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Biomedical subjects

G Goodall

Publications and source records attributed to G Goodall.

18 recordsLinked to original sources
PubMed1999

Attentional and mnemonic deficits associated with infectious disease in humans.

BACKGROUND: Infectious diseases are accompanied by behavioural and psychological changes that suggest the implication of the central nervous system. Among them, cognitive alterations have been reported, but their specificity and implication in everyday life are still largely unclear. The purpose of the present study was to evaluate and specify the everyday memory disturbances in sick human subjects and to determinate the role of fever in the appearance of these alterations. METHODS: The study was carried out in a military training centre for naval recruits. Ninety-one volunteer subjects, healthy (N = 30) or suffering from flu-like syndrome, with (N = 29) or without fever (N = 32), participated in this experiment and were administered a cognitive test (the ERBMT) according to a cross-sectional design for assessing various aspects of everyday memory. RESULTS: Sick subjects were specifically impaired in daily memory tasks that require the temporary management of a large amount of information. This impairment was similar for the feverish and apyretic sick subjects who both differed from the controls. CONCLUSION: These findings suggest that infectious disease disturbs the complex cognitive processes that might be associated with attentional functions. Moreover, these results show that fever is not a necessary condition for the appearance of these cognitive disturbances.

Adolescent↗
PubMed1997

Differential effects of lipopolysaccharide on pup retrieving and nest building in lactating mice.

Behavioral symptoms of sickness that develop in response to lipopolysaccharide (LPS) and proinflammatory cytokines include depressed locomotion, anorexia, and reduced social activities. The way maternal behavior is affected in response to cytokines has, however, not yet been investigated. We checked that lactating mice are sensitive to LPS by showing that LPS- (400 microg/kg, ip) injected mice ate and drank less than saline-injected mothers and displayed a decreased rectal temperature. At an ambient temperature of 22 degrees C, nest building was significantly decreased in LPS-treated mothers compared to saline-treated animals, whereas pup retrieving, while slower, was still present and globally as efficient as for saline-treated mice. In a second experiment, dams were either injected with physiological saline or LPS but were also exposed to a cold ambient temperature (6 degrees C) or kept in standard external condition (22 degrees C). LPS-treated mice exposed to cold expressed not only pup-retrieving but also nest-building activity. These differential results indicate that the behavioral expression of LPS-induced sickness depends on the priority of the behavior under consideration.

Animals↗
PubMed1996

Creating RNA bulges: cleavage of RNA in RNA/DNA duplexes by metal ion catalysis.

The manipulation of a single-stranded RNA target by forming different RNA/antisense hybrids demonstrates the possibility of cleaving the RNA strand within duplexes. This was achieved using the sequence composition of the antisense oligonucleotide, an approach that results in various bulges [unpaired base(s)] in the RNA target, which is then cleavable at these specific bulge sites under free metal ion or metal complex catalysis. RNA cleavages promoted by metal ions were performed under mild conditions and characterized by separating the RNA fragments carrying end label. The observed products result from intramolecular transesterification causing RNA strand scission. No detectable cleavage of the RNA was observed with either a fully complementary RNA/antisense hybrid or a bulged base in the antisense strand. A molecular modeling study of the RNA backbone suggests that the local conformation of the RNA backbone at a bulge in such hybrid duplexes greatly facilitates the metal-assisted catalytic cleavage. Endonucleolytic RNA cleavage within an RNA/antisense hybrid by metal complexes attached to the antisense oligonucleotide might lead to a new approach in antisense technology with artificial ribonucleases which operate with catalytic turnover.

Base Sequence↗
PubMed1996

Cognitive sequelae of propofol anaesthesia.

As with any substance that interferes with nervous system functioning, anaesthetics are likely to have neural effects the duration of which extend beyond the acute loss of consciousness. Studies of recovery after anaesthesia have shown that physiological effects and psychomotor functions return to pre-anaesthesia levels within at most 90 min of the cessation of propofol administration. To date no report has been published concerning the possible longer term effects of propofol anaesthesia on higher cognitive functions such as learning, language, reasoning and planning. We evaluated a range of cognitive tasks (short and long-term memory, attention, language comprehension and planning) up to 6 h after cessation of Propofol administration, and found that this set of cognitive functions was still depressed after 3 h, but had recovered by 6 h. The results suggest that, for their security, patients should be remain in a supervised environment for at least 3 h after propofol anaesthesia, and that oral information to patients within those 3 h should be avoided.

Adolescent↗
PubMed1996

[Evaluation of cognitive functions after anesthesia with propofol].

OBJECTIVES: To assess the disturbances and delay of recovery of cognitive functions following propofol anaesthesia, and to evaluate a series of simple cognitive recovery tests. STUDY DESIGN: Prospective comparative non randomized clinical study. PATIENTS: Two groups of non premedicated patients, of ASA physical class 1 and 2 were studied. The control group (n = 11) included patients undergoing gastric fibroscopy under local anaesthesia. The propofol group (n = 22) consisted of patients scheduled for coloscopy under propofol anaesthesia. METHODS: The gastric fibroscopy was performed under local anaesthesia with lidocaine and the coloscopy under general anaesthesia with propofol as the sole anaesthetic. Five cognitive tests, designed to assess short-term memory, delayed memory, the ability to plan complex tasks, attention, and language comprehension were conducted the day before, and 1 hour, 3 hours and 6 hours after the endoscopy. RESULTS: The cognitive functions remained significantly depressed for at least 3 hours after anaesthesia, and recovered fully about 6 hours after the cessation of propofol administration. The capacity for planning was the most heavily affected. CONCLUSIONS: Complete recovery can be evaluated by simple cognitive tests, which showed that cognitive functions are impaired over a longer period than psychomotor functions. Oral instructions may therefore not be fully understood by the patient within 3 hours after anaesthesia, emphasizing the importance of written instructions and the essential role played by a well-informed accompanying person.

Adolescent↗
PubMed1996

Human interleukin-3 (IL-3) induces disulfide-linked IL-3 receptor alpha- and beta-chain heterodimerization, which is required for receptor activation but not high-affinity binding.

The human interleukin-3 receptor (IL-3R) is a heterodimer that comprises an IL-3 specific alpha chain (IL-3R alpha) and a common beta chain (beta C) that is shared with the receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-5. These receptors belong to the cytokine receptor superfamily, but they are structurally and functionally more related to each other and thus make up a distinct subfamily. Although activation of the normal receptor occurs only in the presence of ligand, the underlying mechanisms are not known. We show here that human IL-3 induces heterodimerization of IL-3R alpha and beta c and that disulfide linkage of these chains is involved in receptor activation but not high-affinity binding. Monoclonal antibodies (MAb) to IL-3R alpha and beta c were developed which immunoprecipitated, in the absence of IL-3, the respective chains from cells labelled with 125I on the cell surface. However, in the presence of IL-3, each MAb immunoprecipitated both IL-3R alpha and beta c. IL-3-induced receptor dimers were disulfide and nondisulfide linked and were dependent on IL-3 interacting with both IL-3R alpha and beta c. In the presence of IL-3 and under nonreducing conditions, MAb to either IL-3R alpha or beta c immunoprecipitated complexes with apparent molecular weights of 215,000 and 245,000 and IL-3R alpha and beta c monomers. Preincubation with iodoacetamide prevented the formation of the two high-molecular-weight complexes without affecting noncovalent dimer formation or high-affinity IL-3 binding. Two-dimensional gel electrophoresis and Western blotting (immunoblotting) demonstrated the presence of both IL-3R alpha and beta c in the disulfide-linked complexes. IL-3 could also be coimmunoprecipitated with anti-IL-3R alpha or anti-beta c MAB, but it was not covalently attached to the receptor. Following IL-3 stimulation, only the disulfide-linked heterodimers exhibited reactivity with antiphosphotyrosine antibodies, with beta c but not IL-3R alpha being the phosphorylated species. A model of IL-3R activation is proposed which may be also applicable to the related GM-CSF and IL-5 receptors.

Animals↗
PubMed1995

Pyrogens specifically disrupt the acquisition of a task involving cognitive processing in the rat.

In addition to changes in body temperature and other metabolic and physiological responses corresponding to immune activation, pyrogens can induce profound behavioral changes referred to collectively as sickness behavior. One feature of sickness behavior, sometimes reported in clinical settings, but rarely exposed to experimental analysis, is depressed cognitive functioning. The present series of five experiments sought to demonstrate the existence of specific cognitive deficits in rats, independently of any confounding performance effects of pyrogen injections. The behavioral task used, called autoshaping, consisted of presenting hungry Wistar rats with a stimulus (introduction of a retractable lever) that predicted food delivery. Control rats quickly learned to press the lever, although this response does not influence the probability of food delivery. When pyrogens (250 micrograms/kg lipopolysaccharide, 4 micrograms/rat interleukin-1 beta, or 300 mg/rat yeast) were injected to rats during acquisition of this task, they severely disrupted acquisition while the pyrogen was active. The same treatments were, however, without effect on performance when injected later, when performance had stabilized. It is argued that these results demonstrate specific, performance-independent effects of pyrogens on the cognitive processes needed for the acquisition of this task. The results are discussed in terms of the relationship between these effects and the cytokines induced in the brain by pyrogens, and in terms of the exact nature of the cognitive process likely to be affected.

Animals↗
PubMed1995

Compared effects of cold ambient temperature and cytokines on macronutrient intake in rats.

To compare the effects of cold and cytokines on spontaneous dietary self-selection, rats (n = 14) were given free access to carbohydrate, protein and fat diets for 4 hours a day. After a 10-day period of habituation to this regimen, they were injected with physiological saline, IL-1 beta (4 micrograms/rat ip) or LPS (83 micrograms/rat ip) or exposed to cold (5 degrees C), the order of treatments being randomized. LPS- and IL-1 beta-treated rats ate less, but ingested relatively more carbohydrate and less protein whereas relative fat intake remained unchanged. In contrast, cold exposed rats slightly increased their food intake but in a non significant manner. They also increased their relative intake of fat but did not change their relative intake of carbohydrate and protein. These results are discussed with respect to the pyrogenic and metabolic effects of cytokines.

Animals↗
PubMed1995

Behaviour problems in childhood and stressors in early adult life. I. A 20 year follow-up of London school children.

The research presented in this paper examined the relationship between the presence of childhood behaviour problems and the rate of life events and difficulties in early adult life. Data are presented from a 20 year follow-up study of a sample of inner London school children first studied when they were aged 10. The key finding was that emotional or behavioural disturbance in childhood was associated with a marked increase in the rate of severely negative events and difficulties some two decades later. This increase was only obtained for stressors with severe negative impact of the type shown in previous investigation to be associated with the onset of psychiatric disorder. Additional results demonstrated that this main finding could not be accounted for by stressors that were a result of adult psychiatric disorder, by the respondent's own behaviour, or by continuing association with the family of origin. The need for a lifespan developmental approach to the well-established stressor-illness is discussed.

Adolescent↗
PubMed1995

Corticosterone regulates behavioral effects of lipopolysaccharide and interleukin-1 beta in mice.

The modulatory role of endogenous corticoids in the behavioral effects of lipopolysaccharide (LPS) and recombinant human interleukin-1 beta (IL-1 beta) was studied in mice. Adrenalectomy enhanced the depression of social exploration induced by subcutaneous injection of 200 ng of IL-1 beta or 2 micrograms of LPS. This effect was mimicked by an acute injection of the progesterone antagonist RU-38486 (0.25-1 mg). Chronic replacement with a 15-mg corticosterone pellet abrogated the enhanced susceptibility of adrenalectomized animals to 200 ng of IL-1 beta but had only partial protective effects on their response to 400 ng of IL-1 beta and LPS. These results suggest that the pituitary-adrenal response to cytokines exerts an inhibitory feedback on the cell targets that mediate the behavioral effects of LPS and IL-1 beta.

Adrenalectomy↗
PubMed1994

Ethological study of the effects of tetrahydroaminoacridine (THA) on social recognition in rats.

Two major difficulties confront ethopharmacological investigations on cognitive abilities such as social recognition in drug-treated animals involved in free social interactions. The first concerns the choice of the most relevant behaviours, those reflecting the cognitive abilities attributed to the animals and assessing the specificity of the drug activity, and those reflecting non-specific drug effects. The second refers to the experimenter's awareness that in contrast to physical objects, social stimuli respond to drug-treated subjects and that their own level of responsiveness may influence the changes of drug-treated subjects' social interest. In addition, their contribution may vary according to the different treatments the drug-treated subjects receive. In examining the effects of tetrahydroaminoacridine (THA) at doses of 0.3, 1 and 3 mg/kg on the ability of adult male rats to recognize previously encountered conspecifics, we attempted to take into consideration such difficulties. A detailed behavioural profile of drug-treated rats was reported to separate specific from non-specific effects of THA. In addition, rats were assigned an index of responsibility for contact which takes into account the interactive dimension of each dyad and allows relevant comparisons between different treatments. The doses of THA which were found to decrease the duration of exploration of a familiar juvenile were also found to decrease the number of contacts initiated by the drug-treated subjects. THA induced a relative increase in body care by comparison to saline treatment. However, it had no effect of locomotor activity and rearing of the subjects. These findings enable dissociation of the effects of THA on cognitive versus non-cognitive processes.

Aging↗
PubMed1987

Abnormal patterns of maze patrolling in the mutant mouse staggerer.

Two experiments describe the abnormal patterns of maze patrolling of adult mutant staggerer mice. The clinical symptoms of this mutant involve exclusively postural and gait abnormalities, apparently due to a disruption of cerebellar architecture leading to a vast reduction in cell numbers and size of this structure. This clinical feature can easily account for the first clear difference reported in these experiments, involving a reduction in the total ambulatory activity in a maze by this mutant. The more interesting result involves different qualitative aspects of the maze patrolling by staggers, compared to normal litter-mate controls. The experiments measured the distribution of subjects' visits to different maze locations, and varied the configuration and the amount of familiarization with the maze. Neither of these factors significantly influenced the basic results. These were the staggerers confined their ambulatory activity to a smaller number of different locations, which were more intensively visited compared to normals, and the staggerers showed a pronounced tendency to return to the place that was most recently visited, compared to a tendency by the normals to avoid that location. It is suggested that these results could be due either to abnormal novelty reactions or to a reduced tendency to pursue an initiated trajectory.

Animals↗
PubMed1985

Permanency of gait improvement induced by vestibular stimulation in the mutant mouse staggerer.

Among the several methods that have been used to investigate the impact of environmental enrichment, on the behavior of an animal, the use of behaviorally deficient mutant mice has been especially useful. The use of this model allows one to investigate functional recovery compared to a known baseline (the normal animal) without the trauma and imprecision associated with surgical intervention. The present study extends a previous investigation that demonstrated a significant improvement in certain measures of the gait of the cerebellar mutant mouse staggerer, as a result of daily vestibular, muscular and visual stimulation. The results of the present study concerned the durability of that observed improvement. No clear-cut conclusion as to the permanency of the stimulation's effects could be drawn, because results differed according to the measures used. When tested two months after the end of the stimulation period the mutants ran more slowly, with as many "errors" as unstimulated mutants, leading one to infer a deleterious effect of the stimulation. On the other hand, if one considers only the number of "errors" during the test, one may conclude that early stimulation has a permanent advantageous effect of increasing the staggerer's receptivity to further stimulation. Other measures lead to more ambiguous conclusions. Finally, it is argued that even though true improvement in the staggerer's gait can be inferred from these results, and that at least some aspects of that improvement seem to be long-lasting, the generality of the findings cannot validly be extended beyond the precise experimental conditions.

Acoustic Stimulation↗
PubMed1984

Morphological complexity and cerebral lateralization.

Fifteen agentive nouns, all with meanings derivable from the meaning of the stem verb, were presented tachistoscopically to right-handed subjects. Non-agentive nouns were also presented, and subjects were asked to produce the plural form in addition to the simple stimulus form. The results show a significant right visual field advantage for the agentive and plural nouns, but no significant advantage in either field for the simple nouns. These findings suggest that the left hemisphere is superior in processing nouns which are morphologically complex.

Adult↗
PubMed1984

Successful overshadowing and blocking in hippocampectomized rats.

Overshadowing (Experiment 1) and blocking (Experiment 2) were investigated using a conditioned suppression paradigm in rats. Neither hippocampectomy nor cortical control lesions affected the extent to which a salient stimulus overshadowed a less salient one. Nor did the lesions affect the extent to which a stimulus that was highly correlated with shock overshadow a stimulus that was less well correlated with shock. Finally, the lesions did not alter the extent to which a previously reinforced stimulus blocked conditioning to another stimulus when both were presented as a reinforced compound stimulus. It is thus possible for hippocampectomized rats to show apparently normal overshadowing and blocking, at least under some testing conditions.

Animals↗