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Biomedical subjects

M Bury

Publications and source records attributed to M Bury.

16 recordsLinked to original sources
PubMed2001

Localization of a proteasomal antigen in human spermatozoa: immunohistochemical electron microscopic study.

The ultrastructural localization of a proteasomal antigen in human spermatozoa was studied by means of immunolabeling with the MPC21 monoclonal antibody and secondary gold labeled antibody with 1.4 nm gold particles in combination with silver enhancement reaction using pre-embedding technique. The labeling was found in the acrosomal and postacrosomal regions, in the connecting-piece (neck) and, in some cases, in the middle-piece and also in the residual bodies. There was no significant reaction in condensed chromatin. In some abnormal forms of spermatozoa, in which the chromatin was not well condensed, the labeling in nuclei was present. The nuclear vacuoles with looser chromatin were usually strongly labeled. The nuclei of cells representing different stages of spermatogenesis, that were present in semen samples, were also labeled.

Acrosome↗
PubMed2001

Effects of an inhibitor of tripeptidyl peptidase II (Ala-Ala-Phe-chloromethylketone) and its combination with an inhibitor of the chymotrypsin-like activity of the proteasome (PSI) on apoptosis, cell cycle and proteasome activity in U937 cells.

AAF-AMC is not a specific TPP II substrate, since it is also hydrolyzed by purified proteasomes. Moreover, AAF-cmk, claimed to be a specific TPP II inhibitor, also inhibits the chymotrypsin-like activity of the proteasome. While AAF-cmk itself is mildly cytostatic to U-937 cells and induces cell cycle block in G1, its combination with PSI does not induce an increase in the cytostatic/cytotoxic effects. This suggests that TPP II is possibly less important for cell metabolism than it was previously believed and it is less probable that it can be able to fully compensate for the loss of the proteasome function.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Effects of proteasome inhibitor PSI on neoplastic and non-transformed cell lines.

In this study we compared the sensitivity of different human and murine cell lines varying in the stage of transformation to dose- and time-dependent cytostatic and/or cytotoxic effects of PSI (a selective proteasome inhibitor), measured by a standard MTT assay. It was found that intensively proliferating cell lines were more sensitive to very small doses of PSI after 24 h incubation than the slow proliferating ones. Non-transformed cell lines showed no sensitivity to PSI, as there was no difference in cell viability in comparison with the control group even after 72 h incubation.

Algorithms↗
PubMed2000

Lovastatin and simvastatin are modulators of the proteasome.

Lovastatin and simvastatin are HMG-CoA reductase inhibitors widely used as antihyperlipidemic drugs, which also display antiproliferative properties. In the present paper, we provide evidence that both lovastatin and simvastatin are modulators of the purified bovine pituitary 20 S proteasome, since they mildly stimulate the chymotrypsin-like activity and inhibit the peptidylglutamylpeptide hydrolyzing activity without interfering with the trypsin-like activity. However, those effects are only observed when the closed ring forms of the drugs are used, while the opened ring form of lovastatin acts as a mild inhibitor of the chymotrypsin like activity. The closed ring form of lovastatin is much more potent as a cytotoxic agent on the Colon-26 (C-26) colon carcinoma cell line than the opened ring form, which is only mildly cytostatic. Moreover, neither the cytotoxic effects nor the effects on 20 S proteasome activities are prevented by mevalonate, which by itself inhibits the trypsin-like activity of the proteasome. Neither the opened ring nor the closed ring form of lovastatin induces an accumulation of ubiquitin-protein conjugates, which is observed after treatment with lactacystin, a selective proteasome inhibitor. In contrast with the opened ring form of lovastatin, the closed ring form induces the disappearance of detectable p27(kip1) from C-26 cells. Altogether, our results indicate that the closed ring form of lovastatin induces cytotoxic effects independent of its HMG-CoA inhibiting activity, however, those effects are mediated by a complex modulation of proteasome activity rather than by inhibition of the 20 S proteasome.

Animals↗
PubMed2000

Comparative tolerability, pharmacodynamics, and pharmacokinetics of a metabolite of a quinolizinone hypnotic and zolpidem in healthy subjects.

The objectives of this double-blind, placebo-controlled study were to assess the single dose tolerability, pharmacodynamics, and pharmacokinetics of Ro 41-3290 (5, 10, and 30 mg) and zolpidem (10 mg) in three sequential groups of 10 healthy male subjects. Pharmacodynamic (tracking, attention, and memory test) and pharmacokinetic measurements were conducted over a period of 24 and 50 h, respectively, after drug intake. Ro 41-3290 was well tolerated at all doses as was zolpidem. Performance in both a tracking and a memory search test was affected at 1.5 h after administration of zolpidem, whereas effects had vanished by 8 h. Ro 41-3290 induced moderate, dose-independent effects, which were most pronounced at 4 h after intake. Long-term memory, as assessed by a word learning and recall test, was not clearly affected by any drug. The pharmacokinetics of Ro 41-3290 were dose proportional with an elimination half-life of approximately 8 h. The relatively slow absorption of Ro 41-3290 (t(max) approximately 2.5 h) and the concentration-effect time delay do not make it a good candidate to replace its parent compound Ro 41-3696 as an investigational hypnotic.

Adult↗
PubMed1995

Stroke patients' views on their admission to hospital.

OBJECTIVE: To explore which components of care were valued by patients admitted to hospital following a stroke. DESIGN: Qualitative study using in depth interviews 10 months after the stroke. SETTING: Two adjacent districts in North Thames Regional Health Authority. SUBJECTS: 82 survivors of stroke taken consecutively from a stroke register, 40 of whom agreed to be interviewed. RESULTS: Patients reported that during the acute stage of the stroke they wanted to put their faith in experienced and trusted experts who would help them make sense of the event, take all the actions necessary to ensure survival, and provide comfort and human warmth during the crisis. In addition to being reassured by the clinical tests and practical nursing help they received, patients valued feeling cared about by the staff. In most cases patients reported that their needs were met; however, the institutional nature of the hospital sometimes obstructed the fulfillment of their needs. CONCLUSION: Patients have important psychosocial needs during the acute stage of the stroke, which are often met by hospital admission. Patients gained benefits from their admission over and above those measurable in terms of morbidity or function. They used a combination of criteria to evaluate their care, focusing on the process as well as the outcome of care. Researchers and clinicians should do likewise.

Adult↗
PubMed1995

Pharmacokinetics and pharmacodynamics of Ro 41-3696, a novel nonbenzodiazepine hypnotic.

This report describes the first evaluation in humans of Ro 41-3696. Based on its preclinical profile, Ro 41-3696, a nonbenzodiazepine partial agonist at the benzodiazepine receptor, offers promising perspectives as an innovative hypnotic drug in that it does not exhibit most of the disadvantages associated with full agonists. Single oral doses of 0.1, 0.3, 1.0, 3.0, 10, and 30 mg were administered sequentially to six groups of six healthy male volunteers in a placebo-controlled, double-blind design. Tolerability was assessed and pharmacokinetic and pharmacodynamic measurements were conducted during a period of 28 hours after drug intake. Ro 41-3696 was well tolerated at all doses, causing no clinically relevant changes in vital signs or laboratory parameters. At doses of 10 and 30 mg there were signs of unsteady gait, indicating a central nervous system depressant effect. Pharmacokinetic analyses revealed that Ro 41-3696 was absorbed and eliminated rapidly (tmax = approximately 1 hour; t1/2 = approximately 4 hours). At all times plasma levels of Ro 41-3290, the desethylated derivative of Ro 41-3696, were higher than those of the parent drug (tmax and t1/2 values = approximately 2 and 8 hours, respectively). Area under the curve (AUC) data indicated dose-proportional pharmacokinetics for both Ro 41-3696 and Ro 41-3290. Performance in both a tracking and a memory search test was significantly affected by doses of 10 and 30 mg, and long-term memory, as assessed by a word learning and recall test, was slightly impaired at these doses. The results of this study support the initiation of therapeutic efficacy studies with Ro 41-3696 in doses up to approximately 5 mg and further exploration of the characteristics of Ro 41-3290.

Administration, Oral↗
PubMed1995

Comparative pharmacodynamics of Ro 41-3696, a new hypnotic, and zolpidem after night-time administration to healthy subjects.

In a double-blind, six-way crossover study the effects on psychomotor performance and memory of single doses of Ro 41-3696 (1, 3, 5 and 10 mg), a novel non-benzodiazepine partial agonist at the benzodiazepine receptor, zolpidem (10 mg) and placebo were compared after night-time administration to 12 healthy young male subjects. Psychomotor performance tests (tracking and attention as part of a standardized task battery) were conducted just before and at 1.5 and 8 h after drug intake. The memory test consisted of the recall of a list of 15 words at 8 h after drug intake which had been learned at 1.5 h after intake. At 1.5 h after drug intake 10 mg zolpidem induced markedly larger psychomotor effects than any dose of Ro 41-3696. The effects of 5 and 10 mg Ro 41-3696 and zolpidem were significantly greater than those of placebo (P < 0.05). The following morning, 8 h after drug intake, the slight residual effects of 5 and 10 mg Ro 41-3696 were statistically significantly greater than placebo, whereas zolpidem effects did not differ from placebo. The results of the memory test showed that learning as well as recall were most clearly impaired by zolpidem. An influence of Ro 41-3696 on these variables was not observed for doses up to 5 mg. In conclusion, Ro 41-3696 at all doses tested induced less effects on psychomotor performance and memory than 10 mg zolpidem at 1.5 h after intake. However, the effects of Ro 41-3696 appeared to be of longer duration.

Adult↗
PubMed1995

Interferon alpha-2a and external beam radiotherapy in the initial management of patients with glioma: a pilot study of the National Biotherapy Study Group.

The National Biotherapy Study Group conducted a phase I/II trial of alpha-interferon (IFN) plus radiation therapy (RT) in glioma patients to confirm the feasibility of combining these two modalities. Patients newly diagnosed gliomasreceived external beam RT as 180 cGy in 33 fractions over six to seven weeks, five days a week, and IFN at a dose of 3 MIU SC Monday, Wednesday and Friday of each week. IFN was increased to 5 MIU after two weeks and was given for up to 16 weeks. Patients were monitored for toxicity and failure-free and overall survival. There were 12 men and seven women with an age range of 24-77, and a median age of 64 years. There were 12 glioblastomas and seven advanced astrocytomas. Complete surgical resection was carried out in two patients, nine had a partial resection, and eight had a biopsy only. Two patients in the latter group deteriorated rapidly and received < 2 weeks of RT/IFN. One patient stopped IFN because of a skin rash, another stopped because of concurrent pneumonia, and one patient was noncompliant. RT and IFN were well-tolerated; 14 of the 19 patients completed the eight weeks of IFN/RT. However, only three patients took IFN for the maximum of 16 weeks. The only grade 4 toxicities noted were increases SGOT in three, increases alk phos in two, and severe fatigue in four patients. The median failure-free survival was two months, median survival was 7.5 months, and four patients survived beyond one year. The longest survivor was 29.1 months, and one patient is still alive after 20.7 months. IFN/RT can be safely co-administered in patients with gliomas. A randomized trial would be needed to establish clinical benefit.

Adult↗
PubMed1994

Health promotion and lay epidemiology: a sociological view.

In this paper two fears about health promotion are identified. The first concerns the ability to choose between proliferating expert advice, and the second concerns the fear of government interference in personal life. The paper goes on to outline the current place of health promotion in British health policy, and to discuss the relevance of recent research on health beliefs. The paper argues that work on 'lay epidemiology' has been overlooked by both critics and supporters of health promotion. From this vantage point the fears about health promotion can be seen to be exaggerated.

Attitude to Health↗
PubMed1994

Views of survivors of stroke on benefits of physiotherapy.

OBJECTIVE: To describe the components of physiotherapy valued by survivors of a stroke. DESIGN: Qualitative study using in-depth interviews. SETTING: Two adjacent districts in North East Thames Regional Health Authority. PATIENTS: 82 survivors of stroke taken consecutively from a stroke register when they reached the tenth month after their stroke, 40 of whom agreed to be interviewed. MAIN MEASURES: Content analysis of interviews. RESULTS: Patients who agreed to the interview were significantly less likely to be disabled 12 months after stroke than those who did not. Twenty four patients had received physiotherapy, and these were more disabled than those who had not. Patients appreciated physiotherapy. It was believed to bring about functional improvement; the exercise component was valued because it was perceived to keep them active and busy and exercise programmes to follow at home were also valued for the structure they gave to each day; and therapists were considered a source of advice and information and a source of faith and hope. CONCLUSIONS: Many of the positive aspects of caring which patients described in the context of physiotherapy could be incorporated into the mainstream of rehabilitation care and training. However, health professionals need to be careful not to promote false expectations about recovery. IMPLICATIONS: The outcome of treatment is of critical importance to patients and should become a central dimension of patient satisfaction questionnaires. The impact of physiotherapy is not confined to reducing physical disability but may also affect wellbeing. The choice of outcome measures in rehabilitation research should reflect this situation.

Adult↗
PubMed1991

Tranquillisers and health care in crisis.

This paper addresses the issue of the crisis of therapeutic efficacy in Britain through a case study of benzodiazepine tranquilliser dependence. The paper traces the rise of tranquillisers and the crisis of legitimacy in prescribing behaviour in the 1980s. It documents growing concern with dependence and the claims made about it by experts and consumer groups. The paper goes on to analyse the importance of the television in these claims-making activity and its influence in shaping perceptions. Finally, we consider the implications of these events for the future of benzodiazepine tranquillisers as a form of treatment.

Anti-Anxiety Agents↗
PubMed1987

Problems in the assessment of outcome in a back pain clinic.

A sample of 72 patients attending the rheumatological back pain clinic of a district general hospital were interviewed at home, before their visit, about their expectations of the clinic. They also completed a Back Pain Disability Questionnaire. Fifty of the patients were recontacted by mail 3 months after their first clinic attendance and asked to complete the Back Pain Disability Questionnaire together with satisfaction questionnaires. Patients' reports, both with regard to expectations and satisfaction, particularly emphasized the importance of communication. One-third of the follow-up sample rated their clinic attendance as unhelpful, and although such views correlated with lack of improvement in pain and disability, other factors are involved in patients' evaluations. Significant correlations were obtained between subjective outcomes and health locus of control, social class and previous hospital treatment. Patient satisfaction may be a valuable measure of outcome in assessing the efficacy of back pain treatment.

Adult↗
PubMed1982

Chronic illness as biographical disruption.

The paper is based on semi-structured interviews with a series of rheumatoid arthritis patients. Chronic illness is conceptualised as a particular type of disruptive event. This disruption highlights the resources (cognitive and material) available to individuals, modes of explanation for pain and suffering, continuities and discontinuities between professional and lay thought, and sources of variation in experience.

Arthritis, Rheumatoid↗