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Biomedical subjects

G Bellon

Publications and source records attributed to G Bellon.

At least 91 records · Page 5Linked to original sources
PubMed1994

Renal and microvascular effects of an aldose reductase inhibitor in experimental diabetes. Biochemical, functional and ultrastructural studies.

Aldose reductase inhibitors, and particularly sorbinil, have been reported to prevent glomerular basement membrane thickening (GBMT) and albuminuria development in diabetic rats, but contradictory observations have been published. The aim of this study was to answer the following questions (i) is the corrective effect of sorbinil on GBMT, if confirmed, associated with an effect on collagen metabolism alterations? (ii) Is it associated with an effect on microvascular functional alterations? We therefore studied the influence of sorbinil on glucosyl-galactosyl-hydroxylysyl-glucohydrolase activity (GGHG; EC 3.2.1.107 which is involved in the catabolism of collagen disaccharide units), 3- and 4-hydroxyproline content and GBMT by ultrastructural morphometry in the kidney cortex of streptozotocin-diabetic rats after 5 months of disease. In parallel, the effects on albumin renal clearance and another functional alteration, the microvascular response to norepinephrine, were evaluated. We confirmed a corrective effect of sorbinil on both renal albumin clearance and GBMT. In the diabetic rats, sorbinil diminished the 3-hydroxyproline (but not the 4-hydroxyproline) content, whether expressed per mg protein or per total kidney cortex relative to body weight. Sorbinil reduced GGHG activity measured in the dialysed 10,000 g supernatant whether expressed per mg protein or per total kidney cortex; this activity has been shown to be increased in diabetes. Sorbinil also corrected the microvascular response to norepinephrine which is altered in diabetes.

Albuminuria↗
PubMed1994

Differential expression of thrombospondin, collagen, and thyroglobulin by thyroid-stimulating hormone and tumor-promoting phorbol ester in cultured porcine thyroid cells.

In the present study, we have investigated the potential regulation of thyroglobulin (Tg) and extracellular matrix components synthesis by thyroid-stimulating hormone (TSH) and tetradecanoyl phorbol-13-acetate (TPA) on thyroid cells. Porcine thyroid cells isolated by trypsin-EGTA digestion of thyroid glands were maintained in serum containing medium on poly (L-lysine)-coated dishes. Cells differentiated into follicular or vesicular-like structures were distinguished by their ability to organify Na[125I] and to respond to TSH stimulation. After an incubation of the cells with radiolabeled proline or methionine, two major proteins were identified, p450-480 and p290 (so named because of their molecular masses). Tg (p290) synthesis was demonstrated by the synthesis of [131I]-labeled polypeptides with electrophoretic properties identical to those of authentic Tg molecules. P450-480 resolved to M(r) 190,000 under reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) conditions. It was identified as thrombospondin by its reactivity with a monoclonal anti-human thrombospondin and by peptide sequencing of some of its tryptic fragments that displayed identity to thrombospondin I. Collagen synthesis was demonstrated by the formation of radioactive hydroxyproline and by the synthesis of pepsin-resistant polypeptides ranging from M(rs) 120,000 to 200,000. When the cells were cultured in the presence of 100 nM TPA, the culture medium contents of thrombospondin and collagen were increased by 2.7 and 1.6-fold, respectively, whereas Tg content was decreased by a factor 3.9. In contrast, the acute treatment of control cells with TPA induced a decrease in both Tg and collagen content by factors 3.0 and 1.5, respectively, and an increase in thrombospondin content by a factor 2.5. In the presence of 100 nM TPA, TSH (1 mU/ml) did not counteract the stimulating effect of TPA on extracellular matrix components synthesis. In contrast, when cells were cultured in the presence of TSH alone at concentrations higher than 0.1 mU/ml, collagen and thrombospondin in the medium were decreased by a factor 2.0 and 1.9, respectively, and TSH preferentially activated Tg synthesis. However, no acute response to TSH was observed in cells incubated for 2 days without effectors (control cells). On TSH differentiated cells, TPA decreased both collagen and Tg accumulation by factors 1.2 and 1.8, respectively, whereas it increased the one of thrombospondin by a factor 2. These results, together with the stimulating effect of TPA on TSH mediated cell proliferation, argue for a role of thrombospondin in cell adhesion and migration events within the thyroid epithelium.

Animals↗
PubMed1994

[Destombes-Rosai-Dorfman syndrome: 2 uncommon clinical forms].

Two cases of Destombes Rosai Dorfman's syndrome are presented. Diagnosis was performed by superficial lymph node biopsy. The first case concerned a nine and half years old girl with cervical adenopathy who developed a compressive mediastinal adenopathy responsible for a right lower lobe atelectasis. Because of local lung suppuration a lobectomy had to be performed. The second case concerned a fourteen years old boy with recurrent fever, diffuse superficial lymph nodes and erythematous skin rash. The two patients showed clinical and biological inflammatory symptoms without any immunodeficiency. No aetiological agent could be identified. Antibiotics and corticoids had no effect but the two patients recovered (after 18 months follow up in case 2). These two particular cases confirm the clinical course heterogeneicity of the syndrome which requires histological diagnosis.

Adolescent↗
PubMed1993

Adhesion and activation of human neutrophils onto collagen chains separated by electrophoresis.

After separation of the various alpha chains of the collagens by SDS-PAGE, the binding of polymorphonuclear neutrophils (PMN) to these chains was detected by a double-antibody technique and the activation of PMN by nitro blue tetrazolium. All of the alpha chains tested were able to bind PMNs. The alpha 1 chain of type I collagen activated the PMN when it had not been treated with pepsin. Pepsinized types II and VI collagens did not activate PMN. The pepsinized alpha 1(III) chains and all three alpha chains from pepsinized type V collagen were able to activate PMN.

Cell Adhesion↗
PubMed1993

Adhesion and activation of human neutrophils on basement membrane molecules.

In a previous study, we found that type I collagen activates human polymorphonuclear neutrophils by binding to a membrane integrin [3]. The activation depends on two sequences, both contained in the alpha 1 (I) CB6 peptide, one is RGD, starting at residue 915, and the second is DGGRYY, starting at residue 1034 of the alpha 1(I) chain. We checked the effect of several other types of collagens, principally type IV collagen from several origins. The basement membrane from bovine lens as well as type IV collagen prepared from it by tartaric acid extraction did not activate the human neutrophils. In contrast, when neutrophils had been previously in contact with type IV collagen their activation by type I or the alpha 1(I) CB6 peptide, or the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine, was inhibited. This effect was abolished when type IV collagen had been previously treated by pepsin. On the other hand, the fractions of type IV collagen that resisted digestion by bacterial collagenase still exhibited this inhibiting effect. This effect probably explains the physiological property of neutrophils to cross vascular walls without being activated.

Amino Acid Sequence↗
PubMed1993

Fibroblastic rheumatism: clinical, histological, immunohistological, ultrastructural and biochemical study of a case.

We report a case of fibroblastic rheumatism (FR). Only eight other cases of this recently described entity have been reported previously. FR is characterized by polyarthralgia and joint stiffness without joint destruction, associated with cutaneous nodules and sclerodactyly. Histology shows an increase in the number of fibroblasts and marked dermal fibrosis. Rheumatological and skin manifestations may improve with corticosteroid therapy. In our patient, immunohistochemical studies of involved and uninvolved skin showed an increase in fibronectin and tenascin deposition. In the dermis, the hyperplastic cells had phenotypic features of muscle, suggesting myofibroblastic differentiation. Ultrastructural study showed an increase in active fibroblastic cells with features of myofibroblasts. A hyperproliferative capacity was observed in fibroblasts cultured from involved skin. Biochemical studies of the production of collagen and non-collagen proteins were performed on these cultured cells, and showed a reduction in collagen and non-collagen protein synthesis by FR fibroblasts. Thus, FR appears to differ from other fibrotic skin diseases such as scleroderma, in that dermal fibrosis may be due predominantly to fibroblast proliferation with myofibroblastic differentiation without any increase in collagen synthesis.

Cell Adhesion Molecules, Neuronal↗
PubMed1993

In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds.

The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) was first described as a growth factor for differentiated cells. Recent in vitro data showed that it possesses several properties of a potential activator of wound repair. We investigated the effects of GHK-Cu in vivo, using the wound chamber model described previously (Schilling, J.A., W. Joel, and M.T. Shurley, 1959. Surgery [St. Louis]. 46:702-710). Stainless steel wire mesh cylinders were implanted subcutaneously on the back of rats. The animals were divided into groups that received sequential injections into the wound chamber of either saline (control group) or various concentrations of GHK-Cu. At the end of the experiments, rats were killed, wound chambers were collected, and their content was analyzed for dry weight, total proteins, collagen, DNA, elastin, glycosaminoglycans, and specific mRNAs for collagens and TGF beta. In the GHK-Cu-injected wound chambers, a concentration-dependent increase of dry weight, DNA, total protein, collagen, and glycosaminoglycan contents was found. The stimulation of collagen synthesis was twice that of noncollagen proteins. Type I and type III collagen mRNAs were increased but not TGF beta mRNAs. An increase of the relative amount of dermatan sulfate was also found. A control tripeptide, L-glutamyl-L-histidyl-L-proline, had no significant effect. These results demonstrate that GHK-Cu is able to increase extracellular matrix accumulation in wounds in vivo.

Animals↗
PubMed1993

[Congenital hypoplasia of the left pulmonary artery and exertion hypoxemia].

The reported case concerns a 12-year-old boy with a congenital hypoplasia of the left pulmonary artery without associated cardiac malformation. At rest, pulmonary function tests were within the normal range, while the patient demonstrated an abnormal dyspnea and hypoxemia during exercise. These symptoms disappeared after left pneumonectomy. Unilateral pulmonary artery hypoplasia can be responsible for exercise hypoxemia due to an intermittent right-to-left shunt or a ventilation-to-perfusion mismatching.

Child↗
PubMed1992

Delayed compliance increase in infants with respiratory distress syndrome following synthetic surfactant.

Recent research has demonstrated that Exosurf (EXSF), a newly synthesized artificial surfactant, increases survival when administered endotracheally to premature infants with RDS. This study examines the effects of EXSF on static respiratory system compliance (Crs). Thirty-four patients received two doses of EXSF in this rescue protocol. Crs (mL/cmH2O/kg) did not significantly change within the first 4 hours after either dose. However, Crs values did increase significantly (paired Student's t-test, P = 0.005) when data collected after the second dose (0.36 +/- 0.13 mL/cmH2O/kg) were compared to first week follow-up data (0.51 +/- 0.21 mL/cmH2O/kg). Crs data collected between 2 and 4 weeks after treatments were again not significantly different from non-concurrent control data collected at 3-4 weeks of life. The measurement of Crs in infants receiving EXSF may have been affected by an increase in lung inflation, which could mask an increase in Crs. We speculate that improved lung inflation may occur with less barotrauma in the first week of life due to surfactant replacement treatment and may in part explain the improved Crs seen at 1 week of age. Many investigators using different surfactants, dosing schedules, and pulmonary function methodologies to evaluate lung mechanics have reported that the improvement in compliance after surfactant treatment usually follows the clinical improvement in gas exchange. Additional studies are needed to explain the mechanism of early improvement following surfactant replacement in infants with RDS.

Drug Combinations↗
PubMed1992

Heart-lung transplantation in a 16-month-old infant.

A 16-month-old boy who had a heart-lung transplantation is doing well 16 months postoperatively. The HLT can be a successful treatment for very young patients. Most of the postoperative management can be assessed with noninvasive techniques. Normally, the allograph grows with the recipient.

Heart-Lung Transplantation↗
PubMed1992

[From acute viral bronchiolitis in infancy to asthma in childhood].

Bronchiolitis and wheezy bronchitis are frequently associated with viral infection of the respiratory tract in infants. They play an important role in the natural history of chronic obstructive airway disease, not only in children, but also in adults. The risk of early recurrent wheezing and subsequent asthma or chronic bronchitis (with anatomical sequelae such as obliterans bronchiolitis) is significant. The precise pathogenic mechanisms of virus-induced wheezing and its sequelae are not clear. Whether airway hyperreactivity is inherited and airway hyperreactivity is present prior to, or is the result of bronchiolitis is not clear. Nevertheless the evidence for viral trigger of wheezing and long-term pulmonary sequelae must be considered and prevention must be undertaken at the first episode.

Acute Disease↗
PubMed1992

Gamma-interferon inhibits extracellular matrix synthesis and remodeling in collagen lattice cultures of normal and scleroderma skin fibroblasts.

Three-dimensional collagen lattice cultures of fibroblasts mimic the in vivo situation better than monolayer cultures. Here, skin fibroblasts from scleroderma patients and healthy controls were cultivated in collagen lattices, and the effects of recombinant human gamma-interferon (IFN-gamma) on these cultures investigated. IFN-gamma inhibited collagen lattice retraction in a dose-dependent way at concentrations ranging from 10 to 10,000 U/ml. This effect was independent of any alteration to the cell proliferation within the lattices. The inhibition was of the same order of magnitude in normal and pathological fibroblasts. The synthesis of collagen and non-collagen proteins, particularly fibronectin, was increased in scleroderma cultures. It was inhibited in both normal and scleroderma fibroblasts by IFN-gamma, with a maximal effect at the concentration 1000 U/ml, but the inhibition of protein synthesis was far more intense in scleroderma than in normal cells. In situ hybridization, Northern blot and dot blot analyses showed that mRNA coding for pro alpha 1(I) collagen was decreased in IFN-gamma-treated cells, indicating an effect at the pretranslational level. IFN-gamma also inhibited glycosaminoglycan synthesis, but in scleroderma cells only. This study shows that IFN-gamma regulates cell behavior in three-dimensional collagen matrices: (i) it decreases protein and specifically glycosaminoglycan synthesis in scleroderma fibroblasts, (ii) it modulates the interactions between cells and matrix that lead to the retraction of the lattice. Whereas collagen synthesis is largely decreased in lattice cultures like in vivo, it remains increased in the case of scleroderma compared to normal fibroblasts and may be down-regulated by IFN-gamma. Similar conclusions may be drawn for fibronectin and glycosaminoglycans. The inhibitory effect of IFN-gamma on the retraction capacity of fibroblasts and on their ability to synthesize increased amounts of extracellular matrix macromolecules may be of potential interest for therapeutic use of IFN-gamma in scleroderma patients.

Adult↗
PubMed1991

Bovine lens capsule basement membrane collagen exerts a negative priming on polymorphonuclear neutrophils.

After a 30 min contact between purified bovine lens capsule basement membrane type IV collagen and polymorphonuclear neutrophils, stimulation of these cells by N-formyl-methionyl-leucyl-phenylalanine, PMA or type I collagen releases a decreased amount of superoxide ions (negative priming). The inhibitory activity is located in the NCl domain. On the other hand, after pepsin digestion, the helical part of type IV collagen determines a positive priming of neutrophils.

Animals↗
PubMed1991

Plasma dopamine, norepinephrine, epinephrine and DOPAC levels in preterm infants prior to and immediately after a sleep ventilation hypercarbia test.

The postnatal maturation and the adaptational ability of the sympathoadrenal system has been investigated in preterm neonates (n = 8), and in sick preterm neonates with respiratory disorders (n = 10). Plasma levels of dopamine (DA), norepinephrine (NE), epinephrine (E) and 3-4 dihydroxyphenylacetic acid (DOPAC) were evaluated at rest during the first month of life, and following an inhalation of a 5% carbon dioxide-21% oxygen mixture for 10 min. During the first month of life the sick preterm neonates exhibited similar NE, E, and DOPAC plasma levels but higher DA amounts than healthy infants. Plasma DA levels were inversely correlated with the transcutaneous oxygen tension (r = -0.636) indicating that hypoxemia was able to enhance the release of DA. Immediately following the hypercarbia test, there were no significant changes of plasma catecholamine levels in the sick preterms, but there was a significant increase of E plasma levels (+140%, p less than 0.05) and a moderate elevation of NE and DA amounts in the healthy preterms. It is concluded that preterm neonates who have had respiratory disorders did not exhibit an immaturity of the sympathoadrenal system at rest, but had a defect in the release of E following hypercarbia exposure, which may be secondary to an alteration in chemoreceptor function and/or reduced catecholamine stores.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

[Determination of nasal transepithelial potential difference (DDPTE) in cystic fibrosis. Analysis of a simplified measurement technique].

Measurements of nasal transepithelial potential differences (TEPD) were performed in 77 patients in order to assess a routine simplified method of recording. TEPD assays were performed in 34 patients with cystic fibrosis aged 1 month to 25 years, in 22 children with another chronic respiratory illness and in 21 subjects without any bronchopulmonary impairment. In the cystic fibrosis group TEPD values (mean +/- SD) were significantly higher (-49.077 +/- 9.38 mV) than in patients with chronic respiratory illnesses (-20.590 +/- 5.011 mV) or in subjects without bronchopulmonary impairment (-19.857 +/- 5.033 mV) (p less than 0.0001). Measurements could not be performed in 10 patients due to major nasal inflammation. The excellent specificity (100%) and sensitivity (93%) of the method confirm its diagnostic value. It may be used from the neonatal period and may represent an alternative to the sweat test, especially in dubious cases.

Child↗
PubMed1991

[Activation of polymorphonuclear neutrophils by contact with collagen I and degradation of collagen].

The contact of polymorphonuclear neutrophils with type I collagen molecules triggers the production of oxygen free radicals by these cells. This activation requires two short collagenic sequences and seems to involve a beta 2 integrin on the neutrophil membrane. Oxygen free radicals are capable to degrade collagen molecules into small peptides. This interaction takes place in inflammatory phenomena.

Collagen↗