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Biomedical subjects

A S Gordon

Publications and source records attributed to A S Gordon.

At least 55 records · Page 3Linked to original sources
PubMed1990

GTP-binding proteins are restricted to signal transduction sites.

We have used the Torpedo electric organ to study GTP-binding protein localization since functionally distinct membrane fractions can be isolated from this tissue. Postsynaptic membranes from the innervated face and membranes from the non-innervated face of the electrocyte, as well as presynaptic membranes from the innervating nerve, can be isolated. alpha s was restricted to the innervated face of the postsynaptic cell; alpha i, alpha o, and ras were found only in the presynaptic membrane fraction of the innervating nerve. 21 and 25 kDa GTP-binding proteins were present in all the membrane fractions. These results suggest that specific GTP-binding proteins are differentially restricted to membrane areas specialized in signal transduction.

Animals↗
PubMed1990

Ethanol increases extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter.

Chronic exposure to ethanol results in heterologous desensitization of receptors coupled to adenylyl cyclase via Gs, the stimulatory guanine nucleotide regulatory protein. Ethanol-induced accumulation of extracellular adenosine is required for the development of heterologous desensitization (Nagy, L. E., Diamond, I., Collier, K., Lopez, L., Ullman, B., and Gordon, A. S., Mol. Pharmacol., in press). To understand the mechanism underlying ethanol-induced increases in extracellular adenosine, we examined the interaction of ethanol with the adenosine transport system in S49 lymphoma cells. We found that ethanol inhibited nucleoside uptake without affecting deoxyglucose or isoleucine transport. Inhibition of adenosine uptake was due to decreased influx via the nucleoside transporter. Thus, ethanol-induced increases in extracellular adenosine appear to be due to inhibition of adenosine influx. After chronic exposure to ethanol, cells became tolerant to the acute effects of ethanol, i.e. ethanol no longer inhibited uptake. Consequently, ethanol no longer increased extracellular adenosine concentrations. Taken together with our previous studies, these results suggest that ethanol inhibition of adenosine influx leads to an increase in extracellular adenosine which causes an initial increase in intracellular cAMP levels and subsequent development of heterologous desensitization of cAMP signal transduction.

Adenosine↗
PubMed1990

The effect of chronic cocaine abuse on human olfaction.

Cocaine has been used for many decades as both a stimulant and as a topical anesthetic/vasoconstrictor. Illicit "snorting" or freebase smoking has increased markedly in recent years. Decreased olfaction has been an often reported subjective complaint of cocaine abusers, but quantification of smell loss using sensitive psychophysical tests has not yet been done, leading to the present study. Eleven cocaine abusers were recruited from a drug treatment clinic. Olfaction was assessed using a butanol threshold test, the UPSIT, and a 7-item discrimination test. One patient tested anosmic, one had a mild discrimination problem, and one had a large septal perforation but was normosmic. From the present study, it appears that most cocaine abusers, even heavy users or those with intranasal damage, do not develop permanent olfactory dysfunction. It is not clear what factors may have resulted in complaints of olfactory loss in previous studies.

Adult↗
PubMed1990

The role of older brothers in younger brothers' drug use viewed in the context of parent and peer influences.

The purpose of this study was to examine the impact of an older brother's drug use on his younger brother's drug use viewed in the context of parent and peer influences. The sample consisted of 278 White, middle-class male college students and their oldest brothers, who were given questionnaires assessing drug behavior. Results indicated that older brother, parental, and peer drug use each had an independent impact on younger brother's use. The degree of influence varied, with drug modeling by peers and older brothers having a stronger association with younger brother drug use than did parental drug modeling. Further, the older brother's advocacy of drugs was associated with his younger brother's use even if the older brother did not serve as a drug model. Similarly, older brother drug modeling was of importance even if he did not advocate use. Finally, interactive results suggested that older brothers who did not use drugs could offset the negative effects of parental drug risks on younger brother use. Also, younger brothers were least likely to use drugs if both older brothers and peers served as models for nonuse.

Adolescent↗
PubMed1990

Copper-induced production of copper-binding supernatant proteins by the marine bacterium Vibrio alginolyticus.

Growth of the marine bacterium Vibrio alginolyticus is temporarily inhibited by micromolar levels of copper. During the copper-induced lag phase, supernatant compounds which complex and detoxify copper are produced. In this study two copper-inducible supernatant proteins having molecular masses of ca. 21 and 19 kilodaltons (CuBP1 and CuBP2) were identified; these proteins were, respectively, 25 and 46 times amplified in supernatants of copper-challenged cultures compared with controls. Experiments in which chloramphenicol was added to cultures indicated that there was de novo synthesis of these proteins in response to copper. When supernatants were separated by gel permeation chromatography, CuBP1 and CuBP2 coeluted with a copper-induced peak in copper-binding activity. CuBP1 and CuBP2 from whole supernatants were concentrated and partially purified by using a copper-charged immobilized metal ion affinity chromatography column, confirming the affinity of these proteins for copper. A comparison of cell pellets and supernatants demonstrated that CuBP1 was more concentrated in supernatants than in cells. Our data are consistent with a model for a novel mechanism of copper detoxification in which excretion of copper-binding protein is induced by copper.

Carrier Proteins↗
PubMed1990

Chronic ethanol-induced heterologous desensitization is mediated by changes in adenosine transport.

Chronic exposure of cultured cell lines to ethanol results in a heterologous desensitization of receptors coupled to adenylate cyclase via GS, the stimulatory guanine nucleotide regulatory protein. This heterologous desensitization is accompanied by a decrease in alpha S, the GTP-binding subunit of GS. Ethanol-induced accumulation of extracellular adenosine is required for the development of heterologous desensitization. To determine the mechanism underlying the ethanol-dependent increase in extracellular adenosine, we investigated the effects of ethanol on the nucleoside transporter responsible for the bidirectional transport of adenosine into and out of the cell. We found that ethanol specifically and non-competitively inhibited nucleoside uptake. Inhibition of adenosine uptake was primarily due to decreased influx via the nucleoside transporter. Thus, ethanol-induced increases in extracellular adenosine appear to be due to inhibition of adenosine influx. After chronic exposure to ethanol, cells became tolerant to the acute effects of ethanol, i.e. ethanol no longer inhibited uptake and, consequently, no longer increased extracellular adenosine concentration. Taken together with our previous studies, these results suggest that acute ethanol inhibition of adenosine influx leads to an increase in extracellular adenosine which in turn activates adenosine A2 receptors to increase cyclic AMP levels, leading to desensitization of receptor-dependent cyclic AMP signal transduction after chronic exposure to ethanol. We next determined whether the same effects of ethanol also occur in alcoholics. We isolated lymphocytes from alcoholics and non-alcoholics and found that alcoholics had a 75% decrease in basal and adenosine receptor-stimulated cyclic AMP production compared with non-alcoholics. To determine whether these differences were due to exposure to ethanol in vivo or to a possible genetic difference between alcoholics and non-alcoholics, we grew lymphocytes in culture in the absence of ethanol. Adenosine receptor-stimulated cyclic AMP levels were higher in alcoholics than non-alcoholics. Moreover, cultured cells from alcoholics were more sensitive to the effects of chronic alcohol on cyclic AMP signal transduction than cells from non-alcoholics. Our results suggest that the cyclic AMP signal transduction system may reflect a genetic alteration in alcoholics and that studies in cultured lymphocytes may allow us to identify individuals at risk of developing alcoholism.

Adenosine↗
PubMed1990

The psychosocial etiology of adolescent drug use: a family interactional approach.

The purpose of this monograph was to propose a framework, family interactional theory, for explaining the psychosocial aspects of adolescent drug use. Three themes are stressed: (a) the extension of developmental perspectives on drug use, (b) the elucidation of family (especially parental) influences leading to drug use, and (c) the exploration of factors that increase or mitigate adolescents' vulnerability to drug use. We present a developmental model with two components; the first deals with adolescent pathways to drug use, and the second incorporates childhood factors. The model was tested in two studies: one cross-sectional study of 649 college students and their fathers, and one longitudinal study of 429 children and their mothers. The subjects were given self-administered questionnaires containing scales measuring the personality, family, and peer variables outlined in the model. The results of each study supported the hypothesized model, with some differences between parental influences. We also found that individual protective factors (e.g., adolescent conventionality, parent-child attachment) could offset risk factors (e.g., peer drug use) and enhance other protective factors, resulting in less adolescent marijuana use. Implications of the findings for prevention and treatment, future research, and public policy are discussed.

Adolescent↗
PubMed1990

Congenital anosmia.

Seven patients with congenital anosmia underwent detailed chemosensory evaluation, followed by the performance of biopsies of the olfactory region. Olfactory epithelium was not found in any of the biopsy specimens. It appears therefore that patients with congenital anosmia lack any olfactory epithelium. Several possible explanations for this finding are discussed. The most attractive hypothesis is that the olfactory placode forms either normally or abnormally during development but later degenerates and is replaced with respiratory epithelium. Only one patient in our series had congenital anosmia in association with a syndrome (Kallmann's syndrome), indicating that congenital anosmia is found more often as an isolated symptom.

Adolescent↗
PubMed1989

Rhinomanometry for preoperative and postoperative assessment of nasal obstruction.

In this retrospective study we used active, anterior mask rhinomanometric methods to measure nasal resistance before and after surgery for nasal obstruction. The study group comprised 60 patients with nasal obstruction who had 63 preoperative and postoperative rhinomanograms and the control group contained 14 asymptomatic patients who underwent rhinomanometric studies before transnasal, transsphenoidal pituitary surgery. Before surgery the study group had significantly higher total and combined unilateral nasal resistances than either the control group before surgery (p less than 0.05 and p less than 0.01, respectively) or the study group after surgery (p less than 0.0001 for both comparisons). Surgery normalized the nasal resistances of the study group in relation to the control group. A total nasal resistance greater than 1 cm H2O/L/sec or a unilateral resistance greater than 3.5 cm H2O/L/sec suggests clinically significant nasal obstruction. Airway narrowing and obstructive symptoms correlated with airway resistance in the preoperative patient, but symptoms did not correlate well with postoperative resistance.

Adolescent↗
PubMed1989

Changes in drug involvement: a longitudinal study of childhood and adolescent determinants.

Previous research has identified childhood and adolescent personality determinants of early adolescent drug involvement. The purpose of the present study was to examine the determinants of increased involvement over time and to compare these results with previous findings regarding early involvement. Data were available on 654 white males and females at three points, Time 1 (T1) at ages 1-10 yr., Time 2 (T2) at ages 9-18 yr., and Time 3 (T3) at ages 11-20 yr. The subjects (at T2 and T3) and their mothers (at all three points) were given structured interviews assessing the child's personality and behavior. Results indicated that T1 traits of conventionality and emotional control were associated with similar traits at T2, which, in turn, were related to lower drug involvement over time (T2 and T3). Interactive effects indicated first that T2 adolescent protective (nondrug-conducive) factors weakened the effect of childhood-risk (drug-conducive) characteristics resulting in lower drug involvement. Second, high levels of earlier drug use interacted synergistically with personality risk leading to increased levels of involvement. Over-all, the personality factors implicated in increased involvement were similar to those related to earlier involvement.

Adolescent↗
PubMed1989

Adenosine is required for ethanol-induced heterologous desensitization.

Recent evidence suggests that ethanol initially causes an increase in receptor-dependent cAMP levels, followed by heterologous desensitization of receptors coupled to GS after chronic exposure. Here we investigated the role of adenosine in mediating these responses. We found that ethanol caused accumulation of extracellular adenosine in NG108-15 and S49 lymphoma cells. This adenosine activated adenosine receptors to increase intracellular cAMP levels. The addition of adenosine deaminase, to degrade accumulated extracellular adenosine, or isobutyl-methylxanthine, an adenosine receptor antagonist, completely blocked ethanol-induced increases in cAMP levels in NG108-15 cells. Chronic exposure of NG108-15 and S49 wild type cells to ethanol resulted in heterologous desensitization of adenosine receptor- and prostaglandin E1 receptor-dependent cAMP signal transduction. Coincubation of NG108-15 and S49 wild type cells with adenosine deaminase and ethanol for 48 hr prevented heterologous desensitization. Moreover, mutant S49 cells, which are unable to transport adenosine, did not accumulate extracellular adenosine after incubation with ethanol and did not develop ethanol-induced heterologous desensitization. Our results suggest that adenosine is an important mediator of both the acute and chronic effects of ethanol on cAMP signal transduction.

Adenosine↗
PubMed1989

The consequences of marijuana use on intrapersonal and interpersonal functioning in black and white adolescents.

We examined the effects of marijuana use on adolescent personality, attitudinal, and behavioral attributes, perceived parent-adolescent relations, and perceived peer factors. Volunteer high school students (292 Blacks, 401 Whites) of middle-class backgrounds filled out questionnaires in their classrooms first when they were in the 9th and 10th grades and again 2 years later when they were in the 11th and 12th grades. Results suggest that regular use of marijuana may lead to lower achievement, increased tolerance of deviance, and more deviant behavior, and greater rebelliousness. Regular use also appears to interfere with adolescents' relationships with their parents and to lead them to associate with more deviant and drug-using friends. The consequences of marijuana use for intrapersonal and interpersonal functioning were for the most part similar in the different sex and age groups, although there were some ethnic differences.

Adolescent↗
PubMed1988

Chronic ethanol causes heterologous desensitization of receptors by reducing alpha s messenger RNA.

One of the biochemical results of ethanol exposure is a change in the amount of the intracellular second messenger cyclic AMP (cAMP) produced in response to receptor stimulation. In general, acute ethanol exposure increases the amount of cAMP produced on stimulation of receptors coupled to the enzyme adenylyl cyclase via the GTP-binding protein Gs, whereas chronic ethanol exposure has the opposite effect (results for receptors coupled via Gi have been more variable). We previously reported that adaptation to continuous ethanol exposure reduces receptor-stimulated cAMP production by 25-35% in a neuroblastoma cell line (NG108-15), and an even greater reduction of 75% was observed in lymphocytes taken from actively-drinking alcoholics. This reduction in receptor-stimulated cAMP levels was recently confirmed in platelets from alcoholics. None of these studies, however, determined whether more than one receptor coupled to adenylyl cyclase activity was affected in the same cell. Here we report that chronic ethanol exposure causes desensitization of heterologous receptors coupled to Gs as cAMP production mediated by prostaglandin E1 as well as by adenosine is reduced by approximately 30% in NG108-15 cells. We show that, after chronic ethanol exposure, the activity of the alpha subunit of Gs is decreased by 29%, the amount of alpha s protein is decreased by 38.5%, and alpha s messenger RNA is decreased by 30%. Thus, cellular adaptation to ethanol involves a reduction in alpha s mRNA and, as a consequence, reduced cAMP production by heterologous receptors coupled to Gs. Such changes in cAMP production may account for the tolerance and physical dependence on ethanol in alcoholism.

Cyclic AMP↗
PubMed1988

Late ear sequelae in cleft palate patients.

This retrospective study looks at the incidence and nature of ear disease in 50 adolescent patients who had cleft palates repaired in infancy. Half of these patients had a history of grommet insertion. We found that most patients had normal hearing (81%) and middle-ear pressures (86%), although about half had tympanic membrane abnormalities. Grommet insertion did not result in better long-term hearing in this study but was strongly associated with tympanosclerosis. Cleft type did not influence the degree of ear disease although more patients with complete clefts had a history of repeated grommet insertion. Otitis media with effusion is almost universal in cleft palate infants and may influence later language, speech and educational development. At the time of palatal repair grommets should be inserted to improve hearing in these infants.

Adolescent↗
PubMed1988

Depressive mood in female college students: father-daughter interactional patterns.

The interrelationship of sets of father and daughter factors in explaining depressive mood in normal female adolescents was examined. Separate questionnaires were given to 403 college students and their fathers. A mediational model was found, in which two sets of paternal variables were related to the daughter personality set, which in turn was related to her depressive mood. In addition, protective personality attributes of the daughter served both to offset the impact of paternal risk factors and to further strengthen paternal protective factors to reduce frequency of depressive mood. Comparisons are made with an earlier study of sons' depressive mood (Brook, Brook, Whiteman, & Gordon, 1983).

Achievement↗
PubMed1987

Regional cerebral glucose metabolism in SLE chorea: further evidence that striatal hypometabolism is not a correlate of chorea.

The pathophysiology of chorea in systemic lupus erythematosus (SLE) is uncertain. Pathologic examination has not identified a specific location for the causative lesion(s) and immunologic mechanisms have been suggested in its etiology. In other choreic disorders, such as Huntington's disease and benign hereditary chorea, glucose hypometabolism in the striatum has been demonstrated by positron computed tomography (PCT) using [18F]deoxyglucose. With this technique we have studied four patients with chorea secondary to SLE. In these patients the regional distribution of cerebral glucose metabolism was normal. In particular, striatal glucose metabolism was within the normal range, even though the ratio of striatal to cortical glucose metabolism was increased. Our results show that striatal hypometabolism, as seen in other disorders manifesting chorea, is not the PCT correlate of the dyskinesia.

Adult↗
PubMed1987

Fathers and daughters: their relationship and personality characteristics associated with the daughter's smoking behavior.

This study examined the interrelationships of domains (i.e., sets) of paternal personality and father-daughter relationship variables and daughter characteristics and their impact on the daughter's smoking. In addition, the interactive effects of individual father and daughter variables on the daughter's smoking were studied. Female college student volunteers (N = 403) and their fathers were given closed-ended questionnaires that included a number of scales assessing father and daughter characteristics. Results indicated that the domains of father and daughter variables each had a direct impact on the daughter's smoking (an independent model). Interactive findings revealed that daughter protective factors (those conducive to her not smoking) could offset the negative impact of paternal risk factors (those conducive to her smoking), and that, to a lesser extent, daughter protective factors further enhanced the positive effect of father protective variables.

Adult↗