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Biomedical subjects

B Dupont

Publications and source records attributed to B Dupont.

At least 379 records · Page 21Linked to original sources
PubMed1981

Transplantation for acute leukaemia with HLA-A and B nonidentical parental marrow cells fractionated with soybean agglutinin and sheep red blood cells.

A new procedure for enrichment of marrow precursors and removal of T lymphocytes from large volumes of human bone marrow, involving initial differential agglutination of T lymphocytes and mature marrow elements with soybean agglutinin, followed by rosetting with sheep red blood cells, was used to fractionate marrow cells from an HLA-A, B, DR non-identical, MLC non-reactive, paternal donor for transplantation into an infant with acute leukaemia. This transplant became completely engrafted and resulted in full recovery of normal, donor-derived haematopoietic function without graft-versus-host disease, sustained for 11 weeks after transplantation, at which time the patient's leukaemia recurred. Subsequently, the patient received chemotherapy and achieved a remission with regeneration of normal marrow cells of donor origin. The patient's course demonstrated the potential of lectin-separated marrow grafts to restore durable haematopoiesis, without graft versus host disease, in a lethally irradiated allogeneic host.

Agglutinins↗
PubMed1981

Human leukocyte anitgen in torticollis and other idiopathic dystonic syndromes.

Two groups totaling 67 patients with idiopathic focal, segmental, and generalized dystonia, including torticollis, were compared with normal controls to determine whether there was a difference in the frequency of A, B, and C locus human leukocyte (HLA) antigens. The results indicated no statistically significant deviations in HLA antigen frequencies between the patients and the normal controls. Thirteen of the patients with idiopathic torsion dystonia were compared with normal controls for DR locus antigens. A trend of increased DR3 antigens observed in the patients may be significant. HLA genotyping of parents and children in nine families was also studied to determine if an HLA-linked factor could be related to the dystonic syndrome in the children. The results were indeterminate, suggesting that further family studies are required to resolve this issue.

Adult↗
PubMed1981

Inheritance and genetic linkage of transcobalamin II.

The genetic polymorphism of the vitamin B12 transport protein transcobalamin II (TC II) was studied in the Caucasian population and in families. There are five codominent alleles of TC II which show a Mendelian mode of inheritance. No genetic linkage of TC II was found with gene loci for ADA, GLO I, Pi, HLA, AB0 and AK1. TC II like proteins could be detected on autoradiograph of PAGE in two patients with congenital homozygosity for functional TC II deficiency. These vitamin B12 binding proteins in the patients' serum were shown not to be normal R-proteins.

Adenylate Kinase↗
PubMed1981

The biochemical basis for genotyping 21-hydroxylase deficiency.

We describe three different forms of 21-hydroxylase deficiency-classical congenital adrenal hyperplasia (CAH), late-onset 21-hydroxylase deficiency, and cryptic 21-hydroxylase deficiency-and we present hormonal standards by which to assign the appropriate 21-hydroxylase deficiency genotype for these disorders. The late-onset and cryptic forms of 21-hydroxylase deficiency are biochemically indistinguishable, although patients with the late-onset disorder present with marked clinical symptoms (e.g. virilization) whereas patients with cryptic 21-hydroxylase deficiency are clinically asymptomatic. Our latest studies suggest that late-onset 21-hydroxylase deficiency, like the classical and cryptic 21-hydroxylase deficiencies, is also genetically linked to HLA, the major histocompatibility complex of man. Our biochemical findings provide evidence that a spectrum of 21-hydroxylase deficiencies exist in the population.

Adolescent↗
PubMed1981

HLA genotypes and HLA-linked genetic markers in Italian patients with classical 21-hydroxylase deficiency.

HLA genotype and HLA-linked marker data for 40 unrelated patients from central Italy and 2 unrelated patients from Sardinia with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OH-def) were analyzed. The results confirm that the HLA-linked 21-OH-def gene is associated with several different HLA determinants and complete HLA haplotypes, although the only determinant with significantly increased frequency was the complement C2 allele C2B. The HLA antigens B8 and DR3 were found in significantly decreased frequencies. The haplotype A3, Cw6, Bw47, BfF, DR7, which is exceptionally rare in the general population but which has been found in many other 21-OH-def patients from diverse geographical origins, was also found in one of the Italian patients. This and other HLA haplotype associations found among the Italian patients may represent mutations that have occurred on HLA haplotypes with genetic linkage disequilibrium or, alternatively, may represent mutations that have not yet had time to become randomly associated with different HLA complex determinants. The marked negative associations with B8 and DR3 could, however, result from an interaction between the gene products of the HLA complex and the 21-OH-def phenotype.

Adrenal Hyperplasia, Congenital↗
PubMed1981

Differential behavior of cytotoxic effector cells against HLA antigens in strong genetic linkage disequilibrium.

Five sets of cytotoxic effector cells were generated, using haplo-identical, first degree relatives in five different families, against the HLA-A3; B7 serological determinants combined with different DR antigens. When tested against a panel of cells bearing combinations of the HLA-A, -B and -DR antigens it was shown that the HLA-B7 antigen was as strong a CML target determinant alone as it was in the presence of HLA-A3. The strength of the HLA-A3 antigen as target determinant varied. With effector cells primed to the HLA-A3; B7; DR2 haplotype, the A3 antigen alone behaved as a weak target determinant. When the same target cells were tested with the effector cells generated against HLA-A3; B7 without DR2, the A3 antigen behaved as a strong target determinant. A number of target cells lacking the serologically detectable HLA determinants present on the sensitizing HLA haplotype were identified as being killed by specific effector cells. These data suggest either a number of new CML target determinants controlled by different loci or the presence of a single, new locus with multiple alleles controlling CML targets.

Cytotoxicity, Immunologic↗
PubMed1981

Differential inhibition of the MLR by iron: association with HLA phenotype.

The effect of iron on the MLR was examined by pretreating peripheral blood mononuclear cells from 77 unrelated Caucasians with five concentrations of Ferric-citrate (10.0 mM, 1.0 mM, 0.1 mM, 0.01 mM and 0.005 mM). After incubation with the metal, the cells were washed and cultured in a one-way MLR with a pool of stimulator cells. Cell viability remained unchanged (greater than 90 percent) during the 6-day culture period. Citrate per se had no effect on either the responder or the stimulator population. Iron treatment influenced the MLR in the following ways: (1) a variable degree of inhibition was observed which related to the dose of Ferric-citrate used and to HLA phenotype, (2) the responder but not the stimulator cells were affected, (3) no statistically significant differences were seen between female and male donor cells and (4) the mean percent response of cells from HLA-A2 donors were significantly (0.005 less than P less than 0.01) less susceptible to iron exposure than those from non-HLA-A2 individuals. The present results indicate that iron can interact with lymphoid cells and influence some immunological functions in vitro. The possibility is discussed that similar interactions take place in vivo which could contribute to the prognosis of certain diseases associated with particular HLA phenotypes.

Adult↗
PubMed1981

Marrow transplantation for juvenile osteopetrosis.

Two children with the juvenile form of osteopetrosis were treated with marrow transplants from their HLA identical siblings. Following transplantation each child exhibited extensive bone reabsorption with a marked augmentation of osteoclastic function attributable to donor osteoclasts, including remodeling of bone with expansion of intramedullary hematopoiesis and correction of associated abnormalities of thymic factor and natural killer cells. Osteopetrosis ultimately recurred in one patient in whom engraftment of donor hematopoietic elements was not achieved. Our studies indicate that marrow transplantation will correct osteopetrosis but that permanent reconstitution necessitates sustained engraftment of marrow precursors of cells with osteoclastic activity.

Bone Marrow Transplantation↗
PubMed1981

Cytotoxic effector cells against HLA antigens in strong linkage disequilibrium: identification of a strong, new CML determinant.

Three sets of cytotoxic effector cells were generated against the A1, B8, DR3 haplotype using haploidentical individuals in three different families. The three sets of effector cells generated against this haplotype showed excellent reproducibility testing, strong cytotoxicity against their specific targets, low autologous kill, and segregation with the sensitizing haplotype within the family. When tested against a panel of cells bearing all combinations of the A1, B8, DR3 antigens, a hierarchy of contribution of the individual HLA antigens as CML target determinants was seen. A new strong target cell determinant was identified by cytotoxicity with one of the effector cells not explicable in terms of the A1, B8, DR3 antigens or known HLA cross-reactivity. A family study demonstrated that this determinant clearly segregates with HLA. The success of this approach in defining new CML determinants may result from the generation of effector cells across a single haplotype in strong linkage disequilibrium or from the presentation of CML determinants in the context of self.

Analysis of Variance↗
PubMed1981

HLA in a selective aldosterone biosynthetic defect due to type 2 corticosterone methyl-oxidase deficiency.

HLA phenotypes were studied in nine Jewish families, originating from Iran, with 18 individuals affected with a selective aldosterone biosynthetic defect and 12 healthy siblings. This disorder is inherited through an autosomal recessive gene and parents were consanguineously related in eight out of nine sibships. Family analysis showed that 18 affected individuals carried 20 different haplotypes and only two patients were homozygous for a haplotype. Yet a peak lod score of 1.128 was obtained for the recombinant fraction of 0.05 and thus linkage to HLA cannot be ruled out.

Aldosterone↗
PubMed1981

HLA-linked genetic markers in Chinese and other Oriental populations.

The polymorphic variants of the HLA-linked genetic markers Bf, C2, C4 and GLO-I were studied in three mongoloid populations. Analysis of linkage dis-equilibrium between these markers and HLA-A, B, C and DR antigens was carried out on test results from 140 unrelated Chinese individuals. The phenotypes BfS and GLO-2 were found at significantly higher frequencies than in Caucasians. BfS was associated with B12 in Japanese but not in Chinese. A single individual with the rare Bf variant S1 was found. No C2 deficient individuals were observed. The C2C (common) allele occurred at a gene frequency of 0.949 and the more basic allele C2B at 0.039. The acidic variant, C2A, was observed at a frequency of 0.011 and appeared to be associated with BfF. Eighty-nine per cent of the Chinese were phenotypically C4FS. In contrast to Bf and C2, each of which is coded for by codominant alleles at a single genetic locus, C4 is coded for by two genes, C4F (Rodgers) and C4S (Chido). The C4F locus allele, C4F1 (extra fast), was strongly associated with HLA-B17, as has been found in other populations, but a new association of the C4S locus deficiency allele, C4so (Ch-), with B17 was also observed. All HLA-B17;C4so haplotypes were BfS position. As has been previously found in Caucasian populations, individuals of the C4F phenotype (i.e. genotypically FsoFso) were all found to be Chido negative. The frequencies of the various HLA-linked genetic markers, however, as much as the frequencies and associations of the HLA antigens themselves, distinguish these populations from other ethnic groups.

Asian People↗
PubMed1981

Genetic and hormonal characterization of cryptic 21-hydroxylase deficiency.

Cryptic 21-hydroxylase deficiency has been previously described in asymptomatic family members of patients with classical congenital adrenal hyperplasia (CAH). These family members were detected by high baseline 17-hydroxyprogesterone levels found in the course of family studies. The hormonal responses to ACTH of the family members with cryptic 21-hydroxylase deficiency were determined and compared to the responses of patients with CAH, patients with acquired adrenal hyperplasia, family members predicted to be heterozygous for CAH, family members predicted to be unaffected, and the general population. The ACTH-stimulated levels of 17-hydroxyprogesterone and delta 4-androstenedione in the cryptic family members were elevated above the level of the general population or family members heterozygous for classical CAH, but below that of patients with CAH. The hormonal profile of patients with cryptic 21-hydroxylase deficiency is similar to that of patients with acquired adrenal hyperplasia. The response of family members heterozygous for the cryptic gene (21-OH CRYPTIC/21-OH NORMAL) was indistinguishable from that of family members heterozygous for the classical CAH gene (21-OH CAH/21-OH NORMAL). These studies support our previous proposal that patients with cryptic 21-hydroxylase deficiency are genetic compounds, having one gene for a severe enzyme deficiency and one gene for a mild 21-hydroxylase deficiency. Thus, the 21-hydroxylase genotype in cryptic 21-hydroxylase deficiency is 21-OH CAH/21-OH CRYPTIC.

Adolescent↗