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G Delsol

Publications and source records attributed to G Delsol.

At least 109 records · Page 6Linked to original sources
PubMed1996

[Testicular biopsy at the stopping of the treatment in acute lymphoblastic leukemia: value of the immunohistochemical detection of residual blasts].

BACKGROUND: The prognostic value of clinical and histological detection of testicular leukemia after completion of therapy is still debated. Immunohistochemical study could improve the results of this detection. PATIENTS AND METHODS: Between 1982 and 1992, 70 consecutive boys with acute lymphoblastic leukemia (ALL) and treated with the same therapeutic regimen were included in the study. Testicular biopsy (TB) was surgical and bilateral. One piece of tissue was fixed and analysed by conventional microscopy. An immunohistochemical study was performed on the other sample with a panel of anti-T and anti-B Mc Ab, including JCB 117 (anti-CD79a) which stains early pre B lymphoblasts. RESULTS: Twenty-five children relapsed while on treatment and did not undergo TB. Among the 45 boys who underwent routine TB, one had a diffuse infiltration seen in conventional histology. Thirty-nine had normal morphological and immunohistochemical study: among them, six relapsed subsequently in bone marrow; in this group, event free survival (EFS) was 85 +/- 10% with a median follow-up of 80 months after the biopsy. In the five remaining boys, anti-CD79a was found positive on blasts in four cases and anti-CD3 in one case; four of those relapsed, including two in the testes during the year following the biopsy; EFS was 20 +/- 36% (P = 0.001). CONCLUSIONS: New Mc Ab such as JCB 117 (anti-CD79a) might detect a minimal residual disease in the testes of children treated for ALL, particularly on routine histological material. These results, if confirmed in larger series, might influence further therapeutic strategy.

Adolescent↗
PubMed1996

Characterization of Epstein-Barr virus-infected cells in benign lymphadenopathy of patients seropositive for human immunodeficiency virus.

The authors investigated 25 benign lymph nodes in patients infected with the human immunodeficiency virus (HIV) by in situ hybridization (ISH) and immunohistochemistry (IHC) to detect and characterize the Epstein-Barr virus (EBV)-infected cells. After ISH, 22 lymph nodes were found to contain various numbers of Epstein-Barr-encoded RNA (EBER)-positive cells. Most of these cells were B cells. In six lymph nodes with numerous EBV-infected cells, EBNA2-positive/LMP1-positive lymphoblastoid cells were detected by IHC. Exceptional cells (in two specimens) were positively labeled with antigen-Z Epstein-Barr replicative activator (ZEBRA) antibody or BamHI Left Frame 1/Not I (BHLF1/Not I) probes, indicating that EBV replication is not enhanced in the lymphocytes. In normal conditions (healthy individuals), small lymphocytes that express a restricted pattern of viral genes do escape immune response, whereas lymphoblastoid cells do not. Thus, impaired immune system may account for the late proliferation of lymphoblastoid cells (Epstein-Barr nuclear antigen [EBNA]2positive/latent membrane protein [LMP]1 positive) in HIV-infected patients, and could explain why EBV-driven, acquired immunodeficiency syndrome (AIDS)-related, non-Hodgkin's lymphoma occur more frequently in patients with low CD4-positive T cells.

AIDS-Related Complex↗
PubMed1996

Myelodysplastic syndromes in childhood: report of 49 patients from a French multicentre study. French Society of Paediatric Haematology and Immunology.

We describe the clinical, cytological and cytogenetic features of 49 cases of myelodysplastic syndromes (MDS) in childhood. Three children had received prior cytotoxic treatment (group 1); all of these had cytogenetic abnormalities and died shortly after diagnosis. 22 children had constitutional anomalies (group 2). The remaining 24 MDS were considered as 'primary' (group 3). Hypoplastic marrow was found in nine cases, and only 53% of the MDS fitted the adult FAB classification. Transformation to AML occurred in 11 cases, development of aplastic anaemia in three cases, and spontaneous remission in one case each of RA and RAEB. Differences were observed between groups 2 and 3 in terms of mean age at diagnosis (11.1 months v 5 years), rate of cytogenetic anomalies (15% v 38%) and rate of progression towards acute leukaemia (13% v 29%). In group 2, all the fur girls studied exhibited a polyclonal pattern of X-inactivation, which suggests that MDS may be only the haematological expression of an embryological defect with different target tissues. This study suggests that some MDS in childhood can exhibit particular features such as congenital anomalies associated with MDS, bone marrow hypoplasia, polyclonality, and spontaneous remission. It emphasizes that the FAB classification is not adequate for children and addresses the question of whether these MDS are always malignant diseases.

Adolescent↗
PubMed1996

Oligonucleotide clonospecific probes directed against the junctional sequence of t(14;18): a new tool for the assessment of minimal residual disease in follicular lymphomas.

Follicular lymphomas are often associated with t(14;18) chromosomal translocation. The rearrangement site (bcl-2/JH junctional region) between the two chromosomes is hypervariable regarding its size and DNA sequence, and is a potential specific marker for the neoplastic clone of each patient. We report the use of the polymerase chain reaction (PCR) technique for detecting and sequencing clonal bcl-2/JH rearrangements in lymph nodes and/or bone marrow specimens from patients with follicular lymphoma. 53 patients at diagnosis (n = 40) or at relapse (n = 13) were studied. 25 of these 53 cases were found to have the t(14;18) translocation involving either the major breakpoint region (MBR) (n = 21) or the minor cluster region (mcr) (n = 4). Since our PCR technique could detect the translocation in 1/10(6) cells we had to distinguish malignant cells from possible t(14;18)-bearing non-malignant cells which could be present during and after treatment. The bcl-2/JH junctional regions were therefore sequenced in order to synthesize an anti-junction oligonucleotide probe specific for each patient's malignant clone (clonospecific probe). Using these clonospecific probes for hybridization it was possible to detect one malignant cell mixed with 10(6) normal cells. 28 patients with advanced stage (stage III and IV), had been enrolled for treatment with myeloablative chemoradiotherapy and autologous bone marrow transplantation (ABMT). In 12 of these patients bcl-2/MBR translocation was found at diagnosis and used as a marker to detect the presence of residual lymphoma cells in serial bone marrow (BM) and peripheral blood (PB) samples. In three relapsed patients (with available tissue samples at diagnosis and relapse), clonospecific probes clearly demonstrated the same bcl-2/JH junction, thus confirming that the relapse occurred from the same malignant clone, and which remained stable without any clonal evolution of its junctional region throughout the course of the disease. These results demonstrate the value of the t(14;18) clonospecific probes as a diagnostic tool in the detection of minimal residual disease and relapses in patients with follicular lymphoma.

Chromosomes, Human, Pair 14↗
PubMed1996

Epstein-Barr virus latent and replicative gene expression in gastric carcinoma.

Recent reports demonstrated the presence of Epstein-Barr virus (EBV) in about 10% of gastric carcinoma cases, particularly in Asian populations. We carried out a retrospective assessment of the detection rate of EBV gene products in 59 cases of gastric carcinoma of various histological subtypes. In situ hybridization using non-isotopic EBER and BHLF1 oligoprobes, and immunohistochemistry using antibodies to latent membrane protein 1 (LMP-1) were applied to paraffin-embedded sections. Tumour cells in five out of 59 cases (8.5%) were found to be EBER positive by in situ hybridization, but no staining was observed with LMP-1 antibodies. Four EBER positive cases were lymphoepithelioma-like carcinomas and one case was a well differentiated adenocarcinoma, suggesting a stronger association with the former subtype. Among the four EBER positive lymphoepithelioma-like carcinomas, BHLF1 transcripts were expressed in one case in a few tumour cells, indicating the possible activation of a lytic cycle. In nine cases (including three EBER positive cases) a few scattered EBV-infected lymphocytes were seen in the normal mucosa but we were unable to detect any EBER positive normal epithelial cells. Our results show that, in a French population, the incidence of EBV-associated gastric carcinoma is similar to that in other geographic areas. The clinical implications of these findings, however, remain unclear.

Adult↗
PubMed1996

Inflammatory pseudotumor of the liver. Evidence for follicular dendritic reticulum cell proliferation associated with clonal Epstein-Barr virus.

We describe an "inflammatory pseudotumor" of the liver that, which on detailed investigation, proved that the spindle-cell component of this lesion is derived from follicular dendritic reticulum cells (FDRC). This contention is supported by morphologic observations and by immunophenotype. The FDRC population contain Epstein-Barr virus (EBV). It is known that FDRC express the EBV receptor CD21. In this particular case, the FDRC contained clonal EBV genomes, EBV RNA (EBER) transcripts, and expressed EBV latent membrane protein (LMP1). DNA sequencing of PCR products showed three point mutations compared with the standard LMP1 sequence of the EBV strain B95-8. The findings in this case corroborate those of other investigators concerning the possible role of EBV in the development of some inflammatory pseudotumors, including the recent production of functionally active EBV-transformed FDRC-like cell lines. This association could prove instructive in delineating the histogenesis of these tumors and further assist in making prognostic and therapeutic decisions.

Aged↗
PubMed1996

Hodgkin's disease following mycosis fungoides: phenotypic and molecular evidence for different tumour cell clones.

AIMS: (1) To assess the clonality of tumour cells in two patients with mycosis fungoides who subsequently developed Hodgkin's disease; and (2) to determine whether there is a clonal relation between these two disorders. METHODS: Cutaneous tissue samples involved by mycosis fungoides and lymph nodes involved by Hodgkin's disease from both patients were investigated by immunohistochemistry and the polymerase chain reaction. RESULTS: Mycosis fungoides tumour cells in both patients expressed multiple T cell associated antigens; Reed-Sternberg (RS) cells had the null phenotype. T cell receptor gamma chain genes were clonally rearranged in mycosis fungoides cells but not in RS cells, including variants, in both patients. In the patient with intermediate transformation to large cell lymphoma, immunoglobulin heavy chain genes were rearranged in the cutaneous tumour, but not in the lymph node involved by Hodgkin's disease. CONCLUSION: The divergent antigen expression and gene rearrangements observed in these two patients strongly suggest that Hodgkin's disease and mycosis fungoides are not derived from a single tumour cell clone.

Clone Cells↗
PubMed1996

Bcl-x gene expression in Hodgkin's disease.

Bcl-x is a Bcl-2-family protein that has been previously detected in cortical thymocytes, plasma cells, and activated lymphocytes. We report here on the high detection rate of the Bcl-x protein found in 86% of Hodgkin's disease samples and on the significance regarding its complex role among the Bcl-2-family of proteins: Bcl-x is known to heterodimerize with Bcl-2 (an anti-apoptosis protein) and with Bax, a potent inducer of cell death. Moreover, recent evidences show that Bcl-x may induce multiple drug resistance in vitro, suggesting that chemical or biological interactions with this protein may have potential therapeutic value in Hodgkin's disease.

Apoptosis↗
PubMed1996

Immunodetection of apoptosis-regulating proteins in lymphomas from patients with and without human immunodeficiency virus infection.

The expression of the apoptosis-regulating genes Bcl-2, Bcl-x, Bax, Mcl-1, and p53 analyzed in 4 cases of human immunodeficiency virus (HIV)-associated Hodgkin's disease, in 36 cases of HIV-related non-Hodgkin's lymphomas (NHLs), and in 109 cases of non-HIV-related NHLs by using immunohistochemistry. HIV-associated Hodgkin's disease samples were positive for all markers. For the HIV-related NHL samples, 36, 66, 88, 100, and 94% of the cases were Bcl-2, Bcl-x, Bax, Mcl-1, and p53 were found to be expressed in 69, 65, 82, 83, and 42%, respectively. No significant differences were observed in Bax and Mcl-1 staining between HIV-unrelated NHLs of B cell and T cell types. In contrast, Bcl-2 was positive in 66/79 (83%) and 10/30 (33%) of B cell and T cell HIV-unrelated NHLs, respectively (P2 < 0.001). Peculiar patterns were observed for hairy cell leukemia (Bax+, Bcl-2+, Mcl-1-) and for anaplastic large cell lymphoma (Bax+, Mcl-1+, Bcl-2-) in HIV-unrelated NHLs. Of interest, all cases with a positive expression of Bax were also found to express either Mcl-1 and/or Bcl-2, suggesting that Mcl-1 and Bcl-2 may counteract the pro-apoptosis function of Bax in vivo by protein-protein interaction within the tumor cell, as demonstrated previously in vitro. These results suggest that apoptosis regulation may have a role in the pathogenesis of some HIV-related and HIV-unrelated NHLs.

Apoptosis↗
PubMed1996

Kaposi's sarcoma-associated herpesvirus in non-AIDS related lymphomas occurring in body cavities.

DNA sequences belonging to the recently discovered Kaposi's sarcoma-associated herpesvirus (KSHV), now provisionally designated human herpesvirus 8, have been previously identified in an uncommonly occurring subset of AIDS-related lymphomas, referred to as body-cavity-based lymphomas (BCBLs), which present as lymphomatous effusions. Pyothorax-associated lymphomas (PALS) are non-Hodgkin's lymphomas that arise in the pleural cavity after long-standing pleural inflammation resulting from therapeutic artificial pneumothorax or from tuberculosis pleuritis. Although PALs present as solid tumor masses, they are otherwise similar to BCBLs in that they also are B cell lymphomas, usually exhibit immunoblastic morphology, and contain Epstein-Barr virus. We investigated whether KSHV sequences are present in 2 BCBLs in patients without AIDS and 12 in Japanese and 2 French PALs. The 2 BCBLs were positive for KSHV sequences, whereaas all 14 PALs were KSHV negative. This finding strongly suggests that BCBLs and PALs are distinct clinicopathological entities and further strengthens the association between the presence of KSHV and an effusion phenotype. Based on these findings, we propose replacing the term body-cavity-based lymphoma with the term primary effusion lymphoma, which describes these non-Hodgkin's lymphomas more accurately and avoids confusion with other lymphomas that may occur in the body cavities, such as the PALs.

Aged↗
PubMed1996

Detection of t(2;5)(p23;q35) translocation by reverse transcriptase polymerase chain reaction and in situ hybridization in CD30-positive primary cutaneous lymphoma and lymphomatoid papulosis.

The t(2;5) generates a chimeric NPM-ALK transcript encoded by the nucleophosmin NPM gene fused to the anaplastic lymphoma kinase gene ALK. Using a reverse transcriptase nested polymerase chain reaction assay we have detected NPM-ALK transcripts within CD30+ primary cutaneous lymphoma and lymphomatoid papulosis (LP). The t(2;5) was identified in 4 out of 9 CD30+ anaplastic lymphomas and in 1 out of 4 CD30+ pleomorphic lymphomas. Moreover, the t(2;5) was detected in 3 out of 10 LPs. All NPM-ALK-positive lymphomas and 1 NPM-ALK-positive LP exhibited a clonal rearrangement of the T cell receptor gamma-chain gene. The t(2;5) was detected in 2 cases of LP without other evidence for a clonal lymphoid population. To identify cells carrying the t(2;5) translocation, we used immunohistochemistry to detect the ALK-encoded p80 protein and in situ hybridization for the specific detection of NPM-ALK transcripts. Both p80 protein and NPM-ALK transcripts were expressed by anaplastic or large CD30+ lymphoma cells with positive NPM-ALK amplification. The presence of t(2;5) in a subset of CD30+ cutaneous lymphoma and LP may indicate a common pathogenesis with a subset of anaplastic nodal lymphoma.

Adult↗
PubMed1996

[Splenic lymphoma with villous lymphocytes: morphologic, immunologic and molecular study. Report of three cases].

Splenic lymphoma with villous lymphocytes (SLVL) is a low grade lymphoproliferation characterized by a massive splenomegaly, an absence of lymphadenopathy and the presence in the peripheral blood of atypical B-lymphocytes with hairy-cell appearance. We have studied the morphological, immunological and molecular characteristics of 3 cases of SLVL. SLVL presented on blood smears characteristic irregularities of the plasma membrane consisting in thin and short villi unevenly distributed. The main phenotype was CD5-, CD11c+, and CD25-, but individual SLVL cases can not be identified by using immunohistochemical criteria alone. Clonal rearrangements of the immunoglobulin heavy chain gene were found in all 3 cases and in one case presented a bcl2-JH rearrangement. SLVL are clonal B-cell lymphoproliferations and can be associated with t(14; 18) translocation.

Aged↗
PubMed1995

A novel antigen detected by the CBF.78 antibody further distinguishes anaplastic large cell lymphoma from Hodgkin's disease.

A novel antigen detected by the CBF.78 monoclonal antibody (MoAb) is strongly expressed on cortical thymocytes and weakly expressed on resting peripheral T lymphocytes. Expression of the antigen is increased on phytohemagglutinin (PHA)- and anti-CD3-activated T lymphocytes and on Epstein-Barr virus-transformed B lymphocytes. The CBF.78 immunoprecipitated a protein of 116 kD from resting and PHA-activated peripheral blood mononuclear cells. CBF.78 MoAb did not inhibit T-cell proliferation induced by anti-CD3 antibody. This MoAb was effective for immunostaining on paraffin sections after microwave-oven heating of tissue sections. Among malignant lymphomas, the antigen recognized by CBF.78 MoAb was found to be mainly expressed by T-cell lymphomas (49+ of 74), particularly those of high-grade malignancy (31+ of 36), whereas only occasional B-cell lymphomas (4+ of 107) expressed the antigen. A distinctive pattern of reactivity was shown by 108 cases of anaplastic large cell lymphomas. Strong positivity for CBF.78 antibody was observed in 86+ of 108 cases, irrespective of B, T, or null phenotype. This multicenter study suggests that CBF.78 MoAb could be of diagnostic value in differentiating Hodgkin's-like anaplastic large cell lymphomas from cases of Hodgkin's disease rich in neoplastic cells. Only a few cases of Hodgkin's disease (13+ of 126) showed rare Reed-Sternberg cells that stained, In these few cases, staining was weak to moderate and confined to cytoplasm. CBF.78 MoAb was nonreactive with all nonhematopoietic neoplasms examined (0+ of 48). Further studies should delineate the function of this new antigen and its clinical utility.

Animals↗
PubMed1995

High expression of the bcl-x gene in Reed-Sternberg cells of Hodgkin's disease.

The expression of bcl-x protein, a bcl-2-related protein present in cortical thymocytes, activated lymphocytes, and plasma cells of reactive lymph nodes, was investigated in 44 cases of Hodgkin's disease (HD) in parallel with bcl-2 and Epstein-Barr virus (EBV) status. Eighty-six percent of the cases were positive for bcl-x, among them 27% with a strong signal in more than 75% of the Reed-Sternberg cells. Positivity for bcl-x was found in, respectively, 100% and 92% of the nodular sclerosis and mixed cellularity subtypes, although 4 cases of lymphocyte predominance subtype were negative. This finding was in contrast with the weaker positivity for bcl-2 staining in 44% of the cases. EBV small RNAs were detected in 43% of the cases by using in situ hybridization. Of interest, 100% of the EBV-positive samples were positive for bcl-x, whereas only 38% of these cases were bcl-2 positive. Our findings show that the bcl-x gene expression is high in HD, suggesting that bcl-x may have a role in the pathogenesis of at least some cases of HD via apoptosis regulation.

DNA, Viral↗
PubMed1995

Rat monoclonal antibodies differentiating between the Epstein-Barr virus nuclear antigens 2A (EBNA2A) and 2B (EBNA2B).

Rat monoclonal antibodies were produced against the C-terminus of Epstein-Barr virus nuclear antigens 2A (EBNA2A) and 2B (EBNA2B) expressed as bacterial trpE fusion proteins. The initial screening was performed using a soluble bacterial extract containing the fusion proteins. Positive hybridomas were confirmed by immunofluorescence on SF158 (Spodoptera frugiperda) insect cells infected with recombinant baculovirus (Autographa californica nuclear polyhedrosis virus) and expressing the complete EBNA2A or EBNA2B genes. We selected a panel of antibodies which reacted either with both antigens or specifically with EBNA2A or with EBNA2B. The antibodies were extensively characterized using immunoprecipitation, Western blotting, epitope mapping on synthesized peptide segments of EBNA2A, immunocytology, and immunohistology on both cryostat sections and paraffin sections of AIDS-associated primary central nervous system lymphomas.

Animals↗
PubMed1995

Mutational hot spots within the carboxy terminal region of the LMP1 oncogene of Epstein-Barr virus are frequent in lymphoproliferative disorders.

We have recently identified in Epstein-Barr virus (EBV) positive Hodgkin's disease (HD) a variant of the latent membrane protein 1 (LMP1) oncogene characterized by four point mutations and a 30 base pair deletion. These findings led us to test whether such mutants were also present in other lymphoproliferative disorders (LPD). We analysed 98 EBV DNA positive cases (67 LPD, 15 benign conditions, 16 lymphoblastoid cell lines) by PCR for deletions within the LMP1 gene. DNA sequencing of the region coding for the carboxy terminal protein domain was performed on 24 cases. In 13 cases the same combination of 4 point mutations at positions 168,320, 168,308, 168,295 and 168,225 was identified. Of these cases, 12 had an additional point mutation at position 168,357 and eight at position 168,355, and nine had a 30 base pair deletion including nucleotides 168,285 to 168,256. These deletion mutants were identified in HD, angioimmunoblastic lymphadenopathy, B-immunoblastic lymphoma, peripheral T-cell lymphoma, and two lymphoblastoid cell lines. Our findings reveal a high frequency of non-random point mutations at preferential sites within the 3' (carboxy terminal) region of the LMP1 oncogene. The association of these mutational hot spots with LPD suggests that they are involved in EBV related lymphomagenesis and that they define a clinically relevant EBV strain.

Antigens, Viral↗