No abstract

The relationship between a history of substance use disorder and the early course of psychotic illness was examined in 96 subjects with schizophrenia and 106 subjects with affective psychosis followed in the Suffolk County Mental Health Project, a longitudinal study of first-admission psychosis. Subjects received a structured diagnostic interview and clinical ratings at baseline assessment and again 6 months later. The 6-month assessment included information about treatment received during the interval. A lifetime history of substance use disorder was associated with worse clinical functioning at 6 months for schizophrenia subjects, but not for those with affective psychosis. There were no significant associations of substance use disorder with type of treatment during the interval or with self-reported compliance with medication. Schizophrenia subjects were more likely than subjects with affective psychosis to report cannabis use during the interval and to meet criteria for cannabis use disorder.

The oxidation of polyamines induced by antitumour polyamine analogues has been associated with tumour response to specific agents. The human spermine oxidase, SMO(PAOh1), is one enzyme that may play a direct role in the cellular response to the antitumour polyamine analogues. In the present study, the induction of SMO(PAOh1) enzyme activity by CPENSpm [N1-ethyl-N11-(cyclopropyl)methyl-4,8,diazaundecane] is demonstrated to be a result of newly synthesized mRNA and protein. Inhibition of new RNA synthesis by actinomycin D inhibits both the appearance of SMO(PAOh1) mRNA and enzyme activity. Similarly, inhibition of newly synthesized protein with cycloheximide prevents analogue-induced enzyme activity. Half-life determinations indicate that stabilization of SMO(PAOh1) protein does not play a significant role in analogue-induced activity. However, half-life experiments using actinomycin D indicate that CPENSpm treatment not only increases mRNA expression, but also leads to a significant increase in mRNA half-life (17.1 and 8.8 h for CPENSpm-treated cells and control respectively). Using reporter constructs encompassing the SMO(PAOh1) promoter region, a 30-90% increase in transcription is observed after exposure to CPENSpm. The present results are consistent with the hypothesis that analogue-induced expression of SMO(PAOh1) is a result of increased transcription and stabilization of SMO(PAOh1) mRNA, leading to increased protein production and enzyme activity. These data indicate that the major level of control of SMO(PAOh1) expression in response to polyamine analogues exposure is at the level of mRNA.

This study provided a method for understanding the student's experience that included student's learning about culture, health disparities, and exposure and reaction to a range of diseases actually encountered. The broad diversity of themes among students indicated that the GCE provided a flexible, personalized experience. How we might design a curriculum to facilitate transformational learning experiences needs further research.