Enhancing the multi-dimensional assessment of quality of life: introducing the WHOQOL-Combi

Quality of Life Research - We revisited the global concept of subjective quality of life (QoL) as assessed by the WHOQOL-BREF to investigate whether it could be elaborated into a conceptually more...     

The neu-protein and breast cancer

The neu-protein is overexpressed in about 20% of invasive duct cell carcinomas of the breast. The only reliable sign for neu-overexpression by immunohistochemistry is membrane staining. Its overexpression is correlated with decreased overall survival and disease free survival due to increased metastatic activity of neu-overexpressing tumour cells. This increased metastatic potential is a consequence of the motility enhancing activity of the neu-protein, which is exclusively expressed on pseudopodia, and to a lesser extent of its growth stimulating effect. From a clinical point of view, the assessment of neu-overexpression in breast cancer might become a useful tool in the future treatment of patients by chemotherapy, since patients whose tumour shows neu-overexpression benefit from higher doses of chemotherapy. The molecule plays a key role in the pathogenesis of Paget's disease of the breast. A chemotactic factor which is secreted by epidermal keratinocytes attracts the Paget cells to spread into the epidermis and acts via the neu-protein. In ductal carcinoma in situ, the combination of neu-overexpression and large cell type is highly correlated with extent of disease and therefore neu-overexpression might be a predictive marker for recurrence of disease after tumour resection.     

Interaction with 14-3-3 proteins promotes functional expression of the potassium channels TASK-1 and TASK-3

The two-pore-domain potassium channels TASK-1, TASK-3 and TASK-5 possess a conserved C-terminal motif of five amino acids. Truncation of the C-terminus of TASK-1 strongly reduced the currents measured after heterologous expression in Xenopus oocytes or HEK293 cells and decreased surface membrane expression of GFP-tagged channel proteins. Two-hybrid analysis showed that the C-terminal domain of TASK-1, TASK-3 and TASK-5, but not TASK-4, interacts with isoforms of the adapter protein 14-3-3. A pentapeptide motif at the extreme C-terminus of TASK-1, RRx(S/T)x, was found to be sufficient for weak but significant interaction with 14-3-3, whereas the last 40 amino acids of TASK-1 were required for strong binding. Deletion of a single amino acid at the C-terminal end of TASK-1 or TASK-3 abolished binding of 14-3-3 and strongly reduced the macroscopic currents observed in Xenopus oocytes. TASK-1 mutants that failed to interact with 14-3-3 isoforms (V411*, S410A, S410D) also produced only very weak macroscopic currents. In contrast, the mutant TASK-1 S409A, which interacts with 14-3-3-like wild-type channels, displayed normal macroscopic currents. Co-injection of 14-3-3ζ cRNA increased TASK-1 current in Xenopus oocytes by about 70 %. After co-transfection in HEK293 cells, TASK-1 and 14-3-3ζ (but not TASK-1ΔC5 and 14-3-3ζ) could be co-immunoprecipitated. Furthermore, TASK-1 and 14-3-3 could be co-immunoprecipitated in synaptic membrane extracts and postsynaptic density membranes. Our findings suggest that interaction of 14-3-3 with TASK-1 or TASK-3 may promote the trafficking of the channels to the surface membrane.     

Efficient propagation of single gene deleted recombinant Sendai virus vectors

Recombinant Sendai virus vectors (SeVV) have become an attractive tool for basic virological as well as for gene transfer studies. However, to (i) reduce the cellular injury induced by basic recombinant SeV vectors (encoding all six SeV genes as being present in SeV wild-type (wt) genomes) and to (ii) improve SeV vector safety, deletions of viral genes are necessary for the construction of superior SeVV generations. As a strong expression system recombinant replication-incompetent adenoviruses, coding for SeV proteins hemagglutinin-neuraminidase (HN), fusion (F), or matrix (M), were generated and successfully employed for the propagation of single gene deleted (DeltaHN, DeltaF, DeltaM) recombinant SeVV. Further investigations of the propagation procedures required for single gene deleted recombinant SeVV demonstrated (i) modifications of the cell culture medium composition as well as (ii) incubation with vitamin E as crucial steps for the enhancement of SeVV-DeltaHN, -DeltaF, or -DeltaM viral particle yield. Such optimized propagation procedures even led to a successful propagation of HN-deleted viral particles (SeVV-DeltaHN), which has not been reported before.     

Large-field S-cone flicker test

Background: Disturbances of blue color vision and of temporal contrast sensitivity can indicate early damage in glaucoma. For the present study a quick and easy test was devised which examines both functions ai one time by testing the temporal contrast sensitivity of a blue flickering light on an intense yellow background. Methods: Large coextensive background and test fields (85°) are used, making fixation uncritical. Detailed experiments were made in two normal subjects to derive spectral sensitivity curves from flicker-fusion frequency (FFF) versus intensity functions and to obtain complete temporal contrast-sensitivity (De Lange) curves under different levels of adaptation and test lights. After selection of appropriate luminances and one stimulation frequency from these experiments, test-retest variability was studied in four subjects in five repetitions. In addition, normal values were collected from 22 subjects. Results: Spectral sensitivities for two levels of FFF (15 Hz and 44 Hz) agree with Stiles' ₁ at the low and with ₄ at the high FFF. Temporal contrast-sensitivity curves show a low-frequency section with peak sensitivity at 1 Hz and a high-frequency section with a peak at around 4 Hz. From the basic experiments the following conditions for the clinical examination were selected: Background luminance 2600 cd/m², test luminance at 451 nm 0.8 cd/m², stimulation frequency 4 Hz. The test-retest variability showed an acceptable intraclass correlation coefficient (0.6). Conclusions: The present experiments carried out with a very large stimulus led to meaningful results which are in rather good agreement with results reported in the literature on small-field stimuli. The blue-on-yellow flicker test carried out under the conditions mentioned above is a quick and easy test which could be helpful in improving early glaucoma diagnosis.