PubMed Health⌕ Search

Biomedical subjects

M Pera

Publications and source records attributed to M Pera.

At least 19 recordsLinked to original sources
PubMed2006

Acetylcholinesterase triggers the aggregation of PrP 106-126.

Acetylcholinesterase (AChE), a senile plaque component, promotes amyloid-beta-protein (Abeta) fibril formation in vitro. The presence of prion protein (PrP) in Alzheimer's disease (AD) senile plaques prompted us to assess if AChE could trigger the PrP peptides aggregation as well. Consequently, the efficacy of AChE on the PrP peptide spanning-residues 106-126 aggregation containing a coumarin fluorescence probe (coumarin-PrP 106-126) was studied. Kinetics of coumarin-PrP 106-126 aggregation showed a significant increase of maximum size of aggregates (MSA), which was dependent on AChE concentration. AChE-PrP 106-126 aggregates showed the tinctorial and optical amyloid properties as determined by polarized light and electronic microscopy analysis. A remarkable inhibition of MSA was obtained with propidium iodide, suggesting that AChE triggers PrP 106-126 and Abeta aggregation through a similar mechanism. Huprines (AChE inhibitors) also significantly decreased MSA induced by AChE as well, unveiling the potential interest for some AChE inhibitors as a novel class of potential anti-prion drugs.

Acetylcholinesterase↗
PubMed2006

Effect of acetylcholinesterase inhibitors on AChE-induced PrP106-126 aggregation.

Transmissible spongiform encephalopaties are caused by an extracellular surface protein, the scrapie prion protein (PrPsc), which is an aberrant form of normal and functional cellular PrP (PrPc). The pathological hallmarks of these diseases are the accumulation and deposition of PrPsc in the form of amyloid fibrils in the central nervous system (Tateishi et al., 1988), similar to amyloid-beta (Abeta) protein in Alzheimer's disease (AD). In some patients, Abeta and prion pathology can coexist (Hainfellner et al., 1998), and a common spatial pattern of protein deposition has been described (Armstrong et al., 2001). In addition, it is well-known that acetylcholinesterase (AChE) colocalizes with Abeta deposits of brains in AD patients and accelerates assembly of Abeta peptides through the peripheral site of the enzyme (Inestrosa et al., 1996). The aim of the present study was to analyze time course and concentration dependence of the AChE proaggregating effect on synthetic peptide-spanning residues 106-126 of human PrP (PrP106-126) and the reversion of this effect by different AChE inhibitors (AChEIs).

Acetylcholinesterase↗
PubMed2005

Incomplete esophageal myotomy and early recurrence of an epiphrenic diverticulum.

The established management of epiphrenic diverticula combines diverticulectomy with myotomy of the distal esophagus including the lower esophageal sphincter. We report a patient with prompt recurrence of an epiphrenic diverticulum after laparoscopic transhiatal diverticulectomy associated with esophagomyotomy and partial posterior fundoplication due to an incomplete myotomy.

Digestive System Surgical Procedures↗
PubMed2004

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer.

This study was undertaken to determine the value of tumour microvessel density (MVD) and the expression of p53 and vascular endothelial growth factor (VEGF) as prognostic markers in patients with gastric cancer operated on for cure. In all, 156 patients with curatively resected gastric cancer constituted the basis of this blinded retrospective evaluation. Patients were treated with either surgery alone (n=53) or surgery plus adjuvant chemotherapy (n=103). Tumour MVD, p53 expression, and VEGF expression were assayed using immunohistochemical techniques. After a mean follow-up of 43 months, 64 (41%) patients had died and 55 (35%) patients developed tumour recurrence. Positive correlations between MVD and both p53 (P=0.005) and VEGF (P=0.005) expression were observed. Both MVD >/=100 (P=0.05) and positive VEGF expression (P<0.02) were associated with shorter disease-free survival, and positive VEGF expression (P=0.01) was also associated with shorter overall survival. Multivariate analysis confirmed that, in addition to the pathological tumour stage, lymph node ratio, the extent of lymphadenectomy and perineural invasion, p53 expression, and VEGF expression were independently associated with both disease-free survival (P<0.0005 and 0.02, respectively) and overall survival (P<0.02 and 0.01, respectively). Finally, patients whose tumours did not show p53 expression had a survival benefit compared to those expressing p53 when treated with adjuvant chemotherapy (P=0.01). This investigation demonstrates that p53 expression and VEGF expression are independent prognostic factors for both disease-free survival and overall survival in patients with curatively resected gastric cancer, and that p53 status may also influence response to chemotherapy.

Adult↗
PubMed2002

Primary systemic amyloidosis presenting as a colonic stricture: successful treatment with left hemicolectomy followed by autologous hematopoietic stem-cell transplantation: report of a case.

Intestinal tract involvement by primary systemic amyloidosis is frequent but usually asymptomatic. Ischemic colitis caused by amyloid infiltration of wall blood vessels can occasionally be observed. We report a 62-year-old female with primary systemic amyloidosis who presented with intestinal obstruction caused by ischemic stricture of the sigmoid colon, secondary to submucosal amyloid deposition. The patient was successfully treated with surgical resection followed by high-dose chemotherapy and hematopoietic stem-cell transplantation. The clinical manifestations and differential diagnosis of gastrointestinal involvement of primary systemic amyloidosis, as well as its current treatment, are discussed.

Amyloidosis↗
PubMed2002

Apoptosis in Barrett's oesophagus following antireflux surgery.

BACKGROUND: Intestinal metaplasia persists in Barrett's mucosa despite control of reflux. Tissue homeostasis is maintained by the balance between apoptosis and proliferation. There is an unexplained temporary increase in proliferation in patients with Barrett's mucosa after antireflux surgery, and the long-term effect of any therapy in altering this balance remains unclear. The aim of this study was to assess apoptosis in Barrett's oesophagus following antireflux surgery. METHODS: Apoptosis was evaluated in endoscopic biopsy specimens from 19 patients with Barrett's oesophagus 4 years after Collis-Nissen gastroplasty using an in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) method. RESULTS: Intestinal metaplasia had a lower apoptosis index than gastric metaplasia (0.27 versus 2.14 per cent; P < 0.001). After operation there was a steady increase of apoptosis in intestinal metaplasia over time (from 0.23 per cent before operation to 0.42 per cent within 2 years and to 0.59 per cent 4 years after operation; P = 0.015). Patients with persistent acid exposure did not show any increase in apoptosis in comparison with patients without acid exposure (0.41 versus 0.59 per cent; P = 0.91). CONCLUSION: Apoptosis is less in intestinal metaplasia than in gastric metaplasia, although there is an increase after antireflux surgery. Persistent acid reflux may predispose to malignancy.

Apoptosis↗
PubMed2002

Cardiomyocyte differentiation of mouse and human embryonic stem cells.

Ischaemic heart disease is the leading cause of morbidity and mortality in the western world. Cardiac ischaemia caused by oxygen deprivation and subsequent oxygen reperfusion initiates irreversible cell damage, eventually leading to widespread cell death and loss of function. Strategies to regenerate damaged cardiac tissue by cardiomyocyte transplantation may prevent or limit post-infarction cardiac failure. We are searching for methods for inducing pluripotent stem cells to differentiate into transplantable cardiomyocytes. We have already shown that an endoderm-like cell line induced the differentiation of embryonal carcinoma cells into immature cardiomyocytes. Preliminary results show that human and mouse embryonic stem cells respond in a similar manner. This study presents initial characterization of these cardiomyocytes and the mouse myocardial infarction model in which we will test their ability to restore cardiac function.

Adult↗
PubMed2001

The management of leaking rectal anastomoses by minimally invasive techniques.

BACKGROUND: The salvage of a leaking rectal anastomosis has been reported in selected cases. Herein we present our experience in the management of rectal anastomotic dehiscence by minimally invasive techniques. METHODS: A total of 94 patients underwent anterior rectal resection for rectal cancer in an 18-month period. The operation was laparoscopic-assisted in 76 cases (81%). RESULTS: Clinical anastomotic dehiscences occurred in 10 cases (10.6%). Conservative therapy, including the percutaneous drainage of pelvic abscesses, was successful in three cases. Among the seven patients who required reoperation, the anastomosis was taken down in only one case. In four of these cases, the reoperation was performed laparoscopically, including peritoneal lavage and the creation of a diverting stoma. There were no complications resulting from the use of laparoscopy in the early postoperative period. Closure of the stoma was possible in eight patients. CONCLUSIONS: The salvage of a leaking rectal anastomosis is feasible in the vast majority of these cases (80%). The combination of laparoscopy and interventional radiology is a good alternative to laparotomy in patients who have had previous laparoscopic rectal excision.

Abscess↗
PubMed2001

Nuclear transfer of adult and genetically modified fetal cells of the rat.

The present study examines the handling, activation, and micromanipulation of rat eggs in an attempt to produce live young using nuclear transfer (NT) of adult and genetically modified rat fetal cells. Mature rat eggs cultured in calcium-free medium showed reduced rates (24%) of chromosomal dispersion ("spontaneous activation" characteristic of this species) compared with eggs cultured in calcium-containing medium (47%), but failed to survive micromanipulation procedures. High rates of parthenogenetic cleavage were obtained with chemical activation using ethanol/cycloheximide (65%) compared with other standard chemical activation methods (4-28%). This type of activation was also effective in reestablishing cleavage capability (19-71%), in a time-dependent manner, of spontaneously activated eggs arrested at a second prophase-like state. At most, two of four tested micromanipulation procedures were effective in producing NT embryos capable of morula or blastocyst development (14-16%) in vivo following transfer to mouse oviducts. NT blastocysts produced from cumulus cells and transfected rat fetal fibroblasts appeared morphologically and karyotypically normal (2n = 42). Nocodazole-assisted metaphase enucleation and piezoelectric-assisted donor cell injection produced significant and equivocal effects on survival and cleavage rates of reconstructed embryos but failed to significantly improve in vivo morula/blastocyst development rates (16-28%) compared with unassisted micromanipulation (16%). Live births have not yet been obtained from early cleavage stage embryos (n = 269) transferred to pseudopregnant recipient rat oviducts. Improvements in reconstituted NT embryo culture and transfer are required for these methods to be an effective means of transgenic rat production.

Animals↗
PubMed2001

Metastatic carcinoma of the breast resembling early gastric carcinoma.

We describe a case of gastric metastasis from a lobular carcinoma of the breast in a 45-year-old woman who had undergone a left mastectomy with axillary dissection 7 years earlier. At the current presentation, she had been experiencing progressive epigastric discomfort for 3 months. The initial diagnosis was early gastric carcinoma, diffuse type, based on gastric biopsy findings and ultrasonographic endoscopy. A definitive diagnosis of metastatic breast cancer was confirmed after subtotal gastrectomy of a presumed primary early gastric carcinoma. Although gastrointestinal metastases from breast cancer are not rare, the early stage of the gastric lesion and the absence of further disease dissemination make this case unusual. The onset of gastrointestinal symptoms in a patient with a history of breast carcinoma should prompt the physician to rule out the possibility of gastric metastases.

Breast Neoplasms↗
PubMed2001

Expression of cyclin D1 and p53 and its correlation with proliferative activity in the spectrum of esophageal carcinomas induced after duodenal content reflux and 2,6-dimethylnitrosomorpholine administration in rats.

Alterations in expression of the p53 and cyclin D1 genes have been implicated in the development of esophageal carcinomas in both humans and animal models. We hypothesize that altered expression of cyclin D1 and p53 may be involved in the sequential development of esophageal carcinomas with glandular differentiation induced by the carcinogen, 2,6-dimethylnitrosomorpholine (DMNM) in rats with duodenal content reflux esophagitis. In the present study Sprague-Dawley rats were given DMNM 15 days after performing an esophago-jejunostomy in order to induce chronic duodenal content reflux esophagitis. Expression and localization of p53, cyclin D1 and Ki-67 were examined by immunohistochemical analyses. Twenty of 24 animals developed different types of esophageal carcinomas, including pure squamous carcinoma, adenosquamous carcinoma and pure adenocarcinoma. Undifferentiated basaloid areas were frequently observed in these tumors. Cyclin D1 overexpression was observed in hyperplastic lesions and increased through dysplasia and in undifferentiated areas of infiltrating carcinoma. Cyclin D1 expression coincided with increased Ki-67 expression and decreased along with cell differentiation. The p53 immunohistochemical pattern was parallel to that of cyclin D1, although the percentage of positive cells was usually smaller in all lesions and increased p53 expression started at the dysplastic stage. These findings suggest that overexpression of cyclin D1 may be an early event in DMNM-induced rat esophageal tumorigenesis, causing increased proliferation of esophageal stem cells. Abnormal p53 expression may then be required to promote the development of neoplastic transformation from dysplastic epithelium through invasive phenotype, being more evident in cancer cells with squamous differentiation.

Adenocarcinoma↗
PubMed2001

Proliferative activity in Barrett's esophagus before and after antireflux surgery.

OBJECTIVE: To assess proliferation in the columnar-lined esophageal mucosa before and after antireflux surgery. SUMMARY BACKGROUND DATA: Intestinal metaplasia persists in Barrett's mucosa after reflux control. It remains at risk for uncontrolled cellular proliferation and adenocarcinoma formation. METHODS: Forty-five patients with Barrett's esophagus had a mean follow-up of 4 years after a Collis-Nissen gastroplasty. Proliferative activity was assayed immunohistochemically for Ki-67 expression in 73 preoperative and 176 postoperative biopsies. Correlation with manometric and 24-hour pH results was obtained. RESULTS: The Collis-Nissen gastroplasty restored the median lower esophageal sphincter gradient from 5.5 mmHg before surgery to 14.5 mmHg at 24 months and 12.9 mmHg at 48 months after surgery. The median esophageal acid exposure was reduced from 8% to 1% and 1% of recording time, respectively. The median Ki-67 labeling index increased from 28.5% before surgery to 36.1% at 12 to 23 months. It returned to preoperative level (26.9%) at 24 to 47 months. After surgery, abnormal intraesophageal acid exposure was documented in 12 patients but could not be correlated with sphincter pressure. After surgery, the pattern of proliferation in patients with acid exposure less than 4% in their esophagus showed significant differences when compared with the proliferation pattern of patients where abnormal intraesophageal acid exposure was recorded. New present dysplasia was observed only in patients with abnormal acid exposure. CONCLUSIONS: In Barrett's mucosa, from preoperative values, proliferation peaked early after surgery and then decreased to preoperative levels. Despite sphincter restoration and global reflux control, abnormal esophageal acid exposure persisted in 12 patients. Patients with abnormal esophageal acid exposure displayed more proliferation and more dysplasia.

Adult↗
PubMed2001

Ulcer associated cell lineage glands expressing trefoil peptide genes are induced by chronic ulceration in ileal pouch mucosa.

BACKGROUND: Chronic ulcerative conditions in the gastrointestinal tract result in the appearance of the ulcer associated cell lineage (UACL). The glands of this new cell lineage secrete epidermal growth factor, transforming growth factor alpha, and the trefoil factor family (TFF) peptides, which are known to participate in repair processes. Pouchitis is the most frequent complication of ileal pouch-anal anastomosis. AIM: Our aim was to determine whether the mucosal ulceration present in pouchitis can induce the development of UACL glands. METHODS: Biopsies from ileal pouches with pouchitis (n=10), healthy pouches (n=5), and normal terminal ileum (n=5) were studied. Expression of TFF mRNA was assessed by in situ hybridisation. TFF1 and TFF2 proteins were localised by immunochemistry. RESULTS: UACL glands containing TFF1 and TFF2 were observed in six patients with pouchitis. In some glands, there was TFF3 mRNA as has been reported for Crohn's UACL. None of the biopsies from ileal reservoirs without pouchitis showed UACL glands (p<0.05). Neither TFF1 nor TFF2 expression was detected in ileal reservoirs without pouchitis. CONCLUSION: UACL glands arise de novo in ileal pouch mucosa of patients with pouchitis and express all three TFF peptide genes. Chronic inflammation alone, present in healthy pouches, is not enough to stimulate the growth of the UACL, and additional stimuli consequent on ulceration may be needed.

Autoradiography↗