Abstract：
:Multiple sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system, is today a leading cause of unpredictable lifelong disability in young adults. The treatment of patients in progressive stages remains highly challenging, alluding to our limited understanding of the underlying pathological processes. In this review, we provide insights into the mechanisms underpinning MS progression from a perspective of epigenetics, that refers to stable and mitotically heritable, yet reversible, changes in the genome activity and gene expression. We first recapitulate findings from epigenetic studies examining the brain tissue of progressive MS patients, which support a contribution of DNA and histone modifications in impaired oligodendrocyte differentiation, defective myelination/remyelination and sustained neuro-axonal vulnerability. We next explore possibilities for identifying factors affecting progression using easily accessible tissues such as blood by comparing epigenetic signatures in peripheral immune cells and brain tissue. Despite minor overlap at individual methylation sites, nearly 30% of altered genes reported in peripheral immune cells of progressive MS patients were found in brain tissue, jointly converging on alterations of neuronal functions. We further speculate about the mechanisms underlying shared epigenetic patterns between blood and brain, which likely imply the influence of internal (genetic control) and/or external (e.g. smoking and ageing) factors imprinting a common signature in both compartments. Overall, we propose that epigenetics might shed light on clinically relevant mechanisms involved in disease progression and open new avenues for the treatment of progressive MS patients in the future.
journal_name
J Intern Medjournal_title
Journal of internal medicineauthors
Kular L,Jagodic Mdoi
10.1111/joim.13045subject
Has Abstractpub_date
2020-07-01 00:00:00pages
82-102issue
1eissn
0954-6820issn
1365-2796journal_volume
288pub_type
杂志文章,评审abstract：:A young, apparently healthy, soldier developed acute muscle weakness and rhabdomyolysis following prolonged exercise. The resultant myoglobinuria caused severe acute renal failure. Further investigation revealed the presence of carnitine palmitoyltransferase deficiency as the cause of the rhabdomyolysis. Renal functio...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.1993.tb00991.x
更新日期：1993-03-01 00:00:00
abstract：OBJECTIVE:The aim of the study was to quantify the inter-relationship between bone mineral density and physical activity, muscle strength, and body mass composition in a group of healthy 16-20-year-old women. DESIGN:A cross-sectional study. SETTING:Reykjavik area. SUBJECTS:Two-hundred and fifty-four Icelandic Caucas...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1046/j.1365-2796.1999.00486.x
更新日期：1999-05-01 00:00:00
abstract：OBJECTIVES:Chronic Chlamydia pneumoniae infection is considered as a cardiovascular risk factor and antibodies are commonly analysed by the subjective microimmunofluorescence (MIF) test. We wanted to investigate the C. pneumoniae IgA- and IgG seroprevalence in young survivors of myocardial infarction and matched contro...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1046/j.1365-2796.2002.00942.x
更新日期：2002-02-01 00:00:00
abstract：:Conventional nonsteroidal anti-inflammatory drugs (NSAIDs), i.e. nonselective cyclooxygenase COX inhibitors have well-documented nephrotoxicity. Adverse renal effects occur because of inhibition of the synthesis of cyclooxygenase-derived prostaglandins which act to modulate pathologic processes that would normally imp...
journal_title：Journal of internal medicine
pub_type： 杂志文章,评审
doi：10.1046/j.1365-2796.2003.01146.x
更新日期：2003-06-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:In the past two decades, an increasing number of nationwide, Swedish Healthcare Quality Registries (QRs) focusing on specific disorders have been initiated, mostly by physicians. Here, we describe the purpose, organization, variables, coverage and completeness of 103 Swedish QRs. METHODS:From...
journal_title：Journal of internal medicine
pub_type： 杂志文章,评审
doi：10.1111/joim.12303
更新日期：2015-01-01 00:00:00
abstract：:We determined whether ketoconazole prophylaxis might reduce Candida colonization and infections in adult patients with acute leukaemia. During first-remission induction therapy 50 patients were treated with 200 mg ketoconazole administered orally daily, while 57 patients received placebo in a double-blind, randomized ...
journal_title：Journal of internal medicine
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1111/j.1365-2796.1992.tb00945.x
更新日期：1992-04-01 00:00:00
abstract：OBJECTIVES:In this study, we explore the associations of decreased thyroid hormone levels with inflammation, wasting and survival in biochemically euthyroid patients with end-stage renal disease (ESRD). DESIGN:After exclusion of 23 patients with thyroid-stimulating hormone (TSH) values outside the normal range (0.1-4....
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.2007.01865.x
更新日期：2007-12-01 00:00:00
abstract：OBJECTIVES:Polymyalgia rheumatica (PMR) is a rheumatic disease that is characterized by intense activation of systemic inflammation. Systemic inflammation has been associated with an imbalance between endothelial injury and repair, defined by an increased number of circulating endothelial microparticles (EMPs) and a re...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.2011.02510.x
更新日期：2012-08-01 00:00:00
abstract：OBJECTIVE:To evaluate primary hyperparathyroidism (HPT) as a risk factor for hip fractures. DESIGN:A population-based, record-linked, prospective study with a mean observation time of 17 years (women) and 16.5 years (men). SETTING:A cohort obtained from a register of hospital admissions in the Uppsala Health Care Reg...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.1993.tb01017.x
更新日期：1993-12-01 00:00:00
abstract：:There is clear heritability of human longevity. However, the genetics of ageing is likely to be complex. Evolution theory tells us not to expect genes that have been selected to promote ageing. Ageing is not programmed but results from accumulation of somatic damage, owing to limited investments in maintenance and rep...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.2007.01901.x
更新日期：2008-02-01 00:00:00
abstract：:Patients with established coronary disease and abnormalities of lipid metabolism represent a particularly important subgroup, since their mortality risk is typically 10 times greater than that amongst-subjects with comparable risk factors but no clinical history. Such patients are commonly treated initially with anti-...
journal_title：Journal of internal medicine
pub_type： 杂志文章,评审
doi：10.1046/j.1365-2796.1997.109132000.x
更新日期：1997-04-01 00:00:00
abstract：OBJECTIVE:To test the relationship between physical activity and physical fitness, and the relationship between these variables and the primordial risk factor blood pressure (BP). DESIGN:A cross-sectional study of all Danish pupils in the same grade at 'gymnasium' (the Danish upper secondary school). SETTING:Tests an...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.1994.tb00803.x
更新日期：1994-09-01 00:00:00
abstract：OBJECTIVE:To analyse the associations between serum gamma-glutamyl transpeptidase activity (GTP) and the components of the metabolic syndrome. DESIGN:Cross-sectional, observational study of hypertensive patients and controls. SETTING:The participating subjects visited the research laboratory of the Department of Inte...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1046/j.1365-2796.2000.00723.x
更新日期：2000-09-01 00:00:00
abstract：:We describe a 48-year-old woman with recurrent severe hypoglycaemia apparently caused by a paraprotein with insulin-binding capacity. Very high fasting values were found for serum insulin (170 and > 250 mU l-1) as well as for proinsulin 125 pmol l-1 and an insulinoma was suspected. Hypoglycaemia developed after an ora...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.1993.tb00766.x
更新日期：1993-10-01 00:00:00
abstract：:In 76 consecutive patients who had received diuretics for 1-17 years for arterial hypertension or congestive heart failure, muscle concentrations of magnesium, potassium, and sodium-potassium pumps were significantly reduced compared to 31 age- and sex-matched controls. Thirty-six patients with muscle magnesium and/or...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.1993.tb00663.x
更新日期：1993-02-01 00:00:00
abstract：BACKGROUND:No survival benefit of using blood stem cells instead of bone marrow (BM) has been shown in matched unrelated donor (MUD) transplantation. DESIGN AND METHODS:In a retrospective registry analysis, we compared the use of blood stem cells (n = 1502) and BM (n = 760) from unrelated donors in patients aged 18-60...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.2012.02547.x
更新日期：2012-11-01 00:00:00
abstract：:Traumatic brain injury (TBI) is a major cause of acquired disability globally, and effective treatment methods are scarce. Lately, there has been increasing recognition of the devastating impact of TBI resulting from sports and other recreational activities, ranging from primarily sport-related concussions (SRC) but a...
journal_title：Journal of internal medicine
pub_type： 杂志文章,评审
doi：10.1111/joim.12900
更新日期：2019-06-01 00:00:00
abstract：OBJECTIVE:Haemostatic imbalance may be an aetiological factor in the development of acute coronary syndromes. Inherited resistance to activated protein C (APC) is a common disorder associated with hypercoagulability and lifelong risk of venous thrombosis. APC resistance is due to a single mutation in the gene coding fo...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1046/j.1365-2796.1996.470808000.x
更新日期：1996-03-01 00:00:00
abstract：BACKGROUND:The aim of the study was to investigate the association between the proximal level of the clot and the severity of pulmonary embolism (PE). METHODS:The cohort consisted of 99 consecutive patients with PE diagnosed by multi-detector computed tomography. A new score was constructed by calculating the mean val...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.2006.01733.x
更新日期：2007-01-01 00:00:00
abstract：OBJECTIVE:To study the short-term efficacy, tolerability and safety of the treatment with gemfibrozil 600 mg twice daily or placebo in male patients with established atherosclerosis, with a lipid profile matching the 'high triglyceride-low high-density lipoprotein (HDL) cholesterol trait'. DESIGN:Double-blind randomiz...
journal_title：Journal of internal medicine
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2796.1994.tb00813.x
更新日期：1994-10-01 00:00:00
abstract：OBJECTIVES:To investigate if an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene associates with HLA-DR alleles previously found to be of prognostic interest in Scandinavian sarcoidosis patients. This may contribute to characteristics associated with these HLA-DR alleles, such as a ...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1046/j.1365-2796.2002.00946.x
更新日期：2002-03-01 00:00:00
abstract：:Evaluation of pro-oxidant/antioxidant dietary factors in relation to individual susceptibility to cancer and cardiovascular disease is justified based on a review of the literature. This working hypothesis is amendable to further scientific validation from biomarkers with end-point sensitivity to oxygen radicals. So f...
journal_title：Journal of internal medicine
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2796.1993.tb00651.x
更新日期：1993-01-01 00:00:00
abstract：:Cardiovascular disease remains the most prevalent cause of human morbidity and mortality in ageing Western societies. Basic and translational scientific efforts have focused on the development and improvement of diagnostic and therapeutic strategies to limit the burden of associated diseases, such as stroke and myocar...
journal_title：Journal of internal medicine
pub_type： 杂志文章,评审
doi：10.1111/joim.12298
更新日期：2014-12-01 00:00:00
abstract：:A 59-year-old male patient presented with invalidating osteomalacia of 2.5 years' duration. The osteomalacia was caused by severe malabsorption due to gluten-sensitive enteropathy (GSE). There were no other signs or symptoms of GSE in this patient. Clinical presentation with monosymptomatic osteomalacia is very unusua...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.1992.tb00554.x
更新日期：1992-07-01 00:00:00
abstract：OBJECTIVES:to examine fatigue variability over time in chronic fatigue syndrome (CFS) and the effect of other symptoms on its predictability. DESIGN:longitudinal cohort study of patients with CFS (Fukuda criteria). SETTING:specialist CFS clinical service. SUBJECTS:phase 1: 100 patients who participated in a study of...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.2010.02306.x
更新日期：2011-02-01 00:00:00
abstract：BACKGROUND:Intravenous nitrate therapy has been shown to improve short-term outcome of acute heart failure patients treated in the intensive care unit. The potential of a noninvasive high-dose nitrate strategy in the Emergency Department and the general ward remains unknown. METHODS:A total of 128 consecutive acute he...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.2009.02146.x
更新日期：2010-03-01 00:00:00
abstract：OBJECTIVES:Cardiac sarcoidosis (CS) without clinically apparent extracardiac disease may escape detection because of the poor sensitivity of endomyocardial biopsy (EMB). We set out to analyse our experience of repeated and imaging-guided biopsies in clinically isolated CS. METHODS:We retrospectively reviewed the medic...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.2011.02396.x
更新日期：2011-11-01 00:00:00
abstract：OBJECTIVE:Waist circumference is a clinical marker of obesity and an established risk factor for cardiovascular (CV) disease. Adiponectin, an adipocyte-derived hormone and new biomarker of obesity, was recently proposed as the missing link between obesity and increased cardiovascular risk. We evaluated waist and adipon...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.2009.02192.x
更新日期：2010-06-01 00:00:00
abstract：:Serum creatine kinase (CK) is an important adjunct in the diagnosis of myocardial infarction or in monitoring for the side-effects of drugs. We report elevation of CK in patients with untreated heterozygous familial hypercholesterolaemia (FH) with no evidence of myocardial infarction. Of a group of 30 patients, 60% ha...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.1990.tb00268.x
更新日期：1990-11-01 00:00:00
abstract：OBJECTIVES:We aimed to characterize the clinical experiences of patients in whom heparin-induced thrombocytopenia (HIT) complicated heparin therapy for venous thromboembolism (VTE) and who switched to argatroban. DESIGN:A retrospective analysis of previously reported prospective, multicentre, historical-controlled Arg...
journal_title：Journal of internal medicine
pub_type： 杂志文章
doi：10.1111/j.1365-2796.2005.01573.x
更新日期：2005-12-01 00:00:00
