Competitive control of the self-renewing T cell repertoire

We develop a mathematical model for the self-renewing part of the T cell repertoire. Assuming that self-renewing T cells have to be stimulated by immunogenic MHC-peptide complexes presented on the surfaces of antigen-presenting cells, we derive a model of T cell growth in which competition for MHC-peptide complexes limits T cell clone sizes and regulates the total number of self-renewing T cells in the animal. We show that for a sufficient diversity and/or degree of cross-reactivity, the total T cell number hardly depends upon the diversity of the T cell repertoire or the diversity of the set of presented peptides. Conversely, for repertoires of lower diversity and/or cross-reactivity, steady-state total T cell numbers may be limited by the diversity of the T cells. This provides a possible explanation for the limited repertoire expansion in some, but not all, mouse T cell re-constitution experiments. We suggest that the competitive interactions described by our model underlie the normal T cells numbers observed in transgenic mice, germ-free mice and various knockout mice.      

ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome

It was shown recently that mutations of the ATRX gene give rise to a severe, X-linked form of syndromal mental retardation associated with alpha thalassaemia (ATR-X syndrome). In this study, we have characterised the full-length cDNA and predicted structure of the ATRX protein. Comparative analysis shows that it is an entirely new member of the SNF2 subgroup of a superfamily of proteins with similar ATPase and helicase domains. ATRX probably acts as a regulator of gene expression. Definition of its genomic structure enabled us to identify four novel splicing defects by screening 52 affected individuals. Correlation between these and previously identified mutations with variations in the ATR-X phenotype provides insights into the pathophysiology of this disease and the normal role of the ATRX protein in vivo.      

Fragile X‐associated tremor/ataxia syndrome (FXTAS) in grey zone carriers

The grey zone (GZ; 45–54 CGG repeats in the FMR1 gene) is considered a normal allele; however, several studies have found a high frequency of GZ in movement disordered populations. Here, we describe neurological features of fragile X‐associated tremor/ataxia syndrome (FXTAS) in two carriers of GZ alleles, although FXTAS has been defined as occurring only in premutation carriers (55–200 CGG repeats). Both patients had family members who had premutation and were diagnosed with FXTAS. The presence of relatively high GZ alleles with elevated fragile X mental retardation 1 mRNA (FMR1‐mRNA) combined with a family history of FXTAS that may represent a facilitating genetic background for FXTAS are the factors that led to the presence of FXTAS in these individuals with a GZ allele. Further research into clinical involvement of GZ alleles is recommended and the definition of FXTAS may require revision.     

Foreign body removal with fine-nosed forceps and assistance of image intensification

Foreign body removal has been developed as a routine radiology department service. Techniques, indications and hazards are described.     

Unusual presentation of perirenal lung metastases

Lung cancer is not commonly known to metastasise to the perirenal space, with only five such cases previously published. We present an unusual case of perirenal lung metastases manifesting as diffuse perinephric stranding which to our knowledge has not been described before.     

Breast cancer cell lines: friend or foe?

The majority of breast cancer research is conducted using established breast cancer cell lines as in vitro models. An alternative is to use cultures established from primary breast tumours. Here, we discuss the pros and cons of using both of these models in translational breast cancer research.     

Paracetamol use, availability, and knowledge of toxicity among British and American adolescents

Paracetamol is the commonest agent employed in self poisoning, however it is not clear whether adolescents possess insight into the serious complications associated with its misuse. Using a one page questionnaire, the availability, usage, and knowledge of toxicity of paracetamol among 1147 American and British adolescents was assessed. Although 90% of all students recognised that paracetamol could kill, the great majority of students overestimated the lethal dose. In addition, while knowledge regarding side effects of paracetamol was poor the drug was widely available to, and used by, the study population. It is proposed that gross overestimation of the number of tablets required to kill, poor understanding of paracetamol side effects, and wide availability of the drug contribute to its frequent use in adolescent suicidal behaviour. The inclusion of some over-the-counter medications in school drug education programs in addition to tighter control of the availability of paracetamol may help reduce the problem of adolescent self poisoning.     

Screening for a raised rectal temperature in Africa

The main purpose of this study was to compare rectal and axillary temperature measurements in African children. Altogether 573 sick children were seen in an outpatient setting in rural West Africa. Rectal and axillary temperatures were measured and the parent or guardian was asked if they thought that the child had a raised body temperature. Normal ranges were defined from an age matched population of 203 healthy children. A raised axillary temperature predicted a raised rectal temperature with a sensitivity of 98% and a specificity of 88%. The parents' impression that their child had a fever was a less sensitive (89%) and less specific (59%) indicator of raised rectal temperature. A raised axillary temperature is a good screening test for a raised rectal temperature in African children.