James E. Fischer

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Mechanisms of DNA adduct formation by antineoplastic 2-chloroethyl-N-nitrosoureas (CNUs) and of DNA damage induced by these compounds are discussed. CNUs are alkylating agents that form DNA-DNA cross-links as well as 2-chloroethylated and 2-hydroxyethylated adducts, the N-7-position of guanine being the predominantly alkylated site. A close correlation(More)
The global gene expression profiling of early T helper (Th) 1 and Th2 differentiation reveals that this process can be divided into two stages, activation and differentiation. The activation stage is manifested in coordinated mobilization of the replication machinery, a process that we hypothesize may be responsible for establishing genomewide opening of(More)
The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) is recognized as the primary target of the fibrate class of hypolipidemic drugs and mediates lipid lowering in part by activating a transcriptional cascade that induces genes involved in the catabolism of lipids. We report here the characterization of three novel PPARalpha(More)
BACKGROUND Austism spectrum disorder (ASD) is a heterogeneous behavioral disorder or condition characterized by severe impairment of social engagement and the presence of repetitive activities. The molecular etiology of ASD is still largely unknown despite a strong genetic component. Part of the difficulty in turning genetics into disease mechanisms and(More)
In this study, we formulate a computational reaction model following a chemical kinetic theory approach to predict the binding rate constant for the siRNA-RISC complex formation reaction. The model allowed us to study the potency difference between 2-nt 3' overhangs against blunt-ended siRNA molecules in an RNA interference (RNAi) system. The rate constant(More)
2-Chloroethyl-N-nitrosoureas are highly active anti-neoplastic drugs in clinical use for many years. Therapy with these DNA cross-linking agents is limited by their toxic side effects, cumulative and delayed bone marrow toxicity being the main dose-limiting one. Since the intrinsic anti-tumour activity of the nitrosourea group is very high, coupling to(More)
Drug-induced cardiac toxicity has been implicated in 31% of drug withdrawals in the USA. The fact that the risk for cardiac-related adverse events goes undetected in preclinical studies for so many drugs underscores the need for better, more predictive in vitro safety screens to be deployed early in the drug discovery process. Unfortunately, many questions(More)
Syntheses of steroid-linked N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-(CNC-) amino acid esters and -amides with potential antineoplastic activity are described. The esters are prepared by reaction of CNC-amino acids with steroids using N,N'-carbonyldiimidazole and N,N'-dicyclohexylcarbodiimide. The corresponding amides are prepared by reaction of(More)
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