No abstract

The prognostic value of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in melanoma was demonstrated more than a decade ago as superior to Breslow score. We have previously shown that intercellular homophilic CEACAM1 interactions protect melanoma cells from lymphocyte-mediated elimination. Here, we study the direct effects of CEACAM1 on melanoma cell biology. By employing tissue microarrays and low-passage primary cultures of metastatic melanoma, we show that CEACAM1 expression gradually increases from nevi to metastatic specimens, with a strong dominance of the CEACAM1-Long tail splice variant. Using experimental systems of CEACAM1 knockdown and overexpression of selective variants or truncation mutants, we prove that only the full-length long tail variant enhances melanoma cell proliferation in vitro and in vivo. This effect is not reversed with a CEACAM1-blocking antibody, suggesting that it is not mediated by intercellular homophilic interactions. Downstream, CEACAM1-Long increases the expression of Sox-2, which we show to be responsible for the CEACAM1-mediated enhanced proliferation. Furthermore, analysis of the CEACAM1 promoter reveals two single-nucleotide polymorphisms (SNPs) that significantly enhance the promoter's activity compared with the consensus nucleotides. Importantly, case-control genetic SNP analysis of 134 patients with melanoma and matched healthy donors show that patients with melanoma do not exhibit the Hardy-Weinberg balance and that homozygous SNP genotype enhances the hazard ratio to develop melanoma by 35%. These observations shed new mechanistic light on the role of CEACAM1 in melanoma, forming the basis for development of novel therapeutic and diagnostic technologies.

Sydenham chorea, a major manifestation of acute rheumatic fever, has been the most common form of acquired chorea during childhood. Despite the recent dramatic decline in both incidence and severity of rheumatic fever in our area, the frequency of carditis was unchanged. This study investigated retrospectively the incidence of chorea in the last three decades (1960-1990) in our area. During the 30 years of the survey, 28 patients with Sydenham chorea were treated in our centre of whom 10 were seen between 1960-1970, 17 between 1970-1980, and only one patient between 1980-1990.

SUMMARY Eight patients with abetalipoproteinaemia had the typical ocular, systemic, and laboratory findings of this disease. Combined therapy with vitamins A and E was administered, starting as early as the first day of life and as late as 26 years of age. The patients were followed up for 2-6 years. Electroretinography was undertaken in all cases and electrooculography in some.

An 11-year-old girl with abetalipoproteinemia was treated with parenteral vitamin A and vitamin E for two and a half years. Some improvement in neurological and visual deficits was noted. On changing to oral vitamin E and later with addition of medium chain triglycerides (MCT) to the diet, a considerable improvement in her general wellbeing, neuromuscular lesions and ophthalmological symptoms was noted. This regimen is being adhered to for five and a half years. The condition is stable with no further improvement.