PubMed Health⌕ Search

Biomedical subjects

D Gaillard

Publications and source records attributed to D Gaillard.

At least 19 recordsLinked to original sources
PubMed1992

Prostacyclin is a specific effector of adipose cell differentiation. Its dual role as a cAMP- and Ca(2+)-elevating agent.

The mitogenic-adipogenic activity of carbaprostacyclin (cPGI2), a stable analogue of prostacyclin (PGI2), has been proposed to be related to its ability to elicit cAMP production and to activate the protein kinase A cascade (Négrel, R., Gaillard, D., and Ailhaud, G. (1989) Biochem. J. 257, 399-405). In the present study, cPGI2 has been compared with other activators of the cAMP pathway, namely isoproterenol, forskolin and 8-bromo-cAMP, with respect to adipose cell differentiation. Carbaprostacyclin behaved as a much more potent and efficient effector of mouse Ob1771 preadipocyte differentiation than the latter agents. Moreover, cPGI2 also exerted a specific amplifying mitogenic-adipogenic role, as compared with isoproterenol in rat as well as human adipose precursor cells in primary culture, suggesting that the prostanoid was able to generate an additional second messenger. The fact that ionomycin was able to potentiate and amplify the differentiation induced by 8-bromo-cAMP led us to give evidence, using preadipocytes preloaded with the fluorescent calcium chelator Indo-1, that cPGI2, besides its ability to activate adenyl cyclase, was also able to induce a transient increase in intracellular free calcium. This phenomenon was independent of cAMP production or inositol phospholipid breakdown and appeared to be mediated after binding to a single class of PGI2 receptor. The potential to generate simultaneously two synergistic intracellular signals allows us to ascribe to PGI2 a key and specific role in the differentiation of adipose precursor cells in vitro that would likely lead in vivo to the recruitment of "dormant" preadipocytes to become adipocytes.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Differential localization of the cystic fibrosis transmembrane conductance regulator in normal and cystic fibrosis airway epithelium.

Deletion of the amino acid residue Phe 508 of the cystic fibrosis transmembrane conductance regulator (CFTR) protein represents the most common mutation identified in cystic fibrosis (CF) patients. A monoclonal and a polyclonal antibody directed against different regions of CFTR were used to localize the CFTR protein in normal and CF airway epithelium derived from polyps of non-CF and CF subjects homozygous for the delta Phe 508 CFTR mutation. To identify the cellular and subcellular localization of CFTR, immunofluorescent light microscopy, confocal scanning microscopy, and immunogold transmission electron microscopy were performed on cryofixed tissue. A markedly different subcellular distribution was identified between normal and CF airway epithelial cells. In normal epithelium, labeling was restricted to the surface apical compartment of the ciliated cells. In contrast, in the epithelium from homozygous delta Phe 508 CF patients, CFTR markedly accumulated in the cytosol of all the epithelial cells. These findings are consistent with the concept that the CFTR delta Phe 508 mutation modifies the intracellular maturation and trafficking of the protein, leading to an altered subcellular distribution of the delta Phe 508 mutant CFTR.

Cystic Fibrosis↗
PubMed1992

Differential response of preadipocytes and adipocytes to prostacyclin and prostaglandin E2: physiological implications.

The major prostaglandins (PGs) locally produced in adipose tissue both in rodent and man are PGE2 and prostacyclin (PGI2). We have recently described PGI2 as an autocrine promoter and/or amplifier of terminal differentiation of cultured preadipocytes in several species. The effectiveness and specificity of PGI2 as an adipogenic agent are related to its ability to induce in preadipocytes intracellular increases of both cAMP and free calcium. Moreover, PGs of the E series are well known to exert an antilipolytic effect in mature adipocytes. These observations have prompted us to address two questions of physiological interest: 1) Is PGI2 still able to increase cAMP in differentiated adipocytes, behaving thus as a lipolytic agent, and 2) Is PGE2 able to negatively modulate cAMP production in adipose precursor cells, behaving thus as a counteracting effector of PGI2 action? Our results, with respect to cAMP production and/or lipolysis and antilipolysis, demonstrate clearly that in adipose tissue of both rat and man, PGI2 exclusively affects adipose precursor cells whereas PGE2 exclusively affects adipocytes. We propose a model of concerted action for both PGs in the development of adipose tissue mass, PGI2 behaving as an adipogenic-hyperplastic effector and PGE2 as an antilipolytic-hypertrophic effector.

Adipose Tissue↗
PubMed1992

Terminal differentiation of mouse preadipocyte cells: the mitogenic-adipogenic role of growth hormone is mediated by the protein kinase C signalling pathway.

The role of growth hormone (GH) in the differentiation process of Ob1771 mouse preadipocyte cells has been studied under culture conditions that were serum-free and hormone-supplemented and which were previously shown to lead to terminal differentiation. In the absence of GH, a dramatic decrease in the adipogenic activity of the culture medium could be observed, as indicated 12 days after confluence by the low levels of glycerol-3-phosphate dehydrogenase activity and the sharp reduction of the number of triacylglycerol-containing cells. This decrease in adipogenic activity was accompanied by a parallel loss of the mitogenic potency of the culture medium. Determination of the half-maximal and maximal concentrations of GH required for the restoration of growth and differentiation were identical, 0.5 and 2 nM, respectively. Despite the presence of insulin-like growth factor-I (IGF-I) to substitute for supraphysiological concentrations of insulin and to saturate IGF-I receptor, GH was still required to induce terminal differentiation of a maximal number of cells. However, protein kinase C activators such as prostaglandin F2 alpha, phorbol esters and diacylglycerol were able to mimic GH in promoting a maximal mitogenic-adipogenic response, indicating that the ability of GH to induce diacylglycerol production (Doglio et al., 1989; Catalioto et al., 1990) plays a prominent role in this process. Furthermore, in agreement with the fact that the mitoses which precede terminal differentiation of Ob1771 preadipocytes are strictly controlled by cAMP and only modulated by protein kinase C, terminal differentiation of Ob1771 preadipocytes occurred in the absence of GH upon supplementation with high concentrations of carbaprostacyclin, added as a cAMP-elevating agent or with 8-Br-cAMP, added as a cAMP analogue. It is concluded that the control exerted by GH on terminal differentiation of mouse preadipocytes corresponds to a modulating mitogenic effect mediated through protein kinase C activation and leading to a potentiation of the cAMP and IGF-I mitogenic signalling pathways.

Adipose Tissue↗
PubMed1992

[Decrease of postoperative morbidity in coronary surgery using the two internal mammary arteries].

The surgical risk of bilateral internal mammary artery grafting was analyzed in 100 successive patients separated chronologically into two groups. These groups were not statistically different in terms of age, severity of angina, and extent of coronary artery disease. The number of grafts per patient and the time of aortic cross clamping were not statistically different in the two groups. The postoperative mortality was 1% in the 100 patients. The incidence of perioperative myocardial infarction was not statistically different in the two groups. No mediastinal suppuration was observed. The mean postoperative hemorrhage was 633 +/- 558 ml in the first 50 patients and 560 +/- 410 ml for the last 50 patients (p < 0.05). The percentage of patients receiving no homologous blood transfusion was 64% in the first 50 patients and 94% in the last 50 patients. The percentage of phrenic palsy was 36% in the first 50 patients and 6% in the last 50 patients (p < 0.05). With surgical experience, the risk of coronary bypass with bilateral internal mammary artery was lowered and very similar to the surgical risk of conventional aorto-coronary bypass with saphenous veins or one mammary artery.

Adult↗
PubMed1992

[Coronary artery bypass with 2 internal mammary arteries. Early clinical and angiographic results in 100 patients].

One hundred patients underwent coronary revascularisation with both internal mammary arteries between 1987 and 1990. The average age of the patients was 55 years. The left internal mammary was used in 97 of the 100 cases as a pediculated graft to revascularise the left anterior descending (66 cases), left lateral (27 cases) or a bissecting artery (4 cases). The right internal mammary was used as a pediculated graft in 51 cases and as a free graft to revascularise a left lateral (51 cases), left anterior descending (29 cases) or right coronary artery (20 cases). There was one death in the first 30 postoperative days. Morbidity was low with no cases of sternal infection. The average postoperative bleeding was 633 +/- 550 ml per patient. The incidence of phrenic nerve paralysis decreased from 36% in the first 50 patients to 6% in the second 50 patients. Angiography at the 10th postoperative day showed 4 occlusions out of 132 internal mammary arteries opacified (97% patency). Ninety four patients are asymptomatic and have negative exercise stress tests. Mortality and morbidity of coronary surgery using the two internal mammary arteries are therefore the same as those of conventional coronary surgery using saphenous veinar only one internal mammary artery, providing that it is reserved for patients in good general condition, under 65 years of age, without obesity or diabetes. This technique of coronary artery revascularization should provide better long-term results because of the high patency rate of the grafts.

Adult↗
PubMed1992

Human airway secretory cells during development and in mature airway epithelium.

The combined secretions of distinct secretory cells of the airway lining mucosa serve to keep the inspired air moist and free of potentially harmful dust particles, organisms and adsorbed gases. Apart from their role in protecting the respiratory zone of the lung, mucus-secreting cells act as pluripotential stem cells during foetal development and, in the adult, following mucosal injury. The variety of secretory cells include the mucous and serous cells of the surface and glandular epithelium, the non-ciliated bronchiolar (Clara) cell and the less frequent dense-core granulated (neuroendocrine) cell. The last-mentioned is the first type to differentiate at about 10 weeks of gestation; mucus-secreting cells are present from the 13th week of gestation, when mature ciliated cells are already present, and Clara cells begin to mature during the 19th week of human development. The alteration of secretory cell number and chemical composition of their secretions during the second trimester of foetal life is similar to that which occurs in chronic bronchitis in the adult. However, in hypersecretory disease the extent and site of the major change appear to be inappropriate to the defence of the lung.

Epithelial Cells↗
PubMed1992

[Use of extracorporeal circulation oxygenators (CEC) in the European Economic Community (EEC)].

This study analyses the growth of CPB in the EEC. The study situates its position in the world taking into account several indexes such as the Gross National Product and its growth the life expectancy and other technical or economic factors. Only a broad analysis could be performed for Europe to the irregular development of CPB. A more detailed analysis was performed for France thanks to a greater number of data. In this type of study the most important problem is to estimate the relevance and consistency of the data provided either by companies or by other organizations because they can change very quickly.

Cardiopulmonary Bypass↗
PubMed1991

Autocrine control of adipose cell differentiation by prostacyclin and PGF2 alpha.

The mitogenic-adipogenic effect exerted by arachidonic acid, which leads to terminal differentiation of Ob1771 mouse preadipocytes, has been shown to be (i) blocked by cyclooxygenase inhibitors, (ii) mimicked by a stable analogue of prostacyclin (carbaprostacyclin) and (iii) potentiated by PGF2 alpha. Since these prostanoids are known to be synthesized and secreted by preadipocytes, we have proposed that both prostacyclin as the key mediator and PGF2 alpha as a modulator control the expression of terminal events of adipose conversion by means of an autocrine mechanism (Gaillard, D. et al. and Negrel, R. et al. Biochem. J. (1989) 257, 389-397 and 399-405). In order to test this hypothesis, the release of prostacyclin, characterized under the form of its stable degradation product 6-keto-PGF1 alpha, and that of PGF2 alpha have been studied in the culture medium of Ob1771 cells. A striking increase in the release of 6-keto-PGF1 alpha and to a minor degree of PGF2 alpha was observed when cells were exposed to arachidonic acid as shown by using [3H]arachidonic acid prelabelled cells or by radio-immunoassays. Since antagonists of PGF2 alpha and PGI2 receptors were not available, specific antibodies directed against PGF2 alpha and 6 beta-PGI1, another stable analogue of prostacyclin, were added as neutralizing agents in the culture medium. These antibodies were able to counteract the mitogenic-adipogenic effect of arachidonic acid. Prostacyclin and PGF2 alpha thus appear as autocrine mediators in the process of adipose conversion.

Adipose Tissue↗
PubMed1991

Control of terminal differentiation of adipose precursor cells by glucocorticoids.

The role of glucocorticoids on adipose conversion has been studied using confluent Ob1771 mouse preadipose cells maintained in a serum-free culture medium able to support the emergence of early but not that of late markers of differentiation. Under these culture conditions, glucocorticoids play, at physiological concentrations, a permissive role for terminal differentiation, characterized by glycerol-3-phosphate dehydrogenase expression and triacylglycerol accumulation within 12 days, whereas progesterone, testosterone, and estradiol are inactive. Glucocorticoids behave as mitogenic-adipogenic stimuli able to trigger growth-arrested, early marker-expressing cells to enter the terminal phase of the differentiation program and thus appear to mimic the mitogenic-adipogenic activity already described for arachidonic acid and cyclic AMP-elevating agents, especially prostacyclin. When compared to corticosterone alone, exposure of Ob1771 cells to both corticosterone and arachidonic acid leads to an additional increase in the glycerol-3-phosphate dehydrogenase activity and number of differentiated cells; this potentiation is further enhanced when the culture medium is supplemented with the cyclic AMP phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. This suggests indirectly the involvement of prostacyclin as a metabolite of arachidonic acid able to induce cyclic AMP accumulation. In agreement with this hypothesis, it is found that a promoting effect is exerted by corticosterone on the metabolism of arachidonic acid, leading in turn to an increase in the production of prostacyclin. These findings allow a better understanding of the role of glucocorticoids on adipose cell differentiation and explain a posteriori the effectiveness of the combination of dexamethasone-isobutyl-methylxanthine used in innumerable studies.

Adipose Tissue↗
PubMed1991

Late expression of alpha 2-adrenergic-mediated antilipolysis during differentiation of hamster preadipocytes.

In order to study the ontogenesis of the beta- and alpha 2-adrenergic control of lipolysis during the adipose conversion process, a model based on preadipocytes isolated from the stromal-vascular fraction of hamster adipose tissue was developed. When cultured in an ITT (insulin, transferrin, triiodothyronine) medium supplemented with 2% fetal calf serum, adipose precursors differentiated into adipose-like cells. On 8-day-post-confluent differentiating preadipocytes, the rank order of potency of activation of lipolysis by various beta-adrenergic agonists (BRL37344 greater than norepinephrine = isoproterenol greater than epinephrine greater than fenoterol) was equivalent to that determined in mature adipocytes isolated from adult hamster adipose tissue. On 8-day-post-confluent differentiating preadipocytes, phenylisopropyladenosine (A1-adenosine agonist) and prostaglandin E1 evoked a strong antilipolytic response whereas that evoked by UK 14304 and clonidine (alpha 2-adrenergic agonists) remained undetectable at this step of differentiation. The activity of UK 14304 and clonidine only appeared on 20- to 25-day-post-confluent differentiating preadipocytes. They induced dose-dependent antilipolysis with a maximal effect reaching 80-85% inhibition of adenosine deaminase-stimulated lipolysis. Their action was blocked by increased concentrations of different alpha 2-adrenergic antagonists with the following order of potency, RX 821002 greater than phentolamine much greater than yohimbine. This order of potency was similar to that determined on mature adipocytes isolated from adult hamsters. Both the density of the alpha 2-adrenoceptors, identified with the selective alpha 2-adrenergic radioligand [3H]RX-821002 (19 +/- 1 vs. 30 +/- 1 fmol/mg protein: P less than 0.01) and the amount of Gi proteins identified by pertussis toxin-catalyzed ADP-ribosylation (31 +/- 4 vs. 43 +/- 4% of the amount defined in mature fat cells from adult hamsters: P less than 0.05) were significantly increased between 8 days and 20-25 days after confluence, explaining the late emergence of the alpha 2-adrenergic control of lipolysis during preadipocyte differentiation. In conclusion, the late emergence of the alpha 2-adrenergic control of lipolysis, which is also supported by previous data obtained in vivo that demonstrated the age and/or the fat cell size dependence of alpha 2-adrenoreceptor expression in mature adipocytes, allows the alpha 2-adrenoceptor to be considered as a marker of adipocyte hypertrophy.

Adipose Tissue↗
PubMed1991

Comparison of different types of cardioplegia and reperfusion on myocardial metabolism and free radical activity.

Current techniques of myocardial protection during global ischemia include hypothermia, cardioplegic arrest and controlled reperfusion. To compare different types of cardioplegia and reperfusion techniques we measured the levels of adenine nucleotides and malondialdehyde (MDA, as free radical activity) in 33 patients undergoing heart surgery. The patients were randomized in three groups according to the characteristics of cardioplegia and reperfusion: cold blood cardioplegia with unmodified blood reperfusion (control group, 11 patients), crystalloid cardioplegia and reperfusion (Hôpital Lariboisière protocol, 11 patients) and crystalloid cardioplegia with allopurinol enriched blood reperfusion (Hôpital Broussais protocol, 11 patients). Myocardial biopsy specimens were obtained before cardioplegic arrest (preischemic values), at the end of ischemia and after 30 minutes of reperfusion. Biopsy specimens were analyzed by high performance liquid chromatography for levels of adenine nucleotides and MDA. In the three groups, the preischemic values of adenine nucleotides and MDA were not significantly different. For AMP and ADP concentrations neither treatment nor biopsy-time effects appeared. ATP concentration decreased significantly with biopsy-time without specific treatment effect. For MDA concentration neither treatment nor biopsy-time effects were observed. This study suggests that there is no statistically significant difference between any of the three cardioplegia and reperfusion techniques for either ATP or MDA; the three reperfusion techniques limit the free radical activity but do not prevent the fall in high energy phosphates.

Adenine Nucleotides↗
PubMed1991

[Value of coronary reperfusion in cases of very low cardiac output following coronary artery bypass grafts].

From January 1986 to December 1988, 244 patients had a coronary artery revascularization at St Joseph Hospital. Four patients (1.8%) died in post operative time (less than 30 days). None died directly from cardiogenic shock. Five patients had a severe low cardiac output (2 h to 48 h post-op) and needed cardiac resuscitation. These patients were immediately taken to the operating room. The coronary bypasses were explored (2 technical errors corrected), the metabolic disorders were treated and a coronary reperfusion was done with the Buckberg's technique. All the patients could be weaned from cardiopulmonary bypass, two with intra aortic balloon pumping. One patient died of digestive complication the 10th postoperative day. The four other patients survived and are in good clinical condition. The severe low cardiac output after coronary revascularization can be reversible with resuscitation in operating room, short assistance, and coronary reperfusion.

Aged↗
PubMed1990

Functional activity of ciliated outgrowths from cultured human nasal and tracheal epithelia.

Primary cultures of respiratory epithelium were produced as outgrowths from human fetal and adult tracheal and nasal polyp explants. Video recordings of the epithelial cell outgrowths were carried out after 5 days of culture and the ciliary beating frequency was analyzed by using a video technique. Uniform fields of differentiated ciliated cells were observed near the edge of the explant. In the transition region of the outgrowth from the explant to the outgrowth periphery, isolated ciliated cells were present, as well as cells with fused cilia. The ciliary beating frequency of the outgrowth of well-differentiated ciliated cells (13.5 +/- 1.4 Hz) was significantly higher (p less than 0.001) than the beating frequency of both the explant (11.9 +/- 0.7 Hz) and the ciliated cells with fused cilia (9.8 +/- 1.7 Hz). The same differentiation stages and functional activities were observed in the outgrowth cultures, whatever their origin. These in vitro models are comparable with each other and therefore could be useful for studying the ciliogenesis and functional activity of the human respiratory epithelium.

Cilia↗
PubMed1990

[Mucin histochemistry of the digestive tract in the human fetus].

Mucin secretion was studied in the gastric, intestinal, left colic and/or rectal mucosa of 42 human fetuses ranging in age from 10 to 41 weeks of gestation (menstrual age). Several histochemical techniques were used at different pH to demonstrate neutral mucins, sialomucins and sulphomucins (Periodic Acid Shiff (PAS) with and without amylase, Alcian Blue (BA) pH 2.5, pH 1 with and without hyaluronidase, BA/PAS pH 2.5 and High Iron Diamine (HID)/BA). The gastric mucosa showed mixed neutral/acid secretions during the second term. The neutral mucins increased during the 3rd term when acid mucins fell and represented only 20 percent of the secretions by the end of gestation, as during the neonatal period. These mixed secretions closely reassembled the intestinal metaplasia described in inflammatory or tumoral lesions of the stomach. The intestinal mucosa secreted mucins as early as 10 weeks before the gastric and rectal mucosa. There were neutral and acid mucins, but unlike in adults, the sulphomucins were secreted by the goblet cells of the villous and crypt epithelia. The secretions of the rectal mucosa were acid and the sulphomucins increased in quantity from 14 to 26 weeks of gestation. The HID positive sulphomucins diffused into the meconium, and probably modified the physical and chemical properties of meconium and influenced anal continence.

Age Factors↗
PubMed1990

Intrauterine versus postnatal repair of created pulmonary artery stenosis in the lamb. Morphologic comparison.

Experimental lamb models were used for intrauterine creation of pulmonary artery stenosis and later intrauterine repair or postnatal repair. Intrauterine creation of pulmonary artery stenosis was performed in 23 fetal lambs at 90 +/- 1 days of gestation. Eight lambs underwent intrauterine repair of pulmonary artery stenosis at 135 +/- 1 days of gestation and were studied 110 +/- 13 days after repair. Seven lambs underwent postnatal repair at 57 +/- 9 days after birth and were studied 162 +/- 32 days after repair. Eight fetal lambs with unrepaired pulmonary artery stenosis were studied 89 +/- 18 days after birth. All study lambs were compared with normal control lambs. The systolic right ventricular pressure was significantly higher after unrepaired stenosis (78.6 +/- 6.8 mm Hg) than in other lambs, but there was no statistically significant difference after intrauterine repair (23.3 +/- 2.9 mm Hg), postnatal repair (25.9 +/- 3.4 mm Hg), and normal lambs (21.6 +/- 1.1 mm Hg). The systolic pulmonary artery pressure was also not statistically different in these three groups. The weight measurements were age-adjusted for comparison of postnatal and intrauterine repair with normal lambs. The adjusted heart weights were similar in the three groups. The comparison of the adjusted heart weight/adjusted body weight ratio (10(-3) showed a significantly higher ratio in postnatal repair (7.4 +/- 0.1) than in intrauterine repair (6.1 +/- 0.1). The adjusted right ventricular weight/adjusted left ventricular weight ratio was significantly higher in the postnatal repair group (0.71 +/- 0.01) than in both the intrauterine repair group (0.59 +/- 0.01) and normal lambs (0.59 +/- 0.01). The transverse myocyte diameter was not statistically different in all groups of animals and there were no ultrastructural changes even when the pulmonary stenosis was unrepaired. We conclude that intrauterine repair was more satisfactory than postnatal repair in terms of age-adjusted heart weight results, but we did not find any advantages of intrauterine repair in terms of histologic and ultrastructural changes.

Animals↗
PubMed1990

[Peroperative autologous transfusion in cardiac surgery. Course, medical and economic evaluation. Prospects].

The authors report their experience since 1979 in the utilization of a system for blood salvaging in cardiac surgery. An initial comparative study showed that the patient group in which blood salvaging was used, received only 0.8 unit of red cells per patient and per hospitalisation and 50% of patients required no transfusion. In the patients receiving ATS, postoperative bleeding was significantly decreased. To confirm the advantages of the technique, a group of 200 patients was studied, consisting of 28 children and 172 adults. Hemodilution was difficult to perform in children weighing less than 15 kg. Nevertheless, ATS allowed for a significant reduction in the number of red cell units transfused. In the adult group, homologous blood consumption was 0.3 unit per patient and per hospitalization. 83% of the patients received no red cells, and 93% had no need for FFP. This reduction in homologous blood transfusion ensures a reduction in the transfusional risk. An improvement in these results will be obtained by a better organization of preoperative ATS and of the retrieval of postoperative blood.

Adolescent↗