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81.
82.
Teresa Frisan Qian-Jin Zhang Jelena Levitskaya Michael Coram Michael G. Kurilla Maria G. Masucci 《International journal of cancer. Journal international du cancer》1996,68(2):251-258
Defects of antigen processing/presentation have been suggested to play a role in the escape of Burkitt's lymphoma (BL) from cytotoxic T lymphocyte (CTL)-mediated rejection. Impaired presentation of an immunodominant HLA AII-restricted epitope from the resident or recombinant vaccinia virus-expressed Epstein-Barr virus nuclear antigen (EBNA)4 was demonstrated in the EBV-positive E95B-BL28 and its EBV-negative parental BL28 cell lines. We have investigated whether this was due to (i) impaired production of the antigenic peptide, (ii) poor peptide translocation into the ER lumen or (iii) inefficient maturation and transport of the MHC-peptide complexes at the cell surface. The defect was not overcome by cytosolic expression of a pre-formed epitope, suggesting that presentation of EBNA4 is not limited by inefficient production of the antigenic peptide. BL28 expressed 5- to 10-fold lower levels of the transporter associated with antigen presentation (TAP) 1 and TAP2 proteins and behaved poorly in a streptolysin-O-mediated peptide translocation assay, whereas E95B-BL28 showed higher TAP expression and virtually normal transporter function. Up-regulation of HLA AII and reconstitution of TAP activity by treatment with IFN-γ did not restore presentation of the resident EBNA4 in E95B-BL28 and did not enhance presentation of the vaccinia virus-expressed intact protein or preformed epitope. Efficient maturation of class I molecules to Endo H-resistant species was demonstrated in pulse-chase experiments. Taken together, our findings identify a previously uncharacterized defect of antigen presentation which appears to affect events occurring after proteasomal degradation but before TAP-dependent peptide transport and MHC class I assembly and maturation. © 1996 Wiley-Liss, Inc. 相似文献
83.
Sergej M. Ostojic Jelena Ostojic Dragana Zanini Tatjana Jezdimirovic Valdemar Stajer 《The Journal of international medical research》2022,50(1)
Acute secondary progressive multiple sclerosis (SPMS) is characterized by escalating neurological disability, with limited disease-modifying therapeutic options. A 48-year-old woman with acute SPMS being treated with interferon beta-1a and oral corticosteroids presented as a clinical outpatient with no disease-modifying effects after treatment. A decision was made to treat her with a combination of guanidinoacetate and creatine for 21 days. She had made clinical progress at follow-up, with the intensity of fatigue dropping from severe to mild. Magnetic resonance spectroscopy revealed increased brain choline, creatine, N-acetylaspartate, and glutathione. Patients with SPMS may benefit from guanidinoacetate–creatine treatment in terms of patient- and clinician-reported outcomes; this requires additional study. 相似文献
84.
Dunja D. Bijelić Katarina D. Milićević Milica N. Lazarević Djordje M. Miljković Jelena J. Bogdanović Pristov Danijela Z. Savić Branka B. Petković Pavle R. Andjus Miljana B. Momčilović Ljiljana M. Nikolić 《Journal of neuroscience research》2020,98(11):2317-2332
Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naïve astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell–astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca2+ increase in astrocytes by promoting glial release of ATP. ATP propagated Ca2+ elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca2+ increase is specifically triggered by the autoreactive CD4+ T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca2+ signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell–astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease. 相似文献
85.
Christin Krause PhD Susen Schaake BSc Karen Grütz PhD Helen Sievert MD Charles Jourdan Reyes MSc Inke R. König PhD Björn-Hergen Laabs MSc Roland Dominic Jamora MD Raymond L. Rosales MD PhD Cid Czarina E. Diesta MD Jelena Pozojevic PhD Timo Gemoll PhD Ana Westenberger PhD Frank J. Kaiser PhD Christine Klein MD Henriette Kirchner PhD 《Movement disorders》2020,35(12):2220-2229
86.
Oksana Savicka Reinis Zeltmatis Jelena Storozenko 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2022,27(11)
BackgroundHepatitis A is an acute infection of the liver caused by hepatitis A virus (HAV). Molecular detection and typing of the HAV VP1/P2A genomic region is used for genotyping and outbreak investigations. After a large hepatitis A outbreak in Latvia in 2007–08, only sporadic cases were registered until 2017 when a rise in cases occurred. During 2017–19, 179 laboratory-confirmed hepatitis A cases were notified in Latvia.AimTo investigate the observed increase in hepatitis A cases during 2017 and to determine whether these cases were linked to one another, to risk groups, or to other outbreaks. The majority of HAV samples (69.8%) were typed.MethodsThe VP1/P2A genomic region of HAV was amplified and sequenced for 125 case serum samples. Information about hepatitis-related symptoms, hospitalisation, vaccination, a possible source of infection and suspected countries of origin of the virus were analysed for sequenced cases.ResultsMost HAV strains were subgenotype IA (n = 77), of which 41 were strains circulating among men who have sex with men (MSM) populations in Europe (VRD_521_2016 (n = 32), RIVM-HAV16–090 (n = 7) or V16–25801 (n = 2)). Forty-four cases were subgenotype IB and four cases subgenotype IIIA. However, other clusters and sporadic cases were detected with or without identifying the epidemiological link.ConclusionThis work represents molecular epidemiological data of hepatitis A cases in Latvia from 2017 to 2019. Molecular typing methods allow identification of clusters for public health needs and establishing links with other outbreaks, and to compare Latvian strains with reported strains from other countries. 相似文献
87.
Jelena Kostić Dejan Orlić Milica Labudović Borović Branko Beleslin Dejan Milašinović Milan Dobrić Milorad Tešić Miodrag Ostojić 《Thrombosis research》2014
Introduction
Coronary artery thrombosis in ST-elevation myocardial infarction (STEMI) is a dynamic process often preceded by episodes of silent plaque rupture and subocclusive thrombosis. Thrombus organization is achieved by ingrowth of endothelial and smooth muscle cells. Clinical significance and impact of thrombus neovascularization on primary percutaneous coronary intervention (pPCI) outcome remain unclear. Therefore we investigated composition and neovascularization of thrombi aspirated during pPCI and their association with clinical and angiographic parameters of STEMI patients.Methods
Aspirated thrombi retrieved from 84 STEMI patients were classified as fresh (< 1 day), lytic (1-5 days) or organized (> 5 days). Thrombus neovascularization was evaluated immunohistochemically using CD34, CD31 and VEGF antibodies. CD34 and CD31 immunopositive (CD34/CD31 +) cells were organized as single, clusters and microvessels. VEGF positivity was graded as low or high, based on thrombus surface immunopositive area.Results
CD34/CD31 + cells were present in 67% of all aspirated thrombi. Thrombus CD34/CD31 positivity was associated with previous history of angina pectoris (χ2 = 6.142, p = 0.013) and lower myocardial blush grade (MBG < 3, χ2 = 12.602, p < 0.001). Organization of CD34/CD31 + cells showed inverse association with the extent of VEGF positivity (χ2 = 10.607, p = 0.005). Fresh thrombi were associated with shorter ischemic time (U = 237.5, p = 0.002) and MBG 3 (χ2 = 6.379, p = 0.012).Conclusions
Older thrombus age and neovascularization are associated with suboptimal myocardial perfusion in STEMI patients. Thrombus VEGF expression is inversely associated with degree of CD34 + cell organization. Therefore, neovascularization of aspirated thrombi may indicate the duration of thrombosis, coronary microcirculation status and outcome in STEMI patients. 相似文献88.
Hajer El Oussini Hanna Bayer Jelena Scekic-Zahirovic Pauline Vercruysse Jérôme Sinniger Sylvie Dirrig-Grosch Stéphane Dieterlé Andoni Echaniz-Laguna Yves Larmet Kathrin Müller Jochen H. Weishaupt Dietmar R. Thal Wouter van Rheenen Kristel van Eijk Roland Lawson Laurent Monassier Luc Maroteaux Anne Roumier Philip C. Wong Leonard H. van den Berg Albert C. Ludolph Jan H. Veldink Anke Witting Luc Dupuis 《Acta neuropathologica》2016,131(3):465-480
89.
Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis 总被引:1,自引:0,他引:1
Couthouis J Hart MP Erion R King OD Diaz Z Nakaya T Ibrahim F Kim HJ Mojsilovic-Petrovic J Panossian S Kim CE Frackelton EC Solski JA Williams KL Clay-Falcone D Elman L McCluskey L Greene R Hakonarson H Kalb RG Lee VM Trojanowski JQ Nicholson GA Blair IP Bonini NM Van Deerlin VM Mourelatos Z Shorter J Gitler AD 《Human molecular genetics》2012,21(13):2899-2911
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Mutations in related RNA-binding proteins TDP-43, FUS/TLS and TAF15 have been connected to ALS. These three proteins share several features, including the presence of a bioinformatics-predicted prion domain, aggregation-prone nature in vitro and in vivo and toxic effects when expressed in multiple model systems. Given these commonalities, we hypothesized that a related protein, EWSR1 (Ewing sarcoma breakpoint region 1), might also exhibit similar properties and therefore could contribute to disease. Here, we report an analysis of EWSR1 in multiple functional assays, including mutational screening in ALS patients and controls. We identified three missense variants in EWSR1 in ALS patients, which were absent in a large number of healthy control individuals. We show that disease-specific variants affect EWSR1 localization in motor neurons. We also provide multiple independent lines of in vitro and in vivo evidence that EWSR1 has similar properties as TDP-43, FUS and TAF15, including aggregation-prone behavior in vitro and ability to confer neurodegeneration in Drosophila. Postmortem analysis of sporadic ALS cases also revealed cytoplasmic mislocalization of EWSR1. Together, our studies highlight a potential role for EWSR1 in ALS, provide a collection of functional assays to be used to assess roles of additional RNA-binding proteins in disease and support an emerging concept that a class of aggregation-prone RNA-binding proteins might contribute broadly to ALS and related neurodegenerative diseases. 相似文献
90.
Marka van Blitterswijk Michael A. van Es Max Koppers Wouter van Rheenen Jelena Medic Helenius J. Schelhaas Anneke J. van der Kooi Marianne de Visser Jan H. Veldink Leonard H. van den Berg 《Neurobiology of aging》2012
Previously, we have reported amyotrophic lateral sclerosis (ALS) families with multiple mutations in major ALS-associated genes. These findings provided evidence for an oligogenic basis of ALS. In our present study, we screened a cohort of 755 sporadic ALS patients, 111 familial ALS patients (97 families), and 765 control subjects of Dutch descent for mutations in vesicle-associated membrane protein B (VAPB). We have identified 1 novel VAPB mutation (p.V234I) in a familial ALS patient known to have a chromosome 9 open reading frame 72 (C9orf72) repeat expansion. This p.V234I mutation was absent in control subjects, located in a region with high evolutionary conservation, and predicted to have damaging effects. Taken together, these findings provide additional evidence for an oligogenic basis of ALS. 相似文献