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Biomedical subjects

N Brousse

Publications and source records attributed to N Brousse.

At least 109 records · Page 6Linked to original sources
PubMed1997

Lack of expression of E-cadherin is associated with dissemination of Langerhans' cell histiocytosis and poor outcome.

Langerhans' cell histiocytosis (LCH) often occurs in children as a cutaneous disease. The course of the disease is characterized by either spontaneous resolution or multivisceral dissemination with poor prognosis. The pathogenesis of LCH is not known. Since E-cadherin mediates homophilic adhesion of normal Langerhans' cells to keratinocytes and is also a ligand of the alpha E beta 7 intraepithelial lymphocyte integrin, this study was undertaken to investigate whether its expression on LCH cells correlates with the clinical behaviour of the disease. Clinical records of 14 children with LCH, all of whom had cutaneous involvement, were retrospectively analysed. The expression of E-cadherin was studied by in situ immunohistochemistry on 22 frozen biopsy samples with two specific monoclonal antibodies. LCH cells of the seven children with only skin involvement were positive for E-cadherin. By contrast, LCH cells of the seven children who further developed extensive LCH disclosed a negative or low expression of E-cadherin. This study shows that dissemination and poor prognosis are associated with lack of E-cadherin expression on LCH cells. Aggressive clinical evolution of LCH may therefore be related to the loss of functions mediated by E-cadherin.

Biomarkers↗
PubMed1997

Epidermal Langerhans' cells in children with primary T-cell immune deficiencies.

Dendritic cells are the major antigen-presenting cells, especially for naive T lymphocytes; it is conceivable therefore that their absence or dysfunction may induce an immune deficiency (ID). Few data are available, however, concerning dendritic cells in human primary ID. Langerhans' cells (LC) are intraepidermal dendritic cells which express specific markers and may therefore be studied by immunohistochemistry on paraffin-embedded skin samples. Skin samples of nine children with primary ID were studied and compared with five age-matched controls. LC were present within the epidermis of two children with X-linked severe combined ID, a condition related to the lack of the common gamma-chain of interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL-15 receptors. LC were also present in skin samples of a child with Omenn syndrome and in three children with combined ID. By contrast, no LC were detected in the skin samples of two children with alymphocytosis and of a child with reticular dysgenesis, a condition characterized by the absence of peripheral blood leukocytes.

Antigens, CD1↗
PubMed1997

Analysis of susceptibility of NOD mice to spontaneous and experimentally induced thyroiditis.

Beside diabetes, non-obese diabetic (NOD) mice develop sporadic lymphoid infiltration of the thyroid gland, mimicking Hashimoto's thyroiditis. We have examined the prevalence of those manifestations in NOD mice, the influence of the major histocompatibility complex (MHC) and the association with autoantibodies. The incidence at 1 year is of 14.3% in wild-type NOD mice versus 19.6% in congenic NOD.H2k mice. The moderate, but statistically significant difference, based on the analysis of 161 NOD and 169 NOD.H2k mice, suggests that MHC genes partially control spontaneous NOD thyroiditis. Autoantibodies against thyroglobulin (Tg) are mouse specific and their presence correlates closely with thyroiditis. The strong correlation between cellular and humoral anomalies therefore resembles Hashimoto's thyroiditis. NOD and NOD.H2k mice actively immunized against Tg develop severe chronic lesions with epithelium necrosis and interstitial tissue fibrosis. Most interestingly, those lesions do not regress spontaneously as in CBA/J mice. Paradoxically, the response to Tg of lymph node cells from NOD mice is weaker both in proliferation and cytokine production. The defect is most evident for interferon-gamma-producing T cells and is reflected in the marked deficit in IgG2a antibodies. Thus a moderate anti-Tg response seems to favor chronicity of thyroiditis. In conclusion, NOD and NOD.H2k mice offer a unique opportunity of analyzing the factors leading to immune chronicity in a genetic context which promotes autoimmune endocrinopathies.

Animals↗
PubMed1997

Distribution of cell adhesion molecules in infants with intestinal epithelial dysplasia (tufting enteropathy).

BACKGROUND & AIMS: Intestinal epithelial dysplasia, or tufting enteropathy, is a newly described clinicopathologic entity with refractory diarrhea in infants. Histological abnormalities include villous atrophy, disorganization of the surface epithelium, and basement membrane abnormalities. The aim of this study was to examine defects in intestinal epithelial cell adhesion, differentiation, or proliferation in the pathogenesis of epithelial dysplasia. METHODS: Histological, immunohistochemical, and ultrastructural characteristics of epithelial dysplasia in a group of 6 children were compared with those groups with normal small bowel and other villous atrophy (celiac sprue and microvillous inclusion disease). Distribution of adhesion molecules, markers of cell polarization and proliferation, and the phenotype of intraepithelial lymphocytes were determined. RESULTS: Alterations suggestive of abnormal cell-cell and cell-matrix interactions were present in patients with epithelial dysplasia. They included abnormal distribution of alpha 2 beta 1 integrin along the crypt-villus axis, increased immunohistochemical expression of desmoglein, and ultrastructural changes of desmosomes increased in length and number. No evidence for abnormalities in epithelial cell polarization, proliferation, or T-cell activation was found. CONCLUSIONS: This study strongly suggests a role played by alterations of cell-cell and cell-matrix interactions in the pathogenesis of epithelial dysplasia.

Antigens, Differentiation↗
PubMed1997

Multiple lymphomatous polyposis of the gastrointestinal tract: prospective clinicopathologic study of 31 cases. Groupe D'étude des Lymphomes Digestifs.

BACKGROUND & AIMS: Multiple lymphomatous polyposis (MLP) is an uncommon type of gastrointestinal lymphoma. The aim of this study was to analyze the clinicopathologic features and outcome of a large series of patients. METHODS: From 1984 to 1995, 31 patients were enrolled prospectively. Exhaustive staging and immunohistochemical analysis were performed. The first 10 patients were treated with cyclophosphamide-vincristine-prednisolone (COP) and the subsequent 21 with doxorubicin-teniposide-cyclophosphamide-prednisolone (AVmCP). Eleven patients were treated with high-dose radiochemotherapy and stem cell autotransplantation because of partial response or relapse. RESULTS: Advanced age and multiple polyps involving several gastrointestinal segments characterized initial clinical presentation. The typical tumor cell phenotype (pan-B+, CD5+, and CD10-) along with Bcl-1 rearrangement indicated that MLP is the gastrointestinal counterpart of mantle cell lymphoma. After COP treatment, only 3 patients achieved partial remissions, whereas 80% of patients after AVmCP treatment achieved complete or good partial remission. High-dose radiochemotherapy changed partial into complete remission in 80% of cases. None of the initial 10 patients survived for 3 years, but the expected 5-year survival rate was 59% in patients receiving the anthracycline-containing regimen (P < 0.0001). CONCLUSIONS: MLP is a distinct entity among gastrointestinal lymphomas. An anthracycline-containing multidrug regimen and high-dose radiochemotherapy supported by autotransplantation seem to improve its poor prognosis.

Adult↗
PubMed1997

Small-intestinal transplantation.

The management of patients with intestinal failure has benefited from progress in parenteral nutrition (PN), especially home-based PN. Intestinal transplantation is therefore possible and is now, in some conditions, the logical therapeutic option. Since 1985, more than 180 small-bowel grafts have been done, involving the isolated small bowel with or without the colon (38%), the liver-small bowel (46%) or several organs (16%). Two-thirds of recipients were under 20 years of age, and indications were short-bowel syndrome (64%), severe intractable diarrhoea (13%), abdominal cancer (13%) or chronic intestinal pseudo-obstruction syndrome (8%). Of the patients, 51% survived > 2 years after the graft. Patient and graft survival depends on the type of immunosuppression, i.e. cyclosporine or FK506. The results must be interpreted carefully as they represent the first experience in numerous centres using different immunosuppressive protocols, without any randomization. The results from the largest of these centres reflect the current situation more closely. Functional grafts lead to gastrointestinal autonomy (weaning of PN) while maintaining satisfactory nutritional status and normal growth in childhood. Intestinal transplantation is theoretically indicated for all patients permanently or dependent for a long time on PN. However, as PN is generally well tolerated, even for long periods, each indication for transplantation must be carefully weighed up in terms of the iatrogenic risk and quality of life. When PN has reached its limits, especially in those associated with vascular, infectious, hepatic or metabolic complications, intestinal transplantation must be undertaken. Transplantation of the small bowel alone remains the first option, as combined liver-small bowel grafting is only indicated in the case of life-threatening progressive cirrhogenic liver disease.

Graft Rejection↗
PubMed1997

Detection of donor-derived Langerhans cells in MHC class II immunodeficient patients after allogeneic bone marrow transplantation.

T-cell dependent immune response is initiated by dendritic cells, which are the only leucocytes able to prime naive CD4-positive T cells. Langerhans cells (LC) are dendritic cells characterized by their localization within the epidermis, their dendritic shape, and their expression of specific markers such as major histocompatibility complex (MHC) class II molecules, CD1a and S100 protein. We retrospectively studied the phenotype of LC in the skin of eight children with MHC class II deficiency (bare lymphocyte syndrome) after allogeneic bone marrow transplantation (BMT). The presence of donor-derived MHC class II positive LC within the epidermis was studied by immunohistochemistry on skin biopsies performed for the determination of graft-versus-host disease. MHC class II positive LC were undetectable in the epidermis of a child who did not engraft and of three children 13-18 d after HLA-mismatched BMT, despite engraftment. However, donor-derived MHC class II positive LC were detected in four children 9-43 d after HLA-identical BMT. Our results demonstrate that LC can differentiate or expand very quickly, as early as within 9 d after BMT.

Biopsy↗
PubMed1997

Histopathology and microbiology of isolated rectal bleeding in neonates: the so-called 'ecchymotic colitis'.

Rectal bleeding in neonates is an alarming event which suggests a possible necrotizing enterocolitis (NEC) but is usually the only symptom of an unexplained colitis characterized endoscopically by ecchymotic mucosal lesions, the so-called 'ecchymotic colitis' (EC). We studied histologically and bacteriologically 18 infants (mean age: 18 days) presenting with rectal bleeding by systematic rectosigmoidoscopy and intestinal biopsies. The 18 infants were hospitalized. Prematurity was found in seven cases and an underlying condition in 14 cases (respiratory distress: six cases; infection: six cases; surgery: two cases). Histology showed a mild to moderate inflammation (10/12) of the mucosa with a prevalence of polymorphonuclear cells (8/10), frequent focal haemorrhages (11/12) and foci of pneumatosis (4/12). Numerous bacteria were seen in the mucus layer focally forming large clusters. Cultures of intestinal biopsies yielded exclusively Enterobacteriaceae species: Escherichia coli (seven cases), Klebsiella spp. (seven cases), and Enterobacter cloacae (three cases); four cases were sterile. Our study demonstrates that neonatal bleeding is associated with endoscopic and histological 'ecchymotic colitis' lesions and with a peculiar microbial flora of EBC strains. EC and necrotizing enterocolitis share similar features raising the question of the link between the two syndromes.

Biopsy↗
PubMed1997

Enteral nutrition modifies gut-associated lymphoid tissue in rat regardless of the molecular form of nitrogen supply.

BACKGROUND: It has been suggested that beneficial effect of elemental enteral diets in the treatment of inflammatory bowel diseases could be mediated by the suppression of protein dietary antigens. The objective of the present work was to study the effect of enteral diet on gut associated lymphoid tissue and on gastric Lactobacillus flora, in rat. METHODS: The effects of three molecular forms of nitrogen supply: amino acids, oligopeptides or whole casein, were compared in rats on continuous enteral diet. Frozen sections of small bowel were studied with monoclonal antibodies anti-CD5, -CD4, -CD8, -CD25, -macrophages, -MHC II. The Lactobacillus flora was also enumerated in the stomach, in order to assess the effect of ED on rat flora. RESULTS: Growth and mucosa morphology were identical in control and enteral groups. Rats on enteral diet showed, whatever was the molecular form of nitrogen supply, a decrease in CD5+, CD4+ and CD8+ intraepithelial cell numbers, but not in lamina propria cell number, and a decreased MHC II epithelial expression, when compared to control rats. The enterally fed rats also showed a decrease in Lactobacillus gastric contents. CONCLUSIONS: The current study demonstrates that continuous enteral nutrition modifies MHC II epithelial expression and gut associated lymphoid tissue cell number in rat, whatever is the molecular form of nitrogen supply. Intestinal flora could be responsible, at least for part, for these results.

Animals↗
PubMed1997

In situ interleukin 5 gene expression in pediatric Crohn's disease.

BACKGROUND: Eosinophils contribute to the intestinal inflammatory infiltrate in Crohn's disease (CD). Eosinophilic infiltration occurs early in Crohn's recurrences, and a release of eosinophil cationic proteins has been observed in active CD. The proliferation, differentiation, and activation of eosinophils are highly dependent on the cytokine interleukin 5 (IL5). In the present study, we used in situ hybridization (ISH) to investigate the expression of the IL5 gene in intestinal specimens from patients with CD. METHODS: We studied 14 intestinal samples from eight children who had undergone ileocolectomy for advanced CD. The samples were examined for the intensity of the inflammatory infiltrate. Normal pediatric intestine specimens served as controls. In situ hybridization was performed on frozen tissue using radiolabeled IL5 mRNA probes. RESULTS: Positive signal with the IL5 antisense probe was observed within numerous cells infiltrating the specimens involved with CD. The number of IL5-expressing cells correlated with the histological grade of inflammation. Most of the labeled cells were eosinophils, characterized by their bilobed nuclei. Rare IL5-positive cells were detected in the control tissues. No positive signal was obtained with the IL5 sense probe. CONCLUSION: These results suggest that IL5 can be produced by eosinophils at the sites of inflammation in active CD and could be involved in the immune response by activating eosinophils, at least in part through an autocrine pathway, and perhaps by interacting with B and T cells.

Adolescent↗
PubMed1997

Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: To evaluate prospectively in patients with follicular lymphoma and a low tumor burden three therapeutic options: delay of any treatment until clinically meaningful progression, immediate treatment with an oral alkylating agent, or treatment with a biologic response modifier, interferon alfa-2b. PATIENTS AND METHODS: Newly diagnosed follicular lymphoma patients with a low tumor burden (n = 193) were randomly assigned to one of three arms: arm 1, no initial treatment (n = 66); arm 2, prednimustine 200 mg/m2/d for 5 days per month for 18 months (n = 64); or arm 3, interferon alfa 5 MU/d for 3 months then 5 MU three times per week for 15 months (n = 63). Clinical characteristics were similar in the three arms. RESULTS: Overall response rates with prednimustine and interferon alfa were 78% and 70%, respectively. The overall response to therapy, when deferred, was similar at 70%. With a median follow-up duration of 45 months after randomization, the median freedom-from-treatment (FFT) interval was 24 months in arm 1 and the interval of freedom from treatment failure (FFTF) was 40 months in arm 2 and 35 months in arm 3. The median overall survival time was not reached and the overall survival rate at 5 years was 78% in arm 1, 70% in arm 2, and 84% in arm 3. Therefore, deferred treatment does not adversely influence survival at 5 years. Patients who progressed within 1 year had a significantly shorter survival duration (median, 48 months). CONCLUSION: Delayed treatment is feasible in patients with follicular lymphoma and a low tumor burden. For patients with early progression, more intensive therapy should be considered. For others, because delay of treatment until significant clinical progression does not seem to hamper the prognosis or subsequent response to treatment, the long-term toxicity of alkylating agents can be reduced.

Adult↗
PubMed1997

[Familial adenomatous polyposis and thyroid cancer].

Familial adenomatous polyposis may exhibit extracolonic tumors which include thyroid carcinoma. It has been recently suggested that thyroid carcinomas associated with familial adenomatous polyposis show distinct histologic features different from sporadic follicular or papillary thyroid carcinomas. We report a case of thyroid carcinoma in a young girl affected by familial adenomatous polyposis, whose thyroid tumor exhibited some of these features. This finding confirms the peculiar histologic phenotype of the thyroid carcinomas associated with familial adenomatous polyposis. Alterations of the APC gene responsible for familial adenomatous polyposis may play a role in the development of these thyroid cancers.

Adenomatous Polyposis Coli↗
PubMed1997

[Congenital asplenia. A childhood immune deficit often detected too late].

We report a case of fatal pneumococcal sepsis in a previously healthy 22 month old child. At postmorten examination the patient was found to have an atrophic spleen. When other malformations are not associated, congenital asplenia is generally diagnosed after death related to pneumococcal infection.

Fatal Outcome↗
PubMed1997

In-situ endothelial cell adhesion molecule expression in ulcerative colitis. E-selectin in-situ expression correlates with clinical, endoscopic and histological activity and outcome.

BACKGROUND AND OBJECTIVES: Little is known of the in-situ expression of adhesion molecules in ulcerative colitis (UC) according to disease activity. In the present study we investigate the vascular expression of endothelial leucocyte adhesion molecule 1 (ELAM-1/E-selectin), vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecules (ICAM-1 and ICAM-3) on the rectal mucosa of patients with UC in order to identify links between in-situ expression of these adhesion molecules and clinical, endoscopic and histological parameters. DESIGN AND METHODS: At inclusion, 16 untreated patients with UC at different stages of disease activity were assessed clinically and endoscopically and underwent rectal biopsy. Ten patients had similar assessments during follow-up. Quantitative histological and immunohistochemical scores were established with anti-E-selectin, VCAM-1, ICAM-1, ICAM-3 and HLA-DR monoclonal antibodies on frozen biopsy specimens. RESULTS: (1) At inclusion, E-selectin in-situ expression correlated with clinical activity (r = 0.7, P = 0.05), endoscopic severity (r = 0.74, P = 0.04), the histological score (r = 0.57, P = 0.02) and in-situ expression of HLA-DR on epithelial cells (r = 0.74, P = 0.01). (2) After remission, there was a significant decrease in ELAM-1 in-situ expression (P = 0.04). (3) In patients with clinical, endoscopic and histological remission the level of residual E-selectin expression appeared to be predictive of clinical relapse. (4) Vascular expression of VCAM-1 and ICAM-1 did not correlate with clinical, endoscopic or histological parameters, or with changes in disease activity. (5) ICAM-3 was never detected on endothelial cells of the colonic mucosa of controls or patients with UC. CONCLUSION: In ulcerative colitis, E-selectin, but not VCAM-1, ICAM-1 or ICAM-3, appears to play a central role in leucocyte migration into the colonic mucosa. Elevated vascular expression of E-selectin after remission may be involved in clinical recurrence.

Adult↗