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Biomedical subjects

V David

Publications and source records attributed to V David.

At least 145 records · Page 8Linked to original sources
PubMed1990

Identification of a novel 110-kilodalton structure expressed on a subset of T cell receptor-gamma delta-bearing cloned lymphocytes.

A small percentage of circulating CD3+ cells express a heterodimeric gamma delta receptor. Most of these cells do not express the surface marker CD4 and only a fraction of them bear CD8 molecules. The specificity and function of TCR-gamma delta are unclear. We obtained a murine mAb produced against an IL-2-dependent human T cell clone defining a novel molecule sTA which is not expressed on resting human peripheral blood CD3+ cells but strongly expressed on a fraction of TCR-gamma delta-bearing clones. Like receptors for growth factors such as IL-2, the sTA Ag is present on clones and cell lines according on the cell cycle. SDS-PAGE analysis of sTA immunoprecipitates from 125I-labeled sTA+ clone lysate demonstrated a single band of molecular mass 110 kDa under reducing conditions. Triggering with anti-sTA mAb did not result in [Ca2+]i mobilization of sTA+ clones. Additionally, the presence of anti-sTA did not alter the cytotoxicity of these sTA+ clones neither against tumor target cells nor against specific PHA blast cells. Interestingly, due to the fact that most sTA+ clones fail to proliferate in response to CD3 triggering, it appears that sTA may serve as a useful marker to study the functional heterogeneity of TCR-gamma delta expressing cells.

Antibodies, Monoclonal↗
PubMed1990

HLA class I gene polymorphism in genetic hemochromatosis.

The authors have studied HLA class I polymorphism in an attempt to identify a genomic marker of the hemochromatosis gene. Five enzymes were used (HindIII, EcoRI, EcoRV, PvuII, and HincII) in 47-106 unrelated patients and 71-91 controls. Both populations were HLA-typed. The relationship between the restriction fragments and HLA-A antigens was considered. Comparison of the two groups revealed a significantly high frequency of one 14 kb EcoRI fragment among the HLA-A3 hemochromatosis patients. The fragment hybridizes to an HLA-A specific probe but not to an HLA-B specific probe, and is associated with the hemochromatosis gene, which is itself associated with HLA-A3.

HLA Antigens↗
PubMed1989

Ferritin H gene polymorphism in idiopathic hemochromatosis.

The authors studied the H ferritin restriction polymorphism in 83 hemochromatosis patients and 84 controls as well as in 19 nuclear families. No significant difference was found with the ten restriction enzymes used (HindIII, EcoRI, EcoRV, PvuII, BamHI, PstI, Bg/I, Bg/II, HincII, and TaqI). Hence, the genomic abnormality responsible for idiopathic hemochromatosis is not a major deletion of an H ferritin gene. A higher frequency of one HindIII fragment, although nonsignificant when the number of comparisons made is taken into account, was observed in the patients. This HindIII fragment hybridizes with the H ferritin probe and with a 28 S ribosomal probe, and its segregation with HLA haplotypes (hence its assignment to chromosome 6) is uncertain. Its possible meaning in the expression of the disease is discussed.

Chromosome Mapping↗
PubMed1989

Immunoactive products of human placenta. II. Direct inhibition of non-MHC restricted cytolytic activity of human CD3 alpha-beta but not CD3 gamma-delta expressing T cell clones.

The effect of human placental supernatant obtained from explant cultures of caesarean delivery placentae was monitored on both alpha-beta human T cell clones, which display both cytotoxic alloreactivity and non-MHC restricted cytotoxicity against K562 target cells, and gamma-delta ones endowed solely with the latter. It was found that, under appropriate experimental conditions, direct inhibition of the cytolytic activity of alpha-beta T cell clones was exerted by the supernatant. In contrast, gamma-delta T cell clones were unaffected. The relevance of these data to the survival of the fetal allograft is discussed.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

[Argininosuccinic aciduria. A new case revealed by psychiatric disorders].

The case of a 4 years old boy, hospitalized for an unexplained coma, is reported. He is the first child of a non-consanguin couple. The psychomotor development of this child was considered as normal up to the age of 18 months; then, a delay in language development, behaviour disorders with an important instability interrupted by episodes of somnolence, were observed. This child was treated for psychotic disorders. At the age of 3 and half, he had two episodes of seizures associated with fever. He was hospitalized for a 24 hours coma (4 years old). An hepatomegaly and a dry, brittle hair were then observed. Hyperammonemia was made obvious by a protein tolerance test. The diagnosis of argininosuccinate lyase (ASAL) deficiency was based on the increased levels of ASA in plasma and urine. The deficiency was proved by a fibroblast culture. With protein restriction, hepatomegaly disappeared, hair became normal, the behaviour disorders and the delay in language development was improved. However, some school difficulties persist. This case shows that an hereditary metabolic syndrome can be revealed by psychotic like symptoms in childhood.

Amino Acid Metabolism, Inborn Errors↗
PubMed1988

Expression of the T cell gamma gene by a functionally defined human T cell clone. Characterization at DNA, RNA, and cell membrane level.

In the present study we describe one CD2+CD3+ clone termed DS6 which expressed neither CD4 nor CD8 differentiation antigens and failed to react with WT31, a monoclonal antibody directed against the T cell antigen receptor alpha/beta heterodimer. This clone was isolated from peripheral blood T lymphocytes of a patient with a prolonged immunodeficiency after allogeneic bone marrow transplantation. Normal-sized T cell gamma gene transcripts were detected in DS6 by northern analysis, whereas no mature beta or alpha chain mRNA were found. The rearrangement of TCR beta chain genes and T cell gamma genes was analysed. While in DS6, TCR beta chain genes remain in germinal configuration, and a unique pattern of monoallelic T cell gamma gene rearrangement was observed. The rearrangement involves the recently described V gamma 5 segment and the J gamma 1 joining segment, which is located upstream of the C gamma 1 constant region. To determine the molecular structure present on DS6, an immunoprecipitation was performed with monoclonal anti-CD3 antibody and a rabbit antiserum raised against gamma protein. We have observed, in association with the CD3 complex, a 90 kDa structure which under reducing conditions resolves into three subunits of 45, 40 and 37 kDa. We demonstrated that the rabbit anti-gamma serum only immunoprecipitates the two lower bands. The upper band corresponds to a presently undefined T cell receptor chain. Next, we showed the non major histocompatibility complex (MHC)-restricted cytolytic activity exhibited by these CD3+CD4-CD8- cloned T cells and inhibition of the natural killer (NK)-like activity by the anti-CD3 monoclonal antibody. The triggering of CD2 or CD3 molecules increased IL-2 receptor expression on DS6 but failed to induce cell proliferation. This contrasts with recent results obtained with gamma-expressing T cell clones and illustrates the functional heterogeneity of the cells bearing the second T cell receptor.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Predominant expression of circulating CD3+ lymphocytes bearing gamma T cell receptor in a prolonged immunodeficiency after allogeneic bone marrow transplantation.

The cell surface expression of alpha:beta heterodimer was studied using WT31 monoclonal antibody, in peripheral blood lymphocytes (PBL) from a patient who developed a prolonged immunodeficiency after allogeneic bone marrow transplantation. This patient, grafted for chronic myelogenous leukemia, received T cell depleted bone marrow from her HLA, A, B, D matched sibling. The late occurrence of opportunistic infection, led us to analyze the phenotype of patient PBL. 70% of PBL were CD3+ and 29% WT31+, indicating that the majority of CD3+ PBL did not express the alpha:beta heterodimer. Transcription of the genes encoding the alpha, beta, and gamma chains was assessed in cell lines derived from PBL, by Northern blot analysis. We showed that the CD3+ WT31- subset expressed a truncated, beta mRNA (1.0 kb) and also truncated alpha transcript (1.4 kb). To determine the CD3-associated structure on CD3+ WT31- cell line, immunoprecipitation assays were performed using monoclonal anti-CD3 and an hetero antiserum against gamma peptides. These CD3+ WT31- cells expressed a disulfide linked dimer, composed of products of gamma gene (37 kD, 40 kD) and of undefined delta chain (45 kD). Functional analyses were performed in PBL before and after sorting with WT31 and anti-CD3 antibody. These circulating CD3+ WT31- cells were unable to proliferate when triggered with anti-T3 beads and they seemed to mediate a suppressor activity on CD3+ WT31+ cells.

Adult↗
PubMed1988

[Biological markers in hepatocellular carcinoma].

Primary cancer of the liver, especially common in inter-tropical Africa and South-East Asia, still remains inaccessible to a really effective therapy, except for a rapid surgical excision. Improvement of its particularly poor prognosis requires therefore early screening based on reliable biological markers. Following alpha-feto-protein, various parameters have been proposed: enzyme, ferritin, desialylated serum protein, decarboxylated prothrombin... However, alpha-feto-protein remains, in practice, the reference diagnostic test, in spite of a moderate specificity below 500 ng/ml and the fact that it is frequently missing in early cancers. Its diagnostic score may be improved either by the use of monoclonal antibodies, or by determining the ratio of fucosylated form, or by concomitant use of other markers: alpha-L-fucosidase, decarboxy-prothrombin.

Antibodies, Monoclonal↗
PubMed1988

Prominent expansion of circulating lymphocytes bearing gamma T-cell receptors, with preferential expression of variable gamma genes after allogeneic bone marrow transplantation.

The presence of two distinct T-cell receptors (TCR) alpha/beta dimers or gamma/delta dimers, was systematically analyzed in peripheral blood lymphocytes form 26 recipients of allogeneic bone marrow transplants for leukemia. When using monoclonal antibody WT31, which recognizes a common epitope on the alpha/beta heterodimer, the expansion of peripheral CD3+, WT31- cells to 40% of the PBLSs was detected in two patients. In patient 2, the presence of circulating TCR gamma-bearing cells was directly demonstrated with monoclonal antibody Ti gamma A directed against the V gamma 9 J gamma p gene products. From CD3, WT31- clones derived from patients 1 and 2, sequential immunoprecipitations were performed with anti-CD3 and anti-C gamma to determine the CD3-associated structure. Molecular weights of gamma subunits were different in both patients, thus indicating structural heterogeneity. The ability of TCR gamma clones to proliferate when stimulated with anti-CD3 beads was observed for clones from patient 2, whereas this response required exogenous interleukin-2 for clones from patient 1. We have already shown that the TCR gamma cells from patient 1 might have played a role in the immunodeficient state. Similar conclusions cannot be drawn from patient 2. Southern blot analysis of total PBL gamma cell lines and clones indicated that this major circulating subset of TCR gamma cells retained a TCR beta gene in germline configuration and preferentially expressed a single V gamma gene, V gamma 5 for patient 1 and V gamma 9 for patient 2.

Antibodies, Monoclonal↗
PubMed1987

Human T cell clones use a CD3-associated surface antigen recognition structure to exhibit both NK-like and allogeneic cytotoxic reactivity.

In the present study, we developed human non-MHC-restricted CTL clones from human peripheral blood mononuclear cells activated in vitro with recombinant IL 2 and subsequently expended with PHA. The CD3/Ti+ clones were selected for their ability to exhibit non-MHC-restricted CTL reactivity by killing various tumor cell lines in culture, including the line K562 which does not express MHC antigens. We report that, at least for some of the NK-like T cell clones, it is possible to establish an allo-CTL activity, and that the CD3-associated surface antigen recognition structure might be involved in both reactivities.

Antibodies, Monoclonal↗
PubMed1987

HLA-A, B and DR antigen frequencies in patients with AIDS-related persistent generalized lymphadenopathy (PGL) and thrombocytopenia.

HLA-A, B, DR phenotype frequencies were studied in 69 homosexual patients with persistent generalized lymphadenopathy (PGL), in 8 patients with LAV/HTLV III related thrombocytopenic purpura and in 21 homosexual controls. Antigen DR5 was significantly increased in PGL patient groups as compared to controls. Our findings suggest that genetic factors associated with HLA-DR5 antigen may predispose individuals infected by the LAV/HTLV III virus to the occurrence of PGL and/or thrombocytopenia.

AIDS-Related Complex↗
PubMed1987

A study of 609 HLA haplotypes marking for the hemochromatosis gene: (1) mapping of the gene near the HLA-A locus and characters required to define a heterozygous population and (2) hypothesis concerning the underlying cause of hemochromatosis-HLA association.

We compared 609 haplotypes carrying the idiopathic hemochromatosis allele with 475 control haplotypes. Four haplotypes were more frequent in hemochromatosis: A3, B7 (actually A3, CW., B7, Bfs, DR2); A3, B14 (actually A3, CW., B14, BfF, DRW6); A11, B35; and A11, B5. The linkage disequilibrium for A3, B7 and A3, B14 (and probably also for A11, B5) was undeniably stronger in hemochromatosis than in controls. Two haplotypes--A3, B12 and A3, B15--were more frequent in hemochromatosis, without linkage disequilibrium. Four haplotypes in linkage disequilibrium in hemochromatosis--i.e., A2, B12; A1, B8; A9, B7; and A29, B12--were also found to have the same frequency and strength of linkage in controls. The dual observation (1) that haplotypes carrying A3 without either B7 or B14 were highly significantly more frequent in hemochromatosis than in controls and (2) that haplotypes carrying B7 or B14 but not A3 had the same frequency in hemochromatosis and controls led to the formal conclusion that only A3 is an independent marker for the hemochromatosis allele, B7 and B14 being involved only owing to the haplotypic mode of marking; the hemochromatosis allele can thus be mapped closer to locus A than to locus B. Our findings fit well with the hypothesis that the hemochromatosis mutation was a rare if not unique event that produced an ancestral HLA marking that was subsequently modified by recombinations and geographical scattering due to migrations.

Alleles↗