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Biomedical subjects

S S Solomon

Publications and source records attributed to S S Solomon.

At least 91 records · Page 5Linked to original sources
PubMed1978

Urinary and plasma cyclic AMP levels during short term starvation in obese man: response to glucagon stimulation.

Glucagon is known to elevate the intracellular concentration of cyclic AMP in the hepatocyte. The increase in intracellular cyclic AMP is reflected by an increase in the plasma concentration of the nucleotide. Intravenous glucagon stimulation was performed on six obese non-diabetic human subjects before and after a three day fast. All patients responded to starvation by a lowering of plasma immunoreactive insulin and blood glucose. Whereas the plasma immunoreactive glucagon concentration increased over the three day period, the plasma and urinary cyclic AMP did not significantly change. Intravenous glucagon promoted qualitatively similar increases in the blood glucose and plasma concentrations of insulin and cyclic AMP before and after three days starvation.

Adult↗
PubMed1977

Corticosteroid-responsive skeletal muscle disease associated with partial carnitine deficiency: studies of liver and metabolic alterations.

A patient with progressive skeletal muscle weakness had lipid-containing vacuoles in type I muscle fibers and partial carnitine deficiency of skeletal muscle. Results of certain liver function tests were abnormal, marked morphologic abnormalities of liver were detected, and a reduced cyclic adenosine 3',5'-monophosphate response to glucagon was present. After the oral administration of prednisone the patient exhibited gradual but striking clinical improvement, skeletal muscle fiber vacuoles could no longer be demonstrated, and the glucagon-provoked cyclic AMP response reverted to normal, but liver abnormalities persisted. At the same time utilization by skeletal muscle of long-chain fatty acids, pyruvate and beta-hydroxybutyrate was depressed. It is possible that the involvement of skeletal muscles was due to an inability of carnitine to attach to or to penetrate the sarcolemmal membrane. Some of the derangement, perhaps related to liver malfunction, was apparently corrected by the oral administration of prednisone although skeletal muscle metabolism remained impaired.

Biopsy↗
PubMed1977

Perifusion of isolated rat adipose cells. Modulation of lipolysis by adenosine.

Incubation of isolated rat epididymal fat cells is associated with the accumulation of adenosine in the incubation medium. To more clearly define the effect of adenosine on lipolysis, isolated rat epididymal adipocytes were studied with the perifusion system. Various combinations of epinephrine, adenosine, and adenosine deaminase were perifused through the adipocytes. Exogenous adenosine, 0.001-10.0 muM, had no discernible influence upon unstimulated lipolysis; but exogenous adenosine inhibited epinephrine-sensitive lipolysis in a concentration-dependent manner. Cells perifused with 0.3 muM epinephrine plus 0.001 muM adenosine did not show any impairment of the lipolytic response to 0.3 muM epinephrine alone. Adenosine, 0.01 muM, inhibited the response to epinephrine by 50%; response to 0.3 muM epinephrine plus 0.1 muM adenosine was similar to the basal rate. Perifusion with adenosine deaminase significantly increased basal lipolysis to 30% of the epinephrine response. Adenosine deaminase and epinephrine were synergistic in stimulating lipolysis to 180% of the response to epinephrine alone. Isolated fat cells were incubated for 30 min, and the cell-free used medium was perifused through fresh fat cells. Epinephrine in used medium was less effective in promoting lipolysis than epinephrine in fresh buffer. High-pressure liquid chromatography identified adenosine in the used medium. Bovine serum albumin possessed adenosine deaminase activity but accounted for negligible conversion of adenosine to inosine. Adenosine is shown to have a modulating effect upon basal and hormone-stimulated lipolysis in the perifusion system. Sufficient endogenous adenosine (<0.01 muM) is present to maximally affect basal lipolysis. Hormone-stimulated lipolysis, although inhibited somewhat by endogenous adenosine, requires the addition of exogenous adenosine for complete inhibition.

Adenosine↗
PubMed1977

Cyclic nucleotide phosphodiesterase. Insulin activation detected in adipose tissue by gel electrophoresis.

In rat adipose tissue, insulin (100 muU./ml.) increases the activity of cyclic AMP (but not cyclic GMP) phosphodiesterase (PDE). Radioisotopic assay, autoradiography, and histochemical stains demonstrated that cyclic nucleotide PDE activity is associated with multiple bands of protein separable by polyacrylamide gel electrophoresis. The insulin activation of cyclic AMP PDE, however, was limited to a single band corresponding to the "low" Km enzyme specific for cyclic AMP; insulin had no effect on the "high" Km enzyme or on PDE bands with activity directed toward cyclic GMP. These data support the concept that insulin may modulate the activity of at least one of the cyclic AMP phosphodiesterases.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

Inhibition of insulin degradation by nonsuppressible insulin-like activity.

Nonsuppressible insulin-like activity, provided by three sources, was evaluated for its effect on the proteolytic degradation of insulin utilizing insulin protease obtained from rat liver homogenate as well as liver cell membranes. All three preparations of nonsuppressible insulin-like activity were found to be competitive inhibitors of insulin degradation. In addition human plasma was fractionated yielding an acetone precipitate which was found to have nonsuppressible insulin-like activity and to be a competitive inhibitor of insulin protease.

Animals↗
PubMed1976

Effect of antecedent hormone administration on lipolysis in the perifused isolated fat cell.

Development of a perifusion system utilizing isolated fat cells (IFC) has converted the static incubation system into one capable of measuring dynamic changes in adipose tissue metabolism. Using this new system, we have studied the initiation by epinephrine and inhibition by insulin of lipolysis in IFC. Perifusion with "low" (10 muU per milliliter) or "high" (50 muU per milliliter) insulin was performed (1) prior to, (2) simultaneous with, and (3) after infusion of epinephrine. Exposure to low insulin prior to or simultaneously with epinephrine produced a greater amount of antilipolysis than the addition of insulin to cells already stimulated by epinephrine. Similar results were obtained with proinsulin. Insulin (50 muU per milliliter) when given prior to or simultaneously with 0.035 mug per milliliter of epinephrine bitartrate completely blocked lipolysis but the antilipolytic effect of insulin could be overcome by increasing the concentration of epinephrine bitartrate. Insulin (50 muU per milliliter) also decreased the sensitivity of the fat cells to subsequent doses of epinephrine bitartrate even after apparent removal of all immunoreactive insulin by continuing buffer infusion. After exposure to 50 muU per milliliter of insulin, followed by buffer alone, the cells failed to release glycerol in response to 0.035 mug per milliliter of epinephrine bitartrate but did respond to 3.5 mug per milliliter of epinephrine bitartrate. Thus, the sequence of hormonal administration as well as hormonal concentration greatly altered the responsiveness of the adipose tissue to both lipolytic and antilipolytic stimuli.

Adipose Tissue↗
PubMed1975

Human islet cell adenoma: metabolic analysis of the patient and of tumor cells in monolayer culture.

Cell cultures were established from a benign pancreatic islet adenoma. Over 200 muU/culture/day immunoreactive insulin were found in culture media. Cultures with medium 199 released insulin for about 2 months; those with medium F12K were maintained for over 7 months, and have been successfully subcultured. Increasing culture medium glucose to 326 mg per 100 ml, alone or with leucine (10 mM) or theophylline (2 mM), failed to increase insulin release above baseline. Studies in the patient prior to surgery using oral glucose, leucine, beef meal, intravenous tolbutamide, and glucagon failed to increase plasma insulin and thus were consistent with cell culture responses. Extracts of tumor tissue contained 23% proinsulin-like material; high insulin containing samples of culture medium had 5% proinsulin and less than 40 pg glucagon/ml. Aldehyde fuchsin positive granulation was sparse in both cultured cells and the original tumor. These studies demonstrate long term viability, in monolayer culture, of cells derived from this islet cell adenoma, with retention of secretory characteristics consistent with data obtained prior to removal of the adenoma from the patient.

Adenoma, Islet Cell↗
PubMed1975

Studies of the biological activity of insulin, cyclic nucleotides and concanavalin A in the isolated fat cell.

The insulin or proinsulin response of the isolated rat adipocyte was destroyed by preincubation with trypsin. After 120 minutes, biological responsiveness partially regenerated. Similarly, the biological responsiveness of the isolated fat cell to non-suppressible insulin-like activity (NSILA) was only partially destroyed following trypsin digestion, and did not regenerate. In contrast to the above, cyclic AMP or dibutyryl cyclic AMP effects were unaltered by trypsin or neuraminidase digestion.

Adipose Tissue↗
PubMed1975

Cyclic 3',5'-nucleotide phosphodiesterase in rat skin. II. Biochemical characterization.

The biochemical characteristics of cyclic 3',5'-nucleotide phosphodiesterase were studied in homogenates of male albino rat skin using preparations which were predominantly epidermal. Enzymatic activity was detected in both the particulate and soluble fractions of these skin homogenates. Two kinetically distinct phosphodiesterase (PDE) activities were detected in the soluble fraction (100,000 times g supernatant). This 100,000 times g supernatant contains at least two distinct protein bands that hydrolyze cyclic AMP as demonstrated by gel electrophoresis. Divalent cations (Mg-++ or Mn-++) and 2-mercaptoethanol were required for maximal enzymatic activity. Epinephrine, dibutyryl cyclic AMP, and methylxanthines inhibited while imidazole and histamine phosphate stimulated the cyclic AMP phosphodiesterase activity at high and low cyclic AMP concentrations. Cyclic GMP competitively inhibited hydrolysis of low, but not high, concentrations of cyclic AMP. Hydrocortisone phosphate in pharmacologic concentrations blocked PDE denaturation by heat. These studies indicate that there are complex interrelationships between cyclic nucleotides and PDE in rat skin.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1975

Bronchodilator drug efficacy via cyclic AMP.

Cyclic adenosine 3', 5'-monophosphosphate (cyclic AMP) as measured by radioimmunoassay is found in diced rat lung in an amount approximating one picomole per milligram of wet weight lung tissue. Incubation of rat lung with adrenaline, a beta adrenergic agent, produced a rapid increase in cyclic AMP, 100% increase at 15 seconds and 340% at 2 minutes. Isoprenaline was more stimulatory than adrenaline; noradrenaline was less stimulatory, and ephedrine produced a negligible effect. The methylxanthines, caffeine and theophylline, produced an increase in cyclic AMP concentration. Of these, caffeine was more potent, and synergism with adrenaline was demonstrated. The beta adrenergic blocking agent, propranolol, completely inhibited the expected rise in cyclic AMP secondary to adrenaline stimulation. In contrast, the alpha blocker, phentolamine, produced no effect. This animal model offers evidence that adrenergic agents and methylxanthines act to increase cyclic AMP in lung tissue. It is likely that many of the beneficial effects of these drugs in pulmonary patients occur through similar changes and modulation of the cyclic AMP system.

Animals↗
PubMed1975

Effect of insulin and lipolytic hormones on cyclic AMP phosphodieterase activity in normal and diabetic rat adipose tissue.

Insulin has been shown to lower cyclic AMP (cAMP) levels in hormonally sensitive tissue. The mechanism by which this lowering occurs has not yet been fully defined. We studied the effects of insulin on rat adipose tissue cyclic nucleotide phosphodiestrase (PDE) in an incubation system. The adipose tissue used was from both normal animals and animals rendered diabetic by intravenous injections of streptozotocin. Rat epididymal fat pads were incubated in a Krebs-Ringer bicarbonate-4% albumin system with O, 100, 1,000 or 10,000 PU/ml insulin (INS); epinephrine (EPI) or glucagon (GLU) at several different concentrations. After 15 min of incubation, each tissue was homogenized, centrifugated, and the supernatant assayed for cAMP PDE activity using the breakdown of (3-H)cAMP. The data was used to characterize cAMP PDE into apparent high and low K-m PDE components. In the normal animals, INS increased Vmax of the low Km PDE components; 100 pU/ml INS, 30%, 1000 p1/ML INS, 40; and 10,000 pU/ml INS, 20%. In contrast, streptoxotocin diabetes lowered this Vmax by 30%. In the diabetic animals, INS also increased Vmax by 30%. In the diabetic animals, INS also increased Vmax of the low Km PDE component; 100 pU/ml INS, 30%; 1000 pU/ml INS, 50% and 10,000 pU/ml INS, 100%. Epinephrine at 1, 10, and 100 pg/ml stimulated low Km cAMP PDE activity by 67%, 73% and 44% respectively. The stimulatory effect of EPI on both the low and high Km cAMP PDE activity was neutralized by propranolol or adenosine. In comparison to EPI, GLU at very low concentrations, 10-9M, stimulated low Km cAMP PDE. These studies suggest that some of the biologic actions of insulin, an antilipolytic substance, are mediated through activation of low Km PDE. Furthermore, this enzymatic activity is lower in experimental diabetes. The stimulation of low Km PDE by lipolytic hormones may reflect a long-range protective action of these agents.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1975

Pseudopseudohypoparathyroidism with fibrous dysplasia.

Pseudopseudohypoparathyroidism and pseudohypoparathyroidism have been thought to represent variants of the same disease process, Albright hereditary osteodystrophy. A 31-year-old woman with the characteristic features of pseudopseudohypoparathyroidism, such as shortened metacarpals and metatarsals, round facies, and normal serum calcium values, was studied. Underdeveloped metacarpal and metatarsal heads produced an important diagnostic sign, Albright dimpling sign, which dermatologists can use to make the correct diagnosis. The presence of this sign, together with roentgenographic evidence, will usually exclude other diagnostic possibilities. Our patient had a normal response to parathyroid hormone infusion, including increased urinary adenosine 3',5' cyclic monophosphate excretion. Radiological, light microscopic, and electron microscopic studies of the mandible showed fibrous dysplasia, a disease commonly reported to be present with hyperparathyroidism, but, to our knowledge, never before reported in association with any variant of hypoparathyroidism.

Adult↗