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Riyad El-Khoury Kia K Kemppainen Eric Dufour Marten Szibor Howard T Jacobs Pierre Rustin 《British journal of pharmacology》2014,171(8):2243-2249
Mitochondrial disorders are nowadays recognized as impinging on most areas of medicine. They include specific and widespread organ involvement, including both tissue degeneration and tumour formation. Despite the spectacular progresses made in the identification of their underlying molecular basis, effective therapy remains a distant goal. Our still rudimentary understanding of the pathophysiological mechanisms by which these diseases arise constitutes an obstacle to developing any rational treatments. In this context, the idea of using a heterologous gene, encoding a supplemental oxidase otherwise absent from mammals, potentially bypassing the defective portion of the respiratory chain, was proposed more than 10 years ago. The recent progress made in the expression of the alternative oxidase in a wide range of biological systems and disease conditions reveals great potential benefit, considering the broad impact of mitochondrial diseases. This review addresses the state of the art and the perspectives that can be now envisaged by using this strategy.
Linked Articles
This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 相似文献4.
King DL El-Khoury Coffin L Maurer MS 《Journal of the American College of Cardiology》2002,40(2):325-329
OBJECTIVES: This study sought to evaluate myocardial contraction fraction (MCF) as an index of myocardial shortening by comparison to conventional shortening indices in patients with hypertensive hypertrophy, athletes with physiologic hypertrophy and sedentary normal adult subjects. BACKGROUND: A significant percentage of patients with hypertensive hypertrophy have "normal" or "preserved" left ventricular (LV) systolic function by conventional echocardiographic measures whereas their systolic function is depressed when measured by the two-dimensional echocardiographic mid-wall shortening fraction (MWSF). A three-dimensional echocardiographic measure of myocardial shortening analogous to MWSF has been lacking. We describe a volumetric measure of myocardial shortening, the MCF, as the ratio of stroke volume (SV) to myocardial volume (MV), and hypothesize that it may be useful to compare myocardial performance in patients with different degrees and types of hypertrophy. METHODS: We compared the MCF using freehand three-dimensional echocardiographic reconstruction of the LV to conventional measures of LV function (ejection fraction [EF], endocardial shortening fraction [SF] and MWSF) in subjects with pathologic hypertensive hypertrophy, heart failure symptoms and preserved EF (n = 17), athletes with physiologic hypertrophy (n = 41) and normal sedentary adults (n = 80). RESULTS: The EF was in the normal range for all three groups. The MCF was lower in hypertensive hypertrophy compared with normal subjects (0.33 +/- 0.05 vs. 0.44 +/- 0.07, p < 0.01). It also successfully differentiated physiologic hypertrophy from normal subjects (0.50 +/- 0.05 vs. 0.44 +/- 0.07, p < 0.01). The endocardial SF did not distinguish athletes from normal subjects and the MWSF did not distinguish hypertensive from physiologic hypertrophy. CONCLUSIONS: The MCF, a volumetric measure of myocardial shortening, demonstrates that myocardial shortening is decreased in hypertensive hypertrophy and increased in physiologic hypertrophy. The MCF may be useful in assessing differences in myocardial performance in patients with similar degrees of hypertrophy. 相似文献
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Mutchler Matt G. Wagner Glenn J. McDavitt Bryce Woldetsadik Mahlet A. Kegeles Susan M. El-Khoury Cynthia Nogg Kelsey A. Klinger Ian A. Mokhbat Jacques Ballan Elie G. 《AIDS and behavior》2022,26(9):3089-3098
AIDS and Behavior - We are not aware of any validated sexual health communication scales for use with young men who have sex with men (YMSM). We used data from an HIV prevention study in Lebanon... 相似文献
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Benoît Mesurolle Laurence Kadoch Mona El-Khoury Andr Lisbona Nandini Dendukuri William D. Foulkes 《Journal of ultrasound in medicine》2007,26(6):817-824
OBJECTIVE: The purpose of this study was to review the sonographic features of breast cancer gene BRCA1- and BRCA2-associated breast carcinomas in comparison with "sporadic" breast carcinomas and benign breast masses. METHODS: Sonograms of 233 breast masses, including 33 BRCA-associated malignant masses (BRCA1, 15; BRCA2, 18), 148 sporadic malignant masses, and 52 benign masses, were reviewed by consensus by 2 radiologists according to American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) terminology. RESULTS: Most of the sporadic and BRCA1-and BRCA2-associated cancers displayed an irregular shape (91.2%, 93.3%, and 83.3%, respectively). BRCA1-associated cancers showed microlobulated margins in 53.3% versus 33.8% (sporadic) and 33.3% (BRCA2). A parallel orientation was most frequently encountered in BRCA1-associated lesions (46.7%) versus sporadic (33.8%) and BRCA2 (33.3%), whereas posterior acoustic shadowing was least frequently seen in BRCA1-associated lesions (13.3%) versus BRCA2 (16.7%) and sporadic (31.1%). Most (73.3%) of the BRCA1-associated lesions were classified as BI-RADS category 4, whereas most of the sporadic and BRCA2-associated lesions were classified as BI-RADS category 5 (66.2% and 72.2%). CONCLUSIONS: Sonographic features of BRCA-associated and sporadic breast carcinomas do not differ substantially. BRCA1-associated breast carcinomas trend toward less malignant sonographic characteristics, but strict application of the BI-RADS categorizations demands that they be classified as category 4 or 5. 相似文献
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Sommers CL Dejarnette JB Huang K Lee J El-Khoury D Shores EW Love PE 《The Journal of experimental medicine》2000,192(6):913-919
The T cell antigen receptor (TCR) and pre-TCR complexes are composed of multiple signal-transducing subunits (CD3 gamma, CD3 delta, CD3 epsilon, and zeta) that each contain one or more copies of a semiconserved functional motif, the immunoreceptor tyrosine-based activation motif (ITAM). Although biochemical studies indicate that individual TCR-ITAMs may bind selectively or with different affinity to various effector molecules, data from other experiments suggest that at least some ITAMs are functionally equivalent. In this study, we examined the role of CD3straightepsilon ITAM-mediated signals in T cell development by genetically reconstituting CD3 epsilon-deficient mice with transgenes encoding either wild-type or ITAM-mutant (signaling defective) forms of the protein. The results demonstrate that signals transduced by CD3 epsilon are not specifically required for T cell maturation but instead contribute quantitatively to TCR signaling in a manner similar to that previously observed for zeta chain. Unexpectedly, analysis of TCR-transgenic/CD3 epsilon-mutant mice reveals a potential role for CD3 epsilon signals in T cell survival. 相似文献
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Magnetic resonance imaging of myxoid containing tumors 总被引:2,自引:0,他引:2
Kirk K. Peterson B.S. Donald L. Renfrew M.D. Richard M. Feddersen M.D. Joseph A. Buckwalter M.D. Georges Y. El-Khoury M.D. 《Skeletal radiology》1991,20(4):245-250
Myxoid tissue forms part of many benign and malignant soft-tissue tumors. The advent of percutaneous needle biopsy has made
it important to be aware of the diagnostic implications of biopsy samples containing myxoid tissue. To determine whether the
magnetic resonance imaging (MRI) characteristics could help establish the diagnosis, we compared the MR images of 11 tumors
containing myxoid tissue with the resected tumor tissue.
In our small series of these rare tumors, the MRI characteristics allowed differentiation of intramuscular myxomas from malignant
neoplasms containing myxoid tissue. Intramuscular myxomas meet the following conditions: (a) they are well circumscribed;
(b) they arise within muscle; (c) T1-weighted images demonstrate uniform, decreased signal intensity; (d) T2-weighted images demonstrate uniform increased signal intensity; (e) contrast-enhanced images exhibit an inhomogeneous increase
in signal intensity. If any of these conditions is not met, then a malignancy containing myxoid tissue should be suspected. 相似文献
10.
E. G. Karam Diantha B. Howard Aimée N. Karam Alice Ashkar Monique Shaaya Nadine Melhem Nazek El-Khoury 《European archives of psychiatry and clinical neuroscience》1998,248(5):225-230
This article examines the effect of war events and pre-war depression on the prevalence of major depression during war. A
total of 658 subjects aged 18-65 years were randomly selected from four Lebanese communities differentially exposed to the
Lebanon Wars and were interviewed using the Diagnostic Interview Schedule (Arabic version). The individual levels of exposure
to war events were assessed through a War Events Questionnaire. The lifetime prevalence of the DSM-III-R-defined major depression
varied across the four communities from 16.3 to 41.9%; the final parameters predicting major depression since the onset of
the wars were: depression before the wars and exposure to the wars. Both, individual levels of exposure to war and a history
of pre-war depression, predict the development of depression during war.
Received: 5 June 1997 / Accepted: 14 July 1998 相似文献