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Biomedical subjects

J Bainbridge

Publications and source records attributed to J Bainbridge.

12 recordsLinked to original sources
PubMed2004

Multiple antigenic peptides facilitate generation of anti-prion antibodies.

Recent reports have demonstrated the ability of anti-prion antibodies to inhibit PrPSc propagation. Due to the relatively poor immunogenic properties of both PrPC and PrPSc, the generation of anti-prion antibodies still causes a significant problem in the development of immunotherapeutic strategies. This study examines the potential of multiple antigenic peptides (MAPs) to raise an antibody response to prion derived sequences in mice. The MAP was constructed of a four spiked ring. Two spikes containing human or mouse derived prion amino acid sequences and two spikes containing the universally promiscuous tetanus toxoid sequence (aa 830-844) which was used to assist T-cell-dependent B-cell antibody production. Following vaccinations with the MAP or MAP plus adjuvant, sera were taken and antibody titres assessed. The MAP containing only the mouse sequence failed to elicit a significant antibody response. MAPs containing human prion sequences elicited antibody production to the corresponding prion sequence. Further analysis also demonstrated that these peptides were able to generate antibody responses that recognize conserved human and mouse sequences. These homologous sequences contain the heralded PrPSc specific sequence 'Tyr-Tyr-Arg' and therefore these MAPs may have some therapeutic potential.

Adjuvants, Immunologic↗
PubMed2003

Cell mediated immune responses against human prion protein.

Vaccination approaches that may provide protection against the abnormal form of prion protein (PrPSc) have recently focused on the ability of antibodies to prevent PrPSc propagation. Progress has been hampered due to the difficulty in generating antibody responses in wild type mice, which is believed to be a consequence of T cell tolerance to the normal form of prion protein (PrPC). The problem of tolerance can be avoided using transgenic mice unable to express PrPC. This study examines active PrP specific T cell responses that can be produced in PrP null (PrP 0/0) mice using simple peptide vaccination procedures. Spleenocytes recovered from vaccinated PrP 0/0 mice were tested in vitro for their specificity with T cell recognition demonstrated through a proliferative response to the peptide. Analysis of mRNA also indicates the stimulation of a heterogenous population of T cells with an increase in cytokines and cytotoxicity associated mRNA. Responsive T cells were expanded using a T cell cloning procedure and demonstrated an ability to recognize the mature human prion protein. These clones may potentially be used to negate the problem of T cell tolerance in wild type mice.

Animals↗
PubMed2001

An immune response after intraocular administration of an adenoviral vector containing a beta galactosidase reporter gene slows retinal degeneration in the rd mouse.

BACKGROUND/AIMS: Retinal degenerations are a leading cause of blindness for which there are currently no effective treatments. This has stimulated interest in the investigation of gene therapy strategies for these diseases in a variety of animal models. A number of attempts have been made to prevent photoreceptor loss in the rd mouse model of retinal degeneration using adenoviral vectors containing either a copy of the missing functional gene or a gene encoding either a neurotrophic factor or an antiapoptotic factor. The authors have previously demonstrated that intraocular administration of an adenoviral vector containing a beta galactosidase gene (AV.LacZ) results in an immune response to viral gene products and beta galactosidase. Here the effect of the immune response on retinal degeneration is examined. METHODS: Juvenile rd mice were injected intravitreally with AV.LacZ and a proportion were depleted of either CD4+ or CD8+ T cells or both. Control animals were injected with PBS. The mice were sacrificed 10 and 20 days post-injection and their eyes embedded in paraffin wax and sectioned. RESULTS: 10 days after intravitreal injection of AV.LacZ, the outer nuclear layer contains an average of 2.5 rows compared with 1.5 in PBS injected animals (p<0.005). The protective effect of AV.LacZ is negated by immune suppression and does not extend beyond 20 days. CONCLUSION: An immune response to vector and transgene products is able to slow degeneration in the rd mouse. This phenomenon should be taken into account when analysing the degeneration in the rd mouse following gene transfer.

Adenoviridae↗
PubMed2000

Some practical issues in the design, monitoring and analysis of a sequential randomized trial in pressure sore prevention.

A sequential double blind (assessor and patient) triangular design was used to compare the incidence of pressure sores following elective major surgery among patients lying on a standard foam mattress with those on a dry visco-elastic polymer pad during their operation. A total of 446 patients were recruited into the trial between 1994 and 1996. Interim analyses were carried out after 181 patients were entered into the trial and then subsequently after approximately every 100 patients recruited. The trial unexpectedly reached a stopping boundary at the first interim analysis, however the Independent Data Monitoring Committee recommended continuation of the trial. They were concerned that there was a need for a larger definitive trial and about an apparent treatment by centre interaction. They required a substudy to be undertaken to further validate the subjective endpoint, and that further sensitivity analyses of the main trail endpoint should be carried out in the second interim analysis. The trial was stopped at the third interim analysis when again a stopping boundary was crossed indicating that the gel pad was associated with significantly fewer pressure sores than the standard mattress (log odds ratio -0.7, (95 per cent confidence interval (CI), -1.28, -0.11), p=0.02) (estimate CI, p-value adjusted for group sequential conduct). The design, monitoring and analysis of this trial will be presented as an example of the practical problems or non-problems encountered for the local hospitals, for the trials unit, for the data monitoring committee and for the funding committee.

Beds↗
PubMed2000

Postoperative evaluation of patients following ophthalmic surgery.

We have used telemedicine to support the postoperative evaluation of patients who have had ophthalmic surgery. Mobile telemedicine workstations connected using three ISDN lines have enabled us to review patients at an outreach clinic on the first postoperative day. Video slit-lamp images of the patient are captured by a trained ophthalmic nurse at the outreach clinic and viewed by surgeons at Moorfields Eye Hospital in central London during live teleconsultations. During the study period, over 80 teleconsultations were carried out on postoperative cataract, trabeculectomy and combined procedures. Preliminary results are very encouraging. Although 8 (33%) of 24 patients were anxious about being involved in the teleconsultation, 20 (83%) had confidence in the system and only one (4%) found the experience unacceptable.

Eye Diseases↗
PubMed1998

Persistent expression of mitogenic/transforming factors at the site of failed orthopaedic implants: the impact on immune reactivity.

The response to wear particles from orthopaedic implants can lead to inflammation, osteolytic lesions, and aseptic loosening. To gain an insight into the development of this pathogenetic process, immunohistochemical techniques were used to identify the expression and tissue distribution of the potent cell mitogen epidermal growth factor (EGF), and the epidermal growth factor receptor (EGF-R) at the site of bone erosion in 30 patients with clinically failed orthopaedic implants. The results showed a large proportion of the macrophage subsets (Mphi) which expressed EGF and EGF-R, also contained wear particles, indicating their expression is a consequence of Mphi phagocytosis of implant material. The surface membrane expression of EGF-R on fusing Mphi suggests its presence is fundamental to the formation of bone-resorbing multi-nucleated giant cells, and the development of osteolysis. Additionally, there is increasing evidence of the long-term systemic spread of wear particles and their accumulation at distal sites including lymph nodes, liver, and spleen. Elevated expression of mitogenic factors in response to wear particles may result in deviation from normal cell growth and regulation, resulting in changes to immune cell function. Such potential transformations at distal sites are clinically significant, as alterations to the patient's immune system may result in acute divergence from normal immune cell responses.

Journal Article↗
PubMed1993

Care plan for documenting pharmacist activities.

At a 393-bed hospital, a pharmaceutical care plan was developed and tested in a surgical intensive care unit (SICU). The trial care plan was developed and implemented with the following objectives: to integrate clinical and distributive elements of patient information in a care plan; to add new monitoring and intervention parameters to the pharmacy profile; and to assess and refine the care plan for implementation in other areas of the institution. One pharmacist performed and documented care for 10 patients in the SICU. The pharmacist planned appropriate drug administration schedules, noted appropriate indications for each medication ordered, established appropriate outcomes, monitored for drug-drug or drug-food interactions and allergies, recorded interventions and averted adverse drug reactions, and recorded the amount of time required for care according to disease state. Pharmacist involvement with medication administration and monitoring seemed to prevent many adverse effects and drug interactions. Because of the diversity of the patient population, there was substantial variation in the time spent on care. A trial pharmaceutical care plan in a surgical intensive care unit was useful for documenting pharmacists' productivity and effectiveness.

Colorado↗