Contemporary aspects of evolution: conclusion.
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Biomedical subjects
Publications and source records attributed to C Petit.
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It has been reported that antigen induces differentiation of two populations of Ig-containing cells: the first one to appear, IgCC, synthesizes nonspecific Ig and the second, AbCC, synthesizes antibodies. Along with other arguments, the observation that nonspecific Ig bear idiotypic determinants, which cross-react with those of antibodies, had led to the hypothesis that IgCC are precursors of AbCC. However, the synthesis of such idiotype-positive nonspecific Ig before the appearance of the antibodies has not yet been proven. This problem was investigated by analyzing the primary response to poly(Glu60-Ala30-Tyr10) (GAT) in F344 rats. Kinetics studies of cells synthesizing Ig expressing a major idiotype (GAT-13), and of cells synthesizing Ig not expressing GAT-13 idiotype, revealed that these two cell populations were undetectable before the appearance of the anti-GAT antibodies. This demonstrates that IgCC differentiation is not a necessary condition for the development of all antibody responses.
An anti-idiotypic antiserum was raised in a rabbit against a pool of purified F.344 rat anti-GAT antibodies. GAT-13, the idiotype defined by this serum, is present in all F.344 anti-GAT sera from primary and secondary anti-GAT responses. Anti-GAT sera of 13 inbred rat strains, with different RT1 haplotypes and with different heavy- and light-chain allotypes, all express idiotypic determinants cross-reacting with GAT-13. Thus, like in mice anti-GAT antibodies from rats express public idiotypic determinants. The anti-idiotypic serum also recognizes a highly conserved idiotypic specificity present on mouse and guinea-pig anti-GAT antibodies. The mouse, rat and guinea-pig express a similar highly conserved idiotypic specificity after immunization with GAT. All anti-GAT antibodies from the mouse and guinea-pig bear this idiotypic specificity. These results confirm the existence in the anti-GAT response of interspecies cross-reactive idiotypic determinants.
Three types of idiotypic specificities compose the major idiotype of anti-poly (L-Glu60-L-Ala30-L-Tyr10) (GAT) antibodies from BALB/c mice (idiotype termed GAT-715). Assays have been designed to analyzed and study the distribution of these specificities. The highly conserved idiotypic specificity (h.c.GAT) has been assayed by the binding of serum 715-7A4 to radiolabeled rat anti-GAT antibodies. Guinea pig and mouse anti-GAT antisera all express the same h.c.GAT specificity. The public specificity (p.GAT) has been shown to be present in an identical form in all anti-GAT antisera from all strains of mice studied. The assay used for p.GAT was the binding of serum 715-7A4 to C57BL/6 anti-GAT antibodies that express only p.GAT. Finally, the strain-restricted specificity s.r.GAT has also been investigated by radioimmunoassay; this specificity is expressed only by strains BALB/c, BALB/b, BUB/J, DBA/2, DBA/1 and ATL. This expression is independent of known allotypic markers. However, the expression of the s.r.GAT specificity of BALB/c mice follows the genetic distribution of VH genes of BALB/c origin indicating that s.r.GAT can be considered as a genetic marker of some VH gene(s) involved in the specific immune response to the GAT terpolymer.
The distribution of sexually efficient males has been analysed in two populations made up of 5 times more females than males. When observation stops as soon as the number of inseminated females equals the number of males, 25 per cent of males in both strains had not mated, 50 per cent of the matings were performed by 50 per cent of the males who mated only once and the other 50 per cent of matings were performed by 25 per cent of the males who mated 2 or 3 times. Productivity of the successive matings falls drastically after the third mating. The relative role of sexual selection and multiple matings as components of fitness are discussed, as well as their implications for the effective population size.
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The heterogeneity of the anti-GAT [terpolymer poly(Glu60, Ala30, Tyr10)] response of GAT responder mice has been analyzed. Purified anti-GAT antibodies from BALB/c mice belong only to the gamma 1 kappa subclass. The isoelectric focusing pattern obtained indicates that the anti-GAT antibodies are particularly basic and restricted. These results have been confirmed by two-dimensional polyacrylamide gel electrophoresis; by this technique, we have shown that the gamma 1 chain and the corresponding kappa chain of anti-GAT antibodies are restricted. All the anti-GAT antibodies from 10 BALB/c mice bear the cross-reactive GAT idiotype previously defined (J. Thèze and G. Sommé, Eur. J. Immunol. 1979, 9: 924). The present results indicate that the anti-GAT repertoire expressed in BALB/c mice is very limited.
The means for diagnosis, treatment and long follow-up of intra epithelial carcinomas of the uterine cervix are assessed by the authors, about 124 cases seen at the Hotel-Dieu de Paris. The diagnosis is given by cytologic means and mostly by colposcopic examination. When the cylindro-pavimental junction (usual initial focus) is seen in totality, direct biopsies always gave an accurate diagnosis. When the junction is not seen, only a diagnostic--conisation can allow a definitive answer. Two types of surgical treatment were applied: amputation of the cervix conservative of menstrual and/or reproductive functions and, hysterectomy led by vaginal or abdominal route. The patients were followed from 1 to 16 years by the triple cytologic, Schiller test and colposcopic examination: none of them showed any recurrence either of intra-epithelial or of invasive type.
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The developmental kinetics of antibody-forming cells (AFC) and of cells synthesizing immunoglobulins without detectable antibody function against the antigen injected (IFC) were compared in lymph nodes of normal mice and tolerant mice receiving an immunogenic challenge. Tolerant states to bovine serum albumin (BSA), induced in adult mice, and to human gamma-globulin (HGG), induced in newborn mice, were studied. Whatever the tolerant state induced, the following main results were obtained: 1) both AFC and IFC were suppressed in tolerant mice, and this to approximately the same extent for the two populations; 2) both the suppression of the AFC and of the antigen-induced IFC were specific to the tolerogen used.
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Allozyme polymorphisms at seven loci have been studied in nine natural populations of Drosophila melanogaster from the Saône and Rhône valleys sampled in 1973 and 1974. A great deal of polymorphism was observed; an individual was on the average heterozygous at 20.2% of its loci. The populations were genetically very homogeneous throughout the region sampled. The number of ovariolae per female varied from one group of populations to another depending on their geographical separation. Yet the number of ovariolae remained constant from one year to the next. The results show that migration alone cannot explain the homogeneity of the allozyme frequencies. It seems reasonable to conclude that selection plays a major role in maintaining the homogeneity of populations living in proximal biotopes.
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The kinetics of development of antibody-synthesizing cells and of cells synthesizing immunoglobulins without detectable antibody function were studied in rats immunized with different doses (0-1, 1, 10, 100 mg) of horse radish peroxidase, bovine serum albumin, human serum albumin, hen ovalbumin, or human IgG, which had been deaggregated or heat-aggregated. Each antigen was injected once or twice as a solution in saline. Antibody and immunoglobulin-producing cells were detected in draining lymph nodes by immunohistochemical staining. In the primary response a few antibody-synthesizing cells were found whatever the dose injected. No increase or some increase was found with the amount of antigen injected, according to the protein used, but with all doses of antigen injected, the population of cells remained small, except with human IgG where a relatively high number of positive cells was detected even after injection of 1 mg of antigen. In the secondary response a few antibody-forming cells were also detected with the lower doses of antigen, but this population increased after boosting with 100 mg of antigen. With human IgG a greater number of positive cells was induced withall the doses tested. A correlation between the number of cells synthesizing immunoglobulins without antibody function and the amount of antigen injected was observed in the primary and secondary responses. The relative size of these two populations varied with the stage of immunity of the animals. In the primary response, the population of cells synthesizing immunoglobulins without antibody function was larger than the population of antibody-forming cells. The same was true in the secondary response, but if after a booster injection the level of antibody-synthesizing cells exceeded that reached in the primary response, the increase of cells synthesizing Ig without antibody function was smaller than the increase in antibody-forming cells. In general the more immunogenic an antigen was, the smaller was the ratio between antibody-forming cells and cells producing immunoglobulin without antibody function.
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