Identification of differentially expressed genes in aflatoxin B1- treated cultured primary rat hepatocytes and Fischer 344 rats

Aflatoxin B1 (AFB1), a mutagen and hepatocarcinogen in rats and humans, is a contaminant of the human food supply, particularly in parts of Africa and Asia. AFB1-induced changes in gene expression may play a part in the development of the toxic, immunosuppressive and carcinogenic properties of this fungal metabolite. An understanding of the-role of AFB1 in modulating gene regulation should provide insight regarding mechanisms of AFB1-induced carcinogenesis. We used three PCR- based subtractive techniques to identify AFB1-responsive genes in cultured primary rat hepatocyte RNA: differential display PCR (DD-PCR), representational difference analysis (RDA) and suppression subtractive hybridization (SSH). Each of the three techniques identified AFB1- responsive genes, although no individual cDNA was isolated by more than one technique. Nine cDNAs isolated using DD-PCR, RDA or SSH were found to represent eight genes that are differentially expressed as a result of AFB1 exposure. Genes whose mRNA levels were increased in cultured primary rat hepatocytes after AFB1 treatment were corticosteroid binding globulin (CBG), cytochrome P450 4F1 (CYP4F1), alpha-2 microglobulin, C4b-binding protein (C4BP), serum amyloid A-2 and glutathione S-transferase Yb2 (GST). Transferrin and a small CYP3A-like cDNA had reduced mRNA levels after AFB1 exposure. Full-length CYP3A mRNA levels were increased. When liver RNA from AFB1-treated male F344 rats was evaluated for transferrin, CBG, GST, CYP3A and CYP4F1 expression, a decrease in transferrin mRNA and an increase in CBG, GST, CYP3A and CYP4F1 mRNA levels was also seen. Analysis of the potential function of these genes in maintaining cellular homeostasis suggests that their differential expression could contribute to the toxicity associated with AFB1 exposure.      

Velopharyngeal insufficiency following adenoidectomy1

Velopharyngeal insufficiency (VPI) is a well recognized but rare complication of adenoidectomy. Twenty children with this condition were seen and assessed at Great Ormond Street Hospital between 1993 and 2000. The commonest aetiology was occult submucous cleft palate (n = 5) but there was a wide range of other causes. Two children with severe behavioural disorders and normal palates developed mild symptoms, an aetiology not previously reported. Only two children had a classical submucous cleft palate. Nine children required surgical intervention and three revision procedures. Of the 15 treated children for whom follow‐up data was available, 13 regained normal or near‐normal speech. Many cases of postadenoidectomy VPI was not foreseeable. Following referral to a specialist cleft unit, normal or near‐normal speech can be achieved in the majority with a combination of surgery and speech therapy.     

Evaluation of Response to Stereotactic Radiosurgery in Brain Metastases Using Multiparametric Magnetic Resonance Imaging and a Review of the Literature

Aims

Following stereotactic radiosurgery (SRS), brain metastases initially increase in size in up to a third of cases, suggesting treatment failure. Current imaging using structural magnetic resonance imaging (MRI) cannot differentiate between tumour recurrence and SRS-induced changes, creating difficulties with patient management. Combining multiparametric MRI techniques, which assess tissue physiological and metabolic information, has shown promise in answering this clinical question.

Total elbow arthroplasty is moving forward: Review on past,present and future

The elbow joint is a complex joint, which, when impaired in function, leads to severe disability. In some cases however, an arthroplasty might be an appropriate treatment. In the past four decades, large steps havebeen taken to optimize this treatment in order to achieve better post-operative outcomes. To understand these progresses and to discover aspects for upcoming improvements, we present a review on the past developments, the present state of affairs and future developments which may improve patient care further.     

Variable expressivity of a novel mutation in the SCN1A gene leading to an autosomal dominant seizure disorder

Mutations in the SCN1A gene can cause a variety of dominantly inherited epilepsy syndromes. Severe phenotypes usually result from loss of function mutations, whereas missense mutations cause a milder phenotype by altering the sodium channel activity. We report on a novel missense variant (p.Val1379Leu) in the SCN1A gene segregating in an autosomal dominant pattern in a family exhibiting a variable epilepsy phenotype ranging from generalized epilepsy with febrile seizures during infancy to a well controlled seizure disorder in adulthood. This report supports the importance of SCN1A mutation analysis in families in which seizure disorders segregate in an autosomal dominant fashion.