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Biomedical subjects

P Brousset

Publications and source records attributed to P Brousset.

At least 19 recordsLinked to original sources
PubMed2001

Increased vascularization in myeloma.

Several studies have shown that the number of intratumoral vessels can predict the aggressiveness of a solid cancer, development of metastases and patient survival. Does angiogenesis play an important role in myeloma? The aim of our study was to quantify bone marrow vascularity in various stages of proliferative plasma cell disorders (monoclonal gammopathies of undetermined significance (MGUS), stage I multiple myeloma (MM), stage III MM and Waldenström's macroglobulinemia (WM)) and to compare it with that of patients with osteoporosis. The study included 15 MGUS patients, 15 patients with stage I MM, 15 patients with symptomatic stage III MM, 7 patients with WM, 10 patients with osteoporosis, and 10 patients with reactive bone marrow (RBM), matched for sex and age. After iliac crest biopsy, the various vessels (arterioles, capillaries and sinusoids) were labeled with monoclonal antibodies CD34 and counted, and a histomorphometric study was done. The number of arterioles and arterial capillaries was significantly increased in MGUS and myeloma compared with osteoporosis. The number of arterioles and arterial capillaries increased moderately according to the stage of gravity of myeloma. The number of arterioles is negatively correlated with the trabecular bone volume and positively correlated with the eroded surfaces.

Adult↗
PubMed2001

Post renal transplantation human herpesvirus 8-associated lymphoproliferative disorder and Kaposi's sarcoma.

Post-transplantation lymphoproliferative disorders (PTLDs) and Kaposi's sarcoma (KS) are immunosuppression-related tumours developing in solid organ transplant patients. Although the Epstein-Barr virus (EBV) is detected in the majority of the PTLDs during the first year after transplantation, the proportion of EBV-negative PTLDs has increased in recent years. We report a case of a 17-year-old man who developed severe immune haemolytic anaemia, KS and human herpesvirus 8 (HHV-8)-associated, polymorphic-type PTLD 9 months after allogeneic renal transplantation from his HHV-8-seropositive father. It is suggested that: (i) HHV-8 may be associated with EBV-negative, polymorphous-type PTLD occurring less than 1 year after transplantation, and (ii) PTLD may be listed among other tumours, including KS, Castleman's disease and primary effusion lymphoma (PEL), that are related to HHV-8 infection.

Adolescent↗
PubMed2001

Colocalization of the viral interleukin-6 with latent nuclear antigen-1 of human herpesvirus-8 in endothelial spindle cells of Kaposi's sarcoma and lymphoid cells of multicentric Castleman's disease.

Human herpesvirus-8 (HHV-8) also called Kaposi's sarcoma-associated herpesvirus infects spindle cells in Kaposi's sarcoma (KS) and lymphoid cells in multicentric Castleman's disease (MCD). In KS cells, HHV-8 is mainly latent with the expression of latent nuclear antigen-1 (LNA-1), whereas in MCD both lytic and latent antigens are produced by lymphoid cells. We show by immunohistochemical labeling that in KS viral interleukin-6 (vIL-6) is expressed in rare spindle cells, whereas in MCD, vIL-6 is detectable in lymphoid cells around lymphoid follicles but also within the follicular dendritic reticulum cell network. The staining of apoptotic bodies with anti IL-6 antibody suggests the achievement of a complete lytic cycle in a subset of lymphoid cells. Interestingly, in MCD, some areas contained vascular spindle cells latently infected by HHV-8 on the basis of LNA-1 expression. This finding might imply that in MCD, both vascular and lymphoid cells proliferate in response to the viral infection. Double immunostaining with anti LNA-1 and anti vIL-6 in MCD and KS identifies 2 subsets of HHV-8 infected (vascular and lymphoid) cells, some with exclusive expression of LNA-1 and some with coexpression of vIL-6 and LNA-1. This suggests that in vivo the regulation of the expression vIL-6 and LNA-1 protein varies with the cell type. In addition, the detection of infected endothelial cells in MCD may indicate that these cells belong to the reservoir for HHV-8.

Apoptosis↗
PubMed2001

Detection and characterization of human herpesvirus-8-infected cells in bone marrow biopsies of human immunodeficiency virus-positive patients.

We studied 15 bone marrow biopsy specimens from patients with human immunodeficiency virus infection for detection of Kaposi sarcoma herpesvirus (KSHV/HHV-8) DNA sequences by a very sensitive and specific polymerase chain reaction (PCR) assay (with 3 different sets of primers). In addition, we used immunohistochemistry with antiviral interleukin-6 (vIL-6) and anti-latent nuclear antigen-1 (LNA-1) antibodies to localize the infected cells on tissue sections. Among the 15 samples, 6 had positive PCR results with the 3 sets of primers (orf26, orf72, orf75). Interestingly, in 2 of these 6 patients (both with Kaposi sarcoma) vIL-6 and LNA-1 were detected in mononuclear lymphoid cells but not in stromal cells of the bone marrow. The detection of vIL-6--positive lymphoid cells in bone marrow suggests a homing for HHV-8--infected elements in this tissue. The local release of vIL-6 may play some role in the plasmacytosis observed in bone marrow in the acquired immunodeficiency syndrome. HUM PATHOL 32:288-291.

Adult↗
PubMed2001

Simultaneous occurrence of Epstein-Barr virus associated Hodgkin's disease and HHV-8 related multicentric Castleman's disease: a fortuitous event?

Previous serological or molecular studies by means of the polymerase chain reaction have failed to show an association between classic Hodgkin's disease (HD) and human herpesvirus 8 (HHV-8). Using immunohistochemistry, this study re-examines (with anti-LNA1 antibody) the possible association of HHV-8 with HD, particularly in human immunodeficiency virus (HIV) infected patients. HHV-8 was not detected in the Reed Sternberg cells of the cases examined (33 HIV negative and 17 HIV positive), thus confirming the lack of involvement of HHV-8 in HD. Interestingly, a case of HHV-8 positive multicentric Castleman's disease was associated with Epstein-Barr virus positive HD in the same lymph node, which was probably a fortuitous occurrence.

AIDS-Related Opportunistic Infections↗
PubMed2001

Anaplastic large cell lymphoma with the t(2;5)(p23;q35) NPM/ALK chromosomal translocation and duplication of the short arm of the non-translocated chromosome 2 involving the full length of the ALK gene.

This report describes a case of anaplastic large cell lymphoma with the canonical t(2;5)(p23;q35) translocation in association with duplication of the short arm of the non-translocated chromosome 2, as demonstrated by two colour fluorescence in situ hybridisation. Because the tumour cells were tetraploid, these abnormalities were in duplicate, with four copies of the full length ALK gene and two copies of the t(2;5)(p23;q35) translocation. Despite multiple copies of the normal ALK gene, immunohistochemical, reverse transcriptase polymerase chain reaction, and western blot analysis demonstrated that only the fusion gene NPM/ALK was expressed and that normal ALK genes remained silent. Although based on a single case, these data indicate that structural rather than numerical abnormalities of the ALK gene are implicated in the pathogenesis of anaplastic large cell lymphomas.

Anaplastic Lymphoma Kinase↗
PubMed2001

Immunohistochemical assessment of human herpesvirus 8 infection in primary central nervous system large B cell lymphomas.

BACKGROUND/AIMS: Primary central nervous system large B cell lymphomas (PCNSLs) are frequently associated with Epstein-Barr virus (EBV) in patients with AIDS and less frequently in those without AIDS. Human herpesvirus 8 (HHV-8) has been detected in these tumours by the polymerase chain reaction (PCR) at low copy number, suggesting its presence in a cell compartment other than the malignant one. The aim of this study was to use immunohistochemistry to assess HHV-8 infection in a series of PCNSLs from patients with and without AIDS. METHODS: The antibody LN53, which reacts with the latent nuclear antigen 1 (LNA1) of HHV-8, was used on tissue sections from 35 patients (17 with and 18 without AIDS) with PCNSL. In addition, DNA was available for PCR (open reading frame 26 (ORF 26), ORF 72, ORF 75) in three patients (two without AIDS, one with AIDS). RESULTS: None of the 35 cases contained either DNA sequences or LNA1 positive cells. CONCLUSIONS: These results confirm the lack of HHV-8 infection in tumour cells of PCNSL. In addition, HHV-8 infected bystander cells do not express LNA1 latent protein in this setting.

Animals↗
PubMed2001

The role of Epstein-Barr virus in neoplastic transformation.

In this review, we focus on new data from basic, translational and clinical research relating to the Epstein-Barr virus (EBV). Beside its well-known tropism for B lymphocytes and epithelial cells, EBV also infects T lymphocytes, monocytes and granulocytes. After primary infection, EBV persists throughout the life span in resting memory B cells, from where it is reactivated upon breakdown of cellular immunity. In the process of neoplastic transformation, the EBV-encoded latent membrane protein 1 (LMP1) oncogene represents the major driving force. LMP1 acts like a constitutively activated receptor of the tumor necrosis factor receptor family and allows the amplification or bypassing of physiological regulatory signals through direct and indirect interactions with proteins of the tumor necrosis factor receptor-associated factor (TRAF) family. TRAF2-mediated NF-kappaB activation, AP-1 induction and JAK3/STAT activation may result in sustained proliferation leading to lymphoma. The ability of LMP1 to suppress germinal center formation and its capacity to mediate its own transcriptional activation shed new light on the pathogenesis of EBV-associated latency type II lymphoproliferations like Hodgkin's disease and angioimmunoblastic lymphadenopathy. The carboxy terminus of LMP1 is also a reliable marker for individual EBV strain identification and thus offers new possibilities in tracing the molecular events leading to posttransplant lymphoproliferative disorders (PTLDs). Cytotoxic T lymphocytes directed against well-characterized epitopes of EBV latency genes represent an already successful and promising therapeutic approach to EBV-associated lymphomas, in particular PTLDs.

Apoptosis↗
PubMed2001

Increased yield of PCR products by addition of T4 gene 32 protein to the SMART PCR cDNA synthesis system.

Under certain conditions, T4 gene 32 protein is known to increase the efficiency of different enzymes, such as Taq DNA polymerase, reverse transcriptase, and telomerase. In this study, we compared the efficiency of the SMART PCR cDNA synthesis kit with and without the T4 gene 32 protein. The use of this cDNA synthesis procedure, in combination with T4 gene 32 protein, increases the yield of RT-PCR products from approximately 90% to 150%. This effect is even observed for long mRNA templates and low concentrations of total RNA (25 ng). Therefore, we suggest the addition of T4 gene 32 protein in the RT-PCR mixture to increase the efficiency of cDNA synthesis, particularly in cases when low amounts of tissue are used.

DNA, Complementary↗
PubMed2001

[Gene expression profiling by suppression subtractive hybridization (SSH): a example for its application to the study of lymphomas].

Suppression subtractive hybridization (SSH) was used to isolate genes that were differentially expressed in anaplastic lymphoma kinase (ALK)-positive and ALK-negative anaplastic large cell lymphoma. In addition, this approach was applied to Hodgkin's disease cases with different clinical outcomes. SSH combines a normalization step that equalizes the abundance of cDNAs within the sequences to be tested and a subtraction step that excludes the common sequences between the target and the control. In a model system, the SSH technique enriches for rare sequences up to 5,000-fold in one round. We have isolated several genes whose expression varied significantly with regard to the tumour subtypes. There were different genes with known or unknown functions. We aim to compare the results of the SSH approach with those obtained with high density filters. In a near future, we would like to design DNA chips specific of each pathology that could be used for clinical purposes (evaluation of prognosis and therapeutic response).

Gene Expression Profiling↗
PubMed2000

PCR analysis of immunoglobulin heavy chain (IgH) and TcR-gamma chain gene rearrangements in the diagnosis of lymphoproliferative disorders: results of a study of 525 cases.

This report summarizes a cumulative 4-year experience in polymerase chain reaction (PCR) analysis of immunoglobin heavy chain (IgH) and TcR-gamma chain gene rearrangements in 525 cases of lymphoproliferative disorders. Because the sensitivity of the PCR methodology was found to be tissue dependent, in the study of the presence of clonal cell population in tissues containing a small number of polyclonal lymphocytes, such as skin and gastrointestinal biopsy specimens, we used the multiple-PCR run approach. In this latter methodology, we repeat the PCR reaction from the same sample at least three times to confirm the reproducibility of the results. In the study of 273 cases of B- or T-cell lymphomas with characteristic immunomorphological and clinical features, a clonal IgH or TcR-gamma chain gene rearrangement was detected in approximately 80% of cases. A clonal rearrangement involving both IgH and TcR-gamma chain genes was found in 10% of cases of both B-cell and T-cell lymphomas. The study of 167 cases of nonneoplastic lymphoid tissue samples showed the presence of clonally rearranged cell populations for IgH or TcR-gamma genes in 3 and 9% of cases, respectively. We also applied PCR for the study of 85 cases of lymphoproliferations with no definite diagnosis (i.e., benign versus malignant) after immunomorphological analysis. In 65 cases (76%), the correlation of immunomorphological features with the presence (48 cases) or the absence (17 cases) of clonal lymphoid cell populations led to a definite diagnosis. In almost all these cases, the final diagnosis was found to be in agreement with the clinical course. In the 20 remaining cases (24%), no definite diagnosis could be made. We also assessed the value of PCR in detecting bcl-2/J(H) gene rearrangement as an additional clonal marker in the diagnosis of follicular lymphoma. Bcl-2/J(H) rearrangement and/or IgH gene rearrangement was found in approximately 85% (71/85) of follicular lymphoma cases studied.

Adolescent↗
PubMed2000

High concentration of leptin stimulates myeloid differentiation from human bone marrow CD34+ progenitors: potential involvement in leukocytosis of obese subjects.

OBJECTIVE AND DESIGN: As well as its involvement in control of adipose mass and body energy balance, several reports suggest a link between leptin and hemopoiesis. To test its putative role in human hemopoiesis, we developed a homologous system, ie recombinant human leptin treatment of purified CD34+ progenitors from adult human bone marrow. RESULTS: Leptin (50-100 ng/ml) significantly stimulated the appearance of granulocyte-macrophage colonies in the presence or absence of erythropoietin. The concentration of leptin required for this effect was rather high but within the range of plasma leptin levels observed in obesity. Two results further support the hypothesis that leptin may be involved in the leukocytosis associated with obesity: (i) leptin concentrations in bone marrow and plasma of subjects studied were highly correlated; (ii) leptin and leukocyte count were correlated only in obese subjects. Paracrine effects of locally released leptin from bone marrow adipocytes could also be involved in the regulation of hemopoiesis, a hypothesis supported by marrow immunocytochemistry revealing the close association of CD34+ cells with adipocytes and by previous demonstration that leptin is secreted at a high level by these cells. CONCLUSION: These results indicate that leptin acts on human multilineage CD34+ cells and that high plasma leptin levels associated with obesity could participate in the differentiation of granulocytes from hemopoietic progenitors.

Adult↗
PubMed2000

Variation in the histological pattern of nodal involvement by gamma/delta T-cell lymphoma.

AIMS: Gamma-delta (gammadelta) T-cell non-Hodgkin's lymphomas (NHLs) usually present with liver, spleen and marrow infiltration. Lymph node involvement by gammadelta T-cell NHL has been rarely documented so far; its histological pattern needs to be further defined. METHODS AND RESULTS: Two cases of nodal gammadelta T-cell NHL are reported: case 1, a 44-year-old man, presented with cytomegalovirus retinitis and superficial lymphadenopathies. Histological analysis of an inguinal lymph node showed complete destruction by a diffuse pleomorphic lymphoid proliferation, which was positive for CD2, CD3, CD43, CD45, TIA-1 and granzyme B, and displayed a gammadelta phenotype (deltaTCR1+, Vdelta1+, Vdelta2-, Vdelta3-, betaF1-). Bone marrow was normal. Case 2, a male 24-year-old patient with a history of renal transplantation, presented with hepatosplenomegaly and supraclavicular lymph node enlargement. Lymph node architecture was globally preserved. Peripheral sinuses contained scattered nests of medium-sized irregular lymphoid cells. Bone-marrow was infiltrated. Phenotype showed positivity for CD2, CD3, CD45 and TIA1 and expression of gammadelta TCR (deltaTCR1+, deltaV1+, deltaV2-, deltaV3-, betaF1-). Both patients died a short time after diagnosis. CONCLUSIONS: These observations suggest that at least two forms of nodal gammadelta T-cell NHL may be encountered: one mimicking classical alphabeta T-cell NHL, with diffuse pleomorphic cell proliferation, and one displaying sinusoidal neoplastic infiltration suggesting a close relationship with hepatosplenic gammadelta T-cell NHL.

Adult↗