bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dentine is biochemically abnormal in osteogenesis imperfecta
Authors: Gage John P. , Francis Martin J. O. , Whitaker Gill E. , Smith Roger 
Published: August 2015

1. In osteogenesis imperfecta the bones are brittle but the teeth, whose dentine contains the same genetic collagen as bone (type I), may be clinically normal.
2. To investigate this paradox we have measured the amino acid composition of insoluble dentine collagen from 16 deciduous and 18 permanent teeth in control subjects and in 59 patients with different forms of osteogenesis imperfecta.
3. In 55 of the patient samples significant differences from normal were found, especially in the number of lysine residues, and in the relative amounts of hydroxylysine to lysine.
4. These results demonstrate the high frequency of biochemical abnormalities in osteogenesis imperfecta. They also suggest that classifications of this disorder based on the presence or absence of clinical dentiogenesis imperfecta are likely to be unsound.
Adenosine receptors in papilla of human kidneys
Authors: Woodcock Elizabeth A. , Leung Edward , Johnston Colin I. 
Published: August 2015

1. Adenylate cyclase activity in homogenates of human papillae was stimulated by adenosine agonist compounds.
2. The rank order of agonist potencies for stimulation was 5′-N-ethylcarboxamidoadenosine &gt; l-N6-phenylisopropyladenosine &gt; 2-chloroadenosine &gt; N6-cyclohexyladenosine &gt; d-N6-phenylisopropyladenosine. This order of agonist potencies is similar to that observed at adenylate cyclase-coupled A2-adenosine receptors in many different tissues.
3. The methylxanthines 8-phenyltheophylline and 1,3-diethyl-8-phenylxanthine acted as competitive antagonists, with 1,3-diethyl-8-phenylxanthine being approximately 10 times more potent than 8-phenyltheophylline.
4. This study demonstrates the presence of A2-adenosine receptors in the papilla of human kidney. These receptors are similar to adenosine receptors previously observed in the renal papillae of the rat in terms of both agonist and antagonist potencies.
Plasma extracellular superoxide dismutase and erythrocyte Cu, Zn-containing superoxide dismutase in alcoholics treated with disulfiram
Authors: Öhman Michael , Marklund Stefan L. 
Published: August 2015

1. Disulfiram has long been used in the treatment of chronic alcoholism. It is in vivo partially reduced to diethyldithiocarbamate, which is an efficient inhibitor of Cu, Zn-containing superoxide dismutase both in vitro and in vivo. The recently described extracellular superoxide dismutase is even more sensitive to diethyldithiocarbamate than Cu, Zn-superoxide dismutase.
2. To test for the possibility that long term treatment with disulfiram leads to inhibition of the superoxide dismutases, plasma extracellular superoxide dismutase and erythrocyte Cu, Zn-superoxide dismutase were determined in 12 disulfiram-treated alcoholics, and compared with 11 non-treated alcoholics and 19 healthy controls.
3. Plasma extracellular superoxide dismutase was moderately reduced (about 20%) in the disulfiram-treated alcoholics as compared with the non-treated alcoholics and the healthy controls. No effect of disulfiram treatment on erythrocyte Cu, Zn-superoxide dismutase activity was demonstrated.
Metabolic rate after massive weight loss in human obesity
Authors: Finer Nicholas , Swan Philip C. , Mitchell Fred T. 
Published: August 2015

1. Resting metabolic rate, measured by the ventilated hood technique in 11 obese subjects before weight loss was 6.5 ± 0.3 kJ/min, not significantly different from the value predicted by regression equations relating metabolic rate to body weight (established from measurements in 106 subjects).
2. After 34.5 kg mean weight loss, and during continued dieting, resting metabolic rate fell an average of 25% to 5.0 ± 0.18 kJ/min, significantly below that predicted for the new slimmed weight.
3. The fall in metabolic rate, over and above that expected from weight loss alone, suggests that the slimmed obese are hypometabolic compared with subjects of the same weight who have not lost weight.
4. The failure of the slimmed obese to maintain their weight loss is unlikely to be due solely to this excessive fall in resting metabolic rate, since they still had quantitatively higher energy expenditure than lean subjects.
Protein losing enteropathy associated with Nippostrongylus brasiliensis infestation and its impact on albumin homoeostasis in rats fed two levels of dietary protein
Authors: Lunn P. G. , Northrop C. A. , Behrens R. H. , Martin J. , Wainwright M. 
Published: August 2015

1. Alterations in plasma albumin concentration and gastrointestinal permeability have been investigated in rats infected with the nematode Nippostrongylus brasiliensis and fed adequate or low protein diets.
2. Infection caused only minor changes in growth and food consumption of well nourished rats but resulted in significant reductions in those fed the low protein diet.
3. Animals in both dietary groups were able to mount an immune response beyond day 10 postinfection (p.i.) which caused expulsion of the parasites, but this was less effective in rats fed the low protein food.
4. Uninfected rats fed the low protein diet had significantly lower plasma albumin concentrations than their well nourished counterparts. Animals of both dietary groups showed a progressive reduction in plasma albumin concentration as the infection developed but values returned towards normal as the parasites were expelled.
5. The reduction in plasma albumin concentration was closely associated with increases in gastrointestinal leakage of plasma protein but losses were far greater in the protein deficiency animals. Beyond day 10 p.i. protein loss decreased in both dietary groups and by day 21 p.i. had returned to normal in well nourished animals but not those fed the low protein diet.
6. Intestinal permeability measured by the lactulose:mannitol ratio technique gave similar results to the protein loss data. Permeability increased as the infection progressed then fell as the worms were expelled but remained above control values in infected protein deficient animals.
7. Overall, animals fed the low protein diet were more severely affected by the parasite than were their well fed counterparts. The data clearly demonstrated that the combined effects of infection and dietary deficiency resulted in a more severe reduction in plasma albumin values than either factor produced alone. The results are discussed with reference to the aetiology of hypoalbuminaemia and kwashiorkor in man.
Sympathetic reflex control of subcutaneous blood flow in patients with congestive heart failure
Authors: Kassis Eli , Amtorp Ole , Skagen Knud 
Published: August 2015

1. Central and local regulation of forearm subcutaneous vascular resistance (FSVR) during postural changes were studied in congestive heart failure (CHF). Blood flow was measured by the local 133Xe-washout technique. Nine patients with severe CHF (baseline angiographic ejection fraction, 23 ± 2%, mean ± sem; cardiac index, 2.2 ± 0.2 litres min−1 m−2; increased left ventricular pressures and dimensions) were compared with seven control subjects who had normal cardiac performance.
2. Baseline FSVR and plasma concentrations of noradrenaline and adrenaline were substantially higher in patients with CHF than control subjects. However, the patients, like control subjects, increased FSVR by 46 ± 3% in response to increase in local venous transmural pressure and disclosed a normal response to decrease in forearm perfusion pressure. Both responses to changes in vascular transmural pressure were preserved after either proximal nervous blockade or local β-receptor blockade.
3. Central sympathetic stimulation was induced with use of 45° upright tilt. Control subjects developed vasoconstriction (FSVR increased by 59 ± 5%), which was completely abolished after proximal nerve blockade. Patients with CHF developed vasodilatation (FSVR decreased by 24 ± 8%), which was not only abolished but reversed after proximal nerve blockade (FSVR increased by 22 ± 7%), probably owing to the increased humoral vasoconstrictor activity. The paradoxical vasodilator response to central sympathetic stimulation in these patients was reversed after local β-receptor blockade (FSVR increased by 19 ± 9%).
4. The local vasoconstrictor reflex responsiveness and intrinsic vascular reactivity were not affected by the augmented baseline sympathetic vasoconstrictor activity in patients with CHF. Central sympathetic stimulation seems to elicit a β-adrenergic reflex effect intended to improve perfusion of the subcutaneous tissue in these patients.
Effects of somatostatin, naloxone and prochlorperazine on the control of ventilation in man
Authors: Maxwell D. L. , Nolop K. B. , Hughes J. M. B. 
Published: August 2015

1. In seven normal subjects the ventilatory responses to progressive isocapnic hypoxia and hyperoxic hypercapnia were measured during rebreathing.
2. During an infusion of somatostatin (10 nmol/mm) the mean hypoxic response decreased by 66% (control: − 1.6 sd 1.2 litres min−1 %−1Sao2: somatostatin: − 0.6 sd 0.7) but the mean hypercapnic response was unchanged (control: 2.0 sd 0.8 litre min−1 mmHg−1; somatostatin: 2.3 sd 1.2). There was no change in resting V˙O2 or V˙CO2 during somatostatin infusion.
3. The opiate antagonist, naloxone (0.1 mg/kg, intravenously), caused little change in either response (mean hypoxic response: − 1.7 sd 1.0 litre min−1 %−1Sao2; mean hypercapnic response: 2.4 sd 0.9 litre min−1 mmHg−1).
4. In five of the subjects the dopamine antagonist, prochlorperazine (10 mg, intravenously), increased the mean hypoxic response by 134% (control: − 1.9 sd 1.4 litres min−1 %−1Sao2; after prochlorperazine: − 3.8 sd 1.6; P &lt; 0.05). The mean hypercapnic response after this drug was also increased (control: 2.1 sd 1.0 litre min−1 mmHg−1; after prochlorperazine: 3.1 sd 1.0) but this change did not achieve significance.
5. The selective effect of somatostatin on the hypoxic response, suggestive of an action on the carotid body, was not inhibited by prior injection of either naloxone or prochlorperazine, and its mode of action remains to be found.
Effects of mucosal removal on guinea-pig airway smooth muscle responsiveness
Authors: Murlas Christopher 
Published: August 2015

1. The contractile response to histamine, acetylcholine (ACh), KCl or electrical field stimulation (EFS) was examined in paired tracheal rings (one of each being denuded by mucosal rubbing), which were mounted in muscle chambers filled with a continuously aerated physiological salt solution at 37°C.
2. Removal of the respiratory mucosa increased the sensitivity of airway muscle to ACh, histamine and EFS, but not to KCl. The hypersensitivity of denuded rings to histamine and EFS was greater than to ACh. Atropine reduced the histamine hypersensitivity observed.
3. Pretreating intact preparations with indomethacin augmented their responsiveness to EFS, histamine and ACh.
4. Indomethacin augmentation of histamine- and EFS-induced responses was greater in preparations without epithelium.
5. We conclude that the airway mucosa may be associated with a factor that reduces airway smooth muscle responsiveness to stimulation.
Glucose oxidation rates in newborn infants measured with indirect calorimetry and [U-13Clglucose
Authors: Sauer P. J. J. , Van Aerde J. E. E. , Pencharz P. B. , Smith J. M. , Swyer P. R. 
Published: August 2015

1. Indirect calorimetry and primed constant infusion of [U-13C]glucose were combined in 16 appropriate-for-gestational age newborn, parenterally fed infants, in order to measure glucose utilization and glucose oxidation respectively.
2. Glucose intake ranged between 10.0 and 24.1 g day−1 kg−1 and energy intake between 156.9 and 439.3 kJ day−1 kg−1.
3. Glucose utilization (P &lt; 0.001), glucose oxidation (P &lt; 0.001) and metabolic rate (P &lt; 0.005) increased significantly with rising glucose intake.
4. The significant difference between glucose utilization and oxidation (P &lt; 0.001) can be accounted for by an increasing storage as fat.
5. As lipogenesis from glucose consumes 15-24% of the original glucose energy, the increasing metabolic rate accompanying rising glucose intake is probably due to increasing lipogenesis.
Cation transport abnormalities in vivo in untreated essential hypertension
Authors: Boon Nicholas A. , Aronson Jeffrey K. , Hallis Keith F. , Grahame-Smith David G. 
Published: August 2015

1. In order to study cation transport in vivo we have measured the changes in plasma and intra-erythrocytic rubidium concentrations after the oral administration of rubidium chloride.
2. In this paper we describe our findings in 22 patients with untreated essential hypertension, compared with the findings in 22 carefully matched control subjects. Our findings in patients receiving short-term digoxin therapy and in patients with chronic renal failure are also included for comparison.
3. Whereas the findings in patients receiving digoxin and in patients with chronic renal failure are compatible with a widespread reduction in sodium, potassium-ATPase activity in vivo, the findings in patients with untreated essential hypertension are not.
4. Further analysis of the data and a similar study of the disposition of 42K after the intravenous administration of 42KC1 suggest that in vivo net cation transport is enhanced in the erythrocytes of patients with untreated essential hypertension.
Lactulose 51Cr-labelled ethylenediaminetetra-acetate, l-rhamnose and polyethyleneglycol 500 as probe markers for assessment in vivo of human intestinal permeability
Authors: Maxton D. G. , Bjarnason I. , Reynolds A. P. , Catt S. D. , Peters T. J. , Menzies I. S. 
Published: August 2015

1. The urinary excretion of lactulose, 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA), l-rhamnose and polyethyleneglycol 400 (PEG-400) has been measured after intravenous and oral administration in healthy volunteers.
2. Intestinal permeation of the probes was compared after their ingestion in iso-osmolar, hyperosmolar and cetrimide-containing test solutions.
3. Urinary recovery of lactulose and 51Cr-EDTA after intravenous administration reached 75% by 5 h, and exceeded 90% at 24 h, and these values were 62 and 72%, respectively, for l-rhamnose. Recovery of PEG-400, however, varied with the relative molecular mass (Mr) of each polymer from 25.9 to 68.5% in 24 h.
4. Intestinal permeation of ingested lactulose and 51Cr-EDTA was low, but that of L-rhamnose was 45-fold, and that of PEG-400 100-fold, greater. Permeation of lactulose and 51Cr-EDTA was markedly increased by cetrimide and hyperosmolar stress, whereas that of l-rhamnose showed little change. PEG-400 permeation was not affected by cetrimide, but was slightly increased by hyperosmolar stress.
5. The 5 h permeation of lactulose, but not of l-rhamnose or PEG-400, correlated with that of 51Cr-EDTA (r = 0.98, P &lt; 0.001).
6. These findings are compatible with three distinct pathways of unmediated mucosal permeation, l-rhamnose (radius &lt; 0.4 nm) passing mainly through small aqueous ‘pores’ of high incidence, lactulose and 51Cr-EDTA (radius &gt; 0.5 nm) through larger aqueous ‘channels' of low incidence susceptible to cetrimide and hyperosmolar stress, and PEG-400, which has appreciable lipid solubility, by partition through cell membrane lipid as well as the aqueous ‘pores’.
Assessment of the sensitivity of leukaemic cells to cytotoxic drugs by bioluminescence measurement of ATP in cultured cells
Authors: Kuzmits Rudolf , Aiginger Paul , Müller Matthias M. , Steurer Günter , Linkesch Werner 
Published: August 2015

1. A short-term test in vitro is described, which can be used to detect resistance to cytostatic agents in leukaemic cells. Leukaemic cell suspensions were incubated with cytostatic agents and the resulting intracellular ATP concentrations were measured by a bioluminescence ATP assay.
2. There was a clear dose-effect relationship in acute leukaemia and chronic lymphocytic leukaemia cells for drugs used in the treatment of leukaemias. A good correlation was found between the ATP content of leukaemic cells and cell viability as determined by the trypan blue dye exclusion test.
3. Preliminary individual clinical correlations suggest a correlation between the chemosensitivity in vitro and the response patterns in vivo in leukaemia patients. This simple, fast and sensitive method may have application for determination of drug-induced cytotoxicity in leukaemic cells in vitro.
Evidence for extrarenal metabolism of 25-hydroxyvitamin D3 in man
Authors: Fraher L. J. , Adami S. , Papapoulos S. E. , Sudan H. L. , McGonigle R. J. , Parsons V. , O'Riordan J. L. H. 
Published: August 2015

1. Metabolites of vitamin D3 were measured in the circulation of four patients on chronic haemodialysis (three of whom were surgically anephric) before and during daily ingestion of 40000 i.u. of cholecalciferol.
2. Circulating 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] was measurable, but abnormally low before treatment; its circulating concentration rose in a substrate dependent manner when serum 25-hydroxyvitamin D3 (25-OHD3) increased, but the response was reduced when compared with the normal relationship.
3. Serum 1,25-hydroxyvitamin D3 [1,25-(OH)2D3] and calcidiol lactone (25-OHD3-lactone) were consistently unmeasurable in sera from these patients before administration of cholecalciferol. However, when serum 25-OHD3 rose with treatment, 1,25-(OH)2D3 became detectable in the sera of three of the four patients and 25-OHD3-lactone could be measured in all of them.
4. These data indicate that extrarenal sites of synthesis of 24,25-(OH)2D3, 25-OHD3-lactone and 1,25-(OH)2D3 exist in chronically dialysed patients but require large amounts of substrate to be significant.
Selective renal medullary damage and hypertension in the rat: The role of vasopressin
Authors: Russell G. I. , Godfrey N. P. , Forsling M. L. , Bing R. F. , Thurston H. , Swales J. D. 
Published: August 2015

1. The induction of selective renal medullary damage by 2-bromoethylamine hydrobromide (BEA) results in polyuria and raised blood pressure. In view of the likely elevation of plasma vasopressin we have investigated the role of vasopressin (AVP) in the elevated blood pressure in this model.
2. Plasma vasopressin levels in BEA pretreated rats were raised significantly (2 ± 0.6 pg/ml vs 0.8 ± 0.1 in normal rat, P &lt; 0.05) but not to pressor levels.
3. In addition, pressor responsiveness was investigated in renal medullary damaged rats. There was a reduced response to vasopressin and noradrenaline but no alteration with angiotensin II. A specific V1 receptor AVP antagonist [d(CH2)5Tyr(Me)AVP] produced no fall in blood pressure but returned the noradrenaline dose-response curve to normal. This suggests an interaction between vasopressin and the sympathetic nervous system in this model.
4. Thus there is no evidence that vasopressin contributes to the rise in blood pressure produced by chemical renal medullectomy and other mechanisms have to be sought.
Plasma noradrenaline in Goldblatt models of renovascular hypertension in the rat, before and after surgical reversal
Authors: Walker S. M. , Bing R. F. , Swales J. D. , Thurston H. 
Published: August 2015

1. Plasma noradrenaline (NA), blood pressure (BP) and heart rate (HR) were measured simultaneously in conscious rats under basal conditions in the early phase (4–6 weeks) of one-kidney, one-clip hypertension (1K1C), in the early (4–6 weeks) and chronic (&gt; 16 weeks) phases of the two-kidney, one-clip model (2K1C) and in age-matched loose clip control animals before and 2 days after unclipping.
2. The elevated BP in all three hypertensive groups fell to normal after unclipping, whereas removal of the constricting clip in loose clip controls had no effect on BP.
3. Plasma NA was elevated in 1K1C hypertension (P &lt; 0.05) and fell slightly but non-significantly on unclipping. However, in the early phase of 2K1C hypertension plasma NA was unaltered before and rose significantly (P &lt; 0.05) after unclipping. Plasma NA did not change with unclipping in the chronic phase of 2K1C hypertension and was not different from controls. Unclipping loose clip control animals produced no change in plasma NA.
4. Changes in HR on unclipping followed a similar pattern to changes in plasma NA: changes in the two variables were significantly correlated in all three models (1K1C: r = 0.61, P &lt; 0.005; early 2K1C: r = 0.45, P &lt; 0.05; chronic 2K1C: r = 0.62, P &lt; 0.01). However, BP was only correlated with plasma NA in 1K1C hypertension (r = 0.49, P &lt; 0.02) and not in either phase of the 2K1C model. There was also a highly significant correlation between HR and plasma NA in 1K1C hypertension (r = 0.71, P &lt; 0.001). The pattern of the changes in plasma NA and HR that occurred with reversal of 1K1C hypertension was significantly different from those in the early phase 2K1C model (P &lt; 0.05).
5. These data suggest that there is sympathetic nervous system (SNS) activation in the early phase of 1K1C hypertension, but provide no evidence for increased sympathetic activity in either the early or chronic phases of the 2K1C model. Neither do they support the hypothesis that the fall in BP with unclipping in this model is mediated by reduced SNS activity.
Altered extracellular calcium homoeostasis in essential hypertension: A consequence of abnormal cell calcium handling
Authors: Strazzullo P. , Galletti F. , Cirillo M. , Siani A. , Nunziata V. , Giannattasio R. , Mancini M. 
Published: August 2015

1. A number of abnormalities in the extracellular and intracellular handling of calcium in arterial hypertension, namely an increased urinary calcium excretion, a reduced serum ionized calcium level and an enhanced intracellular free calcium concentration, have previously been reported by this and other laboratories.
2. The present study aimed to investigate the handling of an exogenous calcium load in hypertensive and normotensive subjects in order to detect possible differences with regard to tissue calcium metabolism in vivo.
3. A constant rate intravenous calcium infusion (0.2 mmol 2 h−1 kg−1 body wt.) was carried out in the participants. Serum calcium concentrations were determined at regular intervals during the infusion and in the 4 h after the end of the calcium load. Over the same period, urinary calcium excretion was evaluated in timed urine collections.
4. Hypertensive subjects had lower serum ionized calcium levels compared with normotensive subjects at all the experimental points, a finding suggestive of a faster disappearance of calcium from the circulation. The total body calcium clearance, calculated from the area under the curve of the serum calcium concentrations, was enhanced in hypertensive patients (P &lt; 0.03).
5. Although the renal calcium excretion was higher in hypertension, the renal calcium clearance accounted for only a minor fraction of the total body clearance, suggesting that the reduced serum calcium levels achieved by the hypertensive patients were not explained by the renal calcium leak.
6. The enhanced total body calcium clearance found in hypertensive subjects is therefore due to an increased tissue calcium uptake. This finding provides indirect evidence of an altered cell calcium handling in hypertension.