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Biomedical subjects

J Dawson

Publications and source records attributed to J Dawson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Analysis of LMW RNA profiles of Frankia strains by staircase electrophoresis.

An optimized technique of polyacrylamide gel electrophoresis, Staircase Electrophoresis (SCE), was applied to determine the stable Low Molecular Weight RNA (LMW RNA) profiles of 25 Frankia strains from diverse geographic origins and host specificity groups as well as species from other actinomycete genera. Application of the technique permits the rapid identification of Frankia strains and their differentiation from other actinomycetes. The isolates used in this study were grouped in eight clusters, each comprising strains with identical LMW RNA profiles. Comparison of these results with others obtained from DNA sequences or DNA hybridization methods suggest a high degree of complexity in the genus Frankia. Application of SCE to profile LMW RNA should in the future facilitate biodiversity studies of Frankia and discrimination of new species.

Actinomycetales↗
PubMed1998

Septic shock: an analysis of outcomes for patients with onset on hospital wards versus intensive care units.

OBJECTIVE: To determine if early interventions for septic shock were associated with reduced mortality. DESIGN: Retrospective cohort study. SETTING: University hospital intensive care unit (ICU) and general wards. PATIENTS: Forty-one consecutive patients prospectively identified with positive blood cultures and septic shock. Although all patients were eventually treated in an ICU, ten (24%) patients were on a general ward at the onset of septic shock, and 31 (76%) were in an ICU setting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over a period of 9 mos, a cohort of 41 patients who had positive blood cultures and septic shock was prospectively identified. The 28-day crude mortality was 46% (19 deaths). We compared the management of septic shock and outcome for patients on a general ward vs. those patients in an ICU setting. Of the ten patients on the ward at time of shock onset (median age 55.5 yrs; median Acute Physiology and Chronic Health Evaluation [APACHE] II score of 18.5), seven (70%) died. In contrast, the 31 patients receiving intensive care when shock developed were older and more ill (median age 66 yrs; median APACHE II 24), yet had a mortality of 39% (12 deaths). The odds ratio (OR) for death for ward patients compared with ICU patients was 3.57 (p=.17). In a multivariate logistic regression analysis, two risk factors for mortality were important: APACHE II score (p=.015) and ward status (p=.08). Candida species in the bloodstream is known to have a high attributable mortality. When type of bloodstream pathogen (Candida species vs. bacteria) was added to the model, APACHE II (OR 2.64 for 10-unit increase) remained significant (p=.014), but ward status (OR 3.97) became statistically nonsignificant (p=.222). The patients who were on a general ward when their shock developed had a median delay of 67 mins before transfer to an ICU setting. Ward patients received an intravenous fluid bolus after a median delay of 27 mins, whereas those in the ICU who received a fluid bolus did so after a median of 15 mins (p=.48). Ward patients also had a median delay of 310 mins to receive inotropic support compared with a median 22.5 mins (p=.037) for the patients in an ICU setting when shock started. CONCLUSIONS: The data suggest that for patients with septic shock on wards, there were clinically important delays in transfer of patients to the ICU, receipt of intravenous fluid boluses, and receipt of inotropic agents. However, the most powerful predictors of mortality were APACHE II scores and bloodstream infection with Candida species.

APACHE↗
PubMed1998

Functional differences between BHRF1, the Epstein-Barr virus-encoded Bcl-2 homologue, and Bcl-2 in human epithelial cells.

BHRF1, a component of the restricted early antigen complex of the Epstein-Barr virus lytic cycle, encodes a 17-kDa protein with both sequence and functional homology to the antiapoptotic Bcl-2 oncogene. Recent work has suggested that BHRF1 behaves like Bcl-2 in protecting cells from apoptosis induced by a range of stimuli. In this study, the effect of BHRF1 and Bcl-2 on the growth and differentiation of the SCC12F human epithelial cell line was examined. The levels of stable transfected BHRF1 expression achievable in SCC12F cells was consistently lower than that obtained with Bcl-2. While both BHRF1 and Bcl-2 inhibited epithelial differentiation, the effect of Bcl-2 was more pronounced, resulting in an almost complete blockade of differentiation in organotypic raft cultures. However, BHRF1-expressing SCC12F cells proliferated at a much higher rate than SCC12F cells expressing Bcl-2, and this effect was supported by cell cycle analysis which demonstrated that BHRF1, but not Bcl-2, promotes rapid transit through the cell cycle. These data highlight important differences between BHRF1 and Bcl-2 and suggest that BHRF1 may function to promote the survival and proliferation of lytically infected cells. The proliferative properties of BHRF1 described in this study, together with the demonstration that other oncogenic gamma herpesviruses encode Bcl-2 homologues, suggests that these proteins may serve to increase the susceptibility of virus-infected cells to oncogenic transformation, thereby contributing to the development of virus-associated tumors.

Apoptosis↗
PubMed1998

Questionnaire on the perceptions of patients about total knee replacement.

We have developed a 12-item questionnaire for patients having a total knee replacement (TKR). We made a prospective study of 117 patients before operation and at follow-up six months later, asking them to complete the new questionnaire and the form SF36. Some also filled in the Stanford Health Assessment Questionnaire (HAQ). An orthopaedic surgeon completed the American Knee Society (AKS) clinical score. The single score derived from the new questionnaire had high internal consistency, and its reproducibility, examined by test-retest reliability, was found to be satisfactory. Its validity was established by obtaining significant correlations in the expected direction with the AKS scores and the relevant parts of the SF36 and HAQ. Sensitivity to change was assessed by analysing the differences between the preoperative scores and those at follow-up. We also compared change in scores with the patients' retrospective judgement of change in their condition. The effect size for the new questionnaire compared favourably with those for the relevant parts of the SF36. The change scores for the new knee questionnaire were significantly greater (p < 0.0001) for patients who reported the most improvement in their condition. The new questionnaire provides a measure of outcome for TKR that is short, practical, reliable, valid and sensitive to clinically important changes over time.

Aged↗
PubMed1998

Scapulothoracic muscle fatigue associated with alterations in scapulohumeral rhythm kinematics during maximum resistive shoulder elevation.

Clinical examinations and biomechanical analysis of the shoulder often include an assessment of the scapulohumeral rhythm. It is important to understand factors which may affect the scapulohumeral rhythm so that optimal diagnostic and therapeutic strategies can be devised. The purpose of this study was to determine if the scapulohumeral rhythm, when assessed under dynamic conditions, is altered as a result of a fatigue-inducing exercise. Twenty-five subjects were required to elevate their arm against maximum resistance until they were no longer able to completely elevate their arm. Three-dimensional kinematics were measured using an electromagnetic tracking system. Electromyographic activity was recorded from the upper trapezius, lower trapezius, serratus anterior, and the middle deltoid muscles. Power frequency spectrum using the Fast Fourier Transform and the root mean square signal amplitudes were determined for each muscle. The scapulohumeral rhythm was determined using least squares regressions of humeral elevation to scapular upward rotation for 20% intervals (phases) of elevation for each subject. The results showed that during the midrange of elevation to maximum elevation [phases 3-5 (60-150 degrees)], the scapulohumeral rhythm decreased with fatigue, and that the decrease in the scapulohumeral rhythm was associated with myoelectric indicators of fatigue (median power frequency). The study suggests that shoulder fatigue affects the way in which the scapula moves concomitantly with the humerus. Fatigue tends to result in increased motion of the scapula, which alters the scapulohumeral rhythm.

Adolescent↗
PubMed1998

Drug interactions and the clinical anaesthetist.

In clinical practice, anaesthetists encounter many patients who are on concurrent medication which may have the potential to interact with drugs used during anaesthesia. Many patients are receiving as many as a dozen drugs of various kinds, thus, increasing the risk of a drug interaction occurring. Unfortunately anaesthetists tend not to report drug interactions which occur during anaesthesia--especially those of a minor nature such as flushing--and hence, the true number of drug interactions is unknown. We have developed a chart indicating the nature of important interactions that the anaesthetist may encounter.

Anesthesia↗
PubMed1997

Cloning and characterization of a corepressor and potential component of the nuclear hormone receptor repression complex.

Nuclear hormone receptors are potent repressors of transcription in the unliganded state. We describe here the cloning of a nuclear receptor corepressor that we call SUN-CoR (Small Unique Nuclear receptor CoRepressor), which shows no homology to previously described nuclear hormone receptor corepressors, N-CoR, or SMRT. SUN-CoR is a highly basic, 16-kDa nuclear protein that is expressed at high levels in adult tissues and is induced during adipocyte and myogenic differentiation. SUN-CoR potentiates transcriptional repression by thyroid hormone receptor and RevErb in vivo, represses transcription when fused to a heterologous DNA binding domain, and interacts with RevErb as well as with thyroid hormone receptor in vitro. SUN-CoR also interacts with N-CoR and SMRT in vitro and with endogenous N-CoR in cells. We conclude that SUN-CoR is a corepressor and may function as an additional component of the complex involved in transcriptional repression by unliganded and orphan nuclear hormone receptors.

Amino Acid Sequence↗
PubMed1997

Simulated car crashes and crash predictors in drivers with Alzheimer disease.

BACKGROUND: Alzheimer disease (AD) is the most common cause of dementia and can impair cognitive abilities crucial to the task of driving. Rational decisions about whether such impaired individuals should continue to drive require objective assessments of driver performance. OBJECTIVE: To measure relevant performance factors using high-fidelity driving simulation. DESIGN: We examined the effect of AD on driver collision avoidance using the Iowa Driving Simulator, which provided a high-fidelity, closely controlled environment in which to observe serious errors by at-risk drivers. We determined how such unsafe events are predicted by visual and cognitive factors sensitive to decline in aging and AD. SETTING: The University of Iowa Hospitals and Clinics, Iowa City, and the Iowa Driving Simulator. PARTICIPANTS: Thirty-nine licensed drivers: 21 with AD and 18 controls without dementia. MAIN OUTCOME MEASURES: We determined the number of crashes and related performance errors and analyzed how these occurrences were predicted by visual and cognitive factors. RESULTS: Six participants (29%) with AD experienced crashes vs 0 of 18 control participants (P = .022). Drivers with AD were more than twice as likely to experience close calls (P = .042). Plots of critical control factors in the moments preceding a crash revealed patterns of driver in-attention and error. Strong predictors of crashes included visuospatial impairment, reduction in the useful field of view, and reduced perception of 3-dimensional structure-from-motion. CONCLUSIONS: High-fidelity driving simulation provides a unique new source of performance parameters to standardize the assessment of driver fitness. Detailed observations of crashes and other safety errors provide unbiased evidence to aid in the difficult clinical decision of whether older or medically impaired individuals should continue to drive. The findings are complementary to evidence currently being gathered using techniques from epidemiology and cognitive neuroscience.

Accidents, Traffic↗
PubMed1997

BHRF1, a viral homologue of the Bcl-2 oncogene, is conserved at both the sequence and functional level in different Epstein-Barr virus isolates.

BHRF 1, a component of the restricted early antigen (EA) complex of the Epstein-Barr virus (EBV) lytic cycle, encodes a 17 kDa putative transmembrane protein with both sequence and functional homology to the Bcl-2 proto-oncogene. To determine whether there was any sequence variation over the BHRF1 open reading frame (ORF), 15 EBV isolates from different geographical regions and from both healthy donors and patients with EBV-associated diseases were sequenced. A small number of base changes which resulted in amino acid substitutions in the BHRF1 protein were found relative to the prototype B95.8 EBV sequence and these were predominantly clustered near the amino terminus of the BHRF1 protein outside conserved domains identified in the Bcl-2 homologues. In transient transfection assays none of the mutations in the BHRF1 ORF from eight different EBV isolates had a significant effect on BHRF1 protein localization compared to the B95.8 BHRF1 protein. However, transient expression of the adenovirus 12 19K protein or Bcl-2 resulted in localization patterns distinct from that observed with BHRF1 protein. Whilst all eight EBV isolates and E1B-19K gave comparable levels of protection to the DNA-damaging agent cis-platin, Bcl-2 did not afford significant protection. Thus, despite several amino acid changes in the BHRF1 ORF of some of the EBV isolates studied, the ability of the protein to protect against cis-platin induced apoptosis is conserved. The highly conserved nature of BHRF1 amongst different EBV isolates at both the sequence and functional level supports the proposed important role of BHRF1 in delaying cell death, thereby maximizing the production of progeny virus and facilitating the establishment of virus persistence.

Cloning, Molecular↗
PubMed1997

Changes in putamen N-acetylaspartate and choline ratios in untreated and levodopa-treated Parkinson's disease: a proton magnetic resonance spectroscopy study.

We have carried out single-voxel proton magnetic resonance spectroscopy centered on the putamen both ipsilateral and contralateral to the worst affected side in nine subjects with drug naive idiopathic Parkinson's disease (IPD); seven chronically levodopa-treated dyskinetic IPD subjects; and 11 age-matched healthy controls. Measurements of N-acetylaspartate (NAA)/choline (Cho), NAA/(Creatine + Phosphocreatine) (Cr + PCr), and Cho/(Cr + PCr) were made. We found a significant reduction in NAA/Cho ratios from the putamen contralateral to the most affected side in the drugnaive group (p = 0.009), but not the levodopa-treated IPD groups compared with controls. There were no significant differences in NAA/(Cr + PCr) or Cho/(Cr + PCr) ratios. In untreated IPD, reduced putaminal NAA/Cho ratios may reflect loss of nigrostriatal dopamine terminals or alternatively indicate a functional abnormality of striatal putaminal neurons, such as membrane dysfunction due to striatal deafferentation. This study suggests that NAA/Cho ratios may be affected by L-dopa therapy and this may provide a reversible marker of neuronal dysfunction in the striatum.

Adult↗
PubMed1997

The echolocation calls of the spotted bat Euderma maculatum are relatively inaudible to moths

Previous studies of the spotted bat Euderma maculatum have demonstrated that this bat emits echolocation calls that are lower in frequency, shorter in duration and fainter in intensity compared with those of most other insectivorous bats, acoustic characteristics which should render it less conspicuous to eared moths. We tested this prediction by monitoring electrophysiologically the ears of sympatric noctuoid (noctuid, arctiid and notodontid) moths in a site in western Canada. Auditory threshold curves demonstrate that most of the moths tested are less responsive to the calls of Eu. maculatum than to those of another sympatric bat, Eptesicus fuscus. Playbacks to moth ears of pre-recorded search- and approach-phase echolocation calls of Eu. maculatum and Ep. fuscus further demonstrate that the calls of Eu. maculatum are poorly detectable to moths and, in some cases, completely inaudible. We estimate that, in the wild, an average noctuoid moth would detect the calls of Eu. maculatum at distances of less than 1 m as opposed to the calls of Ep. fuscus which should be first heard at distances of 20&shy;25 m. Although most moths are unable to adequately hear Eu. maculatum, the observation that two individuals possessed ears sensitive to this bat's calls suggests the existence of auditory pre-adaptation to this type of echolocation.

Journal Article↗
PubMed1997

Forewing asymmetries during auditory avoidance in flying locusts

Flying locusts orient to sounds in their environment. Sounds similar to those produced by echolocating bats cause a flying locust to change its flight path. We used high-speed cinematography and videography to study changes in body posture and wing kinematics of tethered locusts in response to stimulation with bat-like sounds. Locusts showed both negative and positive phonotaxis to this stimulus. Within a few wingbeats of stimulus onset (between 126 and 226ms), locusts deflected their abdomens to one side, and the angle of the left and right forewings with respect to the dorsal&shy;ventral body axis became asymmetrical during the downstroke. This forewing asymmetry, in which the forewing on the inside of the turn became more depressed, ranged from 20 to 45&deg; (37&plusmn;9.7&deg;, mean &plusmn; s.d.) and was correlated with the direction and magnitude of abdomen deflection, a measure of steering in tethered, flying locusts. Hindwing stroke angle asymmetries were minimal or non-existent after stimulation. Coincident with changes in forewing asymmetry and abdomen deflection was a decrease in stroke amplitude (19&plusmn;6.5&deg;) of the forewing on the inside of the attempted turn. Motor patterns from forewing first basalar (M97) muscles showed an asymmetry in the timing of left and right depressor activation that ranged from 10.4 to 1.6ms (4.23&plusmn;2.85ms). The number of spikes per depressor burst increased to a maximum of three spikes in the muscle on the inside of the attempted turn, and depressor frequency (wingbeat frequency) increased by approximately 2Hz (2.17&plusmn;0.26Hz). We suggest that the asymmetry in forewing first basalar activity is causally related to the asymmetry in the timing of the initiation of the downstroke, resulting in an asymmetry in the ranges of the stroke angles of the forewings, which would impart a roll torque to the locust. This would augment the steering torques generated by concurrent changes in the angle of attack of the fore- and hindwings and changes in abdomen position to effect rapid avoidance manoeuvres.

Journal Article↗
PubMed1996

CD40-induced growth inhibition in epithelial cells is mimicked by Epstein-Barr Virus-encoded LMP1: involvement of TRAF3 as a common mediator.

CD40, a member of the tumour necrosis factor receptor family, is expressed on the surface of B lymphocytes where its ligation provides a potent survival signal. CD40 is also expressed in basal epithelial cells and in a number of different carcinomas where its function remains unknown. We observed that contrary to the studies in normal B cells, CD40 ligation in carcinoma cell lines and in normal primary epithelial cells resulted in growth inhibition and enhanced susceptibility to apoptosis induced by anti-neoplastic drugs, TNF-alpha, Fas and ceramide. This effect was also observed in CD40-transfected Rat-1 fibroblasts. The expression of Bcl-2 did not affect growth inhibition induced by CD40 ligation in epithelial cells but the Epstein - Barr Virus-encoded latent membrane protein 1 (LMP1) blocked the effect. Whilst transient expression of LMP-1 resulted in the inhibition of epithelial cell growth, this effect was not observed with a LMP1 mutant lacking the binding domain for TRAF3, a protein which may mediate signal transduction by interacting with the cytoplasmic domains of both CD40 and LMP1. Transient expression of TRAF3 also inhibited epithelial cell growth, whilst expression of a dominant-negative TRAF3 partially blocked the inhibitory effect of CD40 ligation and of transient LMP1 expression. These results suggest that CD40 regulates epithelial cell growth in a manner mimicked by LMP1 and implicate TRAF3 as a common mediator in the transduction of the growth inhibitory signals generated via the CD40 and LMP1 pathways.

Animals↗