Tumour necrosis factor gene polymorphism: a predictive factor for the development of post-transplant lymphoproliferative disease

Epstein–Barr virus-positive post-transplant lymphoproliferative disease (PTLD) is a potentially lethal complication of iatrogenic immunosupression after transplantation. Predicting the development of PTLD allowing early and effective intervention is therefore of importance. Polymorphisms within cytokine genes are implicated in susceptibility to, and progression of, disease however the published data are often conflicting. We undertook investigation of polymorphic alleles within cytokine genes in PTLD and non-PTLD transplant cohorts to determine risk factors for disease. <br/> Methods: SSP-PCR was used to analyse single nucleotide polymorphism within tumour necrosis factor (TNF)-α, interleukin- 1, -6, -10 and lymphotoxin-α genes. The TNF-α levels were measured by standard enzyme-linked immuno-absorbant assay. <br/> Results: We show an association between variant alleles within the TNF-α promoter (−1031C (<i>P</i>=0.005)); −863A (<i>P</i>=0.0001) and TNF receptor I promoter regions (−201T (<i>P</i>=0.02)); −1135C (<i>P</i>=0.03) with the development of PTLD. We also show an association with TNF-α promoter haplotypes with haplotype-3 significantly increased (<i>P</i>=0.0001) and haplotype-1 decreased (P=0.02) in PTLD patients compared to transplant controls. Furthermore, we show a significant increase (<i>P</i>=0.02) in the level of TNF-α in PTLD patient plasma (range 0–97.97 pg ml<sup>−1</sup>) compared to transplant controls (0–8.147 pg ml<sup>−1</sup>), with the highest levels found in individuals carrying the variant alleles. <br/> Conclusion: We suggest that genetic variation within TNF-α loci and the level of plasma cytokine could be used as a predictive risk factor for the development of PTLD

Measurement of Soil Respiration

peer reviewe

From adversity to psychosis: pathways and mechanisms from specific adversities to specific symptoms

Purpose Although there is considerable evidence that adversities in childhood such as social deprivation, sexual abuse, separation from parents, neglect and exposure to deviant parental communication are associated with psychosis in later life, most studies have considered broad diagnoses as outcomes. In this review we consider evidence for pathways between specific types of adversity and specific symptoms of psychosis. Methods We present theoretical arguments for expecting some degree of specificity (although by no means perfect specificity) between different kinds of adversity and different symptoms of psychosis. We review studies that have investigated social–environmental risk factors for thought disorder, auditory–verbal hallucinations and paranoid delusions, and consider how these risk factors may impact on specific psychological and biological mechanisms. Results Communication deviance in parents has been implicated in the development of thought disorder in offspring, childhood sexual abuse has been particularly implicated in auditory–verbal hallucinations, and attachment-disrupting events (e.g. neglect, being brought up in an institution) may have particular potency for the development of paranoid symptoms. Current research on psychological mechanisms underlying these symptoms suggests a number of symptom-specific mechanisms that may explain these associations. Conclusions Few studies have considered symptoms, underlying mechanisms and different kinds of adversity at the same time. Future research along these lines will have the potential to elucidate the mechanisms that lead to severe mental illness, and may have considerable clinical implications