Biomedical subjects
Publications and source records attributed to T Odawara.
The neuroradiological findings are helpful for the diagnosis of toxoplasmic encephalitis. The T1 hypersignal intensity foci on brain magnetic resonance (MR) images without contrast enhancement are presented and can be a pathognomonic sign of this disease.
We present the case of a 56-year-old man suffering from acquired immune deficiency syndrome associated with lymphomatoid granulomatosis. Magnetic resonance imaging performed because of convulsions revealed an ill-defined frontal mass showing hypointense on T1WI and slightly hypointense on T2WI with surrounding edema. An elevated uptake was found on T1-201 single photo emission computed tomography consistent with a central nervous system lymphoma. However, the apparent diffusion coefficient ratio calculated from diffusion-tensor acquisitions was 1.53 and was higher than that of lymphomas in previous reports. Stereotactic brain biopsy was performed and lymphomatoid granulomatosis was confirmed.
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BACKGROUND: Atypical Pick's disease without Pick bodies is a type of frontotemporal dementia characterised by semantic dementia and temporal dominant lobar atrophy with ubiquitinopathy. No neurochemical analyses have ever been reported in this condition. OBJECTIVE: To investigate muscarinic acetylcholine receptors (mAchR) and their subtypes (M1-M4) in atypical Pick's disease. SUBJECTS: Five cases of atypical Pick's disease were studied. They were compared with nine control cases, 11 cases of Alzheimer's disease, and seven cases of dementia with Lewy bodies. METHODS: A [(3)H]quinuclidinyl benzilate (QNB) binding assay and an immunoprecipitation assay using subtype specific antisera were used. RESULTS: The total amount of mAchR in the temporal cortex was lower in atypical Pick's disease than in controls or Alzheimer's disease cases, but there were no significant differences between the three groups in the frontal cortex. In the temporal cortex, there was a smaller proportion of M1 receptors in atypical Pick's disease than in the controls or in the patients with Alzheimer's disease and dementia with Lewy bodies. In contrast, the proportion of M2 receptor was higher in atypical Pick's disease than in the other three groups. CONCLUSIONS: Depletion of postsynaptic cholinoreceptive neurones in the temporal cortex is more severe in atypical Pick's disease than in other neurodegenerative dementing disorders.
We report a 62-year-old Japanese man with familial frontotemporal dementia and a novel missense mutation (N296H) in exon 10 of the tau gene. The patient presented with frontal signs followed by temporal signs and parkinsonism. The brain showed localized frontotemporal lobe atrophy including the precentral gyrus and discoloration of the substantia nigra, and revealed severe neuronal loss with proliferation of tau-positive protoplasmic astroglia in the affected cerebral cortex, tau-positive coiled bodies and threads in the subcortical white matter, and tau-positive pretangle neurons in the subcortical and brain stem nuclei. There were no tau-positive neurofibrillary tangles, Pick bodies, tuft-shaped astrocytes or astrocytic plaques in the cerebral cortex. Immunoelectron microscopically, phosphorylated tau accumulated in both neurons and glial cells in different modalities, such as glial filaments in protoplasmic astroglia, straight tubules in coiled bodies, and free ribosomes in pretangle neurons. These findings suggest that tau proteins are not always assembled in abnormal filaments such as twisted ribbons, paired helical filaments and straight tubules in neurons and glial cells, which have been shown in previous cases with frontotemporal dementia and parkinsonism linked to chromosome 17. Immunoblotting of sarkosyl-insoluble tau exhibited accumulation of four-repeat tau isoforms in the brain. The N296H mutation may interfere with the ability of mutated tau to bind with microtubules and lead to tau aggregation. Further study is necessary to determine whether this mutation can account for the characteristic tau pathology of this case.
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In AIDS vaccine strategies, live attenuated vaccines can confer good resistance against pathogenic virus infections but have the potential risk of inducing disease, whereas safer replication-negative strategies such as DNA vaccinations have so far failed to prevent the disease onset. Here, we developed a novel DNA vaccine strategy to induce restricted replication of an avirulent virus and evaluated it in a simian immunodeficiency virus (SIV) infection model. We generated a chimeric SIV, FMSIV, by replacing SIV env with ecotropic Friend murine leukemia virus (FMLV) env to confine its replication to FMLV receptor (mCAT1)-expressing cells. In primate cells lacking mCAT1, FMSIV did not replicate unless mCAT1 was introduced exogenously. Vaccination to macaques with both the FMSIV DNA and the mCAT1-expression plasmid DNA induced SIV Gag-specific cellular immune responses and resistance against pathogenic SIV(mac239) challenge more efficiently than the replication-negative control vaccination with the FMSIV DNA alone. This strategy may be useful for development of safe and effective vaccines against various kinds of pathogenic viruses.
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Six cases of atypical Pick's disease (PD) without Pick bodies (PB) were examined immunohistochemically. These cases showed severe neuronal loss with gliosis predominantly in the temporal cortices. Ubiquitin immunohistochemistry revealed ubiquitin-positive intraneuronal inclusions in the dentate gyrus and ubiquitin-positive neurites in the cerebral cortex. In the dentate gyrus, the dendrites in the stratum moleculare as well as the intraneuronal inclusions in the granular cells were positively stained. Both structures were composed of ubiquitin-positive ribosome-like granular components and a few filamentous components immunoelectron-microscopically. In the cerebral cortex, ubiquitin-positive neurites were distributed in layers II-IIIab and layers V-VI, and were considered to be the distal dendrites from the small neurons. The dendrites and perikarya of these neurons contained ubiquitin-positive components similar to those in the dentate gyrus. Some ubiquitin-positive neurites were also found in the hippocampal subiculum, amygdala and striatum. The results of this study suggest that the granular cells in the dentate gyrus and the small neurons in the cerebral cortex share common ubiquitin-related and ribosome-associated abnormalities in both the perikarya and dendrites, that the degeneration of the perforant pathway caused by the parahippocampal lesion participates in the ubiquitin related abnormalities in the granular cells, and that PD cases with and without PB have common affected neurons, as shown immunohistochemically.
delta Tth DNA polymerase catalyzed polymerization of dATP and dTTP into a high-molecular-weight d(A-T) copolymer using oligo-d(A-T) as the template/primer (Hanaki et al., Biochem. Biophys. Res. Commun. 244, 210-219). Taking advantage of this reaction, we developed a highly sensitive method for strand-specific detection of DNA or RNA. The probe consisted of a 40- to 50-base-long complementary sequence on the 5' side and 10 repeats of AT on the 3' side. After hybridization using the 5' side, the 3' side AT repeat region was elongated by delta Tth DNA polymerase in the presence of the dATP, dTTP, and digoxigenin (dig)-11-dUTP. The elongation condition was 52-62 degrees C for 3 h. The method named HybrAT (hybridization-AT-tailing) was at least 100-fold more sensitive than the conventional hybridization with 5' end dig-11-dUTP labeled probe.
In patients with progressive supranuclear palsy (PSP), various tau-positive abnormal structures are found in the cerebral cortex as well as in the subcortical nuclei. Similar tau-positive abnormalities are also identified in cortico-basal degeneration (CBD). It is therefore questionable as to whether PSP can be neuropathologically differentiated from CBD. It also remains nuclear whether neurofibrillary tangles (NFT) in the cerebral cortex of PSP patients consist of PSP-NFT or concomitant Alzheimer's disease (AD)-NFT, although there have been some reports suggesting that PSP- and AD-NFT are different with respect to distribution pattern and biochemical character. In this study, a regional quantitative analysis of the distribution and antigenicity of tau-positive neurons (TPN) was performed in PSP cases and compared with that in AD cases. TPN consisted of NFT with tangle-formation and pretangle neurons (PN) without tangle-formation. In addition, NFT were subdivided into mature and immature NFT according to the difference of staining properties with anti-tau-related antibodies. The comparison of the TPN of the PSP cases with those of the AD cases revealed that the degree of tangle-formation in the TPN of AD was similar in all of the examined regions, while that in the TPN of PSP varied according to the region and case. Moreover, the NFT in the PSP and AD cases had different distributions according to the cortical layer and subnucleus, even in the common predilection sites of PSP and AD, suggesting that NFT in these regions of the PSP cases consist mainly of PSP-NFT. In addition, the PSP cases could be divided into two groups according to the difference of the tangle-formation of TPN; group I with typical PSP pathology and group II with atypical PSP pathology similar to CBD. This suggests that there is a continuity between PSP and CBD with respect to the distribution and antigenicity of TPN.
Taq and Tth DNA polymerases catalyzed polymerization of dATP and dTTP into poly d(A-T) without requiring added primer/template (Hanaki et al., Biochem. Biophys. Res. Commun. 238, 113-118), while the Stoffel fragment of Taq DNA polymerase and delta Tth DNA polymerase with respective deletions of ca. 290 and 250 N-terminal amino acids did not. The primer/template-independent polymerization appeared to proceed via two reactions, the slow process of formation of 16-19 nt long oligo d(A-T) without primer/template and the rapid process of elongation of the oligo d(A-T) by self-priming. As the former step was more sensitive to N-ethylmaleimide than the elongation reaction, probably the formation of the oligonucleotide preceded the elongation. But when the substrates were depleted, Taq DNA polymerase degraded the high molecular weigh d(A-T) polymer to the oligomers which were resistant to the further digestion by the 5'-->3' exonuclease activity of Taq DNA polymerase. Probably, the elongation and the degradation reactions proceeded simultaneously, the former process being faster than the latter in the presence of enough dATP and dTTP.
An anti-heparan sulfate proteoglycan (HSPG) monoclonal antibody (3G10) recognized irregular round structures (IRSs) of various sizes adjacent to tau-positive intracellular Pick bodies (PBs) in the granular cell layer of the dentate gyrus and the superficial layers of the parahippocampal and other temporal gyri in Pick's disease. Some intracellular PBs were also weakly immunostained with 3G10. Only part of the IRSs were double-immunostained with 3G10 and anti-tau antibody. Immunoelectron-microscopic examination revealed that IRSs were composed of aggregated fibrillary structures with a diameter of 10-20 nm, corresponding to the appearance of ghost PBs. These findings suggest that 3G10 identifies ghost PBs better than intracellular PBs, and that heparan sulfate proteoglycans are involved in the process of PBs extinction.
The gag-pol readthrough mutant of Moloney murine leukemia virus, MLV-B(CAG) (T. Odawara, H. Yoshikura, M. Oshima, T. Tanaka, D. S. Jones, F. Nemoto, Y. Kuchino, and A. Iwamoto, J. Virol. 65:6376-6379, 1991), was poorly complemented by a mutant encoding only Gag. This is because with all the genetic elements necessary for env expression present in MLV-B(CAG), insufficient Env protein was produced by the cells expressing MLV-B(CAG) for efficient virus production. Since the env mRNA expression per provirus in the MLV-B(CAG)- and wild-type-MLV-producing cells were the same and since the cells expressing the former contained eightfold fewer proviral copies, the insufficient Env expression by the former was found to be due to insufficient proviral copies in the cells. Examination of the cell clones having various proviral copies of Deltawt MLV (M. Oshima, T. Odawara, T. Matano, H. Sakahira, Y. Kuchino, A. Iwamoto, and H. Yoshikura, J. Virol. 70:2286-2295, 1996) showed that mRNA level was proportional to the number of proviral copies while interference and virus production followed a sigmoid curve with a sharp rise at the threshold number of proviral copies of around four per cell. Multicycle infection probably continues until the threshold level of proviral copies is attained in natural infection too.
The 441-nucleotide (nt) region (nt 5325 to 5766) around the splice acceptor (SA) site (nt 5491) was found to be necessary for high-level expression of gag-containing unspliced RNA of Moloney murine leukemia virus (M. Oshima, T. Odawara, T. Matano, H. Sakahira, K. Kuchino, A. Iwamoto, and H. Yoshikura, J. Virol. 70:2286-2295, 1996). Detailed genetic dissection of the 441-nt region revealed that the 5'-end 64 nt (nt 5325 to 5389) were necessary for high-level expression of the unspliced RNA when the spliced RNA was not produced, while the 3'-side 301 nt (nt 5466 to 5766) containing the SA site were necessary for producing spliced RNA. When the spliced RNA was produced, the unspliced RNA could be expressed at a high level even when the 5'-end 64 nt were absent. Probably the virus sequence ensuring the splicing could produce an RNA structure able to compensate for the function of the 5'-end 64-nt region responsible for the expression of the unspliced RNA.
Taq DNA polymerase polymerized dATP and dTTP to poly d(A-T) without requiring added primer/template in the temperature range of 60-70 degrees C. Tth DNA polymerase also catalyzed the reaction, while delta Tth, Vent, Vent(exo-), Pfu, Ultma, BcaBEST, and KOD DNA polymerases did not. The reaction was distinct from the template-nonrequiring terminal deoxynucleotidyl transferase reaction which absolutely required primers.