Coexistence of protease sensitive and resistant prion protein in 129VV homozygous sporadic Creutzfeldt-Jakob disease: a case report

Introduction: The coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, however, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported. Case presentation: A 74-year-old Caucasian woman showed a sporadic Creutzfeldt-Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes. She died at age 77. Neuropathological findings showed: spongiform change in the patient"s cerebral cortex, striatum, thalamus and molecular layer of the cerebellum with proteinase K-sensitive synaptic-like, dot-like or target-like prion protein deposition in the cortex, thalamus and striatum; proteinase K-resistant prion protein in the same regions; and elongated plaque-like proteinase K-resistant prion protein in the molecular layer of the cerebellum. Molecular analysis of prion protein after proteinase K digestion revealed decreased signal intensity in immunoblot, a ladder-like protein pattern, and a 71% reduction of PrPSc signal relative to non-digested material. Her cerebellum showed a 2A prion protein type largely resistant to proteinase K. Genotype of polymorphism at codon 129 was valine homozygous. Conclusion: Molecular typing of prion protein along with clinical and neuropathological data revealed, to the best of our knowledge, the first case of the coexistence of different protease-sensitive prion proteins in the same patient in a rare case that did not fulfill the current clinical diagnostic criteria for either probable or possible sporadic Creutzfeldt-Jakob disease. This highlights the importance of molecular analyses of several brain regions in order to correctly diagnose rare and atypical prionopathies

A common BACE1 polymorphism is a risk factor for sporadic Creutzfeldt-Jakob disease

The β site APP cleaving enzyme 1 (BACE1) is the rate-limiting β-secretase enzyme in the amyloidogenic processing of APP and Aβ formation, and therefore it has a prominent role in Alzheimer"s disease (AD) pathology. Recent evidence suggests that the prion protein (PrP) interacts directly with BACE1 regulating its β-secretase activity. Moreover, PrP has been proposed as the cellular receptor involved in the impairment of synaptic plasticity and toxicity caused by Aβ oligomers. Provided that common pathophysiologic mechanisms are shared by Alzheimer"s and Creutzfeldt-Jakob (CJD) diseases, we investigated for the first time to the best of our knowledge a possible association of a common synonymous BACE1 polymorphism (rs638405) with sporadic CJD (sCJD). Our results indicate that BACE1 C-allele is associated with an increased risk for developing sCJD, mainly in PRNP M129M homozygous subjects with early onset. These results extend the very short list of genes (other than PRNP) involved in the development of human prion diseases; and support the notion that similar to AD, in sCJD several loci may contribute with modest overall effects to disease risk. These findings underscore the interplay in both pathologies of APP, Aβ oligomers, ApoE, PrP and BACE1, and suggest that aging and perhaps vascular risk factors may modulate disease pathologies in part through these key players

Vieraiden grafeemien väistyminen varhaisnykysuomesta etenkin Jakob Johan Malmbergin tuotannon valossa

Summary: The abandonment of foreign graphemes in Early Modern Finnish with special reference to Jakob Johan Malmberg's works

Gonyklisían epouraníon epigeíon kaì katakhthoníon, Philipp. cap. II. vers. 9, 10

Invocatio: Syn tô Theô [kreikkaa].

Philipp Melanchthon als Verfasser von Briefen, als Dichter und als Ethiker

Kirjallisuusarvostelu

Brevskrivaren Philipp Melanchhton

Kirjallisuusarvostelu

Nervander, Johan Jakob

Johan Jakob Nervander f. 23.2.1805 i Nystad d. 15.3.1848 i Helsingfors Johan Jakob Nervander var finländsk diktare, fysiker och meteorolog, samt en nyckelfigur i Lördagssällskapet. Hans inflytande inom den finländska kultureliten var som störst på 1820-40-talen. Fast den vetenskapliga forskningen krävde största delen av Nervanders uppmärksamhet, drogs han också till diktandet. Nervanders viktigaste verk som poet är Jephtas Bok, En Minnes-Sång i Israel, som belönades med Svenska Akademiens andra pris år 1832 och trycktes åtta år senare. Nervanders lyrik var formmässigt slipad. Till innehåll och stämning varierade dikterna kraftig, från starka känslouttryck och fritt flygande fantasi till melankoli och inbundenhet. http://www.blf.fi/artikel.php?id=3567 http://www.kansallisbiografia.fi/kb/artikkeli/3567/

Gummerus, Karl Jakob

Karl Jakob Gummerus f. 13.4.1840 i Karleby d. 20.3.1898 i Helsingfors Karl Jakob Gummerus var en av de mest lästa finskspråkiga författarna under 1860- och 1870-talen, och samtidigt verksam som framgångsrik förläggare. Förlaget K.J. Gummerus, som han grundade tillsammans med sin hustru Gustava, gav i tidens folkbildande anda ut finskspråkig litteratur. Det första utgivna verket på förlaget var Gummerus egna Ylhäiset ja alhaiset (sv. Hög och låg), som baserade sig på texter utgivna som följetonger i tidningar. Detta verk som gavs ut år 1870 kan ses som den första romanen skriven på finska, även om Aleksis Kivis Sju bröder (Seitsemän veljestä) utgavs samma år. Gummerus övriga litterära produktion bestod av det han själv kallade ”uuteloita”. Det var alltså fråga om noveller, en ny litterär genre i tiden. http://www.blf.fi/artikel.php?id=2886 http://www.kansallisbiografia.fi/kb/artikkeli/2886/

Lagervall, Jakob Fredrik

Jakob Fredrik Lagervall urspr. Oxeman f. 19.7.1787 i Kontiolahti (Kontiolax) d. 7.11.1865 i Helsingfors Jakob Fredrik Lagervall har gått till historien framför allt som pionjärförfattare till finskspråkiga dramer. Lagervall var litterärt aktiv särskilt under 1830- och 1840-talen, och är främst känd som dramatiker men skrev även en del poesi och prosa. De flesta av hans dramer är religiöst färgade samt skrivna i versform och på runometer (det versmått som används i Finlands nationalepos Kalevala). Det kändaste av hans dramer är Ruunulinna (sv. Kronoborgen) från år 1834, en finsk version av William Shakespeares klassiska pjäs Macbeth. Detta drama är också den första tragedin skriven på det finska språket. Trots att Lagervall var övertygad fennoman, skrev han både på svenska och finska. http://www.kansallisbiografia.fi/kb/artikkeli/2909/

Nåden och gåvan i Philipp Melanchthons rättfärdiggörelselära 1521-1535

In this thesis Philip Melanchthon’s doctrine of justification is analyzed, especially the aspects of favor and donum in his writings until 1535. The research task is defined in the introduction of the thesis. Researchers agree, that Melanchthon emphasized the forensic aspect of the doctrine of justification, but this is not the case with the effective aspect of his doctrine of justification. Therefore, I have chosen to focus on the concepts of favor (grace) and donum (gift). The thesis begins with an analysis of the first edition of the Loci communes of 1521 in chapter two, and it ends with the second edition from 1535 in chapter seven. Melanchthon’s most important writings from the intervening period are analyzed in chapters three to six. In chapter eight, I describe my final results from the analysis. Although I have focused on how Melanchthon perceived the relationship between favor and donum, I have also taken note of such loci that are associated with his view of justification. I have done this in order to get a clearer picture of Melanchthon’s doctrine of justification, and of the issues which change in his theological thinking over time. In the research overview in chapter one, I divided the researchers in four different groups depending on how they perceive Melanchthon’s doctrine of justification. This classification is of course not comprehensive, since the reality is much more complicated. The main interpretations present in Melanchthon research are: 1. Christ as favor in justification, but donum is excluded from justification. 2. Christ as favor in justification, but the Spirit is donum in justification. 3. Christ as both favor and donum in justification until the early 1530s. 4. Christ as both favor and donum in justification throughout his life. The fourth option is in my opinion the most preferable. The analysis of Melanchthon’s writings shows that he expects both a forensic, and an effective aspect in the doctrine of justification throughout the examined period. Melanchthon strongly emphasizes that justification is by grace alone through faith for Christ’s sake, but also that the Holy Spirit works the justifying faith, and is the gift bestowed on believers in connection with this. Where the opponents according to Melanchthon see deeds, virtues, or a quality in the believer as the cause of the justification, there Melanchthon sees only Christ.

Anáthema maranathá seu exercitatio academica, adumbrans breviter anathematismos Judaeorum

Dedikaatio: Ericus Falander, Bartholdus Fästing.