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Biomedical subjects

C MacLeod

Publications and source records attributed to C MacLeod.

At least 19 recordsLinked to original sources

Antibiotic-associated colitis and cystic fibrosis.

The use of antibiotics in patients with cystic fibrosis is widespread, and fecal carriage of Clostridium difficile occurs in up to 50% of these patients; however, antibiotic-associated colitis appears to be a rare occurrence. The reasons why this is so remain unknown. A case of antibiotic-associated colitis occurring in a patient with cystic fibrosis is described. Possible mechanisms for the rarity of antibiotic-associated colitis are reviewed and implications for prompt diagnosis and therapy are discussed.

Adult

Anxiety and the selective processing of emotional information: mediating roles of awareness, trait and state variables, and personal relevance of stimulus materials.

Previous research has established that anxiety patients demonstrate a cognitive bias that selectively favours the processing of threat related information. The current experiment employs a variant of a well established colour naming paradigm to address three issues concerning the nature of this anxiety linked pattern of selective processing. First, by considering non-clinical subjects and employing an experimental design capable of dissociating the influence of state and trait anxiety, the current study addresses the hypothesis that state anxiety elevations will elicit differential patterns of selectivity in high and low trait anxious subjects. Second, by presenting stimulus materials within or outside awareness, the study addresses the hypothesis that these processing biases occur automatically, without requiring the use of consciously mediated strategies. Third, by including both emotionally valenced stimulus materials which are related to, and which are unrelated to, the particular source of stress experienced by the subjects, the experiment addresses the hypothesis that such anxiety linked processing biases will be restricted to materials falling within the domain of current personal concern. The results of the present study clearly demonstrate that these three issues are not independent. Fundamentally different patterns of anxiety linked selective processing were observed when stimuli were presented outside awareness, permitting only automatic cognitive processing, and when stimuli were presented within awareness, permitting the use of consciously mediated strategies. The relative roles played by state and trait variables, and the degree to which these effects were influenced by the personal relevance of the stimulus materials, differed in each case. The implications of these findings for future research in this field are discussed.

Adult

Individual differences in the selective processing of threatening information, and emotional responses to a stressful life event.

Previous research has established that high levels of trait anxiety commonly are associated with an automatic pattern of encoding selectivity, operating to favour the processing of emotionally threatening information. It has been suggested that this processing bias may play a functional role in mediating emotional vulnerability by moderating affective responses to stressful real life events. The current experiment employs a longitudinal design, capable of addressing the central predictions arising from this theoretical position. Thirty-one women awaiting colposcopy investigation were screened on both traditional questionnaire measures of emotional vulnerability, and on a modified emotional Stroop task that provided objective indices of their automatic and strategic patterns of processing selectivity. Subsequently, those 15 women who later received a diagnosis of cervical pathology reported the degree to which this diagnosis had impaired their level of emotional functioning. The results confirm that, at the initial test time, trait anxiety was indeed associated with an apparently automatic tendency to selectively process threat related distractor information. Furthermore, an index of this initial pattern of automatic processing selectivity was consistently the best predictor of the intensity of emotional distress elicited by the subsequent diagnosis of cervical pathology. None of our conventional questionnaire measures were capable of significantly predicting this later emotional response. We suggest that these findings offer empirical support for the hypotheses that patterns of automatic processing selectivity may moderate individuals' emotional responses to stressful life events.

Adaptation, Psychological

Memory accessibility and probability judgments: an experimental evaluation of the availability heuristic.

Consistent with Tversky and Kahneman's (1973, 1974) availability heuristic hypothesis, the current study found a negative correlation between recall latency for past events and the perceived future probability of similar events. Furthermore, when the relative accessibility of memories of positive and negative events was experimentally manipulated using the Velten mood-induction procedure, the perceived future probabilities of similar events also changed in a manner consistent with the availability heuristic account. Reductions in recall latencies resulting from the mood manipulations were, as predicted, related to increases in perceived probability, and vice versa. Partial correlations indicated that this association between the observed patterns of changes in recall latencies and probability judgments could not be accounted for by the existence of independent associations between each of these effects and the magnitude of mood change.

Adolescent

Implications of rDNA technology in the microbiology laboratory.

The present and potential future roles in service and research microbiological laboratories of recombinant DNA (rDNA) techniques (nucleic acid hybridization, nucleic acid amplification, in situ hybridization, pulsed field gel electrophoresis) are described. Applications rDNA technology include the detection of micro-organisms; an approach to the understanding of their role in disease pathogenesis and provision of alternative strategies for studying the epidemiology of infectious diseases.

DNA, Recombinant

Biased cognitive operations in anxiety: accessibility of information or assignment of processing priorities?

There is considerable evidence that anxiety is associated with a cognitive bias favouring the processing of threat-related information. Bower's (1981) network model attributes this bias to the enhanced availability of mood congruent information from memory. However, certain experimental tasks do not reveal such a bias, when this effect is strongly predicted by the model. We note that all tasks which have demonstrated such mood congruent processing effects in anxious subjects share the requirement that these subjects must assign priorities to simultaneously available, and differentially valenced, alternative processing options. This feature has been consistently lacking in those paradigms we have found insensitive to the influence of anxiety. It is therefore suggested that anxiety is associated with the assignment of high processing priorities to threat-related options, rather than with the facilitated availability of threat-related information from memory. This proposal was experimentally tested using a lexical decision task, which is sensitive to the accessibility of information from memory, under conditions which either do or do not introduce the requirement to assign priorities to alternative processing options. The results indicate that the facilitated processing of threat related stimulus words, shown by generalised anxiety patients, does indeed appear to reflect a bias in the assignment of processing priorities, rather than the enhanced availability of this information from memory.

Adult

Induction of c-fos by an anti-epidermal growth factor receptor monoclonal antibody.

The effect of epidermal growth factor (EGF) or a monoclonal antibody to the human EGF receptor on c-fos and c-myc gene expression was examined in KB epidermoid carcinoma cells. EGF increased c-fos transcripts within 30 min and c-myc transcripts within 6-24 hours. The antibody transiently increased c-fos expression within 30 minutes, but did not alter expression of c-myc. Cycloheximide potentiated the c-fos induction by both EGF and antibody. C-fos induction by antibody was less consistent, and was of briefer duration and lesser intensity than the induction by EGF. Nuclear transcription of c-fos decreased in cells treated with EGF or antibody, indicating that c-fos induction by EGF or antibody resulted from post-transcriptional mechanisms.

Antibodies, Monoclonal

Histoplasmosis in the acquired immunodeficiency syndrome (AIDS).

This case report describes a 50-year-old man from South America with AIDS who developed disseminated histoplasmosis with focal lymph node involvement. Treatment with ketoconazole was initially successful. Six weeks after cessation of ketoconazole he died of what was thought to be relapse of histoplasmosis.

Acquired Immunodeficiency Syndrome

Ganglioside-mediated modulation of cell growth. Specific effects of GM3 and lyso-GM3 in tyrosine phosphorylation of the epidermal growth factor receptor.

Epidermal growth factor- (EGF) dependent tyrosine phosphorylation of the EGF receptor was inhibited by the exogenous addition of GM3 to a membrane preparation and to purified EGF receptor adsorbed to antireceptor-antibody-Sepharose (Bremer, E. G., Schlessinger, J., and Hakomori, S. (1986) J. Biol. Chem. 261, 2434-2440). A specific functional correlation between GM3 and EGF receptor function has been further assessed in this study, employing two variant clones of A431 cells showing completely different growth responses to EGF. The A1S clone showed EGF cell growth stimulation and contained GM3 whereas the A5I clone, whose growth was completely inhibited by EGF addition, lacked detectable GM3. Both the endogenous and EGF-dependent receptor tyrosine-kinase activities were low in the A1S clone and were only minimally inhibited by the exogenous addition of GM3. In contrast the EGF receptor kinase activity in A5I cells was much higher and was more strongly inhibited by GM3 than it was in A1S cells. The EGF receptor fraction prepared from A1S cells, eluted from an anti-EGF receptor antibody-Sepharose column, contained GM3, in contrast to the fraction prepared from A5I cells, which lacked detectable GM3. The receptor kinase activity in vitro was greatly influenced by detergent and ATP concentration. GM3 affected the receptor kinase in a biphasic manner, i.e. GM3 was inhibitory at a low concentration of detergent under a physiological concentration of ATP and stimulatory at a high concentration of detergent. In contrast lyso-GM3 displayed a monophasic inhibitory effect under a wide range of detergent concentrations. Lyso-CDH (lactosylsphingosine) had no detectable effect on the receptor kinase activity. The presence of a small quantity of lyso-GM3 in A431 cells was detected after DEAE-Sepharose chromatography followed by high performance liquid chromatography in a n-propanolyl alcohol-ammonia system. It is possible that de-N-fatty acylation of gangliosides could be an effective means to modulate EGF receptor function in membranes.

Animals

Effects of epidermal growth factor on transferrin receptor phosphorylation and surface expression in malignant epithelial cells.

The transferrin (Tf) receptor is a major transmembrane protein which provides iron for normal and malignant cell growth. Epidermal growth factor (EGF) has been reported to rapidly and transiently alter the number of surface Tf receptors in normal and transformed epithelial cells. To investigate mechanisms of EGF-induced changes in surface Tf display, EGF effects on surface Tf receptors were compared in two cell lines which differ in their number of EGF receptors and growth responses to EGF. In cloned A431 cells with high receptor numbers which are growth-inhibited by EGF, EGF caused a 50% decrease in Tf receptor expression after 30 min. In contrast, EGF induced a rapid, transitory increase (within 5 min) in the number of surface Tf receptors on KB carcinoma cells which returned to basal levels by 15 min. The observed changes in Tf receptor display were due to altered receptor distribution and not changes in ligand affinity or total cellular transferrin receptor pools. Anti-EGF receptor monoclonal antibody blocked effects of EGF on transferrin receptor expression. Since the antibody is internalized and causes EGF receptor down-regulation, effects on transferrin receptor expression were independent of these events. EGF-induced alterations in Tf receptor display occurred even when cells were pretreated with colchicine, suggesting that changes in surface Tf binding were not mediated by cytoskeletal components. Na orthovanadate, which mimics some early cellular effects of EGF, duplicated EGF's effects on A431 Tf receptors, but had no effect on KB cells, suggesting these responses occur by differing mechanisms. To determine whether EGF caused changes in Tf receptor phosphorylation, 32P-labelled Tf receptors were immunoprecipitated after EGF treatment. After exposure to EGF, A431 cells showed no change in Tf phosphorylation, but KB cells showed a transient, 6-fold increase in transferrin receptor phosphorylation on serine residues. In both A431 and KB cells, phorbol ester (PMA) also increased phosphorylation on transferrin receptors, but had little effect on surface Tf receptor expression. In malignant cell lines, EGE induces rapid, variable changes in transferrin receptor expression and phosphorylation which differ from the effects of PMA. These early responses to EGF appear to differ with the cell type and correlate poorly with alterations in Tf receptor phosphorylation. These results suggest Tf receptor phosphorylation does not regulate Tf receptor display in all cells.

Animals

Extrapulmonary tuberculosis--a continuing problem in Australia.

Extrapulmonary tuberculosis (TB) remains a major health problem in Australia, with 24.3% of all new tuberculosis notifications in 1984 of extrapulmonary origin. We have reviewed our recent experience to assess the epidemiology and clinical features that may allow the earlier recognition and treatment of patients at risk for this disease. From 1980-1985, 51 cases of extrapulmonary TB were identified at Westmead Hospital. Thirty-eight patients were born outside Australia, mainly in South-East Asia and Europe. The commonest sites of disease were the lymph nodes, genitourinary tract, pleura and bone. Tuberculous lymphadenitis occurred predominantly in South-East Asians, whilst genitourinary tract disease was confined to Caucasians. A history of previous exposure to tuberculosis was obtained in 45% of patients. Fever, sweats and weight loss were noted in less than half of the cases. Changes consistent with old pulmonary disease were found on routine chest X-ray in 34% of cases. Laboratory confirmation of TB was made in 88% of cases, with typical histopathology in 90% and isolation of Mycobacterium tuberculosis in 69% of specimens submitted for analysis. Drug resistance was confined to isolates from South-East Asian patients.

Asia, Southeastern

Perception of emotionally valenced information in depression.

Bower's (1981) associative network model of mood and cognition predicts that depression will selectively facilitate the perception of negatively toned words. Recent studies by Clark et al. (1983) and by Powell & Hemsley (1984) have, however, produced apparently discrepant results. Alternative means of accommodating the discrepancy are considered, and the current experiment empirically distinguishes between these possibilities. The results are inconsistent with Bower's model.

Adult

A direct radioimmunoassay for human epidermal growth factor receptor using 32P-autophosphorylated receptor.

A simple and reproducible radioimmunoassay of the epidermal growth factor (EGF) receptor which uses 32P-labeled EGF receptor and anti-receptor monoclonal antibodies is reported. In vitro phosphorylation of A431 cell membranes with [gamma-32P]ATP in the presence of 20% dimethyl sulfoxide (which stimulates autophosphorylation of the EGF receptor) and 10 microM Na3VO4 (a potent inhibitor of phosphotyrosyl protein phosphatase) provides radiolabeled EGF receptor for radioimmunoassay without further purification. The most selective phosphorylation of the EGF receptor is achieved at ATP concentrations of 0.1-0.2 microM, which corresponds to the reported Km value for the autophosphorylation reaction of the EGF receptor (W. Weber, P.J. Bertics, and G.N. Gill, 1984, J. Biol. Chem. 259, 14631-14939). The incorporation of 32P into EGF receptors increases in proportion to the increase of ATP concentration up to 6 mol of labeled phosphate at 2.0 microM ATP. The label is entirely on tyrosine residues. The cell membranes can be stored at -70 degrees C for 3 months without loss of immunoreactivity and autophosphorylating activity. Standard curves for the radioimmunoassay were constructed employing either A431 cell membranes or whole cell homogenates containing a known amount of EGF receptor. The assay can detect 7 X 10(10) EGF receptor molecules or 20 ng of the receptor protein, and can quantitatively distinguish the difference in EGF receptor numbers between A431 cells and 29E2 and KB cells with 10-fold and 15-fold fewer receptors than A431 cells, respectively. 29E2 cells and KB cells express twofold more immunoreactive EGF receptors than EGF-binding sites. In contrast, A431 cells possess the same number of immunoreactive sites and receptor sites for EGF binding. To assess total EGF receptor expression, it is necessary to use a method which detects EGF receptors regardless of their intrinsic kinase activity, or capacity to bind EGF. This radioimmunoassay detects immunoreactive receptor molecules, even those which do not bind EGF.

Adenosine Triphosphate

Visual feedback of vocal intensity in the treatment of hysterical aphonia.

This case report describes the successful though temporary removal of a hysterical aphonic symptom in a 49-year-old male patient by using visual feedback of changes in vocal intensity. Following symptom removal the patient experienced considerable emotional distress due to a number of factors. His aphonia returned and has proven resistant to subsequent intervention. At a 1-year follow-up his condition was found to be unchanged. The case is discussed in relation to the common controversy over the wisdom of symptomatic treatment for hysterical reactions, and a practical means of resolving the disagreement is considered.

Aphonia