolysis, was significantly suppressed by branched-chain amino acid infusion (P &lt; 0.002), and forearm phenylalanine production was also inhibited (P &lt; 0.03). With branched-chain amino acid infusion total leucine flux rose, with marked increments in both oxidative and non-oxidative leucine disposal (P &lt; 0.001). Proteolysis, as measured by endogenous leucine production, showed a modest 12% decrease, although this was not significant when compared with saline controls. The net forearm balance of leucine and other branched-chain amino acids changed from a basal net output to a marked net uptake (P &lt; 0.001) during branched-chain amino acid infusion, with significant stimulation of local leucine disposal. Despite the rise in whole-body non-oxidative leucine disposal, and in forearm leucine uptake and disposal, forearm phenylalanine disposal, an index of muscle protein synthesis, was not stimulated by infusion of branched-chain amino acids.
4. The results suggest that in normal man branched-chain amino acid infusion suppresses skeletal muscle proteolysis independently of any rise of plasma insulin. Muscle branched-chain amino acid uptake rose dramatically in the absence of any apparent increase in muscle protein synthesis, as measured by phenylalanine disposal, or in branched-chain keto acid release. Thus, an increase in muscle branched-chain amino acid concentrations and/ or local branched-chain amino acid oxidation must account for the increased disposal of branched-chain amino acids.
Decreased Cyclic Nucleotide Phosphodiesterase Activity in Human Peripheral Blood Mononuclear Cells from Elderly Women
Authors: Meskini N. , MacOvschi O. , Prigent A. F. , Nemoz G. , Chapuy P. , Lagarde M. 
Published: August 2015

1. Both adenosine 3′:5′-cyclic monophosphate and guanosine 3′:5′-cyclic monophosphate phosphodiesterase activities of peripheral blood mononuclear cells were markedly decreased in elderly women as compared with young control women.
2. In contrast, the ability of these cells to bind guanosine 5′-[β, γ-imido]triphosphate, a non-hydrolysable analogue of guanosine 5′-triphosphate, was the same in both groups.
3. These findings are discussed in the context of the decline in immune function which occurs with increasing age.
Systolic Wall Stress and Ventricular Arrhythmia: The Role of Acute Change in Blood Pressure in the Isolated Working Rat Heart
Authors: James M. A. , Jones J. V. 
Published: August 2015

1. The effect of a sudden acute change in blood pressure upon arrhythmia provocation has been studied in an isolated working heart model from the Wistar—Kyoto strain of rat. Twenty-four hearts were studied.
2. They were perfused with two different, modified, Krebs—Henseleit solutions at a fixed left atrial pressure.
3. Acute changes in pressure, both increases and decreases, were arrhythmogenic. Whilst ectopic activity was more predictably produced by pressure reductions, this consisted of simple ventricular ectopics only. Pressure increases, in contrast, were capable of provoking more complex and sustained arrhythmias.
4. The effect of pressure changes were highly dependent upon electrolyte concentrations in the perfusate. Low potassium and magnesium concentrations increased the amount of arrhythmia provoked by pressure increases but tended to reduce that provoked by pressure reductions.
5. We conclude that the direct effect of an acute change in pressure upon the myocardium is arrhythmogenic. However, the myocardial response to a pressure change is interdependent upon prevailing electrolyte concentrations.
Short-Term Infusions of Insulin, Triacylglycerol and Glucose do not Cause Acute Increases in Plasminogen Activator Inhibitor-1 Concentrations in Man
Authors: Grant P. J. , Kruithof E. K. O. , Felley C. P. , Felber J. P. , Bachmann F. 
Published: August 2015

1. To investigate the acute effects of insulin and triacylglycerol (‘triglyceride’) on circulating plasminogen activator inhibitor-1 concentrations, seven healthy volunteers were studied during hyperinsulinaemic clamps in the presence of euglycaemia (mean glucose concentration 5 mmol/l) and hyperglycaemia (mean glucose concentration 9 mmol/l) with and without triacylglycerol infusions.
2. During euglycaemia, plasma insulin levels rose from baseline values [median (range)] of 13 (6.6–20.6) m-units/l to 89 (74–105) m-units/l and 99 (74–109) m-units/l after 1 and 2 h of insulin infusion, respectively. Concentrations of plasminogen activator inhibitor-1 fell from 27.5 (10–47) ng/ml to 25.0 (14.5–55) ng/ml and 15.5 (11.5–28.5) ng/ml (P &lt; 0.02) over the same time.
3. During hyperglycaemia, plasma insulin concentrations were 12.1 (9.3–17.1) m-units/l at the run-in period and rose to 87 (73–112) m-units/l and 91 (84–97) m-units/l after 1 and 2 h of insulin infusion, respectively. Concentrations of plasminogen activator inhibitor-1 again showed a gradual fall from 24.7 (22–50) ng/ml to 14 (8.3–25.5) ng/ml and 13 (6.0–35.0) ng/ml (P &lt; 0.02) over the same period.
4. Infusion of Intralipid in the presence of hyperinsulinaemia with either euglycaemia or hyperglycaemia was associated with a similar fall in concentrations of plasminogen activator inhibitor-1 over the study period.
5. The results from this study indicate that short-term increases in insulin, glucose or triacylglycerol do not cause acute increases in plasma concentrations of plasminogen activator inhibitor-1.
Cyclosporin A and the humoral response to blood transfusion in the rat: definition of antigens which suppress alloantibody formation
Authors: Propper D. J. , Jones M. C. , Stewart K. N. , Catto G. R. D. , Power D. A. 
Published: August 2015

1. Blood transfusions improve renal allograft survival rates, but may induce antibodies which are directed to class I major histocompatibility complex antigens and mediate hyperacute transplant rejection. A model to study the development of such antibodies was developed in inbred strains of rats.
2. The influence of transplantation antigens shared between an initial course of blood transfusions, given with cyclosporin A, and a subsequent antigenic challenge (blood transfusion), given without cyclosporin A, on alloantibody responses to class I major histocompatibility complex antigens was then investigated.
3. Cyclosporin A administration prevented the development of alloantibodies to class I major histocompatibility complex antigens during the initial transfusion period.
4. After the challenge transfusions, alloantibody responses to class 1 major histocompatibility complex antigens were suppressed when class I major histocompatibility complex or minor histocompatibility antigens were shared between the initial and final transfusions.
5. This suppression only extended to third party class I antigens when minor histocompatibility complex antigens were shared between the initial and final transfusions. Sharing of class I or class II antigens had no effect on alloantibody responses to third party class I antigens co-expressed on the same cell.
6. These studies suggest that cyclosporin A given with blood transfusions may prevent clinical sensitization while permitting the development of suppressor activity, mediated by shared minor histocompatibility complex determinants, to a broad range of potential donor antigens.
Changes in electrocardiographic patterns at different stages of Chagas' heart disease in rats
Authors: Bestetti Reinaldo B. , Pinto Lucimara Z. , Soares Edson G. , Muccillo Gerson , Oliveira J. Samuel M. 
Published: August 2015

1. The resting electrocardiogram was obtained from 25 Trypanosoma cruzi-infected rats 30 days after infection (phase I). The resting electrocardiogram was abnormal in 12 (group I) and normal in 13 (group II) animals. Nineteen similar but non-infected animals served as controls. Both the resting electrocardiogram and the ajmaline test were performed 120 and 350 days after infection (phases II and III, respectively).
2. With regard to the resting electrocardiogram of group I animals, left axis deviation was found in 10 of 12 (83%) in phase I, one of 12 (8%) in phase II (P &lt;0.05) and in none in phase III (P &lt;0.05). An intraventricular conduction delay was found in four of 12 (33%) rats in phase I, two of 12 rats (16%) in phase II (P &gt;0.05) and six of 12 rats (50%) in phase III (P &gt;0.05). The ajmaline test was abnormal in nine of 10 (90%) rats of group I with normal resting electrocardiogram in phase II, and in three of six (50%) animals in phase III (P &gt;0.05).
3. An intraventricular conduction delay was found in the resting electrocardiogram of one of 13 (7%) rats of group II in phase III. The ajmaline test was abnormal in one of 13 (7%) rats in phase II and in one of 12 (8%) rats in phase III.
4. No control rat showed pathological changes. Eight of 12 (66%) rats of group I and two of 13 (15%) rats of group II showed histopathological alterations consisting of mononuclear cell infiltrate, cellular vacuolation and myocardial necrosis.
5. We conclude that different abnormal patterns may be seen in the resting electrocardiogram in the same T. cruzi-infected rat over time. The QRS axis changes predominate during acute and intraventricular conduction disturbances in the chronic stage of Chagas' heart disease in rats.
Mechanism of reserpine-induced acute gastric mucosal injury in the rat: role of endogenous 5-hydroxytryptamine
Authors: Saum Aws S. 
Published: August 2015

1. Reserpine (5 mg/kg intraperitoneally) produced gastric mucosal vasoconstriction and injury in all rats within 6 h (injury score 38.8 ± 2.1 mm2, mean ± SEM). Coeliac ganglionectomy or the β-adrenoceptor-blocking drug propranolol (5–15 mg/kg) did not influence these effects of reserpine, but vagotomy protected the rats against them. The α-adrenoceptor-blocking drugs phenoxybenzamine and phentolamine at 5 mg/kg were protective against injury. However, a 10 mg/kg dose of either blocker was more effective (2.2 ± 0.5 mm2 and 3 ± 0.8 mm2, respectively, versus 38.8 ± 2.1 mm2, mean ± SEM, P &lt;0.01) and a dose of 15 mg/kg afforded complete protection.
2. Methysergide, a 5-hydroxytryptamine receptor antagonist, produced a dose-dependent increase in the reserpine-induced injury; a significant (P &lt;0.05) increase was noted with 15 and 20 mg/kg (47.5 ± 2.9 mm2 and 49.4 ± 2.2 mm2, respectively, versus 38.8 ± 2.1 mm2, mean ± SEM).
3. The results suggest that, in the rat, reserpine causes vagal α-adrenoceptor stimulation producing gastric mucosal vasoconstriction and injury. 5-Hydroxytryptamine is not implicated in the mechanism of this injury and affords protection against it.
Platelet thromboxane A2 receptors in type I diabetes
Authors: Modesti Pietro Amedeo , Abbate Rosanna , Gensini Gian Franco , Colella Andrea , Serneri Gian Gastone Neri 
Published: August 2015

1. Human platelet thromboxane A2 receptor expression on the membrane surface is possibly dynamically regulated by changes either in the ligand concentration or in membrane fluidity. An increased thromboxane A2 production and a decreased membrane fluidity has been reported in diabetic patients.
2. In the present study the binding characteristics of platelet thromboxane A2 receptors have been investigated in nine diabetic patients (type I) and in 15 healthy control subjects by a radioligand-binding method using 9,11-dimethylmethane-11,12- methane -16-[3-125I-4- hydroxyphenyl]-13,14-dihydro-13-aza-15-tetranor-thromboxane A2 as the radiolabelled ligand.
3. The maximum concentration of binding sites was 163 (sd 35) fmol/108 platelets (n = 15) with 987 (sd 209) receptors/platelet in controls, whereas in diabetic patients the maximum concentration of binding sites was 74.2 (sd 28) fmol/108 (n = 9) with 447 (sd 172) receptors/platelet (P &lt; 0.001). The dissociation constants were 18 (sd 4) nmol/l and 21 (sd 6) nmol/l (not significant) in control subjects and in diabetic patients, respectively. Glycated haemoglobin, which is reported to reduce membrane fluidity, was found to be negatively correlated (r = 0.60, P &lt; 0.05) with thromboxane A2 receptor number in the diabetic patient group. On the contrary, a positive linear correlation between the equilibrium dissociation constant and glycated haemoglobin was found in diabetic patients (r = 0.75, P &lt; 0.01).
Functional properties in vitro of systemic small arteries from rabbits fed a cholesterol-rich diet for 12 weeks
Authors: Simonsen Ulf , Ehrnrooth Eva , Gerdes Lars Ulrik , Færgemann Ole , Buch Jan , Andreasen Frederik , Mulvany Michael J. 
Published: August 2015

1. Recent evidence has suggested that the impairment of endothelium-dependent cholinergic relaxation in vitro, which is seen in atherosclerotic large arteries of animals and man, could be part of a general deleterious effect to the endothelium of hypercholesterolaemia.
2. This possibility has been investigated in vitro by measuring the response to acetylcholine, sodium nitroprusside, 5-hydroxytryptamine and noradrenaline in segments of aorta and of femoral, mesenteric and cerebral small arteries (internal diameter approximately 200 μm) from control rabbits (n = 12) and from rabbits fed a 1% (w/w) cholesterol and 3% (w/w) coconut oil diet (n = 12) for 12 weeks.
3. Thoracic aorta segments from the control rabbits exhibited a maximal relaxation in response to acetylcholine of 64 ± 11% compared with 10 ± 5% (P &lt; 0.01) for thoracic segments from cholesterol-fed animals. Cerebral, femoral and mesenteric small arteries exposed to acetylcholine (10−9-10−4 mol/l) relaxed to the same degree as arteries from control rabbits. The responses to sodium nitroprusside and bradykinin of the small arteries from the cholesterol-fed rabbits remained unaffected. 5-Hydroxytryptamine evoked comparable contractions in the small arteries, while the sensitivity to noradrenaline of the femoral small arteries was significantly decreased and the response of cerebral small arteries to noradrenaline in cholesterol-fed rabbits slightly increased compared with control rabbits.
4. Aorta from the cholesterol-fed rabbits had extensive atheromatous lesions. Morphological measurements and histological examination showed unchanged thickness and light microscopic appearance of intima and media of small arteries from cholesterol-fed animals compared with control animals.
5. The present study indicates that hypercholesterolaemia in this rabbit model is followed by atherosclerotic lesions and changed function of large arteries, but that both function and structure of systemic small arteries are largely unaffected.
Glomerular binding and contractile response to angiotensin II in rats with chronic experimental cirrhosis of the liver
Authors: Villamediana Luis M. , Velo Mercedes , Olivera Ana , Hernando Luis , Caramelo Carlos , López-Novoa Jose M. 
Published: August 2015

1. The effects of angiotensin II on glomerular filtration rate and renal plasma flow were studied in surgically instrumented conscious control and cirrhotic rats. In addition, angiotensin II binding and the contractile response to angiotensin II were studied in glomeruli isolated from cirrhotic and control rats.
2. Cirrhotic rats had a higher glomerular filtration rate and a higher renal plasma flow than control animals. A non-pressor dose of angiotensin II induced small but significant decreases in glomerular filtration rate and renal plasma flow in both control and cirrhotic rats, the effect on renal plasma flow being the most pronounced.
3. Plasma renin and aldosterone concentrations were similar in control and cirrhotic rats.
4. The cross-sectional area of glomeruli from cirrhotic rats was 42% greater than that of glomeruli from control animals. Angiotensin II (10−9 mol/l) decreased the cross-sectional area of glomeruli from control animals by 6.4 ± 0.9% and of glomeruli from cirrhotic rats by 6.6 ± 0.8% (P = not significant for comparison between control and cirrhotic animals).
5. There were no differences between control and cirrhotic rats in the affinity of angiotensin II for its glomerular receptors. However, the angiotensin II receptor density was higher in cirrhotic than in control rats, thereby producing an increased total angiotensin II binding in cirrhotic rats.
6. Since no functional differences between control and cirrhotic animals were present in the response to angiotensin II, even though angiotensin II binding was increased, a post-receptor blockade of the angiotensin II signal could be present in cirrhotic rats.