Analysis of TP53 and PTEN in gliomatosis cerebri

Gliomatosis cerebri (GC) is a rare glial neoplasm with extensive diffuse brain infiltration but relative preservation of the underlying architecture. Previous molecular studies, mostly analyzing biopsy samples, have suggested an astrocytic origin of GC, but a larger collective of autopsy tissue has not been investigated so far. Furthermore, whether the widespread neoplastic infiltration is based on a monoclonal process is still a matter of debate. In the present study, we screened paraffin-embedded brain tissue from different areas of 18 cases (8 autopsy cases and 10 biopsies) for alterations in the TP53 and PTEN genes. Nuclear accumulation of p53 protein was detected in 9 cases (50%). Somatic TP53 mutations occurred in two autopsy cases (11% of all cases). In the first case, a C-->T transition in codon 273 (Arg-->Cys) was detected in all tumor samples. In the second case, in tumor samples from one hemisphere, nuclear accumulation of p53 was caused by a G-->A transition in codon 244 (Gly-->Asp). In the present series, no mutations within the coding region of PTEN were found. Pten expression was observed in two autopsy cases (25%) and seven biopsy samples (70%). These data suggest that TP53 is affected in some cases, but other yet-unidentified genetic alterations might contribute to tumorigenesis in GC. Furthermore, although GC might be a monoclonal process, the presence of different tumor clones cannot be ruled out.     

Regional patterns of blood-brain barrier breakdown during epileptiform seizures induced by various convulsive agents

In unrestrained rabbits with generalized epileptic seizures induced by systemic application of convulsant drugs, regional changes in blood-brain barrier (BBB) permeability to macromolecules were investigated using Evans Blue (EB) as indicator. BBB leakage due to seizures was present only in animals in which the mean arterial blood pressure rose about 50 mm Hg with the onset of convulsive motor activity. However, a blood pressure increase was not necessarily associated with the occurrence of BBB opening.Pentylenetetrazole-induced seizures resulted in bilateral EB leakage mainly in the hypothalamus, with exception of the mammillary bodies, and the preoptic area, and they were associated, in most cases, with an intensive staining of the cerebellum and also of the midbrain tegmentum. In contrast, seizures due to the GABA receptor blocker bicuculline brought about a penetration of the dye in the region of the pallidum, whereas the GABA synthesis inhibitor methoxypyridoxine produced BBB breakdown in the hippocampus. Methionine-sulfoximine convulsions resulted in a selective stain of the corpora mammillaria, and kainic acid induced a diffuse leakage in neocortical brain areas. As a rule, BBB breakdown was bilateral and confined to anatomically limited brain areas, suggesting that BBB integrity was not only disturbed by abrupt increases in the intraluminal pressure, but was also influenced from the brain tissue.The fluorescence microscopic observations revealed that the tracer penetrated into the neuropil through larger vessels. It had the tendency to accumulate in neurons. In case of the hippocampus, CA2 pyramidal cells revealed more intense uptake of EB than those of the adjacent fields.     

DNA Polymerase Activities in Virions of Visna Virus, a Causative Agent of a “Slow” Neurological Disease

The presence is reported of an RNA-instructed DNA polymerase in visna virus, the causative agent of a "slow" neurological disease in sheep. The product synthesized by the RNA-directed reaction has been shown to be a DNA heteropolymer by the following criteria: synthesis requires the presence of all four deoxyriboside triphosphates; the product is resistant to ribonuclease and alkali but is degraded by DNase; and the product has a density of 1.420 in Cs(2)SO(4) solution, characteristic of DNA.Visna virions, like those of the oncogenic RNA viruses, contain DNA polymerase activities that respond to a variety of double-stranded DNAs and to synthetic DNA.RNA hybrids.     

Visually evoked potentials and selective masking with patterned flashes of different spatial frequencies

Human visually evoked responses (VERs) to pairs of checkerboard patterned light flashes (40 msec interstimulus interval) were investigated in an attempt to assess the electrophysiological nature of temporal visual processing as a function of the spatial frequency of patterned stimuli involved. Four stimuli, all of equal mean luminance, were employed: a diffuse flash and checkerboards with fundamental spatial frequencies of 0.5, 1.0 and 4.0 c/deg (check-sizes of 60′, 30′ and 7.5′). VERs from four adult humans were recorded monopolarly over the occipital area of the scalp (O = to ear reference) and averaged. The purpose of the experiment was to test whether the existence of visual information channels selectively tuned to a specific range of spatial frequencies would be revealed in terms of selective masking effects among the various stimulus combinations.The results indicated that the amplitude of VERs approximately 110 msec after stimulation was particularly sensitive to the presence and size of the pattern. Data were quantified in terms of variations in amplitude of this component as a function of the nature of pattern in the first and second flash. This variability measure indicated that pattern processing of one flash of the pair was impaired by the presence of pattern in the preceding or following flash (forward and backward masking effects respectively). When the first flash contained pattern, the contribution of the second flash was always less than that of the first, forward masking being most pronounced. The 7.5 and 30′ check-sizes were found to be the most effective forward maskers, and elicited the largest amplitude negative potentials at the 110-msec latency after flash onset. Forward masking, furthermore, was specific to the spatial frequency of the pattern in the first (masking) flash, electrophysiological masking being greatest when identical as compared to dissimilar spatial frequencies were presented in the flash pair. This finding of selective masking lends support to the notion that there are multiple visual channels, each selectively sensitive to a limited range of spatial frequencies.     

Diffusions-Tensor-Bildgebung (DTI) bei Patienten im apallischen Syndrom

Zusammenfassung Hintergrund und Ziel: Die Diagnostik des apallischen Syndroms beschränkte sich bisher auf die klinische Untersuchung und Zusatzuntersuchungen mittels EEG und evozierter Potentiale. Die Bildgebung spielte bei der Diagnosesicherung keine Rolle. Mit der Diffusions-Tensor-Bildgebung (DTI) sollte versucht werden, den Defektbereich im Hirnstamm zu visualisieren. Patienten und Methodik: Sieben Patienten im apallischen Syndrom nach Schädel-Hirn-Trauma (SHT) wurden in einem 1,5-Tesla-MRT-Gerät (INTERA, Fa. Philips) mit koronaren diffusionsgewichteten Spinechosequenzen untersucht. Es wurden sechs nicht kolineare Gradientenanregungen entlang den kortikospinalen Bahnsystemen verwendet. Die Untersuchung fand im Mittel 6 Monate nach SHT statt. Die Rekonstruktion der Faserbahnen erfolgte mit einem IDL-basierten (Interactive Data Language; Research System Inc.) Fiber-Tracking-Tool. Im Defektbereich wurden des weiteren der ADC (apparent diffusion coefficient) und die FA (fraktionelle Anisotropie) bestimmt und mit einer Kontrollgruppe von 20 gesunden Probanden verglichen. Ergebnisse: Die Faserdarstellung zeigte bei allen Patienten eine Unterbrechung der kortikospinalen Bahnsysteme auf Höhe des Mesencephalons. Die ADC-Werte im Defektbereich waren im Vergleich zur Kontrollgruppe normal bis leicht erhöht. Die FA-Werte waren um fast 40% reduziert als Ausdruck einer Schädigung auf zellulärer Ebene. Patienten mit Kontrollen nach 5 Monaten zeigten atrophische Hirnstammveränderungen in Pons und Mesencephalon als morphologisches Korrelat einer Schädigung auf zellulärer Ebene. Schlussfolgerung: Mit Hilfe der DTI ist es erstmals gelungen, die Unterbrechung kortikospinaler Bahnsysteme bei apallischen Patienten zu visualisieren. Die FA-Werte können als Marker der Schädigung auf zellulärer Ebene angesehen werden und dürften für den Verlauf und die Verlaufsbeurteilung dieser Patientengruppe von Bedeutung sein.     

Polyp size at CT colonography after electronic subtraction cleansing in an anthropomorphic colon phantom

PURPOSE: To evaluate the effect of various bowel contrast material concentrations and subtraction software on size measurements of well-defined polyp lesions in a colon phantom at CT colonography. MATERIALS AND METHODS: Repeated scanning and a precise reference standard required the use of a colon phantom in which 21 polyps were randomly distributed. Two readers who had each reviewed computed tomographic (CT) colonographic images from more than 100 cases evaluated polyp size on images obtained when the phantom was partially filled with varying concentrations of contrast material, scanned by using CT colonography, and subjected to electronic subtraction cleansing. The single largest dimension was recorded for each reader for a randomized series of polyps. These measurements were compared with a reference standard that was based on a combination of the manufacturer's polyp size specifications and the subsequent verification of these sizes by an independent consensus panel. Six weeks after initial observations, readers evaluated images of the phantom scanned without the presence of contrast material. Polyp size estimations for the two readers for each series were compared with the reference standard to obtain a mean absolute measurement error for each reader for each series. Data for each reader were compared by using a nonparametric Kruskal-Wallis analysis of variance test. A pair-wise comparison of the experimental and control series was then performed by using the Dunn post hoc test. RESULTS: Contrast material dilutions resulting in an average attenuation of less than 500 HU resulted in complete subtraction and the absence of streak artifacts. There was no statistically significant difference between the average measurement error for contrast attenuations between 300 and 500 HU when compared with that of control. Streak artifact was noticeable for the highest dilution (mean, 840 HU). No statistically significant differences were observed for series in which cleansing software was used in the absence of bowel contrast material. CONCLUSION: The combination of electronic cleansing and bowel contrast enhancement in the range of 300-500 HU results in no substantial change in readers' estimations of polyp size at CT colonography.