bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrasplenic blood cell kinetics in man before and after brief maximal exercise
Authors: Allsop P. , Peters A. M. , Arnot R. N. , Stuttle A. W. J. , Deenmamode M. , Gwilliam M. E. , Myers M. J. , Hall G. M. 
Published: August 2015

1. After a 4 min period of maximal exercise in 10 normal subjects (14 studies), there was a consistent decrease in total blood volume and a consistent increase in erythrocyte indices, which were maximal immediately after exercise. Peripheral platelet and leucocyte counts increased, but did not reach maximal values until 5–10 min after the end of exercise.
2. The distributions of 99mTc-Iabelled erythrocytes (five studies), 111In-labelled platelets (five studies) and 111In-labelled granulocytes (four studies) were monitored with a γ-camera immediately after injection and before and after maximal exercise performed 60 min after injection.
3. Labelled erythrocytes equilibrated rapidly between the spleen and circulating blood after injection, whereas labelled platelets and granulocytes equilibrated more slowly. After exercise, each cell type was released from the spleen with a time course that was the reciprocal of the time course of the corresponding cell count in peripheral blood. Thus, whereas the radioactivity of 99mTc-labelled erythrocytes in the spleen, which fell to 0.46 (SD 0.09) of the pre-exercise value, increased towards its baseline value as soon as exercise was completed, the radioactivities of 111In-labelled platelets and 111In-labelled granulocytes decreased, to respective minimum values of 0.61 (0.09) and 0.63 (0.09) of the pre-exercise levels, 5–10 min after the end of exercise. The exercise-induced changes in lung radioactivity for each cell type, and their time courses, broadly reflected those in the corresponding cell counts in peripheral blood. Liver radioactivity tended to decrease for each cell type.
4. Because of the dissociation of the time courses of splenic expulsion of erythrocytes (intrasplenic transit time about 1 min) from those of platelets and granulocytes (intrasplenic transit times both of 8–10 min), we conclude that blood cell expulsion from the spleen in man is not the result of active splenic contraction but probably the passive result of a decrease in splenic blood flow.
Measurement of pelvic blood flow changes in response to posture in normal subjects and in women with pelvic pain owing to congestion by using a thermal technique
Authors: Thomas D. C. , Stones R. W. , Farquhar C. M. , Beard R. W. 
Published: August 2015

1. A method is described for studying pelvic blood flow in women by the indirect method of measuring vaginal temperature changes in response to a posture change. Ten women with chronic pelvic pain and venous congestion and 10 normal subjects were observed during posture changes over a 2 h period.
2. Vaginal temperature minus axillary temperature rose after subjects changed from the supine to the seated position, indicating a fall in the rate of pelvic blood flow.
3. A significantly greater variance in the rate of change in vaginal temperature minus axillary temperature was found in patients with pelvic venous congestion compared with control subjects (P&gt; 0.005).
4. The findings are consistent with a disorder of blood flow regulation in women with pelvic pain owing to congestion.
Sympathoadrenal contribution to plasma dopa (3,4-dihydroxyphenylalanine) in rats
Authors: Grossman Ehud , Hoffman Aaron , Armando Ines , Abassi Zaid , Kopin Irwin J. , Goldstein David S. 
Published: August 2015

1. To determine the sources of dopa (3,4-dihydroxyphenylalanine) in plasma, we measured regional arteriovenous differences, tissue concentrations and urinary excretion of dopa during systemic intravenous infusions of I-[3H]dopa into anaesthetized intact rats and rats pretreated with the sympathetic neurotoxin, 6-hydroxydopamine.
2. In intact rats, large arteriovenous increments in plasma dopa concentrations were noted in the femoral (47%) and adrenal (141%) beds, with a small arterial-portal venous increment (11%), whereas in the kidney there was a substantial (47%) arteriovenous decrement in plasma dopa levels. Skeletal muscle appeared to be a major source of dopa in arterial plasma.
3. Treatment with 6-hydroxydopamine abolished the afferent-efferent increment of plasma dopa concentrations in the femoral bed. The arteriovenous decrement of plasma dopa concentrations in the kidney was preserved, and the arteriovenous increment in the adrenal bed was decreased by about half. Arterial plasma dopa levels fell by 41%.
4. Regional extraction percentages of I-[3H]dopa were used to estimate the clearances and rates of appearance (spillovers) of dopa in plasma. Dopa spillover was detected in the femoral, renal, splanchnic and adrenal beds, with skeletal muscle accounting for about 44% and the kidneys accounting for about 18% of dopa in arterial plasma. Whereas chemical sympathectomy decreased the femoral and renal spillover of dopa by 90% or more, arterial dopa levels and estimated dopa spillover into arterial plasma were decreased by only about 45%.
5. The kidneys accounted for 22% of dopa clearance from arterial plasma. From the renal extraction of I-[3H]dopa and the urinary excretion of [3H]dopamine, it was estimated that 77% of dopa removed in the kidneys was excreted as dopamine in intact animals and 69% was excreted as dopamine in sympathectomized animals. Conversely, about 80% of urinary endogenous dopamine was derived from plasma dopa, regardless of 6-hydroxydopamine treatment.
6. The results indicate that endogenous dopa in arterial plasma is derived substantially but not exclusively from sympathetic nerve endings that are destroyed by 6-hydroxydopamine, especially in skeletal muscle and the kidneys. Regional dopa spillover therefore probably reflects regional catecholamine biosynthesis. In rats, urinary dopamine is derived mainly from renal decarboxylation of circulating dopa.
Comparative study of platelet angiotensin II binding and the angiotensin II sensitivity test as predictors of pregnancy-induced hypertension
Authors: Baker Philip N. , Pipkin Fiona Broughton , Symonds E. Malcolm 
Published: August 2015

1. Platelet angiotensin II binding was measured in 34 primigravid women (between 28 and 32 weeks gestation), in whom the pressor response to infused angiotensin II was also determined.
2. There was a significant correlation between the platelet angiotensin II binding and the slope of the curve relating the diastolic pressor response to infused angiotensin II (P&lt;0.01), suggesting that co-linearity between the two techniques exists and supporting the use of platelet angiotensin II binding as a model of vascular smooth muscle pressor responsiveness.
3. Ten of the 34 women subsequently developed pregnancy-induced hypertension. Platelet angiotensin II binding in the patients who subsequently developed pregnancy-induced hypertension was sixfold higher than in the patients who remained normotensive (P &lt; 0.001). There were, however, no significant differences between the groups in any of the parameters derived from the angiotensin II infusion experiments.
4. The use of platelet angiotensin II binding alone in predicting the outcome of the pregnancies, as assessed using discriminant analysis, was more successful than when any of the infusion parameters were used, with 77% of patients being correctly classified.
Diet as a source of phospholipid esterified 9,11-octadecadienoic acid in humans
Authors: Britton Mary , Fong Christopher , Wickens David , Yudkin John 
Published: August 2015

1. Diene-conjugated fatty acids are one of the products of free-radical attack upon lipids and therefore have been used as markers of such attack. The major diene-conjugated fatty acid in human tissue and serum is an isomer of linoleic acid (9,12-octadecadienoic acid), namely 9,11-octadecadienoic acid. Diet may be another source of this isomer, raising questions as to its value as a free-radical marker. The aim of this study was to determine the importance of diet as a source of 9,11-octadecadienoic acid in phospholipid esterified fatty acids in human serum.
2. Foodstuffs rich in 9,11-octadecadienoic acid were identified. Fourteen subjects volunteered to alter their diets, either increasing ('high diet') or decreasing ('low diet') their intake of these foodstuffs for 3 weeks. Where subjects undertook both diets, a washout period of at least 3 weeks was allowed between phases.
3. Seven-day diet histories were kept and scored with respect to their content of 9,11-octadecadienoic acid. The concentrations of 9,11-octadecadienoic acid and linoleic acid in serum phospholipids were measured by h.p.l.c. with u.v. detection.
4. The percentage molar ratio of 9,11-octadecadienoic acid to linoleic acid was calculated. The percentage molar ratio rose significantly on the ‘high diet’ [1.3(0.4) versus 1.9(0.7), P=0.01, mean (SD)] and fell significantly on the ‘low diet’ [1.6(0.4) versus 1.1(0.4), P=0.004, means (SD)]. There was a significant correlation between the change in dietary intake of 9,11-octadecadienoic acid and the change in the percentage molar ratio (r= 0.829, P = 0.001).
5. The concentration of 9,11-octadecadienoic acid in serum phospholipids is influenced by diet. Its use as a marker of free-radical activity is questionable and at least in need of careful interpretation.
Limits of adaptation to a diet low in protein in normal man: urea kinetics
Authors: Danielsen M. , Jackson A. A. 
Published: August 2015

1. Urea kinetics were measured using prime/intermittent oral doses of [15N15N]urea in six healthy men taking diets adequate in energy and containing either 74 or 30 g of protein/day.
2. On 74 g of protein/day, urea production (199 mg of N day−1 kg−1) was 121% of intake, with 60% of the urea produced being excreted in the urine and 40% being salvaged in the colon; 69% of the salvaged nitrogen was retained in the metabolic nitrogen pool.
3. Nitrogen balance was not maintained on 30 g of protein/day. There was a significant decrease in the urea production rate (123 mg of N day−1 kg−1) and 54% of production was excreted in urine, with 46% being salvaged.
4. The pattern of urea production and salvaging on 30 g of protein/day was different to that seen in an earlier study on 35 g of protein/day, with a significant decrease in both production (71%) and salvaging (50%).
5. These data reinforce the conclusions drawn from an earlier study, that the salvaging of urea nitrogen by the colon is an integral part of the process of adaptation to low protein diets. The salvage system appears to fail on an intake of 30 g of protein/day and nitrogen is no longer conserved in sufficient amounts for balance to be maintained.
6. The changes seen in urea kinetics reinforce the conclusion based upon nitrogen balance that the minimum physiological requirement for protein in normal adult man lies between 30 and 35 g of protein/day.
Glucocorticoids and blood pressure: a role for the cortisol/cortisone shuttle in the control of vascular tone in man
Authors: Walker Brian R. , Connacher Alan A. , Webb David J. , Edwards Christopher R.W. 
Published: August 2015

1. 11β-Hydroxysteroid dehydrogenase converts cortisol to inactive cortisone in man. In distal renal tubules, this inactivation protects mineralocorticoid receptors from cortisol. Congenital 11β-hydroxysteroid dehydrogenase deficiency and inhibition of 11β-hydroxysteroid dehydrogenase by liquorice or carbenoxolone result in cortisol-dependent hypokalaemia and hypertension.
2. 11β-Hydroxysteroid dehydrogenase is expressed in vascular smooth muscle. Both glucocorticoids and mineralocorticoids potentiate vascular responses to noradrenaline. 11β-Hydroxysteroid dehydrogenase activity may therefore influence vascular tone.
3. Experiments were performed in healthy subjects with and without 7 days of oral administration of 11β-hydroxysteroid dehydrogenase inhibitors (liquorice or carbenoxolone), and in a patient with congenital 11β-hydroxysteroid dehydrogenase deficiency. We measured the following parameters: dermal vasoconstriction after topical application of cortisol, forearm blood flow during brachial artery infusion of cortisol or noradrenaline, and blood pressure during systemic infusion of noradrenaline.
4. Cortisol-induced dermal vasoconstriction was increased by liquorice (23 ± 6 to 52 ± 7 units; P&lt;0.04) and in congenital 11β-hydroxysteroid dehydrogenase deficiency (87 units). In congenital 11β-hydroxysteroid dehydrogenase deficiency intraarterial infusion of cortisol caused vasoconstriction (20% reduction in blood flow in the infused arm) and accentuated the response to application of lower-body negative pressure, which stimulates sympathetically mediated vasoconstriction (35% reduction). However, intra-arterial infusion of cortisol had no effect in healthy subjects either with or without administration of liquorice.
5. Carbenoxolone potentiated both noradrenaline-induced forearm vasoconstriction (P&lt;0.01) and pressor response (P&lt;0.001).
6. We conclude that 11β-hydroxysteroid dehydrogenase modulates the access of cortisol to vascular receptors and thereby influences vascular sensitivity to noradrenaline. Complementary to its role in kidney, 11β-hydroxysteroid dehydrogenase could influence blood pressure by this mechanism, which may underlie our observations of impairment of 11β-hydroxysteroid dehydrogenase and increased dermal vascular sensitivity to cortisol in patients with essential hypertension.
Autoimmunity to glomerular antigens in Henoch—Schoenlein nephritis
Authors: O'Donoghue D. J. , Jewkes F. , Postlethwaite R. J. , Ballardie F. W. 
Published: August 2015

1. Henoch—Schoenlein nephritis and IgA nephropathy share clinical and immunological features, but the pathogenesis of neither condition is established. We have recently described IgG autoantibodies to glomerular components in active IgA nephropathy and have now sought evidence for a similar autoimmune component in Henoch—Schoenlein purpura.
2. Sera from 26 patients with Henoch—Schoenlein nephritis and six patients with Henoch—Schoenlein purpura without accompanying nephritis were studied and compared with sera from 20 patients with other forms of glomerulonephritis and 40 normal subjects. E.l.i.s.a.s were developed to detect IgA and IgG binding to the ligand from whole human glomeruli previously described, laminin, DNA, cardiolipin (diphosphatidylglycerol) and a panel of dietary constituents (BSA, α-caesin, β-lactoglobulin, ovalbumin and wheat gliadin).
3. Sera from 16 of the 26 patients with Henoch—Schoenlein nephritis displayed increased IgG binding to the human glomerular extract compared with the normal control group (P&lt;0.001), whereas IgG binding was not significantly raised in the patients with Henoch—Schoenlein purpura without evidence of renal involvement. IgA binding was not raised compared with control subjects. Serum IgA and IgG binding to other potential autoantigens or antigens present on dietary constituents was not significantly different in patients with Henoch—Schoenlein nephritis or patients with Henoch—Schoenlein purpura without nephritis compared with control subjects.
4. Western blotting of the denatured and reduced glomerular extract revealed binding of IgG, from the sera of patients with active Henoch—Schoenlein nephritis, to glomerular components of Mr 48000 and 58000, similar to the Mr of the glomerular antigens identified in IgA nephropathy. Immunoglobulin binding was shown to be specific antibody binding using F(ab')2 fragments from the IgG fraction of e.l.i.s.a.-positive sera.
5. Clinical associations showed in 10 of 11 patients with Henoch—Schoenlein nephritis whose sera were studied in remission: IgG antiglomerular antibody binding fell to within the normal range (P&lt;0.05).
6. These results demonstrate an autoimmune component in Henoch—Schoenlein nephritis, and the close temporal relationship with active nephritis implies that this may be a critical component in the pathogenesis of glomerular injury. The absence of specific antibody, or non-specific immunoglobulin binding, to any of the range of dietary constituents or other putative autoantigens tested suggests that polyclonal B-cell activation is not an important feature of Henoch—Schoenlein nephritis.
A new method to measure renal tubular degradation of small filtered proteins in man using radiolabelled aprotinin (Trasylol)
Authors: Rustom R. , Grime S. , Maltby P. , Stockdale H. R. , Critchley M. , Bone J. M. 
Published: August 2015

1. A method has been developed to measure the renal tubular degradation of small filtered proteins in man using radiolabelled aprotinin (Trasylol), a 6500 Da cationic polypeptide.
2. Aprotinin (0.5 or 5.0 mg) was labelled with either 99mTc (40 MBq) or 131I (1 MBq) and injected intravenously in 19 renal patients (10 with normal renal function and nine on haemodialysis). Activity in plasma and urine was measured over 48 h, and chromatography with Sephadex-G-25-M was used to separate labelled aprotinin from free 99mTcO-4 or 131I-. Renal uptake was measured for 99mTc-labelled aprotinin only.
3. The volumes of distribution were similar in all patients: 18.2 ± 0.4 litres in those with normal renal function and 20.2 ± 0.1 litres in the others. Chromatography showed all plasma activity as undegraded aprotinin and urine activity only as the free labels (99mTcO-4 or 131I-).
4. In patients with normal renal function, activity in the kidneys rose rapidly to 24.2 ± 2.8% of dose after 90 min and to 42.2 ± 3.4% of dose after 24 h. In the dialysis patients, activity over the kidneys was only 2.7 ± 0.8% of dose at 24 h. Extra-renal uptake was insignificant in all patients with normal kidney function.
5. Both 99mTcO-4 and 131I- appeared in the urine promptly after injection, and the rates of excretion of the two isotopes were similar, varying little over 24 h (1.8 ± 0.04% of dose/h and 1.7 ± 0.04% of dose/h for 99mTc and 131I, respectively).
6. Fractional renal tubular degradation of 99mTc-aprotinin (in h−1) is a measure of its turnover value over a given interval and is given by: Mean urinary appearance of free isotope (% of dose/h)/mean cumulative kidney uptake over the same interval (% of dose) The rate of fractional degradation fell rapidly from 0.20 ± 0.02 h−1 between 0 and 90 min to 0.08 ± 0.01 h−1 between 90 min and 3 h to 0.07 ± 0.01 h−1 between 3 and 4.5 h and to 0.05 ± 0.002 h−1 between 4.5 and 24 h.
7. The stability of urinary excretion of free isotope during the 24 h after injection, together with the relative stability of fractional degradation after 4.5 h, and the reproducibility of the technique offer a practical method for the further study of filtered protein catabolism by the renal tubules in man. This has hitherto not been possible.
Technique for the primary culture of human breast cancer cells and measurement of their prostaglandin secretion
Authors: Watson John , Chuah Siew Yeam 
Published: August 2015

1. A method is described for the primary culture of human breast tumour cells on feeder layers of the STO mouse embryo fibroblast cell line.
2. The secretion of the prostaglandins E2 and F2α from the cells was measured and the results indicate that the secretion of both prostaglandins was dependent on oestrogen-receptor status, with cells from oestrogen-receptor-positive tumours secreting significantly more prostaglandin than cells from oestrogen-receptor-negative tumours.
3. Postaglandin E2, but not prostaglandin F2α, secretion was also significantly greater from cells of tumours from postmenopausal women than from cells of tumours from premenopausal women. Small (&lt; 3 cm) tumours secreted significantly more prostaglandin than large (&gt; 3 cm) tumours, and increased levels of prostaglandin were secreted with advancing clinical stage (T1-T4).
4. Additional evidence for increased prostaglandin metabolism in oestrogen-receptor-positive tumours compared with oestrogen-receptor-negative tumours was obtained from studies on the uptake of [14C]arachidonic acid from the cultures. Significantly more labelled arachidonic acid was incorporated into cells from oestrogen-receptor-positive tumours compared with oestrogen-receptor-negative tumours, with the subsequent release of more prostaglandin in response to various stimuli.
Responses of airway rapidly adapting receptors to bradykinin before and after administration of enalapril in rabbits
Authors: Hargreaves M. , Ravi K. , Senaratne M. P. J. , Kappagoda C. T. 
Published: August 2015

1. The present study was performed in anaesthetized, artificially ventilated, open-chested rabbits to examine whether (a) the rapidly adapting receptors of the airways were stimulated by exogenously administered bradykinin, and (b) if this sensitivity could be enhanced by the angiotensin-converting-enzyme inhibitor, enalapril.
2. Rapidly adapting receptor activity (n = 8) was recorded from the cervical vagus. Bradykinin was injected intravenously (0.25–1.0 μg/kg) and a dose—response curve relating receptor activity to bradykinin was elicited. In the control state, the threshold dose of bradykinin required for stimulation of rapidly adapting receptors was 0.53 ± 0.11 μg/kg. Five minutes after the administration of enalapril maleate (2 mg intravenously), the dose—response curve was shifted to the left significantly (P&lt;0.01).
3. In seven other rapidly adapting receptors, enalapril (2 mg) increased the resting activity significantly (P&lt;0.05) over a period of 60 min. This increase was significantly different from the spontaneous variation in neural activity of rapidly adapting receptors (n = 7) recorded over a period of 60 min.
4. Bradykinin either alone (0.25–1.0 μg/kg) or in the presence of enalapril did not stimulate the slowly adapting receptors (n = 5) of the airways.
5. These results show that (a) exogenous bradykinin stimulates the rapidly adapting receptors, (b) the sensitivity of rapidly adapting receptors to bradykinin is enhanced by enalapril and (c) enalapril increases the resting activity of rapidly adapting receptors. It is suggested that the cough reported after the administration of enalapril may be due to stimulation of rapidly adapting receptors of the airways.