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Biomedical subjects

N Brousse

Publications and source records attributed to N Brousse.

At least 199 records · Page 11Linked to original sources
PubMed1992

Control of human B cell tumor growth in severe combined immunodeficiency mice by monoclonal anti-B cell antibodies.

Severe combined immunodeficiency (scid) mice develop EBV (+)B cell tumors after infusion of EBV(+)B cells or of B cells and EBV. In this study, scid mice were infused with B cell lines derived from three patients who developed a B lymphocyte proliferative disorder after bone marrow or organ transplantation. Intraperitoneal injection of 5 x 10(6) B cells induced tumor growth in all mice, leading to death within 60 d. Human B cells were identified in spleen and bone marrow by means of immunofluorescence or EBV genome amplification, and human IgM was detected in serum. Infusion of murine monoclonal antibodies specific for human B cell membrane antigens CD21, CD24, and CD23 was effective in 80% of animals, against two of the three cell lines preventing tumor development or inducing remission according to the time of treatment. The effect was antibody dose dependent and was optimal with four intravenous infusions of at least 0.1 mg 4 d apart. Human IgM in serum and human B cells in spleen and bone marrow became undetectable when peritoneal tumors regressed completely. Infusions of IgG1 isotype-matched anti-CD4 antibody or anti-CD3 antibody had no effect. Tumors developed or recurred in 50% of these animals injected with one of the B cell line 3 mo after treatment was stopped. The same anti-CD21 and anti-CD24 antibodies had been used to treat the three patients, and shown similar degrees of effectiveness as in the scid mouse model. These results indicate that scid mice may be suitable for assessing therapeutic approaches to human B cell proliferation.

Animals↗
PubMed1992

Expression of the bcl-2 gene product in follicular lymphoma.

Expression of bcl-2 protein was analyzed in 140 cases of follicular lymphoma by immunohistologic staining of paraffin-embedded tissue; 85% of cases were positive, the frequency being related to histologic grade (100% for the small-cleaved cell type, 86% for the mixed cell type, and 76% for the large cell group). There was striking heterogeneity of bcl-2 content in a number of cases and the smaller neoplastic cells (i.e., centrocytes) were usually the most strongly labeled. In most cases, bcl-2 protein staining was much weaker in normal lymphoid cells than in the neoplastic cells. In several cases, staining for bcl-2 revealed patterns of neoplastic cell spread into adjacent tissue (e.g., normal follicles, lymphoid sinuses), and bcl-2 protein expression tended to be highest in these migratory cells.

Humans↗
PubMed1991

Aggressive primary gastrointestinal lymphomas: review of 91 patients treated with the LNH-84 regimen. A study of the Groupe d'Etude des Lymphomes Agressifs.

PURPOSE: Patients with aggressive primary gastrointestinal lymphoma undergoing the LNH-84 chemotherapy regimen were analyzed to determine the efficacy of intensive combination chemotherapy, the role of surgical debulking in patients treated with combination chemotherapy, and the toxicity associated with each of these modalities. PATIENTS AND METHODS: Ninety-one patients with primary gastrointestinal lymphoma who participated in the prospective multicenter LNH-84 combination chemotherapy trial (total number of patients in trial, 737) were analyzed. These 91 patients included 69 (76%) with diffuse large cell, nine (10%) with diffuse mixed, and seven (8%) with small noncleaved cell lymphoma. Two patients (2%) had stage IE, 54 patients (59%) stage IIE, and 35 patients (38%) stage IV disease; all patients with stage IE, 22 with stage IIE, and 18 with stage IV disease had bulky (greater than or equal to 10 cm) tumors. Specific sites of gastrointestinal involvement included stomach (47%), small bowel (38%), ileocecum (14%), colon (11%), and rectum (7%). Although surgical resection was attempted in 71 patients (78%), only 28 (31%) had complete tumor excision. All patients received three or four cycles of ACVB (defined in text) induction therapy followed by sequential consolidation as previously described. RESULTS: Responses to treatment in the 91 patients included 71 (78%) complete remissions, six (7%) partial remissions, five (5%) nonresponses, and nine (10%) deaths. With a median follow-up of 3 years, 10 patients (14%) have had relapses; predicted 4-year disease-free survival of complete responders is 85% and predicted 4-year survival of the entire group is 62%. In patients with stage IE or IIE disease, the complete response, survival, and disease-free survival rates were similar in those who underwent complete surgical resection or incomplete or no surgical resection prior to the administration of combination chemotherapy. Prognostic factors predicting for survival in the 91 patients with primary gastrointestinal lymphoma were similar to those in the 646 other patients treated with the LNH-84 regimen. CONCLUSIONS: Patients with aggressive gastrointestinal lymphoma treated with intensive chemotherapy have outcomes and prognostic factors comparable to those of patients with similar-stage aggressive lymphoma without primary gastrointestinal involvement. Surgical resection prior to the administration of combination chemotherapy did not influence the complete response rate, survival rate, or disease-free survival rate in this small group of patients.

Adolescent↗
PubMed1991

Interleukin-2 and interferon-gamma production in follicular lymphomas.

In situ hybridization with specific RNA radiolabeled probes was used to analyze the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) by 21 low-grade follicular lymphomas (FLs). All of the 21 FLs tested contained lymphokine-synthesizing cells in the interfollicular and follicular areas. Enumeration of lymphokine synthesizing cells indicated heterogeneous IL-2 production among lymph nodes tested; 2 of the 21 had much higher densities of IL-2-producing cells (855 and 570/cm2) than did the remaining 19 (mean, 92 +/- 15/cm2). IFN-gamma-producing cells displayed no such variation (mean, 77 +/- 8 IFN-gamma-producing cells/cm2). The mean IL-2/IFN-gamma-producing cell ratio was 2.69 +/- 0.84, indicating preferential induction of IL-2. The detailed distribution of lymphokine-producing cells showed that IL-2 and IFN-gamma-producing cells were located mainly in the follicular areas. The mean follicular/interfollicular ratio was 1.82 +/- 0.16 for IL-2 and 1.92 +/- 0.19 for IFN-gamma-producing cells. The results show that T-cell activation, defined by lymphokine production, occurs in FL lymph nodes in direct contact with malignant B cells. Thus, lymphokine production may play an important role in the control of tumor growth, which is the result of interaction between tumor cells and host-derived immune reaction.

Humans↗
PubMed1991

Restricted heterogeneity of T lymphocytes in combined immunodeficiency with hypereosinophilia (Omenn's syndrome).

We report the immunological characteristics of five patients with Omenn's syndrome, a rare inherited immunodeficiency also known as combined immunodeficiency with hypereosinophilia. The syndrome is characterized by T cell infiltration of skin, gut, liver, and spleen leading to diffuse erythroderma, protracted diarrhea, failure to thrive, and hepatosplenomegaly. Blood T cells as well as those infiltrating the skin and gut were found to express activation markers and were partially activated by mitogens but not by antigens. Although the lesions resembled those in graft-versus-host disease, the blood T cells were shown by DNA haplotype analysis using probes revealing variable number of tandem repeats to belong to the patients as well as the T cells infiltrating the gut and skin in one patient. A given T cell subset (TCR alpha beta+, CD4+/CD8+, or TCR gamma delta+) was predominant in each patient, with a specific distribution in the skin lesions. Moreover, the study of T cell receptor beta, gamma, and delta gene rearrangements in four patients revealed oligoclonality involving C beta 1, C beta 2, or different V gamma J gamma or V delta J delta genes. This indicates that restricted heterogeneity of the T cell repertoire, previously reported in one case, is a major feature of this syndrome. The occurrence of alymphocytosis-type severe combined immunodeficiency in the brother of one of the patients suggests that the restricted heterogeneity of T cell receptor gene usage in Omenn's syndrome may arise from leakiness, within the context of a genetically determined faulty T cell differentiation.

Antigens, CD↗
PubMed1991

[Severe Crohn's disease in children. Retrospective study of 38 cases].

Thirty-eight children presenting with severe Crohn's disease (CD) were studied retrospectively over a mean period of 6 years. The severity of CD was estimated according to an activity score. This was initially 66 +/- 19 reaching 100 in 16% of cases. Initial involvement included ileon and large intestine only (n = 23), large intestine (n = 11) and ileon only (n = 4), with upper GI tract or perineal involvement in 32 and 75% of cases respectively. The treatments consisted of corticosteroids (n = 34), azathioprine (n = 11), continuous enteral feeding (CEF) (n = 25), parenteral nutrition (PN) (n = 30). Mean recurrence rates per patient and per year were 0.6 in the groups including ileon and large intestine or the large intestine only and 0.3 in the ileal group. A surgical resection was performed in 20 cases with a mean rate of reoperation of 40% at 5 years. Reoperations were necessary only in the group involving the ileon and large intestine. Mean weight catch-up in 3 months and height growth speed were 6 kg and 1.7 to 3.1 cm/year under CED and/or PN. After a 6 year follow-up the activity index was decreased by 70% with a quality of life considered to be good in 60% of cases.

Child↗
PubMed1991

[A study of tolerance induced by liver transplantation on intestinal graft in the rat].

In some strain combinations of rats, orthotopic liver transplantation (OLT) permits long-term donor-specific survival of fully allogeneic kidney, heart or skin grafts. The difficulties encountered in the clinical situation to obtain tolerance of small-bowel transplantation (SBT), in spite of massive non-specific immunosuppression, led us to study possible liver-induced tolerance in SBT. Inbred DA (RTIa) and PVG (RT1c) rats were used respectively as donors and recipients and divided in two groups: group 1: SIT alone (n = 6); group 2: combined OLT/SBT (n = 6). SIT was performed 17 days after OLT. No immunosuppressive treatment was given to the recipients. Biopsies of small-bowel grafts were performed in both groups at various times after small bowel engraftment. All animals in group 1 showed evidence of acute rejection of the graft between days 6 and 9 post-graft. The histologic pattern of rejection associated lamina propria (LP) mononuclear cell infiltration, crypt lesions and villous atrophy at the end-point of rejection. In group 2, long-term survival (> 100 days) of small bowel grafts was achieved in five of the six animals in spite of strong mononuclear cell infiltration in the LP, which peaked two months after small bowel grafting but then disappeared partially. This striking mononuclear cell infiltrate contrasted with only minor epithelial damage. These data demonstrate that liver grafting can enhance the survival of a small-bowel graft from the same donor in a rat model. Histological findings show that an intense immunological reaction takes place within liver-induced tolerated small-bowel grafts.

Animals↗
PubMed1991

Non-Hodgkin's lymphoma presenting as a primary tumor of the liver: presentation, diagnosis and outcome in eight patients.

We report the diagnostic, prognostic and therapeutic features of non-Hodgkin's lymphoma in eight patients in whom the disease was seen as a primary tumor of the liver. This series illustrates the variety of situations in which lymphoma might be diagnosed: (a) abdominal pain and hepatomegaly (three cases), (b) incidental finding at evaluation of a patient with cirrhosis (two cases), (c) secondary neoplasm after treatment for Hodgkin's disease (one case) and (d) complication of AIDS (two cases). In most cases, clinical and/or radiological features were nonspecific. However, the combination of the following features must be considered as suggestive: occurrence of an apparently primary hepatic tumor in an immunocompromised patient, absence of the usual serum tumor markers and increased serum lactic dehydrogenase activity. The final diagnosis was based on histological examination of specimens obtained by ultrasonically guided liver biopsies or at surgery. All cases belonged to unfavorable histological subtypes. Immunohistochemical findings on paraffin-embedded sections demonstrated the B-lymphocyte lineage of the seven tumors available for study. In the three patients without coexisting disease, complete remission was obtained by surgery alone or combined with chemotherapy. In the two patients with coexisting cirrhosis, outcome was rapidly unfavorable, with death occurring less than 3 mo after diagnosis. Among the three immunocompromised patients, two experienced a rapid unfavorable outcome, and the remaining one was in complete remission after surgery and chemotherapy. In conclusion, primary non-Hodgkin's lymphoma of the liver arising in patients without coexisting disease has a slow progression and might be successfully treated by surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1990

Subsets of CD3+ (T cell receptor alpha/beta or gamma/delta) and CD3- lymphocytes isolated from normal human gut epithelium display phenotypical features different from their counterparts in peripheral blood.

Intestinal intraepithelial lymphocytes (IEL) were studied, after isolation in humans, for their surface antigens with a large variety of monoclonal antibodies. They show peculiar characteristics when compared with peripheral blood lymphocytes and intestinal lamina propria lymphocytes. Although a majority of human intraepithelial lymphocytes (IEL) express an alpha/beta type of T cell receptor (TcR), 13% express a gamma/delta TcR, a percentage which was significantly higher than that found in blood and in lamina propria. In contrast to observations in mice, there was no evidence that normal human TcR gamma/delta+ intestinal IEL might use preferential variable segments of gamma genes. About 10% of human intestinal IEL expressed the alpha chain but not the beta chain of CD8, thus resembling a subset of CD8 alpha+beta- IEL, which was recently described in mice and found to be of thymoindependent origin. In addition, 10% of human IEL had a unique phenotype of immature T cells, as they bore only CD7, but no other T cell or natural killer cell markers. Finally, even the major population of IEL which expressed the usual markers of the T cell lineage (CD3, TcR alpha/beta, CD2, CD4 or CD8 alpha/beta) differed from peripheral blood T lymphocytes by their peculiar expression of surface antigens associated with activation. Indeed, 80% of IEL were CD45R0+, CD45A-, but co-expression of CD11a, CD29 and LFA-3 was inconstant. In addition, 90% of IEL expressed HML-1.

Antigens, CD↗
PubMed1990

Classification of intractable diarrhea in infancy using clinical and immunohistological criteria.

Several experimental studies have demonstrated that activated intestinal T cells can induce villous atrophy. This observation led us to examine the possible role of activated T cells in the pathogenesis of intestinal lesions in a group of 13 children with intractable diarrhea and villous atrophy of unknown origin. Immunohistochemical study showed signs of intestinal mononuclear cell activation in seven patients. These signs included a marked increase in the number of mucosal T cells, mainly TCR alpha beta+, the appearance of lamina propria interleukin-2-receptor-bearing cells, and an increased expression of HLA-DR antigens by enterocytes. No local cause of intestinal T-cell activation was found. However, four out of seven patients had extradigestive symptoms of autoimmunity, suggesting that the intestine might also be the site of an autoimmune reaction responsible for the epithelial lesions. In these patients, presence of crypt necrosis and colic extension of the lesions suggested poor prognosis. In contrast, in six other patients, no immunohistochemical evidence of mucosal T-cell activation was obtained. In the latter cases, analysis of clinical data favored the hypothesis of a primary inborn defect of enterocyte differentiation.

Atrophy↗
PubMed1990

Peripheral T-cell lymphomas have a worse prognosis than B-cell lymphomas: a prospective study of 361 immunophenotyped patients treated with the LNH-84 regimen. The GELA (Groupe d'Etude des Lymphomes Agressives).

The prognostic significance of phenotype in malignant lymphomas (ML) is a matter of controversy. Here we analyze the clinical presentation, response to treatment, and survival of the 361 phenotyped patients with ML who were treated by the LNH-84 regimen. Histologic subtypes were diffuse-small cell in 10 patients, diffuse mixed in 69, diffuse large-cell in 177, immunoblastic in 94, and anaplastic large-cell in 11. One hundred and eight patients (30%) had a peripheral T-cell ML and 253 (70%) a B-cell ML. Most of B-cell MLs were of diffuse large-cell type, and the T-cell MLs were distributed among diffuse mixed and immunoblastic subtypes. T-cell MLs had an aggressive presentation with more patients having advanced stage (21% versus 41% stage II, 53% versus 45% stage IV, p = .0002), and B symptoms (58% versus 42%, p less than .01). The only significant difference in clinical manifestations were the higher frequency of gastrointestinal involvement in B-cell MLs (20% versus 2%, p less than .0001) and the more frequent spleen (39% versus 21%, p = .0005) and skin (19% versus 3%, p less than .0001) involvement in T-cell MLs. There was no difference in response to the LNH-84 regiment between the two subgroups, but T-cell ML patients relapsed at a higher rate (43% versus 29%, p less than .001). T-cell ML patients have a significantly shorter freedom-from-relapse (FFR) survival (median: 34 months versus not reached, logrank test: p = .002) and a non-significant shorter overall survival (median: 42 versus 50 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Infected cells and immune cells in the gastrointestinal tract of AIDS patients. An immunohistochemical study of 127 cases.

Human immunodeficiency virus (HIV) proteins were detected by immunohistochemistry in the duodenal and rectal mucosa of 30% of 127 AIDS patients studied. HIV-infected cells were present in the lamina propria in 95% of the positive biopsies. They were immune cells, either isolated lymphocytes and macrophages (1-4 per positive biopsy) or dendritic reticulum cells forming a network in the germinal centres of mucosal lymphoid follicles. HIV proteins were not found in the duodenal epithelium or in the superficial rectal epithelium. In two cases (5% of the positive biopsies), they were found in rectal glands: the HIV-infected cells could be either epithelial cells or immune cells. This study confirms that the gut can be a target organ for HIV and that HIV is mainly carried by gut immune cells. The phenotypic study of lymphoid populations and macrophages in the gut mucosa of AIDS patients showed an inverse CD4/CD8 ratio in the lamina propria, compared with normal controls. This was independent of the presence of HIV proteins and is probably responsible for the appearance of opportunistic infections in the mucosa. An increase in activated macrophages was also noted in the mucosa of AIDS patients.

Acquired Immunodeficiency Syndrome↗