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Pierre Moulin

Publications and source records attributed to Pierre Moulin.

At least 19 recordsLinked to original sources
PubMed2007

Assessment of diffusion-weighted MR imaging in liver fibrosis.

PURPOSE: To assess whether hepatic fibrosis is associated with a restriction in the diffusion of water that can be analyzed with diffusion-weighted MR imaging (DWI) of the liver. MATERIALS AND METHODS: DWI was performed in 10 normal rats and 15 rats with liver fibrosis. Echo-planar DWI was performed in the living rats at 1.5 T and repeated immediately after the animals were killed. Afterwards the livers were explanted, fixed in Bouin solution, and imaged with a DW spin-echo sequence at 4.7 T. Fibrosis was quantified by densitometry on Sirius red-stained histological sections. RESULTS: In living rats the apparent diffusion coefficient (ADC) decreased with the severity of liver fibrosis (controls: 1535 +/- 294 mm(2)/second; CCl(4) (5 weeks) 1129 +/- 273 mm(2)/second; CCl(4) (9 weeks): 943 +/- 132 mm(2)/second; P = 0.002). An inverse correlation between ADC and liver fibrosis volume density was observed (r = -0.712, P < 0.001). In contrast, these findings were not observed in the rats after they were killed or in the fixated livers. CONCLUSION: Decreased ADC correlated with increased liver fibrosis in living rats, but not after death. These results suggest that restricted water diffusion cannot be assessed by DWI in liver fibrosis. Other factors, such as a decrease of perfusion, may explain the decrease of the hepatic ADC measured in vivo in rats with liver fibrosis.

Analysis of Variance↗
PubMed2006

Solid and pseudopapillary tumor of the pancreas--review and new insights into pathogenesis.

Solid pseudopapillary tumors (SPT) of the pancreas are rare neoplasms that occur mostly in young women. Despite of a low malignant potential, 10% to 15% of the cases have aggressive behavior with metastatic dissemination possibly leading to death. To date, no pathological factor can reliably predict the outcome of these tumours. Galectin-3, a major actor in the carcinogenesis of pancreatic ductal adenocarcinoma, has not been investigated in SPT. The presence of progesterone receptors is frequently reported in SPT, whereas that of estrogen receptor (ER) is unclear. We studied 5 cases of SPT consisting of 4 pancreatic tumors and 1 metastatic case. The morphological distinctive feature of metastatic nodules was the presence of polygonal or spindle cells with pleiomorphic nuclei and high mitotic count exhibiting a diffuse, infiltrative growth pattern. We found a strong expression of galectin-3 in all SPTs, whereas, interestingly, it was lower in metastatic nodules. Conversely, no galectin-3 expression was found in normal pancreatic endocrine cells or in neuroendocrine tumors. We suggest therefore that galectin-3 is a useful marker to distinguish SPT from neuroendocrine tumor, and also indicator of behavior because its low expression is associated with metastatic spreading. Moreover, the presence of galectin-3 in both SPT and pancreatic ducts rises the hypothesis of a posible ductal origin of these tumors. Specific antibodies for anti-ERalpha and anti-ERbeta demonstrated a strong expression of ERbeta whereas ERalpha was not detected. In conclusion, the present study brings the first evidence of the involvement of galectin-3 in SPT but also brought up clues which allowed to reconcile previously conflicting results on the presence of ER.

Adenocarcinoma, Papillary↗
PubMed2006

Asymptotic global confidence regions for 3-D parametric shape estimation in inverse problems.

This paper derives fundamental performance bounds for statistical estimation of parametric surfaces embedded in R3. Unlike conventional pixel-based image reconstruction approaches, our problem is reconstruction of the shape of binary or homogeneous objects. The fundamental uncertainty of such estimation problems can be represented by global confidenceregions, which facilitate geometric inference and optimization ofthe imaging system. Compared to our previous work on global confidence region analysis for curves [two-dimensional (2-D) shapes], computation of the probability that the entire surface estimate lies within the confidence region is more challenging because a surface estimate is an inhomogeneous random field continuously indexed by a 2-D variable. We derive an asymptotic lower bound to this probability by relating it to the exceedence probability of a higher dimensional Gaussian random field, which can, in turn, be evaluated using the tube formula due to Sun. Simulation results demonstrate the tightness of the resulting bound and the usefulness of the three-dimensional global confidence region approach.

Algorithms↗
PubMed2005

Long-term evolution of endocrine disorders and effect of GH therapy in 35 patients with pituitary stalk interruption syndrome.

We report long-term evolution of endocrine functions and the results of GH treatment in 35 patients (26 male and 9 female) with pituitary stalk interruption. At diagnosis, mean chronological age was 4.8 +/- 2.7 years, mean SDS for height -3.1 +/- 0.8 with a bone age retardation of 2.3 +/- 1.3 years and a mean SDS for growth velocity of -0.5 +/- 1.1; 80% presented complete GH deficiency (GHD) and 20% partial GHD; thyroid deficiency was present in 47.1% of children with complete GHD but absent in all partial GHD. Diagnosis was made during the first months of life in only 2 patients while 23% presented with severe neonatal distress; neonatal signs were only observed in the group with pituitary height below 2 mm (45.7% of patients). GHD was isolated in 40.6% of patients below 10 years while multiple hormone deficiencies was consistent at completion of growth in all patients. Height gain was significantly higher in patients who started GH treatment before 4 years (p = 0.002). GH treatment is very effective: in 13 patients, final height was -0.4 +/- 1.0, total height gain 3.2 +/- 1.2 and distance to target height -0.3 +/- 1.6 SDS.

Adolescent↗
PubMed2005

Human endometrial epithelial cells (EEC) constitutively express more intercellular adhesion molecule (ICAM)-1 than endometrial stromal cells (ESC) in culture.

PROBLEM: Intercellular adhesion molecule-1 (ICAM-1) is thought to play an important role in pathophysiological processes in endometrial tissue. The aim of this study was to quantify and compare the expression of ICAM-1 mRNA and protein in cultured endometrial epithelial cells (EEC) versus endometrial stromal cells (ESC). METHOD OF STUDY: EEC and ESC were isolated from human endometrium and cultured. At confluency, ICAM-1 mRNA was measured by real-time reverse transcriptase-polymerase chain reaction, the membrane-bound form (mICAM-1) by immunocytodensitometry, and the soluble form (sICAM-1) by enzyme-linked immunosorbent assay. RESULTS: At the transcriptional level, we observed a 1.7-fold increase in ICAM-1 expression in EEC versus ESC. mICAM-1 immunostaining in EEC [cell-relative membrane-bound signal-specific optical density (CR-M-SOD): 0.056 +/- 0.05] was stronger (P < 0.05) than in ESC (CR-M-SOD: 0.009 +/- 0.07). EEC were found to secrete more (P < 0.01) sICAM-1 ([sICAM-1] = 15.59 +/- 2.96 ng/mL) than ESC ([sICAM-1] = 5.14 +/- 2.61 ng/mL). CONCLUSIONS: Cultured EEC constitutively express significantly more ICAM-1 mRNA and protein than ESC.

Adult↗
PubMed2004

Cardiomyocyte-restricted overexpression of endothelial nitric oxide synthase (NOS3) attenuates beta-adrenergic stimulation and reinforces vagal inhibition of cardiac contraction.

BACKGROUND: In the heart, nitric oxide synthases (NOS) modulate cardiac contraction in an isoform-specific manner, which is critically dependent on their cellular and subcellular localization. Defective NO production by NOS3 (endothelial NOS [eNOS]) in the failing heart may precipitate cardiac failure, which could be reversed by overexpression of NOS3 in the myocardium. METHODS AND RESULTS: We studied the influence of NOS3 in relation to its subcellular localization on the function of cardiomyocytes isolated from transgenic mice overexpressing NOS3 under the alpha-myosin heavy chain promoter (NOS3-TG). Immunoblot analysis demonstrated moderate (5-fold) NOS3 overexpression in cardiomyocytes from NOS3-TG heterozygotes. Caveolar localization of transgenic eNOS was demonstrated by immunofluorescence, coimmunoprecipitation with caveolin-3, sucrose gradient fractionation, and immunogold staining revealed by electron microscopy. Compared with wild-type littermate, contractility of NOS3-TG cardiomyocytes analyzed by videomicroscopy revealed a lower incidence of spontaneous arrhythmic contractions (n=32, P<0.001); an attenuation of the beta-adrenergic positive inotropic response (isoproterenol, 10(-7) mol/L: 62.1+/-7.8% versus 90.8+/-8.0% of maximum Ca2+ response; n=10 to 17; P<0.05); a potentiation of the muscarinic negative chronotropic response (carbamylcholine, 3.10(-8) mol/L: -63.9+/-14% versus -27.7+/-5.6% of basal rate; n=8 to 10; P<0.05), confirmed by telemetry in vivo; and an attenuation of the accentuated antagonism of beta-adrenergically stimulated contraction (-14.6+/-1.5% versus -3.5+/-1.5; n=7 to 11; P<0.05). Cardiomyocyte NOS inhibition reversed all 4 effects (P<0.05). CONCLUSIONS: Moderate overexpression of NOS3, targeted to caveolae in murine cardiomyocytes, potentiates the postsynaptic muscarinic response and attenuates the effect of high concentrations of catecholamines. Cardiomyocyte NOS3 may represent a promising therapeutic target to restore the sympathovagal balance and protect the heart against arrhythmia.

Adrenergic beta-Agonists↗
PubMed2004

Hyperghrelinemia is a common feature of Prader-Willi syndrome and pituitary stalk interruption: a pathophysiological hypothesis.

BACKGROUND: Elevated plasma ghrelin levels have recently been reported in adults and children with Prader-Willi syndrome (PWS). The aim of the study is to investigate the relationship between obesity, growth hormone (GH) deficiency (GHD) and ghrelinemia in PWS and to examine whether hyperghrelinemia is specific to PWS. METHODS: We measured fasting ghrelinemia in children with PWS, idiopathic GHD (iGHD), obese children, controls and in 6 children presenting another congenital syndrome associated with GHD: pituitary stalk interruption (PSI). RESULTS: Children with PWS exhibited significantly higher ghrelin levels (995 pg/ml (801/1,099, median 1st/3rd quartile)) than iGHD (517 pg/ml (392/775)), obese (396 pg/ml (145/610)) and control (605 ng/ml (413/753)) children. Similar to PWS hyperghrelinemia was found in PSI children (1,029 pg/ml (705/1,151)), and was not modified by GH treatment. CONCLUSION: We conclude that hyperghrelinemia in PWS and PSI is not related to GH secretion. We hypothesize that a major site of ghrelin action is at the hypothalamic level and that a 'ghrelin resistance' syndrome may be present in these patients, primarily due to a hypothalamic defect. Combined alterations such as impaired serotonin receptor regulation associated with abnormal ghrelin responsiveness are probably responsible for obesity in PWS.

Aging↗
PubMed2004

Unusual metastatic features in a patient with concomitant malignant orbital melanoma and prostate carcinoma.

A 73-year-old man with a history of malignant orbital melanoma and prostate carcinoma was admitted for progressive visual disturbance. Brain magnetic resonance imaging showed a suprasellar enhancing nodular lesion with major impingement on the anterior optical ways and sellar invasion. The extensive imaging work-up could not demonstrate with certainty its origin. Surprisingly, the transphenoidal biopsy of this patient revealed a prostate cancer metastasis outlining the importance of a histopathological diagnosis of cerebral metastases in patients with multiple malignancies when there is a doubt about the nature of the lesion.

Adenocarcinoma↗
PubMed2004

Design and statistical analysis of a hash-aided image watermarking system.

This paper develops a joint hashing/watermarking scheme in which a short hash of the host signal is available to a detector. Potential applications include content tracking on public networks and forensic identification. The host data into which the watermark is embedded are selected from a secret subset of the full-frame discrete cosine transform of an image, and the watermark is inserted through multiplicative embedding. The hash is a binary version of selected original image coefficients. We propose a maximum likelihood watermark detector based on a statistical image model. The availability of a hash as side information to the detector modifies the posterior distribution of the marked coefficients. We derive Chernoff bounds on the receiver operating characteristic performance of the detector. We show that host-signal interference can be rejected if the hash function is suitably designed. The relative difficulty of an eavesdropper's detection problem is also determined; the eavesdropper does not know the secret key used. Monte Carlo simulations are performed using photographic test images. Finally, various attacks on the watermarked image are introduced to study the robustness of the derived detectors. The joint hashing/watermarking scheme outperforms the traditional "hashless" watermarking technique.

Algorithms↗
PubMed2003

Aristolochic acid nephropathy and the peritoneum: Functional, structural, and molecular studies.

BACKGROUND: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy linked to the exposure to aristolochic acid (AA) and characterized by extensive fibrosis and urothelial atypia. Although the fibrotic process has been documented in extrarenal tissues, the involvement of the peritoneum, as well as the efficacy of peritoneal dialysis in AAN patients, remain uncertain. METHODS: The structure of the peritoneal membrane and the expression of basic fibroblast growth factor (bFGF), collagen type III, endothelial nitric oxide synthase (eNOS), and aquaporin-1 (AQP1) were investigated in peritoneal biopsies from an index AAN patient, four other AAN patients, four regular peritoneal dialysis patients, and two controls. Similar methods were used to investigate a rabbit model of AAN after intraperitoneal exposure to high-dose AA. AA-DNA adducts were screened by 32P-postlabeling analysis. RESULTS: The AAN patients had renal failure, renal fibrosis, and urothelial atypia. The peritoneum of AAN patients had a normal structure, lacked cellular atypia, and, in comparison with regular peritoneal dialysis patients and controls, did not show abnormal regulation of fibrotic and endothelial markers. Furthermore, specific AA-DNA adducts were not identified in the peritoneum of AAN patients. In contrast, AA-DNA adducts were detected in peritoneal and kidney tissues of all exposed rabbits, and one of them developed a malignant mesothelioma. CONCLUSION: These data demonstrate the lack of fibrotic and vascular alterations and the absence of cellular atypia in the peritoneum from AAN patients. Thus, peritoneal dialysis should not be discouraged in these patients. Nevertheless, studies in a rabbit model of high-dose AA exposure may suggest a potential risk of peritoneal malignancy.

Aged↗
PubMed2003

Altered polarity and expression of H+-ATPase without ultrastructural changes in kidneys of Dent's disease patients.

BACKGROUND: Dent's disease is a proximal tubule (PT) disorder characterized by low-molecular-weight proteinuria (LWMP) that may be associated with hypercalciuria, nephrocalcinosis, and renal failure. It is caused by inactivating mutations of the renal chloride channel ClC-5, which colocalizes with the vacuolar H+-ATPase in PT cells and alpha-type intercalated cells. Examinations of knockout mice have established the role of ClC-5 in PT endocytosis, but the consequences of ClC-5 mutations on the polarity of H+-ATPase and other plasma membrane proteins remain unknown. METHODS: We have studied renal biopsies from eight patients with Dent's disease, due to inactivating ClC-5 mutations, by light and electron microscopy, and by immunohistochemical staining. All patients exhibited LMWP, and renal function ranged from normal to end-stage renal failure. RESULTS: Light microscopy revealed either normal renal architecture or glomerulosclerosis, tubular dedifferentiation and atrophy, and mild interstitial fibrosis. Focal, hyaline casts, sometimes calcified, were identified at all stages. Electron microscopy did not reveal any ultrastructural abnormalities in PT cells, and the endocytic apparatus was apparently normal. However, immunohistochemical studies demonstrated a consistent inversion of H+-ATPase polarity in PT cells to a basolateral distribution contrasting with its apical location in the normal kidney. This inversion of polarity was specific for H+-ATPase and did not affect distribution of aminopeptidase, megalin, and Na+/K+-ATPase. Furthermore, apical H+-ATPase expression was absent in alpha-type intercalated cells. CONCLUSION: ClC-5 mutations are associated with modifications in the polarity and expression of H+-ATPase, but not ultrastructural alterations in PT cells. These findings help further understanding of the role of ClC-5 and the pathophysiology of Dent's disease.

Adolescent↗
PubMed2003

Mice that lack endothelial nitric oxide synthase are protected against functional and structural modifications induced by acute peritonitis.

Pharmacologic studies suggest that the release of nitric oxide (NO) by endothelial NO synthase (eNOS) contributes to functional alterations of the peritoneal membrane (PM) induced by acute peritonitis. In this study, peritoneal permeability parameters in a mouse model of peritoneal dialysis were characterized, and the effects of eNOS deletion on the PM structure and permeability at baseline and after catheter-induced bacterial peritonitis were examined. Exposure of C57BL/6 mice to standard dialysate yielded a transport of urea and glucose, a sodium sieving, and a net ultrafiltration that were remarkably similar to the values obtained in rats. In comparison with controls, mice with catheter-induced peritonitis were characterized by structural changes in the PM (mononuclear cells infiltrate, vascular proliferation), upregulation of endothelial and inducible NOS, increased permeability for urea and glucose, decreased ultrafiltration, and increased protein loss in the dialysate. Comparison of eNOS wild-type and knockout mice revealed that the permeability modifications and structural changes induced by acute peritonitis were significantly reversed in eNOS knockout mice, resulting in a net increase in ultrafiltration. In contrast, the deletion of eNOS in mouse peritoneum was not reflected by permeability modifications or structural changes at baseline. These results are the first to take advantage of a knockout mouse model to demonstrate directly the crucial importance of eNOS in the permeability and structural modifications caused by acute peritonitis. The characterization of this mouse model suggests that genetically modified mice represent useful tools to investigate the molecular bases of the peritoneal changes during peritoneal dialysis.

Acute Disease↗
PubMed2003

Adolescents with partial growth hormone (GH) deficiency develop alterations of body composition after GH discontinuation and require follow-up.

It is now a consensus to resume GH treatment in adolescents with severe GH deficiency (GHD) at retesting to prevent the occurrence of adult GHD syndrome. However, we do not have any data on the follow-up of adolescents with nonsevere GHD at completion of treatment. This report presents preliminary data from a 1-yr prospective study that includes the first 91 patients retested. Anthropometric data, IGF-I and IGF binding protein-3 levels, glycemia and insulinemia, lipid profile, and body composition using dual x-ray absorptiometry and abdominal computed tomography scan were recorded at completion of GH treatment and 1 yr later. Body composition was significantly different at both evaluations, with increased total body fat and decreased lean body mass in the partial GHD group vs. the normal group. Moreover, these alterations worsened after 1 yr without GH in the partial GHD group, whereas there were no modifications in the normal group. We did not find any metabolic alterations such as elevated triglyceride, total cholesterol, or insulin levels. Adolescents with reconfirmed partial GHD exhibit alterations in body composition after 1 yr without GH, whereas those retested normal do not. These changes are similar to those described in severe GHD, although less marked, and justify a precise follow-up.

Abdomen↗
PubMed2003

The focal form of persistent hyperinsulinemic hypoglycemia of infancy: morphological and molecular studies show structural and functional differences with insulinoma.

Paternal mutation of ATP-sensitive K(+) (K(ATP)) channel genes and loss of heterozygosity (LOH) of the 11p15 region including the maternal alleles of ABCC8, IGF2, and CDKN1C characterize the focal form of persistent hyperinsulinemic hypoglycemia of infancy (FoPHHI). We aimed to understand the actual nature of FoPHHI in comparison with insulinoma. In FoPHHI, the lesion consists in clusters of beta-cells surrounded by non-beta-cells. Compared with adjacent islets, proinsulin mRNA is similar and proinsulin production higher (P < or = 0.02), indicating regulation at a translational level, with slightly lower insulin stock and lower ABCC8 peptide labeling (P<0.05). Insulinomas, composed of beta-cell nests or cords, have similar proinsulin mRNA compared with adjacent islets, highly variable proinsulin production, lower insulin stock (P < or = 0.02), and higher ABCC8 peptide labeling (P<0.05). Proinsulin mRNA is lower than in FoPHHI (P<0.001). Islets adjacent to FoPHHI appear to be resting, in contrast to those adjacent to insulinomas, evidencing intrapancreatic regulation of islet beta-cell activity. IGF2 peptide is present inside and outside both lesions, but IGF2 mRNA is restricted to the lesions. The 11p15 LOH and absence of CDKN1C peptide staining are demonstrated in all FoPHHI but also in three of eight insulinomas. Despite some molecular similarities, FoPHHI is thus fundamentally different from insulinoma.

ATP-Binding Cassette Transporters↗
PubMed2002

Experimental diabetes induces functional and structural changes in the peritoneum.

BACKGROUND: Peritoneal dialysis (PD) is an established renal replacement therapy in diabetic patients, but the influence of diabetes on the peritoneal membrane (PM) remains debated. We have used functional, biochemical and molecular studies in vivo and in vitro to substantiate the changes induced by diabetes and hyperglycemia in the PM. METHODS: Peritoneal equilibration tests were performed 2, 4, and 6 weeks after induction of diabetes with streptozotocin (STZ) in rats. Morphological analyses, determination of nitric oxide synthase (NOS) activities, and expression studies for NOS isoforms and advanced glycation end products (AGE) were performed in parallel. Additional studies were conducted in diabetic rats treated with insulin, non-diabetic rats fed with urea, and cultured bovine aortic endothelial cells (BAEC). RESULTS: In comparison with controls, diabetic rats were characterized by: increased permeability for small solutes and decreased sodium sieving; capillary proliferation; increased endothelial NOS (eNOS) and AGE immunoreactivity; up-regulation of eNOS and down-regulation of neuronal NOS; and increased NOS activity in the PM. The changes, which culminated at week 6, were prevented by chronic insulin treatment in diabetic rats. In contrast to hyperglycemia, hyperosmolality alone did not induce functional or structural changes in the PM. Studies in BAEC showed that high glucose incubation led to increased activity and expression of eNOS, a prerequisite for vascular proliferation. CONCLUSIONS: These data demonstrate that chronic hyperglycemia is associated with functional and structural changes in the peritoneum that parallel with selective regulation of NOS isoforms and AGE deposits. The alterations are prevented by insulin treatment, which suggests that adequate control of diabetes can preserve PM integrity in diabetic patients prior to PD.

Animals↗
PubMed2001

Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications in the peritoneum.

Advanced glycation end products (AGE), growth factors, and nitric oxide contribute to alterations of the peritoneum during peritoneal dialysis (PD). These mediators are also involved in chronic uremia, a condition associated with increased permeability of serosal membranes. It is unknown whether chronic uremia per se modifies the peritoneum before PD initiation. A rat model of subtotal nephrectomy was used to measure peritoneal permeability after 3, 6, and 9 wk, in parallel with peritoneal nitric oxide synthase (NOS) isoform expression and activity and structural changes. Uremic rats were characterized by a higher peritoneal permeability for small solutes and an increased NOS activity due to the up-regulation of endothelial and neuronal NOS. The permeability changes and increased NOS activities correlated with the degree of renal failure. Focal areas of vascular proliferation and fibrosis were detected in uremic rats, in relation with a transient up-regulation of vascular endothelial growth factor and basic fibroblast growth factor, as well as vascular deposits of the AGE carboxymethyllysine and pentosidine. Correction of anemia with erythropoietin did not prevent the permeability or structural changes in uremic rats. Thus, in this rat model, uremia induces permeability and structural changes in the peritoneum, in parallel with AGE deposits and up-regulation of specific NOS isoforms and growth factors. These data suggest an independent contribution of uremia in the peritoneal changes during PD and offer a paradigm to better understand the modifications of serosal membranes in uremia.

Anemia↗