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The role of Epstein-Barr virus in multiple sclerosis:from molecular pathophysiology to in vivo imaging

Neural Regeneration Research 2019年第3期14卷 373-386页

作者： Yi Guan Dejan Jakimovski murali ramanathan Bianca Weinstock-Guttman Robert Zivadinov Buffalo Neuroimaging Analysis Center Department of Neurology Jacobs School of Medicine and Biomedical Sciences University at BuffaloState University of New York Jacobs Comprehensive MS Treatment and Research Center Department of Neurology Jacobs School of Medicine and Biomedical SciencesUniversity at Buffalo State University of New York Department of Pharmaceutical Sciences State University of New York Center for Biomedical Imaging at Clinical Translational Science Institute University at Buffalo State University of New York

Multiple sclerosis(MS) is a disease of the central nervous system characterized by inflammation, demyelination, and neuronal damage. Environmental and genetic factors are associated with the risk of developing MS, but the exact cause still remains unidentified. Epstein-Barr virus(EBV), vitamin D, and smoking are among the most well-established environmental risk factors in MS. Infectious mononucleosis, which is caused by delayed primary EBV infection, increases the risk of developing MS. EBV may also contribute to MS pathogenesis indirectly by activating silent human endogenous retrovirus-W. The emerging B-cell depleting therapies, particularly anti-CD20 agents such as rituximab, ocrelizumab, as well as the fully human ofatumumab, have shown promising clinical and magnetic resonance imaging benefit. One potential effect of these therapies is the depletion of memory B-cells, the primary reservoir site where EBV latency occurs. In addition, EBV potentially interacts with both genetic and other environmental factors to increase susceptibility and disease severity of MS. This review examines the role of EBV in MS pathophysiology and summarizes the recent clinical and radiological findings, with a focus on B-cells and in vivo imaging. Addressing the potential link between EBV and MS allows the better understanding of MS pathogenesis and helps to identify additional disease biomarkers that may be responsive to B-cell depleting intervention.

关键词： Epstein-Barr virus multiple sclerosis meningeal inflammation magnetic resonance imaging leptomeningeal contrast enhancement mononucleosis human endogeneous retrovirus-W B-cells

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Effect of angiotensin converting enzyme gene I/D polymorphism in South Indian children with nephrotic syndrome

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The Journal of Biomedical Research 2019年第3期33卷 201-207页

作者： Aravind Selvin Kumar ramanathan Balakrishnan Karuppiah murali Vijayan Kamaraj Raju Dhivakar Mani Rathika Chinniah Manikandan Thirunavukkarasu Padma Malini Ravi Jeyaram Illiayaraja Krishnan Prabha Senguttuvan Department of Pediatric Nephrology Institute of Child Health and Hospital for Children Department of Medical Genetics The Tamil Nadu Dr.M.G.R.Medical University Department of Immunology School of Biological SciencesMadurai Kamaraj University Department of Biotechnology and Genetic Engineering Bharathidasan University Department of Clinical Research Narayana Health City Department of Pediatric Nephrology Dr.Mehta’s Children’s Hospital

Nephrotic syndrome is one of the most common childhood kidney diseases. It is mostly found in the age group of 2 to 8 years. Around 10%-15% of nephrotic syndrome cases are non-responders of steroid treatment(SRNS).Angiotensin converting enzyme(ACE)(I/D) gene association studies are important for detecting kidney disease and herein we assessed the association of ACE(I/D) polymorphism with nephrotic syndrome in South Indian children. We recruited 260 nephrotic syndrome(162 boys and 98 girls) and 218(140 boys and 78 girls) control subjects. ACE I/D polymorphism was analyzed by PCR using genotype allele specific primers. In ACE(I/D), we did not find significant association for the ungrouped data of nephrotic syndrome children and the control subjects. Kidney biopsies were done in 86 nephrotic syndrome cases(minimal change disease, n = 51;focal segmental glomerulosclerosis, n = 27;diffuse mesangial proliferation, n = 8). We segregated them into the minimal change disease/focal segmental glomerulosclerosis groups and observed that the ACE’D’ allele was identified with borderline significance in cases of focal segmental glomerulosclerosis and the ’Ⅰ’ allele was assessed as having very weak association in cases of minimal change disease. ’Ⅱ’ genotype was weakly associated with minimal change disease. Gender specific analysis revealed weak association of’ID’ genotype with female nephrotic syndrome in females. Dominant expression of DD genotype was observed in males with nephrotic syndrome. Our finding indicated that ACE(I/D) has moderate association with focal segmental glomerulosclerosis. However, due to the limited number of biopsy proven focal segmental glomerulosclerosis subjects enrolled, further studies are required to confirm these results.

关键词： angiotensin converting enzyme focal segmental glomerulosclerosis minimal change disease nephrotic syndrome

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