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Biomedical subjects

G Goodall

Publications and source records attributed to G Goodall.

At least 19 recordsLinked to original sources
PubMed2006

Dopamine manipulations limited to preexposure are sufficient to modulate latent inhibition.

Four experiments are reported that demonstrated that dopamine (DA) transmission is involved in the acquisition of latent inhibition (LI) of a conditioned taste aversion. LI refers to weaker conditioning as a consequence of nonreinforced preexposure (PE) of the future conditioned stimulus. Although it is known to depend on DA transmission during the conditioning phase, it is usually thought that the cognitive processes involved in the establishment of LI (during the PE phase) are DA independent. Either amphetamine (AMPH; 0.5 or 1.0 mg/kg) or haloperidol (HAL; 0.1 mg/kg) were injected before 1 or all of the 3 PE sessions. AMPH blocked the acquisition of LI if it was injected before each or before only the last PE session and HAL potentiated LI.

Amphetamine↗
PubMed2005

Ice-active proteins from the Antarctic nematode Panagrolaimus davidi.

The Antarctic nematode Panagrolaimus davidi has an ice-active protein that shows recrystallization inhibition but no thermal hysteresis. It belongs to a class of ice-active proteins found in a variety of freezing-tolerant organisms that display insignificant levels of thermal hysteresis in the context of the environmental temperatures to which they are exposed. The recrystallization inhibition activity of the P. davidi ice-active protein is present at low concentrations, is relatively heat stable, is affected more by acid than by alkaline pH, is not calcium dependant and is not affected by reagents that target carbohydrate residues or sulphydryl linkages. A hexagonal ice crystal growth form also indicates the presence of an ice-active protein. This protein could have important functions in the survival of intracellular freezing by this organism by controlling the stability of ice after its formation.

Acclimatization↗
PubMed2004

Freezing and cryoprotective dehydration in an Antarctic nematode (Panagrolaimus davidi) visualised using a freeze substitution technique.

The pattern of ice formation during the freezing of Panagrolaimus davidi, an Antarctic nematode that can survive intracellular ice formation, was visualised using a freeze substitution technique and transmission electron microscopy. Nematodes plunged directly into liquid nitrogen had small ice crystals throughout their tissues, including nuclei and organelles, but did not survive. Those frozen at high subzero temperatures showed three patterns of ice formation: no ice, extracellular ice, and intracellular ice. Nematodes subjected to a slow-freezing regime (at -1 degrees C) had mainly extracellular ice (70.4%), with the bulk of the ice in the pseudocoel. Some (24.8%) had no ice within their bodies, due to cryoprotective dehydration. Nematodes subjected to a fast-freezing regime (at -4 degrees C) had intracellular (54%) and extracellular (42%) ice. Intracellular ice was confined to the cytoplasm of cells, with organelles in the spaces in between ice crystals. The survival of nematodes subjected to the fast-freezing regime (53%) was less than those subjected to the slow-freezing regime (92%).

Acclimatization↗
PubMed2001

Acute interferon-alpha administration modulates sucrose consumption in the rat.

One of the two core symptoms of depression as defined by the Diagnostic and statistical manual of mental disorders (DSM-IV) (American Psychiatric Association) is anhedonia, or a loss of interest or pleasure. Sucrose consumption has been described as a valid measure of sensitivity to reward. In the present set of studies, changes in sucrose consumption (three-bottle test using 1, 8 and 32% sucrose) were taken as a measure of the anhedonic effect of interferon-alpha (IFN-alpha). Sucrose tests were carried out following the i.p. administration (20 min pre-treatment time) of Recombinant Human Interferon-alphaA (rHIFN-alpha), 10(1), 10(2), 10(4) units(U) and Rat Interferon alpha (rRIFN-alpha), 1,10 and 100 IRU. Both types of IFN-alpha produced a decrease in sucrose consumption and drinking rate (DR) at the highest doses, with the greatest inhibition being at the lowest sucrose concentration (1%). Longer pre-treatment times with rHIFN-alpha (40 and 80 min prior to commencement of 1 h drinking test) resulted in insignificant effects. Significant hypothermia relative to vehicle-injected rats was observed following interferon administration in the 20 min pre-treatment condition, but showed no significant difference when compared to vehicle at 40 or 80 min. Overall these results confirm a depression-like behavioural syndrome (anhedonia) following administration of IFN-alpha.

Animals↗
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

Some preliminary observations on the possible relationship between ammonia production from soiled bedding in calf rearing sheds and calf illness.

A limited field study of covered facilities used for raising dairy calves suggested that respiratory disorders and death rates were highest when calves were continuously housed on bedding composed of wood shavings, where ventilation was poor and where automatic feeders were installed. High concentrations of ammonia were found in the urine-soaked bedding following overnight incubation. A prolific growth of mixed micro-organisms isolated from the shavings rapidly colonised plates of selective urea medium. Death rates of 10% and 13.5% were observed on two properties. Respiratory distress was common and lung disease was intractable to treatment on these farms. A histopathological diagnosis of subacute purulent pneumonia with distal necrotising bronchiolitis was made, similar to lung lesions produced experimentally in cats, guinea pigs and rabbits exposed to ammonia gas.

Journal Article↗
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↗