Angiotensin II (type-1) receptor locus: CA repeat polymorphism and genetic mapping.
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Alleles↗
Biomedical subjects
E Davies
Publications and source records attributed to E Davies.
A cDNA encoding chalcone isomerase from aged pea epicotyls.
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Base Sequence↗
Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension.
We conducted the present study to determine whether the angiotensin II type I receptor (AT1) gene might be implicated in human essential hypertension by using case-control and linkage studies. The entire coding and 3' untranslated regions of the AT1 receptor gene (2.2 kb) were amplified by polymerase chain reaction and submitted to single-strand conformation polymorphism in 60 hypertensive subjects with a familial susceptibility. We identified five polymorphisms (T573-->C, A1062-->G, A1166-->C, G1517-->T, and A1878-->G). However, no mutations that alter the encoded amino acid sequence were detected. A case-control study performed on white hypertensive (n = 206; blood pressure, 168 +/- 16/103 +/- 9 mm Hg) and normotensive (n = 298; blood pressure, 122 +/- 10/75 +/- 9 mm Hg) subjects using three of five polymorphisms showed a significant increase in allelic frequency of C1166 in hypertensive subjects (0.36 versus 0.28 for normotensive subjects, chi 2 = 6.8, P < .01). Frequencies for the alleles of the other two polymorphisms (T573-->C, A1878-->G) were similar in both groups. We performed a linkage study using the affected sib pair method and a highly polymorphic marker of the AT1 receptor gene. There was no evidence for linkage in 267 sib pairs analyzed from 138 pedigrees. These findings would be compatible with a common variant of the AT1 receptor imparting a small effect on blood pressure; further studies will be needed to address this possibility.
Adult↗
Hybridization and detection of digoxigenin probes on RNA blots.
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Adamantane↗
The usefulness of nimodipine, an L-calcium channel antagonist, in the treatment of tinnitus.
Thirty-one patients were drawn from a tinnitus clinic, screened for other medical problems and treated for 4 weeks with 30 mg nimodipine four times daily. Before and after treatment, the intensity of their tinnitus was assessed subjectively on a scale 1-10. Five patients reported to have a great improvement in their tinnitus whilst two claimed a worsening of the condition. Of the five positive responders, four were treated further with 30 mg nimodipine per day for 4 weeks and 60 mg per day for a further 4 weeks. During this treatment they were assessed more objectively by the determination of the minimal masking level using narrow band noise. There was a good correlation between the subjective and objective assessment of their responses.
Audiometry, Pure-Tone↗
A model for long-term intracochlear administration of pharmacologic agents.
A technique is described that provides a method to study the effects of intracochlear pharmacologic agents on the degenerating auditory nerve. The model involves implanting a guinea pig with an osmotic minipump that allows slow perfusion of the cochlea over a period of hours to days with up to two water soluble substances. Neomycin and horseradish peroxidase, whose histopathologic effects on the cochlea are well known, are used in the present study to validate the efficacy of the system.
Animals↗
Mutation of Asp74 of the rat angiotensin II receptor confers changes in antagonist affinities and abolishes G-protein coupling.
Aspartic acid in the second transmembrane domain is a highly conserved amino acid among the G protein-coupled receptors and is functionally important for agonist binding and G-protein coupling in beta 2-adrenergic and luteinizing hormone receptors. To determine whether this aspartic acid is also involved in the function of the rat vascular angiotensin II receptor subtype 1 (AT1a), Asp74 was replaced either by asparagine or by glutamic acid. When expressed in CHO cells, the two mutants and the wild-type receptor displayed similarly high affinities for the agonist [Sar1, Tyr(125I)4]angiotensin II [where Sar is sarcosine and Tyr(125I) is monoiodinated tyrosine] and the other agonists: ([Sar1]angiotensin II > angiotensin II > angiotensin III >> angiotensin I). However, the Asn74 mutant shows striking differences in its affinity for some antagonists when compared with the wild-type receptor: the affinity for DUP753 was decreased 10-fold, whereas it was increased 6-fold for [Sar1,Ala8]angiotensin II and 20-fold for CGP42112A. These pharmacological changes were associated with a major defect in transmembrane signaling, since angiotensin II was unable to stimulate inositol phosphate production and increase cytosolic Ca2+ concentration through the two mutated receptors, whereas a clear dose-dependent stimulation was observed in cells expressing the wild-type receptor. Angiotensin II was able to promote DNA synthesis through the wild type but not through the mutated receptors. These data indicate that the conserved Asp74 residue of the AT1a receptor is important for the binding of angiotensin II antagonists and is essential for the transmembrane signaling cascade.
Amino Acid Sequence↗
Intercellular and intracellular signals and their transduction via the plasma membrane-cytoskeleton interface.
Electrical signals (action potentials) and hydraulic signals (evidenced as variation potentials, graded potentials or slow waves) are discussed as complements to hormones as major means of intercellular communication in plants. It is shown that all three types of signals can be transduced into similar intracellular signals via the appropriate Ca2+ channel (voltage-gated, mechano-sensitive, or hormone-dependent, respectively). A likely role for these signals in modulating gene expression through transcription and translation is presented with special reference given to (de)phosphorylation modulated via Ca(2+)-dependent cytoskeleton-associated proteins.
Calcium↗
Fetal C-reactive protein.
C-reactive protein (CRP) was measured in fetal blood obtained by cordocentesis from 17 patients with preterm prelabour rupture of the membranes (PPROM). CRP was detected in the blood of eight of the 17 fetuses. Six fetuses, five of whom may have been infected had CRP > or = 0.8 mg dl-1. The remaining 11 fetuses as well as 25 healthy term infants who had cord blood taken immediately post delivery had CRP < 0.6 mg dl-1. These results suggest that elevation of fetal CRP levels may be a useful indicator of fetal infection in pregnancies complicated by PPROM.
C-Reactive Protein↗
Clinical role modelling: uncovering hidden knowledge.
Those responsible for the education of nurses are well aware of the need to reconcile the art and science of nursing so that future practitioners can be prepared to offer a humanistic and professional service to society. One way to assist students in this integration is to provide them with opportunities for role modelling as a means of discovering the knowledge embedded in clinical practice. A study of first-year undergraduate students undertaking a course which provides such opportunities in a number of practice settings was carried out to determine whether the observation of clinical role models does lead to knowledge discovery. The study, which used a grounded theory approach, indicated that the major aspect of nursing uncovered by the students through observation of clinical role models was that of provision of direct care. They articulated their values in relation to 'good' and 'bad' care and identified those attributes of nurses which they considered contributed to these care positions. In addition, they were able to recognize creativity and flexibility in practitioners and to relate these attributes to the ability to provide individualized, context-specific care. There was some uncovering of aspects of the nurse's role in maintaining their own professional competence, socializing neophytes into the profession and collaborating with the members of the multi-disciplinary health care team.
Clinical Competence↗
Inter-agency working with homeless people.
Poor communication between the health service and other agencies, particularly local authority departments, frequently compounds the problems of those people most needing their help. Elise Davies reports on a project in Reading in which the problems of multi-agency working are being addressed.
Community Health Nursing↗
The influence of posture on the response to loop diuretics in patients with chronic cardiac failure is reduced by angiotensin converting enzyme inhibition.
The diuretic and natriuretic response to an intravenous dose of frusemide 40 mg was assessed in the erect and supine positions in 10 patients with cardiac failure who were being treated with enalapril 10 mg twice daily in addition to diuretics (Enalapril group) and in 10 patients with cardiac failure taking diuretics alone (Control group). Total 4 h diuresis in the erect position was 728 ml and in the supine position was 824 ml in the patients taking enalapril compared to 655 ml in the erect position and 1166 ml in the supine position in those patients taking diuretics alone. Total 4 h natriuresis in the erect positions was 78 mmol and in the supine position was 85 mmol in patients taking enalapril 10 mg twice daily but in those patients taking diuretics alone total 4 h natriuresis in the erect position was 67 mmol increasing to 120 mmol in the supine position. Measurements of plasma renin activity and plasma angiotensin II concentration confirmed effective converting enzyme inhibition, in the group of patients taking enalapril, but in those patients taking diuretics alone the erect position was associated with an increase in plasma renin activity, and plasma concentrations of angiotensin II and aldosterone. We conclude that the renin angiotensin system is a major factor in mediating the effect of posture on loop diuretic drugs.
Adult↗
Lack of correlation between the acute haemodynamic response to intravenous captopril and plasma concentrations of angiotensin II in patients with chronic cardiac failure.
We have given a series of incremental intravenous injections of captopril to ten patients with chronic cardiac failure. Small doses of captopril produced significant changes in pulmonary artery end-diastolic pressure and right atrial pressure, up to a total cumulative dose of captopril of 2.5 mg, after which further injections had no significant effect. There were large changes in systemic vascular resistance and blood pressure up to a cumulative dose of captopril of 5.0 mg, after which the injection of larger doses caused no further significant changes. Small doses of intravenous captopril produced large increases in plasma renin activity and plasma angiotensin I concentrations up to a total cumulative dose of captopril of 1.25 mg, after which there were no significant further changes in either plasma renin activity or plasma angiotensin I concentration. However the plasma concentration of angiotensin II fell more slowly, no further change being recorded after a total cumulative dose of captopril of 10 mg. These results suggest that plasma renin activity is not the only determinant of plasma angiotensin II concentrations.
Aged↗
Contrasting patterns of arterial and venous dilatation after intravenous captopril in patients with chronic cardiac failure and their relationship to plasma angiotensin II concentrations.
A 25 mg intravenous bolus injection of captopril caused an abrupt and rapid decrease in systemic vascular resistance (time to maximum effect 15 minutes), but a more gradual decrease in right atrial pressure (time to maximum effect 75 minutes) in 12 patients with chronic cardiac failure. Plasma angiotensin II concentrations fell significantly, reaching their lowest concentrations at 75 minutes after the injection of captopril, at which time systemic vascular resistance had begun to return toward control values. There was no correlation between the acute arteriodilator response and pretreatment plasma renin activity or plasma angiotensin II concentrations, or the decrease in plasma angiotensin II concentrations. There was a significant correlation between the decrease in plasma angiotensin II concentrations and the decrease in right atrial pressure (r = 0.67, p < 0.05). These findings suggest that in contrast to the venous response to intravenous captopril, the arterial response is not entirely dependent on a decrease in the circulating plasma angiotensin II concentration.
Aged↗
Serotoninergic stimulation of aldosterone secretion in vivo: role of the hypothalamo-pituitary adrenal axis.
The control of aldosterone secretion in vivo by serotonin was studied in conscious rats. Serial blood samples were taken from indwelling arterial cannulae before and after i.p. administration of 1 ml (4 g/l) 5-hydroxytryptophan (5-HTP), the precursor of serotonin (5-HT), or saline, and analysed for 5-HTP, serotonin, 5-hydroxyindoleacetic acid, plasma renin activity (PRA), corticosterone, aldosterone, sodium and potassium concentration. The relative contribution of the hypothalamo-pituitary adrenal axis was investigated in animals pretreated with the synthetic glucocorticoid dexamethasone. 5-HTP caused a significant increase in all parameters within 45 min except for plasma sodium and potassium. Saline administration showed no significant effect. Dexamethasone pretreatment significantly impaired the corticosterone and aldosterone response to 5-HTP, although the aldosterone response was merely attenuated. No other parameter was affected by dexamethasone pretreatment. The results show that administration of 5-HTP, which increases serum serotonin levels, stimulates PRA, corticosterone and aldosterone secretion. Dexamethasone pretreatment inhibits the aldosterone response, though not completely, suggesting that the stimulatory action of 5-HTP involves the release of ACTH, which stimulates corticosterone and aldosterone secretion by the adrenal cortex. The failure of dexamethasone to block the aldosterone response completely, suggests the involvement of other mechanisms such as the renin-angiotensin system or a direct action of serotonin on the adrenal zona glomerulosa.
5-Hydroxytryptophan↗
Cosedimentation of pea root polysomes with the cytoskeleton.
When conventional, high ionic strength buffers were used for the isolation of polysomes from pea roots, only about 10% were retained in the detergent-insoluble pellet, and they were not degraded by endogenous RNase. A low ionic strength, cytoskeleton-stabilizing buffer increased retention to 60%, but polysomes were severely degraded. The RNase inhibitors, ribonucleoside-vanadyl complexes, heparin, KCl and ammonium sulphate lessened degradation but caused release, while Tris-HCl at 15-25 mM was able to prevent degradation without causing release. Cosedimentation of polysomes with the cytoskeleton is not an artefact of adsorption or trapping since isolated polysomes labelled through their nascent polypeptides and added to unfractionated tissue were not retained in the cytoskeletal pellet.
Buffers↗
The relationship between diuretic dose, and the haemodynamic response to captopril in patients with cardiac failure.
The effect of diuretic dose on the haemodynamic response to captopril was assessed in nine patients with chronic cardiac failure. Each patient was given an intravenous dose of captopril while maintained on (a) a low dose diuretic regime, and (b) a high dose diuretic regime. Activity of the renin angiotensin aldosterone system, as assessed by plasma concentrations of these hormones, was greater when patients were receiving the higher dose diuretic regime. The magnitude of haemodynamic response produced by intravenous captopril was greater when the patients were maintained on the high dose diuretic regime, although no significant correlation was found between resting plasma renin activity and resting plasma angiotensin II concentration and the change produced by captopril in any haemodynamic response on either diuretic regime. An increased dosage of loop diuretic potentiates the haemodynamic effects of captopril in patients with cardiac failure. Reduction of diuretic dose prior to introduction of captopril may protect against severe first dose hypotension.
Adult↗
A randomized prospective study comparing pregnancy rates following clomiphene citrate and human menopausal gonadotrophin therapy.
The anti-oestrogenic effect of clomiphene citrate causes an increased rate of associated cervical factor problems. Theoretically, it may also cause an adverse effect on the endometrium. The hostile mucus may be completely or partially corrected by the use of additional oestrogen after stopping clomiphene, or by intrauterine insemination (IUI). The prospective randomized study presented here was designed to determine whether a higher pregnancy rate might be achieved using human menopausal gonadotrophin (HMG) compared to clomiphene citrate. Thirty-seven women treated with clomiphene citrate for 165 cycles were compared to 33 treated with HMG for 179 cycles. A pregnancy was achieved in 81.1% of clomiphene-treated women (18.2%/cycle) versus 72.7% (13.3% per cycle) of HMG-treated women. The abortion rates of 13.3 and 12.5% respectively, were similar. The data suggest no adverse effect of clomiphene compared to HMG as far as pregnancy rates are concerned. IUI seems to be an effective means of treating cervical factor problems induced by clomiphene.
Clomiphene↗