bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Erythrocyte Choline Uptake in Uraemia: The Role of Intracellular Substrate and An Investigation into the Effects of Haemodialysis
Authors: Flanagan G. J. , O'kelly J. , Rae C. , Winearls C. G. , Ellory J. C. 
Published: August 2015

1. Erythrocyte choline transport was studied in 10 haemodialysis patients immediately before and after a haemodialysis session and in 10 control subjects. Choline uptake was measured in erythrocytes from normal and uraemic patients after washing in vitro and subsequent incubation in autologous plasma. Amines present in uraemic plasma were examined for their effect on choline transport in normal erythrocytes.
2. NMR spectroscopy was used to measure choline, trimethylamine and dimethylamine in erythrocyte extracts from nine control subjects, 32 subjects with renal impairment and nine samples from haemodialysis patients.
3. The increased choline influx in uraemic erythrocytes is significantly decreased by prior haemodialysis (mean Vmax pre-dialysis 146±20 μmol h−1 I−1, postdialysis 113±13 μ/mol h–1 I−1 (P &lt; 0.005). After in vitro washing there is a fall in Vmax, and no longer any significant difference between pre- and post-dialysis samples. There remains a significant difference in the erythrocyte choline Vmax between samples from patients with chronic renal failure and from normal subjects (P &lt; 0.005).
4. Human plasma was found to contain factors capable of increasing choline uptake. Trimethylamine and dimethylamine were found to inhibit choline uptake. Trimethylamine and trimethylamine-N-oxide transstimulated choline efflux, but the major transport substrate present in erythrocyte extracts from all groups was choline, which was higher in those with renal impairment (71 ± 10 μmol/l) than in haemodialysis patients (47 ± 10 μmol/l) and control subjects with normal renal function (40 ± 9 μmol/l).
5. Our data suggest that erythrocyte choline transport is increased in uraemia as a consequence of increased transporter number or activity, rather than the presence of intracellular substrate.
Reproducibility of Heart Rate Variability Measures in Patients with Chronic Heart Failure
Authors: Ponikowski Piotr , Piepoli Massimo , Amadi Aham A. , Chua Tuan Peng , Harrington Derek , Volterrani Maurizio , Colombo Roberto , Mazzuero Giorgio , Giordano Amerigo , Coats Andrew J. S. 
Published: August 2015

1. In patients with chronic heart failure, heart rate variability is reduced with relative preservation of very-low-frequency power (&lt; 0.04 Hz). Heart rate variability has been measured without acceptable information on its stability and the optimal recording periods for enhancing this reproducibility.
2. To this aim and to establish the optimal length of recording for the evaluation of the very-low-frequency power, we analysed 40, 20, 10 and 5 min ECG recordings obtained on two separate occasions in 16 patients with chronic heart failure. The repeatability coefficient and the variation coefficient were calculated for the heart rate variability parameters, in the time-domain (mean RR, SDRR and pNN50), and in the frequency-domain: very low frequency (&lt; 0.04 Hz), low frequency (0.04–0.15 Hz), high frequency (0.15–0.40 Hz), total power (0–0.5 Hz).
3. Mean RR remained virtually identical over time (variation coefficient 8%). The reproducibility of time-domain (variation coefficient 25–139%) and of spectral measures (variation coefficient 45–111%) was very low. The stability of the heart rate variability parameters was only apparently improved after square root and after log transformation.
4. Very-low-frequency values derived from 5 and 10 min intervals were significantly lower than those calculated from 40 and 20 min intervals (P &lt; 0.005). Discrete very-low-frequency peaks were detected in 11 out of 16 patients on the first 40, 20 and 10 min recording, but only in seven out of 16 when 5 min segments were analysed.
5. The reproducibility of both time or frequency-domain measures of heart rate variability in patients with chronic heart failure may vary significantly. Square root or log-transformed parameters may be considered rather than absolute units in studies assessing the influence of management on heart rate variability profile. Recordings of at least 20 min in stable, controlled conditions are to be recommended to optimize signal acquisition in patients with chronic heart failure, if very-low-frequency power in particular is to be studied.
Visualizing Signal Transduction: Receptors, G-Proteins, and Adenylate Cyclases
Authors: Dessauer Carmen W. , Posner Bruce A. , Gilman Alfred G. 
Published: August 2015

1. The first glimpses of heterotrimeric G-proteins came with the discoveries of the ubiquitous adenylate cyclase activator, Gs, and the specialized retinal cGMP phosphodiesterase activator, Gt or transducin. The model that evolved for regulation of adenylate cyclase activity by G-proteins soon proved to be a general paradigm for a large number of signalling pathways. Although many different G-proteins interact with a diverse array of receptors and effectors, each is composed of a guanine-nucleotide-binding α-subunit and a tightly associated complex of a β- and a γ-subunit.
2. Receptors catalyse the activation of G-proteins by promoting exchange of GDP for GTP, while G-proteins catalyse their own deactivation as a result of their intrinsic GTPase activity. Crystallographic analysis has described several of the various conformational states that G-proteins undergo as they are activated and deactivated and has provided great insight into the kinetic models of G-protein-mediated signal transduction.
3. The regulation of adenylate cyclase has proven to be intriguing and complex. Gsα activates all forms of mammalian adenylate cyclase; other G-proteins (Gi, Go and Gz) inhibit certain isoforms of the enzyme. The discovery of new isoforms of adenylate cyclase has revealed synergistic and conditional mechanisms of regulation. These include activation or inhibition by the G-protein βγ-subunit complex, activation by Ca2+-calmodulin, and phosphorylation by protein kinases. The large number of receptors, G-proteins and adenylate cyclases provides a complex signalling network that integrates and interprets a multitude of convergent inputs.
T-Cell Autoimmunity in Primary Biliary Cirrhosis
Authors: Jones David E. J. 
Published: August 2015

1. Primary biliary cirrhosis is a chronic cholestatic liver disease with an autoimmune aetiology. The classical histopathological lesion, of portal tract biliary epithelial cell damage, is accompanied by a T-cell-rich mononuclear cell infiltrate and upregulation of cell surface markers suggestive of local T-cell activation and cytokine release. This suggests that T-cell mediated mechanisms play an important role in tissue damage in primary biliary cirrhosis.
2. CD4+ T-cells specific for the E2 component of human pyruvate dehydrogenase complex (PDC-E2), a highly conserved enzyme which plays a critical role in intermediate metabolism, are present in the peripheral repertoire of the majority of patients with primary biliary cirrhosis. These cells are almost entirely absent from normal and chronic liver disease control subjects. The observations that peripheral blood PDC-E2-specific cells are most commonly seen in early stage disease, when active bile duct damage is occurring, and that PDC-E2-specific cells can be found in the portal tract infiltrate at times when this damage is occurring, suggest that these autoreactive cells may have a role to play in the aetiology of primary biliary cirrhosis.
3. T-cells specific for the whole PDC and its E1 component are seen in significant numbers of normal control subjects as well as patients with primary biliary cirrhosis. Retention of potentially autoreactive cells in the normal T-cell repertoire has been reported for a number of other autoantigens.
4. T-cell epitopes appear to be widely distributed throughout PDC-E2. This is in contrast to the B-cell epitopes which are highly restricted to the inner lipoyl binding domain of the protein.
Effects of High External Concentrations of K+ on 86Rb+ Efflux in Human Platelets: Evidence for Na+/K+/2Cl− Co-Transport
Authors: De Silva H. A. , Carver J. G. , Aronson J. K. 
Published: August 2015

1. Na+/K+/2Cl− co-transport mediates a bidirectional symport of Na+, K+ and Cl−. The important properties of the co-transport system are its requirement for Na+, K+ and Cl− and its inhibition by loop diuretics such as bumetanide. This co-transporter has been described in a number of animal and human tissues. However, its presence in human platelets, although inferred, has not been demonstrated directly.
2. We have studied the efflux of 86Rb+ (a marker for K+) from Rb+-loaded platelets, and have defined their response to stimulation by high concentrations of external K+.
3. KCl (30–120 mmol/l) stimulated a concentration-dependent increase in 86Rb+ efflux from the platelets. This efflux was completely inhibited by bumetanide (10 μmol/l) but was insensitive to ouabain and R(+)-[(dihydroindenyl)oxy]alkanoic acid. It also required Cl− in the external medium, but did not depend on the presence of extracellular Na+.
4. These observations suggest that 86Rb+ efflux from platelets stimulated by external K+ occurs via Na+/K+/2Cl− co-transport acting in a K+/K+ (K+/Rb+) exchange mode.
5. Non-stimulated efflux of 86Rb+ from the platelets (i.e. in the presence of 5 mmol/l K+) had the characteristics of Na+/K+/2Cl− co-transport acting in normal mode.
Changes in the Period of No Respiratory Sensation and Total Breath-Holding Time in Successive Breath-Holding Trials
Authors: Nishino Takashi , Sugimori Kunio , Ishikawa Teruhiko 
Published: August 2015

1. Immediately after breath-holding at end-expiratory level, there is a certain period of no particular respiratory sensation which is terminated by the onset of an unpleasant sensation and followed by progressive discomfort during breath-holding. This period, defined as the time from the start of voluntary breath-holding to the point where the onset of an unpleasant sensation occurs, is designated ‘the period of no respiratory sensation’. Although it has been shown that the maximum breath-holding performance is improved with successive trials, it is not clear whether this training effect exerts a similar influence on the period of no respiratory sensation during breath-holding.
2. Since the training effect seems to be associated with the stresses of breath-holding, we hypothesized that the initial period of no respiratory sensation during breath-holding might be less influenced by the training effect.
3. We studied 13 normal subjects who performed repeated breath holds while continuously rating their respiratory discomfort using a visual analogue scale. In addition, we measured the hypercapnic ventilatory response of each individual and obtained the relationship between the slope of the hypercapnic response curve and breath-holding periods.
4. Our results showed that there was little training effect on the period of no respiratory sensation and that the period of no sensation during breath-holding is inversely related to the slope of the hypercapnic ventilatory response curve.
5. The period of no respiratory sensation was also measured in eight patients with chronic obstructive pulmonary disease. The values of the period of no respiratory sensation in patients with chronic obstructive pulmonary disease were apparently lower than those obtained in normal subjects.
6. These findings suggest that measurement of the period of no respiratory sensation can be a useful clinical test for the study of genesis of dyspnoea.
Regulation of Adipose Cell Number in Man
Authors: Prins Johannes B. , O'rahilly Stephen 
Published: August 2015

1. Adipose tissue mass is dependent on both the average volume and the number of its constituent adipocytes. Significant alteration in body mass involves alteration in both adipocyte volume and number.
2. Increases in adipocyte number occur via replication and differentiation of preadipocytes, a process which occurs throughout life. Decreases in adipocyte number occur via preadipocyte and adipocyte apoptosis, and possibly adipocyte dedifferentiation.
3. Overall regulation of adipose mass involves endocrine, paracrine and possibly autocrine systems. Hypothalamic centres appear to control appetite, metabolic rate and activity levels in a co-ordinated manner. Within the hypothalamus, known weight regulatory molecules include glucagon-like peptide-1, neuropeptide Y and leptin. Leptin is a major afferent signal from adipose tissue to the hypothalamus, providing information on overall adipose tissue mass. However, the precise means by which the hypothalamus signals to adipose tissue is less well understood.
4. In adipose tissue, known molecular regulators of adipose cell number include insulin, ligands for the peroxisome proliferator activated receptor-γ, retinoids, corticosteroids and tumour necrosis factor-α. The net effect of these and other regulators is to effect a concerted alteration in adipocyte volume and number. This review largely focuses on the control of fat cell acquisition and loss and the influence of these processes on adipose tissue mass and regional distribution.
Cardiovascular Pharmacology of Purines
Authors: Rongen Gerard A. , Floras John S. , Lenders Jacques W. M. , Thien Theo , Smits Paul 
Published: August 2015

1. This review focuses on the extracellular actions of ATP and adenosine, and in particular their role in cardiovascular regulation.
2. ATP serves as a co-transmitter within the sympathetic nervous system, and is also released from endothelium and aggregating thrombocytes. ATP acts on P2x purinoceptors on vascular smooth muscle cells to induce vasoconstriction. Stimulation of P2y purinoceptors on endothelial cells releases endothelium-derived relaxing factors and causes vasodilatation. This dual action of ATP may have pathophysiological importance by inducing vasospasm at sites of impaired endothelial function and thrombus formation.
3. Adenosine is generated by enzymic degradation of ATP. Its formation is enhanced during ischaemia. Adenosine inhibits noradrenaline release from sympathetic nerve endings, causes vasodilatation via endothelium-dependent and endothelium-independent actions, has important anti-arrhythmic properties and prevents deleterious sequelae of ischaemia. In humans, adenosine evokes a sympatho-excitatory reflex mediated by chemically sensitive receptors and afferent nerves in the kidney, heart and forearm. This reflex may be active during exercise and ischaemia and, because of its potential adverse consequences, it should be considered when developing new therapies to potentiate the anti-ischaemic actions of endogenous adenosine in humans. Adenosine appears to mediate ischaemia-induced pain; a reduced sensitivity to adenosine may underlie silent ischaemia.
4. New drugs that interact with adenosine formation or degradation or with adenosine receptors are under development. These have potential therapeutic application in the treatment of ischaemia and other circulatory disorders.
Effects of Silicon, Citrate and the Fasting State on the Intestinal Absorption of Aluminium in Rats
Authors: Drüeke Tilman B. , Jouhanneau Philippe , Banide Hélène , Lacour Bernard , Yiou Françoise , Raisbeck Grant 
Published: August 2015

1. The effect of silicon (Si) contained in drinking water and solid food on the intestinal absorption of aluminium (Al) remains a matter of debate. The present study was designed to readdress this issue in the experimental animal, and to examine concomitantly the effects of citrate and the fasting state, respectively.
2. Three groups of young, non-fasted rats (n = 8 per group) were gavaged by solutions containing 3.8 ng of 26Al, 63 ng of 27Al, and either distilled water (&lt;0.1 mg/l Si) or commercial mineral water with a medium (6 mg/l) or high (14 mg/l) Si concentration.
3. Two other groups of eight non-fasted rats each received the same distilled water or high-Si gavage solution, respectively, together with a high citrate concentration (62 g/l). In each case the animals had free access to drinking water for 5 days before and 2 days after the gavage, containing the same Si concentration as in the gavage solution. A sixth group of eight rats was gavaged by low-Si, Al and distilled water in the fasted state.
4. The animals were killed 48 h after gavage, and blood, tissue and urine samples were collected for 26Al measurements by accelerator mass spectrometry.
5. We found that the fraction of absorbed 26Al retained in the skeleton (0.025–0.030%) was of the same order of magnitude as the fraction excreted in the 48 h urine (0.035-0.037%). High Si concentrations in the drinking water failed to depress the 26Al fraction absorbed, as estimated on the basis of skeletal accumulation and urinary excretion.
6. The administration of citrate-containing fluid enhanced 26Al absorption 5- to 10-fold (P &lt; 0.005), but again the Si content of drinking water did not interfere. Finally, the intestinal absorption of 26Al was approximately 15 times higher in the fasted than in the non-fasted state.
7. In conclusion, the provision of large amounts of Si in the drinking water failed to modify physiological intestinal Al absorption under basal conditions or after its stimulation by citrate. However, a prolonged fast greatly enhanced Al absorption, compared with the non-fasted state.
Brisk Walking Reduces Calcaneal Bone Loss in Post-Menopausal Women
Authors: Brooke-Wavell Katherine , Jones Peter R. M. , Hardman Adrianne E. 
Published: August 2015

1. This study examined the influence of brisk walking on skeletal status in post-menopausal women.
2. Subjects were 84 healthy women aged 60–70 years who were previously sedentary and at least 5 years post-menopausal. Subjects were randomly assigned to walking (n = 43) and control (n = 41) groups. Walkers followed a 12-month, largely unsupervised programme of brisk walking. The bone mineral density of the lumbar spine, femoral neck and calcaneus and broadband ultrasonic attention of the calcaneus were measured at baseline and after 12 months.
3. Forty control subjects and 38 walkers completed the study. Walkers built up to 20.4 ± 3.8 min/day (mean ± SD) of brisk walking. Body mass increased in control subjects relative to walkers [mean change (SE) ± 0.9 (0.3) and −0.1 (0.3) kg respectively; P = 0.04]. Predicted maximum oxygen uptake increased in walkers by 2.1 (0.9) ml min−1 kg−1 (P = 0.02). Bone mineral density in the lumbar spine and calcaneus fell in control subjects [–0.005 (0.004) and −0.010 (0.004) g/cm2, respectively] but not in walkers [+0.006 (0.004) and +0.001 (0.004) g/cm2]. The difference in response between groups was significant in the calcaneus (P = 0.04) but not in the lumbar spine (P = 0.08). Mean femoral neck bone mineral density did not change significantly in either group, although changes in walkers were related to the amount of walking completed (r = 0.51, P = 0.001). The change in broadband ultrasonic attenuation of the calcaneus differed between groups [control subjects, −3.7 (0.8); walkers, −0.7 (0.8) dB/MHz; P = 0.01].
4. Walking decreased bone loss in the calcaneus and possibly in the lumbar spine. It also improved functional capacity and enabled walkers to avoid the increase in body mass seen in control subjects.
Comparison of Forearm Vasodilatation to Substance P and Acetylcholine: Contribution of Nitric Oxide
Authors: Newby David E. , Boon Nicholas A. , Webb David J. 
Published: August 2015

1. Forearm blood flow responses to incremental challenges of acetylcholine and substance P, administered via the brachial artery, were measured by venous occlusion plethysmography in eight subjects in the presence of saline, the nitric oxide synthase inhibitor, NG-monomethyl-l-arginine, and a control vasoconstrictor, noradrenaline.
2. Substance P and acetylcholine caused dose-dependent increases in forearm blood flow (P &lt; 0.001). When separated by 30 min saline infusions, repeated responses did not undergo tachyphylaxis.
3. Noradrenaline caused a mean reduction in basal blood flow of 34–51% (P &lt; 0.001), and augmented the percentage increases in blood flow with both substance P (P = 0.05) and acetylcholine (P = 0.03) infusions.
4. NG-Monomethyl-l-arginine caused a mean reduction in basal blood flow of 42–45% (P &lt; 0.001) and significantly inhibited the responses to both substance P (P &lt; 0.001) and acetylcholine (P = 0.05).
5. In comparison with saline responses, NG-monomethyl-l-arginine caused a mean inhibition of 69 ± 8% for substance P-induced vasodilatation and 40 ± 5% for acetylcholine-induced vasodilatation. However, comparing responses with those to the control vasoconstrictor noradrenaline, NG-monomethyl-l-arginine caused a mean inhibition of 81 ± 5% for substance P responses and 58 ± 3% for acetylcholine responses. Inhibition by NG-monomethyl-l-arginine of the response to substance P was significantly greater than inhibition of the response to acetylcholine (P = 0.02).
6. Hence, in healthy men, a greater proportion of the forearm vasodilatation to substance P than to acetylcholine appears to be nitric oxide-mediated. Given its greater stability, substance P may be more suitable as a pharmacological tool in the investigation of stimulated nitric oxide production and endothelial cell function.
Transfection of Cardiac Muscle: Effects of Overexpression of c-myc and c-fos Proto-Oncogene Proteins in Primary Cultures of Neonatal Rat Cardiac Myocytes
Authors: Green Nicola K. , Franklyn Jayne A. , Ohanian Vasken , Heagerty Anthony M. , Gammage Michael D. 
Published: August 2015

1. Studies of cells transfected with specific expression vectors allow functions of specific gene products to be investigated. We first established optimum conditions for transfection of neonatal cardiac myocytes in primary culture. Increased proto-oncogene expression has been implicated in the development of cardiac hypertrophy; we therefore wished to examine the effects of overexpression of the c-myc and c-fos proto-oncogenes induced by cell transfection on cell growth.
2. Neonatal rat ventricular myocytes were transfected by electroporation, voltage and capacitance settings were optimized and these conditions were then used to transfect expression vectors encoding MYC and FOS proteins into this cell type. Effects on cell number, DNA synthesis and protein content were determined.
3. Increased expression of c-myc and c-fos in cells transfected with proto-oncogene expression vectors was confirmed by Northern and Western blotting. Increases in cardiac myocyte cell number, DNA synthesis and total cellular protein were observed in cells transfected with either c-myc or c-fos expression vectors compared with cells transfected with non-coding vectors.
4. Overexpression of MYC and FOS proteins results in hyperplastic rather than hypertrophic growth of the neonatal rat heart, providing evidence for a role of these proteins in the control of myocardial growth.