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Biomedical subjects

L Landsberg

Publications and source records attributed to L Landsberg.

At least 73 records · Page 4Linked to original sources

Sympathetic nervous system responses to cold exposure and diet in rat skeletal muscle.

Norepinephrine (NE) turnover measured in individual skeletal muscles of the rat assessed sympathetic responses to cold (4 degrees C) and diet. Acute cold exposure increased NE turnover slightly (15-50%) in all muscles examined, including gastrocnemius, tibialis anterior, tensor fascia lata, and soleus, in contrast, cold-accelerated NE turnover in heart by one- to twofold and in interscapular brown adipose tissue (IBAT) by more than threefold. Similar results in skeletal muscle and heart were obtained after 1 wk of cold exposure. Examination of dietary effects on NE turnover, comparing rats fed a sucrose-supplemented diet for 3 days with those fasted for 2 days, indicated that sympathetic activity in skeletal muscle was unresponsive to dietary intake. In heart and IBAT, on the other hand, NE turnover in sucrose-fed rats was twice that obtained in fasted animals. Taken together, the lesser effect of cold and the undetectable response to diet indicate that sympathetic outflow to skeletal muscle is regulated differently than that to heart or IBAT and imply that skeletal muscle is not a major site for sympathetically mediated thermogenic responses to cold exposure or to dietary alteration, such as fasting and sucrose feeding.

Acclimatization↗

The effects of various carbohydrates on sympathetic activity in heart and interscapular brown adipose tissue of the rat.

The present studies were undertaken to determine the effect of various carbohydrates on sympathetic nervous system (SNS) activity. Tritiated-norepinephrine (3H-NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of rats fed either chow or chow plus 50% caloric supplements of fructose, sucrose, dextrose, or corn starch. Additional studies were performed to examine whether absorption of carbohydrate plays a role in the SNS response, and to determine whether sweet taste in the form of artificial sweeteners may influence SNS activity. After five to ten days on the respective diets, 3H-NE turnover was increased to a similar extent by all carbohydrates tested (from 38% to 160% greater than controls in different studies). Addition of acarbose (which impairs sucrose absorption) to a sucrose-supplemented diet abolished the SNS stimulatory response, whereas cholestyramine (a drug that blocks fat absorption) had no effect. Finally, the addition of saccharin or aspartame to a chow diet failed to alter SNS activity. Thus, caloric supplementation with several carbohydrates, in addition to sucrose, stimulates both cardiac and IBAT SNS activity, absorption of carbohydrate is required for this effect, and noncaloric sugar substitutes do not alter SNS function.

Acarbose↗

Neuroblastoma in adults. Three case reports and a review of the literature.

Three adult patients with neuroblastoma have been treated recently at the Dana-Farber Cancer Institute. One adult neuroblastoma patient experienced two distinct paraneoplastic syndromes that have not been reported previously in association with neuroblastoma. The clinical data on our three patients are presented in detail and the important features of 27 cases that have been described in the literature are summarized. This study suggests that the distribution of primary neuroblastoma sites in adults is similar to that seen in pediatric cases but that the natural history of the disease may be longer. Furthermore, this study suggests that neuroblastoma in adults may be less sensitive to chemotherapy than is the childhood disease.

Adult↗

Metabolic studies in human obesity during overnutrition and undernutrition: thermogenic and hormonal responses to norepinephrine.

Overfeeding increases the thermogenic response of norepinephrine (NE) in normal but not in certain genetically obese rodents. It has been suggested that human obesity may be associated with a similar thermogenic defect. To determine whether there are differences in the thermogenic sensitivity to NE in human obesity, energy expenditure in response to graded infusions of NE (0.05, 0.10, 0.15, 0.20 micrograms/min/kg fat-free mass) was measured in six lean and six obese subjects (9.5 +/- 1.8 v 36.3 +/- 3.8% body fat P less than 0.005). Resting metabolic rate (RMR), thermogenic response to NE, and thermogenic response to exercise were measured during weight maintenance and during the third week of feeding 1000 extra Kcal/d in the lean and obese subjects. These components of energy expenditure were also measured in the obese subjects during the third week of a 589 Kcal/d diet. Resting metabolic rate increased during overfeeding in lean (6.6%, P less than 0.05) but not in the obese subjects (2.7%, P = NS) and fell during underfeeding in the obese (-9.1%, P less than 0.02). There was a logarithmic increment above baseline in VO2 v plasma NE concentration during the NE infusions (r = 0.75, P less than 0.005) in lean subjects which was unaltered by overfeeding. The obese exhibited equivalent VO2 responses to NE to that measured in the lean. Supine plasma NE concentrations were lower but metabolic clearance rates (MCR) of NE were similar in the obese compared to lean subjects during both weight maintenance and overfeeding. Overfeeding minimally increased plasma concentration but not MCR of NE in both groups. The thermogenic response to exercise was similar in the lean and obese subjects and was unaltered by overfeeding or underfeeding. The increments in plasma glycerol and free fatty acid in response to the NE infusions were proportional to the total fat mass of each individual and were greater in the obese subjects. Overfeeding partially suppressed the lipolytic response to NE in both groups and underfeeding increased the lipolytic response in the obese. There are no differences in thermogenic responses to NE in human obesity to account for excessive fat deposition. Overfeeding does not increase the thermogenetic responses to NE in humans as has been reported in small mammals.

Adult↗

Splanchnic factors enhance the norepinephrine response to oral glucose in aged man.

Oral glucose has been shown to increase sympathetic nervous system (SNS) activity more in old than in young subjects. In contrast intravenous glucose during euglycemic hyperinsulinemia increases SNS activity in young but not in old subjects. To evaluate the role of splanchnic factors in this discrepancy, we employed a modification of the glucose clamp technique in 6 young (24-39 years) and 8 old (65-83 years) normal males. Each subject underwent two studies in which insulin was infused at 120 mU/m2 X min for 3 h and either oral glucose (50 gms) or water was given 60 min after initiating insulin. Euglycemia was maintained in all studies. When compared to control drink, oral glucose elevated norepinephrine in old (p less than 0.01), but not in young subjects. The difference between old and young was significant (p less than 0.02). When compared to control drink, oral glucose increased pulse rate and double product in the young, and pulse rate in the old. These results indicate that oral glucose activates the SNS in the elderly via splanchnic mechanisms independent of changes in circulating levels of glucose or insulin.

Administration, Oral↗

Effect of protein on sympathetic nervous system activity in the rat. Evidence for nutrient-specific responses.

Increased energy intake activates the sympathetic nervous system (SNS) in animals and man. While dietary carbohydrate and fat stimulate, the impact of dietary protein on the SNS is not well defined. The present studies examine the effect of protein ingestion on sympathetic function based upon the measurement of [3H]norepinephrine (NE) turnover in heart and interscapular brown adipose tissue (IBAT) as the index of SNS activity. In these experiments, animals were pair-fed mixtures of laboratory chow and refined preparations of casein, sucrose, and lard to permit comparisons among nutrients with total energy intake held constant or with additional energy provided in the form of a single nutrient. After 5 d of eating a 2:1 mixture of chow and either casein or sucrose cardiac, [3H]NE turnover was less (P less than 0.005) in casein-fed rats (6.4%/h and 28.9 ng NE/h) than in animals given sucrose (11.2%/h and 46.5 ng NE/h). Similar results were obtained in IBAT and in experiments using 1:1 mixtures of chow and casein/sucrose. Casein-fed animals also displayed slower rates of NE turnover than lard-fed rats in both heart (7.8%/h vs. 13.2, P less than 0.001) and IBAT (7.0%/h vs. 12.8, P less than 0.01). Addition of casein (50% increase in energy intake) to a fixed chow ration raised NE turnover slightly, but not significantly, in heart (an average increase of 15% in six experiments). Thus, in distinction to SNS activation seen with dietary carbohydrate or fat, the SNS response to dietary protein is minimal in both heart and IBAT, indicating that the effect of increased energy intake on the SNS is dependent upon diet composition.

Adipose Tissue, Brown↗

Effect of protein ingestion on urinary dopamine excretion. Evidence for the functional importance of renal decarboxylation of circulating 3,4-dihydroxyphenylalanine in man.

Since dietary protein increases urinary dopamine (DA) excretion in animals, this study was undertaken to assess the role of DA production in the acute changes in renal function following protein ingestion in man. Excretion of DA, sodium, potassium, water, solute, and creatinine were measured in six normal men in 30-min intervals over 5 h after oral ingestion of protein and/or carbidopa, an inhibitor of DA formation from 3,4-dihydroxyphenylalanine (DOPA). Overall, protein increased urinary DA 50% (P = 0.031) while carbidopa reduced it 70% (P less than 0.0001), although suppression of DA excretion by carbidopa was not uniform over the 5 h of observation. Carbidopa doubled the level of DOPA in venous plasma and greatly magnified the DOPA response to protein. Inhibition of decarboxylase activity reduced excretion of sodium, potassium, solute and water after protein ingestion. These results indicate that extraneuronal DOPA decarboxylation in kidney contributes to acute protein-induced changes in renal function in man and suggest a general role for the decarboxylation of circulating DOPA in the expression of dopaminergic effects on the kidney in vivo.

Adult↗

Catecholamine modulation of rapid potassium shifts during exercise.

Plasma potassium rises during muscular exercise and falls rapidly when exercise is stopped. Since the sympathoadrenal system is stimulated with exertion and both alpha- and beta-adrenergic agonists affect internal potassium homeostasis, we studied the influence of catecholamines on potassium shifts during and after exercise. Six healthy subjects were given maximal exercise stress tests under three conditions: with no medication (control), during beta-blockade with propranolol, and during alpha-blockade with phentolamine. Compared with a peak rise in plasma potassium of 1.23 +/- 0.27 mmol per liter (mean +/- S.E.M.) during the control study, propranolol caused a rise of 1.89 +/- 0.35 (P less than 0.01) and a sustained elevation during recovery. Phentolamine diminished the rise of potassium (0.70 +/- 0.21 mmol per liter; P less than 0.01) and lowered the potassium level throughout recovery. These effects of catecholamines were independent of the venous pH, the plasma bicarbonate and serum glucose levels, and urinary potassium excretion, and they did not appear to be due to insulin. High norepinephrine and epinephrine levels confirmed the release of catecholamines capable of stimulating alpha- and beta-receptors. Exercise work did not differ among the groups. beta-Adrenergic receptors appear to moderate the acute hyperkalemia of exercise, whereas alpha-adrenergic receptors act to enhance hyperkalemia and may protect against hypokalemia when exertion ceases.

Adrenergic alpha-Antagonists↗

Increased sympathetic nervous system activity in rats fed a low-protein diet.

To examine the state of sympathetic nervous system (SNS) function in animals fed a protein-restricted diet, [3H] norepinephrine ([3H]-NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of rats fed synthetic diets of equal caloric density containing 22% protein (as casein) or 7% protein (the difference being made up by sucrose). Because dietary availability of tyrosine is a potential mediator of SNS responses to protein ingestion, a third diet (7% protein supplemented with tyrosine) was also tested. After 12 days dietary preparation [3H]-NE turnover was increased 35-70% in heart by 7% protein feeding and 93-103% in IBAT. When smaller animals were fed the synthetic diets for 4-5 wk, sympathetic stimulation in those given the protein-restricted formula was also apparent, although demonstration of this response was complicated by comparative problems due to the marked differences in body size between normal and protein-restricted groups. Addition of tyrosine (sufficient to normalize plasma and brain tyrosine levels) was without effect on the stimulation of NE turnover induced by the protein-deficient diet. Similarly, augmented urinary NE excretion observed in animals consuming the 7% protein diet was unaffected by supplemental tyrosine. Urinary dopamine excretion, however, was uniquely and strikingly elevated with restoration of dietary tyrosine to animals fed the low-protein diet. Thus isocaloric substitution of sucrose for casein in the diet activates the SNS in heart and IBAT, a response unrelated to limitation of dietary tyrosine.

Adipose Tissue, Brown↗

Counterregulatory responses to insulin-induced glucose reduction in the elderly.

The impact of age on counterregulatory responses to moderate reductions in blood glucose induced by a constant insulin infusion (20 mU/m2 X min) was studied in normal young (n = 7; aged 20-42 yr) and old (n = 7; aged 66-77 yr) nonobese subjects. Insulin was infused until the whole blood glucose level fell to or below 60 mg/dl. This required an infusion time of 39 +/- 3 (+/- SE) min in the young and 36 +/- 3 min in the old. Mean basal glucose [young, 88 +/- 2 (+/- SE); old, 88 +/- 2 mg/dl), minimum glucose (young, 51 +/- 2; old, 54 +/- 1 mg/dl), time to nadir (young, 48 +/- 3; old, 44 +/- 3), and time to recovery were similar in both groups. Maximal (young, 40.3 +/- 2.3; old, 42.1 +/- 3.3 microU/ml) insulin levels were also similar. Basal and maximal levels of glucagon, epinephrine, and GH were similar in the two groups. Although basal norepinephrine values were higher in the old subjects (young, 243 +/- 38; old, 364 +/- 23 pg/ml; P = 0.02), increments above basal during reduction in blood glucose were not affected by age. Basal cortisol values were similar (young, 13.7 +/- 1.4; old, 14.0 +/- 0.7 micrograms/dl), but maximum cortisol responses were slightly greater in the old subjects (young, 14.6 +/- 1.0; old, 17.7 +/- 0.9 micrograms/dl; P = 0.03). These studies indicate that hormonal responses and counterregulatory efficiency during modest reductions in blood glucose are preserved in healthy elderly subjects.

Adult↗

Chromogranin A.

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Adrenal Gland Neoplasms↗

Metabolic, endocrine, and reproductive changes of a woman channel swimmer.

We report the coordinated metabolic, hormonal, and reproductive data of a female channel swimmer during the pre-swim training period, immediately post-swim, and in the post-swim untrained state. Urine and blood samples collected at these times were assayed for diurnal urinary catecholamines, urinary C-peptide and 3-methylhistidine, total blood ketone bodies, glycerol, the reproductive hormones, adrenal androgens, and thyroid hormones. Subcutaneous fat was measured by ultrasonography. All of the metabolic and hormonal data post-swim except cortisol reflected the severe physiological stress. Urinary catecholamines returned to near-normal levels by 12 hours post-swim. The metabolic changes were associated with reproductive changes, including a shortened luteal phase, absence of ovulation, and increased LH secretion relative to FSH. The swimmer maintained high levels of body fat; she did not become amenorrheic. Metabolic and reproductive hormone levels returned to normal by 2 months post-swim.

Adipose Tissue↗