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Biomedical subjects

Nicole Brousse

Publications and source records attributed to Nicole Brousse.

At least 37 records · Page 2Linked to original sources
PubMed2004

High level of glutathione-S-transferase pi expression in mantle cell lymphomas.

PURPOSE: Prognosis of mantle cell lymphoma (MCL) remains poor. Patients who achieve a response to first line therapy usually relapse, and the probability of cure remains low. Glutathione-S-transferase pi (GST-pi) overexpression has been associated with alkylating agents and anthracycline resistance. GST-pi gene is located in 11q13 and is coamplified along with CCND1 gene in some human solid tumors. EXPERIMENTAL DESIGN: We performed immunohistochemical analysis of GST-pi expression in 24 consecutive MCLs, 12 follicular lymphomas (FLs), and 69 diffuse large B-cell lymphomas (DLBCLs). Cases were classified in three groups: high GST-pi expression (> 50% of cells were stained), moderate (5 to 50% cells were stained), or absent (< 5% cells were stained). GST-pi and CCND1 mRNA levels were also assessed by real-time reverse transcription-PCR analysis. RESULTS: All MCLs exhibit high GST-pi protein expression, compared with 29% of the DLBCLs and none of the FLs. MCLs expressed high levels of GST-pi and CCND1 mRNAs compared with DLBCLs and FLs. There was a strong relation between GST-pi and CCND1 mRNAs transcript levels in MCLs but not in DLBCLs. In conclusion, protein and mRNA GST-pi expression is high in MCL compared with FL and DLBCL. CONCLUSIONS: Overexpression of CCND1 in MCL is associated with a transcriptional up-regulation of the GST-pi gene. Our results suggest that the glutathione system could play a role in drug resistance in MCL.

Adult↗
PubMed2004

New perspectives for children with microvillous inclusion disease: early small bowel transplantation.

BACKGROUND: Microvillous inclusion disease (MVID) is a congenital intestinal epithelial cell disorder leading to lifelong intestinal failure. Despite long-term total parenteral nutrition, life expectancy is extremely reduced because of metabolic or septic complications or liver failure. METHODS: Twelve patients with early-onset MVID were evaluated between 1995 and 2002 for the possibility of small bowel transplantation (SbTx). Three patients died before they could be placed on the waiting list for SbTx, and one patient is still awaiting SbTx. SbTx was contraindicated in one patient. RESULTS: Seven of 12 patients (six boys and one girl) underwent transplantation (three SbTxs and four combined liver-SbTxs). Actuarial survival rates were 100% and 75% in the SbTx and combined liver-SbTx groups, respectively, with a mean follow-up of 3 years (1.1-8.5 years). In contrast, the survival rate was only 40% in the subgroup of five patients who did not undergo transplantation. After transplantation, all patients were weaned from parenteral nutrition: the five patients with an additional colon graft were weaned within 36 days as opposed to the others without colonic transplant who obtained full intestinal autonomy several months after transplantation. The only two surviving patients who did not undergo SbTx remain highly dependent on total parenteral nutrition, which is complicated by repeated episodes of metabolic decompensation. CONCLUSIONS: SbTx alone or in combination with the liver is highly successful in children with MVID, offering them a long-term perspective for the first time. Associated colon grafting markedly improves the outcome and quality of life after SbTx in patients with MVID.

Adolescent↗
PubMed2004

Human herpesvirus 8 (HHV-8)-associated peritoneal primary effusion lymphoma (PEL) in two HIV-negative elderly patients.

Human herpesvirus 8 (KSHV/HHV-8) is associated with all forms of Kaposi sarcoma (KS), with a rare high-grade B-cell non-Hodgkin lymphoma characterized by serous effusions in body cavities called primary effusion lymphoma (PEL) and with some forms of multicentric Castleman disease (MCD). Although mostly observed during AIDS, such disorders have also been described with a lower incidence in human immunodeficiency virus-negative patients. We describe here the features of two novel cases of AIDS-unrelated PEL. Two patients, a 78-year-old man (case 1) and a 86-year-old woman (case 2), both of French origin, presented exudative ascitic effusion containing numerous KSHV/HHV-8(+) EBV(-) large lymphomatous cells of B-cell clonal origin, characterized by a CD45(+) CD30(+) CD19(-) CD20(-) immunophenotype. The PEL tumor cells harbored a homogenous and isolated trisomy 12 in case 1 and an aberrant expression of the T-cell lineage antigen CD7 in case 2. Both patients were lymphopenic at the time of PEL diagnosis and rapidly died with progressive lymphoma. Moreover, patient 2 had a previous history of classic KS and MCD clinically improved after treatment with all-trans-retinoid acid and a concomitant metastatic breast adenocarcinoma. Compared to AIDS-related PEL, these two cases displayed distinct features in particular the advanced age of patients, as observed for Mediterranean KS, and the absence of EBV coinfection.

Aged↗
PubMed2004

Expression of IL-27 in human Th1-associated granulomatous diseases.

Interleukin (IL)-27 is a newly described member of the IL-12 family. It is a heterodimeric cytokine composed of two subunits, p28 and Epstein-Barr virus-induced gene 3 (EBI3). In vitro studies have shown that IL-27 is mainly produced by activated monocytes and dendritic cells. It induces the proliferation of naïve CD4-positive T cells and synergizes with IL-12 for interferon-gamma (IFN-gamma) production. Knock-out mice for the IL-27 receptor (WSX-1/TCCR) have impaired Th1 responses and form abnormal granulomas when injected with bacillus Calmette-Guérin. However, the expression profile of IL-27 in vivo is currently unknown. To investigate the potential role of IL-27 in the development of a Th1 response in humans in vivo, this study has analysed the in situ expression of IL-27 subunits in three types of granulomatous disease (tuberculosis, sarcoidosis, and Crohn's disease), each characterized by a Th1 response. Tissue sections from patients with tuberculosis (n = 9), sarcoidosis (n = 8), or Crohn's disease (n = 7) were analysed by immunohistochemistry with anti-EBI3 and anti-p28 antibodies, in parallel with control tissues (control reactive lymph nodes, n = 14, and control intestinal tissues, n = 11). In granulomatous tissues, EBI3 and p28 co-expression was detected in epithelioid and multinucleate giant cells in granulomas. In addition, sinus or tissue macrophages, endothelial cells, and plasma cells were found to co-express EBI3 and p28. These data support a possible role for IL-27 in human Th1 responses.

Carrier Proteins↗
PubMed2004

Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease).

OBJECTIVES: We tested the hypothesis that defective interactions between adhesion junctions and the cytoskeleton caused by the plakoglobin mutation in Naxos disease lead to remodeling of gap junctions and altered expression of the major gap junction protein, connexin43. BACKGROUND: Naxos disease, a recessive form of arrhythmogenic right ventricular cardiomyopathy, is associated with a high incidence of arrhythmias and sudden cardiac death. Naxos disease is caused by a mutation in plakoglobin, a protein that links cell-cell adhesion molecules to the cytoskeleton. METHODS: Myocardial expression of connexin43 and other intercellular junction proteins was characterized in 4 patients with Naxos disease. Immunohistochemistry was performed in all 4 patients, and immunoblotting and electron microscopy were performed in 1 patient who died in childhood before overt arrhythmogenic right ventricular cardiomyopathy had developed. RESULTS: Connexin43 expression at intercellular junctions was reduced significantly in both right and left ventricles in all patients with Naxos disease. Electron microscopy revealed smaller and fewer gap junctions interconnecting ventricular myocytes. Mutant plakoglobin was expressed but failed to localize normally at intercellular junctions. Localization of N-cadherin, alpha- and beta-catenins, plakophilin-2, desmoplakin-1, and desmocollin-2 at intercalated disks appeared normal. CONCLUSIONS: Remodeling of gap junctions occurs early in Naxos disease, presumably because of abnormal linkage between mechanical junctions and the cytoskeleton. Gap junction remodeling may produce a coupling defect which, combined with the subsequent development of pathologic changes in myocardium, could contribute to a highly arrhythmogenic substrate and enhance the risk of sudden death in Naxos disease.

Adult↗
PubMed2004

[Nodular lymphocyte predominance Hodgkin's disease and its differential diagnosis].

Nodular lymphocyte predominance Hodgkin's disease (NLPHD), previously called nodular paragranuloma, is a rare entity recognized as a clinico-pathological entity distinct from classic Hodgkin's lymphoma. It is an indolent B cell lymphoma derived from a germinal center cell. NLPHD may closely resemble lymphocyte-rich classic Hodgkin's disease (LR-CHD) or T-cell or histiocyte-rich large B-cell lymphoma (TCRLBCL). A reproducible distinction between these entities is difficult but the classification is prognostically relevant. NLPHD is characterized by neoplastic "popcorn" cells CD20+ CD30- CD15- EMA+ Bcl6+ scattered within a nodular background predominantly composed of small B lymphocytes. LR-CHD neoplastic proliferation is composed of CD20+/- CD30+ CD15+/- EMA- Bcl6+/- Reed Sternberg or Hodgkin's cells, scattered within numerous CD3+ T cells. TCRLBCL is an agressive lymphoma composed of CD20+ CD30- CD15- EMA+/- Bcl6+/- polymorphic neoplastic cells, scattered within a mixture of CD3+ T cells and histiocytes. Epstein Barr virus is detectable within half cases of LR-CHD, but never in NLPHD and rarely in TCRLBCL. The transcription factors BOB1, PU-1, BSAP and IRF4 are new markers that could be useful for differential diagnosis.

Antigens, CD↗
PubMed2004

[Histological features of cutaneous secondary syphilitic lesions: a report of two cases].

Syphilis is a sexually transmitted infectious disease, which currently shows a high increase of incidence in HIV negative patients. These patients often seek medical advice at a stage of secondary syphilis, as the lesions of the primary phase may pass unperceived. Very often, the diagnosis is evoked through a cutaneous biopsy, since the clinical presentation is often misleading. Even though the histological signs are not specific, they may suggest the diagnosis, by showing a psoriasiform epidermal hyperplasia with neutrophil exocytosis and a dermal lichenoid infiltrate rich in plasma cells. However, it is important to underline the great polymorphism of these lesions, which can easily vary according to the stage and /or clinical form. It's very important to have a quick and accurate diagnosis, because the lesions are very contagious, but rapidly and completely cured by an early administrated antibiotic treatment.

Aged↗
PubMed2004

[Classical Hodgkin's lymphoma: biology and grey zones].

Advances in the biology of Hodgkin's lymphoma have lead to the distinction between two entities, "classical" Hodgkin's lymphoma and nodular lymphocyte predominance Hodgkin's lymphoma, previously called nodular paragranuloma, which share distinct clinical aspects. The definition of diagnostic criteria has also been helpful to separate Hodgkin's lymphoma from other lymphomas which can mimick Hodgkin's disease such as anaplastic large cell lymphomas, T-cell/histiocyte rich diffuse large B-cell lymphoma, and some peripheral T-cell lymphomas, mainly angioimmunoblastic-type. Reed-Sternberg cell, the neoplastic cell of "classical" Hodgkin's lymphoma, still retains some secrets. Despite some controversies, there is more and more evidence for a lymphoid B cell origin. The involvement of Epstein-Barr virus, cytokines and/or oncogenes expression in the pathogeny can be suggested, although the precise mechanisms leading to transformation and/or accounting for tumour progression are still elusive. Recently, the roles of the pathway implicating the activation of NFkappaB as well as the autocrine secretion of interleukin-13 have been demonstrated.

Hodgkin Disease↗
PubMed2004

[Pediatric non-Hodgkin lymphomas].

Non Hodgkin lymphoma represent about 5% of childhood cancer. They are the third most common group of cancers in children and adolescents, after cerebral tumours and leukemias. They differ from adult lymphomas as they are all high grade tumours, always diffuse and often associated with extra-nodal diseases. Three main histological subtypes predominate: Burkitt, lymphoblastic and anaplastic large cell lymphomas. As the clinical progression is growing fast and treatment different between the 3 subtypes, the diagnosis must be rapidly done and with accuracy.

Adolescent↗
PubMed2004

Autoimmune enteropathy: molecular concepts.

PURPOSE OF REVIEW: Enteropathies causing temporary or permanent intestinal failure are a big diagnostic and therapeutic challenge for pediatric gastroenterologists. A now well-recognized and distinct entity is in the form of "autoimmune enteropathy (AIE)". Recent advances in the molecular workup of AIE gave first insight into the pathophysiology of AIE. In this review, we discuss new molecular concepts of AIE resulting in new diagnostic and therapeutic possibilities. RECENT FINDINGS: The identification of disease-causing mutations in the FOXP3 gene as a basic defect resulting in AIE points to a defect in regulatory T-cell homeostasis. FOXP3, primarily expressed by CD4+CD25+regulatory T cells, is a potent transcriptional suppressor and key modulator of T-cell functions. Nonfunctional FOXP3 leads to a tremendous hyperactivation of T cells, resulting in autoimmune aggression, such as seen in patients with immune dysregulation, polyendocrinopathy autoimmune enteropathy X-linked (IPEX) syndrome, a subgroup of AIE. There is recent evidence suggesting that a defect of regulatory factors other than FOXP3 might cause AIE. Anti-enterocyte autoantibodies, another main characteristic of AIE, seem to be of a secondary nature and can no more be considered as directly disease causing. SUMMARY: Based on the profound immune dysregulation, new treatment strategies emerged for AIE. The use of T-cell immunosuppressive drugs, such as tacrolimus combined to steroids, seems to be beneficial in some patients; however, long-term remission is not always possible. Bone marrow transplantation might be the treatment of choice in those patients who do not respond to immunosuppression; however, the first encouraging results remain to be confirmed since to date long-term outcome remains mixed.

Journal Article↗
PubMed2004

Bone marrow histological patterns can predict survival of patients with grade 1 or 2 follicular lymphoma: a study from the Groupe d'Etude des Lymphomes Folliculaires.

The influence of bone marrow biopsy (BMB) histology on prognosis and management of follicular lymphomas (FL) remains controversial. A total of 390 patients with grade 1 or 2 FL were prospectively included in the multicentric Groupe d'Etude des Lymphomes Folliculaires trial and their BMB reviewed in order (i) to quantify the ratio of lymphomatous foci (LFo) area to that of BMB size (LFo/BMB), (ii) to determine the BMB patterns for a practical grading of marrow infiltration, (iii) to assess the intra- and inter-observer reproducibility of this grading and (iv) to analyse this grading on event-free (EFS) and overall survival (OS), using univariate and multivariate analyses. A total of 267 patients (68%) had BMB involvement, with inter- and intra-observer reproducibility for classifying the patterns of involvement of 91 and 96%, respectively. Uni- and multivariate analyses demonstrated the adverse influence of (i) a ratio of LFo/BMB > or = 0.1, i.e. three or four nodules/medullary space or > or = 1 nodule + foci of diffuse involvement on EFS (P = 0.03) and (ii) two different histological patterns in the same BMB on EFS (P = 0.004) and OS (P = 0.001). This latter finding was only significant in patients with a high tumour burden and remained significant in multivariate analysis. These results indicate that BMB histology can predict survival of FL patients with a high tumour burden, and may help in defining their treatment.

Adolescent↗
PubMed2003

Retinoids regulate survival and antigen presentation by immature dendritic cells.

Maturation of dendritic cells (DCs) is a critical step for the induction of an immune response. We have examined the role of retinoid nuclear receptor pathways in this process. Retinoids induce DC apoptosis, in the absence of inflammatory signals, through retinoic acid receptor (RAR)alpha/retinoic X receptor (RXR) heterodimers. In contrast, via a cross talk with inflammatory cytokines, retinoids increase DNA binding activity of nuclear factor kappaB in DCs, trigger membrane major histocompatibility complex class II and costimulatory molecule expression, induce the differentiation of immature DCs into mature DCs, and enhance antigen-specific T cell response. This maturation of DCs is mediated via a RXR-dependent/RAR-independent pathway and via an RARalpha/RXR pathway distinct from the one responsible for apoptosis. Apoptosis and activation, mediated through distinct nuclear retinoid receptor pathways, can be dissociated from each other with selective synthetic retinoids. We identify a novel cellular function for retinoids and suggest that selective retinoids might be of interest for controlling antigen presentation.

Antigen Presentation↗
PubMed2003

Langerin+ versus CD1a+ Langerhans cells in human gingival tissue: a comparative and quantitative immunohistochemical study.

Langerhans cells (LC) are dendritic cells of the immune system able to capture intraepithelial pathogens and migrate to regional lymph nodes to present them to naive T cells. Up to now immunohistological studies on human gingival LC have been carried out using antibodies against HLA-DR or CD1a molecules. A new marker of LC called Langerin (CD207) and described, among other subcellular localisations, in the Birbeck granules is now available in immunohistochemistry. The purpose of this in situ study was to quantify and to compare Langerin+ versus CD1a+ LC number in order to show differences in the expression of these molecules, if any, and to determine which marker is the most specific. The present study was conducted using nine frozen healthy gingival samples. Double immunofluorescence procedures were performed with an anti-Langerin antibody revealed by FITC and with an anti-CD1a-PE antibody. Mounted slides were analysed by fluorescence microscopy and quantifications were performed on projected slides associated with a grid of 0.015 mm(2). Our results have shown that 1/ the number of CD1a+ LC was significantly increased (P=0.01) when compared with Langerin+ LC 2/ 92% of Langerin+ LC co-expressed CD1a 3/ only 82% of CD1a+ cells co-expressed Langerin 4/ a positive correlation was noted between CD1a+ and Langerin+ LC numbers. The present study has revealed the heterogeneity in the phenotype of gingival LC population and shown that Langerin seems the most specific marker for the study of LC.

Adolescent↗
PubMed2003

Recurrent partial trisomy 1q22-q44 in clonal intraepithelial lymphocytes in refractory celiac sprue.

BACKGROUND & AIMS: Refractory celiac sprue, a low-grade intraepithelial lymphoma characterized by expansion of clonal intraepithelial lymphocytes with intracellular CD3 epsilon but no surface CD3-T-cell receptor complexes, can be an intermediary step between celiac disease and overt T-cell lymphoma. To gain insight into the mechanisms of lymphomagenesis in celiac disease, we have performed the first cytogenetic study in refractory celiac sprue. METHODS: Karyotypes were performed on: (1) 7 cell lines derived from clonal intraepithelial lymphocytes of patients with refractory celiac sprue; (2) 14 control T-cell lines, either from 4 of 7 patients with refractory celiac sprue or from 10 patients with uncomplicated celiac disease; and (3) bone marrow and peripheral blood lymphocytes in 1 of 7 patients with refractory celiac sprue. Rearrangements were confirmed by in situ hybridization using whole-chromosome painting probes and by comparative genomic hybridization in one patient. RESULTS: A recurrent structural chromosomal aberration leading to partial trisomy of the long arm of chromosome 1 was found in 6 of 7 cell lines from patients with refractory celiac sprue but in none of the control T-cell lines. In one patient with circulating abnormal intraepithelial lymphocytes, the partial trisomy 1q was confirmed on cells freshly isolated from bone marrow and blood. CONCLUSIONS: Refractory celiac sprue is strongly associated with partial trisomy of the 1q region. Gain of chromosome 1q, recently found in 16% of enteropathy-type T-cell lymphoma, may be an early event in lymphomagenesis related to celiac disease and provides a key to investigating molecular mechanisms of lymphoid transformation in this disease.

Adult↗
PubMed2003

Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease.

BACKGROUND & AIMS: The mechanism of intraepithelial lymphocyte hyperplasia, a hallmark of celiac disease, is unknown. We have investigated the role of epithelium-derived interleukin (IL)-15 in the alterations of epithelial homeostasis in refractory celiac sprue, a privileged situation to study the first step of lymphoid transformation and the contribution of intraepithelial lymphocytes to villous atrophy in celiac disease. METHODS: IL-15 expression was assessed in biopsy specimens and isolated enterocytes by combining immunohistochemistry, flow cytometry, and real-time quantitative polymerase chain reaction. The ability of IL-15 to induce growth and survival of clonal intraepithelial lymphocytes lacking surface CD3 and to induce their cytotoxicity and secretion of interferon gamma was tested using soluble IL-15 and coculture in the presence of epithelial cell lines expressing membrane IL-15. RESULTS: IL-15 was massively overexpressed not only in lamina propria but also in the intestinal epithelium of patients with active celiac disease and refractory celiac sprue. IL-15 was not secreted but delivered at the surface of enterocytes. IL-15 specifically induced the expansion and survival of the clonal abnormal intraepithelial lymphocytes that characterize refractory celiac sprue and triggered their secretion of interferon gamma and their cytotoxicity against intestinal epithelial cells. Comparable activating signals could be delivered by IL-15 expressed at the membrane of the T84 enterocyte cell line. CONCLUSIONS: These data provide strong evidence that uncontrolled overexpression of IL-15 in refractory celiac sprue perpetuates epithelial damage and promotes the emergence of T-cell clonal proliferations. Blocking IL-15 might prove useful to treat this severe complication of celiac disease.

Adult↗
PubMed2003

Primary lymphoma of the liver: clinical-pathological features and relationship with HCV infection in French patients.

Primary lymphoma of the liver (PLL) is rare. In some cases, the hepatic lymphoma has been diagnosed in patients who were infected by the hepatitis C virus (HCV). It has been suggested that HCV plays a role in the pathogenesis of lymphoma. The aim of our multicentric retrospective study was to assess the characteristics of PLL and to determine the prevalence of HCV infection in PLL. Thirty-one immunocompetent patients (anti-human immunodeficiency virus, anti-human T-cell leukemia/lymphoma virus negative, no history of allograft) with PLL fulfilled the entire selection criteria. The liver biopsy specimens were reassessed by the same pathologist. The non-Hodgkin's lymphomas were classified according to the World Health Organization classification. Blood samples were tested in 28 patients for antibodies to HCV, and HCV RNA was detected by reverse transcription polymerase chain reaction. In the majority of cases, the clinical, biologic, and radiologic data were nonspecific. Twenty-seven of 31 patients presented a B-cell lymphoma corresponding to the centroblastic morphologic variant of a diffuse, large B-cell lymphoma (22 cases), a Burkitt's lymphoma (1 case), an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (3 cases), and unclassified, small B-cell lymphoma (1 case). The 4 other cases were T-cell lymphomas. The prevalence of HCV infection was 21% (6 of 28 cases). All of these patients were positive for HCV RNA by polymerase chain reaction in blood. Most of the HCV-infected patients presented a high-grade, B-cell type lymphoma. In conclusion, our study confirms the rarity of PLL and demonstrates an increased prevalence of HCV infection.

Adult↗
PubMed2003

Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis.

We have previously described the identification of Artemis, a factor involved in the nonhomologous end joining (NHEJ) phase of V(D)J recombination of T and B cell receptor genes. Null mutations of the Artemis gene result in a complete absence of T and B lymphocytes that is associated with increased cell radiosensitivity, causing the radiosensitive T(-)B(-) SCID (RS-SCID) condition. We presently report the occurrence of hypomorphic mutations of the Artemis gene in four patients from two kindreds. Partially preserved in vivo activity of Artemis is associated with the presence of polyclonal T and B lymphocyte populations, albeit in reduced numbers, along with chromosomal instability and development of EBV-associated lymphoma in two of four patients. This syndrome emphasizes the role of Artemis in the NHEJ pathway of DNA repair and suggests that other, yet ill-defined, conditions associating immunodeficiency and lymphoma could be caused by mutations in genes encoding NHEJ factors.

Adolescent↗