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Biomedical subjects

R Moxon

Publications and source records attributed to R Moxon.

14 recordsLinked to original sources
PubMed2002

Should the new pneumococcal vaccine be used in high-risk children?

A new conjugate 7-valent vaccine to prevent pneumococcal infection (Prevenar, Wyeth) has recently received a European licence for use in young healthy children. The vaccine is not currently included in the universal immunisation schedule in the UK or elsewhere in Europe, although it is being used widely in the USA. Its availability for purchase raises the question whether paediatricians should consider using it in high risk children, including those for whom the polysaccharide 23-valent vaccine was previously recommended, until (or unless) it is introduced into general use-indeed the Chief Medical Officer for England and Wales has recently made a recommendation regarding such children aged less than 2 years. We review the evidence concerning use of the vaccine in such children and make suggestions as to how the vaccine may be used while further information is collected.

Anemia, Sickle Cell↗
PubMed2000

Challenge of investigating biologically relevant functions of virulence factors in bacterial pathogens.

Recent innovations have increased enormously the opportunities for investigating the molecular basis of bacterial pathogenicity, including the availability of whole-genome sequences, techniques for identifying key virulence genes, and the use of microarrays and proteomics. These methods should provide powerful tools for analysing the patterns of gene expression and function required for investigating host-microbe interactions in vivo. But, the challenge is exacting. Pathogenicity is a complex phenotype and the reductionist approach does not adequately address the eclectic and variable outcomes of host-microbe interactions, including evolutionary dynamics and ecological factors. There are difficulties in distinguishing bacterial 'virulence' factors from the many determinants that are permissive for pathogenicity, for example those promoting general fitness. A further practical problem for some of the major bacterial pathogens is that there are no satisfactory animal models or experimental assays that adequately reflect the infection under investigation. In this review, we give a personal perspective on the challenge of characterizing how bacterial pathogens behave in vivo and discuss some of the methods that might be most relevant for understanding the molecular basis of the diseases for which they are responsible. Despite the powerful genomic, molecular, cellular and structural technologies available to us, we are still struggling to come to grips with the question of 'What is a pathogen?'

Animals↗
PubMed2000

A joint health and social services initiative for children with disabilities.

The children's disability team in Cambridge provides an integrated health and social care service for children with complex learning and physical disabilities and their families. The team uses a multidisciplinary and multi-agency teamwork approach to care provision. The effectiveness of the team was evaluated using a cooperative review of its functions, in which all the 'subjects' were active participants in defining and delivering the evaluation. This was combined with individual questionnaires regarding the team's perceived strengths and weaknesses. Particular implications for training and supervision emerged from the findings. This article discusses the ways in which the team has successfully refined its practice of collaborative working in a developmental way between 1992-1998.

Child↗
PubMed1999

Immune response to revaccination with meningococcal A and C polysaccharides in Gambian children following repeated immunisation during early childhood.

Forty-two Gambian children randomised to receive two doses of meningococcal A/C polysaccharide vaccine (MPS) in infancy and either MPS (n = 15), meningococcal A/C conjugate (n = 13) or inactivated polio vaccine (IPV n = 14) at 2 years, were revaccinated with MPS at 5 years of age along with 39 matched control children. Meningococcal A and C polysaccharide antibodies were analysed by ELISA and bactericidal assay (SBA) in sera taken before and 10 days after revaccination. The geometric mean group SBA titre in the MPS group following revaccination was about half that of the unvaccinated controls (0.51 95%CI: 0.28, 0.90) for group A and less than half that of the controls for group C (0.41, 95%CI: 0.16, 1.03 P = 0.06). The group C SBA response in the conjugate group was 14-fold higher than in the MPS group (P < 0.001). Multiple doses of meningococcal polysaccharide in childhood may therefore attenuate the SBA response to both group A and group C polysaccharides. In contrast, vaccination with meningococcal A/C conjugate after MPS in infancy gives immunological memory to N. meningitidis group C.

Antibodies, Bacterial↗
PubMed1999

For discussion: live attenuated vaccines for group B meningococcus.

Current attempts at preventing infections caused by group B Neisseria meningitidis are largely directed on generating immune responses to outer membrane proteins or the lipopolysaccharide of this organism. We suggest an alternative approach: the use of a live, attenuated strain of Neisseria meningitidis which could be delivered mucosally to elicit both local and systemic immune responses.

Bacterial Vaccines↗
PubMed1999

Contribution of genomics to bacterial pathogenesis.

Genomics is changing the landscape of modern biology. The impact is far-reaching because it provides both the most economical means of acquiring large amounts of information and because it has forced the creation of new technologies to exploit this information. Five of the six genomes published in the year from August 1998 to August 1999 were human pathogens, all of which are highly host-adapted. Four of these are obligate intracellular pathogens and the study of these genomes is providing novel insights into the intricacies of pathogen-host interactions and co-evolution. These genomes are also significant because they mark the beginning of an important trend in the sequencing of closely related genomes, including the sequencing of more than one strain from a single pathogenic species. As comparative genomics truly comes of age, the ability to compare the genomes of pathogenic and non-pathogenic organisms will hopefully provide insight into what makes certain bacterial strains and species pathogens.

Bacteria↗
PubMed1997

Characterization of monoclonal antibodies recognizing three distinct, phosphorylated carbohydrate epitopes in the lipopolysaccharide of the deep rough mutant I-69 Rd-/b+ of Haemophilus influenzae.

Monoclonal antibodies against the lipopolysaccharide (LPS) of the deep rough mutant I-69 Rd-/b+ of Haemophilus influenzae were obtained after immunization of mice with sheep erythrocytes which had been coated with de-O-acylated LPS. Characterization of antibodies was performed by enzyme immuno assay (EIA) using LPS or neoglycoconjugates containing partial structures of LPS as solid-phase antigens and by haemagglutination with sheep erythrocytes coated with de-O-acylated LPS. Binding data were confirmed by EIA inhibition experiments using deacylated LPS or synthetic partial structures thereof. Three antibodies were specific for 3-deoxy-D-manno-octulopyranosonic acid- (Kdo) 5-phosphate, one for Kdo-4-phosphate, and one required, in addition to a Kdo-phosphate, parts of the phosphorylated glucosamine backbone of lipid A. All antibodies also bound in (i) Western blots to bacterial whole-cell lysates or isolated LPS separated by SDS-PAGE, (ii) bacterial colony blots, and (iii) immunofluorescence with live bacteria. The latter result indicated that Kdo-4- and Kdo-5-phosphate are synthesized by the bacteria and are not the result of phosphate migration.

Animals↗
PubMed1992

Use of chromosomal gene fusions to investigate the role of repetitive DNA in regulation of genes involved in lipopolysaccharide biosynthesis in Haemophilus influenzae.

The lic3 locus of Haemophilus influenzae consists of four open reading frames. The derived amino acid sequences of orf2 and orf4 exhibit homology to Escherichia coli GalE and AdK, respectively. The functions of orf1 and orf3 remain unknown. orf1 contains multiple tandem repeats of the tetrameric DNA sequence CAAT near the 5' end. Two possible translational starts (ATG1 and ATG2) lie upstream. We have used lacZ fusions to investigate whether changes in the number of CAAT repeats in conjunction with differential usage of the upstream frames control the expression of lic3-orf1. Phase-variable expression of lacZ was observed for individual colonies and could be related to variable numbers of CAAT repeats. Of the three possible upstream frames, only one, containing the more downstream of the two possible ATG start codons (ATG2), is used for strong expression of lacZ. Utilization of the more upstream ATG (ATG1) or ATG2 was observed with medium-level expression, while utilization of any of the three possible frames was observed when lacZ was expressed at low to undetectable levels, indicating that other mechanisms may affect expression. To investigate this, lacZ was fused in frame with ATG2 of lic3-orf1, with concomitant deletion of the repeats. Phase-variable expression was still observed, supporting the view that an alternative level of control operates in conjunction with the repeat mechanism.

Amino Acid Sequence↗
PubMed1989

Opsonic requirements and interaction of Haemophilus influenzae with human polymorphonuclear neutrophil leucocytes studied by luminol-enhanced chemiluminescence.

We have used human polymorphonuclear leucocyte (PMNL)-dependent chemiluminescence (CL) to study bacteria opsonised with those factors in serum which are reported to be important in opsonisation of H. influenzae, and to determine whether alteration of various surface characteristics of H. influenzae influence those CL responses by PMNL. Although complement plays a role, immunoglobulin and a heat-labile factor(s) were found to be the principle stimulants of PMNL-dependent CL when H. influenzae was opsonised in pooled normal human serum. Acquisition of capsule (serotype a,b,c,e, or f) by an uncapsulated strain significantly (P less than 0.001) reduced its ability to stimulate PMNL-dependent CL, but the type of capsule did not discriminate between the strains in this regard. Surface-adherent capsule inhibited PMNL-dependent CL stimulation more than capsular material released into the supernatant. Altering the lipooligosaccharide composition of the bacterial cell wall also affected PMNL-dependent CL stimulation independent of capsule. We conclude that, although surface characteristics of H. influenzae influenced its ability to stimulate PMNL-dependent CL, these experiments provide no evidence to support the hypothesis that the increased virulence of serotype b capsulated strains compared with other capsulated types could be explained by any specific ability to avoid opsonisation.

Haemophilus influenzae↗