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Biomedical subjects

Ian Brown

Publications and source records attributed to Ian Brown.

31 records · Page 2Linked to original sources
PubMed2004

Genetic relationships, serological cross-reaction and cross-protection between H1N2 and other influenza A virus subtypes endemic in European pigs.

This study examines the genetic relationships between the recently emerged H1N2 swine influenza virus and viruses of H1N1 and H3N2 subtypes, and the extent of protection against H1N2 challenge in pigs immune after infection or vaccination with the other subtypes. There was low amino acid homology (70.4-71.9%) in the haemagglutinin (HA) gene between H1N1 viruses used for primary infection or vaccination and the H1N2 challenge strain, with 94-99 amino acid changes between these viruses involving all five antigenic sites. The NA genes of H3N2 viruses used for primary infection or vaccination showed higher amino acid homology with H1N2 (88.3-92.6%), while nucleoprotein (95.5-96.3% nucleotide identity) and matrix (96.8-98.4%) genes were most conserved between the three subtypes. Pigs immune as a result of intranasal inoculation with either H1N1 or H3N2 showed partial clinical protection against H1N2 challenge, and nasal virus excretion was 2 days shorter than in naive pigs. Moreover, dually infected (H1N1 + H3N2)-immune pigs showed complete clinical protection and H1N2 virus replication in the lungs and nasal secretions was either undetectable or markedly reduced. In contrast, a double vaccination with a commercial H1N1 and H3N2-based vaccine did not protect against H1N2 challenge. Haemagglutination inhibition (HI) or virus neutralisation (VN) tests of swine sera revealed little if any antigenic cross-reactivity between subtypes. These data suggest that serum HI or VN antibodies are not essential in heterosubtypic protection, but that mucosal or cellular immunity are probably involved. It is still unknown whether this type of cross-subtype protection will also occur in infection-immune pigs in the field.

Animals↗
PubMed2004

Pharmaceutical care model for patients with type 2 diabetes: integration of the community pharmacist into the diabetes team--a pilot study.

OBJECTIVE: To evaluate the feasibility and impact of a structured approach for community pharmacist input as a member of the multidisciplinary team caring for patients with type-2 diabetes and health professional providing advice on medication. METHODS: Prospective pretest-posttest single group study. Sixty-two patients on oral hypoglycaemic therapy, identified as regular customers of four Scottish (UK) community pharmacies, were recruited. Each patient underwent an initial assessment: review of medical general practice notes/community pharmacy PMR (Patient medication record) system and structured interview. Standardised documentation was completed, a pharmaceutical care plan (PCP) prepared, peer-reviewed and then discussed face-to-face with patients' GPs (general practitioners). A second (final) assessment was conducted 24 to 28 weeks from the initial interview. MAIN OUTCOME MEASURES: Pharmaceutical care issues (PCIs) throughout study period; change in parameters from initial to final assessment: patient knowledge of oral hypoglycaemic and anti-hypertensive therapy; HbA1c; blood pressure; total cholesterol; medication compliance. RESULTS: A total of 178 PCIs were identified (mean [range] 2.9 [1-5] per patient) and categorised: drug therapy problems (n = 76); monitoring (n = 21); and patient knowledge (n = 81). Drug therapy problems discussed with the GPs were agreed for 74 (97%) and resolved for 55 (72%) at final assessment. Biological outcome measures were assessed for 59 patients (3 drop-outs). A reduction (P < 0.05) in HbA1 c, blood pressure and total cholesterol was observed over the study period. Patients knowledge was poor for oral hypoglycaemic therapy but improved (initial-51 %, final-72%, P < 0.05). CONCLUSION: This study demonstrated a feasible pharmaceutical care model for diabetes patients in an European country. The results have shown the pharmacist to be effective and well accepted by GPs and patients.

Community Pharmacy Services↗
PubMed2004

Basal defenses induced in pepper by lipopolysaccharides are suppressed by Xanthomonas campestris pv. vesicatoria.

The nonpathogenic hrcC mutant of Xanthomonas campestris pv. vesicatoria 85-10::hrpA22 multiplied in pepper leaves if it was mixed with pathogenic strains of X. campestris pv. vesicatoria. Reactions to the mutant alone included localized deposition of phenolics and callose in papillae, and alterations to the plant cell wall leading to increased electron density. Electron microscopy showed that the localized responses were suppressed in the presence of wild-type bacteria but other wall changes occurred at some sites, involving cellulose-rich ingrowth of the wall. Multiplication of the hrp mutant in mixed inocula was confirmed by tagging 85-10::hrpA22 using immunocytochemical location of AvrBs3 expressed from the plasmid pD36. Elicitors of callose deposition and other wall changes were isolated from the hrcC mutant. Activity in extracts of bacteria was attributed to the presence of high molecular weight lipopolysaccharides (LPS). Wild-type X. campestris pv. vesicatoria suppressed induction of structural changes caused by purified LPS. Results obtained suggest that effector proteins produced by phytopathogenic bacteria and delivered by the type III secretion system may have a key role in suppressing the basal defense responses activated by bacterial LPS, which lead to restricted multiplication of nonpathogens such as hrp mutants.

Bacterial Proteins↗
PubMed2003

Absence of programmed death receptor 1 alters thymic development and enhances generation of CD4/CD8 double-negative TCR-transgenic T cells.

Programmed death receptor 1 (PD-1) is expressed on thymocytes in addition to activated lymphocyte cells. Its ligation is thought to negatively regulate T cell activation, and PD-1(-/-) mice develop autoimmunity. To study the role of PD-1 on the development and function of a monoclonal CD8(+) T cell population, 2C TCR-transgenic/recombination-activating gene 2(-/-)/PD-1(-/-) mice were generated. Unexpectedly, approximately 30% of peripheral T cells in these mice were CD4/CD8 double negative (DN). Although the DN cells were not activated by Ag-expressing APCs, they functioned normally in response to anti-CD3/anti-CD28. These cells had a naive surface phenotype and lacked expression of NK1.1, B220, and gammadelta TCR; and the majority did not up-regulate CD8alphaalpha expression upon activation, arguing that they are not predominantly diverted gammadelta-lineage cells. The thymus was studied in detail to infer the mechanism of generation of DN peripheral T cells. Total thymus cellularity was reduced in 2C TCR-transgenic/recombination-activating gene 2(-/-)/PD-1(-/-) mice, and a relative increase in DN cells and decrease in double-positive (DP) cells were observed. Increased annexin V(+) cells among the DP population argued for augmented negative selection in PD-1(-/-) mice. In addition, an increased fraction of the DN thymocytes was HSA negative, suggesting that they had undergone positive selection. This possibility was supported by decreased emergence of DN PD-1(-/-) 2C cells in H-2(k) bone marrow chimera recipients. Our results are consistent with a model in which absence of PD-1 leads to greater negative selection of strongly interacting DP cells as well as increased emergence of DN alphabeta peripheral T cells.

Animals↗
PubMed2003

Type III protein translocase: HrcN is a peripheral ATPase that is activated by oligomerization.

Type III protein secretion (TTS) is catalyzed by translocases that span both membranes of Gram-negative bacteria. A hydrophilic TTS component homologous to F1/V1-ATPases is ubiquitous and essential for secretion. We show that hrcN encodes the putative TTS ATPase of Pseudomonas syringae pathovar phaseolicola and that HrcN is a peripheral protein that assembles in clusters at the membrane. A decahistidinyl HrcN derivative was overexpressed in Escherichia coli and purified to homogeneity in a folded state. Hydrodynamic analysis, cross-linking, and electron microscopy revealed four distinct HrcN forms: I, 48 kDa (monomer); II, approximately 300 kDa (putative hexamer); III, 575 kDa (dodecamer); and IV, approximately 3.5 MDa. Form III is the predominant form of HrcN at the membrane, and its ATPase activity is dramatically stimulated (>700-fold) over the basal activity of Form I. We propose that TTS ATPases catalyze protein translocation as activated homo-oligomers at the plasma membrane.

Adenosine Triphosphatases↗
PubMed2003

Death of peripheral CD8+ T cells in the absence of MHC class I is Fas-dependent and not blocked by Bcl-xL.

Productive immune responses require an appropriate environment to support peripheral CD8(+) T cell survival. Although host MHC class I molecules appear to be required for this process, the cellular and molecular requirements have not been comprehensively studied. Using adoptive transfer of 2C/recombinase-activating gene-2 (RAG-2)(-/-) TCR-transgenic T cells, we found that the survival of both naive and effector CD8(+) T cells was dependent upon host expression of the same MHC class I alleles that supported thymic selection. Expression of appropriate MHC class Iby either bone marrow- or non-bone-marrow-derived cells was sufficient, suggesting that professional antigen-presenting cells were not mandatory. In contrast to MHC class I, neither T cell expression of CD28 nor host expression of ICAM-1 was required for peripheral T cell survival. Finally, T cell death in the absence of appropriate host MHC class I was overcome by elimination of Fas signaling but not by overexpression of Bcl-x(L) by CD8(+) T cells. These results suggest that, in the absence of a survival signal provided by engagement of host MHC/self peptide complexes, CD8(+) T cells die via a Fas-dependent, mitochondria-independent pathway.

Adoptive Transfer↗
PubMed2002

The Hrp pilus of Pseudomonas syringae elongates from its tip and acts as a conduit for translocation of the effector protein HrpZ.

The type III secretion system (TTSS) is an essential requirement for the virulence of many Gram-negative bacteria infecting plants, animals and man. Pathogens use the TTSS to deliver effector proteins from the bacterial cytoplasm to the eukaryotic host cell, where the effectors subvert host defences. Plant pathogens have to translocate their effector proteins through the plant cell wall barrier. The best candidates for directing effector protein traffic are bacterial appendages attached to the membrane-bound components of the TTSS. We have investigated the protein secretion route in relation to the TTSS appendage, termed the Hrp pilus, of the plant pathogen Pseudomonas syringae pv. tomato. By pulse expression of proteins combined with immunoelectron microscopy, we show that the Hrp pilus elongates by the addition of HrpA pilin subunits at the distal end, and that the effector protein HrpZ is secreted only from the pilus tip. Our results indicate that both HrpA and HrpZ travel through the Hrp pilus, which functions as a conduit for the long-distance translocation of effector proteins.

Bacterial Outer Membrane Proteins↗
PubMed2002

How can the dynamics of the tundra-taiga boundary be remotely monitored?

This paper discusses some of the difficulties in establishing the location of the Arctic treeline and forest line on a circumpolar basis, and the contribution that remote sensing, particularly from spaceborne platforms, can make in resolving them. Spaceborne techniques can provide spatial resolutions as fine as a few meters, although the requirements for regional or global coverage are likely to limit the resolution to 30 to 100 m. Since this will preclude the identification of individual trees, the definition of the treeline will be based on statistical parameters estimated from satellite images. The optimum criteria for these parameters remain to be determined. Most remote-sensing observations that are suited to the measurement of the distribution of vegetation, and identification of its type, are based on the visible and near-infrared (VIR) parts of the electromagnetic spectrum, although there is increasing interest in the use of active microwave (radar) techniques. We discuss the basis of both types of approach and the techniques that follow from them, and present 3 case studies from the Russian Arctic.

Arctic Regions↗
PubMed2000

Involving the public in general practice in an urban district: levels and type of activity and perceptions of obstacles.

This paper reports on a study of the level and type of activity used to involve the public in general practice in a city district in the north of England. The association of these activities with features of the general practice organisation and environment were studied. Service providers' perceptions of obstacles were also studied. Data were collected in a survey of all general practice organisations in the district using a postal questionnaire completed by a practice manager. Interviews were conducted with health service managers responsible for primary care development in the district. The study showed that the district had a good track record for innovation in primary care development and in giving emphasis to developing public involvement. However, it also showed that it was difficult to translate policy rhetoric into practical initiatives at the general practice level without evidence of models of best practice, and with limited resources. The survey had a high response of over 84%. It showed that levels of activity were low across the district and only a small minority of general practice teams had undertaken a range of activities to involve the public. The socio-economic environment did not appear to be a factor, but small practices (one or two partners and/or practice population under 3000) were much less likely to develop activities. Pressures of existing workload, lack of resources and public apathy were given as among the main obstacles by survey respondents. The study indicates the challenges faced by Primary Care Groups in developing strands of public involvement. Primary care teams need a clear strategic framework, models of best practice, and adequate resources to manage, change and develop initiatives.

Journal Article↗
PubMed1999

Patient participation groups in general practice in the National Health Service.

General practice remains the organizational hub of first level health services in the United Kingdom. Patient participation groups are probably the most well known model for public participation in this setting and, although still not widespread, they have been a slowly expanding area of development for almost three decades. This paper sets out to critically asses patient participation groups in general practice by considering the context of their development and reviewing the research literature about groups. Critical issues needing more study and key methodological challenges are then discussed. Patient participation groups have been a somewhat shifting and contested phenomenon, embracing trends and changing as policy priorities have changed over the years. There is some evidence to think that they might have potential as a local element within a public participation strategy in the National Health Service. However, the field studies are very limited and more research of a better quality is needed. The state of knowledge is not adequate to be able to say with any confidence if or how such groups should be developed. A better understanding is needed of the public's perspectives on this and other models of participation. There are many other questions to do with patient participation groups' purpose, equitable access, and effectiveness that need to be addressed. The methodological challenges include issues of how to involve all stakeholders in the research process; and how to study less tangible aspects of general practice organization, such as culture and power, that effect the public's participation.

Journal Article↗
PubMedDate not supplied

The role of the Citizens Advice Bureau in supporting health care.

Increasingly, branches of the Citizens Advice Bureau throughout the UK are playing a vital role in supporting patients and their families, mainly through advising them on financial matters, but with practical and legal help on a range of other issues too. This new role is lifting a significant burden from health care staff.

Counseling↗