Search PubMed⌕ Search

Biomedical subjects

N Brousse

Publications and source records attributed to N Brousse.

At least 55 records · Page 3Linked to original sources
PubMed2000

Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2).

The activation-induced cytidine deaminase (AID) gene, specifically expressed in germinal center B cells in mice, is a member of the cytidine deaminase family. We herein report mutations in the human counterpart of AID in patients with the autosomal recessive form of hyper-IgM syndrome (HIGM2). Three major abnormalities characterize AID deficiency: (1) the absence of immunoglobulin class switch recombination, (2) the lack of immunoglobulin somatic hypermutations, and (3) lymph node hyperplasia caused by the presence of giant germinal centers. The phenotype observed in HIGM2 patients (and in AID-/- mice) demonstrates the absolute requirement for AID in several crucial steps of B cell terminal differentiation necessary for efficient antibody responses.

APOBEC-1 Deaminase↗
PubMed2000

Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma. French Coeliac Disease Study Group.

BACKGROUND: Adult refractory sprue is a poorly defined disorder. We did a multicentre national study of patients with refractory sprue to characterise their clinical and pathological profile and outcome, and to assess the frequency and prognostic significance of phenotypic and molecular abnormalities in the intraepithelial T-cell population. METHODS: Patients with severe symptomatic villous atrophy mimicking coeliac disease but refractory to a strict gluten-free diet, and with no initial evidence of overt lymphoma, were diagnosed at gastrointestinal referral centres between 1974 and 1998. Fixed and/or frozen duodenojejunal biopsy samples were reanalysed and immunostained with CD3 and CD8 monoclonal antibodies to find out the phenotype of intraepithelial lymphocytes (IEL). TCRgamma gene rearrangements were assessed on frozen biopsy samples by multiplex fluorescent PCR. FINDINGS: There were 21 patients with refractory sprue and 20 controls with coeliacs disease. 16 (84%) of 19 assessed patients had an aberrant intraepithelial lymphoid intestinal population expressing intracytoplasmic CD3 but not surface CD8. Clonal intestinal TCRgamma gene rearrangements were found in 13 (76%) of 17 patients assessed; four (out of 12 assessed) had clonal dissemination to the blood. The 16 patients with an aberrant phenotype all had uncontrolled malabsorption; three subsequently developed overt T-cell lymphoma, and eight died. The three (16%) patients without aberrant clonal IEL made a complete clinical and histological recovery with steroid therapy plus a gluten-free diet. INTERPRETATION: An immunophenotypically aberrant clonal intraepithelial T-cell population (similar to that of most cases of enteropathy-associated T-cell lymphoma) can be found in up to 75% of patients with refractory coeliac sprue; its identification by simple diagnostic techniques represents a marker of poor outcome (including occurrence of overt T-cell lymphoma). We suggest that refractory sprue associated with an aberrant clonal IEL may be the missing link between coeliac disease and T-cell lymphoma and may be classified as cryptic enteropathy-associated T-cell lymphoma.

Adult↗
PubMed2000

Langerhans cell deficiency in reticular dysgenesis.

Reticular dysgenesis is a rare inherited immunodeficiency characterized by the lack of blood monocytes and neutrophils and low lymphocyte counts, contrasting with normal red blood cell counts and normal or decreased platelet counts. Whether dendritic cells or macrophages, both of which derive primarily from blood monocytes, are affected in this condition remains unknown. We studied 7 patients with reticular dysgenesis. Macrophages were present in normal numbers in the dermis and in the atrophic lymphoid tissues of these patients, proving that at least some subsets of macrophages can differentiate despite very low monocyte counts. By contrast, Langerhans cells, which are CD1a-positive epidermal dendritic cells, were absent in all (n = 5) patients before bone marrow transplantation. After bone marrow transplantation, Langerhans cells were present (n = 2), suggesting that the defect is not related to keratinocyte dysfunction. A split chimeric reconstitution, characterized by the presence of autologous blood monocytes able to differentiate in vitro into CD1a-positive dendritic cells, was observed in a patient who underwent successful engraftment. These results suggest that an intrinsic cell defect is unlikely and that a bone marrow-derived factor may be defective in reticular dysgenesis; it may be responsible for the Langerhans cell defect but not involved in macrophage differentiation.

Antigens, CD↗
PubMed2000

Immunohistological and morphometric analysis of intra-epithelial lymphocytes and Langerhans cells in healthy and diseased human gingival tissues.

Periodontal diseases are histologically characterized by an infiltration of several inflammatory cell populations into the gingival epithelium and connective tissue, associated with degradation of extracellular matrix components. The purpose of this in situ study was to evaluate the inflammatory state of gingival tissues by the number of intra-epithelial lymphocyte (IEL) subsets and the area fraction (AA%) occupied by collagen fibres in the upper gingival connective tissue, and also to evaluate the number of CD1a+ Langerhans cells (LC) in order to show correlation(s), if any, between these histological findings. The gingival samples were from 10 clinically healthy controls (group C), 8 patients with gingivitis (group G) and 9 with chronic adult periodontitis (group P). A quantitative evaluation of the number of cell populations (CD1a+, CD45RB+, CD3+, CD8+, CD20+, TIA-1+ and GrB+ cells) and the area fraction (AA%) occupied by collagen fibres in the upper gingival connective tissue was made by morphometric and automated image analysis. The results showed that, compared with group C, all IEL subset numbers were significantly increased (p<0.05) in G and P groups, CD20+ excepted. In addition, there was a significant increase in the cytotoxic TIA-1+ IEL number (p<0.05) in group P when compared with group G. The study also showed a significant decrease in the number of CD1a+ LC in groups G and P (p<0.02 and p<0.001, respectively) when compared with group C. No significant difference was found in CD1a+ LC number between groups G and P. The determination of coefficients of correlation (r) with data obtained for each patient showed that in group G, CD1a+ LC number was significantly correlated with CD45RB+ (p<0.05) and CD3+ (p<0.01) IEL numbers whereas during periodontitis, CD1a+ LC number was significantly and inversely correlated with CD20+ (p<0.01), cytotoxic TIA-1+ (p<0.01) and with activated cytotoxic GrB+ (p<0.01) IEL numbers. Moreover, in group P a significant (p<0.05) positive correlation was shown between CD1a+ LC number and the AA% occupied by collagen fibres. This work demonstrates a decrease in CD1a+ LC number according to the severity of the periodontal disease estimated by the number of IEL and by the area fraction occupied by collagen fibres in human gingiva. The decrease of such cells could represent a way to avoid immune overstimulation.

Adolescent↗
PubMed2000

Quantitative morphological analysis of Langerhans cells in healthy and diseased human gingiva.

Langerhans cells (LC) are implicated in the initiation and maintenance of inflammatory periodontal diseases. The purpose of this immunohistological study using morphometric and automated image analysis was to determine the morphological features of CD1a+ LC in healthy and inflammatory gingiva according to their localisation in the upper epithelium or the basal layer. The study was on gingival samples from 11 healthy controls (C), eight patients with gingivitis (G) and 12 patients with severe chronic adult periodontitis (P). The results show that in the basal layer of all experimental groups, the perimeter, surface and equivalent diameter of CD1a+ LC were significantly decreased (P<0.005) when compared with those in the upper epithelium of the same group. Furthermore, CD1a+ LC had become more rounded, reflected by a significant increase in form factor (P<0.005), when located close to the epithelial basal membrane. In the upper epithelium of group P, the perimeter, surface and equivalent diameter of CD1a+ LC were significantly decreased (P<0. 05) and the form factor significantly increased (P<0.05) when compared with the upper epithelium of group C. This work provides evidence for important morphological variations in CD1a+ LC according to their location within the epithelium and the severity of the periodontal disease. The observed morphological changes may reflect a cellular adaptation during the epithelial transmigration and could eventually be involved in immune stimulation during periodontitis.

Adult↗
PubMed2000

Selective expansion of intraepithelial lymphocytes expressing the HLA-E-specific natural killer receptor CD94 in celiac disease.

BACKGROUND & AIMS: Celiac disease is a gluten-induced enteropathy characterized by the presence of gliadin-specific CD4(+) T cells in the lamina propria and by a prominent intraepithelial T-cell infiltration of unknown mechanism. The aim of this study was to characterize the subset(s) of intraepithelial lymphocytes (IELs) expanding during active celiac disease to provide insights into the mechanisms involved in their expansion. METHODS: Flow-cytometric analysis of isolated IELs and/or immunohistochemical staining of frozen sections were performed in 51 celiac patients and 50 controls with a panel of monoclonal antibodies against T-cell and natural killer (NK) receptors. In addition, in vitro studies were performed to identify candidate stimuli for NK receptor expression. RESULTS: In normal intestine, different proportions of IELs, which were mainly T cells, expressed the NK receptors CD94/NKG2, NKR-P1A, KIR2D/3D, NKp46, Pen5, or CD56. During the active phase of celiac disease, the frequency of CD94(+) IELs, which were mostly alphabeta T cells, was conspicuously increased over controls. In contrast, the expression of other NK markers was not modified. Furthermore, expression of CD94 could be selectively induced in vitro by T-cell receptor activation and/or interleukin 15, a cytokine produced by intestinal epithelial cells. CONCLUSIONS: The gut epithelium favors the development of T cells that express NK receptors. In active celiac disease, there is a specific and selective increase of IELs expressing CD94, the HLA-E-specific NK receptor that may be related to T-cell receptor activation and/or interleukin 15 secretion.

Adult↗
PubMed2000

[Lymphomas in children infected with HIV-1].

PURPOSE: To describe the features of lymphoma in human immunodeficiency virus (HIV)-infected children, their treatments and the outcome of patients. RESULTS: We analyzed seven HIV-infected children (four by mother-to-child transmission and three by transfusion) (25 months to 18.5 years old) with lymphoma (one Hodgkin's disease and six non-Hodgkin's lymphomas). All of them presented with a severe immunodepression and a high viral load. Five of six were high grade-B cell non-Hodgkin's lymphoma of large-cell histologies (immunoblastic or centroblastic). Five were extranodular disease and three were metastatic at diagnosis. Epstein-Barr virus was detected in four tumors. Five of seven received a multiagent chemotherapy. Toxicity was high. Treatment for the skin T lymphoma consisted of radiation therapy. Five children were complete responders (with survival three years, 2.5 years, 12, 18 and 18 months) and two died of progression of lymphoma (four and five months later). CONCLUSION: Incidence of lymphoma is increased in HIV-infected children. Anticancer chemotherapy regimens that include aggressive supportive care and concomitant antiretroviral therapy or immunotherapy may yield high survival rates.

Adolescent↗
PubMed2000

High-dose therapy with autologous stem-cell transplantation (ASCT) after first progression prolonged survival of follicular lymphoma patients included in the prospective GELF 86 protocol.

BACKGROUND: Among the 566 patients with follicular lymphomas (FL) included in the GELF 86 prospective trials from October 1986 to September 1995, 372 with progressive/relapsing disease were analyzed retrospectively to identify prognostic factors at first relapse. PATIENTS AND METHODS: For progressive FL, patients received mono- (22%) or polychemotherapy (78%) followed by high-dose therapy (HDT) with ASCT for 83 patients (22%). The median time to progression from initial treatment was 23 months (range 3-102 months) and 24% of documented patients (52 of 217) had histological transformation (HT). Salvage therapy produced an overall response in 64% of patients and the five-year survival from progression was 42%. RESULTS: For patients who underwent HDT with ASCT compared to standard treatment, five-year freedom from second failure was at 42% vs. 16% (P = 0.0001) and five-year survival was 58% vs. 38% (P = 0.0005), respectively. The benefit of HDT and ASCT remained if we consider only patients less than 65 years (five-year survival at 60% vs. 40%; P = 0.001). Multivariate analysis of parameters significant according to univariate analysis found that no ASCT at first progression, age at relapse > 50 years, progression on-therapy were adversely significant on survival. CONCLUSIONS: HDTwith ASCT compared to standard treatment prolonged remission and survival after first progression of FL patients.

Age Factors↗
PubMed2000

Efficacy of autologous stem cell transplantation in mantle cell lymphoma: a 3-year follow-up study.

This study was designed to evaluate the efficacy of therapeutic intensification with autologous stem cell transplantation (ASCT) for mantle cell lymphomas (MCL) in terms of response rate, duration of response, and event-free and overall survivals. Twenty-four patients with confirmed MCL responding to chemotherapy received a high-dose chemo-radiotherapy regimen followed by ASCT. Transplantation was performed during first-line therapy in nine cases, second-line in 13 cases and third-line in two cases. The source of hematopoietic stem cells was peripheral blood for 19 cases. At the time of ASCT, eight patients were in complete remission (33%). Seventeen of the 24 cases received an intensified regimen with TBI and seven received the BEAM or the BEAC regimen. After transplantation, 19 patients were in CR (79%). Nine of these were alive in continued CR at a median follow-up of 34 months, while seven relapsed at a median of 18 months. One patient died from Pneumocystis carinii interstitial pneumonitis and five patients developed secondary malignancies. With a median follow-up after transplantation of 34 months, the 3-year event-free survival was 55% and the 3-year overall survival was 68%. These results indicate that therapeutic intensification with ASCT might be an effective treatment for mantle cell lymphomas. Bone Marrow Transplantation (2000) 25, 251-256.

Adult↗
PubMed2000

Distinction between coeliac disease and refractory sprue: a simple immunohistochemical method.

AIMS: We recently showed that refractory sprue is distinct from coeliac disease, the former being characterized by abnormal intraepithelial T-lymphocytes expressing a cytoplasmic CD3 chain (CD3c), lacking CD3 and CD8 surface expression, and showing TCRgamma gene rearrangements. To take advantage of the abnormal phenotype of CD3c + CD8 - intraepithelial lymphocytes (IEL) in refractory sprue we developed a simple method to distinguish coeliac disease from refractory sprue. METHODS AND RESULTS: Comparative immunohistochemical studies using anti-CD3 and anti-CD8 antibodies were applied on paraffin-embedded and frozen biopsy specimens in refractory sprue (n = 6), coeliac disease (n = 10), healthy controls (n = 5) and suspected refractory sprue (n = 6). Comparable results were obtained on fixed and frozen biopsy specimens. In four of the six patients with suspected refractory sprue, abnormal CD3c + CD8 - IEL and TCRgamma gene rearrangements were found, as in refractory sprue; the remaining two patients had normal (CD3 + CD8 +) IEL and no TCRgamma gene rearrangements. Both patients had coeliac disease, as one failed to comply with a gluten-free diet, while the other was a slow responder. CONCLUSION: This simplified immunostaining method using anti-CD3 and anti-CD8 antibodies on paraffin sections can distinguish active coeliac disease from refractory sprue and should prove useful in clinical practice.

Adult↗
PubMed2000

Role of cytotoxic T cells in chronic alopecia areata.

Cytokines play a role in alopecia areata. We used immunohistochemical and in situ hybridization studies to demonstrate the persistence of pro-inflammatory as well as apoptotic mechanisms in skin biopsies from patients with chronic alopecia areata. In situ hybridization allows the visualization of the distribution of immunocompetent cells in vivo. We studied skin biopsies from 11 untreated alopecia areata patients and two normal controls. In situ hybridization was performed on frozen sections using 35S-radio-labeled riboprobes, specific for IL-1beta, IL-2, IL-6, INFgamma, and granzyme B mRNA. Immunohistochemistry was carried out using an anti-IL-1beta monoclonal antibody, and a monoclonal antibody directed against the human Fas protein. We demonstrated the presence of cells labeled with IL-1beta, IL-6, INFgamma, and granzyme B antisense probes. Similarly, cells labeled with anti-IL-1beta were found in 10 of 11 cases. The labeled cells were located in the mononuclear peri- and intrafollicular infiltrate. Cells expressing granzyme B were found in close contact with the follicle. Fas positivity was demonstrated in four of four cases at the level of the cytoplasmic membrane of the hair follicle keratinocytes. These results, based on visualizing the labeled cells, demonstrate that pro-inflammatory cytokines are produced by the mononuclear cell infiltrate in close contact with follicles in alopecia areata. Furthermore, they demonstrate for the first time that apoptotic mechanisms involving granzyme B and Fas-Fas ligand pathways may play a major role in the persistence of chronic alopecia areata.

Alopecia Areata↗
PubMed2000

Allogeneic fetal small bowel graft in pigs treated with cyclosporin A.

BACKGROUND: The functional integrity of transplanted fetal intestine was proven in rodents. The authors examined the morphology and development of intraperitoneally transplanted fetal intestine under cyclosporin A (CsA) monotherapy in a large mammal. METHODS: Allogeneic fetal intestinal grafts were transplanted intraperitoneally in pigs. The graft was wrapped in omentum. Thirteen recipients received grafts harvested at 60 days of gestation and 5 at 105 days of gestation. All recipients received 25 mg/kg/d CsA. CsA blood levels were measured at the end of the study. The development of the grafts was assessed by inspection and histology studying revascularization, maturation, and immune rejection. RESULTS: All grafts developed neovascularization. The intestinal wall in the 105-day-old group was thick enough to lead to complete mucosal destruction, whereas the 60-day-old group showed viable mucosa. All grafts induced an immune rejection. This immune response was correlated with the CsA blood level. The graft was destroyed within 15 days when CsA trough level was below 70 ng/mL, had a subacute rejection with villi atrophy when CsA trough level ranged from 70 to 150 ng/mL, and had a good appearance in spite of mild blunting of villi when CsA trough level was over 150 ng/mL. CONCLUSION: Allogeneic fetal intestinal transplantation from 60-day-old embryos in pig achieved successful graft.

Animals↗
PubMed2000

Blockade of the integrin alphaLbeta2 but not of integrins alpha4 and/or beta7 significantly prolongs intestinal allograft survival in mice.

BACKGROUND: Small bowel transplantation remains a difficult therapeutic option endangered by a high rate of rejection and infectious complications. To improve these clinical results, it is mandatory to set up animal models to test alternative immunosuppressive regimens which may lead to immunotolerance. AIMS: To determine the value of blockade of alphaLbeta2 (LFA-1) and alpha4 and beta7 integrins (alpha4beta1, alpha4beta7, and alphaEbeta7) in the prevention of rejection of fetal small bowel grafts in mice and the effect of the association of calcineurin dependent drugs in anti-LFA-1 treated mice. METHODS: Adult recipient mice engrafted with allogeneic fetal small bowel received a short course of anti-alpha4 and/or anti-LFA-1 monoclonal antibodies (mAb) with or without FK506 or cyclosporin A. In addition, in a set of experiment, beta7-/- mice were used as recipients. Graft biopsies were performed and processed for standard histology. RESULTS: Blockade of the pathways of the integrins alpha4 and beta7 had a modest or no effect on intestinal graft survival. In contrast, transitory, short administration of anti-LFA-1 monoclonal antibody alone, when started before engraftment (day -1), allowed long term survival of intestinal grafts, even when associated with calcineurin dependent drugs. However, early withdrawal of FK506 reversed the immunosuppressive effect of anti-LFA-1 treatment. CONCLUSION: These results suggest that firstly, anti-LFA-1, but not anti-alpha4 mAb treatment, may be useful in improving the results of intestinal transplantation, and secondly, that this treatment is not incompatible with long term administration of tacrolimus currently used in the prevention of small bowel graft rejection in humans.

Animals↗
PubMed2000

Collagen fibers and inflammatory cells in healthy and diseased human gingival tissues: a comparative and quantitative study by immunohistochemistry and automated image analysis.

BACKGROUND: Periodontal disease is histologically characterized by the degradation of extracellular matrix components associated with a gingival infiltration of inflammatory cell populations. The purpose of this in situ study was to quantify inflammatory cell subsets and the area fraction (AA%) occupied by collagen fibers in healthy and diseased upper gingival connective tissue in order to investigate the association, if any, between collagen loss and inflammatory cell infiltrate. METHODS: Paraffin gingival tissue sections from 10 healthy controls (C), 9 patients with gingivitis (G), and 10 patients with severe chronic periodontitis (P) were immunohistochemically stained by antibodies against CD45, CD3, CD8, CD20, CD68, TIA-1, and GrB molecules, and the collagen fibers were stained using sirius red F3Ba. The quantitative evaluations of inflammatory cell numbers and the AA% occupied by collagen fibers were performed by morphometric and automated image analysis. RESULTS: In group P, CD45+, CD20+, CD68+, TIA-1+, and GrB+ cell numbers were significantly increased (P<0.05) when compared to both C and G groups. The present study revealed significant differences (P <0.01) between means of AA% observed in group C (63%), group G (46%), and group P (26%), and AA% of group G and group P was inversely correlated with the numbers of TIA-1+ cells (P<0.01) and GrB+ cells (P<0.01 and P<0.05, respectively). CONCLUSIONS: This study showed great differences in the number of the distinct inflammatory cell subsets according to the severity of the periodontal disease and suggested that activated cytotoxic cells could play a pivotal role in the loss of collagen fibers observed during these pathological states. During periodontitis, collagen loss was significantly correlated with all inflammatory cell subset numbers. Finally, the quantitative evaluation of the area fraction occupied by gingival collagen fibers may reflect the clinical severity of the periodontal disease.

Adolescent↗
PubMed2000

Detection of circulating prostate derived cells in patients with prostate adenocarcinoma is an independent risk factor for tumor recurrence.

PURPOSE: To determine whether the presence of prostate-derived cells in the peripheral blood circulation is a marker of prostate cancer and to define the clinical impact of the test. MATERIALS AND METHODS: We tested the peripheral blood of 99 patients with prostate adenocarcinoma (PAC), 79 of them undergoing radical prostatectomy, and 92 controls (31 healthy volunteers, 50 patients with adenoma and 11 with prostatitis) using a highly controlled procedure including reverse-transcriptase polymerase chain reaction (RT-PCR) targeted to prostate-specific antigen (PSA) mRNA. Patients were followed for 26 +/- 12 (range: 4 to 49) months. Forty tumor tissues were analyzed by immunohistochemistry for expression of p53 and E-cadherin antigens. RESULTS: Thirty three (33%) patients with PAC and 2 (2%) controls scored positive (p <0.0001) for the test. Detection of circulating prostatic cells was associated with development of metastases (p <0. 001), with relapse (p <0.001) and with a serum PSA level at diagnosis higher than 15 ng./ml. (p = 0.009). The rate of development of metastases according to time was significantly higher in patients who scored positive for the test (p <0.04). In a multivariate analysis, only the RT-PCR test was an independent risk factor associated with relapse (RR: 6.7). Finally, E-cadherin expression was significantly lower in the tumor tissues of positive patients as compared with those who scored negative for the test (p <0.01). CONCLUSIONS: This RT-PCR procedure, performed at diagnosis and with appropriate controls, is a clinically useful assay in evaluating the risk of tumor recurrence after radical prostatectomy in patients with PAC.

Adenocarcinoma↗
PubMed2000

[Lichen striatus: evaluation of histologic criteria in 13 cases].

Lichen striatus (LS) is an uncommon dermatosis that generally affects children. Sometimes biopsy is required to assess the diagnosis. It is usually mentioned that LS has no specific histopathological criteria. Recently Gianotti et al., in 50% of the examined cases, found clues to the diagnosis. We have evaluated 13 biopsies of children affected by LS, in order to evaluate histopathological criteria to allow a diagnosis. The features nearly constantly present (12/13) in each specimen were focally band-like lymphocytic infiltrate with variable exocytosis and necrotic keratinocytes within the epidermis surrounded by lymphocytes. Epidermis hyperplasia, sometimes psoriasiform, was also present. In addition, one of remarkable the features of LS was the alignment of the infiltrate along eccrine ducts and glands and/or follicles. In 3 cases the deep lymphocytic infiltration was particularly dense. These results confirm that helpful clues to histopathological diagnosis of LS exist.

Biopsy↗