Intermediate-term results after en bloc double-lung transplantation with bronchial arterial revascularization

AbstractObjective: Between May 1990 and January 1994, 18 patients underwent en bloc double-lung transplantation with tracheal anastomosis and bronchial arterial revascularization. Because at that time it was already suggested that chronic ischemia could be a contributing factor in occurrence of obliterative bronchiolitis, the purpose of this study was to evaluate, with a follow-up ranging from 22 to 69 months, the midterm effects of bronchial arterial revascularization on development of obliterative bronchiolitis. Results: Results were assessed according to tracheal healing, functional results, rejection, infection, and incidence of obliterative bronchiolitis. There were no intraoperative deaths or reexplorations for bleeding related to bronchial arterial revascularization, but there were three hospital deaths and five late deaths, two of them related to obliterative bronchiolitis. According to the criteria previously defined, tracheal healing was assessed as grade I, IIa, or IIb in 17 patients and grade IIIa in only one patient. Early angiography (postoperative days 20 to 40) demonstrated a patent graft in 11 of the 14 patients in whom follow-up information was obtained. Ten patients are currently alive with a 43-month mean follow-up. Among the 15 patients surviving more than 1 year, functional results have been excellent except in five in whom obliterative bronchiolitis has developed and who had an early or late graft thrombosis. Furthermore, those patients had a significantly higher incidence of late acute rejection (p < 0.02), cytomegalovirus disease (p < 0.006), and bronchitis episodes (p < 0.0008) than patients free from obliterative bronchiolitis. Conclusion: We conclude that besides its immediate beneficial effect on tracheal healing, long-lasting revascularization was, at least in this small series, associated with an absence of obliterative bronchiolitis, thus suggesting but not yet proving the possible role of chronic ischemia in this multifactorial disease. (J THORAC CARDIOVASC SURG 1996;112:1292-300

Morbidité post-opératoire précoce de l'anastomose pancréato-gastrique après duodénopancréatectomies céphaliques (étude rétrospective sur 10 ans à propos de 85 cas avec la même technique opératoire d'intussusception du moignon pancréatique au CHU de Poitiers)

POITIERS-BU Médecine pharmacie (861942103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

The Inhibitor of Apoptosis (IAPs) in Adaptive Response to Cellular Stress

Cells are constantly exposed to endogenous and exogenous cellular injuries. They cope with stressful stimuli by adapting their metabolism and activating various “guardian molecules.” These pro-survival factors protect essential cell constituents, prevent cell death, and possibly repair cellular damages. The Inhibitor of Apoptosis (IAPs) proteins display both anti-apoptotic and pro-survival properties and their expression can be induced by a variety of cellular stress such as hypoxia, endoplasmic reticular stress and DNA damage. Thus, IAPs can confer tolerance to cellular stress. This review presents the anti-apoptotic and survival functions of IAPs and their role in the adaptive response to cellular stress. The involvement of IAPs in human physiology and diseases in connection with a breakdown of cellular homeostasis will be discussed

Les IAP au cœur de la signalisation NF-κB

La fonction des IAP (inhibitors of apoptosis proteins) a longtemps été restreinte à une inhibition de l’apoptose, en raison de leur capacité à lier directement certaines caspases. La mise en évidence d’altérations de l’expression de ces protéines dans des échantillons tumoraux en a fait des cibles privilégiées pour les traitements anticancéreux. De nombreuses molécules ont été développées dans le but d’inhiber la capacité de liaison des IAP avec les caspases. De façon inattendue, ces molécules altèrent considérablement la signalisation NF-κB. Dans cette revue, nous discuterons des travaux récents montrant un rôle central de cIAP1, cIAP2 et XIAP dans la régulation des voies de signalisation conduisant à une activation de NF-κB

Inhibition of Apoptosis by Amphiregulin via an Insulin-like Growth Factor-1 Receptor-dependent Pathway in Non-small Cell Lung Cancer Cell Lines

International audienceSeveral abnormalities in the insulin-like growth factor -1 (IGF1) and erbB receptors pathways stimulate the growth and survival of lung cancer cells, but their mechanisms of action and cooperation are poorly understood. In this report, we have identified a new mechanism of apoptosis inhibition by amphiregulin through an IGF1-dependent survival pathway in non-small cell lung cancer (NSCLC) cells: amphiregulin activates the IGF1 receptor that in turn induces the secretion of am-phiregulin and IGF1. In the absence of serum, the NSCLC cell line H358 resists apoptosis and secretes factors protecting the NSCLC cell line H322 from serum deprivation apoptosis. IGF1 receptor inhibitor AG1024 as well as epidermal growth factor receptor inhibitors AG556 and ZD1839 restore apoptosis in H322 cells cultured in H358-conditioned medium. Accordingly, the an-ti-apoptotic activity of H358-conditioned medium is completely abolished after incubation with anti-amphi-regulin neutralizing antibody and only partially with anti-IGF1 neutralizing antibody. H358-conditioned medium and amphiregulin induce IGF1 receptor phospho-rylation in H322 cells, which is prevented by anti-amphi-regulin neutralizing antibody but not by AG556 or ZD1839. H358 cells secrete a high level of amphiregulin that, in combination with IGF1, prevents serum deprivation apoptosis. Finally, IGF1 receptor inhibitor blocks amphiregulin and IGF1 release by H358 cells

Caffeine Sensitizes Human H358 Cell Line to p53-mediated Apoptosis by Inducing Mitochondrial Translocation and Conformational Change of BAX Protein

International audienceThe mechanisms involved in p53-mediated cell death remain controversial. In the present study, we investigated this cell death pathway by stably transfecting the p53-null H358 cell line with a tetracycline-dependent wild type p53-expressing vector. Restoration of p53 triggered a G 2 /M cell cycle arrest and enhanced BAX protein expression, without inducing apoptosis or potentiating the cytotoxic effect of etoposide, vincristine, and cis-platinum. Accordingly, overexpression of BAX in H358 cells, through stable transfection of a tetracycline-regulated expression vector, did not induce cell death. Interestingly, the methylxanthine caffeine (4 mM) promoted the translocation of BAX from the cytosol to the mitochondria. In the setting of an overexpression of BAX, caffeine induced a conformational change of the protein and apoptosis. The consequences of caffeine were independent of its cell cycle-related activities. All together, caffeine synergizes with p53 for inducing cell death through a cell cycle-independent mechanism, involving mitochondrial translocation and conforma-tional change of BAX protein

Cooperation of amphiregulin and insulin-like growth factor-1 inhibits Bax- and Bad-mediated apoptosis via a protein kinase C-dependent pathway in non-small cell lung cancer cells.: Bad and Bax inactivation by AR/IGF1-PKC-dependent pathway

International audienceAmphiregulin (AR) and insulin-like growth factor-1 (IGF1) are growth factors known to promote non-small cell lung cancer (NSCLC) survival. We have previously published that 1) AR and IGF1, secreted by H358 NSCLC cells, cooperate to protect those cells and H322 NSCLC cells from serum-starved apoptosis; 2) H358 cells resist Bax-induced apoptosis through an inhibition of Bax conformational change. We show here that the antiapoptotic activity of the AR/IGF1 combination is specifically abolished by the PKC inhibitors calphostin C and staurosporine, but not by the MAPK and phosphatidylinositol 3-kinase inhibitors PD98059 and wortmannin, suggesting the involvement of a PKC-dependent and MAPK- and phosphatidylinositol 3-kinase-independent survival pathway. The PKCdelta inhibitor rottlerin restores apoptosis induced by serum deprivation. In addition, phosphorylation of PKCdelta and PKCzeta/lambda, but not of PKCalpha/beta(II), increases in serum-starved H358 cells and in H322 cells treated with an AR/IGF1 combination and is blocked by calphostin C. The combination of AR and IGF1 increases p90(rsk) and Bad phosphorylation as well as inhibiting the conformational change of Bax by a PKC-dependent mechanism. Finally, PKCdelta, PKCzeta, or p90(rsk) small interfering RNAs block the antiapoptotic activity of AR/IGF1 combination but have no effect on partial apoptosis inhibition observed with each factor used alone. Constitutively active PKC expression inhibits serum deprivation-induced apoptosis, whereas a catalytically inactive form of p90(rsk) restores it. Thus, AR and IGF1 cooperate to prevent apoptosis by activating a specific PKC-p90(rsk)-dependent pathway, which leads to Bad and Bax inactivation. This signaling pathway is different to that used by single factor

Thermoplastic filled with magnetocaloric powder

International audienceMagnetic refrigeration is an innovative and promising alternative to traditional refrigeration systems. This technology does not require refrigeration gases and offers a high thermodynamic efficiency, reducing the global environmental impact associatedwith the process. However, the production ofmagnetocaloric components used as regenerators in magnetic refrigeration systems is a significant challenge. This work consists of developing an innovative process to obtainmagnetocaloric components by powder injection or extrusion moulding. A component containing up to 91.5 wt.% magnetocaloric powder was obtained using a gas atomised magnetocaloric powder La–Fe–Si alloy patented by Erasteel. The powder is first mixed with a thermoplastic polymer to obtain a “ready to shape” feedstock. Then, the feedstock is either injected or extruded to obtain the magnetocaloric component. Characterisations of the thermo-physical and mechanical properties are carried out during all stages of processing, from pure powder to injected parts. A study on the modification of the Curie temperature as aresult of dehydrogenation was performed during each processing stages. Good processability was demonstrated for the highly loaded feedstock and conservation of the magnetocaloric properties during the process. Finally, the process does not induce any mass loss and allows the production of stable pieces containing a giant magnetocaloric effect