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J Fauvel

Publications and source records attributed to J Fauvel.

At least 19 recordsLinked to original sources
PubMed2006

Persistent and moderate hypercalcemia related to an ovarian clear cell adenocarcinoma: Pre- and postoperative parathyroid hormone related-peptide and 1,25-dihydroxyvitamin D3 levels.

OBJECTIVE: To evaluate the role of PTH-related peptide (PTH-rP) and 1,25-dihyhydroxyvitamin D3 in a case of hypercalcemia related to an ovarian adenocarcinoma. DESIGN: We report a case of humoral hypercalcemia in a patient aged 74 yr with a clear cell adenocarcinoma of the right ovary at an early stage of its development (stage T1aN0M0) revealed by moderate and persistent hypercalcemia (variable level between 2.7 and 3.2 mmol/l without any treatment) over six months. METHODS: PTH-rP and 1,25-dihydroxyvitamin D3 were measured in blood samples taken before and after hysterectomy and bilateral salpingooophorectomy and in blood samples taken intraoperatively from the right ovarian vein and a peripheral vein. RESULTS: High levels of plasma PTH-rP and 1,25-dihydroxyvitamin D3 concomitant with high serum calcium and low PTH levels were found before surgery, which was followed by normalisation of all parameters studied. A concentration gradient was found regarding plasma PTHrP (right ovarian vein 60.4 pmol/l, peripheral vein 4.5 pmol/l), not 1,25-dihydroxyvitamin D3. CONCLUSION: 1) moderate and persistent hypercalcemia can be observed at an early stage of an ovarian carcinoma; 2) the gradient of PTH-rP concentration between the samples taken from the right ovarian vein and a peripheral vein provides evidence for a direct secretion of PTH-rP by the ovarian tumor; 3) the increased 1,25-dihydroxyvitamin D3 level is not related to a direct ovarian production, but is a consequence of PTH-rP secretion.

Adenocarcinoma, Clear Cell↗
PubMed2004

Normal pregnancy in a woman with nesidioblastosis treated with somatostatin analog octreotide.

OBJECTIVE: We report the case of a 36-yr-old woman with nesidioblastosis treated throughout pregnancy with high doses of octreotide. We studied the course of blood glucose, foetal growth and development. METHODS: Blood samples were obtained every month throughout pregnancy and taken at birth from the umbilical cord. Sonography was performed repeatedly to monitor foetal growth. RESULTS: The daily dose of octreotide was adapted to blood glucose levels: a dose of 1000 microg was infused during the first part of pregnancy, then it was decreased step by step during the last trimester of gestation. An elective cesarean section was performed at 32 weeks of gestation. High octreotide concentrations were obtained during the first part of gestation (range 2888-5021 pg/ml). During the third trimester of pregnancy blood glucose increased despite high insulin levels attesting physiological insulin-resistance. Plasma levels of placental GH and IGF-1 levels were similar to those observed in a normal pregnancy. Despite the presence of octreotide in the umbilical cord, TSH, free T4, PRL and pituitary GH concentrations were normal at birth. The female newborn (weight 3520 g, length 52 cm) had no malformation, and presented with normal postnatal development. CONCLUSION: Our study demonstrates that: 1) octreotide treatment can be effective in controlling endogenous hyperinsulinism during pregnancy; 2) octreotide does not affect physiological changes during pregnancy such as insulin-resistance or placental GH level; 3) exposure of the foetus to octreotide throughout pregnancy does not induce any malformation and does not affect foetal development.

Adult↗
PubMed2004

A simple and reliable method for rapid production and purification of Pseudomonas aeruginosa haemolytic phospholipase C.

AIMS: To design a simple method to produce active recombinant Pseudomonas aeruginosa haemolytic phospholipase C (PLC). METHOD AND RESULTS: Pseudomonas aeruginosa PLC is a virulence factor mainly involved in inflammatory and cytotoxic responses. While ammonium sulphate purification requires large amounts of bacterial suspensions and leads to low yields, production of recombinant protein in Escherichia coli is no more successful because of frequent inclusion bodies and accumulation of inactive PLC in the periplasmic space. Using an inducible system based on the glucose-repressed inv1 promoter in the yeast Schizosaccharomyces pombe, we were able to produce up to 10 IU ml(-1) of pure toxin within 24 h. CONCLUSIONS: This work describes the first method to easily get recombinant haemolytic PLC. SIGNIFICANCE AND IMPACT OF THE STUDY: This method provides a powerful tool to study the mechanisms leading to its cellular toxicity.

Bacterial Toxins↗
PubMed2003

The association of metabolic disorders with the metabolic syndrome is different in men and women.

AIMS: Metabolic disorders depend on genetic, hormonal and environmental factors, whose relations may differ between genders. Therefore, we compared the contribution of metabolic disorders to the metabolic syndrome in women and men. METHODS: To this end, we used a hierarchical classification statistical method to classify subjects into similarity groups according to clinical and biological parameters. Data were collected from 3,508 men and women aged 35-64 years, from a cardiovascular disease survey. RESULTS: In both women and men, hierarchical classification identified a cluster corresponding to the metabolic syndrome representing 14 and 15% of the women's and men's sample, respectively. In women, elevated body weight (women's Z-score: 1.59 vs. men's Z-score: 1.29; p < 0.005), waist girth (1.62 vs. 1.30; p < 0.001) and low HDL cholesterol (-0.95 vs. -0.75; p < 0.05) were significantly larger contributors to the metabolic syndrome than in men. In contrast, systolic (0.59 vs. 0.95; p < 0.0001) and diastolic (0.55 vs. 0.99; p < 0.0001) blood pressure and apolipoprotein B (0.51 vs. 0.71; p < 0.0001) contributed significantly less in women than in men. Finally, insulin (n.s.), glucose (n.s.), triglycerides (n.s.) and LDL-cholesterol (n.s.) contributions were not different between genders. CONCLUSION: These results are consistent with the concept that a clustering of metabolic disorders occurs frequently in both women and men. However, the contribution of several metabolic disorders to the metabolic syndrome is different in men and women. This finding supports the concept that different criteria are necessary to define the metabolic syndrome in women and men.

Adult↗
PubMed2001

An interaction between apo C-III variants and protease inhibitors contributes to high triglyceride/low HDL levels in treated HIV patients.

BACKGROUND: Long-term therapy with protease inhibitors (PI) is associated with hypertriglyceridaemia, low high-density lipoprotein (HDL) levels and accumulation of apolipoprotein (apo) E- and apo C-III-containing lipoproteins. OBJECTIVES: To evaluate the impact, on this dyslipaemic phenotype, of three polymorphisms of the apo C-III gene: two on an insulin response element and one in the 3'-region. Apo E genotypes were evaluated also. DESIGN: Sixty consecutive male patients attending the HIV follow-up consultation were included during a 3-month period. All patients received at least one PI. Apo C-III and apo E genotypes were determined. Besides routine bio-clinical examination, a detailed exploration of lipoproteins and of insulin secretion markers was carried out. METHODS: Plasma lipoparticles, insulin, proinsulin and C-peptide were measured by specific immuno-assays. Determination of apo C-III genotypes (-455C/T, -482C/T and SstI) and of apo E alleles (epsilon2, epsilon3 and epsilon4) were performed by amplification and endonuclease digestion and were confirmed by allele-specific oligonucleotide hybridization. RESULTS: Distribution of apo C-III alleles defined four major haplotypes. Carriers of the -455C variant had 30% lower levels of HDL-cholesterol than non-carriers. Plasma triglycerides increased according to the number of variant alleles. In multivariate analysis, a model including age, body mass index, clinical stage and treatment length, plasma insulin and apo C-III haplotypes explained around 43% of the HDL-cholesterol and triglycerides variability. Measurements of lipids before and after the use of PI demonstrated synergistic effects of the treatment and apo C-III variants on triglyceride levels. CONCLUSIONS: Apo C-III polymorphisms might identify a genetic predisposition to develop dyslipidaemia under PI therapy.

Adult↗
PubMed2001

Enterophilins, a new family of leucine zipper proteins bearing a b30.2 domain and associated with enterocyte differentiation.

Enterocyte terminal differentiation occurs at the crypt-villus junction through the transcriptional activation of cell-specific genes, many of which code for proteins of the brush border membrane such as intestinal alkaline phosphatase, sucrase-isomaltase, or the microvillar structural protein villin. Several studies have shown that this sharp increase in specific mRNA levels is intimately associated with arrest of cell proliferation. We isolated several clones from a guinea pig intestine cDNA library. They encode new proteins characterized by an original structure associating a carboxyl-terminal B30.2/RFP-like domain and a long leucine zipper at the amino terminus. The first member of this novel gene family codes for a 65-kDa protein termed enterophilin-1, which is specifically expressed in enterocytes before their final differentiation. Enterophilin-1 is the most abundant in the small intestine but is still present in significant amounts in colonic enterocytes. In Caco-2 cells, a similar 65-kDa protein was recognized by a specific anti-enterophilin-1 antibody, and its expression was positively correlated with cell differentiation status. In addition, transfection of HT-29 cells with enterophilin-1 full-length cDNA slightly inhibited cell growth and promoted an increase in alkaline phosphatase activity. Taken together, these data identify enterophilins as a new family of proteins associated with enterocyte differentiation.

Amino Acid Sequence↗
PubMed2001

Apoprotein c-III and E-containing lipoparticles are markedly increased in HIV-infected patients treated with protease inhibitors: association with the development of lipodystrophy.

Long-term therapy with protease inhibitors (PIs) can induce hypertriglyceridemia and development of a lipodystrophy. To better understand these metabolic alterations, the apoprotein and lipoparticle profile was investigated in male HIV patients under antiretroviral therapy: 49 received PIs, and 14 were given only two reverse transcriptase inhibitors. As controls, 63 male subjects were selected from a population study carried out in the Toulouse, France, area. Fasting glucose, insulin, and C-peptide were also determined. All patients under PIs displayed low levels of plasma glucose and increased insulin. PI administration was associated with moderate hypertriglyceridemia, low high-density cholesterol and apolipoprotein (apo) A-I levels. The most striking changes were a 2- to 3-fold increase in apo E and apo C-III, essentially recovered as associated to apo B-containing lipoparticles. Levels of those lipoparticles were two to eight times above control values. About 50% of PI-treated patients had developed a patent lipodystrophy. Multivariate analysis revealed that, among the investigated parameters, apo C-III was the only one found strongly associated with the occurrence of lipodystrophy (odds ratio, 5.5; P: < 0.015). Finally, 13 PI-receiving subjects with patent hypertriglyceridemia were given fenofibrate and were reevaluated 2 months later. Triglycerides, apo E, apo C-III, and the corresponding lipoparticles had returned to nearly normal levels. These results document the accumulation of potentially atherogenic lipoparticles under PIs. Apo C-III may play a pivotal role in the development of hypertriglyceridemia and lipodystrophy.

Adult↗
PubMed2000

Polymorphism of the 5' untranslated region of NHE1 gene associated with type-I diabetes.

The ubiquitous form of the sodium-hydrogen exchanger, NHE1, is devoted to the regulation of intracellular pH and cell volume. In addition, NHE1 activity is stimulated by growth factors and increased NHE rates are found in both circulating and immortalized cells during diabetes or diabetic nephropathy. In this context, we searched for polymorphisms of the 5'-flanking regulatory region of NHE1 gene in subjects with type-I diabetes. We identified a C/T transition 696 bases upstream the translation initiation start site which disrupts a repeated palindromic GC sequence. The TT genotype was significantly more frequent in type-1 diabetics and may have functional importance. Genetic linkage between NHE1 and diabetes has been previously described in NOD mice strains with consequences on NHE rates. Hence, the polymorphism described hereby may act as a predisposition factor to type-I diabetes or to diabetic complications, and may be useful to investigate the genetic involvement of NHE1 in human pathophysiology.

5' Untranslated Regions↗
PubMed2000

Toxoplasma gondii secretes a calcium-independent phospholipase A(2).

Phospholipases A(2) (PLA(2)) play an important role in Toxoplasma gondii host cell penetration. They are also key enzymes in the host cell response to the parasite invasion. PLA(2) hydrolyse cellular phospholipids, releasing multiple inflammatory lipidic mediators. We have investigated the biochemical characterisation of T. gondii PLA(2) activity in a mouse-cultured tachyzoite homogenate and in the peritoneal exudate from infected mice, using the hydrolysis of a fluorescent phosphatidylglycerol labelled at the sn-2 position. Spectrofluorimetry and thin-layer chromatography showed a PLA(2) activity (about 0.5-2 nmol/min per mg), calcium-independent, secreted into infected mice peritoneal exudate, with a broad pH activity ranging between 6.5 and 9.5 and resistant to a great number of potential PLA(2) inhibitors except dithio-nitrobenzoic acid (1 mM). An associated phospholipase A(1) activity was also displayed. These results suggest that Toxoplasma gondii displays specific phospholipases different from host enzymes and probably involved at critical steps of infectious cycle.

Animals↗
PubMed1999

New developments in phospholipase A2.

Some of the most recent data concerning various phospholipases A2, with special emphasis on secretory, cytosolic, and calcium-independent phospholipases A2 are summarized. Besides their contribution to the production of proinflammatory lipid mediators, the involvement of these enzymes in key cell responses such as apoptosis or tumor cell metastatic potential is also discussed, taking advantage of transgenic models based on gene invalidation by homologous recombination. The possible role of secretory and cytosolic platelet-activating factor acetyl hydrolases is also briefly mentioned. Finally, the ectopic expression in epididymis of an intestinal phospholipase B opens some novel issues as to the possible function of phospholipases in reproduction.

Animals↗
PubMed1999

Angiotensin I-converting enzyme gene polymorphism in a low-risk European population for coronary artery disease.

An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) has been associated with an increased risk of coronary artery disease (CAD) and myocardial infarction (MI). However, this finding has not been fully investigated in European populations with very low CAD risk. In a case-control study on a population from Southern Europe (Toulouse, France), we evaluated the ACE I/D polymorphism in 405 men, aged 35-65 years, who underwent coronary angiography and in 357 representative control men within the same age range. We also explored associations in the patients between this polymorphism and CAD severity. The ACE genotype was not associated with the presence of either CAD or MI. The ACE genotype was not a marker for angiographically assessed CAD severity. In a sample in one of the European populations with the lowest CAD risk, ACE I/D polymorphism was not associated with an increased risk for CAD or MI and did not influence the extent of CAD.

Adult↗
PubMed1999

Carotid intima-media thickness and coronary heart disease risk factors in a low-risk population.

OBJECTIVE: Coronary heart disease (CHD) risk factors have been consistently related to an increase in carotid intima-media thickness (IMT) in selected populations. However, few studies were population-based and furthermore little attention has been given to the influence of CHD risk factors on IMT in low-risk populations for CHD. DESIGN: We examined the association between carotid IMT and CHD risk factors in a large (n = 1013) and representative sample of middle-aged men and women in one of the European populations with the lowest CHD risk. METHODS: High-resolution B-mode ultrasonography of the common carotid arteries was performed. RESULTS: Age, smoking (not significant in women), body mass index, waist to hip ratio, systolic (SBP) and diastolic blood pressure, alcohol consumption, total and low-density lipoprotein cholesterol, triglycerides, glycaemia, fibrinogen (not significant in women), haematocrit (not significant in men) and insulin (not significant in women) were positively and significantly associated with mean IMT. High-density lipoprotein (HDL) cholesterol (not significant in women) was negatively and significantly associated with mean IMT. In a subsample of 355 men, IMT was not associated with angiotensin I-converting enzyme gene polymorphism. Multivariate analyses showed, in men, independent associations between mean IMT (0.61+/-0.11 mm) and age, pack-years, SBP, HDL cholesterol, alcohol and the interaction between age and alcohol. In women, only age and SBP were independently associated with mean IMT (0.58+/-0.09 mm). CONCLUSIONS: We found thinner IMT than those found in high-risk populations, suggesting that an increased IMT might reflect local atherosclerosis. Protective factors such as HDL cholesterol or regular and moderate alcohol consumption are probably important determinants of the early stages of atherosclerosis in these low-risk populations.

Adult↗
PubMed1998

Ectopic epididymal expression of guinea pig intestinal phospholipase B. Possible role in sperm maturation and activation by limited proteolytic digestion.

Guinea pig intestinal phospholipase B is a calcium-independent phospholipase hydrolyzing sequentially the acyl ester bonds at sn-2 and sn-1 positions of glycerophospholipids, promoting the formation of sn-glycero-3-phosphocholine from phosphatidylcholine. This 140-kDa glycoprotein from the brush border membrane of differentiated enterocytes contributes to lipid digestion as an ectoenzyme. The cDNA coding for guinea pig phospholipase B was revealed to be the homologue of AdRab-B, an mRNA appearing in rabbit upon intestine development. The sequence predicts a polypeptide of 1463 amino acids displaying four homologous repeats, two of them containing the lipase consensus sequence GXSXG. A 5-kilobase transcript was particularly abundant in mature ileal and jejunal enterocytes but was also detected in epididymis, where phospholipase B displayed a higher molecular mass (170 kDa versus 140 kDa in intestine), with no obvious evidence for enzyme activity. Trypsin treatment of phospholipase B immunoprecipitated from epididymal membranes reduced its size to 140 kDa, coinciding with the appearance of a significant phospholipase A2 activity. The same results were obtained in COS cells transfected with phospholipase B cDNA. Since sn-glycero-3-phosphocholine present at high concentrations in seminal plasma mainly stems from epididymis, this suggests a possible role of phospholipase B in male reproduction. This novel localization also unravels a mechanism of phospholipase B activation by limited proteolysis involving either trypsin in the intestinal lumen or a trypsin-like endopeptidase in the male reproductive tract.

Amino Acid Sequence↗
PubMed1998

Regulation of secretory type-II phospholipase A2 and of lysophosphatidic acid synthesis.

Secretory non-pancreatic phospholipase A2 (sPLA2), also called type II-PLA2, is produced in large amounts under inflammatory conditions, thus accumulating in inflammatory fluids. Since the enzyme is virtually inactive on phospholipids from intact cells, we have searched for conditions allowing the action of sPLA2 on membrane phospholipids. Based on an in vitro model, our studies suggest that only those membranes where the transverse distribution of phospholipids has been disturbed offer a convenient surface able to interact with the enzyme, which then achieves significant degradation of all glycerophospholipids. This results in the accumulation of various lysophospholipids such as lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidylserine. However, lysophosphatidic acid (LPA) can also be generated under these conditions involving accumulation of phosphatidic acid in the cytoplasmic leaflet of the membrane, followed by its transfer to the outer monolayer. Since LPA is now considered as a novel phospholipid mediator, this pathway deserves further studies concerning mainly platelets, the main source of LPA identified so far.

Animals↗
PubMed1998

[Prevalence and management of major risk factors in 500 men with stable coronary disease].

Management of major risk factors (smoking, hypercholesterolaemia, hypertension), in the context of secondary prevention, has an impact on recurrence and life expectancy. However, there is a delay between the publication of therapeutic trials and their diffusion within the medical community. The objective of this study was to evaluate the prevalence and management of the main risk factors in a sample of 500 men, with a mean age of 55.1 +/- 7.5 years, presenting with stable coronary artery disease. 11% of subjects had a family history of premature myocardial infarction. Smoking was frequent: 21% of smokers, 60% of ex-smokers. Hypercholesterolaemia (LDL-C > 3.4 mmole/l or treatment) was present in 82% of subjects. Only 45% of treated subjects had an LDL-C < 3.4 mmole/l. Hypertension (systolic blood pressure > or = 140 mmHg or diastolic blood pressure > or = 90 mmHg or treatment) was present in 61% of subjects. Only 33% of treated subjects were controlled. Non-insulin-dependent diabetes mellitus (blood glucose > or = 7.7 mmole/l or treatment) was present in 21% of subjects. Only 43% of treated subjects were controlled. Calculation of the distribution of major risk factors (smoking, pathological obesity, hypercholesterolaemia, hypertension, diabetes) showed that 90% of coronary patients presented at least two risk factors. Overall, the prevalence and management of risk factors in patients with stable coronary artery disease is far from optimal.

Adult↗
PubMed1997

Lysophosphatidic acid as a phospholipid mediator: pathways of synthesis.

From very recent studies, including molecular cloning of cDNA coding for membrane receptors, lysophosphatidic acid (LPA) reached the status of a novel phospholipid mediator with various biological activities. Another strong argument supporting this view was the discovery that LPA is secreted from activated platelets, resulting in its appearance in serum upon blood coagulation. The metabolic pathways as well as the enzymes responsible for LPA production are poorly characterized. However, a survey of literature data indicates some interesting issues which might be used as the basis for further molecular characterization of phospholipases A able to degrade phosphatidic acid.

Animals↗