Wave optics simulation of atmospheric turbulence and reflective speckle effects in CO2 lidar.

Laser speckle can influence lidar measurements from a diffuse hard target. Atmospheric optical turbulence will also affect the lidar return signal. We present a numerical simulation that models the propagation of a lidar beam and accounts for both reflective speckle and atmospheric turbulence effects. Our simulation is based on implementing a Huygens-Fresnel approximation to laser propagation. A series of phase screens, with the appropriate atmospheric statistical characteristics, are used to simulate the effect of atmospheric turbulence. A single random phase screen is used to simulate scattering of the entire beam from a rough surface. We compare the output of our numerical model with separate CO(2) lidar measurements of atmospheric turbulence and reflective speckle. We also compare the output of our model with separate analytical predictions for atmospheric turbulence and reflective speckle. Good agreement was found between the model and the experimental data. Good agreement was also found with analytical predictions. Finally, we present results of a simulation of the combined effects on a finite-aperture lidar system that are qualitatively consistent with previous experimental observations of increasing rms noise with increasing turbulence level.

ACTH-producing pituitary tumors.

Adrenocorticotropin (ACTH)-producing tumors of the pituitary gland usually, though not in all cases, initially show evidence of excess cortisol. The pathogenesis of these tumors--monoclonal versus polyclonal and intermediate lobe versus anterior lobe--continues to prompt debate. Important advances in the diagnostic methods (such as petrosal sinus sampling for ACTH and other hormones) are described. While the mainstay of therapy is still selective adenomectomy via the transsphenoidal approach, total hypophysectomy may occasionally be indicated.

Dexamethasone increases neutral sphingomyelinase activity and sphingosine levels in 3T3-L1 fibroblasts.

The activity of neutral sphingomyelinase (EC 3.1.4.12) in a plasma membrane enriched fraction was found to be increased in dexamethasone treated cells. The elevation of sphingomyelinase activity was blocked by cycloheximide indicating that protein synthesis was required for the steroid action. Ceramidase (EC3.5.1.23) activity was unaffected by the dexamethasone treatment. Levels of sphingosine in 3T3-L1 Cells were also increased after treatment with 10(-7) M dexamethasone for 2 and 4 hours.

Inhibitory action of sphingosine, sphinganine and dexamethasone on glucose uptake: studies with hydrogen peroxide and phorbol ester.

The mechanism of the inhibitory action of glucocorticoids on glucose uptake is incompletely understood. Treatment with corticosteroids of cells in which glucose uptake is stimulated at insulin postbinding and postreceptor sites may clarify the site of the steroid inhibitory action. Hydrogen peroxide, which has been shown to stimulate the insulin receptor tyrosine kinase, and phorbol myristate acetate (PMA) which stimulates protein kinase C were, therefore, used as stimulators of glucose transport in this study. These studies demonstrate that dexamethasone and the sphingoid bases, sphinganine and sphingosine, inhibit glucose uptake that has been stimulated at either the receptor kinase or protein kinase C level in both 3T3-L1 and 3T3-C2 cells. These data confirm glucocorticoid inhibitory action at a post binding level and support the suggestion that some corticosteroid inhibitory effects may be mediated by an action on sphingolipid metabolism.

Alcohol-induced pseudo-Cushing's disease: a study of prevalence with review of the literature.

Alcohol-induced pseudo-Cushing's syndrome has been described in numerous case reports, yet the patients have been thoroughly evaluated in only a few cases and the prevalence of hypercortisolism in the alcoholic population is not known. We studied a group of 56 alcoholic men on admission to a detoxification ward using the overnight 1 mg dexamethasone suppression test as a screening test. Most (82%) had normal cortisol suppression, and of those who did not (18%), three of four who could be retested became normal within four days. A smaller group of 14 patients was evaluated with measurement of 24-hour urinary free cortisol, baseline plasma ACTH and serum cortisol measurements, and measurement of ACTH and cortisol after dexamethasone. One patient with sustained abnormal suppression of serum cortisol by dexamethasone (up to 18 days) also demonstrated a striking lack of suppression of plasma ACTH by dexamethasone, compared to the other alcoholics studied. The data obtained on this patient, as well as information obtained from published case reports, are consistent with the concept that alcohol-induced pseudo-Cushing's syndrome is a centrally mediated defect that occurs uncommonly in alcoholics.

Corticosteroids stimulate an increase in phospholipase A2 inhibitor in human serum.

A corticosteroid induced increase in a circulating inhibitor of serum phospholipase A2 activity is described. Inhibitor activity was found to be normally present in serum in agreement with the findings of other workers, and this activity was significantly increased by either acute or chronic administration of corticosteroids. The possible relation of this inhibitor to the known inhibitory effects of lipocortin and sphingomyelin on phospholipase A2 activity is briefly discussed.

Dexamethasone and sphingolipids inhibit concanavalin A stimulated glucose uptake in 3T3-L1 fibroblasts.

Studies were carried out in 3T3-L1 fibroblasts to determine the effect of sphingolipids and corticosteroids on concanavalin A stimulated glucose uptake. Sphinganine (40 microM) and sphingosine (40 AND 100 microM) significantly inhibited concanavalin A stimulated glucose uptake (P less than 0.025 & less than 0.005). Prior incubation with 10(-7) M dexamethasone also significantly inhibited concanavalin A stimulated glucose uptake (P less than 0.005). The known effects of corticosteroids on sphingolipid synthesis, degradation, and tissue levels, suggest inhibition by corticosteroids of glucose uptake may be through effects of the steroid on sphingolipid metabolism.

Dexamethasone inhibition of cholesterol-stimulated glucose transport in 3T3-L1 cells.

This study investigates the effects of dexamethasone on cholesterol-stimulated glucose uptake in confluent 3T3-L1 fibroblasts. Dexamethasone pretreatment blocked both insulin-stimulated glucose transport, and the increase produced by exogenous free cholesterol. The dexamethasone effect was inhibited in both cases by cycloheximide. Concentrations of cholesterol which increased glucose transport failed to produce a significant increase in measurable free cholesterol content in the plasma membrane.

Dexamethasone inhibition of hydrogen peroxide-stimulated glucose transport.

Although an action of corticosteroids to inhibit glucose transport is well known, the mechanism by which this is brought about has been unclear. Some evidence has suggested an action on insulin receptors, but a postbinding or postreceptor effect has also been reported. As hydrogen peroxide acts at a postbinding site to stimulate glucose transport, studies were carried out in 3T3-L1 fibroblasts to determine whether corticosteroids would inhibit hydrogen peroxide-induced glucose transport. In this cell type, both insulin and hydrogen peroxide produced a marked increase in glucose transport after a 30-min incubation. The increase produced by hydrogen peroxide, as well as insulin, was inhibited by previous incubation of the cells with dexamethasone. These findings give further support to the conclusion that dexamethasone has effects on glucose transport at a postbinding site. As changes in membrane lipids influence the movement and/or activity of glucose transporters, and dexamethasone alters membrane lipids, dexamethasone-induced changes in the lipids of the plasma membrane may be important in the mediation of the steroid effect upon glucose transport.

Sodium excretion and atrial natriuretic peptide levels during mineralocorticoid administration. A mechanism for the escape from hyperaldosteronism.

Urinary sodium excretion initially decreases when mineralocorticoid levels are increased, but if high plasma levels of hormone are maintained, sodium excretion rises to again equal sodium intake. To ascertain if atrial natriuretic peptide (ANP) plays a role in reestablishing sodium balance during mineralocorticoid ingestion, 0.3 to 0.5 mg per day of fludrocortisone were administered for 18 days to four healthy male subjects. The average daily intake of sodium was regulated at 180 +/- 2 meq. ANP levels rose from a mean of 91.7 +/- 13.0 pg/ml during the control week to 179.7 +/- 39.2 pg/ml during the final week on fludrocortisone (p less than 0.05). Urinary sodium excretion fell 27% immediately after fludrocortisone administration was initiated but returned to baseline levels in an average of 5 days. Levels of ANP, normalized for each subject to the mean of his control week values, correlated with the amount of sodium excreted in the subsequent 24 hours (p less than 0.05). Simultaneous with the rise in ANP values, levels of plasma renin activity (PRA) and aldosterone decreased. ANP concentrations throughout the study were inversely correlated with PRA and aldosterone levels (p less than 0.001 for both correlations). Values of serum osmolality and plasma arginine vasopressin did not change significantly during the study. The results obtained demonstrate that increased secretion of ANP is associated with escape from the sodium retaining effect of chronically high mineralocorticoid levels in man and suggest that ANP plays a prominent role in the mechanism of this escape.

Sphingolipids inhibit insulin and phorbol ester stimulated uptake of 2-deoxyglucose.

Studies are presented demonstrating inhibition of both insulin and phorbol myristate acetate stimulated uptake of 2-deoxyglucose uptake by 3T3-L1 fibroblasts. Greatest inhibition of uptake was seen with sphinganine while sphingosine was also potent in this regard. Ceramide inhibited phorbol myristate acetate but not insulin stimulation of uptake. It is suggested that sphingolipid inhibition of glucose transport relates to the previously demonstrated effect of corticosteroids to increase membrane sphingomyelin and inhibit glucose transport.

Intra-arterial monitoring during cardiopulmonary resuscitation.

Because arterial cannulation assists in management of critically ill patients (pts), we assessed the utility of extending intra-arterial monitoring to hospitalized patients suffering in-hospital cardiopulmonary arrest outside of intensive care wards. A totally self-contained, readily portable system for rapid insertion of emergency intra-arterial lines was evaluated in 16 pts from 53 to 89 years old (mean = 66.5 years) undergoing cardiopulmonary resuscitation. Cannulation was successful in 14 pts (88% success rate). In 8 of 14 pts, cannulation was achieved rapidly and efficiently, whereas in six it was slightly delayed, once due to technical problems and five times due to difficulty cannulating the vessel. In addition to providing continuous pressure monitoring and ready access to arterial blood samples, direct feedback from the intra-arterial pressure waveform frequently led to improved compression technique by the resuscitator performing external cardiac massage. We conclude that under selected circumstances emergency intra-arterial monitoring has a potentially important adjuvant role during cardiopulmonary resuscitation.

Dexamethasone increases the synthesis of sphingomyelin in 3T3-L1 cell membranes.

An acute increase in the sphingomyelin content of a plasma membrane-enriched fraction of 3T3-L1 cells was produced by incubation of the cells with 0.1 microM dexamethasone for 4 hr. Dexamethasone also stimulated the activity of the pathway of sphingomyelin synthesis by utilizing the phosphorylcholine of phosphatidylcholine as a donor to ceramide to synthesize the phospholipid (phosphatidylcholine:ceramide cholinephosphotransferase). Dexamethasone-stimulated increase in the utilization of 14C-labeled choline of phosphatidylcholine for the synthesis of sphingomyelin was inhibited by the addition of cycloheximide to the incubation. Therefore, it appears that corticosteroid stimulation of new protein synthesis was required to produce the effect. An increase in the enzymatic pathway by 83% and of the sphingomyelin content of the plasma membrane-enriched fraction by 50% after incubation with dexamethasone for 4 hr demonstrates the rapidity with which the hormone can produce considerable remodeling of the membrane. The increase in the synthetic pathway in the plasma membrane-enriched fraction was sufficient to account for the measured increase in sphingomyelin. It appears likely that the large increase in membrane sphingomyelin could contribute significantly to the many demonstrated effects of corticosteroids upon membrane processes, including transport, receptors, and enzymatic activity.

Adrenalectomy decreases the sphingomyelin and cholesterol content of fat cell ghosts.

Adrenalectomy produces a significant fall in the sphingomyelin and cholesterol content of ghosts isolated from rat epididymal fat cells. Previous studies from this laboratory have demonstrated an effect of dexamethasone in vitro to increase the sphingomyelin content of fat cell ghosts obtained from adrenalectomized animals. The present study demonstrates that adrenalectomy influences the membrane lipid content. Dexamethasone, in vitro, was found to increase the sphingomyelin of epididymal fat cell ghosts isolated from intact animals, as it previously had been shown to affect epididymal fat cell ghosts obtained from adrenalectomized animals. Incubation with dexamethasone for 3 h had no effect on the cholesterol content of the ghosts. Adrenalectomy, on the other hand, resulted in a significant decrease in the cholesterol content of the fat cell ghosts.

Dexamethasone-induced change in the sphingomyelin content of human polymorphonuclear leukocytes in vitro.

Human polymorphonuclear leukocytes were incubated with 8 x 10(-9) M dexamethasone for 2 h. A significant increase in the sphingomyelin content of the cells was found when 8 x 10(-8) M dexamethasone was used, with lesser changes being noted when the concentration was increased or decreased from this level. The increase in the phospholipid was blocked by the addition of cycloheximide to the incubation. Concurrent with the increase in sphingomyelin, an increase in sphingomyelinase was demonstrated. This increased enzymatic activity may have occurred secondary to the increase in substrate or may be involved in the reverse reaction, whereby phosphorylcholine and ceramide combine to form sphingomyelin. Other studies have demonstrated an effect of corticosteroids to suppress the production of superoxide anion and the importance of a membrane oxidase in the production of the anion. An action of dexamethasone to both suppress superoxide anion production and increase sphingomyelin content suggests a possible effect of the lipid changes upon the oxidase responsible for the production of the anion.

Corticosteroid-induced lipid changes in rat liver microsomes.

An influence of corticosteroids on the phospholipid composition of several tissues has been demonstrated previously. Increases in the activity of rat liver microsomal cytochrome c reductase and aryl hydrocarbon hydroxylase after corticoid administration were also demonstrated. The phospholipid composition of liver microsomes is now reported to be altered by similar corticosteroid treatment. Phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin levels in rat liver microsomes were decreased significantly after in vivo cortisol administration. The levels of palmitic, stearic, oleic, linoleic, and arachidonic acids in phosphatidylcholine and of palmitic acid in phosphatidylserine-phosphatidylinositol were also affected. Cholesterol was increased after adrenalectomy and decreased to control levels after the administration of cortisol. Some of the microsomal enzymes which are affected by corticosteroids or adrenalectomy are known to require phospholipids for full activity. The alteration of enzyme activities and membrane phospholipid composition by similar dosage schedules of corticosteroids suggests a possible relation between the two effects. By affecting the lipid composition of the membranes, corticosteroids may regulate or modulate the activity of the lipid-requiring enzyme systems.

Insulin induced alterations of acyl groups of the cerebroside fraction isolated from fat cell ghosts.

Rat epididymal fat cells were isolated and incubated with 25 microunits insulin/ml for 15 minutes. Insulin induced a significant shift in the saturated/unsaturated fatty acid ratio of the cerebroside fraction isolated from fat cell ghosts. This change was due to a decrease of saturated fatty acids and an increase of unsaturated fatty acids which were hydrolyzed from the isolated lipids. There were no significant changes in the amount of phospholipids isolated from the fat cell ghosts after this period of incubation with insulin or of fatty acids associated with them. Isolated adipocytes were also incubated with 8 x 10(-8) M dexamethasone for 2 1/2 hours. Insulin (25 microunits/ml) was then added, and the incubation continued for 15 minutes. Dexamethasone treated cells did not show a statistically significant insulin stimulated decrease in the saturated/unsaturated fatty acid ratio. These studies demonstrate an insulin induced change in membrane lipids which appeared to be partially blocked by previous exposure to dexamethasone.