Lymphotoxin-α Gene and Risk of Myocardial Infarction in 6,928 Cases and 2,712 Controls in the ISIS Case-Control Study

Lymphotoxin-α (LTA) is a pro-inflammatory cytokine that plays an important role in the immune system and local inflammatory response. LTA is expressed in atherosclerotic plaques and has been implicated in the pathogenesis of atherosclerosis and coronary heart disease (CHD). Polymorphisms in the gene encoding lymphotoxin-α (LTA) on Chromosome 6p21 have been associated with susceptibility to CHD, but results in different studies appear to be conflicting. We examined the association of seven single nucleotide polymorphisms (SNPs) across the LTA gene, and their related haplotypes, with risk of myocardial infarction (MI) in the International Study of Infarct Survival (ISIS) case-control study involving 6,928 non-fatal MI cases and 2,712 unrelated controls. The seven SNPs (including the rs909253 and rs1041981 SNPs previously implicated in the risk of CHD) were in strong linkage disequilibrium with each other and contributed to six common haplotypes. Some of the haplotypes for LTA were associated with higher plasma concentrations of C-reactive protein (p = 0.004) and lower concentrations of albumin (p = 0.023). However, none of the SNPs or related haplotypes were significantly associated with risk of MI. The results of the ISIS study were considered in the context of six previously published studies that had assessed this association, and this meta-analysis found no significant association with CHD risk using a recessive model and only a modest association using a dominant model (with narrow confidence intervals around these risk estimates). Overall, these studies provide reliable evidence that these common polymorphisms for the LTA gene are not strongly associated with susceptibility to coronary disease.     

New Medium for the Isolation and Enumeration of Pseudomonads

A new medium containing 200 ppb of 2-hydroxy-2',4,4'-trichlorodiphenyloxide (CH3565) and 10 ppm of cetyl-trimethyl-ammonium bromide (Cetrimide) in tryptic soy agar was developed and tested with 19 pure cultures of Pseudomonas, 20 microorganisms of other genera, commercially prepared ground beef, and laboratory-prepared inoculated ground beef. The new medium, CETCH agar, was compared with an antibiotic-containing medium. CETCH agar provided greater pseudomonad recoveries, a shorter incubation period prior to plate counting, and greater ease of preparation.     

Enhanced rates of acyl transfer to a neighboring hydroxyl group

2-Hydroxymethyl-4-nitrophenyl trimethylacetate is rapidly converted, by an intramolecular pathway, to its benzyl ester counterpart in aqueous solutions of dilute buffers. Intramolecular acyl migration is favored by a factor of 10⁵ over intermolecular transfer of the trimethylacetyl group to surrounding water molecules. The activation parameters of the reaction demonstrate that the rate acceleration is primarily entropic in origin. At constant pH, the apparent first-order rate constant for intramolecular acyl migration displays a linear dependence on the concentration of the basic component of the buffer. For catalysis by imidazole, a solvent deuterium isotope effect of $\text{k}{}_{\mathrm{<mtext>H</mtext>}}\text{k}{}_{\mathrm{<mtext>D</mtext>}}\text{= 2.4}$ is observed, in accord with a general base-catalyzed pathway. Similarities between intramolecular and intracomplex transacylations are discussed with the conclusion that the migration of a trimethylacetyl group from the phenolic oxygen atom of a 2-hydroxymethyl-4-nitrophenol to the adjacent benzylic oxygen atom provides an accurate model for acylation of the serine hydroxyl group at the active site of α-chymotrypsin by nitrophenyl esters.     

Synthesis of Oligonucleotides Containing the Abasic Site Model Compound 1,4-Anhydro-2-Deoxy-D-Ribitol

Abstract

An improved approach for the synthesis of phosphotriester and phosphoramidite derivatives of the 1,4-anhydro-2-deoxy-D-ribitol is presented. The incorporation of these compounds in synthetic DNA and the insertion of purine deoxyribonucleotides opposite the reduced abasic site by DNA polymerase is described.