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T Kitamoto

Publications and source records attributed to T Kitamoto.

At least 19 recordsLinked to original sources
PubMed2006

The MM2-cortical form of sporadic Creutzfeldt-Jakob disease presenting with visual disturbance.

A subclass of sporadic Creutzfeldt-Jakob disease (sCJD) characterized by onset with visual symptoms (Heidenhain variant) has been reported to belong to the MM1 or MV1 type according to Parchi's classification. The authors report a 65-year-old woman with MM2-cortical sCJD with slowly progressive visual disturbance as the initial symptom. Diffusion-weighted MRIs revealed hyperintensity in both occipital cortices at an early stage.

Aged↗
PubMed2005

Clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease.

BACKGROUND: No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease (sCJD) has been established except for pathologic examination. OBJECTIVE: To identify a reliable marker for the clinical diagnosis of MM2-type sCJD. METHODS: CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses. RESULTS: The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on [18F]2-fluoro-2-deoxy-d-glucose PET. CONCLUSION: For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or [18F]2-fluoro-2-deoxy-d-glucose PET for the thalamic form.

14-3-3 Proteins↗
PubMed2005

Involvement of the peripheral nervous system in human prion diseases including dural graft associated Creutzfeldt-Jakob disease.

OBJECTIVE: To investigate abnormal prion protein (PrP) deposition in the peripheral nervous system (PNS) in human prion diseases. METHODS: Eight patients with prion diseases were examined: three with sporadic Creutzfeldt-Jakob disease (sCJD), two with dural graft associated CJD (dCJD), one with Gerstmann-Straussler-Scheinker disease (GSS) with a PrP P102L mutation (GSS102), and two with a P105L mutation (GSS105). An atypical case of sCJD with PrP plaques in the brain presented clinically with peripheral neuropathy, and showed demyelination in 12% of the teased fibres of the sural nerve. The PNS was investigated by immunohistochemical and western blotting analyses of PrP. RESULTS: In immunohistochemical studies, granular PrP deposits were detected in some neurones of dorsal root ganglia and a few fibres of peripheral nerves and spinal posterior roots in one sCJD and two dCJD patients, but not in GSS102 or GSS105 patients. The atypical case of sCJD with peripheral neuropathy showed no obvious PrP deposition in the nerves. Western blotting analysis of the PNS from the dCJD patients revealed a small amount of protease K resistant PrP in the dorsal root ganglia and peripheral nerves. CONCLUSIONS: Abnormal PrP deposition occurs in the dorsal root ganglia and peripheral nerves in sCJD and dCJD. The PrP deposits in the PNS are not correlated with clinical manifestation of peripheral neuropathy in CJD.

Adult↗
PubMed2004

Clinical features of Creutzfeldt-Jakob disease with V180I mutation.

The authors describe the clinical features of Creutzfeldt-Jakob disease (CJD) with the causative point mutation at codon 180. The symptoms never started with visual or cerebellar involvement. The patients showed slower progression of the disease compared with sporadic CJD. They never showed periodic sharp and wave complexes in EEG. MRI demonstrated remarkable high-intensity areas with swelling in the cerebral cortex except for the medial occipital and cerebellar cortices. These characteristic MRI findings are an important clue for an accurate premortem diagnosis.

Aged↗
PubMed2004

MRI characteristics of sporadic CJD with valine homozygosity at codon 129 of the prion protein gene and PrPSc type 2 in Japan.

Two Japanese sporadic Creutzfeld-Jakob disease (sCJD) patients with valine homozygosity at codon 129 of the prion protein gene and protease-resistant prion protein (PrP(Sc)) type 2 (VV2) are described. In contrast with Western countries, this type of sCJD is very rare in Japan. In 123 sCJD cases, only two were recognised as VV2 by the Japanese CJD surveillance committee. The clinical symptoms and pathological findings of the patients were similar to those of European and US patients. The noteworthy finding of diffusion weighted MRI (DWI) was that an abnormal high intensity covered a wide range of the thalamus including the dorsomedial nucleus, the pulvinar, and the ventral anterior, lateral, and posterolateral nuclei. This thalamic pattern has not been recognised in sCJD with methionine homozygosity and PrP(Sc) type 1 (MM1) or methionine/valine heterozygosity and PrP(Sc) type 1 (MV1) which comprises the vast majority of sCJD. This finding may be characteristic to VV2 and may distinguish it from MM1, MV1, and variant CJD. DWI can provide a very important clue for the antemortem diagnosis of VV2 subjects.

Aged↗
PubMed2003

Sporadic Creutzfeldt-Jakob disease with MM1-type prion protein and plaques.

The authors report a 75-year-old woman with atypical sporadic Creutzfeldt-Jakob disease (CJD) characterized by MM1-type prion protein (PrP) (methionine homozygosity at codon 129 in the PrP gene and type-1 protease-resistant PrP) and PrP plaques. This patient is the first case of sporadic CJD with plaque-forming MM1-type PrP, suggesting either a shared prion strain with the plaque-forming subset of dural graft-associated CJD or shared host genetic factors that are unrelated to the PrP genotype.

Aged↗
PubMed2001

Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory.

Surgical, pharmacological and genetic lesion studies have revealed distinct anatomical sites involved with different forms of learning. Studies of patients with localized brain damage and work in rodent model systems, for example, have shown that the hippocampal formation participates in acquisition of declarative tasks but is not the site of their long-term storage. Such lesions are usually irreversible, however, which has limited their use for dissecting the temporal processes of acquisition, storage and retrieval of memories. Studies in bees and flies have similarly revealed a distinct anatomical region of the insect brain, the mushroom body, that is involved specifically in olfactory associative learning. We have used a temperature-sensitive dynamin transgene, which disrupts synaptic transmission reversibly and on the time-scale of minutes, to investigate the temporal requirements for ongoing neural activity during memory formation. Here we show that synaptic transmission from mushroom body neurons is required during memory retrieval but not during acquisition or storage. We propose that the hebbian processes underlying olfactory associative learning reside in mushroom body dendrites or upstream of the mushroom body and that the resulting alterations in synaptic strength modulate mushroom body output during memory retrieval.

Animals↗
PubMed2001

Conditional modification of behavior in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons.

Behavior is a manifestation of temporally and spatially defined neuronal activities. To understand how behavior is controlled by the nervous system, it is important to identify the neuronal substrates responsible for these activities, and to elucidate how they are integrated into a functional circuit. I introduce a novel and general method to conditionally perturb anatomically defined neurons in intact Drosophila. In this method, a temperature-sensitive allele of shibire (shi(ts1)) is overexpressed in neuronal subsets using the GAL4/UAS system. Because the shi gene product is essential for synaptic vesicle recycling, and shi(ts1) is semidominant, a simple temperature shift should lead to fast and reversible effects on synaptic transmission of shi(ts1) expressing neurons. When shi(ts1) expression was directed to cholinergic neurons, adult flies showed a dramatic response to the restrictive temperature, becoming motionless within 2 min at 30 degrees C. This temperature-induced paralysis was reversible. After being shifted back to the permissive temperature, they readily regained their activity and started to walk in 1 min. When shi(ts1) was expressed in photoreceptor cells, adults and larvae exhibited temperature-dependent blindness. These observations show that the GAL4/UAS system can be used to express shi(ts1) in a specific subset of neurons to cause temperature-dependent changes in behavior. Because this method allows perturbation of the neuronal activities rapidly and reversibly in a spatially and temporally restricted manner, it will be useful to study the functional significance of particular neuronal subsets in the behavior of intact animals.

Alleles↗
PubMed2001

Scrapie removal using Planova virus removal filters.

As a possible method for reducing the risk of transmissible spongiform encephalopathy (TSE) infection, Planova virus removal filters were tested for their ability to remove scrapie agent ME7. Albumin solution was spiked with high-titre ME7 and filtered through three different pore sizes of Planova filters. Infectivity of the pre- and post-filtration samples was assayed in log dilutions by intracerebral inoculation into C57B1/6 mice. Filtration of albumin solution in the absence or presence of a detergent (Sarkosyl) with Planova 35N (35+/-2 nm mean pore size) removed the contaminating scrapie agent with reduction factors of 4.93 log10 and 1.61 log10, respectively. Filtration, both in the absence and presence of detergent with Planova 15N (15+/-2 nm mean pore size), and in the presence of detergent with Planova 10N (9+/-2 nm mean pore size), showed high levels of scrapie reduction of >5.87 log10, >4.21 log10, and >3.80 log10, respectively, with no residual infectively detected in any of the filtrate samples. The effectiveness of Planova 35N filtration for the removal of infectivity of this TSE agent is greatly reduced in the presence of a strong detergent, but Planova filters with 15 nm or smaller pore size membranes can remove such infectivity at high reduction rates.

Animals↗
PubMed2001

Catalog of 434 single-nucleotide polymorphisms (SNPs) in genes of the alcohol dehydrogenase, glutathione S-transferase, and nicotinamide adenine dinucleotide, reduced (NADH) ubiquinone oxidoreductase families.

An approach based on development of a large archive of single-nucleotide polymorphisms (SNPs) throughout the human genome is expected to facilitate large-scale studies to identify genes associated with drug efficacy and side effects, or susceptibility to common diseases. We have already described collections of SNPs present among various genes encoding drug-metabolizing enzymes. Here we report SNPs for such enzymes at additional loci, including 8 alcohol dehydrogenases, 12 glutathione S-transferases, and 18 belonging to the NADH-ubiquinone oxidoreductase family. Among DNA samples from 48 Japanese volunteers, we identified a total of 434 SNPs at these 38 loci: 27 within coding elements, 52 in 5' flanking regions, five in 5' untranslated regions, 293 in introns, 20 in 3' untranslated regions, and 37 in 3' flanking regions. The ratio of transitions to transversions was approximately 2.1 to 1. Among the 27 coding SNPs, 13 were nonsynonymous changes that resulted in amino acid substitutions. Our collection of SNPs derived from this study should prove useful for investigations designed to detect associations between genetic variations and common diseases or responsiveness to drug therapy.

Alcohol Dehydrogenase↗
PubMed2001

Catalog of 320 single nucleotide polymorphisms (SNPs) in 20 quinone oxidoreductase and sulfotransferase genes.

Single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolizing enzymes, transporters, receptors, and other drug targets have been widely implicated as contributors to differences among individuals as regards the efficacy and toxicity of many medications, as well as the susceptibility to complex diseases. By combining the polymerase chain reaction (PCR) technique with direct sequencing, we screened genomic DNAs from 48 Japanese volunteers for SNPs in genes encoding three quinone oxidoreductases (NQO1, NQO2, and PIG3) and 17 sulfotransferases (SULT1A1, SULT1A2, SULT1A3, SULT1C1, SULT1C2, SULT2A1, SULT2B1, ST1B2, TPST1, TPST2, SULTX3, STE, CST, HNK-1 ST, CHST2, CHST4, and CHST5). In all, we identified 320 SNPs from these 20 loci: 22 within coding elements, 21 in 5' flanking regions, 10 in 5' untranslated regions, 223 in introns, 19 in 3' untranslated regions, and 25 in 3' flanking regions. The ratio of transitions to transversions was approximately 2.3 to 1. Of the 22 coding SNPs, 6 were nonsynonymous substitutions that resulted in amino-acid substitutions. The high-density SNP maps we constructed from this data for each of the quinone oxidoreductases and sulfotransferases examined here should provide useful information for investigations designed to detect association(s) between genetic variations and common diseases or responsiveness to drug therapy.

Base Sequence↗
PubMed2001

Drosophila cholinergic neurons and processes visualized with Gal4/UAS-GFP.

Using 7.4 kb of 5' flanking DNA from the Drosophila cholinergic gene locus to drive Gal4 expression we can visualize essentially all cholinergic neurons and neuropiles after genetic recombination with a UAS-GFP (S65T) reporter gene. In contrast to previous methods somata and neuropiles can be observed in the same samples. Fluorescence intensity is strong enough to allow observations in live animals at all developmental stages. Three-dimensional reconstructions made from confocal sections of whole-mount preparations reveal the extensive cholinergic connections among various regions of the nervous system.

Journal Article↗
PubMed2001

Severe brain atrophy in a case of thalamic variant of sporadic CJD with plaque-like PrP deposition.

A 30-year-old woman presented with ataxic gait and progressive mental deterioration, and 3 years later developed myoclonus in the limbs. Subsequently, she lapsed into an akinetic state and died more than 6 years after the onset of disease. The brain weighed 670 g, and preferential degeneration was found in the medial thalamus and the inferior olivary nucleus. In the cerebrum and cerebellum, gliosis and neuronal depletion were only mild and disintegration of the parenchymal structures was inconspicuous, despite pronounced atrophy. The patient had methionine homozygosity at codon 129 of the PrP gene and protease-resistant PrP type 2 in the brain. On PrP immunostaining, plaque-like deposits were detected in the cerebral and cerebellar cortices. Severe brain atrophy such as in the present case has never been described in the thalamic variant of sporadic CJD.

Adult↗
PubMed2001

[Prion diseases, update].

In prion diseases, genotypic classification has been useful to understand the clinical course and pathological changes. However, among patients with the same prion protein (PrP) genotype, there are variations in the pathological and clinical phenotype. Recently, PrP typing was proposed by the molecular weight of protease-resistant PrP (PrPres). Combined with genotype and PrPres typing, sporadic Creutzfeldt-Jakob disease (CJD) could be classified precisely. In addition, we found the fragmented PrP molecules to differentiate between dura-classic CJD and dura-plaque type CJD. We report herein that the fragmented PrP is a useful marker to classify human prion diseases, and also a clue to analyze abnormal PrP structures. The fragmented PrP was detected in patients with classic-type CJD, sporadic thalamic-type CJD, familial CJD with codon 200 or 232 mutation, or familial Gerstmann-Straussler syndrome (GSS) with codon 102 mutation. Among patients with type-1 abnormal PrP, the transmission study was successful in sporadic CJD with type 1 PrPres and the fragment PrP, but not in CJD without the fragmented PrP. Thus, in the prion field, type-specific PrP structure contributes to the clinicopathology and transmissibility.

Animals↗
PubMed2000

The amnesiac gene product is expressed in two neurons in the Drosophila brain that are critical for memory.

Mutations in the amnesiac gene in Drosophila affect both memory retention and ethanol sensitivity. The predicted amnesiac gene product, AMN, is an apparent preproneuropeptide, and previous studies suggest that it stimulates cAMP synthesis. Here we show that, unlike other learning-related Drosophila proteins, AMN is not preferentially expressed in mushroom bodies. Instead, it is strongly expressed in two large neurons that project over all the lobes of the mushroom bodies, a finding that suggests a modulatory role for AMN in memory formation. Genetically engineered blockade of vesicle recycling in these cells abbreviates memory as in the amnesiac mutant. Moreover, restoration of amn gene expression to these cells reestablishes normal olfactory memory in an amn deletion background. These results indicate that AMN neuropeptide release onto the mushroom bodies is critical for normal olfactory memory.

Animals↗
PubMed2000

Analyses of Gerstmann-Straussler syndrome with 102Leu219Lys using monoclonal antibodies that specifically detect human prion protein with 219Glu.

Two monoclonal antibodies that specifically detect human prion protein (PrP) were developed. The epitope of both antibodies was mapped using fusion proteins of glutathione-S-transferase and PrP peptides to the C-terminal region encompassing the polymorphic 219 residue. The antibodies recognized human PrP with 219Glu but not that with 219Lys. The unique property of the antibodies was utilized to determine the allelic origin of abnormal PrP deposited in the brain of a patient with Gerstmann-Straussler syndrome (GSS) with 102Leu/219Lys encoded by the same allele. Abnormal PrP was exclusively of mutant allelic origin, suggesting that 219Lys may be permissive to the formation of abnormal PrP in GSS. The antibodies may help to explore the relationship of 219Glu/Lys polymorphism to the pathogenesis of human prion diseases.

Amino Acid Substitution↗