Nuclear proteins obtained from human brain tumor cell lines by differential salt extraction were subjected to high-resolution two-dimensional electrophoresis. Several hundred spots were detectable in the low salt (0.4 M NaCl) extract using silver staining. These patterns exhibited remarkable differences between the different cell lines we analyzed. A less complex pattern occurred when nuclei were subsequently treated with high salt (2.5 M NaCl/5 M urea). We compared the electropherograms from various human glioblastoma cell lines and found them very similar and even a high degree of similarity occurs between glioblastomas and other human tumor cell lines. Beside these more general observations we detected several proteins at least enriched in human glioblastomas which were totally absent in low grade astrocytomas and nonglial tumors. They could be separated from the bulk of nonspecific proteins by simple modifications of the isoelectric focusing conditions. From these results we conclude that nuclear proteins obtained by sequential salt extraction and separated by two-dimensional techniques may provide tumor specific proteins suitable for antibody production.

Brain Neoplasms↗

PubMedDate not supplied

Sodium channel blockade enhances dispersion of the cardiac action potential duration. A computer simulation study.

The goal of this study was to elucidate the causes why the proarrhythmic activity of sodium channel blocking drugs is enhanced during the post-infarction period. Therefore, we studied the effects of a reduction in sodium conductance on the action potential duration and its dispersion in a simulated array of 1600 ventricular myocytes. Cardiac tissue is known to possess anisotropic properties with regard to the intercellular electrical resistances (R). Infarction as well as aging causes deposition of collagen in the cardiac tissue, thereby inducing zones of high electrical resistance leading to a non-uniform anisotropy (Spach et al., Circ Res 62:811, 1988). For our study an array of 40*40 ventricular myocytes was simulated using Beeler-Reuter-algorithms. Physical tissue properties were assumed to be either a) uniform anisotropic (i.e., all longitudinal R = 5000 omega cm, all transversal R = 20,000 omega cm; UA) or b) non-uniform anisotropic (i.e., transversal R for the inner 10*10 cells was set to 10(10) omega cm; NUA). Mean action potential duration (APD) was increased under UA (287 ms. dispersion: 0.8 ms) when compared to NUA (285 ms, disp.: 3.2 ms). Assuming a 25% decrease in sodium conductance, we found the total activation time (TAT) to be increased (from 99 to 139 ms), indicating slowing of conduction, APD to be shortened (from 287 to 259 ms), and the APD-dispersion to be increased (from 0.8 to 29 ms) in UA. These changes were more pronounced in the case of NUA: increase in TAT from 103 to 150 ms, APD-shortening from 285 to 214 ms and a marked increase in APD-Dispersion from 3.2 to 53 ms). From these results it is concluded that a) the effects of a reduced sodium conductance are more pronounced in NUA tissue, and b) that the resulting increase in dispersion may provoke arrhythmia by local differences in APD. This may be one of the mechanisms underlying the increased proarrhythmic risk of class I antiarrhythmic drugs in the postinfarction period.

Action Potentials↗

PubMedDate not supplied

Meropenem monotherapy versus cefotaxime plus metronidazole combination treatment for serious intra-abdominal infections.

In an open, randomised, multicentre trial, the efficacy and tolerability of empirical meropenem monotherapy (1 g intravenously every 8 hours) and cefotaxime (2 g every 8 hours) plus metronidazole (0.5 g intravenously every 8 hours) for 5 to 10 days was compared in 94 patients with serious intra-abdominal infection who required surgery. Eighty-three patients had an evaluable clinical response. Significantly more patients in the meropenem group had a satisfactory clinical response at the end of treatment (41/43 [95.3%] vs 30/40 [75.0%]; p = 0.008). The bacteriological response was also higher in the meropenem group (31/33 vs 26/32). In the bacteriologically evaluable population, a satisfactory clinical response was observed in 31/33 of those who received meropenem compared to 24/32 of the cefotaxime/metronidazole recipients (p = 0.03). Empirical meropenem monotherapy should prove a useful alternative to the currently standard combination treatment for serious intraabdominal infections.

Adult↗

PubMedDate not supplied

Intestinal microsporidiosis in patients with acquired immunodeficiency syndrome--report of three more German cases.

Intestinal microsporidiosis with Enterocytozoon bieneusi was diagnosed in three of 18 HIV-infected patients with chronic diarrhoea. In two cases all known stages of the life cycle of E. bieneusi (merogonial plasmodia, sporogonial plasmodia, sporoblasts, spores) were found in duodenal biopsies by electron microscopical examination, whereas in the third case only merogonial and sporogonial stages were seen. Spores were also visible by light microscopy in semithin sections. Two patients were treated with albendazole (2 x 400 mg/day for 4 weeks) but showed no response. These findings underline the concept of the worldwide distribution of this parasite and verify that it is also frequent in Germany.

AIDS-Related Opportunistic Infections↗