bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Membrane Form of Phosphatidate Phosphohydrolase: A Possible Role in Signal Transduction during Liver Fibrogenesis
Authors: Day Christopher P. , Burt Alastair D. , Brown Ashley Stj. M. , Bennett Mark K. , Farrell Desmond J. , James Oliver F. W. , Yeaman Stephen J. 
Published: August 2015

1. Several growth factors important in liver regeneration and fibrosis stimulate phospholipase D in plasma membranes via a receptor/G-protein-coupled mechanism resulting in hydrolysis of phosphatidylcholine to phosphatidate. Phosphatidate can be further hydrolysed to diacylglycerol by phosphatidate phosphohydrolase. Phosphatidate and diacylglycerol can act as ‘second-messengers’ and regulation of phosphatidate phosphohydrolase activity could control the balance between them.
2. A form of phosphatidate phosphohydrolase, located in the plasma membrane and insensitive to inhibition by N-ethylmaleimide, has recently been identified that is distinct from the ‘metabolic’ form, which is present in the cytosol and microsomes and is sensitive to N-ethylmaleimide.
3. We have investigated the hypothesis that the balance between regeneration and fibrosis is, in part, determined by the activity of plasma membrane phosphatidate phosphohydrolase through its effect on the phosphatidate/diacylglycerol ratio. N-Ethylmaleimide-insensitive and -sensitive phosphatidate phosphohydrolase activities were measured in three hepatic conditions characterized by regeneration and/or fibrosis: alcoholic liver disease in humans (regeneration and fibrosis) and rat livers after either acute CCl-4-induced injury (regeneration) or common bile duct ligation (fibrosis).
4. In patients with alcoholic liver disease, N-ethylmaleimide-insensitive phosphatidate phosphohydrolase activity was higher in cirrhotic biopsies (5.82±0.3 nmol of Pi min−1 mg−1 of protein, n = 19) than in non-cirrhotic biopsies (2.17 ±0.2, n = 23) or in wedge biopsies from healthy subjects undergoing routine cholecystectomy (2.16 ±0.5, n = 6). N-Ethylmaleimide-insensitive phosphatidate phosphohydrolase activity was unchanged in the 10 days after CCl4 treatment but increased progressively in common bile duct-ligated rats (e.g. day 28: ‘sham’ operation, 1.97 ±0.3, chronic bile duct ligation, 6.91 ±1.24 nmol of Pi min−1 mg−1 of protein). N-Ethylmaleimide-insensitive phosphatidate phosphohydrolase activity correlated closely with the degree of fibrosis in humans and rats. N-Ethylmaleimide-sensitive phosphatidate phosphohydrolase activity was unchanged after CCI4 treatment or common bile duct ligation and was not increased in cirrhotic livers.
5. Plasma membrane N-ethylmaleimide-insensitive phosphatidate phosphohydrolase increases in liver fibrosis but not regeneration. Stimulation of phosphatidate phosphohydrolase activity with its effect on the diacylglycerol/phosphatidate ratio may play a role in transduction of the fibrosis signal.
Effect of Acute Mild Hypoglycaemia on Counterregulatory Responses to Moderate Hypoglycaemia Induced Immediately Afterwards in Healthy Men
Authors: Moriarty K. T. , Simpson E. J. , Brown N. S. , MaCdonald I. A. , Tattersall R. B. 
Published: August 2015

1. This study was designed to determine whether a 1 h period of mild hypoglycaemia (33 or 3.7 mmol/l) affected the response to an episode of moderate hypoglycaemia (2.5 mmol/l) immediately afterwards.
2. Eleven non-obese healthy men (age 26 + 1 years, mean + SEM) underwent three separate 3 h hyperinsulinaemic glucose clamps in single-blind, random order. On all three occasions, blood glucose was 4.5 mmol/l for the first hour, and on a control visit was maintained at this level for the second hour. In the other two visits, blood glucose was lowered to 3.7 or 33 mmol/l during the second hour. In the third hour, blood glucose was lowered to 2.5 mmol/l on all three visits.
3. In the second hour, adrenaline rose significantly (P &lt;0.05, analysis of variance) with a blood glucose of 33 and 3.7 mmol/l, as did cortisol and heart rate at 33 mmol/l, but glucagon, prolactin, sweating rate, symptom score and blood pressure were the same during the second hour on all three visits.
4. In the final hour at 2.5 mmol/l, there were no differences in adrenaline, noradrenaline, glucagon, prolactin, cortisol, symptom score, heart rate, blood pressure or sweating rate.
5. Thus, the overall magnitude of hormonal responses to moderate hypoglycaemia (2.5 mmol/l) are not modified by exposure to mild hypoglycaemia (33 or 3.7 mmol/l) for 1 h immediately beforehand.
Cold-induced Increases in Erythrocyte Count, Plasma Cholesterol and Plasma Fibrinogen of Elderly People without a Comparable Rise in Protein C or Factor X
Authors: Neild Penelope J. , Syndercombe-Court Denise , Keatinge W. R. , Donaldson G. C. , Mattock M. , Caunce Maria 
Published: August 2015

1. Six elderly (66-71 years) and six young (20-23 years) subjects (half of each group women) were cooled for 2 h in moving air at 18°C to investigate possible causes of increased mortality from arterial thrombosis among elderly people in cold weather. Compared with thermoneutral control experiments, skin temperature (trunk) fell from 35.5 to 29.5°C, with little change in core temperature.
2. Erythrocyte count rose in the cold from 4.29 to 4.69 × 1012/l, without a change in mean corpuscular volume, indicating a 14% or 438 ml decline in plasma volume; increased excretion of water, Na+ and K+ accounted for loss of only 179 ml of extracellular water.
3. Plasma cholesterol and fibrinogen concentrations rose in the elderly subjects from 4.9 mmol/l and 2.97 g/l (control) to 5.45 mmol/l and 3.39 g/l in the cold, and in the young subjects from 3.33 mmol/l and 1.84 g/l (control) to 3.77 mmol/l and 2.07 g/l in the cold. Increases were significant for the elderly subjects, the young subjects and the group as a whole, except for cholesterol in the young subjects, and all were close to those expected from the fall in plasma volume.
4. Plasma levels of Protein C and factor X did not increase significantly in the cold in the elderly subjects, young subjects, or the group as a whole.
5. The results suggest that loss of plasma fluid in the cold concentrates major risk factors for arterial thrombosis, while small molecules, including protective Protein C, redistribute to interstitial fluid.
Increase in Muscle Nerve Sympathetic Activity in Humans after Food Intake
Authors: Fagius JAN , Berne Christian 
Published: August 2015

1. The influence of the intake of different nutrients on muscle nerve sympathetic activity was studied by use of microneurography. Muscle nerve sympathetic activity, heart rate, blood pressure and the insulin response were monitored for 90 min in 39 healthy, lean, normotensive subjects (mean age 26 years) who received 100 g of glucose in 300 ml of water (n = 8), 50 g of fat in 250 ml of water (n = 8), 100 g of lean meat corresponding to 40 g of protein with 250 ml of water (n = 8), 300 ml of water only (n = 7) or a mixed meal (1750 kJ) (n = 8).
2. All types of food evoked an increase in muscle nerve sympathetic activity whereas water caused no change. The increase in muscle nerve sympathetic activity was already significant at 15–30 min and was still strongly significant at 90 min. The effect of glucose was significantly greater than that of fat and protein; the mixed meal caused an intermediate response. Blood pressure changes were minor.
3. It is concluded that a sustained increase in muscle nerve sympathetic activity occurs regularly after any type of food intake. A rise in muscle nerve sympathetic activity takes place in the absence of an insulin response, and insulin contributes to only part of the increase after ingestion of glucose or a mixed meal. The muscle nerve sympathetic activity response is thought to be of importance for the redistribution of blood to the splanchnic region after a meal. Lack of this response is likely to explain postprandial hypotension in autonomic failure.
Atrial Natriuretic Factor Potentiates the Human Forearm Vasoconstrictor Response to Sympathetic Stimulation
Authors: Jansen Tim L. Th. A. , Smits Dr Paul , Lenders Jacques W. M. , Jacobs Marie-Cécile G. S. , Willemsen Jacques , Thien Theo 
Published: August 2015

1. Atrial natriuretic factor has been suggested to affect human sympathetic nervous system activity. The interaction between atrial natriuretic factor and the sympathetic nervous system has not been fully elucidated yet, but may occur at different sites. We studied this modulator effect at the level of the forearm vascular bed: the forearm vasoconstrictor response was examined after α-adrenergic sympathetic stimulation in healthy subjects during the loco-regional administration of atrial natriuretic factor, sodium nitroprusside and placebo. As a sympathetic stimulation test, the technique of the lower body negative pressure (–20 mmHg) was used.
2. Lower body negative pressure increased the forearm vascular resistance by +37 ± 8% during concomitant intra-arterial infusion of placebo (n = 10). During a predilator state achieved by infusion of atrial natriuretic factor (10 ng min−1 100 ml−1 forearm volume) into the brachial artery, lower body negative pressure subsequently induced a forearm vasoconstrictor response of +153 ± 22% (P &lt; 0.05 versus placebo), whereas this was +64 ± 14% when predilatation was achieved by infusion of an equipotent vasodilator dose of sodium nitroprusside (P &gt; 0.1 versus placebo; P &lt; 0.05 versus atrial natriuretic factor). The potentiation of the forearm vasoconstrictor response to lower body negative pressure by atrial natriuretic factor only occurred in the experimental and not in the contralateral arm. According to calculations on simultaneously sampled arterial and venous plasma catecholamine concentrations, the augmented forearm vasoconstrictor response seemed not to be caused by an increased release of noradrenaline.
3. In a second experiment (n = 10), we demonstrated that atrial natriuretic factor did not alter the forearm vasoconstrictor response to the intra-arterial administration of exogenous noradrenaline, thereby excluding a postsynaptic modulation by atrial natriuretic factor. In the presence of atrial natriuretic factor, the subsequent infusion of two dosages of noradrenaline (0.1 and 1.0 ng min−1 100 ml−1 forearm volume) increased the forearm vascular resistance by +118 ± 29% and +387 ± 79%, respectively, whereas these numbered +129 ± 18% and + 316 ± 41% when atrial natriuretic factor was replaced by an equipotent dose of sodium nitroprusside.
4. We conclude that atrial natriuretic factor potentiates the forearm vasoconstrictor response to α-adrenergic sympathetic stimulation in man, and that this effect may be located at the level of the forearm vascular bed. This potentiation cannot be explained by an increased vascular α-adrenergic sensitivity. More detailed studies are needed to analyse the effects of atrial natriuretic factor on local noradrenaline kinetics to elucidate influences on sympathetic neurotransmission.
Whole Body Protein Turnover in Chronically Undernourished Individuals
Authors: Soares M. J. , Piers L. S. , Shetty P. S. , Jackson A. A. , Waterlow J. C. 
Published: August 2015

1. Two groups of adult men were studied in Bangalore, India, under identical conditions: the ‘normal weight’ subjects (mean body mass index 20.8 kg/m2) were medical students of the institute with access to habitual energy and protein intakes ad libitum. The other group, designated ‘undernourished’, were labourers on daily wages (mean body mass index 16.7 kg/m2).
2. In an earlier study we obtained lower absolute values for both basal metabolic rate and protein synthesis in the undernourished subjects; however, when the data were expressed on a body weight or fat-free mass basis, a trend towards higher rates of protein synthesis, as well as higher basal metabolic rate, was evident. The suggestion was made that such results reflected the relatively higher energy intakes per kg body weight of the undernourished subjects on the day of study. The objective of the present study was therefore to control for the dietary intake during the measurement of whole body protein turnover.
3. In the present study dietary intakes were equated on a body weight basis; however, expressed per kg fat-free mass, the normal weight subjects had received marginally higher intakes of energy and protein. The results, however, were similar to those of the previous study. In absolute terms, basal metabolic rate, protein synthesis and breakdown were lower in the undernourished subjects. When expressed per kg body weight or per kg fat-free mass, the undernourished subjects had higher basal metabolic rates than the well-nourished subjects, whereas no differences were seen in the rate of protein synthesis or breakdown.
4. Estimates of muscle mass, based on creatinine excretion, indicated that the undernourished subjects had a higher proportion of non-muscle to muscle mass. Nitrogen flux (Q) was determined from 15N abundance in two end products, urea (Qu) and ammonia (Qa). The ratio Qu/Qa was increased in the undernourished subjects and was significantly correlated with the ratio of non-muscle to muscle mass (r = 0.81; P &lt; 0.005). These results fit in with our earlier suggestion of a greater proportion of non-muscle (visceral) mass in undernourished subjects.
5. The present data suggest that there are no changes in the rate of protein synthesis or breakdown in chronic undernutrition when results are expressed, conventionally, per kg fat-free mass. It can be theoretically shown, however, that there could be a 15% reduction in the rate of turnover of the visceral tissues in chronic undernutrition. This, together with the reduced urinary nitrogen excretion, would contribute to nitrogen economy in these individuals.
Impaired Renin Stimulation in Pre-Eclampsia
Authors: Brown Mark A. , Reiter Loretta , Rodger Alison , Whitworth Judith A. 
Published: August 2015

1. Pre-eclampsia is characterized by reduced plasma active renin concentration and renal prostacyclin production. The aim of this study was to determine whether the plasma active renin concentration could be stimulated in women with pre-eclampsia by intravenous frusemide, which stimulates renin acutely through a prostacyclin-mediated mechanism.
2. Plasma active renin concentration, plasma aldosterone concentration, haematocrit and urinary sodium, creatinine and 6-keto-prostaglandin F1α were measured before (0) and 15, 30 and 60 min after intravenous frusemide in 10 non-pregnant women, 10 normal pregnant women and nine women with pre-eclampsia. Six normal pregnant and six non-pregnant women underwent the same measurements after injection of 2ml of saline to control for effects of time and posture.
3. Baseline plasma active renin concentration (but not plasma aldosterone concentration) was lower in pre-eclamptic women [4.0 (1.7–6.2) pmol of angiotensin I h−1 ml−1; median (interquartile range)] than in normal pregnant women [6.7 (5.3–12.2) pmol of angiotensin I h−1 ml−1] (P &lt; 0.05). Baseline urinary 6-keto-prostaglandin F1α/creatinine ratio, urinary sodium excretion and fractional sodium excretion did not differ between normal pregnant and pre-eclamptic women.
4. After frusemide, plasma active renin concentration rose significantly in non-pregnant (P = 0.002) and normal pregnant (P = 0.008) women, but not in women with pre-eclampsia. Individual results showed stimulation in all non-pregnant and normal pregnant women but in only six out of nine pre-eclamptic women, significantly fewer than in normal pregnancy (P &lt; 0.05). The overall magnitude of the response of plasma active renin concentration to frusemide was blunted significantly in pre-eclamptic compared with normal pregnant women (P = 0.022).
5. Absolute and fractional sodium excretion and haematocrit rose significantly in all groups and the magnitude of change did not differ among groups for any of these parameters. The urinary 6-keto-prostaglandin F1α/creatinine ratio increased significantly only in non-pregnant women (P = 0.01), with variable individual responses in normal and hypertensive pregnant women.
6. This study shows that normal pregnant women exhibit natriuresis and stimulation of plasma renin after frusemide similar to that of non-pregnant women. However, pre-eclamptic women, as a group, have impaired renin stimulation after frusemide but a similar natriuresis to that of normal pregnant women. The mechanisms of these changes are unclear but are consistent with the notion of ‘exhausted’ renal renin in some women with pre-eclampsia.
Cyclosporin a and Vitamin D Metabolism: Studies in Patients with Psoriasis and in Rats
Authors: Shaw A. J. , Hayes M. E. , Davies M. , Edwards B. D. , Ballardie F. W. , Chalmers R. J. G. , Mawer E. B. 
Published: August 2015

1. Cyclosporin A, an immunosuppressive drug used to treat psoriasis, stimulates renal synthesis of 1,25-dihydroxyvitamin D in rats. 1,25-Dihydroxy vitamin D can also reduce the activity of psoriasis, and in the present study we have examined the possibility that cyclosporin A mediates some of its actions in psoriasis by renal or extra-renal production of 1,25-dihydroxyvitamin D.
2. Treatment of 12 psoriatic patients with cyclosporin A (5 mg day−1 kg−1) for 3 months significantly improved the psoriasis activity and severity index and reduced glomerular filtration rate, but serum 1,25-dihydroxyvitamin D levels were not changed. However, 1–3 months after stopping cyclosporin A treatment, an increase in the psoriasis activity and severity index score was accompanied by a small, but significant, increase in serum 1,25-dihydroxyvitamin D concentration. Plasma 1,25-dihydroxyvitamin D levels in rats gavaged with cyclosporin A (15 mg day−1 kg−1 for 2 weeks) were significantly increased compared with controls, but a lower dose of cyclosporin A (2.4 mg day−1 kg−1) had no effect. Renal 25-hydroxyvitamin D-24-hydroxylase activity in rat kidney homogenates was not different between control and cyclosporin A-treated rats. Renal 25-hydroxyvitamin D-1α-hydroxylase activity was not detectable in these homogenates. Extra-renal production of 1,25-dihydroxyvitamin D by activated macrophages isolated from the synovial fluid of patients with inflammatory arthritis was reduced after incubation with cyclosporin A (0.1–10 μmol/l) for 30 h or 5 days.
3. It is unlikely that alteration of circulating 1,25-dihydroxyvitamin D concentration is one of the modes of action of cyclosporin A in psoriasis. Since cyclosporin A inhibits 1,25-dihydroxyvitamin D production by activated synovial fluid macrophages, it is unlikely that cyclosporin A mediates some of its therapeutic actions by local synthesis of 1,25-dihydroxyvitamin D within the psoriatic lesion.
The Transplanted Human Kidney Does Not Achieve Functional Reinnervation
Authors: Hansen Jesper Melchior , Abildgaard Ulrik , Fogh-Andersen Niels , Kanstrup Inge-Lis , Bratholm Palle , Plum Inger , Strandgaard Svend 
Published: August 2015

1. Previous histological studies have demonstrated partial reinnervation of the human transplanted kidney. However, it remains unknown whether this reinnervation is of any functional significance.
2. The effects of noradrenaline infusion (2 μgh−1kg−1) and lower body negative pressure (−27 mmHg) on renal haemodynamics, sodium excretion and tubular function were investigated in 25 renal transplant recipients and 10 normal subjects. Sixteen of the transplant recipients had all been transplanted for more than 27 months, and nine had all been transplanted for less than 2 months.
3. After an overnight fast, the subjects were water-loaded, and clearance studies were performed with a 1 h baseline period, a 1 h period with noradrenaline infusion, another 1 h baseline period, and a final 1 h period with lower body negative pressure.
4. During noradrenaline infusion the relative decrease in effective renal plasma flow, glomerular filtration rate and clearance of lithium and sodium was significantly more pronounced in the long-term transplanted patients than in the control subjects.
5. Lower body negative pressure only depressed the glomerular filtration rate significantly in the control subjects. Further, the relative decrease in effective renal plasma flow and clearance of lithium and sodium was significantly greater in the control subjects than in the two groups of transplanted patients.
6. The present study thus demonstrated that in short- and long-term transplanted kidneys in man, supersensitivity to circulating noradrenaline and an inadequate response to lower body negative pressure was present. This strongly suggests that the human transplanted kidney remains functionally denervated.
Detection of Changes in Intrathoracic Fluid in Man Using Electrical Impedance Tomography
Authors: Campbell J. H. , Harris N. D. , Zhang F. , Morice A. H. , Brown B. H. 
Published: August 2015

1. The Sheffield electrical impedance tomography system produces information on changes in the distribution of resistivity within tissue. We report on the assessment of electrical impedance tomography in monitoring changes in lung resistivity during a fluid challenge in normal man.
2. Eight normal subjects were studied. Electrical impedance tomography recordings were made at three different lung volumes before, during and after the intravenous infusion of 1 litre of 0.9% NaCl (saline).
3. The mean fall in lung resistivity during the infusion was −22% at total lung capacity (range −10% to −28%), −24% at tidal breathing (−15% to −37%) and −11% at residual volume (-5% to −19%) (P &lt; 0.05 mean pre-infusion resistivity compared with the nadir value after infusion, Wilcoxon).
4. These changes in lung resistivity were probably due to a combination of a fall in haematocrit and an expansion of pulmonary blood volume.
Predictive Value of Soluble Immunological Mediators in Neonatal Infection
Authors: Edgar J. D. M. , Wilson D. C. , McMillan S. A. , Crockard A. D. , Halliday M. I. , Gardiner K. R. , Rowlands B. J. , Halliday H.L. , McNeill T. A. 
Published: August 2015

1. Infection in the neonatal period is difficult to diagnose and is a significant cause of morbidity and mortality in preterm infants.
2. We investigated prospectively the predictive value of plasma measurement of bacterial endotoxin (lipo-polysaccharide), tumour necrosis factor-α, interleukin-6, interleukin-8, intercellular adhesion molecule-1 and C-reactive protein in 60 consecutive newborn infants suspected of having neonatal infection. Plasma samples were taken at the time of acute clinical deterioration. Sixty-two cord blood samples were studied as controls taken at elective Caesarean section.
3. Forty-three infants had confirmed infections, 25 with positive blood cultures. Tumour necrosis factor-α and bacterial endotoxin levels were not significantly elevated over controls, whereas interleukin-6, interleukin-8 and intercellular adhesion molecule-1 levels were all significantly increased in the infected group compared with controls (all P &lt; 0.001).
4. Increased plasma intercellular adhesion molecule-1 levels were a highly sensitive (88%) indicator of clinical infection and were independent of C-reactive protein. Use of these two assays in combination improved the diagnostic sensitivity to 95% and gave a negative predictive value of 97%. Addition of interleukin-6 or interleukin-8 measurements failed to further significantly enhance the prediction of infection.
5. Measurement of intercellular adhesion molecule-1 level may have a clinical role in rapidly confirming, or predicting, the likely diagnosis in cases of suspected neonatal infection.