Search results for "Sclerosis"
showing 10 items of 1583 documents
Mutations in ATP13A2 (PARK9) are associated with an amyotrophic lateral sclerosis-like phenotype, implicating this locus in further phenotypic expans…
2019
Background Amyotrophic lateral sclerosis [1] is a genetically heterogeneous neurodegenerative disorder, characterized by late-onset degeneration of motor neurons leading to progressive limb and bulbar weakness, as well as of the respiratory muscles, which is the primary cause of disease fatality. To date, over 25 genes have been implicated as causative in ALS with C9orf72, SOD1, FUS, and TARDBP accounting for the majority of genetically positive cases. Results We identified two patients of Italian and French ancestry with a clinical diagnosis of juvenile-onset ALS who were mutation-negative in any of the known ALS causative genes. Starting with the index case, a consanguineous family of Ita…
Non-invasive ventilation effectiveness and the effect of ventilatory mode on survival in ALS patients.
2013
Non-invasive ventilation (NIV) prolongs survival in amyotrophic lateral sclerosis (ALS), but there are no data with which to compare the effectiveness of the different ventilator modes – volume (Vol-NIV) or pressure-cycled (Pres-NIV) ventilation – in ALS. We aimed to determine whether the ventilatory mode has an effect on ventilation effectiveness and survival of ALS patients using NIV. We used a retrospective study that included all ALS patients for whom NIV was indicated in two referral units: one using Vol-NIV and the other using Pres-NIV. Demographic, functional and nocturnal gas exchange parameters at NIV initiation were recorded. Eighty-two ALS patients ventilated using Pres-NIV and 6…
Role of Transesophageal Echocardiography in Dissection of the Aorta and Evaluation of Degenerative Aortic Disease
1993
The combination of different ultrasound techniques such as transthoracic, suprasternal, subcostal, and TEE has a high sensitivity and specificity in the diagnosis of aortic dissection. Limitations of this combined ultrasound technique are related to the visualization of the ascending part of the aortic arch, which, because of the interposition of the trachea, cannot be visualized completely. The beginning or end of a dissection in this part of the aorta may be misinterpreted. However, false-negative results are rare. False-positive results due to artifacts resulting from reverberations in an ectatic ascending aorta must be taken into account. The most important diagnostic goals in acute or …
Cyclosporine A Impairs the Macrophage Reverse Cholesterol Transport in Mice by Reducing Sterol Fecal Excretion
2012
Despite the efficacy in reducing acute rejection events in organ transplanted subjects, long term therapy with cyclosporine A is associated with increased atherosclerotic cardiovascular morbidity. We studied whether this drug affects the antiatherogenic process of the reverse cholesterol transport from macrophages in vivo. Cyclosporine A 50 mg/kg/d was administered to C57BL/6 mice by subcutaneous injection for 14 days. Macrophage reverse cholesterol transport was assessed by following [(3)H]-cholesterol mobilization from pre-labeled intraperitoneally injected macrophages, expressing or not apolipoprotein E, to plasma, liver and feces. The pharmacological treatment significantly reduced the …
Stimulation of the AT2 receptor reduced atherogenesis in ApoE−/−/AT1A−/− double knock out mice
2012
AT1 receptor blockers (ARB) and in part ACE inhibitors (ACI) potentially exert beneficial effects on atherogenesis independent of AT1 receptor inhibition. These pleiotropic effects might be related to angiotensin II mediated activation of the AT2 receptor. To analyze this hypothesis we investigated the development of atherosclerosis and the role of ACIs and ARBs in apolipoprotein E-deficient (ApoE(-/-)) mice and in ApoE/AT1A receptor double knockout mice (ApoE(-/-)/AT1A(-/-)). ApoE(-/-) mice and ApoE(-/-)/AT1A(-/-) mice were fed cholesterol-rich diet for 7 weeks. Vascular oxidative stress, endothelial dysfunction, and atherosclerotic lesion formation were evident in ApoE(-/-) mice, but were…
CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-α levels
2004
SummaryMonocytes play a central role in the inflammatory disease atherosclerosis. CD14+CD16+ monocytes are considered proinflammatory monocytes, as they have an increased capacity to produce proinflammatory cytokines, such as TNF-α, and are elevated in various inflammatory diseases. We hypothesized that patients with coronary artery disease (CAD) have increased levels of CD14+CD16+ monocytes, and that CD14+CD16+ monocytes are associated with inflammation markers. We investigated CD14+CD16+ monocytes in 247 patients with CAD and 61 control subjects using flow cytometry. In addition serum concentrations of TNF-α, IL-6, and Hs-CRP were assessed. Patients with CAD had higher levels of CD14+CD16…
Prevalence and Risk Factors of PAD among Patients with Elevated ABI
2008
ObjectivesTo assess the prevalence and clinical significance of elevated ankle-brachial index (ABI) in patients referred to vascular consultation.DesignRetrospective clinical study.Material and methodsIn 1,762 patients referred with a suspicion of peripheral arterial disease (PAD), ABI and toe brachial index (TBI) were measured by photoplethysmography. ABI≥1.3 was considered falsely elevated and TBI<0.60 was the diagnostic criterion for PAD.ResultsThe prevalence of elevated ABI was 8.4% and that of PAD among these patients 62.2%. PAD was significantly more prevalent among subjects with severe symptoms (rest pain, ulcers or gangrene) than in those with intermittent claudication (83.8% and 45…
Large-scale gene-centric analysis identifies novel variants for coronary artery disease.
2011
Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through w…
Integrating genome-wide genetic variations and monocyte expression data reveals trans-regulated gene modules in humans.
2011
One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. So far, few cis expression quantitative trait loci (eQTLs) have been reliably related to disease susceptibility. Trans-regulating mechanisms may play a more prominent role in disease susceptibility. We analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 European unrelated subjects. We applied a method of extraction of expression patterns—independent component analysis—to identify sets of co-regulated genes. These patterns were then related to 675,350 SNPs to identify maj…
Clobetasol promotes neuromuscular plasticity in mice after motoneuronal loss via sonic hedgehog signaling, immunomodulation and metabolic rebalancing
2021
AbstractMotoneuronal loss is the main feature of amyotrophic lateral sclerosis, although pathogenesis is extremely complex involving both neural and muscle cells. In order to translationally engage the sonic hedgehog pathway, which is a promising target for neural regeneration, recent studies have reported on the neuroprotective effects of clobetasol, an FDA-approved glucocorticoid, able to activate this pathway via smoothened. Herein we sought to examine functional, cellular, and metabolic effects of clobetasol in a neurotoxic mouse model of spinal motoneuronal loss. We found that clobetasol reduces muscle denervation and motor impairments in part by restoring sonic hedgehog signaling and …