Differentiating embryonal stem cells are a rich source of haemopoietic gene products and suggest erythroid preconditioning of primitive haemopoietic stem cells.

The difficulties associated with studying molecular mechanisms important in hemopoietic stem cell (HSC) function such as the problems of purifying homogeneous stem cell populations, have prompted us to adapt the murine ES cell system as an in vitro model of HSC generation and function. We now report that careful analysis of the time course of HSC generation in differentiating ES cells allows them to be used as a source of known and novel hemopoietic gene products. We have generated a subtracted library using cDNA from ES cells collected just prior to and just following the emergence of HSCs. Analysis of this library shows it to be a rich source of known hemopoietic and hemopoietic related gene products with 44% of identifiable cDNAs falling into these camps. We have demonstrated the value of this system as a source of novel genes of relevance to HSC function by characterizing a novel membrane protein encoding cDNA that is preferentially expressed in primitive hemopoietic cells. Intriguingly, further analysis of the known components of the subtracted library is suggestive of erythroid preconditioning of the ES cell-derived HSC. We have used dot-blot and in situ analysis to indicate that this erythroid preconditioning is probably restricted to primitive but not definitive HSC.

ESkine, a novel beta-chemokine, is differentially spliced to produce secretable and nuclear targeted isoforms.

Using the murine embryonal stem cell system, we have identified a novel gene encoding a highly divergent member of the beta-chemokine family of proinflammatory mediators and have called this protein ESkine. Much of the coding sequence for ESkine overlaps with the 3'-end of a novel interleukin 11 receptor alpha-like sequence on murine chromosome 4. ESkine is produced as two splice variants. One of these variants encodes a classical chemokine with an associated signal peptide, while the other variant (PESKY) possesses the main body of the chemokine but has replaced the signal peptide with an alternative stretch of amino acids that allows for nuclear targeting of this isoform. This differential splicing arises as a result of alternative 5' exon usage. These differentially spliced forms are expressed at discrete tissue loci. Thus, while ESkine is highly expressed in the placenta, PESKY is mainly expressed in the Testes and brain and weakly in the developing embryo. Studies on the proinflammatory properties of ESkine reveal it to be active in inducing polarization of CD4(+) T cells but to be inactive on other hemopoietic cellular populations.

The Stroop task and attention deficits in schizophrenia: a critical evaluation of card and single-trial Stroop methodologies.

The Stroop task, considered by many to be a paradigmatic measure of selective attention, has often been employed to investigate attention deficits in schizophrenia. Card and single-trial versions of this task have yielded different results. In this study both card and single-trial versions were administered to healthy controls (n = 24) and patients with schizophrenia (n = 55). No differences in reaction time (RT) interference were found on either version. On the single-trial version, patients showed greater RT facilitation and error rate interference, evidence for a deficit in selective attention. Methodologic and analytic issues that account for the mixed results from earlier card Stroop studies are addressed. It is concluded that single-trial versions provide greater sensitivity to selective attention pathology in schizophrenia.

Emergence of obsessive compulsive symptoms during treatment with clozapine.

BACKGROUND: Clozapine differs from other currently available antipsychotics in its prominent serotonin blockade. We explore the relationship between clozapine and obsessive compulsive symptoms, which have been linked to deficient serotonin. METHOD: We reviewed our experience in treating 49 chronic schizophrenic patients with clozapine. RESULTS: Five patients were identified who experienced either de novo obsessive compulsive symptoms or exacerbation of preexistent symptoms. Clinical details are provided for each case. CONCLUSION: Clozapine may produce or unmask obsessive compulsive symptoms. This may reflect a variation on the normal course of clinical improvement, or may more specifically result from clozapine's atypical pattern of CNS receptor antagonism. Further attention to this issue is warranted.