Light and electron microscope studies on extravascular Trypanosoma brucei gambiense in the brain of chronically infected rodents.
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Biomedical subjects
Publications and source records attributed to A Beckers.
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The LOUVAIN rat model is characterized by a high incidence of spontaneous tumors which is extremely rare in animals. Presently, the spectrum of monoclonal immunoglobulins synthetized by these tumors is the largest ever discovered in animals. Particularly, the LOUVAIN rat tumors produced the only IgD and IgE monoclonal immunoglobuling discovered in an animal species up to now. The contributions of this model to experimental cancerology were multiple: some of them originate in its high incidence, its anatomopathological type or its production of homogenous proteins, others, in the antigenic properties of the monoclonal immunoglobulins synthetized by these tumors, allowing the study of their natural analogues in absolutely new experimental conditions.
Intravenously injected monoclonal rat IgA is first removed from rat serum at a very fast rate (93% in 4 h), then at a much slower rate (t/2 = 24 h). The rapid initial disappearance is thought to be due in part to secretion into rat bile. This was demonstrated by rat liver perfusions with semisynthetic medium containing diluted (1:200) IgA myeloma serum. During perfusion, the cannulated bile displayed increasingly high levels of this IgA, with a bile to medium ratio of 38 after 1 h of perfusion; at the same time, there was a 40% drop of the rat monoclonal IgA concentration in the medium, which was not observed for rat IgG2a and albumin. All of the monoclonal biliary IgA was bound to secretory component. The rat liver is thus able to actively secrete a monoclonal IgA from the circulation into bile against a strong concentration gradient.
Monoclonal immunoglobulin-secreting tumors (immunocytomas or plasmacytomas) appear in many species, but they occur at a low incidence and usually originate in lymphoid tissues. However, in the rat, the incidence of malignant spontaneous immunocytomas (or plasmacytomas) was high and the tumors consistently arose in the ileocecal lymph nodes. In inbred LOU/C/Wsl rats, these immunocytomas developed in twice as many males (31%) as females (16%). The susceptibility of the rats to immunocytoma was under genetic control; e.g., LOU/C/Wsl rats had a dominant locus (or loci) of susceptibility that could induce immunocytoma in inbred AUG/Wsl or inbred A X C9935/Wsl rats. However, inbred Okamoto/Wsl rats had at least one dominant locus of resistance that did not exist in LOU/C/Wsl, LOU/M/Wsl, AUG/Wsl, or A X C9935/Wsl rats.
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Fifteen spontaneous immunocytomas originating in the ileocecal lymph nodes of Lou/C/Wsl rats were studied by means of electron microscopy. The histology was characteristic, the tumor being formed by an accumulation of large, rounded cells with slightly eccentric ovoid nuclei, large nucleoli, and finely condensed chromatin along the nuclear walls; the cytoplasma was rich in polyribosomes. The appearance of the rough endoplasmic reticulum was apparently the same whether or not the tumor was secretory. Its development varied from one cell to another, and in only a small proportion of cells did it attain any considerable volume. In all the tumors examined, we noted the presence of intracisternal A-particles. In its morphology, the rat immunocytoma resembled the plasmacytomas induced in mice, and it also resembled certain human tumors such as Burkitt's lymphoma.
The LOU/C/Wsl rat inbred strain presents a high incidence of spontaneous malignant ileocecal immunocytomas or monoclonal immunoglobulin-secreting tumors. Some tumors have been transplanted in histocompatible animals over years without any change in their secretion products. Among approximately 600 different monoclonal proteins we have studied so far, we recognized six showing properties different from those of rat IgM, IgA, IgE, or IgG classes, and characteristic of the IgD class.
Malignant ileo-caecal immunocytomata, which secrete immunoglobulin, frequently arise spontaneously in LOU/C/Wsl rats. The tumors are confined to the ileo-caecal region and could originate either in the wall of the caecum or in the ileo-caecal lymph nodes. After excision of the ileo-caecal lymph nodes, the incidence of the type of tumor was found to be reduced significantly. The results strongly suggest that the first cells to undergo malignant transformation are located in the ileo-caecal nodes.
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The half-lives of two classes of rat immunoglobulins with homocytotropic properties, i.e., IgE and IgG2a, in the circulating blood and in the skin were studied. The catabolism of both normal (reaginic) and pathological (myeloma) IgE proteins in circulation was found to be extremely rapid with a half-life of 12 h. In contrast, the half-life of IgE antibody in the homologous skin was calculated to be 7.4 days. On the other hand, the half-life of IgG2a in circulation was about 5 days regardless of normal or pathological origin. IgG2a protein was, however, rapidly cleared from the injected skin site with a half life of 2.4 days, a value not longer than that obtained with nonskin-sensitizing goat IgG. The results indicate that rat IgE has an extremely short half-life in circulation despite of its sensitization period in tissues, and that the affinity for the target cells, as well as the mode of sensitization, of the two classes of homocytotropic antibodies, IgE and IgG2a, is different.
An antiserum, prepared against partially reduced and alkylated rat milk SIgA, was shown to contain antibodies reacting with a rat milk protein of alpha-2 mobility, which possessed antigenic determinants common with SIaA, eluted from Sephadex G-200 at the same position as mammalian secretory components, and could be released from rat SIgA by mild reduction and alkylation. This protein, called rat secretory component, was also detected in saliva, tears and urine. Rat free secretory component (FSC) possessed antigenic determinants which were inaccessible in rat SIgA, as found in other species. In vitro, ra FSC combined with rat serum polymeric IgA or IgM, but not with monomeric IgA or IgG. These data emphasize the many similarities between the human and rat SIgA systems.
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