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[{"key": "dc.contributor.advisor", "value": "Gilbert, Leona", "language": null, "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Puttaraksa, Kanoktip", "language": null, "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Pirttinen, Heidi", "language": null, "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2016-02-23T20:39:02Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2016-02-23T20:39:02Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2016", "language": null, "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.other", "value": "oai:jykdok.linneanet.fi:1522894", "language": null, "element": "identifier", "qualifier": "other", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/48912", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Ihmisen parvovirus B19 (B19) on laajalle levinnyt, yleinen virus, joka aiheuttaa lapsissa parvorokkoa (viides tauti). Aikuisille B19 aiheuttaa erin\u00e4isi\u00e4 sairauksia, muun muassa nivelkipuja ja \u2013 tulehdusta, anemiaa, sek\u00e4 raskaana oleville siki\u00f6p\u00f6h\u00f6\u00e4. Lis\u00e4ksi B19 infektio saattaa johtaa autoimmuunisairauksiin, kuten punahukkaan (systemic lupus erythematosus, SLE), nivelreumaan ja syd\u00e4nlihastulehdukseen. Toisaalta infektio voi olla my\u00f6s t\u00e4ysin oireeton. Mekanismit, jotka johtavat B19 tartunnasta autoimmuunisairauteen, ovat viel\u00e4 tuntemattomia. Kuitenkin tiedet\u00e4\u00e4n, ett\u00e4 B19:n ei-rakenteellinen proteiini NS1 on soluille tuhoisa ja aiheuttaa niiden kuoleman (apoptoosin) muodostaen solunj\u00e4\u00e4nn\u00f6sten kanssa apoptoottisia kappaleita (ApoBodit). N\u00e4m\u00e4 ApoBodit sis\u00e4lt\u00e4v\u00e4t itseantigeenej\u00e4 sek\u00e4 viruksen NS1 proteiinia. T\u00e4ss\u00e4 ty\u00f6ss\u00e4 tutkittiin B19 NS1 ApoBodien aiheuttamaa immuunireaktiota in vivo k\u00e4ytt\u00e4en hiiri\u00e4 malliorganismina. Hypoteesina oli, ett\u00e4 NS1 ApoBodit aiheuttavat hiiriss\u00e4 SLE:n kaltaisen autoimmuunireaktion, mik\u00e4 ilmenee autovasta-aineiden tuottona, immuunisolujen tunkeutumisena kudoksiin sek\u00e4 kudosvauriona. Hiiriin injektoitiin ApoBodeja kolmessa eri konsentraatiossa: 25 \u00b5g, 50 \u00b5g ja 100 \u00b5g. Hiirist\u00e4 otettiin verin\u00e4ytteet viikon p\u00e4\u00e4st\u00e4 alkuper\u00e4isest\u00e4 immunisaatiosta, ja viikolla nelj\u00e4, ennen tehosteinjektion antamista. Kahdeksannella viikolla hiiret lopetettiin ja veri ker\u00e4ttiin seerumin eristyst\u00e4 varten. Aivot, syd\u00e4n, munuaiset, maksa ja perna irrotettiin kudospatologista tutkimusta varten. Morfologisia ja patologisia muutoksia tarkasteltiin parafiiniin pedatuista, hematoksyliinilla ja eosiinilla v\u00e4rj\u00e4tyist\u00e4 kudosn\u00e4ytteist\u00e4 kirkaskentt\u00e4mikroskopian avulla. Vasta-aineita kaksijuosteiselle DNA:lle (anti-dsDNA vasta-aineet) tutkittiin kaupallisella Crithidia luciliae immunofluoresenssitestill\u00e4, sek\u00e4 t\u00e4ss\u00e4 tutkimuksessa kehitetyll\u00e4 entsyymiv\u00e4litteisell\u00e4 immunosorbenttimenetelm\u00e4ll\u00e4. Anti-dsDNA vasta-aineita, jotka ovat SLE:n biomarkkereita, havaittiin ApoBodeilla immunisoiduissa hiiriss\u00e4 molemmilla k\u00e4ytetyill\u00e4 menetelmill\u00e4. Munuaisista, maksasta ja syd\u00e4mest\u00e4 l\u00f6ytyi immuunisoluker\u00e4ytymi\u00e4. Lis\u00e4ksi kaikkien hiirten aivoissa havaittiin neuronien rappeutumista, sek\u00e4 demyelinaatiota kahdella suurimmalla ApoBodikonsentraatiolla. Samoilla hiirill\u00e4 havaittiin my\u00f6s syd\u00e4nlihassolujen ep\u00e4j\u00e4rjestyneisyytt\u00e4, sek\u00e4 syd\u00e4nlihassolujen rappeumaa, joka oli n\u00e4ht\u00e4viss\u00e4 jo alimmalla ApoBodikonsentraatiolla immunisoiduissa hiiriss\u00e4. 50 \u00b5g:lla immunisoitujen hiirten pernassa oli muodostunut reaktiokeskuksia. Lis\u00e4ksi valkoisen ytimen osuus hiirten pernasta kasvoi huomattavasti ApoBodikonsentraation my\u00f6t\u00e4. N\u00e4m\u00e4 l\u00f6yd\u00f6kset tukevat hypoteesia. B19 NS1 ApoBodit tarjoavat elimist\u00f6lle itseantigeenej\u00e4, johon immuunipuolustus reagoi ja n\u00e4in ollen autoimmuniteetti saa alkunsa. T\u00e4m\u00e4 tutkimus tarjoaa mekanismin B19 osallisuudesta autoimmuunisairauksien kehittymisess\u00e4. Lis\u00e4ksi t\u00e4ss\u00e4 tutkimuksessa kehitetty hiirimalli sek\u00e4 mekanismi ovat sovellettavissa muiden patogeenisten virusten, kuten sytomegaloviruksen ja Epstein-Barr -viruksen tutkimiseen.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Human parvovirus B19 (B19) is a widespread virus that infects people of all ages. In children, it usually causes an erythema infectiosum, a rash illness called the Fifth disease. In adults, it can cause arthralgia, arthritis, different types of anemia, and hydrops fetalis in pregnant women. Furthermore, the infection can lead to severe autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, myocarditis, liver, and kidney diseases. However, the B19 infection can sometimes be asymptomatic. The exact mechanisms by which B19 contributes to autoimmune diseases are still not known. However, the non-structural protein 1 (NS1) of B19 is known as a cytotoxic protein that induces apoptosis in host cells, thus forming apoptotic bodies (ApoBods) that contain self-antigens along with viral NS1 protein. Mice were used as a model organism in this study to investigate the effects of the NS1 ApoBods in vivo. It was hypothesized that the ApoBods initiate an SLE-like autoimmune disease in mice which manifests itself as autoantibody production, immune cell infiltration into the tissues, and tissue damage. Mice were inoculated with 25 \u00b5g, 50 \u00b5g, and 100 \u00b5g of B19 NS1 induced ApoBods. Blood was collected from the mice at week one, and four, before booster injections were administrated. At week eight, the mice were euthanized, blood was collected and serum isolated. Brain, heart, kidneys, liver, and spleen were dissected from each mouse for histopathological analysis. Sections embedded in paraffin, and stained with hematoxylin and eosin were studied for morphological and pathological changes with bright-field microscopy. Presence of anti-double-stranded DNA antibodies was investigated with a commercial Crithidia luciliae immunofluorescence test, and with a newly developed enzyme-linked immunosorbent assay. Anti-double-stranded DNA antibodies, which are the signature biomarker of SLE, were detected with both methods in the mice inoculated with B19 NS1 ApoBods. Immune cell infiltrates were detected in the kidneys, heart, and liver of the mice. In addition, neuronal degeneration was detected in the brain of all the mice treated with B19 NS1 ApoBods, and suspected demyelination was seen in the brain of the mice treated with 50 \u00b5g, and 100 \u00b5g of B19 NS1 ApoBods. Myocardial disarray was observed in the hearts of these two groups. Furthermore, in the hearts of all mice treated with B19 NS1 ApoBods, myocardial degeneration was detected. In the spleen of mice treated with 50 \u00b5g of the ApoBods, germinal centers had formed. Moreover, the proportion of the white pulp in the spleen was significantly increased by the dosage of ApoBods. These findings supported the hypothesis. B19 NS1 ApoBods cause inflammation by providing self-antigens to which the immune system reacts, and autoimmunity is initiated. Hence, this study provided a mechanism of B19 involvement in the pathogenesis of autoimmune diseases. Furthermore, this mechanism and model are applicable to studies of other viruses, such as cytomegalovirus and Epstein-Barr.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted using Plone Publishing form by Heidi Pirttinen (hecapirt) on 2016-02-23 20:38:59.812758. Form: Pro gradu -lomake (https://kirjasto.jyu.fi/julkaisut/julkaisulomakkeet/pro-gradu-lomake). JyX data: [jyx_publishing-allowed (fi) =True]", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by jyx lomake-julkaisija (jyx-julkaisija.group@korppi.jyu.fi) on 2016-02-23T20:39:02Z\nNo. of bitstreams: 2\nURN:NBN:fi:jyu-201602231670.pdf: 18675540 bytes, checksum: b87a3807b0eb1195b6a42d321e713e5c (MD5)\nlicense.html: 4843 bytes, checksum: 62876e0f98ffd1abe87bbfb7e19fb0d9 (MD5)", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2016-02-23T20:39:02Z (GMT). No. of bitstreams: 2\nURN:NBN:fi:jyu-201602231670.pdf: 18675540 bytes, checksum: b87a3807b0eb1195b6a42d321e713e5c (MD5)\nlicense.html: 4843 bytes, checksum: 62876e0f98ffd1abe87bbfb7e19fb0d9 (MD5)\n Previous issue date: 2016", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "1 verkkoaineisto (39 sivua)", "language": null, "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.format.mimetype", "value": "application/pdf", "language": null, "element": "format", "qualifier": "mimetype", "schema": "dc"}, {"key": "dc.language.iso", "value": "eng", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "Ihmisen parvovirus B19", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "ApoBodit", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "parvorokko", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "punahukka", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "autoimmuniteetti", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "DNA-vasta-aineet", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "Human parvovirus B19", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "SLE", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "NS1 ApoBods", "language": null, "element": 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