Biomedical subjects
Publications and source records attributed to R Huestis.
A new algorithm, PfAGSS, for predicting 3' splice sites in Plasmodium falciparum genomic sequences is described. Application of this program to the published P. falciparum chromosome 2 and 3 data suggests that existing programs result in a high error rate in assigning 3' intron boundaries.
The current prediction of genes in the Plasmodium falciparum genome database relies upon a limited number of specially developed computer algorithms. We have re-annotated the sequence of chromosome 2 of P. falciparum by a computer-assisted manual analysis, which is described here. Of 161 newly predicted introns, we have experimentally confirmed 98. We regard 110 introns from the previously published analyses as probable, we delete 3, change 26 and add 135. We recognise 214 genes in chromosome 2. We have predicted introns in 121 genes. The increased complexity of gene structure on chromosome 2 is likely to be mirrored by the entire genome.
Within a 199,866 base pair (bp) portion of a Plasmodium vivax chromosome we identified a conserved linkage group consisting of at least 41 genes homologous to Plasmodium falciparum genes located on chromosome 3. There were no P. vivax homologues of the P. falciparum cytoadherence-linked asexual genes clag 3.2, clag 3.1 and a var C pseudogene found on the P. vivax chromosome. Within the conserved linkage group, the gene order and structure are identical to those of P. falciparum chromosome 3. This conserved linkage group may extend to as many as 190 genes. The subtelomeric regions are different in size and the P. vivax segment contains genes for which no P. falciparum homologues have been identified to date. The size difference of at least 900 kb between the homologous P. vivax chromosome and P. falciparum chromosome 3 is presumably due to a translocation. There is substantial sequence divergence with a much higher guanine+cytosine (G+C) content in the DNA and a preference for amino acids using GC-rich codons in the deduced proteins of P. vivax. This structural conservation of homologous genes and their products combined with sequence divergence at the nucleotide level makes the P. vivax genome a powerful tool for comparative analyses of Plasmodium genomes.
Double-blind crossover comparison of methylphenidate hydrochloride, dextroamphetamine sulfate, and caffeine after placebo washout in 29 children with minimal brain dysfunction (MBD) showed on six ratings that methylphenidate and dextroamphetamine were significantly (P less than .05 to P less than .001) better than placebo and caffeine, but not significantly (P less than .05) different from each other. Placebo, caffeine, and ratings before drug did not differ significantly. Of 26 drug responders, 12 responded best to dextroamphetamine, ten to methylphenidate, and one to caffeine. The latter child showed no improvement at all with either prescription stimulant. Methylphenidate and dextroamphetamine were each efficacious for six children who did not respond to the other stimulant. All three drugs showed significant (P less than .05) weight loss and cardiovascular side effects, the latter possibly spurious. Dextroamphetamine showed a significant (P less than .05) decrease from placebo in "tummyaches."