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Tatsuo Yamada

Publications and source records attributed to Tatsuo Yamada.

At least 19 recordsLinked to original sources
PubMed2006

Aprataxin (APTX) gene mutations resembling multiple system atrophy.

Mutations of the aprataxin (APTX) gene cause early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), also called ataxia with oculomotor apraxia type 1. Recent studies showed clinical heterogeneity in patients with EAOH. We describe 2 patients whose clinical features resembled those of multiple system atrophy of the cerebellar subtype (MSA-C) but without ocular motor apraxia and hypoalbuminemia. Each had a different nucleotide transition in the APTX gene (725G-->A and 457A-->G). These variants on the APTX gene exhibit phenotypic variability.

Adult↗
PubMed2006

A novel membrane protein, encoded by the gene covering KIAA0233, is transcriptionally induced in senile plaque-associated astrocytes.

Beta-amyloid (Abeta) deposition and senile plaque-associated astrocytes are common neuropathological features of Alzheimer's disease (AD). Although the molecular mechanisms by which Abeta contributes to the progression of neuropathologic changes have not been entirely established, there is little doubt that the association of Abeta with astrocytes, the predominant cell type in brain, significantly influences exacerbation of the disease. In an effort to identify astrocyte-derived molecules that may be intimately associated with progression of AD, we identified a novel Abeta-induced rat gene, designated Mib, whose human counterpart covers KIAA0233. Mib-transfected C6 cells express Mib protein in the endoplasmic reticulum and endplasmic reticulum-Golgi-intermediate compartment. To evaluate roles of Mib in AD, we investigated its expression in the AD brain. In non-AD brains, Mib mRNA has been detected in neurons but not in quiescent astrocytes. On the contrary, in AD brains, Mib mRNA is expressed in activated astrocytes associated with senile plaques, but not expressed in neurons around lesions. From these observations, Mib appears to be a novel Abeta-responsive gene that may play a role in astrocyte inflammatory activation around senile plaques in the AD brain.

Alzheimer Disease↗
PubMed2006

Unsaturated fatty acids suppress the expression of the ATP-binding cassette transporter G1 (ABCG1) and ABCA1 genes via an LXR/RXR responsive element.

ATP-binding cassette transporters (ABC) G1 and ABCA1 are membrane cholesterol transporters and have been implicated to mediate cholesterol efflux from cells in the presence of high density lipoproteins and its major protein constituent apolipoprotein A-I, respectively. We previously demonstrated that unsaturated fatty acids suppress the stimulatory effects of oxysterols and retinoids on ABCA1 gene transcription. We here demonstrate that unsaturated fatty acids significantly suppress the stimulatory effects of oxysterols and retinoids on the expression of ABCG1 mRNA and protein and the activity of the wild-type human ABCG1 promoter as well as ABCA1. Mutation or deletion of the DR4 element within the ABCG1 or ABCA1 promoters, to which the transcriptional inducers LXR and RXR bind, abolished the suppressive effects of unsaturated fatty acids. Our observations provide the first evidence that unsaturated fatty acids suppress ABCG1 gene expression by a mechanism which involves the binding of LXR/RXR to the promoters. Suppression of both the ABCA1 and ABCG1 genes may indicate that unsaturated fatty acids suppress not only cholesterol efflux to apoA-I and thereby nascent HDL formation but also HDL-dependent cholesterol efflux from vascular cells.

ATP Binding Cassette Transporter 1↗
PubMed2006

Increased level of DJ-1 in the cerebrospinal fluids of sporadic Parkinson's disease.

DJ-1 is an antioxidant protein whose loss of function by gene mutations has been linked to familial Parkinson's disease (PD). The main objective of the present study was to determine if this molecule was also involved in the pathogenesis of sporadic PD. For this purpose, quantitative immunoblot assays were performed to evaluate DJ-1 in cerebrospinal fluids (CSF) collected from sporadic PD patients (n=40) and non-PD controls (n=38). The results showed that the CSF DJ-1 levels in PD were significantly higher than those in non-PD controls. Especially, upregulation of CSF DJ-1 in the early stage of PD (Yahr I-II) were distinct compared to those in the advanced stage of PD (Yahr III-IV) and non-PD controls (p<0.001 by ANOVA with post hoc Bonferroni's test), suggesting a protective role of DJ-1 against oxidative stress during the early stage. Thus, we propose that CSF DJ-1 could be a possible biomarker for early sporadic PD.

Aged↗
PubMed2006

Relationship between antisocial behavior and regional cerebral blood flow in frontotemporal dementia.

OBJECTIVE: To examine the relationship between antisocial behaviors and reduction of regional cerebral blood flow (rCBF) in patients with frontotemporal dementia (FTD). METHODS: Brain perfusion single photon emission computed tomography (SPECT) was performed in 22 patients with FTD and 76 age-matched healthy volunteers. The statistical analysis was conducted using the SPM99 software. The antisocial behavioral symptoms were assessed independently by three geriatric psychiatrists, who had not been given the information of the SPECT images. RESULTS: Compared with normal controls, FTD patients showed significant reduction of rCBF in the widespread frontal cortical areas. The correlation analysis showed that antisocial behavioral symptoms are associated with reduction of rCBF in the orbitofrontal cortex. CONCLUSION: The functional decline of orbitofrontal cortex is related to antisocial behavioral symptoms in patients with FTD.

Aged↗
PubMed2006

[Serial MRI findings of intracranial tuberculomas: a case report and review of the literature].

Intracranial tuberculoma is an infectious disorder, occurring with or without tuberculous meningitis. Although intracranial tuberculoma is rare in developed countries, its frequency has increased in recent years in association with aging and immunocompromised hosts. Because of the low sensitivity of Mycobacterium tuberculosis cultures or of DNA detection from cerebrospinal fluid, diagnosis of intracranial tuberculoma is often difficult. Conventional magnetic resonance (MR) imaging of the tuberculoma yields variable results and is indistinct from other inflammatory lesions or brain tumors. We report the case of a 74-year-old woman with progressive neurologic deterioration. MR imaging of the brain showed multiple ring-like enhancing lesions in the supra- and infra-tentorial regions, mimicking multiple metastatic brain tumors. Diffusion-weighted imaging (DWI) of the brain showed homogeneous high signals in each lesion. A cavity in the lung suggested systemic involvement of tuberculosis. Despite extensive examination, tuberculosis could not be detected. Nevertheless, anti-tuberculosis treatment was administered. The patient's neurologic condition initially deteriorated for 4 weeks, then gradually improved. MRI showed marked improvement of the lesions after anti-tuberculosis treatment. Whereas conventional MRI is not specific in such cases, DWI might be useful for early assessment of intracranial tuberculosis.

Aged↗
PubMed2005

Relationship between delusions and regional cerebral blood flow in Alzheimer's disease.

UNLABELLED: To investigate the association between delusions and cerebral functional deficits in Alzheimer's disease (AD), we evaluated probable AD patients with and without delusions. METHODS: Functional brain imaging was performed by single photon emission computed tomography with technetium-99m-labeled ethyl cysteinate dimer (99mTc-ECD) in 64 AD patients and 76 age-matched normal healthy volunteers. SPECT data were analyzed by statistical parametric mapping. RESULTS: In AD patients, no differences were found in age and cognitive activities between those with (n = 25) and without (n = 39) delusions. Compared with normal healthy volunteers, AD patients had significantly decreased perfusion in the posterior cingulate gyri, precunei, and parietal association cortex. Moreover, in the patients with delusions, perfusion was significantly decreased in the frontal lobe with right side dominance. In the comparison between the patients with and without delusions, the patients with delusions had significantly decreased perfusion in the prefrontal cortex, anterior cingulate gyri, inferior to middle temporal cortices, and parietal cortex of the right hemisphere (p < 0.01). CONCLUSION: The functional deficits in the right hemisphere may be the cause of delusions in AD.

Aged↗
PubMed2005

Lib, transcriptionally induced in senile plaque-associated astrocytes, promotes glial migration through extracellular matrix.

In an effort to identify astrocyte-derived molecules that may be intimately associated with progression of Alzheimer's disease (AD), Lib, a type I transmembrane protein belonging to leucine-rich repeat superfamily, has been identified as a distinctly inducible gene, responsive to beta-amyloid as well as pro-inflammatory cytokines in astrocytes. To evaluate the roles of Lib in AD, we investigated Lib expression in AD brain. In non-AD brain, Lib mRNA has been detected in neurons but not in quiescent astrocytes. On the contrary, in AD brain, Lib mRNA is expressed in activated astrocytes associated with senile plaques, but not expressed in neurons around lesions. Lib-expressing glioma cells displayed promotion of migration ability through reconstituted extracellular matrix and recombinant Lib protein bound to constituents of extracellular matrix. These observations suggest that Lib may contribute to regulation of cell-matrix adhesion interactions with respect to astrocyte recruitment around senile plaques in AD brain.

Aged↗
PubMed2005

Alterations of T-lymphocyte populations in Parkinson disease.

Immune reaction-related inflammation may be important in the pathogenesis of Parkinson disease (PD). To elucidate peripheral immunologic alterations in PD, we characterized extended peripheral T-lymphocyte populations in 33 patients with PD and 34 normal subjects. Patients with PD had significantly decreased CD4+:CD8(+)T-cell ratios (P<0.001), fewer CD4(+)CD25(+)T cells (P<0.01), and significantly increased ratios of IFN-gamma-producing to IL-4-producing T cells (P<0.001). The characteristics of predominant expression of CD8(+)T cells, depletion of CD4(+)CD25(high) cells, and a shift to a T(H)1-type immune response in the peripheral immune system in PD patients may reflect an immune reaction-associated inflammatory process in the brain.

Aged↗
PubMed2005

Amyloid-beta causes apoptosis of neuronal cells via caspase cascade, which can be prevented by amyloid-beta-derived short peptides.

Amyloid beta 1-42 (Abeta42) and Abeta17-42 are major constituents of diffuse plaque in brains with Alzheimer's disease (AD). We demonstrate the potent cytotoxicity of Abeta42 and Abeta17-42, lesser toxicity of Abeta1-40 (Abeta40) and lack of toxicity of Abeta1-16 (Abeta16) in neuronal cells as measured by inhibition of cell proliferative response using thymidine incorporation assay and that this cytotoxicity can be reduced with Abeta16 and eight-residue Abeta derivatives such as Abeta1-8 and Abeta9-16. FACS analysis also revealed that Abeta16 could dramatically protect against the apoptosis induced by Abeta17-42 with over 80% viable cells. We determined the caspases involved in the Abeta-mediated apoptotic pathway using caspase-specific inhibitors in MTT assays. For all Abetas, the executor was caspase 3, while the initiator was caspase 9 for Abeta42 and caspase 8 for Abeta40 and Abeta17-42. Microscopic observation of lucifer-yellow-labeled neuronal cells demonstrated the occurrence of lysosomal membrane injury of the cells, corresponding to the severe cytotoxic effects of Abeta42. Our findings suggest that the apoptosis of neuronal cells due to Abeta42, Abeta40 and Abeta17-42 is mediated by the different caspase pathways and that this apoptosis can be reduced with the eight-residue Abeta-derived fragments Abeta1-8, Abeta9-16 and Abeta16.

Amyloid beta-Peptides↗
PubMed2005

Homocysteic acid induces intraneuronal accumulation of neurotoxic Abeta42: implications for the pathogenesis of Alzheimer's disease.

The causes of neuronal dysfunction and degeneration in Alzheimer's disease (AD) are not fully understood, but increased production of neurotoxic forms of amyloid beta-peptide-42 (Abeta42) seems of major importance. Large extracellular deposits of aggregated Abeta42 (plaques) is a diagnostic feature of AD, but Abeta42 may be particularly cytotoxic when it accumulates inside neurons. The factors that may promote the intracellular accumulation of Abeta42 in AD are unknown, but recent findings suggest that individuals with elevated homocysteine levels are at increased risk for AD. We show that homocysteic acid (HA), an oxidized metabolite of homocysteine, induces intraneuronal accumulation of a Abeta42 that is associated with cytotoxicity. The neurotoxicity of HA can be attenuated by an inhibitor of gamma-secretase, the enzyme activity that generates Abeta42, suggesting a key role for intracellular Abeta42 accumulation in the neurotoxic action of HA. Concentrations of HA in cerebrospinal fluid (CSF) were similar in AD and control subjects. CSF homocysteine levels were elevated significantly in AD patients, however, and homocysteine exacerbated HA-induced neurotoxicity, suggesting a role for HA in the pathogenic action of elevated homocysteine levels in AD. These findings suggest that the intracellular accumulation of Abeta42 plays a role in the neurotoxic action of HA, and suggest a potential therapeutic benefit of agents that modify the production and neurotoxic actions of HA and homocysteine.

Alzheimer Disease↗
PubMed2005

Diffusion-weighted MRI in familial Creutzfeldt-Jakob disease with the codon 200 mutation in the prion protein gene.

Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) has been reported to be a useful tool for early diagnosis of sporadic Creutzfeldt-Jakob disease (CJD). We report MRI findings with DWI, as well as with fluid-attenuated inversion recovery (FLAIR) and T1-weighted imaging (T1WI), in a case of familial CJD with a mutation at codon 200 of the prion protein gene. DWI in this patient showed high signal intensity in the basal ganglia and the cerebral cortex, similar to findings in sporadic CJD. In addition, T1WI showed areas of high signal intensity bilaterally in the globus pallidus. Despite the clinical diversity and atypical laboratory findings seen in familial CJD with the codon 200 mutation, these neuroimaging studies suggest that common regional distributions and a common pathogenesis might underlie the clinical progression both in sporadic CJD and in familial CJD with the codon 200 mutation in the prion protein gene. DWI abnormalities may be characteristic features that should be considered in the diagnosis of familial as well as of sporadic CJD.

Brain↗
PubMed2005

A novel neurotrophic agent, T-817MA [1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl}-3-azetidinol maleate], attenuates amyloid-beta-induced neurotoxicity and promotes neurite outgrowth in rat cultured central nervous system neurons.

Progressive neuronal loss in Alzheimer's disease (AD) is considered to be a consequence of the neurotoxic properties of amyloid-beta peptides (A beta). T-817MA (1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl}-3-azetidinol maleate) was screened as a candidate therapeutic agent for the treatment of AD based on its neuroprotective potency against A beta-induced neurotoxicity and its effect of enhancing axonal regeneration in the sciatic nerve axotomy model. The neuroprotective effect of T-817MA against A beta(1-42) or oxidative stress-induced neurotoxicity was assessed using a coculture of rat cortical neurons with glia. T-817MA (0.1 and 1 microM) was strongly protective against A beta(1-42)-induced (10 microM for 48 h) or H2O2-induced (100 microM for 24 h) neuronal death. T-817MA suppressed the decrease of GSH levels induced by H2O2 exposure (30 microM for 4 h) in cortical neuron culture; therefore, T-817MA was likely to alleviate oxidative stress. Besides the neuroprotective effect, T-817MA (0.1 and 1 microM) promoted neurite outgrowth in hippocampal slice cultures and reaggregation culture of rat cortical neurons. T-817MA also increased the growth-associated protein 43 content in the reaggregation culture of cortical neurons. These findings suggest that T-817MA exerts neuroprotective effect and promotes neurite outgrowth in rat primary cultured neurons. Based on these neurotrophic features, T-817MA may have a potential for disease modification and be useful for patients with neurodegenerative diseases, such as AD.

Amyloid beta-Peptides↗
PubMed2005

[A case of pseudo Tolosa-Hunt syndrome with bacterial infection and literature review].

We report a case with recurrent orbital pain and unilateral cranial nerve paresis mimicking Tolosa-Hunt syndrome. However, these features were most likely caused by bacterial infection because of beneficial response to antibiotics therapy. A 32-year-old man developed severe right orbital pain and diplopia. Neurological examination revealed right oculomotor paresis and 1st division of the right trigeminal nerve dysfunction. MR imaging revealed thickness of right cavernous sinus region with marked gadolinium enhancement. Cerebrospinal fluid (CSF) examination was initially normal. Treatment with steroid showed marked improvement. However soon after tapering of steroid dosage, his symptoms recurred and deteriorated. He was referred to our hospital because of second opinion. Neurological examination still showed right oculomotor paresis and 1st division of the right trigeminal nerve dysfunction with orbital and retro-orbital pain. Re-examination of CSF showed pleocytosis with neutrocytes dominancy and elevated protein concentration. Intravenous treatment with penicillin was initiated with marked improvement. There have been reported cases with bacterial infection resulting pseudo Tolosa-Hunt syndrome, which have good response to antibiotics treatment with excellent prognosis. It is speculated that bacterial infection might cause clinical features mimicking Tolosa-Hunt syndrome in our case.

Adult↗
PubMed2004

Eight-residue Abeta peptides inhibit the aggregation and enzymatic activity of Abeta42.

Insoluble Abeta1-42 is the main component of the amyloid plaque. We have previously demonstrated that exposure to low pH can confer the molten globule state on soluble Abeta1-42 in vitro [Biochem. J. 361 (2000) 547] and unfolding experiments with guadinine hydrochloride (GdnHCl) have now confirmed this observation. The molten globule state of the protein has many biological properties and understanding the mechanisms of its formation is an important step in devising a therapeutic strategy for Alzheimer's disease (AD). We therefore investigated the ability of a series of synthetic eight-residue peptides derived from Abeta1-42 to inhibit the acid-induced aggregation of Abeta1-42 and identified the potent peptides to be Abeta15-22, Abeta16-23 and Abeta17-24. A1-antichymotrypsin, a member of the serine proteinase inhibitor (serpin) family is another major component of the amyloid plaque. In the present study, we investigated the proteolytic activity of Abeta1-42 against casein at different pHs. Chemical modification of amino acid residues in Abeta1-42 indicated that serine and histidine residues, but not aspartic acid, are necessary for enzymatic activity, suggesting that it is a serine proteinase. Amino acid substitution studies indicate that glutamic acids at positions 11 and 22 participate indirectly in proteolysis and we surmise that amino acid residues 29-42 are required to stabilize the conformer. A study of metal ions suggested that Cu2+ affected the enzymatic activity, but Zn2+ and Fe2+ did not. Interestingly, Abeta14-21 and Abeta15-22 were the only peptides that inhibited the proteolytic activity of Abeta42. Therefore, Abeta15-22 may control both aggregation of Abeta1-42 at acidic pH and its proteolytic activity at neutral pH. Consequently, we suggest that it may be of use in the therapy of Alzheimer's disease.

Acidosis↗
PubMed2004

Results of quinacrine administration to patients with Creutzfeldt-Jakob disease.

Several chemicals inhibit the accumulation of abnormal prion proteins in vitro. We administered one, the antimalarial agent quinacrine, to three patients with sporadic Creutzfeldt-Jakob disease (CJD) and to one with iatrogenic CJD. Quinacrine at 300 mg/day was given enterally for 3 months. Within 2 weeks of administration, the arousal level of the patient with akinetic mutism improved. The other 3 patients, insensible before treatment, had integrative responses such as eye contact or voluntary movement in response to verbal and/or visual stimuli restored. Clinical improvement was transient, lasting 1-2 months during treatment. Quinacrine was well tolerated, except for liver dysfunction and yellowish pigmentation. Although its antiprion activity in the human brain has yet to be proved, these modest effects of quinacrine suggest the possibility of using chemical intervention against prion diseases.

Antimalarials↗
PubMed2004

The effect of cholesterol and monosialoganglioside (GM1) on the release and aggregation of amyloid beta-peptide from liposomes prepared from brain membrane-like lipids.

In order to investigate the influence of cholesterol (Ch) and monosialoganglioside (GM1) on the release and subsequent deposition/aggregation of amyloid beta peptide (Abeta)-(1-40) and Abeta-(1-42), we have examined Abeta peptide model membrane interactions by circular dichroism, turbidity measurements, and transmission electron microscopy (TEM). Model liposomes containing Abeta peptide and a lipid mixture composition similar to that found in the cerebral cortex membranes (CCM-lipid) have been prepared. In all, four Abeta-containing liposomes were investigated: CCM-lipid; liposomes with no GM1 (GM1-free lipid); those with no cholesterol (Ch-free lipid); liposomes with neither cholesterol nor GM1 (Ch-GM1-free lipid). In CCM liposomes, Abeta was rapidly released from membranes to form a well defined fibril structure. However, for the GM1-free lipid, Abeta was first released to yield a fibril structure about the membrane surface, then the membrane became disrupted resulting in the formation of small vesicles. In Ch-free lipid, a fibril structure with a phospholipid membrane-like shadow formed, but this differed from the well defined fibril structure seen for CCM-lipid. In Ch-GM1-free lipid, no fibril structure formed, possibly because of membrane solubilization by Abeta. The absence of fibril structure was noted at physiological extracellular pH (7.4) and also at liposomal/endosomal pH (5.5). Our results suggest a possible role for both Ch and GM1 in the membrane release of Abeta from brain lipid bilayers.

Amyloid beta-Peptides↗