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41.
Ferrera R Cuchet D Zaupa C Revol-Guyot V Ovize M Epstein AL 《Journal of molecular and cellular cardiology》2005,38(1):219-223
OBJECTIVE: The feasibility of gene transfer to myocardial tissue using viral vectors was investigated over the last few years. In this study we report gene transfer using a recently described improved of Herpes simplex virus (HSV-1)-derived amplicon vectors and demonstrate that these vectors are a powerful and potentially very interesting tool for gene transfer into neonatal primary as well as in adult cardiac myocytes. METHODS AND RESULTS: Non-pathogenic HSV-1 amplicon vectors simultaneously expressing GFP and LacZ were constructed using a novel helper system that yields essentially helper-free vector particles. These vectors were used to infect either cultured primary neonatal rat cardiomyocytes or adult cardiac tissue. Transgenic expression was quantified using a FACS (GFP) or X-gal staining (LacZ). Infection of primary cardiomyocytes showed efficient transduction even at very low multiplicity of infection (MOI), and expression increased with the infectious dose. By investigating release of lactate dehydrogenase (LDH) or spontaneous beating of the cells, we failed to detect cytotoxic effects in cardiomyocytes infected at high MOI. Thin slices of adult cardiac tissue placed in medium containing vectors also showed very good levels of transduction, without any evidence of toxic effects. CONCLUSIONS: Helper-free amplicon vectors very efficiently transduce genes into cardiomyocytes. Our results indicate similar or better transduction efficiencies than those reported using other vector systems. Furthermore, the very high transgenic capacity of amplicon vectors (up to 150 kbp) makes these vectors a unique and very suitable system to transduce large genomic sequences into cardiomyocytes. 相似文献
42.
Delphine Sauce Valrie Pourcher Tristan Ferry Jacques Boddaert Laurence Slama Clotilde Allavena 《Medicine》2021,100(17)
HIV infection has become a chronic disease, with a lower mortality, but a consequent increase in age-related noninfectious comorbidities. Metabolic disorders have been linked to the effect of cART as well to the effects of immune activation and chronic inflammation. Whereas it is known that aging is intrinsically associated with hyperinflammation and immune system deterioration, the relative impact of chronic HIV infection on such inflammatory and immune activation has not yet been studied focusing on an elderly HIV-infected population.The objectives of the study were to assess 29 blood markers of immune activation and inflammation using an ultrasensitive technique, in HIV-infected patients aged ≥75 years with no or 1 comorbidity (among hypertension, renal disease, neoplasia, diabetes mellitus, cardiovascular disease, stroke, dyslipidemia, and osteoporosis), in comparison with age-adjusted HIV-uninfected individuals to identify whether biomarkers were associated with comorbidities. Wilcoxon nonparametric tests were used to compare the levels of each marker between control and HIV groups; logistic regression to identify biomarkers associated to comorbidity in the HIV group and principal component analysis (PCA) to determine clusters associated with a group or a specific comorbidity.A total of 111 HIV-infected subjects were included from the Dat’AIDS cohort and compared to 63 HIV-uninfected controls. In the HIV-infected group, 4 biomarkers were associated with the risk of developing a comorbidity: monocyte chemoattractant protein-1 (MCP-1), neurofilament light chain (NF-L), neopterin, and soluble CD14. Six biomarkers (interleukin [IL]-1B, IL-7, IL-18, neopterin, sCD14, and fatty acid-binding protein) were significantly higher in the HIV-infected group compared to the control group, 11 biomarkers (myeloperoxydase, interleukin-1 receptor antagonist, tumor necrosis factor receptor 1, interferon-gamma, MCP-1, tumor necrosis factor receptor 2, IL-22, ultra sensitivity C-reactive protein, fibrinogen, IL-6, and NF-L) were lower. Despite those differences, PCA to determine clusters associated with a group or a specific comorbidity did not reveal clustering nor between healthy control and HIV-infected patients neither between the presence of comorbidity within HIV-infected group.In this highly selected geriatric HIV population, HIV infection does not seem to have an additional impact on age-related inflammation and immune disorder. Close monitoring could have led to optimize prevention and treatment of comorbidities, and have limited both immune activation and inflammation in the aging HIV population. 相似文献
43.
David Emmanuelle Fauvernier Mathieu Saadoun David Gerfaud-Valentin Mathieu Maurcort-Boulch Delphine Sève Pascal Jamilloux Yvan 《Clinical rheumatology》2022,41(6):1749-1758
Clinical Rheumatology - To examine the mortality rates and causes of death among French decedents with Behçet’s disease (BD). Data collected between 1979 and 2016 by the French... 相似文献
44.
Karine Adel-Patient Guillaume Lezmi Florence Anne Castelli Sibylle Blanc Hervé Bernard Pascale Soulaines Pascale Dumond Sandrine Ah-Leung Florence Lageix Delphine de Boissieu Naima Cortes-Perez Stéphane Hazebrouck François Fenaille Christophe Junot Christophe Dupont 《Clinical and translational allergy》2018,8(1):38
Background
Food Protein-Induced Enterocolitis Syndrome (FPIES) is considered to be a non-IgE mediated food allergy. However, its pathogenesis remains poorly understood and biomarkers are lacking. We aimed to perform in-depth characterization of humoral and cellular immune responses in children with cow’s milk (CM)-FPIES and investigated whether there is a FPIES metabolomic signature.Methods
Children with CM-FPIES and control subjects with an IgE-mediated CM allergy (IgE-CMA), both avoiding CM, were recruited on the day of an oral food challenge. Blood samples were collected before the challenge. Total and specific levels of IgE, IgG1-4, IgA, IgM and IgD to various whey and casein allergens and to their gastroduodenal digestion products were measured in plasma, using plasma from CM-tolerant peanut allergic patients (IgE-PA, not avoiding CM) as additional controls. Cytokine secretion and cellular proliferation were analyzed after stimulation of PBMC with different CM allergens. Metabolomic profiles were obtained for plasma samples using liquid chromatography coupled to high-resolution mass spectrometry.Results
Nine children with CM-FPIES and 12 control subjects (6 IgE-CMA and 6 IgE-PA) were included. In children with CM-FPIES, total Ig concentrations were lower than in control subjects, specific Ig against CM components were weak to undetectable, and no specific IgE against CM digestion products were detected. Moreover, in CM-FPIES patients, we did not find any Th cell proliferation or associated cytokine secretion after allergen reactivation, whereas such responses were clearly found in children with IgE-CMA. Plasma metabolic profiles were different between CM allergic patients, with significantly lower concentrations of various fatty acids and higher concentrations of primary metabolites such as amino acids in CM-FPIES compared to IgE-CMA patients.Conclusions
In CM-FPIES, both humoral and cellular specific immune responses are weak or absent, and this is not related to CM avoidance. A metabolomic signature was identified in patients with CM-FPIES that may be useful for the diagnosis and management of this disease.45.
Single‐use flexible bronchoscopes compared with reusable bronchoscopes: Positive organizational impact but a costly solution 下载免费PDF全文
46.
47.
Jacques DA Ndawinz Xavier Anglaret Eric Delaporte Sinata Koulla-Shiro Delphine Gabillard Albert Minga Dominique Costagliola Virginie Supervie 《Bulletin of the World Health Organization》2015,93(8):521-528
Objective
To propose two new indicators for monitoring access to antiretroviral treatment (ART) for human immunodeficiency virus (HIV); (i) the time from HIV seroconversion to ART initiation, and (ii) the time from ART eligibility to initiation, referred to as delay in ART initiation. To estimate values of these indicators in Cameroon.Methods
We used linear regression to model the natural decline in CD4+ T-lymphocyte (CD4+ cell) numbers in HIV-infected individuals over time. The model was fitted using data from a cohort of 351 people in Côte d’Ivoire. We used the model to estimate the time from seroconversion to ART initiation and the delay in ART initiation in a representative sample of 4154 HIV-infected people who started ART in Cameroon between 2007 and 2010.Findings
In Cameroon, the median CD4+ cell counts at ART initiation increased from 140 cells/μl (interquartile range, IQR: 66 to 210) in 2007–2009 to 163 cells/μl (IQR: 73 to 260) in 2010. The estimated average time from seroconversion to ART initiation decreased from 10.4 years (95% confidence interval, CI: 10.3 to 10.5) to 9.8 years (95% CI: 9.6 to 10.0). Delay in ART initiation increased from 3.4 years (95% CI: 3.1 to 3.7) to 5.8 years (95% CI: 5.6 to 6.2).Conclusion
The estimated time to initiate ART and the delay in ART initiation indicate that progress in Cameroon is insufficient. These indicators should help monitor whether public health interventions to accelerate ART initiation are successful. 相似文献48.
Vynckier Pieter Ferrannini Giulia Rydén Lars Tokgözoğlu Lale Bruthans Jan Kotseva Kornelia Wood David De Backer Tine Gevaert Sofie De Bacquer Dirk De Smedt Delphine 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2021,35(4):801-808
Cardiovascular Drugs and Therapy - This study is aimed at investigating gender differences in the medical management of patients with coronary heart disease (CHD). Analyses were based on the ESC... 相似文献
49.
Six E Ndiaye D Laabi Y Brou C Gupta-Rossi N Israel A Logeat F 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(13):7638-7643
Notch signaling is involved in numerous cell fate decisions in invertebrates and vertebrates. The Notch receptor is a type I transmembrane (TM) protein that undergoes two proteolytic steps after ligand binding, first by an ADAM (a distintegrin and metalloprotease) in the extracellular region, followed by gamma-secretase-mediated cleavage inside the TM domain. We demonstrate here that the murine ligand Delta1 (Dll1) undergoes the same sequence of cleavages, in an apparently signal-independent manner. Identification of the ADAM-mediated shedding site localized 10 aa N-terminal to the TM domain has enabled us to generate a noncleavable mutant. Kuzbanian/ADAM10 is involved in this processing event, but other proteases can probably substitute for it. We then show that Dll1 is part of a high-molecular-weight complex containing presenilin1 and undergoes further cleavage by a gamma-secretase-like activity, therefore releasing the intracellular domain that localizes in part to the nucleus. Using the shedding-resistant mutant, we demonstrate that this gamma-secretase cleavage depends on prior ectodomain shedding. Therefore Dll1 is a substrate for regulated intramembrane proteolysis, and its intracellular region possibly fulfills a specific function in the nucleus. 相似文献
50.
Galusca B Zouch M Germain N Bossu C Frere D Lang F Lafage-Proust MH Thomas T Vico L Estour B 《The Journal of clinical endocrinology and metabolism》2008,93(1):110-117
CONTEXT: Low fat mass and hormonal or nutritional deficiencies are often incriminated in bone loss related to thinness. Constitutional thinness has been described in young women with low body mass index (BMI) but close-to-normal body composition, physiological menstruation, no hormonal abnormalities, and no anorexia nervosa (AN) psychological profile. OBJECTIVE: Our objective was to determine whether constitutional thinness is associated with impaired bone quality. DESIGN, SETTING, AND PARTICIPANTS: This was an observational, cross-sectional study on 25 constitutionally thin and 44 AN young women with similar low BMI (<16.5 kg/m2) and 28 age-matched controls. MAIN OUTCOME MEASURES: Femoral and lumbar spine bone mineral density by dual-energy x-ray absorptiometry, distal tibia and radius bone architecture and breaking strength by three-dimensional peripheral quantitative computed tomography, and bone turnover markers were determined. RESULTS: Constitutionally thin subjects displayed a higher percentage of fat mass than AN subjects but had similar lumbar and femoral bone mineral density, which were significantly lower than in controls (P < 0.001). Constitutionally thin subjects displayed more markedly impaired trabecular and cortical bone parameters in the distal tibia than in the radius. AN bone structure was impaired only in subjects with a long history of disease. Calculated breaking strength was decreased in constitutional thinness and long-standing AN in both the radius and the tibia. Bone markers in constitutionally thin subjects were similar to those of controls. Osteoprotegerin to receptor activator of nuclear factor kappa B ligand ratio was higher in constitutionally thin subjects than in controls or AN women. CONCLUSIONS: Young women with constitutional thinness present an unexpectedly high prevalence of low bone mass (44%) associated with small bone size, overall diminished breaking strength, but normal bone turnover. Mechanisms related to insufficient skeletal load and/or genetics are proposed to explain this new phenotype of impaired bone quality. 相似文献