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Biomedical subjects

L Degos

Publications and source records attributed to L Degos.

At least 217 records · Page 12Linked to original sources
PubMed1987

Platelet acquired defect in PDGF and beta thromboglobulin content in hairy cell leukaemia: improvement after interferon therapy.

To investigate the platelet contribution to the development of myelofibrosis in hairy cell leukaemia (HCL), we have studied two platelet alpha granule components in 15 patients with HCL before chemotherapy: mitogenic activity was measured by 3H thymidine incorporation in BALB/C 3T3 cells and beta thromboglobulin (beta TG) assayed by radioimmunoassay (RIA). Platelet mitogenic activity and beta TG content were significantly decreased in the patients as compared to the control subjects. The nine patients who were treated with recombinant human interferon (IFN alpha A) were restudied after 4 months of therapy. The levels of both mitogenic activity and beta TG platelet content were significantly increased after IFN alpha-treatment with a complete response in five of the nine treated patients, a partial response in two and no response in the two others. HCL seemed therefore to be responsible for an acquired platelet alpha granule defect. As in the grey platelet syndrome a relationship between this abnormal platelet granule storage and the development of myelofibrosis is suggested in HCL.

Blood Platelets↗
PubMed1987

Present results of the treatment of myelodysplastic syndromes with low-dose cytosine arabinoside. Preliminary results of a cooperative protocol (38 patients) and review of the literature.

In vitro differentiating agents causing little bone marrow aplasia have been proposed as a specific therapy of myelodysplastic syndromes with excess of blasts. A critical review of the published data is presented. The preliminary results of a cooperative protocol using very low dosage of cytosine arabinoside (3mg/m2/twice daily) with or without androgens are given.

Aged↗
PubMed1987

[Differentiation of human malignant myeloid and lymphoid cells].

In vitro differentiation of malignant cells was obtained with various agents such as DMSO, retinoids, and low concentrations of ARA-C. In vivo treatment with low dose ARA-C in acute non-lymphoblastic leukemia, especially in elderly patients, induced complete remissions. Interferon was active in hairy cell leukemia, not through cytotoxic cell activation but by a direct effect on cell growth of the hairy cells and changes in the expression of some genes.

Cell Differentiation↗
PubMed1987

Proliferative response of hairy cells to B cell growth factor (BCGF): in vivo inhibition by interferon-alpha and in vitro effects of interferon-alpha, -beta, and -gamma.

Hairy cell leukemia (HCL) is a pre-plasma B cell tumor which responds to interferon (IFN)-alpha therapy. In vitro, B cell growth factor (BCGF) can induce proliferation of hairy cells. We have investigated the effect of in vitro and in vivo treatments with different recombinant IFN on the capacity of hairy cells to proliferate in response to human BCGF. In vitro treatment of leukemic cells from HCL patients with recombinant IFN-alpha-2 (5/5 cases) or IFN-beta (4/5 cases) resulted in a marked inhibition of the BCGF-dependent response. This suppressive effect was obtained with IFN concentrations of 1000, 100 IU/ml, and even occasionally 10 IU/ml. In contrast, no such inhibition was observed with IFN-gamma, despite the presence of specific IFN-gamma receptors on hairy cells at densities similar to receptors for IFN-alpha/beta. The IFN-alpha-induced suppression of the proliferative response of hairy cells to BCGF was also observed in vivo in two patients within 6-12 hr after administration of single doses of IFN-alpha. When hairy cells were maintained in culture for 1 week, they recovered their capacity to be stimulated by BCGF. This reversion was also shown in vivo in hairy cells isolated 1 week after IFN administration. Since in vivo growth of hairy cells could possibly result from the autocrine secretion of BCGF, we propose that the therapeutic effect of IFN-alpha on HCL may be due in part to an inhibition of such autocrine loop.

2',5'-Oligoadenylate Synthetase↗
PubMed1987

[Implication of HLA class I molecule from monocyte in T-cell activation by CD2 or CD3 monoclonal antibodies].

The role of monocytes in human T-cell activation by monoclonal antibodies (mAb) recognizing CD3 molecule or by 2 mAb pairs directed against different epitopes of CD2 "GT2+T11(1)" or "D66+T11(1)" has been studied. It appears that HLA-cl I molecules from monocytes are involved in the early activation phase of T-cells stimulated by CD3 or CD2 when direct contacts between T-cells and monocytes are required. Thus, pretreatment of monocytes with HLA-cl I mAb inhibited IL 2 receptor appearance and IL 2 synthesis on T-cells stimulated by CD3 mAb or CD2 "GT2+T11(1)" mAb pair.

Antibodies, Monoclonal↗
PubMed1987

[Improved results in the treatment of acute monoblastic leukemia: analysis of 91 patients treated in the 01 AM 81 protocol].

A total of 91 patients with acute monoblastic leukemia (AML) were treated following two induction regimens (ARA-C + RBZ, with of without CPA), and a unique maintenance therapy (CNS prophylaxis and reinductions every 6 weeks, for 36 months). Complete remission (CR) was obtained in 84% of patients. The only prognostic factor significantly influencing the CR rate was age, with 92% for the less than 40 years group and 75% for the greater than or equal to 40 years group. CR was not influenced by sex, tumoral syndrome, leukocytosis, cytological subclassification (M5A, M5B), or induction regimen with or without CPA. The duration of CR in these forms which have a traditionally poor prognosis, was no different from other forms of AML (21 months), and the disease-free survival at 50 months was 45%. These results, pertaining to the largest published series treated by the same protocol, are the best reported in literature and confirm the role of induction and maintenance therapy in CR.

Adult↗
PubMed1987

[Criteria for assessing granulocytic or platelet cytopenia caused by drugs. Results of consensus meetings].

The use of an official drug adverse reaction assessment procedure became compulsory in France in 1984. The method proposed various qualifications for the semiologic and chronologic criteria used to ascribe a disorder to a specific drug but did not define them. Consensus meetings have been organized in order to define, in the main pathological fields, the adverse reactions themselves and the various qualifications of the criteria. This paper reports the results of meetings attended by hematologists, members of the French national network of Pharmacovigilance and representatives of Roussel Uclaf Drug Monitoring Department for drug-induced granulocyte and platelet cytopenias. Participants studied (a) the limits of the time interval between the appearance of the adverse reaction and the beginning or the end of the treatment with the suspected drug; (b) interpretation of a possible rechallenge; and (c) diagnostic value of in vitro tests proposed to confirm the responsibility of a specific drug in a granulocytic or platelet cytopenia.

Agranulocytosis↗
PubMed1987

Phenotypic and genotypic heterogeneity in large granular lymphocyte expansion.

The cellular heterogeneity of large granular lymphocyte expansions has been illustrated by the phenotypic and genotypic findings in five patients. In one patient whose circulating cells were CD2+, CD3-, CD5-, CD7+, CD8-, CD11+, Leu7+, CD16+, and displayed strong natural killer activity, no rearrangement of the T cell receptor beta-chain gene and T cell rearranging gene gamma was detected. The four other patients presented with neutropenia without overt lymphocytosis. In these patients the circulating lymphocytes expressed a predominant T cell phenotype CD2+, CD3+, CD5+, CD7+, CD8+, Leu7+. In three of them the presence of a T cell clone was demonstrated on the basis of a unique pattern of rearrangement of the T cell receptor beta-chain genes.

Aged↗
PubMed1987

Results of treating 53 hairy cell leukemia patients with alpha-interferon.

Fifty-three hairy cell leukemia patients were treated with low dose recombinant and natural alpha-interferon for 7 or 13 months with a marked improvement in peripheral blood and bone marrow findings. Our results suggest that daily injections have no advantage over three weekly injections, but longer treatment (12-13 months) is better than shorter treatment (6-7 months). The possibility of a relapse raises the issue of the place of splenectomy in the treatment strategy. Since the definition of remission and of relapse is based on the histological changes in the bone marrow, the necessity for the quantification of the hairy cell infiltration on bone marrow sections is stressed.

Dose-Response Relationship, Drug↗
PubMed1986

Human T lymphocyte clones with killer or natural killer activity.

We describe a reliable method for obtaining a significantly higher frequency of human cloned T lymphocytes with killer and/or NK-like activity. Human peripheral blood mononuclear cells were treated with recombinant interferon-gamma (rIFN-gamma) and recombinant interleukin-2 (rIL-2) in a culture medium containing autologous serum and were then cloned by single cell micromanipulation. The cloned T lymphocyte populations were tested simultaneously for their ability to proliferate in response to exogenous IL-2, to exhibit lectin-dependent cytolysis and to kill the tumor cell line K562. Results indicate that the cloning technique allowed each isolated T lymphocyte to undergo cell expansion. Furthermore when T cells were pretreated with rIFN-gamma and rIL-2, 88% of the T cell clones were capable of mediating cytotoxicity in the presence of PHA. Moreover one third of the clones which exhibited lectin-dependent lysis were able to kill K562 target cells.

Clone Cells↗
PubMed1986

Biochemistry of HLA-DRw6: evidence for seven distinct haplotypes.

The DRw6 specificity, which has a frequency of 11% in the Caucasian population, cannot be positively defined, since no monospecific allo-antiserum is available. This particular status among DR specificities led us to study the DRw6 haplotypes at the molecular level. We performed 2D-PAGE analysis of HLA-DR molecules in 44 different DRw6 haplotypes. The data were obtained from six homozygous typing cells, eight families informative for the segregation of the DRw6 haplotype, and 15 unrelated donors. Five unique beta-chain electrophoretic patterns were detected, indicating the existence of five structurally distinct DRw6 beta-chains. Each haplotype expresses one or two beta-chains. The different combinations of the DR beta-chains present in a single haplotype allow to characterize seven unique DRw6 haplotypes. In contrast to what has been previously found for DR2 and DR4, there is no DR beta-chain common to all the DRw6 cells. Correlation of the biochemical data with the recent serologic (DRw13 vs DRw14) and cellular (Dw9, Dw18, Dw19) splits of the DRw6 specificity will be discussed.

Antibodies, Monoclonal↗
PubMed1986

Interferon alpha in the treatment of hairy cell leukemia.

Fifty-four patients with hairy cell leukemia were treated for 7 months with three types of subcutaneously injected interferon: recombinant interferon alfa-2a from Hoffmann-La Roche (3 X 10(6) U daily); recombinant interferon alfa-2b from Schering (2 X 10(6) U/m2, three times per week); and partially purified human leukocyte interferon alpha from the Finnish Red Cross (3 X 10(6) U daily). After 4 months, in 27 patients hairy cells decreased dramatically (P less than 0.01) while platelets (P less than 0.05), monocytes (P less than 0.01), polymorphonuclear leukocytes (P less than 0.01) and hemoglobin (P less than 0.01) increased (in this order) as treatment progressed. Morphometric parameters were used to estimate the relative volume of hairy and myeloid cells present in bone marrow. Biopsies were performed at the beginning of the study and in the second, fourth, and seventh months thereafter. Bone marrow disorders were slower to improve as compared with blood. Six severe cases of hairy cell leukemia were responsive to treatment, but required special monitoring during the first 2 months. All three interferons studied are efficient. Interferon receptors, oncogene (mRNA levels) expression, and the relationship between PDGF and fibrosis in hairy cell leukemia are under investigation.

Adult↗
PubMed1986

Correlation between an HLA-DQ alpha length polymorphism of messenger RNA and serologically defined specificities (DQw1, DRw53, DR3+5).

mRNAs for the two chains of the HLA-DQ molecule were analyzed, in particular the DQ alpha mRNA whose polymorphism had previously been suggested (Schenning et al. 1984). Northern blot transfers of the mRNA of 12 LCLs and of B lymphocytes from a healthy donor were carried out. We report that a length polymorphism of DQ alpha mRNA exists, and we show that it can be correlated with serologically defined specificities (DQw1, DRw53, DR3+5). This correlation could be explained by a linkage disequilibrium, as these specificities are considered to be different from those carried by the DQ molecule (except for the DQw1 specificity).

DNA Restriction Enzymes↗
PubMed1986

1-B-D arabinofuranosyl cytosine and all-trans retinoic acid in combination accelerates and increases monocyte differentiation of myeloid leukemic cells.

The effect of the combination of two different agents on myeloid differentiation was studied. Human promyelocytic cells (HL-60) and monoblast-like cells (U-937) were treated with 1-B-D arabinofuranosyl cytosine (Ara-C) alone, or in combination with retinoic acid (trans-RA). The known dual potentiality of HL-60 promyelocytes was confirmed by their ability to mature into granulocytes following induction by retinoic acid and into monocyte-like cells following treatment with 1-B-D arabinofuranosyl cytosine. The U-937 cell line differentiated to monocyte-like cells with either of the two drugs. The differentiation induced by Ara-C involved an irreversible step after 24-h incubation with the drug, was concentration dependent, and far more superior on U-937 cells than on HL-60 cells. The outcome of these two cell lines after treatment with both Ara-C and trans-RA was also different: this combination maintained the monocyte differentiation in the HL-60 cell line, and resulted in a higher sensitivity of U-937 cells to Ara-C, as indicated by a cell response to low Ara-C concentrations and a more rapid expression of monocyte specific properties.

Antibodies, Monoclonal↗
PubMed1986

Structure-activity relationships of aromatic retinoids on the differentiation of the human histiocytic lymphoma cell line U-937.

The differentiation-inducer activity of a series of derivatives modified on the terminal ring, the polyene side-chain or the polar end group of the retinoic acid molecule was tested on the human histiocytic lymphoma cell line U-937 and compared with that of all-trans-retinoic acid. Only retinoids with both an unsaturated terminal end ring and a free carboxyl polar end group were found to be active in this system. Introduction of an aromatic ring in place of the first double bond of the side chain increased highly the activity whereas cyclisation of the last two double bonds decreased it. Replacement of the unsaturated terminal ring by an aromatic ring abolished the activity as did the esterification of the carboxyl end group or its replacement by a sodium sulfinate, sodium sulfonate or ethyl sulfone end group. All but only the active retinoids induced the same morphological and biochemical changes on U-937 cells, suggesting that they have the same route of action. However, biologically inactive retinoids were shown to be able to inhibit the differentiation of U-937 cells, induced by active ones, indicating that they can compete for a common "receptor".

Cell Differentiation↗
PubMed1986

What is a T-cell clone? Effect of rIFN on T-cell clone function and T-cell receptor gene rearrangement.

A T4+ proliferative, noncytotoxic cloned line acquires specific lytic function by treatment with recombinant interferon alpha or gamma. Simultaneous with the acquisition of this new cell function, a rearrangement of the T-cell receptor alpha gene occurs. These changes necessitate a revised concept of a T-cell clone regarding its T-cell receptor gene configuration and cell function.

Cell Line↗