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Biomedical subjects

L Degos

Publications and source records attributed to L Degos.

At least 163 records · Page 9Linked to original sources
PubMed1990

Linkage of a nasopharyngeal carcinoma susceptibility locus to the HLA region.

The frequency of nasopharyngeal carcinoma is nearly 100-fold higher in southern Chinese than in most European populations. Earlier studies have suggested that an increased risk of nasopharyngeal carcinoma is associated with specific haplotypes in the HLA region: relative risks slightly over twofold were found for haplotypes A2, Bw46 and the antigen B17. We now report a linkage study based on affected sib pairs which suggests that a gene closely linked to the HLA locus confers a greatly increased risk of nasopharyngeal carcinoma. The maximum likelihood estimate is of a relative risk of approximately 21. The relationship between this suspected disease susceptibility gene (or genes) and known viral and environmental aetiological factors remains to be elucidated.

China↗
PubMed1990

Structural organization of the hCTLA-1 gene encoding human granzyme B.

Cytotoxic T lymphocytes (CTLs) and natural killer/lymphokine-activated cells produce granzymes, a family of serine esterase proteins located in cytoplasmic granules. These might be involved in different cytotoxic pathways. We report the structural organization of the human gene encoding granzyme B (hCTLA-1). A 4.75-kb genomic DNA fragment containing all the sequences of granzyme B-encoding cDNA clones has been sequenced. The gene is composed of five exons and four introns. A comparison with the genomic organization of murine CCP1/CTLA-1 showed very similar structure and a 76% nucleotide homology in the coding sequences. This suggests that both genes may have a common ancestor. No typical regulatory element was detected in the 1160 bp upstream from the ATG start codon. The detection of a second locus related to hCTLA-1 is also described.

Amino Acid Sequence↗
PubMed1990

Regulation of transcription of the human T cell antigen receptor delta chain gene. A T lineage-specific enhancer element is located in the J delta 3-C delta intron.

We have defined transcriptional enhancing sequences inside the TCR-delta gene locus, using transient transfections with constructs containing DNA fragments cloned upstream to a reporter gene fused to a heterologous promoter. A 14-kb DNA region extending from the J delta 3 segment to 6 kb 3' to C delta was analyzed. We show the presence of positive regulatory sequences inside the J delta 3-C delta intron and have localized these sequences to two DNA fragments of approximately 300 and 258 bp. Analysis of cell specificity of the activation of such sequences demonstrates a T cell pattern for one of the two fragments. The nucleotide sequence of the T cell-specific element shows motifs sharing homology with previously described core enhancers.

Base Sequence↗
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

Differentiating agents in the treatment of leukemia.

The aim of differentiation therapy is to induce a maturation of the leukemic clone. Various approaches have been used: suppression of proliferation by low dose Ara-C in acute myeloid leukemia (AML); enhancement of differentiation by retinoic acid derivatives in acute promyelocytic leukemia (APL) or by differentiation-inducing factors; modulation of cell metabolism by breaking an autocrine loop in hairy cell leukemia (HCL). In all cases the treatment is given continuously at small doses over a long period of time. The very significant clinical results which have been obtained mainly in APL with all-trans retinoic acid and in HCL with alpha-interferon are briefly discussed.

Cell Differentiation↗
PubMed1990

Differentiating agents in the treatment of leukemia and myelodysplastic syndromes.

Differentiation therapies try to change the malignant cell in order to acquire a more mature or normal phenotype. Various ways were tested in leukemia: suppression the proliferative pressure by low dose Ara-C, enhancement of the differentiation by retinoic acid derivatives or by differentiation factors, and modulation of the cell metabolism interrupting an autocrine loop (a growth factor and its receptor). The treatment is given continuously at small doses, during a long period of time. In all these cases it seems necessary to tailor the differentiation therapy to each category of leukemia.

Cell Differentiation↗
PubMed1990

Nucleotide sequence of the HLA-A26 class I gene: identification of specific residues and molecular mapping of public HLA class I epitopes.

A cosmid clone bearing an HLA class I gene has been isolated from a human genomic library by hybridization to a class I-specific probe. This clone encodes the HLA-A26 molecule characterized by immunologic reagents on murine transfected L cells. Nucleotide sequencing of the A26 allele has been performed, and the deduced amino acid sequence was compared with previously published HLA class I sequences. Amino acid sequence homologies between HLA-A26 molecules and members of the HLA-AW19 cross-reactive group were observed and allowed us to demonstrate that residue Q144 is the only critical residue involved in the binding of the 4E monoclonal antibody defining an epitope common to all HLA-B, -C, and -Aw19 alleles. This study also permitted designation of a V residue at position 189 in the third domain as possibly involved in the binding of the B1-23-2 monoclonal antibody. Furthermore, we located clusters of variability in reference to the three-dimensional structure of the HLA-A molecules, i.e., the ninth residue of the first beta-strand domain, the upper surface of the first helical region, and both beta and alpha structures of the alpha 2 domain.

Amino Acid Sequence↗
PubMed1990

A combination of HLA-DQ beta Asp57-negative and HLA DQ alpha Arg52 confers susceptibility to insulin-dependent diabetes mellitus.

Family and population studies indicate that predisposition to insulin-dependent (type I) diabetes mellitus (IDDM) is polygenic. It has been shown that the absence of the aspartic acid in position 57 (Asp57) of the DQ beta chain is positively correlated to IDDM. However, Asp57-negative haplotypes do not always confer susceptibility and conversely, some Asp57-positive haplotypes seem to be disease associated. It has been suggested that other HLA class II sequences, probably belonging to the HLA DQA1 gene, confer susceptibility to IDDM. This report, based on extensive oligonucleotide dot blot hybridization of PCR-amplified DQA1 and DQB1 genes, reinforces the importance of the Asp57-negative DQ beta chain, but also introduces the possibility that a DQ alpha chain bearing an arginine in position 52 (Arg52) confers susceptibility to IDDM. A molecular model of susceptibility to IDDM is proposed. This model strongly suggests that the disease susceptibility correlates quantitatively with the expression at the cell surface of a heterodimer, composed of a DQ alpha-chain bearing an Arg52 and a DQ beta chain lacking an Asp57. In view of the respective positions of the two residues and their charge, we might anticipate that both residues DQ beta Asp57 and DQ alpha Arg52 are critical for modulation of susceptibility, presumably via viral-antigenic peptide and/or autoantigen presentation.

Base Sequence↗
PubMed1990

Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly.

We conducted a randomized multicenter trial comparing low-dose cytarabine (LD ARA-C) (20 mg/m2 for 21 days) with an intensive chemotherapy (rubidazone [a daunorubicin-derived agent], 100 mg/m2 for 4 days, ARA-C 200 mg/m2 for 7 days) in 87 patients over 65 years of age with de novo acute nonlymphocytic leukemia (ANLL). Forty-one patients received LD ARA-C and 46 received intensive chemotherapy. The number of complete remissions (CRs) but also of early deaths was higher in the intensive chemotherapy group, while partial remissions (PRs) and failures were more frequent in the LD ARA-C group (P less than .001). Infectious complications during induction treatment were more numerous and more severe in the intensive chemotherapy group (P less than .01). Patients treated with LD ARA-C required fewer RBC transfusions (P less than .02), fewer platelet transfusions (P less than .01), and had a shorter hospital stay for induction treatment (P less than .01). Overall survival and CR duration were not significantly different in either group. In the LD ARA-C group, the survival of patients with PR and those of patients in CRs was identical. We conclude that in a selected group of elderly patients with de novo ANLL a higher number of CRs may be obtained with intensive chemotherapy, but that with LD ARA-C, the number of early deaths is lower, and long-lasting PRs are obtained, resulting in a similar overall survival.

Aged↗
PubMed1990

HLA-DP genotyping in HLA-A,B, and DR identical intrafamilial bone marrow transplantation.

In a study carried out for patients receiving intrafamilial HLA-A,B,DR identical, MLC negative bone marrow transplants, RFLP profiles of HLA-class II for 27 donor recipient pairs were analyzed. Twenty-four pairs were found HLA-class II identical while three pairs were HLA-DP incompatible. The patients of these three pairs did not reveal any acute GVHD greater than or equal to grade II. The seven cases of acute GVHD greater than or equal to grade II found in our panel were HLA-DR, DQ, and DP compatible. Thus, in practical terms pretransplantation HLA-DP typing does not seem necessary for intrafamilial HLA-identical, MLC negative BMT. On the other hand, this work confirmed that it is possible to type for HLA-DP using molecular biological techniques, and this in itself may have some important implications for unrelated BMT.

Adolescent↗
PubMed1990

HLA DQ alpha/beta molecule associated with the susceptibility to insulin-dependent diabetes mellitus. A model for HLA/autoimmune disease association.

We have proposed a molecular model of susceptibility to Insulin-Dependent Diabetes Mellitus (IDDM) based on the proportional expression at the cell surface of the following susceptible (S-S) HLA-DQ heterodimere composed of a chain DQ alpha Arg 52 positive (S) and a chain HLA-DQ beta Asp 57 negative (S). All other DQ alpha/beta chains associations are considered as protective molecules. This model allows a predictive scale of risk for the disease.

Alleles↗
PubMed1990

The retinoic acid receptor alpha gene is rearranged in retinoic acid-sensitive promyelocytic leukemias.

All-trans retinoic acid (RA), the active metabolite of vitamin A, has recently been demonstrated to be an efficient alternative to chemotherapy in the treatment of acute promyelocytic leukemia (M3 subtype of the French-American-British cytological classification). Complete remission is obtained by inducing terminal granulocytic differentiation of the leukemic cells. To elucidate whether the effect of retinoic acid on the differentiation of M3 leukemic cells was related to any specific characteristics of its receptor, we analyzed the structure and expression of retinoic acid receptor (RAR) genes in 16 M3 patients. Abnormal RAR alpha transcripts were detected in 13 cases. In nine patients, the genomic DNA was analyzed by Southern blotting and evidence for a rearranged RAR alpha gene was found generated in four cases. Normal RAR transcripts and germline restriction fragments were found in samples from normal or other leukemic cells, suggesting that this alteration of the RAR alpha gene is specifically seen in M3 leukemias. These results suggest that alteration of the retinoic acid receptor alpha may be implicated in M3 leukemogenesis.

Adult↗
PubMed1990

In vitro effects of retinoic acid.

Retinoids, synthetic and natural analogues of vitamin A, play fundamental roles both in directing the spatial organization of cells during the development of vertebrate limbs and in the maintenance of growth and differentiation of many adult tissues. They also block the phenotypic expression of cancer in vitro; inhibit growth and induce differentiation in many animal and human malignant cell types. They have proved beneficial in skin diseases, cancer prevention and in acute promyelocytic leukemia.

Animals↗
PubMed1990

Retinoic acids in the treatment of acute promyelocytic leukemia.

Retinoic acid, the active metabolite of vitamin A has been shown to differentiate in vitro human leukaemic cells from patients with acute promyeolocytic leukaemia (APL). The results obtained in vivo with the 13-cis isomer of retinoic acid in combination with or after chemotherapy in four cases of APL are described. More recently Huang et al from the Shangai Institute of Haematology have treated 24 cases of APL with all-trans retinoic acid alone. They obtained 24 complete remissions. This success prompted us to treat patients with APL and a contra-indication to chemotherapy with all-trans retinoic acid. The results confirm the great efficacy of all-trans retinoic acid in APL.

Aged↗
PubMed1990

Typing for HLA DQ using oligonucleotidic probes.

We have typed 25 homozygous B lymphoblastoid cell lines, defined as reference panel during the Xth International Histocompatibility Workshop, using PCR (Polymerase Chain Reaction) and oligonucleotidic probes recognizing sequences of DQA and DQB genes. The polymorphism of 8 HLA-DQA1, and 12 DQB1 alleles is reported and the advantages of this technique are compared to that of other typing methods, currently used.

Cell Line↗
PubMed1990

Infiltrating lymphocytes in benign and malignant naevomelanocytic lesions.

Cutaneous melanocytic tumors include benign (naevi) and malignant (melanoma), potentially metastatic lesions. In this report, we show that infiltrating lymphocytes from benign tumors may be expanded in vitro as TIL from melanoma in the presence of autologous tumoral cells and recombinant IL2. Moreover it seems that TIL from primary cutaneous benign or malignant lesions more frequently express the T-cell receptor gamma delta than TIL from metastatic melanoma. Otherwise, a gamma delta + line and a gamma delta + clone extracted from a primary cutaneous melanoma exhibit a specific non MHC-restricted cytotoxic activity against autologous tumor cells. This is the first report of a TCR gamma delta + T lymphocyte cytotoxic activity against a human solid cutaneous tumor.

Cytotoxicity, Immunologic↗