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Biomedical subjects

M Peuchmaur

Publications and source records attributed to M Peuchmaur.

At least 19 recordsLinked to original sources
PubMed1992

In vivo production of interleukin-10 by malignant cells in AIDS lymphomas.

Expression of the interleukin (IL)-10/BCRF1 gene was studied by in situ hybridization in tissue samples from acquired immunodeficiency syndrome (AIDS) lymphomas using a BCRF1 probe which also recognizes the human IL-10 sequence. Hybridization was detected in 8 out of 15 lymphomas. In contrast, the IL-10/BCRF1 gene expression was detected in only 1 out of 11 lymphomas from human immunodeficiency virus (HIV)-seronegative patients (p = 0.05). In AIDS lymphomas, the number of cells labeled with a BCRF1-specific probe was dramatically lower than that of cells labeled with the IL-10/BCRF1 probe. Thus, the IL-10 rather than the BCRF1 gene was expressed. Production of IL-10 was associated with that of IL-10 mRNA, as shown by immunodetection of the protein in numerous cells. In contrast, BCRF1-producing cells were rarely detected. Both in situ hybridization and immunochemical experiments indicated that malignant cells were involved in this IL-10 synthesis. IL-10 production in AIDS lymphomas was associated with the presence of Epstein-Barr virus (EBV) in lymphomatous cells (p = 0.02). As IL-10 is a potent growth factor for human B lymphocytes, these results suggest that IL-10 may stimulate the proliferation of malignant cells in an autocrine pathway in a number of AIDS lymphomas, and that EBV and HIV may synergistically trigger its production.

Gene Expression↗
PubMed1992

Production of cytokines in sarcoid lymph nodes: preferential expression of interleukin-1 beta and interferon-gamma genes.

Sarcoidosis is a chronic granulomatous disease that may be considered to be a human model for the delayed-type hypersensitivity reaction. The expression of cytokine genes in organs displaying sarcoid granulomas was analyzed by in situ hybridization with several cytokine probes using biopsies from 11 sarcoid lymph nodes. We detected cells expressing interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-2, and interferon-gamma (IFN-gamma) genes in all lymph nodes. The major finding of this study was that cytokine genes are independently expressed. Of the monokine genes, the IL-1 beta gene was preferentially expressed. The distribution of cells containing IL-1 beta mRNA was characterized by their amalgamation in clusters inside sarcoid granulomas. Cells expressing the TNF-alpha gene were located exclusively inside granulomas and were always scattered. Cells expressing the IL-6 gene or the IL-1 alpha gene were found scattered inside sarcoid granulomas and in the residual lymphoid tissue. The number of cells expressing the IL-1 beta gene was significantly higher than that of cells expressing TNF-alpha gene (P = .001), IL-6 gene (P = .007), or IL-1 alpha gene (P less than .001). Of the cells expressing lymphokine genes, those expressing the IFN-gamma gene were 31.9 (+/- 7.6) times more frequent than those expressing the IL-2 gene (P less than .001). Cells containing IFN-gamma mRNA were detected mainly inside sarcoid granulomas, whereas cells containing IL-2 mRNA were randomly distributed. These results show that each monokine gene or lymphokine gene can be independently expressed in vivo. The high expression level of the IL-1 beta gene and the IFN-gamma gene inside granulomas may be specific to delayed-type hypersensitivity immune reactions.

Cytokines↗
PubMed1992

Multicentric Kaposi's sarcoma in a 5-year-old human immunodeficiency virus-negative renal allograft recipient.

We describe the clinical and pathologic features of a case of pediatric multicentric Kaposi's sarcoma (KS) associated with allograft transplantation in a human immunodeficiency virus (HIV)-negative child. A lethal polyadenopathic and visceral KS occurred in a 5-year-old Caribbean boy who had undergone an allogenic renal transplantation for diffuse mesangial sclerosis with end-stage renal failure 4 months previously. The HIV-1 and HIV-2 serologies were negative. Despite its rarity, KS must be considered as a differential diagnosis in posttransplantation polyadenopathic or multisystemic syndromes in children.

Autopsy↗
PubMed1992

Treatment of central nervous system B lymphoproliferative syndrome by local infusion of a B cell-specific monoclonal antibody.

A 9-month-old infant developed Epstein-Barr virus-induced lymphoproliferative syndrome with mediastinal and central nervous system localizations, associated with mediastinal tuberculosis, 5 months after heart transplantation. As a combination of anti-B cell antibodies (CD21- and CD24-specific) and recombinant interferon alpha 2b, given intravenously, was not effective on the central nervous system disease, the anti-CD21 antibody was infused intrathecally via an Ommaya reservoir. High local concentrations of monoclonal antibodies were achieved, with no adverse effects. A dramatic clinical response was obtained, with clearance of abnormal cells from the cerebrospinal fluid and a clear reduction in the abnormalities on the brain images. The patient is well 7 months later. This observation indicates that treatment of B lymphoproliferative syndrome with central nervous system localization is feasible using a nontoxic, local B cell-specific approach.

Antibodies, Monoclonal↗
PubMed1992

Rejection in lung transplantation--an immunohistochemical study of transbronchial biopsies.

The number, distribution, and phenotype of mononuclear cells infiltrating the allograft lung transplant were determined immunohistochemically with monoclonal antibodies directed against cellular antigens (CD3, CD4, CD8, CD22, CD25, CD16, CD56, CD68, HLA-DR) on frozen sections of transbronchial biopsies. Seventy-two transbronchial biopsies from 21 patients undergoing lung or heart-lung transplantation were evaluated histologically and immunohistologically in a prospective study. Four major results were obtained in the graft lung parenchyma: (1) whatever the histological grading of rejection, T lymphocytes expressing CD3 were present and in a significantly higher number than in control subjects (P < 0.0005); (2) there was a positive correlation between histological rejection and the number of CD3+, CD8+, CD25+, CD16+ cells (P < 0.01); (3) the CD4/CD8 ratio was inverted (0.52 +/- 0.04), with no correlation with the histological rejection; and (4) the number and location of CD3+, CD25+ cells did not correlate with CMV identification in bronchoalveolar lavage. Immunohistochemical criteria could be used for diagnosis of rejection in the management of heart-lung transplantation.

Adolescent↗
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

Interleukin-6 gene expression in Castleman's disease.

Defined by histological criteria, Castleman's disease (CD) is a clinically and histologically heterogeneous syndrome. The functional status of immune cells in affected tissues may vary between the different forms of the disease. To address this question, the expression of cytokine genes in eight CD lymph nodes was analyzed by in situ hybridization. Two lymph nodes were taken from patients with a localized form of the disease associated with systemic manifestations, two from patients with a localized form without systemic symptoms, and four from patients with a multicentric form. Five lymph nodes exhibiting a benign follicular hyperplasia were used as controls. The interleukin-6 (IL-6) gene was expressed at a very high level in two cases: the two localized forms of CD associated with systemic manifestations. IL-6 gene overexpression occurred inside follicles of these lymph nodes. The morphology of follicular cells hybridizing with the IL-6 probe or labeled with an anti-IL-6 monoclonal antibody suggested that follicular dendritic cells expressed the IL-6 gene. In contrast, no IL-6 gene expression was detected inside follicles of the six other CD lymph nodes or of the five control lymph nodes. In interfollicular areas, IL-6 gene-expressing cells were detected in all lymph nodes by both in situ hybridization and immunohistochemistry. In CD lymph nodes, positive cells were located outside sinuses, in close contact with blood vessels and plasma cells. This distribution was clearly different from that observed in control lymph nodes, in which IL-6 gene-expressing cells were present inside sinuses. A similar difference between CD and control lymph nodes was observed for the distribution of IL-1 beta and IL-1 alpha gene-expressing cells in interfollicular areas. The morphology of interfollicular IL-6-producing cells was heterogeneous, consistent with that of macrophages, interdigitating cells, lymphocytes, and endothelial cells, and different from that of plasma cells. Taken together these results show that CD is consistently associated with a particular pattern of IL-6 gene expression in interfollicular areas whereas elevated IL-6 gene expression inside follicles only occurs in the localized form of the disease associated with systemic manifestations. The variable pattern of IL-6 gene expression as well as the clinical and histologic heterogeneity of CD indicate that different immune mechanisms may be involved in the different forms of this disease.

Adolescent↗
PubMed1991

In situ production of interleukins in hyperplastic thymus from myasthenia gravis patients.

We analyzed by in situ hybridization the expression of four interleukin genes (interleukin-beta [IL-1 beta], IL-6, IL-2, and interferon-gamma) in seven thymuses displaying a follicular hyperplasia. The seven thymuses were obtained from patients with myasthenia gravis. Interleukin-1 beta- and IL-6-producing cells were detected in similar amounts and with similar distributions: mainly in perifollicular areas and in the connective structures emerging from the septae at the site of cortex disruption. The comparison of in situ hybridization and immunohistochemical results suggested that thymic epithelial cells and/or perifollicular macrophages were responsible for this production. Interleukin-2-producing cells were detected in perifollicular areas and, to a lesser extent, inside follicles. They were clearly outnumbered by CD25-positive cells which were similarly distributed. Despite the expression of these molecular and immunohistochemical markers of T-cell activation, interferon-gamma-producing cells were extremely rare in myasthenic thymuses. The pattern of interleukin production (which was virtually absent in normal control thymuses) in myasthenic thymuses was different from that in benign hyperplastic lymph nodes. This interleukin production may play a role in the development of follicular hyperplasia in myasthenic thymuses, a phenomenon which is associated with the in situ production of autoantibodies.

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

HIV proteins absent from placentas of 75 HIV-1-positive women studied by immunohistochemistry.

Recent epidemiological and virological data suggest that the incidence of maternofetal transmission of HIV-1 infection is between 20 and 30%. The available evidence points to a possible role of peri- and postnatal contamination, but the isolation of HIV from fetuses shows that transplacental transmission also occurs. We attempted to detect, by means of an immunohistochemical method, HIV proteins in frozen placentas from 75 HIV-1-positive women (30 at term, 45 induced abortions). In addition, in situ hybridization using HIV-specific probes was performed in three cases. Neither HIV proteins nor nucleic acid sequences were detected, but CD4+ mononuclear cells were present in the chorion and villi, regardless of the clinical and biological status of the mother (particularly in the nine cases in which the infants were infected). There are several possible mechanisms involving the placenta in the maternofetal transmission of HIV, including active transport of the HIV-immunoglobulin G complex via Fc receptors on trophoblastic cells, passive transplacental passage of HIV during a viraemic episode, the passage of infected maternal cells, and infection of the placenta itself. The methods we used could not rule out the presence of HIV DNA provirus within the genome of placental cells. In any event, immunohistochemical detection of HIV proteins in the placenta is not a technique suitable for the prenatal diagnosis of HIV infection or for identifying newborns likely to develop HIV infection.

Adult↗
PubMed1991

Activation of cytotoxic cells in hyperplastic lymph nodes from HIV-infected patients.

Serine esterase B (SE B) is a protein contained in cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells; SE B gene is transcribed upon activation of these cytotoxic cells. In order to show the in vivo interactions between HIV-infected cells and anti-HIV cytotoxic cells we analysed, by in situ hybridization, the expression of the SE B gene in eight hyperplastic lymph nodes from HIV-1-infected patients presenting with persistent generalized lymphadenopathy. We detected numerous cells expressing the SE B gene. The mean number of positive cells was 3.2 times higher in HIV lymph nodes than in six non-HIV hyperplastic lymph nodes studied in parallel (P less than 0.05). In control lymph nodes, the SE B gene was expressed only in interfollicular areas; virtually no cells expressed the SE B gene within follicles. In contrast, in HIV lymph nodes cells expressing the SE B gene were distributed either in interfollicular areas or within follicles. Expression of the SE B gene inside follicles was thus a specific feature of HIV lymph nodes (P less than 0.001) and was associated with the presence of HIV antigens and RNA at the same site. These results suggest that cytotoxic cells are activated in follicles of HIV lymph nodes and may be involved in the lysis of HIV-infected cells. Such a phenomenon may explain the development of follicle lysis, a specific feature of HIV lymph nodes. It may also inhibit the spreading of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Parotid carcinoma in children. Apropos of 3 cases].

Three pediatric cases of parotid carcinoma are reported two are acinic cell carcinoma of relatively good prognosis. The third case is a cystic variety of salivary duct carcinoma, more exceptional, which prognosis remains uncertain. A review of the parotid tumors of this age range is done.

Adenocarcinoma↗
PubMed1990

Cystic benign lymphoepithelial lesion of the salivary glands in HIV-positive patients. Report of two cases with immunohistochemical study.

Two cases of cystic benign lymphoepithelial lesions (CBLL) of the submandibular and parotid glands occurring in HIV-positive patients are reported. The clinical and pathological criteria are defined and the differences from Sjögren's syndrome discussed. The presence, in the epithelial component, of T-cells labelled by the human mucosal lymphocyte antibody argues for a primary involvement of epithelial structures in CBLL, the lymphoid hyperplasia occurring secondarily.

Adult↗
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↗