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M Peuchmaur

Publications and source records attributed to M Peuchmaur.

At least 55 records · Page 3Linked to original sources
PubMed1998

Interleukin-12 expression is focally enhanced in the gastric mucosa of pediatric patients with Crohn's disease.

The stomach is frequently involved in children suffering from Crohn's disease (CD). Diagnosis of specific gastritis may be difficult when granulomas are absent. We have used in situ hybridization to examine the expression of interleukin (IL)-12, a key cytokine in the Th1 response. IL-12 p35 and p40 antisense probes were used to examine ileal specimens from 9 children with CD and gastric biopsies from 24 children (13 with CD, 6 with Helicobacter pylori chronic gastritis, and 5 with a normal gastric mucosa). In all patients with CD, many clusters of IL-12-positive cells were present in the lamina propria. This was the case in the ileal specimens as well as in gastric mucosa showing granulomatous gastritis or nongranulomatous gastritis. The same distribution patterns were found for the IL-12 p35 and p40. In three patients with Helicobacter pylori gastritis, few scattered IL-12-positive cells were found. No positive cells were found in the normal gastric mucosa. The focally enhanced IL-12 expression in the gastric mucosa of pediatric patients with CD, with or without specific lesions, suggests that both are indeed linked to the disease and supports the major part of IL-12 in initiating and maintaining of the cascade resulting in the Th1 responses.

Adolescent↗
PubMed1998

Inflammation: "a natural experiment" for the systemic pathogenicity of cytokines.

It has previously been demonstrated that the overproduction of interleukin-6 (IL-6) is a key element in the clinical and biological abnormalities encountered in Castleman's disease (CD). The particular case of a male child with a localized form of CD is reported. In this patient, evidence was found of a correlation between systemic manifestations and circulating IL-6, and IL-6 gene overexpression in the germinal centers of hyperplastic lymph nodes. Circulating IL-6 levels were 10- to 100-fold higher than in all CD cases previously documented. This unique biological feature was closely associated with high levels of circulating IL-1 and tumor necrosis factor-alpha (TNF-alpha), which are known for their ability to induce and/or amplify IL-6 production. One month after surgical removal of the pathological lymph node, the clinical and biological abnormalities diminished, while circulating IL-6 levels dropped dramatically eight months later. It is worth noting that after resection, the time-course of the IL-6 decrease closely correlated with that of IL-1 and TNF-alpha. Considering that in various inflammatory diseases IL-1, TNF-alpha and IL-6 may act in a synergistic manner in inducing systemic manifestations, this case report raises new questions as to the nature of the systemic pathogenicity of cytokines in CD.

Castleman Disease↗
PubMed1998

[Surgical aspects of renal transplantation in children].

Review of a series of 90 renal transplantations performed in 86 children revealed 3 cases of early or late mortality and 28 cases of major surgical complications, predominantly vascular (13 cases) and urological complications (12 cases). The time to onset, the diagnosis and the management of these complications are reviewed. This study again emphasizes the importance of graft selection (donor age) and the value of living related donor renal transplantation.

Adolescent↗
PubMed1997

Long-term malignant hematopoiesis in human acute leukemia bone marrow biopsies implanted in severe combined immunodeficiency mice.

Bone marrow (BM) trephine biopsies from 15 pediatric patients with acute lymphoid (ALL) or myeloid (AML) leukemia were engrafted subcutaneously into severe combined immunodeficiency (SCID) mice conditioned by 200 cGy total-body irradiation. Implants were harvested 5 to 19 weeks later for histologic, cytologic, and/or flow cytometric analysis of the residing marrow. Eighteen of 19 grafts contained viable human leukemic cells to various extents as assessed by one or more of these methods. Thirteen of 14 implants analyzed by flow cytometry included high numbers of tumor cells, accounting for 85% to 100% of the total nucleated cells in seven of them. Histologically, engrafted marrow samples exhibited areas of blastic infiltration, and tumor-specific gene rearrangements were retrieved in long-term engrafted biopsies. Importantly, engrafted mice remained perfectly healthy even 5 months posttransplantation, and no human tumor cell dissemination was detected in the hematolymphoid and nonhematopoietic tissues at the time of autopsy. These results demonstrate that human malignant hematopoiesis can be sustained long-term in its original, intact marrow stromal environment transplanted in appropriately conditioned immunodeficient mice.

Acute Disease↗
PubMed1997

Gene transfer by guanidinium-cholesterol cationic lipids into airway epithelial cells in vitro and in vivo.

Synthetic vectors represent an attractive alternative approach to viral vectors for gene transfer, in particular into airway epithelial cells for lung-directed gene therapy for cystic fibrosis. Having recently found that guanidinium-cholesterol cationic lipids are efficient reagents for gene transfer into mammalian cell lines in vitro, we have investigated their use for gene delivery into primary airway epithelial cells in vitro and in vivo. The results obtained indicate that the lipid bis(guanidinium)-tren-cholesterol (BGTC) can be used to transfer a reporter gene into primary human airway epithelial cells in culture. Furthermore, liposomes composed of BGTC and dioleoyl phosphatidylethanolamine (DOPE) are efficient for gene delivery to the mouse airway epithelium in vivo. Transfected cells were detected both in the surface epithelium and in submucosal glands. In addition, the transfection efficiency of BGTC/DOPE liposomes in vivo was quantitatively assessed by using the luciferase reporter gene system.

Adenoviridae↗
PubMed1997

Production and roles of IL-6, IL-10, and IL-13 in B-lymphocyte malignancies and in B-lymphocyte hyperactivity of HIV infection and autoimmunity.

We analyzed the production and the roles of IL-6, IL-10, and IL-13 in B-lymphoid malignancies and in specific diseases with B-lymphocyte hyperactivity. Both IL-13 and IL-10 genes are expressed in B-cell lymphomas. However, their contribution to tumor progression is unclear. In certain lymphoproliferative disorders that develop in transplanted patients, IL-6 is produced by malignant cells and is a major factor of their proliferation. In other lymphomas, the IL-6 gene is expressed only in malignancies where differentiated malignant cells are present. In these lymphomas, IL-6 is produced by stromal cells, and the malignant cells express the IL-6 receptor. In patients with HIV infection, the level of production of IL-6, IL-10, and IL-13 is not higher than those of other conditions with immune activation. However, IL-6 contributes to increased production of IgG and IgA in vivo. In Castleman's disease, IL-6 is produced in the lymph node germinal centers, partly originating from follicular dendritic cells, which may explain some of the pathogenesis of this disease. In systemic lupus erythematosus, the critical cytokine is IL-10, which is produced in large amounts by B lymphocytes and monocytes and is responsible for autoantibody production. Taken together, these data emphasize the roles of IL-6 and IL-10, usually produced by nonlymphoid cells, on B lymphocytes, either malignant or hyperactivated.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Down-regulation of CD95 (Fas/Apo-1) in the epithelia of adenovirus-infected appendices.

AIMS: Adenoviral inclusions are commonly seen in appendices from infants with intussusception. They are associated with focal epithelial budding and less frequently with epithelial shedding. These morphological changes could depend on the opposing effects of adenoviral gene products on CD95-mediated apoptosis. METHODS AND RESULTS: Appendices from intussusceptions with viral inclusions (n = 4) and normal appendices (n = 10) were studied by immunochemistry with anti-adenovirus, anti-CD95 and anti-HLA-DR antibodies. Apoptosis was studied by the TUNEL method. The mucosa of normal appendices contained no adenoviral protein. CD95 was present in all epithelial cells except Paneth cells. HLA-DR was absent in epithelial cells and apoptosis was seen only in germinal centres and in a few surface epithelial cells. The epithelium of appendices from intussusceptions contained nuclear inclusions labelled with anti-adenovirus antibody, always found in the epithelial buds. The epithelial CD95 pattern was drastically altered in adenovirus-infected appendices. CD95 was absent from the budding foci. In these foci, HLA-DR was overexpressed. There was also increased epithelial apoptosis in areas remote from those lacking CD95 antigen. CONCLUSIONS: The appearance of epithelial budding or shedding in appendices from intussusception could be due to focal in situ differences in the expression of adenoviral genes.

Adenoviridae Infections↗
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

Increased TIA1-expressing intraepithelial lymphocytes in cow's milk protein intolerance.

BACKGROUND: Although a high level of intraepithelial lymphocytes (IELs) has been demonstrated in intestinal biopsies from children with cow's milk protein intolerance (CMPI), the properties of IELs in food-sensitive enteropathies remain unclear. In the present study, we analyzed the cytotoxic potential of IELs in CMPI, using a monoclonal antibody directed against the cytotoxic granule-associated protein TIA1. METHODS: The study included 18 duodenal biopsies from 10 children previously diagnosed with CMPI and on a cow's milk-free diet of various duration. Six normal duodenal biopsies from children free of food intolerance served as controls. Immunostaining of formalin-fixed tissues was used to determine in the intraepithelial compartment (1) the number of TIA1-expressing cells per 100 epithelial cells, (2) the number of IELs per 100 epithelial cells, (3) the ratio of TIA1-expressing IELs (TIA1/IEL ratio). RESULTS: In CMPI, the number of IELs and TIA1-positive cells, as well as the TIA1/IEL ratio was significantly increased compared with controls. Moreover, a negative correlation between the TIA1/IEL ratio and the duration of the diet was observed. CONCLUSIONS: These results suggest that the recruitment of IELs with cytotoxic potential is increased in CMPI, and that IEL-mediated cytotoxicity could be involved in the pathogenesis of the disease.

Antibodies, Monoclonal↗
PubMed1997

In situ Rantes and interferon-gamma gene expression in pediatric small bowel Crohn's disease.

BACKGROUND: Rantes (regulated upon activation, normal T cell expressed and secreted) is a chemotactic cytokine for memory T lymphocytes, monocytes, and eosinophils. The cytokine interferon-gamma (IFN-gamma) plays a key in the immune response. Their distributions and possible roles in the selective accumulation of inflammatory cells in Crohn's disease (CD) were examined by determining the expression of Rantes and IFN-gamma genes in patients with CD using in situ hybridization (ISH) on frozen and paraffin-embedded tissue sections. METHODS: Intestinal and mesenteric lymph node samples from 9 children who had undergone ileal resection for CD were examined for the presence of epithelioid-giant cell granulomas (EGCG) and Rantes and IFN-gamma messenger RNA (mRNA). Normal pediatric intestine (n = 5) and lymph nodes (n = 2) served as controls. RESULTS: Many cells in all CD specimens in the epithelial compartment, lamina propria, and the EGCG gave positive signal with the Rantes antisense probe. Labelled cells were identified on paraffin sections as lymphocytes, macrophages, and epithelioid cells. There were Rantes-positive cells in the control intestinal tissues, but many Rantes-positive cells in control lymph nodes that showed follicular hyperplasia. IFN-gamma-positive cells were present in all CD ileal and lymph node specimens, predominantly in close contact with EGCC. No positive signal was obtained with the Rantes and IFN-gamma sense control probes. CONCLUSIONS: These findings suggest that Rantes and IFN-gamma contribute to the selective accumulation of macrophages and memory T helper lymphocytes inside the granulomas and inflammatory infiltrates that are characteristic of CD.

Adolescent↗
PubMed1997

[Adenovirus and intranuclear inclusions in the appendix in children with acute intussusception].

One hundred and five appendices removed at the time of surgical reduction of intussusception in children were studied by light microscopy after routine procedures to search for aetiological factors involved in intussusception. Normal pediatric appendix specimens served as controls (n = 30). Light microscopic examination showed viral inclusions in epithelial cells in 48 of 105 appendices (45%) from the cases of intussusception. No viral inclusion was observed in controls. Immunohistochemistry performed on 21 appendices from intussusception with a monoclonal antibody against adenovirus showed intranuclear positivity in all appendices with viral inclusions. Viral inclusions seen in epithelial cells of appendices from cases of intussusception are caused by virus and in particularly by adenovirus. The etiological factors involved in intussusception without viral inclusion in appendix remain unknown.

Acute Disease↗
PubMed1996

[Contribution of endosonography to the diagnosis and follow-up of pediatric gastric neurofibroma revealing von Recklinghausen's disease].

BACKGROUND: Gastrointestinal involvement in von Recklinghausen's disease (RD) is rare during childhood; its symptoms are late and its prognosis is poor, related to local recurrence and risk of malignant transformation. CASE REPORT: A 13 year-old boy was admitted for hematemesis revealing gastric ulcer. A second episode of hematemesis led to identify a sessile gastric tumor in this patient having numerous skin café-au-lait spots. Recurrent bleeding required laparotomy that showed diffuse infiltration into the anterior gastric wall: histological examination of the excised piece showed characteristic features of neurofibromatosis. The patient was not compliant to the endosonographic survey so that a symptomatic relapse led to total gastrectomy: histological examination did not show malignant transformation. CONCLUSION: Endoscopy is a major tool for identifying gastrointestinal localization of RD but endosonography is necessary to precise the extent of the tumor.

Adolescent↗
PubMed1996

Immunolocalization of vitamin D receptor and calbindin-D28k in human tooth germ.

The role of vitamin D in ameloblasts and odontoblasts has been studied experimentally in rodents. Dental dysplasias have also been reported in clinical studies of children with rickets. Vitamin D acts via a nuclear receptor which binds the major metabolite, 1,25-dihydroxyvitamin D3, and positively or negatively controls the expression of specific genes. The most extensively studied markers of 1,25-dihydroxyvitamin D3 action are calbindin-D9k, calbindin-D28k, and osteocalcin. Therefore, to study in more detail the potential role of 1,25-dihydroxyvitamin D3 in human dental development, 1,25-dihydroxyvitamin D3 receptor (VDR) was localized by immunofluorescence in forming teeth (8-26 wk of gestation). Calbindin-D28k was also mapped by immunoperoxidase in antenatal and postnatal forming and formed teeth. VDR were detected in both dental epithelium and mesenchyme of bud, cap, and bell stages of tooth germs. Nuclei of overtly differentiated ameloblasts and odontoblasts were also immunostained. Calbindin-D28k was present in differentiated ameloblasts and odontoblasts. The presence of VDR and calbindin-D28k in ameloblasts and odontoblasts suggests that 1,25-dihydroxyvitamin D3 may contribute to the regulation of enamel and dentin formation, as classically reported for bone formation. Finally, the early appearance of VDR supports the concept that 1,25-dihydroxyvitamin D3 may also control forward stages of tooth crown development in humans.

Ameloblasts↗
PubMed1996

[Solitary infantile myofibromatosis of bone].

We report one case of Solitary infantile Myofibromatosis of Bone in a 14-year old girl. Radiologic features of the tibial lesion were consistent with the diagnosis of a benign bone tumor. The final diagnosis was made on a total resection of the tumor. Histologically, the tumor consisted of nodules, hyalinized or cellular, with spindle-shaped cells resembling fibroblasts or smooth-muscle cells. There were numerous vascular spaces in close contact with these nodules. The tumor cells were immunoreactive with anti-alpha-smooth muscle actin antibodies. These data were consistent with the diagnosis of Myofibromatosis. The histologic features were similar to those of Infantile Myofibromatosis of other sites such as skin and soft tissue. The case reported is rare and not yet published, due to the age and sex of the patient, and the location of the tumor.

Adolescent↗