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Biomedical subjects

E Krebs

Publications and source records attributed to E Krebs.

15 recordsLinked to original sources

BMP-4 regulates the dorsal-ventral differences in FGF/MAPKK-mediated mesoderm induction in Xenopus.

Recent studies on Xenopus development have revealed an increasingly complex array of inductive, prepatterning, and competence signals that are necessary for proper mesoderm formation. In this study, we establish that fibroblast growth factor (FGF) signals through mitogen-activated protein kinase kinase (MAPKK) to induce mesodermal gene expression. We demonstrate that a partially activated form of MAPKK restores expression of the mesodermal genes Xcad-3 and Xbra, eliminated by the dominant-negative FGF receptor (delta FGFR). Similar to the results reported earlier with delta FGFR, expression of a dominant-negative form of MAPKK (MAPKKD) preferentially eliminates the dorsal expression of Xcad-3 and Xbra. We tested whether the regional localization of bone morphogenetic protein-4 (BMP-4) could explain why both MAPKKD and delta FGFR eliminate the dorsal and not the ventral expression of Xcad-3 and Xbra. We show that ectopic expression of BMP-4 is sufficient to maintain the dorsal expression of Xcad-3 and Xbra in embryos containing delta FGFR and that expression of a dominant-negative BMP receptor reduces the dorsal-ventral differences in delta FGFR embryos. These results indicate that regional localization of BMP-4 is responsible for the dorsal-ventral asymmetry in FGF/MAPKK-mediated mesoderm induction.

Animals

[Psychotherapy with elderly patients].

Psychotherapy of the elderly is a necessary, however also difficult task for the therapist. The increasing number of mental problems in the elderly leads to the fact, that therapists of different basic training and different direction occupy themselves with different aspects of psychopathology in the elderly. Their variable experiences show that there could be different methods of working with the elderly, both in the clinic and in the private practice. The existing sources of literature are encouraging, even if some authors can see only minimal changes of the mental condition in the case of an deteriorating organic disturbance. The evaluation of the used psychotherapeutical methods have been only sporadically performed. A continuation of the methodological research in this area is necessary.

Aged

Investigation of the effect of fluperlapine on the EEG in schizophrenic patients.

The investigations of the EEG during an open study with the antipsychotic drug fluperlapine in acute schizophrenic patients are reported. Due to ethical and practical considerations some of the common pharmaco-electroencephalographic procedures as well as placebo controlled study designs could not be applied in these patients. To overcome at least partly these limitations, intraindividual as well as interindividual correlations were used. They were computed between plasma concentrations of unchanged fluperlapine as well as its metabolite N-oxide fluperlapine, on one hand, and EEG variables, on the other. The intraindividual correlations can be computed either on the first day of the active treatment over various time points of that day (acute effects) or across several appointed treatment days always taking values at the same time during these days (chronic effects). The intraindividual correlations of a set of subjects were submitted to a sign test to obtain an overall result for the relation between the EEG and blood plasma levels of the drug. In this way an acute and a chronic effect of fluperlapine on the EEG could be shown consisting mainly of an increase in slow waves, a decrease in the alpha-activity and a tendency of beta-activity to decrease. A comparison of the correlations between the plasma levels of fluperlapine and the EEG variables with the correlations between the plasma levels of N-oxide fluperlapine and the EEG gives rise to the hypothesis that unchanged fluperlapine has a stronger effect on the EEG than its metabolite.

Adult

Antipsychotic efficacy of fluperlapine. An open multicenter trial.

In an open multicenter trial 46 schizophrenic patients were treated with fluperlapine for 20 days. A mean daily dosage of 300-400 mg appeared to be an effective antipsychotic treatment in most cases. The marked antipsychotic effect was accompanied by a good improvement of depressive symptoms. Extrapyramidal side effects were extremely rare.

Adult

Pharmaco-EEG studies with fluperlapine.

In the first of 2 studies, the effects of 3-fluoro-6-(4-methyl-piperazinyl)- 11H -dibenz[b,e]azepine ( fluperlapine , NB 106-689) 5 and 10 mg, clozapine 5 and 10 mg, and placebo on the EEG and on subjective mental and emotional state were investigated in 8 healthy male volunteers. The study was carried out as a double-blind within-subject comparison, with randomized sequence of treatments. Quantitative spectral analysis of the EEG revealed that changes after fluperlapine were strikingly similar to those after clozapine, i.e. an increase in delta and theta and a decrease in alpha activity. These changes were associated with a reduction in self-rated "wakefulness" and are evidence of a sedative effect. The drugs' effects differed only in the magnitude of the increase in beta activity in the 20-40 cps frequency band (beta 2), which was greater after fluperlapine than after clozapine. Since increased beta 2 activity has been reported with tricyclic antidepressants, it is suggested that fluperlapine , besides possessing neuroleptic properties, might also have some properties of a (sedative) antidepressants. It is estimated from the EEG findings that, at equal doses, fluperlapine (capsules) has approximately one half of the sedative potency of clozapine (tablets). A second study in schizophrenic patients revealed strong correlations between EEG effects and blood levels of unchanged fluperlapine during long-term treatment.

Adult

Antibody to the nonapeptide Glu-Glu-Glu-Glu-Tyr-Met-Pro-Met-Glu is specific for polyoma middle T antigen and inhibits in vitro kinase activity.

Middle T antigen of polyoma virus has an associated tyrosine kinase activity which phosphorylates tyrosine residue 315 on middle T in immunoprecipitates. A peptide representing the sequence of middle T from residue 311 to 319 has been synthesized. This peptide acts as a weak inhibitor of the kinase reaction. An antiserum has been raised against this peptide after conjugation to bovine serum albumin. The antibody is middle T-specific. Middle T antigen precipitated by this serum is largely inactive in the kinase reaction. Dissociation of the immune complex with peptide releases middle T in a kinase-active form.

Animals