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N Le Berre

Publications and source records attributed to N Le Berre.

11 recordsLinked to original sources
PubMed2001

Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part I: Phenotypic characterisation.

OBJECTIVES: The KCNQ1 gene encodes the KvLQT1 potassium channel, which generates in the human heart the slow component of the cardiac delayed rectifier current, I(Ks). Mutations in KCNQ1 are the most frequent cause of the congenital long QT syndrome. We have previously cloned a cardiac KCNQ1 human isoform, which exerts a strong dominant-negative effect on KvLQT1 channels. We took advantage of this dominant-negative isoform to engineer an in vivo model of KvLQT1 disruption, obtained by overexpressing the dominant-negative subunit under the control of the alpha-myosin heavy chain promoter. RESULTS: Three different transgenic lines demonstrated a phenotype with increasing severity. Functional suppression of KvLQT1 in transgenic mice led to a markedly prolonged QT interval associated with sinus node dysfunction. Transgenic mice also demonstrated atrio-ventricular block leading to occasional Wenckebach phenomenon. The atrio-ventricular block was associated with prolonged AH but normal HV interval in His recordings. Prolonged QT interval correlated with prolonged action potential duration and with reduced K(+) current density in patch-clamp experiments. RNase protection assay revealed remodeling of K(+) channel expression in transgenic mice. CONCLUSIONS: Our transgenic mouse model suggests a role for KvLQT1 channels not only in the mouse cardiac repolarisation but also in the sinus node automaticity and in the propagation of the impulse through the AV node.

Action Potentials↗
PubMed1997

Interobserver agreement in the staging of rectal cancer using endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: In rectal tumors invasion of the rectal fat and perirectal lymph nodes are generally regarded as independent prognostic factors in most prospective series. There are no studies in the literature concerning interobserver agreement on the staging of rectal cancer by endorectal ultrasonography (EUS). The aim of the present study was to assess interobserver agreement using EUS in the TN staging of rectal cancer. PATIENTS AND METHODS: Thirty-seven patients with rectal cancer were investigated at two centers using EUS as part of the pretherapeutic staging (Olympus EUM-3 or EUM-20). All examinations were videotaped and reviewed six months later by four independent observers who assessed the stage of the tumor (from uT1 to uT4) and lymphatic invasion on a blinded basis. When the tumor was assessed as uT3, the observers specified the degree of involvement of the rectal fat (in millimeters). Interobserver agreement was estimated using the kappa coefficient (k) and the intraclass correlation coefficient (ICC). Agreement was classed as poor (k < 0.40), fair to good (0.40 < or = k < 0.75) or excellent (k < or = 0.75). RESULTS: Agreement was fair for uT1 tumors (k = 0.40) and poor for uT2 tumors (k = 0.20). Agreement was good (k = 0.58; CI 0.51 to 0.65) for uT3 tumors; there was a significant interobserver correlation for the exact measure of the extent of rectal fat (ICC = 0.65). The agreement was also good (k = 0.54, CI 0.47 to 0.61) for metastatic lymph nodes. CONCLUSION: As in the case of esophageal cancer, interobserver agreement on the staging of uT2 tumors is poor with EUS. The evaluation of rectal tumors with a poor prognosis shows good interobserver agreement.

Adenocarcinoma↗
PubMed1997

Significance of interleukin-1beta and interleukin-1 receptor antagonist genetic polymorphism in inflammatory bowel diseases.

OBJECTIVE: Genetic susceptibility to inflammatory bowel disease is well recognized. There is also increasing evidence for the activation of the mucosal immune system and the production of inflammatory cytokines, i.e., interleukin (IL)-1ra and IL-1beta in the inflammatory bowel disease. The aim of this study was to analyze the IL-1beta and IL-1ra gene polymorphism and linkage disequilibrium coefficient between the different alleles of these genes in patients with Crohn's disease (CD) or ulcerative colitis (UC), according to the severity of the disease. METHODS: Two hundred twenty-eight inflammatory bowel disease patients (87 UC and 141 CD) were included in this study and compared with 113 unrelated controls. The IL-1beta and IL-1ra gene polymorphism was studied after specific amplification of variable regions by PCR. A penta-allelic polymorphism, corresponding to a VNTR region located in intron 2 of the IL-1ra gene, was analyzed, whereas bi-allelic RFLPs displayed by two restriction enzymes (TaqI and AvaI) at position -511 of the IL-1beta gene were analyzed. RESULTS: There was no significant difference of genotype distribution between controls and CD or UC patients. However, surgically treated UC patients were characterized by a higher frequency of genotype IL-1ra 1-2 (39 vs 16%, pc < 0.01) compared with nonoperated UC patients. Moreover, nonoperated UC patients displayed a lower frequency of IL-1ra allele 2 than surgically treated UC patients (14 vs 34%, pc < 0.002) or controls (14 vs 30%, pc < 0.005). Furthermore, simultaneous analysis of the IL-1beta and IL-1ra genes that are located in the same region of chromosome 2 revealed that CD patients carrying the IL-1beta allele 2 were more often noncarriers of IL-1ra allele 2 (p < 0.005). Moreover, UC and CD patients were, characterized by a lower frequency of the association of IL-1ra allele 2 and IL-1beta allele 2 compared with controls (8.3 vs 20.3% and 10.6 vs 20.3%, p < 0.03). CONCLUSIONS: IL-1ra and IL-1beta gene polymorphism analysis from a clinical standpoint might help in defining UC prognosis. However, functional studies at both the circulating and mucosal level with stratification on allele associations, especially IL-1ra allele 2-IL-1beta allele 2 subgroups must be realized before therapeutic implications.

Adult↗
PubMed1996

[Giant hyperplastic polyposis with adenomatous tissue].

Hyperplastic polyps are the most common type of colorectal polyps. They are usually multiple and localized in the rectosigmoid area. They are easily recognized by their small size (< 10 mm), sessile form, smooth-surface and translucid appearance. Typically, these polyps have no malignant potential. We report the case of a 68-year-old man who had multiple rectosigmoid polyps, some of them having macroscopic features of adenomatous polyps. Because of the occurrence of bleeding after endoscopic polypectomy of two polyps corresponding to adenomas at examination, because of the multiplicity of these polyps and their localization in diverticulosis, a left colectomy followed by coloanal anastomosis was performed. Histologic examination of the surgical specimen revealed the hyperplastic nature of all polyps with, in two of them, a focus of adenomatous tissue.

Adenomatous Polyps↗
PubMed1995

Histological discrimination of idiopathic inflammatory bowel disease from other types of colitis.

AIMS: To assess the value of histology in diagnosing inflammatory bowel disease (IBD) in colorectal biopsy specimens. METHODS: Retrospective, double blind evaluation of colorectal biopsy specimens from 41 patients with colitis (28 with ischaemic colitis and 13 with acute self-limited colitis) and 84 patients with IBD (42 with Crohn's disease and 42 with ulcerative colitis). RESULTS: The features distinguishing IBD from other forms of colitis included distorted architecture, lymphocyte and plasma cell infiltrate, excess of polymorphonuclear leucocytes, polymorphonuclear cryptitis, crypt abscesses, and basal lymphoid aggregates. The features discriminating between Crohn's disease and ulcerative colitis included an irregular or villous surface, distorted architecture, decrease in mucus content, and polymorphonuclear cryptitis. Using multivariate analysis, 90% of patients with Crohn's disease and 71% of those with ulcerative colitis were correctly classified, the former being strongly defined by epithelioid granulomas, microgranulomas and isolated giant cells, and the latter best defined by an irregular or villous surface, decrease in mucus content and crypt atrophy. CONCLUSIONS: Examination of colorectal biopsy specimens is a reliable method for diagnosing IBD. In the absence of epithelioid granulomas, microgranulomas and isolated giant cells a diagnosis of Crohn's disease is based on the absence of histological criteria favouring ulcerative colitis. The histological spectrum of indeterminate colitis remains to be clarified.

Adolescent↗
PubMed1994

Synthesis of novel inhibitors of the HIV-1 protease: difunctional enols of simple N-protected amino acids.

A series of enol HIV-1 protease inhibitors which show competitive inhibition and the structure-activity relationship study which led to the design of these compounds are reported. By systematically modifying simple amino acids, Boc-Phe enol and Boc-Tyr enol derivatives yield nanomolar Kiapp values (Kiapp = 0.485 microM and Kiapp = 0.425 microM, respectively). These enols are of low molecular weight (< 500 g/mol) and of non-peptidic nature. The enols are synthesized in a one step chemical synthesis and modifications to increase their potency could easily be performed. Boc-Phe enol and Boc-Tyr enol showed low inhibitory effect on pepsin, Kiapps of 23 and 149 microM, respectively, and Boc-Phe enol showed a Kiapp of 20 microM for cathepsin D. Neither of these two compounds inhibited renin (< 10% inhibition at 200 microM).

Amino Acids↗
PubMed1993

Bladder substitutes, bile acids and the risk of colorectal cancer: an experimental study.

There is a large body of evidence relating the causation of colon cancer to bile acids. Using an animal model, we attempted to address the question, i.e., the incidences of carcinogenesis in the colon as consequences of resection of different bowel segments, predominantly employed in the construction of various forms of intestinal bladder substitutes. 60 male Wistar rats were operated. Group 1 served as control, in group 2, 20 cm of terminal ileum was resected, and rats in group 3 underwent resection of the distal 10 cm of the ileum and 7 cm of the proximal colon. All rats were killed 6 months after surgery and the colon was removed. After examination under 40-fold magnification, in the absence of tumors, 3 biopsies were performed at predetermined positions and underwent histological processing. Even if no tumor was found it would be incorrect to conclude that these results would have an appeasing relevance. The complex and highly different fecal bile acid profiles of the rat compared to man makes it impossible in this context to draw analogies between the rat model and human colonic carcinogenesis. Furthermore, 6 months of observation in the rat might be too short for 'spontaneous' colonic carcinogenesis. Nevertheless, there exists evidence from epidemiological studies to implicate bile acids as an etiological factor in the development and growth of colorectal cancer. Therefore, the importance of colorectal cancer in urologic surgery patients must be kept in perspective. In this direction, further studies are required besides the application of known appropriate preventive measures.

Animals↗
PubMed1993

[Cystic tumors and endocrine tumor of the pancreas. An unusual association].

Cystadenomas and cystadenocarcinomas are the most common cystic tumors of the pancreas. Their inner lining contains neuroendocrine cells that may, in rare cases, produce a systemic syndrome. Similarly, digestive or pancreatic endocrine tumors have been reported in association with cystic tumors of the pancreas. We report a case of cystadenocarcinoma of the pancreas head, associated with a serous cystadenoma and an endocrine tumor of the body of the pancreas. In a 70 year old patient, jaundiced due to obstruction of the extra-hepatic bile ducts, the abdominal ultrasound and CT scan showed a hypoechogenic hypodense lesion of the pancreas head resulting in an enlargement of the common bile duct and pancreatic duct. Echoendoscopy confirmed the diagnosis and gave additional information; it showed that the cephalic lesion was heterogeneous, with anechogene spaces separated by coarse echogenic septae associated to a solid contingent. Also detected by echoendoscopy was a cystic lesion containing thin septae and a contiguous hypoechogenic nodule of the body of the pancreas. Histology of the specimen following total pancreatectomy revealed a cephalic cystadenocarcinoma associated with a serous cystadenoma and a non-secreting endocrine tumor of the body region. This observation highlights the usefulness of echoendoscopy in the work-up of cystic lesions of the pancreas; indeed, the tumors of the body of the pancreas were not detected by others methods. Furthermore, there are reports in literature on endocrine secretion syndromes secondary to digestive endocrine tumors or neuroendocrine cells in the lining of cystic tumors of the pancreas.

Aged↗
PubMed1992

[Villous tumors of the Wirsung's duct and pancreatic intraductal adenocarcinoma: interrelation or accidental association?].

Villous neoplasms of the main pancreatic duct are uncommon. Two cases of neoplasm of the main cephalic pancreatic duct in 61- and 42-year-old patients presenting with long standing (10 and 12 years) history of abdominal pain are reported. In both cases, duodenal fistula was present and mucus was observed by endoscopy at the fistula and major papilla levels. Endoscopic retrograde pancreatography showed a stricture of the main pancreatic duct in the pancreatic head. In one case, with incomplete stricture, pancreatic ducts disclosed typical features of chronic obstructive pancreatitis and contained mucus casts. Histologic examination of total and proximal duodenopancreatectomy showed a villous neoplastic pattern with focal malignant changes within the main pancreatic duct. The adjacent pancreatic tissue showed signs of stromal invasion without lymph node or nervous infiltration. Glandular parenchyma was atrophic in the pancreatic body and tail, with extensive fibrosis, and the pancreatic duct depicted signs of nonpapillary hyperplasia. Histochemical study disclosed a predominant sialomucin secretion by villous adenoma and sulfomucin secretion by epithelial cells lining the accessory or main caudal pancreatic ducts. These results lead us to suggest a possible relationship between villous adenoma of ducts and pancreatic adenocarcinoma.

Adenocarcinoma↗