A number of 2-substituted-a-i and -0-2'-deoxyadenosines have been prepared, and their growth inhibitory activity against leukemia L-1210, Streptococcus faecium, and Escherichia coli has been evaluated in vitro. Fusion of 2,6-dichloropurine with 1,3,5-tri-0-acety 1-2-deoxy-D-erythro-pentofuranose or with methyl 3,5-di-0-p-toluyl-2-deoxy-D-eryf/vo-pentofuranoside gave the anomeric mixtures of the acetyl-(80%) or p-toluyl-(30%) blocked deoxynucleosides. The acetylated mixture was treated with liquid ammonia, and the resulting2-chloro-2'-deoxy-

This article describes an intensive, inpatient behavioral rehabilitation program for patients with schizophrenia who have been considered "treatment-refractory" at state hospitals. The program is a public-private partnership involving state and private hospitals and community residence providers. The essential elements of this program are described, along with the conceptual and philosophical bases of its treatment and examples of staff behaviors critical to treatment success. Outcome data are then discussed to emphasize the point that when evidence-based psychological treatment is implemented with this population, outcomes can be positive in most cases, and therefore, the number of treatment-refractory patients is actually far less than is estimated on the basis of response to medication alone.

No abstract

The synthesis of a series of 4'-thio-5-halogenopyrimidine nucleosides, including the 5-fluoro, chloro, bromo and iodo derivatives, has been carried out by condensation of the 2,4-bis-O-trimethylsilyl derivatives of the corresponding pyrimidine bases with the protected 4-thio-D-ribofuranosyl chloride. Among these, the alpha and beta anomers of 4'-thio-5-fluorouridine inhibited the growth of leukemia L1210 cells at concentrations of 4 x 10(-7) and 2 x 10(-7) M, respectively, and that of S. faecium at 4 x 10(-9) and 6 x 10(-10) M, respectively. These compounds retained marked activity against strains of S. faecium resistant to 10(-3) M 5-fluorouracil or 5-fluorouridine. As determined in S. faecium cultures, 4'-thio-5-fluorouridine decreased the total protein content of the cells more markedly than it did their RNA or DNA content. X-Ray crystallography showed that substitution of sulfur for the oxygen in the carbohydrate ring markedly changes the conformation of that moiety.

A series of nucleoside analogues has been prepared, wherein the cyclic carbohydrate moiety is replaced by aliphatic side chains attached to cytosine, thymine, uracil, and 5-fluorouracil. The 1-[(2-hydroxyethoxy)methyl] derivatives of these heterocycles were synthesized by reacting the silylated bases with 2-(chloromethoxy)ethyl benzoate, followed by removal of the protecting groups with methanolic ammonia. The hydroxy groups of a number of these derivatives was subsequently replaced by an azido, amino, or carbamoyloxy moiety. The 1-(2-oxo-3-butyl) and 1-(2-oxo-3-nonyl) derivatives of cytosine were also prepared, their synthesis being accomplished by condensation of the silylated heterocycle with the appropriate alpha-halo ketone. At 10(-4) M concentrations, the newly prepared compounds were inactive against leukemia L-1210 cells in culture. However, a number of the agents inhibited the in vitro growth of Escherichia coli K-12, the most potent among these, 1-[(2-hydroxyethoxy)methyl]-5-fluorouracil being active at an IC50 of 1.2 micro M. This compound was equally active in preventing the growth of a 5-fluorouracil resistant strain of E. coli. Some of the analogues were also found to selectively interfere with herpes simplex virus replication in vitro. None of the cytosine derivatives tested served as either substrates or inhibitors of human liver cytosine nucleoside deaminase.