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The vertebrate midbrain-hindbrain boundary (MHB) organizes patterning and neuronal differentiation in the midbrain and anterior hindbrain. Formation of this organizing center involves distinct steps, including (i) positioning of the MHB in the neural plate, (ii) establishment, and (iii) maintenance of its regional identity and signaling activity. How MHB-specific gene expression is achieved is not yet understood. We are studying the role of the spiel-ohne-grenzen (spg) gene in MHB formation. We have identified pou2, a member of the POU family of transcription factors, as the gene affected in the spg mutation, pou2 is transiently expressed during late gastrulation and early somitogenesis in the mid- and anterior hindbrain. Expression of otx2 and gbx2 initiates accurately, indicating that positioning of the MHB is normal in spg mutants. In contrast, early MHB markers such as wntl, pax2.1, and eng2 require spg/pou2 for proper initiation of their MHB expression domains during late gastrulation. Our data show that spg/pou2 is required for the establishment of the MHB and that it plays a critical role in the regulation of MHB-specific genes.

Background: To assess the efficacy, safety, tolerability and pharmacokinetics of BIBF 1120 in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC).Methods: Patients with locally advanced or metastatic relapsed NSCLC in whom first- or second-line platinum-based chemotherapy failed were randomly allocated to daily 250 mg BIBF 1120 b.i.d. or 150 mg BIBF 1120 b.i.d. Primary end points were progression-free survival (PFS) and objective tumour response (RECIST). Incidence and severity of adverse events (AEs) were reported.Results: Seventy-three patients received BIBF 1120. Median PFS was 6.9 weeks, with no significant difference between treatment arms. Median overall survival (OS) was 21.9 weeks. Eastern Cooperative Oncology Group (ECOG) 0–1 patients (n = 56) had a median PFS of 11.6 weeks and a median OS of 37.7 weeks. Tumour stabilisation was achieved in 46% of patients (ECOG 0–1 patients: 59%), with one confirmed partial response (250 mg b.i.d.). Most commonly reported drug-related AEs were nausea (57.5%), diarrhoea (47.9%), vomiting (42.5%), anorexia (28.8%), abdominal pain (13.7%) and reversible alanine transaminase (13.7%) and aspartate aminotransferase elevations (9.6%). BIBF 1120 displayed dose-linear pharmacokinetic characteristics.Conclusion: Continuous treatment with BIBF 1120 was well tolerated, with no difference in efficacy between treatment arms. PFS and objective response with single-agent treatment in advanced disease warrants further exploration. [ABSTRACT FROM AUTHOR]

The purpose of this pilot study was to determine the influence of oral contraceptives (OC) on electromyography (EMG) and mechanomyography (MMG) during isometric (ISO) muscle actions of the rectus femoris. Two groups of women (Mean ± SEM, 24 ± 1 yrs, 1.68 ± 0.02 m, 70.97 ± 4.81 kg) were recruited and tested five times throughout one complete menstrual cycle. The first group (n=7) were not taking hormonal treatment (NOC) and the OC group (n=6) had been taking exogenous hormones for at least six months prior. Each participant performed maximal ISO muscle actions (MVC) of the leg extensors on a Cybex II isokinetic dynamometer followed by randomly assigned sub-maximal ISO muscle actions. Bipolar surface EMG electrodes were placed over the rectus femoris with a piezoelectric MMG recording device placed between the two electrodes. Three separate three way (group × day × %MVC) mixed factorial repeated measures ANOVAs were used to determine differences in torque, EMG and MMG between NOC and OC subjects. There were no significant three-way interactions involving group for normalized torque, EMG or MMG. These results indicated that OC does not have an effect on torque, EMG or MMG during ISO muscle actions of the rectus femoris. [Copyright &y& Elsevier]