7 results on '"Elbayed, Karim"'
Search Results
2. Metabolome Profiling by HRMAS NMR Spectroscopy of Pheochromocytomas and Paragangliomas Detects SDH Deficiency: Clinical and Pathophysiological Implications12
- Author
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Imperiale, Alessio, Moussallieh, François-Marie, Roche, Philippe, Battini, Stéphanie, Cicek, A. Ercument, Sebag, Frédéric, Brunaud, Laurent, Barlier, Anne, Elbayed, Karim, Loundou, Anderson, Bachellier, Philippe, Goichot, Bernard, Stratakis, Constantine A., Pacak, Karel, Namer, Izzie-Jacques, and Taïeb, David
- Subjects
Male ,Models, Molecular ,Succinic Acid ,Pheochromocytoma ,Sensitivity and Specificity ,Article ,Protein Structure, Secondary ,Paraganglioma ,GSH, glutathione ,Humans ,Metabolomics ,NMR, nuclear magnetic resonance ,Nuclear Magnetic Resonance, Biomolecular ,PHEO, pheochromocytoma ,Middle Aged ,Immunohistochemistry ,HRMAS, 1H high-resolution magic angle spinning ,Succinate Dehydrogenase ,ROC Curve ,PGL, paraganglioma ,Positron-Emission Tomography ,SDH, succinate dehydrogenase ,Mutation ,Metabolome ,Female ,Tomography, X-Ray Computed ,Metabolic Networks and Pathways - Abstract
Succinate dehydrogenase gene (SDHx) mutations increase susceptibility to develop pheochromocytomas/paragangliomas (PHEOs/PGLs). In the present study, we evaluate the performance and clinical applications of 1H high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy–based global metabolomic profiling in a large series of PHEOs/PGLs of different genetic backgrounds. Eighty-seven PHEOs/PGLs (48 sporadic/23 SDHx/7 von Hippel-Lindau/5 REarranged during Transfection/3 neurofibromatosis type 1/1 hypoxia-inducible factor 2α), one SDHD variant of unknown significance, and two Carney triad (CTr)–related tumors were analyzed by HRMAS-NMR spectroscopy. Compared to sporadic, SDHx-related PHEOs/PGLs exhibit a specific metabolic signature characterized by increased levels of succinate (P < .0001), methionine (P = .002), glutamine (P = .002), and myoinositol (P < .0007) and decreased levels of glutamate (P < .0007), regardless of their location and catecholamine levels. Uniquely, ATP/ascorbate/glutathione was found to be associated with the secretory phenotype of PHEOs/PGLs, regardless of their genotype (P < .0007). The use of succinate as a single screening test retained excellent accuracy in distinguishing SDHx versus non–SDHx-related tumors (sensitivity/specificity: 100/100%). Moreover, the quantification of succinate could be considered a diagnostic alternative for assessing SDHx-related mutations of unknown pathogenicity. We were also able, for the first time, to uncover an SDH-like pattern in the two CTr-related PGLs. The present study demonstrates that HRMAS-NMR provides important information for SDHx-related PHEO/PGL characterization. Besides the high succinate–low glutamate hallmark, SDHx tumors also exhibit high values of methionine, a finding consistent with the hypermethylation pattern of these tumors. We also found important levels of glutamine, suggesting that glutamine metabolism might be involved in the pathogenesis of SDHx-related PHEOs/PGLs.
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- 2015
3. Metabolic Characterization of Caviar Specimens by H NMR Spectroscopy: Towards Caviar Authenticity and Integrity.
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Heude, Clement, Elbayed, Karim, Jezequel, Tangi, Fanuel, Mathieu, Lugan, Raphael, Heintz, Dimitri, Benoit, Philippe, and Piotto, Martial
- Abstract
The specific metabolic profile of aqueous extracts of caviar samples ( n = 91) originating from producers in the Aquitaine region in France was determined using H NMR spectroscopy. This metabolic profile was used to develop multivariate statistical models (Soft Independent Modeling by Class Analogy (SIMCA) and Orthogonal Partial Least Square Discriminant Analysis (OPLS-DA)) for the purpose of differentiating the Aquitaine production from other productions. The main purpose of these models is to help Aquitaine producers establish a protected geographical indication (PGI) to protect their know-how in caviar production from aquaculture. The parameters characterizing both the OPLS-DA and the SIMCA models were quite satisfactory, and the analysis of blind test samples with the two models provided a good level of discrimination between Aquitaine caviars and other caviars. The same NMR metabolic profile could also be used to provide an estimation of the freshness of caviar samples and define a shelf life for caviar cans. The first characterization of the different metabolites detected in caviar specimens by H NMR spectroscopy is also presented. The statistical models obtained could be used to prevent counterfeiting of Aquitaine caviar and guarantee an adequate level of freshness. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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4. NMR HRMAS spectroscopy of lung biopsy samples: Comparison study between human, pig, rat, and mouse metabolomics.
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Benahmed, Malika A., Elbayed, Karim, Daubeuf, François, Santelmo, Nicola, Frossard, Nelly, and Namer, Izzie J.
- Abstract
Purpose Using the metabolomics by NMR high-resolution magic angle spinning spectroscopy, we assessed the lung metabolome of various animal species in order to identify the animal model that could be substituted to human lung in studies on fresh lung biopsies. Methods The experiments were conducted on intact lung biopsy samples of pig, rat, mouse, and human using a Bruker Advance III 500 spectrometer. Thirty-five to 39 metabolites were identified and 23 metabolites were quantified. Principal component analysis, partial least-squares discriminant analysis, and analysis of variance tests were performed in order to compare the metabolic profiles of each animal lung biopsies to those of the human lung. Results The metabolic composition between human and pig lung was similar. However, human lung was distinguishable from mouse and rat regarding: Trimethylamine N-oxide and betaïne which were present in rodents but not in human lung, carnitine, and glycerophosphocholine which were present in mouse but not in human lung. Conversely, succinic acid was undetected in rat lung. Furthermore, fatty acids concentration was significantly higher in rodent lungs compared to human lung. Conclusion Using the metabolomics by NMR high-resolution magic angle spinning spectroscopy on lung biopsy, samples allowed to highlight that pig lung seems to be close to human lung as regarding its metabolite composition with more similarities than dissimilarities. Magn Reson Med 71:35-43, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
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- 2014
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5. A New Specific Succinate-Glutamate Metabolomic Hallmark in Sdhx-Related Paragangliomas.
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Imperiale, Alessio, Moussallieh, François-Marie, Sebag, Frédéric, Brunaud, Laurent, Barlier, Anne, Elbayed, Karim, Bachellier, Philippe, Goichot, Bernard, Pacak, Karel, Namer, Izzie-Jacques, and Taïeb, David
- Subjects
SUCCINATES ,GLUTAMIC acid ,METABOLOMICS ,PARAGANGLIOMA ,GENETIC mutation ,ENERGY metabolism - Abstract
Paragangliomas (PGLs) are frequently associated with germline mutations in genes involved in energy metabolism. The purpose of the present study was to assess whether the tumor metabolomic profile of patients with hereditary and apparently sporadic PGLs enables the distinction of different subtypes of tumors. Twenty-eight unrelated patients with a histological diagnosis of PGLs were included in the present study. Twelve had germline mutations in SDHx genes (5 SDHB, 7 SDHD), 6 VHL, and 10 were apparently sporadic. Intact tumor samples from these patients (one per patient) were evaluated with
1 H high-resolution magic angle spinning (HRMAS) NMR spectroscopy. SDHx-related tumors were characterized by an increase in succinate levels in comparison to other tumor subtypes (p = 0.0001 vs VHL and p = 0.000003 vs apparently sporadic). Furthermore, we found significantly lower values of glutamate in SDHx-related tumors compared to other subtypes (p = 0.0007 vs VHL and p = 0.003 vs apparently sporadic). Moreover, SDHx-tumors also exhibited lower values of ATP/ADP/AMP (p = 0.01) compared to VHL. VHL tumors were found to have the highest values of glutathione (GSH) compared to other tumors. Based on 4 metabolites (succinate, glutamate, GSH, and ATP/ADP/AMP), tumors were accurately distinguished from the other ones on both 3- and 2-class PLS-DA models. The present study shows that HRMAS NMR spectroscopy is a very promising method for investigating the metabolomic profile of various PGLs. The present data suggest the existence of a specific succinate-glutamate hallmark of SDHx PGLs. The relevance of such a metabolomic hallmark is expected to be very useful in designing novel treatment options as well as improving the diagnosis and follow-up of these tumors, including metastatic ones. [ABSTRACT FROM AUTHOR]- Published
- 2013
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6. Metabolomic profile of the adrenal gland: from physiology to pathological conditions.
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Imperiale, Alessio, Elbayed, Karim, Moussallieh, François-Marie, Reix, Nathalie, Piotto, Martial, Bellocq, Jean-Pierre, Goichot, Bernard, Bachellier, Philippe, and Namer, Izzie-Jacques
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ADRENAL gland cancer , *METABOLOMICS , *PHEOCHROMOCYTOMA , *MAGNETIC resonance imaging of cancer , *ADRENAL cortex , *TISSUE analysis , *NUCLEAR magnetic resonance spectroscopy - Abstract
In this study, we i assessed the metabolic profile of the normal adrenal cortex and medulla of adult human subjects by means of ¹H-high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy; ii) compared the biochemical profile of adenoma (Ad), adrenal cortical carcinoma (ACC), and pheochromocytoma (PCC) samples with that of healthy adrenal tissue samples; and iii) investigated the metabolic differences between ACCs and Ads as well as between ACCs and PCCs. Sixty-six tissue samples (13 adrenal cortical tissue, eight medullary tissue, 13 Ad, 12 ACC, and 20 PCC samples) were analyzed. Adrenaline and noradrenaline were undetectable in cortical samples representing the metabolic signature of the tissue derived from neural crest. Similarity between the metabolic profile of Ads and that of the normal adrenal cortex was shown. Inversely, ACC samples clearly made up a detached group exhibiting the typical stigmata of neoplastic tissue such as choline-containing compounds, biochemical markers of anaerobic processes, and increased glycolysis. Significantly higher levels of lactate, acetate, and total choline-containing compounds played a major role in the differentiation of ACCs from Ads. Moreover, the high fatty acid content of ACCs contributed to the cluster identification of ACCs. Of the 14 sporadic PCC samples, 12 exhibited predominant or exclusive noradrenaline secretion. The noradrenaline: adrenaline ratio was inverted in the normal medullary tissue samples. Multiple endocrine neoplasia type 2- and NF1-related PCC samples exhibited both adrenaline and noradrenaline secretion. In the von Hippel-Lindau disease-related PCC samples, only noradrenaline secretion was detected by HRMASNMRspectroscopy. This study is one of the first applications of metabolomics to adrenal pathophysiology and it is the largest study to report HRMASNMR data related to the adrenal cortex and adrenal cortical tumors. [ABSTRACT FROM AUTHOR]
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- 2013
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7. The assessment of the quality of the graft in an animal model for lung transplantation using the metabolomics 1H high-resolution magic angle spinning NMR spectroscopy.
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Benahmed, Malika A., Santelmo, Nicola, Elbayed, Karim, Frossard, Nelly, Noll, Eric, Canuet, Mathieu, Pottecher, Julien, Diemunsch, Pierre, Piotto, Martial, Massard, Gilbert, and Namer, Izzie J.
- Abstract
Standards are needed to control the quality of the lungs from nonheart-beating donors as potential grafts. This was here assessed using the metabolomics
1 H high-resolution magic angle spinning NMR spectroscopy. Selective perfusion of the porcine bilung block was set up 30 min after cardiac arrest with cold Perfadex® . Lung alterations were analyzed at 3, 6, and 8 h of cold ischemia as compared to baseline and to nonperfused lung. Metabolomics analysis of lung biopsies allowed identification of 35 metabolites. Levels of the majority of the metabolites increased over time at 4°C without perfusion, indicating cellular degradation, whereas levels of glutathione decreased. When lung was perfused at 4°C, levels of the majority of the metabolites remained stable, including levels of glutathione. Levels of uracil by contrast showed a reverse profile, as its signal increased over time in the absence of perfusion while being totally absent in perfused samples. Our results showed glutathione and uracil as potential biomarkers for the quality of the lung. The metabolomics1 H high-resolution magic angle spinning NMR spectroscopy can be efficiently applied for the assessment of the quality of the lung as an original technique characterized by a rapid assessment of intact biopsy samples without extraction and can be implemented in hospital environment. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]- Published
- 2012
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