Low frequency of the disease-associated DRB1*15-DQB1*06 haplotype may contribute to the low prevalence of multiple sclerosis in Sami

2007 ◽  
Vol 69 (4) ◽  
pp. 299-304 ◽  
Author(s):  
H. F. Harbo ◽  
E. Utsi ◽  
Å. R. Lorentzen ◽  
M. T. Kampman ◽  
E. G. Celius ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Low Frequency ◽  
Low Prevalence

The 795CT polymorphism in osteopontin gene is not associated with multiple sclerosis in a Spanish population

2007 ◽  
Vol 13 (2) ◽  
pp. 250-252 ◽  
Author(s):  
A Mas ◽  
A Martínez ◽  
V De Las Heras ◽  
M Bartolomé ◽  
Eg De La Concha ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Low Frequency ◽  
Interleukin 10 ◽  
Interleukin 12 ◽  
Italian Population ◽  
Cytokine Network ◽  
Activated T Cells ◽  
Negative Finding ◽  
The Central Nervous System ◽  
Ms Pathogenesis

Multiple sclerosis (MS) is an inflammatory disease affecting the central nervous system. The dysregulation of the cytokine network is an important component of its pathogenesis. One of the cytokines produced by activated T-cells is osteopontin (OPN). OPN enhances the production of the pro-inflammatory cytokines, interleukin-12 and interferon-gamma, while reducing interleukin-10 levels. Therefore, OPN is considered a pro-inflammatory cytokine, and could play a key role in MS pathogenesis. The OPN gene contains several common polymorphisms, distributed in two main haplotypes, which may modulate its production or activity. A total of 326 MS patients and 484 healthy controls were typed for 795CT OPN polymorphism. In order to perform a familial study, 51 progenitor pairs were also included. No difference was found in the case-control or family study. This negative finding is inconsistent with a previous haplotype study in an Italian population, where the haplotype associated carried the low-frequency allele in position 795. In a Japanese population, a similar study yielded no association with this polymorphism. In conclusion, our data suggest that the 795 polymorphism does not play an etiological role per se and the haplotype structure may differ from one population to another. Multiple Sclerosis 2007; 13: 250–252. http://msj.sagepub.com

scholarly journals Long-term efficacy and safety of three times weekly dosing regimen of glatiramer acetate in relapsing multiple sclerosis patients: Seven-year results of the Glatiramer Acetate Low-frequency Administration (GALA) open-label extension study

2021 ◽  
Vol 7 (4) ◽  
pp. 205521732110615
Author(s):  
Peter Rieckmann ◽  
Robert Zivadinov ◽  
Alexey Boyko ◽  
Krzysztof Selmaj ◽  
Jessica K. Alexander ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Low Frequency ◽  
Exposure Period ◽  
Similar Efficacy ◽  
Open Label ◽  
Open Label Extension ◽  
Multiple Sclerosis Patients ◽  
Relapsing Multiple Sclerosis

Objective Describe the long-term outcomes of early-start (ES) and delayed-start (DS) glatiramer acetate 40 mg/mL treatment three times weekly (GA40) for up to seven years in the Glatiramer Acetate Low-frequency Administration (GALA) study in patients with relapsing multiple sclerosis (RMS). Methods Patients were evaluated every three to six months. The primary efficacy endpoint was annualized relapse rate (ARR); additional endpoints were exploratory or post hoc. For efficacy, data from the entire exposure period were used for the ES and DS cohorts. For safety, exposure only under GA40 was considered. Results Of the patients who continued into the open-label extension (OLE), 580/834 (70%) ES and 261/419 (62%) DS completed the OLE. For the entire placebo-controlled and OLE study period, ARR was 0.26 for ES and 0.31 for DS patients (risk ratio = 0.83; 95% confidence interval [CI]: 0.70–0.99). ES prolonged median time to first relapse versus DS (4.9 versus 4.3 years; hazard ratio = 0.82; 95% CI: 0.6–0.96). OLE-only results showed DS patients experienced similar efficacy for relapse and disability outcomes as ES patients. Adverse events were consistent with the well-established GA safety profile. Conclusions GA40 treatment conferred clinical benefit up to seven years, resulting in sustained efficacy and was generally well tolerated in RMS patients.

scholarly journals Frequency of HIV in Obstructive Lung Disease Patients

2018 ◽  
Vol 2 (2) ◽  
pp. 18-25
Author(s):  
Waqas Ahmed ◽  
Qudrat Ullah ◽  
Mughees Ahmed ◽  
Asif Hanif
Keyword(s):  
Lung Disease ◽  
Sample Size ◽  
Obstructive Lung Disease ◽  
Low Frequency ◽  
Smooth Muscle Contraction ◽  
Hiv Positive ◽  
Mortality And Morbidity ◽  
Causes Of Mortality ◽  
Low Prevalence ◽  
Very High

AbstractBackground: Obstructive lung disease (OLD) is one of the main causes of mortality and morbidity worldwide. Obstructive lung disease is the narrowing of bronchioles mainly due to excessive smooth muscle contraction. The objective of this study is to evaluate the Frequency of HIV in obstructive lung disease patients.Methodology: Samples were collected randomly, and study was completed in almost six months. 100 samples were taken with an informed consent taken from all the patients. EDTA and Clotted blood was collected for HIV ELISA and HIV screening.Results: In this study, 69% Males and 31%Females, 34% Smokers, 26% patients were Hypertensive, 10% patients were diabetic, 3% patients were diagnosed HIV positive by screening and ELISA.Conclusion: The frequency of HIV in obstructive lung disease patients in this research is not very high as compared to the previous researches, showing high frequency and relationship between HIV and obstructive lung disease patients. The reason behind low frequency is due to low sample size so by increasing the sample size we can get better understanding of frequency of HIV in obstructive lung disease patients. Another reason of insignificant results is low prevalence of HIV in Pakistan as compared to the previous researches in certain countries. 

Effect of fingolimod on cardiac autonomic regulation in patients with multiple sclerosis

2015 ◽  
Vol 22 (8) ◽  
pp. 1080-1085 ◽  
Author(s):  
Sakari Simula ◽  
Tomi Laitinen ◽  
Tiina M Laitinen ◽  
Tuula Tarkiainen ◽  
Päivi Hartikainen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
High Frequency ◽  
Frequency Ratio ◽  
Low Frequency ◽  
Autonomic Regulation ◽  
Rr Interval ◽  
Cardiac Autonomic Regulation ◽  
Multiple Sclerosis Patients

Background: Fingolimod modulates sphingosine-1-phosphate receptors that are also found in cardiovascular tissue. Objective: To investigate the effects of fingolimod on cardiac autonomic regulation prospectively. Methods: Twenty-seven relapsing–remitting multiple sclerosis patients underwent 24-hour electrocardiogram recording before, at the first day of fingolimod treatment (1d) and after three months of continuous dosing (3mo). The time interval between two consecutive R-peaks (RR-interval) was measured. Cardiac autonomic regulation was assessed by the various parameters of heart rate variability. Parasympathetic stimulation prolongs the RR-interval and increases heart rate variability while the effects of sympathetic stimulation are mainly the opposite. The low frequency/high frequency ratio reflects sympathovagal balance. Results: From baseline to 1d, a prolongation of the RR-interval ( P<0.001), an increase in the values of various heart rate variability parameters ( P<0.05 to P<0.001) and a decrease in the low frequency/high frequency ratio ( P<0.05) were demonstrated. At 3mo, although the RR-interval remained longer ( P<0.01), the values of various heart rate variability parameters were lower ( P<0.01 to P<0.001) as compared to baseline. At 3mo, the low frequency/high frequency ratio ( P<0.05) was higher in men than in women although no such difference was found at baseline or at 1d. Conclusions: After an initial increase in parasympathetic regulation, continuous fingolimod dosing shifts cardiac autonomic regulation towards sympathetic predominance, especially in men. Careful follow-up of fingolimod-treated relapsing–remitting multiple sclerosis patients is warranted as sympathetic predominance associates generally with impaired outcome. ClinicalTrials.cov: NCT01704183

Protein expression profiles in pediatric multiple sclerosis: potential biomarkers

2009 ◽  
Vol 15 (4) ◽  
pp. 455-464 ◽  
Author(s):  
KN Rithidech ◽  
L Honikel ◽  
M Milazzo ◽  
D Madigan ◽  
R Troxell ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mass Spectrometry ◽  
Protein Expression ◽  
Expression Profiles ◽  
Low Frequency ◽  
Complement Factor ◽  
Protein Biomarkers ◽  
Two Dimensional Gel Electrophoresis ◽  
Pediatric Multiple Sclerosis ◽  
Proteomic Approach

The diagnosis of pediatric multiple sclerosis (MS) is challenging due to its low frequency and the overlap with other acquired childhood demyelinating disorders of the central nervous system. To identify potential protein biomarkers which could facilitate the diagnosis, we used two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry to identify proteins associated with pediatric MS. Plasma samples from nine children with MS and nine healthy subjects, matched in aggregate by age and gender, were analyzed for differences in their patterns of protein expression. We found 12 proteins that were significantly up regulated in the pediatric MS group: alpha-1-acid-glycoprotein 1, alpha-1-B-glycoprotein, transthyretin, apoliprotein-C-III, serum amyloid P component, complement factor-I, clusterin, gelsolin, hemopexin, kininogen-1, hCG1993037-isoform, and vitamin D-binding protein. These results show that 2-DE in combination with mass spectrometry is a highly sensitive technique for the identification of blood-based biomarkers. This proteomic approach could lead to a new panel of diagnostic and prognostic markers in pediatric MS.

scholarly journals Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Cell ◽  
2018 ◽  
Vol 175 (6) ◽  
pp. 1679-1687.e7 ◽  
Author(s):  
Mitja Mitrovič ◽  
Nikolaos A. Patsopoulos ◽  
Ashley H. Beecham ◽  
Theresa Dankowski ◽  
An Goris ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Low Frequency ◽  
Multiple Sclerosis Risk

scholarly journals Acute Fingolimod Effects on Baroreflex and Cardiovascular Autonomic Control in Multiple Sclerosis

2019 ◽  
Vol 11 ◽  
pp. 117957351984994 ◽  
Author(s):  
Vittorio Racca ◽  
Marco Rovaris ◽  
Rosella Cavarretta ◽  
Emanuele Vaini ◽  
Anastasia Toccafondi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Baroreflex Sensitivity ◽  
Low Frequency ◽  
Acute Effect ◽  
Mean Value ◽  
Autonomic Control ◽  
Oral Drug ◽  
Pulse Interval ◽  
Dose Administration ◽  
Parasympathetic System

Background: Fingolimod, an oral drug used in multiple sclerosis (MS) treatment, exerts its action through S1P-receptor engagement. These receptors are also expressed in heart and endothelial cells. The engagement of receptors on the atrial heart myocytes may cause a slowing effect on heart rate (HR). We aimed to explore the acute effect of fingolimod on the cardiac autonomic control, a side-effect of the drug that still needs to be clarified. Methods: In 10 MS patients, we investigated the influence of the first administration of fingolimod (0.5 mg) on sympathetic and parasympathetic indexes via the analysis of the HR variability, and on the baroreflex sensitivity via sequence and alpha coefficient techniques. Results: Fingolimod produced an average HR maximal drop of 12.7 (7.8) beats/min and the minimal HR occurred after 2.73 (0.38) hours from the dose administration. The pulse interval (PI) mean value and the pNN50 and RMSSD indexes of parasympathetic drive to the heart significantly increased. Interestingly, in 6 out of 10 patients also the power in the low-frequency band (LF) increased. The baroreflex sensitivity was not modified by the first dose of the drug. Conclusions: Our findings indicate that although the first dose of fingolimod invariably activates the parasympathetic system, in several subjects, it may induce also a surge in the sympathetic cardiac drive. This suggests that not only the vagal, as usually assumed, but also the sympathetic autonomic branch should be considered in the risk profile assessment of MS patients starting treatment with fingolimod.

scholarly journals C6orf10 Low-Frequency and Rare Variants in Italian Multiple Sclerosis Patients

2019 ◽  
Vol 10 ◽  
Author(s):  
Nicole Ziliotto ◽  
Giovanna Marchetti ◽  
Chiara Scapoli ◽  
Matteo Bovolenta ◽  
Silvia Meneghetti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Rare Variants ◽  
Low Frequency ◽  
Multiple Sclerosis Patients

-308 G > A of TNF-α gene promoter decreases the risk of multiple sclerosis: a meta-analysis

2010 ◽  
Vol 17 (6) ◽  
pp. 658-665 ◽  
Author(s):  
Yan Yang ◽  
Rulin Sun ◽  
Heng Yang ◽  
Fang Zheng ◽  
Feili Gong
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Factors ◽  
Association Studies ◽  
Meta Analysis ◽  
Low Frequency ◽  
Gene Promoter ◽  
Tnf Α ◽  
Control Association ◽  
Necrosis Factor ◽  
Reduced Risk

Background: Environmental and genetic factors are thought to be involved in the pathogenesis of multiple sclerosis (MS). Polymorphisms of tumor necrosis factor (TNF)-α −308 were implicated in MS risk in several case–control association studies. However, the studies have shown inconsistent results. Objectives: To address the association of G/A polymorphisms of TNF-α −308 with MS risk by meta-analysis. Methods: Thirteen studies were included. Pooled odds ratios (ORs) together with 95% confidence intervals (CIs) were calculated. Results: A total of 1870 cases and 2769 controls were included in the meta-analysis. The pooled result indicated that −308 A allele is significantly associated with reduced risk of MS compared with −308 G allele (A vs. G, p = 0.022). The same pattern of the result was also obtained in the contrasts of AA + GA vs. GG ( p = 0.008) and GA vs. GG ( p = 0.007). For AA vs. GG or AA vs. GA + GG, no significant association was detected most likely caused by very low frequency or non-availability of homozygote genotype AA for all of the studies. Conclusions: TNF-α −308 A allele is associated with reduced risk of MS.

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