Biomedical subjects
Publications and source records attributed to A Ganguly.
We have studied a case of renal angiomyolipoma by electron microscopy and found juxtaglomerular cells with typical rhomboid and spherical granules, in addition to smooth muscle cells, fat cells, and abnormal blood vessels. To our knowledge, this is the first ultrastructural demonstration of juxtaglomerular cells in renal angiomyolipoma.
Electroacupuncture (EA), a form of transcutaneous electrical stimulation, produces opiate-like antinociception and catalepsy in rats. This effect of EA cannot be produced in hypophysectomised rats, whereas adrenalectomised rats show increased sensitivity. In intact rats, adrenocorticotrophic hormone and dexamethasone have been found to be effective to sensitise the animals to the analgesic effect of EA. Deoxycorticosterone, on the contrary, attenuates this effect. Spironolactone is also effective to potentiate EA response, which is accompanied with severe respiratory depression. Drugs that are known to affect adrenal aldosterone secretion also modulate the effect of EA. Naloxone administration, 15 min prior to the initiation of EA stimulation, potentiates the effect of EA, whereas it counteracts the effect of EA if administered after initiation of EA stimulation. Moreover, this counteracting ability of naloxone increases with the increase in time interval between initiation of stimulation and naloxone challenge. Pretreatment with drugs that impair adrenal mineralocorticoid response to physiological stimuli inhibits the counteracting effect of naloxone. On the contrary, mineralocorticoid supplemented rats show greater sensitivity to naloxone counteraction.
Explore the source record for details and available documents.
A radioimmunoassay procedure for the measurement of urinary 18-oxocortisol was developed. The antibody was raised against 18-oxocortisol 3-carboxymethyloxime-BSA and had relatively high specificity, except for aldosterone (26.3%). The RIA required a preliminary HPLC purification using a Lichrosorb diol column eluted with toluene:acetonitrile:isopropanol:acetic acid (83:11.9:5.1:0.01). The eluate portion corresponding to 18-oxocortisol was evaporated and subjected to RIA. The RIA procedure had an intraassay variability of 11% when using a pool containing 10.8 micrograms/24 hr (n = 6) and 17% with a pool containing 3.28 micrograms/24 hr. The interassay variability was 11% (n = 4). The recovery of added 18-oxocortisol was 90 +/- 10%. The urinary excretion of 18-oxocortisol in 22 white normal subjects was 3.26 +/- 1.98 (SD) micrograms/24 hr (range 0.8 to 7.1 micrograms/24 hr). The mean excretion of 18-oxocortisol in 4 patients with glucocorticoid-suppressible aldosteronism (GSA) was 38.6 micrograms/24 hr (range 25.5 to 54.6 micrograms/24 hr). The excretion of 18-oxocortisol in 3 patients with adenomas producing primary aldosteronism (APA) varied between 11.1 to 17.3 micrograms/24 hr and in 3 patients with idiopathic aldosteronism (IA) varied between 2.5 to 10.6 micrograms/24 hr. 18-Oxocortisol excretion is increased markedly in the urine of patients with GSA: what role this relatively weak mineralocorticoid plays in the pathogenesis of their hypertension is unknown. Its elevation is probably a reflection of a postulated lack of involution of the 18-methyloxidase in the inner layers of the adrenal.
Chromatin of chicken erythrocyte nuclei was extracted by digestion with micrococcal nuclease. The length distribution of the soluble chromatin was determined by gel electrophoresis and electron microscopy. These results were fitted with a theoretical distribution which was an outcome of the domain model proposed by Igo-Kemenes and Zachau (Igo-Kemenes, T. and H.G. Zachau (1977) Cold Spring Harbour Symp. Quant. Biol. 42, 109-118). A domain length of 45 kbp was obtained.
Explore the source record for details and available documents.
We examined the effects of alpha adrenergic receptor blockade with phenoxybenzamine on various parameters related to blood pressure regulation in 10 normotensive and 12 essential hypertensive subjects. The responses were observed before and after phenoxybenzamine treatment during standardized maneuvers of volume expansion with saline infusion and volume contraction with a diuretic. Alpha adrenergic blockade produced a significantly greater (P less than 0.02) reduction in blood pressure in the hypertensive group than in the normotensive subjects. The baroreceptor response, evaluated by comparing the change in plasma norepinephrine concentration in relation to the change in blood pressure, was significantly reduced (P less than 0.05) in hypertensives compared to normal subjects. Plasma and urinary norepinephrine concentration, which were similar in the two groups, increased in both during phenoxybenzamine treatment. There was no significant change in the mean levels of plasma renin activity or plasma aldosterone concentration in either group after phenoxybenzamine treatment. However, the relationship between plasma renin activity and plasma aldosterone levels, as judged by linear regression analysis, was significantly altered (P less than 0.05) by phenoxybenzamine therapy in both groups. The latter may reflect an effect of phenoxybenzamine on the metabolism or secretion of aldosterone. These results, utilizing an alpha adrenergic antagonist, confirm the enhanced vascular reactivity and diminished baroreceptor function in essential hypertension; no evidence for an alpha adrenergic effect on plasma renin activity could be demonstrated in normotensive or hypertensive subjects.
We investigated the status of the renin-angiotensin-aldosterone axis in 5 patients with Cushing's syndrome and 7 patients with pheochromocytoma. In most of the patients with Cushing's syndrome no significant abnormalities of the renin-angiotensin-aldosterone system could be detected. In 4 out of 7 patients with pheochromocytoma, plasma renin activity remained high after saline suppression and decreased into the normal range in all 4 patients after removal of pheochromocytoma. These results imply that the postulated mineralocorticoid excess was not present in the patients with Cushing's syndrome studied. In pheochromocytoma, high levels of plasma catecholamines contribute to a high renin state which may have pathophysiologic implications.
To investigate possible dopaminergic effects on aldosterone production, we administered the dopamine antagonist metoclopramide to 11 normal subjects, 8 patients with primary aldosteronism due to adenoma or hyperplasia, and 5 other patients with the glucocorticoid-suppressible form of hyperaldosteronism (GSH). All subjects except for those with GSH responded to metoclopramide with an increase in plasma aldosterone concentration even when endogenous ACTH was suppressed by dexamethasone pretreatment. This increase occurred without apparent mediation of other recognized stimuli for aldosterone secretion. In contrast, the patients with GSH failed to show any aldosterone response while receiving dexamethasone, but demonstrated a rise in plasma aldosterone concentration when dexamethasone was withheld. The responses in the patients with both forms of primary aldosteronism were greater in magnitude than in the normal subjects or in the subjects with GSH when not receiving dexamethasone. These studies, while demonstrating differences between the subtypes of hyperaldosteronism in their responsiveness to metoclopramide, indicate that ACTH or some other factor may exert a permissive effect in GSH for the aldosterone response to metoclopramide. A graded infusion of ACTH revealed a greater aldosterone response in GSH compared to that in the other groups, further suggesting the importance of ACTH in this disorder.
In 3 patients with longstanding hypertension and spontaneous or diuretic-induced hypokalemia, the diagnosis of primary aldosteronism was established by the dual criteria of non-suppressible plasma aldosterone level and suppressed plasma renin activity. Preoperative studies of the etiology for the hyperaldosteronism using the postural plasma aldosterone test and adrenal venous steroid measurements gave conflicting results. On the basis of the differential adrenal venous steroid content, which suggested an unilateral adrenal source for the aldosterone hypersecretion, presumed to be adrenal adenoma, each patient was operated upon. In each case the excised adrenal revealed adenomatous or macronodular hyperplasia. Reinvestigation of the patients 3 to 12 months after the adrenalectomy showed that the dynamics of the renin-aldosterone axis was now restored to the normal state even though the patients remained hypertensive. These findings indicate that unilateral hypersecretion of aldosterone associated with adrenal hyperplasia can occur in some patients with primary aldosteronism simulating that due to an aldosteronoma. Such observations also raise questions about the pathogenesis of the adrenal hyperplasia and seem to add further complexity to the evaluation of patients with hyperaldosteronism.
The effect of single, acute (7 pulses/sec., 0.75 volt) and chronic (4 pulses/sec., 0.75 volt) electroacupuncture (EA) treatment on alternate days for a period of 21 days on hepatic functions of rats were studied at cellular and subcellular levels. The points used for EA were Shenshu, Dachangshu and Zusanli. After chronic treatment, (a) protein, RNA, phospholipid, and cholesterol contents of whole liver and liver microsomal fraction increased significantly, (b) liver microsomal G-6-Pase activity increased significantly, (c) microsomal lipid peroxidation value decreased, (d) lipase activity increased. After acute treatment, (e) phospholipid, and cholesterol contents of the whole liver and liver microsomal fraction increased significantly, (f) liver microsomal G-6-Pase activity increased significantly, (g) liver microsomal lipid peroxidation value decreased, (h) GPT and lipase activity of liver increased. The parameters unchanged in acute treatment were as follows: (i) protein, RNA content, (j) GOT activity of the liver, (k) SGOT and SGPT activity, (1) hepatic triglyceride. The parameters unchanged in chronic treatment were as follows: (m) GOT and GPT activity of the liver, (n) SGOT and SGPT activity, (o) hepatic triglyceride. No apparent harmful effect of EA on rat hepatic functions is obvious from present study.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To evaluate the role of the renin-angiotensin-aldosterone system in the hypertension associated with primary hyperparathyroidism, we measured plasma renin activity and aldosterone concentration before and after maneuvers to suppress and stimulate this system in 11 hypertensive patients with primary hyperparathyroidism. We also measured plasma or urinary norepinephrine concentration to examine the role of catecholamines in the hypertension. The results were compared with an age- and race-matched control population. While the mean plasma aldosterone concentrations were normal, the mean plasma renin activity in response to furosemide stimulation was subnormal in subjects with hyperparathyroidism. Plasma or urinary norepinephrine concentrations were within the normal range. Thus a specific abnormality of the renin-angiotensin-aldosterone system or catecholamines could not be identified in these hypertensives with primary hyperparathyroidism.
The relative roles of ACTH, angiotensin and potassium in influencing aldosterone secretion in primary aldosteronism were assessed by direct or indirect means. In untreated patients with primary aldosteronism caused either by adrenal adenoma or hyperplasia plasma aldosterone and cortisol concentrations fluctuated in unison and dexamethasone reduced both hormones markedly. Only when renin-angiotensin system was greatly activated and plasma potassium normalized by medical treatment was dexamethasone less successful in lowering plasma aldosterone concentration. Potassium infusion of 10,20 and 30 mEq/hr in patients with adenoma failed to elicit any increase in plasma aldosterone concentration despite significant increases in plasma potassium levels. These results suggest that patients with primary aldosteronism due to adrenal adenoma are relatively more sensitive to small changes in plasma ACTH level than those in plasma angiotensin or potassium levels. In recumbent patients with adrenal hyperplasia ACTH also modulates plasma aldosterone concentration.
Little is known regarding the response of the renin-angiotensin-aldosterone system to dynamic maneuvers after surgical removal of an aldosterone-producing adenoma or whether normal renin-aldosterone relationships are restored following surgery. We utilized maneuvers designed to assess the adequacy of aldosterone suppression and renin stimulation to rapid changes in sodium and fluid volume status to examine these relationships in 21 patients before and after surgery for primary aldosteronism. All patients failed to suppress plasma aldosterone normally after intravenous saline infusion and failed to stimulate renin activity into the normal range following diuretic-induced sodium and volume depletion. No relationship between renin and aldosterone was discerned. The studies were repeated 6 mo. to 4 yrs. after unilateral adrenalectomy in all 21 patients. In every case the normal suppression of aldosterone and stimulation of renin was observed. Moreover a significant (p less than 0.001) relationship between renin and aldosterone was demonstrable. Thus in this population of patients with surgically responsive primary aldosteronism, no abnormality of aldosterone production persisted.
Explore the source record for details and available documents.
Metoclopramide (MP), a dopamine antagonist, stimulates secretion of aldosterone by a mechanism which has not been defined. We examined a potential role for either the kidney or the pituitary to mediate MPs effect on aldosterone secretion. Responses to MP administered i.v. were measured in six anephric and six hypopituitary patients as well as in six normal subjects. MP increased the plasma aldosterone concentration (PAC) in normal subjects in a fashion similar to what had previously been reported. MP produced no increase in plasma levels of renin activity (PRA), cortisol, potassium, or sodium. Three of six anephric patients (all of whom had undetectable PRA) responded to MP with increases in PAC; the magnitude of these responses correlated with the plasma potassium concentration. All six hypopituitary patients showed increases in PAC after MP administration. MP increased plasma prolactin levels in normal subjects and anephric patients; one hypopituitary patient had high basal plasma prolactin levels which increased with MP. In conclusion, neither the kidney nor the pituitary is involved in the mechanism for MP stimulated aldosterone production. These observations suggest that MP may act on the adrenal to evoke secretion of aldosterone.