Biomedical subjects

John B Levine

Publications and source records attributed to John B Levine.

4 recordsLinked to original sources

PubMed2004

Clinical utility as a criterion for revising psychiatric diagnoses.

OBJECTIVE: Changes in DSM-IV were guided by empirical data that mostly focused on improving diagnostic validity and reliability. Although many changes were made explicitly to improve clinical utility, no formal effort was made to empirically determine actual improvements in clinical utility. The authors propose that future revisions of DSM empirically demonstrate improvement in clinical utility to clarify whether the advantages of changing the diagnostic criteria outweigh potential negative consequences. METHOD: The authors provide a formal definition of clinical utility and then suggest that the merits of a proposed change to DSM be evaluated by considering 1) its impact on the use of the diagnostic system, 2) whether it enhances clinical decision making, and 3) whether it improves clinical outcome. RESULTS: Evaluating a change based on its impact on use considers both user acceptability and accuracy in application of the diagnostic criteria. User acceptability can be measured by surveying users' reactions, assessing user acceptability in a field trial setting, and measuring the effects on ease of use. Assessment of the correct application of diagnostic criteria entails comparing the clinician's diagnostic assessment to expert diagnostic assessment. Assessments of the impact on clinical decision making use methods developed for evaluating adherence to practice guidelines. Improvement in outcome entails measuring reduction in symptom severity or improvement in functioning or in documenting the prevention of a future negative outcome. CONCLUSIONS: Empirical methods should be applied to the assessment of changes that purport to improve clinical utility in future revisions of DSM.

Attitude of Health Personnel↗

PubMed2004

The good-enough mentoring relationship.

OBJECTIVE: This study aimed to describe the state of mentoring in today's academic environment. METHODS: Resident focus groups from across the nation discussed their opinions about mentoring and experiences with mentoring, and individual faculty members were videotaped discussing the same. RESULTS: Sixty-six residents and five faculty members participated in the project. There was consensus among residents and faculty regarding important qualities of a mentoring relationship, obstacles to forming a mentorship, and methods to improve the mentorship experience in psychiatric training. CONCLUSION: Mentoring is still believed to be a vital component of a successful residency experience. Specific components that warrant further research include boundaries within the relationship, ethnicity and gender factors, and potential need for resident and faculty curricula on the topic of mentoring.

Attitude of Health Personnel↗

PubMed2003

Clozapine inhibits isolated N-methyl-D-aspartate receptors expressed in xenopus oocytes in a subunit specific manner.

Antipsychotic agents have typically been viewed as acting through dopaminergic targets, although mounting evidence suggests that drugs such as clozapine may act on glutamatergic systems. In order to explore the effects of clozapine on the NMDA class of glutamate receptors, oocytes expressing the NMDA receptor NR1 subunit, coupled with different NR2 subunits, were exposed to clozapine and NMDA induced current was measured with two electrode voltage-clamp techniques. Our results indicate that clozapine inhibits the NMDA receptor, but that this inhibition is subunit specific, being significantly greater for receptors containing NR2A and NR2B than for those containing NR2C. Interestingly, the inhibition required pretreatment with clozapine before activation of the receptor with NMDA. In addition to providing mechanistic insights, this finding may help to explain divergent results in the literature regarding the effects of antipsychotic agents on glutamate receptors.

Animals↗

PubMed2003

Novel functional interactions between Trk kinase and p75 neurotrophin receptor in neuroblastoma cells.

To understand the functional interactions between the TrkA and p75 nerve growth factor (NGF) receptors, we stably transfected LAN5 neuroblastoma cells with an expression vector for ET-R, a chimeric receptor with the extracellular domain of the epidermal growth factor receptor (EGFR), and the TrkA transmembrane and intracellular domains. EGF activated the ET-R kinase and induced partial differentiation. NGF, which can bind to endogenous p75, did not induce differentiation but enhanced the EGF-induced response, leading to differentiation of almost all cells. A mutated NGF, 3T-NGF, that binds to TrkA but not to p75 did not synergize with EGF. Enhancement of EGF-induced differentiation required at least nanomolar concentrations of NGF, consistent with the low-affinity p75 binding site. EGF may induce a limited number of neuronal cells because it also enhanced apoptosis. Both NGF and a caspase inhibitor reduced apoptosis and, thereby, enhanced differentiation. NGF seems to enhance survival through the phosphatidylinositol-3 kinase (PI3K) pathway. Consistent with this hypothesis, Akt, a downstream effector of the PI3K pathway, was hyperphosphorylated in the presence of EGF+NGF. These results demonstrate that TrkA kinase initiates differentiation, and p75 enhances differentiation by rescuing differentiating cells from apoptosis via the PI3K pathway. Even though both EGF and NGF are required for differentiation of LAN5/ET-R cells, only NGF is required for survival of the differentiated cells. In the absence of NGF, the cells die by an apoptotic mechanism, involving caspase-3. An anti-p75 antibody blocked the survival effect of NGF. Brain-derived neurotrophic factor also enhanced cell survival, indicating that in differentiated cells, NGF acts through the p75 receptor to prevent apoptosis.

Animals↗