bluuebunny/crossref_metadata_2025_split huggingface dataset:
Purine Metabolism and Immunodeficiency: Urinary Purine Excretion as a Diagnostic Screening Test in Adenosine Deaminase and Purine Nucleoside Phosphorylase Deficiency
Authors: Simmonds H. Anne , Sahota A. , Potter Catherine F. , Cameron J. S. 
Published: August 2015

1. We have compared urinary purine excretion by two different methods in three separate paediatric disorders of purine metabolism: purine nucleoside phosphorylase deficiency, adenosine deaminase deficiency and adenine phosphoribosyltransferase deficiency.
2. The abnormal purines identified in each case were specific for the defect and directly related to it: adenine in adenine phophoribosyltransferase deficiency; the abnormal nucleosides inosine, guanosine and their corresponding deoxyribosides in purine nucleoside phosphorylase deficiency; deoxyadenosine in adenosine deaminase deficiency, the latter having previously been identified erroneously as adenine after degradation in the acidic conditions used.
3. Deoxyriboside excretion was specific for the two defects associated with immunodeficiency; adenine for adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadenine urolithiasis. The results obtained by a quantitative method were reflected in a simple rapid qualitative technique, isotachophoresis of the urine.
4. Purine overexcretion (principally inosine) was evident only in purine nucleoside phosphorylase deficiency, which emphasizes the importance of hypoxanthine salvage for the overall control of purine production in man. In none of these disorders was any inhibition of pyrimidine biosynthesis as reflected by oroticaciduria noted. Orotic acid excretion was within normal limits in all cases.
5. From these results it is suggested that the associated immunodeficiency in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency relates directly to the intracellular accumulation of 2′-deoxyribosides and not indirectly to an inhibitory effect on pyrimidine metabolism.
Effect of Blood Transfusion on the Carbon Monoxide Transfer Factor of the Lung in Man
Authors: Clark Elizabeth H. , Woods R. L. , Hughes J. M. B. 
Published: August 2015

1. Ten studies were performed on nine patients with haematological disorders but with normal lungs, who required intermittent blood transfusions. The transfer factor for carbon monoxide and uptake of carbon monoxide per unit lung volume (KCO) were measured with the single breath technique before and at various intervals after transfusion.
2. The mean haemoglobin concentration increased from 7·7 to 11·1 g/dl.
3. The TLCO increased according to a formula based on the Roughton & Forster (1957) diffusion equations, TLCO (standardized) = TLCO (observed). (10·2 + Hb)/1·7 Hb, where haemoglobin (Hb) is expressed as g/dl.
4. The correlation between measured and predicted values was slightly better if changes in alveolar volume were taken into account, by using the KCO value.
The Nature of Inactive Renin in Human Plasma and Amniotic Fluid
Authors: Shulkes A. A. , Gibson R. R. , Skinner S. L. 
Published: August 2015

1. The properties of inactive and active renin in human plasma and amniotic fluid were studied chromatographically. Activation was achieved at pH 3.3 with and without added pepsin.
2. Acid activation of renin was time- and temperature-dependent but was inhibited by dilution of the sample. The dilution effect was corrected by adding pepsin. Such characteristics indicate that activation at low pH is catalysed by intrinsic enzymes.
3. Separation and/or dilution of the activating enzyme during ion-exchange chromatography concealed the eluted position of inactive renin and reduced the amount recovered. Only after full activation of the eluted renin was achieved with added pepsin was a distinct peak of inactive renin exposed.
4. At pH 7.5 inactive renin carried a lower negative charge than the active enzyme. This charge difference was lost after activation.
5. No molecular-weight differences between active, inactive renin or the International Renin Standard were detected by gel filtration. No renin of larger molecular weight was present.
6. These findings will be helpful in purification studies of human inactive renin.
Catecholamines in Peripheral Venous Plasma in Patients on Chronic Haemodialysis
Authors: McGrath B. P. , Ledingham J. G. G. , Benedict C. R. 
Published: August 2015

1. Concentrations of noradrenaline and adrenaline from peripheral venous plasma were measured after 60 min of supine rest in 55 patients on chronic haemodialysis (including six anephric patients) and in 18 normal subjects. In the patients, plasma catecholamine measurements were related to concurrent measurements of blood pressure, pulse rate, plasma renin activity, plasma angiotension II, blood volume and sulphate space.
2. Mean resting peripheral venous plasma noradrenaline concentration was higher by almost twofold, but mean resting plasma adrenaline concentration was lower, in the 49 non-nephrectomized patients than in the normal subjects. In the six anephric patients, resting peripheral venous plasma noradrenaline concentrations were similar to those of normal subjects.
3. Mean resting plasma noradrenaline concentrations in peripheral venous blood were similar in normotensive and hypertensive non-nephrectomized patients; mean plasma adrenaline concentration was higher in the hypertensive patients. A positive correlation was found between plasma adrenaline and plasma renin activity but not between plasma noradrenaline and plasma renin activity.
4. Resting concentrations of both catecholamines were positively correlated with resting pulse rate and inversely related to blood volume.
5. After renal transplantation resting peripheral venous plasma noradrenaline concentrations were normal in eight patients in whom high values had been recorded whilst on chronic haemodialysis.
6. In response to 40° of head-up tilt, plasma noradrenaline increased significantly in six non-nephrectomized patients, whether sodium replete or depleted, and the changes observed in both these states were similar to those of 14 normal subjects studied on a normal diet.
7. Diastolic blood pressure increased on standing in the majority (41/55) of patients: in only four patients was there a fall in diastolic pressure of more than 5 mmHg in the erect position and in two of these blood volumes were low.
8. The cause of increased peripheral plasma noradrenaline concentrations in haemodialysis patients is uncertain.
Impaired Skeletal Muscle Vasomotor Response to Infused Noradrenaline in Baboons with Obstructive Jaundice
Authors: Bomzon L. , Wilton P. B. , McCalden T. A. 
Published: August 2015

1. We have measured muscle blood flow by a 133Xe clearance technique, and its response to noradrenaline in baboons before and 2 weeks after ligation of the bile ducts when they were jaundiced.
2. In the normal baboons, the response to noradrenaline was a dose-dependent decrease in muscle blood flow.
3. Bile-duct ligation caused no significant alteration in skeletal muscle blood flow but the response to noradrenaline in the jaundiced baboons was significantly attenuated. This effect was not observed in four sham-operated baboons.
Revised Standards for Normal Resting Dead-Space Volume and Venous Admixture in Men and Women
Authors: Harris E. A. , Seelye Eve R. , Whitlock R.M.L. 
Published: August 2015

1. Data have been combined from three previous series to provide revised standards for the prediction of physiological dead-space volume (VD), arterial oxygen tension (Pa,o2), alveolar-to-arterial oxygen-tension difference (Pa,o2 - Pa,o2) and venous admixture fraction (Q̇va/Q̇t) in the sitting position.
2. These standards, based on measurements in 96 healthy men and women aged from 20 to 74 years, largely confirm conclusions drawn from the first series of 48 subjects.
3. VD is best predicted on age, height, tidal volume and the reciprocal of respiratory frequency. Pa,o2, (Pa,o2 - Pa,o2) and Q̇va/Q̇t are adequately predicted on age alone.
Metabolism of Intact and Desialylated α1-Antitrypsin
Authors: Jones E. A. , Vergalla J. , Steer C. J. , Bradley-Moore P. R. , Vierling J. M. 
Published: August 2015

1. To study the metabolism of α1-antitrypsin in man, radioiodinated purified α1-antitrypsin of protease inhibitor type MM was injected intravenously into seven normal volunteer subjects of protease inhibitor type MM and plasma and urine radioactivity data were analysed. The purified glycoprotein inhibited trypsin and exhibited micro-heterogeneity characteristic of α1-antitrypsin on acid starch-gel electrophoresis.
2. The intravascular mass was 116 ± 16.1 mg/kg (mean ± sem); extravascular/intravascular pool ratio was 1.07 ± 0.067; the fractional catabolic rate was 33.3 ± 1.37% of the intravascular pool/day; half-life was 4.6 ± 0.21 days; synthetic rate was 33.8 ± 6.3 mg day−1 kg−1.
3. The data indicated that the serum concentration of α1-antitrypsin varies independently of its fractional catabolic rate and that it is catabolized in, or in close relationship to, the intravascular compartment.
4. Plasma curves of protein-bound radioactivity were also defined after the intravenous administration of 131I-labelled desialylated α1-antitrypsin to two additional subjects. The fractional plasma disappearance rates were approximately 150 times as great as those for the intact protein. The rapid disappearance of 131I-labelled desialylated α1-antitrypsin from plasma coincided with an equally rapid uptake of radioactivity by the liver.
5. The results are compatible with the existence of receptor sites for desialylated glycoproteins in the surface membrane of human hepatocytes and emphasize that the catabolism of α1-antitrypsin can be influenced by the structure of its carbohydrate moiety.
Peptide Excretion in Experimental Fanconi Syndrome in the Rat
Authors: Asatoor A. M. , Bending M. R. , Milne M. D. 
Published: August 2015

1. A study has been made of urinary peptide output in rats before and after production of a Fanconi syndrome induced by a single injection of sodium maleate. There was an unequivocal increase of urinary peptides on the first and second days after the injection, without any detectable change in the concentration of plasma peptides.
2. Similar results were obtained in osteolathyritic rats in which skeletal lesions had been produced by ingestion of β-aminopropionitrile.
3. The fractional amino acid content of urinary peptides after maleate and β-aminopropionitrile is shown to be significantly different from that in control animals.
4. Evidence is presented that the increased output of peptides is mainly due to increased renal clearance similar to that previously described for amino acids, glucose and several electrolytes in this type of experimental Fanconi syndrome.
Intestinal Cholecalciferol Absorption in the Elderly and in Younger Adults
Authors: Barragry J. M. , France M. W. , Corless D. , Gupta S. P. , Switala S. , Boucher B. J. , Cohen R. D. 
Published: August 2015

1. A method for assessing cholecalciferol absorption in man is described.
2. The intestinal absorption of [3H]cholecalciferol was studied in 20 female geriatric patients, most of whom were vitamin D-depleted.
3. The plasma [3H]cholecalciferol response after oral ingestion was significantly lower than that of a group of younger female subjects.
4. The plasma response of labelled polar metabolites of cholecalciferol was also lower in the geriatric than in the younger group, suggesting that increased removal of label by conversion into more polar metabolites could not account for the reduced plasma [3H]cholecalciferol response.
5. There was no evidence that alteration in gastrointestinal motility could account for the different rate of appearance of the labelled vitamin in the plasma in the two groups.
6. It is suggested that there is a defect in intestinal absorption of cholecalciferol in the elderly.
Post-Mortem Migration of Bone-Seeking Radionuclides in the Rat and Rabbit and its Effect on Estimates of Bone Uptake
Authors: Tothill P. , MaCpherson J. N. 
Published: August 2015

1. The continued uptake of 18F, 85Sr and 47Ca by bone after death has been studied in rats and rabbits after aortic injection followed by quick killing, a period of recirculation of tracer before death, and perfusion of the carcase. In each case an approximately linear increase of bone radioactivity was observed during a period of 1 h at about the same rate. The proportionate increase depended on the initial concentration of bone-seeking nuclide, ranging from a factor of 1.5 to 4.5. Boiling the carcase did not increase the migration rate.
2. Delay between death and dissection may therefore lead to spuriously high bone concentrations of these radionuclides, leading to overestimates of bone uptake, extraction ratio or bone blood flow.
Abnormalities of Renal Transport of Sodium o-[131I]Iodohippurate (Hippuran) in Essential Hypertension
Authors: Reeve J. , Crawley J. C. W. , Goldberg A. D. , Kennard Cherry , Kenny D. , Smith I. K. 
Published: August 2015

1. Renal function has been studied in 312 hypertensive patients by quantitative renography with sodium o-[131I]iodohippurate (131I-labelled Hippuran) and estimation of overall effective renal plasma flow. In 59% of the patients the results were normal.
2. Severe hypertension was associated not only with reduced effective renal plasma flow but also a characteristic abnormality of Hippuran transport in 10% of the patients in which there was a wider than normal variation in transit times of Hippuran through the kidney, which may reflect non-uniformity of reabsorption of filtrate by different groups of nephrons.
3. Plasma renin activity was higher in a group of 14 patients with multimodal transit time spectra than in a matched hypertensive control group, with very substantial overlap between the two groups.
4. The renographic abnormality was usually reversed by treatment.
Effect of Unconjugated and Conjugated Phenol and Uraemia on the Synthesis of Adenosine 3′:5′-Cyclic Monophosphate in Rat Brain Homogenates
Authors: Turner G. A. , Wardle E. N. 
Published: August 2015

1. The effects of phenol and phenyl glucuronide on the responses of normal rat brain adenyl cyclase to noradrenaline and dopamine have been investigated. Neurotransmitter responses have also been examined in brains from uraemic and normal rats.
2. A depressive effect of phenol on the adenosine 3′: 5′-cyclic monophosphate response of the neostriatum to dopamine was shown to be completely abolished if the toxin was present in the conjugated form; the response of the cortex to noradrenaline was stimulated by the presence of phenyl glucuronide, even though the unconjugated form had no effect.
3. The uraemic state in the rat also resulted in a depression of the neostriatum response to dopamine, yet an enhancement of the cortical response to noradrenaline.
4. The action of phenols on the brain is relevant to hepatic and uraemic coma.
The Distribution of Cardiac Output in the Anaesthetized Spontaneously Hypertensive Rat
Authors: Hiley C. R. , Yates M. S. 
Published: August 2015

1. Radioactive 15 μm and 50 μm diameter microspheres were used to determine cardiac output, its regional distribution and tissue blood flow in adult normotensive Wistar and Okamoto spontaneously hypertensive rats.
2. Cardiac output in the spontaneously hypertensive rats was the same as in Wistar normotensive rats, but its distribution in the hypertensive rats appeared to differ: there was a significant increase in the proportion of microspheres trapped in the liver whereas fewer were found in the gastrointestinal tract. This indicates that a greater fraction of the cardiac output passes along the hepatic artery and less through the splanchnic bed.
3. Blood flow in skin and skeletal muscle in spontaneously hypertensive rats was approximately 50% of that in Wistar normotensive rats.
Pressure-Independent Hypertrophy of Veins and Pulmonary Arteries of Spontaneously Hypertensive Rats. Characterization of Function, Structural and Histochemical Changes
Authors: Greenberg Stan , Palmer Eugene C. , Wilborn Walter M. 
Published: August 2015

1. Portal veins, vena cavae and pulmonary arteries from spontaneously hypertensive (SH) rats were found to undergo medial smooth-muscle hypertrophy when compared with corresponding blood vessels from age- and sex-matched Wister—Kyoto (WKy) normotensive rats. There was an increase in the density of the mucopolysaccharide and glycoprotein staining in veins, pulmonary arteries vena venorum and ventricular myocardium of SH rats.
2. Electron-microscopic examination of the blood vessels and myocardium of SH rats suggested enhanced protein synthesis and hypertrophy both in the smooth muscle and endothelial cells. Central venous, portal venous and right ventricular pressures were measured in SH rats and were not elevated when compared with corresponding values for WKy rats. Veins and pulmonary arteries from SH rats developed more tension when challenged with vasoconstrictor stimuli than corresponding vessels obtained from WKy rats.
3. Veins and pulmonary arteries obtained from SH rats demonstrated a greater uptake of [14C]glycosamine than corresponding blood vessels from WKy rats.
4. These findings demonstrate the existence of pressure-independent hypertrophy of smooth muscle in blood vessels obtained from SH rats, associated with an increase in glycoprotein synthesis and an enhanced contractile activity of the muscle. The data suggest that the enhanced contractility of blood vessels from SH rats reflects the enhanced muscle mass. It may represent an aberrant humoral or cellular mechanism which results in the hypertension.
Cardiovascular Reflexes and Autonomic Neuropathy
Authors: Ewing D. J. 
Published: August 2015

Clinical features of autonomic neuropathy include postural hypotension, sweating abnormalities, disturbance of body temperature regulation, gastric fullness and nausea, intermittent nocturnal diarrhoea, constipation, bladder problems and impotence. In diabetic patients, gustatory sweating and hypoglycaemic unawareness also sometimes occur (Johnson & Spalding, 1974). The onset of symptoms is usually insidious and permanent, but may occasionally be acute and reversible (Young, Asbury, Corbett & Adams, 1975). Autonomic dysfunction can arise from three main causes: first, those where the damage to the autonomic nervous system is isolated, as in primary postural hypotension (Bannister, Sever & Gross, 1977) and familial dysautonomia (Brunt & McKusick, 1970); secondly, those caused by toxic or pharmacological agents which interfere with autonomic reflexes; thirdly, those associated with systemic disease, of which diabetes mellitus is the most common. Other diseases which may cause autonomic dysfunction include amyloidosis, porphyria, tetanus, polyneuritis, tabes dorsalis, parkinsonism, chronic renal failure and alcoholism, and occasionally autonomic neuropathy has been associated with carcinoma of the bronchus or the pancreas (Johnson & Spalding, 1974).
Although it is possible to localize lesions within the autonomic nervous system to afferent or efferent sympathetic or parasympathetic pathways (Johnson & Spalding, 1974; Moskowitz, 1977), many of the available tests are complex and invasive and often lack adequate control measurements (Young et al., 1975). Because of the patchy nature of autonomic neuropathy, current interest has centred around the search for bedside tests that are ‘global’, reproducible and non-invasive. This review summarizes the present state of knowledge of simple tests of cardiovascular reflex function in the clinical evaluation of autonomic neuropathy, particularly in diabetic subjects.
Effect of Prolactin on Glomerular Filtration Rate
Authors: Riley A. L. , Hagen T. C. , Stefaniak J. E. 
Published: August 2015

1. The effect of infusion of ovine prolactin was studied in anaesthetized dogs pretreated with bromocryptine to reduce the release of endogenous prolactin.
2. Prolactin, injected intravenously and also directly into one kidney, resulted in a 12–18% increase in glomerular filtration rate (GFR) by both kidneys.
3. This increased GFR was not associated with any demonstrable changes in whole-kidney blood flow, distribution of intrarenal blood flow, fractional excretion of sodium or osmolar or free-water clearance.
4. We conclude that ovine prolactin produced an increase in GFR not dependent on an increase in whole-kidney plasma flow.
The Compliance of the Resistance Vessels in Skeletal Muscle of Hypertensive Patients
Authors: Hartling O. J. , Svendsen T. L. , Nielsen P. E. , Trap-Jensen J. 
Published: August 2015

1. The compliance of the resistance vessels in the anterior tibial muscle was compared in normotensive and hypertensive subjects by measuring the increase in muscle blood flow produced by an increase in vascular transmural pressure.
2. The transmural pressure was increased by exposing the leg to a pressure of 50 mmHg below atmospheric pressure. Muscle blood flow was measured by means of the local 133xenon wash-out technique, and the measurement was performed during reactive hyperaemia to avoid reflex vasoconstriction when the transmural pressure was augmented.
3. At ambient pressure, muscle blood flows were equal in the two groups. However, when the subatmospheric pressure was applied the blood flow increased twice as much in the normotensive as in the hypertensive subjects. This suggested a smaller compliance of the resistance vessels in hypertensive subjects and supported the concept that there are structural changes of the resistance vessels in arterial hypertension.
4. In a small group of hypertensive patients who were well treated for two years, and had a normal blood pressure, the compliance was reduced to the same extent as in the untreated hypertensive patients, indicating that structural vascular changes are not readily reversible despite appropriate antihypertensive treatment.
Changes in Hepatic Enzymes and Organelles in Alcoholic Liver Disease
Authors: Seymour Carol A. , Peters T. J. 
Published: August 2015

1. Liver biopsy specimens obtained from patients with alcoholic liver disease of varying severity were assayed for lysosomal and microsomal enzyme activities, the results being compared with values previously obtained in control subjects.
2. Analytical subcellular fractionation by sucrose-density-gradient centrifugation was performed on extracts of the biopsies and the properties of the lysosomes, plasma membrane, biliary canaliculi and endoplasmic reticulum membranes were determined. Increased activities of plasma membrane marker enzymes, particularly γ-glutamyl transpeptidase believed to be localized to the biliary canalicular membrane, were demonstrated. These findings were most marked in alcoholic cirrhosis. The centrifugation studies revealed no abnormalities in the properties of these membranes.
3. Although the total activities of the endoplasmic reticulum marker enzyme neutral α-glucosidase were unaltered in alcoholic liver disease, centrifugation studies showed a decrease in the density distribution of the membrane-bound enzyme in cirrhosis indicating an increase in the proportion of smooth endoplasmic reticulum membranes.
4. Apart from a small decrease in activity of certain acid hydrolases in fatty liver and in cirrhosis the activities of the lysosomal enzymes were unaffected by alcoholic liver disease.
5. Measurements of lysosomal integrity and density-gradient-centrifugation studies revealed no significant abnormalities in the various patient groups apart from increased stability and reduced equilibrium density of certain lysosomes in fatty liver. It is concluded that lysosomal disruption is not implicated in the pathogenesis of alcoholic liver disease.