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Biomedical subjects

J M Feldman

Publications and source records attributed to J M Feldman.

At least 109 records · Page 6Linked to original sources

The effect of harmine and other monoamine oxidase inhibitors on N-acetyltransferase activity.

Prior studies indicate that the monoamine oxidase inhibitors (MAOI) harmine and iproniazide inhibit N-acetyltransferase activity from liver. In this report we have demonstrated that harmine and harmaline are potent inhibitors of N-acetyltransferase, purified from hamster and rat liver. However, other MAOI such as deprenyl, clorgyline, methysergide, cyproheptadine, phenelzine, pargyline, methyltryptamine and tranylcypromine have either no effect, or only trivial effects on N-acetyltransferase. There is no correlation between a compound's properties as an MAO and N-acetyltransferase inhibitor. One must consider the inhibitory effect of harmine and harmaline on both MAO and N-acetyltransferase when evaluating the effects of these compounds on physiological processes.

Acetyltransferases↗

The role of altered tissue norepinephrine concentration in the hereditary obese-hyperglycemic syndrome of mice.

The purpose of this study was to determine if the elevated concentration of norepinephrine in the hypothalamus of the obese-hyperglycemic mouse plays a role in the development of this syndrome. We treated normal and obese mice with the monoamine oxidase inhibitors pargyline or clorgyline for 25 weeks. This resulted in significant inhibition of monoamine oxidase in their hypothalamus, cerebral cortex, kidney, heart and epididymal fat. There was a significant increase in the norepinephrine concentration of the hypothalamus of the normal mice and the cerebral cortex of the obese mice. The obese mice receiving clorgyline had an increase in plasma glucose (313 +/- 9 mg/dl). However, the increase in tissue norepinephrine concentration did not result in increased weight gain or alterations in organ weights in the mice. Thus, the elevated hypothalamic norepinephrine concentration in obese mice is probably not the cause of their obesity.

Animals↗

Plasma norepinephrine response to standing in patients with pheochromocytoma or medullary carcinoma of the thyroid.

We determined the effect of a lying/standing test on 22 patients with medullary carcinoma of the thyroid (MCT), seven patients with pheochromocytoma (six of whom also had MCT), six healthy first-degree family members of patients with MCT, and nine normal subjects who did not have a family history of MCT. The purpose of the study was to determine if the patients with MCT had an altered noradrenergic response to standing and to determine if this test would be useful in screening MCT patients for the presence of pheochromocytoma. All of the patients with MCT, as well as all of the healthy family members, had normal urinary excretion of catecholamines and their metabolites. Plasma norepinephrine (NE) concentrations, plasma cortisol levels, and blood pressure (BP) were determined during the lying/standing test. The plasma NE concentration showed the expected increase with a change in posture; the plasma cortisol concentration did not change. There was no significant difference in the plasma NE, plasma cortisol, and BP response in the four study groups. Only one of the seven patients with pheochromocytoma had a hypertensive episode in response to standing. We conclude that there is probably a normal noradrenergic response to standing in patients with MCT, and the standing/lying test, as performed in this study, is of limited value in screening for the presence of pheochromocytoma.

Adolescent↗

Plasma and tumor dopamine-beta-hydroxylase activity in patients with familial pheochromocytomas.

The majority of patients with sporadic pheochromocytomas (pheos) have been noted to have normal plasma dopamine-beta-hydroxylase (DBH) activity. We determined the activity of DBH in the plasma of 8 patients with pheos, secondary to multiple endocrine neoplasia Type 2 (MEN II) (medullary carcinoma of the thyroid [MCT], pheochromocytoma(s), and parathyroid hyperplasia). We also determined the activity of DBH in the pheos of six of the patients. Three of the eight patients (38%) had elevated plasma DBH in the preoperative period. After surgical resection of their pheos, the plasma DBH of two of the subjects, in whom it could be measured, returned to normal. Although two of the other patients had bilateral pheos containing large amounts of DBH and norepinephrine (NE), their plasma DBH was normal in the preoperative and postoperative periods. Despite elevated urinary vanillylmandelic acid (VMA) excretion in all eight patients, their homovanillic acid (HVA) excretion was normal. VMA reflects NE plus epinephrine (E) excretion, while HVA reflects dopamine (DA) excretion. We conclude that the majority of patients with pheos, associated with MEN II, have normal plasma DBH activity.

Adolescent↗

Effects of aging on monoamine oxidase activity of mouse and rabbit tissues.

The effect of aging on the monoamine oxidase (MAO) activity in tissues of mice and rabbits was evaluated. There were no alterations in the MAO activity of liver, kidney, pancreas and brain (adult mice and rabbits) or testis and heart (adult mice) with aging. There were no alterations in the norepinephrine content of the brain, kidney and heart of older mice. The present study indicates that increased MAO activity is not inevitably associated with aging in all species.

Aging↗

Alterations in plasma norepinephrine concentration during surgical resection of pheochromocytoma.

Using a sensitive and specific radioenzymatic assay, the plasma norepinephrine (NE) concentration was measured in seven patients with pheochromocytoma, one patient with bilateral adrenal medullary hyperplasia, one patient with a retroperitoneal paraganglioma, and two patients undergoing bilateral adrenalectomies for palliation of metastatic breast carcinoma. Surgical manipulation of the pheochromocytomas resulted in striking increases in plasma NE concentration with concomitant increases in blood pressure. There were either small changes or no changes in the patients' plasma NE and blood pressure during resection of the normal adrenal glands, the adrenal glands with medullary hyperplasia, or the retroperitoneal paraganglioma. Plasma dopamine-beta-hydroxylase (DBH) was measured in one patient with pheochromocytomas and the patient with medullary hyperplasia. There was no change in plasma DBH in either patient, supporting the concept that exocytosis is not the primary mechanism for catecholamine secretion from pheochromocytomas. It was also noted that enflurane is an excellent general anesthetic for the resection of pheochromocytomas, and that sodium nitroprusside (rather than phentolamine) may be the agent of choice for the management of the hypertensive episodes that occur during surgical manipulation of pheochromocytomas.

Adolescent↗

Effect of hyperprolactinemia on pituitary-adrenal function.

Three patients with hyperprolactinemia (2 with pituitary tumors and 1 with a hypothalamic disturbance) underwent evaluation of their hypothalamic-pituitary-adrenal axis using ACTH, metyrapone and in one case repetitive insulin tolerance tests. With the exception of a suggestion of a slight increase in adrenal responsiveness to pharmacological doses of ACTH in one of the patients, there was no alteration in the adrenal responsiveness of the 3 patients evaluated. We conclude that hyperprolactinemia probably does not systematically modify the responsiveness of the hypothalamic-pituitary-adrenal axis.

Adenoma, Chromophobe↗

Serotonin metabolism in patients with carcinoid tumors: incidence of 5-hydroxytryptophan-secreting tumors.

The urinary excretion of 5-hydroxyindoleacetic acid, 5-hydroxytryptophan, serotonin, tryptamine, and tyramine and the serum serotonin concentration were determined in 38 consecutive patients with metastatic carcinoid tumors. Four of the 23 patients with the carcinoid syndrome (15%) had markedly elevated excretion of 5-hydroxytryptophan. None of the patients had markedly elevated excretion of tryptamine or tyramine; a substantial number of patients had moderately low urinary excretion of these amines. All of the patients with the carcinoid syndrome had elevated urinary 5-hydroxyindoleacetic acid excretion; 2 of these patients had normal serum serotonin concentrations, suggesting that quantitative 5-hydroxyindoleacetic acid excretion is the most reliable test for the carcinoid syndrome. Although tryptamine secretion by carcinoid tumors is rare, 5-hydroxytryptophan secretion may be more common than is recognized.

5-Hydroxytryptophan↗

Effect of hyper- and hypothyroidism on platelet monoamine oxidase activity and serotonin metabolism.

We evaluated platelet monoamine oxidase (MAO) activity in 13 hyperthyroid and 9 hypothyroid patients. The platelet MAO activity of these patients did not differ from that of age- and sex-matched euthyroid control subjects. Nineteen hyperthyroid and twelve hypothyroid subjects had serum serotonin concentrations similar to those of age- and sex-matched euthyroid control subjects. We also determined the urinary excretion of 5-hydroxy-indoleacetic acid (5-HlAA), serotonin, tryptamine, and tyramine in five hyperthyroid and four hypothyroid subjects. Two hyperthyroid patients had increased tyramine excretion; one of these patients also had increased tryptamine excretion. Three hypothyroid patients and one hyperthyroid patients had slightly decreased serotonin excretion. Both the hyper- and the hypothyroid subjects had normal urinary 5-HIAA excretion. There was no relationship between platelet MAO activity and monoamine excretion in the patients with thyroid dysfunction. We conclude that there is no systematic change in platelet MAO activity or serum serotonin concentration in patients with hyper- or hypothyroidism.

Adult↗

Pituitary-gonadal function in the carcinoid syndrome: effect of parachlorophynylalanine therapy.

Six patients with the carcinoid syndrome (C.S) had serum luteinizing hormone (LH) concentrations that were greater than age and sex matched control subjects. The serum follicle stimulating hormone (FSH) and testosterone concentrations of the groups did not differ. Four of the 5 C.S. patients tested had an increase in serum testosterone after human chorionic gonadotropin administration and 5 of the 5 subjects tested had an increase in serum LH after clomiphene citrate administration. One of the 4 subjects treated with the tryptophan hydroxylase inhibitor parachlorophenylalanine (PCPA) had a reduction in serum testosterone. He was also receiving methysergide. The other 3 subjects treated with PCPA did not have any persistent alterations in serum testosterone.

Aged↗

Monoamine oxidase and catechol-O-methyl transferase activity in Tetrahymena.

Tetrahymena pyriformis strain HSM was found to have monomine oxidase (MAO) and a catechol-3-methyl transferase-like (COMT) activity. As in mammalian tissues, the MAO activity is predominantly localized in the mitochondrial pellet and COMT in the cytosol. The COMT-like activity was present in amounts comparable to several mouse tissues and was inhibited by tropolone. MAO activity was much lower than in any of the mouse tissues tested, and its activity varied greatly from preparation to preparation. The substrate preference of Tetrahymena MAO was tryptamine greater than serotonin greater than dopamine, and activity increased with increasing pH from pH 6.5 to pH 7.8, as does that of mouse liver MAO. Teh Km of Tetrahymena MAO for tryptamine was approximately 4 micrometer, an order of magnitude lower than that of mouse liver MAO. Sensitivity of inhibition by MAO inhibitors was variable. In some preparations, no inhibition was observed. In others clear inhibition was obtained, harmine and clorgyline being among the most potent inhibitors.

Animals↗

Species variation in pancreatic islet monoamine uptake and action.

There are conflicting data in the literature regarding the role of monamines in the secretion of insulin. In order to clarify the contribution that species variation may make to these divergent results, the uptake of serotinin (5-HT), dopamine (DA), and their precursor amino acids, 5-hydroxytryptophan (5-HTP) and L-dopa, into islets was studied. Islets from golden hamsters, rabbits, guinea pigs, and obese, hyperglycemic mice were isolated by the collagenase technique. The islets were incubated in Krebs-Ringer buffer in the presence of 14C-labeled monamines or their precursors. At 30-minute intervals after initiating the study, the incubation mixture was passed through a Millipore filter. The retained islets were disrupted by sonication and the radioactivity counted. The ratio of the uptake of 5-HTP to 5-HT was at least 3:1 in the hamster, guinea pig, and mouse. In the rabbit the ratio was 1:1. A similar relationship was noted for the uptake of L-dopa and DA. The in-vitro results were confirmed by the in-vivo studies, in which hamsters were injected with 14C5-HT or 5-HTP, followed by isolation of the islets. We conclude that there is significant species variation inthe uptake of these monoamines and their precursors.

5-Hydroxytryptophan↗

99mTc-pyrophosphate bone scans in patients with metastatic carcinoid tumors.

Three patients with foregut (bronchial), hindgut (rectal) or (ovarian) carcinoid tumors had symptomatic bone metastasis with abnormal 99m Tc pyrophosphate bone scans and bone roentgenograms. Six patients with midgut (small intestine or caecal) carcinoid) carcinoid tumors who had no symptoms of bone metastasis had no evidence of bone metastasis on bone scan or bone roentgenographic examination. This study supports the clinical impression that patients with midget carcinoid tumors have a low incidence of bone metastasis.

Bone Neoplasms↗