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Biomedical subjects

J Bourbon

Publications and source records attributed to J Bourbon.

At least 19 recordsLinked to original sources
PubMed2003

[Normal and abnormal alveolar development].

INTRODUCTION: Alveolar growth predominantly occurs post-natally and is characterised by the multiplication of alveoli, the thinning of inter-alveolar walls, and the maturation of capillary vessels. STATE OF THE ART: Alveolar growth is controlled by numerous factors whose interactions remain poorly understood. Many phenomena can interfere with normal alveolar growth resulting in abnormal development and a reduction in alveolar surface. This is especially the case in premature human neonates, whose lungs are structurally and functionally immature. Oxygen therapy, mechanical ventilation, and airway inflammation may induce alveolar growth disorders in these children, resulting in the development of bronchopulmonary dysplasia. PERSPECTIVES AND CONCLUSIONS: Further studies are needed to improve our knowledge about alveolar growth regulatory mechanisms so that better strategies can be developed to prevent these respiratory complications in premature neonates.

Bronchopulmonary Dysplasia↗
PubMed2001

Novel mechanisms in murine nitrofen-induced pulmonary hypoplasia: FGF-10 rescue in culture.

We evaluated the role of the key pulmonary morphogenetic gene fibroblast growth factor-10 (Fgf10) in murine nitrofen-induced primary lung hypoplasia, which is evident before the time of diaphragm closure. In situ hybridization and competitive RT-PCR revealed a profound disturbance in the temporospatial pattern as well as a 10-fold decrease in mRNA expression level of Fgf10 but not of the inducible inhibitor murine Sprouty2 (mSpry2) after nitrofen treatment. Exogenous FGF-10 increased branching not only of control lungs [13% (right) and 27% (left); P < 0.01] but also of nitrofen-exposed lungs [23% (right) and 77% (left); P < 0.01]. Expression of mSpry2 increased 10-fold with FGF-10 in both nitrofen-treated and control lungs, indicating intact downstream FGF signaling mechanisms after nitrofen treatment. We conclude that nitrofen inhibits Fgf10 expression, which is essential for lung growth and branching. Exogenous FGF-10 not only stimulates FGF signaling, marked by increased mSpry2 expression, in both nitrofen-treated and control lungs but also substantially rescues nitrofen-induced lung hypoplasia in culture.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Retinoic acid protects against hyperoxia-mediated cell-cycle arrest of lung alveolar epithelial cells by preserving late G1 cyclin activities.

The epithelium of the lung alveolus is a major target for oxidant injury, and its proper repair after injury is dependent on the proliferative response of the alveolar epithelial type 2 cells. Recently, we have provided evidence that retinoic acid (RA) stimulates proliferation of type 2 cells. In the present study, we examined the effects of RA on the proliferative response of alveolar type 2 cells exposed to elevated oxygen (O(2)). We showed that pretreatment by RA was able to prevent the growth arrest and cell loss of O(2)-exposed cells. To gain insights into the mechanisms involved, we studied the effects of RA on the cyclin-dependent kinase (CDK) system. The activity of cyclin E-CDK2 complex was found to be decreased in O(2)-exposed cells. Interestingly, this decrease was no longer observed when cells were pretreated with RA. Analysis of p21(CIP1), an inhibitor of CDK, revealed an increased expression in O(2)-exposed cells that was no longer observed in cells treated with RA. These effects were associated with a reduced association of p21(CIP1) with cyclin E-CDK2 complexes in the presence of RA. In addition, studies of Smad activity strongly suggest that the mechanisms through which RA preserves late G(1) cyclin-CDK complex activity may involve interference with the transforming growth factor-beta signaling pathway.

Animals↗
PubMed1997

Tracheal obstruction in experimental diaphragmatic hernia: an endoscopic approach in the fetal lamb.

Congenital diaphragmatic hernia (CDH) is associated with a neonatal mortality of up to 50 per cent resulting from pulmonary hypoplasia. Experimental ligation of the trachea increases pulmonary growth in fetuses with experimental diaphragmatic hernia (EDH). To provide a potentially reversible tracheal occlusion (TO) using a minimally invasive procedure, we designed the endoscopic placement of a latex tracheal balloon in fetal lambs with EDH. Following surgical creation of a left EDH at 85 days' gestation, endoscopic occlusion of the fetal trachea was performed at 120 days. The fetuses were retrieved at 139 days. The procedure was successful in 5/11 attempts, resulting in liveborns in which the balloon occluded the trachea completely with expanded lungs and reduction of the herniated viscera into the abdomen. These cases were compared with five cases of EDH without TO and six controls. In the TO group, the lung weight was significantly greater but the radial alveolar count, DNA content, and protein content were similar to normal controls. All lung growth parameters were greater in the TO than in the EDH group. Occlusion of the trachea using an endoscopic technique could provide a useful alternative to open fetal surgery in fetuses with CDH.

Airway Obstruction↗
PubMed1995

[Surfactants in the digestive tube].

Epithelia of the gastrointestinal tract both synthesize and secrete surfactant-like materials. Like the pulmonary surfactant, these materials contain not only phospholipids, but also surfactant apoproteins, regarded until recently as specific products of the bronchoalveolar epithelium. Presented here are the various roles, most of them still speculative, of these phospholipids-containing products in the gastro-intestinal tract.

Animals↗
PubMed1992

Characterization of the rat pulmonary surfactant protein A promoter.

The expression of the pulmonary surfactant protein A (SP-A) is developmentally regulated and controlled by several hormones. In an attempt to characterize cis-acting elements involved in the regulation of SP-A expression, we have cloned the 5' flanking sequence of the rat SP-A gene. The promoter region contains a TATA box but no CAAT box. The transcription start site has been identified by anchored polymerase chain reaction and S1 nuclease mapping of the mature and precursor transcripts. S1 mapping of precursor transcripts has confirmed the stimulating effect of glucocorticoids on SP-A rat gene transcription in vivo. This hormonal effect may be mediated by a putative glucocorticoid responsive element located 140 bp upstream from the initiation site and protected against DNase 1 digestion in footprinting experiments. In vitro transcription of a G-free reporter cassette linked to the 212-bp 5' flanking DNA fragment has established that this putative promoter region is functional. Efficient transcription of the G-free reporter cassette was obtained with cell-free fetal lung extracts, whereas no transcript was detectable with cell-free liver extracts. Comparative analysis of the human and rat 5' flanking sequences shows the presence of strongly conserved motifs, unrelated to previously known consensus sequences. Some of these motifs, specifically protected in DNase 1 footprinting studies, could therefore be involved in the regulation of SP-A gene expression.

Animals↗
PubMed1989

Effects of the antiglucocorticoid RU 486 on the maturation of fetal rat lung surfactant.

The role of endogenous glucocorticoids in the control of surfactant system maturation was investigated in the fetal rat using an antiglucocorticoid molecule synthesized by Roussel-UCLAF, RU 486. The drug was administered to the mother from day 16 of gestation on. In a preliminary step, the transplacental transfer of RU 486 and its antiglucocorticoid effects on fetal target tissues were verified by evidencing RU 486-receptor complexes in fetal liver and lung, by measuring liver glycogen content, and by evaluating fetal blood corticosterone. The maturational state of fetal lungs was assessed biochemically on days 19, 20, and 21 of gestation by measuring their glycogen content, the phospholipid content of whole lung tissue and isolated surfactant fraction, and the incorporation of [methyl-3H]choline into DSPC. Morphological development was studied by analyzing electron micrographs of type II cells. The measured parameters clearly indicated a slowing of maturational processes in lungs of fetuses from RU 486-treated mothers, thereby demonstrating that endogenous glucocorticoids are actually involved in the control of lung maturation. In addition, the obtained results showed that endogenous corticosteroids specifically acted on the surfactant system of the fetal lung.

Animals↗
PubMed1987

Optimization of fetal lung organ culture for surfactant biosynthesis.

Lung organ culture has been a widely used system for studying differentiation and maturation of alveolar epithelium through various culture conditions. The purpose of this work was to carefully characterize in vitro lung biochemical differentiation through isolation of surfactant fraction from tissue and to search for optimal culture conditions. Fetal rat lung was explanted on the 18th gestational day for studying glycogen storage, and on the 20th gestational day for studying surfactant accretion, and cultivated for 48 h. Morphologic differentiation was studied by electron microscopy on tissue explanted on the 17th or 18th gestational days and cultivated for various times. Glycogen storage was greater on fluid medium, although less than occurring in vivo. Cellular integrity and surfactant accumulation were maximal on a semisolid medium containing 0.5% agar. Use of O2-CO2 instead of air-CO2 for gassing the explants slightly decreased phospholipid accumulation. Among media used in previous lung culture studies, Waymouth MB 752/1 was the only one to allow net glycogen accumulation in vitro. The most favorable media for surfactant phospholipid accretion were Waymouth MB 752/1, Eagle's minimum essential and its Dulbecco's modification, CMRL 1066, and NCTC 109. They allowed a 12- to 14-fold increase of surfactant fraction phospholipids in vitro, which is similar to the increase occurring in vivo during the same period. Ham's F10 and F12 media allowed a six fold increase. RPMI 1640 and medium 199 (M199) allowed only a three fold increase. Phospholipid concentration in nonsurfactant fraction only doubled during culture, and differences between various media were much less marked. DNA concentration changed little during culture. Morphologic differentiation of epithelial cells was advanced as compared with in vivo timing in a medium allowing maximal surfactant accretion (Waymouth MB 752/1) but not in a medium allowing low surfactant increase (RPMI 1640). The possible role of compositional differences between media is discussed.

Animals↗
PubMed1987

Lung maturation in the hyperinsulinemic rat fetus.

Hyperinsulinemic rat fetuses were obtained either by repeated in utero injections of long-acting insulin (resulting in fetal hypoglycemia) or by chronically infusing intravenous glucose to the mother (resulting in fetal hyperglycemia). Fetuses were examined at term. In insulin-injected fetuses (n = 15), surfactant (S) fraction phosphatidylcholine (PC) and disaturated phosphatidylcholine (DSPC) were significantly decreased (3.6 +/- 0.1 nmol Pi/mg tissue; p less than 0.001 and 2.8 +/- 0.1 nmol/mg; p less than 0.025, respectively) as compared with their saline-injected controls (4.8 +/- 0.2 and 3.3 +/- 0.1 nmol/mg, respectively, n = 19). However, residual (R) fraction was unchanged, and there was no difference in whole-lung phospholipids (combined S and R fractions). These results are consistent with morphological data showing a lower lamellar body area per type II cell profile in insulin-injected fetuses as compared with their controls [1.41 +/- 0.13 micron 2 (n = 72) versus 1.99 +/- 0.14 micron 2 (n = 129) p less than 0.01]. Glycogen content was slightly higher in insulin-injected fetuses (18.5 +/- 1.0 micrograms/mg, n = 17) than in their controls (15.1 +/- 0.8 micrograms/mg, n = 18; p less than 0.05). In the second model, changes in S fraction PC and DSPC were similar to those observed after insulin-injections: 4.3 +/- 0.25 and 3.4 +/- 0.2 nmol Pi/mg in fetuses of glucose-infused rats (n = 10) versus 5.7 +/- 0.45 and 4.3 +/- 0.3 nmol Pi/mg, respectively, in controls (n = 10, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

[Decrease of pulmonary phosphatidylglycerol in the fetuses of rats made diabetic by streptozotocin].

Phosphatidylglycerol and phosphatidylinositol were studied on gestational day 21.5 in the lung of Rat fetuses from streptozotocin-diabetic mothers (severe diabetes; maternal glycemia, 16.5 16.5 mmol/l). A 55% decrease of phosphatidylglycerol and a concomitant 60% increase of phosphatidylinositol were shown. These changes are qualitatively similar to those previously observed in amniotic fluid of human fetuses from diabetic mothers. Since in the severely diabetic pregnant Rat, the fetuses present hyperglycemia and hypoinsulinemia, instead of reactional hyperinsulinemia as the human fetus does, the changes observed in fetal lung are probably due to a direct effect of glucose excess, possibly through an increase of blood myoinositol.

Animals↗
PubMed1981

Role of fetal insulin in glycogen metabolism in the liver of the rat fetus.

In the near-term rat fetus liver, insulin decreased phosphorylase a activity, slightly increased synthase a activity and increased both glycogen content and 14C-glucose incorporation into glycogen; anti-insulin serum increased phosphorylase a activity and decreased glucose incorporation but did not modify synthase a activity. When pregnant rats were previously rendered hypoglycemia, insulin injection to the fetus enhanced glycogen accumulation. It is concluded that insulin is a regulatory factor of secondary importance for liver glycogen storage through its action on phosphorylase activity.

Animals↗
PubMed1980

Effects of acute variation of fetal glycemia on glycogen storage and on glycogen synthase and phosphorylase activities in the liver of the rat fetus.

The effects of variations of glycemia from 1.7 to 35 mM on the activity of glycogen synthase and phosphorylase, on glycogen content, and on U-14C-glucose incorporation into glycogen in the liver of the near-term rat fetus were investigated. Hypoglycemia did not affect the activities of phosphorylase and synthase; total glycogen content was not modified, but incorporation of labeled glucose was markedly decreased. This is consistent with a decreased glycogen synthesis. A slight hyperglycemia (about 5.5 mM) sharply decreased phosphorylase a (active) activity but increased slightly glycogen synthase a activity; liver glycogen content and labeled glucose incorporation were both enhanced. Higher levels of glycemia induced a decrease of phosphorylase a activity of the same order, but by contrast, glycogen synthase a activity increased progressively with increasing glycemia. Sequential study showed that hyperglycemia first induced the decrease of phosphorylase activity, then increased synthase activity. Marked hyperglycemia strongly enhanced liver glycogen content and labeled glucose incorporation. The fetal liver appears very responsive to acute variations of glycemia. The mechanisms seem to be oriented toward maximal glycogen accumulation.

Animals↗
PubMed1979

[Plasma growth hormone in the rabbit fetus. Relation to maturation of the liver and lung].

Day 25 after insemination is a date of peculiar importance in the maturation of several organs in the Rabbit fetus. From day 25 onward the fetal liver stores increasing amounts of glycogen and the lung stores increasing amounts of lecithins, concomitant with sudden rise in the activity of lung phosphatidic-acid phosphohydrolase. Earlier studies on decapitated fetuses established that glycogen storage in the liver is dependent on a dual hormonal control, comprising a pituitary hormone like growth hormone or prolactin (some placental hormones share the same activity) and corticosteroids (Jost, 1961). Since the variations in endogenous corticosteroids do not seem to herald these liver or lung changes (Mulay et al., 1973), a study was made of growth hormone. Plasma immunoreactive growth hormone--determined with a heterologous Rat system (Kervran et al., 1976)--increases eightfold between days 23 and 25. During the same time plasma prolactin does not change according to McNeily and Friesen, 1978, and to unpublished data obtained with Dr McNeilly. In preliminary assays, Rat growth hormone was seen to increase phosphorylase "a" activity in the lung of 18.5 day-old Rat fetuses, thus anticipating normal development. We suggest that growth hormone plays a role in initiating liver and lung maturation.

Age Factors↗
PubMed1979

Glucocorticosteroid receptors in the liver of normal and decapitated rabbit foetuses.

The affinity and the number of receptor sites for the synthetic steroid triamcinolone acetonide were studied in the livers of foetal rabbits. Twenty-two-, 24- and 29-day-old control and 29-day-old foetuses decapitated on day 22 were used to determine whether a change in steroid receptors occurs in the liver when it accumulates glycogen, and whether decapitation impairs such a change. Steroid receptors were found as early as day 22, when they were as numerous (0.091 pmol/mg protein) as on days 24 (0.098 pmol/mg) and 29 (0.104 pmol/mg). The binding affinity was found to be slightly higher on day 24 than on day 22 and it remained the same on days 24 and 29. The binding affinity of the receptors was the same in decapitated foetuses as in 29-day-old controls but the number of sites was slightly lower. The labelled steroid was transferred to the nucleus of the liver cells in vivo. It seems unlikely that steroid receptors are the limiting factor preventing the accumulation of glycogen in the liver of the rabbit foetus before day 26 or after decapitation.

Animals↗
PubMed1978

Turnover of liver glycogen in the rat foetus.

Incorporation and release of the radioactivity in the liver glycogen of 18.5- and 19.5-day-old rat foetuses were studied after intravenous injection of E11-14C]glycerol. Incorporation occurred during 1 h after injection of the radioactive tracer to the foetus; then, the incorporated radioactivity decreased. Glycogen content in the liver, and glycogen phosphorylase and glycogen synthase were not modified during the experiment. It is therefore postulated that a physiological turnover of glycogen exists in the liver of the rat foetus.

Animals↗