The IR4 gene (inverted repeat gene 4) of equine herpesvirus type 1 (EHV-), the homolog of the herpes simplex virus type 1 ICP22 gene, is differentially expressed as a 1.4-kb early transcript and a 1.7-kb late transcript that encode a series of proteins that migrate between 42 to 47 kDa, localize to the nucleus of EHV-1-infected cells, and become packaged within EHV-1 virions (V. R. Holden, G. B. Caughman, Y. Zhao, R. N. Harty, and D. J. O'Callaghan, J. Virol. 68, 4329-4340, 1994). To assess the role of the IR4 protein in EHV-1 gene regulation, an IR4 expression vector was cotransfected with EHV-1 chimeric promoter-CAT reporter constructs and EHV-1 effector plasmids to determine the effects of the IR4 protein on the expression of immediate-early (IE), early, and late promoters. These studies revealed that the IR4 protein: (i) minimally trans-activates EHV-1 promoters, (ii) acts synergistically with the UL3 (ICP27) gene product to trans-activate the IE promoter, (iii) does not interfere with the trans-repression of the IE promoter by the IE protein, (iv) enhances transactivation of early promoters by the IE protein, (v) enhances the transactivation of both early and late promoters by the IE and UL3 proteins, and (vi) interacts synergistically with the IE protein to trans-activate the heterologous HSV-1 ICP4 promoter. These data suggest that the IR4 gene product plays a significant role in EHV-1 gene regulation.

Objective: The purpose of this study was to determine the most appropriate dose of oral glutamine to use in a further clinical study in paediatric oncology patients. Design: This was a phase I, pharmokinetic study. Setting: The study was carried out at The Yorkshire Regional Centre for Paediatric Oncology and Haematology, St James's University Hospital, Leeds, UK. Subjects: Thirteen patients undergoing treatment for paediatric malignancy participated in this study. All 13 completed the study. Interventions: The most appropriate dose was determined by patient acceptability and by plasma glutamine and ammonia levels measured at timed intervals after ingestion of a single glutamine dose. Results: Doses of 0.35, 0.5 and 0.65 g=kg were well tolerated with no untoward plasma glutamine and ammonia levels. One patient was recruited to a higher dose of 0.75 g=kg, but the plasma glutamine and ammonia levels peaked at 2601 and 155 mmol=l, respectively. The ammonia level was greater than the acceptable upper limit. It was difficult to disperse the glutamine adequately at this dose, resulting in the suspension being found to be unpalatable and therefore no further patients were recruited at this dose. Conclusion: It was concluded that 0.65 g=kg is a safe dose of glutamine to use in a clinical study in paediatric oncology patients. Sponsorship: Scientific Hospital Supplies UK Ltd provided the L-glutamine and financial help for the biochemical analysis.