Biomedical subjects

Nicole Brousse

Publications and source records attributed to Nicole Brousse.

At least 19 recordsLinked to original sources

PubMed2006

Do Langerhans cells behave similarly in elderly and younger patients with chronic periodontitis?

OBJECTIVE: The purpose of this study was to compare the number, the distribution and the expression of markers of maturation of Langerhans cells (LC) in elderly and younger patients with chronic periodontitis in order to evidence the effect of aging on LC in inflammatory gingival tissue. METHODS: Gingival tissue specimens presenting chronic periodontitis from 8 elderly patients aged >75 (group E) and from 8 younger patients aged 50-60 (considered as controls, group C) were used for immunohistochemistry with monoclonal antibodies against CD45RB (leucocytes), CD1a (LC), markers of LC maturation (DC-LAMP, CD83) and number of immunolabelled cell subsets was evaluated using image analysis. RESULTS: The difference in the number of CD45RB+ leucocytes in the upper connective tissue between groups was not significant. In group E, the number of CD1a+ LC was significantly decreased (P<0.002) in the epithelium and significantly increased (P<0.0004) in the upper connective tissue. Furthermore, in group E, intraepithelial CD1a+ LC are more often observed in the upper epithelium and their dendritic processes were shorter and less numerous. Concerning the expression of markers of maturation, the numbers of intraepithelial DC-LAMP+ cells and CD83+ cells were significantly increased (P<0.0007 and P<0.02, respectively) in group E. CONCLUSION: During chronic periodontitis in elderly patients, the decrease in the number of intraepithelial LC and the alteration of dendritic processes could be balanced by a cellular distribution often observed in the upper epithelium associated with changes in cell maturation in response to bacterial elements.

Age Factors↗

PubMed2006

Anti-LFA-1 antibody postpones T-cell receptor triggering while preserving generation of regulatory T cells in T-cell receptor anti-HY transgenic mice.

BACKGROUND: Anti-LFA-1 (CD11a) antibody increases allograft survival and/or induces tolerance in murine models, but its mechanisms of action remain to be elucidated. METHODS: Rag-2-/- H-2b recipient mice, bearing a transgenic T-cell receptor specific for the male antigen HY presented by MHC class II molecule, were transplanted with a C57BL/6 (H-2b) male heart with or without administration of anti-LFA-1 antibody from days -1 to 9. RESULTS: Treatment prevented the transient episode of acute graft rejection observed in nontreated mice and maintained a naive phenotype and proliferative characteristics comparable to that of naive transgenic lymphocytes on day 7 during treatment, with decreased IFN-gamma mRNA and increased IL-4 mRNA. On day 14, phenotype and proliferative response of lymphocytes in treated mice was comparable to those of untreated animals. Furthermore, treatment did not interfere with the generation of CD4+Vbeta6+CD25+ (Foxp3) cells that were observed in long-term nontreated tolerant mice. CONCLUSIONS: This in vivo model demonstrates that anti-LFA-1 treatment induced a transient blockade of antigen recognition, which inhibited and postponed induction of signal 1 via the TCR and decreased the intensity of the Th1 response. Importantly, LFA-1 blockade did not disturb spontaneous generation of regulatory mechanism. This treatment would be compatible in clinical settings with other therapeutics inducing regulatory mechanisms.

Animals↗

PubMed2006

Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA).

The purpose of this study is to compare our standard chemotherapy regimen (CHVP [cyclophosphamide, doxorubicin, teniposide, and prednisone]) plus interferon with 4 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by high-dose therapy with autologous stem cell transplantation (ASCT) in treatment-naive patients with advanced follicular lymphoma. Four hundred one patients were included from July 1994 to March 2001: 209 received 12 cycles of CHVP plus interferon alpha for 18 months (CHVP-I arm) and 192 received 4 cycles of CHOP followed by high-dose therapy (HDT) with total body irradiation and ASCT (CHOP-HDT arm). Overall response rates were similar in both groups (79% and 78% after induction chemotherapy, respectively). One hundred thirty-one of the 150 patients eligible for HDT underwent transplantation (87%). Intent-to-treat analysis after a median follow-up of 7.5 years showed that there was no difference between the 2 arms for overall survival (P = .53) or event-free survival (P = .11). Patients with a complete response at the end of the induction therapy had a statistically longer event-free survival and overall survival (P = .02 and < .001, respectively). After long-term follow-up, our study showed that there was no statistically significant benefit in favor of first-line high-dose therapy in patients with follicular lymphoma. High-dose therapy should be reserved for relapsing patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Study of the impact of liver transplantation on the outcome of intestinal grafts in children.

BACKGROUND: Successful small bowel transplantation remains a challenge due to the septic and immune content of the gut. The possible beneficial role of the liver was assessed in pediatric recipients of isolated intestinal and liver intestinal combined transplantation, receiving the same immunosuppressive therapy. METHODS: Fifteen children who underwent small bowel transplantation (seven SbTx) or combined liver-small bowel transplantation (eight LSbTx) at a single center between 1994 and 1998 were retrospectively reviewed and compared with fifteen controls (eight normal and seven appendicitis as inflammatory control). Transplant and patient survival, acute rejection episodes were analyzed and compared. Epithelial apoptotic body counts (ABC) and NF-kB (p65), Caspase-3 and Bax intestinal immunostaining from days 0 to 20 after transplantation were assessed. RESULTS: Graft and patient survivals at 5 years were respectively 75% and 75% in LSbTx; 43% and 57% in SbTx (NS). Histological analysis showed higher ABC in LSbTx intestinal mucosa (P = 0.05 on day 5, P < 0.01 thereafter). Immunostaining of biopsies on day 0 after reperfusion showed different expression of NF-kB, Caspase-3 and Bax on endothelial (P < 0.05 for NF-kB and Bax), mononuclear (P < 0.05 for Bax) and epithelial cells in LSbTx and SbTx. CONCLUSIONS: Our results suggest a protective role of the liver toward intestinal transplantation even in absence of significative difference, probably due to the small number of children. Early changes in NF-kB immunostaining in the biopsies sampled on day 0, pointed to a possible beneficial effect of the liver in the very early phase following transplantation, perhaps through the differential control of ischemia-reperfusion.

Biomarkers↗

PubMed2006

Characteristics and outcome of diffuse large B-cell lymphoma in hepatitis C virus-positive patients in LNH 93 and LNH 98 Groupe d'Etude des Lymphomes de l'Adulte programs.

PURPOSE: Epidemiologic studies show an association between hepatitis C virus (HCV) and B-cell non-Hodgkin's lymphoma (NHL). Treatment and outcome of patients with diffuse large-cell lymphoma (DLCL) and HCV infection are still a matter of debate. PATIENTS AND METHODS: We studied the HCV-positive patients with B-cell DLCL included in the Groupe d'Etude des Lymphomes de l'Adulte (GELA) programs LNH 93 and LNH 98. They were compared with the other patients with DLCL included in these programs. HCV infection prevalence was 0.5% (26 of 5,586 patients). RESULTS: Histologic types of HCV-positive DLCL were more frequently transformed from low-grade lymphoma than DLCL in HCV-negative patients (32% v 6%, P = .02). This is also supported by more frequent spleen involvement in HCV-positive patients (46% v 17%, P < .001). HCV-positive patients had more frequently elevated lactate dehydrogenase levels than other patients (77% v 55%, P = .02). Outcome of HCV-positive patients was poorer for overall survival (P = .02) but not for event-free survival (P = .13). After matching on age and prognosis factors, at 2 years of follow-up, the overall survival was 56% (95% CI, 33% to 76%) among HCV-positive patients, versus 80% (70% to 89%), and the event-free survival was 53% (33% to 72%) versus 74% (64% to 84%). The short-term hepatic toxicity of chemotherapy was strongly increased among HCV-positive patients. After exclusion of the two subjects with chronic hepatitis B virus infection, the overall proportion of subjects undergoing hepatic toxicity was 65% (15 of 23 patients). CONCLUSION: HCV-positive patients with DLCL differ from other patients both at presentation and during chemotherapy. Specific protocols evaluating antiviral therapy should be designed for these patients.

Adult↗

PubMed2006

Implication of the folate-methionine metabolism pathways in susceptibility to follicular lymphomas.

The incidence of follicular lymphoma (FL) in industrialized countries has been increasing since the 1950s. Polymorphisms in genes encoding key enzymes controlling folate-methionine metabolism, including methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MS or MTR), serine hydroxymethyltransferase (SHMT), and thymidylate synthase (TS or TYMS), modify the risk of various cancers and possibly FL. This study specifically looks for an association between MTHFR, MTR, TYMS, and SHMT polymorphisms and the risk of FL. We carried out a case-control study with 172 patients diagnosed with FL and 206 control subjects. We report that the risk of FL was doubled by the association of one mutant allele at both MTHFR polymorphisms. Individuals with MTR 2756AA had 2-fold higher risk of FL, and subjects not having at least one TYMS 2R allele showed a 2-fold higher risk of FL. The MTR 2756AA genotype conferred a greater multivariate-adjusted relative risk of FL, and the risk was multiplied by almost 5 in the TYMS2R(-)/MTR 2756AA combination. In conclusion, common polymorphisms in key enzymes of the folate-methionine metabolism pathway result in an increased risk of FL and suggest that inadequate intake of dietary folate and other methyl donor nutrients may contribute to the development of this malignancy.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2006

Omenn syndrome in an infant with IL7RA gene mutation.

Omenn syndrome (OS) is a rare combined immunodeficiency characterized by erythroderma, lymphadenopathy, and autoimmune manifestations. Most cases are due to mutations in the RAG genes. We report a case of OS due to mutations of IL7RA, thus defining Omenn syndrome as a genetically heterogeneous condition.

Amino Acid Substitution↗

PubMed2006

A novel form of non-X-linked hyperigm associated with growth and pubertal disturbances and with lymphoma development.

HyperIgM syndrome is a heterogenous immunodeficiency characterized by impaired class-switch recombination due to different molecular abnormalities. We report on two female patients affected by a novel syndrome associating HIGM, growth and pubertal disturbances, and severe lymphoid hyperplasia with eventual development into lymphomas, suggesting a DNA repair defect.

Adolescent↗

PubMed2006

Implication of TNF-related apoptosis-inducing ligand in inflammatory intestinal epithelial lesions.

BACKGROUND & AIMS: Few data exist on the molecular events causing intestinal epithelial destruction during inflammatory processes, such as inflammatory bowel disease (IBD). In this work, we analyzed the potential implication of tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) in these inflammatory lesions. METHODS: TRAIL and TRAIL-receptor expression were analyzed in normal, inflammatory ileum/colon and human intestinal epithelial cell (IEC) lines (HIEC), Caco-2, and HT-29 using RNase protection assay, real-time and reverse-transcription polymerase chain reaction (RT-PCR), immunohistochemistry, and Western blot analysis. TRAIL-induced activation of NF-kappaB was determined by electrophoretic mobility shift assay. Caspase-recruitment domain (CARD)15 expression and interleukin-(IL)8 production were studied by RT-PCR and enzyme-linked immunosorbent assay. Apoptosis was monitored using Annexin-V/caspase-3 assays. RESULTS: Normal mature IEC expressed low TRAIL levels, whereas, in inflammatory lesions, TRAIL messenger RNA and protein were markedly up-regulated in IEC and lamina propria lymphocytes at levels comparable with trinitrobenzene sulfonic acid-induced colitis. Interferon-gamma and TNF-alpha potently induced TRAIL in IEC. In vitro analyses revealed a dual biologic effect of TRAIL on HIEC: Under noninflammatory conditions, TRAIL up-regulated via nuclear factor-kappaB CARD15 and IL-8, whereas, under inflammatory conditions, TRAIL became a potent inducer of apoptosis in HIEC, which was confirmed ex vivo using ileal organ cultures. TNF-alpha markedly increased the expression of the proapoptotic receptor TRAIL-R2. TRAIL-induced IEC apoptosis required a functional caspase cascade. CONCLUSIONS: TRAIL is a new inflammatory mediator implicated in the homeostasis of intestinal epithelial barrier functions. TRAIL is highly up-regulated in IEC in inflammatory ileum and colon. It may augment in an auto-/paracrine fashion the elimination of IEC via apoptosis.

Animals↗

PubMed2006

European multi-centre study on coeliac disease and non-Hodgkin lymphoma.

INTRODUCTION: Coeliac disease (CD) is associated with an increased risk of non-Hodgkin lymphoma (NHL), but there is little information about whether this is true for clinically silent CD. OBJECTIVE: To investigate the frequency of CD in two European populations; one with NHL and another derived from the general population. METHODS: A prospective, multi-centre, case-control study in 10 European countries was conducted between May 1998 and April 2001. A total of 1446 consecutive patients with newly diagnosed NHL aged over 18 years was collected. The control group consisted of a population of 9676 individuals who were screened for CD. The number of patients with a previous diagnosis of CD and those with silent CD detected by screening were determined in the two groups. RESULTS: The patients with CD had a significantly increased risk of developing NHL [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4-4.9]. This risk was only present in patients with CD diagnosed clinically before the study (OR 3.3, 95% CI 1.4-7.9), but not in those with silent CD detected by screening (OR 1.3, 95% CI 0.6-2.7). CONCLUSION: Patients with CD have an increased risk of developing NHL, although this is lower than previously thought. Clinically silent CD is rare in patients with NHL.

Adult↗

PubMed2006

Fas ligand-mediated lethal hepatitis after rapid lysis of a localized natural killer cell lymphoma.

Natural killer (NK) cell malignancies have been associated with neutropenia and disturbances of liver function tests, thought to be related to high levels of soluble Fas ligand (FasL) in the circulation. We report a case of fulminant hepatitis occurring 3 weeks after the initiation of salvage therapy by arginine butyrate and ganciclovir for refractory Epstein-Barr virus-positive NK cell lymphoma. Pathologic examination revealed disappearance of the NK tumor and massive liver injury caused by apoptosis of virtually all hepatocytes. Immunohistochemistry revealed an intense staining for FasL. To our knowledge, this is the first description of the occurrence of FasL-mediated lethal hepatitis after lysis of a NK cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Dramatic clinical efficacy of cladribine in Rosai-Dorfman disease and evolution of the cytokine profile: towards a new therapeutic approach.

Rosai-Dorfman disease (RDD) is a rare disorder, often benign but with possible life-threatening prognosis. In most cases, specific treatment is not necessary; when required, the management of RDD is not codified to date, and various chemotherapies have been shown to be ineffective. Here, we report a patient with RDD who presented a dramatic and sustained response with cladribine. Analysis of the cytokine profile evolution shows a clear correlation between serum levels of TNF-alpha and IL-6 and disease activity. Our findings show the promising efficacy of cladribine and suggest that therapies targeting specifically cytokines might be useful in some cases of active RDD.

Antimetabolites↗

PubMed2005

Enhanced in situ expression of NF-kappaBp65 is an early marker of intestinal graft rejection in rats.

BACKGROUND: Although intestinal transplantation provides a unique situation of free access to the graft because of the presence of temporary enterostomas, evaluation of local immunosuppression is still an unresolved issue and may constitute one of the causes of grafting failure. AIMS: To study in a rat model of allogeneic intestinal transplantation the expression of transcription factors involved in lymphocyte activation in situ in the graft and to identify factors reflecting the efficiency of drug immunosuppression. METHODS: Intestinal transplantation was performed in a Brown Norway (RT1n-donors)-Lewis (RT1(l)-recipients) rat strain combination. The animals were treated with tacrolimus to induce tolerance or left untreated. Syngeneic intestinal grafts and intestine from donor rats with peritonitis were used as controls. NF-kappaBp65, p-c-Jun, interleukin 2 receptor (CD25), and major histocompatibility complex class II antigen (OX-6) expression was studied in graft biopsies on days 2 and 5 by immunohistochemistry. RESULTS: On day 2, before the onset of histologic signs of rejection, the number of cells expressing NF-kappaBp65 in the pericryptic lamina propria was significantly higher in untreated recipients of allogeneic grafts than in the other groups (P = .009). NF-kappaBp65 expression then fell between days 2 and 5 (P = .009). Classic markers of T-cell activation (CD25 and OX-6) were expressed during rejection in the lamina propria and on crypt enterocytes, respectively. p-c-Jun expression did not differ among the 3 groups. CONCLUSION: NF-kappaBp65 expression in intestinal grafts is a precocious sign of local activation during rejection and could thus serve to optimize the management of immunosuppressive therapy.

Animals↗

PubMed2005

Analysis of interleukin-27 (EBI3/p28) expression in Epstein-Barr virus- and human T-cell leukemia virus type 1-associated lymphomas: heterogeneous expression of EBI3 subunit by tumoral cells.

Interleukin (IL)-27 is a novel heterodimeric cytokine of the IL-12 family that is composed of two subunits, Epstein-Barr virus (EBV)-induced gene 3 (EBI3) and p28. EBI3 is expressed at high levels in EBV-transformed B-cell lines and is induced in vitro by the EBV oncogene LMP1 in a nuclear factor (NF)-kappaB-dependent manner. We show here that EBI3 expression is up-regulated in human T-cell leukemia virus type 1 (HTLV-1)-infected cell lines and IL-2-dependent leukemic cells from adult T-cell leukemia/lymphoma (ATL) patients, compared to normal activated T cells. EBI3 expression was decreased in HTLV-1-transformed cells after treatment with the NF-kappaB inhibitor BAY11-7082 and was induced in Jurkat cells by expression of HTLV-1 wild-type Tax oncoprotein, but not by the Tax mutant M22, which is defective for NF-kappaB activation. In situ analysis of EBI3 and p28 expression in Hodgkin's lymphomas (HLs), in various EBV-associated lymphoproliferative disorders (LPDs) (including post-transplant LPDs and nasal-type NK/T-cell lymphomas), and in ATL showed that EBI3 was expressed by neoplastic cells in all cases of HL and of LMP1-positive EBV-associated LPD, at variable levels in ATL cases, but rarely in control T-cell lymphomas. In contrast, in all lymphomas tested, no or few tumoral cells expressed p28. Consistent with these data, no significant p28 or IL-27 expression was detected in HL-derived cell lines, or in EBV- or HTLV-1-transformed cell lines. This selective overexpression of EBI3 by transformed cells suggests that EBI3 may play a role, independently from its association to p28, in regulating anti-viral or anti-tumoral immune responses.

Blotting, Western↗

PubMed2005

Plexiform fibrohistiocytic tumor: three unusual cases occurring in infancy.

BACKGROUND: Plexiform fibrohistiocytic tumor is a soft-tissue tumor of intermediate malignancy occurring in children and young adults but is only rarely found in infants. The tumor usually involves the upper limbs and is slow growing and painless. Recurrence rate is high. Lymph node and systemic metastases can occur, but have never been reported in infants. Clinical behavior in infancy is not known. Histologically, the tumor is characterized by nodules of histiocyte-like and multinucleated cells and fascicles of spindle cells arranged in a plexiform pattern. Mitosis, atypia, and nuclear pleomorphism are common but not pronounced. METHODS AND RESULTS: We report three cases in infants, one of which is congenital, having an unusual topography and a broad histological spectrum. CONCLUSION: In infants, wide excision with large safety margins should be performed as the behaviour of this tumor remains uncertain. Leclerc S, Hamel-Teillac D, Oger P, Brousse N, Fraitag S. Plexiform fibrohistiocytic tumor: three unusual cases occurring in infancy.

Biomarkers, Tumor↗

PubMed2004

Fetal intestinal obstruction induces alteration of enteric nervous system development in human intestinal atresia.

Intestinal motility disorders are a major cause of morbidity after surgical repair of intestinal atresia of unknown mechanism. We hypothesized that interruption of antenatal peristalsis may disturb the normal development of the enteric nervous system. Using a series of neuronal (synaptophysin, neuronal nitric oxide synthase, neurofilaments) and nonneuronal markers (glial acidic fibrillary protein and c-Kit) and immunohistochemistry, we have defined developmental steps of the enteric nervous system in normal intestine (12 fetuses, 15 children, and 4 adults) and their alterations above and below the obstacle in 22 human intestinal atresia compared with age-matched controls. Antisynaptophysin antibody revealed the progressive conversion of the myenteric plexus from a continuous belt into regularly spaced ganglions during normal fetal gut development and, by contrast, the significantly delayed appearance of individual neuronal ganglions in the distal segments of atresia (p < 0.05). Staging using three other markers for neuronal (neurofilaments and neuronal nitric oxide synthase) and nonneuronal cells (glial acidic fibrillary protein) confirmed that maturation of the myenteric plexus was significantly delayed below atresia (p < 0.01). These results indicate that intestinal atresia impairs the development of the enteric nervous system and provide an anatomical substrate for the motility disorders observed after surgical repair. They point to the role of peristalsis in normal gut development and suggest that stimulation of peristalsis might be used to accelerate recovery.

Biomarkers↗

PubMed2004

Staphylococcus aureus isolates associated with necrotizing pneumonia bind to basement membrane type I and IV collagens and laminin.

To investigate how Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus (PPSA) strains associate with specific bronchial lesions during community-acquired necrotizing pneumonia, we examined PPSA strains and PVL-negative S. aureus (PNSA) strains for their binding behavior to extracellular matrix (ECM) proteins, primary human airway epithelial cell (HAEC) cultures, and human airway mucosa damaged ex vivo. Compared with PNSA strains, PPSA strains exhibited increased affinity for damaged airway epithelium and especially for exposed basement membrane. PPSA strains, compared with PNSA strains, showed stronger affinity for type I and IV collagens and laminin, a property associated with the presence of the cna gene. PPSA and PNSA culture supernatants similarly damaged HAEC layers, whereas recombinant PVL had no effect, suggesting that an S. aureus exoprotein other than PVL might contribute to the observed airway epithelial damage. These results suggest that epithelial damage, possibly due to viral infection (which usually precedes necrotizing pneumonia) and/or to a non-PVL S. aureus exoproduct action, may permit binding of PPSA to exposed type I and IV collagens and laminin--the PVL cytotoxin being involved later during necrotizing pneumonia.

Adhesins, Bacterial↗

PubMed2004

Food allergens are protected from degradation during CD23-mediated transepithelial transport.

BACKGROUND: CD23 (FcepsilonRII) is expressed by intestinal epithelial cells (IEC) following allergic stimulation and increases the uptake of IgE/allergen complexes. The aim of this study was to further analyze the role of CD23 in the intraepithelial processing of food allergens during transepithelial transport. METHODS: Balb-C mice were sensitized intraperitoneally with horseradish peroxidase (HRP) or beta-lactoglobulin (beta-LG) in the presence of pertussis toxin. In control and sensitized mice, 3H-HRP, intact HRP, or 14C-beta-LG fluxes were measured across jejunal segments mounted in Ussing chambers, in the presence or absence of mucosal anti-CD23 antibodies. HPLC analysis of serosal buffer was performed to detect HRP- or beta-LG-derived radiolabelled metabolites generated during transepithelial transport. RESULTS: In HRP-sensitized mice, 3H-HRP fluxes and intact HRP fluxes (3,836 +/- 476 and 290 +/- 86 ng/h x cm2, respectively) were significantly increased compared to control mice (1,677 +/- 297 ng/h x cm2, p < 0.01, and 106 +/- 23 ng/h x cm2, p < 0.02, respectively). HPLC analysis indicated the presence of intact HRP in the serosal compartment already 10 min after addition of HRP to the mucosal compartment, a result not observed in the control mice. In the presence of anti-CD23 antibodies, intact HRP fluxes were significantly decreased (131 +/- 27 ng/h x cm2) compared to control values in sensitized mice (290 +/- 86 ng/h x cm2, p < 0.02), suggesting that CD23 is involved is this 'protected' transport pathway. A similar protection during intestinal transport was observed for beta-LG in beta-LG sensitized mice. CONCLUSIONS: These results confirm that CD23 is involved in the rapid transepithelial transport of intact allergens in sensitized animals, and indicate that CD23 opens a 'protected' transport pathway in IECs.

Allergens↗