Famoxadone: the discovery and optimisation of a new agricultural fungicide.

Famoxadone (3-anilino-5-methyl-5-(4-phenoxyphenyl)-1,3-oxazolidine-2,4-dione), is a new agricultural fungicide recently commercialized by DuPont under the trade name Famoxate. Famoxadone is a member of a new class of oxazolidinone fungicides that demonstrate excellent control of plant pathogens in the Ascomycete, Basidiomycete, and Oomycete classes that infect grapes, cereals, tomatoes, potatoes and other crops. DuPont's entry into the oxazolidinone area resulted from the procurement of 5-methyl-5-phenyl-3-phenylamino-2-thioxo-4-oxazolidinone (1) from Professor Detlef Geffken, then at the University of Bonn. An extensive analog program was initiated immediately after the fungicidal activity of 1 was discovered through routine greenhouse testing. The discovery program in the oxazolidinone area eventually culminated in the advancement of famoxadone to commercial development in the early 1990s. The synthesis of various oxazolidinone ring systems and the development of the structure-activity relationships that led to the discovery of famoxadone are described.

Pseudomonas aeruginosa killing of Caenorhabditis elegans used to identify P. aeruginosa virulence factors.

We reported recently that the human opportunistic pathogen Pseudomonas aeruginosa strain PA14 kills Caenorhabditis elegans and that many P. aeruginosa virulence factors (genes) required for maximum virulence in mouse pathogenicity are also required for maximum killing of C. elegans. Here we report that among eight P. aeruginosa PA14 TnphoA mutants isolated that exhibited reduced killing of C. elegans, at least five also exhibited reduced virulence in mice. Three of the TnphoA mutants corresponded to the known virulence-related genes lasR, gacA, and lemA. Three of the mutants corresponded to known genes (aefA from Escherichia coli, pstP from Azotobacter vinelandii, and mtrR from Neisseria gonorrhoeae) that had not been shown previously to play a role in pathogenesis, and two of the mutants contained TnphoA inserted into novel sequences. These data indicate that the killing of C. elegans by P. aeruginosa can be exploited to identify novel P. aeruginosa virulence factors important for mammalian pathogenesis.

Treatment of obesity by very low calorie diet, behavior therapy, and their combination: a five-year perspective.

Seventy-six obese women with a mean age of 42.1 years and weight of 106.0 kg were randomly assigned to one of three treatments: (a) very low calorie diet alone; (b) behavior therapy alone; or their combination (i.e. combined treatment). Weight losses for the three conditions at the end of treatment were 13.1, 13.0, and 16.8 kg, respectively, with losses for combined treatment significantly greater than those for the two other conditions. Weight losses 1 year after treatment were 4.7, 6.6, and 10.6 kg, respectively. A significantly greater percentage of subjects in the behavior therapy alone (36 percent) and combined treatment conditions (32 percent) maintained their full end-of-treatment weight losses than in the very low calorie diet alone condition (5 percent). Five years after treatment, a majority of subjects in all three conditions had returned to their pretreatment weight, and 55 percent of the total sample had received additional weight reduction therapy. The short and long term effects of treatment are discussed in terms of their implications for practice and research.