Showing papers by "Vanderbilt University published in 1970"

Plasma propranolol levels in adults with observations in four children.

Abstract: Plasma levels of the f3‐adrenergic‐blocking drug, propranolol, have been measured fluorometrically in man after oral and intravenous administration. Following oral administration, peak plasma levels in 5 sub/ects varied sevenfold, while, after intravenous administration, levels in the same sub/ects varied only twofold, indicating considerable variability among individuals in the amount of drug reaching the systemiC circulation after oral administration. However, plasma levels were relatively constant in sub/ects given repeated, single doses. The plasma half‐life of the drug was 2.3 hours after intravenous administration. A plasma half‐life of 3.2 hours was found after oral administration; its greater duration was attributed to continuing absorption. After intravenous administration, the rate of decline of the levels of propranolol in the plasma was biexponential, and the volume of distribution during the late phase of elimination was found to be about 150 liters, indicating concentration of the drug in the tissues. The drug was administered orally to 4 children at dose levels calculated on the basis of body weight and on the basis of body surface area. It was found that a dose intermediate to the two tested would be required to obtain plasma levels approximating the average level in adults given an equivalent dose.

Effects of xanthine derivatives on lipolysis and on adenosine 3',5'-monophosphate phosphodiesterase activity.

Abstract: The lipolytic potencies of 64 compounds, mostly xanthine derivatives, were determined in epididymal fat cells. Nine of the compounds of widely varying lipolytic potency were examined as inhibitors of cyclic AMP phosphodiesterase activity. Substantial lipolytic effects were seen at concentrations producing less than 20% inhibition of phosphodiesterase activity. The most active compound, 1-methyl-3-isobutylxanthine, was about 15 times more potent than theophylline in both systems. Over a 20-fold range of concentrations, there was close agreement between the lipolytic activities of the compounds and their activities as inhibitors of phosphodiesterase. The close correlation between these two activities strongly indicates that the lipolytic activity of the xanthine derivatives is a result of inhibition of cyclic AMP phosphodiesterase.

Isolation of rat liver plasma membranes. Use of nucleotide pyrophosphatase and phosphodiesterase I as marker enzymes.

Abstract: Nucleotide pyrophosphatase and phosphodiesterase I of rat liver have been found to be localized primarily in cell particulates highly enriched with respect to the most commonly accepted plasma membrane marker, 5'-nucleotidase, and therefore should themselves be assigned a plasma membrane localization. The observation that plasma membranes sediment in isotonic sucrose with both nuclear and microsomal fractions was exploited to obtain plasma membrane preparations from each fraction. Both preparations are similar in chemical and enzymic composition. Moreover, the preparative method developed in this study appears to give the best combination of yield, purity, and reproducibility available. The question of the possible identity of nucleotide pyrophosphatase and phosphodiesterase I is considered, and evidence is presented suggesting that these activities may be manifestations of the same enzyme.

Geochemical Balance of a Small Watershed and Its Geomorphic Implications

Abstract: A detailed input-output study of a small forested watershed draining the Wissahickon Formation in the Piedmont of Maryland revealed that chemical solution is five times as effective in removing material as is mechanical erosion. Solution weathering removes 16.9 tons/sq mi/yr of material compared with 3.2 tons/sq mi/yr by mechanical erosion. Plant activity during the growing season increased the concentration of silica, bicarbonate, calcium, and potassium, thus increasing total dissolved solids by one-third. Autumn leaf fall also caused a short-term increase of these ions. Rainfall does not simply dilute floodwaters as the concentration of sulfate, potassium, and calcium increases whereas silica and bicarbonate decrease in concentration during a flood cycle. Our data suggest that during the first half of a flood cycle, both the flood water and the dissolved solids in it come from an area in and immediately adjacent to the flood plain. The weathering model derived from our study suggests that on a long-term basis approximately one-half of the erosion of the Pond Branch watershed is caused by chemical solution of the silicate minerals kaolinite, vermiculite, biotite, and oligoclase. This contrasts to short-term ratio of solutional to mechanical weathering of five to one.

The hormonal control of hepatic gluconeogenesis.

Abstract: Publisher Summary This chapter discusses the studies of the control of gluconeogenesis Although the data presented are almost exclusively derived from studies in the isolated perfused rat liver, an attempt has been made to relate them to results obtained in vivo and to relevant investigations in other tissues The findings indicate that variations in substrate supply are important in the physiological regulation of gluconeogenesis and that insulin, glucagon, glucocorticoids, and catecholamines exert important effects at the hepatic level They also point to the central role played by adenosine 3', 5'-monophosphate (cyclic AMP) in the control of gluconeogenesis The chapter describes the technique of rat liver perfusion and the methods of analysis of tissue and medium used in studies described in the chapter In a study described in the chapter, rat liver was perfused in situ with recirculating or nonrecirculating medium composed of washed bovine erythrocytes suspended in Krebs–Henseleit bicarbonate buffer containing 3% bovine albumin Labeled and unlabeled substrates and hormones were added to the medium in the desired concentrations, and the synthesis of glucose and glycogen was measured by chemical or isotopic means The method of perfusion was found to be very satisfactory as judged by the gross and electron microscopic appearance of the liver and by the maintenance of steady rates of oxygen consumption and bile flow The maximum rates of all synthetic processes were equal to or greater than those determined in vivo with the possible exception of glycogen deposition

Predicting Effects of Dead Zones on Stream Mixing

Abstract: Longitudinal mixing in open-channel flow is described by two coupled partial differential equations, the solution of which, in the frequency domain, is a function of four parameters: mean residence time; Peclet number or dimensionless dispersion coefficient; fraction of stream volume which is dead zone; and mean residence time in a dead zone. The solution is given and methods of estimating the parameters from hydraulic data are described. The fraction of stream volume which is dead zone is a function of the friction factor, and the ratio of mean dead zone residence time to mean residence time in a reach is essentially a constant. The effects of errors in estimating values of the parameters are discussed and illustrated.

Estrogenic induction of ornithine decarboxylase in vivo and in vitro.

Abstract: Injection of estrogens (17β-estradiol or diethylstilbestrol) into immature chicks results in a marked (30- to 50-fold) increase in the ornithine decarboxylase activity of oviductal homogenates within a 4-hour period. Similar stimulations were obtained when estrogen was injected into hypophysectomized or castrated rats and the uterus was examined for decarboxylase activity. An elevation of decarboxylase activity was obtained in vitro when oviducts from immature chicks were incubated in the presence of estrogen. These data indicate a direct action of estrogen on oviduct tissue to promote a rapid increase in the activity of a specific enzyme and represent the first example of a completely in vitro enzyme response to estrogen.

Increment detection thresholds during binocular rivalry suppression

Abstract: In two experiments, two-choice forced-choice duration thresholds for increment test flashes were estimated during phases of rivalry suppression and nonsuppression and for a nonrivalry monocular control condition. In both experiments thresholds of both eyes of each S were measured and, to maximize correct detections, feedback was given after every trial and Ss were relieved of the task of continually reporting changes in rivalry phases. Results of both experiments support the conclusion that suppression constitutes an elevation in threshold, on the order of .5 log units relative to thresholds found during nonsuppression and monocular conditions. These data, in concert with others, reinforce the general conclusion that rivalry suppression is an inhibitory state that nonselectively attenuates all classes of inputs falling within the spatial boundaries of the suppressed target.

Steroid Hormones: Effects on Adenyl Cyclase Activity and Adenosine 3',5'-Monophosphate in Target Tissues

Abstract: The adenyl cyclases of chick oviduct and rat prostate were not stimulated by estrogen and testosterone, respectively, suggesting that growth and differentiation of these target tissues are not mediated by adenosine 3',5'-monophosphate. Estrogen acutely activated adenyl cyclase in the castrate rat uterus, but this was prevented by administration of DL-propranolol, suggesting that the effect was mediated by catecholamines. Progesterone produced a delayed stimulation of oviduct adenyl cyclase preceding and concomitant with the induction of synthesis of avidin.

Cyclic AMP and adenyl cyclase in the developing rat brain.

Abstract: The level of endogenous cyclic AMP in the rat brain in vivo began to increase markedly between the third and sixth days after birth, as did the ability of norepinephrine to stimulate the formation of cyclic AMP in brain tissue in vitro. Adenyl cyclase activity in broken cell preparations, when measure in the absence of sodium fluoride, increased with age up to a point, but began to decline between the fifth and ninth days postpartum. Activity continued to increase when measured in the presence of fluoride, suggesting that the apparent stimulatory effect of this ion may in fact be the reversal of an inhibitory influence which is absent or almost absent at birth. Cyclase activity at all ages was restricted to particulate matter, whereas apparent phosphodiesterase activity was present in particulate as well as soluble fractions. The catabolic system for cyclic AMP developed in a similar manner in both fractions. Theophylline produced the same degree of inhibition of this system at all ages.

A serum fraction with "sulfation factor activity" stimulates in vitro incorporation of leucine and sulfate into protein-polysaccharide complexes, uridine into RNA, and thymidine into DNA of costal cartilage from hypophysectomized rats.

Abstract: A serum fraction which contains the so-called sulfation factor activity was found to stimulate in vitro incorporation of either (UC) or (3H) leucine and (35S) sulfate into proteinpolysaccharide complexes (PP), (3H) uridine into RNA, and (3H) thymidine into DNA of costal cartilage from hypophysectomized rats. Tissue was incubated in a medium containing 14 amino acids and glucose. The serum fraction consistently increased incorporation of leucine into protein of PP prior to the increase of sulfate incorporation into polysaccharide of PP. Stimulation of uridine incorporation into RNA did not necessarily precede stimulation of leucine incorporation into protein of PP, and the former could be profoundly inhibited with actinomycin without seriously affecting the latter. In experiments of 4 hr duration or less actinomycin inhibited incorporation of uridine into RNA≫leucine into protein of PP>sulfate into polysaccharide of PP. Stimulation of thymidine incorporation into DNA by the serum fraction occurred later th...

The early history of electrodermal research.

Abstract: The historical origins and early development of electrodermal research are reviewed in the light of a substantial number of previously unexamined sources. Relevant literature in electrophysio logy, neurology, electrodiagnosis, and electrotherapy is examined with regard to the technology and the context of ideas in science and medicine. The first reports of basal skin resistance (BSR) and stimulated skin resistance (GSR) change by Vigouroux and Fere, respectively, are related to their other research and that of other workers. Hermann's early work on the sudomotor system is seen as much more advanced than has been realized, providing a sound basis for theory which the French apparently never noticed. Several additional sources suggest that TarchanofE's work was performed with awareness of Fere's and was probably not an independent discovery. The growth of the field following "rediscovery" of the GSR by Mueller and Veraguth is seen as a product of interest in indexing "mental events." The earlier work is seen as conceptually closer to current interest in the phenomena as aspects of the arousal system. DESCRIPTORS: Electrodermal research, History of electrodermal research. Skin resistance, GSR, PGR, Electrophysiology, Electrotherap y, Magnetotherap y, Metallotherapy, Detection of emotions. (R. Blanton) The first observations of psychological factors in relation to electrodermal phenomena are generally attributed to Romain Vigouroux (1879). Yet intensive research in the area was not begun until twenty-five years later, when Veraguth and Jung performed the first experiments with word association. During that I)eriod, four other workers made reports, and two of these, Fere and Tarchanoff, did work of fundamental significance. The field has been extensively reviewed (Prideaux, 1920; Landis ct DeWick, 1929; Landis, 1932; McCleary, 1950), but as has been customary, these reviews were directed toward current questions of theory and method rather than the historical development of the ideas which This paper was supported in part by Grant i^RD-2552-S from the Rehabilitafion Services

In Vitro Stimulation of Leucine Incorporation Into Muscle and Cartilage Protein by a Serum Fraction with Sulfation Factor Activity: Differentiation of Elfects from Those of Growth Hormone and Insulin

Abstract: Effects of growth hormone, insulin and a serum fraction with sulfation factor activity on in vitro incorporation of (3H) leucine into TCA-insoluble protein by diaphragm and costal cartilage of hypophysectomized rats were compared. Tissues were incubated in a medium containing 14 amino acids and glucose. Cartilage was very sensitive to growth hormone in vivo but relatively insensitive in vitro. This tissue was also relatively insensitive to insulin in vitro but very sensitive to sulfation factor. Muscle was less sensitive than cartilage to growth hormone in vivo or sulfation factor in vitro. In all muscle studies combined, the maximum effect of growth hormone in vivo and the maximum effect of either sulfation factor or insulin in vitro each exceeded the maximum effect of growth hormone in high concentration in vitro. Sulfation factor in serum of normal rats was sufficient for stimulation of both muscle and cartilage from hypophysectomized rats in vitro, and the effects were not augmented by a high concentr...

Identity of very low density lipoprotein apoproteins of plasma and liver Golgi apparatus.

Abstract: In the rat, very low density lipoproteins isolated from hepatocyte Golgi apparatus, liver perfusates, and whole plasma appear identical in many respects. With specific immunochemical techniques and polyacrylamide-gel electrophoresis it can be demonstrated that the very low density lipoproteins from all three sources contain the same major lipoprotein apoproteins.

Stimulation of Adrenal Cholesterol Uptake from Plasma by Adrenocorticotrophin

Abstract: The effect of ACTH on adrenal cholesterol accumulation was examined in the rat. Hypophysectomized rats treated with ACTH demonstrated a greater in vivo uptake by adrenal tissue of 3H-cholesterol from plasma than did hypophysectomized control animals. Treatment with either amino-glutethimide or cycloheximide to inhibit the conversion of cholesterol to steroids increased the observed differences in adrenal 3H-cholesterol uptake between ACTH-treated and control groups. The effects seen could not be accounted for by differences between ACTH-treated and control animals in adrenal mass, in labeled cholesterol retained in the adrenal intravascular space, or in the plasma concentrations of labeled and unlabeled cholesterol perfusing the adrenal; nor was the effect of ACTH a result of the increase in glucocorticoid secretion occurring with ACTH stimulation. Inhibition of new protein synthesis to 1.5% of control values with cycloheximide did not prevent ACTH from causing an increase in adrenal uptake of cholesterol...