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Biomedical subjects

J M Feldman

Publications and source records attributed to J M Feldman.

At least 73 records · Page 4Linked to original sources

Serotonin content of foods: effect on urinary excretion of 5-hydroxyindoleacetic acid.

Using a highly specific radioenzymatic assay we determined the serotonin concentration in 80 types of foods. The following fruits had a high serotonin concentration (mean +/- SEM) expressed in micrograms/g weight: plantain 30.3 +/- 7.5; pineapple 17.0 +/- 5.1; banana 15.0 +/- 2.4; Kiwi fruit 5.8 +/- 0.9; plums 4.7 +/- 0.8; and tomatoes 3.2 +/- 0.6. Only nuts in the walnut or hickory family had a high serotonin concentration expressed in micrograms/g weight; butternuts 398 +/- 90; black walnuts 304 +/- 46; English walnuts 87 +/- 20; shagbark hickory nuts 143 +/- 23; mockernut hickory nuts 67 +/- 13; pecans 29 +/- 4; and sweet pignuts 25 +/- 8. Ingestion of these fruits and nuts resulted in an increase in urinary 5-hydroxyindoleacetic acid excretion with no change in platelet serotonin concentration. The above foods should not be eaten while a urine is being collected for 5-hydroxyindoleacetic acid analysis.

Adult↗

Effects of diabetes on the dietary lipid alteration of R3230AC mammary carcinoma growth in rats.

To examine the effects of diabetes on the alteration of R3230AC mammary tumor growth by dietary lipids, streptozotocin-induced diabetic rats were fed diets containing either 20% corn oil (HF), 20% hydrogenated cottonseed oil (HCTO), or 0% fat (FF). Diabetes resulted in lower tumor weights and body weights compared to those of intact animals. Unlike intact animals, relative tumor weight (g tumor/100 g body wt) of diabetic animals fed HF diets were not greater than those from animals fed FF diets. However, in these diabetic animals, growth of tumors in HF-fed rats was faster than in HCTO-fed rats, a relationship similar to that seen in intact rats. A surprising result was the almost twofold greater tumor weight/100 g body wt observed in diabetic FF-fed rats compared to those fed HCTO diets. Insulin binding to tumor plasma membranes from diabetic animals was higher in rats fed HF diets than in rats fed FF or HCTO diets. The tumor plasma membrane fatty acid composition of diabetic rats fed FF and HCTO diets displayed higher proportions of the monounsaturates (C18:1 and C21:1) and decreased amounts of the polyunsaturates (C18:2 and C20:4) compared to the levels observed in membranes from HF-fed rats. These results, as well as the insulin binding data, were similar to those obtained using intact animals. The data presented here indicate that the more rapid growth of the R3230AC mammary tumor seen in intact animals fed high polyunsaturated fat vs fat-free diets did not occur in diabetic animals.

Animals↗

A role of estrogens and insulin binding in the dietary lipid alteration of R3230AC mammary carcinoma growth in rats.

The importance of estrogens in the dietary lipid alteration of R3230AC mammary carcinoma growth and insulin binding was studied. Animals were divided into three groups [intact, ovariectomized, and ovariectomized treated with estradiol valerate (EV)] and were fed diets containing either 0% fat (fat free), 0.5% corn oil (low fat), or 20% corn oil (high fat). An alteration of tumor burden between animals fed high-fat versus either low-fat or fat-free diets was observed and appeared to be influenced by the estrogen status of the animal. The difference in tumor burden attributed to dietary lipid seen in intact rats was less in ovariectomized rats and greater in ovariectomized rats treated with EV, despite the fact that absolute tumor burden was reduced by this treatment. A similar relationship was observed for dietary lipid-induced differences in insulin binding to plasma membranes from these tumors. Reduction of tumor growth resulting from estrogen treatment was greater in low-fat- and fat-free-fed animals than in high-fat-fed rats. Again, tumor growth behavior appeared to be related to the reduction of insulin binding induced by estrogen treatment; insulin binding to plasma membranes from animals fed a low unsaturated lipid diet was decreased to a greater extent by EV treatment than in membranes from high-fat-fed rats. Altered tumor growth and membrane insulin binding, resulting from dietary perturbations and/or EV treatment, were not invariably related to serum insulin levels, nor to differences in membrane preparation, as reflected by 5'-nucleotidase activity, nor to membrane fatty acid composition or uptake of proline. Taken together, these results suggest a potential role of estrogens and insulin receptors as mediators of the dietary lipid alterations of growth of the R3230AC mammary carcinoma.

Animals↗

Failure of indomethacin to inhibit growth of the R3230AC mammary tumor in rats.

The relationship between the dietary lipid-induced growth of the R3230AC mammary tumor and prostaglandin E2 (PGE2) levels as well as the effect of the prostaglandin synthetase inhibitor indomethacin (Ind) on these parameters was examined. F344 rats fed a high-fat (HF) diet containing 20% corn oil demonstrated more rapid tumor growth and higher tumor and plasma PGE2 levels than rats fed a 20% hydrogenated cottonseed oil (HCTO) diet. Addition of 0.004% Ind to the HF diet markedly reduced tumor and plasma PGE2 levels. However, Ind had no effect on tumor growth. Neither the fatty acid composition nor the insulin-binding capacity of the tumor plasma membranes was affected by Ind. Membranes from animals fed HF diets with or without Ind bound more 125I-labeled insulin than membranes from HCTO-fed rats. The results suggest that, for the R3230AC mammary tumor, reduction in both tumor and plasma PGE2 levels by Ind did not result in reduced tumor growth in animals fed diets high in polyunsaturated fatty acids.

Animals↗

Platelet uptake of the pheochromocytoma-scanning agent 131I-meta-iodobenzylguanadine.

The pheochromocytoma-scanning agent 131I-meta-iodobenzylguanadine (131I-MIBG) was concentrated in the platelets of ten subjects undergoing scans for suspected pheochromocytomas. In vitro studies also demonstrated that 131I-MIBG was concentrated in platelets. In contrast to serotonin, which had maximum in vitro platelet uptake of one hour, the peak in vitro platelet uptake of 131I-MIBG did not occur until six hours. In vitro platelet 131I-MIBG uptake was decreased by 79% to 98% following the neuronal-uptake-blocking agent imipramine. These studies suggest that pheochromocytomas take up 131I-MIBG by a neuronal-pump mechanism. Further studies to determine if 131I-MIBG is taken up by other tumors with a neuronal-pump mechanism, such as carcinoid tumors, will be valuable.

3-Iodobenzylguanidine↗

Pseudocystic liver metastases in patients with carcinoid tumors: report of three cases.

Three of 30 patients (10%) with carcinoid tumors metastatic to the liver had large hepatic pseudocysts. One of the patients had an atypical carcinoid tumor that was markedly deficient in aromatic aminoacid decarboxylase and thus secreted 5-hydroxytryptophan as well as ACTH. Postmortem examination of this patient suggested that the mechanism of pseudocyst formation was probably infarction with liquefaction necrosis of tumor nodules. The authors' observations suggest that carcinoid tumors metastatic to the liver may not infrequently result in hepatic pseudocysts.

5-Hydroxytryptophan↗

Biochemical composition of edge and center of malignant hamster insulinoma.

The purpose of this study was to determine if there is a difference in the biochemical composition of the edge of a tumor and the center of a tumor. There was a greater concentration of histamine in the edge (mean +/- SEM, 9.3 +/- 1.2 pmole/mg of wet weight) than in the center (3.6 +/- 0.4 pmole/mg of wet weight) of a transplantable golden hamster insulinoma. There was, however, no difference in the concentration of norepinephrine, protein, DNA, or phosphate, or in the activity of the enzymes, monoamine oxidase, catechol-O-methyltransferase, L-dopa decarboxylase, or 5'-nucleotidase in the edge or in the center of the tumor. Using chemical analysis and autoradiography, there was a comparable incorporation of tritiated thymidine in the edge and in the center of the tumor.

Adenoma, Islet Cell↗

Leg motion analysis during gait by multiaxial accelerometry: theoretical foundations and preliminary validations.

A theoretical formulation for studying limb motions and joint kinetics by multiaxial accelerometry is developed. The technique is designed to study the swing phase of human gait, modeling the lower leg as a rigid body. Major advantages of the approach are that acceleration information needed for the calculation of forces and moments is generated directly, and that the method automatically generates its own initial conditions. Results of validation experiments using both artificial and experimental data demonstrate that the method is theoretically valid, but that it taxes available instrumentation and requires further development before it can be applied in a clinical setting.

Acceleration↗

Treatment of metastatic pheochromocytoma with streptozocin.

A 58-year-old man who had a malignant pheochromocytoma with hepatic metastasis was treated with 2 g/mo of intravenous streptozocin for 18 months. There was a reduction in his urinary excretion of dopamine (from 33,840 to 731 micrograms/24 hr), homovanillic acid (from 48 to 8 mg/24 hr), and vanillylmandelic acid (from 350 to 74 mg/24 hr). There also was a reduction in the size of his hepatic metastasis (50%) and a right adrenal mass (25%), as well as a marked clinical improvement in his condition. Based on this evidence, I believe further attempts to treat patients with metastatic pheochromocytoma with streptozocin seem warranted.

Adrenal Gland Neoplasms↗

Comparison of monoamine oxidase in golden hamster islets and insulinoma.

We compared the properties of monoamine oxidase (MAO) in hamster islets and insulinomas. The tryptamine concentration at which the monoamine oxidase velocity was half maximal (Km) was higher in islets than insulinomas; the maximal velocity (Vmax) of monoamine oxidase was greater in islets than insulinomas. Both islet and insulinoma are more sensitive to inhibition by pargyline than clorgyline. After pargyline administration the monoamine oxidase activity of insulinoma returns faster than activity of islets. This may occur because both synthesis of new MAO in pre-existing cells and formation of new cells occurs in the insulinoma.

Adenoma, Islet Cell↗

Histaminuria from histamine-rich foods.

Using a highly specific and sensitive assay, the histamine content of foodstuffs and the effect of ingesting these foodstuffs on urinary histamine excretion were measured. Certain vegetables (spinach, eggplant), cheeses (Parmesan, blue, Roquefort), and red wines (Chianti and Burgundy) had a high content of histamine. Although only 0.21% of the ingested histamine was excreted unchanged in the urine, the histamine content of some of the foods was so high (Parmesan cheese, 185 micrograms/g; spinach, 60 micrograms/g; baked eggplant, 26 micrograms/g) that they caused histaminuria. Patients collecting urine for analysis for 24-hour histamine excretion for diagnosis of systemic mastocytosis or carcinoid syndrome should avoid intake of these foods and beverages on the day of the urine collection.

Adult↗

Metabolic acidosis in patients with the carcinoid syndrome: treatment with parachlorophenylalanine.

Four of 46 patients with carcinoid tumors and the carcinoid syndrome developed severe life-threatening diarrhea. Although only 11% of the patients in this series had bronchial carcinoid tumors, three only the four patients with severe diarrhea had this type of tumor. Three of the patients with severe diarrhea developed metabolic acidosis while the fourth patient had severe hypokalemia. In the three patients in which it was used, parachlorophenylalanine, an inhibitor of serotonin synthesis, improved the life-threatening diarrhea.

Acidosis↗

Carcinoid syndrome from gastrointestinal carcinoids without liver metastasis.

Although patients with bronchial and ovarian carcinoid tumors can develop the carcinoid syndrome (diarrhea and/or flushing) in the absence of hepatic metastasis, it is believed that development of the carcinoid syndrome in patients with carcinoid tumors of gastrointestinal origin occurs only after the patient has hepatic metastasis. This is explained by hepatic inactivation of most of the serotonin in the portal circulation or by the fact that hepatic metastases are larger than the primary tumor in the gastrointestinal tract. Three patients with ileal and jejunal carcinoid tumors who developed the carcinoid syndrome without obvious hepatic metastasis are described. Two of the patients had intra-abdominal, but extrahepatic, metastasis that probably drained directly into the systemic circulation. The third patient had an ileal carcinoid with clinical involvement limited to adjacent mesenteric lymph nodes. Following resection of her tumor, her urinary 5-HIAA excretion and platelet serotonin level returned to normal, and her attacks of carcinoid flushing virtually ceased. She has occasional spells of "blushing" that are thought to be benign; however, further close follow-up study will be needed to be certain that she is free of disease. It is suggested that each patient with the carcinoid syndrome be evaluated with CT and technetium-99 pertechnetate liver scans. If there is no liver involvement detected with these studies, one should consider hepatic arteriogram or laparotomy to determine if the patient's tumor might be totally resectable.

Adult↗

Effect of chronic tolbutamide administration on normal and obese-hyperglycemic mice: evidence for post-receptor potentiation of insulin action.

Obese-hyperglycemic mice (genotype ob/ob) have hyperglycemia, hyperinsulinemia, increased resistance to insulin action and decreased insulin receptors on their liver, fat cell and muscle plasma membranes. Hypoglycemic sulfonylureas are reported to improve diabetic control by decreasing the insulin resistance of subjects with Type II diabetes mellitus: however, it is not clear if their mechanism is to increase plasma membrane insulin receptors or to decrease post-receptor insulin resistance. In this study we treated obese-hyperglycemic mice and their normal weight litter mates with the oral hypoglycemic sulfonylurea tolbutamide for 28 to 34 weeks. Tolbutamide administration to normal mice resulted in the following changes that were indicative of increased insulin action: (1) increased body weight; (2) increased epididymal fat-pad weight; (3) increased 2-deoxyglucose transport into the intact diaphragm muscle preparation. There was no alteration in plasma glucose, plasma insulin or pancreatic insulin content suggesting that the tolbutamide effect was an extrapancreatic effect that was probably not mediated by increased insulin secretion. There was no change in the insulin receptor number or affinity of liver cell membranes prepared from tolbutamide treated mice supporting the notion that the extrapancreatic effect of tolbutamide may occur at a post-insulin receptor location. In contrast to the normal mice, tolbutamide did not increase the body weight, epididymal fat pad weight, the already increased 2-deoxyglucose transport into diaphragm muscle or the decreased number of insulin receptors on hepatic plasma membranes. The tolbutamide caused a striking decrease in pancreatic insulin concentration and degranulation of the islets in obese but not normal mice. This is compatible with previous information that the obese mice have abnormal islets that are not under the normal feed-back control of ambient insulin concentration as are the islets of normal mice. We conclude that tolbutamide potentiates insulin action in normal, but not obese, mice and that this potentiation may be due to a post-insulin receptor action.

Animals↗

Elevated platelet norepinephrine concentration in patients with pheochromocytomas.

With a radioenzymatic method of analysis we determined the concentration of plasma and platelet norepinephrine in simultaneously drawn blood samples from six patients with pheochromocytomas. All six subjects had elevated platelet norepinephrine concentrations in the preoperative or intraoperative period. Three of the six patients had a normal plasma norepinephrine concentration in their sample. After resection of benign pheochromocytomas the platelet and plasma norepinephrine of five patients returned to normal. The platelet and plasma norepinephrine concentration of a patient with a malignant, non-resectable pheochromocytoma remained elevated. Eight of 30 patients (27%) with hypertension, not thought to be due to pheochromocytoma, had elevated platelet norepinephrine concentrations, All 8 of these patients had diastolic blood pressures of 120 mm Hg or greater at the time the blood samples were drawn. In contrast, the six patients with pheochromocytomas had elevated platelet norepinephrine concentrations while normotensive. Only five of 60 "sick" patients (8%) without a history of hypertension had elevated platelet norepinephrine concentration. Platelet norepinephrine concentration is an excellent test to screen patients, with a history of spells of hypertension but presently normotensive, for pheochromocytomas. An elevated value should be followed up with measurement of vanillylmandelic acid (VMA) and/or catecholamines in a 24-h urine collection.

Adrenal Gland Neoplasms↗

Radioenzymatic assay of platelet serotonin, dopamine and norepinephrine in subjects with normal and increased serotonin production.

Platelet serotonin, dopamine and norepinephrine concentrations were determined with sensitive and specific radioenzymatic methods in normal volunteers and in sick subjects with both normal and increased serotonin production. In the assays, a 3H-labeled methyl group is transferred from [3H]S-adenosyl methionine to the monoamine under investigation by a semi-purified enzyme. The platelet serotonin concentration (expressed as pmol serotonin/mg platelet protein) was significantly higher in the patients with increased serotonin production from carcinoid tumors (5400 +/-0 500) than in the normal volunteers (900 +/- 100) or the sick subjects with normal serotonin production (900 +/- 100). Although eight of the subjects with increased serotonin production had symptoms of the carcinoid syndrome such as flushing and diarrhea, two of the subjects with increased serotonin production did not have these symptoms. The radioenzymatic method of platelet serotonin measurement was as effective as a conventional fluorometric technique for serum serotonin in detecting patients with serotonin overproduction from carcinoid tumors, and had the advantages of being more sensitive and specific. The great sensitivity and specificity of the radioenzymatic techniques suggest that it might be useful in evaluating disease states in which platelet serotonin is decreased. Using these techniques we found that dopamine and norepinephrine were also present in platelets, although in much lower amounts than serotonin. Despite the markedly increased serotonin concentration in the platelets of subjects with serotonin overproduction from carcinoid tumors, there was no alteration in the dopamine or norepinephrine concentration of their platelets.

Adult↗