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Biomedical subjects

N Brousse

Publications and source records attributed to N Brousse.

At least 217 records · Page 12Linked to original sources

Role of in vivo activated T cells in the mechanisms of villous atrophy in humans: study of allograft rejection.

Four children aged 6 months to 9 years received fully HLA-mismatched ABO identical small intestinal allografts. In order to monitor the rejection process and to study epithelial changes induced by intestinal T cells activated by an allogeneic reaction, iterative biopsies were performed through the ileal enterostomy and processed for histology and immunohistochemistry. Episodes of acute histological reaction were observed in all 4 patients between day 10 and 160. It was preceded by appearance of pericryptic CD3+CD4+ or CD8+ T cells of recipient origin, increasing numbers of which expressed CD25. Simultaneously, early epithelial changes were noted: increased HLA-DR expression by enterocytes and decreased mitotic rate as shown by decreased numbers of KI67+ cells in crypts. During acute histological rejection, massive infiltration of mucosa by CD25+CD3+ T-cells and activated macrophages (KIM6+CD25+), was associated with crypt necrosis and then, destruction of surface epithelium. Successful treatment of graft rejection episodes with antilymphocytic serum (2), anti-CD3 monoclonal antibody (2), anti-CD25 monoclonal antibody (1) resulted in a rapid decrease of CD3+ cells, a more progressive decrease of CD25+ and KIM6+ macrophages, reappearance of KI67+ cells in crypts followed after a variable delay by recovery of villous architecture. Chronic histological rejection was observed in 1 patient after 7 months. It was characterized by total villous atrophy, fibrosis, endarteritis, infiltration of lamina propria and epithelium by CD3+CD8+ cells, a small number of which CD25+, strong HLA-DR expression by crypt and surface epithelium, increased numbers of KI67 enterocytes. Altogether these data suggested that activated T cells can induce two types of villous atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrophy↗

Production of interleukins in human immunodeficiency virus-1-replicating lymph nodes.

To document the in vivo interactions occurring between the immune system and HIV replicating cells, we analyzed using in situ hybridization the production of IL-1 beta, IL-6, IL-2, and INF-gamma in eight hyperplastic lymph nodes from HIV-1 infected patients. Numerous IL-1 beta- and IL-6-producing cells associated in clusters were detected in sinuses. Few individual IL-1 beta- and IL-6-producing cells were present in interfollicular and follicular areas. IL-2- and INF-gamma-producing cells were observed in all lymph node compartments, with a selective enrichment in germinal centers. The amount and distribution of IL-1 beta, IL-6-, and IL-2-producing cells in HIV lymph nodes were not different from those found in six HIV unrelated hyperplastic lymph nodes. In contrast, a higher level of INF-gamma production was observed in HIV-1 lymph nodes. The CD8+ cells that accumulate in germinal centers of HIV lymph nodes (and not in non-HIV germinal centers) were actively involved in this INF-gamma production. INF-gamma synthesizing cells were in direct contact with cells containing HIV core antigens and HIV RNA. Thus a high INF-gamma production may characterize anti-HIV T cell immune response, potentially contributing to control of viral spreading as well as to the development of follicle lysis.

Adult↗

[Treatment of aggressive non-Hodgkin's lymphoma in aged patients with a combination of methyl-GAG, etoposide and prednimustine].

The authors report the results of a chemotherapy regimen of methyl-GAG, etoposide and prednimustine in 21 elderly patients (median age = 78 years) with aggressive non-Hodgkin's lymphoma. Sixteen patients responded (11 complete remissions, 5 partial remissions) with minor toxic side-effects. This regimen could be proposed for patients whose age and/or cardiovascular status prohibit treatment with usual anthracycline-containing chemotherapy programs.

Aged↗

Immune cells associated with M cells in the follicle-associated epithelium of Peyer's patches in the rat. An electron- and immuno-electron-microscopic study.

Follicle-associated epithelium of Peyer's patches can be differentiated from nearby villous epithelium by the presence of M cells which are antigen-sampling epithelial cells, and by an increase in intraepithelial lymphocytes that are in close contact with M cells. The phenotype of the immune cells close to the M cells of the follicle-associated epithelium of rat Peyer's patches was determined by immunohistochemistry and compared with that of the intra-epithelial lymphocytes of the villous epithelium. Lymphoid T cells, predominantly of the cytotoxic/suppressor phenotype, were observed both in follicle-associated epithelium and in villous epithelium. Lymphoid B cells, mainly immunoblasts and plasma cells containing intracytoplasmic IgM, were present only in the follicle-associated epithelium, near M cells. Macrophages were also present, in contact with M cells, in follicle-associated epithelium, but not in villous epithelium. In addition, M cells bore Ia molecules on their apical membranes. These findings reinforce the concept of immune specialization of the follicle-associated epithelium, by demonstrating that this epithelium contains all the effector cells of immune responses.

Animals↗

LNH-84 regimen: a multicenter study of intensive chemotherapy in 737 patients with aggressive malignant lymphoma.

From July 1984 to September 1987, 737 patients with aggressive malignant lymphoma (ML) were treated by an intensive regimen (LNH-84) comprising three or four courses of doxorubicin, 75 mg/m2; cyclophosphamide, 1,200 mg/m2; vindesine, 2 mg/m2 x 2; bleomycin, 10 mg x 2; and prednisolone, 60 mg/m2 x 5 (ACVB), consolidation with high-dose methotrexate, ifosfamide, etoposide, asparaginase, and cytarabine, and a randomized late intensification with two courses of cytarabine, cyclophosphamide, teniposide, bleomycin, and prednisone (AraCVmB). Four hundred forty-two patients had intermediate-grade ML, 221 highgrade ML, and 74 unclassified ML. Most of the patients had advanced disease: stage IIE (23%), III (13%), or IV (47%); 38% disseminated nodes; 38% two or more extranodal sites; and 41% a tumoral mass greater than 10 cm. Five hundred fifty-three patients (75%) went into complete remission (CR), 63 (9%) into partial remission, 62 (8%) failed to respond, and 59 (8%) died during ACVB courses, 17 of them from progression of the disease. With a median follow-up of 23 months, the estimated 2-year overall survival time to failure (TTF), and time to relapse (TTR) survival are 67%, 56%, and 67%, respectively. Patients receiving a late intensification had the same relapse rate as the other patients. A persistent fibronecrotic mass was found in 150 patients (20%) and did not influence the relapse rate. Toxicity was mainly neutropenia and infection during the ACVB courses, with 40 patients (5%) dying from septic complications while responding to treatment. Fifty-three percent of the patients had a neutropenia less than 0.500 x 10(9)/L, 58% fever (6% grade 4), and 49% a documented infection (8% grade 4). These results obtained with the LNH-84 regimen demonstrate that this therapeutic scheme is an effective treatment for aggressive ML.

Adolescent↗

Lymphoid follicular proctitis. A condition different from ulcerative proctitis?

A heterogeneous group is formed by patients presenting with clinical features suggestive of inflammatory bowel disease limited to the rectum and whose rectal biopsies show lymphoid follicular hyperplasia of the mucosa. All these cases are traditionally considered as one variant of chronic ulcerative colitis, so-called ulcerative proctitis. Twenty such cases were critically assessed on clinical, endoscopic, and histologic grounds, as well as on response to treatment and follow-up data. While 11 patients showed clinicopathologic features consistent with typical chronic ulcerative colitis, the other nine patients appeared to form a different group, for which the term "lymphoid follicular proctitis" seemed justified. Lymphoid follicular proctitis was, overall, characterized by rectal bleeding, a congested and granular mucosa without ulceration, abnormal and coalescing hyperplastic lymphoid follicles without acute inflammation, and failure to respond to local steroid therapy. The nature of lymphoid follicular proctitis is uncertain at present but seems unrelated to chronic ulcerative colitis.

Adolescent↗

Same peculiar subset of HML1 + lymphocytes present within normal intestinal epithelium is associated with tumoral epithelium of gastrointestinal carcinomas.

The present study shows that the distribution of T lymphocytes in gastrointestinal carcinomas and their metastases mimic the distribution of T lymphocytes in normal intestine. The composition of the peritumoral reaction resembled that of normal lamina propria with a predominance of CD3 + CD4 + T cells. In contrast, lymphocytes located between carcinomatous cells showed phenotypical features similar to those of intraepithelial lymphocytes (IEL) in normal intestine; in particu(abstractlar they expressed the antigen defined by HML-1, a monoclonal antibody raised against normal human intestinal IEL which reveals 95% IEL but very few cells in lymphoid (abstractorgans and blood. As normal intestinal IEL, the majority of intratumoral lymphocytes had the CD3+ CD8+ phenotype. A panel of monoclonal antibodies and double immunostaining techniques permitted a better characterisation of minor subsets of IEL. Two subsets of HML1 + CD3 + CD4- CD8- and of HML1+ CD3- cells, representing 2% and 3% of normal intestinal IEL respectively, did not significantly increase in carcinomatous epithelium. In contrast, in carcinomatous epithelium, but not in normal intestinal epithelium, we observed the appearance of a few lymphocytes displaying the phenotype of activated T cells (CD25+) or of natural killer cells (NKHI+) or of suppressor cells (CD11+). Such cells may participate in antitumoral defence. Although a similar population of HML1+ lymphocytes is associated with normal and carcinomatous intestinal epithelium, some interactions between lymphocytes and epithelial cells may not be maintained in tumoral epithelium. It has previously been shown that HLA-DR expression by enterocytes is modulated by intraepithelial lymphocytes. In our study, no correlation could be shown between the degree of lymphocytic infiltration and the expression of HLA-DR antigens on carcinomatous cells.

Adenocarcinoma↗

Enteropathy-associated T cell lymphoma (malignant histiocytosis of the intestine) is recognized by a monoclonal antibody (HML-1) that defines a membrane molecule on human mucosal lymphocytes.

Enteropathy-associated T cell lymphoma (EATCL; malignant histiocytosis of the intestine) arises in patients with enteropathy, which in some cases is known to be a result of gluten sensitivity. The lymphoma arises in the intestine, where it may remain localized, although eventual dissemination is the rule. Intraepithelial tumour cells often are seen at the mucosal tumor margin. These features suggest that EATCL may be a tumor of intraepithelial lymphocytes. A monoclonal antibody (HML-1) has been produced recently that recognizes the entire intraepithelial lymphocyte population and 50% of lamina propria T cells but very few cells outside the mucosa. Immunocytochemistry has shown that all cases of enteropathy-associated T cell lymphoma studied are HML-1 positive and all peripheral T cell lymphomas and mucosal B cell lymphomas are HML-1 negative. This suggests strongly that EATCL is a tumor of mucosal T cells, possibly the intraepithelial T cell component.

Antibodies, Monoclonal↗

[Digestive lymphomatous polyposis: study of a case diagnosed by rectal biopsy].

We report a case of gastrointestinal lymphomatous polyposis revealed by a rectal tumor. Numerous polypoid lesions, 5 to 20 mm in diameter, were found at various levels of the gastrointestinal tract. Microscopic examination of gastric, duodenal, colic and rectal specimens led to the diagnosis of small cleaved-cell type lymphoma. The immunohistochemical study showed a monotypic surface staining of the lymphomatous cells with anti-IgM, IgD, kappa, C3b, and CD5 antibodies. This type of lymphoma is rare and presents as multifocal polyposis of the gastrointestinal tract. Only histologic and immunohistologic studies can establish diagnosis. Gastrointestinal lymphomatous polyposis is classified as a low-grade malignant lymphoma, with frequent nodal, hepatosplenic, bone marrow, and blood involvement. Chemotherapy is the appropriate treatment.

Aged↗