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Biomedical subjects

S J Wilson

Publications and source records attributed to S J Wilson.

At least 73 records · Page 4Linked to original sources
PubMed1999

Immunohistochemical analysis of the activation of NF-kappaB and expression of associated cytokines and adhesion molecules in human models of allergic inflammation.

To investigate the role of NF-kappaB in regulating allergic inflammation, a monoclonal antibody directed to the activated form of NF-kappaB has been developed and immunohistochemistry has been employed to study the pro-inflammatory transcriptive function of NF-kappaB and the adhesion molecules and cytokines that it regulates. Human umbilical vein endothelial cells (HUVECs) exposed to physiological levels of TNFalpha demonstrated dose- and time-dependent cytoplasmic and nuclear activation of NF-kappaB, followed by up-regulation of ICAM-1. This was suppressed by the selective inhibitors of NF-kappaB activation, calpain and gliotoxin. Using monoclonal antibodies directed to NF-kappaB and associated cytokines and adhesion molecules, immunohistochemistry was applied to bronchial explants stimulated ex vivo with TNFalpha, and to nasal polyp tissue, embedded in glycol methacrylate. Stimulation of the bronchial explants increased expression of NF-kappaB, IL-8, and GM-CSF in the epithelium and endothelium and ICAM-1 in the endothelium. In nasal polyp, expression of NF-kappaB was in the epithelium, the endothelium and in submucosal mast cells, eosinophils, T and B lymphocytes, and macrophages. Thus, immunohistochemistry can be used to determine the cellular provenance of NF-kappaB and its activation status in single cell and complex tissue systems, in parallel with appropriate inflammatory markers.

Animals↗
PubMed1999

Outcome of temporal lobectomy: expectations and the prediction of perceived success.

PURPOSE: This study examined the independent contributions of medical and psychosocial factors to perceived surgical success. We aimed to develop a multidimensional model predictive of perceived surgical outcome. METHODS: Fifty anterior temporal lobectomy (ATL) patients were prospectively assessed, using a formally coded, semistructured clinical interview. This has been routinely administered pre- and post-operatively as part of a larger, nationwide study of Australian ATL patients. The interview covers a broad range of epileptological, psychiatric, neuropsychological and psychosocial issues. Variables from these domains were examined in relation to the patient's perception of surgical success at the 6-month post-operative review. RESULTS: Variables that correlated with success were analysed using principal components analysis and multiple regression. A predictive model of perceived surgical success emerged, which highlighted the multidimensionality of outcome. Independent effects were observed for both medical and psychosocial factors. These included the patients' pre-operative expectations of surgery, their post-operative seizure outcome, and affective state. The findings also highlighted the importance of discarding sick role behaviours associated with chronic epilepsy, after surgery. CONCLUSIONS: Traditional outcome measures (seizure frequency, post-operative affect) are significant in the patient's evaluation of surgical success. These traditional measures, however, do not account for the process of psychosocial adjustment surrounding seizure surgery. This process involves two major components: (1) positive anticipation of change prior to surgery, and (2) learning to discard roles associated with chronic epilepsy after surgery.

Adult↗
PubMed1999

Patient readmission and support utilization following anterior temporal lobectomy.

The aim of this study was to examine factors precipitating patient readmission, following anterior temporal lobectomy (ATL) for refractory epilepsy. A second aim was to explore the use of hospital outpatient and community support services ('outpatient services') by this patient population. These aims served the more general goal of identifying patients most likely in need of services additional to those routinely provided by our Seizure Surgery Follow-up and Rehabilitation Programme. The medical records of 100 consecutive ATL patients were retrospectively examined for the incidence and diagnoses precipitating acute readmission, and the utilization of additional outpatient services. Twenty-one patients (21%) required readmission post-ATL, totalling 47 readmissions between them. Psychiatric diagnoses were the most prevalent (53%), including anxiety, depression and/or post-ictal psychosis. Epileptological diagnoses were the other main precipitant (28%). Additional outpatient services were predominantly utilized for ongoing psychological support. Of the 21 patients requiring readmission, 10(10%) also needed additional outpatient services. These patients were predominantly female or unemployed, in contrast to male or employed patients who tended to require readmission only. Seventeen patients (17%) were maintained within the community using additional outpatient services only. Characteristics of these patients included disrupted family dynamics, limited social networks, and/or a psychiatric history. These patients were also more frequently beyond the 24-month follow-up period of the programme. A profile of patients most in need of additional support services can be constructed to assist team planning of proactive management strategies for the rehabilitation phase of ATL.

Acute Disease↗
PubMed1999

Influence of right atrial pressure on the cardiac pacemaker response to vagal stimulation.

We have recently shown that the intrinsic rate response to an increase in right atrial pressure is augmented when cardiac muscarinic receptors are activated. This present study examines the cardiac pacemaker response to vagal stimulation at different values of right atrial pressure in isolated rat right atrium and in the rabbit heart in situ. In the rat atrium, when pressure was raised in steps from 2 to 10 mmHg, there was a progressive reduction in the response to vagal stimulation [40.5 +/- 7.2% reduction (mean +/- SE) at 8 mmHg, P < 0.01], which was independent of the level of vagal bradycardia, that persisted in the presence of the beta-adrenergic agonist isoproterenol. In barbiturate-anesthetized rabbits with cervical vagi cut and beta-adrenergic blockade, raising right atrial pressure approximately 2.5 mmHg by blood volume expansion reduced the bradycardia elicited by electrical stimulation of the peripheral end of the right vagus nerve (9.1 +/- 1.1% reduction, P < 0.0001). These results demonstrate that vagal bradycardia is modulated by the level of right atrial pressure and suggest that normally right atrial pressure may interact with cardiac vagal activity in the control of heart rate.

Animals↗
PubMed1999

Anatomical distribution of prolactin-releasing peptide and its receptor suggests additional functions in the central nervous system and periphery.

A recently identified neuropeptide with PRL-releasing capabilities binds to and activates a previously known orphan G protein-coupled receptor, GPR10. We initiated a study to define the pharmacology of the peptide/receptor interaction and to identify the distribution of the peptide and its receptor in the central nervous system to elucidate sites of action of the peptide. The PRL-releasing peptide (PrRP) is a C-terminally amidated, 31-amino acid peptide derived from a 98-amino acid precursor. Radioiodinated PrRP-(1-31) binds to its receptor with high affinity (1 nM) and stimulates calcium mobilization in CHOK1 cells stably transfected with the receptor. A series of N-terminal deletions reveals that the PrRP-(12-31) amino acid is equipotent to PrRP-(1-31). Further N-terminal deletions reduce the affinity of the ligand considerably, although PrRP-(25-31) is still able to compete for binding and behaves as an agonist. The arginine residues at position 26 and 30 are critical for binding, as substitution with either lysine or citrulline reduces the affinity substantially. In situ hybridization reveals a distinct tissue distribution for both the peptide and receptor messenger RNAs. The receptor is expressed abundantly in the reticular thalamic nucleus, periventricular hypothalamus, dorsomedial hypothalamus, nucleus of the solitary tract, area postrema, anterior pituitary, and adrenal medulla. The peptide messenger RNA is expressed in the dorsomedial hypothalamus, nucleus of the solitary tract, ventrolateral reticular nucleus, and intestine. This tissue distribution suggests an alternative function of PrRP than its purported hypophysiotropic function, such as a potential role for PrRP in the central feedback control of neuroendocrine and autonomic homeostasis. Further work using selective agonists and antagonists should help define additional physiological roles of this novel mammalian neuropeptide.

Animals↗
PubMed1999

The persuasiveness of synthetic speech versus human speech.

Is computer-synthesized speech as persuasive as the human voice when presenting an argument? After completing an attitude pretest, 193 participants were randomly assigned to listen to a persuasive appeal under three conditions: a high-quality synthesized speech system (DECtalk Express), a low-quality synthesized speech system (Monologue), and a tape recording of a human voice. Following the appeal, participants completed a posttest attitude survey and a series of questionnaires designed to assess perceptions of speech qualities, perceptions of the speaker, and perceptions of the message. The human voice was generally perceived more favorably than the computer-synthesized voice, and the speaker was perceived more favorably when the voice was a human voice than when it was computer synthesized. There was, however, no evidence that computerized speech, as compared with the human voice, affected persuasion or perceptions of the message. Actual or potential applications of this research include issues that should be considered when designing synthetic speech systems.

Adult↗
PubMed1999

Cloning and functional expression of the human histamine H3 receptor.

Histamine regulates neurotransmitter release in the central and peripheral nervous systems through H3 presynaptic receptors. The existence of the histamine H3 receptor was demonstrated pharmacologically 15 years ago, yet despite intensive efforts, its molecular identity has remained elusive. As part of a directed effort to discover novel G protein-coupled receptors through homology searching of expressed sequence tag databases, we identified a partial clone (GPCR97) that had significant homology to biogenic amine receptors. The GPCR97 clone was used to probe a human thalamus library, which resulted in the isolation of a full-length clone encoding a putative G protein-coupled receptor. Homology analysis showed the highest similarity to M2 muscarinic acetylcholine receptors and overall low homology to all other biogenic amine receptors. Transfection of GPCR97 into a variety of cell lines conferred an ability to inhibit forskolin-stimulated cAMP formation in response to histamine, but not to acetylcholine or any other biogenic amine. Subsequent analysis revealed a pharmacological profile practically indistinguishable from that for the histamine H3 receptor. In situ hybridization in rat brain revealed high levels of mRNA in all neuronal systems (such as the cerebral cortex, the thalamus, and the caudate nucleus) previously associated with H3 receptor function. Its widespread and abundant neuronal expression in the brain highlights the significance of histamine as a general neurotransmitter modulator. The availability of the human H3 receptor cDNA should greatly aid in the development of chemical and biological reagents, allowing a greater appreciation of the role of histamine in brain function.

Adenylyl Cyclase Inhibitors↗
PubMed1998

Prefrontal cortex involvement in selective letter generation: a functional magnetic resonance imaging study.

Cerebral responses to alternating periods of a control task and a selective letter generation paradigm were investigated with functional Magnetic Resonance Imaging (fMRI). Subjects selectively generated letters from four designated sets of six letters from the English language alphabet, with the instruction that they were not to produce letters in alphabetical order either forward or backward, repeat or alternate letters. Performance during this condition was compared with that of a control condition in which subjects recited the same letters in alphabetical order. Analyses revealed significant and extensive foci of activation in a number of cerebral regions including mid-dorsolateral frontal cortex, inferior frontal gyrus, precuneus, supramarginal gyrus, and cerebellum during the selective letter generation condition. These findings are discussed with respect to recent positron emission tomography (PET) and fMRI studies of verbal working memory and encoding/retrieval in episodic memory.

Adult↗
PubMed1998

The intrinsic rate response of the isolated right atrium of the rat, Rattus norvegicus.

Experiments were performed on rat right atria maintained at 37 degrees C in oxygenated Krebs-Henseleit solution, at a baseline diastolic transmural pressure of 2 mmHg. A step increment in right atrial pressure caused an increase in atrial rate which reached a steady value after 2-3 min (rate response). An 8-mmHg increase in atrial pressure caused an 8% increase in atrial rate (n = 9, P < 0.01). When the atrial rate was reduced by carbamylcholine, the rate response was augmented. After a 34% reduction in atrial rate, an 8-mmHg increase in atrial pressure increased atrial rate by 51% (n = 7, P < 0.01). When atrial rate was elevated 71% by isoprenaline, the rate response was reversed (atrial rate decreased 3% following an 8-mmHg increase in atrial pressure; n = 7, P < 0.01). In another series of experiments, atrial rate was adjusted to a wide range of values by exposure to carbamylcholine and isoprenaline, first applied singly, and then in combination. At any given atrial rate, the rate response was always larger when both agonists were present; this difference was greatest when atrial rate was near the control untreated value.

Animals↗
PubMed1998

Inflammatory mediators in naturally occurring rhinitis.

BACKGROUND: The mediators released during the allergic inflammatory reaction induce the clinical symptoms of the allergic disease and although there have been numerous studies investigating mediator release in allergen challenge models of allergic rhinitis very few have extended this approach to the study of natural disease. OBJECTIVE: The aim of this investigation was therefore to measure mast cell and eosinophil mediator levels and indices of vascular permeability in naturally occurring rhinitis. METHODS: Three groups of subjects were studied, normal non-rhinitics, seasonal allergic rhinitics in and out of the grass pollen season and perennial allergic rhinitics. Mediators were recovered using the technique of nasal lavage and the levels of tryptase, histamine, eosinophil cationic protein and albumin were determined. In addition, eosinophils were enumerated in nasal smears as an indices of underlying inflammation. RESULTS: The levels of tryptase, eosinophil cationic protein and albumin were significantly higher in the lavage recovered from the symptomatic seasonal allergic rhinitics than when asymptomatic (P = 0.05, P = 0.003, P = 0.009, respectively). These levels of eosinophil cationic protein and albumin were also significantly higher than those of the normal non-rhinitics (P = 0.0008, P = 0.0.003, respectively). In the perennial allergic rhinitics the levels of tryptase, eosinophil cationic protein and albumin were higher than the normal non-rhinitics (P < 0.0001, P = 0.0003, P = 0.0001, respectively). The levels of tryptase and histamine were higher in the perennial allergic rhinitics than the seasonal allergic rhinitics (P = 0.0003, P = 0.006, respectively). These changes in mediator levels were accompanied by a significant influx of eosinophils into the nasal mucosa of both the symptomatic seasonal rhinitics, compared with asymptomatic (P = 0.04) and normal controls (P = 0.0006) and the perennial rhinitics compared to normal controls (P = 0.03). CONCLUSION: These results indicate that in both naturally occurring seasonal allergic rhinitis and perennial allergic rhinitis mast cell and eosinophil activation occurs and this is accompanied by an increase in vascular permeability. These measurements in lavage fluid provide a method of monitoring the mucosal cellular events in response to therapy.

Adult↗
PubMed1998

Patient expectations of temporal lobe surgery.

PURPOSE: The purpose of this study was to examine expectations of postoperative quality of life expressed by patients undergoing anterior temporal lobectomy (ATL) for the control of intractable seizures. An important component of this study was an exploration of the relationship between preoperative expectations and perceived success of the operation. METHODS: Psychosocial functioning of 60 patients was assessed pre- and postoperatively, using a standardised, semistructured clinical interview. Preoperative assessment included a detailed examination of the patients' expectations of surgery, while postoperative assessment at 6 months examined the patients' perception of surgical success with respect to seizure outcome and postoperative psychosocial status. RESULTS: A range of expectations were expressed about postoperative outcome. These were classified into 11 posthoc categories. Patients who perceived the operation as a success tended to endorse 'practical' expectations (i.e., driving, employment, activities) preoperatively, rather than expectations of a psychologic or social nature (i.e., self-change, relationships). These patients experienced fewer postoperative seizures and psychosocial difficulties. In contrast, a perceived lack of success was associated with greater emphasis on psychosocial expectations preoperatively. These patients experienced a greater number of perceived postoperative psychosocial difficulties, and more postoperative seizures. CONCLUSIONS: Preoperative expectations of surgery formed an important baseline against which to assess postoperative outcome, and should constitute a routine part of assessment in studies of psychosocial outcome of ATL.

Adaptation, Psychological↗
PubMed1998

Measuring tidal volume and functional residual capacity change in sleeping infants using a volume displacement plethysmograph.

The noninvasive measurement of infant lung function during unsedated sleep in infants has been a long-standing objective in paediatric respiratory medicine. This note reports on the design and performance of a head-out volume-displacement plethysmograph (VDP) that overcomes some of the limitations of traditional lung function apparatus. The VDP comprises a rigid acrylic box with an integral water-sealed spirometer and a novel neck seal. The bilayer neck seal is of variable compliance and is comfortable and simple to use. The spirometer permits volume resolution of 1.5 mL and a dynamic range in excess of 100 mL. The frequency response extends from 0-7 Hz. Spirometer inertance was measured as 0.0015 kPa.L(-1).s(-2), resistance 0.021 kPa.L(-1).s(-1) and box capacitance 0.18L.kPa(-1). Tidal volume, respiratory rate and changes in functional residual capacity can be recorded during unsedated rapid eye movement and nonrapid eye movement whilst monitoring with conventional polysomnographic methods. The head-out configuration allows additional instrumentation to be implemented with ease, avoids facial stimulation and allows unimpeded access to the upper airway. A polysomnograph illustrating the limitations of respiratory inductance plethysmography signals and typical changes in functional residual capacity are shown.

Functional Residual Capacity↗
PubMed1998

Effects of controlled heat stress on ovarian function of dairy cattle. 1. Lactating cows.

The objective of this experiment was to determine the effects of controlled heat stress on ovarian function of lactating dairy cows. Estrus was synchronized (estrus = d 0), and cows were randomly assigned to either heat stress (n = 11; 29 degrees C, 60% relative humidity) or thermoneutral (n = 11; 19 degrees C, 60% relative humidity) treatment. For cows undergoing heat stress, ambient temperature (19 degrees C) was increased from d 11 to 13 of the estrous cycle (3.3 degrees C/d increase) and remained at 29 degrees C until d 21. Beginning on d 11, the growth and regression of ovarian follicles and corpora lutea were measured by using ultrasonography. Blood was collected daily by coccygeal venipuncture for measurement of serum concentrations of progesterone and estradiol. The second wave dominant follicle was more likely to ovulate in cows in the thermoneutral treatment than in cows undergoing heat stress (91 vs. 18% ovulation, respectively). Patterns of follicular growth in cows under-going heat stress were associated with decreased serum estradiol from d 11 to 21 and on the day of luteolysis. The average day of luteolysis was delayed by 9 d in heat-stressed cows. Conclusions were that follicular growth and development and luteolytic mechanisms were compromised in heat-stressed cows; as a result, luteolysis was delayed, and second wave dominant follicles did not ovulate.

Animals↗
PubMed1998

Effects of controlled heat stress on ovarian function of dairy cattle. 2. Heifers.

The objective of this experiment was to determine the effects of controlled heat stress on ovarian function of dairy heifers. Estrus was synchronized in Holstein heifers (estrus = d 0), and heifers then were randomly assigned to either heat stress (n = 10; 33 degrees C, 60% relative humidity) or thermoneutral (n = 11; 21 degrees C, 60% relative humidity) treatment. For heat-stressed heifers, ambient temperature was increased from thermoneutrality to heat stress (33 degrees C) between d 9 and 14 (2.4 degrees C/d increase) after the synchronized estrus and remained between 31 and 33.5 degrees C until d 22. From d 11 to 21, the growth and regression of ovarian follicles and corpora lutea were measured by using ultrasonography, and blood was collected daily for serum progesterone and estradiol analyses. The second wave dominant follicle was larger for the heifers in the thermoneutral environment than for heat-stressed heifers, and ovulation of the second wave dominant follicle occurred in 9 of 11 thermoneutral heifers. For 6 of 10 heat-stressed heifers, the second wave dominant follicle regressed and was replaced by an ovulatory third wave dominant follicle. Smaller follicular size in heat stressed heifers was associated with decreased serum estradiol concentrations between d 11 and 21. Serum concentrations of progesterone during the luteal phase were similar, but luteolysis was delayed in heat-stressed heifers compared with onset in heifers in the thermoneutral treatment. Conclusions were that heat stress inhibited the growth and function of the dominant follicle so that most of the heat-stressed heifers had three follicular waves and a delay in corpus luteum regression.

Animals↗
PubMed1997

The representation of tonality and meter in children aged 7 and 9.

The aim of this study was to explore the development of the representations of tonality and meter in children. Eighty children with a mean age of 7 (Grade 2) and 9 years (Grade 4) were compared on both melodic and rhythmic discrimination and classification tasks. The findings were considered in relation to their specificity to both task and age effects. The results revealed a developmental progression in the representation of tonality that was consistent across tasks. The rhythmic results also supported the existence of a representation of meter that developed with age, however these findings were more subject to task effects. The influence of stimulus length and likeableness on subject performance was also examined. Increased length was found to assist discrimination performance particularly with tonal, nontonal, and nonmetrical stimuli. No effects of stimulus likeableness were observed in the data.

Analysis of Variance↗
PubMed1997

Response of dairy cows treated with bovine somatotropin to a luteolytic dose of prostaglandin F2 alpha.

The objective of this study was to evaluate the timing of follicular waves in cows treated with bovine somatotropin (bST) by measuring ovarian responses to a luteolytic dose of PGF 2 alpha on d 12 of the estrous cycle. Thirty lactating cows (26 Holstein and 4 Guernsey) were assigned to receive bST (500 mg; n = 18) or saline (control; 1.5 ml; n = 12) every 14 d for three injection cycles. On d 12 of a synchronized estrous cycle, cows were injected with PGF 2 alpha to induce luteolysis. Following PGF 2 alpha, 9 cows ovulated from the dominant follicle during the first follicular wave (4 cows treated with bST and 5 control cows), and 14 cows ovulated from the dominant follicle during the second follicular wave (8 cows treated with bST and 6 control cows). Of the cows that ovulated during the second follicular wave, cows treated with bST had more class 3 follicles (> or = 10 mm) than did control cows. Concentrations of estradiol rose earlier after PGF 2 alpha injection in cows treated with bST than in control cows. This rise in estradiol was parallel to the development of dominant follicles. Serum concentrations of FSH were decreased in cows treated with bST. During the first and second estruses, equivalent numbers of cows treated with bST and control cows ovulated, but fewer cows treated with bST expressed estrus. These results are consistent with the hypothesis that cows treated with bST have reduced FSH, a faster turnover of dominant follicles, and differences in the timing of follicular waves. Treatment of cows with bST also increased the incidence of undetected estrus.

Animals↗
PubMed1996

Benzodiazepine site pharmacokinetic/pharmacodynamic quantification in man: direct measurement of drug occupancy and effects on the human brain in vivo.

To date, the study of the relationship between drug occupancy and action in the brain has had to rely on the use of either animal models or of indirect kinetic measures in man, e.g. serum concentrations of unbound drug (as a measure of "free" drug in brain). We describe the first set of experiments which directly measure agonist-induced changes in both pharmacodynamic effects and pharmacokinetic parameters simultaneously and which demonstrate the feasibility of these studies in man. Five healthy volunteers each had two PET scans using [11C]flumazenil (a radiolabelled benzodiazepine site antagonist) as part of a study investigating kinetic models and the relationship between occupancy and effect of benzodiazepine site ligands. In both studies the [11C]flumazenil was displaced from the brain by infusion of midazolam administered i.v. 30 min into the scan. In one study a higher dose of midazolam was administered than in the other (range 12.5-50 micrograms/kg). Time-activity curves of the concentration of radioligand were derived in 17 different brain regions using a stereotactic automatic method of region selection. We demonstrated that there are significant differences in an index of occupancy, induced by the two different doses of midazolam, both across brain regions and within subjects. There was a significant correlation between measured occupancy index change and pharmacodynamic effects as measured by the peak change in beta 1 spectral power on EEG. There was no significant correlation between dose administered and EEG changes; plasma concentrations of midazolam were correlated with the occupancy index and with the EEG measures. In addition, we have demonstrated that a non-regional total index of brain occupancy can be obtained by analysing the non-tomographic data obtained with the PET scanner (total radioactivity counts head curve) and that this index shows significant correlations both with the dose administered and with the pharmacodynamic measure. This last finding validates the use of other non-tomographic counting techniques (Malizia et al., 1995a) where an index of displacement can be obtained after the administration of less than 1% of the dose of radiation needed for a PET study. These studies are likely to be useful in human psychopharmacology, in particular in the assessment of tolerance and of putative changes in benzodiazepine sensitivity in anxiety disorders. The same principles can be applied to other ligand studies and will be useful to validate current PK/PD models.

Adult↗