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Showing papers by "Vanderbilt University published in 1975"


Journal ArticleDOI
TL;DR: The proposed classification of drug metabolism based on the hepatic extraction ratio allows prediction and interpretation of the effects of individual variations in drug‐metabolizing activity, route of administration, pharmacokinetic interactions, and disease states on hepatic drug elimination.
Abstract: A physiological approach has been developed recognizing that hepatic blood flow, the activity of the overall elimination process (intrinsic clearance), drug binding in the blood, and the anatomical arrangement of the hepatic circulation are the major biological determinants of hepatic drug clearance. This approach permits quantitative prediction of both the unbound and total drug concentration/time relationships in the blood after intravenous and oral administration, and any changes that may occur as a result of alterations in the above biological parameters. These considerations have led to a classification of drug metabolism based on the hepatic extraction ratio. The proposed classification allows prediction and interpretation of the effects of individual variations in drug-metabolizing activity, route of administration, pharmacokinetic interactions, and disease states on hepatic drug elimination.

1,895 citations


Book
01 Jun 1975

845 citations


Journal ArticleDOI
09 Oct 1975-Nature
TL;DR: The effect of electroconvulsive treatment, as it is generally accepted to be one of the most effective treatments for severe depression, is tested, on the reactivity of the cyclic AMP-generating system to NA.
Abstract: STUDIES on the pharmacology of the noradrenergic cyclic AMP-generating system in slices from the limbic forebrain of the rat1 and on adaptive properties of this system in conditions of persistent changes in the availability of nor-adrenaline (NA) have revealed that the system may serve as a model for the central NA receptor in this area, and that its sensitivity to NA increases or decreases when the availability of NA at the receptor site decreases or increases respectively2,3. Thus, hypersensitivity of the system has been achieved by treatment with reserpine2, a drug known to precipitate occasionally severe depressive reactions in man4, and the syndrome of which, when elicited in animals, is widely used as a model for depression5–7. Conversely, the monoamine oxidase (MAO) inhibitors, pargyline and nialamide, caused a marked reduction in the reactivity of the cyclic AMP-generating system to NA after chronic administration3. To determine whether or not antidepressant drugs which do not elevate the level of monoamines in brain share the effect of MAO inhibitors on the noradrenergic cyclic AMP-generating system, we studied the effect of the tricyclic antidepressants, desipramine and iprindole, on the reactivity of the system to NA. Desipramine blocks the uptake of NA through the neuronal membrane8,9 whereas iprindole neither blocks the neuronal uptake of NA nor alters its metabolism or turnover10,11, but is nevertheless a potent antidepressant12–14. In addition, we have tested the effect of electroconvulsive treatment (ECT), as it is generally accepted to be one of the most effective treatments for severe depression15.

586 citations


Journal ArticleDOI
TL;DR: The results of these experiments are consistent with the interpretation that (1) the electron dense material inside heavy vesicles may be referable to Ca-2+ binding and/or M55 proteins, and (2) light andheavy vesicle may be derived from the longitudinal sections and terminal cisternae of sarcoplasmic reticulum, respectively.

401 citations


Journal ArticleDOI
TL;DR: The set of allowable edit operations is extended to include the operation of interchanging the positions of two adjacent characters under certain restrictions on edit-operation costs, and it is shown that the extended problem can still be solved in time proportional to the product of the lengths of the given strings.
Abstract: The string-to-string correction problem asks for a sequence S of "edit operations" of minimal cost such that ~(A) = B, for given strings A and B The edit operations previously investi- gated allow changing one symbol of a string into another single symbol, deleting one symbol from a string, or inserting a single symbol into a string This paper extends the set of allowable edit opera- tions to include the operation of interchanging the positions of two adjacent characters Under certain restrictions on edit-operation costs, it is shown that the extended problem can still be solved in time proportional to the product of the lengths of the given strings

350 citations


Journal ArticleDOI
TL;DR: A detailed account of major developments in psychometrics over the last 25 years, as seen through my eyes and evaluated from my particular points of view, can be found in this article.
Abstract: This is an account of major de­ velopments in psychometrics dur­ ing the last 25 years, as seen through my eyes and evaluated from my particular points of view. Although I will make some guesses regarding future developments, I mainly want to bring the story up to date. I picked the year 1950 as a starting point for two reasons —one impor­ tant to many researchers in psy­ chology and education and one per­ sonal. The important reason is that 1950 was in the center of an Au­ gustan age for the development of psychometrics, extending from 1940 to 1960 —a period of intense activ­ ity and important developments, the likes of which may not come again nor even be needed again. The per­ sonal reason was that in 1950, as a graduate student at the University of Chicago, I was being introduced to the field of psychometrics under the tutelage of William Stephenson and Leon Thurstone.

238 citations


Journal ArticleDOI
TL;DR: Cytoplasmic microtubules, vinblastine-induced paracrystals and the full spectrum of mitotic figures can be visualized by immunofluorescence and show that the tubulin structure has been highly conserved during evolution.

201 citations


Journal ArticleDOI
TL;DR: Golgi apparatus isolated from both rat liver and rat kidney have been characterized with respect to their neutral and phospholipid content and their phosphopipid composition and compared with mitochondria, rough endoplasmic reticulum and plasma membranes.

195 citations


Journal ArticleDOI
TL;DR: In one abnormal owl monkey, a portion of the upper quadrant was represented twice in DM, and this abnormal case may provide some clues as to how the normal pattern of visuotopic organization is established in the developing brain.

191 citations


Journal ArticleDOI
05 Sep 1975-Science
TL;DR: An immune affinity column extraction technique was used to purify partially a substance from human urine which was similar to the mouse hormone in both its biological activity and immunoreactivity.
Abstract: Epidermal growth factor is a polypeptide hormone that was previously identified only in mice. It causes proliferation and keratinization of epidermal tissues. An immune affinity column extraction technique was used to purify partially a substance from human urine which was similar to the mouse hormone in both its biological activity and immunoreactivity.

189 citations


Journal ArticleDOI
TL;DR: Thiono-sulfur-containing compounds administered by intraperitoneal injection to untreated, phenobarbital-pretreated and 3-methylcholanthrene-pret treated adult male rats significantly decreased the concentration of cytochrome P-450 in the microsomes from each treatment group, and similar reductions in benzphetamine metabolism were seen.

Journal ArticleDOI
TL;DR: The aim of this brief review is to summarize the main clinical and biochemical features of the principal conditions associated with significant fatty infiltration of the liver as the primary pathologic finding.
Abstract: Fatty liver may be defined as an acctJmulation of lipid, consisting principally of triglycerides in most cases, which exceeds 5~ of the liver weight. The clinical importance of excess fat varies with its cause and quantity. In some instances (ie, obesity) it may be of little consequence, whereas in others (ie, fatty liver of pregnancy) it may lead to hepatic failure and death. The aim of this brief review is to summarize the main clinical and biochemical features of the principal conditions associated with significant fatty infiltration of the liver as the primary pathologic finding.

Journal ArticleDOI
TL;DR: This paper reported that graduate schools of management and business administration are increasingly attracting more students who view their careers as vehicles for implementing social change, and that more students view their career as a vehicle for social change.
Abstract: This article reports that graduate schools of management and business administration are increasingly attracting more students who view their careers as vehicles for implementing social change. Pro...

Journal ArticleDOI
TL;DR: It is concluded that the biosynthesis and function of prostaglandins can be augmented in man by oral administration of an esterified precursor fatty acid.
Abstract: Ethyl arachidonate was administered orally to 4 healthy male volunteers in a dose of 6 gm daily for a 2 to 3 wk period after 10-day control period. The increased intake of this precursor of the dienoic prostaglandins resulted in significant increases in the relative and absolute amount of arachidonate in plasma triglycerides, phospholipids, and cholesteryl esters. Similar changes in lipid composition were noted in platelets. The excretion of 7alpha-hydroxy-5,11-diketotetranoprostane-1,16-dioic acid, the major urinary metabolite of E prostaglandins in man, was increased by an average of 47% in 3 of the 4 volunteers. Platelet reactivity was assessed by determining the threshold concentration of adenosine diphosphate (ADP) necessary to induce secondary, irreversible aggregation of platelet-rich plasma. This threshold concentration dropped significantly in all volunteers (10% to 60% of control values). It is concluded that the biosynthesis and function of prostaglandins can be augmented in man by oral administration of an esterified precursor fatty acid.

Journal ArticleDOI
TL;DR: Most (85% or more) of the cyclic nucleotide phosphodiesterase (3' :5' -cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17) activity of pig coronary arteries was found in the supernatant fraction of homogenates of the intima plus media layer, and hydrolysis by peak I or peak II was more rapid in the presence of Mn-2+ than Mg-2+.

Journal ArticleDOI
TL;DR: The evidence supports the hypotheses proposing that hyperglycemia will impair the intracellular availability of vitamin C.
Abstract: A system for measuring the rate of transport of dehydroascorbate into human red blood cells shows Michaelis-Menten type kinetics with substrate inhibition at levels above 150 muM DHA. The addition of sugars impairs this transport in the diminishing hierarchy D-glucose, D-mannose, D-xylose, D-galactose, L-lyxose, D-araboascorbate, L-sorbose and 2-deoxy-D-ribose. The effect of glucose on transport of ascorbate is marked at physiological levels. Transport of DHA is accelerated by copper ion and allows dehydroascorbate to move against a concentration gradient. The evidence supports the hypotheses proposing that hyperglycemia will impair the intracellular availability of vitamin C.

Book ChapterDOI
TL;DR: The stimulation of epidermal proliferation in organ cultures of chick embryo skin is dependent upon a number of conditions, among which are the age of the embryo and the presence of dermal cells.
Abstract: Publisher Summary This chapter discusses the interaction of epidermal growth factor (EGF) with cultured fibroblasts. EGF is a single-chain polypeptide containing a total of 53 amino acid residues. All the common amino acids are present except lysine, alanine, and phenylalanine. The molecule contains six half-cystine residues in disulfide bridges. EGF is antigenic and is sensitive to proteolytic digestion. It is heat stable, nondialyzable, and has an isoelectric point at pH 4.6. The chapter also discusses the complete amino acid sequence of EGF and presents the location of the three disulfide bridges. A direct stimulatory effect of EGF on epithelial cell proliferation in vitro has been demonstrated in a number of organ culture systems. These include embryonic skin, embryonic cornea, and mammary gland expiants. The effects of EGF are not species specific; expiants derived from the chick, mouse, and human are responsive. The stimulation of epidermal proliferation in organ cultures of chick embryo skin is dependent upon a number of conditions, among which are the age of the embryo and the presence of dermal cells.

Journal ArticleDOI
01 Jun 1975-Diabetes
TL;DR: It is demonstrated that in normal man fasted twelve to fourteen hours, glucagon at supraphysiblogic levels can double the rate of gluconeogenesis from alanine and indicate that this stimulatory effect of glucagon is exerted within the liver by shunting the extractedAlanine toward new glucose formation rather than by increasing the hepatic extraction of alanines.
Abstract: Although the stimulatory effect of glucagon on gluconeogenesis has been well demonstrated in certain systems in vitro, this effect has never been established in man. The present study was undertaken, therefore, to determine whether glucagon could stimulate gluconeogenesis from alanine in normal fasting man. Glucagon might stimulate this process by increasing the hepatic alanine uptake and/or by shunting the extracted alanine within the liver into the gluconeogenic pathway. In order to be able to examine these two aspects of gluconeogenesis, we combined the hepatic veinbrachial artery catheterization technic with an isotopic infusion of alanine- 14 C. Alanine- 14 C specific activity was measured in whole blood and plasma by use of a rapid chromatographic technic. Since plasma contributed 93 per cent of the alanine extracted by the splanchnic bed with a specific activity three times that of the red blood cells, plasma alanine specific activity was used to study the conversion of alanine to glucose. A constant infusion of alanine- 14 C achieved a relatively stable arterial specific activity by forty minutes. The administration of glucagon by constant infusion (15–50 ng./kg./min.) had no effect on the splanchnic extraction of alanine. Net splanchnic glucose- 14 C production, however, doubled during the glucagon infusion, and the conversion of alanine to glucose increased from 30 ± 2 to 58 ± 9 μmol/min. These data (1) demonstrate that in normal man fasted twelve to fourteen hours, glucagon at supraphysiblogic levels can double the rate of gluconeogenesis from alanine and (2) indicate that this stimulatory effect of glucagon is exerted within the liver by shunting the extracted alanine toward new glucose formation rather than by increasing the hepatic extraction of alanine.

Journal ArticleDOI
TL;DR: The measurement of the magnitude of the MAE when the inducing motion was phenomenally suppressed for > 50 per cent of the inspection period is interpreted to mean that the site of suppression is cortical.

Journal ArticleDOI
TL;DR: In this article, the role of cognitive bias in manuscript review, designated more and less politically liberal area specialists and nonspecialists were sent either of two versions of a brief empirical report contrasting student political activists' and nonactivists' psychological well-being.
Abstract: To clarify the role of cognitive bias in manuscript review, designated more and less politically liberal area specialists and nonspecialists were sent either of two versions of a brief empirical report contrasting student political activists' and nonactivists' psychological well-being. The forms were identical, except that all references to activists and to nonactivists in the results and discussion sections were interchanged. The referees, led to think that they were participating in a study of the usefulness of a closed-ended manuscript evaluation procedure, were asked to rate the article's publishability and the degree to which specific criteria for scientific quality were met. The main results confirmed the expectation that publication verdicts handed down about a paper containing information of social import are sometimes biased by a reviewer's political orientation. However, the results were largely null regarding the susceptibility to value-intrusion of scholarly inferences anchored to discrete criteria. Ego involvement is implicated as a mediator of biasing effects in the editorial process.

Journal ArticleDOI
TL;DR: Hog renin obtained after 180,000-fold purification at an overall yield of 25%, is stable at pH6.35 and −20°.

Journal ArticleDOI
TL;DR: In this paper, the authors examined the role of cultural diversity in the diffusion of country music in the United States and concluded that the massification hypothesis was correct in observing that the old patterns of culture diversity along ethnic, regional, and even class lines are being destroyed or buried.
Abstract: The regionalization, commercialization, and subsequent diffusion of country music are examined in terms of the massification hypothesis. Each of the data sets examined suggests that the massification theorists were right in observing that the old patterns of cultural diversity along ethnic, regional, and even class lines are being destroyed or buried. But they have erred in their prediction of ever-increasing cultural homogeneity. While country music is increasingly embraced by mid-life, working and lowermiddle class whites irrespective of regional origin, "easy listening" music is the preferred music in the same segment of the population. These data bring into question the assumption that social classes have distinct cultures and lead to the conjecture that these musical styles may represent convenient indicators of emerging culture classes. The impact of modernization on cultural diversity has long held the attention of scholars. Industrialization, urbanization, and particularly the mass media are said to destroy regional, ethnic, religious, occupational, and similar forms of cultural diversity, replacing these with the homogenized products of mass culture. This massification hypothesis,was derived from observations made during the 1930s of the effects of commercial radio, popular music, movies, and mass circulation magazines on cultural traits in the United States, and also the propaganda uses made of these media by the rising totalitarian governments of Europe. The hypothesis was fully articulated in diverse essays and research studies made in the decade following World War II (Jacobs, 1959; Rosenberg and White, 1957). Dwight Macdonald (1957:62) puts the hypothesis most succinctly, "Mass culture is a dynamic, revolutionary force, breaking down the old barriers of class, tradition, taste, and dissolving all cultural distinctions. It mixes and scrambles-everything together, producing what might be called * This project was funded in part by grant RO7855-73-154 from the National Endowment for the Humanities which is gratefully acknowledged. Johnny Bond, Norman Cohen, George Collier, Gregory Daniels, Skeeter Davis, Archie Green, William Ivey, Grelun Landon, Ronnie Light, Jens Lund, Anthony Oberschall, Ruth Slack, and James D. Thompson provided much information, insight and encouragement along the way; Victoria Bransford and Russell Davis helped in the coding; while Patricia Averill, George Lewis, Claire Peterson, Neil V. Rosenberg, and Richard Simpson have added greatly to the clarity of the argument by their careful reading of an earlier draft of the paper. This content downloaded from 207.46.13.183 on Thu, 29 Sep 2016 05:49:50 UTC All use subject to http://about.jstor.org/terms 498 / SOCIAL FORCES / vol. 53:3, march 1975 homogenized culture." Comprehensive critiques of the theory, data, and metaphysics of massification can be found in Bauer and Bauer (1960) and Gans (1966). For our purposes, it is convenient to separate the massification hypothesis into two elements: first, that the forces of modernization significantly reduced cultural diversity; and second, that an increasingly homogeneous mass culture has emerged. All available evidence supports the first assertion that many cultural differences have been destroyed. This can be seen whether one looks at general processes such as the "Americanization" of immigrants or traces the ebb of regional differences in a particular culture realm such as blues music or linguistic dialects. The second assertion, that of increasing homogeneity, is however an oversimplification at best. Although the few well-researched studies that have been made do show little significant difference in cultural tastes across a wide range of social classes or occupations, this may be, as Wilensky (1964) recognized, in part an artifact of the way measurements are made. First, media with little available diversity, such as radio in the 1940s and television in the 1950s and 1960s, are often used; and second, cultural taste is frequently conceptualized simply as "high art" versus "popular culture" or some similar distinction which arbitrarily restricts to one dimension the range of cultural diversity

Journal ArticleDOI
TL;DR: Although it was established that these findings do not apply to all drugs, the data suggest that collection methods should be routinely checked at intervals unless separate venipuncture and all glass collection tubes are used.
Abstract: Spuriously low values of plasma propranolol concentrations resulted when one commercial brand of collection tube was used. The mechanism of this effect was established and was due to the presence of the stopper containing substances that reduced plasma propranolol binding and resulted in a redistribution of the drug in whole blood so that more was present in the cells and less in the plasma. A similar phenomenon was noted some years ago when a needle for intravenous infusion was used as an indwelling cannula. Th mechanism in this case could not be established as in the interim the phenomenon was no longer detectable. Although it was established that these findings do not apply to all drugs, the data suggest that collection methods should be routinely checked at intervals unless separate venipuncture and all glass collection tubes are used.


Journal ArticleDOI
03 Oct 1975-Science
TL;DR: The presence of the retinoic acid binding protein in malignant tissue may be another case of the occurrence of a cellular component inmalignant tissue which normally is observed only at the fetal stage, as has been reported for some other proteins.
Abstract: Extracts of human carcinomas from lung and breast contain a protein which binds retinoic acid (vitamin A acid) with high specificity. The binding protein was not detected in normal lung or breast t...

Journal ArticleDOI
20 Nov 1975-Nature
TL;DR: It is found that previous illuminations not only reduced the sensitivity of photoreceptors in Limulus lateral eye but also decreased the latency of the responses to subsequent stimuli, and that the reduction in latency was greater with brighter adapting lights.
Abstract: IN a photoreceptor cell, light induces a change in membrane voltage (the ‘receptor potential’). The sensitivity of the photoreceptor (defined as the amplitude of the receptor response per unit of stimulus energy) depends on its history of illumination. After a cell has been stimulated by light, its sensitivity becomes reduced (that is, the cell becomes ‘light adapted’). Fuortes and Hodgkin1 reported that previous illuminations not only reduced the sensitivity of photoreceptors in Limulus lateral eye but also decreased the latency of the responses to subsequent stimuli. They found that the reduction in latency (referred to as a shortened ‘time scale’) was greater with brighter adapting lights, and that the shortening of the time scale was much smaller proportionally than was the reduction in sensitivity. Similar changes in time scale also have been found in Limulus ventral photoreceptors2,3.

Journal ArticleDOI
TL;DR: The ability to modify 20 : 3Omega6 levels selectively in certain tissues is of interest in light of such pharmacologic differences from 20 : 4.

Journal ArticleDOI
TL;DR: The peculiar arrangement of endothelial cells and undifferentiated mesenchymal cells, the examples of apparent atrial wall invasion, and the cases of embolic "metastases" provide no conclusive evidence of neoplasia, since these features may also be seen with ordinary mural thrombi.

Journal ArticleDOI
TL;DR: Two therapeutic regimens were compared in 16 infants with protracted diarrhea and malnutrition suggesting that patients given enteral feedings early tended to have a more rapid return of intestinal function and of some intestinal enzymes.

Journal ArticleDOI
TL;DR: There exists in the rat a dual system of intestinal thiamine transport, which at low concentrations is absorbed by an active process; at high concentrations, transport across the intestine is largely a passive movement.