[The hemodialysis-transplantation association makes possible yearly economizing of hospital costs].
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Biomedical subjects
Publications and source records attributed to J Dausset.
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In order to study the mixed lymphocyte culture reactivity of human lymphocytes primed in vitro, a nucleopore culture chamber technique allowing human lymphocytes to be cultured for a period of at least two weeks has been developed. During the primary culture period in nucleopore chambers, human lymphocytes were sensitized against mitomycin-treated allogenic stimulating cells. It was shown that the stimulated lymphocytes underwent a blastogenic reaction and the results suggest a reversion to the state of small, resting, primed lymphocytes. In vitro primed lymphocytes displayed allogenic memory. This was characteristic of a secondary response, which is shown by the following: 1) acceleration, the peak of thymidine incorporation occurring on day 4,2) specificity, the accelerated response was observed only when the primed lymphocytes were confronted with the cell used for priming. Contact with a third party cell did not produce this kind of activation. 3) Amplitude; the peak DNA synthesis response was greater than that of unprimed lymphocytes cultivated for the same length of time.
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Data from the three preceding studies on the possible relationship of HL-A type with Burkitt's lymphoma were combined to see whether any trends in the data, not significant in the individal studies, would show significance when the three groups were combined. A statistical method for combining data from different studies is developed. Although in this analysis even the combined data failed to show any significant association of HL-A type with disease, it is suggested that the statistical methods used will be helpful in analysing other sets of data where it seems desirable to combine information from several studies.
Three cases of crossing over between the LA and FOUR loci of HL-A system are presented in this note. Recombination fractions between those two loci are also calculated from familial data kindly provided by other European laboratories. It is suggested that differences found in maternal and paternal recombination frequency are due to the heterogeneity of estimates of each laboratory.
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A study conducted in 30 normal human colons, obtained from cadaveric kidney donors, has evidenced the presence of two polymorphic antigenic specificities, W and Z, in the secretory cells of the colon mucosa. Three phenotypes have been demonstrated so far: W-Z- (frequency: 0.17), W-Z+ (frequency: 0.23), and W+Z+ (frequency: 0.60). Specific anti-WZ and anti-W alloantibodies, independent of anti-A and B agglutinins, were found in normal sera from blood donors. No apparent correlation was found between the WZ specificities and the ABH Lewis specificities, the other blood group systems specificities, and the leucocyte group (HL-A) specificities.
Five sera which detect two alleles of the third HL-A locus (T2 and T4) are described. Statistical analysis of a panel of 220 donors gave gene frequencies in a French Parisian population which are comparable to the results of Scandinavian authors. Segregation observed in 50 families emphasized the linkage disequilibrium with SD2 alleles. T1 was found to be associated with one part of W22 (Da30) and T3 with the other part non-Da30). No recombination was observed between SD2 and SD3, and the distance between these two loci can be estimated at less than 0.0042 U. Differential capping experiments showed that redistribution of SD3 antigens did not affect the SD2 or SD1 products, indicating that they are borne on the cell surface by independent structures. Moreover, capping of SD1, SD2 and SD3 antigens did not provoke complete redistribution of beta2microglobulin which suggests that not all beta2M molecules are linked to HL-A antigens.
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It was possible to obtain a successful evaluation of the quantity of HL-A antigens on lymphocytes using a fluorochromatic test with double marking by fluorescine diacetate and ethidium bromide. It was also possible to detect anti-HL-A antibodies, to study their cross-reactions and to perform tissue typing using this automatic, sensitive and repeatable method.
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Cell-mediated lympholysis (CML) in eighteen patients suffering from primary immune deficiencies was studied. Fourteen of these patients had the variable type. Mixed lymphocyte response (MLR) and CML were clearly found to be independent: as well as two groups of patients in whom the two functions were either both normal or both deficient, two other groups were found in whom they were definitely separate. In one group MLR and T-cell mitogen responses were normal but no CML occurred against allogenic lymphocytes, and in the other cytotoxic effectors were generated normally but MLR and T-cell mitogen responses were very much lower than normal. These results show that the functions are independent, and are compatible with the theory that more than one subpopulation of T cells is involved. Neither the MLR or T-cell mitogen responses of these patients can predict their ability to generate cytotoxic effectors.
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The extreme polymorphism of the HL-A system is due to the presence of two (SD1, SD2) and perhaps three linked polyallelic genes. The distinction of "bridging antibodies" (reacting with several HL-A specificities recognizing separate sites on the HL-A molecule) from the main HL-A determinant as it is demonstrated by absorption/inhibition experiments increases this complexity. The HL-A linkage group is composed of other systems: LD1, LD2, PGM3, ADA (?), P, ME1, IPO-B and possibly a "hay fever gene". No gametic or zygotic selection was found in spite of the presence of HL-A antigens on spermatozoa. Mixed lymphocyte reaction (MLR) is principally governed by LD genes. The main (LD2) gene is probably situated outside the interval SD1, SD2, near SD2. Other LD genes (LD1 inside the interval SD1-SD2 and LD3) are suspected. The presence of an immune response gene (Ir) has not yet been demonstrated although several diseases associated with specific SD2 antigens are known. These different genes (SD1, SD2, LD1, LD2, LD3 and Ir) probably form a functional unit in the allo-immunozation.