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Biomedical subjects

J Douglas

Publications and source records attributed to J Douglas.

At least 127 records · Page 7Linked to original sources
PubMed1981

Congenital mitral stenosis. Anatomical and functional assessment by echocardiography.

Digitised left ventricular echocardiograms were studied in nine children with congenital mitral stenosis to assess the severity of inflow obstruction. In six children the two prime indices of mitral stenosis were abnormal, with a prolonged time from minimum dimension to 20 per cent dimension change and a reduced peak dimension change during diastole. In three, however, these values did not suggest inflow obstruction, depsite significant gradients at cardiac catheterisation. Two-dimensional echocardiography was performed in 10 children with congenital mitral stenosis to determine the mitral annular size and the morphology of the valve and subvalvular apparatus. The annular size and number of papillary muscles could be assessed along with the detection of combined mitral abnormalities. Two-dimensional studies can reliably delineate the type of mitral abnormality, and should be performed in all cases with congenital heart disease having a high incidence of associated left ventricular inflow obstruction. Digitised M-mode left ventricular echocardiography is in general unreliable in assessing congenital obstruction, though it may be of some value in individual cases.

Adolescent↗
PubMed1980

Angiotensin II receptors and in vitro aldosterone responses of aldosterone-producing adenomas, adjacent nontumorous tissue, and normal human adrenal glomerulosa.

Angiotensin II (angio II) receptors have been compared using tissues from aldosterone-producing adenomas (APAs), adjacent nontumorus tissue, and normal human adrenal glomerulosa. Plasma membrane-rich subcellular fractions were employed in a radioreceptor assay with [125I]angio II. In vitro aldosterone secretory response to angio II were determined using isolated cells obtained by collagenase digestion. Results are reported as the mean +/- SE. Normal glands have high and low affinity receptor sites for angio II. The Ka values for a normal adrenal obtained at surgery were 2.5 and 0.4 nM-1, while autopsy adrenals were 1.1 +/- 0.4 and 0.3 +/- 0.15 nM-1 (n = 3). APAs and adjacent nontumorous tissue possessed only low affinity receptor sites (0.22 +/- 0.05 nM--1; n = 11). The receptor concentration for a surgically obtained adrenal was 1562 fmol/mg protein, contrasted with 466 +/- 135 from autopsy adrenals. APA and adjacent tissue bound 462 +/- 112 fmol/mg protein. Cells from seven of eight APAs produced aldosterone when stimulated by angio II (3 x 10(-10)-10(-6) m). The increments were 16-105% above basal levels. The response were similar to but less senstive than cells from normal adrenals. The only tumor that failed to respond had 1/50th of the receptors of the other APAs. In contrast, only three of seven adjacent tissues responded, and then only negligibly. ACTH (10(-8) M) increased aldosterone production by APAs 10-158%, by normal cells 283% and by three of six adjacent nontumorous tissues 170-400%. The observations that APAs have angio II receptors and aldosterone responses to angio II is consistent with the fact that some patients with APA have postural increments of plasma posture. The presence of receptors of adjacent tissue and no in vitro response suggest a defect in the aldosterone biosynthetic pathway as a cause of the prolonged absence of response to angio II after removal of APAs.

Adenoma↗
PubMed1978

Angiotensin II receptors and aldosterone production in rat adrenal glomerulosa cells.

Specific receptors for angiotensin II (A II) were demonstrated in membrane fractions and collagenase-dispersed cells from the zona glomerulosa of the rat adrenal gland. The equilibrium association constant (Ka) of the A II binding sites was similar in particulate fractions (2.0 +/- 0.4 (SE) X 10(9) M-1) and intact glomerulosa cells (1.8 +/- 0.3 X 10(9) M-1). Specific binding of [125I]iodo-A II was enhanced by increasing sodium concentration, and in the presence of dithiothreitol, EDTA, and EGTA. Plasma membrane fractions prepared by density gradient centrifugation showed increased binding of [125I]iodo-A II, and were correspondingly enriched in adenylate cyclase and sodium-potassium-dependent ATPase. Steroid production by collagenase-dispersed adrenal glomerulosa cells was highly responsive to A II and ACTH. Significant increases in aldosterone and corticosterone production were elicited by A II concentrations as low as 3 X 10(-11) M, equivalent to normal blood levels of A II in rats (5 X 10(-11) M). The maximum increase in aldosterone production, of 6--7 times the basal value, was obtained at 10(-9) M A II. Dispersed capsular cells were also highly sensitive to ACTH, responding to concentrations down to 3 X 10(-12) M with increased aldosterone production, reaching a maximum aldosterone response of 20-fold above the basal value. The magnitudes of the aldosterone and corticosterone responses to A II in capsular and fasciculata-reticularis cells were commensurate with the distribution of A II receptors, which were 11-fold more concentrated in capsular cells. The ability of A II to evoke aldosterone production at physiological concentrations, and the correspondence between A II binding and steroidogenesis in capsular cells, demonstrate the functional importance of A II receptor sites in the zona glomerulosa of the rat adrenal cortex.

Adrenal Glands↗
PubMed1978

Formation of DES-ASP1-angiotensin II is not an obligatory step in the steroidogenic action of angiotensin II in the canine adrenal.

A comparison of the receptor binding properties and in vitro metabolism of angiotensin II and [des-Asp1]-angiotensin II was performed in collagenase-dispersed glomerulosa cells from dog adrenal glands. Each peptide was bound rapidly and reversibly to isolated glomerulosa cells, with similar equilibrium and kinetic constants of association and dissociation. The labeled peptide that was bound to glomerulosa cells after incubation with 125I- and 3H-angiotensin II at 37C for 30-60 minutes was predominantly angiotensin II, with about 15% [des-Asp1]-angiotensin II. These findings demonstrate that local formation of the heptapeptide is not an obligatory step in the action of angiotensin II on aldosterone production in the canine adrenals.

Adrenal Glands↗
PubMed1978

An examination of possible mechanisms of angiotensin II-stimulated steroidogenesis.

Dog and rat adrenal glomerulosa cells and subcellular fractions have been utilized to evaluate the mechanism of angiotensin II- and angiotensin III-induced aldosterone production. The effects of angiotensin, ACTH, and potassium have been compared on cyclic AMP and cyclic GMP in isolated glomerulosa cells and adenylate cyclase activity in subcellular fractions. The effect of angiotensin II has also been assessed on Na+-K+-activated ATPase of plasma membrane enriched fractions of dog and rat adrenals. We have demonstrated no effect of angiotensin II or angiotensin III on either adenylate cyclase, cyclic AMP, cyclic GMP, or Na+-K+-dependent ATPase activity over a wide range of concentrations. Potassium ion in concentrations that stimulate significant aldosterone production was also without effect. The negative effects of angiotensin and potassium were contrasted against a positive correlation between an ACTH-induced effect on aldosterone production, adenylate cyclase, and cyclic AMP accumulation. These studies have served to demonstrate that neither adenylate cyclase, cyclic AMP, cyclic GMP, or Na+-K+-activated ATPase seem to be directly involved in the mechanism of action of angiotensins on aldosterone production in the rat and dog adrenal glomerulosa.

Adrenal Glands↗
PubMed1977

One hundred kidney transplants in the Belfast city hospital.

100 kidney transplants have been carried out on 91 patients (7 had 2 transplants and 2 had 3 transplants). 4 transplants were from living related donors and 96 from cadavers. 76 patients survive, all but one with functioning kidneys. The cumulative survival of patients was 82% at 2 years and 80-7% at 5 years. 8 patients died with functioning grafts, and 2 of the other deaths took place more than 3 months after removal of a rejected kidney and resumption of haemodialysis. There were no deaths from sepsis in the first 60 days after transplantation. The cumulative survival of all grafts was 82-1% at 2 and 5 years. The cumulative survival of first grafts was 82-5% at 2 and 5 years.

Adolescent↗
PubMed1977

Aldosterone production by isolated glomerulosa cells: modulation of sensitivity to angiotensin II and ACTH by extracellular potassium concentration.

The influence of extracellular potassium concentration on adrenal sensitivity to angiotensin II and ACTH was studied in isolated canine adrenal glomerulosa cells. When potassium was absent from the incubation medium, the aldosterone response to angiotensin II or ACTH was completely abolished. At physiologic angiotensin II concentrations (2.5 x 10(-11) M), aldosterone formation increased 4-fold when potassium concentration was increased from 2.5 to 5.0 mM, and rose 6-fold as potassium was increased from 2.5 to 7.5 mM. In the absence of angiotensin II, the same changes in potassium concentration increased aldosterone production only to 2-fold and 3.5-fold, respectively. The effect of potassium concentration upon the aldosterone response to ACTH was similar but less marked. The concentration and binding affinity of angiotensin II receptor sites in glomerulosa cells were not changed by increasing potassium concentrations from 0 to 7.5 mM. These observations demonstrate that the aldosterone response to the glomerulosa cell to angiotensin II is potassium-dependent within the physiological range for each of these stimuli. Such an interaction suggests that the in vivo effect of potassium upon aldosterone secretion includes a significant modulating action upon adrenal sensitivity to angiotensin II, as well as a direct action of potassium upon the adrenal glomerulosa cell.

Adrenal Glands↗
PubMed1976

Vasectomy.

Fifty consecutive patients who underwent vasectomy were followed up over a period of two years, and were subjected to a questionnaire, and the results were analysed. The technique for vasectomy is described and a few modifications are suggested, so that there is a reasonable chance of reversing the operation if need be. Special emphasis has been placed on the poorly understood medicolegal implications of vasectomy.

Adult↗
PubMed1976

Receptor binding of angiotensin II and antagonists. Correlation with aldosterone production by isolated canine adrenal glomerulosa cells.

The binding properties of the angiotensin II receptors of the adrenal cortex have been studied in isolated cells prepared by collagenase dispersion of the zona glomerulosa of the canine adrenal gland. Such cell preparations are responsive to physiological concentrations of angiotensin II, and permit correlation of binding of angiotensin II and its analogues with aldosterone production in vitro. Uptake of 125I-angiotensin II (5 X 10(-11) M) by glomerulosa cells at 37 degrees C reached a steady state at 45 minutes, with a subsequent plateau for at least 60 minutes. Angiotensin II binding was also dependent upon the hormone and cell concentrations employed during uptake studies. Bound angiotensin II was rapidly dissociated from canine adrenal cells after addition of the unlabeled octapeptide. High affinity sites with equilibrium association constant (Ka) of 3.3 X 10(9) M-1 comprised 25-33% of the receptor population and the remainder of the sites were of lower affinity, 2.5 X 10(8)M-1. Binding of angiotensin II analogues and antagonists was found to be consistent with their biological activities. The analogue most extensively evaluated was [Sar-1]angiotensin II, which exhibited enhanced binding activity when compared to angiotensin II, and had a higher equilibrium association constant by kinetic analysis and direct binding studies. Direct binding of labeled angiotensin II to the adrenal glomerulosa receptor has been correlated with a progressive response in aldosterone production. The steroidogenic response to angiotensin II was maximal when 25% of the receptor population was occupied; this fraction corresponds to the proportion of high affinity receptor sites measured by binding analysis. In addition, inhibition of angiotensin II binding to receptor sites by the competitive antagonist [Sar-1, Ala-8]angiotensin II has been correlated with inhibition of aldosterone production. These findings serve to demonstrate the biological significance of the angiotensin II binding sites of the adrenal cortex, and confirm their role as receptors which mediate the steroidogenic responses to angiotensin II.

Adrenal Cortex↗
PubMed1976

Regulation of angiotensin II receptors in the rat adrenal cortex by dietary electrolytes.

The binding affinity and concentration of specific angiotensin II receptor sites of rat adrenal cortical cells and homogenates were determined after 1 and 6 wk of altered sodium and potassium intake. Sodium deprivation caused marked increases in plasma renin, blood angiotensin II, and plasma aldosterone, and was accompanied by a significant increase (+74%) in the number of specific angiotensin II receptor sites per adrenal cortical cell. High potassium intake was followed by increased serum potassium and markedly elevated plasma aldosterone, with subnormal levels of renin and angiotensin II and a 170% increase in the number of angiotensin II receptors per cell after 1 wk. Sodium loading and potassium deprivation were followed by the opposite effect upon adrenal receptors, with reduction of the angiotensin II-binding capacity. None of the dietary electrolyte changes were accompanied by an ancrease in receptor affinity above the control value of 2 nM-1. A decrease in receptor affinity was noted after 6 wk of either low sodium or low potassium intake, when the renin and angiotensin II levels were increased by 104-129%. The adrenals of normal rats infused acutely with synthetic angiotensin II, or anesthetized with ether or sodium pentobarbital, which markedly increased plasma renin activity, contained fewer angiotensin receptors. These reductions in binding site concentration were not accompanied by changes in affinity and were attributed to occupancy by angiotensin II. These studies have demonstrated that chronic changes in sodium or potassium balance and acute changes in blood angiotensin II levels can exert modulating effects upon the adrenal content and/or affinity of specific receptor sites for angiotensin II.

Adrenal Cortex↗