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Biomedical subjects

L M Fishman

Publications and source records attributed to L M Fishman.

At least 37 records · Page 2Linked to original sources
PubMed1989

Content and biosynthesis of cortisol in aldosterone-producing adenomas.

The content and biosynthesis of aldosterone and cortisol were examined and compared in the aldosterone-producing adenomas and adjacent adrenal glands from patients with primary aldosteronism that resulted from solitary, benign adrenocortical tumors (0.8 to 32.3 gm). Histologic examination of the six aldosterone-producing adenomas studied confirmed a predominance of cells resembling zona fasciculata rather than zona glomerulosa, as reported in previous studies. Measurement by radioimmunoassay of the tissue content of steroids preformed in vivo demonstrated that aldosterone was present in concentrations 8 times higher in aldosterone-producing adenomas (1.5 +/- 0.5 micrograms/gm tissue; mean +/- SEM) than in adrenal glands (0.2 +/- 0.06 micrograms/gm tissue). Cortisol concentration in aldosterone-producing adenomas (5.4 +/- 1.4 micrograms/gm tissue) was approximately one third that in adrenal glands (15.8 +/- 6.3 micrograms/gm tissue), but cortisol was by far the major steroid in both types of tissue. In vitro, the most important metabolic product quantitatively from 4-carbon 14-labeled cholesterol incubated with mitochondria plus microsomes and from 4-14C-labeled pregnenolone incubated with tissue slices was cortisol, formed in a time-dependent manner in both types of preparations; cortisol synthesis greatly exceed that of aldosterone in adrenal glands, but even in aldosterone-producing adenomas the formation of cortisol was at least 5 times greater than that of aldosterone. The fasciculata structure and dual biosynthetic capacity of aldosterone producing adenomas for cortisol and aldosterone are interpreted in the light of developing concepts of the roles of adrenocorticotropic hormone and of alterations in the microenvironment of the cell in the zonal differentiation of the normal adrenal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1988

Corticosteroid effects on cholinergic enzymes in ethanol-treated fetal brain cell cultures.

In the presence of ethanol, corticosterone and dexamethasone inhibit choline acetyltransferase and acetyl-cholinesterase activities in cultured fetal brain cells of the rat. These results suggest that corticosteroids may have an important influence on the activity of cholinergic enzymes in the fetal brain may antagonize the effects of ethanol in this setting.

Acetylcholinesterase↗
PubMed1987

The adrenal gland of stranded whales (Kogia breviceps and Mesoplodon europaeus): morphology, hormonal contents, and biosynthesis of corticosteroids.

Histochemical assays, hormonal quantitation, and steroid biosynthetic studies were carried out with adrenal glands obtained from four stranded whales of two different species (Kogia breviceps and Mesoplodon europaeus), and selected comparisons were made with the results of similar studies of adrenals from terrestrial mammals (man, beef, rat). Histochemical chemical assays of the whale glands for succinic dehydrogenase activity (SDA) showed an intense SDA-positive reaction in the peripheral cortex, and an SDA-negative central medulla, a pattern similar to that found in terrestrial mammals; the whale adrenals, however, demonstrated a markedly pseudolobulated appearance because of a festooned corticomedullary junction. On radioimmunoassay of preformed cortical steroid hormones, corticosterone (B) exceeded cortisol (F) levels by a factor of 3 in the whale adrenals and aldosterone (Aldo) concentrations were 20-100 times lower than in the terrestrial mammals studied. HPLC determinations of preformed medullary catecholamines showed that, contrary to the findings in the terrestrial mammals studied, norepinephrine predominated over epinephrine and the levels of dopamine were much higher in the whale adrenals. In vitro, surviving sections of whale adrenals elaborated B from endogenous substrates, but not F or Aldo. Incubations of subcellular fractions of the whale adrenals with 14C-labeled precursors resulted in the isolation of several steroid intermediates (pregnenolone, progesterone, deoxycorticosterone) as well as the glucocorticoid end-product B, but again without evidence of the formation of either F or Aldo. In keeping with studies in terrestrial mammals, the enzymatic reactions involved in the conversion of [14C]cholesterol to B occurred under aerobic conditions, required the presence of an exogenous NADPH-generating system, and had identical subcellular localization in the whale adrenals. The process of steroid biosynthesis thus appears generally similar in aquatic and terrestrial mammals. It is possible that some of the unusual findings in the whale adrenals studies here may be related to the profound stress of stranding experienced by these marine mammals.

Adrenal Cortex Hormones↗
PubMed1987

The adrenal gland of stranded whales (Kogia breviceps and Mesoplodon europaeus): in vitro modulation of mitochondrial steroid enzyme activities.

The effects of adrenocorticotropic hormone (ACTH), cyclic AMP (cAMP), NADPH, Krebs cycle intermediates (KCl), and metyrapone on the two key mitochondrial reactions in the biosynthesis of glucocorticoids--11 beta-hydroxylation and cholesterol cleavage--were studied in preparations from the adrenal glands of stranded whales (Kogia breviceps and Mesoplodon europaeus) and some terrestrial mammals. ACTH (30 pM) and cAMP (1.0 mM) enhanced the 11 beta-hydroxylation of [11-3H]deoxycorticosterone ([3H]DOC) in monolayer cultures of whale adrenal cells during a 4-hr incubation period. Mitochondria from whale and beef adrenals responded in a similar dose-related fashion to NADPH generated by the addition of increasing amounts of NADP (0-0.6 mM) to the in vitro system: at each level of NADPH, 11 beta-hydroxylation of [14C]DOC was several-fold greater than the cleavage of [14C]cholesterol. Metyrapone interfered in a dose-related manner with both the 11 beta-hydroxylation of [14C]DOC and the cleavage of [14C]cholesterol by mitochondria from whale and beef adrenals; inhibition of 11 beta-hydroxylation exceeded 60% at 0.1 mM metyrapone and was virtually complete at 1.0 mM in both species, while inhibition of [14C]cholesterol cleavage averaged 25% at 0.1 mM metyrapone and 50% at 1.0 mM. The effect of exogenous NADPH in supporting the 11 beta-hydroxylation of [14C]DOC could be maintained in beef and rat adrenal mitochondria to the extent of 70-100% by substitution with any of the KCl. This phenomenon was not found in similar whale studies where the KCl were all ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1984

Thyrotoxic periodic paralysis in a black male.

The findings and course in a 55-year-old Black man with thyrotoxic periodic paralysis are described. This disorder appears to have a strong predilection for Orientals (approximately 90% of reported cases) with occasional reports in Caucasians and only one previous description in a Black. HLA phenotyping of the reported patient demonstrated neither of the two genetic markers previously noted among Chinese with thyrotoxic periodic paralysis, indicating that these haplotypes do not serve as markers for the disorder in Blacks.

HLA Antigens↗
PubMed1983

Familial pheochromocytoma.

During a 15-year period, 24 patients were treated operatively for pheochromocytoma at this medical center. In this group a father and three daughters were recognized to have the familial variety of this disease. Malignant hypertension, which began at an early age, was the most prominent characteristic. Operative treatment of the three sisters occurred at the ages of 9, 15, and 17 years. All pheochromocytomas were bilateral and were confined to the adrenal glands except for hepatic extension in the father. In contrast to most recent reports of familial pheochromocytoma, there was no evidence of multiple endocrine adenomatosis in this family. Total adrenalectomy was performed in only the youngest patient and, although normotensive, she requires close observation and steroid replacement. Three patients underwent a controversial partial adrenalectomy after excision of bilateral tumors. The father has remained hypertensive for 8 years and has evidence of a residual tumor in the liver. The two daughters who have had subtotal adrenalectomies remain normotensive, require no medication, and have normal urine catecholamine values 7 and 3 years after operation. These results show that removal of bilateral pheochromocytomas without total adrenalectomy may allow normal adrenal function free of recurrence for several years in patients without multiple endocrine adenomatosis.

Adolescent↗
PubMed1982

Steroid enzyme activities in extraadrenal pheochromocytomas.

The adrenal medulla and tumors derived from it have been shown to be capable of converting radioactive steroid intermediates into glucocorticoid end products in vitro. This capacity for partial steroid synthesis was explored in two large extraadrenal pheochromocytomas and compared to the results of parallel studies with intraadrenal pheochromocytomas and adrenal cortex; in one experiment, all three types of tissue were obtained from a single patient and studied simultaneously. Slice preparations of extraadrenal pheochromocytoma transformed 14C-labeled pregnenolone (3 beta-hydroxypregn-5-en-20-one) into corticosterone and cortisol. Incubations of subcellular fractions demonstrated that, as in the adrenal cortex and intraadrenal chromaffin tissue, delta 5-3 beta-hydroxysteroid dehydrogenase-isomerase, 17 alpha-hydroxylase, and 21-hydroxylase activities in extraadrenal pheochromocytomas were associated with the microsomes and 11 beta-hydroxylase was associated with the mitochondria, where metyrapone was an effective inhibitor, these findings tend to dissociate steroid-metabolizing activity in the adjacent chromaffin tissue perfused by glucocorticoid intermediates in high concentrations.

Adenoma↗
PubMed1980

Silent thyrotoxic thyroiditis in association with chronic adrenocortical insufficiency.

A 23-year-old woman had silent thyrotoxic thyroiditis and chronic adrenocortical insufficiency (Addison's disease). Recent evidence suggests that silent thyroiditis is an autoimmune disease characterized by lymphocytic infiltration of the thyroid and by transient hyperthyroidism, followed occasionally by transient hypothyroidism and eventual recovery. This case would seem to expand the spectrum of autoimmune thyroid diseases (Graves' disease, lymphocytic [Hashimoto's] thyroiditis, and hypothyroidism) associated with chronic adrenocortical insufficiency.

Addison Disease↗
PubMed1978

Adrenal cysts: hormonal contents and functional evaluation.

Cortisol, corticosterone, epinephrine and norepinephrine have been identified for the first time in two adrenal cysts removed from patients without endocrine dysfunction. Total concentrations of corticosteroids and catecholamines in both capsule and fluid of these cysts were higher than in plasma of normal subjects but lower than in human adrenal tissue. The cysts contained preformed cholesterol in concentrations similar to normal adrenal parenchyma. Contrary to adrenal tissue, however, homogenates of cyst components failed to utilize [4-14C] cholesterol for steroid formation. The data presented suggest that hormones in adrenal cysts probably arise by passive diffusion from the surrounding gland and that the endocrine status of patients bearing adrenal cysts is determined by the adjacent non-cystic tissue.

Adrenal Cortex Hormones↗
PubMed1977

Hyporeninemia and hypoaldosteronism in diabetes mellitus.

The changes in plasma renin activity (PRA) and plasma aldosterone concentration (PA) in response to postural stimuli were evaluated in 12 patients with stable diabetes mellitus and in five volunteers. Seven diabetic patients had hyperkalemia, and several had renal insufficiency and neurological complications. Five diabetics and had normal serum potassium concentration, a mean creatinine clearance within the normal range, and few complications. PRA and PA were measured in these patients and in the control subjects, all of whom were receiving a diet containing 10 mEq of sodium and 50 mEq of potassium while they were in a supine position, after they were tilted to a 90 degrees position, and after upright posture for two hours. The results indicate that impaired responsiveness of PRA and PA may occur in patients with complicated and those with uncomplicated diabetes and may be responsible in part for a relatively high prevalence of hyperkalemia especially in those diabetic patients with reduced renal function.

Adult↗