Biomedical subjects

P Mitchell

Publications and source records attributed to P Mitchell.

At least 433 records · Page 24Linked to original sources

PubMed1990

The three-dimensional structure and function of Escherichia coli ribosomal RNA, as studied by cross-linking techniques.

A large number of intra-RNA and RNA-protein cross-link sites have been localized within the 23S RNA from E. coli 50 S ribosomal subunits. These sites, together with other data, are sufficient to constrain the secondary structure of the 23 S molecule into a compact three-dimensional shape. Some of the features of this structure are discussed, in particular, those relating to the orientation of tRNA on the 50 S subunit as studied by site-directed cross-linking techniques. A corresponding model for the 16S RNA within the 30 S subunit has already been described, and here a site-directed cross-linking approach is being used to determine the path followed through the subunit by messenger RNA.

Base Sequence↗

PubMed1990

Effect of the anesthetic agent propofol on hormonal responses to ECT.

Propofol is a new anesthetic induction agent that reduces electroconvulsive therapy (ECT) seizure duration. To indirectly investigate the effect of propofol on ECT-induced acute central neurotransmitter changes, we studied neuroendocrine responses in 25 primary depressed subjects treated with ECT under either propofol or thiopentone anesthesia. Blood samples were taken prior to ECT, and then at regular intervals for 2 hr. Only the prolactin response correlated significantly with seizure duration (r = 0.52, p less than 0.01). Subjects given propofol had significantly reduced adrenocorticotropin (ACTH) (p less than 0.01) and cortisol (p less than 0.05) responses compared to thiopentone, which were independent of seizure duration. There was a trend towards a reduction in the prolactin response with propofol compared to thiopentone, but this was dependent upon the diminished seizure duration. The results indicate that propofol affects endocrine responses to ECT by two distinct mechanisms: decreasing prolactin by reducing the seizure duration and decreasing ACTH and cortisol by another process, possibly via a reduction in central noradrenergic activation.

Adrenocorticotropic Hormone↗

PubMed1990

Selective isolation and detailed analysis of intra-RNA cross-links induced in the large ribosomal subunit of E. coli: a model for the tertiary structure of the tRNA binding domain in 23S RNA.

Intramolecular RNA cross-links were induced within the large ribosomal subunit of E. coli by mild ultraviolet irradiation. Regions of the 23S RNA previously implicated in interactions with ribosomal-bound tRNA were then specifically excised by addressed cleavage using ribonuclease H, in conjunction with synthetic complementary decadeoxyribonucleotides. Individual cross-linked fragments within these regions released by such 'directed digests' were isolated by two-dimensional gel electrophoresis and the sites involved in the cross-links determined using classical oligonucleotide analysis techniques. Using this approach, seven 'new' cross-links could be precisely localised, between positions 1782 and 2608-2609, 1940 and 2554, 1941-1942 and 1964-1965, 1955 and 2552-2553, 2145-2146 and 2202, 2518-2519 and 2544-2545, and between positions 2790-2791 and 2892-2895 in the 23S RNA sequence. These data, in conjunction with data from RNA-protein cross-linking studies carried out in our laboratory, were used to define a model for the tertiary organisation of the tRNA binding domain of 23S RNA 'in situ', in which the specific nucleotides associated with tRNA binding in the 'A' and 'P' sites are clustered at the base of the 'central protuberance' of the 50S subunit.

Base Sequence↗

PubMed1990

When do children overestimate their knowledge of unfamiliar targets?

We report four investigations in which 5 to 7 year olds judged whether or not they knew familiar- and unfamiliar-named targets. Under some conditions judgments were made in relation to performance on a relevant task, e.g., children judged whether they knew the picture they had picked from a set was the target. Under other conditions, children judged their state of knowledge not in relation to performance, e.g., they answered "Do you know who (target) is?" Under both types of condition, children nearly always made correct "know" judgments when targets were familiar. Correct "don't know" judgments about unfamiliar targets were relatively common when judgments were not made in relation to performance on a task (average scores 80-90% correct), but were less frequent when knowledge was judged in relation to performance on a task (average scores 40-70% correct). Knowledge judged in relation to performance was overestimated even when children did not choose the picture they thought might be the target before making their judgment, when the pictures were face-down, and when children predicted performance on a task not yet present. It seems that although children can make relatively accurate judgments of their own knowledge states, they tend to overestimate their competence when assessing their knowledge in relation to performance on a task. We discuss why this might be.

Attention↗

PubMed1990

Hormonal responses to fenfluramine in depressed and control subjects.

To investigate central neurotransmitter function in depression, baseline levels of serum cortisol and prolactin and the responses of these hormones to the putative serotonin agonist fenfluramine (60 mg, oral) were examined in 27 depressed patients and 14 normal subjects. Baseline cortisol was significantly elevated (P less than 0.01) in depressed subjects, whilst baseline prolactin was significantly reduced (P = 0.01) after covarying for cortisol. Although there were no significant abnormalities in either the prolactin or the cortisol response to fenfluramine in the total depressed group, the peak increase in prolactin levels (delta PRL) was significantly reduced (P less than 0.05) in subjects with endogenous depression. Analysis of covariance demonstrated, however, that the reduced delta PRL was partially dependent upon the abnormal baseline prolactin and cortisol levels. These results indicate the necessity of accounting for these baseline effects when investigating hormonal responses to the putative serotonergic challenges. The abnormal baseline findings are consistent with increased central noradrenergic activity in depression.

Adult↗

PubMed1990

Perceived dysfunctional intimate relationships: a specific association with the non-melancholic depressive subtype.

Associations between perceptions of dysfunctional current intimate relationships and subtypes of depressive disorders were quantified in a sample of 136 patients, using the Intimate Bond Measure (IBM). Deficient care was two to three times more likely to be reported by patients with non-melancholic disorders than by matched subjects, but was no more likely to be reported by patients with melancholic disorders, suggesting a risk factor selective for depressive type. Patients who reported markedly deficient care in childhood were more likely to report very poor current intimate relationships. For the remaining patients, however, no evidence of continuity between a dysfunctional parental relationship and a current dysfunctional intimate relationship was found.

Adult↗

PubMed1990

Dose-response effects of pentoxifylline on erythrocyte filterability: clinical and animal model studies.

Ten patients with chronic occlusive arteriosclerosis received single oral doses of 100, 200, 400, 800, and 1200 mg pentoxifylline in a single-blind, placebo-controlled study. Blood samples were drawn at baseline and at 2 hour intervals for 6 hours. Drug and metabolite levels, as well as red cell filterability (deformability), were determined on all blood samples. Statistically significant dose-response increases of red cell filterability were found 4 and 6 hours after oral medication with the dosages of 200 to 1200 mg pentoxifylline. These changes were proportional to the plasma levels of pentoxifylline and metabolites 1 and 5 of this agent. Attempts were made to develop a suitable animal-screening method for agents with similar activity and to determine whether red blood cells in the absence of disease-related abnormalities may respond to this type of therapy. Five healthy Macaca arctoides monkeys were given 24 mg/kg pentoxifylline intravenously, and measurable but lesser increases in red cell deformability were recorded than in the patients.

Animals↗

PubMed1990

Effect of backrest position on intracranial and cerebral perfusion pressures.

Prevention of secondary injury resulting from increased intracranial pressure (ICP) and the promotion of adequate cerebral blood flow are major concerns of health care professionals caring for the neurologic patient. For the past two decades studies have indicated raising the head of the bed lowers ICP. However, when perfusion pressure has been measured along with ICP, results have been conflicting. Some investigators found cerebral perfusion pressure (CPP) decreased with head elevation; others found no change. This study examined the effect of four backrest positions (flat, head elevated 30 degrees, head elevated 30 degrees with knee gatch elevated and reverse Trendelenberg) on ICP, CPP and transcranial doppler flow velocities in four subjects. Each was placed in the flat position for 15 minutes followed by 15 minutes in one of the three randomly assigned elevated backrest positions. Findings suggest backrest position should be individually assigned after analysis of the response of the ICP, CPP and blood flow velocities to that position.

Adult↗

PubMed1990

Update and implications from the Newcastle diabetic retinopathy study.

Over 11 years from 1977 a large study of diabetic retinopathy has been conducted in Newcastle and in 1988, 5519 diabetic subjects had been assessed. Where possible, all had retinal photography. Prevalence rates for any retinopathy, proliferative retinopathy and maculopathy were assessed in relation to the known duration of diabetes for subjects diagnosed before or after age 30 years. These data indicate a peak of retinopathy prevalence in the second or third decade of diabetes with slightly lower rates in longer survivors. Treatment with insulin was associated with a higher retinopathy prevalence. Incidence rates for the new development of background retinopathy in previously unaffected subjects show a peak late in the first decade of diabetes in young-onset cases, while in the older-onset group, the peak occurs in the second decade of diabetes. Over all, 8% of diabetics without retinopathy developed it per year. The implications of this data for the routine management of diabetic patients is discussed and the current recommendations for retinal screening by the Australian Diabetes Society are outlined.

Adult↗

PubMed1990

Depressive type and state effects on personality measures.

We examine the hypothesis that the effect of mood state on personality questionnaire scores is more a function of diagnosis than of depression severity. Sixteen endogenous and 83 neurotic depressives completed a battery of personality questionnaires at a baseline assessment and again 20 weeks later. Scores on the personality measures changed significantly. Endogenous depressives were found to have more pronounced changes on measures of dependence and timidity, but when change in mood state was partialed out only one of the dependence measures and timidity remained significant. Thus the hypothesis only received partial support--change in mood state appears to be the major factor in elevating personality questionnaire scores.

Adolescent↗

PubMed1990

Personality differences between patients with remitted melancholic and nonmelancholic depression.

Seventy-five patients with remitted depression were categorized as having melancholic-endogenous or non-melancholic-nonendogenous depression according to DSM-III criteria, Research Diagnostic Criteria, and the Newcastle endogeneity scale. The patients' scores on four personality scales--the Eysenck Personality Inventory, the Interpersonal Dependency Inventory, locus of control, and the Interpersonal Sensitivity Measure--were then compared. Patients with nonmelancholic-nonendogenous depression were generally rated as having more vulnerable personality styles, but the differences were dependent on the particular diagnostic system used. A principal components analysis isolated three underlying personality constructs--dependency, introversion, and timidity. Patients with nonmelancholic-nonendogenous depression scored as significantly more dependent.

Adult↗

PubMed1990

Classifying depression by mental state signs.

The possibility that separation of a categorical depressive disease ('melancholia') from remaining depressive disorders can be improved by assessment of mental state signs was examined in patients treated by representative Sydney psychiatrists and patients referred to a specialised mood disorders unit. A set of signs, principally assessing retardation, was derived within the two samples by principal-components and latent-class analyses. Scores were significantly correlated with clinical, DSM-III, and RDC diagnoses, and appeared independent of severity, suggesting that melancholia can be defined phenomenologically. Scores were also associated with several 'validating' factors. Comparative analyses of a refined list of melancholia symptoms suggested that ratings of defined signs are likely to have greater capacity than symptom ratings to differentiate melancholia from residual depressive disorders.

Adjustment Disorders↗

PubMed1990

Hormonal responses to fenfluramine in depressive subtypes.

In order to study putative differences in central neurotransmitter function in depressive subtypes, serum cortisol and prolactin responses to the putative serotonin agonist fenfluramine were examined in 30 subjects with major depression. Patients with endogenous depression (melancholia) as defined by each of ICD-9, DSM-III, RDC and Newcastle scale demonstrated a reduced prolactin response to 60 mg oral fenfluramine when compared with non-endogenous subjects. This was independent of either prolactin or cortisol baseline levels, and indicates that there are differences in brain neurotransmitter function in the endogenous and non-endogenous subtypes of depression. Basal prolactin levels were reduced in bipolar compared with unipolar subjects, and delusional compared with non-delusional patients, although there were no differences in the prolactin responses to fenfluramine between these subgroups. Basal cortisol levels and cortisol response to fenfluramine did not distinguish between any of the subtypes.

Administration, Oral↗

PubMed1990

The Bourdon illusion occurs with straight-, right-angle-, and parallel-edge figures.

The Bourdon illusion is the apparent bentness of the straight edge of a figure consisting of two elongated triangular components arranged apex to apex. In three experiments, the illusion was shown to occur in the opposite direction, with the components arranged base to base. It was also shown to occur with the component edges at right angles and parallel. With the edges at right angles, the illusion also occurred in one direction when the components were apex to apex and occurred in the opposite direction when they were base to base. Supplementary observations indicated that the illusion is stronger when the components are relatively small and widely separated and eliminated when one of the two edges is curved.

Adult↗

PubMed1990