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M J Wilkinson

Publications and source records attributed to M J Wilkinson.

At least 19 recordsLinked to original sources
PubMed2000

In-situ atomic force microscopy study of beta-amyloid fibrillization.

We report the use of atomic force microscopy to observe the initial stages of beta-amyloid fibrillization in situ. The growth of individual beta-amyloid protofibrils on a mica substrate was followed over several hours. The first in situ visualization of protofibril formation from single aggregate units of beta-amyloid is reported. The growth of these protofibrils through the subsequent addition of these aggregate units is also observed. Growth of the protofibrils is bi-directional and the outgrowth of protofibrils from a common amyloid/heterogeneous core is also observed. Elongation also occurred by the addition of protofibrils from solution. This data provides an exciting insight into the early stages of beta-amyloid fibrillization and can be used to enhance the understanding of the mechanism(s) by which beta-amyloid fibrillizes and may consequently enable inhibition of one or more stages of fibrillization as a potential therapeutic strategy.

Adsorption↗
PubMed2000

Attempted eradication of salmonellosis from a colony of short-tail grey opossums (Monodelphis domestica).

Prior to re-housing a colony of laboratory short-tail grey opossums, the animals were found to harbour salmonella. This paper describes an unsuccessful attempt to eradicate the infection from the colony by means of antibiotic treatment and hygienic measures. A pilot treatment of five animals which received enrofloxacin 10 mg/kg for 5 days appeared to be successful in that no salmonellae were recovered from faeces or organs sampled after treatment. The process was repeated on the whole colony prior to a change of accommodation but 2 animals were found to be still infected, 5 weeks after cessation of treatment.

Animals↗
PubMed1999

Morphological development of beta(1-40) amyloid fibrils.

The Alzheimer's disease-related peptide beta(1-40) amyloid self-associates to form fibrils exhibiting a morphology characteristic of amyloidogenic proteins. The mechanism of this fibrillization process has yet to be fully elucidated. In this study we have immobilized the beta(1-40) amyloid to flat gold surfaces using thiol-based self-assembled monolayers. Atomic force microscopy reveals the presence of spherical units of beta(1-40) amyloid immediately following the initiation of fibrillization. Short fibrillar structures, termed nascent fibrils, which appear to be formed by the association of these units are also present at this time point. At later time points extended, branching networks of fibrils are observed. Some fibrils exhibit a more beaded appearance and greater axial periodicity than others. No nascent fibrils are seen to be present. We believe that these data identify an early fibril structure which could act as an intermediate in beta-amyloid fibrillization. The oligomeric units of which these nascent fibrils are comprised are also determined.

Amino Acid Sequence↗
PubMed1999

Low probability of chloroplast movement from oilseed rape (Brassica napus) into wild Brassica rapa.

Pollen-mediated movement of transgenes from transplastomic oilseed rape (Brassica napus) into wild relatives will be avoided if chloroplasts are maternally transmitted. We assess the probability of chloroplast exchange between conventional oilseed rape and wild Brassica rapa to model the future behavior of transplastomic cultivars. Primers specific to cpDNA were used to demonstrate maternal inheritance of chloroplasts in 47 natural hybrids between cultivated B. napus and wild B. rapa. We conclude that there will be no or negligible pollen-mediated chloroplast dispersal from oilseed rape. Transgene introgression could still occur in mixed populations, however, if B. napus acted as the recurrent female parent. Rate of transfer would then depend on the abundance of mixed populations, their persistence as mixtures, and hybridization frequency within stands. A low incidence of sympatry (0.6-0.7%) between wild B. rapa and cultivated B. napus along the river Thames, UK, in 1997 and 1998, suggests mixed stands will form only rarely. Eighteen feral populations of B. napus also showed a strong tendency toward rapid decline in plant number, seed return, and ultimately, extinction within 3 years. Conversely, hybrid production is significant in mixed stands, and the absence of control practices means that oilseed rape will have slightly greater persistence. We infer that some introgression from transplastomic B. napus into B. rapa is inevitable in mixed populations even though such populations will occur infrequently and will tend to lose B. napus plants relatively quickly. Chloroplast exchange will be extremely rare and scattered.

Brassica↗
PubMed1998

Counselling.

Explore the source record for details and available documents.

Counseling↗
PubMed1997

Rapid assessment of antibiotic effects on Escherichia coli by bis-(1,3-dibutylbarbituric acid) trimethine oxonol and flow cytometry.

The effects of selected antibiotics on Escherichia coli were studied by flow cytometry with the fluorescent anionic membrane potential probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol [DiBAC4(3)]. The actions of azithromycin, cefuroxime, and ciprofloxacin at five times the MIC on E. coli were compared by the traditional CFU assay and flow cytometry. Changes in viable counts of bacteria determined with DiBAC4(3) and by flow cytometry following treatment with the antibiotics showed trends similar to those found by the CFU assays. However, viable counts determined by flow cytometry following antibiotic treatment were 1 to 2 logs higher than those determined by the corresponding CFU assays. All the results obtained by flow cytometry were provided within 10 min after sampling, whereas the conventional CFU assay results took at least 18 h. The results indicated that flow cytometry is a sensitive analytical technique that can rapidly monitor the physiological changes of individual microorganisms following antibiotic action and can provide information on the mode of action of a drug. The membrane potential probe DiBAC4(3) provides a robust flow cytometric indicator for bacterial cell viability.

Anti-Bacterial Agents↗
PubMed1997

Does the BJGP need more fizz and pop?--A Midland Faculty readership survey.

BACKGROUND: The British Journal of General Practice (BJGP) is the leading primary care journal in the world. By impact factor, it ranks 24th of all medical journals. However, despite major changes in the journal since its inception in 1954, there have been no published readership surveys since a limited report in 1969. AIM: To canvass members of the Midland Faculty and to add to the debate about the future of the BJGP. METHOD: A postal questionnaire was sent to a random sample of 299 members, fellows and associates of the Midland Faculty asking for their views about the BJGP. RESULTS: Two hundred replies were received (a response rate of 67%). The median year of qualification of responders was 1981, and 32 (16%) held academic posts. Ninety-nine (49%) disagreed with the present format of the BJGP, which compared poorly with the British Medical Journal (BMJ) in simple rank order of importance. Readership was equal to that of the BMJ (93% reading it within 28 days of arrival), but fewer people read it within a week of receiving it. The most popular sections were the editorials, original articles and letters; least popular were the book reviews and the pull-out magazine, Connection. All sections were rated excellent to average. Readers wished for an expansion of the BJGP to include clinical reviews, medical politics and humorous pieces. Most responders felt that Connection should remain separate. There was dissatisfaction with the delay between submission and publication of original articles, particularly among the academic general practitioners (GPs). Academics and fundholders did not differ from other readers in their views of the content or style of the BJGP. Half of the responders stated that the BJGP should be self-financing and should be open to more advertising. Responders' free comments largely related to improving the style of articles and expanding the BJGP. CONCLUSION: There is a view that the present BJGP is not relevant to the non-academic GP. This is probably due to style rather than content. Simple comparisons with a weekly multi-disciplinary journal may not be valid. The style could be updated to improve retention of information and to highlight areas of particular relevance. Readers are satisfied with the core content of the BJGP but want it to expand to include humour, clinical reviews and medical politics, for example. There is no evidence that the BJGP is more appealing to the academic GP. This study supports an expanded BJGP with an improved style.

Data Collection↗
PubMed1996

Feulgen staining of intact plant tissues for confocal microscopy.

A method was developed to prepare plant structures for confocal laser scanning microscopy by combining Feulgen staining with pararosaniline and embedding in LR White(TM). This procedure preserves intact, delicate structures for three-dimensional imaging without loss from sectioning or squashing, and the slides can be viewed several times without serious photo-bleaching.

Acrylic Resins↗
PubMed1995

Scanning tunnelling microscopy studies of beta-amyloid fibril structure and assembly.

Alzheimer's disease is in part characterised by the deposit of beta-amyloid peptide in the form of fibrils in the brain. In this study, the scanning tunnelling microscope (STM) has been used to provide high resolution images of synthetic fibril structure and formation as a function of time. Short fibrils are observed following brief peptide incubation times. At longer incubation periods ribbon like filaments were observed. These results suggest that beta-amyloid self-assembly is an ordered process, with a correlation between time of incubation and length of beta-amyloid filament growth.

Amino Acid Sequence↗
PubMed1995

Evidence for somatic translocation during potato dihaploid induction.

Potato dihaploid PDH55 (Solanum tuberosum) is exclusively euploid (2n = 24) but apparently contains and expresses DNA from dihaploid inducer IVP48 (S. phureja). Genomic in situ hybridization (GISH) suggested IVP48 DNA incorporated stably into PDH55 by somatic translocation. This finding has two important implications. Firstly, the long-held implicit assumption that euploid dihaploids produced by dihaploid inducers are pure S. tuberosum seems incorrect. This may complicate meiotic, genetical and molecular studies involving potato dihaploids. Secondly, if such translocations are not rare, the phenomenon may offer a novel way to introduce useful traits directly from wild dihaploid-inducing species into S. tuberosum.

Base Sequence↗
PubMed1995

Love is not a marketable commodity: new public management in the British National Health Service.

This paper describes the historical developments and current role of new public management (NPM) in the British National Health Service (NHS). It is argued that NPM concern for efficiency improvements has resulted in threats to equality and needs-based service delivery. The relevance of NPM values to health care and nursing is explored. Finally, comments are provided on how nurses can advocate for a more loving NHS environment, and one which is therefore more conducive to nurse and patient health.

Efficiency, Organizational↗
PubMed1995

When the talking is over: using action learning.

Outlines the workings of action learning sets, team-building and cultural change, and explores the use of action learning methodology in the development of health-care managers. Outlines the spin-off benefits of the implementation of action learning at Ashworth Hospital, such as self-discipline, commitment, improved morale, empowerment, etc. Concludes that it could be a powerful tool for future health-care management.

Competency-Based Education↗
PubMed1995

Does 48 hours' bed rest influence the outcome of acute low back pain?

BACKGROUND: Bed rest is a traditional treatment for back pain, yet only in recent years has the therapeutic benefit of this been questioned. AIM: The aim of this pilot study was to ascertain whether or not 48 hours' bed rest had an effect on the outcome of acute low back pain. METHOD: The study was conducted as a randomized controlled trial to compare a prescription of 48 hours' strict bed rest with controls; the control subjects were encouraged to remain mobile and to have no daytime rest. Nine general practitioners from practices in the West Midlands recruited patients in the age range 16-60 years who presented with low back pain of less than seven days' duration, with or without pain radiation. The outcome measures assessed were: change in straight leg raise and lumbar flexion after seven days, Oswestry and Roland-Morris disability scores after seven days and 28 days, and time taken from work. RESULTS: Forty two patients were recruited: 20 were allocated to bed rest and 22 as controls. Compared with the bed rest group the control group had statistically better Roland-Morris scores at day seven (P < 0.05) but not at day 28. At day seven, there were no statistically significant differences between groups in straight leg raise or lumbar flexion measurements although the control group had a better mean lumbar flexion than the bed rest group. The improvement in disability scores at day seven compared with day one was similar for the two groups but more of the control group had fully recovered (defined as scores of one or zero on the Roland-Morris disability scale and five or less on the Oswestry disability scale) by day seven. Remaining mobile did not appear to cause any adverse effects. The number of days lost from work in both groups was equal. A large number of self-remedies and physical therapies were recorded by subjects from both groups. CONCLUSION: The results of this pilot study did not indicate whether bed rest or remaining mobile was superior for the treatment of acute low back pain; however, the study sample was small. Subjects in the control group possibly fared better as they appeared to have better lumbar flexion at day seven. It appears that 48 hours' bed rest cannot be recommended for the treatment of acute low back pain on the basis of this small study. Large-scale definitive trials are required to detect clinically significant differences.

Acute Disease↗
PubMed1994

A phase I/II study of alternating constant rate infusion floxuridine with constant rate infusion vinblastine for the treatment of metastatic renal cell carcinoma.

BACKGROUND: Metastatic renal cell carcinoma (RCC) is largely chemoresistant. The efficacy of cell cycle specific chemotherapeutic agents, particularly those with short half-lives, may be enhanced by the use of constant rate infusion schedules. Infusional floxuridine has been demonstrated to have a response rate of approximately 20%. Infusional vinblastine has not been tested extensively in patients with metastatic RCC. The sequential use of these agents was designed to increase efficacy and limit toxicity. METHODS: Fifteen patients with metastatic RCC were treated with constant rate infusion floxuridine, 0.075 mg/kg/day for 14 days, followed by a constant rate infusion of vinblastine, 0.7 mg/m2/day for 14 days. The cycle repeated every 28 days and floxuridine and vinblastine doses were incrementally increased until the maximum tolerated dose (MTD) for each patient was reached. RESULTS: Four patients had partial responses (27%), which were maintained for 3, 9, 16 and 19+ months, whereas five patients had stable disease for 3-15 months. Median survival from initiation of therapy was 379 days. Three of four responses occurred in nonpulmonary locations, and all responses occurred in patients who had a prior nephrectomy. MTD for floxuridine was 0.1 mg/kg/day and for vinblastine, 0.7 mg/m2/day. Toxic reaction to floxuridine was limited to diarrhea, whereas the principle dose-limiting toxic reaction for vinblastine was neutropenia. Catheter-related complications were also observed. CONCLUSIONS: Alternating constant rate infusion floxuridine and constant rate infusion vinblastine is active in the treatment of metastatic RCC. Whether this regimen is superior to infusional floxuridine is undetermined. Although the toxicity associated with this regimen is manageable, it appears to be more severe than that reported with infusional floxuridine alone.

Adult↗