The clinical and laboratory correlates of an increased urinary 5-hydroxyindoleacetic acid.

Over a five-and-a-half-year period, there were 298 laboratory requests for urinary 5-hydroxyindoleacetic acid (5-HIAA). The clinical and laboratory associations of the 24 patients in which there were 43 urinary 5-HIAA 24-h collection results greater than the laboratory upper reference limit are detailed. Four were confirmed carcinoid tumours and two were phaeochromocytomas. Flushing was a prominent symptom in 46% and diarrhoea or altered bowel habit in 37%. Associated with the raised urinary 5-HIAA values were increased levels of 4-hydroxy-3-methoxymandelic acid and homovanillic acid in 14.3% and 21%, respectively, of those collections where the metabolites were requested. Diagnostic imaging was performed in 57%. While the specificity was 88%, 5-HIAA is relatively insensitive in the diagnosis of carcinoid tumours and a more widespread use of diagnostic imaging including isotope scanning with labelled metaiodo-benzylguanidine, vasoactive intestinal peptide and octreotide is suggested.     

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.      

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.