Identification of differentially expressed thyroid hormone responsive genes from the brain of the Mexican Axolotl (Ambystoma mexicanum).

The Mexican axolotl (Ambystoma mexicanum) presents an excellent model to investigate mechanisms of brain development that are conserved among vertebrates. In particular, metamorphic changes of the brain can be induced in free-living aquatic juveniles and adults by simply adding thyroid hormone (T4) to rearing water. Whole brains were sampled from juvenile A. mexicanum that were exposed to 0, 8, and 18 days of 50 nM T4, and these were used to isolate RNA and make normalized cDNA libraries for 454 DNA sequencing. A total of 1,875,732 high quality cDNA reads were assembled with existing ESTs to obtain 5884 new contigs for human RefSeq protein models, and to develop a custom Affymetrix gene expression array (Amby_002) with approximately 20,000 probe sets. The Amby_002 array was used to identify 303 transcripts that differed statistically (p<0.05, fold change >1.5) as a function of days of T4 treatment. Further statistical analyses showed that Amby_002 performed concordantly in comparison to an existing, small format expression array. This study introduces a new A. mexicanum microarray resource for the community and the first lists of T4-responsive genes from the brain of a salamander amphibian.

Faecal incontinence: A late side-effect of pelvic radiotherapy.

AIMS: Despite advances in pelvic radiotherapy, damage to normal tissue can lead to chronic gastrointestinal problems. The frequency with which this affects quality of life is controversial. Faecal incontinence is not widely perceived to be a major issue after pelvic radiotherapy. The aim of this paper is to review the frequency and mechanisms for the development of faecal incontinence after pelvic radiotherapy, and to review treatment options for faecally incontinent patients. MATERIALS AND METHODS: A search of original literature was carried out using MEDLINE and EMBASE databases from 1966 to 2005. RESULTS: The reliability of the published data is poor because patients frequently fail to admit to faecal incontinence, and because prospective studies are lacking that assess faecal incontinence as a specific end point using adequate, validated and reproducible methodology. The published rates of late new-onset faecal incontinence after pelvic radiation are between 3% and 53%. Patients treated for prostate rather than gynaecological, bladder, rectal or anal cancer may have a lower rate. Only 8-56% of affected patients state that faecal incontinence reduces their quality of life. Studies examining the physiological changes occurring after radiotherapy are generally not adequately controlled or powered, assessment of ano-rectal function is rarely comprehensive and loss of patients to follow-up frequently makes it difficult to extrapolate results to a wider population. Where there is agreement over the physiological changes that occur after radiotherapy, it is not clear at what threshold these changes cause symptoms. No prospective studies of any non-surgical treatment for faecal incontinence after radiotherapy have been published. Surgery other than colostomy probably carries a high risk of complications in this group of patients, but few data have been published. CONCLUSIONS: Now that improvements in outcome from combination treatments, including radiotherapy for pelvic cancer, are being achieved, it is time that serious attention is paid to determining how frequently significant gastrointestinal toxicity arises, and how best to optimise the quality of life of long-term survivors.