bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Cadmium and Zinc in Human Hypertension
Authors: Thind G. S. , Fischer Grace M.
Published: August 2015

1. Plasma cadmium and zinc were determined by atomic absorption spectrophotometry in inferior venal caval or peripheral venous blood in thirty hypertensive patients and fifteen normal subjects.

2. The mean plasma cadmium in hypertensive patients was significantly higher than in normal control subjects.

3. The plasma cadmium/zinc ratio was significantly greater in hypertensive patients.

4. There was a significant positive correlation between the plasma cadmium/zinc ratio and the mean arterial blood pressure.
Vascular Lesions in Hypertensive Rats under Salt Loading: Kidney Renin and Lysosomal Enzymes
Authors: Saito N. , Mukaino S. , Ogino K. , Kawai C.
Published: August 2015

1. Renal and cerebral vascular lesions occurred more often and earlier in spontaneously hypertensive rats (SHR) given a high salt diet than in SHR given a normal diet.

2. Kidney renin activity was low during high salt loading; the kidney renin activity of rats with hypertensive renal vascular lesions was moderately elevated. Kidney renin activity or cathepsin D activities were higher in stroke-prone SHR (SHRSP) aged 9 months than in stroke-resistant SHR (SHRSR).

3. β-Glucuronidase, cathepsin D and deoxyribonuclease activities were greater in the kidney of Wistar/Kyoto (WK) rats or SHR when there were hypertensive vascular lesions. These three enzyme activities were also greater in the aorta of SHR aged 13–14 months than in the aorta of WK rats.

4. It was supposed that kidney renin activity and lysosomal enzyme activities were related to hypertensive vascular lesions.
The Specificity of Antisera for the Radioimmunoassay of Arginine-Vasopressin in Human Plasma and Urine during Water Loading and Dehydration
Authors: Thomas T. H. , Lee M. R.
Published: August 2015

1. Rabbit antisera against arginine-vasopressin (AVP) were evaluated for sensitivity and specificity in a radioimmunoassay based on the extraction of AVP from plasma and urine on to Florisil.

2. Comparison of the immunoreactivity of AVP with analogues showed that one antiserum (R2) reacted principally with the hexapeptide ring and another (R4) bound to the tripeptide tail and was reactive with some reduction and hydrolytic products of the native peptide.

3. The minimum amount of AVP measurable in the radioimmunoassay was 1 pg. The extraction of AVP from plasma and urine gave a recovery of 93% (sd 5%). A plasma sample repeatedly assayed with R2 gave a value of 1·4 ng/l (sd 0·2, n = 12).

4. The antiserum specific for the hexapeptide ring (R2) showed that in normal subjects AVP concentration ranged from 3·2 ± 2·52 ng/l after dehydration to 0·16 ± 0·1 ng/l after water loading.
Renin Inhibitory Effect of Synthetic Phosphorylethanolamine (PE-104) in the Rat
Authors: Miyazaki M. , Yamamoto K. , Hosoki K.
Published: August 2015

1. The renin inhibitory effect of 2-[4-(4′-chlorophenoxy)phenoxy - acetylamino]ethylphosphoryl - ethanolamine (PE-104) was examined both in vitro and in vivo.

2. PE-104 inhibited the rate of angiotensin formation from dog renin and renin substrate reaction. The Ki value was 2 mmol/l and the inhibition was competitive.

3. In normotensive rats, infusion of PE-104 abolished the increases of blood pressure and plasma angiotensin I concentration due to renin injection. In renal hypertensive rats, infusion of PE-104 decreased blood pressure and this was associated with a decrease of plasma angiotensin I concentration.

4. These observations confirm that PE-104 is a renin inhibitor.
The Nature of the β-Adrenoreceptor Controlling Plasma Renin Activity in Man
Authors: Johnson B. F. , Smith I. K. , Labrooy J. , Bye Carole
Published: August 2015

1. Seven healthy sodium-replete male volunteer subjects remained supine during and for at least 1 h before the study. Heart rate and blood pressure were recorded continuously, and peripheral venous blood samples were taken every 15 min for determinations of plasma renin activity.

2. All subjects were studied twice: after 3 days of oral practolol (100 mg, three times daily) and after a similar period on placebo. Each study consisted of an intravenous infusion of isoprenaline in graded doses (0–2·0 μg/min in the placebo phase; 0–16 μg/min in the practolol phase), followed after rest for 2 h by an intravenous infusion of salbutamol (0–20 μg/min after placebo; 0–80 μg/min after practolol).

3. Both salbutamol and isoprenaline produced dose-related increases in systolic blood pressure, heart rate and plasma renin activity and decreases in diastolic pressure.

4. The increases in heart rate and plasma renin activity induced by either agonist were competitively blocked by practolol, as was the fall in diastolic blood pressure induced by isoprenaline; the salbutamol-induced fall of diastolic blood pressure was unaffected by practolol.

5. Comparison of dose ratio — 1 estimates confirmed that practolol selectively blocked increases in heart rate and plasma renin activity due to salbutamol; no selective blockade against isoprenaline-induced changes was shown.

6. Selective blockade of salbutamol-induced changes indicate that a β1-adrenoreceptor mediates changes in plasma renin activity.
Tissue iso-renins
Authors: Ganten D. , Hutchinson J. S. , Haebara H. , Schelling P. , Fischer H. , Ganten U.
Published: August 2015

1. Several extrarenal tissues contain enzymes which are similar to kidney renin: They hydrolyse angiotensinogen to form angiotensin I; they have characteristic substrate specificity; the physicochemical properties of kidney renin and of extrarenal tissue iso-renin are similar.

2. Results indicate that tissue iso-renins are part of a complex enzyme system with mainly local function. A possible biological role has been demonstrated in brain, adrenal gland and tissue culture.
Salt, Frusemide and Renin in Severe Experimental Renal Hypertension
Authors: Fernandes M. , Onesti G. , Dykyj R. , Fiorentini R. , Gould Anne B. , Kim K. E. , Swartz C.
Published: August 2015

1. Sodium-deficient diet failed to alter development and maintenance of severe renal hypertension produced in the rat by ligation of the aorta between the renal arteries.

2. High sodium diet did not alter the early phase of this hypertension, but significantly decreased blood pressure elevation in the late phases.

3. The decrease in blood pressure produced by high sodium intake does not appear to be mediated by renin suppression.

4. Frusemide effectively reduced blood pressure and renin at all phases.
Surgical Intervention in Severe and Complicated Renal Hypertension: Report of the Sydney Renal Hypertension Group (1969–75)
Authors: Graham R. M. , Sebel E. F. , Stokes G. S.
Published: August 2015

1. A prospective study was undertaken in seventy-eight patients with renal hypertension (fifty-eight with renovascular disease and twenty with renal parenchymal disease), after their presentation to an advisory group as possible candidates for surgical management.

2. Vascular repair and/or nephrectomy were performed in forty-four patients, and the remainder were treated with anti-hypertensive drugs. The control of blood pressure was then assessed over periods of 6–70 months.

3. Of the patients treated surgically, fifteen (34%) were normotensive without medication and fifteen had improved blood pressure control; the morbidity rate was the same as in the medically treated group, but mortality was lower and blood pressure control was better, particularly among patients under 40 years of age.

4. Surgery undertaken primarily to conserve renal function was beneficial in four of nine patients with bilateral renal artery stenosis and severe, progressive uraemia.

5. The blood pressure response to surgical correction of unilateral renal lesions was predicted correctly by the preoperative renal vein renin ratio in fifteen of eighteen cases.
The Immediate Plasma Renin Response to Propranolol: Evidence for a Different Mode of Renin Release in Essential and Renal Hypertension
Authors: Skrabal F. , Czaykowska W. , Dittrich P. , Braunsteiner H.
Published: August 2015

1. The immediate short-term effects of intravenous injections of propranolol on plasma renin activity were studied in thirty-one normal subjects, 102 patients with benign essential and sixty-six patients with renal hypertension.

2. In essential hypertensive patients and normal subjects a marked fall in plasma renin activity was observed within 15 min, which was directly proportional to initial plasma renin values. In contrast, in patients with renal hypertension the fall observed was much less pronounced, or totally absent.

3. These differences in response to propranolol, which were particularly pronounced in patients with high initial renin values, suggest a dominant role of sympathetic tone at the juxtaglomerular apparatus for basal renin release in normal individuals and essential hypertensive subjects only.

4. The observations also indicate that sympathetic activity plays no part in the control of basal renin secretion in patients with renal hypertension, in whom basal renin secretion may be maintained by the renal baroreceptors.
Enhancement of the Anti-Hypertensive Effect of Methyldopa and other Anti-Hypertensive Drugs by Carbidopa in Spontaneously Hypertensive Rats
Authors: Scriabine A. , Ludden C. T. , Stone C. A. , Wurtman R. J. , Watkins C. J.
Published: August 2015

1. A peripheral inhibitor of l-aromatic amino acid decarboxylase, carbidopa [(—)-l-α-hydrazino-3,4-dihydroxy-α-methylbenzenepropanoic acid monohydrate], at doses up to 25 mg/kg intraperitoneally or 30 mg/kg orally had no effect on directly recorded arterial pressure of spontaneously hypertensive rats derived from the Wistar/Okamoto strain. It enhanced, however, the anti-hypertensive effects of methyldopa, hydrallazine, guanethidine and clonidine, and, to a lesser extent, reserpine and hydrochlorothiazide. The mechanism of this enhancement is presently unknown, but biochemical studies support the assumption that carbidopa is likely to reduce sympathetic nervous system activity.

2. The conversion of [3H]tyrosine (given intraperitoneally) to dopa (3,4-dihydroxyphenylalanine) and catecholamines was measured in the hearts and adrenals of control rats and animals pretreated with carbidopa (100 mg/kg, intraperitoneally). Carbidopa significantly decreased the accumulation of 3H-labelled catecholamines in both organs and increased their total tyrosine content and the specific radioactivity of tyrosine.
Anti-Hypertensive Effect of Metoprolol in Spontaneously Hypertensive Rats
Authors: Ljung B. , Åblad B. , Drews L. , Fellenius E. , Kjellstedt A. , Wallborg M.
Published: August 2015

1. Oral and intravenous administration of metoprolol to adult spontaneously hypertensive rats (SHR) with established hypertension lowered arterial blood pressure within 4 days of treatment.

2. Steady-state plasma concentrations of metoprolol were similar to those of patients during antihypertensive treatment with this drug.

3. The neuroeffector function of portal veins of SHR treated orally for 14 days or intravenously for 4 days was not impaired when studied in vitro. This is in contrast to previous findings after long-term treatment.

4. It is concluded that the anti-hypertensive effect of metoprolol in SHR in many respects resembles that observed in patients. It is suggested that impairment of vasomotor nerve control may contribute to the anti-hypertensive effect of β-adrenoreceptor antagonists.
Interaction of Dopamine, Methyldopa and Reserpine in the Sympatho-Adrenal System in Essential Hypertension
Authors: Abe K. , Aoyagi H. , Yasujima M. , Miyazaki S. , Kusaka T. , Seino M. , Otsuka Y. , Irokawa N. , Chiba S. , Sakurai Y. , Saito K. , Yoshinaga K.
Published: August 2015

1. The interactions of dopamine, reserpine and methyldopa on blood pressure of normal subjects and of those with essential hypertension were examined.

2. When biosynthesis of noradrenaline from dopamine was blocked by reserpine, dopamine induced a prominent depressor effect in essential hypertension.

3. The long-term treatment with methyldopa induced a marked potentiation of the pressor action of domapine in hypertension, although no significant pressor response was found in normal subjects.

4. It is suggested that methylnoradrenaline may accumulate in peripheral nerve endings of patients with essential hypertension in comparison with normal subjects, and this accumulated methylnoradrenaline potentiates the pressor response to dopamine in essential hypertension.
Effect of Long-Term Anti-Hypertensive β-Receptor-Blocking Treatment on Haemodynamic and Metabolic Responses to Prolonged Exercise in Man
Authors: Frisk-Holmberg M. , Juhlin-Dannfeldt A. , Jorfeldt L. , Åström H.
Published: August 2015

1. Central and regional haemodynamics and leg metabolism at rest, during and after a prolonged exercise were studied in seven untreated hypertensive males before and after a long-term treatment (6 weeks) with an unselective β-receptor-blocking drug (alprenolol).

2. Alprenolol treatment (200–400 mg, twice daily) decreased arterial blood pressure at rest and during exercise; it reduced heart rate in relation to drug plasma concentrations during and after exercise; it left cardiac output unchanged; it reduced leg blood flow at rest, but had no effect on leg blood flow during exercise.

3. Alprenolol treatment also decreased lipolysis and lactate release in relation to drug plasma concentrations during exercise.
Evaluation of the Effect of Timolol Alone and in Combination with Hydrochlorothiazide and Amiloride in the Treatment of Mild to Moderate Arterial Hypertension: A Double-Blind, Controlled Study
Authors: Muiesan G. , Magnani B. , Agabiti-Rosei E. , Alicandri C. , Ambrosioni E. , Miele N.
Published: August 2015

1. The effects of timolol alone and in combination with a fixed dose of hydrochlorothiazide and amiloride have been studied in a double-blind, controlled study in fifty-four patients with mild to moderate essential hypertension.

2. After a 4 weeks placebo period patients were randomly assigned to enter groups receiving timolol alone (group A), hydrochlorothiazide + amiloride (group B) or timolol + hydrochlorothiazide + amiloride (group C). Each treatment was carried out for 6 weeks.

3. The use of timolol (10 mg), hydrochlorothiazide (25 mg) and amiloride (2·5 mg) in a combination tablet given twice daily gave better control of blood pressure in patients with mild to moderate essential hypertension than did equivalent dosages of timolol alone or of hydrochlorothiazide and amiloride.

4. Clinical and laboratory side effects were minimal.
Clinical Trial of the β-Adrenoreceptor-Blocking Agent Tolamolol with the use of 24 Hour Blood Pressure Recordings
Authors: West M. J. , Sleight P. , Honour A. J.
Published: August 2015

1. The average blood pressure over 24 h and its variability were measured in eight unrestricted subjects before and after commencing therapy with a new β-adrenoreceptor-blocking agent, tolamolol.

2. The drug caused a fall of 15±6 mmHg in mean arterial pressure and heart rate fell by 13 beats/min. The variation in blood pressure and heart rate over 24 h was unchanged after treatment.
A Cross-Over Study between Hydrallazine and Prazosin
Authors: Rasmussen K. , Jensen H. Æ.
Published: August 2015

1. In a cross-over study between hydrallazine and prazosin in fifteen patients, also treated with the β-receptor-blocking agent propranolol, 1 mg of prazosin was found to be equipotent with 30 mg of hydrallazine.

2. All patients were known to tolerate hydrallazine. In one patient prazosin treatment was discontinued because of severe headache. In four patients minor, non-persistent initial side effects were found. These might have been avoided by using a smaller starting dose. One patient fainted on the second day of prazosin treatment, probably from a micturition syncope.

3. Prazosin may be used as an alternative to hydrallazine.

4. The final status of prazosin as an anti-hypertensive drug is uncertain.
Initial Treatment of the Young Hypertensive: Thiazide Diuretic or β-Adrenoreceptor-Blocking Agent in a Single Daily dose?
Authors: Gordon R. D.
Published: August 2015

1. Nine men aged 20–33 years with essential hypertension measured their own blood pressure at home, lying and standing, three times daily, under conditions of everyday living. The last 14 days' readings (eighty-four observations) from control and treatment periods of at least 4 weeks’ duration were used to calculate mean pressures.

2. In eight patients, propranolol (40 mg thrice daily with meals) significantly lowered ‘mean blood pressure’ (diastolic + ⅓[systolic — diastolic]) but methyclothiazide (5 mg with breakfast) did not. In five subjects, prindolol (5 mg thrice daily with meals) significantly lowered ‘mean blood pressure’ but methyclothiazide (5 mg with breakfast) did not.

3. In six subjects there was no significant difference between ‘mean blood pressure’ when taking propranolol doses 120 mg with breakfast, 60 mg with breakfast and with the evening meal, and 40 mg with each meal. In five subjects there was no significant difference between ‘mean blood pressure’ when taking metoprolol 200 mg with breakfast and 100 mg with breakfast and with the evening meal. In four subjects there was no significant difference between ‘mean blood pressure’ when taking prindolol 30 mg with breakfast, 15 mg with breakfast and with the evening meal, and 10 mg with each meal.

4. In young males with essential hypertension, β-adrenoreceptor blockers were more effective than a thiazide diuretic in lowering blood pressure, and were effective in a single daily dose.
Relative Effectiveness of Chlorothiazide, Reserpine and Hydrallazine in Spontaneously Hypertensive Rats
Authors: Freis E. D. , Ragan D. O.
Published: August 2015

1. Previous studies in this laboratory indicated that a mixture of anti-hypertensive agents in the drinking water controlled the blood pressure of spontaneously hypertensive rats (SHR). The present study was designed to determine which of the agents exerted the greatest anti-hypertensive effect.

2. Treatment was begun at 12 weeks of age in groups of eleven to seventeen rats with one of the following drugs: reserpine, chlorothiazide or hydrallazine. Blood pressures were recorded by the tail method under light ether anaesthesia every 2 weeks until the rats were approximately 70 weeks of age.

3. At 50 weeks of age, blood pressure of chlorothiazaide-treated rats averaged 40 mmHg below untreated control SHR; reserpine-treated SHR were also 40 mmHg lower than control rats, and hydrallazine-treated SHR were 85 mmHg below the control rats.

4. Rats in all groups gained weight normally and appeared in good health. Although all drugs were active, hydrallazine was considerably more effective than chlorothiazide or reserpine in the SHR.
Effectiveness of Screening for Hypertension in Scotland
Authors: Hawthorne V. M. , Beevers D. G. , Gilmour H. , Stewart G. M. , Watt Helen
Published: August 2015

1. Data from long-term follow-up of subjects screened for hypertension indicate that elevation of blood pressure represents a major contribution to community-attributable risk of death.

2. Attendance rates at screening, and dropout rates from follow-up, have been assessed in studies in Glasgow.

3. Screening and follow-up are probably best conducted from general practice, and should be regarded as an extension of good primary care.
Effect of Weight on Prevalence of Hypertension, and its Interaction with the arm Circumference: Belgian Hypertension Committee Epidemiological Study
Authors: Demanet J. C. , Rorive G. , Samii K. , Van Cauwenberge H. , Smets P.
Published: August 2015

1. A first sample of a cross-section of the Belgian population was studied.

2. The presence of hypertension or borderline hypertension was established on the basis of two examinations at 1–3 weeks intervals, during which the blood pressure was measured four times after 10 min rest.

3. The prevalence of both hypertension and borderline hypertension increased with age in the two sexes and, independently of age, with the relative weight.

4. The probable effect of arm circumference in overestimation of blood pressure in heavy subjects was analysed by multivariate correlations. It was concluded that if the influence of arm circumference is excluded, the effect of relative weight on blood pressure is less marked but still present.
Blood Pressure and Heart Rate Response to Isometric Exercise and Mental Arithmetic in Normotensive and Hypertensive Subjects
Authors: Nyberg G.
Published: August 2015

1. Sustained hand-grip exercise and mental arithmetic were performed by normal and hypertensive subjects. Blood pressure and heart rate were recorded with a device which allows blind and unbiased measurements, based on the conventional cuff method.

2. Both stimuli caused increases in heart rate and systolic and diastolic blood pressure, which were greater for isometric exercise than for mental arithmetic.

3. Normal females had a greater response to repeated exercise, and had a smaller systolic pressure elevation during mental arithmetic than the other groups.

4. Repeated testing showed good reproducibility in normal subjects.
Oestrogen-Associated Disease of the Renal Microcirculation
Authors: Jones K. , Naish P. F. , Aber G. M.
Published: August 2015

1. The effect of oestrogen-containing compounds on platelet factor 3, platelet life span, renal platelet localization and the fibrinolytic activity of forearm venous blood has been studied in eleven women with the renal vascular abnormalities of the loin pain and haematuria syndrome. The results were compared with those obtained in twenty-nine healthy female volunteer subjects.

2. Platelet factor 3 (PF3) availability was found to be increased in patients with the loin pain and haematuria syndrome during normal menstrual cycles. Oestrogens produced an increase in PF3 availability in both patients and control subjects.

3. Platelet life span was shortened and the index of renal platelet localization increased when patients with the loin pain and haematuria syndrome received oestrogens. No change in platelet kinetics was found in the healthy control subjects receiving oestrogens.

4. The fibrinolytic activity of forearm venous blood, both at rest and after venous occlusion, was increased in the healthy control subjects in response to oestrogens. No such response was seen in the patients with the loin pain and haematuria syndrome.

5. It is suggested that the change in platelet function may be causally related to the intra-renal vascular abnormalities.

6. The possible role of oestrogens in causing these disturbances or unmasking pre-existing abnormalities of platelet function or fibrinolysis is discussed.
Acid-Base and Respiratory Changes after Prolonged Exposure to 1% Carbon Dioxide
Authors: Pingree B. J. W.
Published: August 2015

1. The acid-base and respiratory status of fifteen healthy male subjects living in an atmosphere of 1% CO2 in air was studied over the course of 44 days, during an operational patrol in a nuclear submarine.

2. Observations were made during a control period before exposure to CO2, at 4 day intervals during the patrol, and finally during the period after its completion. Samples of arterial blood from each subject were analysed for Pa,co2, pH and Po2 immediately after collection. Concurrently mixed expired Pco1 and Po2, together with minute volume and respiratory rate, were measured.

3. A mild uncompensated respiratory acidosis in which arterial pH was depressed by 0·02 pH unit was demonstrated throughout the period of exposure to CO2. This was associated with an acute rise in Pa,co2 of 0·14 kPa, accompanied by an increase in minute volume from 11·5 to 15 l/min. By mid-patrol minute ventilation had returned to control value and a further elevation in Pa,co2 of 0·31 kPa was detected together with a rise in plasma bicarbonate of almost 1 mmol/l.

4. On return to air after completion of the patrol, the acid-base changes appeared to be quickly reversed. Minute volume decreased slightly initially, but it too subsequently returned to the control value. A fall in Pa,o2 of about 2·5 kPa was recorded at this time, together with a reduction in forced vital capacity of 8%.
Epitaxial Relationships in Urolithiasis: The Brushite—Whewellite System
Authors: Meyer J. L. , Bergert J. H. , Smith L. H.
Published: August 2015

1. Whewellite (calcium oxalate monohydrate) crystals were found to induce epitaxially the heterogeneous nucleation of brushite (calcium monohydrogen phosphate dihydrate) from its metastable supersaturated solution in approximately one-quarter of the time required for spontaneous precipitation in the absence of added nucleating agents. Scanning electron-microscope observation of the crystalline phase showed brushite crystals originating from the whewellite seed crystals.

2. Crystal growth, upon nucleation, proceeded rapidly, and the metastable solutions quickly approached saturation.

3. Brushite crystals also induced the precipitation of calcium oxalate crystals in about one-quarter of the time required for spontaneous precipitation; however, the rate of crystal growth was considerably slower. In support of the chemical data, scanning electron micrographs showed few crystals of calcium oxalate nucleated on the surface of the brushite seed.

4. The results provide some insight into the cause of stones containing calcium oxalate or calcium phosphate (or both), which form in the normally acid environment of human urine.
The Course of Arterial Pressure and the Effect of Sarxd1-Thr8-Angiotensin II in a New Model of Two-Kidney Hypertension in Conscious Dogs
Authors: Masaki Z. , Ferrario C. M. , Bumpus F. M. , Bravo E. L. , Khosla M. C.
Published: August 2015

1. We describe a new method of producing two-kidney hypertension in dogs by a two-step procedure with complete occlusion of a renal artery 2 weeks after it was partially constricted.

2. Control mean arterial pressure (96 ± 3 mmHg) of nine conscious, trained dogs rose to 107 ± 3 mmHg 2 weeks after partial constriction of a renal artery, and it stabilized at a sustained hypertensive plateau (124 ± 7 mmHg) 3 weeks after complete occlusion.

3. Intravenous infusion of an angiotensin II antagonist (Sar1-Thr8-angiotensin II) caused arterial pressure to fall during the acute but not the chronic phase of renal hypertension. In this latter phase plasma renin activity had returned to control values.

4. We conclude that the renin—angiotensin system appears not to be directly involved in the chronic phase of two-kidney hypertension in the dog.
Lysosomal Changes in Liver Tissue from Patients with the Dubin—Johnson—Sprinz Syndrome
Authors: Seymour Carol A. , Neale G. , Peters T. J.
Published: August 2015

1. Clinical, morphological and biochemical data, including data obtained from the application of subcellular fractionation techniques to liver biopsy specimens, are presented for two patients with the Dubin-Johnson-Sprinz (DJS) syndrome.

2. Subcellular fractionation experiments demonstrate that the lysosomes, which have strikingly reduced equilibrium densities, accumulate melanin. Morphological studies confirm the presence of pigments within lysosomes.

3. Although there are increased activities of lysosomal acid hydrolases in the liver tissue from patients with the DJS syndrome, the integrity of these organelles is essentially normal and therefore the accumulation of pigment would not be expected to initiate liver damage. The DJS syndrome is thus a benign type of secondary lysosomal storage disease.
Interaction of Mental Factors with Hypercapnic Ventilatory Drive in Man
Authors: Rigg J. R. A. , Inman E. M. , Saunders N. A. , Leeder S. R. , Jones N. L.
Published: August 2015

1. The effect of mental arithmetic tasks on ventilation, breathing pattern, oxygen intake and carbon dioxide output was studied during air breathing and carbon dioxide rebreathing in healthy subjects.

2. Ventilation and breathing frequency increased significantly on performance of the task during 4 min air breathing and 4 min rebreathing; tidal volume was unchanged. The slopes of the ventilatory, frequency and tidal volume responses to carbon dioxide changed little during task performance.

3. During 15 min air breathing, oxygen intake was unchanged with task performance. Carbon dioxide output increased significantly with task performance, as a result of wash-out of carbon dioxide from body stores by the increased ventilation.

4. Mental arithmetic had no effect on the coefficients of variation of the slope and position variables of the ventilatory, frequency and tidal volume responses to carbon dioxide. It is concluded that task performance does not improve the reproducibility of these responses.
Oxygen Affinity in Vivo and in Vitro in Chronic Ventilatory Failure
Authors: Tweeddale P. M. , Leggett R. J. E. , Flenley D. C.
Published: August 2015

1. The oxygen affinity in vitro, haematological indices, erythrocyte 2,3-diphosphoglycerate and plasma inorganic phosphate were determined in 20 patients with chronic ventilatory failure and in 20 healthy non-smokers of similar age.

2. No significant difference was observed between the mean oxygen affinity or phosphate concentrations of the patients and healthy subjects but the mean haemoglobin and packed cell volume were significantly higher in the patients.

3. There was a positive correlation between plasma and intraerythrocytic pH which was similar in both patients and healthy subjects.

4. The arteriovenous difference in oxygen saturation in vivo (directly measured at cardiac catheterization) correlated closely with that calculated from the individual patient's oxygen affinity determined in vitro and arterial and mixed venous oxygen and carbon dioxide tensions, suggesting that oxygen affinity in vitro accurately reflects the curve in vivo.
Non-Steady-State Studies of Low-Density-Liproprotein Turnover in Familial Hypercholesterolaemia
Authors: Thompson G. R. , Spinks T. , Ranicar A. , Myant N. B.
Published: August 2015

1. The non-steady-state turnover of low-density lipoprotein (LDL), labelled in its apoprotein moiety (apo-B) with 131I, was determined in four patients with familial hypercholesterolaemia, three of them homozygotes.

2. The fractional and absolute catabolic rates (FCR and ACR) of LDL-apo-B were determined by relating the excretion of radioactivity, measured in urine in vitro and by whole-body counter in vivo, to plasma radioactivity and to LDL specific radioactivity respectively.

3. The FCR remained relatively constant, even after marked reduction of LDL pool size by means of plasma exchange. This confirms the existence of an intrinsic defect in LDL catabolism in familial hypercholesterolaemia.

4. LDL-apo-B synthesis, determined by summing the ACR and the daily increment in plasma LDL, was much higher in the three homozygotes than in the one heterozygote, in whom the synthetic rate was normal.

5. These results illustrate the usefulness of combining plasma exchange and whole-body radioactivity counting as a means of examining the relationship between the turnover and pool size of a 131I-labelled protein, such as LDL.
Sodium Restriction and Inhibition of the Renin—Angiotensin System in Renovascular Hypertension in the Rat
Authors: Swales J. D. , Thurston H.
Published: August 2015

1. In the early phase of hypertension produced by renal artery constriction with the opposite kidney intact, infusion of the angiotensin antagonist Sar1-Ala8-angiotensin II or bilateral nephrectomy lowered blood pressure. However, the extent of the fall was variable and some animals remained hypertensive after each procedure.

2. To assess whether sodium retention was the additional factor which maintained blood pressure when the renin—angiotensin system was suppressed, rats were maintained on a low-salt diet before and during the development of hypertension. The blood pressure-lowering effect of bilateral nephrectomy or antagonist infusion was not enhanced.

3. Infusion of antagonist or converting-enzyme inhibitor 6 h after bilateral nephrectomy had only a minor blood pressure-lowering action, indicating that, at this late stage after nephrectomy, the renin—angiotensin system makes only a very small contribution to blood pressure maintenance.
A New Open-Circuit Method for Estimating Carbon Dioxide Tension in Mixed Venous Blood
Authors: Al-Dulymi Reiah , Hainsworth R.
Published: August 2015

1. A new open-circuit respiratory method was developed to estimate mixed venous Pco2 more rapidly and accurately than is possible with rebreathing techniques.

2. The subject breathes a mixture of CO2 in air from an open circuit. Carbon dioxide is added to the air flowing through the circuit at a rate such that the Pco2 in the inspired and expired gases (recorded continuously with a CO2 analyser) are almost identical.

3. Results from respiratory and cardiac patients showed that equilibrium occurred in less than 10 s. There was good agreement between the tensions of CO2 in the respiratory plateaux and in mixed venous and arterial blood withdrawn during equilibrium.

4. During exercise, the tensions of CO2 of the plateaux and arterial blood at equilibrium also showed good agreement.

5. It is suggested that the new method represents an improvement over rebreathing methods as equilibrium is achieved rapidly before the mixed venous tension rises from recirculation.
Muscle Metabolism in Patients with Chronic Obstructive Lung Disease and Acute Respiratory Failure
Authors: Gertz Ingrid , Hedenstierna Göran , Hellers Göran , Wahren J.
Published: August 2015

1. The concentration of metabolites in intercostal and quadriceps muscle, and pulmonary function, were studied in twelve patients with chronic obstructive lung disease and acute respiratory failure before, during and after standardized treatment at an intensive care unit. The findings were compared with those obtained in hospitalized patients of comparable age with non-pulmonary diseases.

2. On admission, when the patients had marked hypoxaemia, hypercapnia and acidosis, the concentrations of ATP and creatine phosphate were low in both intercostal and quadriceps muscle, particularly the latter. The lactate concentration was increased in relation to control values but glycogen did not differ significantly.

3. In response to therapy, the Pa,co2 and the patient's acidosis decreased, the vital capacity increased and lung mechanics improved along with the clinical condition. At the same time there were significant increases in the concentrations of ATP, creatine phosphate and glycogen in intercostal and quadriceps muscles, to values similar to, and for glycogen in excess of, those found in control subjects. Lactate concentration fell significantly during treatment.

4. In view of the low initial muscle concentrations of ATP and creatine phosphate in the patients, it is suggested that dysfunction of the respiratory muscles may be an important component of respiratory failure. Moreover, the concentration of energy-rich compounds in muscle rose significantly as the patients responded to treatment, which emphasizes the importance of adequate nutritional therapy in this disorder.
Analytical Subcellular Fractionation of Human Granulocytes with Special Reference to the Localization of Enzymes Involved in Microbicidal Mechanisms
Authors: Segal A. W. , Peters T. J.
Published: August 2015

1. Granulocytes were isolated from 40–400 ml of human blood, disrupted and subjected to analytical subcellular fractionation by centrifugation on sucrose density gradients.

2. The principal subcellular organelles, characterized by their respective marker enzymes, were resolved on the density gradients. The subcellular localization of hitherto unassigned enzymes was determined by comparison with the marker enzymes.

3. NAD(P)H-dependent reduction of nitroblue tetrazolium at high nucleotide concentration (2·5 mmol/l) and NAD(P)H/cytochrome c reduction has a complex distribution with activity in the plasma membrane, mitochondria and cytosol fractions.

4. At a lower, physiological concentration of pyridine nucleotides (25 μmol/l), NADH-dependent nitroblue tetrazolium reduction was confined to the plasma membrane whereas NADPH dependent-reduction of the dye was undetectable. NAD(P)H/nitroblue tetrazolium reductase activity was partially inhibited by superoxide dismutase.

5. NADPH and NADH oxidase activities, measured by the production of oxidized nucleotide, were localized with the azurophil granules.

6. Superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase were localized predominantly to the cytosol.

7. Neutral α-glucosidase and γ-glutamyl transpeptidase showed a bimodal distribution with localizations to both endoplasmic reticulum and specific granule components.

8. It is suggested that the plasma membrane, and thus the wall of phagocyte vacuoles, contains a free radical generating NADH-dependent enzyme which plays a primary bactericidal role. The cytosol contains mechanisms which detoxify hydrogen peroxide, superoxide and free radicals and protect the granulocyte from these compounds.
Proline and Hydroxyproline Excretion and Vitamin C Status in Elderly Human Subjects
Authors: Bates C. J.
Published: August 2015

1. Plasma and buffy-coat vitamin C, urinary proline, hydroxyproline, creatinine and total amino acid concentrations were measured in 23 healthy elderly subjects at intervals of 3 months.

2. There was a strong positive correlation between plasma vitamin C and buffy-coat vitamin C.

3. There were no significant correlations between plasma or buffy-coat vitamin C and total urinary hydroxyproline, whether expressed on a creatinine basis or on a total amino acid basis. Similarly, no significant correlations could be detected involving the proline/hydroxyproline ratio in urine hydrolysates.

4. There was a significant negative correlation between plasma or buffy-coat vitamin C and total urinary proline, when expressed per unit of total amino acids in the hydrolysates. This correlation was not observed with unhydrolysed urine, and it appeared to reside in the diffusible fraction, part of whose proline could be liberated by prolidase digestion. In addition, in the men, there was some evidence for a positive correlation between plasma or buffy-coat vitamin C and the ratio of total urinary amino acids to creatinine.

5. These results support the view that poor vitamin C status in elderly humans may be associated with a defect in collagen proline hydroxylation, reflected by increased excretion of proline-rich, collagen-derived peptides. If this interpretation is correct, it indicates a potential defect in connective tissue repair, and could form the basis of a functional test for subclinical vitamin C deficiency.
Intestinal Absorption of Glycine and Glycyl-L-Proline in the Rat
Authors: Heading R. C. , Schedl H. P. , Stegink L. D. , Miller D. L.
Published: August 2015

1. Absorption of [3H]glycine and [14C]-glycyl-l-proline at concentrations between 0·5 and 4 mmol/l was studied by perfusion in vivo of rat jejunal and ileal segments. Absorption was defined as net removal of radioisotope from the perfusate. Radioactivity assays and amino acid analyses were performed on perfusates and on mucosal tissue samples obtained from the perfused segments.

2. At the concentrations studied, absorption rates of glycine and glycylproline were proportional to concentration. Ileal rates were approximately 60% of jejunal rates. Glycylproline absorption was slightly faster than glycine absorption and was associated with the appearance in the perfusate of free glycine and proline in the ratio approximately 3:1. Intraluminal hydrolysis was insufficient to account for the amounts of free amino acids found and glycylproline hydrolase activity at the brush border is known to be minimal.

3. Glycylproline absorption apparently occurred by transport of the intact peptide followed by its intracellular hydrolysis. However, more than one-third of absorbed glycine and one-eighth of absorbed proline returned to the lumen as free amino acid. This reflux of glycine and proline was not proportional to their concentrations in the mucosa.
The Effect of Chronic Frusemide Administration on Intracellular Potassium, Sodium and pH of Cardiac and Skeletal Muscle
Authors: Hall R. J. C. , Cameron I. R.
Published: August 2015

1. Chronic administration of frusemide in large doses of 4 mg day−1 kg−1 for 3 weeks caused a significant reduction of cell water in rabbit cardiac and skeletal muscle. Intracellular Na+ concentration, intracellular pH and extracellular space were unchanged in both tissues. Intracellular K+ concentration increased slightly in both cardiac and skeletal muscle.

2. It is concluded that frusemide does not reduce intracellular K+ concentration in cardiac or skeletal muscle of normal animals receiving a normal oral potassium intake.
Effect of Pharmacological Inhibitors on Urate Transport during Induced Uricosuria
Authors: Diamond H. S. , Meisel A. D.
Published: August 2015

1. The effect on urate excretion of administration of probenecid and pyrazinamide was observed in normal subjects under control conditions and after induction of uricosuria by exogenous urate loading by ribonucleic acid feeding in seven subjects, by volume loading with hypertonic sodium chloride solution infusion in 11 subjects and by partial inhibition of net urate reabsorption with uricosuric drugs in 20 subjects.

2. After ribonucleic acid feeding, the uricosuric response to probenecid was intact and ribonucleic acid feeding did not produce uricosuria after pyrazinamide.

3. After volume loading, the uricosuric response to probenecid was again intact, but infusion of sodium chloride solution still produced uricosuria after pyrazinamide administration.

4. After uricosuric drugs, the uricosuric response to probenecid was diminished.

5. These responses to probenecid and pyrazinamide may reflect different mechanisms of uricosuria. Response to pharmacological inhibitors of urate reabsorption or urate secretion may be useful for classification of induced and clinical uricosuric states.
The Association between Fasting Hyperbilirubinaemia and Serum Non-Esterified Fatty Acids in Man
Authors: Cowan R. E. , Thompson R. P. H. , Kaye J. P. , Clark Gillian M.
Published: August 2015

1. The concentrations of plasma total and unconjugated bilirubin and of serum non-esterified fatty acids (NEFA) have been measured in two healthy subjects during fasts of up to 21 h.

2. Fasting was either continuous or interrupted by various procedures that altered the concentrations of NEFA and total bilirubin.

3. When NEFA concentrations were increased by the administration of noradrenaline, heparin or caffeine, bilirubin concentrations also rose.

4. When NEFA concentrations were lowered by insulin, bilirubin concentrations fell.

5. Meals of 3·138 kJ and more, taken during the fasting period, lowered total bilirubin and NEFA concentrations in both subjects, whereas the effects of smaller meals were less consistent.

6. These studies demonstrate a statistically significant correlation between total bilirubin and NEFA during uninterrupted fasting and an association between these variables under other experimental conditions. They suggest that the control of bilirubin concentrations in the blood is linked to lipid metabolism.
Nitrogen Metabolism in Neonatal Citrullinaemia
Authors: Walser M. , Batshaw M. , Sherwood G. , Robinson B. , Brusilow S.
Published: August 2015

1. The pathways of disposition of waste nitrogen were studied in a male infant with neonatal citrullinaemia during 3 months of normal growth on a protein-restricted diet supplemented by a mixture of amino acids and nitrogen-free analogues of amino acids.

2. The rate of excretion of urea averaged one-sixteenth, and the rate of excretion of total urinary nitrogen one quarter, of that reported in normal infants retaining the same amount of nitrogen per kg. Thus the efficiency of retention of dietary nitrogen for growth in this infant was very high. Plasma urea varied from 0·35 to 1·30 mmol/l.

3. The small amount of urea formed was apparently derived entirely from dietary arginine via arginase, as indicated by the observation that urea excretion and plasma urea were linear functions of arginine intake with intercepts of zero or less. These relationships imply that urea synthesis would cease at zero arginine intake. This hypothesis could not be verified because arginine intakes below 2·2 mmol day−1 kg−1 led to hyperammonaemia.

4. The high intake of arginine was required chiefly to replenish ornithine skeletons lost as citrulline in the urine (0·7 mmol day−1 kg−1). Smaller amounts of arginine were estimated to be required for protein synthesis and for creatine synthesis. The rate at which ornithine was utilized in reactions other than citrulline synthesis appeared to be excessively high.

5. Citrulline was the principal end-product of nitrogen metabolism, accounting for 51% of urinary nitrogen.

6. The results suggest that normal growth can be obtained in the virtual absence of the ability to dispose of waste nitrogen as urea.
The Role of Alanine and Glutamine in Steroid-Induced Nitrogen Wasting in Man
Authors: Sapir D. G. , Pozefsky T. , Knochel J. P. , Walser M.
Published: August 2015

1. Administration of dexamethasone, 8 mg/day (0·02 mmol/day), for 5 days to normal subjects produced negative nitrogen balance, due to early and sustained increases in urinary urea nitrogen excretion.

2. In eight subjects ingesting 0·9–1·6 g of protein day−1 kg−1 body weight the cumulative increment in urea nitrogen excretion averaged + 12·5 g (sem 2·8, P < 0·01) over the 5 days of glucocorticoid administration.

3. Increases in urinary urea nitrogen excretion could be related to both plasma alanine and blood glutamine changes by using a multiple regression equation.

4. These results suggest that corticosteroids induce increased release of alanine and glutamine by peripheral tissues, which may augment urea formation and negative nitrogen balance.

5. The correlation between increments in urea nitrogen excretion and increases in plasma arginine remains unexplained.
Effects of Adrenaline Injection on Human Plasma Tryptophan and Non-Esterified Fatty Acids
Authors: Gentil V. , Lader M. H. , Kantamaneni B. D. , Curzon G.
Published: August 2015

1. Subcutaneous injection of adrenaline into normal male volunteer subjects caused large increases of plasma non-esterified fatty acids and free tryptophan, but plasma total tryptophan fell considerably. Therefore increases of the percentage of plasma tryptophan in the free state were more marked than absolute increases of free tryptophan.

2. Plasma tyrosine fell slightly and plasma phenylalanine and cortisol were unaffected.

3. It is suggested that catecholamine release could lead to abnormalities of tryptophan disposition in stress and psychiatric illness.
The Effect of Certain Chelating Compounds on the Urinary Excretion of Copper by the Rat: Observations on their Clinical Significance
Authors: Gibbs Kathleen , Walshe J. M.
Published: August 2015

1. A screening procedure is described to assess rapidly the clinical potential of chelating agents for the treatment of Wilson's disease.

2. Rats were used as the test animal; they were kept in metabolic cages and the urine was collected in copper-free containers. The compounds investigated were given by mouth as a standard dose of 100 mg. Copper was determined by atomic absorption spectrophotometry.

3. Basal urine copper excretion was 65·1 ± se 2·93 nmol/24 h (4·1 μg ± 0·185). After penicillamine this rose to 367·1 nmol and after trien to 305·9 nmol.

4. Certain compounds caused a reduction in the amount of copper excreted in the urine, probably by forming insoluble chelates with the metal, hence rendering it unavailable for excretion at the glomerulus.