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F Lluis

Publications and source records attributed to F Lluis.

At least 19 recordsLinked to original sources
PubMed2001

p53 and K-ras mutations in pancreatic juice samples from patients with chronic pancreatitis.

BACKGROUND: Mutations in p53 and ras genes are frequent in pancreatic carcinoma. Several ras mutations are consistently detected in the pancreatic juice from patients with chronic pancreatitis. The p53 gene mutations have been detected occasionally in chronic pancreatitis tissue. It was the aim of this study to evaluate the presence and clinical significance of p53 and ras mutations in clinical pancreatic juice samples from patients with chronic pancreatitis. METHODS: Pancreatic juice was obtained from 66 patients with chronic pancreatitis and no evidence of pancreatic carcinoma (51 men, 15 women; age 17-86 years [mean 49.6 +/- 12.9]). Patients were followed prospectively for 26 +/- 3 (4-54) months. Detection of p53 gene mutations was by temperature gradient gel electrophoresis (TGGE) and single strand conformation polymorphism (SSCP) for exons 5-8. Analysis of ras mutations was performed by SSCP/polymerase chain reaction, restriction fragment length polymorphism/polymerase chain reaction. All mutations were confirmed by sequencing. RESULTS: Five of 66 (7.5%) pancreatic juice samples contained p53 mutations, and ras mutations were detected in 6 cases (9%). Cytology was negative in all cases. No pancreatic carcinoma developed during follow-up and neither cancer cells nor preneoplastic lesions could be detected histologically in resected specimens. Although no correlation between p53 mutations and duration of pancreatitis or drinking habits was found, K-ras mutations correlated with both heavy smoking and severity of the disease. CONCLUSION: p53 and ras mutations can be detected in a minority of pancreatic juice samples from patients with chronic pancreatitis in the absence of malignancy.

Adolescent↗
PubMed1996

Loss of sst2 somatostatin receptor gene expression in human pancreatic and colorectal cancer.

Five somatostatin receptor subtypes (sst1 to sst5) have been cloned. We demonstrated previously that sst2 and sst5 mediate the antiproliferative effect of the somatostatin analogues octreotide and vapreotide. Using reverse transcription-PCR, we investigated gene expression of the five receptors in 47 human normal and cancerous tissues or cell lines from pancreatic and colorectal origin. mRNAs of somatostatin receptor subtypes were detected in 98% of samples, with more than two mRNA subtypes being expressed in 55% of cases. sst1, sst4, and sst5 were heterogeneously expressed in both normal and cancerous tissues; sst3 was rarely or not expressed. sst2 was present in normal pancreatic tissues but was absent in exocrine pancreatic carcinomas and their metastases. sst2 mRNAs were detected in normal colon, sporadic polyadenomas, and 50% of Dukes' stage B and 20% of Dukes' stage C carcinomas but were undetectable in Dukes' stage D carcinomas, hepatic metastases, and adenomas from familial adenomatous polyposis. The loss of sst2 expression could represent a growth advantage in these tumors and provide an explanation for the lack of therapeutic effect of somatostatin analogues in such adenocarcinomas. A subtyping of somatostatin receptors should be carried out before considering a somatostatin analogue treatment in patients with colorectal or pancreatic cancer.

Cell Line↗
PubMed1996

Growth hormone upregulates gastrin and peptide YY gene expression.

The purpose of these studies was to examine the effects of excess growth hormone (GH) on gastrin and peptide YY (PYY) gene expression. Transgenic mice with the bovine GH gene linked to a mouse metallothionein I promoter were used as a model of chronic GH excess. Antral gastrin mRNA and peptide levels were elevated significantly (P < 0.05) in GH transgenic mice compared with wild type littermates. Ileal PYY mRNA and ileal and colonic PYY levels were significantly elevated in GH transgenic mice compared with wild type littermates. The elevations in gastrin and PYY gene expression in GH transgenic mice were independent of food intake. Serum concentrations of gastrin and PYY were also elevated in GH transgenic mice. Immunohistochemical analysis showed that the density of PYY-containing cells in the colon of GH transgenic mice and wild type littermates did not differ. In addition, the mRNA and protein levels of chromogranin A, a marker of endocrine cells, were not increased in the colon of GH transgenic mice. Together, these data indicate that GH, insulin-like growth factor I, or both can upregulate gastrointestinal gastrin and PYY gene expression directly.

Animals↗
PubMed1995

[Low incidence of mutations in codon 12 of the c-K-ras gene in bladder cancer].

During vesical carcinogenesis a variety of genetic alterations such as oncogene mutation or loss of suppressor genes have been detected. Codon 12 mutation of the c-K-ras gene has been seen with a high frequency in several human neoplasias but its participation in the development of vesical cancers has not been fully dilucidated. Using the DNA restriction fragments polymorphism (RFLP) technique enhanced by a polymerase chain reaction (PCR) a study has been made of codon 12 mutation at the c-K-ras gene in 55 patient with vesical cancer undergoing surgery between 1991 and 1992. The tumoral stage was superficial (Ta-Tl) in 24 cases, infiltrant (T2-T4) in 28 cases and unknown in 3 cases. Two patients (3.6%) showed codon 12 mutation at the c-K-ras gene. One case was a fast evolving infiltrant tumour (T2-T3) which caused death of the patient after 4 months while the other case was a surface tumour (G2Ta) which relapsed early, the pathological anatomy revealing a stage T2-T3 squamous carcinoma. Our results suggest that codon 12 mutation at the c-K-ras gene is not a meaningful genetic change in the genesis of vesical cancer. Its emergence, however, appears to be related to a more aggressive tumoural behaviour.

Aged↗
PubMed1993

Neural regulation of peptide YY secretion.

The purpose of these experiments was to investigate the neural control of peptide YY (PYY) secretion. The effects of various pharmacological manipulations and vagotomy on peptide YY (PYY) secretion was examined in dogs. Atropine, hexamethonium and atropine plus hexamethonium treatment blocked food-induced release of PYY significantly. Integrated release of PYY in response to food alone and in combination with atropine, hexamethonium and atropine plus hexamethonium were 8.8 +/- 2.2, -1.1 +/- 2.3, -2.7 +/- 2.2 and -3.2 +/- 3.1 (ng (0-150) min/ml), respectively. beta-Adrenergic blockade with propranolol or depletion of nerve terminal stores of catecholamines with reserpine did not affect food-stimulated release of PYY. Truncal vagotomy resulted in significant elevations of basal and food-induced release of PYY. IV administration of bethanechol, a cholinergic agonist, and electrical stimulation of the vagus nerve resulted in release of PYY. Together, these data suggest that food-stimulated PYY secretion is dependent on ganglionic transmission and an atropine-blockable postganglionic parasympathetic pathway; and that PYY release is inhibited tonically, probably through a vagal cholinergic mechanism. Adrenergic pathways do not participate in food-stimulated PYY release; however, electrical stimulation of the splanchnic nerves increased basal levels of PYY, suggesting that the sympathetic nervous system affects release of PYY.

Animals↗
PubMed1992

[Rebound hyperglycemia and peroperative normalization of insulinemia. Complete excision of insulinoma?].

Clinical usefulness of the hyperglycemic rebound and the normalization of plasma insulin level as intraoperative markers of complete removal of insulinoma was assessed. Surgical removal was curative (no clinical or biological recurrence) in six patients harboring a single adenoma (mean follow-up = 32.2 months). In these patients plasma glucose increased an average of 32 mg/dl 30 minutes after resection, 68 mg/dl after 60 minutes, and 91 mg/dl after 90 minutes. Sensitivity of hyperglycemic rebound (defined as a plasma glucose increment of at least 30 mg/dl after tumor removal) as a marker of complete resection of the insulinoma was 40% at 30 min and 83% at 60 minutes after resection. Preresectional values of plasma immunoreactive insulin were elevated in 3 out of 4 patients with adenoma. All postresectional values were within normal ranges. Two patients operated on because of malignant insulinoma, underwent partial tumor resection; hyperglycemic rebound was also present, and high preresectional insulin values became normal 30 minutes after partial tumor removal. We conclude that information provided by intraoperative monitoring of both plasma glucose and insulin cannot be used as the only markers of complete resection of all insulinomas. Only long term clinical and biological follow-up can guarantee the complete resection of an insulinoma.

Blood Glucose↗
PubMed1992

[The treatment of a simple pancreatic pseudoaneurysm or one associated with hemosuccus pancreaticus].

When a permanent communication occurs between an artery and a pancreatic pseudocyst, the pseudocyst becomes a pseudoaneurysm. Pancreatic pseudoaneurysms are primarily found in patients with alcoholic chronic pancreatitis. Fistulization of a pseudoaneurysm into the main pancreatic duct results in ductal hemorrhage. From 1980 to 1990, 43 cases of pancreatic pseudoaneurysm and 24 cases of ductal hemorrhage (15 of these secondary to pancreatic pseudoaneurysm) have been published. Pancreatectomy, ligation of the affected vessel (alone or in combination with a drainage procedure), or intraarterial embolization have all been used to treat pancreatic pseudoaneurysms. We herein describe two patients with alcoholic chronic pancreatitis and pancreatic pseudoaneurysm; one patient presented with ductal hemorrhage. The inferior pancreatico-duodenal artery was the affected vessel. Both patients were treated with suture-ligation; an internal drainage was added to the patient presenting with ductal hemorrhage.

Alcoholism↗
PubMed1991

Intracolonic fat inhibits gastric acid secretion independent of gastrin release in the dog.

The purpose of this study was to examine the effect of perfusion of the colon with a fatty acid (oleic acid) on peptone-stimulated gastric acid secretion and release of gastrin in conscious dogs. Gastric acid secretion was monitored by continuous intragastric titration. Perfusion of the colon with sodium oleate (24 mmol/hr) inhibited gastric acid secretion (14.2 +/- 2.6 meq/hr) stimulated by a peptone meal (1%) significantly (P less than 0.05) when compared to perfusion of the colon with saline alone (20.1 +/- 1.6 meq/hr). The serum elevation in gastrin in response to intragastric instillation of the peptone meal was not affected by the colonic perfusion of oleic acid. Plasma concentrations of peptide YY (PYY) increased significantly in response to perfusion of the colon with saline or sodium oleate, and the integrated release of PYY in response to sodium oleate [6.9 +/- 2.8 ng (60-120) min/ml] was significantly greater than the response to saline [3.1 +/- 0.7 ng (60-120) min/ml]. The results of this study indicate that inhibition of gastric acid secretion by perfusion of the colon with fat is not due to an inhibition of gastrin release. In addition, because PYY is an inhibitor of gastric acid secretion, it is possible that PYY participates as an inhibitor of gastric acid secretion by the colon.

Animals↗
PubMed1990

Stimulatory effect of pancreastatin on gastric acid secretion in conscious dogs.

Pancreastatin, a new 49-amino acid peptide, has recently been isolated and characterized from extracts of the porcine pancreas. The objective of the present study was to examine the effect of various doses of pancreastatin on gastric acid secretion in conscious dogs that were prepared with chronic gastric cannulas. Pancreastatin, administered IV at 400 pmol.kg-1 x h-1, enhanced peptone meal [peptone (5%), phenylalanine (90 mmol/L), glucose (12 g/dL)]-stimulated gastric acid secretion by 50%; pancreastatin at 800 pmol.kg-1 x h-1 enhanced peptone meal secretion by 165% (P less than 0.05). Intravenous administration of pancreastatin did not affect basal or peptone-stimulated release of gastrin. In addition, IV pancreastatin (400 pmol.kg-1 x h-1) failed to influence basal gastric acid secretion. Pancreastatin did not affect acid secretion stimulated by 2-deoxyglucose, histamine, or pentagastrin. The present study shows that pancreastatin can selectively enhance gastric acid secretion by a mechanism independent of cholinergic, histaminergic, or gastrin input.

Animals↗
PubMed1989

Pancreatic juice enhances fat-stimulated release of enteric hormones in dogs.

The presence of pancreatic juice in the intestinal lumen results in the hydrolysis of dietary fat. The hydrolytic products of dietary fat are potent stimulants of pancreatic exocrine secretion and potent inhibitors of gastric acid secretion. In this study, residual pancreatic enzyme activity in the intestinal lumen may account for the observed increase of triglyceride-stimulated pancreatic exocrine secretion and the release of peptides during diversion of pancreatic juice. The presence of pancreatic juice enhanced the pancreatic protein output that was stimulated by the intraduodenal administration of a triglyceride (corn oil, 2 g/kg/h) by 240% (p less than .05). The presence of pancreatic juice during the intraduodenal administration of a triglyceride nearly abolished the output of gastric acid as well as the release of gastrin (p less than .05) that had been stimulated by the intragastric placement of a 10% peptone meal. Pancreatic juice in the duodenum significantly enhanced the triglyceride-stimulated release of cholecystokinin-33/39, secretin, neurotensin, peptide YY, pancreatic polypeptide, and insulin (p less than .05) when compared with the release of these enteropancreatic hormones during the diversion of pancreatic juice. This study shows that the presence of pancreatic juice in the duodenal lumen enhances the fat-stimulated release of enteric hormones that have a stimulatory action on the enteroacinar and enteroinsular axis as well as an inhibitory action (enterogastrone-like activity) on the postprandial regulation of gastric function.

Animals↗
PubMed1989

Effect of pancreastatin on pancreatic endocrine and exocrine secretion.

Pancreastatin is a novel peptide that was recently purified from extracts of the porcine pancreas. The present study shows that pancreastatin (10(-9)-10(-8) M) can stimulate release of insulin from both the isolated perfused rat pancreas and from cultured rat islet cells in the presence of a low, non-insulinotropic concentration of glucose (4.2 mM). Pancreastatin (10(-9) M) can also inhibit release of insulin stimulated by a high concentration of glucose (16.7 mM). Pancreastatin, at 10(-8) M, can enhance glucose (8.3 mM) induced release of insulin in the static islet cell incubation. In addition, pancreastatin (10(-9)-10(-8) M) can inhibit, in a dose-dependent fashion, cholecystokinin (CCK)-8 stimulated release of amylase from dispersed guinea pig pancreatic acini. Pancreastatin alone, however, did not affect basal release of amylase. Our study shows that pancreastatin can exert a direct effect on both pancreatic endocrine and exocrine secretion.

Amylases↗
PubMed1989

A comparison of intraduodenally and intracolonically administered nutrients on the release of peptide-YY in the dog.

The objective of this study was to compare the effects of various nutrients (fats, proteins, amino acids, and carbohydrates), given directly into the duodenum or the colon, on the release of peptide-YY (PYY) in conscious dogs. As reported previously, this study showed that plasma levels of PYY increased significantly (P less than 0.05) within 15 min in response to an oral mixed meal. Intraduodenal (ID) administration of a fatty acid (oleic acid; 100 mmol/L; 100 ml/h) stimulated a robust release of PYY, whereas ID administration of an amino acid mixture (phenylalanine plus tryptophan; 100 mmol/L each; 100 ml/h), glucose (1 g/kg), or a liver extract (10%; 100 ml/h) failed to elevate plasma levels of PYY. ID administration of glucose at 2 g/kg caused a mild but significant elevation in plasma PYY levels. Intracolonic administration of saline, a fatty acid, an amino acid mixture, glucose, or a liver extract significantly stimulated PYY release. This study suggests that as chyme moves from the stomach to the proximal bowel, fat is the primary constituent of food that stimulates the prompt release of PYY. However, unabsorbed nutrients can release PYY by a direct contact with the PYY-containing cells lining the intestinal lumen of the terminal ileum, colon, and rectum. Both mechanisms probably participate in the release of PYY.

Amino Acids↗
PubMed1989

[Cellular localization, half-life, and secretion of peptide YY].

Tissue and plasma concentration of peptide YY (PYY) were measured by means of a radioimmunoassay (RIA) developed in our laboratory, using a specific PYY antiserum generated in New Zealand white rabbits against synthetic PYY, and dextran-coated charcoal to terminate the assay. Cellular localization of PYY was studied immunohistochemically using the peroxidase-antiperoxidase (PAP) technique. The highest tissue concentration of PYY was found in the mucosa of the terminal ileum and colon. PYY-containing secretory granules were primarily found in the basal pole of open-type endocrine cells. Basal plasma concentration of PYY was 70 +/- 9 pg/ml and rose to 357 +/- 30 pg/ml during the IV administration of PYY at 400 pmol/kg-h. A significant correlation was found (r = 0.94, p less than 0.05) between dose of PYY (12.5, 25, 50, 100, 200, 400 pmol/kg-h, IV) and plasma concentration of PYY. The calculated half-life of PYY in plasma was 8.3 +/- 1.9 minutes. Plasma concentration of PYY during the intraduodenal administration of sodium oleate (150 +/- 20 pg/ml) or long-chain triglyceride (187 +/- 37 pg/ml) was similar to plasma concentration of PYY obtained during the IV administration of PYY at 100 pmol/kg-h. Plasma concentration of PYY raised (126 +/- 10 pg/ml) after the administration of bombesin (400 pmol/kg-h, IV). Bile enhanced release of PYY. The present study suggests a hormonal role for PYY.

Amino Acids↗
PubMed1988

Regulation of the release of cholecystokinin by bile salts in dogs and humans.

The objective of these studies was to investigate the role of bile salts in the regulation of release of cholecystokinin in response to nutrients in dogs and humans. In dogs, the intraduodenal administration of a bile salt sequestrant, cholestyramine (2, 4, or 8 g/h), resulted in a dose-related enhancement of the release of cholecystokinin-33/39 and pancreatic protein secretion in response to intraduodenal administration of amino acids. Intraduodenal administration of cholestyramine alone did not affect basal levels of cholecystokinin-33/39 or pancreatic protein secretion. Total diversion of bile also significantly increased the release of cholecystokinin and pancreatic protein secretion in response to intraduodenal administration of amino acids. Replacement of the bile salt pool by intraduodenal administration of taurocholate completely reversed the enhancement effect of both cholestyramine and bile diversion. In humans, oral ingestion of cholestyramine (12 g) significantly increased the release of cholecystokinin-33/39 and gallbladder contraction in response to the oral ingestion of either a triglyceride or amino acids. These results support a physiologic role of bile salts in the negative feedback regulation of release of cholecystokinin in response to luminal nutrients.

Adult↗