bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Vasoconstrictor Systems in Experimental Glucocorticoid-Hypertension in Rats
Authors: Waeber Bernard , Gavras Haralambos , Bresnahan Margaret R. , Gavras Irene , Brunner H. R.
Published: August 2015

1. The blood pressure effect of SKF 64139, a phenylethanolamine N-methyltransferase (PNMT) inhibitor acting both in the central and peripheral nervous system, was studied in conscious normotensive and glucocorticoid-hypertensive rats maintained for 2 weeks on a salt-deficient diet. On the day of the experiment, mean blood pressure was 119.2 ± 1.1 mmHg (mean ± sem) in the normotensive and 143.2 ± 1.9 mmHg (P < 0.001) in the hypertensive rats. In all animals, the blood pressure was followed for 4 h after oral gavage by either SKF 64139 (50 mg/kg) or its vehicle (5% glucose solution).

2. In the vehicle-treated rats, no change in blood pressure occurred. However, after SKF 64139 administration, a 17.9 ± 3.8 mmHg (P < 0.001) blood pressure fall was observed in the hypertensive rats whereas normotensive animals did not decrease their pressure.

3. Plasma catecholamines were determined in all these rats at the end of the observation period. No significant difference in plasma noradrenaline and adrenaline levels was observed between normotensive and hypertensive as well as vehicle- and SKF 64139-treated rats, though both catecholamines tended to be higher after administration of the PNMT inhibitor.

4. In two additional groups of glucocorticoid-hypertensive rats, the blood pressure effects of an infusion of saralasin, a competitive antagonist of angiotensin II, or of a bolus injection of a vasopressin analogue antagonizing the pressor action of vasopressin, were investigated over a 20 min period.

The vasopressin antagonist had no blood pressure effect whereas saralasin decreased mean blood pressure from 144 ±1.9 to 136 ± 3.2 mmHg (P < 0.005).

5. These data suggest that the sympathetic nervous system is the main vasoconstrictor system involved in the maintenance of established glucocorticoid hypertension. Since SKF 64139 is also known to inhibit to some degree α-adrenoceptors, monoamine oxidase and neuronal uptake processes, it remains unclear, however, whether the blood pressure-lowering effect of this PNMT inhibitor can be attributed to central blockade of adrenaline synthesis.
Detection of Morquio a Syndrome Using Radiolabelled Substrates Derived from Keratan Sulphate for the Estimation of Galactose 6-Sulphate Sulphatase
Authors: Hopwood John J. , Elliott Helen
Published: August 2015

1. The following radiolabelled disaccharide and tetrasaccharide were prepared from keratan sulphate and evaluated as substrates for galactose 6-sulphate sulphatase present in cultured human skin fibroblasts: O-(β-d-6-sulphogalactosyl)−(1 → 4)−2,5-anhydro-d-[1-3H] mannitol 6-sulphate (Gal6S-anM6S) and the tetrasaccharide equivalent Gal6S-GlcNAc6S-Gal6S-anM6S. Radiolabelled trisaccharide substrates, N-acetylgalactosamine 6-sulphate (β, 1 → 4)-glucuronic acid-(β 1→3)-N-acetyl[l-3H]galactosaminitol 6-sulphate (GalNAc6S-GlcA-GalitolNAc6S), and N-acetylgalactosamine 6-sulphate (β, 1 → 4)-glucose-(β, 1 → 3)-N-acetyl-[1-3H]galactosaminitol 6-sulphate (GalNAc6S-GlcGalitol-NAc6S), were prepared from chondroitin 6-sulphate and used to assay N-acetylgalactosamine 6-sulphate sulphatase.

2. Sulphatase activity obtained with Gal6S-anM6S was approximately the same, 100 and 30–50 times less than values obtained with Gal6S-GlcNAc6S-Gal6S-anM6S, GalNAc6S-GlcA-Galitol-NAc6S and GalNAc6S-Glc-GalitolNAc respectively. Less than 5% of normal activity resulted when these substrates were incubated with fibroblasts from Morquio A patients. These results demonstrate that the trisaccharide substrates derived from chondroitin 6-sulphate although de-O-sulphated at a considerably higher rate than was observed for the de-O-sulphation of the disaccharide and tetrasaccharide derived from keratan sulphate, are acted upon by the same sulphatase.

3. Galactose 6-sulphate sulphatase activity in fibroblast homogenates assayed with Gal6S-anM6S as substrate clearly distinguished Morquio A patients from normal controls, and Morquio B and Sanfilippo D patients.

4. We recommend the use of both the radiolabelled disaccharide derived from keratan sulphate and the trisaccharide derived from chondroitin 6-sulphate to assess sulphatase activity in fibroblasts of atypical Morquio patients.
Dietary Fat and Platelet Function
Authors: Sanders T. A. B.
Published: August 2015

1. Platelets are needed for haemostasis. Platelets adhere to damaged tissue, activation being mediated by exposed collagen, thrombin and ADP. The activated platelets then release compounds that cause vasoconstriction, such as thromboxane A2, and activate the clotting cascade culminating in the formation of a stable fibrin plug. Overactive platelets, however, may play an important role in causing coronary vasospasm and acute myocardial infarction. For almost two decades it has been widely held that the substitution of vegetable oils for animal fats in the diet decreases the reactivity of platelets. A reappraisal of this view seems long overdue in the light of new knowledge concerning the control of platelet function.
Kinetics of Proliferation of Rat Aortic Smooth Muscle Cells in Goldblatt One-Kidney, one-Clip Hypertension
Authors: Carlier P. G. , Rorive G. , Barbason H.
Published: August 2015

1. Wistar female rats were made hypertensive by applying a silver clip to the left renal artery and removing the right kidney. In aortas, the proliferation fraction of smooth muscle cells, DNA synthesis and wet weight have been correlated with the blood pressure increase subsequent to the operation.

2. A wave of proliferation of smooth muscle cells in the aortic media is triggered immediately after the highest increased rate of blood pressure. When blood pressure stabilizes at high values, the metabolism of nucleic acid within the aortic media resumes its normal level but the arterial changes previously established persist.

3. The sequence of pathological events responsible for these changes could be: increment of blood pressure; increase in wall stress; proliferation of smooth muscle cells; thickening of arterial wall; correction of the wall stress; end of proliferation.

4. The consequence of this early proliferation of aortic smooth muscle cells is not clear but it is probably one of the mechanisms through which high blood pressure is sustained. It can also participate in atherogenesis, being in this way one of the bases of the well-known relationship between hypertension and atherosclerosis.
Decreased Liver δ-Aminolaevulinate Dehydratase Activity in Porphyria Cutanea Tarda and in Alcoholism
Authors: Kondo Masao , Urata Gumpei , Shimizu Yoshitaka
Published: August 2015

1. δ-Aminolaevulinate dehydratase activity was measured in liver biopsy specimens from 13 patients with porphyria cutanea tarda, 13 alcoholics and 10 control subjects.

2. The mean enzyme activities in liver of porphyria cutanea tarda and alcoholics were 34% (P < 0.001) and 49% (P < 0.001) respectively of the control level.

3. Heat treatment of liver supernatant caused slight inhibition of the enzyme activity in porphyria cutanea tarda and in controls.

4. Addition of Zn2+ to liver supernatants slightly increased the enzyme activity in both porphyria cutanea tarda and controls.

5. The addition of liver supernatant from the porphyria cutanea tarda to purified bovine 6–aminolaevulinate dehydratase did not result in suppression of the enzyme activity.

6. The apparent Km value of δ-aminolaevulinate dehydratase was 4.3 × 10–4 mol/l for porphyria cutanea tarda livers and 3.3 × 10–4 mol/l for control livers. The difference between the two was not significant.
Renal Function in Pregnancy
Authors: Atherton J. C. , Green R.
Published: August 2015

Although our understanding of many renal mechanisms has been advancing rapidly over the past few years, there is still a dearth of information about changes that occur in renal function during pregnancy — surely one of the greatest physiological disturbances possible. It is difficult in many instances to find a description of the changes that occur quite apart from the underlying alterations in mechanisms that are responsible for them.

Part of the difficulty has arisen because of the ethical and methodological problems that arise when women are used as ‘experimental animals’ until recently there has not been a suitably documented animal model, though whether this was because of technical difficulties or lack of interest on the part of investigators is not known. Recently, however, it has become apparent that many changes in renal function in the rat are similar to those occurring in women and some aspects of renal function in the rat have been investigated in detail. Since not all aspects of renal function can be covered in this review we shall concentrate on three of the more important areas, namely haemodynamics, sodium and water handling and glucose excretion, and discuss how these are changed during pregnancy; comments on the possible mechanisms involved in these changes are presented where appropriate.
The Assessment of Nocturnal Oxygen Saturation
Authors: Meanock C. I. , Guyatt A. R. , Cumming G.
Published: August 2015

1. Existing methods of assessing nocturnal episodic hypoxaemia are either insensitive or ignore the majority of the available data.

2. We describe a method of analysis using offline digital processing. A distribution of oxygen saturation (Sao2) with time is produced from all the available data, and subjected to moment analysis to produce a simple index which describes an entire night's Sao2.

3. Our results suggest that the mean and the coefficient of skew fully described a night's Sao2. However, in subjects with chronic air-flow obstruction, the third moment about 100% oxygen saturation (M3100), a single figure, has the same descriptive power as mean and skew.

4. In 17 subjects with chronic air-flow obstruction a significant correlation was found between both daytime Sao2 and Paco2 when plotted against either the M3100 or the skew.

5. Measurements made on two occasions in seven subjects showed good reproducibility for the skew and M3100 indices.
Effect of Hypoxia and Hypercapnic Acidosis on Renal Autoregulation in the Dog: Role of Renal Nerves
Authors: Anderson Robert J. , Pluss Richard G. , Pluss William T. , Bell Jon , Zerbe Gary G.
Published: August 2015

1. Previous studies suggest that hypoxia and hypercapnic acidosis exert a renal nerve mediated adverse effect on renal haemodynamic function. We therefore examined the effect of hypoxia and hypercapnic acidosis on renal blood flow and glomerular filtration rate responses to lowering renal perfusion pressure from 125 to 75 mmHg in the anaesthetized dog. To study the role of renal nerves in these responses, paired innervated and denervated kidneys were studied in each animal.

2. Hypoxia (Po2 43 ± 3 mmHg) affected neither renal blood flow nor glomerular filtration rate responses to decreasing renal perfusion pressure.

3. Hypercapnic acidosis (Pco2 71 ±2 mmHg; pH 7.03 ± 0.01) significantly decreased both renal blood flow and glomerular filtration rate as renal perfusion pressure was lowered. This effect of hypercapnic acidosis could be abolished by renal denervation.

4. These findings suggest that hypercapnic acidosis results in renal nerve stimulation, which prevents the usual decrease in renal afferent arteriolar tone that occurs in response to lowering of renal perfusion pressure.
Serum Amyloid a Levels in Human Renal Allograft Rejection
Authors: Maury C. P. J. , Teppo A. M. , Eklund B. , Häyry P. , Ahonen J.
Published: August 2015

1. Serum amyloid A (SAA) levels were studied in 35 recipients of cadaveric renal transplants. Marked SAA elevations were seen during all acute allograft rejection episodes. The mean peak SAA level in well-documented rejections was 446 mg/l (median 415 mg/l, range 132–1040 mg/l; controls < 1 mg/l).

2. Rejections in patients receiving cyclosporin-A alone as post-transplantation immunosuppressive medication were characterized by a significantly higher peak SAA level than rejections in patients receiving cyclosporin-A in combination with methylprednisolone (539 ± 53 mg/l, mean ± sem, vs 226 ± 9 mg/l, P < 0.01).

3. Excluding surgery-induced SAA elevations in the immediate postoperative period, seven significant SAA peaks not related to allograft rejection were observed. These were associated with surgical complications and infections, and in one case probably with the underlying rheumatic disease, which was complicated by amyloidosis.

4. The results show that acute renal allograft rejection induces a dramatic acute phase SAA response. Since SAA is an easily measured serum component and the rejection-induced elevation is an early event, monitoring of SAA in kidney transplant patients-5-have considerable clinical significance.
Proteins of the Kidney Microvillar Membrane; Analysis by Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis and Crossed Immunoelectrophoresis
Authors: Abbs Michael T. , Kenny A. John
Published: August 2015

1. A microvillar fraction was prepared from human kidney cortex. This fraction was seven to 10 times enriched in aminopeptidases N and A, γ-glutamyltransferase, dipeptidyl peptidase IV, neutral endopeptidase and alkaline phosphatase.

2. Dipeptidyl peptidase IV activity of human renal microvilli could be inhibited by di-isopropylphosphorofluoridate and neutral endopeptidase activity by phosphoramidon.

3. Nearly all the activity of aminopeptidases A and N could be removed from the membrane by treatment with papain, but only 19% and 33% of dipeptidyl peptidase IV and γ-glutamyltransferase activities were released under the same conditions. Neutral endopeptidase and alkaline phosphatase were not solubilized by papain. Treatment with elastase gave results similar to papain, except that γ-glutamyltransferase was not released.

4. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis under reducing conditions of microvilli revealed 36 polypeptide bands, 12 of which contained carbohydrate. A band of apparent Mr 130 000 was labelled with [3H]di-isopropylphosphorofluoridate and hence identified as dipeptidyl peptidase IV.

5. Antibodies raised to human kidney microvilli produced 11 precipitates with detergent solubilized proteins and six with papain released proteins. Several of the precipitates were identified histochemically.

6. Microvilli prepared from human kidney are very similar to microvilli from pig and rabbit kidney with respect to enzymology, response to papain treatment, sodium dodecyl sulphate-polyacrylamide gel patterns and immunochemistry.
Allogeneic Kidney Transplantation after Active Immunological Enhancement: A Model to Study Post-Transplantation Hypertension in Rats
Authors: De Keijzer M. H. , Provoost A. P. , Van Aken M. , Weyma I. M. , Kort W. J. , Wolff E. D. , Molenaar J. C.
Published: August 2015

1. A model was developed to study post-transplant hypertension after allogeneic kidney transplantation between two inbred normotensive rat strains. Prolongation of graft survival was achieved by ‘active immunological enhancement’.

2. Renal function, systolic blood pressure and plasma renin concentration were determined.

3. The systolic blood pressure started to rise in the second week after allogeneic transplantation. The glomerular filtration rate was impaired to a greater extent than the effective renal plasma flow.

4. Histopathological changes occurred indicating immunological reactions in the renal graft.

5. The plasma renin concentration was lower in transplant recipients than in controls.

6. We hypothesize that retention of sodium is mediately involved in the post-transplant hypertension observed in this model.
Effects of Smoking on Oral Fat Tolerance and High Density Lipoprotein Cholesterol
Authors: Elkeles R. S. , Khan S. R. , Chowdhury V. , Swallow M. B.
Published: August 2015

1. Changes in serum triglyceride and high density lipoprotein (HDL) cholesterol after a fatty meal have been studied in smokers and non-smokers.

2. Average serum triglyceride during the study was higher in smokers than in non-smokers.

3. In non-smokers there was a rise in the HDL2/HDL3 cholesterol ratio after oral fat, but not in smokers.

4. These findings are compatible with the hypothesis that smoking interferes with the lipolysis of triglyceride rich lipoproteins and the conversion of HDL3 into HDL2.
Vascular Angiotensin-Converting Enzyme Activity in Man and other Species
Authors: Miyazaki Mizuo , Okunishi Hideki , Nishimura Kazuo , Toda Noboru
Published: August 2015

1. Angiotensin-converting enzyme (ACE) activity in blood vessels of different species was determined.

2. ACE was solubilized by Nonidet P-40, and assayed by reversible phase high performance liquid chromatography. Approximately 98% ACE was recovered in the liquid phase by the use of the detergent.

3. The ACE activity varied with chloride ion (Cl−) concentrations; the maximum activities in dog, human, monkey and rabbit tissues were obtained at the concentrations of 800, 600, 600 and 300 mmol/l respectively. The optimal Cl− concentration was quite similar in different tissues and plasma obtained from the same species.

4. The ACE activity in the cerebral, mesenteric, pulmonary and renal arteries was in a range between 1.01 and 1.60 m-units/mg of protein in dogs and between 0.43 and 0.94 m-unit/mg of protein in monkeys. The activity in dog aortae was 0.20 ± 0.02 m-unit/mg of protein, and the activity in aortic endothelial cells was 2.61 ± 0.65 m-units/mg of protein. ACE activities in the dog lung, kidney cortex and cerebral cortex were 28.6 ± 2.6, 15.7 ± 3.0 and 3.5 ± 0.6m-units/mg of protein respectively. SA-446, a captopril-like ACE inhibitor, reduced the ACE activity in arteries in a dose-dependent manner.

5. Vascular ACE appears to be concentrated in the endothelium and may contribute to regulate vascular muscle tone and local blood flow by a conversion of angiotensin I into II.
The Relationship between Oxygen Delivery and Consumption in the Conscious Rat before and after Expansion of Body Fluid Volumes
Authors: Ledingham J. M. , Gofford S. , Evans S. J. W.
Published: August 2015

1. Oxygen consumption and delivery (defined as the product of cardiac output, haemoglobin concentration and arterial oxygen saturation) and haemodynamic variables were examined in the conscious resting rat throughout the day and after the expansion of body fluid volumes. Cardiac output was measured in arbitrary units by electromagnetic flowmetry and oxygen consumption by respirometry.

2. The variability of blood pressure in the basal state was significantly less than that of cardiac output.

3. Oxygen consumption was significantly correlated with cardiac output and oxygen delivery.

4. In studies undertaken throughout the day, both oxygen consumption and delivery fell in the afternoon and there was evidence that the relationship between these two variables was curvi- rather than recti-linear.

5. During oral sodium chloride administration for 7 days, blood pressure rose and some evidence was found for an alteration in the relationship between oxygen consumption and delivery, with an excess of delivery relative to consumption, particularly on the first day of salt loading.

6. Intravenous injection of sodium chloride solution (0.171 mol/l) did not alter the relationship between oxygen consumption and delivery.

7. Expansion of blood volume, while the packed cell volume was maintained nearly constant, raised oxygen delivery transiently and evidence was obtained that the relationship between oxygen consumption and delivery was altered, with oxygen delivery rising relatively more than oxygen consumption.

8. The findings are discussed in relation to the autoregulatory hypothesis of circulatory control and for the role of autoregulation in hypertensive states. The importance of relating oxygen delivery to metabolic requirements in studies of the role of autoregulation is emphasized.
The Antihypertensive Effect of Dietary Potassium Chloride Loading in Rats with Adrenal Regeneration Hypertension
Authors: Milmer K. E. , Bennett T. , Gardiner S. M.
Published: August 2015

1. Adrenal regeneration hypertension was induced in male Wistar rats by unilateral adrenal enucleation, contralateral adrenalectomy and the provision of a 1% (w/v) NaCl solution for drinking.

2. A fivefold increase in dietary KCl content caused a significant reduction in the systolic blood pressure of hypertensive rats but not of control rats.

3. During the increase in potassium intake there was a marked polydipsia. When 1% NaCl solution was the drinking fluid, the resultant increase in sodium intake was associated with an abolition of the antihypertensive effect of potassium loading, but when the sodium intake was held constant, the antihypertensive effect was maintained.

4. In rats with adrenal regeneration hypertension, plasma volume was significantly higher, and packed cell volume and plasma protein concentrations were significantly lower than in control rats. These differences were abolished after 4 days of dietary KCl supplementation.

5. Increased dietary potassium intake was associated with significantly lower serum aldosterone concentrations and significantly higher plasma potassium concentrations in adrenal enucleated rats compared with controls.

6. The possibility that a reduction in extracellular fluid volume (due to a natriuresis) and/or a peripheral vasodilatation contributed to the antihypertensive effect of KCl loading is discussed.
The Influence of Acute Starvation on the Cardiovascular Responses to Lower Body Subatmospheric Pressure or to Standing in Man
Authors: Bennett T. , MacDonald I. A. , Sainsbury R.
Published: August 2015

1. The cardiovascular responses to lower body subatmospheric pressure or to standing were measured in the same nine normal male subjects after a 12 h and after a 48 h fast.

2. After the 48 h fast there was a significant reduction in diastolic blood pressure and forearm vascular resistance (relative to the values after a 12 h fast) when subjects were supine.

3. During exposure to lower body subatmospheric pressure, subjects who had fasted for 48 h showed an inability to maintain systolic blood pressure, accompanied by an impairment of forearm vasoconstriction and an exaggerated tachycardia (relative to their responses after a 12 h fast). Similar disorders of cardiovascular homoeostasis were seen on standing.

4. The results are consistent with an inhibition of sympathetic nervous activity after a 48 h fast, but other possibilities are discussed.
Urinary Adenosine Cyclic 3′,5′-Monophosphate in Idiopathic Calcium Stone-Formers: Response to An Oral Calcium Load
Authors: Walker V. R. , Sutton R. A. L.
Published: August 2015

1. Idiopathic calcium stone-formers with hypercalciuria during fasting have significantly lower urinary cyclic AMP levels (nmol/dl of glomerular filtrate) than fasting normocalciuric stone-formers.

2. Female subjects, including both normal subjects and idiopathic calcium stone-formers, have higher urinary cyclic AMP levels than their male counterparts, and this difference is significant when urinary cyclic AMP is expressed in the units μmol/g of creatinine. Expressing urinary cyclic AMP in nmol/dl of glomerular filtrate reduces this difference but does not abolish it. Thus, in comparing urinary cyclic AMP levels in various subgroups of the calcium stone-formers and in normal subjects, both sex differences and the units of urinary cyclic AMP expression must be taken into consideration.

3. The magnitude of the change in urinary cyclic AMP in response to an oral calcium load appears to depend on the antecedent urinary cyclic AMP excretion rate, whereby those individuals (either normal subjects or calcium stone-formers) having the highest urinary cyclic AMP levels demonstrate the greatest fall in urinary cyclic AMP after a calcium load.
The Importance of Urinary Immunoglobulin Light Chain Isoelectric Point (Pi) in Nephrotoxicity in Multiple Myeloma
Authors: Coward R. A. , Delamore I. W. , Mallick N. P. , Robinson E. L.
Published: August 2015

1. There is clinical and experimental evidence to imply that urinary immunoglobulin light chains are nephrotoxic yet some patients pass large amounts for years with little renal damage. Animal experiments suggest that a light chain is more nephrotoxic if it has a high isoelectric point (i.e. is cationic in relation to urine pH).

2. We studied 23 patients with multiple myeloma, measuring light chain excretion rate, light chain isoelectric point (pI) and creatinine clearance.

3. Light chain excretion rate was independent of light chain isoelectric point and did not correlate with creatinine clearance.

4. Light chain isoelectric point correlated with creatinine clearance, suggesting that this characteristic may be an important determinant of the nephrotoxic effect of these immunoglobulin constituents.
Calcium Antagonists and Hormone Release
Authors: Millar J. A. , Struthers A. D.
Published: August 2015

Introduction: Calcium (Ca2+) has been aptly entitled the ‘universal provocateur’ [1] in recognition of its many indispensable metabolic actions. The class of drugs popularly known as calcium antagonists (calcium slow channel blockers) provokes a variety of pharmacological effects and these drugs are useful as probes of calcium-dependent mechanisms. One area where such application appears particularly appropriate is the study of hormone release, since it has been demonstrated that secretion of at least some hormones is dependent on translocation of extracellular Ca2+ across the cell membrane. Furthermore, specific physiological stimuli to secretion of most hormones can be applied in vivo or mimicked in vitro, and hormone levels may be measured by specific assays. Calcium antagonists also provide a possible means of studying the role of Ca2+ in hormone release in the intact organism. In many studies an inhibitory effect of a calcium antagonist on hormonal responses to secretory stimuli has been taken as evidence that transmembrane flux of Ca2+ is an obligatory event in the response. Such a conclusion begs several questions, which will be discussed in this review. For example, it is important to define the extent to which calcium antagonists represent a homogeneous class of drugs, whether ‘antagonism’ is restricted to inhibition of inward calcium flux, and whether the pharmacological actions vary according to the agent used or the cell type under study. Answers to such questions are necessary to exclude actions of calcium antagonists other than prevention of calcium uptake which may inhibit hormone release.
The Effect of a Reduced Sodium Intake on Post-Renal Transplantation Hypertension in Rats
Authors: De Keijzer M. H. , Provoost A. P. , Wolff E. D. , Kort W. J. , Weijma I. M. , Van Aken M. , Molenaar J. C.
Published: August 2015

1. In an experimental model of post-renal transplantation hypertension in rats, we studied the effect of a reduction of sodium intake on the development of this type of hypertension.

2. Systolic blood pressure, plasma- renin concentration and renal function were measured regularly in recipients of an allogeneic kidney transplant that had previously undergone active immunological enhancement.

3. Transplant recipients on a normal diet showed a rise in systolic blood pressure during the second week after transplantation. The systolic blood pressure of recipients on a low sodium diet remained normotensive throughout the 15 weeks follow-up period.

4. The plasma renin concentration was low in the hypertensive recipients on a normal diet, as compared with unilaterally nephrectomized controls. Although the plasma renin concentration of recipients on a low sodium diet fell below that of unilaterally nephrectomized controls on a low sodium diet, it was higher than that of recipients on a normal diet.

5. The renal function of transplant recipients was greatly reduced compared with that of control rats. The glomerular filtration rate was reduced to a greater extent than the effective renal plasma flow.

6. In a separate experiment it was revealed that a similar reduction in the glomerular filtration rate of kidneys permanently damaged by temporary ischaemia did not result in an increase in the systolic blood pressure.

7. Survival up to 6 weeks after transplantation was the same for both groups of recipients. Recipients on a low sodium diet, however, showed a better 15 weeks survival, probably owing to the absence of hypertension in this group.

8. The prevention of the development of hypertension by means of a reduction of sodium intake, points to an involvement of sodium retention in this post-transplantation hypertension model.
The Effects of Immobilization, after Lower Leg Fracture, on the Contractile Properties of Human Triceps Surae
Authors: White M. J. , Davies C. T. M.
Published: August 2015

1. The contractile properties of the triceps surae were evaluated in 11 patients after unilateral fracture of the lower leg and subsequent immobilization for 135 ± 68 days. Calf muscle cross-sectional area (plus bone: CSA) was assessed from anthropometric measurement.

2. It was shown that the injured leg had a faster time to peak tension and increased half-relaxation time (1/2RT); twitch force (Pt) was reduced by 25%. Evoked maximal tetanic tensions (P0) at 10 and 20 Hz were reduced by 51% and 46% respectively compared with the uninjured leg. The force of a maximal voluntary contraction (MVC) was also reduced, by 50%, but calf circumference and CSA were only 5% and 16% respectively lower in the injured leg.

3. It was concluded that the changes in contractile speed may indicate a relatively greater atrophy of slow (type I) muscle fibres.

4. The relationship between CSA and tension generation in the injured limb was shown to be poor after immobilization and during recovery. Anthropometric estimation of CSA does not appear to reflect the degree of muscle wasting, as indicated by reduced tension development after immobilization.
The Logical Description of a Disease Class as a Boolean Function with Special Reference to the Irritable Bowel Syndrome
Authors: Card W. I. , Lucas R. W. , Spiegelhalter D. J.
Published: August 2015

1. Although some disease classes can be defined by a single defining characteristic, in terms of traditional logic one that is both necessary and sufficient, other disease classes, such as the so-called ‘irritable bowel syndrome’ (IBS), have only a set of symptoms, signs etc. which are said to chatacterize it in some undefined way.

2. This characterization might be made definite by using simple Boolean algebra to give a logical description of the disease class.

3. This method can only be used if the individual doctor can be shown to be consistent in his assignment of a set of data to the disease class and also if his assignment agrees independently with that of another doctor.

4. To test such consistency and concordance, 100 case records were collected of supposed IBS and not-IBS; 20 of these were replicated to test consistency, and the total of 120 records was examined by five consultants independently, who assigned them either to an IBS or a not-IBS class.

5. From the 1500 pair-wise comparisons, analysis revealed that the disagreement in assignment between doctors was only slightly greater than the disagreement within doctors, suggesting that the group of doctors acted as if there were an implicit description of IBS with which each of them broadly agreed. This implicit description, if made explicit, could form a basis for diagnosis by logical implication.

6. This method of logical definition has general application in medicine and a set of defined cases could be used to establish entry criteria for multicentre trials of a previously ill-defined class.
Blood Pressure and Intra-Erythrocyte Sodium during Normal and High Salt Intake in Middle-Aged Men: Relationship to Family History of Hypertension, and Neurogenic and Hormonal Variables
Authors: Gudmundsson Ottar , Herlitz Hans , Jonsson Olof , Hedner Thomas , Andersson Ove , Berglund Goran
Published: August 2015

1. During 4 weeks 37 normotensive 50-year-old men identified by screening in a random population sample were given 12 g of NaCl daily, in addition to their usual dietary sodium intake. Blood pressure, heart rate, weight, urinary excretion of sodium, potassium and catecholamines, plasma aldosterone and noradrenaline and intra-erythrocyte sodium content were determined on normal and increased salt intake. The subjects were divided into those with a positive family history of hypertension (n = 11) and those without such a history (n = 26).

2. Systolic blood pressure and weight increased significantly irrespective of a positive family history of hypertension.

3. On normal salt intake intra-erythrocyte sodium content was significantly higher in those with a positive family history of hypertension. During high salt intake intra-erythrocyte sodium content decreased significantly in that group and the difference between the hereditary subgroups was no longer significant.

4. In the whole group urinary excretion of noradrenaline, adrenaline and dopamine increased whereas plasma aldosterone decreased during the increased salt intake.

5. Thus, in contrast to some earlier studies performed in young subjects, our results indicate that moderately increased sodium intake acts as a pressor agent in normotensive middle-aged men whether there was a positive family history of hypertension or not. We confirm that men with positive family history of hypertension have an increased intra-erythrocyte sodium content, and that an increase in salt intake seems to increase overall sympathetic activity.
Calmodulin and Cell Function
Authors: Tomlinson S. , MacNeil S. , Walker S. W. , Ollis C. A. , Merritt J. E. , Brown B. L.
Published: August 2015

Introduction: The importance of calcium in the regulation of cell function has become increasingly recognized in the past 20 years. It is now known that changes in intracellular calcium concentration, like changes in adenosine 3′:5′-monophosphate (cyclic AMP), are of crucial importance in stimulus-response coupling. Thus, the second messenger theory originally proposed by Sutherland et al. [1], in which a hormone or nerve impulse is first messenger and cyclic AMP the second intracellular messenger, has been expanded to include calcium ions as well as cyclic nucleotides. Moreover, there is now evidence in many cellular systems that calcium ions and cyclic nucleotides act as dual interrelated messengers [2], and, therefore, some cellular processes are regulated by calcium as well as by cyclic nucleotides, as shown in Table 1. Evidence has accumulated that it is changes in free intracellular calcium concentration that are, in some way, responsible for activation of the enzymes involved in the processes shown in this Table.
Evidence for Angiotensin-Stimulated Proximal Tubular Fluid Reabsorption in Normotensive and Hypertensive Rats: Effect of Acute Administration of Captopril
Authors: Harris P. J. , Navar L. G. , Ploth D. W.
Published: August 2015

1. The effects of captopril on mean arterial blood pressure and proximal tubular fluid re-absorption (Jv) were examined in anaesthetized normotensive rats and in the non-clipped kidneys of two-kidney, one-clip Goldblatt hypertensive rats.

2. In the normotensive animals, captopril reduced arterial blood pressure from 121 ± sd 9 to 106 ± 10 mmHg and Jv decreased from 3.78 ± 0.45 to 2.57 ± 0.58 × 10−4mm3mm−2s−1. Captopril had a greater effect on blood pressure in the hypertensive animals (172 ± 17 reduced to 133 ± 23 mmHg) although the decrease in Jv from 3.62 ± 0.12 to 2.40 ± 0.40 was similar to that observed in normotensive animals.

3. These results provide evidence that, in the anaesthetized rat, angiotensin II contributes to the maintenance of the rate of proximal fluid re-absorption. The magnitude of the angiotensin-stimulated component of proximal fluid absorption is similar in normotensive and two-kidney, one-clip Goldblatt hypertensive rats.
Cyclic AMP Responses to Parathyroid Hormone and Glucagon during Lithium Treatment
Authors: Waller D. G. , Albano J. D. M. , Millar J. G. B. , Polak A.
Published: August 2015

1. Inhibition of adenylate cyclase has been proposed as a mechanism for hypothyroidism and nephrogenic diabetes insipidus occurring during lithium treatment, but these disorders are rarely found in the same patients.

2. We have measured plasma levels of adenosine 3′:5′-cyclic monophosphate (cyclic AMP) after an intravenous injection of glucagon in eight patients receiving long term lithium treatment and in six control subjects. Urinary cyclic AMP levels after an intravenous injection of bovine parathyroid hormone (PTH) were also measured in the patients.

3. The plasma cyclic AMP response to glucagon in the patient group was significantly lower than that of the controls. No correlation was demonstrated between the plasma cyclic AMP response after glucagon and the urinary cyclic AMP response after PTH.

4. We have previously shown that impairment of the response to PTH correlates with reduced urine concentrating ability during lithium treatment. In contrast, there was no correlation between the responses to PTH and glucagon in individual patients. These results are consistent with the hypothesis that inhibition of adenylate cyclase is an important factor in lithium-induced endocrine dysfunction.
Acute effects of moderate alcohol consumption on blood pressure and plasma catecholamines
Authors: Ireland M. A. , Vandongen R. , Davidson L. , Beilin L. J. , Rouse I. L.
Published: August 2015

1. This study examines the response of blood pressure, plasma catecholamines and cortisol to acute alcohol intake in young men with light to moderate drinking habits.

2. Ingestion of alcohol was associated with a highly significant increase in systolic blood pressure and heart rate which occurred before blood alcohol reached its peak concentration of 16.9 ± 1.1 mmol/l (80 mg/100 ml). After an initial non-specific rise, diastolic pressure fell below values observed after drinking water only. This predominant effect of alcohol on systolic blood pressure is also seen with chronic alcohol consumption.

3. Drinking water and non-alcoholic cold liquids caused a marked fall in plasma adrenaline and a transient rise in noradrenaline concentration. In contrast, drinking alcohol resulted in a relative rise in adrenaline and a delayed increase in noradrenaline concentration.

4. Blood glucose increased after alcohol, supporting a physiological effect of adrenaline on liver glycogenolysis. Plasma cortisol concentration was also significantly higher after drinking alcohol.

5. It is proposed that the relative rise in adrenaline together with higher cortisol levels, repeated over a variable period in susceptible individuals, are implicated in the elevation of blood pressure associated with long term alcohol consumption. It concurs with observations in man and experimental animals of a slow pressor mechanism mediated by adrenaline.

6. The study emphasized that an evaluation of the acute effects of alcohol requires careful measurement of blood pressure, precise assay of catecholamines and recognition of the confounding effects of drinking cold liquids.
Methacholine dose-response curves in normal and asthmatic man: Effect of starting conductance and pharmacological antagonism
Authors: Chung K. F. , Snashall P. D.
Published: August 2015

1. The bronchial response of 11 normal and ten stable asthmatic subjects to increasing concentrations of methacholine aerosol was assessed by serial measurements of specific airways conductance (scaw) in a body plethysmograph.

2. Cumulative log dose-response curves were constructed. The threshold provocative dose of methacholine needed to cause a 35% fall in starting sCaw (pD35) and the steepest slope of the response were measured from each curve.

3. On separate days subjects were premedicated with 0.9% NaCl solution (control) in duplicate, chlorpheniramine, salbutamol and atropine, the last-named at two different doses, one twice the other.

4. Asthmatic subjects had a lower mean PD35 and a lower mean slope than normal subjects.

5. Pretreatment with salbutamol resulted in a greater increase in sGaw than after atropine but caused a smaller increase in PD35 in both groups. There was a dose-dependent increase in PD3s after the two doses of atropine, but no significant difference in bronchodilatation between doses. Mean steepest slope approximately doubled in these three sets of challenges.

6. Chlorpheniramine caused a small degree of bronchodilatation and there was a non-significant increase in mean PD3s and in mean steepest slope in both normal and asthmatic groups.

7. There was a positive linear correlation between starting sGaw and steepest slope in each group of premedicated challenges, such that when
A circulating inhibitor of leucocyte sodium transport in patients with advanced liver cirrhosis
Authors: Sewell R. B. , Poston Lucilla , Wilkinson S. P. , Williams Roger
Published: August 2015

1. Leucocyte sodium efflux was measured in control leucocytes pre-incubated for 90 min with serum from patients with advanced liver cirrhosis.

2. Serum from patients with advanced alcoholic liver cirrhosis was inhibitory to sodium transport in control leucocytes. The degree of inhibition was similar to that seen in the patients' own leucocytes; the defect induced by patient serum was primarily inhibition of ouabain-insensitive sodium efflux, whereas in the patients' own leucocytes, inhibition was seen in both ouabain-sensitive and -insensitive sodium efflux, as shown previously.

3. The results suggest that a circulating factor, present in patients with advanced cirrhosis, is capable of inhibiting sodium transport in leucocytes.
Pathogenicity of Cationized Albumin in the Dog: Renal and Extrarenal Effects
Authors: Lambert P. P. , Doriaux M. , Sennesael J. , Vanholder R. , Lammens-Verslijpe M.
Published: August 2015

1. The effects of 21 cationized serum albumin samples of various degrees of cationization on renal function were studied in the dog. The samples were perfused intra-aortically to obtain preferential perfusion of the left kidney in 25 dogs. Standard clearance techniques were used, associated in six dogs with sieving studies of 125I-labelled polyvinylpyrrolidone (125I-PVP) and with an extensive morphological study in 15 dogs.

2. Renal effects were observed. (a) Renal effects in left kidneys. The perfusion with weakly cationized albumin (group 1) produced moderate proteinuria associated with the deposition of cationized albumin on the anionic sites of the basement membrane. Glomerular filtration rate (GFR) was unaltered. Perfusion with highly cationized samples (group 2) produced more severe proteinuria and a significant decrease in GFR. Glomerular permeability to 125I-PVP increased. Perfusion with the four samples of highest pI (group 3) was followed by anuria. (b) Renal effects in right kidneys. A retarded mild proteinuria appeared only in group 2 and group 3 animals without alteration of GFR. All the kidneys (group 1 included), with the exception of two (group 3), showed deposition of the protein in the anionic sites.

3. The following extrarenal effects were observed essentially in group 2 and group 3 animals: erythrocyte agglutination and haemolysis, platelet aggregation and thrombocytopenia, and a decrease in plasma fibrogen level due to fibrinogen precipitation. These effects produced progressive obstruction in the glomerular capillaries, thus explaining the occurrence of anuria. The structural damage in group 2 and group 3 left kidneys bears remarkable resemblance to that observed in the fulminant form of the human so-called ‘haemolytic-uraemic syndrome’.

4. The neutralization alone of the fixed negative charges in the glomerular wall appears to produce only mild proteinuria, whereas the various extrarenal effects combine to produce more severe proteinuria associated with functional alteration and vascular obstruction.
Role of the Splanchnic Bed in Extracting Circulating Adrenaline and Noradrenaline in Normal Subjects and in Patients with Cirrhosis of the Liver
Authors: Keller U. , Gerber P. P. G. , Bühler F. R. , Stauffacher W.
Published: August 2015

1. Splanchnic extraction rates of adrenaline and noradrenaline were determined in seven normal subjects and in nine patients with cirrhosis of the liver using arterial-hepatic venous catherization.

2. Both catecholamines were effectively removed when the blood passed through the splanchnic area: splanchnic fractional uptake of adrenaline in normal subjects was 90 ± 3%, and lower for noradrenaline, 68 ± 4% (P < 0.001). Net splanchnic extraction rates were higher for noradrenaline (126 ± 16 ng/min) than for adrenaline (40 ± 10 ng/min, P < 0.001), probably due to the higher arterial plasma levels of noradrenaline.

3. Resting arterial adrenaline and noradrenaline levels were significantly higher in cirrhotic patients than in normal subjects (adrenaline: 121 ± 27 vs 54 ± 8 pg/ml, P < 0.05; noradrenaline: 678 ± 89 vs 251 ± 26 pg/ml, P < 0.005). Net splanchnic catecholamine uptake was increased in cirrhotic patients.

4. The results demonstrate that the splanchnic bed in normal and cirrhotic subjects extracts plasma catecholamines efficiently; they suggest that elevated plasma catecholamines in cirrhosis are not the result of impaired splanchnic catecholamine removal.
A Paradoxical Fall in Urine Dopamine Output When Patients with Essential Hypertension Are Given Added Dietary Salt
Authors: Harvey J. N. , Casson I. F. , Clayden A. D. , Cope G. F. , Perkins C. M. , Lee M. R.
Published: August 2015

1. The effect of dietary sodium on the urine dopamine excretion of eight hypertensive patients and six matched controls was studied under metabolic balance conditions over a 2 week period during which dietary sodium intake was increased from 20 to 220 mmol/day.

2. The control group showed the expected increase in dopamine excretion in response to sodium but the hypertensive patients showed an initial fall followed by a return to baseline values.

3. Neither group showed a rise in blood pressure but the hypertensive patients showed a greater weight gain on salt loading, although this change was not significant. The cumulative sodium balance was greater and more prolonged in the hypertensive patients, although this difference also did not attain statistical significance.

4. This defect in dopamine mobilization may be important in relation to renal sodium handling by patients with essential hypertension.
Receptor-Cyclase Coupling Protein in Erythrocytes of Patients with Essential Hypertension
Authors: Farfel Zvi , Iaina Adrian , Eliahou Haskel , Cohen Zohara
Published: August 2015

1. In order to define the alteration of the function of the adrenergic system in hypertension, we studied directly the receptor-cyclase coupling protein (N protein), which is one of the components of the enzyme adenylate cyclase.

2. N protein was determined in erythrocyte membranes of patients with essential hypertension and normal subjects, with a complementation assay in vitro. Fifteen normal subjects and 18 patients with essential hypertension (eight untreated and ten treated with β-adrenoreceptor blocking drugs alone or in combination with other antihypertensive drugs), and two patients with pseudohypoparathyroidism type Ia (known to have deficient N protein activity), were studied.

3. Erythrocyte N protein activities in the various groups expressed as percentages of the means ± sd of normals were: normal subjects 100 ± 13.7, untreated hypertensive 108.9 ± 20.4, treated hypertensive 104.3 ± 11.3 and pseudohypoparathyroidism type Ia 43%.

4. The difference between N protein activity in the hypertensive patients and normals was not statistically significant. We suggest that the molecular basis for the altered sympathetic responsiveness in essential hypertension may reside in other components of the cyclic AMP protein kinase effector system.