Failure to detect viral genomic sequences of three viruses (herpes simplex, simian virus 40 and adenovirus) in human and rat brain tumors

Little is known about oncogenesis in brain tumors. Viruses are thought to be involved in some neurological diseases, the presence of subfractions of viral DNA has been reportedin various circumstances and the oncogenicity of some viruses has been demonstrated in animal experiments. The discovery of homologies between retroviral ancogenes and normal cellular genes (proto-oncogenes) has stimulated once again the search for viral responsability in oncogenesis. Having a large bank of tumor material available, we systematically examined 39 brain tumors usign Southern blot hybridization with DNAs of three viruses, known to be involved in neurological diseases: herpes simplex virus (HSV), simian virus 40 (SV40) and adenovirus type 2 (Ad 2). We detected no homology between the DNAs of the examined material and the viral DNA probes. We compare these negative results with those of other published studies and discuss the experimental conditions, with special reference to the possibility of non-specific hybridization, which could account for the positive results reported. The present negative results could be interpreted either as absence of involvement of the three investigated viruse in brain tumor oncogenesis, or an indirect involvement through a hit-and-run mechanism or a highly dispersed state of the viral sequences among the host genome, which would prevent hybridization with the probe, as it has been supposed to be the case during the latency phase of herpes virus.

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Sommario Poco si sa su oncogenesi dei tumori cerebrali. Si pensa che i virus siano coinvolti in alcune malattie neurologiche e la presenza di sottofrazioni di DNA virale è stata riportata in varie cirkostanze e l'oncogenicità di alcuni virus è stata dimostrata in animali da esperimento. Inoltre la scoperta di omologia tra gli oncogeni retrovirali e i normali geni cellulari ha stimolato la ricerca sulla responsabilità virale dell'oncogenesi. Gli Autori hanno sistematicamente esaminato 39 tumori cerebrali usando la ibridizzazione con DNA di 3 virus coinvolti in malattie neurologiche: quello dell'herpes simplex (HSV), il virus 40 (SV40) e l'adenovirus tipo 2 (Ad2). Non si è trovata omologia tra i DNA del materiale esaminato e il DNA virale. Sono stati allora comparati questi risultati negativi con quelli positivi di altri Autori riferendosi soprattutto alla possibilità di una ibridizzazione non specifica che può giustificare i risultati positivi riportati. Questa ricerca negativa può essere interpretata sia come un'assenza di coinvolgimento dei tre virus investigati nella oncogenesi dei tumori cerebrali, sia come espressione di una disposizione delle sequenze virali nel genoma ospite con conseguente prevenzione della ibridizzazione, come è stato supposto avvenga durante le fasi di latenza del virus herpetico.

     

Renal artery stenosis: evaluation with intravenous digital subtraction angiography

The ability of diagnostic intravenous digital subtraction angiography (IVDSA) to demonstrate the degree of renal artery stenosis was compared with that of intraarterial angiography in 45 patients with 92 arteries. Stenotic lesions on both IVDSA and intraarterial studies were classified as normal (0% stenosis), minor (less than 50%), low grade (50%-80%), and high grade (80%-99%). There was agreement about the degree of stenosis in 90% of the cases. IVDSA grading was correct in 94% of atheromatous lesions and in 56% of the fibromuscular dysplastic lesions. In the high-grade atheromatous lesions, the degree of stenosis was slightly overestimated on IVDSA studies in 22.5% of the cases. In fibromuscular dysplasia, stenosis was underestimated in 33% of the cases.     

STREPTOCOCCAL ANTIBODY CROSS-REACTIVITY WITH HLA-DR4+VE B-LYMPHOCYTES. BASIS OF THE DR4 ASSOCIATED GENETIC PREDISPOSITION TO RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE?

B-lymphocytes obtained from patients with either rheumatic feveror rheumatic heart disease and from normal subjects were reactedwith serum obtained from rabbits immunized with streptococcalcell wall antigen. The presence of cytotoxicity was sought usingan inverted phase microscope after differential uptake of eosindye. The serum was found to be significantly more cytotoxicto HLA-DR4 containing cells of both patients and normals comparedwith DR4 negative cells (P<0. 0001). KEY WORDS: Streptococcal cell wall antigen, Antiserum, Cytotoxicity     

Multiple correlative studies of stereotaxic biopsies of brain tumors

The opportunity of having several samples at the same site which could be spatially localized allows an intensive exploitation of stereotactic biopsies of brain tumors: the pathological data may be correlated to other measures, performed at the same site (electrical impedance X ray absorption coefficient) or on other samples (NMR relaxation times, water content, nucleic acids). These samples are available for oncology experiments in cellular biology (cell cultures, grafts on nude mice) or in molecular biology (DNA and RNA hybridization with specific nucleic acid probes). We were therefore able: 1) to study the diagnostic homologies between pathology and histology examinations; 2) to show that T1 and T2 NMR relaxation times are 2 times longer in tumor tissues than in normal brain; 3) to show that the electrical impedance is decreased by a factor 2 in brain tumors; 4) to show the absence of integrated viral genomic sequences and the existence of oncogenes association patterns in brain tumors by hybridization of specific sequences; 5) to establish permanent cell lines, the tumorigenicity of which is assayed by grafting on nude mice. Therefore, stereotactic biopsies appear to be, provided they are intensively and rationally exploited, a major research tool in an area which remains unsensitive to the various therapeutic approaches.     

An algorithm for rapid calculation of a probabilistic functional atlas of subcortical structures from electrophysiological data collected during functional neurosurgery procedures

The paper introduces an optimal algorithm for rapid calculation of a probabilistic functional atlas (PFA) of subcortical structures from data collected during functional neurosurgery procedures. The PFA is calculated based on combined intraoperative electrophysiology, pre- and intraoperative neuroimaging, and postoperative neurological verification. The algorithm converts the coordinates of the neurologically most effective contacts into probabilistic functional maps taking into account the geometry of a stimulating electrode. The PFA calculation comprises the reconstruction of the contact coordinates from two orthogonal projections, normalizing (warping) the contacts modeled as cylinders, voxelizing the contact models, calculating the atlas, and computing probability. In addition, an analytical representation of the PFA is formulated based on Gaussian modeling. The initial PFA has been calculated from the data collected during the treatment of 274 Parkinson's disease patients, most of them operated bilaterally (487 operated hemispheres). It contains the most popular stereotactic targets, the subthalamic nucleus, globus pallidus internus, and ventral intermedius nucleus. The key application of the algorithm is targeting in stereotactic and functional neurosurgery, and it also can be employed in human and animal brain research.     

Effects of Procainamide on the Excitable Gap Composition in Common Human Atrial Flutter

The composition of the excitable gap (EG) in common atrial flutter (AFI) was determined before and during infusion of procainamide (PA) in 9 patients (6 men and 3 women; age 70 ± 7 years). The EG was determined by introducing a premature stimulus after every 20th AFI complex detected using a quadripolar electrode catheter placed just above the tricuspid valve. Diastole was scanned in 2- to 4-ms decrements to the atrial effective refractory period (ERP). The relationship between the coupling interval and the return cycle length (CL) determined a reset-response curve (RRC), which described the EG. PA (15 mg/kg) was administered during AFl over 30 minutes and RRC was repeated at maximum AFI CL. PA prolonged AF1 CL from 227 ± 29 to 296 ± 62 ms (P < 0.01) but did not terminate AFI. ERP during AFl prolonged from 169 ± 24 to 219 ± 41 ms (P < 0.01). Control EG was 57 ± 16 ms or 25%± 6% of AFl CL and on PA EG was 77 ± 30 ms (P = 0.01), which was still 26%± 7% of the CL. Without drug, RRC was mixed in eight cases demonstrating an EG composed of fully excitable tissue (10 ± 4 ms or 19%± 10% of the EG) and partially refractory tissue (48 ± 18 ms), PA did not change the duration of the fully excitable region (13 ± 10 ms or 19%± 15% of EG). Peak PA plasma concentration was 47 ± 20 μmol/L. PA prolonged AFI CL, ERP, and EG duration but did not change the proportion of AFI CL occupied by the EG. The persistence of fully excitable tissue at the head of the wavefront in the presence of PA may largely explain its inefficacy in the acute termination of common AFl.