[Angioneurotic edema].
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Anabolic Agents↗
Biomedical subjects
F André
Publications and source records attributed to F André.
Insulin-like growth factor-I protects colon cancer cells from death factor-induced apoptosis by potentiating tumor necrosis factor alpha-induced mitogen-activated protein kinase and nuclear factor kappaB signaling pathways.
Resistance of cancer cells against apoptosis induced by death factors contributes to the limited efficiency of immune- and drug-induced destruction of tumors. We report here that insulin and insulin-like growth factor-I (IGF-I) fully protect HT29-D4 colon carcinoma cells from IFN-gamma/tumor necrosis factor-alpha (TNF) induced apoptosis. Survival signaling initiated by IGF-I was not dependent on the canonical survival pathway involving phosphatidylinositol 3'-kinase. In addition, neither pp70(S6K) nor protein kinase C conveyed IGF-I antiapoptotic function. Inhibition of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) with the MAPK/ERK kinase inhibitor PD098059 and MAPK/p38 with the specific inhibitor SB203580 partially reversed, in a nonadditive manner, the IGF-I survival effect. Inhibition of nuclear factor kappaB (NF-kappaB) activity by preventing degradation of the inhibitor of NF-kappaB (IkappaB-alpha) with BAY 11-7082 also blocked in part the IGF-I antiapoptotic effect. However, the complete reversal of the IGF-I effect was obtained only when NF-kappaB and either MAPK/ERK or MAPK/p38 were inhibited together. Because these pathways are also those used by TNF to signal inflammation and survival, these data point to a cross talk between IGF-I- and TNF-induced signaling. We further report that TNF-induced IL-8 production was indeed strongly enhanced upon IGF-I addition, and this effect was totally abrogated by both MAPK and NF-kappaB inhibitors. The IGF-I antiapoptotic function was stimulus-dependent because Fas- and IFN/Fas-induced apoptosis was not efficiently inhibited by IGF-I. This was correlated with the weak ability of Fas ligation to enhance IL-8 production in the presence or absence of IGF-I. These findings indicate that the antiapoptotic function of IGF-I in HT29-D4 cells is based on the enhancement of the survival pathways initiated by TNF, but not Fas, and mediated by MAPK/p38, MAPK/ERK, and NF-kappaB, which act in concert to suppress the proapoptotic signals. In agreement with this model, we show that it was possible to render HT29-D4 cells resistant to Fas-induced apoptosis provided that IGF-I and TNF receptors were activated simultaneously.
Adenocarcinoma↗
Hepatitis B epidemiology in Asia, the Middle East and Africa.
Asia and Africa have previously been classified as areas of high endemicity for hepatitis B virus (HBV), but in some countries highly effective vaccination programmes have shifted this pattern towards intermediate or low endemicity. Thus, China is now the only country in Asia where HBV endemicity is high. Countries with intermediate endemicity include India, Korea, the Philippines, Taiwan and Thailand, and those with low endemicity include Japan, Pakistan, Bangladesh, Singapore, Sri Lanka and Malaysia. Most countries in Africa have high HBV endemicity, with the exceptions of Tunisia and Morocco, which have intermediate endemicity. Zambia has borderline intermediate/high endemicity. In the Middle East, Bahrain, Iran, Israel and Kuwait are areas of low endemicity, Cyprus, Iraq and the United Arab Emirates have intermediate endemicity, and Egypt, Jordan, Oman, Palestine, Yemen and Saudi Arabia have high endemicity. All of these Middle East countries reach a large proportion of their population with hepatitis B vaccination, which is reducing the infection rate, particularly in Saudi Arabia. The vaccination programme in Taiwan has also greatly reduced the HBV infection rate. Future vaccination programmes must take into account the mode of transmission of HBV, the healthcare infrastructure to deliver vaccination, and the socioeconomic and political factors in each individual country, to determine the most cost-effective way of infection control.
Africa↗
Ultra trace detection of a wide range of anabolic steroids in meat by gas chromatography coupled to mass spectrometry.
The control on use of anabolic agents in meat producing animals is generally based on urine, faeces or hair analysis. This exercise, which is usually performed in slaughterhouses or on farms, is not relevant to imported carcasses or retail meat. A single sensitive method for a wide range of anabolic steroids was developed. After extraction of the lyophilised meat, enzymatic hydrolysis was used for deconjugation. Solid-phase extraction on a polymeric stationary phase was performed prior to hydrolysis of ester residues under alkaline conditions. Liquid-liquid partitioning was used to separate the analytes into two main categories: phenol containing molecules, such as phenolic steroids, resorcylic acid lactones and stilbenes, and delta4-3-one containing molecules, such as most androgens and progestagens. Solid-phase extraction on silica columns was performed before applying a specific derivatisation for each compound sub-group. The combination of high-resolution chromatography with a quadrupole mass spectrometer permitted detection of 23 steroids in the 5-100 ng/kg range. Ion chromatograms for residue positive samples are shown and discussed.
Anabolic Agents↗
Collision-induced dissociation of corticosteroids in electrospray tandem mass spectrometry and development of a screening method by high performance liquid chromatography/tandem mass spectrometry.
A screening method based on liquid chromatography/electrospray tandem mass spectrometry was developed in order to control the illegal use of corticosteroids as growth promoters in cattle. The objective was the detection of low residue levels of corticosteroids or metabolites in biological matrices. Relative to other studies published on this subject, the present work focused on enhancing specificity and sensitivity. Firstly, fragmentation of corticosteroids by collision-induced dissociation was studied. In positive mode, the losses of H(2)O for each hydroxyl group fixed on the molecule, as well as the loss of HF or HCl for halogenated compounds, were observed. For higher collision energy, fragmentations in the B, C and D rings were induced. The negative mode was found to be more specific, inducing a cleavage of the C(20)-C(21) bond with concomitant loss of formaldehyde (CH(2)O). Secondly, three acquisition methods in the negative mode were studied and evaluated, recorded signals being the parent ion [M + acetate](-) and the two daughter ions, [M - H](-) and [M - H - CH(2)O](-). For dexamethasone, MS/MS instrumental detection limits of fragment ion and neutral loss scans, and of multiple reaction monitoring (MRM), were 250, 20 and 5 pg injected, respectively. The MRM method was then evaluated with the objective of use for the detection of corticosteroid residues in biological samples (urine, hair, muscle) and for a metabolism study.
Acetates↗
The growing teratoma syndrome: results of therapy and long-term follow-up of 33 patients.
Growing teratoma syndrome (GTS) is defined as an increase in tumour size during or after chemotherapy for germ cell tumour (GCT), and only mature teratoma at histological analysis of the resected tumour specimen. Between 1985 and 1997, 30 male patients fulfilling GTS criteria were included in the present study. 3 female patients were also included but analysed separately. A mature teratoma component was found in 86% of the primary GCT. 3 male patients (10%) had a complication at diagnosis of GTS. One male patient (4%) having undergone complete resection (n=24) had a recurrent GTS, compared with all but 1 patient (83%) in whom resection was partial (n=6) (P<0.001). 2 (8%) and 3 (50%) male patients treated with complete and partial resection subsequently developed a malignant NSGCT respectively (P=0.01). 2 female patients treated with partial resection presented a recurrent GTS. One of them died of this recurrent GTS. GTS is an entity in its own right with respect to complications and the natural history of the disease. Complete surgical resection is the treatment of choice for GTS.
Adolescent↗
Phase I study of cinchonine, a multidrug resistance reversing agent, combined with the CHVP regimen in relapsed and refractory lymphoproliferative syndromes.
Overexpression of P-glycoprotein (P-gp) in cancer cells reduces intracellular accumulation of various anticancer drugs including anthracyclines and vinca alkaloids. This multidrug resistance (MDR) phenotype can be reversed in vitro by a number of non-cytotoxic drugs. We have identified the quinine's isomer cinchonine as a potent MDR reversing agent, both in vitro and in animal models. Here, we report an open phase I dose escalation trial in patients with refractory or relapsed malignant lymphoid diseases. Cinchonine dihydrochloride was administered by continuous i.v. infusion for 48 h and escalated over five dose levels ranging from 15 to 35 mg/kg/d. Cinchonine infusion started 24 h before i.v. doxorubicin (25 mg/m2), vinblastine (6 mg/m2), cyclophosphamide (600 mg/m2) and methylprednisolone (1 mg/kg/d) (CHVP regimen) and lasted for 24 h after chemotherapy infusion. Thirty-four patients received 87 cycles of CHVP/cinchonine. The MTD of cinchonine administered by continuous i.v. infusion was 30 mg/kg/d. Prolonged cardiac repolarization was the main dose-limiting toxicity. No ventricular arrhythmia including 'torsade de pointes' was observed. An MDR reversing activity was identified in the serum from every patient and correlated with cinchonine serum level. When infused at 30 mg/kg/d, cinchonine demonstrated a limited influence on doxorubicin pharmacokinetic. We conclude that i.v. infusion of cinchonine might be started 12 h before MDR-related chemotherapy infusion and requires continuous cardiac monitoring but no reduction of cytotoxic drug doses.
Adult↗
Enzymatic hydrolysis of conjugated steroid metabolites: search for optimum conditions using response surface methodology.
The optimum conditions for hydrolysing conjugated metabolites of steroid hormones in bovine urine were performed with Helix pomatia juice, beta-glucuronidase from bovine liver and preparations of limpets and abalone entrails using response surface methodology. The experimental design and empirical modelling used allowed us to assess the main effects of factors (time, temperature, pH and enzyme quantity) and to predict the optimum conditions for each enzyme preparation. Confirmatory experiments were applied to check the predicted values and to validate the model. The comparison of the enzyme preparation efficiency for various conjugate steroids and the study of possible by-product synthesis led us to select abalone entrails to hydrolyse natural dehydroepiandrosterone, etiocholanolone, epitestosterone; 17 alpha-estradiol and estrone in bovine urine. The optimum conditions were found to be 20 h at 42 degrees C with the pH adjusted to 5.2 and using 12,000 units of enzyme preparation.
Anabolic Agents↗
[Antitumor cellular immunotherapy: the breakthrough of dendritic cells].
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Animals↗
Anticoagulant activity and pharmacokinetic properties of a sub-cutaneously administered mixed micellar formulation of argatroban in experimental animals.
We have studied the anticoagulant properties of a novel mixed micellar formulation containing 14 mg/ml argatroban administered by the sub-cutaneous (s.c.) route to rats, rabbits, dogs and primates. Blood samples were taken at various times post-treatment for the determination of the thrombin time (TT), Ecarin clotting time (ECT) and the activated partial thromboplastin time (aPTT). Plasma levels of argatroban were determined in the dog and primate. Mixed micelles alone (0.15 M sodium glycocholate and 0.15 M egg lecithin) were without effect on the clotting parameters. The mixed micellar formulation of argatroban dose-dependently increased all three clotting parameters in the rat (1-4 mg/kg), the rabbit (1 and 2 mg/kg), the dog (1 and 2 mg/kg) and the primate (0.25 and 0.5 mg/kg). In each case the TT was the most sensitive parameter, followed by the ECT and the aPTT. The duration of action of argatroban in each species was dose dependent and varied from 3 h in the rat to 6 h in the dog. In the latter, the mixed micelle formulation had a significantly increased plasma half-life and mean residence time without affecting the overall area under the curve. The increases in the clotting time were strongly correlated with the plasma levels of argatroban and were linear across the range of concentrations obtained in the dog and the primate, although the aPTT plasma concentration response curve was very flat. Species differences were noted between the increase in clotting time for a given plasma concentration, with the primate being more sensitive than the dog (e.g. 4.7 times more so in terms of the ECT). Thus, a mixed micellar formulation of argatroban, which markedly enhances its solubility, could be useful as a potential anticoagulant for sub-cutaneous administration.
Animals↗
[L'oncologie médicale : le point de vue des internes de spécialités]
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Journal Article↗
[Medical oncology: the point of view of specialty interns].
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France↗
[Randomized comparison of 4F and 6F catheters for diagnostic coronary angiographies via the femoral approach].
The use of 6F catheters has been validated for coronary angiography. The use of small-caliber catheters is a more recent development. The aim of this study was to assess the feasibility, the cost and complications of coronary angiography using the femoral approach with 4F catheters. The authors undertook a randomized prospective study of 4F Care Infiniti catheters (N = 100) and 6F Spertorque Plus catheters (N = 100) in hospitalised patients. Criteria of non-inclusion were valvular pathology, acute myocardial infarction, aorto-coronary bypass or aorto-femoral bypass procedures. No statistical difference was observed between the two groups with respect to feasibility, to duration of the procedure, or of irradiation or to cost. The quality of the angiograms was good except in one patient in the 4F group; 4 patients in the 6F group required a 4F catheter to complete their examination. Left ventricular catheterisation was more difficult with 4F catheters (p = 0.016). Use of 4F catheters was associated with injection of significantly less contrast (p = 0.00007), reduced the duration of compression (p < 10(-6)) and its complications (p = 0.004). The authors conclude that 4F catheters are safe and well tolerated. They are associated with less patient morbidity, without any loss in quality of the angiogrammes. Other studies in valvular heart disease and after coronary bypass surgery should lead to the generalisation of their use in all coronary patients.
Aged↗
Integrins and E-cadherin cooperate with IGF-I to induce migration of epithelial colonic cells.
Although the detailed mechanisms of cell migration remain largely unknown, it is now clear that growth factors and cell adhesion molecules are crucial for this process. We have shown that type I insulin-like growth factor (IGF-I) promotes migration of human colonic tumour cells. Since morphological analysis suggested an involvement of adhesion molecules, we have now examined the role of integrins (cell-matrix adhesion molecules) and E-cadherin/catenins complex (cell-cell adhesion molecules) in the IGF-I-induced migration. Using a monolayer wounding assay, we have determined that, except for alpha2beta1, all of the integrins expressed in HT29-D4 cells are involved in the induced cell migration. Immunofluorescence studies revealed that upon IGF-I stimulation the integrins reorganized at the leading edge of migrating cells. We also demonstrate that E-cadherin is involved in cell migration. A rapid tyrosine phosphorylation of E-cadherin and beta-catenin was detected upon IGF-I stimulation. Tyrosine phosphorylation was associated with reduced membranous expression of E-cadherin and promotion of cell motility, suggesting a regulation of the E-cadherin/catenins complex. This effect can be reversed by incubating cells with tyrosine kinase inhibitors. Taken together, our results suggest that IGF-I promotes colonic cell migration through reorganization of integrin receptors and through modulation of E-cadherin/catenins complex function.
Antibodies, Monoclonal↗
Evidence for the presence of endogenous 19-norandrosterone in human urine.
In 1997, in the scope of antidoping control in sport, a not inconsiderable number of urine analysed by official laboratories revealed the presence of 19-nortestosterone (19-NT: 17beta-hydroxyestr-4-en-3-one) metabolites: 19-norandrosterone (19-NA: 3alpha-hydroxy-5alpha-estran-17-one) and 19-noretiocholanolone (19-NE: 3alpha-hydroxy-5beta-estran-17-one). These repeated results on a short period of time generated some investigations and especially the verification of the possible production of these metabolites by an unknown endogenous route in adult entire male. Some experiences were led on different persons known to be non-treated with steroids and more precisely with nandrolone. Extractive methods were developed focusing on their selectivity, i.e. searching to eliminate at best matrix interferences from the target analytes. Gas chromatography coupled to mass spectrometry (quadrupole and magnetic instruments) was used to detect, identify and quantify the suspected signals. Two types of derivatization (TMS and TBDMS), a semi-preparative HPLC as well as co-chromatography proved unambiguously the presence, in more than 50% of the analysed urine (n = 40), of 19-NA at concentrations between 0.05 and 0.60 ng/ml. 19-NE was not detected with the developed methods (LOD<0.02 ng/ml). Experiments led on athletes showed that after a prolonged intense effort, the 19-NA concentration can be increased by a factor varying between 2 and 4. Even if some complementary researches have to be done in order to determine the maximal physiological level of 19-NA and 19-NE, these results should considerably change the strategy of antidoping laboratories.
Adult↗
Kinetic analysis of tentoxin binding to chloroplast F1-ATPase. A model for the overactivation process.
The mechanism of action of tentoxin on the soluble part (chloroplast F1 H+-ATPase; CF1) of chloroplast ATP synthase was analyzed in the light of new kinetic and equilibrium experiments. Investigations were done regarding the functional state of the enzyme (activation, bound nucleotide, catalytic turnover). Dialysis and binding data, obtained with 14C-tentoxin, fully confirmed the existence of two tentoxin binding sites of distinct dissociation constants consistent with the observed Kinhibition and Koveractivation. This strongly supports a two-site model of tentoxin action on CF1. Kinetic and thermodynamic parameters of tentoxin binding to the first site (Ki = 10 nM; kon = 4.7 x 10(4) s-1.M-1) were determined from time-resolved activity assays. Tentoxin binding to the high affinity site was found independent on the catalytic state of the enzyme. The analysis of the kinetics of tentoxin binding on the low affinity site of the enzyme showed strong evidence for an interaction between this site and the nucleotide binding sites and revealed a complex relationship between the catalytic state and the reactivation process. New catalytic states of CF1 devoid of epsilon-subunit were detected: a transient overstimulated state, and a dead end complex unable to bind a second tentoxin molecule. Our experiments led to a kinetic model for the reactivation phenomenon for which rate constants were determined. The implications of this model are discussed in relation to the previous mechanistic hypotheses on the effect of tentoxin.
Chloroplasts↗
Protein kinases C-gamma and -delta are involved in insulin-like growth factor I-induced migration of colonic epithelial cells.
BACKGROUND & AIMS: The mechanisms by which epithelial cells migrate during the repair of damaged colonic mucosa are poorly understood. This study investigated the insulin-like growth factor I (IGF-I) signaling pathway leading to HT29-D4 human colonic epithelial cell line migration. METHODS: IGF-stimulated cell migration was determined using a wound model in the presence or absence of kinase inhibitors. Activation of protein kinase C (PKC) was determined by immunodetection. RESULTS: IGF-I and insulin induce cell migration without affecting cell proliferation through their cognate receptors. Des(1-3)-IGF-I, a truncated analogue of IGF-I, was more potent than IGF-I, suggesting that IGF-binding proteins secreted in the medium modulated IGF-I-induced cell migration. Inhibition of phosphatidylinositol 3-kinase, PKC, and mitogen-activated protein kinases eliminated cell restitution. Long-term exposure of cells to phorbol myristate acetate caused the depletion of PKC-delta and -gamma and prevented also IGF-I-induced cell motility. IGF-I also induced activation of PKC-delta and -gamma only. CONCLUSIONS: IGF-I stimulates colonic restitution through the activation of multiple signaling pathways including activation of phosphatidylinositol 3-kinase, PKC-delta and -gamma, and mitogen-activated protein kinases.
Calcium-Calmodulin-Dependent Protein Kinases↗
Cdx1 promotes differentiation in a rat intestinal epithelial cell line.
BACKGROUND & AIMS: Homeobox genes are involved in establishing and maintaining differentiated patterns in adult tissues. Cdx1 might carry out that function in the intestinal epithelium because its expression is specific to that tissue and increases during development. METHODS: Cdx1 expression was induced in IEC-6 intestinal epithelial cells by stable transfection, and subsequent changes in cell growth, resistance to apoptosis, migration, and differentiation were monitored. RESULTS: Compared with control, IEC-6/Cdx1 cells proliferated more rapidly, were more resistant to apoptosis, and migrated 3-4 times faster, as shown by an in vitro wound assay. IEC-6/Cdx1 cells in culture formed multilayers. Morphology of the top layer was similar to that of columnar epithelium, with cells showing typical features of differentiated enterocytes, including complex junctions and well-developed microvilli with glycocalix. Expression of 2 markers of enterocyte differentiation, aminopeptidase N and villin, was induced in IEC-6/Cdx1 cells. Aminopeptidase N was targeted to the basolateral membrane, and villin was localized to the cytoplasm. Actin filaments, which were mostly present in transcytoplasmic stress fibers in control cells, were redistributed to the cortex in Cdx1-transfected cells. CONCLUSIONS: Cdx1 expression in IEC-6 cells induces phenotypic changes characteristic of differentiating enterocytes, suggesting an important role for Cdx1 in the transition from stem cells to proliferating/transit cells.
Actins↗