Biomedical subjects
G Dixon
Publications and source records attributed to G Dixon.
Parvalbumin-immunoreactive neurons in the human anteroventral thalamic nucleus.
We immunohistochemically characterised the expression of the calcium-binding protein parvalbumin in the normal human anteroventral thalamic nucleus (AVN). Two morphologically distinct neuronal populations were found to be parvalbumin-immunoreactive (PV-IR): a large population of lightly staining PV-IR neurons and a smaller population of intensely PV-IR neurons. This second type of neuron, which displayed many characteristics normally associated with GABAergic interneurons, has not previously been described in human thalamus. Thus, presumptive thalamic interneurons in the human brain can be further subtyped on the basis of immunoreactivity to parvalbumin. This may have implications for the understanding of thalamocortical function in the normal state and in dysfunctional conditions such as Wernicke-Korsakoff syndrome and schizophrenia.
Acquired immunoparalysis in paediatric intensive care: prospective observational study.
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Circulating platelet-neutrophil complexes represent a subpopulation of activated neutrophils primed for adhesion, phagocytosis and intracellular killing.
Platelets play a prominent role in linking the processes of inflammation, haemostasis and thrombosis. Recent studies have shown that platelets form heterotypic aggregates with leucocytes via platelet CD62P and leucocyte beta2 integrins. These interactions have been observed in vitro in blood taken from healthy volunteers and in clinical conditions in which thrombosis and inflammation are prominent. This study investigated the properties of platelet-neutrophil complexes (PNCs) in anticoagulated whole blood. At rest, neutrophils in PNCs exhibit a significantly more activated adhesion molecule profile than free neutrophils with increased CD11b expression and activation (increased binding of the CD11b/CD18 'activation reporter' monoclonal antibody 24) and decreased CD62L expression. In addition, neutrophils in PNCs phagocytosed significantly more Neisseria meningitidis and produced more toxic oxygen metabolites than free neutrophils. Stimulation with the platelet agonist adenosine diphosphate (ADP) led to further increases in CD11b expression and activation, loss of CD62L as well as increased phagocytosis and toxic oxygen metabolite production throughout the whole neutrophil population. When these experiments were repeated with the CD62P blocking antibody G1 the effects were inhibited to a variable extent, dependent upon the parameter under investigation. These results indicate that both soluble and contact-dependent factors contribute to platelet-mediated neutrophil activation. Platelet neutrophil complexes represent a large subpopulation of neutrophils with a more activated adhesion molecule profile, and a greater capacity for phagocytosis and toxic oxygen metabolite production. This study provides further support for a role for PNCs in both health and disease.
The clinical course of patients with acute myocardial infarction who are unsuitable for thrombolytic therapy because of the presenting electrocardiogram. UK Heart Attack Study Investigators.
OBJECTIVE: To examine the clinical characteristics and 30-day fatality rate among patients with electrocardiograms (ECGs) ineligible for fibrinolysis in a consecutive series in four general hospitals in the UK. METHODS: We studied 2439 consecutive patients who were identified from regular ward visits, surveillance of results from hospital laboratories, and hospital discharge coding. RESULTS: Thirty percent (732) of patients did not have ECGs eligible for fibrinolysis therapy, while indications were uncertain in 55 (2%). Within the ineligible group, patients presenting with ST depression (n = 294) had a higher 30-day fatality rate than those with ST elevation or left bundle branch block (26% versus 17%; P < 0.001); they represented 40% of the group ineligible for fibrinolysis therapy, or 12% of the total cohort. Thirty-day fatality rates in patients presenting with pathological Q waves and no diagnostic ST segment changes (n = 130), those with T wave changes but no other abnormality (n = 168) and those with a normal ECG (n = 128) were 10%, 5% and 3%, respectively. Despite their high fatality rate, fewer patients with ST depression were admitted to coronary care units than those with ECGs eligible for fibrinolysis therapy (61% versus 85%; P < 0.001) and 23% did not receive heparin. The coronary anatomy in a subset of patients with ST depression showed two- or three-vessel disease in 79% and left main stenosis in 9%. The rates of coronary revascularisation were low in all groups (< 10%). CONCLUSION: Patients with ECGs ineligible for fibrinolysis therapy are a disparate group, with a high rate of fatality occurring in patients who present with ST depression. The high prevalence of multiple vessel coronary disease in patients with ST depression suggests that a more active management strategy is required.
The Saccharomyces cerevisiae CCH1 gene is involved in calcium influx and mating.
The yeast Saccharomyces cerevisiae gene CCH1 (ORF YGR217w) shows high homology with animal calcium channel alpha1-subunit genes. Knock-out mutants were constructed of Cch1 and of Mid1 which is known to mediate Ca2+ influx in response to the alpha-mating pheromone. Cch1 is involved in calcium influx and the late stage of the mating process. The cch1 mutant sensitivity against the alpha-mating pheromone can be reduced by the addition of extra calcium. The product of this gene is likely to interact with the MID1 gene product in Ca influx or its control.
A reporter gene assay for fungal sterol biosynthesis inhibitors.
Acetoacetyl-CoA thiolase (ACoAT) catalyses the condensation of two acetyl-CoA molecules, the first step in the sterol biosynthetic pathway. We constructed a yeast strain containing a fusion of the promoter of the Saccharomyces cerevisiae ACoAT gene to a reporter gene (Escherichia coli beta-galactosidase). Reporter gene activity in this strain can be induced by a variety of inhibitors of sterol biosynthesis. These results suggest that the ACoAT gene is feedback regulated at the transcriptional level by products of the sterol biosynthetic pathway. The reporter gene approach described here may be used to screen chemical collections for compounds which inhibit fungal sterol biosynthesis.
Molecular biology and the major psychoses.
OBJECTIVE: To highlight the potential role of molecular biological studies in examining the expression of genes of interest in brain tissue to elucidate the pathophysiological basis of the major psychoses. METHOD: To review the principles underlying the available techniques for expression studies. RESULTS: Detection of messenger RNA by in situ hybridisation and quantitation by Northern analysis are powerful tools to detect abnormalities in gene expression in brain tissue. CONCLUSION: The availability of simple techniques to examine the expression of RNA and protein products of individual genes, including examination at the level of individual cells, offers a clear opportunity to define the molecular basis of the major psychoses.
Molecular biological investigations into the role of the NMDA receptor in the pathophysiology of schizophrenia.
OBJECTIVE: There is increasing acceptance that schizophrenia is associated with a generalised disorder in cortical neurodevelopment. The aim of this paper is to review the evidence that this disorder may be accounted for by abnormalities in mechanisms mediated by the main family of excitatory neuroreceptors in cortical brain systems, the N-methyl-D-aspartate (NMDA) glutamatergic receptors. METHOD: The neurobiological evidence is presented for an abnormality in cortical development related to synaptic pathology in schizophrenia. The unique functions of the NMDA receptor in information processing are described, especially its role in learning and memory, and in neural plasticity and brain development. It is argued that the cellular and molecular mechanisms which underlie learning and memory also govern normal brain development. Studies examining abnormalities in glutamatergic transmission in schizophrenia are reviewed. RESULTS: There is a substantial literature in support of the possibility that NMDA receptor abnormalities may be involved in the neurodevelopmental predisposition to schizophrenia, as well as in symptom production. CONCLUSIONS: Research to determine the role of the NMDA receptor in the pathophysiology of schizophrenia is warranted and now feasible. To be successful, this research will require the application of molecular biology techniques to postmortem brain tissue studies, in addition to traditional histochemical approaches.
Utilising molecular biological and histopathological techniques to study the dopaminergic system in patients with melancholia.
OBJECTIVE: To describe the rationale for investigating the dopaminergic system in patients with melancholia by applying molecular biological (notably, in situ hybridisation) and histopathological techniques in postmortem brain tissue. METHOD: Relevant advances in the functional neuroanatomy of frontostriatal circuits, as well as insights from clinical neuroimaging studies in primary and secondary depressive disorders, are presented. These are integrated with developments in the pharmacological and molecular characteristics of dopamine receptor subtypes and recognition of their selective anatomical distribution. RESULTS: Converging data from the basic and clinical neurosciences suggest that the pathophysiology of depressive disorders characterised by psychomotor phenomena, such as melancholia, may involve dysregulation of dopaminergic mechanisms within complex frontostriatal circuits. CONCLUSIONS: The key feature of in situ hybridisation is its capacity to test for variations in the functional components of designated biochemical systems within highly specific anatomical regions. We utilise this approach, in combination with relevant histopathological techniques, to test the structural and functional integrity of the dopaminergic system within key fronto-striatal circuits in patients who had exhibited psychomotor phenomena. The same approach can also be used to study the integrity of other relevant biochemical systems, such as the serotoninergic and noradrenergic systems, in patients with other mood disorders.
The changing profile of undergraduate dental students at the University of Otago 1992-1994.
Incoming students to the School of Dentistry, University of Otago, were surveyed in 1992, 1993, and 1994. Since 1992 there has been a marked trend for the students to originate from an overseas culture, to have more wealthy parents who support their education, and an increase in the numbers who expect to practice overseas upon graduation. This has implications for workforce planning in New Zealand and raises issues relating to equality of access to tertiary education.
Expression of the BCL-2 protein in normal and dysplastic bronchial epithelium and in lung carcinomas.
Although expression of the bcl-2 protein has been investigated in a number of non-haematological malignancies, little is known of its distribution in premalignant lesions. Expression of bcl-2 was investigated immunohistochemically in archival biopsies of normal (n = 8) and dysplastic bronchial epithelium (n = 56) and in 31 bronchial resection margins and their corresponding carcinomas. All dysplasias had lost the prominent basal staining pattern seen in histologically normal epithelium. Two were negative and six had occasional basal positive cells. In 37 cases up to 66% of the epithelial cells throughout the full epithelial thickness were bcl-2 positive with weak to moderate staining intensity. In 11 cases, all severe dysplasias, strong expression was observed in > 90% of the epithelial cells. Four patterns of bcl-2 expression in dysplasias were identified and an increasingly aberrant pattern of bcl-2 expression correlated with an increasing grade of dysplasia (Spearman's rank correlation, P < or = 0.0001). Sixty-five per cent of the carcinomas contained bcl-2-positive cells. Patients with non-small-cell lung carcinomas (n = 27) in which > 50% of the tumour cells were bcl-2 positive showed a survival advantage compared with those with 0-25% bcl-2-positive cells (P = 0.02). No correlation was found between p53 expression (Walker et al., 1994) and bcl-2 expression in dysplasias or carcinomas.
Disability in late adolescence. III: Utilization of health services.
Adolescent health service usage is a neglected research area. Data are important for planning of services and for prioritizing needs. A sample of 871 18-year-olds was surveyed about its use of health services in the preceding year. A significant proportion had made a consultation and were mostly satisfied with the service received. For a subsample of that cohort, who had a difficulty in their daily living, only a third had consulted a health professional for that difficulty over the past year. Help-seeking was related to the severity of that difficulty, particularly for the limitations that it imposed on everyday life. Some dissatisfactions with consultations were expressed in relation to expectations of the efficacy of treatment and to the communication of the health professionals.
Ergosterol biosynthesis inhibition: a target for antifungal agents.
The isoprenoid sterols play a crucial role in the viability of all fungi; those unable to synthesise ergosterol because of inhibition, growth conditions or mutation must take it up from the environment. A range of compound types have been discovered which interfere with the biosynthetic pathway from acetate to ergosterol and these compounds have antifungal actions. Inhibition of several of the steps has yielded agents which have been used with great success as medical and agrochemical agents. The most important biosynthetic steps that have been exploited are inhibition of squalene epoxidase, (the allylamines and tolnaftate) C14 demethylation (the azoles), delta 7,8 isomerase and delta 14 reductase which are inhibited by the morpholines. Recent research has shown that inhibition of C24 methyltransferase and C4 demethylation also yield antifungal agents. Combination studies demonstrate that synergy between agents of different types can be measured. Fungicidal effects were observed when a combination of two fungistatic agents was used.
Thermal transport in silicate glasses. II. Extended phonons.
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Depression in Parkinson's disease.
OBJECTIVE: The authors assessed the prevalence of major depression (DSM-III-R) among Parkinson's disease patients and compared this rate with that of matched physically disabled subjects. METHOD: The 30-item General Health Questionnaire and measures of physical disability were completed by all patients in Dunedin, New Zealand, identified as having Parkinson's disease. Patients scoring over 5 on the General Health Questionnaire were interviewed with the Structured Clinical Interview for DSM-III-R--Non-Patient Version. Each patient living in the community was matched for age, sex, and level of physical disability with a comparison subject who did not have a neurological condition. RESULTS: Of the 73 subjects with Parkinson's disease who agreed to participate and were judged not to be demented, 34.2% scored higher than 5 on the 30-item General Health Questionnaire, but only 2.7% met the criteria for major depression. No difference from the comparison group was found. CONCLUSIONS: The prevalence of major depression in patients with Parkinson's disease may be no greater than in age- and sex-matched physically disabled persons.
Durable power of attorney for health care. Legislature enacts specific format and guidelines.
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Fish hook injuries--wounded anglers and string theory.
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