Odds ratio and relative risk.
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Probability↗
Biomedical subjects
B C Williams
Publications and source records attributed to B C Williams.
The preparation of D-myo-inositol 1,4-bisphosphate and D-myo-inositol 1,4,5-trisphosphate in milligram quantities from a readily available starting material.
The optimisation of a reaction for the conversion of glycerophosphoinositols to phosphoinositols is described. This reaction has been used in a scheme, described in detail, for the formation of D-myo-inositol 1,4-bisphosphate and D-myo-inositol 1,4,5-trisphosphate in mg quantities from a readily available preparation of mixed phosphoinositides. An optimised procedure is also detailed for the recovery of these products to high yield and purity. The identity of the products has been confirmed both by high resolution anion-exchange column chromatography and by 1H nuclear magnetic resonance studies. We report for the first time the 1H nuclear magnetic resonance spectrum for D-myo-inositol 1,4-bisphosphate.
Chromatography, Thin Layer↗
Angiotensin II-stimulated cortisol secretion is mediated by a hormone-sensitive phospholipase C in bovine adrenal fasciculata/reticularis cells.
Conditions have been established for the incorporation of [3H]inositol ([3H]Ins) into the phosphoinositides of cultured bovine adrenal zona fasciculata/reticularis (ZFR) cells. Stimulation of these prelabelled cells with angiotensin II (10(-11)-10(-7) M AII) resulted in the dose-dependent (max. 16-fold at 10(-7) M AII), time-dependent formation of water-soluble radiolabelled products which show the same chemical and chromatographic properties as [3H]InsP, [3H]InsP2 and [3H]InsP3 standards. The results of the time-course studies of the changes in these products are consistent with the view that AII rapidly (less than 15 s) induces the activation of a polyphosphoinositide-specific phospholipase C. The action of this phospholipase on the polyphosphoinositides is sustained throughout 15 min of stimulation. The dose dependency of this response correlates closely with cortisol output and is reduced (to 52%, P less than 0.00005), but not abolished, in the absence of extracellular Ca2+. To our knowledge these results are the first clear demonstration that AII stimulates a polyphosphoinositide-specific phospholipase C in bovine ZFR cells.
Angiotensin II↗
Inhibitory role of Ca2+ in the control of renin secretion: a study using superfused dispersed rat renal cortical cells.
1. The role of Ca2+ in the control of renin release was investigated using a collagenase-dispersed rat kidney cortex cell preparation. 2. Superfusion with a series of low [Ca2+] buffers in either ascending or descending order of concentration increased renin release. Exposure to 0.06 mmol/l Ca2+ increased release by 120% (P less than 0.001) when presented as the first buffer in ascending order of concentration and by 79% (P less than 0.001) when presented as the fourth and last in a series of descending order. 3. The Ca2+ entry blocking drug diltiazem in a range of concentrations increased renin release and at 10(-5) mol/l diltiazem the mean stimulation was 35% (P less than 0.01). 4. 8-(N.N-Diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) reduces the release of Ca2+ from intracellular stores and, studied over a range of concentrations, this compound increased renin release. At 10(-5) mol/l TMB-8 the mean increase was 44% (P less than 0.001). 5. None of these experimental manipulations, low [Ca2+], diltiazem or TMB-8, had any effect on the release of adenosine 3':5'-cyclic monophosphate into the cell superfusate, indicating that a decrease in intracellular [Ca2+] increases renin release by a mechanism which is independent of changes in adenosine 3':5'-cyclic monophosphate production. 6. Effects of low [Ca2+], diltiazem and TMB-8 on renin secretion were all shown to be reversible when superfusion with control buffer was resumed.
Animals↗
Characterization of the steroidogenic responsiveness and ultrastructure of purified zona fasciculata/reticularis cells from bovine adrenal cortex before and after primary culture.
Analysis by electron microscopy indicated that after 3 days of primary culture, purified bovine adrenal zonal fasciculata/reticularis (ZF/ZR) cells showed improved integrity of their ultrastructure, with an increased density of lipid droplets and smooth endoplasmic reticulum. The basal cortisol output was significantly (P less than 0.05) greater on day 3 of culture than for the freshly isolated cells in six out of seven experiments. Similarly, in six experiments with ACTH (1 nmol/l) and five experiments with angiotensin II (10 nmol/l), the stimulated cortisol secretion was significantly (P less than 0.01 for all 11 experiments) higher on day 3 of culture than in freshly isolated cells. No significant increase in cortisol secretion above basal was observed with noradrenaline at any concentration in the freshly isolated cells, whereas a dose-dependent increase in cortisol secretion was observed on day 3 of culture in all of four experiments. These findings were supported by cyclic (c) AMP output measured in one such experiment. Thus the basal cAMP output and that stimulated by ACTH (1 nmol/l) were significantly higher after culture (P less than 0.001, n = five wells for basal comparison; P less than 0.05, n = three wells for ACTH at 1 nmol/l). In agreement with the cortisol results, cAMP production was unaffected by any concentration of noradrenaline in the freshly isolated cells, whereas a dose-dependent rise was found after culture. Angiotensin II at all concentrations had no effect on cAMP production in freshly isolated or cultured cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenocorticotropic Hormone↗
Blood pressure, renin-angiotensin-aldosterone axis and cortisol changes during withdrawal from alcohol.
Nineteen patients who had been drinking on the day of admission had significantly raised levels of renin, aldosterone and cortisol and a non-significant increase in angiotensin II. Five patients were hypertensive (systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 95 mmHg) at some point during the study and there was a significant tachycardia. Over the first 4 days of abstinence there were falls in all of the measures reaching significance for renin, cortisol, systolic blood pressure and pulse. There were no correlations between blood pressure and any of the hormones measured although there was a significant association between pulse and both aldosterone and cortisol. It is concluded that the activity in the renin-angiotensin axis and hypothalamic-pituitary-adrenal axis is not responsible for alcohol-related changes in blood pressure.
Adult↗
The stability of tritiated serotonin stored at 4 degrees C--implications for platelet uptake studies.
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Blood Platelets↗
Catecholamine stimulation of cortisol secretion by 3-day primary cultures of purified zona fasciculata/reticularis cells isolated from bovine adrenal cortex.
Primary cultures of zona fasciculata/reticularis cells derived from bovine adrenal cortex secreted cortisol and corticosterone in response to isoprenaline, noradrenaline and adrenaline on the third day of culture. The potency order was isoprenaline greater than noradrenaline, adrenaline with an ED50 for all three agonists within the range 1-5 x 10(-8) M. A dose-dependent increase in medium content of cyclic AMP was also observed. Secretion of cortisol in response to these catecholamines was specifically blocked by propranolol but unaffected by phentolamine. The beta-agonist effect on cortisol secretion was specifically and progressively reduced, in a time- and dose-dependent manner, by pre-incubation of the cells with adrenaline.
Adrenal Cortex↗
Development and validation of an improved radioimmunoassay for serotonin in platelet-rich plasma.
A radioimmunoassay (RIA) using a 125I-tracer is described for measurement of serotonin (5-hydroxytryptamine, 5-HT) in human platelet-rich plasma (PRP). Antisera were raised against 5-HT-succinamate conjugated to bovine albumin and, to improve assay sensitivity, the analyte was made chemically similar to the immunogen by conversion to N-acetylserotonin prior to assay, using the specific amino reagent N-acetoxysuccinimide. The assay shows good correlation with a high-pressure liquid chromatography (HPLC) reference method (5-HT RIA = 1.007 X 5-HT HPLC + 29.3, r = 0.936, p less than 0.001, n = 40), indicating that no significant cross-reactions were detected. Samples of PRP are diluted 1/20 to fall within the working range (80-15% B/B0) of the assay, which is 4.75-325 nmol/l, (0.95-65.0 pmol/tube), corresponding to 95-6500 nmol/l in PRP. Intra- and interassay coefficients of variation were 5.0-10.5% and 12.0-21.2% respectively for serotonin concentrations of 250-2,500 nmol/l added to platelet-poor plasma. With this improved assay, it is possible to analyse up to 100 samples/day, compared with 10-20 samples/day by HPLC.
Acetylation↗
The role of renal dopamine and PGE2 in mediating the renal effects of the antihypertensive loop diuretic piretanide.
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Dinoprostone↗
Renal production of prostaglandin E2 is not deficient in essential hypertension.
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Adult↗
The value of clinical findings in the detection of normal pressure hydrocephalus.
We conducted a retrospective study of 627 individuals with dementia to determine whether clinical characteristics could identify individuals with normal pressure hydrocephalus (NPH) on computed tomography (CT) brain scanning. Fifty (8%) individuals had classical clinical characteristics of NPH: dementia, urinary incontinence, and gait disturbance. When this clinical trial was present, 12% of individuals had NPH on CT scan; when absent, only 3% had NPH. The clinical findings identified individuals with a 4-fold increase (p less than .001) of NPH on CT scan. Of the 50 individuals with the clinical trial, 6 had both clinical and CT scan findings consistent with NPH; 2 of these had shunt surgery, and 1 improved clinically. None of the 577 individuals without clinical findings had shunt surgery performed, including those with CT scan abnormalities consistent with NPH. We conclude that clinical characteristics can be used to identify individuals who need CT scanning for detection of NPH.
Aged↗
Adrenal synthesis of corticosterone in response to ACTH in rats is influenced by leukotriene A4 and by lipoxygenase intermediates.
The possible involvement of the lipoxygenase pathway of arachidonic acid metabolism in the events which take place during ACTH-induced stimulation of corticosterone secretion has been studied using an isolated rat adrenal cell system. Incubation with arachidonic acid resulted in an inhibition of ACTH-stimulated corticosterone production. The lipoxygenase pathway inhibitors nordihydroguaretic acid (NDGA), eicosatetraynoic acid (ETYA) and compound BW755C also produced inhibition of ACTH-stimulated corticosterone synthesis. The concentrations of the inhibitors at which 50% inhibition occurred were 15, 34 and 37 mumol/l respectively. The inhibitions produced by NDGA and ETYA were independent of cyclic AMP output. NDGA also inhibited corticosterone production induced by dibutyryl cyclic AMP but had no effect on corticosterone synthesis induced by pregnenolone. Preincubation of adrenal cells with the lipoxygenase products 5, 12 and 15 hydroxyeicosatetraenoic acid (HETE) and with leukotrienes A4, B4, C4, D4 and E4 resulted in significant inhibitions of corticosterone production in response to ACTH with leukotriene A4 (LTA4) and with 15HETE and 5HETE. Conversely, incubation with glutathione (GSH), which is known to reduce intracellular LTA4 levels, produced stimulation (at 5 mmol GSH/l) and inhibition (at 50 mmol GSH/l) of corticosterone output. These studies suggest that the lipoxygenase pathway may be involved in ACTH-stimulated corticosterone synthesis.
Adrenal Glands↗
High sodium intake increases platelet aggregation in normal females.
Platelet activation and aggregation appear to play an important part in the development of vascular disease. We studied the effect of varying sodium intake on total plasma serotonin and in vitro aggregation of blood platelets. A total of 12 normal female volunteers were studied after 5 days on a 10 or 200 mmol/day sodium diet. Aggregation studies were performed by incubating stirred platelet-rich plasma (PRP) with adenosine diphosphate (ADP) at final concentrations of 1 and 4 mumol/l; we also studied the effect of pre-incubating PRP with ketanserin or saralasin (1 mumol/l and 1 nmol/l final concentration, respectively). Salt-loading produced a significant increase in platelet aggregation induced by both 1 and 4 mumol/l ADP, and also a significant fall in PRP in serotonin concentration; since there was also a significant drop in the yield of platelets in PRP during salt-loading, the difference in serotonin concentration was not significant when expressed as pmol serotonin/10(8) platelets. There was a significant negative correlation between log serotonin levels (nmol/l) and % aggregation induced by 4 mumol/l ADP. Ketanserin decreased aggregation (induced by 4 mumol/l ADP) in PRP obtained during high salt intake; saralasin had no effect on aggregation, but did cause a decrease in light transmission. These results indicate that in normal females: (1) in vitro platelet aggregation is increased with high sodium intake, and this effect was reduced by addition of ketanserin; (2) PRP platelet count and total plasma serotonin levels are both significantly altered by changes in sodium status; (3) aggregation (%) is inversely proportional to log serotonin concentration (nmol/l).
Adult↗
Development and application of a superfusion technique for the study of renin secretion in rat renal cortical cells.
A dynamic column superfusion system has been developed for the study of renin secretion in rat renal cortical cells. Cells were isolated by collagenase digestion and mechanical dispersion, before suspension with polyacrylamide beads and superfusion with oxygenated physiological medium. Renin was detected in the superfusate by incubation of fractions with excess nephrectomized sheep substrate in the presence of angiotensinase inhibitors followed by radioimmunoassay of the angiotensin I generated. Optimized methodology included a purpose-built polytetrafluorethylene flow cell, a 1 h equilibration to achieve a steady state, 5 min eluate collections, a 15 min stimulatory and a 30 min recovery period, and duration of perfusion of up to 270 min. Significant increments above baseline renin release were seen with the stimuli of adrenaline, noradrenaline and isoprenaline. These could be demonstrated with concentrations of 10(-9) mol/l (adrenaline), 5 X 10(-10) mol/l (noradrenaline) and 10(-9) mol/l (isoprenaline). This technique has significant advantages over previous methods for the study of renin secretion in vitro at the cellular level. It is reproducible and sensitive, and avoids many of the limitations of static cell suspension and kidney slice methods.
Animals↗
Intravenous captopril treatment in patients with severe cardiac failure.
The effect of intravenous captopril was studied in 26 patients with severe chronic heart failure. Fourteen patients received a 25 mg intravenous bolus dose and 12 patients were given a series of incremental intravenous doses over the range 0.3125-45 mg. After the 25 mg bolus dose there was a rapid reduction in systemic vascular resistance and systemic blood pressure. The effect was greatest five minutes after the dose when cardiac output was increased by 20%. Mean right atrial pressure and pulmonary end diastolic pressure fell more slowly and reached their nadir 60 minutes after administration. Plasma free captopril concentration was significantly correlated with percentage reduction in systemic vascular resistance 15 minutes after the bolus injection, but was not correlated with either changes in right atrial or pulmonary artery pressures. With the series of incremental doses there was a progressive fall in systemic vascular resistance until a cumulative dose of 5.0 mg was reached; beyond this there was no further significant change. The rapid response to intravenous captopril indicates that it may be useful in the treatment of patients with severe heart failure who require intensive treatment. After intravenous injection of captopril haemodynamic responses in patients with heart failure were greatest at plasma concentrations of 100 g/ml to 150 ng/ml. This is considerably higher than the plasma free captopril concentrations found after conventional oral doses of captopril.
Adult↗
Arginine infusion blocks the action of parathyroid hormone but not arginine vasopressin on the renal tubule in man.
Six male volunteers were infused with arginine (0.5 g/kg body weight) over 30 min, after an overnight fast and water deprivation. There was a significant decrease in renal phosphate clearance (P less than 0.025) and urinary cyclic adenosine monophosphate (cAMP) output (P less than 0.025) during the 60- to 90-min period after the beginning of the infusion; both returned to the preinfusion basal levels within 150 min. The plasma levels of parathyroid hormone (PTH) were not affected by the infusion and remained unchanged during the subsequent 150 min. Plasma levels of arginine vasopressin (AVP) were also not significantly affected although plasma osmolality increased by 6-9 mmol/kg in all subjects. The infusion resulted in a diuresis, and a fall in urine osmolality but a decrease in free-water clearance; creatinine clearance was not affected. Six other subjects were given a bolus of 230 i.u. PTH intravenously, and 20 days later this was repeated during an infusion of arginine (0.5 g/kg body weight). There was a significant decrease in urinary phosphate (P less than 0.025) and cAMP excretion (P less than 0.05) when PTH was given with arginine. It is suggested that arginine blocks the action of PTH on the proximal renal tubule but not that of vasopressin on the distal nephron and collecting ducts.
Arginine↗