Search results for "Sclerosis"

Association between multiple biomarkers and classical risk factors with early carotid atherosclerosis

2013

Is there a link between liver steatosis, carotid atherosclerosis and C-reactive protein in metabolic and non-metabolic patients?

2008

Prediction of cardiovascular events with traditional risk equations and total plaque area of carotid atherosclerosis

2021

Abstract A large number of cardiovascular events occur in seemingly healthy individuals. Atherosclerosis imaging can improve the outcome and treatment regime of such subjects. We aim to assess the predictive value of atherosclerosis imaging beyond traditional risk calculators in subjects aged 40–65 years. We compared PROCAM, SCORE and FRAM with carotid ultrasound (total plaque area, TPA) and arterial age (AA) was calculated in subjects without known cardiovascular diseases. Follow-up was obtained by phone or mail. In 2842 subjects (age 50 ± 8, 38% women) 154 (5.4%) cardiovascular events occurred (ASCVD: 41 myocardial infarctions, 16 strokes or TIA, 21 CABG, 41 PTCA, 35 coronary artery disea…

Integrated non-invasive approach to atherosclerosis with cardiac CT and carotid ultrasound in patients with suspected coronary artery disease

2017

The aim of the study was to compare the atherosclerotic disease in the coronary and carotid arteries in patients who underwent non-invasive imaging for suspected stable coronary artery disease (CAD). 107 patients (64 men, age 59 ± 12) with atypical chest pain underwent cardiac CT (CCT) and carotid ultrasound (US) on the same day. Severity (obstructive or not-obstructive disease), location, shape, and composition of atherosclerotic plaques in the two districts were evaluated. Patients presented normal coronary arteries in 36 % (n = 38), not-obstructive CAD in 36 % (n = 39), and obstructive CAD in 28 % (n = 30), while had normal carotid arteries in 53 % (n = 57), not-obstructive disease in 44…

Hypersusceptibility of neutrophil granulocytes towards lethal action of free fatty acids contained in enzyme-modified atherogenic low density lipopro…

2008

Abstract Objective The bulk of LDL entrapped in the arterial intima is modified by hydrolytic enzymes, leading to extensive cleavage of cholesterylesters and liberation of fatty acids. The latter induce apoptosis in endothelial cells but are far less cytotoxic towards macrophages. We have compared the cytotoxic effects of enzymatically modified LDL (E-LDL) on macrophages and polymorphonuclear granulocytes (PMN). Methods and results E-LDL displayed toxicity towards PMN at far lower concentrations than towards monocyte-derived macrophages. Native or oxidized LDL had no effect. Free fatty acids contained in E-LDL were the cause of the observed toxicity, which could be mimicked by linoleic acid…

ALS-linked FUS mutations confer loss and gain of function in the nucleus by promoting excessive formation of dysfunctional paraspeckles

2019

Mutations in the FUS gene cause amyotrophic lateral sclerosis (ALS-FUS). Mutant FUS is known to confer cytoplasmic gain of function but its effects in the nucleus are less understood. FUS is an essential component of paraspeckles, subnuclear bodies assembled on a lncRNA NEAT1. Paraspeckles may play a protective role specifically in degenerating spinal motor neurons. However it is still unknown how endogenous levels of mutant FUS would affect NEAT1/paraspeckles. Using novel cell lines with the FUS gene modified by CRISPR/Cas9 and human patient fibroblasts, we found that endogenous levels of mutant FUS cause accumulation of NEAT1 isoforms and paraspeckles. However, despite only mild cytoplasm…

Heterodimer formation of wild-type and amyotrophic lateral sclerosis-causing mutant Cu/Zn-superoxide dismutase induces toxicity independent of protei…

2008

Recent studies provide evidence that wild-type Cu/Zn-superoxide dismutase (SOD1(hWT)) might be an important factor in mutant SOD1-mediated amyotrophic lateral sclerosis (ALS). In order to investigate its functional role in the pathogenesis of ALS, we designed fusion proteins of two SOD1 monomers linked by a polypeptide. We demonstrated that wild-type-like mutants, but not SOD1(G85R) homodimers, as well as mutant heterodimers including SOD1(G85R)-SOD1(hWT) display dismutase activity. Mutant homodimers showed an increased aggregation compared with the corresponding heterodimers in cell cultures and transgenic Caenorhabditis elegans, although SOD1(G85R) heterodimers are more toxic in functiona…

Multiple sclerosis patient-derived CSF induces transcriptional changes in proliferating oligodendrocyte progenitors.

2014

Background: Cerebrospinal fluid (CSF) is in contact with brain parenchyma and ventricles, and its composition might influence the cellular physiology of oligodendrocyte progenitor cells (OPCs) thereby contributing to multiple sclerosis (MS) disease pathogenesis. Objective: To identify the transcriptional changes that distinguish the transcriptional response induced in proliferating rat OPCs upon exposure to CSF from primary progressive multiple sclerosis (PPMS) or relapsing remitting multiple sclerosis (RRMS) patients and other neurological controls. Methods: We performed gene microarray analysis of OPCs exposed to CSF from neurological controls, or definitive RRMS or PPMS disease course. R…

In Vivo Imaging of Partially Reversible Th17 Cell-Induced Neuronal Dysfunction in the Course of Encephalomyelitis

2010

SummaryNeuronal damage in autoimmune neuroinflammation is the correlate for long-term disability in multiple sclerosis (MS) patients. Here, we investigated the role of immune cells in neuronal damage processes in animal models of MS by monitoring experimental autoimmune encephalomyelitis (EAE) by using two-photon microscopy of living anaesthetized mice. In the brainstem, we detected sustained interaction between immune and neuronal cells, particularly during disease peak. Direct interaction of myelin oligodendrocyte glycoprotein (MOG)-specific Th17 and neuronal cells in demyelinating lesions was associated with extensive axonal damage. By combining confocal, electron, and intravital microsc…

High anti-JCPyV serum titers coincide with high CSF cell counts in RRMS patients

2020

Background: Progressive multifocal leukoencephalopathy (PML) can in rare cases occur in natalizumab-treated patients with high serum anti-JCPyV antibodies, hypothetically due to excessive blockade of immune cell migration. Objective: Immune cell recruitment to the central nervous system (CNS) was assessed in relapsing-remitting multiple sclerosis (RRMS) patients stratified by low versus high anti-JCPyV antibody titers as indicator for PML risk. Methods: Cerebrospinal fluid (CSF) cell counts of 145 RRMS patients were quantified by flow cytometry. Generalized linear models were employed to assess influence of age, sex, disease duration, Expanded Disability Status Scale (EDSS), clinical/radiol…