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Biomedical subjects

S Margolis

Publications and source records attributed to S Margolis.

At least 73 records · Page 4Linked to original sources
PubMed1981

Pulmonary injury caused by free fatty acid: evaluation of steroid and albumin therapy.

Intrapulmonary free fatty acid (FFA) release has been suggested as a pathogenetic mechanism in respiratory failure caused by acute pancreatitis and fat embolism. Utilizing the isolated perfused ventilated canine pulmonary lobe, we evaluated the effects of FFA infusion and its subsequent modification by albumin and steroid therapy. In control lobes perfused for a 4-hour period, there was minimal weight gain (11 gm), intrapulmonary shunting did not occur, and compliance remained within normal limits. When 1 ml of oleic acid was infused into the pulmonary artery lobe weight tripled (188 gm), intrapulmonary shunting (20%) developed, and compliance was significantly decreased compared to controls. When 30 gm of human salt-poor albumin was added to the perfusate immediately after FFA infusion, the lobe response was similar to that of untreated oleic acid lobes. In contrast, when 400 mg of methylprednisolone succinate was added to the perfusate immediately after FFA infusion, lobe weight gain was significantly reduced (94 gm) compared to oleic acid lobes, intrapulmonary shunting did not occur, and compliance was within normal limits. This study suggests that steroids may be of benefit in the treatment of respiratory insufficiency secondary to acute pancreatitis and fat embolism.

Airway Resistance↗
PubMed1980

Anophthalmia in an infant of parents using LSD.

We have described a unilateral anophthalmia in an infant with normal chromosome studies born to parents who took LSD before and during pregnancy. In view of the lack of any other fetal abnormalities in this child, known to be associated with LSD, we report this case to suggest that anophthalmia may be a new drug-related defect. A complete drug history of the parents should be taken in cases of congenital abnormalities to accumulates further data, which will point conclusively to the etiology of anophthalmia and possibly other congenital defects.

Abnormalities, Drug-Induced↗
PubMed1980

Respiratory failure in acute pancreatitis: the role of free fatty acids.

Hypertriglyceridemia has been noted in patients with acute pancreatitis and respiratory failure. Utilizing an isolated, perfused, canine pulmonary lobe, the effect of triglyceride infusion on pulmonary function was evaluated. When heparin was used to anticoagulate the perfusion circuit, the addition of triglyceride to the autologous blood perfusate resulted in massive weight gain (226 gm), intrapulmonary shunting (36%), and a marked drop in pulmonary compliance (congruent to 50%). Heparin activates lipoprotein lipase, and therefore some triglyceride in the perfusate was lipolyzed with a resultant increase in serum free fatty acids (FFAs) to 253 mumole/dl. When anticoagulation of the perfusion circuit was accomplished by defibrinogenation with Arvin, the addition of triglyceride to the autologous blood perfusate caused minimal weight gain (28 gm), no intrapulmonary shunting, and only a slight decrease in pulmonary compliance (22%). Arvin has no effect on lipoprotein lipase, and the FFA level in the perfusate remained normal (less than 70 mumole/dl). Thus it appears that FFA release secondary to the action of pulmonary lipoprotein lipase on blood triglyceride is the important pathogenic step in the induction of respiratory failure in this model.

Acute Disease↗
PubMed1979

A gold foil electrode: extending the horizons for clinical electroretinography.

A gold foil ERG electrode is described. The device is inexpensive and simple to fabricate. Since it is hooked over the lower lid and makes minimal touch contact with the inferior limbal area, it can be used in circumstances which require prolonged testing of retinal function or in eyes with corneal pathology. Because the optics of the eye are not compromised, it is possible, with the use of appropriate stimuli and response-averaging techniques, to record local EFGs from relatively small retinal areas.

Child↗
PubMed1979

Respiratory failure in acute pancreatitis: a possible role for triglycerides.

Respiratory failure is a frequent complication of acute pancreatitis. Two clinical studies of this association have demonstrated a high incidence of concomitant hypertriglyceridemia. Experimental studies were carried out using an ex vivo, isolated, perfused, ventilated, canine pulmonary lobe to evaluate the effects of triglyceride elevations on pulmonary mechanics and gas exchange. Control lobes perfused for a four hour period remained stable. When 5g and 10g of triglyceride were added to the perfusate, the lobes became grossly edematous and hemorrhagic. Intrapulmonary shunting developed (23 and 46%), weight gain occurred (130 and 189g), effective compliance decreased, and the pressure-volume deflation curves became abnormal. Free fatty acid (FFA) levels increased markedly during the perfusion periods. When small quantities of FFA were infused directly into the pulmonary artery, similar changes, but less severe, occurred. These studies demonstrate that triglyceride elevations are capable of adversely affecting pulmonary gas exchange and mechanics. Such changes probably occur secondary to FFA release. These data thus add support to the concept that the respiratory insufficiency that is seen in acute pancreatitis could be mediated through triglyceride elevations.

Acute Disease↗
PubMed1978

Release of phospholipase A and triglyceride lipase from rat liver.

A new, rapid, and sensitive assay for phospholipase A, utilizing commercially available [14C]phosphatidylethanolamine with 14C label in both palmitic acid moieties, was used to study phospholipase A release from perfused liver, hepatocytes, and intestinal cells from rats. Heparin triggered a prompt release of phospholipase A from perfused liver. Phospholipase A and triglyceride lipase were released from hepatocytes at a linear rate for 1 h and 30 min, respectively. Heparin (20 u/ml) doubled the release of phospholipase A and triglyceride lipase from hepatocytes. Colchicine (0.1 mM), but not puromycin (0.2 mM), inhibited basal and heparin-stimulated phospholipase A release by 40%. Since the amount of phospholipase A and triglyceride lipase released into the medium greatly exceeded intracellular activities, it is possible that secretion is coupled with intracellular conversion from inactive to active forms of the enzymes. Dibutyryl cyclic AMP (1 mM) inhibited phospholipase A (48%) and triglyceride lipase (82%) release from hepatocytes. Epinephrine, dexamethasone, and clofibrate inhibited release of triglyceride lipase but not phospholipase A. Phospholipase A activity of intestinal cells was greater than in hepatocytes, but neither heparin nor dibutyryl cyclic AMP affected phospholipase A release from intestinal cells. These results suggest that the liver is a major source of phospholipase A of postheparin plasma. The fact that dibutyryl cyclic AMP affects the release of these enzymes suggests an additional mechanism for hormonal regulation of lipid and lipoprotein metabolism.

Animals↗
PubMed1978

Alterations in human high-density lipoproteins, with or without increased plasma-cholesterol, induced by diets high in cholesterol.

High-density lipoproteins (d=1.095--1.21) (H.D.L.( were isolated from six healthy men and women who added 4 to 6 eggs per day to their diet for 4 weeks and from five individuals who gradually increased their egg consumption to 3 per day over an 18-week period. Pre-diet and post-diet H.D.L.-binding activities for the cell-surface receptors of fibroblasts were compared by determining the quantity of 125I-labelled low-density lipoprotein which was competitively displaced by H.D.L. in binding, internalisation, and degradation assays. Irrespective of whether plasmacholesterol changed during the course of the diet, the binding activity of the post-diet H.D.L. was enhanced 2.6-fold to 4-fold compared with pre-diet activity. Furthermore, the increased binding activity in the H.D.L. could be accounted for by a minor, but potent, H.D.L. subfraction precipitated by heparin/manganese. Both binding activity and heparin precipitability appeared to correlate with an increase in arginine-rich apoprotein (apo-E) in the active H.D.L. subfraction. These data show that consumption of large numbers of eggs, whether or not it leads to an increase in plasma-cholesterol, does alter the properties of human H.D.L.

Adult↗
PubMed1978

Cyclic AMP-sensitive activation of hepatic sterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A reductase.

We previously showed that preincubation of a 10,000 g supernatant (S(10)) from rat liver for 20 min at 37 degrees C dramatically increased the subsequent incorporation of [(14)C]acetate into sterols. No activation was seen with [(14)C]mevalonate as substrate. In the present studies we have examined the effect of preincubation on HMG CoA reductase. When microsomes were isolated from S(10) by calcium precipitation, preincubation of S(10) increased the specific activity of HMG CoA reductase threefold. No activation of HMG CoA reductase was observed in microsomes isolated by ultracentrifugation. Activation was cyclic AMP-sensitive. When cyclic AMP (0.001-1.0 mM) and MgATP (1 mM) were present during the preincubation period, there was little or no activation of HMG CoA reductase activity or of sterol synthesis from acetate. MgATP alone did not prevent activation. Neither cyclic AMP nor MgATP was inhibitory when present only during the assay of sterol synthesis. We propose that the in vitro activation represents the reversal of a physiologic cyclic AMP-mediated mechanism for the control of hepatic HMG CoA reductase. That a phosphoprotein phosphatase may catalyze the activation was supported by the observation that sodium fluoride, an inhibitor of phosphoprotein phosphatases, inhibited the activation. These results suggest that hormone-induced changes in the cellular level of cyclic AMP may regulate the activity of HMG CoA reductase and the rate of hepatic cholesterol synthesis.

Adenosine Triphosphate↗
PubMed1978

Lipid synthesis in isolated intestinal cells.

Since the small intestine contributes significantly to serum cholesterol and very low density lipoprotein levels, acute regulation of lipid synthesis was investigated in isolated rat intestinal cells incubated in Krebs-Ringer bicarbonate buffer with 5 mM glucose and [14c]acetate or 3H2O. Incorporation of [14c]acetate into cellular lipids was 6- to 8-fold greater in crypt than in villus cells. In both cell types the distribution of 14C among the various lipid classes was as follows: 52.5% in triglycerides, diglycerides, and monoglycerides; 22.3% in cholesterol; 8.3% in cholesteryl esters; 1.9% in fatty acids; and 15.0% in phospholidpids. In contrast, the medium lipids contained significantly higher amounts of tri-, di- and monoglycerides (61.1%) and lower amounts of cholesteryl esters (2.3%) and phospholipids (11.9%). After saponification, 2/3 of the recovered 3H2O was in fatty acids and 1/3 in cholesterol. Ethanol (10 mM) tripled 3H2O incorporation into cellular lipids but had no effect on [14c]acetate incorporation. Epinephrine and norepinephrine (10 micron), glucagon (10 micron), dibutyryl cyclic AMP (1MM), dexamethasone (1 mM and 1 micron), and cholera toxin (1 microgram/ml) did not affect [14c]acetate incorporation. We concluded that ehtanol stimulates intestinal lipid synthesis; however, in sharp contrast to their inhibition of lipid synthesis in hepatocytes and adipocytes, catecholamines, glucagon, and dibutyryl cyclic AMP do not inhibit lipid synthesis in intestinal cells.

Acetates↗
PubMed1978

[14C]palmitate uptake in isolated rat liver mitochondria: effects of fasting, diabetes mellitus, and inhibitors of carnitine acyltransferase.

The rapid association of Na-[16-(14)C]palmitate with isolated rat liver mitochondria was measured by an oil separation method. This association was time and temperature-dependent and was absolutely dependent on the presence of exogenous ATP and CoASH and partially dependent on exogenous carnitine. Carnitine dependence was enhanced at lower concentrations of [(14)C]palmitate. At 6.5 micro M [(14)C]palmitate (molar ratio of palmitate to albumin equal to 0.54), the rate of association was linear for 20 sec and was increased more than 100% in the presence of carnitine. Carnitine-dependent association was inhibited by 2-bromopalmitate, an inhibitor of carnitine acyltransferase I, but not by (+)-octanoylcarnitine, a presumed inhibitor of carnitine acyltransferase II. The association of [(14)C]palmitate with mitochondria was enhanced from 190 to 330% in mitochondria isolated from fasted animals and from 160 to 230% in mitochondria isolated from diabetic, ketotic animals as compared to control animals. The enhanced association with mitochondria from fasted animals was inhibited by 2-bromopalmitate. These studies demonstrate a method of evaluating fatty acid association with mitochondria which, because of its dependence on carnitine and carnitine acyltransferase I activity, most likely represents true uptake into mitochondria. Furthermore, these studies indicate that the carnitine-dependent uptake of fatty acids into mitochondria is enhanced in the two ketotic states evaluated and that the carnitine acyltransferase system may be a regulatory site in ketone body production.

Acyltransferases↗
PubMed1977

Ocular pathology of the congenital varicella syndrome.

Congenital anomalies are rare in infancy following maternal varicella during pregnancy. Abnormalities do occur, however, and form a specific pattern including cicatrical skin lesions, atrophic limb, low birth weight, and chorioretinal scarring. We saw an infant who had immunologic evidence of varicella-zoster virus contact in utero, microphthalmos of one eye, and chorioretinal scarring of the fellow eye. Ophthalmologists confronted with such ocular anomalies in children should inquire about the possibility of maternal varicella during pregnancy. Conversely, infants born of mothers known to have had varicella during pregnancy should be examined for fundus abnormalities.

Chickenpox↗