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Biomedical subjects

F Andre

Publications and source records attributed to F Andre.

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

Migration properties of the human ovarian adenocarcinoma cell line IGROV1: importance of alpha(v)beta3 integrins and vitronectin.

Cell migration of ovarian tumoral cells is essential for cell dissemination and for invasion of the submesothelial extracellular matrix (ECM). We have conducted a study of the migratory properties of an ovarian adenocarcinoma cell line (IGROV1) by using 2 distinct methods for the evaluation of cell migration. We found that in a short-term transfilter migration assay, IGROV1 cells migrated toward vitronectin, fibronectin, type IV collagen and laminin in an integrin-dependent manner. When migration was evaluated in a wound healing assay, the restitution of the wounded area was stimulated solely by added, exogenous vitronectin and was almost totally dependent on alpha(v)beta3 integrin function. Moreover, we demonstrated that alpha(v)beta3 was localized in focal contacts restricted to the leading edge of migrating cells, whereas vitronectin notably localized with actin stress fibers and cortical actin. On the other hand, several kinase inhibitors were found to impede migration of IGROV1 induced by vitronectin. It thus appears that alpha(v)beta3-vitronectin interactions lead to the activation of multiple signaling pathway including activation of protein kinase C, phosphatidyl-inositol-3-phosphate kinase and protein tyrosine kinase. The "alpha(v)beta3-vitronectin system" is therefore essential to the migration of human ovarian carcinoma cells.

Adenocarcinoma↗
PubMed1998

N-methyl-N-alkylsilyltrifluoroacetamide-I2 as a new derivatization reagent for anabolic steroid control.

Analytical methods for the control of growth promoters have to be specific and sensitive. At low concentration levels, it is difficult to identify some molecules unambiguously even with the improved performance of analytical methods. GC-MS analysis of 17 beta-trenbolone and its major metabolite, 17 alpha-trenbolone, is a good example. A new derivatization agent has been developed which is based on silylation of the 3- and 17-oxygenated functions and nucleophilic substitution in the 4-position. The structure of the derivatized products was demonstrated using a simple model, cyclohex-2-en-1-one, by NMR and MS spectrometry. In contrast to data found in the literature, this derivative permitted specific mass spectra for trenbolone, sensitive signals for high mass ions and reproducible gas chromatograms to be obtained. The addition of an N(CH3)COCF3 radical to the steroid nucles allowed highly specific detection in GC-high resolution MS even following extraction from complex matrices; sensitive responses were also observed in the negative chemical ionization mode. Moreover, there are significant differences in the electron ionization mass spectra of the two stereoisomers, 17 alpha- and 17 beta-trenbolone. These preliminary results and those obtained for androsta-1,4-dien-3-one and pregna-4,6-dien-3-one indicate useful advances for the determination of steroids and potential applications for metabolism studies on such compounds.

Anabolic Agents↗
PubMed1998

4-Chlorotestosterone acetate metabolites in cattle after intramuscular and oral administrations.

The use of 4-chlorotestosterone acetate by farmers for cattle fattening was recently demonstrated although the use of this anabolic steroid is strictly forbidden in the European Union. We investigated the metabolism of 4-chlorotestosterone acetate in the bovine species after intramuscular and oral administration. Nineteen metabolites were detected in urine after intramuscular injection, and eight metabolites were identified. For this purpose, preparative HPLC, mass spectrometry with different ionization modes (electronic impact and chemical ionization), and different acquisition techniques were used (high resolution, selected ion monitoring, and scan measurement). Metabolite stereoisomerism was determined on the basis of retention time and organic synthesis. 4-Chloroepitestosterone (M2), 4-chloroandrost-4-en-3alpha-ol-17-one (M3), and 4-chloroandrost-4-ene-3,17-dione (M4) were identified as the main urinary markers of intramuscular administration. On the other hand, 4-chloroandrost-4-ene-3alpha,17beta-diol (M7), 4-chloroandrostan-3beta-ol-17-one (M5), and M2 were the primary indicators of an oral administration. In addition, we have shown that 95% of the metabolites were sulfo-conjugated, except for M3, which was partially conjugated to glucuronic acid. Finally, the main metabolites (M2, M3, and M4) were easily identified for 1.5 months after intramuscular administration.

Administration, Oral↗
PubMed1997

Metabolism of tentoxin by hepatic cytochrome P-450 3A isozymes.

The interaction between rat and human liver cytochrome P-450 with tentoxin, a natural phytotoxic cyclotetrapeptide having chlorotic properties, was studied by difference ultraviolet visible spectroscopy. Tentoxin interacted with rat liver microsomes and the difference spectrum was characteristic of binding to a protein site close to the heme. The intensity of this spectrum was clearly dependent on the amounts of P-450 3A in the microsomes and was optimal in dexamethasone-treated rat microsomes. Tentoxin exhibited a high affinity for P-450 3A (Ks approximately 10 microM). Similar results were observed with human P-450 isozymes expressed in yeast. Only P-450 3A4 and 3A5 were able to give spectral interactions with tentoxin. Liver microsomes from rats pretreated with dexamethasone, a specific inducer of P-450 3A, were found to be particularly active for the oxidation of tentoxin, which occurs mainly on its Ala(Me) function leading to demethylation. Yeast-expressed P-450 3A also exhibited high activity to metabolize tentoxin. The metabolites were identified by their ultraviolet and mass spectra in fast atom bombardment and collision-activated dissociation modes. In addition to the major N-demethylated metabolite, other hydroxylated metabolites were formed. Preliminary analysis showed that as tentoxin, some metabolites were still efficient chloroplast ATPase inhibitors, while at least one of them exhibited even at low concentration stimulatory effects.

Animals↗
PubMed1997

Identification of endogenous 19-nortestosterone in pregnant ewes by gas chromatography-mass spectrometry.

Considered as a xenobiotic for many years, 19-nortestosterone has been extensively studied. Analyses developed to control the illegal use of this steroid in meat-producing animals led researchers to demonstrate the endogenous presence of 19-nortestosterone in several species. In this paper, the natural occurrence of 19-nortestosterone in its alpha form (epinandrolone) in the urine of pregnant sheep was demonstrated using gas chromatography-mass spectrometry. This reference method allowed 17 alpha-nandrolone to be detected and identified, and the absence of the beta epimer in the urine of pregnant sheep to be demonstrated. 17 alpha-Nandrolone was accurately determined at different stages of pregnancy. The analyses showed that epinandrolone, which was not detectable in the urine of non-pregnant sheep, was excreted in small amounts (leading to a < 0.5 ppb concentration) during the first 4 months of pregnancy. 17 alpha-Nandrolone concentrations then increased during the last month until parturition. The origin of this molecule was not determined.

Animals↗
PubMed1997

Influence of late reopening of the infarct-related artery on left ventricular remodelling after myocardial infarction. IRIS Study Group.

AIMS: This trial was undertaken to assess the impact of late reopening of the infarct-related artery on left ventricular remodelling in post-myocardial infarction patients. METHODS: One hundred and fifty seven patients with recent myocardial infarction were routinely submitted to delayed (second week) catheterization. They also underwent systematic angioplasty of a significantly narrowed infarct-related artery with a suitable anatomy, or reopening of a totally occluded infarct-related artery, and repeat follow-up catheterization after 4 months. Changes in left ventricular ejection fraction, left ventricular volumes, and percent of regional hypokinesia were assessed over the study period. RESULTS: One hundred and thirty-two patients had two interpretable left ventriculograms and two interpretable coronary angiograms. At initial angiography, 56 out of 96 patients with a patent infarct-related artery were successfully submitted to percutaneous coronary angioplasty, of whom 25 had restenosis and eight had total reocclusion at follow-up angiography. Percutaneous transluminal coronary angioplasty was not attempted in the remaining 40 patients due to unsuitable anatomy in 18 or a nonsignificant lesion in 22. The infarct-related artery was totally occluded in 36 patients at initial angiography, and successfully reopened by means of angioplasty in 19, of whom seven showed a reocclusion at follow-up angiography. The independent predictors of left ventricular enlargement, identified by means of multivariate regression analysis, were initial stroke volume index < 40 ml.m-2 (odds ratio = 6.3, 95% confidence interval = [2.5; 16.6]), initial end-systolic volume index > 50 ml.m-2 (odds ratio = 7.1, 95% confidence interval = [1.5; 25.8]), anterior infarct location (odds ratio = 4.1, 95% confidence interval = [1.4; 11.5]) and reocclusion of the infarct-related artery (odds ratio = 7.3, 95% confidence interval = [1.3; 27.3]). Angioplasty of a patent but significantly narrowed infarct-related artery was not found predictive. CONCLUSIONS: This study demonstrates that reocclusion of a previously open infarct-related artery, as well as the initial low stroke volume index, enlarged end-systolic volume index and anterior infarct location are independent predictors of long-term left ventricular enlargement. These results emphasize the impact of long-term sustained patency of the infarct-related artery on the prevention of left ventricular dysfunction. The need for a larger randomized trial is recognised.

Adrenergic beta-Antagonists↗
PubMed1994

Merosin is synthesized by thyroid cells in primary culture irrespective of cellular organization.

The in vitro synthesis and deposition of laminin family glycoproteins were studied using primary porcine thyroid cells cultured as monolayers or in follicles. The latter organization mimics the in vivo state of these polarized epithelial cells. In both cell systems a trimeric molecule was immunoprecipitated by using polyclonal antibodies against EHS-laminin. When the cells were fully polarized the protein was found at the basal pole of cells, irrespective of their organization. However, this molecule was different from laminin purified from a traditional source, the murine Engelbreth-Holm-Swarm (EHS) tumor. Thyroid cell laminin was composed of two light chains, analogous to EHS B1 and B2, and a disulfide-bonded heavy chain not found in EHS-laminin. The heavy chain was first synthesized as a 380 kDa polypeptide, then rapidly cleaved to a doublet of 350-380 kDa, which was subsequently found in both cell extracts and conditioned culture media. This thyroid laminin variant was compared with merosin, another variant found in the basement membranes of trophoblast, Schwann cells, striated muscle and liver. The heavy chain (M) of merosin shows homology to EHS-laminin heavy chain at the C-terminal domain, and is usually found as two polypeptides of 80 kDa and 300 kDa (Ehrig K., Leivo I., Argraves W. S., Ruoslahti E. and Engvall E. Proc. Nat. Acad. Sci. 87, 3264-3268, 1990). mRNA of the M chain was identified by RT-PCR in freshly isolated thyrocytes as well as in 6-day-old cultured thyroid cells. Furthermore, both the classical laminin heavy chain and the 350 kDa variant were detected by immunoblotting and immunofluorescence in the thyroid gland in vivo. All these results suggest strongly that merosin is a basement membrane component of thyroid cells in vivo and in vitro.

Animals↗
PubMed1992

Amiodarone pneumonitis. Bronchoalveolar lavage findings in 15 patients and review of the literature.

UNLABELLED: Amiodarone (Am) pneumonitis is currently a common and potentially severe adverse reaction, the accurate diagnosis of which remains difficult to establish. OBJECTIVES: To determine the contribution of bronchoalveolar lavage (BAL) in the diagnostic workup of patients suspected of having Am pneumonitis. METHODS: Diagnosis of Am pneumonitis was established on the basis of (1) development of recent symptoms and pulmonary opacities while receiving the drug, (2) exclusion of other possible causes, and (3) improvement following cessation of Am and/or steroid therapy. (4) Confirmatory changes were obtained by histopathologic examination in eight cases. BAL was performed in each patient at the time of initial evaluation. RESULTS: Am pneumonitis was diagnosed in 15 consecutive patients between 1985 and 1991. The disease was associated with significant morbidity and mortality. Six patients died; four died of Am pneumonitis. A neutrophilic BAL was found in nine patients (average PMN = 26.6 percent). A mixed pattern (lymphocytic + neutrophilic) was seen in four patients (average: Ly = 19.9 percent; PMN = 11.9 percent). Two patients had a normal BAL. No patient had a lymphocytic pattern. A low CD4+/CD8+ ratio was seen in two patients. A literature survey indicated 70 cases of Am pneumonitis with detailed information on BAL. The BAL pattern was mixed in 23 (33 percent), neutrophilic in 18 (26 percent), lymphocytic in 15 (21 percent), and normal in 14 (20 percent). No correlation was found between BAL pattern and prognosis. Also, BAL pattern was related neither to daily or total dose of Am nor to duration of treatment with Am. CONCLUSION: The cellular profile of BAL in Am pneumonitis is highly variable, and no cellular pattern of BAL seems to be predictive of a detrimental outcome or of irreversible fibrosis. Aside from excluding other illnesses, and due to its extreme variability, the contribution of BAL differential in the initial workup of patients suspected of having Am pneumonitis is limited.

Aged↗
PubMed1988

Characterization of six nucleotide-binding sites on chloroplast coupling factor 1 and one site on its purified beta subunit.

By using gel filtration chromatography, following the technique of Hummel and Dreyer (Hummel, J., and Dreyer, W. (1962) Biochim. Biophys. Acta 63, 532-534), the adenine nucleotide-binding sites of isolated soluble chloroplast ATPase (CF1) and of the beta subunit were studied. CF1 possesses six adenine nucleotide-binding sites: two high affinity sites for ADP or ATP (KdH = 1-5 microM) in addition to one site where endogenous not-exchangeable ADP is bound, and three low affinity sites binding ADP or ATP with a dissociation constant (KdL = 15-20 microM) which is considerably increased in the presence of pyrophosphate. KdH is not modified by addition of pyrophosphate. The stability of nucleotide binding at the low affinity sites increases after heat activation of CF1. Removal of the delta or epsilon subunits on CF1 affects neither the number nor the binding parameters of the nucleotide-binding sites. The purified beta subunit possesses one easily exchangeable site/subunit. It is proposed that the low affinity sites on CF1 are the catalytic sites.

Adenosine Diphosphate↗
PubMed1988

Assessment of the lactulose-mannitol test in Crohn's disease.

The mannitol-lactulose intestinal permeability test was evaluated in 100 healthy controls and 47 patients with Crohn's disease. These patients were further separated into three subgroups of increased activity (Harvey-Bradshaw index) and in two subgroups, with elective colonic lesions and associated ileal and colonic lesions. Results were given as percentages of urinary recoveries for mannitol (M), lactulose (L), and L/M ratio. As a whole, patients with Crohn's disease have lower mean M and higher mean L and mean L/M ratios than controls. The magnitude of alterations in M, L, and L/M increased with activity. The sensitivity of the test, however, reached interesting figures (67%:L and 86%:L/M) only in subgroup III which was composed of relapsing patients. Mean M was lower in patients with associated ileal lesion but, whatever the criterion (M, L, or L/M), the test does not provide any clue for the detection of a possible infraclinical associated ileal localisation.

Adolescent↗
PubMed1988

[Tolerance and prognostic value of Thallium 201 myocardial tomoscintigraphy with dipyridamole in the aged subject].

The authors present a retrospective study of 46 consecutive patients aged from 70 to 79 years (mean 73.3 +/- 2.5 years) with suspected coronary artery disease who, being unfit for exercise tests, were explored by myocardial scintigraphy with thallium 201 after coronary dilatation with intravenous dipyridamole. The examination was well tolerated by 30 patients. Such classical side-effects as chest pain, malaise, dizziness, headache, flushing, vomiting and transient arrhythmia or repolarization disorders were recorded, but they were not more frequent than in younger subjects. However, the occurrence of severe hypotensive malaise relieved by theophylline in two cases and of angina in about one third of patients with myocardial ischaemia means that the procedure must be performed under close supervision. A fall in blood pressure (-11 mmHg on average) and a rise in heart rate (+8 beats/min on average) were usual. Post-scintigraphy follow-up of patients over a mean period of 11.1 +/- 6.2 months showed that a reversible defect of thallium 201 uptake, due to redistribution, is a highly selective indicator of patients who are particularly exposed to a cardiac accident in the short--or mid-term. Only one out of 26 patients without reversible ischaemia (4 p. 100) subsequently presented with a major coronary event (unstable angina). In contrast, in the group of 20 patients with reversible ischaemia three required early myocardial revascularization; furthermore, five serious accidents (29 p. 100) occurred among the 17 patients who were left under medical treatment, including two sudden deaths, two cases of unstable angina and one case of myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Biochemical and proton NMR characterization of the isolated functional beta-subunit of coupling factor one from spinach chloroplasts.

Beta subunits have been dissociated from CF1 of spinach chloroplasts, purified by HPLC and characterized by two-dimensional electrophoresis and fluorescence emission. The solutions of isolated beta subunits are able to hydrolyze MgATP; this ATPase activity is an intrinsic property of the beta molecule. From proton NMR at 300 and 500 MHz, it is shown that the preparations are fully reproducible and that beta subunits remain monomeric with 75% aliphatic protons associated with rigid parts of the molecule. The other 25% give rise to separate resonances and belong to mobile side-chains and/or to flexible regions. The measurement of the transverse relaxation times T2 has permitted a detailed characterization of the molecular dynamics of the isolated beta subunits.

Chloroplasts↗
PubMed1987

Measurement of intestinal permeability to mannitol and lactulose as a means of diagnosing food allergy and evaluating therapeutic effectiveness of disodium cromoglycate.

Gastrointestinal permeability was evaluated in 90 fasting healthy subjects and 60 patients with food allergy by oral administration to both groups of 5 g of mannitol, a marker of absorption of small molecules, and 5 g of lactulose, a marker of abnormal absorption of large molecules, and subsequent measurement of urinary excretion of mannitol and lactulose. In healthy subjects, mean 5-hour urinary excretion of mannitol was 14.11% and of lactulose 0.26%. In the fasting state, the 60 patients with food allergy exhibited a mean urinary recovery of mannitol of 13.22%, not significantly different from that in healthy subjects. Mean recovery of lactulose in the patients with food allergy was 0.55%, significantly greater than in the healthy patients. After ingestion of food allergens by the patients, mean mannitol recovery fell to 11.57% and mean recovery of lactulose rose to 1.04%, both values being significantly different from those obtained in the fasting patients. On challenging the patients after they had taken sodium cromoglycate, mean mannitol and lactulose recoveries (13.53% and 0.62%, respectively) were not significantly different from those in fasting patients but were significantly different from those obtained on challenging patients unprotected by sodium cromoglycate. Evaluation of intestinal permeability in this way provides an objective means of diagnosing food allergy and assessing the effectiveness of anti-allergic agents such as sodium cromoglycate.

Cromolyn Sodium↗