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P Brousset

Publications and source records attributed to P Brousset.

At least 73 records · Page 4Linked to original sources
PubMed1997

[Etiological aspects of reactive hemophagocytoses: retrospective study in 99 patients].

We describe the causes of reactive hemophagocytic process in a retrospective study including 99 patients. The main diagnosis were: lymphomas (18 cases), pyogenic bacteria infections (15 cases), herpes virus infections (12 cases), other infections (multiple, parasitic, fungal, mycobacterial, unidentified) (11 cases), acute hepatitis (five cases), systemic lupus erythematosus (three cases). We also found numerous other diseases involving the reticuloendothelial system. The cause remained undetermined in 16 cases. Lymphoma accounted for 64% of the cases in previously healthy patients who had been febrile for more than 10 days at the time of the diagnosis of reactive hemophagocytic process, and for 31% in HIV-positive patients. Lymphomas were rare (5%) in non HIV-positive, immunosuppressed patients. In this setting and in previously healthy patients who had been febrile for less than 10 days, infectious diseases were widely dominant (respectively 60% and 86% of the cases). Those were mainly due to pyogenic bacteria and to herpes virus. A rapidly fatal evolution occurred in some cases of lymphomas-related hemophagocytic process. These data support the choice of aggressive investigations in order to diagnose lymphoma in previously healthy patients presenting with reactive hemophagocytic process who have been febrile for more than 10 days, and in selected HIV-patients. Such a procedure is not recommended in the other cases.

Adolescent↗
PubMed1997

Reed-Sternberg cells and "bystander" lymphocytes in lymph nodes affected by Hodgkin's disease are infected with different strains of Epstein-Barr virus.

In most cases of Epstein-Barr virus (EBV)-associated Hodgkin's disease (HD), EBV-positive Reed-Sternberg (RS) cells and rare EBV-positive reservoir lymphocytes coexist in lymph nodes. Here we show that, in two cases of EBV-associated HD, strains infecting RS cells and reservoir lymphocytes of the same patient have different BNLF-1 genes. This suggests that RS cells and reservoir lymphocytes of the same patient are infected by different EBV strains.

Animals↗
PubMed1997

Telomerase activity in human thyroid carcinomas originating from the follicular cells.

Telomerase activity is known to be absent from most normal and well-differentiated tissues, although being detectable in the vast majority of malignant tumors. An increasing number of reports demonstrate that telomerase may be activated in benign tumors, such as adenomas. We have investigated a series of normal and neoplastic thyroid tissues for the presence of telomerase activity. As expected, all normal thyroid tissues (n = 20) had no display of telomerase activity. Amongst cancers, the incidence of telomerase activity varied with the histological subtypes. Telomerase activity was present in only 3/15 cases (20%) of papillary carcinomas. Telomerase activity was more frequently detected in follicular (4/6) and in undifferentiated (2/3) carcinomas. Unexpectedly, one case (1/12) of adenoma contained high levels of telomerase activity. Taken together, these results indicate that telomerase may play some role in the pathogenesis of thyroid tumors, in particular in follicular and undifferentiated carcinomas that are known to have the most aggressive behavior.

Adenocarcinoma, Follicular↗
PubMed1997

Deletion variants within the NF-kappaB activation domain of the LMP1 oncogene in acquired immunodeficiency syndrome-related large cell lymphomas, in prelymphomas and atypical lymphoproliferations.

The latent membrane protein 1 (LMP1) oncogene of Epstein Barr virus (EBV) is expressed in tumor cells of acquired immunodeficiency syndrome (AIDS) related lymphomas, HIV-negative, EBV-associated malignant lymphoproliferations, nasopharyngeal carcinoma, as well as in reactive immunoblasts of infectious mononucleosis. Naturally occurring LMP1 deletion variants (LMP1-del), characterized by clustered mutations and a distinct 30 base pair deletion within the carboxy terminal domain of LMP1, essential for maximal NF-kappaB stimulation, have been identified in the same conditions. These variants prevail in AIDS-related lymphomas, and are associated with clinically aggressive behaviour in HIV-negative lymphomas, and are frequent in prelymphomatous and reactive states. Functional studies showing a growth advantage of cells infected by these variants may explain the accumulation of LMP1-del in these entities. In the carboxy terminal NF-kappaB activation domain of LMP1, evidence of a hypervariable region close to the highly conserved 23 outermost amino acids essential for malignant transformation, may reflect the natural selection of growth promoting variants involved in signalling pathways. The prevalence of the same mutational pattern in AIDS-related lymphoma as well as in hyperplastic reactive states and prelymphomas supports the hypothesis that these variants confer a growth advantage manifested under impaired cellular immunity.

Amino Acid Sequence↗
PubMed1997

[Techniques for detection of telomerase activity in tissue samples. Diagnostic and prognosis importance].

Telomerase activation has been shown to be an almost universal property of malignant tumors evoking its role in the immortalisation process. We used the recently described sensitive and rapid detection assay called telomeric repeat amplification protocol (TRAP) to detect telomerase activity in neoplastic and non neoplastic tissues. Human telomerase is a ribonucleoprotein which functions as a telomere terminal transferase by adding multiple repeats of the TTAGGG hexamer at the 3'-OH ends of either telomeres or oligonucleotide specifically designed for the TRAP assay. Whenever present, telomerase activity is revealed on acrylamide gel by a six nucleotide ladder of extension products. Detection of telomerase activity may be evaluated for differentiating neoplastic from non neoplastic tissues. In addition, quantitation of telomerase activity may serve as prognostic marker for malignant tumors.

Autoradiography↗
PubMed1997

Cutaneous non-epidermotropic lymphoma associated with human immunodeficiency virus infection.

A case of pure non-epidermotropic cutaneous lymphoma in a human immunodeficiency virus-infected patient is reported following a viral opportunistic infection [cytomegalovirus (CMV) hepatitis]. The lymphoid infiltrate was Epstein-Barr virus and CMV negative with a CD30-positive T-cell phenotype. Molecular analysis demonstrated T cell receptor gene rearrangement, but a non-aggressive disease course was noted supporting a cautious therapeutic approach in this case.

Cytomegalovirus Infections↗
PubMed1996

Epstein-Barr virus (EBV)-associated lymphoproliferations in severe combined immunodeficient mice transplanted with Hodgkin's disease lymph nodes: implications of EBV-positive bystander B lymphocytes rather than EBV-infected Reed-Sternberg cells.

To establish an in vivo model for the study of Hodgkin's disease and Reed-Sternberg (RS) cells, 25 lymph node tissue samples involved by Hodgkin's disease were grafted into severe combined immunodeficiency (SCID) mice. Ten Epstein-Barr virus (EBV)-associated tumors were obtained in SCID mice. EBV-positive tumors growing in SCID mice were correlated with the presence of EBV-positive nonneoplastic B cells in patient tumors (90% v 26.6%; P<.01) and was independent of the EBV status of RS cells. Our results suggested that EBV-positive tumors growing in SCID mice originated from normal EBV-positive small lymphocytes (bystander B lymphocytes). We also compared the characteristics of these tumors with those obtained after transplantation of 15 non-Hodgkin's lymphoma and four reactive lymph nodes. The latent period to observe a growing tumor in SCID mice was similar between the two groups (12.86 +/- 5.59 weeks for Hodgkin's disease v 13.6 +/- 5.36 weeks for non-Hodgkin's lymphoma and reactive lymph nodes). The relatively high number of EBV-positive small lymphocytes detected in Hodgkin's disease and T-cell lymphoma compared with B-cell lymphoma may account for the greater percentage of EBV-positive tumors obtained in SCID mice. Our results show that SCID mice do not provide the growth conditions that are required for in vivo growth of RS cells. We noted in some SCID tumors, the presence of binucleated and/or multinucleated giant cells resembling RS cells. However, the presence of such cells was not restricted to mice grafted with lymph nodes involved by Hodgkin's disease. We postulate that in previous reports, cells resembling RS cells were just binucleated EBV-positive lymphoma blastoid cells rather than actual RS cells.

Adult↗
PubMed1996

Frequent expression of the cell death-inducing gene Bax in Reed-Sternberg cells of Hodgkin's disease.

The expression of a cell death-inducing gene, Bax, was investigated in 52 cases of Hodgkin's disease in parallel with Epstein-Barr virus and was compared with the immunodetection of other apoptosis-regulating proteins, Mcl-1, Bcl-2, and Bcl-x. Bax immunostaining was found in 92% of the cases, among them 28% with a strong signal in more than 75% of the Reed-Sternberg cells. Mcl-1 was positive in 80% of the cases, whereas Bcl-2 and Bcl-x were found in 53% and 88% of the cases, respectively. Of 48 (89%) Bax-positive tumors, 43 were found to express apoptosis-inhibiting proteins such as Mcl-1 or Bcl-2. With the exception of 1 case, all Bax-positive tumors also expressed either Bcl-2, Bcl-x, Mcl-1, or combinations of these anti-apoptotic proteins. No correlation was found between Bax expression and the presence of apoptotic cells as detected by morphology and the in situ 3' OH-DNA end-labeling technique. Our findings show that the apoptosis-inducing gene Bax expression is frequently expressed in Hodgkin's disease, providing a potential explanation for the good chemoresponses generally obtained for patients with this neoplastic disorder.

Apoptosis↗
PubMed1996

Deletion variants within the NF-kappa B activation domain of the LMP1 oncogene prevail in acquired immunodeficiency syndrome-related large cell lymphomas and human immunodeficiency virus-negative atypical lymphoproliferations.

This sequencing study of 17 acquired immunodeficiency syndrome-related lymphomas (9 primary brain, 8 systemic) and 8 human immunodeficiency virus-negative atypical lymphoproliferations expressing large amounts of the latent membrane protein 1 (LMP1) of Epstein-Barr virus was performed to characterize the carboxy terminal NF-kappa B activation domain of LMP1 at the molecular level in an immunocompromised host. In-frame deletions within the NF-kappa B activation domain were identified in all but 2 primary brain lymphomas, 4 systemic lymphomas, and 4 atypical lymphoproliferations, ie, in 60% of cases. In addition, non silent point mutations (range 1 to 5, mean 3.3) were detected in all cases. Although all changes occurred within the first 100 nucleotides of the carboxy terminal NF-kappa B activation domain--a critical sequence for the protein half-life--not a single point mutation was found in the remaining 62 nucleotides, necessary for malignant transformation. Such a clustering of nonrandom sequence variations, associated with a high oncoprotein expression in immunocompromised hosts, suggests that this part of the LMP1 oncogene behaves as a hypervariable region with natural selection of growth-promoting variants through prolongation of the protein half-life.

Amino Acid Sequence↗
PubMed1996

[Kikuchi syndrome, Hashimoto thyroiditis and lupus serology. Apropos of a case].

Histiocytic necrotizing lymphadenitis (Kikuchi's disease) is an uncommon disease of the cervical lymph nodes occurring in young women, commonly associated with various auto-immune or infectious diseases. We describe the case of a 17 year-old girl who presented a Kikuchi's lymphadenitis occurring concomitantly with Hashimoto's thyroiditis and lupus serology as anti-nuclear, anti-DNA, anticardiolipid antibodies and hypocomplementemia. The patient was treated with prednisone and hydroxychloroquine. Thirty months after, she is doing well and hydroxychloroquine is continued.

Adolescent↗
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

Predominant expression of the long isoform of Bcl-x (Bcl-xL) in human lymphomas.

Bcl-x is a member of the bcl-2 family of proteins which are characterized by their ability to modulate apoptosis. Alternative splicing results in two distinct bcl-x mRNAs encoding a long isoform, bcl-xL, which acts as a bcl-2 agonist; and a short isoform, bcl-xS, which inhibits bcl-2 effects. The aim of the study was to determine whether bcl-x is expressed in lymphoma tissues and to characterize the respective production of bcl-xs and bcl-xL. We investigated the expression of bcl-x mRNA in a series of 50 non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) cases using a RT-PCR method in order to amplify both transcripts simultaneously, and to estimate their relative abundance. The rearrangements of the bcl-2 gene were analysed by RT-PCR expression of the hybrid bcl-2-lgH mRNA. In addition, 20 PCR-positive NHL cases and three HD cases were analysed by immunohistochemistry using bcl-x polyclonal antisera. RT-PCR showed bcl-x expression in 43/45 NHLs and 5/5 HD cases. The bcl-xL transcript was predominant in all positive cases and was associated with variable amounts of bcl-xS. There was no significant correlation between the profile of bcl-xL/bcl-xS expression and the histological and immunological subtyping. Bcl-x immunodetection was positive in the neoplastic cell component in all analysed cases, but the degree of staining was highly variable between cases. Expression of the hybrid bcl-2-IgH gene was detected by RT-PCR in five cases of follicular NHL and in one case of HD, but this group of tumours did not display a particular profile of bcl-xL/bcl-xS expression. We conclude that bcl-x is commonly expressed by malignant cells in various types of malignant lymphomas, with a predominance of the bcl-xL transcript. Since the corresponding bcl-xL isoform can block the cell death machinery and potentialize bcl-2 effects, it may be involved in some pathways of lymphomagenesis.

Base Sequence↗
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↗