bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelium-derived prostacyclin: effect of serum from women with normal and hypertensive pregnancy
Authors: Zammit Vivienne C. , Whitworth Judith A. , Brown Mark A. 
Published: August 2015

1. Pregnancy-induced hypertension (or pre-eclampsia) is characterized by vasoconstriction, platelet aggregation and altered capillary permeability, implying disordered endothelial function and/or structure. Serum from women with pregnancy-induced hypertension has been reported by others to be cytotoxic to endothelial cells in vitro. We hypothesized that such serum contains a factor that limits the ability of endothelial cells to produce and/ or release prostacyclin.
2. Prostacyclin production by intact and damaged cultured human umbilical vein endothelial cells was measured after incubating these cells with serum from non-pregnant and normal pregnant women and women with pregnancy-induced hypertension. Confluent human umbilical vein endothelial cell monolayers (intact and damaged) were incubated with sera for 24 h at 37°C followed by 1 h of incubation with added thrombin (stimulated production) or media (basal production). Supernatants were then collected for measurement of 6-keto-prostaglandin F1α by radioimmunoassay.
3. Basal production of 6-keto-prostaglandin F1α was greater in response to serum from non-pregnant women than to that from pregnant women. Within each group, sub-lethally damaged cells had a similar basal production of 6-keto-prostaglandin F1α to that of intact cells.
4. Basal production of 6-keto-prostaglandin F1α by intact or damaged cells incubated with sera from normal pregnant women and from women with pregnancy-induced hypertension was similar.
5. In all groups the addition of thrombin to intact endothelial cells increased 6-keto-prostaglandin F1α production approximately 15–30-fold over basal levels, but only three- to five-fold in damaged endothelial cells. Stimulated production of 6-keto-prostaglandin F1α by intact or damaged cells was similar with sera from normal pregnant women and women with pregnancy-induced hypertension.
6. These results indicate that any cytotoxic factor present in the sera of women with pregnancy-induced hypertension is unlikely to act by reducing basal endothelial production of prostacyclin. Secondly, if endothelial cell injury occurs in these women they may have a reduced capacity to increase endothelial production of prostacyclin in response to thrombin and possibly other important physiological stimuli.
Stimulation of human breast cancers by dietary l-arginine
Authors: Park Kenneth G. M. , Heys Steven D. , Blessing Karen , Kelly Peter , McNurlan Margaret A. , Eremin Oleg , Garlick Peter J. 
Published: August 2015

1. The amino acid L-arginine has been shown to enhance immune mechanisms and inhibit tumour growth in experimental animals, but although many of the immunological effects of arginine have been reproduced in man there have been few studies of its effects on human tumours. In this study the effects of arginine on human breast cancers were determined by measuring tumour protein synthesis and comparing this with immunohistochemical assessments of cell proliferation.
2. Patients with breast cancer were randomized to receive either a standard diet or arginine supplementation. At the time of surgery, the rate of tumour protein synthesis was measured by the incorporation of the stable isotope [1-13C]leucine into tumour protein. Tumours were also assessed histologically and by staining for the presence of the activation antigen Ki67.
3. The median rate of tumour protein synthesis was 10%/ day (range 5.5–15.8%/day) in the control patients and 25.6%/day (range 9-37%/day) in the patients receiving arginine supplements (P &lt; 0.005, Wilcoxon rank sum test). The rates of protein synthesis correlated with Ki67 expression within these tumours (r=0.78, P &lt; 0.001). A double-staining technique confirmed that tumour cells, rather than tumour-infiltrating lymphoreticular cells, expressed Ki67.
4. This study demonstrates that, in contrast to animal studies, L-arginine stimulates human tumours in vivo. This represents the first direct evidence that a single amino acid can modulate the behaviour of a human cancer.
Effect of acute and chronic administration of ethanol on the pancreatic exocrine response to cholecystokinin in rats fed different diets
Authors: Manso M. A. , Gallego H. A. , de Dios I. 
Published: August 2015

1. The effects of a diet rich in protein and fat, compared with a control diet, with or without chronic ingestion of ethanol on the pancreatic response to cholecystokinin were studied in rats after a 7-month treatment period. The acute effects of intraduodenal administration of 20% (v/v) ethanol were also analysed under these experimental conditions.
2. Animals receiving a diet rich in protein and fat showed a greater percentage increase in pancreatic output in response to cholecystokinin.
3. Chronic ethanol consumption reduced the basal secretion of protein and amylase; and even though the response capacity to cholecystokinin (considered as the percentage secretion on cholecystokinin stimulation with respect to basal secretion) was maintained, this led to hormone-stimulated secretion being decreased in comparison with the animals receiving water. In contrast, a lack of inhibition of basal volume flow and flow after cholecystokinin stimulation was seen after long-term ingestion of ethanol.
4. Acute administration of ethanol generally depressed cholecystokinin-stimulated pancreatic secretion.
5. On stimulation with cholecystokinin, the diet rich in protein and fat combined with long-term ingestion of ethanol led to non-parallel changes in the release of pancreatic enzymes, since an increase in trypsin secretion and a decrease in amylase secretion occurred concomitantly.
Perforin gene expression in T lymphocytes correlates with disease activity in immunoglobulin A nephropathy
Authors: Nakamura Tsukasa , Ebihara Isao , Osada Shiori , Okumura Ko , Tomino Yasuhiko , Koide Hikaru 
Published: August 2015

1. We studied perforin gene expression in T lymphocytes obtained from 26 patients with IgA nephropathy and from 15 healthy age-matched control subjects.
2. The majority of patients with IgA nephropathy (96%) had elevated perforin mRNA expression, whereas no perforin mRNA expression was detected in the T lymphocytes of normal control subjects.
3. A positive correlation was noted between perforin mRNA expression and urinary protein excretion.
4. Perforin mRNA expression correlated also with the histopathology in the renal tissue of patients with IgA nephropathy.
5. Sixty per cent of patients with grade III or IV histopathology had high perforin mRNA expression in T lymphocytes [more than (++)].
6. These studies suggest that disregulation of perforin gene expression in T lymphocytes may be associated with the progression of IgA nephropathy and could be used as an indicator of disease activity.
Platelet cytosolic free calcium concentration, total plasma calcium concentration and blood pressure in human twins: a genetic analysis
Authors: Williams P. D. , Puddey I. B. , Martin N. G. , Beilin L. J. 
Published: August 2015

1. We used path analysis and maximum-likelihood model fitting to evaluate the relative contributions of genetic and environmental factors to the relationships observed between level of blood pressure and both total plasma calcium concentration and platelet cytosolic free calcium concentration in 109 twin pairs.
2. Total plasma calcium concentration was positively associated with systolic (r = 0.26, P &lt; 0.001) but not diastolic blood pressure, a relationship which remained significant after adjustment for albumin, age and body mass index. A relationship between platelet cytosolic free calcium concentration and both systolic and diastolic blood pressure (r=0.17 and r=0.13, respectively, P ≤ 0.05) was no longer significant after adjustment for age and body mass index.
3. Additive genetic influences, unique environmental effects and age contributed to 60%, 30% and 10% of the variance in systolic blood pressure, respectively. Additive genetic effects explained 78% of the variance in plasma total calcium concentration and at least 48% of the variance in platelet cytosolic free calcium concentration in females and 37% in males.
4. Bivariate factor models provided evidence of genetic, but not environmental, co-variation of total plasma calcium concentration and systolic blood pressure, suggesting that a common genetic factor (or factors) contributes to their univariate relationship. In contrast, there was evidence of environmental, but not genetic, covariation of platelet cytosolic free calcium concentration and systolic blood pressure, suggesting that some of the individual experiences specific to each twin may be causing these two traits to vary together.
5. The possible confounding effects of adiposity and environmental factors should be considered in future studies investigating the role of intracellular calcium levels in the pathogenesis of hypertension.
Growth regulatory peptides in gastric mucosa
Authors: Jankowski J. , Al-Rawi H. J. , Johnston D. A. , Hopwood D. , Filipe M. I. , Coghill G. , Wormsley K. G. 
Published: August 2015

1. Epidermal growth factor and the related peptide transforming growth factor α have been implicated in the stimulation of gastric mucosal proliferation. We assessed the immunohistochemical distribution of these peptides and their receptor, epidermal growth factor receptor, in mucosa from the antrum and body of the stomach from 28 patients. Twenty-three of the 56 biopsies were histologically normal (12 antrum and 11 body), whereas the other 33 showed varying degrees of inflammation.
2. Epidermal growth factor, transforming growth factor α and epidermal growth factor receptor had maximal density of distribution on the apical surfaces of the superficial epithelial cells, but were also expressed to a lesser extent on neck and body cells of the glandular tissue (P &lt; 0.05). We also demonstrated that epidermal growth factor expression was greater in the epithelial cells of inflamed mucosa than in those of normal mucosa (P &lt; 0.05).
3. We assessed mucosal proliferation by the Ki-67 labelling index. Ki-67-positive cells were found predominantly in the neck area of the glands and were more frequent in glandular antral tissue than in body glandular tissue (P &lt; 0.05). Expression of epidermal growth factor receptor in the neck and isthmus cells had a significant correlation with the Ki-67 labelling index (P &lt; 0.05).
4. We conclude that epidermal growth factor and epidermal growth factor receptor may be important in the adaptation of gastric mucosa to inflammation.
Absorption of human calcitonin across the rat colon in vivo
Authors: Hastewell J. , Lynch S. , Williamson I. , Fox R. , Mackay M. 
Published: August 2015

1. We studied the absorption of human calcitonin across the colon of juvenile female rats in vivo. Both pharmacokinetic and pharmacodynamic parameters were monitored to measure absorption.
2. Intracolonically administered human calcitonin at doses of 0.1–5.0 mg/kg resulted in a dose-dependent reduction in plasma calcium levels.
3. The bioavailability of intracolonically administered human calcitonin at doses of 5.0, 1.0 and 0.1 mg/kg was 0.5%, 0.9% and 0.2%, respectively.
4. Immunohistochemistry showed that human calcitonin transport across the rat colon was rapid and that a significant amount was via a transcellular pathway.
5. We conclude that human calcitonin crosses the gastrointestinal tract of rats in significant amounts and that this demonstrates the feasibility of an oral form for clinical use.
Clearance of brain natriuretic peptide in patients with chronic heart failure: indirect evidence for a neutral endopeptidase mechanism but against an atrial natriuretic peptide clearance receptor mechanism
Authors: Lang Chim C. , Motwani Joseph G. , Coutie Wendy J. R. , Struthers Allan D. 
Published: August 2015

1. Brain natriuretic peptide is a new natriuretic hormone with striking similarity to atrial natriuretic peptide, but there are no previous data concerning its clearance in man. Two pathways of clearance for atrial natriuretic peptide are recognized: degradation by neutral endopeptidase and binding to atrial natriuretic peptide clearance receptors. We have examined the effect of candoxatril, an inhibitor of neutral endopeptidase (dose range 10–200 mg), and the effect of an infusion of a pharmacological dose [45 μg (90 μg in two patients)] of synthetic human atrial natriuretic peptide on plasma human brain natriuretic peptide-like immunoreactivity levels in seven patients with mild to moderate chronic heart failure.
2. Plasma human brain natriuretic peptide-like immunoreactivity levels were elevated in all patients (mean ± sem 22.0 ± 6.2 pmol/l) compared with healthy control subjects (1.3 ± 0.2 pmol/l, n = 11).
3. In all patients, candoxatril increased both plasma atrial natriuretic peptide (P &lt; 0.05) and plasma human brain natriuretic peptide-like immunoreactivity (P &lt; 0.05) levels.
4. By contrast, an exogenous infusion of atrial natriuretic peptide had no effect on plasma human brain natriuretic peptide-like immunoreactivity levels despite increasing the plasma atrial natriuretic peptide concentration to 424 ± 74 pmol/l, which is a level of atrial natriuretic peptide which would have ‘swamped’ all atrial natriuretic peptide clearance receptors.
5. We have therefore shown that plasma human brain natriuretic peptide-like immunoreactivity levels in chronic heart failure are increased by a neutral endopeptidase inhibitor, but are unchanged by an exogenous infusion of atrial natriuretic peptide. Our results suggest that in patients with chronic heart failure, degradation by neutral endopeptidase is an important pathway for clearance of brain natriuretic peptide. By an indirect approach, we did not find any evidence of a role for atrial natriuretic peptide clearance receptors in the metabolism of brain natriuretic peptide in these patients. Although this is in agreement with work in vitro, there could be alternative explanations for the lack of a change in circulating human brain natriuretic peptide-like immunoreactivity during exogenous administration of atrial natriuretic peptide.
Isolation of an ultrafilterable Ca2+−ATPase inhibitor from the plasma of uraemic patients
Authors: Zidek W. , Rustemeyer T. , Schlüter W. , Karas M. , Kisters K. , Graefe U. 
Published: August 2015

1. Calcium concentration and Ca2+ -ATPase activity under basal conditions and after maximal stimulation with calmodulin were measured in erythrocytes from 32 patients with end-stage renal failure on haemodialysis and from 27 healthy subjects.
2. In patients with renal failure the Ca2+ concentration in erythrocytes was elevated compared with healthy subjects (4.27 ± 1.02 versus 2.86 ± 0.57 μmol/l, P &lt; 0.05).
3. Basal Ca2+ -ATPase activity was lower in the patients with renal failure than in healthy subjects (4.62 ± 1.34 versus 5.43 ± 1.23 pmol of phosphate min−1 10−6 erythrocytes). After maximal stimulation, Ca2+−ATPase activity reached 6.93 ± 2.81 pmol of phosphate min−1 10−6 erythrocytes in the patients with renal failure, whereas in healthy subjects stimulation yielded a Ca2+−ATPase activity of 32.54 ± 8.48 pmol of phosphate min−1 10−6 erythrocytes.
4. Incubation of erythrocytes from healthy subjects with plasma from uraemic patients caused inhibition of Ca2+−ATPase. Likewise, the ultrafiltrate from plasma obtained by haemofiltration treatment inhibited Ca2+−ATPase.
5. Gel chromatography of the ultrafiltrate and laser desorption/ionization mass spectroscopy revealed that a fraction containing substances with a molecular mass of about 300 Da inhibited Ca2+−ATPase.
6. It is concluded that, in uraemia, a Ca2+−ATPase inhibitor accumulates in the plasma, and this could contribute to the toxicity of uraemia by inhibiting cellular Ca2+ transport in erythrocytes and possibly other tissues.
Relationship between spontaneous dyspnoea and lability of airway obstruction in asthma
Authors: Peiffer C. , Toumi M. , Razzouk H. , Marsac J. , Lockhart A. 
Published: August 2015

1. As marked lability of bronchial obstruction is a risk factor for asthma severity, it may influence dyspnoea, the most common subjective complaint in asthma. We therefore studied the relationship between spontaneous dyspnoea and the degree of bronchial lability, as assessed by the daily variability in peak expiratory flow rate and the bronchial responsiveness to either carbachol or salbutamol, in 33 stable symptomatic asthmatic patients.
2. Three times daily, for 10 consecutive days, the patients rated the intensity of their dyspnoea on a visual analogue scale and immediately afterwards recorded their peak expiratory flow rate. Within the next 5 days, we determined the bronchial response by measuring the forced expiratory volume in 1 s and the specific resistance of airways to either carbachol or salbutamol according to baseline airway obstruction.
3. We characterized dyspnoea for each patient by using two parameters: (1) the relationship with underlying airway obstruction, as assessed by the correlation coefficient r between dyspnoea scores and corresponding values of peak expiratory flow rate (r DSc-PEFR), and (2) the intensity, as assessed by the mean visual analogue scale dyspnoea score adjusted for comparable airway obstruction. Bronchial lability was characterized by (1) variability in mean daily peak expiratory flow rate and (2) bronchial responsiveness to either carbachol (as assessed by the threshold dose and the slope of the dose-response curve) or salbutamol (as assessed by the threshold dose and maximal response). We assessed the relationship between dyspnoea and bronchial lability by correlating each of their respective characteristics.
4. We found large inter-subject differences in both characteristics of dyspnoea, r DSc-PEFR was unrelated to variability in mean daily peak expiratory flow rate and to all characteristics of bronchial responsiveness used, except for maximal salbutamol-induced increase in forced expiratory volume in 1 s (as a percentage of predicted). Adjusted visual analogue scale dyspnoea scores were unrelated to all characteristics of bronchial lability.
5. Our results suggest that spontaneous dyspnoea, as characterized by its intensity at comparable levels of airway obstruction and by its relationship with underlying airway obstruction, is poorly related to the degree of bronchial lability in stable symptomatic asthmatic patients.
Selective downregulation of rat renal clearance receptors for atrial natriuretic peptide by chronic high-salt intake: study on isolated membranes using 125I-labelled c-atrial natriuretic peptide-(4–23)
Authors: Michel Harald , Bäcker Angela , Kramer Herbert J. 
Published: August 2015

1. 125I-labelled c-atrial natriuretic peptide-(4–23) was used as radioligand for the direct quantification of atrial natriuretic peptide clearance receptors, and 125I-labelled rat atrial natriuretic peptide-(1–28) was used for the determination of total and biologically active atrial natriuretic peptide receptors, in renal glomerular and papillary membrane preparations of chronically salt-loaded and control rats.
2. The membrane preparation technique included acid-washing (pH 5), and receptor binding was assessed by saturation studies at 4°C for 3 h. Chronic salt loading revealed a 35% decrease in clearance receptor number in the glomerular membrane and a 42% decrease in the papillary membranes. The absolute decrease in clearance receptor number was almost identical with the observed reduction in absolute number of total atrial natriuretic peptide receptors. Biologically active receptors were not affected by chronic salt loading.
3. Selective downregulation of clearance receptors for atrial natriuretic peptide may reflect an important role for the rat renal atrial natriuretic peptide system in long-term fluid and electrolyte regulation.
Effect of angiotensin-converting enzyme inhibition on plasma brain natriuretic peptide levels in patients with heart failure
Authors: Lang Chim C. , Motwani Joseph G. , Rahman Abdul R. , Coutie Wendy J. , Struthers Allan D. 
Published: August 2015

1. The aim of this study was to examine the effect of captopril, an angiotensin-converting enzyme inhibitor, on plasma levels of human brain natriuretic peptide-like immunoreactivity (hBNP-li) in patients with congestive heart failure.
2. Six male patients (aged 52–74 years) with mild to moderate congestive heart failure were studied on two occasions in the semi-recumbent position. After a 30 min rest, patients were randomized to receive oral tablets of either captopril (6.25 mg followed by 25 mg 2 h later) or placebo in a single-blind manner. Plasma hBNP-li, atrial natriuretic peptide-like immunoreactivity (ANP-li) and angiotensin II-like immunoreactivity (ANG II-li) levels and blood pressure were measured.
3. Baseline plasma hBNP-li and ANP-li levels in these patients with mild to moderate congestive heart failure were 13.5 ± 3.2 pmol/l and 50.9 ± 11.8 pmol/l, respectively. In 11 healthy male subjects aged 20–23 years, the peripheral plasma hBNP-li and ANP-li levels were 1.3 ± 0.2 pmol/l and 5.6 ± 1.7 pmol/l, respectively. In all patients, captopril decreased the plasma ANG II-li level (from 24.3 ± 8.1 to 6.6 ± 3.2 pmol/l, P&lt;0.05) and mean arterial blood pressure (from 92 ± 3 to 80 ± 3 mmHg, P&lt;0.05). Compared with placebo, captopril treatment was associated with significant reductions in plasma hBNP-li (from 14.3 ± 3.0 to 12.8 ± 2.1 pmol/l, P&lt;0.05) and in plasma ANP-li (from 53.9 ± 1.11 to 36.8 ± 7.6 pmol/l, P&lt;0.05) levels.
4. Our results show that in patients with heart failure, acute inhibition of angiotensin-converting enzyme with captopril results in falls in both plasma hBNP-li (10% fall) and ANP-li (32% fall) levels. Our results do not support a major role for angiotensin-converting enzyme in the metabolism of human brain natriuretic peptide in heart failure, although a minor role cannot be excluded since the fall in the plasma ANP-li level was greater than the fall in the plasma hBNP-li level. However, the fall in the plasma hBNP-li level is most probably related to the changes induced in intra-cardiac volume/pressure by the angiotensin-converting enzyme inhibitor.
Disparities in circulatory adjustment to standing between young and elderly subjects explained by pulse contour analysis
Authors: Wieling W. , Veerman D. P. , Dambrink J. H. A. , Imholz B. P. M. 
Published: August 2015

1. The circulatory adjustment to standing was investigated in two age groups. Young subjects consisted of 20 healthy 10–14-year-old girls and boys. Elderly subjects consisted of 40 70–86-year-old healthy and active females and males. Continuous responses of blood pressure and heart rate were recorded by Finapres. A pulse contour algorithm applied to the finger arterial pressure waveform was used to assess stroke volume responses.
2. During the first 30 s (initial phase), an almost identical drop in mean blood pressure was found in both age groups (young, 16 ± 10 mmHg; old, 17 ± 10 mmHg), but the initial heart rate increase was attenuated in the elderly subjects (young, 29 ± 7 beats/min; old, 17 ± 7 beats/min).
3. During the period from 30 s to 10 min of standing, mean blood pressure increased from 96 ± 12 to 106 ± 12 mmHg in the elderly subjects compared with almost no change in the young subjects (from 82 ± 8 to 84 ± 7 mmHg). In the elderly subjects a progressive increase in total peripheral resistance (from 114 ± 14% to 146 ± 29%) was found, compared with an initial rapid increase in total peripheral resistance (126 ± 18% after 30 s) with no further change during prolonged standing (124 ± 17% after 10 min) in the young subjects. In this age group the decrease in stroke volume and the increase in heart rate after 10 min of standing were large (young, −37 ± 11% and 27 ± 11 beats/min; old, −31 ± 9% and 7 ± 6 beats/min, respectively).
4. In conclusion, young subjects adjust to orthostatic stress mainly by a marked increase in heart rate. In healthy elderly subjects an attenuation of the heart rate response during orthostatic stress is compensated by a pronounced increase in total peripheral resistance resulting in an increase in blood pressure.