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D Gaillard

Publications and source records attributed to D Gaillard.

At least 37 records · Page 2Linked to original sources
PubMed1999

Long chain fatty acids as modulators of gene transcription in preadipose cells.

During the last years, it has been clearly established that long-chain fatty acids act as modulators of gene expression in various tissues, such as adipose tissue, intestine and liver. This transcriptional action of fatty acids explains in part adaptation mechanisms of tissues to nutritional changes and especially to high-fat diets by increasing expression of proteins involved in lipid catabolism in liver and fatty acid uptake and utilization in other tissues. It is now clearly demonstrated that some of these transcriptional effects of fatty acids are mediated by activation of specific nuclear hormone receptors, called peroxisome proliferator-activated receptors (PPARs). These findings will be discussed with a special reference to control of gene expression in preadipocytes and adipose tissue development.

3T3 Cells↗
PubMed1998

Selective up-regulation of chemokine IL-8 expression in cystic fibrosis bronchial gland cells in vivo and in vitro.

Accumulating evidence suggests that the early pulmonary inflammation pathogenesis in cystic fibrosis (CF) may be associated with an abnormal increase in the production of pro-inflammatory cytokines in the CF lung, even in the absence of infectious stimuli. We have postulated that if baseline abnormalities in airway epithelial cell production of cytokines occur in CF, they should be manifested in the CF bronchial submucosal glands, which are known to express high levels of CFTR (cystic fibrosis transmembrane conductance regulator) protein, the gene product mutated in CF disease. Immunohistochemical analyses showed that CF bronchial submucosal glands in patients homozygous for the deltaF508 deletion expressed elevated levels of the endogenous chemokine interleukin (IL)-8 but not the pro-inflammatory cytokines IL-1beta and IL-6, compared with non-CF bronchial glands. Moreover, basal protein and mRNA expression of IL-8 were constitutively up-regulated in cultured deltaF508 homozygous CF human bronchial gland cells, in an unstimulated state, compared with non-CF bronchial gland cells. Furthermore, the exposure of CF and non-CF bronchial gland cells to an elevated extracellular Cl- concentration markedly increased the release of IL-8, which can be corrected in CF gland cells by reducing the extracellular Cl- concentration. We also found that, in contrast to non-CF gland cells, dexamethasone did not inhibit the release of IL-8 by cultured CF gland cells. The selective up-regulation of bronchial submucosal gland IL-8 could represent a primary event that initiates early airway submucosal inflammation in CF patients. These findings are relevant to the pathogenesis of CF and suggest a novel pathophysiological concept for the early and sustained airway inflammation in CF patients.

Adolescent↗
PubMed1998

Distribution of integrins during human fetal lung development.

Interactions between epithelial cells and the extracellular matrix through integrins play a key role in the development of the lung by modulating branching morphogenesis, epithelial cell polarization, and differentiation. To determine the role of integrins during the different stages of lung development, we investigated the distribution of eight integrin subunits in the trachea and lung from human fetuses. In distal airways, during the early pseudoglandular stage of development, the alpha2-, alpha5-, alpha6-, alphav-, and beta1-subunits were detected in all epithelial cell plasma membranes, and polarized but undifferentiated tracheal epithelial cells expressed alpha3-, alpha6-, and beta1-subunits in the plasma membrane of the cells facing the basement membrane. The alpha6- and beta4-chains were detected along the basal plasma membrane of the basal cells in differentiated tracheal epithelia. The alpha4-subunit was detected in all respiratory cells throughout fetal development. In the submucosal glands, myoepithelial cells expressed the integrin subunits found in the undifferentiated cells of the developing airways, whereas the secretory cells expressed only alpha2-, alpha3-, alpha4-, alpha6-, and beta1-subunits. These results demonstrate differential expression of integrins during lung development and suggest that integrins may play multiple roles in organogenesis and maturation of respiratory surface epithelium and glands.

Antigens, CD↗
PubMed1997

ATP depletion induces a loss of respiratory epithelium functional integrity and down-regulates CFTR (cystic fibrosis transmembrane conductance regulator) expression.

To mimic the effect of ischemia on the integrity of airway epithelium and expression of cystic fibrosis transmembrane conductance regulator (CFTR), we induced an ATP depletion of the respiratory epithelium from upper airway cells (nasal tissue) and human bronchial epithelial 16HBE14o- cell line. Histological analysis showed that 2 h of ATP depletion led to a loss of the epithelium integrity at the interface between basal cells and columnar cells. The expression of connexin 43 (Cx43, subunit of the gap junctions) and desmoplakins 1 and 2 (DPs 1 and 2, major components of the desmosomes) proteins was inhibited. After 90 min of ATP depletion, a significant decrease of the transepithelial resistance (25%) was observed but was reversible. Similar results were obtained with the 16HBE14o- human bronchial epithelial cell line. ATP depletion led to actin filaments depolymerization. The expression of the mature CFTR (170 kDa) and fodrin proteins at the apical domain of the ciliated cells was down-regulated. The steady-state levels of CFTR, Cx43, DPs 1 and 2 mRNAs, semiquantified by RT-polymerase chain reaction kinetics, remained constant throughout ATP depletion in nasal tissue as in the homogeneous cell population of 16HBE14o- human bronchial epithelial cell line. This suggests that the down-regulation of these proteins might be posttranscriptional. The intercellular diffusion through gap junctions of Lucifer dye was completely inhibited after 90 min of ATP depletion but was reversible. The volume-dependent and the cAMP-dependent chloride secretion were inhibited in a nonreversible way. Taken together, these results suggest that an ATP depletion in human airway epithelium, mimicking ischemia, may induce a marked alteration in the junctional complexes and cytoskeleton structure concomitantly with a loss of apical CFTR expression and chloride secretion function.

Adenosine Triphosphate↗
PubMed1997

Trans-differentiation of myoblasts to adipoblasts: triggering effects of fatty acids and thiazolidinediones.

Long-chain fatty acids (LCFA) and thiazolidinediones are potent activators of differentiation of preadipose cells. These adipogenic effects are, at least in part, mediated by nuclear receptors of the peroxisome proliferator-activated receptor (PPAR) subfamily. This report describes the effects of these agents on the differentiation pathway of myoblasts. Exposure of C2C12 myoblasts to LCFA or thiazolidinediones prevents the formation of multinucleated myotubes and the expression of specific muscle markers, leading in parallel to the expression of a typical adipose differentiation program. Similar transdifferentiation also occurs in mouse muscle satellite cells maintained in primary cell culture. These observations indicate that PPAR activators, such as LCFA or thiazolidinediones, convert the differentiation pathway of myoblasts into that of adipoblasts. This phenomenon could explain the appearance of adipocytes into muscle which occurs in some pathological states characterized by an increase of fatty acid disposal, such as obesity or mitochondrial myopathy.

Adipocytes↗
PubMed1997

Early alterations in airway mucociliary clearance and inflammation of the lamina propria in CF mice.

In cystic fibrosis (CF), whether cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction leads to decreased mucociliary clearance and mucus hypersecretion, before bacterial infection, remains an open question. To answer this question, we quantified in a blind trial the mucociliary transport velocity, the histological state, and the degree of inflammation of the tracheal mucosa in 23 cftr(m1HGU/cftr(m1HGU) transgenic mice (Dorin, J. R., P. Dickinson, E. W. F. W. Alton, S. N. Smith, D. M. Geddes, B. J. Stevenson, W. L. Kimber, S. Fleming, A. R. Clark, M. L. Hooper, L. Anderson, R. S. P. Beddington, and D. J. Porteous. Nature Lond. 359: 211-215, 1992) and in 30 control littermates housed in pathogen-free conditions. The nasal and tracheal transepithelial potential difference (PD) measured in basal conditions was significantly more negative in the cftr(m1HGU) mutant mice as compared with the control mice (nasal PD: -7.1 +/- 0.6 and -4.6 +/- 0.5 mV, respectively, P < 0.01; tracheal PD: -30.8 +/- 2.1 and -21.4 +/- 1.8 mV, respectively, P < 0.04). In the cftr(m1HGU)/cftr(m1HGU) mice, the mucociliary transport velocity was significantly lower (14.2 +/- 4.4 microm/mm, P < 0.04) compared with the control mice (30.6 +/- 5.9 microm/mm). The number of inflammatory cells in the lamina propria was significantly higher in the cftr(m1HGU)/cftr(m1HGU) mice (1048.7 +/- 124.7 cells/mm2, P < 0.03) compared with the control mice (640.5 +/- 58.2 cells/mm2). These results suggest that in CF, decreased airway mucociliary clearance and airway submucosal inflammation represent early alterations, before any airway infection.

Animals↗
PubMed1997

[Diagnosis of meconium ileus].

Meconium ileus represents a functional disorder mainly detected during the second trimester of gestation. The diagnosis can be recognized by bowel hyperechogenicity or by the pathologist after a systematic examination. It must lead to etiologic diagnosis and specific investigations according to the history. Even in absence of family history, cystic fibrosis must be considered with pancreatic study and with frozen fetal material in order to be able to search for the most common mutations. Meconium ileus can also be associated with infection, fetal blood swallowing, chromosomal aberrations and multiple fetal abnormalities. Only good investigations for specific diagnosis can lead to a genetic counsel and a good follow up of the next gestation.

Cystic Fibrosis↗
PubMed1997

[Vitamin-resistant rickets cured by removal of a bone tumor. Review of the literature].

PURPOSE OF THE STUDY: Rickets secondary to bone or soft tissue tumors are rare in children. Majority of the reported cases occurred in adults older than thirty. This entity can be cured after tumor removal. The authors present a case in a ten year boy and literature review. MATERIAL: A ten year boy complained of diffuse bone and muscle weakness for two years. A diagnosis of arthritis was made but the patient continued to complain. Serum calcium level was normal (2.33 mmol/l), phosphorus was very low (0.43 mmol/l), serum alkaline phosphatase was high, parathyroid hormone and vitamin D level were normal. Urinalysis showed abnormal phosphate excretion. METHODS: The absence of malabsorption, no family history of rickets or hypophosphatermy presence of a marked excess of urinary phosphate, very low serum phosphate and normal serum calcium, vitamin D and parathyroid hormone levels led us to consider a diagnosis of tumor induced osteomalacia. Radiographs showed a large round radiolucent lesion in the left superior pubic ramus and generalized demineralisation. RESULTS: We performed a complete tumor resection and the space was filled with bone graft. On histopathologic examination it was a benign mesenchymal tumor. Rapid reversal of biochemical anomalies, radiographs anomalies and clinical manifestation were observed after complete tumor resection. DISCUSSION: The authors have described the tumor, the osteomalacia and the pathogenesis of tumor rickets. Histologically the most common causative tumors were vascular tumors, mesenchymal tumors and non ossifying tumors. The tumor were of bone or soft tissue origin. Clinical symptoms were muscular weakness, bone and muscle pain. Biochemically there is a very low phosphate level, a normal serum calcium level as well as a normal vitamin D and PTH level. There is a significant high level of urinal phosphate. The mechanism proposed to explain oncogenic osteomalacia includes tumor secretion of phosphaturic substance other than PTH and calcitonin. Another hypothesis is a substance interfering with normal vitamin D metabolism. The pathogenesis is not clearly defined. CONCLUSION: Regardless to the mechanism of osteomalacia, complete removal of the tumor will cure the patient. A diligent search for tumors should be done in patients with vitamin D resistant rickets.

Bone Neoplasms↗
PubMed1996

Changes in adenosine A1- and A2-receptor expression during adipose cell differentiation.

Two adenosine receptors A1 and A2 are associated with either stimulation (A2) or inhibition (A1) of adenylate cyclase. Using the clonal cell line Ob1771, we have studied the expression of the two receptors during the process of adipose conversion accelerated by exposure to dexamethasone and 3-isobutyl-l-methylxanthine (IBMX) during the first 3 days post-confluence. The effects mediated by the two receptors on preadipocyte differentiation and adipocyte metabolism were also investigated. The two adenosine agonists NECA and PIA were used as preferential agonists of the A2- and A1-receptor, respectively. In preadipose cells (just confluent), both of the mouse clonal line and human primary culture, NECA dose-dependently stimulated cAMP production with a significant higher potency (P < 0.01) than did PIA. In adipose cells (16-day post-confluent) NECA was found to exert a biphasic effect on forskolin-stimulated cAMP production: i.e., NECA was clearly inhibitory in the femto- to picomolar concentration range whereas this effect gradually diminished at higher concentrations. The effect of PIA in 16-day post-confluent adipose cells however, was purely inhibitory on both cAMP production (IC50: 33.52 +/- 0.44 fM) and lipolysis (64% +/- 7%; P < 0.01). These findings were corroborated by Northern blot analysis which revealed A1-receptor mRNA to be exclusively expressed in the mature adipocytes, whereas A2-receptor mRNA gradually declined during the differentiation process except in 16-day post-confluent cells. In addition, NECA significantly enhanced the effect of corticosterone-induced differentiation by 46.8% (P < 0.05) but failed to have any adipogenic potency acting either alone or in concert with carbaprostacyclin (cPGI2). Thus, endogenous adenosine may have a bimodal action on adipose tissue metabolism mediated through stimulatory A2- and inhibitory A1-receptors, respectively, as a function of adipose conversion.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Fryns syndrome phenotype and trisomy 22.

Trisomy 22 was detected in a 32-week-old fetus born to an overweight mother with hypertension. Severe intrauterine growth retardation was associated with phenotypic manifestations of Fryns syndrome: diaphragmatic hernia, facial defects, and nail hypoplasia with short distal fifth phalanges. This is the second report of congenital diaphragmatic hernia in trisomy 22. This case demonstrates the importance of karyotyping malformed fetuses or newborns, even if a nonchromosome syndrome seems identifiable on clinical grounds. To date, at least 10 cases of Fryns syndrome have been reported without chromosome analysis.

Adult↗
PubMed1996

Effects of two different crystalloid cardioplegic solutions assessed by myocardial pH, tissue lactate content and energy metabolism.

OBJECTIVE: The influence of composition of crystalloid cardioplegia is imprecise in clinical practice. Therefore, we investigated changes in intramyocardial pH, tissue lactate content and energy metabolism during cardioplegic arrest with 2 different crystalloid cardioplegic solutions. METHODS: Twenty patients were randomly allocated to 2 groups: 10 patients had crystalloid cardioplegia buffered with bicarbonate (neutral pH of 7.8 at 20 degrees) with no additives (St Thomas' II solution) and 10 patients had a non buffered crystalloid cardioplegia (mildly acidic pH of 7.4 at 20 degrees) enriched with glutamate and mannitol (Menasché's solution). Tissue lactate and energy metabolism were measured on myocardial biopsy specimens and intramyocardial pH were continuously measured during cardioplegic arrest by a miniature glass electrode. RESULTS: There were no statistical differences in hemodynamic results and in AMP, ADP, ATP, lactate values measured on biopsy specimens. The curves of intramyocardial pH were very similar in the 2 groups, the median values were 7.42 +/- 0.1 in group 1 and 7.41 +/- 0.1 in group 2 (temperature corrected values) and the areas under the curves were 260 +/- 4 and 259 +/- 4 in groups 1 and 2 respectively (P = NS). CONCLUSIONS: Glutamate provided no additive metabolic myocardial protection, bicarbonate had a weak buffering capacity in cold cardioplegic solutions and the 2 studied crystalloid solutions warranted a good myocardial protection in clinical practice.

Acid-Base Equilibrium↗
PubMed1996

Bilateral skeletonized mammary artery grafting: experience with 560 consecutive patients.

OBJECTIVE: To test the hypothesis that the skeletonized technique of harvesting the internal thoracic artery improves the surgical results of bilateral internal thoracic artery grafting, we reviewed our 7-year experience with this technique. METHODS: Between July 1987 and December 1994, 560 patients received bilateral internal thoracic artery grafts and 236 additional grafts (average 2.6 +/- 0.6 anastomoses per patient). There were 515 men (92%) and the average age was 56.9 +/- 8.8 years. There were 63 diabetic patients (11.3%). During harvesting, the internal thoracic arteries were always totally skeletonized from the surrounding tissues without the use of electrocautery. RESULTS: Postoperative complications included reoperation for bleeding, 17 patients (3%), phrenic nerve paresis, 17 patients (3%), acute respiratory distress syndrome, 9 patients (1.6%), digestive complications, 8 patients (1.4%), neurologic complications, 6 patients (1.1%), and sternal complications, 6 patients (1.1%). No wound complications were observed in diabetic patients. The hospital mortality rate was 1.6% (9 patients, 2 cardiac causes). The early patency of internal thoracic artery grafts was 97.9%. Follow-up averages 29 +/- 20 months. There were 14 late deaths (4 cardiac causes). Angina recurred in 51 patients and the maximal stress test was abnormal in 47 patients. CONCLUSION: Bilateral internal thoracic artery grafting with skeletonized harvesting carried low post-operative mortality and morbidity and therefore it could be applied routinely without the fear of increased complication rate.

Adult↗
PubMed1996

Expression and localization of epidermal growth factor, transforming growth factor-alpha, and localization of their common receptor in fetal human lung development.

Transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), and their common EGF receptor have been shown to be involved in cell proliferation and lung maturation. The aim of the study was to determine the site of production of TGF-alpha and EGF mRNA and the cellular distribution of TGF-alpha/EGF proteins and EGF receptor, in fetal human lung. By using in situ hybridization with 35S-labeled cDNA probes in frozen sections from eight lungs from fetuses ranging from 12 to 33 wk of gestation, TGF-alpha and EGF mRNA transcripts appeared to be confined to the mesenchymal cells and mainly found in the dense connective tissue along the pleura, bronchi, and large vessels, but undetected in bronchial epithelial cells. The streptavidin-biotin immunoperoxidase method, applied to paraffin-embedded specimens from 39 fetuses ranging from 10 to 41 wk, showed that TGF-alpha, EGF, and EGF receptor exhibited a similar cellular distribution during the whole period of gestation. They were detected in the undifferentiated cells of the airway surface epithelium, mesothelial cells, smooth muscle, and a few mesenchymal cells, as early as 10 wk. After 12 wk, the immunoreactivity was strong in the ciliated, secretory, and basal cells, and in growing glands along the large airways, but proved lower in the distal airways. After 24 wk, the immunoreactivity remained in the airway epithelium, but was mainly localized in the apical domain of ciliated cells, in alveolar cells, and in the serous cells of the glands. The presence of TGF-alpha, EGF, and EGF receptor during the whole period of fetal lung development suggests that these factors are not only mitogenic, but can also be involved in epithelial maturation, through paracrine secretion, as most TGF-alpha and EGF mRNA transcripts are expressed in mesenchymal cells.

Antibody Specificity↗
PubMed1995

Thiazolidinediones and fatty acids convert myogenic cells into adipose-like cells.

Fatty acids and thiazolidinediones act as potent activators of the adipose differentiation program in established preadipose cell lines. In this report, the effects of these agents on the differentiation pathway of myoblasts have been investigated. Exposure of C2C12N myoblasts (a subclone of the C2C12 cell line) to thiazolidinediones or fatty acids prevents the expression of myogenin, alpha-actin, and creatine kinase, thus abolishing the formation of multinucleated myotubes. These treatments lead in parallel to the expression of a typical adipose differentiation program including acquisition of adipocyte morphology and activation of adipose-related genes. A similar transition toward the adipose differentiation pathway also occurs in mouse muscle satellite cells maintained in primary culture. Thiazolidinediones exert their adipogenic effects only in non-terminally differentiated myoblasts; myotubes are insensitive to the compounds. Continuous exposure to inducers after growth arrest is not required to maintain the adipose phenotype, but proliferation of adipose-like C2C12N cells leads to a complete reversion toward undifferentiated cells able to undergo either myogenic or adipogenic differentiation depending on the composition of culture medium. These results indicate that adipogenic inducers, such as thiazolidinediones or fatty acids, specifically convert the differentiation pathway of myoblasts into that of adipoblasts.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1995

Determination of reliable histological features associated with early triploidy using DNA image cytometry.

In order to determine reliable histological features characterizing triploidy, the following features were examined and graded by three pathologists on 46 early abortion specimens: hydropic swelling of the villi, cisterns, villous scalloping, trophoblastic hyperplasia with syncytial vacuolization, single cytotrophoblastic cells in villous stroma, trophoblastic inclusions, microcalcifications and fibrosis. At the same time, the DNA content of the 46 specimens was quantified cytophotometrically using the CAS 200 image analyzer, in order to confirm or not the diagnosis of triploidy. Triploidy was confirmed in 45.7%, and in the triploid group, the grading of three features differed significantly from the non triploid group i.e. cisterns (p < 0.001), trophoblastic hyperplasia (p < 0.05) and trophoblastic inclusions (p < 0.05). Using these three features we were able to give a triploid score per slide which represents the sum of the grades of each of these three features. The minimum score obtained was 0, the maximum was 6. The average of these scores in the triploid group was 3.095, and 1.45 in the non triploid group (p < 0.001). This scoring method on the three significant features (cisterns, trophoblastic hyperplasia and trophoblastic inclusions) appears to be useful to classify an abortion specimen as triploid or not, and to select the specimens for which a DNA quantification may be necessary.

Abortion, Spontaneous↗