A study of a consecutive series of 99 children with neuroblastoma seen at two major Toronto hospitals between 1951 and 1971 is reported. The children who were aged 24 months or less at diagnosis showed an overall two-year survival rate of 59 percent. Analysis, including fitting of a log-linear model, showed that increased probability of survival was associated with younger age at onset, nonadrenal site, and lower staging and the each of these factors acted independently. The sex of the child had no prognostic effect. This study thus extends earlier work by demonstrating the independent prognostic influence of site of tumor. The implications for treatment policy are discussed.
We
report how the rearrangement of highly reactive nitrile imines
derived from
N
-2-nitrophenyl hydrazonyl bromides
can be harnessed for the facile construction of amide bonds. This
amidation reaction was found to be widely applicable to the synthesis
of primary, secondary, and tertiary amides and was used as the key
step in the synthesis of the lipid-lowering agent bezafibrate. The
orthogonality and functional group tolerance of this approach was
exemplified by the
N
-acylation of unprotected amino
acids.
Cylindrospermopsin (CYN) is a naturally occurring alkaloid produced by a variety of cyanobacteria and known to induce oxidative stress-mediated toxicity in eukaryotic cells. Despite extensive research on the mechanism of CYN toxicity, an understanding of the structural features responsible for this toxicity and the mechanism by which it can enter the cell are still not clear. It was established that the presence of both the uracil and guanidine groups is essential in biological activity of CYN whilst not much is known in this regard on the role of tether that separates them and the attached hydroxyl group. Therefore, in the present study we have prepared three synthetic analogues possessing uracil and guanidine groups separated by a variable length tether (4-6 carbons) and containing a hydroxyl function in a position orientation to CYN, together with a tetracyclic analogue of CYN lacking the hydroxyl group at C-7. The toxicity of these compounds was then compared with CYN and guanidinoacetate (GAA; the primary substrate in CYN biosynthesis) in an in vitro model using human neutrophils isolated from healthy subjects. The lowest activity measured by means of reactive oxygen species generation, lipid peroxidation and cell death was observed for GAA and the tetracyclic analogue. The greatest toxicity was found in an analogue with a 6-carbon tether, but all three analogues and CYN caused rapid onset of redox imbalance. These results add to the general understanding of CYN toxicity and preliminary findings suggest that the -OH group at C-7 may be significant for the cellular transport of CYN and/or be involved in its toxic activity inside the cell, a hypothesis which requires further testing.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.