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Hitaru Kishida

Publications and source records attributed to Hitaru Kishida.

8 recordsLinked to original sources
PubMed2006

Intracerebroventricular delivery of dominant negative prion protein in a mouse model of iatrogenic Creutzfeldt-Jakob disease after dura graft transplantation.

We have developed a novel procedure in which a small collagen sheet (3 mm x 3 mm) absorbing prion-infected brain homogenates was transplanted onto the brain surface of highly prion-susceptible transgenic mice (Tg(MoPrP)4053/FVB), as an animal model of iatrogenic Creutzfeldt-Jakob disease (iCJD) caused by prion-contaminated cadaveric dura graft transplantation. Using the iCJD model, we further investigated the in vivo efficacy of dominant negative recombinant prion protein with lysine substitution at mouse codon 218 (rPrP-Q218K), which is known to inhibit prion replication in vitro (H. Kishida, Y. Sakasegawa, K. Watanabe, Y. Yamakawa, M. Nishijima, Y. Kuroiwa, N.S. Hachiya, K. Kaneko, Non-glycosylphosphatidylinositol (GPI)-anchored recombinant prion protein with dominant-negative mutation inhibits PrPSc replication in vitro, Amyloid, vol. 11, 2004, pp. 14-20.). Following 7-day intracerebroventricular administration of the rPrP-Q218K via an indwelling catheter connected to the implanted osmotic pump, the median incubation period of Tg(MoPrP)4053/FVB was prolonged considerably from 117 days to 131 days (p=0.016, log-rank test) in the rPrP-Q218K-treated group, even after a lengthy latency period of as long as 30 days by starting the rPrP-Q218K injection. Whether wild-type rPrP, other mutant rPrPs, or the combination of rPrP-Q218K with other anti-prion compounds might extend the survival period in that condition must be further investigated.

Animals↗
PubMed2006

Three-repeat Tau 69 is a major tau isoform in laser-microdissected Pick bodies.

By utilizing a novel combinatorial method of a Laser Microdissection System and Western blot analysis, we demonstrate that a distinct isoform of abnormally phosphorylated tau (69 kDa, Tau 69) predominantly aggregated in laser-microdissected Pick bodies (PBs) in sporadic Pick's disease. By contrast, tau migrated as two major bands of 60 and 64 kDa (Tau 60 and 64) in total brain homogenates as previously reported. Comparative immunohistochemical analysis with anti-4-repeat antibody revealed that a major component of the abnormally phosphorylated tau in these PBs was 3-repeat tau (3R-tau). Whether 29 amino acid repeat encoded by exons 2 and 3 in the Tau 69 might accelerate the formation of PBs remains to be further investigated. Such a combination of morphological and biochemical techniques significantly complements the existing histopathological methods.

Aged↗
PubMed2006

Autopsy case of Creutzfeldt-Jakob disease with Met/Val heterozygosity at codon 129 and type 1 protease-resistant prion protein presenting some florid-type plaques and many Kuru plaques in the cerebellum.

We report an atypical case of CJD. The clinical course was similar to a classic CJD phenotype, but histopathological study revealed several florid-type plaques in the amygdale and abundant Kuru plaques in the cerebellum that are atypical of classic CJD. Molecular analysis showed methionine/valine heterozygosity at codon 129 and no pathogenic mutation in the coding region of the prion protein gene. Western immunoblots revealed type 1 protease-resistant prion protein (PrPres), and a ration analysis of PrPres showed a high ratio of the diglycosylated form and a low ratio of the non-glycosylated form. Our case could not be precisely classified in any of Parchi's six variants. It suggests the existence of some factors that determine the phenotypic variability other than the codon 129 genotypes in the PrP gene or the physicochemical properties of PrPres.

Autopsy↗
PubMed2005

Association study of the chemokine, CXC motif, ligand 1 (CXCL1) gene with sporadic Alzheimer's disease in a Japanese population.

Inflammation is profoundly involved in the development of Alzheimer's disease (AD) and other neurodegenerative diseases. Chemokine, CXC motif, ligand 1 (CXCL1; or GRO1) is an inflammatory cytokine and appears to be implicated in the pathogenesis of AD. It is of interest and importance to see if the CXCL1 gene, mapped on chromosome 4q12-q13, has potential for conferring the predisposition to AD. Here we report on an association study of the CXCL1 gene with sporadic AD patients in a Japanese population; three single nucleotide polymorphisms (SNPs) in the CXCL1 locus were investigated in 103 AD patients and 130 healthy individuals. The results indicate that neither genotype frequencies nor allele frequencies of the examined SNPs attained statistical significance even after being stratified by the presence or absence of the Apolipoprotein E epsilon4 allele. Therefore, the data presented here suggests that the CXCL1 gene could not be associated with the susceptibility to AD in a Japanese population.

Aged↗
PubMed2004

Non-glycosylphosphatidylinositol (GPI)-anchored recombinant prion protein with dominant-negative mutation inhibits PrPSc replication in vitro.

Dominant-negative mouse prion protein (PrP) with a lysine mutation at codon 218 (Q218K) is known to inhibit prion replication. In order to gain further mechanistic insight into such dominant negative inhibition, non-glycosylphosphatidylinositol (GPI)-anchored recombinant PrP with Q218K (rPrP-Q218K) was investigated. When applied into scrapie-infected mouse neuroblastoma (ScN2a) cells, rPrP-Q218K but not wild-type rPrP (rPrP-WT) exclusively inhibited abnormal protease-resistant pathogenic isoform (PrPSc) replication without reducing the viability of the cells. It was even more efficient than quinacrine, which has already been prescribed for sporadic Creutzfeldt-Jakob disease (CJD) patients; 50% effective concentration (EC50) = 0.20 microM, 99% effective concentration (EC99) = 0.86 microM vs. EC50 = 0.45 microM, EC99 = 1.5 microM. Besides, no apparent cell damage was observed at the concentration of up to 4.3 microM (100 micrograms/ml). In combination treatment with 0.43 microM (10 micrograms/ml) of rPrP-Q218K, EC99 of quinacrine was decreased from 1.5 microM to 0.5 microM, and the cell viability was recovered from 50% to over 90% as inversely proportional to the concentration of quinacrine. Such combination could alleviate the side effects of quinacrine by reducing its effective concentration without changing or even acceleration the inhibition efficacy. Since homogeneous, high-quality rPrPs could be easily prepared from Escherichia coli in large quantities, rPrP-Q218K is a good candidate for a prion replication antagonist.

Amino Acid Substitution↗
PubMed2004

[Kuru].

Explore the source record for details and available documents.

Animals↗
PubMed2003

Lack of association between TrkA single nucleotide polymorphisms and sporadic Alzheimer's disease in a Japanese population.

Nerve growth factor and its receptor with tyrosine kinase activity (TrkA) have been implicated in the development of Alzheimer's disease (AD). Entire coding regions of TrkA gene harboring exons 1 through 17 were sequenced in 114 patients with sporadic AD and 112 control subjects in a Japanese population, and six known and two novel single nucleotide polymorphisms were identified, but no mutation associated with sporadic AD was identified. Concurrently, case-control analysis of TrkA gene A1674G polymorphism in 534 patients with sporadic AD and 454 control subjects has revealed no significant differences in TrkA genotype or allele frequencies even after stratification for Apolipoprotein E epsilon4 carrier statuses. Thus, the TrkA genotype does not appear to influence the risk of developing sporadic AD in a Japanese population.

Age of Onset↗