bluuebunny/crossref_metadata_2025_split huggingface dataset:
Further studies on the activity and subcellular distribution of alanine: Glyoxylate aminotransferase in the livers of patients with primary hyperoxaluria type 1
Authors: Danpure Christopher J. , Jennings Patricia R. 
Published: August 2015

1. The activity of alanine:glyoxylate aminotransferase (AGT; EC 2.6.1.44) has been measured in the unfractionated livers of 20 patients with primary hyperoxaluria type 1 (PH1), three patients with other forms of primary hyperoxaluria and one PH1 heterozygote. The subcellular distribution of AGT activity was examined in four of the PH1 livers and in the liver of the PH1 heterozygote.
2. The mean AGT activity in the unfractionated PH1 livers was 12.6% of the mean control value. The activities of other aminotransferases and the peroxisomal marker enzymes were normal. When corrected for cross-over from glutamate:glyoxylate aminotransferase (GGT; EC 2.6.1.4), the mean AGT activity in the PH1 livers was reduced to 3.3% of the control values.
3. The livers from a patient with primary hyperoxaluria type 2 (d-glycerate dehydrogenase deficiency) and one with an undefined form of primary hyperoxaluria (possibly oxalate hyperabsorption) had normal AGT levels. The livers of a very mild PH1-type variant and a PH1 heterozygote had intermediate levels of AGT activity.
4. Subcellular fractionation of four PH1 livers by sucrose gradient isopycnic centrifugation demonstrated a complete absence of peroxisomal AGT activity. The subcellular distribution of the residual AGT activity was very similar to that of GGT activity (i.e. mainly cytosolic with a small amount mitochondrial). There were no alterations in the subcellular distributions of any of the peroxisomal marker enzymes. The subcellular distribution of AGT activity in the PH1 heterozygote liver was similar to that of the control (i.e. mainly peroxisomal).
5. The residual AGT activity in two of the PH1 livers, which could be accounted for largely by cross-over from GGT, was only slightly dependent on substrate (glyoxylate and alanine) concentration and virtually independent of cofactor (pyridoxal phosphate) concentration.
6. These data confirm our previous findings (C. J. Danpure & P. R. Jennings, FEBS Letters, 1986, 201, 20–24), but on a much larger number of patients, that AGT deficiency is pathognomic for PH1, and is not found in other forms of hyperoxaluria.
Ultrafiltration of renin in the mouse kidney studied by inhibition of tubular protein reabsorption with lysine
Authors: Mazanti Ingrid , Hermann Kirstine Lintrup , Nielsen Arne Høj , Poulsen Knud 
Published: August 2015

1. In order to study the role of the kidney in the elimination of endogenous plasma renin, renin was measured in the plasma and urine of female mice.
2. The renin concentration was two orders of magnitude lower in urine than in plasma, but it increased after intraperitoneal injection of submandibular mouse renin. No correlation between the plasma renin concentration and the urinary renin concentration and renin excretion rate could be demonstrated.
3. Blockade of the tubular reabsorption of proteins by intraperitoneal injection of the basic amino acid lysine increased the urinary renin concentration, renin excretion rate and renin clearance two to three orders of magnitude, without affecting the plasma renin concentration.
4. This finding demonstrates that ultrafiltered renin is reabsorbed almost completely in the renal tubules and that the mechanism most likely is the same as for other filtered proteins.
5. The large renal renin clearance obtained after intraperitoneal lysine is in accordance with a major role of the kidneys in the elimination of renin from the circulation, by a glomerular ultrafiltration and tubular reabsorption and metabolization of renin.
Quantity of anti-leucoprotease relative to α1-proteinase inhibitor in peripheral airspaces of the human lung
Authors: Kramps Johannes A. , Franken Claus , Dijkman Joop H. 
Published: August 2015

1. Peripheral airspaces were selectively lavaged using balloon-tipped catheters of 2 mm diameter.
2. Molar anti-leucoprotease/α1-proteinase inhibitor ratios as determined in these lavage fluids by enzyme immunoassays ranged from 0.02 to 0.14 (mean 0.08).
3. These data indicate that peripheral airspaces contain minor amounts of anti-leucoprotease relative to α1-proteinase inhibitor. This observation does not necessarily mean that anti-leucoprotease is of minor importance in protecting the lung interstitium.
Effect of gut-derived acetate on oral glucose tolerance in man
Authors: Scheppach W. , Cummings J. H. , Branch W. J. , Schrezenmeir J. 
Published: August 2015

1. Dietary fibre has a moderating impact on glucose metabolism. To test the hypothesis that this effect of fibre may be mediated by its breakdown product acetate, oral glucose tolerance tests were carried out in healthy volunteers with and without acetate.
2. Five subjects received 50 g of glucose orally while taking either acetate (15 mmol every 15 min) by mouth or chloride as control. Oral acetate made no detectable difference to glucose tolerance or to levels of free fatty acids, 3-hydroxybutyrate, lactate, insulin, glucagon and gastric inhibitory polypeptide.
3. The 50 g dose of glucose temporarily depressed acetate levels in blood. This was probably due to an interaction between glucose and acetate in the gastrointestinal lumen as the same effect was seen with 50 g of xylose in three subjects.
4. Plasma acetate concentrations were unaffected by 50 g of oral glucose in one subject when acetate was instilled into the sigmoid colon.
5. It is unlikely that the improvement of glucose tolerance by dietary fibre is mediated by acetate.
Contrasting plasma atrial natriuretic factor concentrations during comparable natriuresis with infusions of atrial natriuretic factor and saline in normal man
Authors: Richards A. Mark , Tonolo Giancarlo , Polonia Jorge , Montorsi Piero 
Published: August 2015

1. To explore the role of atrial natriuretic factor (ANF) in the response to an acute saline load, we compared plasma hormone and urinary electrolyte interrelationships during administration of ANF and saline. Plasma concentrations of ANF, renin, angiotensin II and aldosterone, together with urine volume and electrolytes, were measured during infusions of placebo, ANF [α-human ANF (99–126)] and 0.9% (w/v) NaCl solution in normal subjects under standardized conditions of diet and posture.
2. Saline loading and ANF infusions initially induced similar natriuresis and suppression of renin–angiotensin– aldosterone system activity in association with markedly disparate values of plasma ANF. Plasma ANF levels rose to two- and eight-fold placebo values with saline and ANF, respectively (P &lt; 0.001). Conversely, in the period after infusion plasma ANF values were similar while natriuresis differed significantly. Peak natriuresis lagged behind peak plasma ANF values with both stimuli.
3. ANF, but not saline, enhanced urinary excretion of calcium and magnesium. Saline, but not ANF, caused increased kaliuresis.
4. The data suggest that ANF makes only a minor contribution to natriuresis induced by saline challenge, although full confirmation of this point requires quantification of end-organ responses to endogenous ANF in the face of changing arterial pressure and circulating volume.
Haemodynamic effects of physiological concentrations of circulating noradrenaline in man
Authors: Chang Peter C. , Kriek Eugene , Van Der Krogt Jacques A. , Blauw Gerard-Jan , Van Brummelen Peter 
Published: August 2015

1. To define the role of circulating noradrenaline in cardiovascular regulation, threshold concentrations for haemodynamic effects were determined in arterial and venous plasma of eight healthy volunteers.
2. Five doses of noradrenaline, 0–54 ng min−1 kg−1, were infused intravenously in random order and single-blind for 15 min per dose. Changes in intra-arterial blood pressure, heart rate, forearm blood flow and forearm vascular resistance were determined, and plasma noradrenaline was measured in arterial and venous blood samples.
3. Significant increases in systolic and diastolic blood pressure were found at arterial and venous plasma noradrenaline concentrations (means ±sem) of 3.00 ± 0.23 and 1.35 ±0.12 nmol/l, respectively. A significant decrease in heart rate was found at arterial and venous plasma noradrenaline concentrations of 8.99 ± 0.69 and 3.09 ± 0.60 nmol/l, respectively. The lower doses of noradrenaline tended to increase forearm blood flow and to decrease forearm vascular resistance, whereas the higher doses had no consistent effect on forearm haemodynamics.
4. During the noradrenaline infusions 73 ± 5% of the increase in arterial plasma noradrenaline concentration was extracted in the forearm.
5. The venous plasma noradrenaline threshold concentration was found to be much lower than previously reported. It is concluded that arterial and venous plasma noradrenaline concentrations which are readily encountered in physiological circumstances elicit haemodynamic effects.
Measurement of the transfer of the nitrogen moiety of intestinal lumen glutamic acid in man after oral ingestion of l-[15N]glutamic acid
Authors: Johnson A. W. , Berrington J. M. , Walker I. , Manning A. , Losowsky M. S. 
Published: August 2015

1. The measurement of the intestinal metabolism of the nitrogen moiety of glutamic acid has been investigated by oral ingestion of l-[15N]glutamic acid and sampling of arterialized blood.
2. Measurements have been made in six normal adults weighing an average of 72.8 kg ingesting 100 mg of l-[15N]glutamic acid after an overnight fast.
3. Measurement of the enrichment of arterial glutamic acid, glutamine and alanine was by gas chromatography–mass spectrometry. Isotopic enrichment of the amino acids was followed for 150 min after the ingestion of the amino acid.
4. Arterialized venous blood amino acid concentrations, measured by h.p.l.c., demonstrated no significant changes during the course of the experiment.
5. From the observed appearance of label in arterialized glutamic acid, alanine and glutamine, little luminal glutamic acid reaches the extracellular pool. The majority of the administered nitrogen label appears in the arterial alanine and glutamine components.
Cyclosporin-induced hypomagnesaemia and renal magnesium wasting in rats
Authors: Wong Norman L. M. , Dirks John H. 
Published: August 2015

1. Twenty-four hour clearance studies were performed on three groups of rats to determine the hypomagnesaemic effect of cyclosporin. Group I rats served as controls, whereas group II rats received 10 mg of cyclosporin/kg and group III rats received 20 mg of cyclosporin/kg daily.
2. After 7 days of cyclosporin treatment, plasma magnesium concentration was 1.04 ±0.01 mmol/l in control rats compared with 0.85 ±0.01 mmol/l in group II and 0.81 ±0.02 mmol/l in group III. After 14 days of cyclosporin administration, group III rats developed severe hypomagnesaemia (0.67 ± 0.01 mmol/l). This reduction in plasma magnesium was associated with an increase in the urinary excretion of magnesium.
3. This reduction in plasma magnesium and increment in magnesium excretion returned to normal 7 days after cessation of treatment.
4. Additional three-phase acute clearance experiments were performed on eight normal and 12 cyclosporin-treated rats (20 mg/kg). These animals were subjected to acute magnesium chloride infusion. After graded magnesium chloride infusion, despite a similar rise in plasma magnesium, the fractional magnesium excretion was significantly higher in the cyclosporin-treated animals.
5. Analysis of the fractional intestinal absorption of magnesium suggested that the development of hypomagnesaemia after cyclosporin treatment is due to magnesium loss by the kidney. Furthermore, this effect of cyclosporin on magnesium transport is only present during cyclosporin treatment and is reversible when treatment with cyclosporin is withdrawn.
Lithium clearance and renal tubular sodium handling during acute and long-term nifedipine treatment in essential hypertension
Authors: Bruun Niels Eske , Ibsen Hans , Skøtt Peter , Toftdahl Dorthe , Giese Jørn , Holstein-Rathlou Niels Henrik 
Published: August 2015

1. In two separate studies the lithium clearance method was used to evaluate the influence of acute and long-term nifedipine treatment on renal tubular sodium reabsorption.
2. In the acute study, after a 4 week placebo period two doses of 20 mg of nifedipine decreased supine blood pressure from 155/101 (20.6/13.5) ± 11/4 (1.5/0.5) to 139/88 (18.5/11.7) ± 16/9 (2.1/1.2) mmHg (kPa) (means ± sd; P &lt; 0.01). Lithium clearance, glomerular filtration rate and sodium clearance did not change. Therefore the calculated values of absolute proximal and absolute distal sodium reabsorption rates were also unchanged, as were potassium clearance, urine flow and body weight.
3. In the long-term study, lithium clearance, glomerular filtration rate, sodium clearance, potassium clearance, urine flow and body fluid volumes were measured after a 4 weeks placebo period and after 6 and 12 weeks of nifedipine treatment. As compared with placebo, mean supine blood pressure decreased significantly. The glomerular filtration rate did not change but lithium clearance fell by 30%. Consequently, the absolute and the fractional proximal sodium reabsorption increased significantly. The fractional distal sodium reabsorption did not change. Sodium clearance, fractional sodium excretion, potassium clearance, plasma volume and extracellular fluid volume were also unchanged.
4. In conclusion, we found no changes of renal tubular sodium reabsorption during acute nifedipine treatment, whereas long-term nifedipine treatment caused a redistribution of tubular sodium reabsorption without a change in overall sodium excretion or body fluid compartments.
Alanylglutamine reduces muscle loss of alanine and glutamine in post-operative anaesthetized dogs
Authors: Roth Erich , Karner Josef , Ollenschläger Günter , Karner Judith , Simmel Annette , Fürst Peter , Funovics Josef 
Published: August 2015

1. The present study examined the effect of an infusion of the dipeptide alanylglutamine or of the corresponding amino acids alanine and glutamine in equimolar amounts (10 μmol min−1 kg−1) on the canine hindlimb exchange of alanine and glutamine in the post-operative anaesthetized dog. In contrast to glutamine, the dipeptide alanylglutamine is stable in aqueous solution and therefore would be a suitable substrate for parenteral nutrition.
2. The infusion of alanylglutamine increased (a) the arterial concentration of alanylglutamine to a plateau level (120 ± 9.5 μmol/l, mean ± sem) 20 min after start of the infusion, (b) the mean arterial alanine concentration from 761 ± 42 to a plateau of 1500–1700 μmol/l (P &gt; 0.01) and (c) the arterial glutamine concentration from 407 ± 51 to a plateau of 1050–1500 μmol/l (P &gt; 0.01). Alanine and glutamine levels were slightly higher (14% and 26%, respectively, NS) in the group receiving the equimolar amount of alanine and glutamine.
3. Infusion of alanylglutamine for 1 h abolished the net efflux of glutamine (from −0.80 ± 0.1 to −0.03 ± 0.2 μmol min−1 kg−1; P &gt;0.05) and invoked a net influx of alanine (from −0.50 ± 0.19 to + 0.27 ± 0.14 μmol min−1 kg−1; P &gt; 0.01). These changes were similar to those achieved when the two amino acids were infused.
4. This study demonstrates that during short-term administration of alanylglutamine or of the corresponding amino acids the nitrogen release from the hindlimb of the anaesthetized post-operative dog via alanine and glutamine is reduced.
Determinants of the serum concentration of 1,25-dihydroxyvitamin D in primary hyperparathyroidism
Authors: Lalor B. C. , Mawer E. B. , Davies M. , Lumb G. A. , Hunt L. , Adams P. H. 
Published: August 2015

1. The serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 44 patients with primary hyperparathyroidism.
2. In 14 patients the serum concentration of 1,25-dihydroxyvitamin D was greater than normal (142–337 pmol/l). One patient had a subnormal concentration of 1,25-dihydroxyvitamin D (36 pmol/l) but no other evidence of vitamin D deficiency.
3. The possible biological determinants of the serum concentration of 1,25-dihydroxyvitamin D were sought by multivariate analysis of relevant variables. The serum concentration of 1,25-dihydroxyvitamin D was found to be significantly and positively correlated with the serum concentrations of 25-hydroxyvitamin D (P &lt; 0.001) and parathyroid hormone (P &lt; 0.003), and with the glomerular filtration rate (P &lt; 0.03), and negatively correlated with the serum concentrations of calcium (P &lt; 0.02) and phosphate (P = 0.055) (multiple R = 0.638,P &lt; 0.002).
4. In primary hyperparathyroidism the major determinant of serum 1,25-dihydroxyvitamin D is the availability of precursor 25-hydroxyvitamin D.
5. The finding that serum 1,25-dihydroxyvitamin D is commonly normal in patients with primary hyperparathyroidism despite an adequate state of vitamin D nutrition, can be explained in terms of the constraining influences of hypercalcaemia and variable degrees of renal dysfunction on the biosynthesis of 1,25-dihydroxyvitamin D.
Paradoxical effect of respiration on ventricular rate in atrial fibrillation
Authors: Rawles John M. , Pai G. R. , Reid Susan R. 
Published: August 2015

1. In 50 subjects with atrial fibrillation we have attempted to demonstrate variation of ventricular rate with respiration, as evidence of cardioregulatory reflex activity.
2. The electrocardiogram was recorded for 3 min during spontaneous respiration. The presence of respiratory variation of R-R intervals was analysed by multiple regression against a cosine function (cosinor analysis), making it possible to determine the phase of respiration when the intervals were longest.
3. Variation in ventricular rate with respect to respiration was demonstrated (P &lt; 0.05) in seven (14%) cases. On average, R-R intervals were longest at the end of inspiration; this contrasts with sinus rhythm where P-P, P-R and R-R intervals are longest around the time of end-expiration.
4. These results suggest that in atrial fibrillation the beat-to-beat ventricular rate may be under the influence of cardioregulatory reflexes, but the effect of respiration is weak and paradoxical.
Human whole-blood granulocyte aggregation in vitro
Authors: Fisher T. C. , Belch J. J. F. , Barbenel J. C. , Fisher A. C. 
Published: August 2015

1. Aggregation assays are a commonly used technique for the study of granulocyte activation. These studies are usually performed using a pure cell suspension in buffer. This necessitates a separation procedure which is time-consuming and may modify the function of the cells. Interaction between different cell types is precluded.
2. To avoid these disadvantages a method was developed which quantifies granulocyte aggregation in whole blood. Samples drawn from an incubated vessel before and after the addition of a chemotactic stimulus were fixed with formaldehyde to prevent disaggregation. Erythrocytes were then removed by chemical lysis and using an electronic cell-sizing device the number of single cells and aggregates could then be easily measured.
3. Results from a group of volunteers showed a rapid and reversible response to a chemotactic tripeptide, with a fall in single granulocyte count and the appearance of doublets and triplets. Lymphocytes were unaffected. Intra-assay reproducibility was better than ± 5%.
4. Using this assay, a significant elevation in aggregability was observed in blood from patients after acute myocardial infarction.
5. This novel technique, by avoiding the separation step, is faster, simpler and more physiological than previous methods, and as such is useful for both assays of drug action in vitro and the study of cell activation in disease states.
Effects of hypoxia and hypercapnia on atrial natriuretic factor and plasma renin activity in conscious dogs
Authors: Clozel Jean-Paul , Saunier Claude , Hartemann Denise , Allam Mustapha , Fischli Walter 
Published: August 2015

1. The aim of the present study was to assess the effects of hypercapnia or hypoxia on plasma concentrations of atrial natriuretic factor (ANF) in conscious unrestrained dogs.
2. For this purpose, chronically instrumented dogs were exposed in a random order to either room air, or to an atmosphere containing 21% O2/10% CO2/69% N2 to produce hypercapnia, or 10% O2/3% CO2/87% N2 to produce hypoxia without respiratory alkalosis.
3. Plasma concentrations of ANF did not change significantly during hypoxia.
4. In contrast, during hypercapnia, plasma concentrations of ANF increased by more than 100% and returned to baseline at the end of hypercapnia.
5. Hypercapnia, but not hypoxia, induced an increase in left atrial and central venous pressures.
6. We conclude that hypercapnia increases plasma ANF concentration, and that this increase may be secondary to an increase of the left and right atrial pressures. These phenomena may explain the increase in diuresis and natriuresis which has been described during hypercapnia.
Multi-organ damage resulting from experimental faecal peritonitis
Authors: Tighe D. , Moss R. , Boghossian S. , Heath M. F. , Chessum B. , Bennett E. D. 
Published: August 2015

1. Using specific-pathogen-free New Zealand White rabbits, we have compared the effects of faecal peritonitis over a period of 5 h in eight test animals with eight controls in which a sham operation was performed.
2. There was morphological damage to lungs, liver and spleen of test animals. Lung capillaries and sinusoids of the liver showed occlusion by cell debris and leucocytes, with endothelial damage. The lungs also showed alveolar epithelial disruption, basement membrane exposure and type II pneumocytes lacking lamellar bodies. In the liver there was fibrin deposition and swollen Kupffer cells. The spleen showed degranulating neutrophils, fibrin deposits, platelet aggregates and activated macrophages, with no damage to the endothelium.
3. There was no morphological damage to the kidney or heart of test animals or to any organs of sham-operated animals.
4. There were mixed anaerobes and aerobes in faecal material used to induce peritonitis. Cultures of liver, spleen and kidney isolated four different types of micro-organisms. Blood cultures showed two types of micro-organisms. Cultures of lung and heart showed one type of micro-organism.
5. The presence of micro-organisms in an organ could not be correlated with the degree of histological damage to that organ.
6. In test animals an early significant reduction in circulating leucocytes and platelets was sustained for the duration of the experiment with significant diffuse intravascular coagulation.
7. There was no change in test animal neutrophil adhesiveness until 120 min, when significant reduction was observed.
8. Serum phospholipase A2 (EC 3.1.1.4) activity in the test group showed a threefold increase at 300 min.