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.     

The frequency and avidity of committed cytotoxic T lymphocytes (cCTL) for donor HLA class I and class II antigens and their relation with graft vascular disease

Cellular immune processes may trigger the development of graft vascular disease (GVD). CD4 and CD8 cytotoxic T lymphocytes that infiltrate the allograft could play a role in the development of GVD. We studied the presence of in vivo primed or committed CTL (cCTL) and their avidity for donor HLA class I and class II antigens in graft-infiltrating lymphocyte cultures propagated from endomyocardial biopsies derived from patients with and without signs of GVD. The fraction of cCTL with high avidity for HLA class I or class II antigens was estimated by the addition of anti-CD8 or anti-CD4 MoAbs to the cytotoxic phase of the limiting dilution analysis. In the first year after transplantation no difference in the frequency of donor-specific class I cCTL between patients with and without GVD was found. Addition of anti-CD8 MoAb revealed that most cultures predominantly consisted of cCTL with low avidity for donor HLA class I antigens, irrespective of the development of GVD at 1 year after transplantation. However, in patients who did not develop GVD, the frequency of cCTL with donor HLA class II specificity was significantly higher than in patients who did develop GVD. The avidity for donor HLA class II antigens was comparable in both groups. A high frequency of donor-specific cCTL for HLA class II antigens seems to be a protective factor against the development of GVD. These cCTL might be cytotoxic for cells involved in GVD development, e.g. activated endothelium and smooth muscle cells of donor origin.     

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.     

Percutaneous burrhole trephination of the skull: a study of 519 cases

We want to report on our experiences with the percutaneous trephination using a 2.35 mm round dental drill with serrated saws around it, a Rosenbohrer. It is a methodically similar activity as described by J. Zentner [11].From 1981 to 1992 519 patients were treated and 546 trephinations were performed.At the beginning this treatment was only used in connection with intracerebral bleedings and biopsies.In a considerable short time the indication could be extended to the subdural hematoma, tumor cyst, obstructive hydrocephalus as well as to the abscess and the subdural epyema.The rate of infection was 1.28% and the risk of bleeding 0.36%.In our opinion the advantages of this small electrical trephination are the easy handling, the universal use and mobility and the avoidable risk of anesthesia as well as the sterilisation at the same time and the stopping of blood, caused by the contact surface friction.     

Epidemiology of lyme disease in France: Lyme borreliosis in the region of Berry sud: A six year retrospective

The purpose of this epidemiologic retrospective is to recognize the endemic nature of Lyme borreliosis in Berry, region of France. Fifty-nine cases have been reported here during the past six years (1988–1994). An erythema migrans (EM), or a late manifestation concurrent with positive ELISA-test represents the main inclusion criterion (case definition used by the CDC). The results reveal a high incidence considering the limited information available in France. The farmer has been found to be mainly at risk, with EM being observed in 49% of cases. In general, late manifestations are rarely described. Peripheral neurological manifestations occur more frequently than those reported in the USA. The steps taken as a result of our study of Lyme disease are in accordance with the recommendations of the World Health Organization.Participants in this survey: GEEP, Groupe d'Etudes Epidémiologiques et Prophylactiques, Centre Hospitalier Intercommunal de Villeneuve Saint Georges, France; and ORMAT, Observatoire Rural des Maladies Transmissibles, Antenne du GEEP, Centre Hospitalier de La Châtre, France}     

Ethics consultation: a dangerous, antidemocratic charlatanry?

Giles Scofield's argument indicates ethics consultants may need to better clarify what in fact they are and what they are not doing, claiming, and striving for. But we must not step back too far. We must neither engage in putting in envious professional claims for exclusive rights in the area of difficult and momentous decisions in healthcare nor get stuck in discussing normative ethics at the level of metaphysics, ontology, and dogmatics (as has happened in Germany for decades). We must not do so especially in view of the achievements of ethics consultation and the growing demand for it by all parties involved, conceded even by sceptics. Ethics consultation, according to Scofield, appears to be dangerous....Let us look more closely at the logic of the argument by discussing the presumed "antidemocratic" nature. The "new tyranny" of thoughts, and the "proper" role of bioethics consultation. Some considerations about the possibility of ethics expertise shall be left for the end.     

Effects of 8-methoxypsoralen plus 365 nm UVA light on Candida albicans cells

Summary Candida (C.) albicans cells were exposed to 8-Methoxypsoralen (8-MOP) concentrations of 1.0 g/ml and 10.0 g/ml medium and irradiated with 365 nm light. The amount of energy emitted was 4.8 J/cm². Two divergent types of cell damage occured concerning yeast cell cytoplasm and cell wall. Two hours after exposure cytoplasmic changes involving mitochondria, which showed irregularities in shape, blurred appearance or loss of mitochondrial cristae and outer membrane were seen. The number of vacuoles was increased. The cytoplasm showed large electron transparent areas, the cytoplasmic membrane disappeared in some areas completely. Nucleus and nuclear envelope usually remained intact in early stages. 24h after exposure conspicuous cell wall alterations were observed in addition to cytoplasmic changes. Newly produced cell wall material formed ball-like protrusions or was adherent sickle-shaped to the cell wall. The investigations strongly suggest that the results found after 8-MOP-UVA treatment of C. albicans cells can not be interpreted in the sense of a general cytotoxic effect. Apparently it takes the form of a combination of events involving regressive and progressive alterations.