Study for highly sensitive PMCA amplification with vCJD prions

• Project/Area Number: 25257506
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: KITAMOTO TETSUYUKI 東北大学, 医学系研究科, 教授 (20192560)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥44,850,000 (Direct Cost: ¥34,500,000、Indirect Cost: ¥10,350,000); Fiscal Year 2016: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2015: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000); Fiscal Year 2014: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000); Fiscal Year 2013: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
• Keywords: プリオン / BSE / ｖCJD感染 / PMCA法 / 鋭敏な検出法 / 増幅法 / 微量検出法 / 2次感染予防 / vCJD / 高感度検出法 / ２次感染予防

Outline of Final Research Achievements

To establish a highly sensitive PMCA method, we studied the method to perform PMCA in a short period, the standardization in UK, and the exclusion of the inhibitory factor in plasma. Fortunately, we found the special carrier to enhance PMCA sensitivity in a short period. We also succeeded the standardization between Tohoku University and Scotland blood bank research group in the same amplification level. Now, UK group is going to examine plasma samples with or without vCJD infection. Finally, we found the new method to exclude the inhibitory factor in plasma samples

Research Products

• [Journal Article] Significant association of cadaveric dura mater grafting with subpial Aβ deposition and meningeal amyloid angiopathy. (2016)
  • Author(s): Hamaguchi T, Taniguchi Y, Sakai K, Kitamoto T, Takao M, Murayama S, Iwasaki Y, Yoshida M, Shimizu H, Kakita A, Takahashi H, Suzuki H, Naiki H, Sanjo N, Mizusawa H, Yamada M.
  • Journal Title: Acta Neuropathol. Volume: 132(2) Issue: 2 Pages: 313-5
  • DOI: 10.1007/s00401-016-1588-3
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of Conformational Stability of Abnormal Prion Protein Aggregates across the Spectrum of Creutzfeldt-Jakob Disease Prions. (2016)
  • Author(s): Cescatti M, Saverioni D, Capellari S, Tagliavini F, Kitamoto T, Ironside J, Giese A, Parchi P.
  • Journal Title: J Virol. Volume: 90(14) Issue: 14 Pages: 6244-54
  • DOI: 10.1128/jvi.00144-16
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Distinctive properties of plaque-type dura mater graft-associated Creutzfeldt-Jakob disease in cell-protein misfolding cyclic amplification (2016)
  • Author(s): Atsuko Takeuchi, Atsushi Kobayashi, Piero Parchi, Masahito Yamada, Masanori Morita, Shusei Uno and Tetsuyuki Kitamoto
  • Journal Title: Laboratory Investigation Volume: in press Issue: 5 Pages: 581-7
  • DOI: 10.1038/labinvest.2016.27
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Efficient propagation of variant Creutzfeldt-Jakob disease prion protein using the cell-protein misfolding cyclic amplification technique with samples containing plasma and heparin. (2016)
  • Author(s): Oshita M, Yokoyama T, Takei Y, Takeuchi A, Ironside JW, Kitamoto T, Morita M.
  • Journal Title: Transfusion. Volume: 56(1) Issue: 1 Pages: 223-30
  • DOI: 10.1111/trf.13279
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Quantifying prion disease penetrance using large population control cohorts. (2016)
  • Author(s): Minikel EV, Vallabh SM, Lek M, Estrada K, Samocha KE, et al
  • Journal Title: Sci Transl Med. Volume: 8 Issue: 322
  • DOI: 10.1126/scitranslmed.aad5169
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An autopsy-verified case of FTLD-TDP type A with upper motor neuron-predominant motor neuron disease mimicking MM2-thalamic-type sporadic Creutzfeldt-Jakob disease. (2016)
  • Author(s): Hayashi Y, Iwasaki Y, Takekoshi A, Yoshikura N, Asano T, Mimuro M, Kimura A, Satoh K, Kitamoto T, Yoshida M, Inuzuka T.
  • Journal Title: Prion. Volume: 10(6) Issue: 6 Pages: 492-501
  • DOI: 10.1080/19336896.2016.1243192
  • Peer Reviewed
• [Journal Article] Preserved regional cerebral blood flow in the occipital cortices, brainstem, and cerebellum of patients with V180I-129M genetic Creutzfeldt-Jakob disease in serial SPECT studies. (2016)
  • Author(s): Hayashi Y, Yoshikura N, Takekoshi A, Yamada M, Asano T, Kimura A, Satoh K, Kitamoto T, Inuzuka T.
  • Journal Title: J Neurol Sci. Volume: 370 Pages: 145-151
  • DOI: 10.1016/j.jns.2016.09.043
  • Peer Reviewed
• [Journal Article] An autopsied case of MM1 + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease presenting with hyperintensities on diffusion-weighted MRI before clinical onset. (2016)
  • Author(s): Iwasaki Y, Mori K, Ito M, Mimuro M, Kitamoto T, Yoshida M.
  • Journal Title: Neuropathology. Volume: 37(1) Issue: 1 Pages: 78-85
  • DOI: 10.1111/neup.12327
  • Peer Reviewed
• [Journal Article] Specific clinical signs and symptoms are predictive of clinical course in sporadic Creutzfeldt-Jakob disease. (2016)
  • Author(s): Nakatani E, Kanatani Y, Kaneda H, Nagai Y, Teramukai S, Nishimura T, Zhou B, Kojima S, Kono H, Fukushima M, Kitamoto T, Mizusawa H.
  • Journal Title: Eur J Neurol. Volume: 23(9) Issue: 9 Pages: 1455-62
  • DOI: 10.1111/ene.13057
  • Peer Reviewed
• [Journal Article] Sporadic Creutzfeldt-Jakob Disease MM1+2C and MM1 Are Identical in Transmission Properties. (2015)
  • Author(s): Kobayashi A, Matsuura Y, Iwaki T, Iwasaki Y, Yoshida M, Takahashi H, Murayama S, Takao M, Kato S, Yamada M, Mohri S, Kitamoto T.
  • Journal Title: Brain Pathol Volume: in press Issue: 1 Pages: 95-101
  • DOI: 10.1111/bpa.12264
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Neuropathological and biochemical criteria to identify acquired Creutzfeldt-Jakob disease among presumed sporadic cases. (2015)
  • Author(s): Kobayashi A, Parchi P, Yamada M, Mohri S, Kitamoto T.
  • Journal Title: Neuropathology. Volume: - Issue: 3 Pages: 305-310
  • DOI: 10.1111/neup.12270
  • NAID: 120006219897
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Decreased regional cerebral blood flow in the bilateral thalami and medulla oblongata determined by an easy Z-score (eZIS) analysis of (99m)Tc-ECD-SPECT images in a case of MM2-thalamic-type sporadic Creutzfeldt-Jakob disease. (2015)
  • Author(s): Hayashi Y, Iwasaki Y, Yoshikura N, Asano T, Hatano T, Tatsumi S, Satoh K, Kimura A, Kitamoto T, Yoshida M, Inuzuka T.
  • Journal Title: J Neurol Sci Volume: 358 Issue: 1-2 Pages: 447-452
  • DOI: 10.1016/j.jns.2015.09.356
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Factors influencing the survival period in Japanese patients with sporadic Creutzfeldt-Jakob disease. (2015)
  • Author(s): Iwasaki Y, Akagi A, Mimuro M, Kitamoto T, Yoshida M.
  • Journal Title: J Neurol Sci. Volume: 357 Issue: 1-2 Pages: 63-8
  • DOI: 10.1016/j.jns.2015.06.065
  • Peer Reviewed
• [Journal Article] The influence of PRNP polymorphisms on human prion disease susceptibility: an update (2015)
  • Author(s): Kobayashi A, Teruya K, Matsuura Y, Shirai T, Nakamura Y, Yamada M, Mizusawa H, Mohri S, Kitamoto T.
  • Journal Title: Acta Neuropathologica Volume: 130 Issue: 2 Pages: 159-170
  • DOI: 10.1007/s00401-015-1447-7
  • Peer Reviewed / Open Access
• [Journal Article] Creutzfeldt-Jakob disease with homozygous M232R mutation: A case report. (2015)
  • Author(s): Kon T, Miki Y, Arai A, Funamizu Y, Ueno T, Haga R, Nishijima H, Suzuki C, Nunomura J, Baba M, Oyama Y, Shiga Y, Kitamoto T, Tomiyama M.
  • Journal Title: J Neurol Sci Volume: 352 Issue: 1-2 Pages: 108-9
  • DOI: 10.1016/j.jns.2015.03.017
  • Peer Reviewed
• [Journal Article] Descriptive Epidemiology of Prion Disease in Japan: 1999–2012 (2015)
  • Author(s): Nakamaura Y, Ae R, Takumi I, Sanjo N, Kitamoto T, Yamada M, Mizusawa H.
  • Journal Title: Journal of Epidemiology Volume: 25 Issue: 1 Pages: 8-14
  • DOI: 10.2188/jea.JE20140022
  • NAID: 130004694366
  • ISSN: 0917-5040, 1349-9092
  • Peer Reviewed
• [Journal Article] Transmission properties of atypical Creutzfeldt-Jakob disease: a clue to disease etiology?. (2015)
  • Author(s): Kobayashi A, Parchi P, Yamada M, Brown P, Saverioni D, Matsuura Y, Takeuchi A, Mohri S, Kitamoto T
  • Journal Title: J. Virol Volume: 89(7) Issue: 7 Pages: 3939-46
  • DOI: 10.1128/jvi.03183-14
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Evaluating Prion Models Based on Comprehensive Mutation Data of Mouse PrP. (2014)
  • Author(s): Shirai T, Saito M, Kobayashi A, Asano M, Hizume M, Ikeda S, Teruya K, Morita M, Kitamoto T.
  • Journal Title: Structure. Volume: 22 Issue: 4 Pages: 560-571
  • DOI: 10.1016/j.str.2013.12.019
  • Peer Reviewed
• [Journal Article] Molecular barriers to zoonotic transmission of prions (2014)
  • Author(s): Barria MA, Balachandran A, Morita M, Kitamoto T, Barron R, Manson J, Knight R, Ironside JW, Head MW.
  • Journal Title: Emerg Infect Dis Volume: Jan;20(1) Issue: 1 Pages: 88-97
  • DOI: 10.3201/eid2001.130858
  • Peer Reviewed
• [Journal Article] Clinical features of genetic Creutzfeldt-Jakob disease with V180I mutation in the prion protein gene. (2014)
  • Author(s): Qina, T., N. Sanjo, M. Hizume, M. Higuma, M. Tomita, R. Atarashi, K. Satoh, I. Nozaki, T. Hamaguchi, Y. Nakamura, A. Kobayashi, T. Kitamoto, S. Murayama, H. Murai, M. Yamada and H. Mizusawa
  • Journal Title: BMJ Open Volume: 4 Issue: 5 Pages: e004968-e004968
  • DOI: 10.1136/bmjopen-2014-004968
  • NAID: 120006986552
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of the clinical course of Japanese MM1-type sporadic Creutzfeldt-Jakob disease between subacute spongiform encephalopathy and panencephalopathic-type. (2014)
  • Author(s): Iwasaki Y, Tatsumi S, Mimuro M, Kitamoto T, Yoshida M.
  • Journal Title: Clin Neurol Neurosurg. Volume: 121 Pages: 59-63
  • DOI: 10.1016/j.clineuro.2014.03.024
  • Peer Reviewed
• [Journal Article] Relation between clinical findings and progression of cerebral cortical pathology in MM1-type sporadic Creutzfeldt-Jakob disease: Proposed staging of cerebral cortical pathology. (2014)
  • Author(s): Iwasaki Y, Tatsumi S, Mimuro M, Kitamoto T, Hashizume Y, Yoshida M
  • Journal Title: J Neurol Sci. Volume: 341(1-2) Issue: 1-2 Pages: 97-104
  • DOI: 10.1016/j.jns.2014.04.011
  • Peer Reviewed
• [Journal Article] Distinct origins of dura mater graft-associated Creutzfeldt-Jakob disease: past and future problems. (2014)
  • Author(s): Kobayashi A, Matsuura Y, Mohri S, Kitamoto T.
  • Journal Title: Acta Neuropathol Commun. Volume: 2 Issue: 1 Pages: 32-32
  • DOI: 10.1186/2051-5960-2-32
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Creutzfeldt-Jakob Disease with a Codon 210 Mutation: First Pathological Observation in a Japanese Patient (2014)
  • Author(s): Tajima Y, Satoh C, Mito Y, Kitamoto T.
  • Journal Title: Internal Medicine Volume: 53 Issue: 5 Pages: 483-487
  • DOI: 10.2169/internalmedicine.53.0916
  • NAID: 130003392674
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Extensive cortical spongiform changes with cerebellar small amyloid plaques: The clinicopathological case of MV2K+C subtype in Creutzfeldt-Jakob disease. (2014)
  • Author(s): Araki K, Nakano Y, Kobayashi A, Matsudaira T, Sugiura A, Takao M, Kitamoto T, Murayama S, Obi T
  • Journal Title: Neuropathology Volume: 34(6) Issue: 6 Pages: 541-6
  • DOI: 10.1111/neup.12133
  • Peer Reviewed
• [Journal Article] Gerstmann-Straeussler-Scheinker disease with P102L prion protein gene mutation presenting with rapidly progressive clinical course. (2014)
  • Author(s): Iwasaki Y, Mori K, Ito M, Nokura K, Tatsumi S, Mimuro M, Kitamoto T, Yoshida M.
  • Journal Title: Clin Neuropathol Volume: 33(5) Issue: 09 Pages: 344-53
  • DOI: 10.5414/np300733
  • Peer Reviewed
• [Journal Article] Panencephalopathic-type sporadic Creutzfeldt-Jakob disease with circumscribed spongy foci (2014)
  • Author(s): Iwasaki Y, Tatsumi S, Mimuro M, Mori K, Ito M, Kitamoto T, Yoshida M.
  • Journal Title: Clin Neuropathol Volume: Mar-Apr;33(2) Issue: 03 Pages: 160-4
  • DOI: 10.5414/np300684
  • Peer Reviewed
• [Journal Article] Relationships between Clinicopathological Features and Cerebrospinal Fluid Biomarkers in Japanese Patients with Genetic Prion Diseases (2013)
  • Author(s): Higuma M, Sanjo N, Satoh K, Shiga Y, Sakai K, Nozaki I, Hamaguchi T, Nakamura Y, Kitamoto T, Shirabe S, Murayama S, Yamada M, Tateishi J, Mizusawa H
  • Journal Title: PLoS One Volume: 8(3) Issue: 3 Pages: e60003-e60003
  • DOI: 10.1371/journal.pone.0060003
  • NAID: 120006985964
  • Peer Reviewed
• [Journal Article] Glycoform-selective prion formation in sporadic and familial forms of prion disease (2013)
  • Author(s): Xiao X, Yuan J, Haik S, Cali I, Zhan Y, Moudjou M, Li B, Laplanche JL, Laude H, Langeveld J, Gambetti P, Kitamoto T, Kong Q, Brandel JP, Cobb BA, Petersen RB, Zou WQ.
  • Journal Title: PLoS One Volume: 8(3) Issue: 3 Pages: e58786-e58786
  • DOI: 10.1371/journal.pone.0058786
  • Peer Reviewed
• [Journal Article] Quantitative analysis of wet-heat inactivation in bovine spongiform encephalopathy (2013)
  • Author(s): Matsuura Y, Ishikawa Y, Bo X, Murayama Y, Yokoyama T, Somerville RA, Kitamoto T, Mohri S.
  • Journal Title: Biochem Biophys Res Commun Volume: Mar 1;432(1)(Epub 2013 Jan 30) Issue: 1 Pages: 86-91
  • DOI: 10.1016/j.bbrc.2013.01.081
  • Peer Reviewed
• [Journal Article] An autopsied case of Creutzfeldt-Jakob disease with mutation in the prion protein gene codon 232 and type 1+2 prion protein (2013)
  • Author(s): Iwasaki Y, Yokoi F, Tatsumi S, Mimuro M, Iwai K, Kitamoto T, Yoshida M.
  • Journal Title: Neuropathology Volume: Jan 16;33(5) Issue: 5 Pages: 568-75
  • DOI: 10.1111/neup.12013
  • Peer Reviewed
• [Journal Article] Characterization of variant Creutzfeldt-Jakob disease prions in prion protein-humanized mice carrying distinct codon 129 genotypes (2013)
  • Author(s): Takeuchi A, Kobayashi A, Ironside JW, Mohri S, Kitamoto T
  • Journal Title: J Biol Chem Volume: 288(30) Issue: 30 Pages: 21659-66
  • DOI: 10.1074/jbc.m113.470328
  • Peer Reviewed
• [Journal Article] Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein (2013)
  • Author(s): Kobayashi A, Iwasaki Y, Otsuka H, Yamada M, Yoshida M, Matsuura Y, Mohri S, Kitamoto T.
  • Journal Title: Acta Neuropathol Commun Volume: Nov 13;1(1) Issue: 1 Pages: 74-74
  • DOI: 10.1186/2051-5960-1-74
  • Peer Reviewed
• [Journal Article] Graft-related disease progression in dura mater graft-associated Creutzfeldt-Jakob disease: a cross-sectional study (2013)
  • Author(s): Sakai K, Hamaguchi T, Noguchi-Shinohara M, Nozaki I, Takumi I, Sanjo N, Nakamura Y, Kitamoto T, Saito N, Mizusawa H, Yamada M
  • Journal Title: BMJ Open Volume: 3(8) Issue: 8 Pages: e003400-e003400
  • DOI: 10.1136/bmjopen-2013-003400
  • Peer Reviewed
• [Journal Article] Critical significance of the region between Helix 1 and 2 for efficient dominant-negative inhibition by conversion-incompetent prion protein (2013)
  • Author(s): Taguchi Y, Mistica AM, Kitamoto T, Schatzl HM
  • Journal Title: PLoS Pathog Volume: 9(6) Issue: 6 Pages: e1003466-e1003466
  • DOI: 10.1371/journal.ppat.1003466
  • Peer Reviewed
• [Journal Article] Insight into the frequent occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan (2013)
  • Author(s): Hamaguchi T, Sakai K, Noguchi-Shinohara M, Nozaki I, Takumi I, Sanjo N, Sadakane A, Nakamura Y, Kitamoto T, Saito N, Mizusawa H, Yamada M
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 84(10) Issue: 10 Pages: 1171-5
  • DOI: 10.1136/jnnp-2012-304850
  • Peer Reviewed