Effects of glucocorticoids on expression of the fos protooncogene in AtT-20 cells.

Glucocorticoid regulation of expression of the protooncogene fos has been examined in AtT-20 cells at both the RNA and protein levels. When cells were incubated continuously in the presence of dexamethasone, an early (30 min) rise in the expression of fos mRNA was observed, which declined by 1 h, but rose again after 2 h of hormone treatment. Six hours after hormone treatment, fos mRNA levels had returned to control levels in spite of the continued presence of dexamethasone. Serum treatment resulted in a sustained increase in fos mRNA levels; however, the glucocorticoid and serum effects were additive. Dexamethasone and/or serum both increased the steady state levels of fos protein. Glucocorticoid treatment of AtT-20 cells results in complex changes in fos expression, but does not affect their viability or growth rate; these results suggest that fos may play a role in mediation or modulation of glucocorticoid effects other than growth.     

Reconstruction of mandibular defects with metallic prostheses and microvascular jejunal autografts: an experimental study

A study was undertaken to determine the adequacy of vascularised jejunum to provide stable mucosal cover over a non-biological mandibular substitute. Employing a canine model, composite intra-oral bone-mucosal defects were created and reconstructed with a metal plate covered by a microvascular jejunal patch. These were followed for six months and were assessed clinically, histologically and radiologically. Rapid mucosal healing occurred in all cases. The autografts conformed to the contour of the prosthesis and adequate tongue mobility was preserved. All mandibles remained stable throughout the follow-up period. Histologically, short villi covered the jejunal grafts to three months whilst at six months both normal and abnormal jejunal mucosal morphology was evident.     

Novel quinuclidine-based ligands for the muscarinic cholinergic receptor

Recent clinical studies on Alzheimer's patients have implied that only agents displaying high efficacy at the cortical muscarinic receptor have yielded encouraging results. This paper describes the design, synthesis, and biochemical characterization of novel quinuclidine-based muscarinic agonists which can readily penetrate into the central nervous system and which are capable of displaying high efficacy at cortical sites. With use of a biochemical assay capable of measuring receptor affinity and predicting cortical efficacy, it has been discovered that an oxadiazole ring and related heterocycles can function as bioisosteric replacements for the ester moiety found in several known muscarinic ligands. Within this series there exist compounds which span the efficacy range from high-efficacy agonist through partial agonists to antagonists with affinity comparable or superior to that of classical quaternary ammonium ligands. Consistent with recent molecular biology studies, structure-activity trends are interpreted in terms of separate binding sites for agonists and antagonists with H-bonding interactions characterizing agonist behavior and lipophilic binding characterizing antagonist behavior. Thus the aminooxadiazole moiety has structural features which are optimized for an agonist profile.     

Attempted suicide in bipolar disorder pedigrees: evidence for linkage to 2p12.

BACKGROUND: We are interested in identifying susceptibility genes that predispose subjects to attempted suicide. METHODS: We conducted a secondary analysis of genome-wide linkage data from 162 bipolar pedigrees that incorporated attempted suicide as a clinical covariate. RESULTS: The strongest covariate-based linkage signal was seen on 2p12 at marker D2S1777. The logarithm of odds (LOD) score at marker D2S1777 rose from 1.56 to 3.82 after inclusion of the suicide covariate, resulting in significant chromosome-wide empirically derived p-values for the overall linkage finding (p = .01) and for the change in LOD score after the inclusion of the covariate (p = .02). CONCLUSIONS: The finding on chromosome 2 replicates results from two previous studies of attempted suicide in pedigrees with alcohol dependence and in pedigrees with recurrent early-onset depression. Combined, these three studies provide compelling evidence for a locus influencing attempted suicide on 2p12.     

Quality of life in patients with seasonal affective disorder: summer vs winter scores.

OBJECTIVE: To compare perceived quality of life (QoL) in patients diagnosed with seasonal affective disorder (SAD) during the winter and summer months. METHODS: Twenty-six patients who were enrolled in an ongoing multicentre study in Canada completed 2 measures of QoL (the 20-item Medical Outcomes Study Short-Form General Health Survey [SF-20] and the Quality of Life Enjoyment and Satisfaction Questionnaire, [Q-LES-Q]) during the winter, when suffering from depression, and again during the summer months. RESULTS: Both general and health-related QoL scores were significantly improved in patients with SAD during the summer months, with scores for the most part falling within normal range. CONCLUSIONS: Perceived QoL in patients with SAD is markedly impaired during the winter months but shows a substantial rebound during the summer months. The findings of this study provide further evidence that SAD is a distinct diagnostic entity.