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G Bellon

Publications and source records attributed to G Bellon.

At least 55 records · Page 3Linked to original sources
PubMed1999

Transforming growth factor beta-1 up-regulates clusterin synthesis in thyroid epithelial cells.

Porcine epithelial cells in primary culture seeded on plastic substratum form a monolayer containing pseudo-vesicles. When cultured in the presence of thyreotropin (TSH) thyrocytes adopted a follicular-like structure and formed clusters. Transforming growth factor beta-1 (TGFbeta1) induced a rapid spreading of the TSH-treated cells only. At the same time, TGFbeta1 enhanced clusterin protein and mRNA expression. The increase of clusterin synthesis was proportional to the TGFbeta1 concentration in the culture medium. Tunicamycin abolished the up-regulation of whole clusterin synthesis and morphological changes. The activator protein-1 binding site partly directed the TGFbeta1-stimulated clusterin expression. Phorbol ester caused rapid spreading of the cells with disappearance of vesicular and follicular structures. It decreased clusterin mRNA and protein expression, but increased Mr 45, 000 protein secretion in both TSH-treated and nontreated cells. Up-regulation of clusterin expression may be a marker of TGFbeta-mediated thyrocyte dedifferentiation.

Animals↗
PubMed1999

Biochemical alterations of uterine leiomyoma extracellular matrix in type IV Ehlers-Danlos syndrome.

Collagens and glycosaminoglycans were assessed in 6 leiomyomas from otherwise healthy ("control") patients and 1 leiomyoma from a patient with type IV Ehlers-Danlos syndrome. The type IV Ehlers-Danlos leiomyoma contained less type III collagen and dermatan sulfate than control leiomyomas. This might contribute to the formation of a defective collagen network in type IV Ehlers-Danlos syndrome.

Adult↗
PubMed1999

Sclerosing cholangitis in adults with cystic fibrosis: a magnetic resonance cholangiographic prospective study.

BACKGROUND/AIMS: Liver disease is a leading cause of morbidity in adult patients with cystic fibrosis. Diagnosis of limited liver involvement in asymptomatic patients is important since a safe and effective treatment with ursodeoxycholic acid can be used. We carried out a prospective open study to describe the intrahepatic biliary lesions using magnetic resonance cholangiography. METHODS: Twenty-seven adult patients with cystic fibrosis were prospectively enrolled, whatever their hepatobiliary status. All patients underwent liver function tests, ultrasonography and magnetic resonance cholangiography. Magnetic resonance cholangiograms were acquired on a Philips 1.5 Tesla unit using a 3D TSE MR sequence. Acquisition parameters (120 slices, 1.6 mm thickness, interslice overlap 0.8 mm) were followed by MIP reconstruction in two orthogonal planes. Magnetic resonance cholangiography images were assessed for the presence of stenosis, dilatations and rigidity corresponding to current criteria of cholangitis. Among the 27 cystic fibrosis patients, 18 (Group I) fulfilled none of the clinical, biological or ultrasonographic criteria of liver disease; the remaining nine (Group II) fulfilled the criteria for liver disease. In every patient, current causes of secondary sclerosing cholangitis had been excluded. RESULTS: All the Group II patients had abnormal magnetic resonance cholangiograms with features resembling those of primary sclerosing cholangitis in five, and simple biliary lesions in four. Nine Group I patients had abnormal magnetic resonance cholangiograms with primary sclerosing cholangitis-like lesions in five and simple biliary lesions in four. Magnetic resonance cholangiography anomalies were always dilatations, either isolated or associated with strictures and rigidity, both resembling those seen in cholangitis. They were seen in all the patients with known liver disease and in half the patients without evidence of liver disease. CONCLUSION: This study confirms the high frequency of intrahepatic biliary abnormalities in CF patients, which is probably underestimated by clinical, biological and ultrasonographic evaluation. The magnetic resonance cholangiography technique could be useful to detect early intrahepatic biliary tract involvement in cystic fibrosis patients.

Adult↗
PubMed1999

Immunohistochemical study of thrombospondin and its receptors alpha root of beta 3 and CD36 in normal thyroid and in thyroid tumours.

AIM: To describe the pattern of distribution of thrombospondin (TSP1) and its receptors, alpha root of beta 3 integrin and CD36, in normal human thyroid tissue and to compare their expression in different benign and malignant thyroid conditions. METHODS: Immunohistochemistry was used to study TSP1 and its receptors in 40 surgical thyroidectomy specimens (normal parenchyma, 7; follicular adenoma, 4; multinodular goitre, 13; papillary carcinoma, 6; follicular carcinoma, 8; anaplastic carcinoma, 2). RESULTS: In the normal thyroid parenchyma, there was weak expression of TSP1 limited to the vessels with no staining of the extracellular matrix. In goitres, the expression of TSP1 was more pronounced in areas of fibrosis, with staining of alpha root of beta 3 on thyrocytes located in the vicinity. In thyroid adenomas, expression of TSP1 was slightly enhanced compared with normal tissue, located in the basement membrane of vessels. In papillary carcinomas, TSP1 was abundant in the desmoplastic stroma with a cytoplasmic distribution of alpha root of beta 3 integrin in thyrocytes. In follicular carcinomas, TSP1 was less abundant in the extracellular matrix, limited to the vessels of the stroma with a weaker expression of alpha root of beta 3 on thyrocytes than in papillary carcinomas. In anaplastic carcinomas, TSP1 was only present in the numerous capillaries of the stroma, with a marked positivity for alpha root of beta 3 in one case. No immunostaining of thyrocytes is observed with CD36. CONCLUSIONS: These results suggest the importance of the interaction between alpha root of beta 3 integrin and TSP1 during remodelling of the matrix in fibrous goitres with areas of early sclerosis comparable with wound healing. In papillary carcinomas, the overexpression of TSP1 restricted to the stroma suggests protective effects against tumour progression.

CD36 Antigens↗
PubMed1999

Fas and Fas ligand expression in cystic fibrosis airway epithelium.

BACKGROUND: Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and defective expression of CFTR protein in epithelial cells. The main cause of mortality in CF is linked to chronic inflammatory and infectious airway processes. Recent studies have suggested perturbations in the apoptotic process in CF cell lines and enterocytes. A study was undertaken to investigate the expression of Fas and Fas ligand (FasL) in CF bronchial epithelium and CF tracheal cell lines. METHODS: Immunohistochemical staining for Fas (alkaline phosphatase anti-alkaline phosphatase) and FasL (immunoperoxidase) was performed in eight CF bronchial epithelial samples and four controls and immunohistochemical DNA fragmentation (TUNEL) was carried out in four CF patients and four controls. Immunofluorescence staining and flow cytometric analysis of Fas and FasL expression was performed in two human tracheal epithelial cell lines (HTEC) with normal and CF genotype. The dosage of serum soluble FasL was examined in 21 patients with CF and 14 healthy volunteers. RESULTS: FasL expression was markedly increased in patients with CF in both the ciliated and submucosal glandular bronchial epithelium compared with controls; Fas was similarly expressed in bronchial samples from controls and CF patients in both the ciliated epithelium and submucosal glands. High levels of DNA fragmentation were observed in CF but with some epithelial cell alterations. Serum concentrations of soluble FasL were frequently undetectable in patients with CF. In vitro, HTEC expressed Fas and FasL in both genotypes. A higher mean fluorescence intensity for FasL expression was noted in CF genotype HTEC with median (range) for six experiments of 74 (25-101) for CF cells and 42 (21-70) for non-CF cells. CONCLUSION: Fas/FasL interaction is probably implicated in the human CF airway apoptotic pathway. The mechanisms of induction of FasL expression and its role in inducing tissue damage or remodelling or in controlling local inflammatory cell apoptosis remain to be determined.

Adolescent↗
PubMed1999

Influence of transforming growth factor beta1 (TGF-beta1) on the behaviour of porcine thyroid epithelial cells in primary culture through thrombospondin-1 synthesis.

Transforming growth factor beta1 (TGF-beta1) is a secreted polypeptide that is thought to play a major role in the regulation of folliculogenesis and differentiation of thyroid cells. On porcine thyroid follicular cells cultured on plastic substratum, TGF-beta1, in a concentration-dependent way, promoted the disruption of follicles, cell spreading, migration and confluency by a mechanism that did not involve cell proliferation. TGF-beta1 strongly activated the production of thrombospondin-1 and (alpha)vbeta3 integrin in a concentration-dependent manner whereas the expression of thyroglobulin was unaffected. Anisomycin, an inhibitor of protein synthesis, inhibited the effect of TGF-beta1 on cell organization. Thrombospondin-1 reproduced the effect of TGF-beta1. In the presence of thrombospondin-1 cells did not organize in follicle-like structures but, in contrast, spreaded and reached confluency independently of cell proliferation. This effect is suppressed by an RGD-containing peptide. The adhesive properties of thrombospondin-1 for thyroid cells were shown to be mediated by both the amino-terminal heparin-binding domain and the RGD domain of thrombospondin-1. Adhesion was shown to involve (alpha)vbeta3 integrin. The results show that TGF-beta1 exerted an influence upon function and behaviour of follicle cells partly mediated by the synthesis of thrombospondin-1 and of its receptor (alpha)vbeta3 integrin.

Animals↗
PubMed1999

Lipid peroxidation and antioxidant defenses in cystic fibrosis patients.

Lipid peroxidation biomarkers and antioxidant status were measured in 76 cystic fibrosis (CF) patients and compared to 40 control subjects. Univariate and multivariate statistics were performed in this study. Results showed that indicators of lipid peroxidation were higher in CF patients than in controls; thiobarbituric acid reactants and autoantibodies against oxidized low-density lipoproteins were significantly increased in CF patients. Red blood cells and whole blood glutathione peroxidase activities were lower in CF patients than in controls. No difference in red blood cell superoxide dismutase activity was observed. Measured concentration of glutathione peroxidase in plasma showed a higher mean value of this protein in CF patients than in controls. Retinol, alpha-tocopherol and beta-carotene concentrations were all reduced in CF patients as compared to controls; this was particularly pronounced for beta-carotene. The decreased alpha-tocopherol concentration was associated with higher percent hemolysis in CF patients. The results of this study indicate that both lipid peroxidation biomarkers and antioxidant status were disturbed in CF patients, despite medical assistance. Measures of oxidative stress parameters, such as thiobarbituric acid reactants, glutathione peroxidase, and beta-carotene concentrations can be considered as significant indicators to discriminate CF patients and control subjects.

Adolescent↗
PubMed1998

Biochemical assessment of the nutritional status of cystic fibrosis patients treated with pancreatic enzyme extracts.

We examined the protein and fat nutritional status of 65 cystic fibrosis patients aged 4-26 y (x +/- SD: 11.2 +/- 5.6 y). Patients were treated with pancreatic enzyme extracts to improve nutrient absorption; in addition, most patients were supplemented with vitamins A and E. Results were compared with those in a control group of 39 subjects aged 5-29 y (x: 14.3 +/- 5.6 y) with no digestive diseases or nutritional deficiencies. Protein determination showed low albumin concentrations in 42% of the cystic fibrosis patients and decreased blood concentrations of retinol binding protein in 12% of the patients. Lipoprotein components were characterized by decreased cholesterol concentrations in 25% of the cystic fibrosis group. Also, mean concentrations of apolipoprotein A-I were significantly lower in the cystic fibrosis group than in control subjects. The results of fatty acid status, expressed in relative (%) and absolute (mg/L) values, showed concentrations of essential fatty acids, represented by linoleic and arachidonic acids, to be significantly decreased in cystic fibrosis patients; this decrease was markedly significant for fatty acid status expressed in absolute values, especially in the cholesteryl ester subfraction. Serum retinol and alpha-tocopherol concentrations were lowered by 8% and 46% in cystic fibrosis patients and control subjects, respectively: retinol, 1.80 +/- 0.50 and 2.37 +/- 0.60 micromol/L, P < 0.001, and alpha-tocopherol, 18.1 +/- 8.7 and 25.7 +/- 5.0 micromol/L, P < 0.001. In conclusion, despite regular treatment with pancreatic enzyme replacements, neither protein nor fat malnutrition in cystic fibrosis patients was completely corrected.

Adolescent↗
PubMed1998

Subepithelial fibrosis and degradation of the bronchial extracellular matrix in cystic fibrosis.

Cystic fibrosis is a genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator gene. Chronic inflammation and proteolysis lead to progressive damage of the bronchial wall. Extracellular matrix determines the structural organization and the mechanical properties of lung airways. It was thus examined in nine patients with cystic fibrosis (six bronchial biopsies and three lobectomies) in order to assess its level of alteration. The submucosal changes in matrix protein distribution were analyzed by immunochemistry and electron microscopy: the subepithelial basal lamina was thinned; an acellular collagen fiber layer composed of interstitial collagens (types I and III) subtended by tenascin and devoid of elastin-associated microfibrils was deposited beneath the basal lamina; this dense fibrous deposit generally formed a thick layer and could extend into the bronchial wall; the bronchial elastic framework lost arborescent distribution and appeared slender, packed, or lacunar; ultrastructural observation gave evidence for elastic and collagenic fiber lysis. Proteolytic activity is probably the major cause of matrix degradation. Fibrosis appears as a repair process rather than as an active fibrogenesis. The reversibility of extracellular matrix alterations is an important challenge and various interventions such as anti-inflammatory treatments can be targeted to halt or reverse this degradation process.

Adolescent↗
PubMed1998

Localization of Staphylococcus aureus in infected airways of patients with cystic fibrosis and in a cell culture model of S. aureus adherence.

Staphylococcus aureus causes chronic respiratory tract infections in patients with cystic fibrosis (CF). Using immunofluorescence and scanning and transmission electron microscopy we located S. aureus in lung specimens of three infected CF patients, in a nasal polyp of one CF patient, and in a suspension cell culture system of primary nasal epithelial cells in vitro. Very little of S. aureus was attached to the lung epithelium, whereas abundant S. aureus was detectable in the mucus of obstructed airways. Similarly, S. aureus adhered to components of secreted mucus on primary nasal epithelial cells of CF patients and healthy control subjects, grown as cell balls in vitro (bacteria/cell +/- SD: CF: 21.9 +/- 1.5; controls: 22. 0 +/- 5.8). Mucus depletion of cell balls prior to incubation with S. aureus resulted in a significantly reduced binding (bacteria/cell +/- SD: CF: 4.2 +/- 0.3; P < 0.001; controls: 5.0 +/- 1.3; P < 0. 007). Binding of S. aureus to cell balls from CF patients or control subjects did not differ significantly. When cell balls were treated with human neutrophil elastase, hypersecretion caused removal of S. aureus from cell-associated mucus. The results suggest that S. aureus adheres primarily to mucus components of the respiratory epithelium and that significant differences do not exist in binding of S. aureus to CF or non-CF cells.

Adolescent↗
PubMed1997

Aerosol administration of a recombinant adenovirus expressing CFTR to cystic fibrosis patients: a phase I clinical trial.

Ad CFTR, a replication-deficient adenovirus expressing the human cystic fibrosis transmembrane conductance regulator (CFTR), was administered by aerosolization in a single escalating dose to three pairs (cohorts) of cystic fibrosis (CF) patients. Buffer only was administered to the nose and lungs 9-14 days before nasal instillation of virus followed the day after by aerosolization of Ad CFTR to the lung. Nasal doses (defined in terms of viral plaque forming units, pfu) were 10(5), 10(7), and 4 x 10(8), whereas aerosolized doses were 10(7), 10(8), 5.4 x 10(8) for each cohort, respectively. No acute toxic effects were observed in the first 4 weeks after virus treatment. Shedding of infectious Ad CFTR was never detected, whereas detection of vector DNA sequences and CFTR expression demonstrated DNA transfer to the nose and airways of patients. No significant deviations in immunological and inflammatory parameters were observed in serum and in bronchoalveolar lavage (BAL). Importantly, for all patients, the serum anti-adenovirus antibody levels did not change significantly from baseline and no antibodies against adenovirus were found in BAL.

Adenoviridae↗