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J Dausset

Publications and source records attributed to J Dausset.

At least 163 records · Page 9Linked to original sources

Facilitation of skin allograft survival by blood leucocyte extracts. A possible mechanism for the beneficial effects of blood transfusion in human transplantation.

Fresh and frozen-stored mitochondrial, microsomal, and endoplasmic reticulum extracts of blood leucocytes act as potent alloantigens in human recipients. Similar results were obtained with freshly prepared extracts consisting of mixtures of all cytoplasmic fractions; storage of such mixtures at--20 C, followed by 1-2 hr thawing at 37 C abrogated their capacity to induce allograft sensitivity in 45 of 47 recipients. Donor-specific skin allografts and grafts from other sources exhibited significant attenuations in the tempo and intensity of rejection, ranging from first-set rejection to chronic rejection and/or to prolongations in allograft survival. In contrast with the 66.2% rejection rate of first-set skin grafts at 10 days in 71 normal subjects, only 29% of skin grafts from the leucocyte donor applied to 24 recipients of 0.1 to 9 Transplantation Antigen (T.A.) units of pooled cytoplasmic mixtures were rejected by that time. Only 17.4% similar grafts in 23 recipients of 25 to 515 T.A. units were rejected at 10 days. Seventeen skin grafts placed on recipients of 45 to 140 T.A. units of the same cytoplasmic preparation exhibited a slow rejection characterized by progressive shrinkage and eventual disappearance, with no evidence of hemorrhagic necrosis (chronic skin graft rejection). These results support the possibility that the attenuations in allograft reactivity observed in patients with end-stage renal disease after blood transfusions may be related to the leucocyte components of such transfusions. The capacity of blood transfusions to decrease reactivity to renal allografts in uremic patients maintained on hemodialysis stands in contrast with the ability of such transfusions to sensitize normal human recipients to donor-specific skin allografts. The differential effect may be related to the immunosuppressed state(s) documented in the uremic population, and/or the use of immunosuppressive drug therapy in such patients at the time of transplantation and thereafter.

Adult↗

Non HLA antigenic determinants expressed on activated T and B human lymphocytes.

Human antigenic determinants present on activated T and B lymphocytes and not on resting B and T cells defined by serological studies are reported. The reactivity of 13 sera against human PBM activated by various agents was tested using microlymphocytotoxicity technique. Results showed that generally similar reactions are present on B and T blasts whatever the technique of activation (PHA, ConA, PWM, TCGF, EBV and allo activation). Absorption elution studies with 5 sera on 10 alloactivated cells clearly demonstrated their independence from DR determinants. The analysis of results obtained by these 15 sera on blasts from 50 donors showed no correlation with HLA-A, -B, -C, DR and -MB antigens, neither can it be HT (Qa-like) antigens. Furthermore, 5 clusters of sera are reported. The weak correlation coefficients cannot affirm the existence of a system with an allelic distribution although each cell except one out of a panel of 50 individuals carries at most 2 specificities. The segregation of 3 of these specificities within 5 informative families showed no linkage with HLA genes.

B-Lymphocytes↗

The birth of MAC.

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Blood Transfusion↗

HLA-DR genotype risks in seropositive rheumatoid arthritis.

We studied the distribution of HLA-A, B, C, and -DR antigens in 77 Caucasian patients with sero-positive rheumatoid arthritis. Forty-four patients were genotyped and compared with the control panel of 110 unrelated Caucasian genotyped donors. The data obtained confirm the association of DR4 with RA, and reveal an increased risk of disease for patients carrying DR1, DR2, and DR3, compared to the risk for those carrying other antigens, such as DR5, DRw6, and DR7. There is a higher risk for DR4/4 homozygotes than for DR4/1, DR4/2, or DR4/3 heterozygotes. DR4/5, DR4/6, and DR4/7 have a lower risk than the previously mentioned genotypes. The genotype risks are compatible with the inheritance of a single, linked genetic determinant of disease susceptibility, but we are unable to distinguish between recessive and dominant inheritance of susceptibility using the "antigen-frequencies-amongst-diseases" method. DR4 seems to be more frequent in patients in whom onset occurs before the age of 35 (79% vs. 54% DR4 positive). A significant excess of DR3 + is observed in patients with toxic complications following treatment with gold salts (X2(1) = 8.96).

Adult↗

Specific immune responses after booster immunization with tetanus toxoid in man: study of kinetics, family segregation, and linkage to HLA of in vitro lymphocyte proliferative responses and serum-antibody responses.

Kinetics and family transmission of antigen-specific in vitro cell-mediated responses were investigated in 68, and serum-antibody responses to tetanus toxoid (TT) in 73 individuals from a total of 12 families. Proliferative responses to highly purified TT monomer were studied in 6- to 7-day lymphocyte cultures. The effect of booster immunization was detectable 7 (D7) and 30 (D30), but not 120 days (D120) later. The sex of donors was not found to have any influence. A significant influence of the time interval since the last immunization was found for the responses at D7 and D30. Data were correspondingly adjusted for segregation and linkage analyses. Several transmission hypotheses for the data obtained at D7 and D30 were evaluated by likelihood ratio tests. Observations at D30 were compatible with the hypothesis of a control by a dominant genetic determinant for high responses closely linked to the major histocompatibility complex region. No such evidence could be found for D7. After booster immunization, mean antibody levels determined on D7, D30 (peak of response), and D120 were found to be higher than those prior to immunization (D0). The sex of the donors was found to have no influence on antibody responses. The time interval since the last immunization and the age of donors both had a slight influence, and data were correspondingly adjusted for segregation and linkage analyses, which showed no evidence of genetic control of the antibody responses or of linkage to HLA.

Adolescent↗

Analysis of HLA class I genes with restriction endonuclease fragments: implications for polymorphism of the human major histocompatibility complex.

Cellular DNA from HLA-typed individuals was digested with the restriction endonucleases HindIII, EcoRV, and EcoRI. The separated restriction endonuclease fragments were hybridized with a HLA class I cDNA probe by using the Southern transfer technique. Digestion of cellular DNA with HindIII generated 22 restriction endonuclease fragments, 11 of which showed polymorphism for presence or absence in a population sample. With EcoRV, 13 fragments were identified; 6 showed polymorphism. EcoRI generated 11 fragments, of which 1 was polymorphic. Of these 18 polymorphic fragments generated by the three restriction endonucleases, each of 5 was found to be positively associated with one allele of the HLA-A or -B allelic series (HLA-Aw24, -B8, -B15, -Bw35, and -B40). One fragment was positively associated with two HLA-A series alleles (HLA-A1 and -A11). Another fragment was positively associated with five HLA-B series alleles (HLA-B5, -B7, -B14, -Bw16, and -Bw35) and one fragment was positively associated with alleles at two loci (HLA-B14 and -Cw5). The serologically defined allele HLA-Aw24 was associated with two polymorphic fragments, one association showing a positive correlation and the other a negative correlation. Each informative family studied thus far has shown segregation of the restriction fragment with the associated serologically defined allele. The fragments associated with serologically defined alleles occurred in the population sample studied at low or moderate frequencies. The remaining polymorphic fragments occur at high frequency, suggesting that class I genes not serologically detected show less polymorphism than serologically defined class I genes.

Alleles↗

Polymorphic restriction endonuclease fragment segregates and correlates with the gene for HLA-B8.

Cellular DNA from HLA-typed individuals was digested with the restriction endonuclease EcoRV. After electrophoresis and transfer to a hybridization membrane, the restriction endonuclease fragments were probed with cDNA carrying the nucleotide sequence encoding a class 1 HLA gene. Polymorphism for presence or absence of various EcoRV fragments was noted in a panel of unrelated HLA-typed individuals. A polymorphic 8.6-kilobase pair EcoRV fragment was found which correlated in the panel with the serologically defined gene HLA-B8. A family study revealed that this fragment segregated with the haplotype carrying the HLA-B8 gene. This fragment may carry the gene for HLA-B8 or it may represent another class 1 gene (or pseudogene) in linkage disequilibrium with HLA-B8.

DNA Restriction Enzymes↗

HLA and susceptibility to Hodgkin's disease.

Strong arguments supporting a genetic linkage between susceptibility to HD and HLA are reported. These observations are based on data from 33 multiplex case families, gathered from international series and from our own studies. They confirm the disturbed segregation of HLA haplotypes among pairs of affected siblings (P less than 0.0005). An excess of a shared haplotype among first cousin pairs of patients is also observed (P less than 0.05). When both sib pairs and cousins are taken together, the segregation distortion is even greater (P less than 0.0002). Although the excess of HLA-identical affected sib pairs would favor a recessive mode of transmission of the disease, the lod score analyses do not allow one to conclude a simple genetic pattern. A two-gene model, based on epistatic cooperation, is discussed and could fit with an intermediate mode of transmission. The review of population data confirms the generally admitted trend of higher susceptibility borne by HLA-A1. There are converging arguments in favor of the prevalence of A1, B5, B18 in HD, and in particular A1 in the mixed cellularity form, while the haplotype, A1, B8, predominant in long survivors seems to possess a protective effect. It is expected that more data from multiplex families and prospective series of unrelated patients, fully HLA typed, may help to bring about a better understanding of the first reported HLA linkage with malignancy.

Disease Susceptibility↗

[Genetic effect on specific human immune responses to tetanus anatoxin].

Kinetics and family transmission of antigen specific immune responses were investigated before and 7, 30 and 120 days after booster immunization with tetanus toxoid (TT) in 73 individuals from 12 families. The study of TT specific in vitro lymphocyte proliferative response and of TT antibody levels by radioimmunoassay were performed in parallel; the effect of booster immunization was detectable 7 and 30 days later and still 120 days later for antibody response. No influence of the sex of donors was found. Because of the significant influence on the level of responses of the time interval since last immunization, data were correspondingly adjusted for segregation and linkage analysis. Observations at day 30 were compatible with the hypothesis of control by a dominant genetic determinant for high proliferative responses closely linked to the major histocompatibility complex region.

Antibodies, Bacterial↗

[Polymorphism of HLA genes: I. Demonstration of a close correlation between DNA fragments determined by BglI restriction enzyme and HLA class I antigens].

Description of DNA fragments associated to HLA class I gene is possible by using restriction enzymes which determine these fragments and specific DNA probes which permit their detection. In one family, with a child presenting a recombination between HLA-A and C, six fragments determined by the enzyme BglI were found to be polymorphic. The informative fragments segregate with HLA, either with a whole haplotype or with one of the two recombinant segments of the HLA complex. In a small sample of population they correlate with one (A11) or with a group of known cross-reactive antigens serologically defined (A3 and A11; A25 and A26. Another fragment is associated with unknown cross-reactive antigens (A2 and A29).

DNA↗

HLA-and Gm-linked genes affecting the degradation rate of antigens (sheep red blood cells) endocytized by macrophages.

Phagocytosis and catabolism of sheep red blood cells by human peripheral blood phagocytes were studied in 100 normal caucasoid subjects (44 males and 56 females). Both phenomena are highly reproducible, and their indices seem to be biological constants. There is no correlation between these two indices and the indices do not have a correlation with ABO or Rh markers. Further, the phagocytic index has no correlation with HLA and GM markers. However, a low speed of degradation is significantly correlated (p = 0.001) with the HLA-DR3 antigen, and most of the low degraders are significantly correlated (p = 0.006) with both DR3 and Gm 3,23,11 (probably Gm homozygous). Thus the gradient of antigen degradation could be related to an interaction between MHC and Gm immunoglobulin genes, as is found in the mouse [Biozzi's high (H) and low (L) responder strains.

Adult↗

Monocytotoxic antibodies after bone marrow transplantation in aplastic anemia.

Pre- and post transplant sera from 51 cases of bone marrow transplants performed for severe aplastic anemia were tested on monocytes (M) and corresponding B cells (B) from a panel of unrelated donors. One-third of the sera were cytotoxic for B and M either from different or from the same individuals, while 45% reacted only to M and appeared to recognize non-HLA M-associated antigens. No significant reaction to endothelial cells was obtained from these sera. The subsequent clinical course was not associated with any reaction pattern of pre-transplant sera. There was a significant relationship between rejection and the development of M antibodies after grafting, but since these were also found in many other patients without rejection, their occurrence has no predictive value for an individual patient.

Anemia, Aplastic↗

HLA haplotype study of 53 juvenile insulin-dependent diabetic (I.D.D.) families.

R4 heterozygotes was observed. By contrast, the observed frequency of patients homozygous for DR3 or DR4 was not increased, but even slightly decreased. The data support a model of inheritance comprising at least two closely linked specifically "diabetic" loci (most of the time marked by B18, BfF1, DR3 and B15, BfS, DR4) and a non-specifically "diabetic" haplotype favouring auto-immunisation (most of the time marked by B8, BfS, DR3). This model is discussed in the light of the presented data and of those of the literature.

Adolescent↗