The binding of transformed aromatic hydrocarbon (Ah) receptor to its DNA recognition site is not affected by metal depletion.

The biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), a potent environmental contaminant, are mediated by a soluble intracellular protein, the aromatic hydrocarbon (Ah) receptor (AhR). TCDD:AhR complexes activate gene transcription by binding to specific DNA sequences termed dioxin-responsive elements adjacent to TCDD-responsive genes. Analogies between the AhR and receptors for steroid hormones imply similarities in their mechanism of action. The presence of chelatable, protein-bound metal(s), presumably zinc, is required for DNA binding of several proteins, including steroid hormone receptors and the transcription factor SP1. Utilizing gel retardation and DNA-cellulose binding assays we have investigated the importance of metal in DNA binding of transformed TCDD:AhR complexes. Here, we report that although 1,10-phenanthroline, a metal ion chelating agent, inhibited the DNA binding of SP1 and transformed glucocorticoid receptor, no inhibition of transformed AhR was observed. EDTA was similarly ineffective in inhibiting DNA binding of transformed AhR. Our findings suggest that the AhR, although similar to steroid receptors, appears not to require metals for binding to its specific DNA recognition sequence.

Behavioral covariation in the treatment of chronic pain.

The successful use of operant procedures to alter behaviors associated with various medical conditions suggests that such behaviors may be learned and that the principles of learning may be applied not only to treatment but also to the study of the pathogenesis of illness behavior. The present study, conducted within an ongoing neuromuscular research project, assessed the covariation of behaviors associated with chronic pain within and across behavioral and drug approaches to treatment. Problems of screaming and five other behaviors (including self-reports of pain) were measured across conditions of varying behavioral contingencies (noncontingent reinforcement vs the removal of reinforcement contingent upon screaming) and varying administration (time since medication and dosage) of Parsidol during attempts to treat the muscle pain of a 24-year-old male with a severe, chronic neuromuscular disorder diagnosed as dystonia musculorum deformans (DMD). Results indicated that: (a) pain behaviors covaried during behavioral and drug conditions even though the behavioral intervention only targeted screaming; (b) effects were greater on nontargeted behaviors during periods that followed rather than preceded drug administration; (c) in contrast to behavioral observation data, physiological measures of neuromuscular activity (EMG) did not differ across conditions. These results suggest that functional response-response relationships exist in patients as the result of their illness experience.

Reduction of food theft and long-term maintenance of weight loss in a Prader-Willi adult.

Behavioral interventions have had limited success in managing the chronic hyperphagia and obesity that are of presumed organic etiology in Prader-Willi syndrome. Thus, frequent foraging for food and covert consumption continue to be health-threatening problems for many Prader-Willi individuals. This case study was designed to replicate methods for assessment and treatment of food theft. A token program based on differential-reinforcement-of-other-behavior and response-cost eliminated theft in three hospital settings. Prior to discharge, the program was expanded to include contingencies on exercise behavior and weight loss, and staff from the subject's group home residence were trained to implement a modified program in the natural environment. Reduced food theft and continued weight loss were maintained in the group home and an apartment-living arrangement. A total of 81 lb (37 kg) was lost during a 2-yr period.