Coming to grips with the naming of viruses; continuing discord, or a way out?
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Biomedical subjects
Publications and source records attributed to L Bos.
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PURPOSE: To develop and verify a multisegment technique for prostate irradiation that results in better sparing of the rectal wall compared to a conventional three-field technique, for patients with a concave-shaped planning target volume (PTV) overlapping the rectal wall. METHODS AND MATERIALS: Five patients have been selected with various degrees of overlap between PTV and rectal wall. The planned dose to the ICRU reference point is 78 Gy. The new technique consists of five beams, each having an open segment covering the entire PTV and several smaller segments in which the rectum is shielded. Segment weights are computer-optimized using an algorithm based on simulated annealing. The score function to be minimized consists of dose-volume constraints for PTV, rectal wall, and femoral heads. The resulting dose distribution is verified for each patient by using point measurements and line scans made with an ionization chamber in a water tank and by using film in a cylindrical polystyrene phantom. RESULTS: The final number of segments in the five-field technique ranges from 7 to 9 after optimization. Compared to the standard three-field technique, the maximum dose to the rectal wall decreases by approximately 3 Gy for patients with a large overlap and 1 Gy for patients with no overlap, resulting in a reduction of the normal tissue complication probability (NTCP) by a factor of 1.3 and 1.2, respectively. The mean dose to the PTV is the same for the two techniques, but the dose distribution is slightly less homogeneous with the five-field technique (Average standard deviation of five patients is 1.1 Gy and 1.7 Gy for the three-field and five-field technique, respectively). Ionization chamber measurements show that in the PTV, the calculated dose is in general within 1% of the measured dose. Outside the PTV, systematic dose deviations of up to 3% exist. Film measurements show that for the complete treatment, the position of the isodose lines in sagittal and coronal planes is calculated fairly accurately, the maximum distance between measured and calculated isodoses being 4 mm. CONCLUSIONS: We developed a relatively simple multisegment "step-and-shoot" technique that can be delivered within an acceptable time frame at the treatment machine (Extra time needed is approximately 3 minutes). The technique results in better sparing of the rectal wall compared to the conventional three-field technique. The technique can be planned and optimized relatively easily using automated procedures and a predefined score function. Dose calculation is accurate and can be verified for each patient individually.
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The identification of the causative agent of tobacco mosaic disease as a novel pathogen by the Dutch microbiologist Beijerinck is now acknowledged as being the foundation of virology as a discipline distinct from bacteriology. However, as this was contrary to the prevailing theories of the time, it took many years for virology to become firmly established as a separate discipline. The history of virology illustrates how accepted concepts in science evolve by trial and error and the need for a balanced approach when manipulating natural systems.
Beijerinck's entirely new concept, launched in 1898, of a filterable contagium vivum fluidum which multiplied in close association with the host's metabolism and was distributed in phloem vessels together with plant nutrients, did not match the then prevailing bacteriological germ theory. At the time, tools and concepts to handle such a new kind of agent (the viruses) were non-existent. Beijerinck's novel idea, therefore, did not revolutionize biological science or immediately alter human understanding of contagious diseases. That is how bacteriological dogma persisted, as voiced by Loeffler and Frosch when showing the filterability of an animal virus (1898), and especially by Ivanovsky who had already in 1892 detected filterability of the agent of tobacco mosaic but kept looking for a microbe and finally (1903) claimed its multiplication in an artificial medium. The dogma was also strongly advocated by Roux in 1903 when writing the first review on viruses, which he named 'so-called "invisible" microbes', unwittingly including the agent of bovine pleuropneumonia, only much later proved to be caused by a mycoplasma. In 1904, Baur was the first to advocate strongly the chemical view of viruses. But uncertainty about the true nature of viruses, with their similarities to enzymes and genes, continued until the 1930s when at long last tobacco mosaic virus particles were isolated as an enzyme-like protein (1935), soon to be better characterized as a nucleoprotein (1937). Physicochemical virus studies were a key element in triggering molecular biology which was to provide further means to reveal the true nature of viruses 'at the threshold of life'. Beijerinck's 1898 vision was not appreciated or verified during his lifetime. But Beijerinck already had a clear notion of the mechanism behind the phenomena he observed. Developments in virology and molecular biology since 1935 indicate how close Beijerinck (and even Mayer, Beijerinck's predecessor in research on tobacco mosaic) had been to the mark. The history of research on tobacco mosaic and the commitments of Mayer, Beijerinck and others demonstrate that progress in science is not only a matter of mere technology but of philosophy as well. Raemaekers' Mayer cartoon, inspired by Beijerinck, artistically represents the crucial question about the reliability of our images of reality, and about the scope of our technological interference with nature.
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OBJECTIVE: To assess the occurrence of arterial remodelling types and its relation with the severity of luminal stenosis in atherosclerotic coronary arteries. PATIENTS AND METHODS: Twenty one de novo coronary lesions of 20 patients, who were scheduled for percutaneous transluminal coronary angioplasty (PTCA), were investigated with intravascular ultrasound before PTCA. Local arterial remodelling at the lesion site was studied by measuring the cross sectional area circumscribed by the external elastic lamina (EEL) relative to the reference site: (EEL area lesion/reference EEL area) x 100%. Three groups were defined. Group A: relative EEL area of less than 95% (shrinkage), group B: relative EEL area between 95% and 105% (no remodelling), group C: relative increase in EEL area of more than 105% (compensatory enlargement). RESULTS: All three types of remodelling were observed at the lesion site: group A (shrinkage) n = 8, group B (no remodelling) n = 5, group C (compensatory enlargement) n = 8. The mean (SD) relative EEL area at the lesion site in group A and C was 83(9)% and 132(30)%, respectively. In group A, 33% of the luminal area stenosis at the lesion site was caused by shrinkage of the artery. In contrast, group C showed that 87% of the plaque area did not contribute to luminal area stenosis because of compensatory arterial enlargement. CONCLUSIONS: These results show that both compensatory enlargement and paradoxical shrinkage occurs in the atherosclerotic coronary artery. Next to plaque accumulation, the type of atherosclerotic remodelling is an important determinant of luminal narrowing.
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At first potyviruses were easily distinguished by biological and serological properties because only a few were known and information on their host ranges was limited. The first evidence of serological cross reaction between two of these viruses was reported in 1951 and was further corroborated for three obviously distinct members of the group in 1960. In 1968 attention was drawn to the fact that some legume and non-legume potyviruses have much wider host ranges than previously known and that within the potyvirus group there is as much biological variation within viruses and overlap between viruses as there is in serology. The concept of continuity within the group was soon supported by others and became known as the "continuum hypothesis." Results with highly sensitive serological methods using polyclonal antisera were conflicting, and nucleic acid hybridization techniques did not unambiguously discriminate between potyviruses. Recent results, obtained with antibodies directed toward epitopes located in the N-termini of the coat proteins of potyviruses, suggest that there are ways to more definitely group strains of one potyvirus and distinguish them from other potyviruses. However, there are exceptions to this rule, as in the case of bean yellow mosaic virus and clover yellow vein virus which are clearly distinct in host range, inclusion bodies, and migration velocity of coat protein, but which still react with antibodies to the N-terminal epitopes of one virus. So the question remains of whether coat-protein properties, especially the serological reactivity of N-termini, which do not alter overall virus integrity when lost, sufficiently represent the genome of a pathogenic virus entity as a single criterion for classification.
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Clover yellow vein virus (CYVV) isolate H and the related potyvirus isolates E178, E197, and E242 could be distinguished from bean yellow mosaic (BYMV) isolates by their wider host range among non-legume test plant species, the peculiar enlargement of the nucleolus in infected plants, and the larger size of their coat protein as evidenced by slower migration in SDS-PAGE. Serologically, they are qualitatively indistinguishable in electro-blot immunoassay (EBIA) also with antibodies specific to the N-terminal part of BYMV-B25 coat protein, implying therefore that CYVV and BYMV coat proteins contain identical amino acid sequences in the N-terminal region. The faba-bean virus isolates from Sudan, Syria, and The Netherlands could be identified as BYMV isolates especially adapted to faba bean. All of them were weakly pathogenic to Phaseolus bean with the exception of SV205, assuming an intermediate position between Phaseolus-bean isolates, with low pathogenicity to faba bean, and faba-bean isolates, usually having low pathogenicity to Phaseolus bean. Strains of BYMV are thus hard to delimit.
Germinal center cells from the rabbit appendix were fractionated by velocity sedimentation and isopycnic gradient centrifugation. Subsets were analysed with respect to cell size and surface markers, and were functionally characterized by testing the capacities for primary antibody synthesis, memory cell production, and formation of new germinal centers in an autologous transfer system. The migratory behaviour of the germinal center cell subsets within the spleen of homologous recipients was also studied using autoradiography. Both cell fractionation methods yielded a separation of large and small cells. Surface immunoglobulin and C3 receptors were equally expressed on germinal center cells differing in size and density. The different subsets were also equally capable in giving rise to IgM-antibody-forming cells and memory cells upon antigenic stimulation. Furthermore, large germinal centers were newly formed in the spleen of the recipients, irrespective of the cell subset injected. It was concluded that the results do not support the hypothesis that, inside germinal centers, the differentiation of large lymphoid cells (centro-blasts) into small centrocytes also implies a maturation process. Subsets of germinal center cells, however, showed a different and characteristic migratory behaviour; while small cells migrated preferentially to the corona of lymphocytes in spleen follicles, large, light cells showed an affinity for the germinal center area. We postulate that, upon stimulation, immature B cells develop an affinity for the germinal center microenvironment, to participate in a germinal center reaction.
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Available methods for separation of cells by velocity sedimentation at unit gravity allow a maximum cell load of 2 x 108 lymphoid cells. Here we describe a method, based on the 'tilting' procedure of Bont et al. (1979), which allows separation of up to 4.5 x 109 lymphoid cells, while retaining full separation and rapidity. Percoll instead of Ficoll was used as gradient medium. The relationship between cell sedimentation velocity and cell volume was analyzed by two different methods, i.e., electronic cell sizing and diameter measurements of cytocentrifuged cells.
The migration pattern of germinal center cells of the rabbit appendix was studied and compared with that of appendix dome cells, spleen cells, thymus cells and thoracic duct lymphocytes. To discriminate T- and B-cell migration pathways, normal or T-cell-depleted rabbits were used as donors. Cell suspensions were labeled in vitro with 3H-leucine followed by intravenous transfer. The migration of labeled cells in lymphoid organs was studied using autoradiography, particular attention being paid to the spleen of the recipient. B-cells from the appendix dome, spleen and thoracic-duct lymph migrate to primary follicles or the corona of secondary follicles via thymus-dependent areas of peripheral lymphoid organs. In contrast, a B-cell subpopulation from the germinal centers of the appendix migrates to the center of splenic primary follicles and into germinal centers. The migration of germinal center cells to splenic follicle centers is not enhanced by specific antigens. The migration properties of B-cells, possibly changing during differentiation, may be instrumental in the two types of immune reactions, i.e., plasma-cell reaction and germinal-center reaction.
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