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Biomedical subjects

N Brousse

Publications and source records attributed to N Brousse.

At least 19 recordsLinked to original sources
PubMed1995

Expression of GM-CSF receptor by Langerhans' cell histiocytosis cells.

Langerhans' cell histiocytosis (LCH) is characterized by the proliferation of large mononucleated cells containing Birbeck granules and expressing CD1a. Recent studies have demonstrated that LCH is a clonal proliferation; however, its aetiology is still unknown. Growth and differentiation of bone-marrow-derived cells are controlled by cytokines. The proliferation, differentiation and activation of normal Langerhans cells are controlled by granulocyte/macrophage colony-stimulating factor (GM-CSF) in vitro. Therefore, GM-CSF could be implicated in the pathogenesis of LCH. Indeed, LCH cells contain GM-CSF, and children with disseminated LCH have an elevated GM-CSF serum level. As a cytokine only acts on cells expressing a specific receptor, we investigated the presence of GM-CSF receptor on LCH cells. Fourteen frozen tissue samples from children with LCH were studied by in situ immunohistochemistry with two mouse monoclonal antibodies specific for the alpha chain of the GM-CSF receptor (CDw116). LCH cells of all the samples were positively stained with both antibodies. This study suggests that GM-CSF may be a growth factor for LCH cells.

Animals↗
PubMed1995

Intractable diarrhea of infancy with epithelial and basement membrane abnormalities.

We describe a form of intractable diarrhea in six children (four girls) with similar clinical histories and identical histopathologic features. The children had watery diarrhea of neonatal onset requiring total parenteral nutrition. Two had siblings who had died of diarrhea in the first year of life; two others are sisters. Repeated duodenal or jejunal biopsies revealed villous atrophy with normal or hyperplastic and regenerative cryptae, normal cellularity of the lamina mesenterii propria, and no signs of T-cell activation. The main histologic features are epithelial dysplasia with focal crowding and disorganization of the surface enterocytes, pseudocystic formation of the glands, and abnormal regenerative cryptae. The basement membrane components were studied with polyclonal antibodies on frozen specimens, and were compared with biopsy specimens from patients with celiac disease or autoimmune enteropathy. Relative to the control subjects, there was faint and irregular deposition of laminin at the epithelium-lamina mesenterii propria interface, whereas deposits of heparan sulfate proteoglycan were large and lamellar. The primary or secondary nature of these modifications of the basement membrane remains to be determined, but the modifications might be related to epithelial abnormalities and to the severity of this neonatal diarrhea, which resisted all treatment and necessitated permanent total parenteral nutrition.

Basement Membrane↗
PubMed1995

Langerhans' cell histiocytosis. Definitive diagnosis with the use of monoclonal antibody O10 on routinely paraffin-embedded samples.

The histological and immunohistochemical findings of 34 biopsy specimens from patients with Langerhans' cell histiocytosis (LCH) are reported, with special emphasis on the findings with CD1a mouse monoclonal antibody (MAb) O10 using paraffin-embedded material. Eighteen patients were treated in an adult hospital (mean age, 26.3 years), and the 16 others were children (mean age, 3 years) from a pediatric center. Specimens included 17 bone, 14 skin, two lung, and one lymph node. Tissue was fixed in formalin or Bouin's, and most bone samples were decalcified in nitric acid. Frozen sections were available for 16 cases and electron microscopy for one. Light microscopy was suggestive of LCH in all cases, characterized by large mononucleated cells with abundant eosinophilic cytoplasm and "coffee bean" nucleus. In 33 of the 34 paraffin-embedded LCH samples, mononucleate cells were stained by MAb O10. As controls, we investigated seven tumors expressing S-100 protein (three nevi, two melanomas, two neurofibromas): all were negative with MAb O10. Five non-Langerhans' cell histiocytoses (three juvenile xanthogranulomas and two Rosai-Dorfman lymphadenopathies) were also negative with MAb O10. The results show that in most cases a definitive diagnosis of LCH can be assessed on paraffin-embedded tissue specimens with the help of immunohistochemistry using MAb O10.

Adult↗
PubMed1995

Hepatic toxicity associated with 2'-3' dideoxyinosine in children with AIDS.

Among 34 children with AIDS enrolled in a trial with 2'-3' dideoxyinosine (ddI), six (aged 1-6 years) developed liver abnormalities within 2-18 months after institution of ddI. Two children died of fulminant hepatic failure (one had also an adenovirus infection), and four had a striking elevation of alkaline phosphatases (AP: 1120-7000 IU/L). All of them received sulfa drugs and antifungic treatment with ketoconazole or fluconazole. Three had a serology positive for hepatitis C virus. The evolution of liver enzymes following withdrawal and rechallenge with ddI in the children with elevated AP was an indication of drug-induced toxicity in two patients. In both of the others, readministration of ddI did not cause any subsequent problems. Liver histology in the patients with fulminant hepatitis showed an extensive hepatic necrosis. Liver biopsy done in two other patients revealed a mild granulomatous hepatitis in one and nonspecific changes (i.e., steatosis and a mild inflammation) in the other. Hepatic toxicity has been described with ddI and other nucleoside analogs in adult patients. These six children had many potential causes of liver disease. It may be that ddI is not hepatotoxic per se but that it precipitates liver disease in predisposed patients. We recommend that liver functions be carefully monitored when using this drug.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Description of a novel FR1 IgH PCR strategy and its comparison with three other strategies for the detection of clonality in B cell malignancies.

PCR amplification of IgH gene V-D-J junctional variability (IgH PCR) is increasingly replacing Southern analysis for the detection of clonal lymphoid populations in cases presenting diagnostic difficulties. In order to determine the most efficient strategy, we have compared three known methods, using consensus primers against the VH FR3 or FR2 (FR256) regions, or a mix of six primers against the FR1 region (FR1f), with a new approach using a consensus primer against FR1 (FR1c), never previously described for diagnostic purposes, on DNA from 89 monoclonal B-cell proliferations (16 ALL, 28 CLL/PLL, 15 myelomas, 30 NHL). We obtained a detection rate of 70% for FR3, 64% for FR1f and 77% and 78% for FR256 and FR1c, respectively. Polyclonal lymphocytes and mature T cell malignancies tested negative for all systems. Differences in the detection rate were related not only to the choice of VH primer but also the JH primer(s) used and the pathological subtype. All strategies led to adequate detection of leukaemic DNA, whereas the detection rate in myeloma varied between strategies from 47 to 80% and that of follicular lymphoma from 13 to 63%. The lowest detection rates were observed in follicular lymphoma and in mature CD5 negative proliferations, reflecting the probable correlation between somatic mutation and PCR false-negativity. The combined use of FR1c and FR256 allowed detection in at least one system of 92% of cases overall and at least 75% in all pathological subtypes, thus providing a simple, reliable and rapid non-radioactive system for the detection of B cell clonality.

Alleles↗
PubMed1994

Langerhans' cell histiocytosis cells are activated Langerhans' cells.

Langerhans' cell histiocytosis (LCH) is characterized by the presence of large mononucleated cells, associated with inflammatory cells. The Langerhans' cell (LC) lineage of the mononucleated cells is suggested by the presence of Birbeck granules and the expression of CD1a. We investigated the presence of 14 markers expressed by normal LCs in vitro. Nine skin and one lymph node frozen biopsies of LCH children were analysed by in situ immunohistochemistry. The data were compared with six skin and five lymph node frozen biopsies. LCH cells of the ten samples were positive for all 14 LC markers. We observed three different groups of markers, according to the respective staining of normal LCs and LCH cells. Group 1 included DR, DQ, CD1a, CD1c, and ICAM-3. Markers of group 1 were present on the majority of both normal LCs and LCH cells. Group 2 included CD1b, CD4, LFA-1, LFA-3, CD32, and CD68. Markers of group 2 were detected on the majority of LCH cells, but only on a fraction of normal LCs. Group 3 included CD11b, CD24, and B7/BB1. Markers of this group were detected on LCH cells, but not on normal LCs. This in situ immunohistochemical study confirms that LCH cells belong to the LC lineage. The different clinical LCH syndromes had the same immunohistochemical staining. The expression of some markers of groups 2 and 3 is known to be related to the activation of LCs in vitro. Our study suggests that LCH cells are activated LCs.

Antibodies, Monoclonal↗
PubMed1994

Detection of GM-CSF in the sera of children with Langerhans' cell histiocytosis.

GM-CSF induces proliferation and activation of Langerhans' cells in vitro. The density of Langerhans' cells in human tumours is correlated to the in situ density of GM-CSF, and intradermal injection of GM-CSF induces local accumulation of Langerhans' cells. Therefore, we investigated the presence of GM-CSF in the sera of children with Langerhans' cell histiocytosis (LCH). We detected GM-CSF in the sera of all children with disseminated and active LCH, but not in the sera of patients with localized (i.e. bone) LCH. These results suggest that GM-CSF level is related to extent and the activity of LCH.

Adolescent↗
PubMed1994

In situ detection of activated cytotoxic cells in follicular lymphomas.

The presence of cytotoxic cells and their activation status were analyzed in tissue sections of 26 follicular lymphomas. To this end, expression of the perforin and granzyme B genes was studied by in situ hybridization experiments, and expression of the TIA-1 antigen was analyzed by immunohistochemistry. Cells expressing the granzyme B gene and the perforin gene were detected in all cases. Their density was, however, highly heterogeneous from case to case, ranging from 160 to 7,040 positive cells/cm2 of tissue sections. TIA-1-positive cells were also evidenced in the 10 follicular lymphomas tested. Virtually all cytotoxic cells were located in interfollicular areas. Double labeling immunochemical experiments showed that most cytotoxic cells belonged to the CD8+ T lymphocyte population, although few CD4+ T lymphocytes and CD56+ natural killer cells also expressed the TIA-1 antigen. These findings show that development of a malignant B lymphocyte proliferation is associated with a host-derived immune response involving intratumoral cytotoxic T lymphocytes. Further studies comparing the density of such cells with the final outcome are required to determine whether the intensity of this immune response has a prognostic value.

Adult↗
PubMed1994

Donor B cell lymphoma of the brain after allogeneic bone marrow transplantation for acute myeloid leukemia.

We present a case of EBV-induced cerebral B cell lymphoproliferation of donor origin after HLA-matched allogeneic BMT for AML. The presentation was note-worthy as this 4-year-old girl was grafted after a conditioning regimen without irradiation, with an unmanipulated, HLA-matched graft. Furthermore, the cerebral mass developed long after reduction of immunosuppressive therapy following improvement of severe GVHD. To our knowledge, such cerebral lymphoproliferation, under these transplant conditions, has never been described.

Blotting, Southern↗
PubMed1993

Implications of de novo ELAM-1 and VCAM-1 expression in human cardiac allograft rejection.

Both cytokines produced by activated monocytes and T cells and direct cell-to-cell contact with antigen-primed T cells during inflammatory reactions are known to induce the expression of several adhesion proteins on endothelial cells. In this prospective longitudinal study, we analyzed the expression of ELAM-1, VCAM-1, and ICAM-1 on myocardial allograft biopsy specimens taken from 16 cardiac allograft recipients either for routine monitoring or for the investigation of suspected rejection. Infiltrating T cells were identified using anti-CD3 antibodies. Three to six sequential biopsies taken at one-week intervals were analyzed by means of conventional histology and immunohistochemistry. Seven patients did not develop rejection during the study; their biopsies were negative for VCAM-1 and ELAM-1, although faint ICAM-1 staining was present on capillaries, reflecting constitutive expression. Three patients entered the study with clear-cut clinical and histologic signs of acute rejection. Intense VCAM-1 and ICAM-1 expression was detected on capillary and postcapillary venules, together with a heavy CD3+ T cell infiltrate; VCAM-1 was also expressed on arteriolar endothelial cells. ELAM-1 was undetectable in all three cases. Six patients developed acute rejection during the course of the study. In four, ELAM-1 and VCAM-1 were expressed on both capillary and postcapillary venules one or two weeks before the histological diagnosis of rejection (heavy CD3+ cell infiltrate). Importantly, ELAM-1 expression was short-lived and had disappeared by the time CD3+ cellular infiltrate was detected, thus extending in vivo the finding that ELAM-1 expression is usually transient in vitro. Only VCAM-1 expression was observed in the other two patients, one week prior to the histological diagnosis of rejection. These results suggest that ELAM-1 and VCAM-1 might represent early predictive markers of acute cardiac allograft rejection. ELAM-1 expression is, however, usually transient, necessitating frequent testing.

Adolescent↗
PubMed1993

Immunohistochemical detection of granulocyte/macrophage colony-stimulating factor in Langerhans' cell histiocytosis.

Granulocyte/macrophage-colony stimulating factor (GM-CSF) induces in vitro activation of Langerhans' cells. The association of GM-CSF and tumour necrosis factor alpha (TNF alpha) induces the differentiation of Langerhans' cells from CD34 positive haematopoietic progenitors. Intradermal administration of recombinant GM-CSF is associated with local accumulation of Langerhans' cells. We investigated the presence of GM-CSF in tissue samples of 10 patients with Langerhans' cell histiocytosis. Four patients had skin involvement, three had bone and three had diffuse disease. Eight normal skin samples were analysed as controls. Immunohistochemistry was performed on frozen tissue samples with two specific monoclonal antibodies directed against two different epitopes of GM-CSF. We detected GM-CSF in all the histiocytosis tissue samples. The GM-CSF was detected within the cytoplasm of all the tumoral Langerhans' cells. We did not find GM-CSF in any other cell type. These results suggest that GM-CSF may be implicated in the pathogenesis of Langerhans' cell histiocytosis.

Antigens, CD↗