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Biomedical subjects

M Peuchmaur

Publications and source records attributed to M Peuchmaur.

At least 37 records · Page 2Linked to original sources
PubMed2000

Intestinal pseudo-obstruction and acute pandysautonomia associated with Epstein-Barr virus infection.

We report the association of neurological and intestinal disorders with the reactivation of Epstein-Barr virus (EBV) in a child. This previously healthy 13-yr-old boy presented with pharyngitis and acute abdominal ileus. Laparotomy excluded a mechanical obstruction. Postoperatively, he suffered from prolonged intestinal obstruction, pandysautonomia, and encephalomyelitis. Histological examination of the appendix and a rectal biopsy taken 3 months after the onset showed an absence of ganglion cells (appendix) and hypoganglionosis (rectum), with a mononucleate inflammatory infiltrate in close contact with the myenteric neural plexuses. EBV-PCR was positive in the blood and cerebrospinal fluid, and in situ hybridization with the Epstein-Barr virus encoded RNA probe showed positive cells throughout the appendix wall including the myenteric area, in a mesenteric lymph node, and in the gastric biopsies. EBV spontaneous lymphocytic proliferation was noted in the blood. The serology for EBV showed previous infection but anti-early antigen antibodies were present. No immunodeficiency was found. Neurological and GI recovery occurred after 6 months of parenteral nutrition and bethanechol. The omnipresence of EBV associated with the neurointestinal symptoms suggest that the virus was the causal agent. This is the first documented case of acquired hypoganglionnosis due to EBV reactivation.

Acute Disease↗
PubMed1999

Intestinal dysplasia and adenoma in transgenic mice after overexpression of an activated beta-catenin.

Mutations in the adenomatous polyposis coli gene or activating mutations in the beta-catenin gene itself are thought to be responsible for the excessive beta-catenin signaling involved in intestinal carcinogenesis. We generated transgenic mice that expressed large amounts of a NH2-terminally truncated mutant beta-catenin (deltaN131beta-catenin) in the intestine. These mice had multifocal dysplastic lesions in the small intestine, reminiscent of the early lesions observed in the mouse models of familial adenomatous polyposis. The number of apoptotic cells in the villi of these transgenic mice was 3-4-fold higher than in nontransgenic mice. Expression of the truncated beta-catenin mutant in the kidney led to the development of severe polycystic kidney disease. Our findings support the concept that deregulation of the beta-catenin signaling pathway is the major oncogenic consequence of adenomatous polyposis coli mutations in intestinal neoplasia.

Adenoma↗
PubMed1999

Inflammatory alterations in mesenteric adipose tissue in Crohn's disease.

BACKGROUND & AIMS: Abnormalities of fat in the mesentery including adipose tissue hypertrophy and fat wrapping have been long recognized on surgical specimens as characteristic features of Crohn's disease. However, the importance, origin, and significance of the mesenteric fat hypertrophy in this chronic inflammatory disease are unknown. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a crucial factor involved in the homeostasis of adipose tissue, a major source of biologically active mediators. METHODS: Intra-abdominal fat accumulation was quantified using a magnetic resonance imaging method in patients with Crohn's disease and controls. PPARgamma and inflammatory cytokines synthesized by mesenteric adipose tissues were assessed by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. RESULTS: In vivo, patients with Crohn's disease have an important accumulation of intra-abdominal fat. This mesenteric obesity, present from the onset of the disease, is associated with overexpression of PPARgamma and tumor necrosis factor (TNF)-alpha, synthesized, at least in part, by adipocytes. CONCLUSIONS: These results suggest that confined increased PPARgamma mesenteric concentrations could lead to the mesenteric fat hypertrophy, which could actively participate through the synthesis of TNF-alpha in the inflammatory response.

Abdomen↗
PubMed1999

Up-to-date evolution of small bowel transplantation in children with intestinal failure.

PURPOSE: The aim of the authors was to report an up-to-date review of their experience with 26 intestinal transplantations in children since 1987. METHODS: A retrospective study was conducted of 26 patients with a mean age of 5 years (range, 0.3 to 14 years). Three groups were isolated. In group A (1987 to 1990), seven patients received nine isolated intestinal transplants for short bowel syndrome. Immunosuppression therapy consisted of cyclosporine, aziathioprine, and corticosteroids. In group B (1994-current), nine patients received nine isolated intestinal transplants for short bowel syndrom (n = 2), intestinal pseudoobstruction (n = 2), neonatal intractable diarrhea (n = 3), and Hirschsprung' disease (n = 1); hepatic biopsy results showed weak cholestasis or fibrosis. In group C (1994-current), 10 patients received 10 combined liver-small bowel transplants for short bowel syndrome (n = 3), neonatal intractable diarrhea (n = 4), and Hirschsprung' disease (n = 3); hepatic cirrhosis related to total parenteral nutrition (TPN) was shown in all cases. Groups B and C received immunosupressive treatment consisting of tacrolimus, aziathioprine, and corticosteroids. Posttransplant follow-up included intestinal biopsies of the small bowel twice a week and more frequently or combined with liver biopsy if rejection was suspected. RESULTS: Overall patient survival (PS) and graft survival (GS) are 61% (16 of 26) and 50% (13 of 26), respectively. In group A, severe intestinal allograft rejection occurred in six patients leading to graft removal (GS, 11%). Five patients died of TPN complications after graft removal (PS, 28%). One survivor is off TPN, and one currently is waiting for a second graft. In group B, six patients survived (PS, 66%). Causes of death include hepatic failure (n = 1), renal and liver failure (n = 1), and systemic infection (n = 1). Severe intestinal allograft rejection occurred in five patients, which neccessitated aggressive immunosuppression (antilymphocyte serum) leading to an incomplete functional recovery of the graft. Only two patients currently are off TPN. In group C, eight patients survived (PS, 80%) all of which are currently off TPN. One patient died during the procedure, and one died of severe systemic infection. Intestinal graft rejection occurred in six patients; rejection of the liver allograft occurred in five patients, yet all rejections were weak and successfully treated by corticosteroids (GS, 80%). CONCLUSIONS: Intestinal transplantation is a valid therapeutic option for children with definitive intestinal failure and not only for short bowel syndrome. Tacrolimus improves graft and patient survival (group A v group B). The lower severity of graft rejection in combined liver-small bowel transplantation improves functional results of intestinal transplantation in children without additional mortality or morbidity (group B vgroup C).

Adolescent↗
PubMed1999

Aberrant gene expression in epithelial cells of mixed odontogenic tumors.

Comparative investigations of odontogenic cells in normally forming teeth and tumors may provide insights into the mechanisms of the differentiation process. The present study is devoted to late phenotypic markers of ameloblast and odontoblast cells, i.e., proteins involved in biomineralization. The in situ expression of amelogenins, keratins, collagens type III and IV, vimentin, fibronectin, osteonectin, and osteocalcin was performed on normal and tumor odontogenic human cells. The pattern of protein expression showed some similarities between ameloblasts and odontoblasts present in normally developing human teeth and cells present in neoplastic tissues of ameloblastic fibroma, ameloblastic fibro-odontomas, and complex odontomas. Amelogenins (for ameloblasts) and osteocalcin (for odontoblasts) were detected in cells with well-organized enamel and dentin, respectively. In contrast, "mixed" cells located in epithelial zones of mixed odontogenic tumors co-expressed amelogenins and osteocalcin, as shown by immunostaining. The presence of osteocalcin transcripts was also demonstrated by in situ hybridization in these cells. Keratins and vimentin were detected in the same epithelial zones. Tumor epithelial cells were associated with various amounts of polymorphic matrix (amelogenin- and osteocalcin-immunoreactive), depending on the types of mixed tumors. No osteocalcin labeling was found in epithelial tumors. This study confirms that the differentiation of normal and tumor odontogenic cells is accompanied by the expression of some common molecules. Furthermore, the gene products present in normal mesenchymal cells were also shown in odontogenic tumor epithelium. These data may be related to a tumor-specific overexpression of the corresponding genes transcribed at an undetectable level during normal development and/or to an epithelial-mesenchymal transition proposed to occur during normal root formation. A plausible explanation for the results is that the odontogenic tumor epithelial cells are recapitulating genetic programs expressed during normal odontogenesis, but the tumor cells demonstrate abnormal expression patterns for these genes.

Ameloblastoma↗
PubMed1998

Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.

Cytotoxic T lymphocytes (CTL) are potent effector cells that could provide long term antitumor immunity if induced by appropriate vaccines. CTL recognize 8-14 amino acid-long peptides processed intracellularly and presented by MHC class I molecules. A well-characterized example of a potential tumor antigen in childhood pre-B Acute Lymphoblastic Leukemia (ALL) results from the chromosomal translocation 12;21 leading to the fusion of the ETV6 and AML1 genes. This translocation is observed in > 25% of ALL-patients. In this study, we have examined whether the chimeric ETV6-AML1 protein could serve as a tumor specific antigen for CTL in HLA-A2.1 individuals. We have identified a nonapeptide (RIAECILGM), encoded by the fusion region of the ETV6-AML1 protein, that binds to HLA-A2.1 molecules and induces specific primary CTL in peripheral blood lymphocytes from healthy donors. These CTL specifically lysed HLA-A2.1 tumor cells endogeneously expressing the ETV6-AML fusion protein. CTL with similar functional capacities were found with high frequencies and cloned from one patient's bone marrow indicating that ETV6-AML1-specific anti-ALL CTL are, at least in some patients, spontaneously stimulated and might participate to host antileukemia defense.

Amino Acid Sequence↗
PubMed1998

Collagenous gastritis revealed by severe anemia in a child.

Collagenous gastritis is a rare histopathological disorder of unknown origin, characterized by a subepithelial collagen deposit greater than 10 microm thick, associated with an inflammatory infiltrate of the gastric mucosa. This report describes a second pediatric case of collagenous gastritis, revealed by severe anemia caused by gastric bleeding, as was the first case. Unlike the adult cases of collagenous gastritis, lesions were limited to the stomach, and remained unchanged on six series of biopsies taken during a 30 month follow-up, despite treatment with omeprazole, sucralfate and corticosteroids. An immunohistochemical study showed signs of local immune activation on all biopsy specimens, including overexpression of HLA-DR by epithelial cells, increased numbers of CD3+ intraepithelial lymphocytes, and CD25+ cells in the lamina propria. Although the cause of the disease remains unclear, our findings suggest that the histopathological lesions of collagenous gastritis may result from a local immune process.

Anemia↗
PubMed1998

CD44 variant expression in inflammatory colonic mucosa is not disease specific but associated with increased crypt cell proliferation.

AIMS: A recent study reported increased epithelial expression of CD44 variants in ulcerative colitis (UC) compared with Crohn's disease (CD). However, the use of CD44 expression for diagnostic purposes in inflammatory bowel disease has been controversial, and the meaning of the appearance of CD44 variants in epithelial colonic cells remains unknown. We investigated the relationship between CD44 isoform expression and crypt cell proliferation in paediatric colitis. METHODS AND RESULTS: The expression of CD44v3, CD44v6, and MIB1 (proliferation marker) was studied by immunohistochemistry on surgical colonic samples of UC (n = 13), CD (n = 10), colostomy resections with non-specific mucosal inflammation (NSMI) (n = 3), and normal controls (N = 5). The proliferation index (% of MIB1 positive cells) was assessed in both v6 positive and v6 negative crypts. Epithelial expression of CD44v3 and v6, negative in normal controls, was variable and focal in colitis. No preferential expression of CD44 variants was found in UC. The proliferation index was dramatically increased in v6 positive crypts compared with v6 negative crypts in UC, CD and NSMI. CONCLUSIONS: These data suggest that CD44 variant staining is not a useful marker for distinguishing paediatric UC from CD, and that CD44v6 expression in the inflamed colonic mucosa is not disease specific but is related to crypt cell proliferation.

Antigens, Nuclear↗
PubMed1998

Identification of constitutional WT1 mutations, in patients with isolated diffuse mesangial sclerosis, and analysis of genotype/phenotype correlations by use of a computerized mutation database.

Constitutional mutations of the WT1 gene, encoding a zinc-finger transcription factor involved in renal and gonadal development, are found in most patients with Denys-Drash syndrome (DDS), or diffuse mesangial sclerosis (DMS) associated with pseudohermaphroditism and/or Wilms tumor (WT). Most mutations in DDS patients lie in exon 8 or exon 9, encoding zinc finger 2 or zinc finger 3, respectively, with a hot spot (R394W) in exon 9. We analyzed a series of 24 patients, 10 with isolated DMS (IDMS), 10 with DDS, and 4 with urogenital abnormalities and/or WT. We report WT1 heterozygous mutations in 16 patients, 4 of whom presented with IDMS. One male and two female IDMS patients with WT1 mutations underwent normal puberty. Two mutations associated with IDMS are different from those described in DDS patients. No WT1 mutations were detected in the six other IDMS patients, suggesting genetic heterogeneity of this disease. We analyzed genotype/phenotype correlations, on the basis of the constitution of a WT1 mutation database of 84 germ-line mutations, to compare the distribution and type of mutations, according to the different symptoms. This demonstrated (1) the association between mutations in exons 8 and 9 and DMS; (2) among patients with DMS, a higher frequency of exon 8 mutations among 46, XY patients with female phenotype than among 46,XY patients with sexual ambiguity or male phenotype; and (3) statistically significant evidence that mutations in exons 8 and 9 preferentially affect amino acids with different functions.

Amino Acid Sequence↗
PubMed1998

Postoperative outcome of Crohn's disease in 30 children.

BACKGROUND: Thirty children operated on for Crohn's disease (CD) were reviewed (1975-1994). The aim of the study was to assess their postoperative outcome. PATIENTS: 19 boys and 11 girls, aged 15.3 (2) years (range 11.3-20) at surgery were studied. RESULTS: Surgical indications were acute complications of CD and chronic intestinal illness. Six months after surgery, 11 of 12 patients had been weaned off steroids, and 22 of 23 patients were weaned off nutritional support; 17 patients without recurrence had a mean (SD) weight gain of 2.1 (8) kg and a height gain of 3.36 (3) cm. During 3.1 (2.7) years follow up, 12 patients (40%) had a recurrence of the disease after 19.4 (14) months (means (SD)): supra-anastomotic recurrence (six), severe perianal disease (two), and chronic illness (four). Six of 14 patients who were treated with mesalazine (13) or azathioprine (one) had recurrences. The postoperative recurrence rate was 50% at two years. CONCLUSION: Surgical treatment modifies the immediate outcome of severe or complicated CD, but does not prevent recurrence, despite localised resection or prophylactic postoperative treatment. Extension of the disease before surgery seems to be a major risk factor for postoperative recurrence in children.

Adolescent↗
PubMed1998

Ticlopidine induced colitis: a histopathological study including apoptosis.

AIMS: To describe ticlopidine related microscopic colitis and to assess the occurrence of apoptosis in the colon epithelium. METHODS: A series of colorectal biopsy samples from nine patients with ticlopidine related chronic diarrhoea were analysed. Biopsies were also taken from five of these patients between two and four months after ticlopidine withdrawal. The number of apoptotic cells in the crypts/mm2 (apoptotic index) was calculated using in situ labelling by terminal deoxyribonucleotidyl transferase (TdT) mediated dUTP-biotin nick end labelling (TUNEL). All specimens were matched to normal colorectal specimens from a control group of comparable age and sex distribution. RESULTS: Histological examination of the colon biopsy specimens taken from all nine patients with ticlopidine related chronic diarrhoea showed characteristic features of microscopic colitis. The histology returned to normal when ticlopidine was withdrawn. Apoptotic cells were rarely found in controls, and the mean apoptotic index was 0.53. The apoptotic index was significantly higher (16.53) in ticlopidine related colitis, but decreased dramatically to control value when ticlopidine was withdrawn. CONCLUSION: Microscopic colitis can be induced by ticlopidine and is accompanied by an increase in epithelial apoptosis. Hence, increased apoptosis might be related to drug injury or might be part of microscopic colitis.

Aged↗