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J R Kerr

Publications and source records attributed to J R Kerr.

78 records · Page 5Linked to original sources
PubMedDate not supplied

Pathogenesis of parvovirus B19 infection: host gene variability, and possible means and effects of virus persistence.

Since conducting follow-up studies of patients with acute symptomatic parvovirus B19 infection which showed that a significant proportion of patients develop prolonged arthritis and chronic fatigue syndrome (CFS), we have become interested in the mechanisms of this phenomenon. We showed that these cases have high levels of pro-inflammatory cytokines in their circulation and that this correlates with the symptoms. However, the underlying mechanisms were not apparent, and we have used various approaches to begin studying this phenomenon. DNA polymorphisms were looked for and several were shown to be more common in these subjects compared with controls; these occur within genes of both the immune response [human leucocyte antigen (HLA)-DRB1, HLA-B, transforming growth factor (TGF)-beta1] and those involved in several other cellular functions (predominantly the cytoskeleton and cell adhesion). Interestingly, one particular single-nucleotide polymorphism (SNP) which is associated with symptomatic B19 infection occurs in the Ku80 gene which has recently been shown to be a B19 co-receptor. B19 persistence is probably the key to this phenomenon, and some new data are presented on short regions of sequence homology (17-26 bp) between human, mouse and rat parvoviruses and their respective hosts which occur in many host genes. This homology may provide a foothold for virus persistence and may also play a role in the genesis of disease through gene disruption. Finally, we used microarrays and TaqMan real-time polymerase chain reaction in 108 normal persons to study human gene expression in persons who are B19-seropositive versus B19-seronegative (age- and sex-matched) to examine the hypothesis that gene regulation may be altered in subjects harbouring the B19 virus DNA. Six genes were found to be differentially expressed with roles in the cytoskeleton (SKIP, MACF1, SPAG7, FLOT1), integrin signalling (FLOT1, RASSF5), HLA class III (c6orf48), and tumour suppression (RASSF5). These results have implications not only for B19 but also for other persistent viruses as well and confirmation is required. In conclusion, these disparate findings contribute to our understanding of the pathogenesis of B19 disease. We are using these studies as a starting point to study the phenomenon of chronic immune activation following B19 infection.

Genetic Predisposition to Disease↗
PubMedDate not supplied

Penicillin allergy: a study of incidence as reported by patients.

To assess the incidence of penicillin allergy as reported by patients to doctors, a 5-month study was undertaken in a university teaching hospital. The study design was prospective, and included all hospital patients for whom advice on clinical management was given by one bacteriology registrar and in whom the previous response to penicillin was considered. Of the 271 patients included in the study, 21 reported penicillin allergy. The most commonly reported symptom was localised rash (8 cases), followed by unknown reaction symptoms (6), nausea with or without vomiting (3), generalised itchy rash with difficulty in breathing (3), and localised rash with chest pain (1). Three of 21 cases reported generalised rash with difficulty in breathing; two of these followed intravenous penicillin administration. If the three cases of generalised itchy rash with difficulty in breathing are taken as true type-1 hypersensitivity to penicillin, the incidence of this was 1.11% (3 of 271), and the incidence of true allergy among patient-reported allergy was 14.3% (3 of 21). In two cases of reported penicillin allergy a penicillin was administered for treatment of the current infection, despite the history and without any ill-effects. Penicillins are non-toxic and inexpensive and, despite the number of alternatives for antibacterial therapy, are still the treatment of choice for many infections. More attention should therefore be paid to details of the clinical history relating to penicillin allergy with a view to decreasing the number of patients labelled 'penicillin-allergic'.

Adolescent↗