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Biomedical subjects

E P Noble

Publications and source records attributed to E P Noble.

At least 19 recordsLinked to original sources
PubMed1992

Regulation of phosphoinositide hydrolysis in cultured astrocytes by sphingosine and psychosine.

The effects of sphingosine and psychosine on phosphoinositide hydrolysis in primary cultured astrocytes were determined. Exposure to sphingosine produced a dose-dependent stimulation of phosphoinositide hydrolysis requiring the presence of external Ca++ for optimal activity. The addition of 10 microM norepinephrine resulted in a stimulation additional to that with sphingosine. The alpha 1-antagonist prazosin completely inhibited norepinephrine-induced phosphoinositide hydrolysis but had no effect on that produced by sphingosine. Psychosine (108 microM), when co-incubated with sphingosine, produced complete inhibition of sphingosine-induced phosphoinositide hydrolysis at all doses of sphingosine tested (33-668 microM). Likewise, psychosine totally inhibited norepinephrine-induced phosphoinositide hydrolysis. The protein kinase C inhibitor staurosporine (1 microM) had no effect on sphingosine-induced phosphoinositide hydrolysis. These findings suggest that lysosphingolipids such as sphingosine and psychosine may play an important role in the regulation of phosphoinositide turnover in astrocytes by a mechanism dependent on extracellular Ca++ and independent of the alpha 1-adrenergic receptor and protein kinase C.

Alkaloids↗
PubMed1992

Developmental patterns of ganglioside sialosylation coincident with neuritogenesis in cultured embryonic chick brain neurons.

Chick brain precursor neurons were observed to introduce sialic acid biosynthetically into only three specific gangliosides: monosialosyl lactosyl ceramide (GM3), disialosyl lactosyl ceramide (GD3), and disialosyl gangliotrihexosyl ceramide (GD2), when sialic acid was labeled metabolically by its obligate precursor, [3H] ManNAc. Sialosyl donor CMP-[3H]NeuAc supplied in the culture medium gave rise uniquely to surface-labeled GD3. Thus sialosyl transferase/GD3 synthase activity is expressed both intraneuronally and in the neuronal exofacial surface. Upon epidermal growth factor-induced onset of neurite outgrowth, labeled complex sialosyl gangliotetrahexosyl ceramide species of gangliosides began to appear in the embryonic neuronal plasma membrane. However, intraneuronal and exofacial sialosyl transferase/GD3 synthase activities remained constant, with or without neurite outgrowth. Moreover, simpler species of gangliosides maintained a steady quantitative sialosyl level (1.6 +/- 0.2 micrograms of sialic acid/mg of protein), whereas more complex species completely absent before neurite outgrowth accrued and reached 4.8 +/- 0.9 micrograms of sialic acid/mg of protein with full neurite development. This analysis of developmental patterns of ganglioside sialosylation has provided evidence that stable neurite outgrowth depends upon generation by the neuron of special plasma membrane with a massive content of complex higher species of gangliosides.

Animals↗
PubMed1991

Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism.

The allelic association of the human D2 dopamine receptor gene with the binding characteristics of the D2 dopamine receptor was determined in 66 brains of alcoholic and non-alcoholic subjects. In a blinded experiment, DNA from the cerebral cortex was treated with the restriction endonuclease Taql and probed with a 1.5-kilobase (kb) digest of a clone (lambda hD2G1) of the human D2 dopamine receptor gene. The binding characteristics (Kd [binding affinity] and Bmax [number of binding sites]) of the D2 dopamine receptor were determined in the caudate nuclei of these brains using tritiated spiperone as the ligand. The adjusted Kd was significantly lower in alcoholic than in nonalcoholic subjects. In subjects with the A1 allele, in whom a high association with alcoholism was found, the Bmax was significantly reduced compared with the Bmax of subjects with the A2 allele. Moreover, a progressively reduced Bmax was found in subjects with A2/A2, A1/A2, and A1/A1 alleles, with subjects with A2/A2 having the highest mean values, and subjects with A1/A1, the lowest. The polymorphic pattern of the D2 dopamine receptor gene and its differential expression of receptors suggests the involvement of the dopaminergic system in conferring susceptibility to at least one subtype of severe alcoholism.

Alcoholism↗
PubMed1991

Personality characteristics of alcoholic fathers and their sons.

Recovering alcoholic fathers with a positive family history of alcoholism and their 10-15 year-old sons were assessed on a variety of personality measures and compared to a matched group of nonalcoholic fathers with a negative family history of alcoholism, and their sons. Assessment instruments for the sons included the Personality Inventory for Children, High School Personality Questionnaire, Junior Eysenck Personality Inventory and the Tridimensional Personality Questionnaire. Comparable questionnaires were administered to the fathers: the MMPI, 16 Personality Factor Questionnaire, Eysenck Personality Inventory and the Tridimensional Personality Questionnaire. No psychopathology or extreme personality variants were observed in either fathers' or sons' groups. However, MANOVAS and linear discriminant functions revealed significant differences on several personality measures between fathers' and sons' groups. Compared to sons of nonalcoholics, sons of alcoholics were relatively more compulsive, insecure and fearful while being more subdued and detached. The recovering alcoholics were more impulsive and regimented than the nonalcoholics. An index resulting from the combination of the best personality discriminators was significantly correlated in father-son pairs. In addition, this index was significantly correlated with key neurocognitive variables from our previous study which assessed the same father-son pairs. This atypical CNS profile, encompassing altered electrophysiology, neuropsychological performance and personality traits, may be useful in identifying those at increased risk for developing alcoholism.

Adult↗
PubMed1990

Allelic association of human dopamine D2 receptor gene in alcoholism.

In a blinded experiment, we report the first allelic association of the dopamine D2 receptor gene in alcoholism. From 70 brain samples of alcoholics and nonalcoholics, DNA was digested with restriction endonucleases and probed with a clone that contained the entire 3' coding exon, the polyadenylation signal, and approximately 16.4 kilobases of noncoding 3' sequence of the human dopamine D2 receptor gene (lambda hD2G1). In the present samples, the presence of A1 allele of the dopamine D2 receptor gene correctly classified 77% of alcoholics, and its absence classified 72% of nonalcoholics. The polymorphic pattern of this receptor gene suggests that a gene that confers susceptibility to at least one form of alcoholism is located on the q22-q23 region of chromosome 11.

Alcoholism↗
PubMed1979

Changes in neuropsychological performance during treatment for alcoholism.

A battery of 24 neuropsychological tests was administered to drug-free alcoholic inpatients (n = 91) within 7 days of their last drink and again 17 days later. Comparisons between this group and a nonalcoholic group of medical inpatients (n = 20) also given the same test battery twice indicated very little improvement due to abstinence (short-term improvement) in the alcoholics after controlling for practice effects. Similarly, when early postwithdrawal performance of the alcoholics was compared to an alcoholic control group (n = 32), which took the test battery only once 21 days after their last drink, little evidence for short-term recovery of cognitive functions was obtained. Insofar as decisions about the initiation of therapeutic treatments which rely on cognitive processes are based on neuropsychological performance, we conclude that such treatments may commence as soon as the clinical symptoms associated with acute withdrawal have subsided.

Adult↗
PubMed1978

Studies on the effects of chronic ethanol ingestion on the properties of rat brain ribosomes.

Previous observations have demonstrated decreased in vivo and in vitro protein synthesis by brain ribosomal systems following long-term ethanol ingestion. For further investigation of the properties of brain ribosomes, the 40S and 60S ribosomal subunits were successfully isolated from control and chronic 10% ethanol-drinking rats. For a successful dissociation of ribosomes into subunits NH4Cl, puromycin and a high-salt treatment at 10 degrees C were essential with a critical concentration of Mg2+ since ribosomes could not be resolved at less than 7 mM Mg2+. Analysis of the A260 profile of the subunits on the sucrose gradients showed no significant differences between the control and ethanol-ingesting groups. Studies on 3H-labeled ribosomes following in vivo RNA labeling showed correspondence of the radioactive profiles from the incorporation of [5(-3) H) orotic acid into RNA with the sucrose gradient absorbance profile of 60S and 40S ribosomal subunits. Furthermore, active reassociation of both subunits occurred at 37 degrees C as demonstrated by the increased [14 C]-phenylalanine incorporation in the presence of poly(U). Results further showed that the poly(U)-dependent [14C]phenylalanine incorporation was significantly reduced by the subunits from the ethanol-ingesting animals. These findings suggest that long-term ingestion of ethanol caused functional changes in the properties of brain ribosomes, specifically on the reassociation process of the two subunits.

Alcohol Drinking↗
PubMed1978

The fluorometric assay of rat plasma corticosterone: evaluation of nonspecific fluorescence.

An analysis of 168 plasma samples from intact rats, one to 35 days of age, was performed using both brief and specific fluorometric procedures. The amount of fluorescence produced by the brief procedure which could be attributed to corticosterone ranged from a maximum of 72% to a minimum of 16% of the total fluorescence value. Corticosterone represented 50% or more of the brief assay value in only five out of 18 groups of animals assayed. Following statistical analysis of the nonspecific fluorescence, a significant variation was found due to the age of the animal. A highly significant increase in nonspecific fluorescence was found in 21-day old animals following histamine injection. It was concluded that the brief fluorometric assays for corticosterone were of little value if specificity was desired.

Aging↗
PubMed1978

Effects of long term ethanol ingestion on RNA metabolism by inner membranes of rat brain mitochondria.

Recent laboratory endeavors have been primarily concerned with determining the effects of chronic ethanol ingestion on cerebral RNA metabolism within the inner mitochondrial membrane (IMM). Toward this goal, a series of experiments were carried out by determining the RNA and protein synthetic activity of the organelle. Brain mitochondria actively incorporated [5-3H]orotic acid into RNA under in vivo conditions. In addition, data showed that a major portion of the radioactivity present in the cold TCA insoluble residue from labeled intact mitochondria could be recovered in the digitonin treated purified IMM fraction. Maximum incorporation of [5-3H]orotic acid into RNA took place within 24 hrs followed by a rapid decline in activity on the 5th day of the pulse in both 'control' and 'ethanol' ingesting rats. Data revealed that ethanol ingestion affected the degree of incorporation of labeled RNA precursor into the mitochondrial RNA fraction. The observed effect was in the form of inhibition and was dependent on the duration of the initial pulse. Thus, while at earlier time points a decreased incorporation of the precursor into mitochondrial RNA was obtained in the ethanol imbibing rats, the inhibition was not observed when the pulse time was extended to 5 days. Such results indicate the possibility of a rapid turnover rate for the brain mitochondrial RNA with the 'ethanol' group having a faster rate of turnover when compared to the 'control' group.

Alcoholism↗
PubMed1978

Relationship between neuropsychological performance and alcohol consumption in alcoholics.

Cognitive performance in drug-free alcoholic patients (n = 95) within 7 days of their last drink was significantly predicted by chronic and recent drinking practices. Conceptually distinct cognitive functions were differentially influenced by various combinations of drinking variables. Consideration of curvilinear relationships enhanced the amount of variance explained, and it is suggested that certain patterns of consumption may accelerate the alcohol-induced decline of brain function.

Adult↗
PubMed1978

In vitro protein synthesis by inner membranes of rat brain mitochondria.

Prior investigation of the protein synthesizing properties of mitochondria involved the whole organelle. In order to better characterize these properties, the present study was concerned more specifically with the activity of the inner mitochondrial membranes (IMM) which recent investigation has implicated as the primary location of mitochondrial ribosomes. To further define mitochondrial protein synthesis simultaneous experimentation was also conducted utilizing cytoplasmic ribosomes thus enabling both qualitative and quantitative comparison between the two systems. Results from this series of investigations reveal a dramatic amino acid incorporating ability by the IMM fraction of the brain mitochondria. This activity, in turn, was shown to be highly independent of exogenous sources of ATP, GTP, pH 5 enzymes, and cytoplasmic ribosomes. Furthermore, the addition of an exogenous source of messenger RNA, polyuridylic acid or (poly (U)) which resulted in an increased incorporation of [14C]phenylalanine into polypeptide in the cytoplasmic system was found to have no effect on the IMM system. Upon comparison of the in vitro protein synthesizing properties of the IMM fraction with those of the cytoplasmic ribosomal system, it became evident that obvious differences existed in the degree of amino acid incorporation and in the sensitivity of this process to the various protein synthesizing inhibitors. Cytoplasmic ribosomes demonstrated a much greater [14C]leucine and [14C]phenylalanine incorporating activity than the IMM fraction. In addition, RNase and cyclohexamide had their greatest effect on the cytoplasmic system while the action of chloramphenicol was most potent on the IMM system. Although puromycin inhibited both protein synthesizing systems, this effect was greatest in the presence of cytoplasmic ribosomes.

Animals↗
PubMed1977

Reversal of ethanol intoxication in humans: an assessment of the efficacy of L-dopa, aminophylline, and ephedrine.

The effect of postethanol treatment with L-Dopa, aminophylline and/or ephedrine was investigated. In one experiment, healthy, male, moderate drinkers ingested ethanol (0.8 g/kg) and then either L-Dopa (1.5 g), or placebo. In a second experiment, subjects ingested ethanol followed by aminophylline (200 mg), ephedrine (50 mg), aminophylline (200 mg) plus ephedrine (50 mg), or placebo. Double-blind, within-subjects, crossover designs were employed. Treatment with L-Dopa significantly reduced ethanol's effect on the electroencephalogram, motor coordination, and divided attention performance (t-test for paired data). Treatment with aminophylline and/or ephedrine also significantly reduced ethanol's effects on the electroencephalogram and motor coordination. The ethanol-antagonism may result from central noradrenergic stimulation.

Adult↗
PubMed1977

Alterations in cell free brain protein synthesis following ethanol withdrawal in physically dependent rats.

The effects of ethanol withdrawal were determined on cell free brain protein synthesis in physically dependent rats. Following the development of physical dependence, ethanol abstinence for 24 h resulted in decreased protein synthesis in cerebral tissue. The observed inhibition of [14C]leucine incorporation into protein was found to be reversible after 7 days of ethanol withdrawal. Although the ribosomes from control, ethanol-treated and ethanol-withdrawn animals were highly responsive to polyuridylic acid stimulation, the ribosomes from the control group consistently exhibited higher activity. The determination of protein content of the ribosomal fraction showed a significant increase following ethanol administration and was further enhanced by ethanol abstinence. The results suggest that ethanol-induced changes at the ribosomal level may result in defective association of mRNA causing depression of brain protein synthesis.

Alcoholism↗
PubMed1977

Drinking practices and cognitive functioning.

The relationships between drinking practices and cognitive functioning were examined in a non-patient sample. Neither the amount of alcohol consumed over a lifetime nor current frequency of drinking occasions was significantly (ps greater than .05) correlated with cognitive test scores. However, the quantity of alcohol consumed per drinking occasion was inversely related to performance on tests of abstraction, adaptive abilities and concept formation. The results suggest that social drinking may have deleterious effects on cognitive processes.

Adult↗