PubMed Health⌕ Search

Biomedical subjects

F Sigaux

Publications and source records attributed to F Sigaux.

At least 127 records · Page 7Linked to original sources
PubMed1988

[Establishment of a T lymphoid cell line producing a retrovirus of HTLV-I type, from peripheral blood of a patient with tropical spastic paraparesis].

HTLV-I, the causative agent of Adult T cell Leukemia, has recently been found to be associated with chronic neuromyelopathies common in tropical areas and in Japan. We report here the establishment of a lymphoid T cell line from peripheral blood lymphocytes of a patient with Tropical Spastic Paraparesis. This cell line produces a retrovirus whose morphologic, antigenic and genetic characteristics show no detectable difference from the leukemogenic prototype of HTLV-I.

Antigens, Viral, Tumor↗
PubMed1988

The human T-cell V gamma gene locus: cloning of new segments and study of V gamma rearrangements in neoplastic T and B cells.

The authors have analyzed the involvement of V gamma and J gamma segments in TRG gamma rearrangement from a series of 40 acute lymphoblastic leukemia (ALL), including 25 T- and 15 B-lineage cases, in which TRG gamma are rearranged. Sixty-five rearranged alleles were studied. The authors first describe the cloning and sequencing of two variable segments, V gamma 11 and psi V gamma 12, which rearrange in T- and B-neoplastic cells. To date three subgroups of translatable V gamma segments have been described. The authors show that V gamma 11 is the unique member of a new fourth V gamma subgroup that also rearranges in normal polyclonal T cells and that psi V gamma 12 is located at 5-kilobase (kb) downstream to V gamma 11. As shown by DNA sequence analysis, V gamma 11 shares a 60% homology with V gamma 10 (third subgroup) and a 50% homology with V gamma 9 (second subgroup) but no appreciable homology with the V gamma segments from the first family. In contrast to psi V gamma 12, V gamma 11 is translatable. In this paper the authors have also attempted to determine which V gamma segments were rearranged in the ALL cases by hybridization with a J gamma probe and genomic probes specific of the four subgroups. In the 54 instances in which the rearrangement was consistent with J gamma 1 or J gamma 2 involvement, the authors have identified the corresponding V gamma segments and have not found any other rearrangements suggestive of the existence of further V regions. The V gamma segments, belonging to the first subgroup, were the most frequently used (41 alleles). V gamma 9, V gamma 10, V gamma 11, and psi V gamma 12 were found rearranged in cases 3, 4, 5, and 1, respectively. No cases using the pseudo psi V gamma 1, psi V gamma 5, and psi V gamma 6 segments were found. Pseudo V gamma segments were not found rearranged in T cells, while V gamma 2 and V gamma 4, segments are frequently used. In contrast to the V gamma I gene rearrangement, the involvement of the V gamma II, V gamma III, and V gamma IV subgroups was most frequently observed in T-ALL with stage II differentiation (CD7+, CD4+, and/or CD8+, CD3-), than in those with stage I (CD7+, CD4-, CD8-, CD3-), than in those with stage I (CD7+, CD4-, CD8-, CD3-) and stage III (CD7+, CD4+/-CD8+/-CD3+).(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, Differentiation, T-Lymphocyte↗
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↗
PubMed1988

[Detection of residual disease: analysis of the gene arrangement of immunoglobulins and T-cell antigen receptors].

T and B cells specifically recognize antigens using a receptor located at the cell surface. The repertoire of lymphoid cells chiefly results from somatic rearrangements involving the variable segments of the genes encoding these receptors. The modifications of the DNA structure induced by these rearrangements are found in all cells of the same clone. Immunoglobulin (Ig) or T-cell antigen receptor (TCR) gene rearrangements are usually found in most lymphomas as well as in B or T lineage acute lymphoblastic leukemias. Thus, the study of Ig or TCR gene rearrangement could be useful in the detection of minimal disease in such malignancies. However the sensitivity of molecular hybridization on Southern blots is still not a sensible enough technique to be used in clinical practice.

Gene Expression Regulation↗
PubMed1988

[T lymphocyte receptors after allogenic bone marrow transplantation].

Following allogeneic bone marrow transplantation, prominent expansion of peripheral T cells (40%) bearing gamma T cell receptor was observed in some patients. Biochemical, functional and molecular analyses were performed to characterize this T cell receptor and to understand its role in the immunodeficient state after transplantation.

Antibodies, Monoclonal↗
PubMed1988

Philadelphia-positive acute leukemia: lineage promiscuity and inconsistently rearranged breakpoint cluster region.

Six patients with Philadelphia-positive (Ph1+) acute nonlymphocytic leukemia (ANLL) were studied by morphological, immunological, cytogenetic, and molecular techniques. Seven Ph1+ acute lymphocytic leukemia (ALL) cases were also studied for comparison. Three of ANLL cases were classified in M1, M2, and M4 groups of the FAB nomenclature, while the three other cases do not fit with any FAB subgroup and are described as M0. Immunophenotypical marker studies, double immunolabeling, and combined immunological and cytogenetic studies of metaphases showed that these ANLL expressed several lineage differentiation antigens. Rearrangements of immunoglobulin heavy chain gene (C mu) were detected in the six ANLL cases and in the seven ALL cases studied, as well as, in most cases, rearrangement of T cell receptor beta chain genes and/or T cell rearranging gamma genes. The results favored the assumption that the Ph1 translocation originated from a multipotent stem cell in Ph1+ ANLL. A common t(9;22) translocation was found in all cases, and additional chromosomal abnormalities were present in the six ANLL cases and in five of the seven ALL cases. Molecular studies of bcr gene configuration and c-abl transcription allowed two groups of Ph1+ ANLL to be distinguished. Three cases had bcr rearrangement and c-abl mRNA expression comparable to those reported in Ph1+ chronic myeloid leukemia, while three others had not detectable bcr rearrangement and a 7.2-7.5 kb c-abl mRNA. The existence of Ph1+ ALL with and without classical bcr rearrangement was confirmed.

Adolescent↗
PubMed1987

Human T cell gamma genes are frequently rearranged in B-lineage acute lymphoblastic leukemias but not in chronic B cell proliferations.

T cell rearranging gene gamma (TRG gamma) and T cell antigen receptor beta (TCR beta) chain gene rearrangement and transcription were studied in a series of patients with B-lineage acute lymphoblastic leukemia (ALL), in which the Ig H chain genes are rearranged and the surface phenotype reproduces the stages of normal pre-B maturation. For comparison, polyclonal T cells from peripheral blood of healthy donors and blast cells from 19 cases of T lineage ALL were also studied. In this study we demonstrate the presence of a clonal rearrangement of the TRG gamma in 18 of the 22 B-lineage ALL cases and establish that this rearrangement, which generally involves the J gamma 1 region, is often monoallelic and appears different from the biallelic J gamma 2 rearrangement frequently seen in T-cell ALLs. In 9 of 22 cases, we found rearrangement of the genes of the TCR beta chain, which never involved the J beta 1 region. Conversely, the TRG gamma were seen in germline configuration in all 19 cases of B chronic lymphoid malignancies. In none of the 9 AML cases studied was TRG gamma and TCR beta chain gene rearrangement found. The TCR beta chain genes were rearranged in one B cell chronic lymphocytic leukemia (CLL). We also show that in B-lineage ALL, the cells probably use the same V gamma genes for TRG gamma rearrangements as the malignant cells in T-ALL and the polyclonal T cells. In none of the 13 B-lineage ALL cases investigated by Northern analysis was TCR beta mRNA expression detected, whereas a weak expression of TRG gamma transcripts was found in two of these cases. The correlations between surface phenotype, rearrangement of TRG gamma, TCR beta, and Ig H chain genes were analyzed. The significance of rearrangement of TRG gamma and TCR beta chain genes in B or pre-B cells is also discussed.

B-Lymphocytes↗
PubMed1987

[An aid in decision-making in hematology: characteristics and performances of the program. 200 cases of anemia].

An aid to decision programme has been applied to 200 cases of anaemia. Evaluation by the bayesian method rested on clinical data (age, sex, race) and laboratory data (blood count and differential, erythrocyte morphology). An accurate diagnosis was made initially in 107 cases, and for the first 5 diseases in 173 cases. The programme proved more effective than two clinicians recently trained in haematology. Devised for micro-computers, it can be used in routine practice and for teaching purposes.

Anemia↗
PubMed1987

Alpha-interferon in hairy cell leukaemia: direct effects on hairy cells or indirect cytotoxicity?

This report presents the results of a clinical trial on 53 patients with hairy cell leukaemia using low-dose alpha-interferon as therapy. Improvement of cytopenia and/or bone marrow hairy cell infiltration occurred in all but one patient. Often, blood and bone marrow improvements were dissociated and, after 7 or 13 months of therapy, complete remission was only observed in about 40% of patients. Recurrence of the disease was observed in some cases after cessation of therapy. A summary of the following results is presented: alpha-interferon receptor analysis, oncogene expression, study of the sensitivity of hairy cells to natural killer cells, and the effects of interferon on T-cell receptor gene rearrangement and on the function of T-cell clones. Results are also presented which show that myelofibrosis may be due to a release of platelet derived growth factor. The immunological findings and oncogene expression in 2 patients with a variant form of hairy cell leukaemia for which resistance to therapy was observed are also described. All the results show that interferon acts on hairy cells and are consistent with a direct effect by interferon in the treatment of hairy cell leukaemia.

Blood Platelets↗
PubMed1987

Cytogenetic studies on 519 consecutive de novo acute nonlymphocytic leukemias.

Cytogenetic studies were performed in the same laboratory on 519 untreated cases of de novo acute nonlymphocytic leukemia (ANLL) between 1977 and 1985. The overall incidence of clonal chromosome abnormalities was 54.3%; higher in children (67.5%) than in adults (50.4%). The distribution of chromosome abnormalities was uneven, according to the categories of the FAB nomenclature. The highest frequency of chromosome changes was observed in ANLL-M3 and the lowest in M1 and M6. The frequency of specific chromosome abnormalities and of their associated changes were also estimated. Monosomy 7 was detected in three patients with acute megakaryocytic leukemia (M7). Six cases with two abnormal chromosomally unrelated clones were observed and six constitutional chromosome abnormalities were detected. A clearer knowledge of the incidence of various chromosomal changes in ANLL seems necessary for better differentiation between the so-called primary and secondary chromosome abnormalities and for prognostic evaluation.

Acute Disease↗
PubMed1987

Prognostic significance of chromosomal abnormalities in acute nonlymphocytic leukemia: a study of 343 patients.

Clonal chromosome abnormalities of 343 patients with de novo acute nonlymphocytic leukemia (ANLL) have been tentatively correlated with prognosis. All the patients were treated according to therapeutic protocols in the same hospital. The complete remission rate and median survival were generally lower in AA-ANLL (ANLL with only karyotypically abnormal metaphases) when compared with NN- and AN-ANLL. Similarly, AA-ANLL had the poorest prognosis in the majority of the classes of the French-American-British nomenclature. ANLL with inversion and/or deletion of chromosome #16 had the best prognosis, and ANLL with t(8;21) was not particularly favorable, nor was acute promyelocytic leukemia with t(15;17). ANLL with complex chromosomal abnormalities had the poorest prognosis. The conclusion is that chromosomal aberrations do have a prognostic significance in ANLL, but that this significance is dependent on the types of chromosomal aberrations.

Acute Disease↗
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

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

T cell-derived blast crisis in chronic myelocytic leukemia.

We describe herein the occurrence of a T cell-derived blast crisis of chronic myelocytic leukemia which presented as a typical T cell leukemia on clinical (thymic mass and high white blood cells) and immunological grounds (T6+ T4+ T8+), with rearranged T cell receptor genes and germ line immunoglobulin genes. A Philadelphia chromosome was detected in all blast cell mitoses. The significance of T cell involvement during the chronic and acute phases of chronic myelocytic leukemia is discussed.

Adult↗