[Rapid detection of a depressive disorder in persons with epilepsy. Validation of a German version of the NDDI-E]. / Schnelle Erkennung einer depressiven Störung bei Menschen mit Epilepsie. Validierung einer deutschsprachigen Version des NDDI-E.

The prevalence of psychiatric disorders in people with epilepsy is high. Depression and anxiety disorders are especially frequent. These comorbid disorders are, however, easily overlooked. The neurological disorders depression inventory for epilepsy (NDDI-E) was developed and validated as a screening instrument with six questions. The aim of the present study was to validate a German version of the NDDI-E. After translation into German and back translation into English, the NDDI-E was presented to 144 patients at the Bethel Epilepsy Center. The Beck depression inventory II (BDI-II), the revised symptom check list by Derogatis (SCL-90-R) and the state-trait anxiety inventory (STAI) were also used. The patients were examined using the mini international neuropsychiatric interview plus (MINI Plus). The German version of the NDDI-E proved to be valid, internally consistent and easy to use.

[Clinical application of functional MRI for chronic epilepsy]. / Klinischer Einsatz der funktionellen MRT bei chronischer Epilepsie.

Functional magnetic resonance imaging (fMRI) is frequently used in the presurgical diagnostic procedure of epilepsy patients, in particular for lateralization of speech and memory and for localization of the primary motor cortex to delineate the epileptogenic lesion from eloquent brain areas. fMRI is one of the non-invasive procedures in the presurgical diagnostic process, together with medical history, seizure semiology, neurological examination, interictal and ictal EEG, structural MRI, video EEG monitoring and neuropsychology. This diagnostic sequence leads either to the decision for or against elective epilepsy surgery or to the decision to proceed with invasive diagnostic techniques (Wada test, intra-operative or extra-operative cortical stimulation). It is difficult to evaluate the contribution of the fMRI test in isolation to the validity of the entire diagnostic sequence. Complications such as memory loss and aphasia in temporal lobe resections or paresis after frontal lobe resections are rare and rarely of disastrous extent. This further complicates the evaluation of the clinical relevance of fMRI as a predictive tool. In this article studies which investigated the concordance between fMRI and other diagnostic gold standards will be presented as well as the association between presurgical fMRI and postsurgical morbidity.

Coordination of three signaling enzymes by AKAP79, a mammalian scaffold protein.

Multivalent binding proteins, such as the yeast scaffold protein Sterile-5, coordinate the location of kinases by serving as platforms for the assembly of signaling units. Similarly, in mammalian cells the cyclic adenosine 3',5'-monophosphate-dependent protein kinase (PKA) and phosphatase 2B [calcineurin (CaN)] are complexed by an A kinase anchoring protein, AKAP79. Deletion analysis and binding studies demonstrate that a third enzyme, protein kinase C (PKC), binds AKAP79 at a site distinct from those bound by PKA or CaN. The subcellular distributions of PKC and AKAP79 were similar in neurons. Thus, AKAP79 appears to function as a scaffold protein for three multifunctional enzymes.

The Wnt-1 proto-oncogene regulates MAP kinase activation by multiple growth factors in PC12 cells.

PC12/Wnt-1 cells display morphological changes in response to stimulation by select growth factors but do not respond to NGF. Furthermore, stimulation by EGF can induce neuronal differentiation in these cells but not in wild type cells. We have found that in these cells, compared to wild type PC12 cells, FGF and EGF stimulation of MAP kinase activity is enhanced, while NGF stimulation of MAP kinase in diminished. Finally, in cells expressing Wnt-1, the effect of cyclic adenosine monophosphate (cAMP) on MAP kinase activation is reversed; cAMP stimulates MAP kinase in wild type PC12 cells but inhibits MAP kinase in PC12/Wnt-1 cells. These data suggest that Wnt-1 expression alters the specificity of growth factor signaling in neuronal cells.

Cyclic adenosine monophosphate can convert epidermal growth factor into a differentiating factor in neuronal cells.

The rat pheochromocytoma (PC12) cell line is a model for studying the mechanism of growth factor action. Both epidermal growth factor and nerve growth factor stimulate mitogen-activated protein (MAP) kinase in these cells. Recent data suggest that the transient activation of MAP kinase may trigger proliferation, whereas sustained activation triggers differentiation in these cells. We have tested this model by asking whether agents that stimulate MAP kinase without inducing differentiation can act additively to trigger differentiation. Neither forskolin nor epidermal growth factor can stimulate differentiation, yet both activate MAP kinase in these cells. Together, their actions on MAP kinase are synergistic. Cells treated with both agents differentiate, measured morphologically and by the induction of neural-specific genes. We propose that cellular responses to growth factor action are dependent not only on the activation of growth factor receptors by specific growth factors but on synchronous signals that may elevate MAP kinase levels within the same cells.

Identification of the binding site for the Shc protein to the avian erythroblastosis virus (AEV-H) v-erbB protein.

Activation of tyrosine kinase growth factor receptors leads to autophosphorylation of specific tyrosine residues within the intracellular region of the receptor. The phosphorylated tyrosines serve as binding sites for various cytoplasmic proteins. The Shc protein is one such protein. Upon activation of the chicken c-erbB protein by ligand Shc binds to the c-erbB protein and becomes phosphorylated on tyrosine. Similarly, Shc is found bound to the constitutively phosphorylated v-erbB protein encoded by the avian erythroblastosis virus strain H, AEV-H. Utilizing various mutant forms of the v-erbB protein, the residue equivalent to tyrosine 1154 in the chicken c-erbB protein was shown to serve as a binding site for the Shc protein to the AEV-H v-erbB protein. However, binding to this site was not essential for transformation since v-erbB oncoproteins which lacked this site still transform both erythroid cells and fibroblasts.

Analysis of the role of the Shc and Grb2 proteins in signal transduction by the v-ErbB protein.

The epidermal growth factor receptor, EGFR, has been implicated in cell transformation in both mammalian and avian species. The v-ErbB oncoprotein is an oncogenic form of the chicken EGFR. The tyrosine kinase activity of this oncoprotein is required for transformation, but no transformation-specific cellular substrates have been described to date. Recently activation of the ras signal transduction pathway by the EGFR has been shown to involve the Shc and Grb2 proteins. In this communication, we demonstrate that the Shc proteins are phosphorylated on tyrosine residues and are complexed with Grb2 and the chicken EGFR following ligand activation of this receptor. In fibroblasts and erythroid cells transformed by the avian erythroblastosis virus (AEV) strains H and ES4, the Shc proteins are found to be constitutively phosphorylated on tyrosine residues. The tyrosine-phosphorylated forms of the AEV strain H v-ErbB protein are found in a complex with Shc and Grb2, but the Shc proteins do not bind to the AEV strain ES4 v-ErbB protein. Mutant forms of the v-ErbB protein (in which several of the tyrosines that become autophosphorylated have been deleted by truncation) are unable to transform erythroid cells but can still transform fibroblasts. Analysis of cells transformed by one of these mutants revealed that the truncated v-ErbB protein could no longer bind to either Shc or Grb2, but this oncoprotein still gave rise to tyrosine-phosphorylated Shc proteins that complexed with Grb2 and led to activation of mitogen-activated protein (MAP) kinase. The results suggest that stable binding of Grb2 and Shc to the v-ErbB protein is not necessary to activate this signal transduction pathway and assuming that the mutant activate MAP kinase in erythroid cells in a manner similar to that of fibroblasts, that activation of this pathway is not sufficient to transform erythroid cells.