Abstract:
OBJECTIVE:To investigate the effects of leptin on different T-cell populations, in order to gain more insight into the link between leptin and obesity. METHODS:Three hundred and nine RRMS patients and 322 controls participated in a cross-sectional survey, to confirm whether excess weight/obesity in adolescence or early adulthood increased the risk of MS. Serum leptin levels were determined by ELISA. MBP83-102 , and MOG63-87 peptide-specific T cells lines were expanded from peripheral blood mononuclear cells. Leptin receptor expression was measured by RT-PCR and flow cytometry. Bcl-2, p-STAT3, pERK1/2, and p27kip1 expression were assayed using ELISA, and apoptosis induction was determined by Annexin V detection. Cytokines were assessed by ELISPOT and ELISA, and regulatory T cells (Tregs) by flow cytometry. RESULTS:Logistic regression analysis, showed excess weight at age 15, and obesity at 20 years of age increased MS risk (OR = 2.16, P = 0.01 and OR = 3.9, P = 0.01). Leptin levels correlated with BMI in both groups. The addition of Leptin increased autoreactive T-cell proliferation, reduced apoptosis induction, and promoted proinflammatory cytokine secretion. Obese patients produced more proinflammatory cytokines compared to overweight/normal/underweight subjects. Inverse correlation was found between leptin levels and circulating Treg cells (r = -0.97, P < 0.0001). Leptin inhibited Treg proliferation. Effects of leptin on CD4+ CD25- effector T cells were mediated by increased STAT3 and ERK1/2 phosphorylation, and down modulation of the cell cycle inhibitor P27kip1 . In contrast, leptin effects on Tregs resulted from decreased phosphorylation of ERK1/2 and upregulation of p27kip1 . INTERPRETATION:Leptin promotes autoreactive T-cell proliferation and proinflammatory cytokine secretion, but inhibits Treg-cell proliferation.
journal_name
Ann Clin Transl Neuroljournal_title
Annals of clinical and translational neurologyauthors
Marrodan M,Farez MF,Balbuena Aguirre ME,Correale Jdoi
10.1002/acn3.51291subject
Has Abstractpub_date
2020-12-28 00:00:00issn
2328-9503pub_type
杂志文章abstract:OBJECTIVE:Infantile spasm syndrome (ISS) is an epileptic encephalopathy without established treatment after the failure to standard of care based on steroids and vigabatrin. Converging lines of evidence indicating a role of NR2B subunits of the N-methyl-D-aspartate (NMDA) receptor on the onset of spams in ISS patients,...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50998
更新日期:2020-03-01 00:00:00
abstract::Myotonic dystrophy type I (DM1) is an autosomal dominant disease of which clinical manifestations resemble premature aging. We evaluated the contribution of telomere length in pathogenesis in 361 DM1 patients (12 with serial measurements) and 223 unaffected relative controls using qPCR assay. While no differences in b...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50954
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVE:Epilepsy is a common neurological disorder that affects 1% of the population. Approximately, 30% of individuals with epilepsy are refractory to treatment, highlighting the need for novel therapies. Conventional anticonvulsant screening relies predominantly on induced seizure models. However, these models may ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.413
更新日期:2017-04-26 00:00:00
abstract::Rho-associated kinase (ROCK) is an emerging target in acute ischemic stroke. Early pre-hospital treatment with ROCK inhibitors may improve their efficacy, but their antithrombotic effects raise safety concerns in hemorrhagic stroke, precluding use prior to neuroimaging. Therefore, we tested whether ROCK inhibition aff...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.569
更新日期:2018-05-01 00:00:00
abstract:OBJECTIVE:Brain connectivity at rest is altered in temporal lobe epilepsy (TLE), particularly in "hub" areas such as the posterior default mode network (DMN). Although both functional and anatomical connectivity are disturbed in TLE, the relationships between measures as well as to seizure frequency remain unclear. We ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.173
更新日期:2015-04-01 00:00:00
abstract::Three relatives carrying a t(4;8)(p15.2;p23.2) translocation had juvenile myoclonic epilepsy, self-limited photosensitive occipital epilepsy and migraine with aura. The t(4;8) translocation interrupted the coding sequence of CSMD1 gene and occurred immediately to the 3'UTR of STIM2 gene. STIM2 was overexpressed in the...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51040
更新日期:2020-05-01 00:00:00
abstract:OBJECTIVE:Examine whether cognitive reserve moderates the association of 1) vascular risk factors and 2) white matter hyperintensity burden with risk of clinical progression and longitudinal cognitive decline. METHODS:BIOCARD Study participants were cognitively normal and primarily middle-aged (M = 57 years) at baseli...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51120
更新日期:2020-08-01 00:00:00
abstract:OBJECTIVE:Given their diverse phenotypes, mitochondrial diseases (MDs) are often difficult to diagnose. Fibroblast growth factor 21 (FGF-21) and growth differentiation factor 15 (GDF-15) represent promising biomarkers for MD diagnosis. Herein we conducted a meta-analysis to compare their diagnostic accuracy for MDs. M...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51104
更新日期:2020-07-01 00:00:00
abstract:OBJECTIVE:Increased translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), in glial cells of the brain has been used as a neuroinflammation marker in the early and middle stages of neurodegenerative diseases, such as Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB). I...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50837
更新日期:2019-08-01 00:00:00
abstract::Many observations suggest that mutations of mitochondrial DNA (mtDNA) could be responsible for the neurodegenerative changes of Alzheimer's disease (AD). Here we examined the signal intensity of the four alleles of each mtDNA nucleotide position (np) in whole blood of AD patients and age-matched controls using MitoChi...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.42
更新日期:2014-04-01 00:00:00
abstract:OBJECTIVE:To determine the frequency of distinctive EGFr cysteine altering NOTCH3 mutations in the 60,706 exomes of the exome aggregation consortium (ExAC) database. METHODS:ExAC was queried for mutations distinctive for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASI...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.344
更新日期:2016-09-28 00:00:00
abstract:Objective:Immunological studies have demonstrated a plethora of beneficial effects of dimethyl fumarate (DMF) on various cell types. However, the cellular and molecular targets are incompletely understood and response markers are scarce. Here, we focus on the relation between nuclear factor (erythroid-derived 2)-like 2...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.553
更新日期:2018-04-16 00:00:00
abstract:OBJECTIVE:Multiple sclerosis (MS) is a heterogenous, inflammatory disease of the central nervous system. Microbiota alterations in MS versus healthy controls (HC) are observed, but results are inconsistent. We studied diversity, enterotypes, and specific gut microbial taxa variation between MS and HC, and between MS su...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51004
更新日期:2020-04-01 00:00:00
abstract:OBJECTIVE:Analysis of the T-cell receptor (TCR) repertoire in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) can reveal antigen-specific immune responses potentially implicated in the disease process. We applied a new unbiased deep-sequencing method for TCR repertoire analysis to accurately meas...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.310
更新日期:2016-04-20 00:00:00
abstract:Objective:We aimed to study the occurrence and development of axonal pathology and the influence of astrocytes in vanishing white matter. Methods:Axons and myelin were analyzed using electron microscopy and immunohistochemistry on Eif2b4 and Eif2b5 single- and double-mutant mice and patient brain tissue. In addition, ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.540
更新日期:2018-03-01 00:00:00
abstract:Objective:Clinical assessment of auditory attention in patients with disorders of consciousness is often limited by motor impairment. Here, we employ intersubject correlations among electroencephalography responses to naturalistic speech in order to assay auditory attention among patients and healthy controls. Methods...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.470
更新日期:2017-09-27 00:00:00
abstract:OBJECTIVE:To study the safety of antiepileptic drug (AED) withdrawal after temporal lobe epilepsy (TLE) surgery. METHODS:We reviewed patients who underwent TLE surgery from 1995 to 2011, collecting data on doses, dates of AED initiation, reduction, and discontinuation. Predictors of seizure outcome were defined using ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.35
更新日期:2014-02-01 00:00:00
abstract:Introduction:It is unknown if treatment with rt-PA in mild acute ischemic stroke (MIS) is associated with improvement in long term cognition. Methods:Forty-five patients with suspected acute mild stroke or transient ischemic attacks with NIHSS ≤6 were enrolled in a prospective cohort. Cognitive testing was performed w...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.719
更新日期:2019-01-22 00:00:00
abstract:Objective:There is no consensus on the treatment of progressive multifocal leukoencephalopathy (PML) occurring in multiple sclerosis (MS) patients treated with natalizumab (Nz). We report novel immune activating treatment with filgrastim of Nz-associated PML in MS patients treated at Rush University Medical Center. Me...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.776
更新日期:2019-04-08 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate if urinary sediment cells offered a robust alternative to muscle biopsy for the diagnosis of single mtDNA deletions. METHODS:Eleven adult patients with progressive external ophthalmoplegia and a known single mtDNA deletion were investigated. Urinary sediment cells were u...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51119
更新日期:2020-08-01 00:00:00
abstract:Objectives:The aim of this study was to investigate whether short-term inverse occlusion, combined with moderate physical exercise, could promote the recovery of visual acuity and stereopsis in a group of adult anisometropic amblyopes. Methods:Ten adult anisometropic patients underwent six brief (2 h) training session...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.698
更新日期:2018-12-28 00:00:00
abstract:Objective:Features of cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy ( CADASIL) caused by NOTCH3 mutations vary between ethnicities and regions. In Taiwan, more than 70% of CADASIL patients carry the mutation hot spot of p.R544C. We investigated the prevalence of NOTCH3 p.R544...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章,多中心研究
doi:10.1002/acn3.690
更新日期:2018-11-20 00:00:00
abstract:Objective:We aimed to investigate mutation-specific white matter (WM) integrity changes in presymptomatic and symptomatic mutation carriers of the C9orf72,MAPT, and GRN mutations by use of diffusion-weighted imaging within the Genetic Frontotemporal dementia Initiative (GENFI) study. Methods:One hundred and forty muta...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.601
更新日期:2018-07-11 00:00:00
abstract:OBJECTIVE:To compare the values of arterial spin-labeled (ASL) MRI and fluorodeoxyglucose (FDG) PET in the diagnosis of behavioral variant of frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). METHODS:Partial least squares logistic regression was used to identify voxels with diagnostic value in cerebral blo...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.330
更新日期:2016-08-30 00:00:00
abstract:OBJECTIVES:Isradipine is a dihydropyridine calcium channel inhibitor that has demonstrated concentration-dependent neuroprotective effects in animal models of Parkinson's disease (PD) but failed to show efficacy in a phase 3 clinical trial. The objectives of this study were to model the plasma pharmacokinetics of israd...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51300
更新日期:2021-01-18 00:00:00
abstract:OBJECTIVE:Trinucleotide GGC repeat expansion in the 5'UTR of the NOTCH2NLC gene has been recognized as the pathogenesis of neuronal intranuclear inclusion disease (NIID). Previous studies have described that some NIID patients showed clinical and pathological similarities with multiple system atrophy (MSA). This study ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51021
更新日期:2020-04-01 00:00:00
abstract:OBJECTIVE:The objective of this study was to investigate the genetic etiology of the X-linked disorder "Hypomyelination of Early Myelinating Structures" (HEMS). METHODS:We included 16 patients from 10 families diagnosed with HEMS by brain MRI criteria. Exome sequencing was used to search for causal mutations. In silic...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.203
更新日期:2015-06-01 00:00:00
abstract:OBJECTIVE:Human T-cell leukemia virus-1 (HTLV-1) associated myelopathy/tropic spastic paraparesis (HAM/TSP) is induced by chronic inflammation in spinal cord due to HTLV-1 infection. Cerebrospinal fluid (CSF) neopterin or proviral load are clinically measured as disease grading biomarkers, however, they are not exactly...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.169
更新日期:2015-03-01 00:00:00
abstract::Charcot-Marie-Tooth disease type-1A (CMT1A) is one of the most common types of inherited peripheral nerve diseases. It is caused by the trisomy of chromosome 17p12 (c17p12), a large DNA segment of 1.4 Mb containing PMP22 plus eight other genes. The size of c17p12 is formidable for any cloning technique to manipulate, ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.432
更新日期:2017-06-15 00:00:00
abstract:OBJECTIVE:Multiple sclerosis (MS) is an autoimmune demyelinating disorder, which is characterized by relapses and remissions. Serum neurofilament light chain (sNfL) is an emerging biomarker of disease activity but its clinical use is still limited. In this study, we aim to characterize the temporal association between ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51060
更新日期:2020-06-01 00:00:00