Biomedical subjects
A Davies
Publications and source records attributed to A Davies.
The practical management of claudication.
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Doctors and nurses. Doing it together with PAMs.
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Functional interactions of Mycobacterium leprae RuvA with Escherichia coli RuvB and RuvC on holliday junctions.
The Mycobacterium leprae RuvA homologue (MlRuvA) was over-expressed in Escherichia coli and purified to homogeneity. The DNA-binding specificity and the functional interactions of MlRuvA with E. coli RuvB and RuvC (EcRuvB and EcRuvC) were examined using synthetic Holliday junctions. MlRuvA bound specifically to Holliday junctions and produced similar band-shift patterns as EcRuvA. Moreover, MlRuvA formed functional DNA helicase and branch-migration enzymes with EcRuvB, although the heterologous enzyme had a lower efficiency. These results demonstrate that the RuvA homologue of M. leprae is a functional branch-migration subunit. Whereas MlRuvA promoted branch-migration in combination with EcRuvB, it was unable to stimulate branch-migration-dependent resolution in a RuvABC complex. The inability to stimulate RuvC was not due to its failure to form heterologous RuvABC complexes on junctions, since such complexes were detected by co-immunoprecipitation. Most likely, the stability of the heterologous RuvABC complex and, possibly, the interactions between RuvA and RuvC were impaired, as gel-shift experiments failed to show mixed MlRuvA-EcRuvC-junction complexes. These results demonstrate that branch-migration per se and the assembly of a RuvABC complex on the Holliday junction are insufficient for RuvAB-dependent resolution of the junction by RuvC, suggesting that specific and intimate interactions between all three proteins are required for the function of a RuvABC "resolvasome".
Agitation induced mycelial fragmentation of Aspergillus oryzae and Penicillium chrysogenum.
Given the impact of mycelial morphology on fermentation performance, it is important to understand the factors that influence it, including agitation-induced fragmentation. The successful application of the energy dissipation/circulation function (EDC) to correlate fragmentation of Penicillium chrysogenum with agitation intensity and with different impeller types [5] has already been demonstrated. The EDC function takes into account the specific energy dissipation rate in the impeller swept volume and the frequency of mycelial circulation through that volume. In order to explore whether the EDC function can be used more generally to correlate fragmentation of different filamentous species, the present study extended the concept to agitation-induced, off-line fragmentation of Aspergillus oryzae grown in chemostat culture. The work shows that at EDC values off-line greater than that in the chemostat, fragmentation with different impellers can be correlated with the EDC. For EDC values less than those used in the chemostat, fragmentation did not occur. The earlier results of Jüsten et al. [5] with Penicillium chrysogenum are also reconsidered and found to behave similarly.
Anti-coagulant monitoring service delivery: a comparison of costs of hospital and community outreach clinics.
Anti-coagulated patients are monitored at regular intervals to ensure that their warfarin dosage is appropriate for their target International Normalized Ratio. The traditional setting for this monitoring has been the hospital clinic. Technological advances allow-- and with growing numbers of anti-coagulated patients, are leading to-- greater provision of monitoring clinics outside the hospital, at a more convenient location nearer patients' homes. This paper discusses the differences in organization between a hospital clinic and one set in the community (although provided by the hospital), and compares their costs. The comparison demonstrates the greater average cost per appointment in outreach of pound sterling 13.12 under current arrangements. Estimates are presented of incremental cost per appointment of pound sterling 3.93 and pound sterling 15.88 for a 10% increase in weekly patient numbers put through hospital and outreach clinics, respectively. Cost estimates are also presented for suggested alterations to hospital clinics that may reduce patient inconvenience, and the conditions under which outreach provision might be expanded at comparable cost to hospital provision are also examined.
Host immune response to intracellular bacteria: A role for MHC-linked class-Ib antigen-presenting molecules.
MHC-linked class-Ib molecules are a subfamily of class-I molecules that display limited genetic polymorphism. At one time these molecules were considered to have an enigmatic function. However, recent studies have shown that MHC-linked class-Ib molecules can function as antigen presentation structures that bind bacteria-derived epitopes for recognition by CD8+ effector T cells. This role for class-Ib molecules has been demonstrated across broad classes of intracellular bacteria including Listeria moncytogenes, Salmonella typhimurium, and Mycobacterium tuberculosis. Additionally, evidence is emerging that MHC-linked class-Ib molecules also serve an integral role as recognition elements for NK cells as well as several TCR alpha/beta and TCR gamma/delta T-cell subsets. Thus, MHC-linked class-Ib molecules contribute to the host immune response by serving as antigen presentation molecules and recognition ligands in both the innate and adaptive immune response to infection. In this review, we will attempt to summarize the work that supports a role for MHC-linked class-Ib molecules in the host response to infection with intracellular bacteria.
3-monochloropropane-1,2-diol (3-MCPD) in soy sauces and similar products available from retail outlets in the UK.
A survey of the level of 3-monochloropropane-1,2-diol (3-MCPD) in soy sauces and similar products available in the UK is reported. The survey was carried out by the Joint Ministry of Agriculture, Fisheries and Food/Department of Health Food Safety and Standards Group (JFSSG) to check for compliance with the Food Advisory Committee's (FAC) recommended limit for 3-MCPD of 0.01 mg/kg following reports that soy sauces in several European countries had been found to contain high levels (up to 124 mg/kg) of 3-MCPD. Forty samples of soy sauce and similar products purchased from retail outlets were analysed using a GC-MS procedure which had been formally validated by an earlier collaborative trial. 3-MCPD was undetectable in 21 (52%) of samples analysed in the survey, with a further five samples containing very low levels of between 0.01 and 0.02 mg/kg. Five samples (13%) contained 3-MCPD at levels in the range 0.020-1 mg/kg while nine samples (23%) were found to contain 3-MCPD at levels greater than 1 mg/kg, with the highest level being 30.5 mg/kg.
Comparison of the protective efficacy of bacille calmette-Guérin vaccination against aerosol challenge with Mycobacterium tuberculosis and Mycobacterium bovis.
The aim of this study was to compare protection by bacille Calmette-Guérin (BCG) vaccination against aerosol challenge with either Mycobacterium bovis or Mycobacterium tuberculosis in guinea pigs. Animals were challenged 5 weeks after vaccination with 10 or 100 lung lesion-forming units (lfu) of M. bovis or M. tuberculosis. Four weeks after challenge, numbers of lung lesions and counts of viable mycobacteria in spleens were high in saline-immunized animals. In contrast, BCG vaccination resulted in fewer lung lesions; after challenge with 10 and 100 lfu, the reduction was greater in animals infected with M. bovis (mean number of lesions, 1.17 and 31.2, respectively; P<.02) than in those infected with M. tuberculosis (mean number of lesions, 16.2 and 75.8, respectively). No mycobacteria were recovered from spleens of BCG-vaccinated animals after challenge with 10 lfu of M. bovis, whereas 4 of 6 animals had detectable spleen mycobacterial counts after challenge with M. tuberculosis. Collectively, the results suggest that BCG vaccination may confer greater protection against challenge with M. bovis than challenge with M. tuberculosis.
Identification of a new glucosinolate-rich cell type in Arabidopsis flower stalk.
Distribution of K, Ca, Cl, S, and P in freeze-dried sections of Arabidopsis flower stalk was analyzed by energy dispersive x-ray imaging. Concentrations of these elements in different cell types were quantified by microanalysis of single-cell samples and phloem exudates. Results showed a differential pattern of distribution for all five elements. K concentration was found to be highest in the parenchymatous tissue around vascular bundles. Ca and Cl were present mainly in the central part of the flower stalk. P was largely located in the bundles and in the parenchyma surrounding them. S signal was extraordinary high in groups of cells (S-cells) situated between the phloem of every vascular bundle and the endodermis. Enzymatic hydrolysis by thioglucosidase of cell sap collected from S-cells using a glass microcapillary resulted in the release of glucose, indicating that these cells contain glucosinolates at high (> 100 mM) concentration, which is consistent with the concentration of S (> 200 mM) estimated by x-ray analysis of cell sap samples. Since their position outside of the phloem is ideally suited for protecting the long-distance transport system from feeding insects, the possible roles of these cells as components of a plant defense system are discussed.
Failure of thrombolysis by streptokinase: detection with a simple electrocardiographic method.
OBJECTIVE: To determine whether simple, readily applicable ECG criteria will allow early prediction of inadequate (< TIMI 3) flow in the infarct related vessel in patients receiving thrombolytic treatment for acute myocardial infarction; and to determine the success of streptokinase in achieving adequate antegrade flow in the infarct related vessel two hours after starting treatment. DESIGN: Cohort study. SETTING: Regional cardiothoracic unit. PATIENTS: 100 sequential patients with acute myocardial infarction. INTERVENTIONS: Coronary angiography two hours after the initiation of thrombolytic treatment, proceeding to rescue angioplasty for inadequate flow in the infarct related vessel where appropriate. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of six ECG criteria for the detection of inadequate antegrade flow in the infarct related vessel. RESULTS: The ECG test that performed best as a positive test for < TIMI 3 flow in the infarct related vessel was < 50% resolution of the ST segment elevation in the worst lead and no accelerated idioventricular rhythm. This had a sensitivity of 81%, specificity of 88%, positive predictive value of 87%, negative predictive value of 83%, and overall accuracy of 85%. CONCLUSIONS: Sensitive, specific, and simple ECG criteria are defined for diagnosing failure of thrombolytic treatment with streptokinase. These allow the early detection of patients at high risk of further adverse events from a persistently occluded vessel. They may be used without recourse to sophisticated equipment or complex analyses. Such patients can then be considered for alternative treatments or enrollment into appropriate research protocols.
Failure of thrombolysis: experience with a policy of early angiography and rescue angioplasty for electrocardiographic evidence of failed thrombolysis.
OBJECTIVE: To assess the outcome of a policy of emergency coronary angiography with or without rescue angioplasty in patients with acute myocardial infarction and ECG evidence of failed reperfusion after thrombolysis. DESIGN: A cohort study. SETTING: Regional cardiothoracic unit. PATIENTS: 197 patients with acute myocardial infarction fulfilling a simple ECG criterion of failed reperfusion. INTERVENTIONS: Emergency coronary angiography proceeding to rescue angioplasty for inadequate antegrade flow. MAIN OUTCOME MEASURES: Hospital mortality for all 197 patients; incidence of successful and failed rescue angioplasty; need for additional revascularisation in those receiving rescue angioplasty compared with those not treated in this way. RESULTS: 197 patients had emergency angiography for ECG evidence of failed reperfusion; 156 patients received immediate rescue angioplasty. Overall hospital mortality for those undergoing rescue angioplasty was 11.5%. Rescue angioplasty achieved TIMI 2 (11) or TIMI 3 (124) in 135 patients, who had a hospital mortality of 5.9%. Failure to achieve at least TIMI 2 flow following rescue angioplasty occurred in 21 patients, with a hospital mortality of 48%. In the 41 patients in whom immediate rescue angioplasty was not performed, reinfarction or requirement for revascularisation occurred in 37%. Reinfarction occurred in three patients (1.9%) who had immediate rescue angioplasty. Hospital mortality for the whole cohort was 10.7%. CONCLUSIONS: A policy of emergency coronary angiography proceeding to rescue angioplasty where appropriate reduces mortality in a high risk group to a level less than expected for patients with acute myocardial infarction and ECG evidence of failed reperfusion. Unsuccessful rescue angioplasty is associated with a high mortality.
Is provisional stenting the effective option? The WIDEST study (Wiktor stent in de novo stenosis). Widest Trial Investigators' Group.
AIM: To compare the immediate and late outcomes of patients treated by a policy of routine stent implantation with routine balloon angioplasty and the use of stents only when an ideal result has not been obtained. METHODS: A nine centre, multinational, randomised study of 300 patients with coronary artery disease thought suitable for treatment of a single lesion by balloon angioplasty or stent implantation. Only new lesions in patients who had not undergone previous bypass surgery were included, and totally occluded vessels were excluded. RESULTS: The initial procedure was considered successful in 96% of patients. There was more complete angiographic restoration of luminal diameter in patients treated by elective stent (minimum lumen diameter (MLD) 2.68 mm for stent v 2.27 mm for balloon; p < 0.007), but analysis of the subgroup of balloon angioplasty patients who crossed over to stenting showed that they achieved similar results to the elective stent group. Late luminal loss was greater in stented patients than in those undergoing balloon angioplasty only, and by six months the angiographic benefit of stenting had disappeared (MLD 1.90 mm for stent group v 2.00 mm for balloon angioplasty). Angiographic and clinical results in the balloon angioplasty group were assisted by the high crossover rate (30.1%). Both groups had similar symptom relief, with 58.9% of patients improving by two or more angina grades. The need for further revascularisation was also similar in the two groups at one year (18.2% in the stented group v 17.1% in the balloon angioplasty group). Haemorrhagic complications at the local arterial entry site were more common than expected and were distributed equally between the patients receiving full anticoagulation and those receiving antiplatelet treatment only. The results of both Wiktor stent placement and balloon angioplasty were similar to the findings in the stent group in previous randomised studies (Benestent II, STRESS). CONCLUSIONS: Provisional stenting appears to offer the same longer term outcome as elective stenting in this selected group of patients. Improvement in the results of conventional balloon angioplasty in the past 10 years means that a policy of obtaining an ideal result without the use of stents appears to be practicable in many of these patients, with consequent cost savings.
The management of Chlamydia trachomatis: combined community and hospital study.
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Midazolam-induced dyskinesia.
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Endoscopic reconstruction of the anterior cruciate ligament with an ipsilateral patellar tendon autograft. A prospective longitudinal five-year study.
A total of 90 patients with an isolated rupture of the anterior cruciate ligament (ACL) had a reconstruction using the ipsilateral patellar tendon secured with round-headed cannulated interference screws. Annual review for five years showed three failures of the graft (two traumatic and one atraumatic); none occurred after two years. Ten patients sustained a rupture of the contralateral ACL. At five years, 69% of those with surviving grafts continued to participate in moderate to strenuous activity. Using the International Knee Documentation Committee assessment, 90% reported their knee as being normal or nearly normal and had a median Lysholm knee score of 96 (64 to 100). Most patients (98%) had a pivot shift of grade 0 with the remaining 2% being grade 1; 90% of the group had a Lachman test of grade 0. The incidence of subsequent meniscectomy was similar in the reconstructed joint to that in the contralateral knee. Radiological examination was normal in 63 of 65 patients. Our study supports the view that reconstruction of the ACL is a reliable technique allowing full rehabilitation of the previously injured knee. In the presence of normal menisci there is a low incidence of osteoarthritic change despite continued participation in sporting activity.
Autofluorescence in the oocysts of marine and freshwater fish coccidia.
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Discrete cell- and stage-specific localisation of fibroblast growth factors and receptor expression during testis development.
Fibroblast growth factors (FGFs) are a family of heparin binding proteins involved in many biological processes. These growth factors act through tyrosine kinase receptors (FGFRs); we have previously used immunohistochemistry to study FGFRs-1-4 in foetal, immature and adult rat testes, and found a discrete cell- and stage-specific localisation. Alternative mRNA splicing of FGFRs-1-3 leads to functional variants (IIIb and IIIc) with distinct ligand binding affinities, therefore we have identified the specific expression of functional FGFR variants and the expression and localisation of FGF ligands in testes from foetal, immature and adult rats. Using reverse transcriptase-polymerase chain reaction (RT-PCR), we found that mRNAs for FGFR-1 IIIb and IIIc, FGFR-2 IIIc, FGFR-3 IIIc and FGFR-4 were expressed in foetal, immature and adult testes. Ligands FGFs-1-5, and -8, which can signal through these receptors, were also expressed in testes at each age. Localisation of the ligands FGFs-1, -3 and -4 to rat testes by immunohistochemistry showed a discrete cell- and stage-specific localisation that altered during testis development. This study has shown that the ligands FGFs-1, -3 and -4 are expressed in the testis and have the capacity to signal through appropriate receptors that are also co-localised or expressed in adjacent cell types in the testis. Collectively, the expression profiles of the seven FGFR variants and FGFs-1-5 and -8 suggest a functional importance in testicular development and spermatogenesis. It is concluded that, future studies on the role of other FGF ligands, in particular FGFs-1-4, are warranted.