Symptomatic response to divalproex in subtypes of conduct disorder.

To investigate response to Divalproex sodium (DVPX) with respect to Reactive/Affective/Defensive/Impulsive (RADI) and Proactive/Instrumental/Premeditated (PIP) aggression among adolescent males with conduct disorder (CD), using results from a randomized, double-blind, placebo-controlled trial. It was hypothesized that DVPX response among participants with RADI aggression would be greater than among those with PIP aggression. Fifty-eight ethnically diverse males with severe CD were assigned to High Distress (HDCD) or Low Distress (LDCD) Conduct Disorder, corresponding with RADI and PIP aggression, respectively.

Practice parameter for the assessment and treatment of children and adolescents with oppositional defiant disorder.

Oppositional defiant disorder (ODD) is a common clinical problem in children and adolescents. Oppositionality and associated types of aggressive behavior are among the most common referral problems in child psychiatry. Grouped among the disruptive behavior disorders, ODD is frequently comorbid with other psychiatric conditions and often precedes the development of conduct disorder (CD), substance abuse, and severely delinquent behavior.

Inhibition of c-src transcription by mithramycin: structure-activity relationships of biosynthetically produced mithramycin analogues using the c-src promoter as target.

The aureolic acid antitumor antibiotic mithramycin (MTM) inhibits both cancer growth and bone resorption by cross-linking GC-rich DNA, thus blocking binding of Sp-family transcription factors to gene regulatory elements. Transcription of c-src, a gene implicated in many human cancers and required for osteoclast-dependent bone resorption, is regulated by the binding of Sp factors to specific elements in its promoter. Therefore, this gene represents an important anticancer target and a potential lead target through which MTM displays its so far uncharacterized action against osteoclastic bone resorption.

Mithramycin SK, a novel antitumor drug with improved therapeutic index, mithramycin SA, and demycarosyl-mithramycin SK: three new products generated in the mithramycin producer Streptomyces argillaceus through combinatorial biosynthesis.

To gain initial structure-activity relationships regarding the highly functionalized pentyl side chain attached at C-3 of mithramycin (MTM), we focused on a post-polyketide synthase (post-PKS) tailoring step of the MTM biosynthesis by Streptomyces argillaceus ATCC 12956, which was proposed to be catalyzed by ketoreductase (KR) MtmW. In this last step of the MTM biosynthesis, a keto group of the pentyl side chain is reduced to a secondary alcohol, and we anticipated the generation of an MTM derivative with an additional keto group in the 3-side chain. Insertional inactivation of mtmW, a gene located ca.