bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of Folate Polyglutamates in Human Cells
Authors: Hoffbrand A. V. , Tripp E. , Lavoie A. 
Published: August 2015

1. Synthesis of polyglutamate derivatives from radioactively labelled folic acid, folinic acid and methotrexate has been studied in human phytohaemagglutinin-transformed lymphocytes.
2. With labelled folic acid as the precursor, approximately 20% of the labelled cell folate was found in each of the mono-, tetra-, penta- and hexaglutamate peaks after 72 h of incubation. At earlier times, the amounts of labelled folate monoglutamate and lower folate polyglutamates were proportionately greater and the amount of labelled higher folate polyglutamates was lower. After only 4 h incubation over 80% of the intracellular labelled folate was still in the monoglutamate form.
3. With labelled folinic acid used as precursor, approximately 30% of labelled cell folate after 72 h incubation was in the form of folate pentaglutamate, with tri- and tetra-glutamate forming the other major peaks. The speed of formation of polyglutamate derivatives was substantially more rapid than from folic acid.
4. Methotrexate was found to decrease considerably the amount of folate polyglutamate formation from labelled folic acid in lymphocytes but nevertheless some di-, tri- and traces of tetra-glutamate were formed. On the other hand, methotrexate had no effect on folate polyglutamate formation with labelled folinic acid used as the precursor.
5. Polyglutamate derivatives of labelled methotrexate were formed by human lymphocytes with mean amounts of 4·5% of di-, 1·5% of tri-, 1·0% of tetra- and 0·7% of penta-glutamate derivatives being formed over the period 48–72 h of culture.
6. Pentaglutamate derivatives probably constitute the largest group of intracellular folates in human cells but a complex mixture exists.
7. The enzyme synthesizing polyglutamate derivatives of folate in human cells prefers a reduced folate as substrate but the requirement for a reduced form is not absolute. The nature of the reduced folate is uncertain but it is suggested on the basis of previous work that tetrahydrofolate rather than methylhydrofolate or any other reduced folate monoglutamate is the preferred substrate.
The Effect of Acidosis on Lactate Removal by the Perfused Rat Kidney
Authors: Yudkin J. , Cohen R. D. 
Published: August 2015

1. The isolated perfused kidneys of fed rats in normal acid-base status showed a constant rate of lactate removal from the perfusate between 5 and 90 min of perfusion at a perfusate pH of 7·4–7·5.
2. Lactate removal by kidneys of rats in normal acid-base status was stimulated within 30 min by a reduction in perfusate pH to 7·1–7·2, but depressed when perfusate pH was reduced further.
3. Kidneys taken from rats previously made acidotic and perfused with media of various pH values showed a progressive fall in the rate of lactate removal during the perfusion.
4. Glucose output by the kidneys of rats in normal acid—base status perfused with lactate as substrate was not affected by an alteration in perfusate pH. The kidneys of acidotic rats generally showed an increased rate of glucose output compared with those of control rats.
Distribution of Blood Flow in the Hypothermic (27°C) Dog Kidney
Authors: Withey W. R. , Chapman B. J. , Munday K. A. 
Published: August 2015

1. Renal function was measured in seven normo thermic (38°C) and seven hypothermic (27°C) dogs.
2. The glomerular filtration rate was 60% lower in the hypothermic animals, and the renal blood flow was 51% lower. The intrarenal distribution of blood flow was measured by the uptake of 86Rb from the blood into different regions of the kidney. Hypothermia reduced flow by 34% in the outer cortex, 72% in the inner cortex, 61 % in the outer medulla and 69% in the inner medulla.
3. Radioautography indicated a high blood flow to an area of the outer medulla of hypothermic kidneys, which may indicate medullary blood flow ‘shunting’.
4. The results have been discussed in relation to a number of clinical and experimental observations.
The Role of Small Intestine and Kidney in Bromosulphthalein Conjugation
Authors: Datta D. V. , Singh Sarban , Chhuttani P. N. , Nair C. R. 
Published: August 2015

1. The roles of the kidney and the small intestine in the conjugation of bromosulphthalein have been compared with that of the liver.
2. Studies with homogenates indicated that the liver has a higher bromosulphthalein—glutathione-conjugating activity than the intestine and kidney. The reduced glutathione content of the liver is greater than that of the small intestine and kidneys, which contain comparable amounts.
3. Experiments in vitro with tissue slices confirmed that the three organs are able to extract significant amounts of bromosulphthalein. In carbon tetrachloride-induced hepatic necrosis the uptake and conjugation of the dye by the liver were reduced but were increased in the kidney and unchanged in the small intestine.
4. After an intravenous injection of bromosulphthalein, the percentages conjugated in the liver, kidney and gut were similar.
A Competitive Protein-Binding Assay for 25-Hydroxyvitamin D
Authors: Pettifor J. M. , Ross F. P. , Wang J. 
Published: August 2015

1. We describe a modified competitive protein-binding assay for 25-hydroxyvitamin D, which does not require the prior separation of vitamin D from 25-hydroxyvitamin D.
2. Bovine albumin was used in the buffer, at a concentration of 1 mg/ml, as a protein stabilizer and lipid solubilizer. Bovine albumin from different manufacturers produced very different non-specific binding of 25-[3H]hydroxycholecalciferol (ranging from 3·3% to 58·9%).
3. The mean concentration of 25-hydroxyvitamin D in sera from normal children in Johannesburg was 76·75 ± 24·75 μnol/ml (30·7 ± 9·9 ng/ml).
Control of Renin Secretion in Vivo and in Vitro in Rats: Arguments in Favour of a Precursor Form of Renin and of a Role of a Microtubular System
Authors: Banichahi F. , Capponi A. , Pricam C. , De Senarclens C. , Vallotton M. B. 
Published: August 2015

1. The morphology of the juxtaglomerular apparatus, plasma renin activity, plasma renin substrate and renal renin have been studied in rats after maximal stimulation by bilateral adrenalectomy and salt depletion, and also after blocking this stimulation by deoxycorticosterone and salt load.
2. After stimulation the juxtaglomerular apparatus showed a well-developed granular endoplasmic reticulum and a low secretory granule content. Plasma renin activity was markedly elevated and plasma renin substrate was low. After blockade numerous specific granules with crystalline structures were seen and the granular endoplasmic reticulum was less developed. Plasma renin activity was now low and plasma renin substrate elevated.
3. After prior acidification of the kidney extract a significant increase of renal renin was observed in both conditions but was greater in the second group at the time when large numbers of young granules containing crystalline material were seen.
4. Kidney slices from the adrenalectomized salt-depleted rats released more renin than control slices. Vincristine did not affect this release, but inhibited release from slices stimulated by isoprenaline.
An Investigation of the Prolonged Pressor Response to Renin in the Nephrectomized Rat
Authors: Boyd G. W. 
Published: August 2015

1. In an investigation of the prolonged pressor response to renin that develops after nephrectomy, angiotensin I dose—response curves and rat renin clearances were studied in nephrectomized rats and paired sham-nephrectomized control animals under pentobarbitone anaesthesia.
2. Both threshold and slope of the angiotensin I dose—response curves were decreased at 15–27 h after nephrectomy.
3. The ratio of renin clearance (determined during renin infusions) in the nephrectomized rat to that in the paired sham-nephrectomized control animals was 0·49 ± 0·03 (sem), P < 0·001 (n = 12 pairs).
4. Both factors contribute towards the prolongation of the blood pressure increase after intravenously administered renin in the nephrectomized animal.
Anti-Hypertensive Action of dl-α-Tocopheryl Esters in Rats
Authors: Igarashi T. , Nakajima Y. , Kobayashi M. , Ohtake S. 
Published: August 2015

1. Oral administration of dl-α-tocopheryl nicotinate (EN) (0·04 or 0·2 mmol day—1 kg—1) or dl-α-tocopheryl acetate (EA) (0·2 mmol day—1 kg—1) delayed the progress of hypertension in unilaterally nephrectomized rats, which were treated with deoxycorticosterone and salt, and in genetically hypertensive rats (SHR) which were given sodium chloride solution. Suppression of body weight gain, incidence of pneumonia and mortality were reduced by treatment with EN or EA.
2. Severe hypertension in old SHR (9 months) further progressed, when drinking water was replaced by sodium chloride solution, and four out of ten of these animals died of cerebral haemorrhage during 4 weeks. The administration of EN or EA prevented the increase in blood pressure and incidence of stroke.
Reduced Plasma Renin Activity in Essential Hypertension: Effects of Blood Pressure, Age and Sodium
Authors: Thomas G. W. , Ledingham J. G. G. , Beilin L. J. , Stott A. N. 
Published: August 2015

1. Supine plasma renin activity and its responsiveness to erect posture and frusemide were reduced in fifty-one patients with essential hypertension, compared with fifty-one age- and sex-matched control subjects.
2. Twenty-four hour urinary sodium excretion was similar in hypertensive patients and control subjects, but after intravenous frusemide hypertensive patients excreted significantly less sodium.
3. A significant inverse relationship between plasma renin activity and diastolic blood pressure was demonstrated in hypertensive patients and in normotensive control subjects.
4. A significant inverse relationship between plasma renin activity and age, independent of blood pressure, was shown in hypertensive patients and control subjects.
5. It is concluded that the reduced renin values found in essential hypertension are, in part, the result of the elevated blood pressure acting on the kidney.
Angiotensin II Blockade in Normal Subjects and Essential Hypertensive Patients
Authors: MacGregor G. A. , Dawes P. M. 
Published: August 2015

1. Saralasin (Sar1-Ala8-angiotensin II), a competitive inhibitor of angiotensin II (AII), has been infused into normal subjects and patients with essential hypertension when deprived of sodium by 5 days of a 10 mmol/day sodium diet.
2. When saralasin was given by an incremental rate of infusion starting at 0·25 μg min—1 kg—1, sodium-deprived normal subjects showed a fall in standing blood pressure with no change in lying blood pressure, sodium-deprived normal-renin hypertensive patients showed no change in lying or standing blood pressure and sodium-deprived low-renin patients showed a significant sustained rise in lying and standing blood pressure.
3. These findings suggest that: (a) standing blood pressure in sodium-deprived normal subjects is angiotensin II dependent; (b) normal-renin hypertensive patients when sodium deprived by diet alone do not appear to be angiotensin II dependent (angiotensin II is unlikely therefore to be directly maintaining their blood pressure on their normal sodium intake); (c) the rise in blood pressure seen in low-renin hypertensive patients with saralasin may be a further way of distinguishing this group of patients.
Plasma Renin Activity, Plasma Angiotensin II and Extracellular Fluid Volume in Patients after Renal Transplantation
Authors: Horvath J. S. , Baxter C. , Furby F. , Hood V. , Johnson J. , McGrath B. , Tiller D. J. 
Published: August 2015

1. Patients with cadaveric renal transplants and plasma creatinine less than 177 μmol/l who had their own kidneys removed were studied.
2. The renin—angiotensin system appeared to behave in a normal fashion in response to alterations in sodium intake and posture.
3. The renin—angiotensin system had no major role in the establishment or maintenance of hypertension.
4. Mean arterial pressure was directly related to expansion of the extracellular fluid volume.
Diazoxide-induced Stimulation of Renin Release in Renal Vein Renin Sampling
Authors: Stockigt J. R. , Higgs E. J. , Sacharias N. 
Published: August 2015

1. The acute effect of diazoxide (150–300 mg, intravenously) on renal venous renin has been evaluated in forty-four patients with suspected renal hypertension.
2. In twenty-seven studies which showed no lateralization, diazoxide raised the mean peripheral renin to 175% of control (P < 0·05) but the renal vein renin ratio showed an insignificant change (1·15 to 1·21).
3. In seventeen studies which showed lateralization the increase in peripheral renin was similar, but mean renal vein renin ratio increased from 1·90 to 3·52 (P < 0·005), and the mean ratio of contralateral renal vein to peripheral renin showed no change (1·05 to 1·07), indicating persistence of contralateral suppression.
4. Diazoxide accentuates the distinction between lateralizing and non-lateralizing renal vein renin studies.
Angiotensin II Analogues and Aldosterone Secretion in Sodium-Deficient Sheep
Authors: Blair-West J. R. , Coghlan J. P. , Denton D. A. , Niall H. D. , Scoggins B. A. , Tregear G. W. 
Published: August 2015

1. The angiotensin analogues Sar1-Ala8-angiotensin II (AII), Sar1-Ile8-AII, Sar1-Leu8-AII, Sar1-Thr8-AII, [Des1-Asp]-Ile8-AII and [Des1-Asp]-Sar2-Ile8-AII and converting enzyme inhibitor (SQ 80221) infused by intra-adrenal arterial infusion had no effect on aldosterone secretion in sodium-deficient sheep at doses in excess of those shown to block exogenous angiotensin II or III infusion.
2. It is suggested that the intrinsic agonist activity of the analogues may fulfil the requirements for a permissive role for angiotensin in the aldosterone response to sodium deficiency.
Factors Influencing the Carotid Baroreceptor Response to Pressure Changes in a Neck Chamber
Authors: Ludbrook J. , Mancia G. , Ferrari A. , Zanchetti A. 
Published: August 2015

1. Transmission of pneumatic pressure from a neck chamber to the region of the carotid sinus is imperfect and asymmetric (86% of positive pressure, 64% of negative pressure). This has to be taken into account in the correct analysis of the carotid baroreceptor reflex.
2. There is no evidence for a reduction in cerebral blood flow nor of carotid chemoreceptor stimulation in response to an increase in neck chamber pressure of about 45 mmHg. Thus it is likely that the pressor response to this manoeuvre is in fact due to reduction in carotid baroreceptor activity.
Time-Course of the Reduction of Baroreceptor Sensitivity in Experimental Hypertensive Rabbits
Authors: Angell-James Jennifer E. , George M. J. 
Published: August 2015

1. Hypertension was produced experimentally in three groups of rabbits by atherosclerosis, medial sclerosis and renal encapsulation.
2. The sensitivity of afferent baroreceptor fibre recordings, obtained from an isolated perfused aortic arch preparation, was reduced in all three treated groups.
3. The reduction of baroreceptor sensitivity was directly related to the increase in the lability of the blood pressure in the intact animal and to the reduction of the distensibility of the perfused region.
4. There was a closer relationship between the length of time the rabbits had been hypertensive and the reduction in the baroreceptor sensitivity, than to the level of their blood pressure.
5. The reduction of baroreflex sensitivity obtained by the infusion of phenylephrine was also directly correlated with the period of the hypertension.
6. Baroreceptor resetting occurred to a higher pressure in the renal hypertensive group.
Cardiac Function in the Treatment of Arterial Hypertension with Propranolol
Authors: Guazzi M. , Polese A. , Fiorentini C. , Olivari M. T. , Magrini F. , Bartorelli C. 
Published: August 2015

1. Propranolol, when used for treating arterial hypertension, may influence determinants of both cardiac and vascular function; the consequent changes in cardiac performance may result from the interaction of different and possibly opposite effects.
2. Cardiac function was investigated in fifty-four primary hypertensive men in the pretreatment state and after 3 weeks of propranolol therapy at a daily dose of 320 mg.
3. β-Receptor blockade caused depression of pre-injection left ventricular function, which was unrelated to the direction and the extent of changes in peripheral circulation.
4. The ejection left ventricular function could be either depressed or improved depending on the direction to which treatment shifted the vascular resistance, and consequently, the impedance to left ventricular ejection.
5. Withdrawal of the adrenergic support is probably the major factor responsible for the poor ventricular adaptation to an augmented impedance.
Prazosin and Hydrallazine in the Treatment of Hypertension
Authors: Kincaid-Smith Priscilla , Hua A. S. P. , Myers J. B. , Macdonald Ileene , Fang P. 
Published: August 2015

1. Two vasodilators, prazosin and hydrallazine, have been compared in three double-blind cross-over studies designed to test their effect when used in combination with a β-adrenoceptor-blocking agent and a thiazide.
2. Single doses of 3 mg of prazosin or 75 mg of hydrallazine were administered to patients whose blood pressures remained uncontrolled on a thiazide and a β-adrenoceptor-blocking agent. Both agents produced significant falls in systolic and diastolic blood pressure apparent at 1 h. The effects of prazosin persisted for 6–7 h and those of hydrallazine for 4–6 h. Tachycardia was more marked and more prolonged after hydrallazine and continued after the blood pressure had risen to base-line levels or above.
3. In 6 week and 12 week double-blind cross-over studies, mean falls in blood pressure were similar with prazosin and hydrallazine. Similar falls in the supine diastolic blood pressure were achieved with 1 mg of prazosin and 20 mg of hydrallazine, but for a given fall in supine diastolic blood pressure, prazosin produced a significantly lower standing diastolic blood pressure.
4. Severe side effects were more pronounced after hydrallazine, which necessitated withdrawal of seven patients, whereas only one patient on prazosin withdrew from the trial because of side effects.
Increased Renal Excretion of Arginine-Vasopressin during Mild Hydropenia in Young Men with Mild Essential Benign Hypertension
Authors: Khokhar A. M. , Slater J. D. H. 
Published: August 2015

1. The rate of renal excretion of arginine-vasopressin was determined during unrestricted fluid intake for 24 h and in response to fluid deprivation for 18 h in nine young men with very mild essential hypertension and compared with that in sixteen normotensive men of similar age.
2. Despite an equilavent osmolar stimulus, excretion of arginine-vasopressin was significantly greater in the hypertensive group than in the reference group. This difference increased progressively with increasing dehydration.
3. We suggest that these findings are mainly due to an increased rate of secretion of arginine-vasopressin in response to mild hydropenia in hypertensive patients and that a moderate increase of release of arginine-vasopressin during periods of fluid deprivation may exert vascular effects and thus influence the perpetuation of hypertension.
Evidence for Renal Control of Urinary Excretion of Bile Acids and Bile Acid Sulphates in the Cholestatic Syndrome
Authors: Summerfield J. A. , Cullen Julia , Barnes S. , Billing Barbara H. 
Published: August 2015

1. The bile acids and bile acid sulphates in the urine, serum and bile of eight cholestatic patients were studied quantitatively by gas-liquid chromatography and gas-liquid chromatography/mass spectrometry.
2. The primary bile acids (cholic acid and chenodeoxycholic acid) comprised on average 94% of the total bile acids in bile, 70% in the serum and 64% in urine.
3. The percentage composition of bile acids in bile was relatively constant and was not influenced by the degree of cholestasis. In contrast, in the serum only the primary bile acids were increased, the concentrations of the secondary bile acids (deoxycholic acid and lithocholic acid) and the minor bile acids remaining constant.
4. The data do not support the hypothesis that monohydroxy bile acids accumulate in cholestasis and are related to the pathogenesis of this syndrome.
5. The pattern of bile acid urinary excretion was similar to that in the serum. But in one patient, 3α,7β,12α-trihydroxy-5β-cholan-24-oic acid was a principal urinary bile acid, although very low concentrations of the compound were found in that patient's serum, suggesting that some of the minor bile acids in urine may originate by epimerization in the kidney.
6. In bile only a small proportion of the bile acids was sulphated (range 2·1–4·6%) and in serum the degree of sulphation was very variable (9–50%). However, in urine, sulphate esters accounted for a large proportion of the total bile acids (33–72%).
7. The output of bile acid sulphate in the urine was related to the urine total bile acid output but the serum concentration of bile acid sulphate remained relatively constant. Consequently, in contrast to the non-sulphated bile acids, whose renal clearance was relatively constant, the renal clearance of sulphated bile acids was directly related to the urine total bile acid output. This finding is inconsistent with the earlier hypothesis that their predominance in urine was due to a high renal clearance. It may indicate renal synthesis of some of the bile acid sulphates in the urine and/or inhibition of active renal tubular reabsorption of sulphated bile acids by non-sulphated bile acids.
Effects of Metabolic Alkalosis, Metabolic Acidosis and Uraemia on Whole-Body Intracellular pH in Man
Authors: Tizianello A. , De Ferrari G. , Gurreri G. , Acquarone N. 
Published: August 2015

1. Whole-body intracellular pH (pH1) was measured by the 14C-labelled DMO method in twenty-four control subjects, eighteen normal subjects with induced acute metabolic alkalosis, ten normal subjects with induced acute metabolic acidosis, twelve normal subjects with chronic acidosis and in fifteen patients with chronic renal insufficiency and acidosis.
2. The change in pH1 per unit change in extracellular pH is significantly larger in acute metabolic alkalosis than in acute metabolic acidosis. In chronic metabolic acidosis, pH1 decreased in proportion to the total amount of ammonium chloride administered; pH1 was normal in patients with uraemic acidosis.
3. These observations confirm the role that tissue buffers play in the protection of the cellular environment in some forms of acidosis. When the acid load overwhelms tissue buffer capacity, pH1 becomes a function of extracellular pH.
4. Cells seem more protected from acute acidosis than from acute alkalosis.
Resolution of Hypoxic Changes in the Heart and Pulmonary Arterioles of Rats during Intermittent Correction of Hypoxia
Authors: Leach Enid , Howard P. , Gwenda R. Barer 
Published: August 2015

1. Rats kept in a hypoxic chamber (10% O2) for 3 or more weeks developed right ventricular hypertrophy, muscularization of pulmonary arterioles and polycythaemia. These changes resemble those found in human hypoxic disease and, in particular, in patients dying from chronic airways obstruction.
2. Resolution of these changes was studied in a normal environment and in an intermittently normal, intermittently hypoxic environment. The latter regimen modelled the situation of patients with cor pulmonale receiving long-term intermittent oxygen therapy.
3. In a normal environment right ventricular hypertrophy and polycythaemia were resolved in 6 weeks but vessel changes were not resolved in 12 weeks.
4. In the intermittently normoxic environment (40 or 80 h in air per week) there was some resolution of right ventricular hypertrophy in 6 weeks but no significant reduction in vessel thickening or in polycythaemia in 12 weeks.