Characterization of Parameters Required for Effective Use of Tamoxifen-Regulated Recombination

Conditional gene targeting using the Cre-loxp system is a well established technique in numerous in vitro and in vivo systems. Ligand regulated forms of Cre have been increasingly used in these applications in order to gain temporal and spatial control over conditional targeting. The tamoxifen-regulated Cre variant mer-Cre-mer (mCrem) is widely utilized because of its reputation for tight regulation in the absence of its tamoxifen ligand. In the DT40 chicken B cell line, we generated an mCrem-based reversible switch for conditional regulation of a transgene, and in contrast with previous work, observed significant constitutive activity of mCrem. This prompted us to use our system for analysis of the parameters governing tamoxifen-regulated mCrem recombination of a genomic target. We find that robust mCrem expression correlates with a high level of tamoxifen-independent Cre activity, while clones expressing mCrem at the limit of western blot detection exhibit extremely tight regulation. We also observe time and dose-dependent effects on mCrem activity which suggest limitations on the use of conditional targeting approaches for applications which require tight temporal coordination of Cre action within a cell population

Nightmares: Personality dimensions and psychopathological attributes

In this article, in an attempt to integrate recent findings with existing knowledge, we provide an overview of issues related to nightmares that could be useful as a guide to clinical work. After defining what should be considered as a nightmare, we look into the relationship of nightmares with issues such as normal development and maturation, as well as culture. Issues of stress and personality are then discussed in their relation to situational and chronic nightmares. State and trait factors are further elaborated on as we explore the relationship of nightmares and psychopathology. A brief review of organic and pharmacological causes of nightmares follows before we embark on a discussion of issues that relate nightmares to psychological trauma. Some final remarks on treatment conclude our review

Risperidone-induced obsessive-compulsive symptoms: A series of six cases

Risperidone is a novel and atypical agent with a dual antagonistic effect on 5-HT2 and D-2 receptors. Open-label reports and one controlled study suggest that risperidone addition is effective in patients with obsessive-compulsive disorder refractory to treatment with serotonin reuptake inhibitors. However, risperidone has also been implicated in the production or exacerbation of obsessive-compulsive symptoms. We report six cases (schizophrenia, five cases; psychotic depression, one case) in which risperidone was effective in the treatment of the psychotic symptoms but produced de novo obsessive-compulsive symptoms (four cases) or caused exacerbation of previous obsessive-compulsive symptoms (two cases). In all but one case, obsessive-compulsive symptoms emerged shortly after initiation of risperidone treatment with a dose above 3 mg/day. The mechanisms and risk factors for risperidone and other atypical antipsychotics to induce or exacerbate obsessive-compulsive symptoms are as yet not clear. Risperidone-induced obsessive-compulsive symptoms appear to be dose-dependent and are probably produced by serotoninergic-dopaminergic imbalance. Close monitoring of the patients receiving risperidone, especially those vulnerable to the development of obsessive-compulsive symptoms, may be of value. Gradual escalation and low final dose may be helpful

A survey of the attitudes of Greek medical students toward electroconvulsive therapy

Data on attitudes toward electroconvulsive therapy have been reported from various countries; no information, however, is available from Greece. In this survey, we report the results of a questionnaire reflecting the general attitude of Greek medical students toward ECT. A total of 161 sixth (final)-year medical students who had no previous exposure to a formal didactic experience on ECT, were asked to complete a questionnaire before attending a scheduled 90-minute lecture on ECT, as part of their regular curriculum. Questions in the questionnaire could be grouped to indicate a positive, a reserved, or a negative attitude toward ECT Overall, before the lecture, 50.3% held a positive attitude toward ECT, 43.5% were reserved, and 6.2% held a negative attitude. A subgroup of these students (n = 137) were asked again to score the same questionnaire immediately following the lecture to rate the impact of the didactic seminar. The proportion of students with a positive attitude after the lecture was increased to 78.1%, (P < 0.001), while the proportion of students with reserved and negative attitudes were reduced to 20.4% (P < 0.001) and 1.5%, respectively. These encouraging findings reflect, however, only the immediate effects of the lecture and do not guarantee persistence of this change in attitudes over time

EFFECTS OF METHYSERGIDE AND RITANSERIN ON THE PROLACTIN AND THYROTROPIN RESPONSES TO TRH IN DEPRESSED-PATIENTS

Despite extensive study of the effects of various pharmacological agents on the thyrotropin (TSH) and prolactin (PRL) responses to TRH challenge, the effect of serotoninergic agents remains inconclusive. We studied the effect of the serotonin antagonists methysergide (non-selective 5-HT1/5-HT2 blocker with dopaminergic properties) and ritanserin (selective 5-HT2 blocker) on the TSH and PRL responses to TRH stimulation in two groups of medication-free female depressed patients in a double-blind, within-subject design. Methysergide was found to decrease significantly the PRL response to TRH, while ritanserin had no effect. Neither compound influenced the TSH response. Results suggest that 5-HT2 mechanisms do not mediate the PRL and TSH responses to TRH challenge in depression. The reduction in PRL observed after methysergide is probably due to either 5-HT1 or dopaminergic mechanisms

Olanzapine and obsessive-compulsive symptoms

Clozapine and risperidone have been implicated in the development of obsessive-compulsive symptoms. We present three cases in which olanzapine caused a significant exacerbation of obsessive-compulsive symptoms in schizophrenia (two cases) and obsessive-compulsive disorder (one case). (C) 2000 Elsevier Science B.V. All rights reserved